Shridhar C. Ghagane

By Maya Kulshekar, Shridhar C. Ghagane, Sridevi I. Puranik, Rajendra B. Nerli and Murigendra B. Hiremath

The idea of utilizing immunotherapy for the treatment of cancers has been appealing to scientists and clinicians for over a several decades. Immunotherapy for cancers encompasses knowledge gained from a wide range of disciplines and has the potential to procure the ‘magic bullet’ for the treatment of cancer. Monoclonal antibody-based treatment of cancer has been recognized as one of the most successful therapeutic strategies for both hematologic malignancies and solid tumours in the last 20 years. The discovery of hybridoma technology in late 1975 and the development of chimeric, humanized, and human antibodies have increased the availability and utility of immunotherapy for the treatment of cancer. Metastatic or recurrent cancer continues to be the bane of the urological oncologist. Despite recent improvements in therapeutic management and outcomes for clinically localized disease overall survival rate in patients with the majority of metastatic and recurrent genitourinary malignancies remains relatively unchanged. By targeting tumours through specific or associated antigens, it is possible to selectively eliminate tumour cells and maintain an acceptable toxicity profile. Therapeutic antibodies that target immune cells are also being developed with the goal of breaking local tolerance and stimulating the patient’s anti-tumor immune response. As with other treatment modalities, immunotherapy is far from perfect and requires additional study to optimize clinical response and overcome therapeutic resistance. Modern advances in the field of immunotherapy hold the promise of providing the clinical urologist/oncologist with new tools to fight urological cancer. However, the literature on monoclonal antibody-based immunotherapy with a particular emphasis on target antigens, monoclonal antibody design and potential applications in the field of urology is limited. Hence, the present chapter focuses on the applications of Immunotherapy using monoclonal antibodies for urologic oncology settings such as prostate, bladder, renal, testicular and penile with a hope to highlight its clinical efficacy and also its mechanisms of action in each of these cancer types.

Part of the book: Monoclonal Antibodies

By Surayya Siddiqui, Sridevi I. Puranik, Aimen Akbar and Shridhar C. Ghagane

Genetic polymorphism and prostate cancer (PC) are the most pernicious and recurrently malignancy worldwide. It is the most dominating cause of cancer related casualty among men in the US. Asian countries are inflicted with PC at an alarming rate though still the prevalence of PC is lower than European and American men. Some of the genetic and environmental factors that might play a role in PC risk include: age genetic predilection, family history, race/ethnicity, lifestyle, and dietary habits and non-dietary environmental risk factors such as smoking. Socio-economic factors including economic, scholastic and intellectual factors do not, intrinsically seem to straight away influence the risk of acquiring PC. Other genetic changes that may support an increased risk of developing PC include HPC1, HPC2, HPCX, CAPB, ATM,s HOXB13 and mismatch repair genes. PC occurrence rates are highly variable. Almost all PC mortalities are due to metastatic disease, generally through tumors the progress to be hormone refractory or castrate resistant. PC, developing research has acknowledged a number of candidate genes and biological pathways associated with PC. Indirect pathways such as P13K/AKT signaling pathway is one of most well known alternate pathway in PC Vascular endothelial growth factor (VEGF) is widely known to be potent stimulator of angiogenesis. The over expression of EGFR in a very large majority of cases is accompanied by the succession of PC, implying that this may play a mechanistic role. Numerous occupational factors have been proposed to cause PC. Some of the risk factors include; farmers/agricultural workers, pesticides, shift work and flight personnel. PC treatment can be done through surgery, radical prostatectomy is the main type of surgery. Risks of injury are many – reactions to anesthesia, loss of blood, blood clumps in the legs/lungs, injury to surrounding organs, infection at the site of surgery and many more. The other treatments are hormone therapy, chemotherapy and radio therapy chemotherapy. Chemotherapeutic drugs are typically used one at a time for PC such as transurethral resection of prostate (TURP). Some of the chemotherapeutic drugs are Docetaxel, Cabazitaxel, Mitoxantrone and Estramustine. Among the score of biomarkers being studied, numerous markers and techniques deserve awareness and acceptability for both patients and urologists in clinical practice.

