\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
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\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
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\r\n\r\n\tGeochemistry of the elements is the study in metals, rocks, and earth covers of the distributing of chemical elements and their forms of presence. This section has found numerous facts concerning the distribution of chemical components. Light elements with atomic weights of less than 29 are the most prevalent elements on the earth's crust. The oxygen, hydrogen, silicon, and aluminum elements are the most common and most important elements in the formation of Earth crust and earth coverings. The first is roughly 50% of the Earth's composition and its life significance and the first and the second constitute water, and the combined elements consist of rocks which are more than half of the sedimentary rocks and are more widespread than other elements, with their numbers and weights of atomic material. There are however many questions that need to be solved, such as the high variability in chemical elements' concentrations and the presence of scarcity elements in the case of dispersion among other metals, such as rubidium.
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In Western countries the incidence of osteomyelitis and septic arthritis is 5-12 per 100.000 infants [3]. The overall incidence rate for bone and joint infections is 0.12 per 1000 live births and 0.67 per 1000 neonatal intensive care (NICU) admissions [4], with a mortality rate of 7.3% [5]. Some recent studies have reported an estimated incidence of 1-7 per 1000 hospital admissions for neonatal osteomyelitis [6,7]. In a review of more than 300 cases of neonatal osteomyelitis male infants are seen to predominate over females (1.6:1) and preterm infants to be at higher risk than term infants [8-10]. Risk factors for osteomyelitis and septic arthritis in preterm infants are mostly iatrogenic, including invasive procedures, intravenous or intra-arterial catheters, parenteral nutrition, ventilatory support, and bacteremia with nosocomial pathogens [11,12]. Two subgroups of neonates are affected: premature neonates with prolonged hospitalization and otherwise healthy newborns presenting within 2 to 4 weeks of discharge [13].
Neonatal osteomyelitis arises as a consequence of hematogenous spread of microorganisms, which is the most common route of infection. In preterm infants, neonatal osteomyelitis frequently results from directly inoculated bacteria (secondary to heel or venipuncture, umbilical catheterization, infected cephalhematoma, etc.) [14,15]. Premature rupture of membranes and transplacental infection have also been described as risk factors for neonatal osteomyelitis [16].
The most common bacterial pathogen causing osteomyelitis in children is
Hematogenous infection of the long bones, which are most frequently affected, begins in the capillary loops of the metaphysic, adjacent to the cartilaginous growth plate (physis). These areas are very susceptible to hematogenous infection, because of its high vascularity and because the blood flow within the vessels is slow [22]. Bacteria can pass through gaps from the sinusoidal veins to the capillaries into the tissue, where they are provided an ideal environment to grow, resulting in abscess formation. These abscesses frequently rupture into the joint [23]. In neonates acute hematogenous osteomyelitis and septic arthritis co-exist in up to 76% of all cases as a result of this unique vascular anatomy of the epiphysis; the bone marrow compartment is seldom involved [10,24]. The epiphysis receives its blood supply directly from metaphyseal blood vessels (transphyseal vessels) and the adjacent cartilaginous growth plate is traversed by capillaries, allowing spread of the pathogenic bacteria to the physis, epiphysis and joint and resulting in slipped epiphyses, fractures, premature physeal closure and chronic infection (Figure 1) [25].
Characteristics of the neonatal bone prevent many of the features of chronic osteomyelitis: cortical sequestra are often completely absorbed due to extensive bone blood supply in the newborn and, in addition, efficient vasculature of the inner layer of the periosteum encourages early development of new bone formation [26,27]. Complete destruction of joints is rare, but serious growth disturbances may occur.
Diagnosis of osteomyelitis in the neonate can be challenging and is often delayed, as it is rare in the neonatal period and frequently presents with non-specific signs of illness. Diagnosis is based on clinical signs and symptoms, laboratory findings, radiological and microbiological criteria.
In general, two distinct clinical syndromes have been postulated to be associated with neonatal osteomyelitis: 1) a benign form, with little or no evidence of infection other than local swelling, and 2) a severe form, with the predominant manifestation of a sepsis-like syndrome with multiple bone sites being noted as manifestations [28]. In neonates, almost half of all cases involve two or more bones.
Anatomic depiction of blood supply to the epiphysis and metaphysis in the developing bone that influences the progression of osteomyelitis in the neonate (modified and redrawn from Kaye JJ et al, [
Clinical symptoms and signs of osteomyelitis in the neonate are at first frequently unspecific and mild. They may include temperature instability, feeding intolerance, irritability or reduced movement, frequently giving rise to the suspicion of secondary sepsis. Fever is a rare condition that could be explained by a rather poorly developed immune system. As the disease progresses, more specific signs may become present, including disability, local swelling or erythema. Focal tenderness over a long bone should catch the physician\'s attention. In some cases subcutaneous abscess formation prompts the diagnosis of osteomyelitis. Hip, knee and shoulder are most frequently involved [7,28,29].
In general, there is no specific laboratory test for osteomyelitis. Neonates with osteomyelitis frequently show normal leukocyte counts and erythrocyte sedimentation rates in the first days. Thus, normal values do not preclude the diagnosis [30]. The C-reactive protein (CRP) is a rapid indicator of systemic inflammation and tissue damage, is useful as acute phase reactant, but not specific for skeletal infection. Procalcitonin has also been described as a potential marker in the diagnosis of osteomyelitis in children, but needs to be investigated in larger trials, especially in newborns [31,32]. Elevated values of CRP and erythrocyte sedimentation rates could be used to monitor response to therapy or identify complications.
Radiological investigations confirm the suspicion of neonatal osteomyelitis, define the infection site, differentiate between unifocal and multifocal disease patterns and identify secondary complications. Computed tomography, magnetic resonance imaging, ultrasound, radiography and bone scintigraphy scanning have been reported to be useful in detecting osteomyelitis. However, awareness of radiation exposure, need for sedation and transfer to another unit must be considered in the selection of technique.
Radiographs should be the first diagnostic assessment to be performed in patients with suspected osteomyelitis, because they may suggest the correct diagnosis and exclude other pathologic conditions (Figure 2a). However, the specificity of plain radiographs for detecting osteomyelitis is greater (75% to 83%) than its sensitivity (43% to 75%) [33]. Plain radiography can show soft tissue swelling and destroyed fascial planes within days after onset of infection, but may be subtle and not obvious until day 5 to 7 in children [34]. In the neonate even soft tissue swelling may not be present, because subcutaneous fat is lacking and fascial planes are poorly defined. Joint effusions might be suspected if widening of the joint space or bulging of the soft tissues is detected. Additional early changes are as follows: periosteal thickening/elevation, lytic lesions, osteopenia, loss of trabecular architecture, and new bone apposition [35]. Of importance, destructive bone changes do not appear until 7 to 14 days of disease [25].
