Analysis of Influencing Factors on the Occurrence and Development of Gastric Cancer in High-Incidence Areas of Digestive Tract Tumors Based on High Methylation of GPX3 Gene

Stomach cancer is the second largest cause of cancer-related mortality globally, and it continues to be a reason for worry today. Inhalation of the stomach cancer risk factor H. pylori produces large levels of reactive oxygen species (ROS). When combined with glutathione reductase, glutathione peroxidase 3 (GPX3) catalyzes the reduction of hydrogen peroxide and lipid peroxides. To get a better understanding of the GPX3 gene’s role in the illness, the researchers used quantitative real-time RT-PCR to examine the gene’s expression and regulation in gastric cancer cell lines, original gastric cancer samples, and 45 normal stomach mucosa adjacent to malignancies. According to the research, GPX3 expression was decreased or silenced in eight of nine cancer cell lines and 83 percent of gastric cancer samples (90/108) as compared to normal gastric tissues in the vicinity of the tumor ( P < 0.0001 ). It was found that 60 percent of stomach cancer samples exhibited DNA hypermethylation after analyzing the GPX3 promoter ( P = 0.007 ) (a methylation level of more than 10 percent, as measured by bisulfite pyrosequencing). In stomach tumors, we found a statistically significant reduction in the amount of GPX3 DNA copies ( P < 0.001 ). The gene expression of SNU1 and MKN28 cells was restored after treatment with 5-Aza-2′ Deoxycytidine to reduce GPX3 promoter methylation. Genetic and epigenetic alterations lead GPX3 to be dysfunctional in gastric cancer. This indicates that the systems that regulate ROS have been disrupted, and GPX3 may be implicated in the development of gastric cancer, as shown by our results when evaluated alone and in combination.

Generation of Human Stomach Cancer iPSC-Derived Organoids Induced by Helicobacter pylori Infection and Their Application to Gastric Cancer Research

There is considerable cellular diversity in the human stomach, which has helped to clarify cell plasticity in normal development and tumorigenesis. Thus, the stomach is an interesting model for understanding cellular plasticity and for developing prospective anticancer therapeutic agents. However, many questions remain regarding the development of cancers in vivo and in vitro in two- or three-dimensional (2D/3D) cultures, as well as the role of Helicobacter pylori (H. p.) infection. Here, we focus on the characteristics of cancer stem cells and their derived 3D organoids in culture, including the formation of stem cell niches. We define the conditions required for such organoid culture in vitro and examine the ability of such models for testing the use of anticancer agents. We also summarize the signaling cascades and the specific markers of stomach-cancer-derived organoids induced by H. p. infection, and their stem cell niches.

Prognostic Ferroptosis-Related lncRNA Signatures Associated With Immunotherapy and Chemotherapy Responses in Patients With Stomach Cancer

Ferroptosis is associated with the prognosis and therapeutic responses of patients with various cancers. LncRNAs are reported to exhibit antitumor or oncogenic functions. Currently, few studies have assessed the combined effects of ferroptosis and lncRNAs on the prognosis and therapy of stomach cancer. In this study, transcriptomic and clinical data were downloaded from TCGA database, and ferroptosis-related genes were obtained from the FerrDb database. Through correlation analysis, Cox analysis, and the Lasso algorithm, 10 prognostic ferroptosis-related lncRNAs (AC009299.2, AC012020.1, AC092723.2, AC093642.1, AC243829.4, AL121748.1, FLNB-AS1, LINC01614, LINC02485, LINC02728) were screened to construct a prognostic model, which was verified in two test cohorts. Risk scores for patients with stomach cancer were calculated, and patients were divided into two risk groups. The low-risk group, based on the median value, had a longer overall survival time in the KM curve, and a lower proportion of dead patients in the survival distribution curve. Potential mechanisms and possible functions were revealed using GSEA and the ceRNA network. By integrating clinical information, the association between lncRNAs and clinical features was analyzed and several features affecting prognosis were identified. Then, a nomogram was developed to predict survival rates, and its good predictive performance was indicated by a relatively high C-index (0.67118161) and a good match in calibration curves. Next, the association between these lncRNAs and therapy was explored. Patients in the low-risk group had an immune-activating environment, higher immune scores, higher TMB, lower TIDE scores, and higher expression of immune checkpoints, suggesting they might receive a greater benefit from immune checkpoint inhibitor therapy. In addition, a significant difference in the sensitivity to mitomycin. C, cisplatin, and docetaxel, but not etoposide and paclitaxel, was observed. In summary, this model had guiding significance for prognosis and personalized therapy. It helped screen patients with stomach cancer who might benefit from immunotherapy and guided the selection of personalized chemotherapeutic drugs.

