Pre-Cancer Diagnosis via TP53 Gene Mutations Applied Ensemble Algorithms

According to current study, individuals with cancer who have a gene mutation have a bad prognosis. Young women with breast cancer had a poorer prognosis than older women, although it is unknown if the p53 gene mutation contributed to this. Due in part to the devastation of cancer, the appropriate technology may help cancer sufferers in regaining their lives. Researchers seek for mutations in cancer-causing gene sequences in order to identify the precancerous stage. While genetic testing may be used to forecast some kinds of cancer, there is presently no effective technique for identifying all cancers caused by TP53 gene mutations. It is one of the most often discovered genetic anomalies in human cancer is a malfunction in the action of the protein P53. As a consequence, the Universal Mutation Database is used to identify gene mutations (UMDCell-line2010). The issue is that, although many basic databases (for example, Excel format databases) exist that include datasets of TP53 gene mutations associated with disease (cancer), this huge database is incapable of detecting cancer. Thus, the purpose the objective of this study is to create an approach for data mining that utilizes a neural network to ascertain the pre-cancerous state. To begin, bioinformatics techniques such as BLAST, CLUSTALW, and NCBI were used to determine whether or not there were any malignant mutations; second, the proposed method was carried out in two stages: to begin, bioinformatics techniques such as BLAST, CLUSTALW, and NCBI were used to determine whether or not there were any malignant mutations; and third, the proposed method was carried out in two stages: to begin, bioinformatics techniques such as To begin, bioinformatics tools such as BLAST and CLUSTAL Vote Algorithms were utilized to classify pre-cancer by malignant mutations in the disease's early stages. The writers teach and evaluate their subjects using a variety of situations, including cross validation and percentages. This page contains a review of the algorithms discussed before.

Human papillomavirus. Diagnostic issues

Тhe article presents an analysis of current information on the etiology, pathogenesis, and laboratory diagnosis of the human papillomavirus (HPV). HPV is a trigger factor in the pathogenesis of proliferative and inflammatory diseases. HPV-associated cervical cancer is one of the few forms of malignant tumors that can be detected at the precancerous stage or at the earliest stage of cancer: the disease is widespread, has a recognizable preclinical phase, a long period of development, there is a reliable screening test - cytological examination of smears taken from ecto- and endocervix and HPV-testing. Laboratory diagnostics is based on a combination of microscopic (cytological studies) and molecular genetic (PCR) diagnostic methods.

TOBACCO PRODUCTS: CHEMICAL ANALYSIS AND COMPARATIVE HARMFULNESS

Tobacco consumption is a major social health problem in India as well as throughout the world, because it harms both health and wealth of an addict. Tobacco is a Sthavara Patra Visha received from the plant Nicotiana tobacum/ Nicotiana rusticum leaves by curing them. Tobacco contains an alkaloid nicotine in abundant amount, which is sufficient to make addict like alcohol, cocaine and morphine. There are so many different forms of smoking and smokeless tobacco in India, like cigarette, bidi, gutka, jarda, pan masala etc. Long timed use of Tobacco like adductive products by oral route, acts as a slow poison (Dushi Visha) induces chronic toxicity to the gastrointestinal tract like oral diseases, gingivitis and periodontitis, Leukoplakia (precancerous stage), and may lead to cancer also in advance stage. This chronic toxicity affects cardiovascular system and results as increasing coronary blood flow, heart rate and blood pressure which may trigger the chances of heart attack rate in addict person. Before we can do any effort for reducing toxicity produced by tobacco products its mandatory to knowing the basic knowledge of tobacco products, their chemical composition, their mechanism of action with comparative toxicity and specific tobacco product related to a specific mouth part cancer. Because we can’t stop a person to start tobacco use but we can circulate the knowledge of tobacco products in adolescent groups so that when the beginner chose a tobacco product, he will be aware about the toxicity and affecting organ because of its use. So that, the toxicity can be minimised. Keywords: Tobacco consumption, nicotine, slow poison, cancer, comparative toxicity

Normal tissue architecture determines the evolutionary course of cancer

Cancer growth can be described as a caricature of the renewal process of the tissue of origin, where the tissue architecture has a strong influence on the evolutionary dynamics within the tumor. Using a classic, well-studied model of tumor evolution (a passenger-driver mutation model) we systematically alter spatial constraints and cell mixing rates to show how tissue structure influences functional (driver) mutations and genetic heterogeneity over time. This approach explores a key mechanism behind both inter-patient and intratumoral tumor heterogeneity: competition for space. Time-varying competition leads to an emergent transition from Darwinian premalignant growth to subsequent invasive neutral tumor growth. Initial spatial constraints determine the emergent mode of evolution (Darwinian to neutral) without a change in cell-specific mutation rate or fitness effects. Driver acquisition during the Darwinian precancerous stage may be modulated en route to neutral evolution by the combination of two factors: spatial constraints and limited cellular mixing. These two factors occur naturally in ductal carcinomas, where the branching topology of the ductal network dictates spatial constraints and mixing rates.

