Certain Forms Of Cancer Research Articles

Drug Repurposing for Rare (Orphan) Diseases—Scope and Limitations

Effective and affordable treatment for rare diseases remains a huge challenge. Only a few drugs have made inroads into the therapeutic arena for rare diseases. The current focus is shifted to different uses for expensive new drugs, referred to as drug repurposing. It is also called drug repositioning or reprofiling, refers to the identification of new therapeutic applications of existing or investigational drugs. This concept and novel approaches have promising role in the treatment of many potentially incurable diseases, particularly certain forms of cancer, neurodegenerative conditions, immunological disorders and uncommon infectious diseases. There are huge expectations filled with optimism that the drug repurposing would offer fresh opportunities for the treatment and management of rare diseases. This is undoubtedly more relevant for low and middle income countries.

The Nexus between Polyphenols and Gut Microbiota and Their Interplay in Human Health: A Brief Review

Polyphenols are a broad class of naturally occurring substances in plants and have drawn extensive attention as they may possess promising health-promoting benefits. Recently, gut microbiota and polyphenol interactions have been directly linked to the well-being of humans. The classification, sources, and interactions of polyphenols with the gut microbiota are presented in this review, highlighting their key health benefits in humans. Polyphenols undergo complex transformations within the gastrointestinal tract and interact with the gut microbiota, a varied collection of bacteria living in the digestive system. The interactions substantially influence the composition, functioning, metabolic activity, and gut microbiota diversity. Research indicates that polyphenols may possess prebiotic-like properties, favouring Lactobacilli and Bifidobacteria growth, among other beneficial bacteria. The fermentation of polyphenols is aided by these bacteria, which produce bioactive metabolites that may improve human health and well-being in various ways. Moreover, the alteration of gut microbiology caused by polyphenols has been linked to improvements in several health outcomes, including enhanced metabolic health, fortified immunological function, and a decreased susceptibility to chronic conditions like heart disease and certain forms of cancer. In summary, the intriguing relationship between polyphenols and gut microbiota has significant health implications for humans. Understanding these relationships can open the door to tailored dietary treatments and the development of functional foods to support a balanced gut microbiota and general well-being.

Preparing the soil: Adjusting the metabolic health of patients with chronic wounds and musculoskeletal diseases.

In recent years, systemic inflammation has emerged as a pivotal player in the development and progression of various degenerative diseases. This complex, chronic inflammatory state, often undetected, can have far-reaching consequences for the body's physiology. At the molecular level, markers such as C-reactive protein, cytokines and other inflammatory mediators serve as indicators of systemic inflammation and often act as predictors of numerous musculoskeletal diseases and even certain forms of cancer. The concept of 'meta-inflammation', specifically referring to metabolically triggered inflammation, allows healthcare professionals to understand inflammatory responses in patients with metabolic syndrome. Driven by nutrient excess and the expansion of adipose tissue, meta-inflammation is closely associated with insulin resistance, further propagating the metabolic dysfunction observed in many Western societies. Wound persistence, on the other hand, exacerbates the detrimental effects of prolonged inflammation at the local level. Acute inflammation is a beneficial and essential process for wound healing and infection control. However, when inflammation fails to resolve, it can impede the healing process, leading to chronic wounds, excessive scarring and even the activation of fibrotic pathways. This approach significantly reduces the efficacy of regenerative biological therapies. Our review focuses on the vital role of proteins, vitamins and minerals in collagen synthesis and cell proliferation for tissue healing. We also examine hormonal influences on regeneration, noting the negative effects of imbalances, and emphasize glucose regulation's importance in creating a stable environment for chronic wound healing.

Cytokine Biopharmaceuticals with "Activity-on-Demand" for Cancer Therapy.

Cytokines are small proteins that modulate the activity of the immune system. Because of their potent immunomodulatory properties, some recombinant cytokines have undergone clinical development and have gained marketing authorization for the therapy of certain forms of cancer. Recombinant cytokines are typically administered at ultralow doses, as many of them can cause substantial toxicity even at submilligram quantities. In an attempt to increase the therapeutic index, fusion proteins based on tumor-homing antibodies (also called "immunocytokines") have been considered, and some products in this class have reached late-stage clinical trials. While antibody-cytokine fusions, which preferentially localize in the neoplastic mass, can activate tumor-resident leukocytes and may be more efficacious than their nontargeted counterparts, such products typically conserve an intact cytokine activity, which may prevent escalation to curative doses. To further improve tolerability, several strategies have been conceived for the development of antibody-cytokine fusions with "activity-on-demand", acting on tumors but helping spare normal tissues from undesired toxicity. In this article, we have reviewed some of the most promising strategies, outlining their potential as well as possible limitations.

