Apoptosis, a type of "Programmed Cell Death" is a tightly regulated essential event of the life process of a cell. However, induced apoptosis in normal cell often causes damage to the system leading to several critical disorders. With the increasing load of environmental contaminants, arsenic and mercury are of special attention world wide including India and Bangladesh. Beyond conventional toxicological studies, molecular mechanism underlying arsenic and mercury induced apoptosis in rat hepatocytes has been depicted here. Moreover, free radical induced apoptotic signals and relationship with cellular thiol homeostasis has been demonstrate.The goal is to understand the regulatory mechanism of heavy metal induced free radical toxicity and apoptosis as well as to identify the targets in order to inhibit cell death.There is an ample scope and immense need to proceed further in this area. Amalgamation and computation of the innovative research outcome is also of significant importance which will serve as a platform of future study. Looking forward to participate in any shots of exchange of ideas.
Bladder cancer is a global health issue. In the endemic areas of Egypt, schistosomiasis is a leading cause of bladder cancer. Prognostic indicators are required to further identify which tumor should be treated aggressively early on, in order to improve surveillance. The Fas-Fas Ligand (Fas-FasL) system has been recognized as a major pathway for the induction of apoptosis in cells and tissues. Fas-mediated apoptosis is deeply involved in cancer cell death, brought about by the immune system. The interaction of Fas and Fas Ligand contributes to cytotoxic T-lymphocyte and natural killer-cell mediated cytotoxicity against cancer cells. This study was performed to assess the importance of the apoptosis markers (Fas and FasL) in bilharzial versus non-bilharzial bladder cancer, in order to detect the possible diagnostic &/or prognostic potentials of this factor.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important human pathogens. There is an estimated number of 350 million carriers of HBV and 170 million people are chronically infected with HCV worldwide. These are at high risk of developing chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC).Apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C. Whereas pathomorphologic features of increased a apoptosis process appears to be a host defense mechanism against viral infections and tumourigenesis.The presence of excess oxygen radicals and/or the lack of sufficient antioxidants to scavenge these radicals can either directly contribute to hepatocyte necrosis or enhance the inflammatory response associated with necrosis. Oxygen radicals appear to cause hepatocyte necrosis by modifying DNA, lipids and proteins in the cells This research study was meant to provide Detailed information on the role of apoptosis and oxidative stress mechanisms in the pathogenesis of viral hepatitis, which ultimately leads to hepatocellular carcinoma using biochemical and immunological techniques
We are now at an exciting era when our increased understanding of cancer biology jointly with the rapid advances in biotechnologies are allowing us to test fundamental concepts in cancer and ultimately translate them into the evolution of targeted cancer therapy. Resistance to cell death, especially to apoptosis, is an important feature of tumor cells, which is also described as one of the hallmarks in cancer. The research presented in this book supports the concept that apoptosis induction in tumor cells is a vital player in anticancer therapies. Although we already have a good knowledge of apoptosis machinery in cancer, various seemingly unrelated pathways (for example PAI-1 - uPA system) may also have linked to this important hallmark of cancer. Overall, a thorough understanding about cancer biology including taking tumor microenvironment into consideration is the foundation for the development of “targeted cancer therapy”.
In this revised and expanded second edition, seasoned experts describe in step-by-step detail their best state-of-the-art techniques for studying neuronal cell death. These readily reproducible methods solve a wide variety of research problems, including the detection of the key proteins involved in neuronal apoptosis (Bax protein, cytochrome c, and caspases), the direct assessment of the role of pro-apoptotic proteins in neurons by viral infections and microinjections, and the detection of pro-apoptotic proteins in situ. There are also hands-on methods for the study of apoptosis mechanisms in neuronal compartments, for studying synaptosis, and for establishing gene expression profiles in neurodegenerative brain tissues by using DNA microarrays.
Beta Amyloid peptide (A?), specifically A? (1-42) is toxic to neurons and is hence strongly associated with loss of brain function through the course of Alzheimer’s disease. This deposition induces neuronal death and apoptosis. Extensive studies in recent years have focused on A?-mediated microglia activation with regard to secretion of pro inflammatory cytokines such as TNF-?. TNF-? induces two distinct pathways: one of them is apoptosis and the other one is NF-?B activation and eventually cell survival and proliferation.One of the questions that came to us was whether there is any relationship between these two path ways and blocking one pathway results in boosting the other one. To probe this issue, we blocked apoptosis and measure NF-?B activation. Another question arose as the role of apoptosis in neuroinflammation. Whether apoptosis is a protective or destructive mechanism? To achieve this goal, we inhibited apoptosis and evaluated some intracellular changes such as: c-Myc as a proto-oncogene, Hsp70 as a hallmark of cancer that is up regulated by stress and toxins and p53 as a tumor suppressor protein.
The book details an insight in the pathological mechanisms of experimental malaria by comparing the patterns of cytokine responses in mice. The study is intended for scientific community dealing with infectious diseases. In the book different courses and outcomes of cytokine excess or deficiency have used to deduce instances of malaria infection. The cytokine levels for IFN-? and TNF-? appears to coincide with the development of CM. The dual roles of the cytokines in pathogenesis by induction of apoptosis has been discussed.
