Hypoxia is an inherent condition of tumors and contributes to cancer development and progression. Hypoxia-inducible factors (HIFs) are the major transcription factors involved in response to low O2 levels, orchestrating the expression of hundreds of genes involved in cancer hallmarks’ acquisition and modulation of epigenetic mechanisms. Epigenetics refers to inheritable mechanisms responsible for regulating gene expression, including genes involved in the hypoxia response, without altering the sequence of DNA bases. The main epigenetic mechanisms are DNA methylation, non-coding RNAs, and histone modifications. These mechanisms are highly influenced by cell microenvironment, such as O2 levels. The balance and interaction between these pathways is essential for homeostasis and is directly linked to cellular metabolism. Some of the major players in the regulation of HIFs, such as prolyl hydroxylases, DNA methylation regulators, and histone modifiers require oxygen as a substrate, or have metabolic intermediates as cofactors, whose levels are altered during hypoxia. Furthermore, during pathological hypoxia, HIFs’ targets as well as alterations in epigenetic patterns impact several pathways linked to tumorigenesis, such as proliferation and apoptosis, among other hallmarks. Therefore, this review aims to elucidate the intricate relationship between hypoxia and epigenetic mechanisms, and its crucial impact on the acquisition of cancer hallmarks.

Therefore we can consider the hydroalcoholic extract of Solanum cernuum Vell as practically non-toxic in acute administration and safe in the sub-chronic administration, as hepatotoxicity was observed only with the highest dose used, not with the dose routinely used by the native population.

Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.

AimsJumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types.Methods and resultsWe aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk.ConclusionJMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.

The HIF-1 transcriptional complex is responsible for controlling transcription of over 100 genes involved in cell hypoxia response. HIF-1alpha subunit is stabilized in hypoxia conditions, creating the HIF-1 nuclear transcription factor. In inflammatory cells, high HIF-1alpha expression induces lymphocytic immunosuppression, decreasing tumoral antigen recognition, which promotes tumor growth. The present work investigated the relationship between HIF-1alpha expression in lymphocytes populating the intratumoral and peritumoral region of 56 patients with oral cancer. Our data indicates a prognostic value for this expression. High HIF-1alpha expression in peritumoral inflammatory cells is significantly related to worse patient outcome, whereas high expression in the intratumoral lymphoid cells correlates with a better prognosis. A risk profile indicating the chance of disease relapse and death was designed based on HIF-1alpha expression in tumoral inflammatory cells, defining low, intermediate and high risks. This risk profile was able to determine that high HIF-1alpha expression in peritumoral cells correlates with worse prognosis, independently of intratumoral expression. Low HIF-1alpha in tumor margins and high expression in the tumor was considered a low risk profile, showing no cases of disease relapse and disease related death. Intermediate risk was associated with low expression in tumor and tumor margins. Our results suggest that HIF-1alpha expression in tumor and peritumoral inflammatory cells may play an important role as prognostic tumor marker.

Oral cancer squamous cell carcinoma (OCSCC) mainly affects individuals aged between 50 and 70 years who consume tobacco and alcohol. tobacco smoke contains hundreds of known toxic and carcinogenic molecules, and a few studies have sought to verify the relationship of such trace elements as risk or prognostic factors for head and neck cancer. We obtained 78 samples of tumor tissues from patients with ocScc, and performed a qualitative elemental characterization using the micro X-Ray fluorescence technique based on synchrotron radiation. We found the presence of magnesium, phosphorus, sulfur, chlorine, potassium, calcium, chromium, manganese, iron, zinc, cobalt, nickel, copper, arsenic and bromine in ocScc samples. Magnesium, chlorine, chromium, manganese, nickel, arsenic and bromine are associated with smoking. We observed a significant association between relapse and chlorine and chromium. the presence of chlorine in the samples was an independent protective factor against relapse (oR = 0.105, CI = 0.01-0.63) and for best disease-free survival (HR = 0.194, CI = 0.04-0.87). Reporting for the first time in oral cancer, these results suggest a key relationship between smoking and the presence of certain elements. in addition, chlorine proved to be important in the context of patient prognosis and survival. Squamous cell carcinoma (SCC) accounts for more than 90% of oral cancer cases 1,2 and mainly affects individuals aged between 50 and 70 years who consume tobacco and alcohol. It may also be associated with human papillomavirus infection, genetic susceptibility and passive smoking exposure 1-5. Tobacco smoke itself, which contains hundreds of known toxic and carcinogenic molecules 6,7 , can induce DNA damage 8. Among these substances are several inorganic compounds, such as arsenic, calcium, chlorine, cobalt, copper, chromium, iron, magnesium, manganese, nickel, potassium, zinc and others 9,10. The analysis of trace elements is quite uncommon in the head and neck cancer field. Over the past two decades, a few studies have sought to verify the identity of these and other trace elements as risk or prognostic factors for head and neck cancer. Some authors verified the differences in the profile of trace elements in the blood (plasma/serum) of patients with or without head and neck cancer 11-19. Differences were also found in the analyses performed on the hair and nails of patients with head and neck cancer 15,17,20,21. However, in studies carried out