Biomaterial-Based Therapeutic Delivery of Immune Cells.

Immune cell therapy (ICT) is a transformative approach used to treat a wide range of diseases including type 1 diabetes, sickle cell disease, disorders of the hematopoietic system, and certain forms of cancers. Despite excellent clinical successes, the scope of adoptively transferred immune cells is limited because of toxicities like cytokine release syndrome and immune effector cell-associated neurotoxicity in patients. Furthermore, reports suggest that such treatment can impact major organ systems including cardiac, renal, pulmonary, and hepatic systems in the long term. Additionally, adoptively transferred immune cells cannot achieve significant penetration into solid tissues, thus limiting their therapeutic potential. Recent studies suggest that biomaterial-assisted delivery of immune cells can address these challenges by reducing toxicity, improving localization, and maintaining desired phenotypes to eventually regain tissue function. In this review, recent efforts in the field of biomaterial-based immune cell delivery for the treatment of diseases, their pros and cons, and where these approaches stand in terms of clinical treatment are highlighted.

Elevated levels of IL-12/IL-23p40 in Nova Scotia Duck Tolling Retrievers with autoimmune disease and lymphoma

The Nova Scotia Duck Tolling Retriever (NSDTR) is predisposed to immune mediated rheumatic disease (IMRD), steroid-responsive meningitis-arteritis (SRMA) and certain forms of cancer. Cytokines are the main regulators of the immune system. Interleukin 2 is a cytokine involved in activation of T regulatory cells, playing a role in central tolerance and tumor immunity. Interleukin 12 and interleukin 23 share the same subunit, p40, and are both pro-inflammatory cytokines. The aim of this study was to compare levels of IL-2 in healthy NSDTRs to those with cancer or autoimmune disease and to compare levels of IL-12/IL-23p40 in healthy NSDTRs and beagles versus NSDTRs with cancer or autoimmune disease. 62 dogs were included in the analysis of IL-12/IL-23p40; healthy NSDTRs (n = 16), healthy beagles (n = 16), NSDTRs autoimmune (n = 18) and NDSTRs lymphoma/mastocytoma (n = 12) and 68 dogs for IL-2; healthy (n = 20), autoimmune (n = 36) and lymphoma/mastocytoma/adenocarcinoma (n = 12). NSDTRs with autoimmune disease had higher levels of IL-12/IL-23p40 compared to healthy dogs (p = 0.008). NSDTRs with lymphoma also had higher levels of IL-12/IL-23p40 compared to healthy NSDTRs (p = 0.002). There was no difference in levels of IL-2 between healthy and diseased NSDTR. Statistical analysis was performed using Bonferroni corrections for multiple testing. These findings can contribute to the knowledge of autoimmune disease and cancer in dogs.

Abstract 131: Utilizing human induced pluripotent stem cells (hiPSCs) as a model to study the genetic drivers of rhabdomyosarcoma

