HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma.

BACKGROUND: Anal residual tumors are consensually identified within six months of chemoradiotherapy and represent a persistent lesion that may have prognostic value for overall survival. The aim of this study was to evaluate the association of HPV and HIV status, p16 expression level and TP53 mutations with the absence of residual tumors (local response) in Squamous Cell Carcinoma (SCC) of the anal canal after chemoradiotherapy. METHODS: We performed a study on 78 patients with SCC of the anal canal who submitted to chemoradiotherapy and were followed for a six-month period to identify the absence or presence of residual tumors. HPV DNA was identified by polymerase chain reaction and direct sequencing, HIV RNA was detected by TaqMan amplification, p16 expression was detected by western blotting, and the mutational analysis of TP53 was performed by direct sequencing; additionally, samples carrying mutations underwent fluorescent in sit hybridization. The evaluation of the tumor response to treatment was conducted six months after the conclusion of chemoradiotherapy. The following classifications were used to evaluate the outcomes: a) no response (presence of residual tumor) and b) complete response (absence of residual tumor). RESULTS: The significant variables associated with the absence of residual tumors were HPV positive, p16 overexpressed, wild-type TP53, female gender, and stages I and II. Only the presence of HPV was independently correlated with the clinical response; this variable increased the chances of a response within six months by 31-fold. CONCLUSIONS: The presence of HPV in tumor cells was correlated with the absence of a residual tumor. This correlation is valuable and can direct future therapeutic approaches in the anal canal.

Therapeutic effect of andiroba oil (Carapa guianensis Aubl.) against oral mucositis: an experimental study in golden Syrian hamsters.

OBJECTIVES: The aim of this study was to investigate the healing activity of andiroba (Carapa guianensis Aubl.) against oral mucositis (OM) induced by 5-fluorouracil in golden Syrian hamsters. MATERIALS AND METHODS: A total of 122 animals were randomized and divided into six groups: andiroba oil 100%, andiroba oil 10%, andiroba oil 10% refined, no treatment group, all n = 28; and negative control (NC) and cyclophosphamide (CPA) groups, both n = 5. OM was induced by intraperitoneal administration of 60 mg/kg 5-FU on days 0, 5 and 10 followed by mechanical trauma on the oral mucosa on days 1 and 2. From day 1 to day 15, the animals of the andiroba group were treated three times a day. On days 4, 8, 12 and 15, the mucosa was photographed and removed for clinical and histopathological analysis. The bone marrow of the femur was removed and the micronucleus test was performed to evaluate the cytotoxicity and genotoxicity. The data were subjected to analysis of variance, followed by the Tukey and Bonferroni test. RESULTS: Treatment with 100% andiroba oil reduced the degree of OM compared to that reported in the other groups (p < 0.05). Andiroba oil at both concentrations was not cytotoxic, but treatment with 100% andiroba oil showed a genotoxic potential (p < 0.001). CONCLUSIONS: Frequent administration of andiroba oil accelerated the healing process in an experimental model of 5-fluorouracil-induced OM. However, the genotoxicity of andiroba in other cell systems and under other conditions are being tested. CLINICAL RELEVANCE: The use of andiroba in topical form may be associated with reduced intensity of OM. Seek therapeutic alternatives to minimize the pain and suffering that these side effects cause cancer patients is an important scientific step.

Genetic diversity of human papillomavirus types 35, 45 and 58 in cervical cancer in Brazil.

In Brazil, most studies of intra-type variants of human papillomavirus (HPV) have focused on HPV16 and HPV18, but other high-risk HPV types have not been studied. Here, we report the prevalence of lineages and variants of HPV35, HPV45 and HPV58 in cervical cancers from the Amazonian and Southeast Brazilian regions. The most frequent sublineages were A1 for HPV35, B2 for HPV45, and A2 for HPV58. The Southeast region had a higher frequency of the B2 sublineage of HPV45, and for HPV35, the genetic and nucleotide sequence diversity were higher in the Southeast region, suggesting that regional factors are influencing the diversity and lineage prevalence.

Cytotoxic and mutagenic effects of the food additive tartrazine on eukaryotic cells.