Fluorescent dyes are of great importance for investigation of biological processes. In 2007 the first ratiometric fluorescent probe for apoptosis detection (F2N12S) has been reported. This book is focused on a development of the improved analogs of F2N12S. Firstly, the systematic studies of F2N12S in model membranes and cells are described for better understanding of its mechanism of response to apoptosis. Secondly, synthesis of new membrane probes is presented. All the molecules are classified into three types according to their sensitivity profiles (sensitive both to the surface charge and to the phase state, only to the surface charge and only to the phase state of lipid membranes). Nile Red derivative NR12S is introduced as a molecular sensor for apoptosis and cholesterol content in cell membrane. Also, the general principle for the design of fluorescent membrane probe is proposed. Finally, two new classes of environment-sensitive fluorophores are presented (on the base of fluorene and chromone units). This book should be interesting for those who are working in the field of biological membranes and on the development of new molecular tools for fluorescence imaging.
Urinary tumor markers that help in the early detection of bladder cancer promise a particular improvement in sensitivity, specificity and convenience over conventional, invasive diagnostic tests. This book present our research work which assessed the diagnostic efficacy of urinary survivin RNA for early detection of bladder cancer. The study included 78 bladder cancer patients, 61 patients with Schistosomal cystitis and 50 healthy volunteers. All underwent serological assessment of Schistosomiasis antibody, urine cytology, and survivin RNA estimation by qualitative and semiquantative reverse transcriptase- nested polymerase chain reaction in urothelial cells from voided urine. The study revealed significant difference in the positivity rate of survivin RNA among the 3 groups. Survivin RNA mean rank using semi quantitative method was increased in the malignant group vs the other groups. The best cutoff value for survivin RNA was 0.91. Using this cutoff value, survivin RNA sensitivity was 78.2% and specificity was 100%. Urine cytology sensitivity improved when combined with survivin RNA. We conclude that survivin RNA is a promising urine marker for bladder cancer detection.
Abnormalities during the life span of cell lead to serious fault and hence cell cannot function well and hence due to apoptosis the cell get suicide without harming the neighbor cell. Apoptosis is strictly regulated by cell machinery using Fas, Caspases, Death receptor and TNF receptors. Pancratistatin, alkaloids from the amaryllidaceae family induce the apoptosis in cancer cell by different mechanism like upregulation of Fas, increase in caspase-3, destabilization of mitochondrial membrane potential and flipping of phosphatidyl serine. Pancratistatin promises to induce the apoptosis in the cancer cells and produce lesser cytotoxic effect on the normal cells. This natural product can reveal and unveil the horizon for the new-targeted therapy, which is more effective and promising. Due to lesser yield of pancratistatin from the plant source, chemical synthesis by chemoenzymatic process is beneficiary to us for making library for the pancratistatin and its derivatives.
Apoptosis (Programmed Cell death) is one of the essential processes. Balance between cell division and cell death is of utmost importance for the development and maintenance of multi-cellular organism. Disorders of either process have pathologic consequences and can lead to disturbed embryogenesis, neuro-degerative diseases, or the development of cancers. This book reviews the apoptotic as well as anti-apoptotic molecules along with molecular pathways, which may alter in many diseases. The elucidations of the molecular mechanisms of apoptosis and their correlation with a vast array of human diseases have generated optimism for implementation of this knowledge for treatment purposes.
Cancerous cells are persistently exposed to more oxidative stress than adjacent normal cells as a result of abnormal regulation of some enzymes. Consequently, excessive amounts of hydrogen peroxide are accumulated in tumour cells. Iron-containing compounds, such as ferrocene, can react with hydrogen peroxide through Fenton reaction where highly reactive hydroxyl radicals are formed. These radicals possess a damaging effect on the DNA of the cancer cells, thereby inducing the apoptosis and inhibiting cancerous cell growth. Ferrocene on its own has no affinity for tumour cells and if administered as it is, it will not be specifically delivered to these targets. This book outlines a simple approach for targeting the ferrocene via conjugation with nucleoside. The ferrocene-linked nucleosides are supposed to be preferentially taken up by actively dividing cancerous cells where they are phosphorylated intracellularly into the corresponding nucleotides. These nucleotides will then become incorporated into the cellular DNA. This is advantageous as the radicals will be generated near the DNA, thus making the damage more significant.
Apoptosis, a major form of cell death, is characterized by several unique features, including cell shrinkage, nuclear collapse, membrane blebbing, and internucleosomal DNA cleavage. Defects in apoptosis facilitate tumor progression, by rendering cancer cells resistant to death mechanisms relevant to metastasis, growth factor deprivation and chemotherapy. To date, the cervical carcinoma is the second most common cancer in women, and is one of the major causes of death among women in the world. Chondrosarcoma is a malignant primary bone tumor and the third most common primary malignancy of bone after myeloma and osteosarcoma. Thus, we chose human cervical cancer cells (Hela) and human chondrosarcoma cells (SW1353) for the study. Marine-derived fungi have proved to be a promising source of bioactive metabolites and a growing number of marine fungi have been reported to produce bioactive secondary metabolites. Several fungal metabolites isolated from Aspergillus sp. It has been shown to exert antitumor, antiinflammator, induced cytotoxicity and antibacterial activity.
The scope and purpose of this book is to make available to the university students a handy volume containing complete exposition of cell cycle, cell division molecular events of the cell cycle apoptosis programmed cell death and cancer. It is simplified and conceptual and will clear all the doubts related to different events of cell cycle and differentiate between normal cell death and cancer. It will also relate with the molecular aspects of the cell cycle and information related to genes and protein responsible for controlling normal cell cycle.