Predominately in children, ultrasound can detect features of acute osteomyelitis several days earlier, than radiographs [34]. Even though findings may not be specific and standardized reports for neonates with osteomyelitis are lacking, ultrasound should be taken into account as a useful additional diagnostic tool for the early detection and management of osteomyelitis in neonates as it has many advantages: it is non-invasive, readily accessible, performed bedside, of minimal discomfort for the patient, does not use ionizing radiation and does not need sedation [36,37]. Even though ultrasound cannot exclude the diagnosis of osteomyelitis, its main value lies in its ability to identify involvement of the adjacent soft tissue (subperiosteal fluid collection or abscess formation), periosteal thickening or elevation, joint effusions and irregularities or interruptions of the cortical bone (Figure 2b) [38,39]. Color Doppler imaging further supports the diagnostic assessment, showing coexisting presence of hyperemia surrounding the periost and soft tissue abscess formation. Ultrasound can also be used to image guided-needle aspiration of the subperiosteal fluid for pathogenic organism isolation or subperiosteal abscess drainage. Furthermore, ultrasound has been described as being helpful in differentiating between epiphyseal separation and subluxation following septic arthritis [40]. However, ultrasound cannot exclude the diagnosis of acute osteomyelitis, and thus further imaging diagnostics may be required [41,42].
a
b
Acute osteomyelitis of the right humerus. a) periosteal elevation and soft tissue swelling b) joint effusion and synovial thickening
Magnetic resonance imaging (MRI) has high specificity (94%) and sensitivity (97%) for the diagnosis of acute osteomyelitis, showing changes as early as day 3 to 5 after the onset of infection [43,44]. MRI gives excellent tissue characterization and high resolution, showing detailed anatomic presence of the inflammatory process and its complications (abscess formation, physeal involvement, septic arthritis), further allowing the assessment of involvement of the growth plate and epiphysis. MRI has been proven useful in the diagnosis of clinically suspected osteomyelitis in children [45-48], but for its use in neonatology it has several limitations: first and foremost the need for sedation and transfer to the MRI unit.
Three-phase bone imaging, using technetium 99m is very sensitive (90%-95%) for the detection of acute osteomyelitis in the early stages of disease and allows detection within 24 to 48 hours after onset of symptoms [34,49]. Bone scintigraphy is especially useful for detecting multiple foci of infection or if the infection site is poorly localized. Technetium-99 methylene diphosphonate accumulates in areas of increased bone turnover and is for now the preferred agent of choice for radionuclide bone imaging. In neonates bone scintigraphy is the subject of controversy: only a few reports support its use and have shown that sensitivity is much lower, than in older infants because of poor bone mineralization [18,48,50].
Successful cure of osteomyelitis during the newborn period is dependent on a fast and true diagnosis and sufficient treatment. Empirical selection of antibiotic therapy depends on the age and the clinical situation of the infant. Antimicrobial therapy should be started as soon as the diagnosis is made and directed against the most common bacterial isolates responsible for hematogenous osteomyelitis according to age group. Delay in therapy commencement increases the risk for complications. If a definitive organism is isolated, antimicrobial treatment should be accordingly adjusted.
For neonates an empiric regimen should include excellent coverage against S. aureus, group B streptococcus and enteric gram-negative bacteria, thus consisting of a third-generation cephalosporin (cefotaxime) plus an antistaphylococcal agent (amoxicillin). Infants at risk for hospital-acquired infection (methicillin-resistant or coagulase negative Staphylococcus aureus) should receive vancomycin instead of amoxicillin.
Duration of treatment depends on the extent of infection, the clinical response and the presence of underlying risk factors [51]. In the case of unifocal osteomyelitis continuation of treatment for six weeks and in the case of complex disease, defined as multifocal, significant bone destruction, resistant unusual pathogen, septic shock, continuation for more than six weeks to months might be required. Antimicrobial treatment is frequently administered intravenously for two to three weeks and then switched to oral medication [52]. Surgery is indicated to drain acute abscesses or when no improvement is achieved with antibiotic treatment.
Several studies have documented poor outcome even with modern treatment facilities. In neonates the reported incidence of permanent sequelae varies from 6% to 50% [2,11]. Neonatal osteomyelitis can lead to permanent joint disabilities, disturbances in bone growth secondary to damage to the cartilaginous growth plate, limb-length discrepancies, arthritis, decreased range of motion and pathologic fractures [51].
Neonatal osteomyelitis, although a rare complication, remains a diagnostic and therapeutic challenge and poses the infant at high risk for long term morbidity. Osteomyelitis should be considered in newborn infants presenting with clinical signs of sepsis, but lacking an obvious focus, in order to facilitate early diagnosis and prompt initiation of appropriate therapy.
A certain minimal level of progesterone must be maintained from ovulation until delivery to allow the birth of a full-term live baby [1]. Progesterone (P), acting in conjunction with the P receptor, causes the production of a large number of various molecules needed for the development of an appropriate secretory endometrium to allow attachment of the blastocyst to the endometrium and adequate invasion to the proper depth of the fetal placental unit [1].
Some of the molecules induced are also needed to suppress rejection of the fetal semi-allograft. One of these immunomodulatory proteins has been termed the progesterone induced blocking factor (PIBF) [2]. There is evidence that PIBF is one of the most important immunomodulatory factors produced during pregnancy to inhibit immune rejection of the fetal semi-allograft [3, 4].
Progesterone-induced blocking factor is an immunomodulatory protein that can suppress or block various aspects of the immune system, especially, but not limited to, natural killer (NK) cells [5, 6]. The blocking effect on cellular immunity, especially NK cell cytolytic activity, may be related, at least in part, to a shift from thymic helper (TH)-1 to TH2 cytokine dominance [7]. One mechanism by which PIBF can suppress NK cell cytolytic activity is by inhibiting degranulation of perforin granules, one mechanism used by NK cells to kill other cells [8].
The “parent” form has a molecular mass of 90 kDa and is localized in the centrosome [9]. Various splice variants of this nuclear protein lead to smaller intracytoplasmic molecules that have immunosuppressive activity [9]. The actual full-length protein contains 757 amino acids, and the 48 kDa N terminal part is biologically active [10]. The PIBF gene has been identified on chromosome 13 in the vicinity of breast cancer 1 (BRCA1) or BRCA2 or p53 [11, 12].
Progesterone-induced blocking factor rises precipitously in the serum after exposure to P (even in males injected with progesterone) and the source seems to be circulating gamma/delta T cells [2]. However, it seems that the main source of PIBF that allows the early feta-placental to escape immune surveillance are actually cells of the fetal placental unit namely embryonic cells, mesenchymal cells, and trophoblast cells [1, 9].
In 2001, Check et al. hypothesized that it is likely that cancer cells might “borrow” some of the same mechanisms to escape immune surveillance as the fetal-placental unit [13]. Based on their previous research with the PIBF protein, they considered that, whereas treatment for infertility or recurrent miscarriage should be aimed at increasing the production of the PIBF protein, theoretical treatment for cancer could be therapy aimed at suppressing the PIBF protein [13].
Support for this concept was provided by Lachman et al., who showed that many different types of cancer cells express this PIBF protein [9]. Though one may think that highly proliferating cancer cells may be the ones that have the classic nuclear progesterone present, the study by Lachman et al., found many of the cancers associated with PIBF were not known to be positive for the nuclear P receptor [9].
Based on this hypothesis, it was considered that a P receptor antagonist/modulator should cause suppression of PIBF production in rapidly growing cancer cells which could overcome the theoretical block of immune function of cellular immune cells in the tumor microenvironment.
Mifepristone was the first P receptor antagonist developed [14]. It was a derivative of the synthetic progestin norethindrone [14]. It was purposely developed to be an abortifacient to alter the endometrium and cause decidual necrosis and cause the trophoblast to separate from the decidua [14, 15, 16]. Mifepristone sensitizes the pregnant uterus and cervix to endogenous and exogenous prostaglandins increasing uterine contractility and helps to induce cervical softening [14, 15, 16].
