Assessment of Traffic Policemen Exposure To Benzene by Using Trans, Trans-Muconic Acid Biomarker in Ahvaz City, Iran

Benzene is known as an environmental and industrial pollutant. One way to check the amount of exposure to benzene is to measure its metabolites in the urine. Trans, Trans-Muconic Acid which is one of its metabolites is also as a biological indicator of exposure to benzene. In this study, the relationship between the amount of this biomarker and the environmental benzene concentration was investigated in two groups of policemen working outdoors in the traffic-congested areas and indoor in the same area. The results showed that the highest amount of benzene was in Salman Farsi Station at 4.44 ppm. At the same time, the biomarker measured in the urine showed 127.20 μg / L, which was the highest amount. In addition, the amount of benzene in the outdoor was approximately 3 times more than indoor and the amount of biomarker measured in outdoor employees was two times more than indoors ones. In general, wherever there was more benzene, the biomarker would also show a higher amount.

Allele Based Inference on Evolution and Extinction; A Genetic Drift Approach

In other to present a series of stochastic models from population dynamics capable of describing rudimentary aspects of genetic evolution, we studied two-allele Wright–Fisher and the Moran models for evolution of the relative frequencies of two alleles at a diploid locus under random genetic drift in a population of fixed size “simplest form, selection, and random mutation”. Principal results were presented in qualitative terms, illustrated by Monte Carlo simulations from R and http://www.radford.edu/~rsheehy/Gen_flash/popgen. Moran and the Wright-Fisher Models exhibited the same fixation probabilities, only that the Moran model runs twice as fast as the Wright-Fisher Model. A clue that can help us to understand this result is provided by the variance in reproductive success in the two models. Genetic changes due to drift were neither directional nor predictable in any deterministic way. Nonetheless, genetic drift led to evolutionary change in the absence of mutation (P=0.5), natural selection or gene flow. In general, alleles drift to fixation is significantly faster in smaller populations. Probability of fixation of an allele A was approximately equivalent to the initial frequency of that allele. With the inclusion of selection in our model, probability of fixation of a favoured allele due to natural selection increased with increase in fitness advantage and population size. The time taken to reach fixation is much slower, in case of no selective advantage, than a fixation under mutation with selective advantage.

Alpha-Fetoprotein and its Receptor: More Than Oncofoetal Antigens.

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Long Non-Coding RNAs Emerging as Potential Epigenetic Biomarkers for Tobacco and/or Alcohol-Induced Head and Neck Cancer

Head and Neck cancer (HNC) is one of the most prevalent and lethal cancer globally. The incidence of tobacco-induced HNC is gradually increasing in low and middle income countries. Among the various causative factors associated with HNCs, tobacco and alcohol play synergistic effect and are frequently associated with the risk of HNC. Tobacco-induced HNCs show distinct genetic and epigenetic alterations leading to different clinical outcomes in comparison to HPV-infected HNCs. Tobacco-induced HNCs are often associated with tumor aggressiveness, poor prognosis and low or nil prevalence of HPV infection. Apart from carcinogenic effects of these causative factors (use of tobacco products, alcohol intake and HPV or EBV infections), recent studies show that exposure to these factors alter/disrupt the regulation of non-coding RNAs including the long non-coding RNAs (lncRNAs). Altered lncRNA regulation is brought about by signalling networks that regulate cellular differentiation, apoptosis, angiogenesis and inflammatory pathways which play key functions in the genesis of different cancers including HNCs. There are numbers of studies supporting the emerging role of lncRNAs in development of HNC; however, reports connecting lncRNAs expression and addiction habits in HNC are still preliminary and sparse. Therefore, identification and characterization of lncRNAs that are differentially expressed upon exposure to risk-factors can serve as unique therapeutic targets and potential biomarker(s) for effective treatment of HNC subtypes. In this short review, we briefly reviewed the emerging role of lncRNAs in tobacco and alcohol induced HNCs.

Melanoma of the Breast with Smoothened (SMO) Mutation: Case Report and review of the Literature

We report the case of a 75 year-old female with past history of ampullary adenocarcinoma presenting with a rapidly enlarging breast mass, initially misclassified on fine needle aspiration as a probable sarcoma, which was ultimately diagnosed as melanoma on resection in the absence of a known cutaneous primary lesion. Next-generation sequencing (NGS) of the tumor revealed a mutation in the Smoothened oncogene (SMO) of unknown significance and wild-type BRAF. To our knowledge, SMO mutation in melanoma of any site has not been previously reported, though the effectiveness of SMO inhibitors has been studied in both in vivo and in vitro models of melanoma. Currently, these inhibitors have not been studied in SMO mutant melanoma. The patient declined further therapy after resection due to multiple comorbidities. She expired two years after presenting with the breast mass from complications of high grade urothelial carcinoma.