Abstract Rhabdomyosarcoma (RMS) is a childhood soft tissue sarcoma composed of skeletal myoblast-like cells that lack the capacity to differentiate despite their high expression of terminal differentiation markers like myogenin. There are two main types of RMS: fusion-positive RMS (FP-RMS), which is associated with a chromosomal translocation resulting in an oncogenic fusion protein (PAX3-FOXO1), and the more common form, fusion-negative RMS (FN-RMS) which lacks this translocation and is instead thought to be driven by numerous other oncogenes. Our lab used a Bayesian-based computational algorithm to analyze NGS sequencing data from 290 RMS samples and identified 25 potential genetic drivers of RMS. We aim to use induced pluripotent stem cells as a new model to study how these drivers, including the PAX3-FOXO1 fusion gene, influence RMS formation and progression. To this aim, we have successfully made a doxycycline inducible lentiviral vector containing the full-length sequence of human PAX3-FOXO1 which we used to ectopically express PAX3-FOXO1 in two well-characterized iPSC lines. We subcutaneously injected these iPSCs into NOD/SCID mice and treated them with doxycycline to form teratomas, non-malignant tumors containing tissue from all three germ layers. We hypothesized that PAX3-FOXO1 induction in these differentiating teratomas, may have transforming capabilities and may deregulate transcriptional programs to form FP-RMS-like tumors. We have found that PAX3-FOXO1 overexpressing teratomas grew faster and histologically look more “immature” than their control counterparts but do not seem to give rise to rhabdo-like tumors. We want to further understand what other critical factors are necessary to drive RMS formation by focusing on one of our drivers of interest EZH2, a histone methyltransferase implicated as either an oncogene or a tumor suppressor in certain forms of cancer. We have data suggesting that EZH2-dependent histone methylation activity may act as a proto-oncogene with PAX3-FOXO1 to silence the expression of key tumor suppressor genes CDKN2A and CDKN2B in RMS. To this aim, we reasoned that iPSCs differentiated into myogenic progenitors, one of the potential cells of origin of RMS, will be a novel way to study the role of oncogenes like PAX3-FOXO1 and EZH2 in RMS. We have derived myogenic progenitors from iPSCs (iPSC-MPCs) that express key myogenic factors like PAX7 and MYOD and differentiate and fuse to form mature myofibers. We plan to next explore how ectopic expression of EZH2 and/or PAX3-FOXO1 alters gene expression and histone methylation and whether these alterations can drive RMS formation in these iPSC-MPCs. Using this model system of iPSC-MPCs to drive expression of these oncogenes has the potential to offer new and exciting ways to identify the most important genes in driving cancer formation hopefully providing insight into better targets for treatment of RMS. Citation Format: Celeste Romero, Yanbin Zheng, Lin Xu, Stephen Skapek. Utilizing human induced pluripotent stem cells (hiPSCs) as a model to study the genetic drivers of rhabdomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 131.

Identification of Mortalin as the Main Interactor of Mycalin A, a Poly-Brominated C-15 Acetogenin Sponge Metabolite, by MS-Based Proteomics.

Mycalin A (MA) is a polybrominated C-15 acetogenin isolated from the marine sponge Mycale rotalis. Since this substance displays a strong antiproliferative bioactivity towards some tumour cells, we have now directed our studies towards the elucidation of the MA interactome through functional proteomic approaches, (DARTS and t-LIP-MS). DARTS experiments were performed on Hela cell lysates with the purpose of identifying MA main target protein(s); t-LiP-MS was then applied for an in-depth investigation of the MA-target protein interaction. Both these techniques exploit limited proteolysis coupled with MS analysis. To corroborate LiP data, molecular docking studies were performed on the complexes. Finally, biological and SPR analysis were conducted to explore the effect of the binding. Mortalin (GRP75) was identified as the MA's main interactor. This protein belongs to the Hsp70 family and has garnered significant attention due to its involvement in certain forms of cancer. Specifically, its overexpression in cancer cells appears to hinder the pro-apoptotic function of p53, one of its client proteins, because it becomes sequestered in the cytoplasm. Our research, therefore, has been focused on the possibility that MA might prevent this sequestration, promoting the re-localization of p53 to the nucleus and facilitating the apoptosis of tumor cells.

Hronične nezarazne bolesti uzrokovane poremećajima ishrane kod adolescenata

Decreased satisfaction with physical appearance during adolescence is significantly linked to reduced self-esteem and an increased prevalence of obesity and other chronic non-communicable diseases (NCDs). A major issue in today's world is the influence of media, which serves as the primary channel through which ideals of physical appearance and attractiveness are transmitted. According to a 2015 study, adolescents spend an average of 17 hours per week watching television. Scientific evidence indicates that an active lifestyle provides health benefits and prevents the occurrence of numerous chronic non-communicable diseases, while improper diet and physical inactivity among adolescents contribute to the development of these diseases. Improper nutrition during adolescence can be a significant risk factor for the development of NCDs. These diseases, including cardiovascular diseases, diabetes, and certain forms of cancer, often have complex causes, but dietary habits can be identified as a common risk factor. Excessive intake of saturated and trans fats, cholesterol, and a high consumption of processed foods are associated with an increased risk of cardiovascular diseases. Improper dietary habits can also contribute to the development of type 2 diabetes and increase cancer risk. Adopting a balanced and nutritionally rich diet, along with regular physical activity, can help prevent and manage these conditions. This review paper is based on a search of the scientific literature published in the last ten years, with a special focus on original research articles published in the last five years from the scientific databases: PubMed, SCOPUS, MEDLINE, and SCI index.

