Epidemiology and Molecular Biology of HPV Variants in Cervical Cancer: The State of the Art in Mexico.

Cervical cancer (CC) continues to be a major public health problem in Mexico, ranking second among cancers in women. A persistent infection with human papillomaviruses (HPV) is the main risk factor for CC development. In addition, a significant fraction of other cancers including those of the anus, oropharynx, and penis are also related to HPV infection. In CC, HPV-16 is the most prevalent high-risk HPV type, followed by HPV-18, both being responsible for 70% of cases. HPV intratype variant lineages differ in nucleotide sequences by 1-10%, while sublineages differ by 0.5-1%. Several studies have postulated that the nucleotide changes that occur between HPV intratype variants are reflected in functional differences and in pathogenicity. Moreover, it has been demonstrated that HPV-16 and -18 intratype variants differentially affect molecular processes in infected cells, changing their biological behavior that finally impacts in the clinical outcome of patients. Mexico has participated in providing knowledge on the geographical distribution of intratype variants of the most prevalent HPVs in premalignant lesions of the cervix and cervical cancer, as well as in other HPV-related tumors. In addition, functional studies have been carried out to assess the cellular effects of intratype variations in HPV proteins. This review addresses the state of the art on the epidemiology of HPV-16 and HPV-18 intratype variants in the Mexican population, as well as their association with persistence, precancer and cervical cancer, and functional aspects related to their biological behavior.

Hygiene-Eliciting Brood Semiochemicals as a Tool for Assaying Honey Bee (Hymenoptera: Apidae) Colony Resistance to Varroa (Mesostigmata: Varroidae).

Despite numerous interventions, the ectoparasitic mite Varroa (Varroa destructor Anderson and Trueman [Mesostigmata: Varroidae]) and the pathogens it vectors remain a primary threat to honey bee (Apis mellifera Linnaeus [Hymenoptera: Apidae]) health. Hygienic behavior, the ability to detect, uncap, and remove unhealthy brood from the colony, has been bred for selectively for over two decades and continues to be a promising avenue for improved Varroa management. Although hygienic behavior is expressed more in Varroa-resistant colonies, hygiene does not always confer resistance to Varroa. Additionally, existing Varroa resistance selection methods trade efficacy for efficiency, because those achieving the highest levels of Varroa resistance can be time-consuming, and thus expensive and impractical for apicultural use. Here, we tested the hypothesis that hygienic response to a mixture of semiochemicals associated with Varroa-infested honey bee brood can serve as an improved tool for predicting colony-level Varroa resistance. In support of our hypothesis, we demonstrated that a mixture of the compounds (Z)-10-tritriacontene, (Z)-8-hentriacontene, (Z)-8-heptadecene, and (Z)-6-pentadecene triggers hygienic behavior in a two-hour assay, and that high-performing colonies (hygienic response to ≥60% of treated cells) have significantly lower Varroa infestations, remove significantly more introduced Varroa, and are significantly more likely to survive the winter compared to low-performing colonies (hygienic response to <60% of treated cells). We discuss the relative efficacy and efficiency of this assay for facilitating apiary management decisions and selection of Varroa-resistant honey bees, as well as the relevance of these findings to honey bee health, pollination services, and social insect communication.

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer.

Cancer cells exhibit exacerbated metabolic activity to maintain their accelerated proliferation and microenvironmental adaptation in order to survive under nutrient-deficient conditions. Tumors display an increase in glycolysis, glutaminolysis and fatty acid biosynthesis, which provide their energy source. Glutamine is critical for fundamental cellular processes, where intermediate metabolites produced through glutaminolysis are necessary for the maintenance of mitochondrial metabolism. These include antioxidants to remove reactive oxygen species, and the generation of the nonessential amino acids, purines, pyrimidines and fatty acids required for cellular replication and the activation of cell signaling. Some cancer cells are highly dependent on glutamine consumption since its catabolism provides an anaplerotic pathway to feed the Krebs cycle. Intermediate members of the glutaminolysis pathway have been found to be deregulated in several types of cancers and have been proposed as therapeutic targets and prognostic biomarkers. This review summarizes the main players in the glutaminolysis pathway, how they have been found to be deregulated in cancer and their implications for cancer maintenance. Furthermore, non-coding RNAs are now recognized as new participants in the regulation of glutaminolysis; therefore, their involvement in glutamine metabolism in cancer is discussed in detail.