Over the years other benefits of mifepristone, related to its anti-progesterone effect, have been developed, including treating uterine leiomyomata and endometriosis [17]. The anti-abortifacient drug comes in 200 mg tablets. Since mifepristone in higher dosages blocks the glucocorticoid receptor, it has been approved as a 300 mg tablet to treat Cushing’s syndrome [18].
Thus, we set up a study to determine if we could detect PIBF in various leukemia cell lines, and, if so, determine if adding mifepristone to the medium could reduce PIBF secretion. To do so we collaborated with Dr. Srivastava from the Roswell Park Cancer Institute, who for many years studied protein production by leukemia cell lines. Twenty-nine cell lines of diverse lineage were all found to express messenger (m) RNA for PIBF [19]. In fact, there was more mRNA dedicated to the production of the PIBF protein, by far, than any mRNA for any other protein previously studied in these leukemia cell lines [19]. Ten cell lines positive for mRNA for PIBF were tested for the PIBF protein using a much less sensitive assay for PIBF than is presently available. Four tested positive for the PIBF protein. Addition of progesterone to the media of the cell lines up-regulated mRNA for PIBF and also the PIBF protein [19]. In contrast, the addition of mifepristone to the media down-regulated both mRNA for PIBF and the 35 kDa PIBF intracytoplasmic splice variant protein (similar in size to the PIBF splice variant in fetal-placental cells) [19].
Subsequently studies using other cancer cell lines supported the conclusions from the leukemia cell line studies. Kyurkchiev et al. found that glioblastoma multiforme also express the intracytoplasmic PIBF protein, but in this case the splice variant measured 57 kDa [20]. Gonzalez-Arenas et al. found, similar to the aforementioned leukemia cell line studies, adding P to the media up-regulates the 57 kDa intracytoplasmic splice variant of PIBF in glioblastoma multiforme cell lines [21]. Interestingly, in addition they added PIBF protein to the media and found that PIBF increased the number of U87 cancer cells on days 4 and 5 of treatment. This suggests that PIBF promotes proliferation of human glioblastoma cancer cells independent of an intact immune system, which would require a whole intact animal or human [21].
Mifepristone has been also found to inhibit the growth of cell lines or murine tumor transplantation from endometrial cancer, breast cancer, prostate cancer, gastric cancer, ovarian cancer, and lung cancer [22, 23, 24, 25, 26, 27].
Goyeneche’s group published some interesting findings concerning mifepristone and ovarian cancer cell lines. They have found that mifepristone inhibits ovarian cancer cell growth in vitro and in vivo [28]. They have published several studies showing the benefit of the combination of mifepristone and chemotherapy with cisplatin therapy or cisplatin-paclitaxel treatment of ovarian cell lines [29, 30, 31].
Based on these cell line studies, more support was provided that cancer cells may borrow some of the same escape mechanisms as the fetal-maternal unit to escape immune surveillance. Thus, therapy aimed to suppress these immune factors could lead to novel effective anticancer therapies [32]. Dr. Szekeres-Bartho, another pioneer in determining that the immunomodulatory protein, PIBF, plays a major role in allowing the fetus to avoid immune surveillance, in 2010 wrote a treatise entitled “PIBF: the double-edged sword. Pregnancy and tumor” [33].
In an opinion entitled “Pregnancy is a model for tumors, not transplantation,” the renowned immunologist Kenneth Beaman, and his group, in 2016, stated “Nearly 65 years have passed since Peter Medawar posed the following question: “How does the pregnant mother contrive to nourish within itself for many weeks or months, a fetus that is an antigenic foreign body.” Now, understanding of reproductive immunology has demonstrated that the HLA antigens in the placenta are non-classical and do not induce rejection. In the placenta and in tumors, 50% or more of the cells are cells of the immune system and were once thought to be primed and ready for killing tumors or “the fetal transplant” but these cells are not potential killers but abet the growth of either the tumor or the placenta. By examining the similarities of the placenta’s and tumor’s immune cells, novel mechanisms to cause tumors to be eliminated can be designed. Thus, 15 years later, the concept we published in 2001 is starting to be accepted by top immunologists in the field [34]. Though Beaman et al. do not refer at all to the PIBF protein, I recommend an article in gynecologic oncology to those readers wanting further knowledge into the immune similarities between pregnancy and cancer to open the door for other novel treatments of malignant tumors other than blocking the progesterone receptor [35].
In humans, the progesterone receptor (PR) is expressed in prostate stroma. Reduced PR expression in cancer-associated stroma can be conducive to a tumor microenvironment favorable for cancer cell invasion and tumor metastases [36]. Thus, if the presence of the PR somehow inhibits tumor invasion and metastases, treating with a PR antagonist may worsen the condition.
However, it may be that the loss of the PR receptor merely suggests a higher percentage of more aggressive cells, and thus, mifepristone, by suppressing PIBF, may inhibit prostate cancer proliferation. Indeed, gavaging mice with spontaneous prostate cancer with mifepristone (which on a weight basis was equivalent to 200 mg daily in humans) improved longevity of survival and body condition scores compared to placebo gavaged C57BL/6 mice [37].
Controlled studies were also performed in mice where there was no knowledge of the presence of the classic nuclear PR. Beneficial effect on longevity and quality of life (body conditioning score) were observed in 129 Pd/J mice with a strong predisposition for testicular cancer, in aldo-keto reductase/J mice with spontaneous lymphocytic leukemia and A/J mice with spontaneous lung cancer [37, 38, 39]. As an example, in A/J mice with spontaneous lung cancer, 67.4% treated with mifepristone survived 1 year vs. 27% of the controls [39]. Even more important, there were 66.7% of mice gavaged with the equivalent of 200 mg/day in humans with mifepristone who had no sick days (body conditioning score less than 4) vs. zero % for controls [39]. These murine carcinoma studies supported the concept that the benefit of mifepristone is not merely for cancers positive for the classic nuclear PR. If the mechanism of improvement did operate through the PIBF mechanism, the presence of the classic nuclear PR is not needed for production of PIBF expression by the tumor cells.
Based on cell line studies and controlled animal studies, we wanted to determine if the mifepristone could provide increased longevity and/or improved quality of life in human patients with advanced cancer. Unfortunately, though physicians generally have the right to use drugs off-label, there was a restriction for mifepristone. This was not related to risk of the drug, but related to appeasing antiabortion groups who feared that the drug could find easy use to cause abortions. Thus, to use mifepristone as an anticancer drug, one needs to obtain from the Food and Drug Administration a compassionate use investigational new drug (IND) approval to use mifepristone to treat cancer.
The first patient we treated with oral daily mifepristone 200 mg/day was a 46-year-old woman diagnosed with a rare thymic epithelial cell cancer. Over a one-year period following initial surgery and radiotherapy more cancerous lesions developed in the lung. There was no standard chemotherapy, but she was approved for experimental octreotide. However, the cancer still progressed. After starting mifepristone 200 mg/daily, though, her lung and mediastinum lesions did not regress, they remained stable. Clinically, she was feeling much better in that she had much less shortness of breath, much less cough and, marked improvement in fatigue. This clinical improvement persisted for over 2 years. Her oncologist decided that since the lesions were stable, this could be the opportunity to attempt a “cure” by a second course of radiotherapy to the mediastinum. She developed pulmonary fibrosis from this second course of radiotherapy. According to the thymic Cancer Carcinoma Society, she had survived the second longest time of any patient with this type of cancer [40]. Now, with more clinical experience, she would have been advised against more radiotherapy and just continue the mifepristone. Most metastatic cancers will not be “cured.” The end point of treatment with mifepristone should be quality of life and increased longevity. This first case of our series of anecdotal cases treated with mifepristone first started treatment in 2004. It is important to note that thyroid epithelial cell cancer is not known to be associated with the classic nuclear P receptor.