Infiltration of Immunoinflammatory Cells and Related Chemokine/Interleukin Expression in Different Gastric Immune Microenvironments

Gastric mucosal immune microenvironment plays an important role in the occurrence and development of diseases such as inflammation and cancer. In the present study, single-sample gene set enrichment analysis (ssGSEA) was used to evaluate the expression of cytokines and the degree of immune cell infiltration in four different gastric mucosa tissues from normal gastric mucosa, simple gastritis, and atrophic gastritis to gastric cancer. Here, we show the immune microenvironments of these four gastric mucosae were significantly different. From inflammation to gastric cancer, most immunoinflammatory cells showed a downward trend such as central memory CD4 T cell. Instead, several cells showed an upward trend such as macrophage. Additionally, we found some chemokines/interleukins were illustrated to be low expressed (or highly expressed) in precancerous stage and highly expressed (or low expressed) in postcancerous stage, which demonstrated an opposite expression characteristic in pre-/postcancerous stage.

DNA hypermethylation of the ZNF132 gene participates in the clinicopathological aggressiveness of “pan-negative”-type lung adenocarcinomas

Although some previous studies have examined epigenomic alterations in lung adenocarcinomas, correlations between epigenomic events and genomic driver mutations have not been fully elucidated. Single-CpG resolution genome-wide DNA methylation analysis with the Infinium HumanMethylation27 BeadChip was performed using 162 paired samples of adjacent normal lung tissue (N) and the corresponding tumorous tissue (T) from patients with lung adenocarcinomas. Correlations between DNA methylation data on the one hand and clinicopathological parameters and genomic driver mutations, i.e. mutations of EGFR, KRAS, BRAF, and HER2 and fusions involving ALK, RET, and ROS1, were examined. DNA methylation levels in 12,629 probes from N samples were significantly correlated with recurrence-free survival. Principal component analysis revealed that distinct DNA methylation profiles at the precancerous N stage tended not to induce specific genomic driver aberrations. Most of the genes showing significant DNA methylation alterations during transition from N to T were shared by two or more driver aberration groups. After siRNA knockdown of ZNF132, which showed DNA hypermethylation only in the pan-negative group and was correlated with vascular invasion, the proliferation, apoptosis and migration of cancer cell lines were examined. ZNF132 knockdown led to increased cell migration ability, rather than increased cell growth or reduced apoptosis. We concluded that DNA hypermethylation of the ZNF132 gene participates in the clinicopathological aggressiveness of “pan-negative” lung adenocarcinomas. In addition, DNA methylation alterations at the precancerous stage may determine tumor aggressiveness, and such alterations that accumulate after driver mutation may additionally modify clinicopathological features through alterations of gene expression.

Promoter methylation, transcription, and retrotransposition of LINE-1 in colorectal adenomas and adenocarcinomas

Background: LINE-1, Alu, and SVA elements are non-LTR retrotransposons that create approximately one-third of the human genome. The loss of tight control mechanisms on the function of mobile elements has been implicated in many human diseases. The methylation of the CpG islands of the LINE-1 promoter is one of these mechanisms. In this study, we determined the promoter methylation and the expression of LINE-1 in three stages of colorectal non-advanced adenoma, advanced adenoma, and adenocarcinoma. In addition, we analyzed the insertion of LINE-1, Alu, and SVA elements in the genome of colorectal advanced adenomas.Results: We found that the LINE-1 hypomethylation index in advanced adenoma and adenocarcinoma were significantly higher than that in non-advanced adenomas. The copy number of LINE-1 transcripts in advanced adenoma was significantly higher than that in non-advanced adenomas, and in adenocarcinomas was significantly higher than that in the advanced adenomas. Analysis of the genome of colorectal advanced adenomas revealed that at this stage de novo insertions of LINE-1, Alu, and SVA were approximately 16%, 51%, and 74%, respectively.Conclusions: Our findings showing a decreased methylation of LINE-1 promoter accompanied by the higher level of LINE-1 transcription, and de novo genomic insertions in advanced (high-grade) adenoma, a precancerous stage before colorectal carcinoma, suggests that the early and advanced polyp stages may host very important pathogenic processes concluding to cancer.

Cholesterol: A prelate in cell nucleus and its serendipity. .