Identifying novel amyloid candidates using bioinformatics algorithms and a yeast model approach

Amyloids are protein aggregates characterized by their insolubility in detergents and ability to form fibrils. They are often associated with various diseases, including neurodegenerative disorders, type 2 diabetes and certain forms of cancer. Amyloids also play important roles in bacteria and different physiological processes in both lower and higher eukaryotes.
 Together with the laboratory of Prof. Y.O. Chernoff we have developed a comprehensive approach for screening new potentially amyloidogenic proteins. This involves using bioinformatics algorithms to predict protein amyloidogenicity and further verifying using a yeast model. We have created a yeast test system specifically designed to study changes in phenotype in genetically modified Saccharomyces cerevisiae strains [1]. This system involves the production of recombinant amyloidogenic proteins fused with reporter proteins Sup35N or YFP. Using yeast assay, we have investigated 22 human proteins that were predicted to be amyloidogenic by ArchCandy algorithm [2]. Currently, additional in vitro biochemical tests are underway with proteins that have shown the potential to form amyloids in yeast models. There are also plans to evaluate the amyloid-forming ability of specific human proteins in mammalian cell cultures. These various approaches appear to be enhancing our comprehension of the impact of amyloid formation in health and disease.

Impact of NLRP3 gene polymorphisms (rs10754558 and rs10733113) on HPV infection and cervical cancer in southern Chinese population

ObjectiveMutations in the NLRP3gene have previously been linked to certain forms of cancer, but there have not been any specific studies examining the association between NLRP3 polymorphisms and cervical cancer (CC). This study was therefore designed to investigate the effect of NLRP3 gene polymorphisms on HPV infection and cervical cancer in southern Chinese population.MethodsMultiplex PCR and next-generation sequencing approaches were used to assess the NLRP3 rs10754558 and rs10733113 polymorphisms in 404 cervical lesion patients, including 227 diagnosed with CC and 177 diagnosed with cervical intraepithelial neoplasia(CIN), with 419 healthy female controls being included for comparison. Correlations between the rs10754558 and rs10733113 genotypes and alleles in these patients and CC and CIN were then analyzed.ResultsNo correlations were found between NLRP3 rs10754558 and rs10733113 and human papillomavirus(HPV) infection status. Relative to the healthy control group, the NLRP3 rs10754558 GG genotype, CG + GG genotype, and G allele frequencies were significantly increased among patients with cervical lesions (CC and CIN) (OR = 1.815,P = 0.013;OR = 1.383, P = 0.026; OR = 1.284, P = 0.014,respectively), whereas no such differences were observed for rs10733113. A higher cervical lesion risk was detected for patients over the age of 45 exhibiting the rs10754558 GG genotype (OR = 1.848, P = 0.040). Additionally, the risk of CC was elevated in patients with the rs10754558 GG genotype or the G allele relative to patients with the CC genotype or the C allele(OR = 1.830, P = 0.029; OR = 1.281, P = 0.039). The rs10733113 genotypes or alleles were not significantly associated with CC risk (P > 0.05). No association between rs10754558 and rs10733113 genotypes and CC patient clinicopathological features were observed (P > 0.05). Serum NLRP3, IL-1β, and IL-18 levels were significantly elevated in CC patients relative to healthy controls(P < 0.05). Relative to the CC genotype, CC patients harboring the rs10754558 GG genotype exhibited significantly elevated IL-1β and IL-18 levels(P < 0.05).ConclusionThe rs10754558 polymorphism in the NLRP3 gene may contribute to an elevated risk of CC, although it is not significantly correlated with HPV infection and CC progression.