The second case of advanced cancer that we obtained a compassionate use IND to treat was a 61-year-old woman with a 6.5 cm invasive moderately differentiated adenocarcinoma of the transverse colon with extensive metastasis to the liver, peritoneum, ovary and uterus. She had marked ascites. The two largest liver metastases measured 3.1 × 1.3 cm and 2.3 × 1.9 cm. She was advised by her oncologist that even with chemotherapy she would only have a 15% chance of living 6 months.
After 1 year of mifepristone therapy 200 mg orally per day her carcinoembryonic antigen level had dropped all the way down to 1.6 ng/mL. After 18 months, there had not been any growth of her metastatic lesions nor did any new ones appear. She had no pain, no vomiting, and she stated her energy was great.
A CT-scan at 22 months showed some growth of the lesions. Nevertheless, she was pain free with good energy even at 27 months when ascites began to return (it had completely disappeared). She was still ambulatory at 30 months when she died.
Several years later talking to her sister we found out that at 18 months, to save money, she started taking the mifepristone every other day. Thus, this case helps to establish that the daily dosage should not be less than 200 mg/day. The case also supports the concept that mifepristone can prolong life and provide palliation for cancers not known to be associated with the classic P nuclear receptor [41].
Another 43-year-old woman with stage IV metastatic colon cancer, who had progressed despite standard chemotherapy, began single agent mifepristone therapy. Similar to the aforementioned case, there was a halt to cancer progression, her energy markedly improved, and she had great relief of pain. After 18 months some of her metastatic lesions began to grow. She assumed that this was the end of her remission, so she stopped the mifepristone, and decided to try a new experimental drug. She died 3 months later [40]. Based on subsequent clinical experience, we would have advised her that even though the lesions are starting to grow again, mifepristone will still prolong a high quality of life, and will prevent rapid spread, thus advising her not to stop mifepristone.
An 83-year-old man with rapidly growing stage IV colon cancer with metastases to his lungs, liver, peritoneum, and lymph nodes showed no improvement to either capecitabine or cetuximab. He was so weak that he could not get out of bed. Within 2 weeks of 200 mg mifepristone tablets daily obtained with compassionate use his energy returned, and he was able to resume normal function and go to restaurants and other social events and completely take care of himself (ECOG 0 now). His appetite also returned, and he was pain free.
After 4 ½ months of therapy none of his previously rapidly growing metastatic lesions grew with the exception of 1 lung lesion that grew 0.3 cm. He had no side effects from treatment. Though he had no kidney metastases, he had pre-existing marked renal impairment. He became uremic. His wife was deciding on dialysis or not when he died of a sudden myocardial infarction [41].
Sometimes, instead of the mifepristone therapy causing stable disease, or changing the pattern from rapid progression to slow progression, the lesions may show marked regression. This is evidenced by a 45-year-old woman who had widely metastatic leiomyosarcoma despite previous treatment with total abdominal hysterectomy and bilateral oophorectomy, letrozole (the tumor was estrogen receptor positive), and gemcitabine/docetaxel, and resection of lung metastases [40].
She was started on mifepristone 200 mg/day orally. This caused an almost total remission, with disappearance of almost all lesions, and those remaining had shown marked decrease in size. After 6 months, some lesions began to appear, but they were still very small. Nevertheless, without experience with the nature of this drug, the oncologist opted to stop mifepristone and place her in an experimental trial. She died within 1 month from complications of this new drug [40].
Another case of very rapidly growing advanced cancer showing complete remission following ingestion of 200 mg/day oral mifepristone was an 80-year-old woman with a history of chronic lymphocytic leukemia who developed sudden onset respiratory failure with a po2 of 72 mmHg. Chest X-ray revealed many lung lesions with a radiographic diagnosis of probable advanced lung cancer with multiple metastatic lesions. Her serum sodium was 118 mmol/L. She refused a surgical diagnosis or chemotherapy based on the presumptive clinical diagnosis of small cell lung cancer with the syndrome of inappropriate anti-diuretic hormone (SIADH) and the bleak prognosis, even with chemotherapy [42].
She sought an alternative treatment and agreed to mifepristone therapy 200 mg orally daily. Within 1 month her po2 returned to 99-100 mmHg without supplemental oxygen. Her serum sodium increased to normal at 145 mmol/L. Her CT-scans showed complete disappearance of all lung lesions even 5 years after initial diagnosis. There did remain, however, a ground glass appearance in the lungs. She died 5½ years later at the age of 85.5 from an acute myocardial infarction, not from lung cancer [42].
Interestingly, though we know that PIBF is secreted by leukemia cell lines and is suppressed by mifepristone, this woman’s CLL slowly progressed while her rapidly growing presumed small cell lung cancer had a complete remission [19]. This could suggest that mifepristone acts better on rapidly growing cells than slowly growing cancers. Of course, it is possible that the mifepristone helped keep the CLL slow growing, but that could simply be related to the normal situation of slow progression with CLL even without treatment. It should be noted that lung cancer, whether small cell or non-small cell (which is still possibly the type of cancer this woman had though small cell was more likely because of the clinical picture) is not known to be associated with nuclear P receptors.
Many cancer therapies are ineffective for brain metastases or primary brain cancers because they cannot cross the blood-brain barrier. There is anecdotal evidence that mifepristone can cross the blood brain barrier and provide palliative benefits for primary brain cancer and brain metastases.
A 43-year-old male with a 3-week history of severe protracted headaches was found to have a large glioblastoma multiforme grade IV that originated in the temporal lobe but involved also the frontal, parietal and temporal lobes and metastases to the spinal cord. Despite surgery, radio and chemotherapy, the tumor rapidly progressed. He was not considered a candidate for any other therapy. At the time of starting mifepristone therapy, he was paralyzed from the neck down and his hands were fixed in the clenched position. He slept most of the day, and when awake, was not able to carry out conversations [43].
Within 2 weeks of treatment with 200 mg oral mifepristone daily, he became much more alert and was able to carry out intelligent conversations. He was now able to open his clenched fists and move his hands. He continued treatment for 3 months and remained alert. However, his paralysis slowly progressed to the point where he was having trouble breathing and swallowing. The mifepristone was stopped, and he died 2 weeks later [43].
Another case demonstrating that mifepristone can cross the blood brain barrier to thwart brain metastases from progressing is a case of a 68 year old male with stage IV metastatic non-small cell adenocarcinoma lung cancer with brain metastases who was referred by his oncologist for mifepristone therapy [44]. Based on the experimental data with efficacy of mifepristone inhibiting growth of cancer cell lines, the beneficial effect in controlled various murine carcinomas, and the anecdotal benefits in individual causes with various advanced cancers following single agent mifepristone therapy the FDA approved our investigator imitated study entitled “A phase II study of treatment with oral mifepristone as salvage therapy in patients who have failed two or more previous chemotherapy regimens” (www.clinicaltrials.gov).
