Testicular Cancer

Recent Progress of Phenazines as Anticancer Agents

Phenazines are nitrogen-containing heterocycles which possess a wide range of biological activities and in particular, cytotoxic effects. Moreover, various phenazines have been prepared having alkyl, amide, carboxylic acid, aldehyde, and pyrano groups. These synthetic phenazines possess significant anticancer effects towards various cancers. On the other hand, only a few natural phenazines have been reported with anticancer effects. This chapter presents a comprehensive overview of the most recent patents related to the phenazines as anticancer agents.

Clinical Approach to Male Infertility

The clinical approach to the infertile man begins with a careful medical history and physical examination, assessing both the andrological and internal medicine aspects. The main objectives of the evaluation are to identify modifiable risk factors and appropriate treatments which may improve male fertility, and to exclude the presence of comorbidities such as testicular cancer, osteoporosis, and endocrine or genetic problems that can be associated with infertility. The laboratory tests described include the evaluation of endocrine tests, of the spermiogram and of genetic studies.

Endocrine Disruptors: What Do We Know about the Effects and Risk Factors in Humans?

In the last few decades, the theme of endocrine disruption and endocrine disrupting chemicals has become more and more relevant, raising alarm in the scientific community and amongst public health officials, as well as questioning the traditional concepts of toxicology. This chapter is a revision and summary of the latest information and articles concerning this subject. It discusses the terms and definitions of endocrine disruption, the sources and mechanisms of action of these chemicals both naturally and artificially made, reviewing the potential adverse development, reproductive, neurological, and immune effects that they can have on the different systems in the body, and how they can relate to the different epidemics of cancer, diabetes and obesity. It also provides the latest up-to-date information on the tests and methods used to detect and assess these entities, offering ideas and lines of future investigation to attempt to better understand the knowledge in this field and reduce the potential threat of these environmental hazards to mankind.

Polyhydroxyalkanoates as Promising Materials in Biomedical Systems

Polyhydroxyalkanoates (PHAs) are the natural polymers that have been a subject of a significant research interest in the past few decades. The PHAs (natural as well as their synthetic analogs) as biodegradable and biocompatible polymers were studied intensively for biomedical applications, that is, scaffolds for tissue engineering. Drug-loaded implants or scaffolds based on these polyesters were also used in the drug release systems. Drug delivery systems should provide an optimal release profile of an active compound that allows to increase therapeutic effect, decrease side effects, and improve patient convenience and compliance. Therefore, recently, the increasing interest is focused on the use of PHA as drug carriers because of significant improvement in the bioavailability of bioactive substances. Recent developments introduced such strategies as conjugation of the drug with low-molecular-weight poly(3-hydroxybutyrate) or preparation of PHA particles loaded with the drug. On the contrary, there is a growing interest in functionalized PHA technology. The advancement of these strategies allows to obtain the targeting systems based on the chemical modification, for example, by folic acid attachment or biosynthesis of targeting proteins on the PHA particle surface. In addition, the PHAs were presented as materials that could be used in transdermal administration of bioactive substances for medical or cosmetic purposes. The development of novel functionalized PHAs has opened new possibilities to combine good biocompatibility of PHA-based drug delivery systems with improved drug loading and release properties, targeting, or imaging possibilities. Further progress in PHA-based drug delivery systems is expected because of the combination of excellent biocompatibility of these biopolymers and strong beneficial effect on drug administration.

Cancer and its Treatment: Development of Anticancer Chemotherapeutic Agents from Natural Products

Over the last 5 decades, biologically active compounds derived from natural resources have provided a number of useful cancer chemotherapeutic drugs. The search for natural product based drug candidates is growing rapidly with the advancements in drug discovery and development techniques in recent years, with the active fractions and isolates of marine organisms along with terrestrial plants. Microorganisms are also being explored for their anti-cancer activities. The present review highlights the information about occurrence, types, clinical features pathophysiology and etiology of cancer as well as conventional and recent advancements in anticancer drug development along with description of selected medicinal plants and compounds derived from natural sources or their derivatives with potential use as cancer chemotherapeutic agents. It is expected that such promising leads from natural origin tend to create extensive interest among researchers including medicinal chemists and pharmacologists working in anticancer drug research and therefore the availability of a given brief information about cancer and anticancer drug development focused on natural product may be proved useful to develop preliminary ideas of biochemical pathways and key enzymes regulating these pathways as well as new targets involved in different stages of the disease along with chemotherapeutic agents which selectively target a specific signaling pathway through structure-activity relationships and preclinical trials.