Risk assessment of gastric cancer in the presence of Helicobacter pylori cagA and hopQII genes

Helicobacter pylori bacterium is one of the most common bacterial infections globally and is the leading cause of indigestion, gastric and duodenal ulcers, and gastric cancer. This bacterium can escape the antibacterial effects of stomach acid by adapting to the inner layers of the stomach. It combines with the natural sugars in the gastric mucosa. The compound is so effective that it makes bacterium resistant. For genes related to the pathogenesis of H. pylori, using the existence of genes such as cagA, hopQI, and hopQII, PCR is performed on some of these genes to amplify fragments of different lengths. One of the less-studied cases is that two or more pathogenic genes are simultaneously associated with H. pylori. This study examined the frequency of diseases and healthy individuals infected with H. pylori and cagA and hopQII genotypes. To diagnose H. pylori infection in healthy and stomach cancer patients, the PCR products are electrophoresed on the agarose gel after glmM gene amplification by PCR. To this aim, stomach tissue biopsies were used for patients, and saliva was used for healthy individuals. For this purpose, 150 gastric biopsy samples from stomach cancer patients and 150 saliva samples from healthy people were collected. Data showed a significant relationship between the coexistence of two genes, cagA and hopQII, and stomach cancer. 34.2% of patients and 10.1% of healthy individuals showed two genotypes, while other healthy people (89.9%) infected with H. pylori did not have this genotype. Therefore, the simultaneous presence of these two bacterial genes in human societies can be an essential biomarker for the diagnosis and prognosis of gastric cancer.

Cancer Scenario in Kashmir—A Study Conducted in a Tertiary Care Center, Srinagar, Kashmir, India

Background Cancer can have profound social and economic consequences for the people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1.2 billion. It accounts for about 23 and 7% deaths in United States and India, respectively. The world's population is expected to be 7.5 billion by 2020 and approximations predict that about 15.0 million new cancer cases will be diagnosed, with deaths of about 12.0 million cancer patients. Early detection of cancers is a challenging task because clinical symptoms develop slowly. Objective The aim of the present study was to analyze the cancer scenario in the Kashmir valley. Materials and Methods This was a retrospective study. So, all patients were included who had histopathologically confirmed neoplasm registered at Regional Cancer Centre of Government Medical College Srinagar, Kashmir between 2015 and 2018. All the patient characteristics including age, sex, and anatomical site of the disease were studied in detail. Results The number of cancer patients in 2015, 2016, 2017, and 2018 were 230, 239, 391, and 511, respectively, with a combined total of 1,371. Thus, it is clear from these figures that the number of cancer cases has increased gradually with time. Stomach cancer is the most common cancer in the Kashmir territory. In males the most common cancer is stomach cancer with 175 (12.8%) reported cases and in females the most common cancer is breast cancer with 151 (11%) reported cases. The male to female ratio was 1.4:1. Conclusion A careful reading the reported cancer cases indicates an increased number of cancer patients every year in Indian-occupied Kashmir. Kashmir is a growing state in India playing a crucial role in the development of India and, hence, it needs special attention on this issue. A multidisciplinary approach to cancer treatment is essential and this has to be made available at all regional cancer centers. Cancer control is an area in which we need participation from all sectors of the society.

