Search

Heavy metals are well-recognised as environmental hazards due to their toxicity, environmental persistence, and bioaccumulation in living organisms. Human health is a crucial concern related to terrestrial and aquatic ecosystems poisoned by harmful heavy metals. Most heavy metals pollute the air, water, and soil, which can be fatal to humans. Humans and other species can be exposed to heavy metals through the food chain if the metals oxidise or combine with other environmental elements (such as water, soil, or air). Their entry into the food chain assures interactions with biological macromolecules in living systems, including humans, resulting in undesirable outcomes. Human poisonings have typically been caused by mercury, lead, chromium, cadmium, and arsenic. The build-up of these metals in living organisms causes various harmful consequences on different organs and tissues. The gravitas of heavy metal toxicity regarding molecular impact and carcinogenesis needs in-depth understanding despite the plethora of available data. Hence, additionally, we attempt to elaborate on the multi-level impact of five heavy metals and emphasise their role in cancer development. The rationale of this essay is thus to understand the role of five heavy metals, viz., lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As), and mercury (Hg), in carcinogenesis. Heavy metals interfere with various biological functions, including proliferation, differentiation, repair of damage, and apoptosis. By comparing their modes of action, we see that these metals share common mechanisms for inducing toxicity, such as reactive oxygen species (ROS) production, antioxidant defence weakening, enzyme inactivation, and oxidative stress. [ABSTRACT FROM AUTHOR]

Melanoma is a relentless type of skin cancer which involves myriad signaling pathways which regulate many cellular processes. This makes melanoma difficult to treat, especially when identified late. At present, therapeutics include chemotherapy, surgical resection, biochemotherapy, immunotherapy, photodynamic and targeted approaches. These interventions are usually administered as either a single-drug or in combination, based on tumor location, stage, and patients' overall health condition. However, treatment efficacy generally decreases as patients develop treatment resistance. Genetic profiling of melanocytes and the discovery of novel molecular factors involved in the pathogenesis of melanoma have helped to identify new therapeutic targets. In this literature review, we examine several newly approved therapies, and briefly describe several therapies being assessed for melanoma. The goal is to provide a comprehensive overview of recent developments and to consider future directions in the field of melanoma. [ABSTRACT FROM AUTHOR]

Development is a sophisticated process maintained by various signal transduction pathways, including the Hedgehog (Hh) pathway. Several important functions are executed by the Hh signaling cascade such as organogenesis, tissue regeneration, and tissue homeostasis, among various others. Considering the multiple functions carried out by this pathway, any mutation causing aberrant Hh signaling may lead to myriad developmental abnormalities besides cancers. In the present review article, we explored a wide range of diseases caused by aberrant Hh signaling, including developmental defects and cancers. Finally, we concluded this minireview with various treatment strategies for Hh-induced diseases. [ABSTRACT FROM AUTHOR]

Background: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is on the rise. Although the clinicopathologic characteristics of NENs have been previously reviewed in the literature, the data published in the Indian literature so far are sparse. This study aims to review the clinicopathological features of GEP-NENs, diagnosed at our institution, and that were classified and graded according to the World Health Organization 2010 classification system. Materials and Methods: One hundred patients with GEP-NENs presenting to our institute from August 2012 to May 2016 were analyzed retrospectively. Demographic data and tumor characteristics were expressed as number, percentage, and mean value. Tumor grade was correlated to metastasis through the Chi-square test. P < 0.05 was considered statistically significant. Results: Of the 100 cases studied, 58 were male and 42 were female. The most common primary site was the pancreas (n = 36), followed by the small intestine (n = 19), esophagus (n = 17), stomach (n = 15), colon (n = 6), rectum (n = 4), and appendix (n = 3). The incidence of neuroendocrine tumor (NET) Grade 1 (NET G1) was higher (n = 40) compared to NET Grade 2 (NET G2) (n = 25) and neuroendocrine carcinoma Grade 3 (NEC G3) (n = 35). Overall in these 100 cases, NET G1 tumors and NET G2 tumors were most common in the pancreas (n = 18/36) and (n = 13/36), respectively. NEC G3 tumors were most common in the esophagus (n = 16/17). The most common site of distant metastasis was the liver (n = 23/26). Conclusion: We elucidated the epidemiological and clinicopathological features of patients presenting to our institute with GEP-NENs. [ABSTRACT FROM AUTHOR]

Protection of Telomeres 1 (POT1) is a significant protein of the Shelterin complex found in the telomere region of chromosomes. It inhibits DNA repair machinery from recognizing the telomeres by binding to telomeric ssDNA and associating with the TPP1 protein of Shelterin complex. C-terminal mutations in POT1 can affect its interaction with TPP1. The main aim of this study is to screen for the highly deleterious mutations of POT1 using in-silico tools that are associated with various cancers, some of which have not been previously studied. P357S has been found to cause thyroid cancer; H437P, V439G, F566C cause malignant melanoma; G534C causes carcinoma of the large intestine. We further performed a comparative docking analysis of the mutated POT1 and native TPP1 through PatchDock, ClusPro and Hex docking software. We found that C591W, M587T and V439G showed significantly lower binding scores than the native while H437P, G534C and P475L showed marginally low binding scores and the rest displayed binding energies almost similar to that of the native POT1-TPP1 structures. Molecular Dynamics (MD) Simulation of mutated POT1 and TPP1 having significantly lower scores gives a new insight in understanding the consequences of the erroneous interactions that will provide an impetus to further research. [ABSTRACT FROM AUTHOR]