He had no tumor markers that could provide him targeted therapy. His cancer progressed despite 3 rounds of multi-agent chemotherapy including carboplatin/avastin/docetaxel, pemetrexed, and gemcitabine. In October of 2015 he had a seizure and magnetic resonance imaging indicated a 1 cm right frontal lobe metastatic lesion. He received palliative stereotactic radiotherapy to the brain lesion which was completed in November 2015.
With deteriorating symptoms, for example, dyspnea on exertion and fatigue and with no other treatment options available (PD-L1 marker was negative and check-point inhibitors were not approved for PD-L1 negative patients at this time), he was referred for our FDA study.
In all previous cases, the 200 mg mifepristone tablets were obtained from Danco Inc. at a cost of about $500 per month. For the FDA approved investigator-initiated study, we decided to use mifepristone 300 mg tablets daily because the company Corcept, Inc. which manufactures the 300 mg tablet for treatment of Cushing’s syndrome (though the dosage is generally much higher than 300 mg to block the glucocorticoid receptor) was willing to provide the drug free to approved patients.
His clinical symptoms improved significantly within 1 month of treatment with single agent oral mifepristone 300 mg daily. He was ECOG 1 at the start of therapy and after 1 month was ECOG zero. He remains ECOG zero after 4.8 years of treatment, and for the majority of visits, he answers his 43 questions on the quality of life evaluation as “not at all” (the best answer that could be given). There has been no evidence of growth of his previous brain metastases or any new lesions by MRI testing.
One additional important piece of information that his case provides. His metastatic lesions remained stable for 1.5 years. But after 1½ years, some lesions began to grow slowly. His oncologist, based on his experience with other anticancer agents, thought that once disease progression began, it usually accelerates rapidly. He thus suggested to the patient that he stop the mifepristone, and consider nivolumab or pembrolizumab, which had at this time been tried on some patients who were PD-L1 negative, or consider another biopsy to determine if a new tumor marker could be found that would allow targeted therapy. The patient feeling so good on mifepristone therapy and feeling so poorly on all of his previous chemotherapy regimens, opted to take our advice and continue on the mifepristone therapy. Now 3.5 years later and still feeling great, he is very satisfied with his decision not to stop mifepristone therapy [44].
This case exemplifies the mistakes, from lack of experience, that we alluded to in some of the previous case reports, that is, one should not stop the drug if there is the start of tumor progression. There is still a good chance the drug will provide continued extension of a good quality life. Naturally, if a new therapy is likely to be more effective than the mifepristone therapy, then it would make sense to try the new agent. But it makes no sense to try a completely new experimental drug with unknown side effects, as tried by some of the previous described cases. Furthermore, experience suggests that mifepristone inhibits metastases, but cessation of therapy results in rapid spread. This progression can be so rapid that it could be too late to resume mifepristone therapy if the new anticancer therapy is not working.
Therapy with mifepristone could be considered hormonal therapy, but because its hypothesized mechanism is that it removed a block (i.e., PIBF), and thus allows the cellular immune system (especially NK cells) to attack cancer cells, it could also be considered a form of immunotherapy. The question arises as to whether the drug would be effective in cancers positive for the programmed cell death protein ligand 1 (PD-L1) marker where there was initial response to immunotherapy with a check-point inhibitor but where the tumor was now showing resistance.
We did describe a case of a 66-year-old woman with stage IV non-small cell lung cancer, who not only had the PD-L1 marker, but also her cancer was positive for the epidermal growth factor receptor (EGFR). When her cancer began progressing following chemotherapy with carboplatin, pemetrexed and bevacizumab regimen and the carboplatin and docetaxel regimen, she was started on a targeted therapy for the EGFR marker, erlotinib [45]. At that time, there was only first-generation tyrosine kinase inhibitors.
When her cancer progressed despite erlotinib, she was treated with 11 cycles of the check-point inhibitor nivolumab. It was stopped after 11 months because it was apparent the drug was no longer inhibiting her cancer progression. She qualified for the investigator-initiated study, and thus she was treated with the 300 mg oral daily dose of mifepristone [45].
After 18 months of oral 300 mg single agent mifepristone therapy, there had been no cancer progression based on lung CT scans performed every 2 months. In fact, some lesions were actually smaller. She was considered ECOG 1 at the start of mifepristone therapy. At the end of 1 year, she was still ECOG 1 with a good quality of life and normal physical activity.
After 1 year, her pre-existing severe chronic obstructive pulmonary disease (COPD) worsened and she required supplemental oxygen to keep her po2 above 80 mmHg. Based on her COPD, but not her cancer which still had not progressed, at 18 months from initiation of treatment, she was an ECOG 3. She died 2 months later from pneumonia.
Thus, this patient not only showed that mifepristone can prolong life and provide a good quality of life not only in a patient whose lung cancer is positive for the PD-L1 marker, but a person who also has the EGFR mutation [45].
Anecdotal cases are important, but more influential to other physicians would be a larger series. Even better would be a controlled trial with sufficient power, and the very best, a study that has all these qualifications, but is also multi-centered. The FDA approved the aforementioned investigator-initiated study for 40 patients. It is not considered ethical to have patients with such severe disease and subject them to placebo controls. Thus, the study was to evaluate in a larger series the efficacy of mifepristone therapy for advanced lung cancer and compare outcome to historical controls, that is, from quality of life to life expectancy, when dealing with a similar group of patients with lung cancer that has stage IV and failed at least two chemo or immunotherapy regimens.
We were allowed two principal investigators. However, as an investigator-initiated study with no funds provided to the principal investigator by a pharmacological company or a grant, we could not find a principal investigator who treats a larger population of patients with lung cancer. Thus, we became, by default, the only principal investigator. Unfortunately, it is not totally clear to us as to the reasons, but despite our efforts we have only recruited the two aforementioned patients that were treated in this investigator-initiated study. Perhaps some of the fault lies in making the criteria for registering too harsh, but most of the problem is that we have not been referred very many patients to even screen for the study. Even the physician who referred us our first case who still is doing so well after almost 5 years of single agent mifepristone therapy, plus years with no side effects, has not referred us another patient [44]. We asked him if he had more patients and he stated that he could send us 40 patients in 1 year, but patients do not want to travel 100 miles every month to receive the medication. This seem unbelievable but this was also related to us by an oncologist whose research with us involving PIBF helped him get into medical school, where the patients would only have to travel only 15 miles. He was supposed to be our first principal investigator, but his associates objected. Even our own well renowned cancer facility at our institution turned down the opportunity to be a principal investigator and has never referred one patient for treating cancer whether they had lung cancer for this investigator-initiated study, or for compassionate use for other cancers. From what we have ascertained, they refer the patients to hospice when they are at the stage eligible for our study. Yet they kindly refer to us many patients to consider oocyte freezing or embryo banking before potential ovary damaging therapy.
Actually, there were two patients with lung cancer that we screened that would have qualified for the investigator-initiated study. They both had stage IV non-small cell lung cancer positive for the EGFR mutation that were at the end of targeted therapy (erlotinib, afatinib, and osimertinib) because the lesions were progressing. They both responded very well to single agent mifepristone. Their case reports were accepted for presentation at the 2020 American Association for Cancer Research (“Improvement in quality and length of life following treatment with mifepristone in women with stage IV non-small cell lung cancer positive for the EGFR mutation that previously progressed on targeted therapy”). Because our study was not recruiting very well, we advised these two patients to try compassionate use 200 mg mifepristone, where the drug can be shipped to their homes, rather than travel thousands of miles monthly to receive the medication gratis as required by the study design.