VITAMIN B1 BIOLOGICAL FUNCTION IMPLEMENTATION IN THE BLOOD OF PATIENTS WITH STOMACH CANCER UNDER SURGICAL INTERVENTION

Background. The probability of undergoing surgery always predetermines the state of stress in a person; therefore, it is advisable to search for ways to optimize and (or) reduce this unfavourable effect. Objective. To find out the mechanism of vitamin B1 antistress activity during surgery. Material and methods. Metabolism intensity was investigated on donors’ blood lysates (n = 19) and those of patients with stage III stomach cancer (n = 64), referred to an elective surgery, aged 51-70. The blood was taken from the cubital vein three days before the operation, after premedication, during the most traumatic moment of the operation, after extubation, as well as on the first and third days of the postoperative period. The surgery was performed under combined multicomponent anesthesia using nitric oxide, sodium hydroxybutyrate, and epidural block. Thiamine and thiamine diphosphate kinase activities were assessed by the concentration of the formed thiamine di- and triphosphates of the vitamin. The activities of thiamine mono-, di- and triphosphatases were determined by the release of inorganic phosphate. The concentration of inorganic phosphate was recorded colorimetrically. The content of B1 and its derivatives in the blood was determined by the method of ion-pair reversed-phase HPLC. Results. There has been observed an increased content of thiamine monophosphate and that of free thiamine in the blood of donors and patients with stomach cancer. The registered rate of the hydrolytic thiamine monophosphatase reaction is not high. At the stages of premedication and maximum trauma of surgical exposure, the concentration of monophosphoric ester rapidly decreases alongside with monophosphatase activation. Therefore, the thiamine monophosphate hydrolysis is the rate-limiting link of vitamin B1 metabolism. The level of free thiamine remains persistently increased at all stages of surgical treatment. Thiamine monophosphatase activity is manifested at two pH optima – of 6.0 and 9.0. Thiamine monophosphate hydrolysis at pH of 9.0 is catalyzed by alkaline phosphatase. At pH of 6.0, in addition to thiamine monophosphoric ester, the enzyme hydrolyzes only p-nitrophenyl phosphate, flavin mononucleotide and phosphotyrosine, that allows it to be classified as hepatic acid phosphatase. The noted changes in B1 metabolism under stress concern mainly non-coenzyme forms - thiamine mono-, triphosphate, and free thiamine, which are used at the stages of thiol reduction as important components of insulin synthesis. Conclusions. The use of vitamin B1 allows to optimize the development of the stress response at all stages of surgical treatment. Its protective effect is achieved through the activation of the insulin-synthetic function of the pancreas, which increases the level of immunoreactive insulin in the blood. The formation of the most favorable physiological conditions for insulin synthesis provides an increased background of free thiamine, which is created due to the hydrolysis of noncoenzyme forms of the vitamin. The relationship between thiamine metabolism and B2 exchange and regulation of intracellular signaling pathways has been traced.

The Main Patterns in the Trend Change of Stomach Cancer Incidence amongst Selected African Countries

Aim. The current study aimed to investigate the trend changes of stomach cancer incidence amongst African countries and identify the main patterns. Methods. The annual reports of stomach cancer incidence rate (per 100,000 people) for males and females in 53 African countries from 1990 to 2016 were maintained from the World Health Organization archive. The growth mixture model was used for fitting the models in Mplus 7.4. The estimated linear trend in each pattern was characterized by intercept (the rate at 1990) and slope (the observed biennial trend changes), and finally, each country was grouped into a cluster with the most similar pattern. Results. Three main patterns for males and two main patterns for females were determined. For males, the first cluster, containing Cape Verde, Central African Republic, and Mauritius, showed a sharp fall, while countries in the second pattern including Algeria, Côte d’Ivoire, Egypt, Gambia, Libya, Malawi, Morocco, Namibia, Nigeria, and Tunisia were categorized in a pattern with a slight decrease, and other 43 countries were in the third pattern with a moderate falling trend. For females, 19 countries including Angola, Botswana, Burundi, Cape Verde, Central African Republic, Congo Republic, Equatorial Guinea, Ethiopia, Gabon, Kenya, Mali, Mauritius, Rwanda, Sao Tome and Principe, Sudan, Swaziland, Uganda, Zambia, and Zimbabwe were categorized in the moderate-to-high falling pattern, but the other 34 countries had a gentle downward pattern. Conclusion. Although most of the observed trends of stomach cancer were falling, only a few countries had experienced a favorable decreasing trend (three countries in male incidence and nineteen countries in female incidence). Therefore, taking effective actions to accelerate the observed falling trends seems necessary.