BACKGROUND: Among the food additives used in the food industry, food dyes are considered the most toxic. For instance, tartrazine (TRZ) is a food colorant commercially available with conflicting data regarding its cytotoxic, genotoxic, and mutagenic effects. Therefore, this study aimed to evaluate the cytotoxic and mutagenic potential of TRZ using different eukaryotic cells (in vitro). METHODS: This study employed 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), brine shrimp lethality, Allium cepa and Saccharomyces cerevisiae tests. Different concentrations of TRZ and different exposure times were used in this study. RESULTS: The results demonstrate that TRZ induced a concentration-dependent toxic effect on the test systems. It also exerted cytotoxicity in fibroblasts and human gastric cells. In addition, TRZ showed mutagenic effects on the A. cepa test system. However, its toxicogenic effects may not relate to the oxidizing activity, which was confirmed by the S. cerevisiae test model. CONCLUSION: Taken together, TRZ exerted toxicogenic effects on the test systems. Therefore, it may be harmful to health, especially its prolonged use may trigger carcinogenesis.

Mebendazole induces apoptosis via C-MYC inactivation in malignant ascites cell line (AGP01).

The objective of study was to examine the role of MBZ on malignant ascites cells and the involvement of C-MYC. Comet assay was used to assess the genotoxic effects of MBZ in AGP01 cells and human lymphocytes; differential staining by ethidium bromide and acridine orange, caspase 3/7 and flow cytometry assay was done to access the mechanisms of apoptosis and cell cycle analysis of MBZ in AGP01 cells. C-MYC amplification, C-MYC mRNA and C-MYC protein expression were evaluated by FISH, RT-qPCR and Western blotting, respectively. In addition, cytotoxicity of MBZ was evaluated in AGP01 and AGP01 shRNA MYC by MTT. MBZ significantly increased the damage index and no produced in human lymphocytes. MBZ caused remarkable cell cycle arrest in G0/G1 and G2/M phases at 0.5µM and 1.0 µM, respectively and induced significantly apoptosis in higher concentrations. Additionally, MBZ (0.5 µM and 1.0 µM) increased caspase 3 and 7 activities. MBZ decreased signals, C-MYC mRNA and C-MYC protein expression in AGP01 cells. MBZ induced lower cell viability in AGP01 cells compared AGP01 shRNA MYC in the same concentration. Therefore, our results show the evidence of C-MYC gene as one of the pathways by which MBZ induces cell death in gastric cancer cells.

Small benzothiazole molecule induces apoptosis and prevents metastasis through DNA interaction and c-MYC gene supression in diffuse-type gastric adenocarcinoma cell line.

Chemo-resistance has been reported as a relevant barrier for the efficiency of gastric cancer treatment. Therefore, the development of effective and safe drugs for cancer chemotherapy is still a challenge. The purpose of this study was to evaluate the anticancer potential of (E)-2-(((2-(benzo[d]thiazo-2-yl)hydrazono)methyl)-4-nitrophenol) (AFN01) against gastric cancer cell lines. Our results showed promising anticancer activity against gastric cancer cells ACP-02 (IC50 = 1.0 µM) and mild activity against other cell lines including non-malignant gastric cell MNP-01 (IC50 = 3.4 µM). This compound significantly induced S phase cell cycle arrest, prevented cell migration and triggered apoptosis in a concentration-dependent manner. Moreover, AFN01 was significantly more genotoxic against tumoral cell ACP-02, when compared to non-malignant cells, such as MNP-01 and healthy peripheral mononuclear blood cells. AFN01 also synergistically interacts with doxorubicin suppressing cell proliferation and c-MYC gene expression in gastric cancer cell line model, with remarkable c-MYC overexpression. Although further pre-clinical and clinical studies are required to explore its safety and efficiency, AFN01 may represent a promising lead anticancer agent for the treatment of gastric cancer.

Mebendazole, an antiparasitic drug, inhibits drug transporters expression in preclinical model of gastric peritoneal carcinomatosis.

The present study aimed to investigate whether MBZ down-regulates drug transporter expression (ABCB1, ABCC1, SLC47A1). mRNA expression level of ABCB1, ABCC1 and SLC47A1 was evaluated by qPCR and protein expression levels MDR-1 was performed by western blotting in malignant ascites cells (AGP-01) treated with MBZ for 24h. The mRNA expression level of ABCB1 and ABCC1 significantly decreased at a 1.0µM of MBZ compared to negative control, while SLC47A1 extremely decreased at all tested concentrations of MBZ. Protein expression levels MDR-1 significantly decreased at a 1.0µM of MBZ compared to negative control. Therefore, our results showed MBZ may play an important role in inhibiting MDR gene expression in malignant ascites cells.