Peritoneopericardial diaphragmatic hernia (PPDH) is a rare condition that is caused by defective diaphragm and pericardium development. It occurs in dogs and cats and is most prevalent in Weimaraner and Persian breeds. This study presents the first report of a congenital peritoneopericardial diaphragmatic hernia in a geriatric cat in Espírito Santo in Brazil. A 12-year old male Persian cat was referred to the veterinary hospital. Clinical examination revealed hyporexia, cachexia, alopecia, dyspnea, and an adherent and irregularly shaped nodule in the left caudal breast. Cytopathological examination of the abdominal nodulation revealed a mammary carcinoma. Thoracic radiography revealed PPDH. The animal was euthanized. On necropsy, the abdominal cavity revealed a part of the liver inside the diaphragm, and the thoracic view revealed the heart and liver inside the pericardial sac. Histopathological analysis confirmed mammary carcinoma and revealed dermatophytic pseudomycetoma. This is the first report of PPDH, which was incidentally detected, in a geriatric Persian cat that had survived for several years without diagnosis in Espírito Santo, Brazil. From the observations made, we conclude that comprehensive clinical examination, involving imaging, is important in detecting congenital abnormalities such as PPDH.

Fasciolosis is a zoonotic disease that infects especially ruminants and the liver damages in chronic infection caused by the parasite are very severe. The aim of this study was to evaluate the histopathological findings in liver of cattle naturally infected with Fasciola hepatica, as well as propose a classification of liver damage caused by this disease based on the chronic inflammation and fibrosis. Were used fragments of the right lobe and left of one hundred livers the cattle. Those fragments were subjected to histological processing and staining with haematoxylineosin and Masson's trichrome. Assigned to graduate I to III for the classification of lesions according to the intensity of the inflammatory and fibrotic changes. The lesions more prevalent were biliary duct proliferation, mononuclear cell infiltration, arteriosclerosis, and periportal and periductal fibrosis. Fibrotic lesions were more intense than the inflammatory and 45% of the samples belonged to category II, followed by 39% in category I and 16% in category III. The proposed categorization of pathological liver injury in chronic fasciolosis in naturally infected cattle proved is a valuable method of microscopic evaluation, since it allows determining the evolution of this disease. Key Words: cattle, Fasciola hepatica, fascioliasis, liver ASPECTOS HISTOPATOLÓGICOS E AVALIAÇÃO DE FIBROSE EM FÍGADOS BOVINOS NATURALMENTE INFECTADOS POR FASCIOLA HEPATICARESUMO: Fasciolose é uma zoonose que infecta especialmente os ruminantes e os danos ao fígado causado pela infecção crônica pelo parasito são graves. Objetivou-se com este estudo avaliar os achados histopatológicos no fígado de bovinos naturalmente infectados com Fasciola hepatica, bem como propor a classificação de lesão hepática causada por essa doença baseado na inflamação crônica e fibrose. Foram utilizados fragmentos do lobo direito e esquerdo de 100 fígados bovinos com fasciolose. Os fragmentos foram submetidos a processamento histológico e coloração com hematoxilina e eosina (HE) e Tricrômico de Masson. Atribuiu-se a graduação de I a III para a classificação das lesões, de acordo com a intensidade das alterações inflamatórias e fibróticas. As lesões mais prevalentes foram a proliferação do ducto biliar, infiltração de células mononucleares, arteriosclerose e fibrose periportal e periductal. Lesões fibróticas foram mais intensas que as inflamatórias e 45% das amostras foram classificadas na categoria II, seguido de 39% na categoria I e 16% na categoria III. A proposta de categorização histopatológica da lesão hepática em fasciolose crônica em bovinos naturalmente infectados é um método valioso de avaliação microscópica, uma vez que permite determinar a evolução da doença. Palavras-chave: bovinos, Fasciola hepatica, fasciolose, fígado 62Histopathology aspects and fibrosis evaluation of bovine naturally infected livers by Fasciola hepatica