The Current Immunoassays and Merging immunogenomic Approaches for Immunomonitoring Cancer and Infectious Diseases

As remarkable advances have been made in immunotherapies, the overall goal of immunotherapy has become the selection of patients and evaluating the benefits of treatment. One of the major obstacles to develop immunotherapies is the lack of effective immune monitoring. Monitoring of key changes in the immune system during immunotherapy (immunomonitoring) provides important insights into efficacy as well as the immune mechanisms of response at the molecular and cellular levels. Immunomonitoring techniques include traditional immunoassays that use specific antibodies to recognize the analytes of interest, new high-throughput immunoassays that target immune cells and nucleic acids, and less classical immunogenomic approaches that rely on genome-wide profiling and computational analysis on various types of clinical samples. Substantial progress has been made in the application of immunomonitoring strategies to pre-clinical and clinical studies, especially for patients with cancer and infectious diseases. Current and emerging immunoassays performed in clinical practice will be examined herein, and immunogenomic approaches that complement these techniques will be highlighted and compared with traditional methods. Finally, we will discuss several new computational methods for analyzing gene signatures for immunomonitoring, including gene expression data profiling by microarray, the nCounter technique, regular RNA-seq, and single-cell RNA-seq. Novel immunomonitoring techniques, especially immunogenomic approaches, will continue to be developed to facilitate assessment of immunotherapeutic response and predict patient outcomes in cancer and infectious disease.

Epigenetic Biomarkers in Head and Neck Cancer

Head and neck cancers (HNCs) are the most prevalent and aggressive type of cancers. Genetic, epigenetic, environmental and viral risk-factors are associated with HNC carcinogenesis. Persistent infection of oncogenic human papillomaviruses (HR-HPVs) represent distinct biological, molecular and epigenetic entities in HNCs. There are three main epigenetic mechanisms that regulate transcription, these are DNA methylation, histone modifications and alteration in non-coding RNA networks, which can dissected to identify innovative and accurate epigenetic biomarkers for diagnosis and prognosis of HNC patients. Due to the lacunae of accurate distinctive biomarkers for the definite diagnosis of HNC, the identification of predictive epigenetic markers is necessary that might modify or increase HNC patient’s survival. In this mini review, we briefly summarize the current knowledge of different epigenetic biomarkers in HNC.

Molecular and Cell Biological Considerations in the Initiation and Development of Sporadic Non-Hereditary Solid Cancers

This paper reviews the state of cancer research in the post-mutation era. It presents cancer as a highly complex disease viewed differently by scientists from various research fields. Histopathologists considered cancer as a disease of cell differentiation, cancer cell biologists overestimated the causal role of accumulated DNA mutations. More recently molecular biologists have focused on driver genes and driver mutations, regulatory gene networks and deregulation of the genomic balance between unicellular and multicellular gene sets (UG/MG balance). From a developmental biological standpoint, there is a clear analogy between the reproductive life cycles of cancer and protists. The key player of both analogous life cycles is the polyploid cyst, the atavistic cyst-like structure aCLS (PGCC). In the analogy to protists, we assume that the first aCLS initiating cancer originates from a mitoticly blocked cell (cell of origin of cancer, protoprecursor) that escapes death entering an atavistic reproductive process of polyploidisation and depolyploidisation; it forms the atavistic cyst-like structure aCLS and numerous daughter cells (microcells). The microcell progeny develops a multi-lined cell lineage containing stem cells as well as somatic and reproductive cells and clones. Subsequent aCLSs are formed sequentially by committed daughter cells or occasionally by stressed somatic cells. Accordingly, cancer initiation occurs by genomic changes leading to the amitotic cell state and reactivation of an atavistic life cycle. In humans, atavistic life cycles and hyperpolyploidisation (n >16) are mostly repressed by stable gene regulatory networks – but not in cancer. The permanent UG/MG gene conflict and robust ancient surveillance mechanisms trigger a cascade of molecular lesions leading to genomic heterogeneity and aberrant cancer cell states.