Tumor cells must generate sufficient ATP and biosynthetic precursors in order to maintain cell proliferation requirements. Otto Warburg showed that tumor cells uptake high amounts of glucose producing large volumes of lactate even in the presence of oxygen, this process is known as "Warburg effect or aerobic glycolysis." As a consequence of such amounts of lactate there is an acidification of the extracellular pH in tumor microenvironment, ranging between 6.0 and 6.5. This acidosis favors processes such as metastasis, angiogenesis and more importantly, immunosuppression, which has been associated to a worse clinical prognosis. Thus, lactate should be thought as an important oncometabolite in the metabolic reprogramming of cancer. In this review, we summarized the role of lactate in regulating metabolic microenvironment of cancer and discuss its relevance in the up-regulation of the enzymes lactate dehydrogenase (LDH) and monocarboxilate transporters (MCTs) in tumors. The goal of this review is to expose that lactate is not only a secondary product of cellular metabolic waste of tumor cells, but also a key molecule involved in carcinogenesis as well as in tumor immune evasion. Finally, the possible targeting of lactate production in cancer treatment is discussed.
BackgroundThe canine transmissible venereal tumor (CTVT) or Sticker’s sarcoma is a neoplastic disease affecting dogs. This disease is presented as a tumoral mass in the genital organs of both, male and female individuals. Up to date, there is no clear evidence indicating a viral agent as the causative mediator for CTVT development.PurposeThe present work aims to analyze 21 samples from canines with CTVT for molecular identification of Papillomavirus DNA sequences. In addition, microbiological analysis, cytologic and histopathologic evaluations were also performed.ResultsAll patients showed no biochemical and microbiological alterations. Molecular analysis demonstrated the viral DNA presence in the samples using different primer sets. The MY primers amplified a 450 bp band in seven out of 21 samples (33%). The PVF and Fap64 primer set, targeting the L1 sequence of Canine Papillomavirus (CPV), showed positivity in 16 out of 21 samples (76%).ConclusionThese results support the possible causative association between CPV and CTVT; nevertheless, additional studies are required to uphold such statement. This work presents evidence indicating that a viral agent might be involved in the pathogenesis of CTVT and set the bases for a better understanding of the CTVT pathobiology.
Background: Worldwide prevalence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has increased, affecting mostly young males. OPSCC associated with Human Papillomavirus (HPV) infection exhibits particular characteristics in terms of response to treatment, hence HPV has been proposed as a prognostic factor. The impact of HPV positivity and associated biomarkers on OPSCC in the Mexican population has not been addressed. Therefore, the analysis of OPSCC prognostic markers in the Mexican population is necessary. Methods: Retrolective study in Mexican OPSCC patients, where HPV prevalence, p16 and EGFR levels were assessed using INNO-LiPA and immunohistochemistry. Results: We found an HPV prevalence of 57.6% in OPSCC cases treated at a reference center in Mexico. HPV and p16 positivity, as well as EGFR, associate with better outcomes in OPSCC patients, and they also promote reduced death risk. Notably, HPV presence and p16 positivity showed a significant association with disease-free survival (DFS), with a HR of 0.15 (p = 0.006) and a HR of 0.17 (p = 0.012), respectively, indicating a possible role as predictive biomarkers in Mexican OPSCC patients. Conclusions: Our results reflect the clinical utility of p16 analysis to improve overall survival (OS) and to predict recurrence in oropharyngeal cancer. These results position p16 and HPV as predictive biomarkers for OPSCC.
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