There were two other abstracts accepted by the annual 2020 AACR meeting. The title of one tells it all – “Treatment with oral mifepristone enables a patient with end-stage pancreatic cancer, in hospice, on a morphine drip, to restore a decent quality of life.” The only other patient who we treated with mifepristone from pancreatic cancer, similar to the aforementioned patient, demonstrated a marked relief of her severe pain that had been present despite opiates. However, her husband, a physician, was informed by a major oncologic center of a new phase I research study. He quickly brought his wife there for treatment and she died 2 days later from cardiac complications of the new drug [40].
A third abstract accepted for the 2020 annual AACR meeting is entitled “Palliative benefits of oral mifepristone for metastatic osteosarcoma.” This shows the wide diversity of different advanced cancers that have responded to extremely well tolerated oral mifepristone, frequently providing the patients their best quality of life even when their cancers had not been as advanced. The reason is that even in less advanced stages, many of these patients suffered from side effects of chemotherapy or even immunotherapy.
Pancreatic cancer and fibrous osteosarcoma are not known to be associated with the nuclear P receptor. Other patients with some rare advanced cancers have demonstrated significant palliative benefit following mifepristone therapy include a malignant fibrous histiocytoma in a 23-year-old male and an extremely aggressive transitional cell carcinoma of the renal pelvis [40].
The presence of the classic nuclear P receptor in breast cancer tumors has been known for at least 40 years [26]. The thinking in those days was that the presence of the hormone receptor may be needed for the tumor to proliferate. Thus, intervening with the hormone receptor interaction may inhibit cancer growth while not creating serious adverse effects in the patient as long as the hormone-receptor interaction was not essential to life or well-being.
Based on the beneficial effects of blocking the estrogen receptor with selective estrogen receptors, that is, tamoxifen, it is not surprising that mifepristone was evaluated for treating advanced breast cancer with the thought that the interaction of progesterone with the classic nuclear progesterone receptor could somehow allow tumors, for example, breast and ovarian cancer to proliferate.
Mifepristone is a type II progesterone receptor antagonist which promotes DNA binding and also promotes progesterone receptor phosphorylation [46]. Mifepristone was given to advanced stage tamoxifen resistant women (second line setting) and the authors reported a complete or partial response in about 10% [47]. However, 6 of the 11 showed stable disease [47]. Another small study found an objective response rate of 18% [48]. For first line, mifepristone for untreated metastatic breast cancer, a 10% objective response rate was observed [49].
The main method of evaluating efficacy of anticancer treatments 25–40 years ago, and even today, is inhibition of disease progression. Thus, the improvement did not seem adequate enough compared to other “more encouraging therapies”. Thus, interest waned in treating advanced breast cancer with mifepristone. Subsequently, more experience with mifepristone therapy for a variety of advanced cancers will show that although sometimes the treatment will cause a very good objective remission, the majority of the time the drug provides significant palliation and extension of a higher quality life while it slows disease progression.
For ovarian cancer not only is the classic nuclear progesterone receptor present but it also predicts a favorable outcome [50]. For similar reasoning as with breast cancer, mifepristone was given about 20 years ago to patients with ovarian cancer who had persistent lesions or recurrent lesions despite one round of chemotherapy [51]. Mifepristone 200 mg/day was given daily and continued until disease progression was found. They were treated for a mean of only 2 months. For 34 patients there was a response in 26.5% (9% complete and 17.5% partial) [51]. A second study of this drug conducted 10 years later showed a partial response in 42% of patients [52]. Again, the drug was stopped if there was any evidence of progression. The median time of treatment was 2 months [52]. From what we know today, if they would have continued the drug, the ovarian cancer may have progressed slowly while the patient maintained a high-quality extension of life [53].
Should biopsy specimens be tested for PIBF to see if a given patient should be treated with mifepristone?
We do not think it would be unreasonable to see if a given specimen produces PIBF, but can we be sure that the tests are sensitive enough to deprive a patient the potential great benefit of treatment with mifepristone?
Can measurement of serum PIBF be helpful in determining if the cancer is responding to mifepristone or if mifepristone therapy is no longer working?
There have been developed more sensitive and specific serum PIBF assays [2]. However, based on measurement of serum PIBF in patients with gynecologic cancers or breast cancers that are P receptor positive, or even associated with breast cancer antigen 1 or 2, the serum level of PIBF may not be helpful for these purposes [54, 55]. It is the PIBF in the tumor microenvironment that seems to be most important, and this, of course, would be difficult to measure.
The 200 mg daily dosage of mifepristone does not appear high enough to block the glucocorticoid receptor. So, another important question, is if it is the action of mifepristone on blocking the P receptor that leads to its efficacy in treating cancer why does it seem to work in cancers that are not associated with the classic nuclear P receptor?
The evidence supports the fact that it acts on membrane P receptors. Activation of the nuclear P receptor initiates transcription, which is a slower process, whereas rapid activation of the membrane P receptor is a more rapid signaling action [46].
Do cancers need to secrete P to activate the membrane P receptor?
It is possible that at a certain stage cancer cells can make P or a P-like substance sufficient to interact with membrane P receptors. There is evidence that a large variety of cancer cells express the human chorionic gonadotropin (hCG)-beta subunit gene [56]. Activation of the hCG beta subunit gene to produce hCG could lead to local P production by the cancer cells. Alternatively, there may be some other mechanism to activate the membrane P receptor to make PIBF. Even with this scenario, mifepristone could still block the effect of this theoretical non-P membrane P receptor agonist.
Does mifepristone only works when the cancer is at the stage of rapid metastasis?
It is possible that all cancers have mRNA to produce PIBF, but only at a certain level, that is, perhaps stem cell level is the membrane progesterone receptor is activated and PIBF is manufactured. Thus, it is possible that activation of tumor secretion of PIBF only occurs at the stage when it is ready to rapidly metastasize. About 20% of meningiomas are associated with the classic nuclear P receptor. However, a large study comparing mifepristone vs. placebo for unresectable tumors did not find any therapeutic benefit for mifepristone vs. placebo [57]. This could be because meningiomas are slow growing tumors and the PIBF mechanism is only seen with rapidly growing tumors. However, it is also possible that some meningiomas are considered benign. Thus, maybe it is the ability to make PIBF that is one factor allowing the tumor to follow a benign vs. malignant course. One benefit of this large study was to demonstrate a very good safely profile for mifepristone with few side effects [57].
Since a compassionate use IND is required by the FDA, that organization is reluctant to grant an off-label use unless all “standard” treatments have been exhausted. Thus, most of the study subjects in our center have been patients with very advanced cancers where there are few, if any, reasonable treatment options.
One exception is a man, who at the age of 58 was found to have bilateral renal cell carcinoma with metastases to local lymph nodes [42]. Renal cell carcinoma can be multifocal, and even when several lesions are present, the tumor is generally not extremely aggressive. Today the recommendation is renal sparing surgery and to remove the tumors every time one reaches a certain critical size [58, 59, 60]. But 16 years ago, the recommendation was bilateral nephrectomy.
Since there were no chemotherapy or immunotherapy agents16 years ago for renal cell carcinoma, and the patient did not want to become a dialysis cripple, the FDA approved a compassionate use IND for oral mifepristone following a laparoscopic hemi-nephrectomy with retention of a kidney with three lesions left untreated.