Testicular Cancer, Erectile Dysfunction and Male Reproductive Health

In recent years, there has been growing awareness that male reproductive performance has declined. Numerous studies have focused on various aspects of adverse trends in male reproductive health. There is a wealth of data that congenital disorders, such as hypospadias, undescended testis, testicular atrophy and testicular cancer have increased among young males. Testicular cancer, in particular germ cells tumors, are the most common malignancy among young males accounting more than 10 cases per 100000 men per year in Europe. Both genetic predisposition and environmental contaminants probably contribute for its etiology. Testicular germ cell tumors arise from malignant transformation of testicular germ cells in a multistep process where several aberrant modifications occur in genes involved in proliferation/survival and differentiation. Individuals with testicular germ cell tumors present a high survival rate but during treatments they are exposed to radio- and/or chemotherapy that may induce permanent damages in male fertility. In this context, it is essential to decipher the molecular mechanisms underlying testicular-related cancers. However, other pathologies have also contributed to the decline of male reproductive health, and particularly affect male sexual behavior. Inadequate penile erection, commonly termed as erectile dysfunction (ED) mostly occurs in men older than 40 years. It is quite common in developed countries and compelling evidences have linked the development of ED to diabetes mellitus, hypertension, hyperlipidemia, metabolic syndrome and depression. In fact, it has been shown that certain environmental and factors related to daily life, such as smoking, obesity, and limited or an absence of physical exercise may also be key predictors of ED. Physicians have looked with particular concern to these issues, but also for the sexually transmitted diseases (STDs). Some STDs are resolved without treatment, but others have chronic lifelong infections. In this chapter those topics will be discussed from a biochemical point of view and the pathways that regulate the most relevant processes.

Natural Products as a Unique Source of Anti- Cancer Agents

Cancer is a major public health problem and the second leading cause of premature deaths worldwide, accounting for an incident rate of 2.6 million cases per year, mainly in Europe and the United States. This book chapter describes the historical aspect of cancer, its treatment modalities and history of natural compounds being used as anti-cancer agents. Role of marine natural compounds and their derivatives in cancer prevention, like, alkaloids, amine derivatives, macrolides, peptides and polypeptides are described in this chapter. Both, role of natural compounds extracted from plants and microbial sources are discussed along with their molecular targets and interactions to kill the cancer cells. Most of the medicinal compounds derived naturally are synthesized semi-synthetically for commercial purposes. They are then formulated into proper dosage increasing their costs. But for many natural compounds clinical trials are still to be carried out to validate their use in cancer therapy.

Molecular Mechanisms of Cellular Transport, Resistance and Cytotoxic Side Effects of Platinum and Adjuvant Anti-cancer Drugs – A Molecular Orbital Study

The side effects, acquired resistance, reversal of resistance, and combination of Pt drugs with adjuvant drugs has been examined using an extensive review of the literature and molecular orbital computations. It is concluded that Pt chemotherapeutical regimes are dominated by side reactions, particularly hydrolysis in blood serum and delivery efficiency. For example, it is shown that transplatin is therapeutically inactive because it hydrolyses faster in blood serum than cisplatin, so little transplatin reaches its target DNA. The reactivity of charged hydrolysis products determines the severity of side effect. The reactivity determining properties of the approved Pt drugs and their various hydrolysed species are calculated. The cellular uptake of Pt and adjuvant drugs is fastest for neutral species, with high lipophilicity, since their desolvation penalties for crossing the cell membrane are lowest. Pt resistant cell lines generally have lower levels of drug uptake, indicating this is a dominant first order cause of cellular resistance. Resistance can be caused by complexation of charged Pt species to phosphatidylserine (PS) headgroups, or by Pt complexation to the inner terminii of the trans-membrane pore of the hCtr1 transporter. Drugs that are known to reverse induced Pt resistance can decomplex the Pt-PS or Pt-hCtr1 complexes, restoring normal PS or hCtr1 functions. Molecular biophysical properties of adjuvant drugs used in combination with Pt drugs (e.g., paclitaxel, doxorubicin, gemcitabine, Folfox) can assist the clinical evaluation of combinatorial Pt based chemotherapeutic regimes. These drugs have similar properties to the approved Pt drugs, and fit into the same “therapeutic window” in sterms of their likely cellular uptakes and reduction potentials. The role of free radical species involved in Pt drug induced apoptosis via electron transfer from the guanine base of DNA, and the reactions of oxidizing hydroxyl radicals and reducing hydrated electrons reactions with cisplatin, transplatin and carboplatin under physiological pH and Cl ion condition have been examined.

Free radical sensitisers such as TMPD and TETA when combined with Pt drugs may allow targeting of the more hypoxic environments in solid cancerous tumours (and less damage to normal cells). The calculated biophysical parameters ionization energy and electron affinity, which are related to the redox environments found in cells, may be useful predictors of likely cytotoxic efficacy of combination therapies involving sensitisers and Pt drugs.