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.

Epidemiological Profile of Ophir Loyola Cancer Hospital: A Snapshot of the Incidence of Solid Neoplasms in the Eastern Amazon.

BACKGROUND: Solid neoplasms have a heterogeneous incidence worldwide and in Brazil. Thus, the region delimited by the Legal Amazon has a distinct epidemiological profile. In Pará, Ophir Loyola Cancer Hospital(OLCH) accounts for 71.11% of hospital visits in the state. METHODS: This was an ecological, exploratory, and mixed descriptive studythat investigated the epidemiological profile of patients with cancer treated at OLCH from January to December 2020. Sociodemographic data at admission were the primary variables, which were analyzed according to spatial distribution. RESULTS: In this study, the data of 2952 patients were analyzed, with the majority being between the ages of 50 and 79 years (62.47%), female (59.49%), and diagnosed but without previous treatment (87.30%). The most common cancers were breast (16.50%), cervical (13.40%), stomach (8.98%), and prostate (7.72%). Of the 12 integration regions, Guajará had the highest number of referrals (49.86%), followed by Guamá (12.94%) and Caeté River (8.98%). CONCLUSION: The profile of care at OLCH showed a high incidence of solid malignancies compared to that in other regions of Brazil, indicating environmental and sociocultural influences on the carcinogenic profile present in the eastern Amazon.

Association between the rs820218 Variant within the SAP30BP Gene and Rotator Cuff Rupture in an Amazonian Population.

BACKGROUND: Rotator cuff disease is one of the leading causes of musculoskeletal pain and disability, and its etiology is most likely multifactorial but remains incompletely understood. Therefore, the objective of this research was to investigate the relationship of the single-nucleotide rs820218 polymorphism of the SAP30-binding protein (SAP30BP) gene with rotator cuff tears in the Amazonian population. METHODS: The case group consisted of patients who were operated on due to rotator cuff tears in a hospital in the Amazon region between 2010 and 2021, and the control group was composed of individuals who were selected after negative physical examinations for rotator cuff tears. Genomic DNA was obtained from saliva samples. For the genotyping and allelic discrimination of the selected single nucleotide polymorphism (rs820218) in the SAP30BP gene, real-time PCR was performed. RESULTS: The frequency of the A allele in the control group was four times as high as that in the case group (AA homozygotes); an association of the genetic variant rs820218 of the SAP30BP gene with rotator cuff tears was not established (p = 0.28 and 0.20), as the A allelic frequency is ordinarily low in the general population. CONCLUSIONS: The presence of the A allele indicates protection against rotator cuff tears.

In vitro assessment of cytotoxic, genotoxic and mutagenic effects of antimalarial drugs artemisinin and artemether in human lymphocytes.

Artemisinin is a substance extracted from the Chinese plant Artemisia annua L. widely used in natural medicine for the treatment of various diseases. Artemether is a substance synthesized from artemisinin, and both drugs are commonly administered in the treatment of malaria. Although considered effective antimalarial drugs, very little is known about the genotoxic, cytotoxic and mutagenic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin (12.5, 25 and 50 µg/mL) and artemether (7.46; 14.92 and 29.84 µg/mL) in cultured human lymphocytes using the comet assay, the micronucleus test and the cytotoxicity assay for detection of necrosis and apoptosis by acridine orange/ethidium bromide staining. Our results showed a significant increase (p < 0.05) in the rate of DNA damage measured by comet assay and in the micronucleus frequency after treatment with both drugs. It was also observed that only artemisinin induced a statistically significant increase (p < 0.05) in the number of lymphocytes with death by necrosis 48 h after treatment. The results demonstrated that these two drugs induce mutagenic, genotoxic and cytotoxic effects in cultured human lymphocytes. Our data indicate the need for caution in the use of such drugs, since genotoxic/mutagenic effects may increase the risk of carcinogenesis.

Effect of diterpenoid kaurenoic acid on genotoxicity and cell cycle progression in gastric cancer cell lines.

The goal of our study was to evaluate the effect of kaurenoic acid, obtained from copaiba oil resin, in gastric cancer (GC) and a normal mucosa of stomach (MNP01) cell lines. The compound was tested at concentrations of 2.5, 5, 10, 30 and 60µg/mL. Comet and micronucleus assays were used to access its potential genotoxicity in vitro. Moreover, we evaluated the effect of kaurenoic acid in cell cycle progression and in the transcription of genes involved in the control of the cell cycle: MYC, CCND1, BCL2, CASP3, ATM, CHK2 and TP53. Kaurenoic acid induced an increase on cell DNA damage or micronucleus frequencies on GC cell lines in a dose-dependent manner. The GC and MNP01 cell lines entering DNA synthesis and mitosis decreased significantly with kaurenoic acid treatment, and had an increased growth phase compared with non-treated cells. The treatment induced apoptosis (or necrosis) even at a concentration of 2.5µg/mL in relation to non-treated cells. GC cell lines presented reduced MYC, CCND1, BCL2 and CASP3 transcription while ATM, CHK2 and TP53 increased in transcription in relation to non-treated cells, especially at a concentration above 10µg/mL. The gene transcription in the MNP01 (non-treated non-cancer cell line) was designated as a calibrator for all the GC cell lines. In conclusion, our results showed that kaurenoic acid obtained from Copaifera induces DNA damage and increases the micronuclei frequency in a dose-dependent manner in GC cells, with a significant genotoxicity observed above the concentration of 5µg/mL. Moreover, this compound seems to be able to induce cell cycle arrest and apoptosis in GC cells.

Presence of c.3956delC mutation in familial adenomatous polyposis patients from Brazil.

AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis (FAP) in northern Brazil. METHODS: A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP, family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the João de Barros Barreto University Hospital (Belem, Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations, Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system. RESULTS: Through interviews with relatives and a search of medical records, it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene, and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP, family members without disease symptoms showed the mutation in the APC gene. In the present study, we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956delC mutation was found in all families from this study, and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration (i.e., a de novo mutation that arose in one member belonging to this state from Brazil). CONCLUSION: Regardless of its origin, the c.3956delC mutation is a strong candidate biomarker of this hereditary cancer syndrome in families of northern Brazil.

In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100).

Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3-(4,5-methylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P < 0.05). PG100 also showed a significant dose-dependent increase in DNA damage index at concentrations of 119.4 and 238.8 µg ml(-1) (P < 0.05). Our results showed that artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 µg ml(-1), for all the tested harvest times (P < 0.05). In lymphocytes, artemether induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 µg ml(-1), for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes were more sensitive to the cytotoxic effects of the antimalarial drug than the gastric cancer cell line PG100.