Part of the book: Genetic Polymorphisms

By Kalyani Killekar, Sridevi I. Puranik, Aimen Akbar A., Shridhar C. Ghagane, Rajendra B. Nerli and Murigendra B. Hiremath

The number of patients diagnosed with prostate and bladder cancer is increasing worldwide and one of the most important challenges remains the development of effective, safe and economically viable antitumor drugs. Clinical approval for drugs tested in preclinical studies enabling them to enter phase I clinical trials is essential. Cell lines are in vitro model systems that are widely used in different fields of medical research, especially basic cancer research and drug discovery. Their usefulness is primarily linked to their ability to provide an indefinite source of biological material for experimental purposes. Under the right conditions and with appropriate controls, authenticated cancer cell lines retain most of the genetic properties of the cancer of origin. Studies conducted during the initial development of drugs such as toxicity, corrosion and drug activity were carried out on animals; however, in the past two decades, alternatives have been sought due to the fact that animals do not effectively model to human in vivo conditions and unexpected responses are observed in the studies. Also, more than 100 million animals were used and billion dollars were spent for animal toxicity experiments. Cell culture studies made positive contributions to the initial development of drugs and is highly desirable, as it provides systems for ready, direct access and evaluation of tissues. Contrary to animal studies, less cost and the need for low drug and a short response time are the characteristics for in vitro cell culture methods. In vitro tumor models are a necessary tool, in not only the search for new substances showing antitumor activity but additionally for assessing their effectiveness. This chapter reviews the main features of primary cancer cell cultures, provides an overview of the different methods for their selection and management, and summarizes the wide range of studies that can be performed with them to improve the understanding of prostate and bladder cancer preclinical treatment processes.

Part of the book: Cell Culture

By Makhadumsab Toragall, Shridhar C. Ghagane, Rajendra B. Nerli and Murigendra B. Hiremath

Human reproduction and development is a succession of symbiotic events. Nearly, at every point of this phenomenon found to be the principle target of one or more reproductive toxicants. Chemical agents, physical factors, as well as biological intruders can pose antagonistic effects on reproductive potential of an organism. The pathways are different viz., either damaging embryo and sometimes fetus or inducing mutation in a parent’s germ cell. The outcomes are declined fertility to impulsive abortion, functional discrepancies, developmental retardation, structural anomalies, etc. It is a now essential to establishing proper databases for reproductive and developmental toxicity chemicals, physical and biological factors including appropriate awareness among the society. Although many in vitro and in vivo toxicology studies are in pipeline which are independent studies but combination with other hazardous studies could give us an accurate numbers.

Part of the book: Male Reproductive Anatomy

By Akshata Sangolli, Shridhar C. Ghagane and Rajendra B. Nerli

Kidney stone disease is an oldest known and widespread medical condition characterised by its high prevalence in all over the world. Literature suggests that around 9–12% of population in industrialised countries have kidney stone disease in their lives with the 30–50% of reoccurrence rate. Because of high prevalence, recurrent and unpredictable nature of stone formation and its predominance mainly in adults contributes to the substantial impact on society, individual and health care system. In light of these trends, it’s imperative to use optimum preventive strategies to reduce the burden of kidney stone disease on individual and society. The aetiology of kidney stone disease is a multifactorial and it’s related to diet, environmental factors, genetics, metabolic syndromes and various life style factors. Its noteworthy that dietary and life style modification are the major contributors in the prevention of kidney stone reoccurrence. Dietary interventions aim to reduce the urinary abnormalities known to promote lithogenesis. Therefore, modification in the dietary factors is appealing way to patients and physicians in the treatment and prevention of stone recurrence as it is relatively inexpensive and safe. So, the present chapter is focusing on the role of dietary supplements in prevention of renal stones.

Part of the book: B-Complex Vitamins