: Cholesterol is a chameleon bio-molecule in cellular multiplex. It acts as a prelate in almost every cellular compartment with its site specific characteristics viz. regulation of structural veracity and scaffold fluidity of bio-membranes, insulation of electrical transmission in nerves, controlling of genes by making steroid endocrines, acting as precursors of metabolic regulators and many more with its emerging prophecy in cell nucleus to drive new cell formation. Besides the crucial legacy in cellular functionality, cholesterol is ostracized as a member of LDL particle which has been proved responsible to clog blood vessels. LDL particles get deposited in the blood vessels because of its poor clearance owing to the non-functioning LDL receptor on vessel wall and surrounding tissues. Blocking of blood vessel promotes heart attack and stroke. On the other hand cholesterol has been targeted as pro-cancerous molecule. At this phase again cholesterol is biphasic. Although cholesterol is essential to construct nuclear membrane and its lipid-rafts; in cancer tumour cells cholesterol is not under control of intracellular feedback regulation and gets accumulated within cell nucleus by crossing nuclear membrane and promotes cell proliferation. In precancerous stage the immune cells also die because of lack of requisite concentration of intracellular and intranuclear cholesterol pool. Existence of cholesterol within the cell nucleus has been found in nuclear membrane, epichromosomal location and nucleoplasm. The existence of cholesterol in the microdomain of nuclear raft has been reported to be linked with gene transcription, cell proliferation and apoptosis. Hydrolysis of cholesterol esters in chromosomal domain is linked with new cell generation. Apparently Cholesterol is now a prelate in cell nucleus too ------ A serendipity in cellular haven.

A study of evaluation of unhealthy cervix by various diagnostic modalities

Background: This study was carried out to evaluate cases of unhealthy cervix by using Pap (Papanicolaou) smear, colposcopy and cervical biopsy and to arrive at a definitive diagnosis. It correlated the findings of Pap smear, colposcopy and histopathology. It is important to strictly implement the screening program and spread awareness of the disease symptoms and its management to reduce the overall incidence of morbidity and mortality reported due to cervical cancer.Methods: A total 120 patients satisfying the inclusion/exclusion criteria were recruited for the study and informed consent was taken from all the participants. Pap smear was taken for all the cases. Then cases were subjected to colposcopy followed by biopsy. All the findings were correlated and analyzed. The findings of Pap smear and colposcopy were correlated with the gold standard of histopathology.Results: The sensitivity and specificity of Pap smear and colposcopy with respect to cervical biopsy were 53.1% and 98.7%, 87.87% and 72.72% respectively. Colposcopy had higher sensitivity and lower specificity than Pap smear for screening of cancer cervix.Conclusions: Cervical cancer is one of the preventable and highly curable conditions when diagnosed in the precancerous stage. The incidence of deaths resulting from cervical cancer can be brought down with adequate cervical cancer screening. Colposcopy and colposcopy directed biopsy should be done along with Pap smear in screening for early detection of cervical cancer since the accuracy of detection of cervical abnormalities is higher when these two methods are used complementarily.

A novel faecal Lachnoclostridium marker for the non-invasive diagnosis of colorectal adenoma and cancer

ObjectiveThere is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma.DesignThis study included 1012 subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR.ResultsMetagenomic analysis identified ‘m3’ from a Lachnoclostridium sp., Fusobacterium nucleatum (Fn) and Clostridium hathewayi (Ch) to be significantly enriched in adenoma. Faecal m3 and Fn were significantly increased from normal to adenoma to CRC (p<0.0001, linear trend by one-way ANOVA) in group I (n=698), which was further confirmed in group II (n=313; p<0.0001). Faecal m3 may perform better than Fn in distinguishing adenoma from controls (areas under the receiver operating characteristic curve (AUROCs) m3=0.675 vs Fn=0.620, p=0.09), while Fn performed better in diagnosing CRC (AUROCs Fn=0.862 vs m3=0.741, p<0.0001). At 78.5% specificity, m3 and Fn showed sensitivities of 48.3% and 33.8% for adenoma, and 62.1% and 77.8% for CRC, respectively. In a subgroup tested with faecal immunochemical test (FIT; n=642), m3 performed better than FIT in detecting adenoma (sensitivities for non-advanced and advanced adenomas of 44.2% and 50.8% by m3 (specificity=79.6%) vs 0% and 16.1% by FIT (specificity=98.5%)). Combining with FIT improved sensitivity of m3 for advanced adenoma to 56.8%. The combination of m3 with Fn, Ch, Bacteroides clarus and FIT performed best for diagnosing CRC (specificity=81.2% and sensitivity=93.8%).ConclusionThis study identifies a novel bacterial marker m3 for the non-invasive diagnosis of colorectal adenoma.