Leisure-time physical activity and gastric cancer risk: a pooled study within the StoP project

Abstract Background Although physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully comprehended. For this reason, this study aims provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC. Methods Six case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. Heterogeneity was assessed using Q and I2 statistics. We performed stratified analyses according to demographic, lifestyle and clinical covariates. Results The meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]). Conclusions An association between leisure time PA and GC, apart from some suggestion of decreased risk below age 55, was not found. This may reflect specific characteristics of GC at younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC. Key messages • An association between leisure time PA and GC, apart from some suggestion of decreased risk below age 55, was not found. • GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old.

Protein citrullination: inhibition, identification and insertion.

Protein citrullination is a post-translational modification (PTM) that is catalysed by the protein arginine deiminase (PAD) family of enzymes. This PTM involves the transformation of an arginine residue into citrulline. Protein citrullination is associated with several physiological processes, including the epigenetic regulation of gene expression, neutrophil extracellular trap formation and DNA damage-induced apoptosis. Aberrant protein citrullination is relevant to several autoimmune and neurodegenerative diseases and certain forms of cancer. PAD inhibitors have shown remarkable efficacy in a range of diseases including rheumatoid arthritis (RA), lupus, atherosclerosis and ulcerative colitis. In RA, anti-citrullinated protein antibodies can be detected prior to disease onset and are thus a valuable diagnostic tool for RA. Notably, citrullinated proteins may serve more generally as biomarkers of specific disease states; however, the identification of citrullinated protein residues remains challenging owing to the small 1 Da mass change that occurs upon citrullination. Herein, we highlight the progress made so far in the development of pan-PAD and isozyme selective inhibitors as well as the identification of citrullinated proteins and the site-specific incorporation of citrulline into proteins. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.

Predictors of obesity among school-age children in Debre Berhan City, Ethiopia.

Obesity causes a serious diet-related chronic disease, including type-2 diabetes, cardiovascular disease, hypertension, osteoarthritis, and certain forms of cancer. In Sub- Saharan Africa including Ethiopia, most nutritional interventions mainly focused on a child undernutrition and ignored the impacts of obesity among children. In Ethiopia, the magnitude and associated factors of obesity among school-age children were not clearly described. Therefore this study assesses the predictors of obesity among school- age children in Debre Berhan City, Ethiopia, 2022. A cross-sectional study design was conducted from June to July, 2022. Participants were selected by using multistage sampling method. Data were collected using pre-tested and structured questions. Data were coded and entered in Epi-data version 4.6 and exported and analyzed using SPSS version 25. A total of 600 children were participating in the study. The prevalence of obesity was 10.7% (95% CI: 8.3, 13.2). In this study, attending at private school (AOR = 4.24, 95% CI: 1.58, 11.32), children aged between 10-12years (AOR = 2.67, 95% CI: 1.30, 5.48), soft drink available in home (AOR = 2.27, 95% CI: 1.25,18.13), Loneliness (AOR = 1.67 95% CI: 1.12, 3.15) and mothers with occupational status of daily labour (AOR = 8.54 95% CI: 1.12, 65.39) were significantly associated with childhood obesity. In this study, the overall magnitude of childhood obesity was (10.7%) which means one in eleven children and relatively high as compare to the EDHS survey. Therefore, more attention should be given to strengthening physical activities, providing nutritional education, and creating community awareness about healthy diets as well as other preventive measures.

The role of sperm-specific glyceraldehyde-3-phosphate dehydrogenase in the development of pathologies-from asthenozoospermia to carcinogenesis.

The review considers various aspects of the influence of the glycolytic enzyme, sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDS) on the energy metabolism of spermatozoa and on the occurrence of several pathologies both in spermatozoa and in other cells. GAPDS is a unique enzyme normally found only in mammalian spermatozoa. GAPDS provides movement of the sperm flagellum through the ATP formation in glycolytic reactions. Oxidation of cysteine residues in GAPDS results in inactivation of the enzyme and decreases sperm motility. In particular, reduced sperm motility in diabetes can be associated with GAPDS oxidation by superoxide anion produced during glycation reactions. Mutations in GAPDS gene lead in the loss of motility, and in some cases, disrupts the formation of the structural elements of the sperm flagellum, in which the enzyme incorporates during spermiogenesis. GAPDS activation can be used to increase the spermatozoa fertility, and inhibitors of this enzyme are being tried as contraceptives. A truncated GAPDS lacking the N-terminal fragment of 72 amino acids that attaches the enzyme to the sperm flagellum was found in melanoma cell lines and then in specimens of melanoma and other tumors. Simultaneous production of the somatic form of GAPDH and sperm-specific GAPDS in cancer cells leads to a reorganization of their energy metabolism, which is accompanied by a change in the efficiency of metastasis of certain forms of cancer. Issues related to the use of GAPDS for the diagnosis of cancer, as well as the possibility of regulating the activity of this enzyme to prevent metastasis, are discussed.