After 10 years of single agent treatment, there were no new tumors. The three lesions previously noted on the left kidney remained stable [42]. After 10 years his diabetes caused kidney failure and the start of dialysis. Thus, he had the 1½ kidneys removed. After 2 years of hemo-dialysis, he was approved for a kidney transplant. He is still doing well 16 years from initial diagnosis [42].
This case showed that mifepristone can also work to inhibit tumor growth even when not at the rapidly growing cell stage. Whether this is specific only for renal cell carcinoma, or applies to other malignancies, needs to be determined. Thus, perhaps one should consider using mifepristone in earlier stage metastatic cancers following tumor remission following treatment with chemotherapy or immunotherapy to possibly inhibit recurrence or negate the need to treat with another chemotherapy or immunotherapy regimen with morbid side effects.
One final thought. Frequently, once a tumor has widely metastasized chemotherapy or even immunotherapy may frequently extend life somewhat at the expense of significant side effects from treatment. Mifepristone therapy is devoid of major side effects, and thus may provide possibly a longer higher quality life than “approved therapy.” The treatment of patients with cancer has provided huge profits both for the pharmaceutical companies and the treating institutions. So realistically it is unlikely that mifepristone therapy will become popular in capitalistic societies.
However, in some countries needed to provide effective, yet inexpensive treatment, one could consider offering patients oral government provided mifepristone rather than expensive chemo or immunotherapy agents. The cost of a mifepristone pill in China is 50 cents. In fact, since growth of tumors is still consistent with a prolonged good quality life, one could save money on expensive diagnostic tests to monitor progression. Possibly mifepristone could be considered first line therapy for metastatic disease with consideration of other therapeutic modalities only if health deteriorates despite mifepristone therapy.
Since the drug is available as a generic already, it is unlikely any pharmaceutical company will invest in larger studies to prove its efficacy. Hopefully, the published anecdotal cases, and the easing of the requirements for compassionate use, will encourage other clinicians treating patients with advanced cancer to try the drug and publish their findings. If enough treating physicians request compassionate use IND for mifepristone use, perhaps the FDA will eventually drop the requirement of compassionate use IND, facilitating the use for treating physicians around the world. Many countries, similar to the United States, at this time also restrict the use of mifepristone solely for the purpose of therapeutic abortions, and in some countries, it is completely illegal, at least at the relatively inexpensive price for the 200 mg dosage to use this drug. The use of the 300 mg dosage that does not require a compassionate use IND is cost prohibitive. Possibly the manufactures may one day reduce the price considerably or it will be manufactured by a generic company at a much lower price when the patent expires. Perhaps at a lower cost, insurance companies will be happy to pay for off-label use of mifepristone realizing how much cheaper it is for cancer therapy than conventional chemo or immunotherapy regimens.
As previously mentioned, clinical trials with mifepristone for cancers associated with the classic nuclear P receptor were “disappointing” and thus clinical trails were not pursued. When these studies were initiated 20–30 years ago, the hope was that metastatic cancer can be “cured.” It is now realized that the best hope for advanced cancer is a truce with extension of a better quality of life. Also, at that time the goal of therapy was to induce a tumor response as evidenced by complete or partial tumor regression. We think if they had used the endpoints of quality and length of life, they would have had the satisfaction of treatment as we have had in these anecdotal cases. The majority of cases do not show tumor regression but stable disease and improved quality and length of life.
As far as side effects, the drug has been well tolerated. In higher dosages mifepristone can, by blocking the glucocorticoid receptor, lead to higher serum cortisol levels which acts on the mineralocorticoid receptor leading to hypokalemia. One has to be careful when using other drugs that can interfere with the metabolism of mifepristone leading to hypokalemia. We had one unreported case of a woman adding mifepristone to her ongoing treatment with alpelisib, which in itself can cause hypokalemia. Whereas the combination led to hypokalemia, neither drug by itself caused it. She was taking just the 200 mg dosage of mifepristone.
Similarly, case number 9, who was taking the 300 mg dosage, did develop hypokalemia when she was switched to another bronchodilator for her COPD, but reverted back to normal when it was stopped. She was taking the 300 mg dosage of mifepristone [45].
One man with stage IV non-small cell lung cancer became more somnolent when adding mifepristone to his fentanyl that he was using for pain. Though we advised him to reduce the dosage of fentanyl, he chose to just stop the mifepristone and died 2 weeks later. He had only taken the mifepristone for 2 days.
The authors declare no conflict of interest.
IntechOpen - where academia and industry create content with global impact
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As the science gets more advanced and the information about these two points becomes clearer, the view of this information might modify our understanding to these processes. Then, some topics might be dropped, and others might be raised or become more obvious. However, the feeding of halophyte forages as per se has several drawbacks and therefore, they have to be fed in mixed rations, fortifying these rations with energy supplements.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Salah A. 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CW has been successfully applied as an adsorbent for removing pollutants from wastewater and gas, a precursor for obtaining activated carbon, and a feedstock for producing energy and valuable products using mono-process extraction and biorefinery.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Felipe J. Cerino-Córdova, Nancy E. Dávila-Guzmán, Azucena M. García León, Jacob J. Salazar-Rabago and Eduardo Soto-Regalado",authors:null},{id:"56029",doi:"10.5772/intechopen.69614",title:"Production of Spineless Cactus in Brazilian Semiarid",slug:"production-of-spineless-cactus-in-brazilian-semiarid",totalDownloads:1889,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The term “spineless cactus” is used in Brazil to designate cultivars of Opuntia ficus indica Mill and Nopalea cochenillifera Salm Dyck. The spineless cactus was consolidated in Brazilian semiarid as a strategic fundamental food resource in several production livestock systems, constituting a plant with enormous productive potential. Thus, the spineless cactus has been widely cultivated and used for several decades, by enabling the animal feeding in critical periods of year because of its characteristics, morpho‐anatomical and physiological (CAM), which makes it tolerant to long droughts, being a crop that presents high productivity in droughts conditions, when compared to other forages. Nevertheless, the spineless cactus is a crop relatively picky about soil and climate characteristics of region, presenting greater growth in fertile soils, as well as in regions where nighttime temperatures are cool and the air humidity is relatively high. Although the crop be adapted to long droughts periods, many times it’s necessary to perform irrigation in its production system, mainly in regions of low rainfall, for to supply its water needs, thus ensuring productivity and survival of crop. Therefore, the knowledge of characteristics of plant, as well as of appropriate management techniques to crop, is essential for the good performance of spineless cactus.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Wilma Cristina Cavalcante dos Santos Sá, Edson Mauro Santos,\nJuliana Silva de Oliveira and Alexandre Fernandes Perazzo",authors:[{id:"139631",title:"Dr.",name:"Edson Mauro",middleName:null,surname:"Santos",slug:"edson-mauro-santos",fullName:"Edson Mauro Santos"},{id:"180036",title:"Dr.",name:"Juliana",middleName:null,surname:"Oliveira",slug:"juliana-oliveira",fullName:"Juliana Oliveira"},{id:"203022",title:"MSc.",name:"Wilma",middleName:null,surname:"Sá",slug:"wilma-sa",fullName:"Wilma Sá"},{id:"207265",title:"Dr.",name:"Alexandre",middleName:null,surname:"Perazzo",slug:"alexandre-perazzo",fullName:"Alexandre Perazzo"}]},{id:"70151",doi:"10.5772/intechopen.89224",title:"The Harvest and Post-Harvest Management Practices’ Impact on Coffee Quality",slug:"the-harvest-and-post-harvest-management-practices-impact-on-coffee-quality",totalDownloads:1802,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Coffee is one of the most important agricultural commodities in the world. The coffee quality is associated with pre-harvest and post-harvest management activities. Each step starting from selecting the best coffee variety for plantation until the final coffee drink preparation determines the cupping quality. The overall coffee quality influenced by the factors which involve in changes the physicochemical properties and sensorial attributes, including the post-harvest operations. The post-harvest processing activities contribute about 60% of the quality of green coffee beans. The post-harvest operations include pulping, processing, drying, hulling, cleaning, sorting, grading, storage, roasting, grinding, and cupping. This chapter comprises the harvest and post-harvest operations of coffee and their impacts on coffee quality.