Homocystein, Vitamin B12 and Folic Acid as Screening Biomarkers in Early Diagnosis and Gastric Cancer Monitoring.

Gastric cancer has been demonstrating a reduction in the number of cases over the past decades, largely attributed to advancements in public health practices and increased accessibility to educational initiatives for the general population. Nevertheless, it persists as the third leading cause of mortality globally among both men and women. These fatalities are typically associated with delayed disease detection. The current study assessed the levels of homocysteine, vitamin B12, and folic acid as a means of establishing a screening biomarker profile that could be integrated into routine testing protocols to facilitate swift diagnosis of the illness. A total of 207 control subjects and 207 individuals with gastric cancer were scrutinized, with biochemical measurements conducted using chemiluminescence for homocysteine, folic acid, and vitamin B12. The two groups were matched based on age, tumor location, subtype, tumor classification, presence of Epstein-Barr Virus infection (EBV), and Helicobacter pylori (H. pylori). Significant statistical variances were identified in the mean levels of the triad of substances among cancer patients when compared to the control group for all corresponding variables. In conclusion, our study indicated that analyzing the triad of homocysteine, vitamin B12, and folic acid holds diagnostic value for gastric cancer and could potentially serve as an effective screening marker for this type of cancer in the future.

CDC25B Inhibition by Menadione: A Potential New Therapeutical Approach.

Gastric cancer (GC) is the fifth most common type of tumor and the third leading cause of cancer death worldwide. The evolution of gastric carcinogenesis is still poorly understood and, for this reason, preclinical research protocols were established that included the development of gastric cancer cell lines and the establishment of models of gastric carcinogenesis in non-human primates such as Sapajus apella. A comprehensive literature search was performed in relevant databases such as PubMed, ResearchGate, and Google Scholar to identify studies related to the topic. After an in-depth study of these reports, significant data were collected and compiled under appropriate headings. The main result of the studies carried out by the group on GC is the demonstration of the MYC gene overexpression as a common phenomenon in stomach carcinogenesis. Furthermore, we revealed that reducing the expression of the CDC25B gene, regulated by the MYC protein, is a therapeutic strategy against stomach tumors. This review article reveals preclinical evidence that treatment with menadione in experimental models of gastric tumorigenesis, in vivo and in vitro, inhibits the action of the phosphatase CDC25B and, consequently, prevents cell proliferation, invasion, and migration.

PD-L1 Expression Associated with Epstein-Barr Virus Status and Patients' Survival in a Large Cohort of Gastric Cancer Patients in Northern Brazil.

Gastric cancer (GC) is a worldwide health problem, making it one of the most common types of cancer, in fifth place of all tumor types, and the third highest cause of cancer deaths in the world. There is a subgroup of GC that consists of tumors infected with the Epstein-Barr virus (EBV) and is characterized mainly by the overexpression of programmed cell death protein-ligand-1 (PD-L1). In the present study, we present histopathological and survival data of a thousand GC patients, associated with EBV status and PD-L1 expression. Of the thousand tumors analyzed, 190 were EBV-positive and the vast majority (86.8%) had a high relative expression of mRNA and PD-L1 protein (p < 0.0001) in relation to non-neoplastic control. On the other hand, in EBV-negative samples, the majority had a low PD-L1 expression of RNA and protein (p < 0.0001). In the Kaplan-Meier analysis, the probability of survival and increased overall survival of EBV-positive GC patients was impacted by the PD-L1 overexpression (p < 0.0001 and p = 0.004, respectively). However, the PD-L1 low expression was correlated with low overall survival in those patients. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.

Association between Helicobacter pylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas.

AIM: To correlate Helicobacter pylori (H. pylori), Epstein-Barr virus (EBV) and human papillomavirus (HPV) with gastric cancer (GC) cases in Pará State, Brazil. METHODS: Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eber1 RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients. RESULTS: The majority of the 302 samples analyzed were obtained from men (65%) aged 55 years or older (67%) and were classified as the intestinal subtype (55%). All three pathogens were found in the samples analyzed in the present study (H. pylori: 87%, EBV: 20%, HPV: 3%). Overall, 78% of the H. pylori-positive (H. pylori +) samples were cagA+ (H. pylori-cagA +), and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA + and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens. CONCLUSION: HPV was not involved in gastric tumorigenesis. Prophylactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

Frequency of the Loss of Heterozygosity of the NF2 Gene in Sporadic Spinal Schwannomas.