The anthelmintic drug mebendazole inhibits growth, migration and invasion in gastric cancer cell model.

The present study aimed to investigate the effects of MBZ on a human malignant ascites cell line derived from a primary gastric cancer tumor. Our data reveal that MBZ showed high cytotoxicity in vitro, displaying an IC50 of 0.39 µM and 1.25 µM in ACP-02 and ACP-03, respectively. The association between MBZ and 5-FU increased slightly the cytotoxicity when compared to MBZ and 5-FU alone. Furthermore, MBZ disrupted the microtubule structure of AGP-01 cells and inhibited significantly the invasion and migration of these cells. Activity of active MMP-2 significantly decreased at all tested concentration of MBZ compared to negative control. These results support the indication of MBZ in combination with chemotherapeutic agents as a possible adjuvant therapy for the management/treatment of patients with advanced gastric cancer since MBZ is a drug of low cost with acceptable safety profile and reduced toxicity to normal cells. However, clinical trials must be performed in o to evaluate its efficacy in gastric cancer patients.

Effects on DNA repair in human lymphocytes exposed to the food dye tartrazine yellow.

Tartrazine is a food additive that belongs to a class of artificial dyes and contains an azo group. Studies about its genotoxic, cytotoxic and mutagenic effects are controversial and, in some cases, unsatisfactory. This work evaluated the potential in vitro cytotoxicity, genotoxicity and effects on DNA repair of human lymphocytes exposed to the dye. We assessed the cytotoxicity of tartrazine by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test and the response of DNA repair through comet assay (alkaline version). We used different concentrations of the dye, ranging from 0.25-64.0 mM. The results demonstrated that tartrazine has no cytotoxic effects. However, this dye had a significant genotoxic effect at all concentrations tested. Although most of the damage was amenable to repair, some damage remained higher than positive control after 24 h of repair. These data demonstrate that tartrazine may be harmful to health and its prolonged use could trigger carcinogenesis.

Determinação e Avaliação do Fator de Correção de Hortaliças em uma Unidade de Alimentação e Nutrição de Guarapuava - PR / Determination and Evaluation of the Correction Factor on Greeneries at a Nutrition and Feeding Unity in Guarapuava - PR

As perdas existentes no pré-preparo dos alimentos nas Unidades de Alimentação e Nutrição (UANs) podem auxiliar na avaliação do desperdício, um fato de suma importância devido aos custos gerados ao impacto social e ambiental. Diante disso, o presente estudo teve como objetivo determinar e avaliar o fator de correção de hortaliças utilizadas em uma UAN e comparar os valores encontrados com os dados presentes em outros estudos, a fim de avaliar o desperdício. Para o cálculo do fator de correção, utilizou-se a relação entre o peso bruto e o peso líquido. Foi aferido o peso de três amostras distintas, de cada um das quinze hortaliças (acelga, alface, alho, abobrinha, batata doce, batata inglesa, berinjela, beterraba, cebola, cenoura, repolho branco, pepino, pimentão, tomate e chuchu). Verificou-se que seis hortaliças apresentavam fatores de correção em conformidade com as três referências comparadas. Porém, a alface, o alho, a batata doce, batata inglesa, cenoura, acelga, cebola, o pepino e a beterraba apresentaram fator de correção acima do estabelecido por algum estudo. Com isso, vários fatores como condições de recebimento e de armazenamento (tempo e temperatura), assim como técnicas de pré-preparo, deveriam ser padronizados na UAN para diminuição do desperdício.

The losses in the preparation of foods at the Nutrition and Feeding Unity (NFU) can measure the waste, which is very important due to the high costs generated and the social and environmental impact. The present study aimed to determine and evaluate the correction factor on greeneries used in a NFU, and to compare the values with the data presented on other studies. To calculate the correction factor, the relation between the gross weight and net weight was used. Three distinct samples were measured, from the fifteen greeneries (chard, lettuce, garlic, zucchini, yam, English potato, eggplant, beetroot, onion, carrot, white cabbage, cucumber, pepper, tomato and chayote). It was observed that six greeneries presented correction factors complying with three references in literature. However, the lettuce, garlic, yam, English potato, carrot, chard, onion, cucumber, and beetroot presented correction factor above the one established by another study. Thereby, various factors including conditions of reception and storage (time and temperature), and processing techniques should be standardized at NFU in order to decrease the waste production.