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Mesfin Haile and Won Hee Kang",authors:null},{id:"69900",doi:"10.5772/intechopen.89508",title:"Coffee By-Products: Nowadays and Perspectives",slug:"coffee-by-products-nowadays-and-perspectives",totalDownloads:1148,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Coffee is one of the most consumed products around the world; 2.25 billions of coffee cup are consumed everyday in the world. For coffee crop production, different by-products are produced, such as coffee peel, coffee husk, parchment, and spent coffee grounds. These by-products have several problems associated at the final disposition. In this book chapter, we study the main coffee varieties produced in the world, the by-products produced, and its composition and finally assess the potential of supramolecular solvents (SUPRAS) and water as green solvents for high-added-value compound extractions. Bioactive compounds were extracted from fresh and dried coffee peel in an acceptable rate for industrial applications. SUPRAS offer advantages in terms of rapidity (5 min) and simplicity (stirring and centrifugation at room temperature), thus avoiding costly processes based on high pressure and temperature. Extractions carried out using water as solvent is another technique of extraction mixing temperature (above 60°C) and time (4.5 min) obtained a beverage or solution with presence a bioactive compounds how caffeine, chlorogenic acid and polyphenols.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Laura Sofía Torres-Valenzuela, Johanna Andrea Serna-Jiménez and Katherine Martínez",authors:null}],mostDownloadedChaptersLast30Days:[{id:"71528",title:"A Detail Chemistry of Coffee and Its Analysis",slug:"a-detail-chemistry-of-coffee-and-its-analysis",totalDownloads:2331,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"This review article highlights the detailed chemistry of coffee including its components; chemical constituents like carbohydrates, proteins, lipids, and caffeine; aromatic principles; oil and waxes; and minerals and acids. The high extent of caffeine can be found in the coffee plants; hence, in the second part of the study, various analytical methods are designed for the proper identification, separation, optimization, purification, and determination of caffeine present in coffee, tea, and marketed coffee. These analytical methods are appropriated for the separation and quantification of caffeine. The various analytical methods include spectroscopy methods like UV, IR, and NMR spectroscopy; chromatographic methods like paper, TLC, column, HPLC, and gas chromatography; and hyphenated techniques like LC–MS, GC–MS, and GC–MS/MS. This article compares and contrasts the amount of caffeine by various analytical methods.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Hemraj Sharma",authors:null},{id:"70151",title:"The Harvest and Post-Harvest Management Practices’ Impact on Coffee Quality",slug:"the-harvest-and-post-harvest-management-practices-impact-on-coffee-quality",totalDownloads:1793,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Coffee is one of the most important agricultural commodities in the world. The coffee quality is associated with pre-harvest and post-harvest management activities. Each step starting from selecting the best coffee variety for plantation until the final coffee drink preparation determines the cupping quality. The overall coffee quality influenced by the factors which involve in changes the physicochemical properties and sensorial attributes, including the post-harvest operations. The post-harvest processing activities contribute about 60% of the quality of green coffee beans. The post-harvest operations include pulping, processing, drying, hulling, cleaning, sorting, grading, storage, roasting, grinding, and cupping. This chapter comprises the harvest and post-harvest operations of coffee and their impacts on coffee quality.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Mesfin Haile and Won Hee Kang",authors:null},{id:"72400",title:"Factors Affecting Efficiency of Vegetable Production in Nigeria: A Review",slug:"factors-affecting-efficiency-of-vegetable-production-in-nigeria-a-review",totalDownloads:803,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Vegetables are important for maintenance of good health; their production and marketing are veritable sources of employment and livelihood. To promote vegetables’ contribution to the above, there is a need for sustainable and efficient production process. The paper reviewed production, socioeconomic factors, and constraint affecting efficiency of production of three important vegetables (tomato, pepper, and onion). The review showed that socioeconomic factors found to increase technical efficiency in vegetable production were educational level, extension contact, and household size. Influence of farmer age on technical efficiency was inconclusive due to varied opinions. Increase in farm size, quantity of seed, amount of fertilizer, and agrochemical were found to have positive influence on output. Majority of the literature reviewed opined that increase in quantity of labour raises productivity; however, it must be utilized efficiently. The mean technical efficiency of the vegetables varied from the southern to the northern part of the country. The cross cutting constraints in vegetables production are pest and diseases, inadequate storage facilities, and high cost of improved inputs. The study recommends increase awareness and sensitization on optimum levels of resource use for increased productivity and appropriate intervention to constraints in the value chain.",book:{id:"10142",slug:"agricultural-economics",title:"Agricultural Economics",fullTitle:"Agricultural Economics"},signatures:"Iyabo Bosede Adeoye",authors:[{id:"317695",title:"Dr.",name:"Iyabo Bosede",middleName:null,surname:"Adeoye",slug:"iyabo-bosede-adeoye",fullName:"Iyabo Bosede Adeoye"}]},{id:"65591",title:"Insect Pest Management in Organic Farming System",slug:"insect-pest-management-in-organic-farming-system",totalDownloads:2595,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"Due to the regulations of organic farming, few options remain for organic farmers to manage pests and diseases in their crops compared to conventional farming. However, major pests could still be managed through manipulation of the agroecosystem processes in advantage of the crops and disadvantage of pests. The limited number of active plant protection substances authorized for use in organic farming can provide support to natural and biological control agents in suppression of pests and diseases. This chapter highlights the principles and strategies of crop protection in organic farming, the cultural practices adopted, the active substances allowed for use to suppress pests, and the impacts on faunal and floral biodiversity. 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As the cultivation is carried out primarily in the rainy season, these world climate variations have affected crops yields and fruits quality, requiring innovative actions that promote efficient use of water stored in the soil. Among several soil management practices that promote a more rational use of water, deep tillage combined with liming, gypsum and fertilizer amendments lead to an increase in effective depth of coffee roots, therefore reducing water stress. Moreover, intercropping with Urochloa sp. is highly efficient in enhancing soil structure, water infiltration and plant available water capacity. Additionally, other innovative techniques and practices are also introduced in this chapter.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Bruno Montoani Silva, Geraldo César de Oliveira, Milson Evaldo Serafim, Carla Eloize Carducci, Érika Andressa da Silva, Samara Martins Barbosa, Laura Beatriz Batista de Melo, Walbert Junior Reis dos Santos, Thiago Henrique Pereira Reis, César Henrique Caputo de Oliveira and Paulo Tácito Gontijo Guimarães",authors:null}],onlineFirstChaptersFilter:{topicId:"27",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. 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Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. 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His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. 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His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. 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Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}}]}},subseries:{item:{id:"26",type:"subseries",title:"Machine Learning and Data Mining",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11422,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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