BACKGROUND/AIM: Individuals with type 2 Neurofibromatosis are predisposed for the appearance of schwannomas. In the present study we analyzed the loss of heterozygosity and mutations in the NF2 gene in patients with sporadic Schwannoma without Neurofibromatosis type 2. MATERIALS AND METHODS: We analyzed 39 patients with sporadic spinal schwannoma. We quantified the number of alleles by FISH and sequenced the NF2 gene. RESULTS: We identified 16/39 patients with point mutations and/or LOHs in the tumor samples analyzed. The LOHs were found in 7/39 patients. Two homozygous mutations were detected in 4/39 tumors, and the presence of the mutation in heterozygosis was revealed in 3/39 patients. In two tumors, we detected the loss of one allele of the NF2 gene, with no mutation. CONCLUSION: The genetic alterations observed in the NF2 gene indicated that spinal schwannomas are associated with genetic alterations also found in other schwannomas and type 2 Neurofibromatosis, which reinforces the etiological role of this gene.

Identificação do papilomavírus humano em doentes com carcinoma de células escamosas do canal anal e sua relação com o grau de diferenciação celular e estadiamento / Identification of human papillomavirus in patients with anal squamous cell carcinoma and its relation with the grade of cellular differentiation and staging

OBJETIVO: Identificar os tipos de papilomavírus humano (HPV) nos portadores de carcinoma do canal anal (CCA), relacionando-os ao grau de diferenciação celular e estadiamento da lesão, em pacientes do Belém, Pará, entre 1998 e 2000. MÉTODOS: Foi realizado um estudo de caso-controle com 75 pacientes, divididos em: Grupo Teste, com 33 portadores de carcinoma do canal anal, e o Grupo Controle, com 42 portadores de doenças não-neoplásicas do canal anal. Os tipos virais foram identificados por PCR e dot blot. O teste exato de Fischer foi utilizado para avaliar a ocorrência de HPV. Adotou-se a tabela de contingência 3x2 para representar a distribuição dos tipos de HPV. Nos testes de hipóteses, foi prefixado o nível de significância alfa=0,05 para a rejeição da hipótese de nulidade. RESULTADOS: A prevalência do HPV foi significante entre os Grupos Teste (60,6 por cento) e Controle (26,2 por cento) (p=0,0027). Os tipos virais mais comuns foram 16 (42,4 por cento) e 18 (15,2 por cento). Observaram-se diferenças entre grupos na prevalência do HPV 16 (p=0,027) e 18 (p=0,043) no Grupo Teste, e o tipos 16 (19,0 por cento,) e 18 em (2,4 por cento) no Grupo Controle. No Grupo Teste, avaliou-se a distribuição dos tipos de HPV em relação ao estadiamento e ao grau de diferenciação celular, não apresentando diferenças estatisticamente significativas. CONCLUSÃO: O carcinoma de células escamosas do canal anal está associado à presença de HPV, e os tipos 16 e 18 são os mais frequentes.

OBJECTIVE: To identify the most predominant types of human papillomavirus (HPV) in carriers of the anal canal carcinoma (ACC), relating them to the cell differentiation and lesion staging degree, in patients from Belém, Pará, Brazil, between 1998 and 2000. METHODS: A case-control study was conducted with 75 patients, divided into Test Group, with 33 carriers of the anal canal carcinoma, and Control Group, with 42 carriers of non-neoplastic diseases of the anal canal. The methods employed to identify the viral types were the polymerase chain reaction and the dot blot. The Fisher's exact test was used to assess the HPV occurrence. The distribution of HPV types was analyzed by 3x2 contingency tables, representing the distribution of HPV types. For hypothesis testing, the significance level alfa=0.05 was previously established for rejection of the null hypothesis. RESULTS: HPV was significantly prevalent (p=0.0027) in the Test (60.6 percent) and Control Groups (26.2 percent) (p=0.0027). The most prevalent viral types were HPV 16 (42.4 percent) and 18 (15.2 percent). Significant differences related to the prevalence of HPV 16 and 18 were verified between both groups (p=0.027 and p=0.043, respectively). In the Control Group, HPV 16 was found in 19.0 percent, whereas HPV 18 was observed in 2.4 percent. In the Test Group, we evaluated the distribution of HPV types according to the staging and degree of cell differentiation, and found no significant differences between the results of the different groups. CONCLUSION: Squamous cell carcinoma of the anal canal is associated with the HPV presence, and the 16 and 18 types are the most frequently found.