Leisure-time physical activity and gastric cancer risk: A pooled study within the Stomach cancer Pooling (StoP) Project.

Although physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC. Six case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates. The meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93]). No association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk.

Nitrates in industrial and traditional tomato paste from Arsenjan City, Iran: a health risk assessment study

ABSTRACT A comprehensive approach was used for the first time to measure NO3 – risk in tomato paste consumption; besides a robust deterministic and probabilistic method was used. The mean levels of NO3 – in homemade and industrial tomato paste were 7.36 mg/kg and 43.69 mg/kg, respectively. The Monte Carlo simulation confirmed that these values were below normal levels (HQ less than 1). The sensitivity analysis displayed that FIR was the main factor affecting the risk to human health in both groups. The interactive plot demonstrated the interaction between C and IR for children and adults in both types of tomato paste. This study concludes that NO3– ingestion due to tomato paste consumption poses no significant health risk. However, considering that food and water constitute the primary sources of NO3 – intake, continuous monitoring is recommended due to potential health risks associated with excessive NO3 – consumption, including certain forms of cancer.

NGS and Mutational Profile Analysis of Non-Small-Cell Lung Carcinoma (NSCLC)

Abstract: Computational analysis imitates the functioning of biological information systems to anticipate and offer novel perspectives on the biological realm. Genome sequencing analysis interactive techniques with the aim of improving the standards of cancer patient, has progressed greatly over the last decades, and is now considered to be one of the major scientific fields that promote innovation in the technology and healthcare sectors. In the field of bioinformatics, the first widespread application of data analysis was the creation of the first collection of systematic data representing the genome sequences of the eukaryotic organisms, termed as the eukaryotic genome, or the "de novo" genome. Tumor suppressor proteins are a class of proteins that are involved in preventing cancer from occurring. Several tumor suppressor proteins have been found to be mutated in certain forms of cancer, resulting in the loss of their tumor suppressing properties. Lung cancer develops when normal lung cells change, or mutate, in a way that alters their natural growth and death cycle, resulting in unregulated cell division that produces too many cells.Deep sequence analysis of non-small cell lung cancer and integrated analysis of gene expression. Understanding the biology of cancer is required to improve patient outcomes. Next-generation sequencing (NGS) is a powerful tool for whole genome characterization, enabling comprehensive exploration and understanding of the complex interactions between genes, proteins and their environment. NGS in the field of oncology is still in its infancy and the wealth of data that it is capable of generating is revolutionizing our understanding of cancer. ORFs have led to many exciting discoveries in the field of oncology, including the identification of tumor suppressor proteins. One of the most exciting recent discoveries is in the field of tumor suppressor proteins. Tumor suppressor proteins are proteins that play a role in the regulation of cell proliferation and division. Mutations in certain tumor suppressor genes cause cancer, and as a result, a great deal of research has gone into the identification of new tumor suppressor genes

Contributions of the Department of Defense Congressionally Directed Medical Research Programs to Advances in Cancer Therapeutics.

Nearly a billion dollars is spent annually in the Military Health System (MHS) on cancer diagnosis and treatment, with a large portion of that directed toward breast, prostate, and ovarian cancers. Multiple studies have demonstrated the impact of specific cancers on MHS beneficiaries and Veterans, highlighting the fact that active duty and retired military members have a higher incidence than the general public for many chronic diseases and certain forms of cancer. The Congressionally Directed Medical Research Programs have supported research that has contributed to the development, clinical testing, and commercialization of 11 cancer drugs approved by the Food and Drug Administration to treat breast, prostate, or ovarian cancers. In addition to hallmark funding mechanisms that prioritize innovative, groundbreaking ideas, the Congressionally Directed Medical Research Program's cancer programs continue to identify new approaches to fill critical gaps across the full research spectrum, including bridging the translational research gap toward developing new treatments for cancer patients in the MHS and in the general American public.

Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.