Correction to: Intratype variants of the E2 protein from human papillomavirus type 18 induce different gene expression profiles associated with apoptosis and cell proliferation.

The Given names of the author Alma Mariana Fuentes-González was incorrectly tagged in original publication and corrected here. The original article has been corrected.

Intratype variants of the E2 protein from human papillomavirus type 18 induce different gene expression profiles associated with apoptosis and cell proliferation.

Persistent infections with high-risk human papillomaviruses (HR-HPVs) are linked to the development of cervical cancer due to a deregulation of the productive viral cycle in the host cell, leading to cell transformation. The E2 viral protein is expressed early during an HPV infection and regulates viral replication and transcription. Other functions have been attributed to E2, such as the promotion of apoptosis that are independent of its role in the regulation of the expression of E6 and E7 viral oncogenes. Moreover, it has been shown that the HPV16 E2 protein has regulatory effects on cellular gene expression, suggesting that it participates in the modulation of different cellular processes. Intratype genomic variations within high-risk HPV types have an impact on the prognosis of HPV-related lesions. Nevertheless, the biological significance of HPV18 E2 intratype variations has not been analysed previously. The aim of this study was to determine whether HPV18 E2 intratype variations differentially modulate gene expression and whether cell-death-related genes are affected by variations in E2. We demonstrate that HPV18 E2 intratype Asian Amerindian (AsAi) and African (Af) variants differentially affect gene expression profiles. Although the E2-AsAi variant was found to modulate a larger number of cellular genes, both E2 variants affected similar cellular processes. Nevertheless, E2-AsAi and E2-Af variants showed differences in their ability to induce apoptosis, where E2-Af had a stronger effect. The differences in gene expression profiles in cells harbouring E2 intratype variants suggest a possible effect on diverse cellular signalling pathways, and this might suggest an approach for identifying biological processes regulated by HPV18 E2 intratype variants.

Prognostic value of neutrophil-to-lymphocyte ratio in castration resistant prostate cancer: Single-centre study of Nigerian men.

BACKGROUND: Elevated neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a useful prognosticator of overall survival (OS) in several cancers including castration resistant prostate cancer. However, its utility in black populations known to have benign ethnic neutropenia is unknown. We evaluated the prognostic value of NLR in Nigerian men with CRPC in terms of OS. MATERIALS AND METHODS: We retrospectively analysed 58 patients with castration resistant prostate cancer who received androgen deprivation therapy (ADT) and docetaxel chemotherapy at our institution. Baseline NLR was calculated from available complete blood counts. NLR cut-off point value was determined based on receiver operator characteristic (ROC) curves for mortality. A multivariate analysis was performed to investigate the association between NLR and OS. RESULTS: Based on the ROC curves, the NLR (AUC 0.85, 95% CI 0.74-0.97, P = 0.0001) cut-off point was determined to be 1.8. This cut-off point has a sensitivity of 92% and specificity of 70%. Median OS was 20 months (95% CI 14-27 months); the median OS in patients with NLR <1.8 and those with NLR of ≥1.8 was 40 months and 12 months respectively. Kaplan-Meier plots showed that a higher NLR of ≥1.8 correlated significantly with an increased risk of mortality, Log rank P = 0.001. Multivariate Cox regression analyses confirmed NLR as an independent prognostic biomarker for OS (HR = 1.49, 95% CI: 1.18-1.87). CONCLUSIONS: This study demonstrated that NLR is a useful prognostic biomarker in Nigerian men with CRPC and that elevated baseline NLR ≥1.8 is associated with poorer OS.

HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/ß-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor.

The Wnt/ß-catenin signaling pathway regulates cell proliferation and differentiation and its aberrant activation in cervical cancer has been described. Persistent infection with high risk human papillomavirus (HR-HPV) is the most important factor for the development of this neoplasia, since E6 and E7 viral oncoproteins alter cellular processes, promoting cervical cancer development. A role of HPV-16 E6 in Wnt/ß-catenin signaling has been proposed, although the participation of HPV-18 E6 has not been previously studied. The aim of this work was to investigate the participation of HPV-18 E6 and E6*I, in the regulation of the Wnt/ß-catenin signaling pathway. Here, we show that E6 proteins up-regulate TCF-4 transcriptional activity and promote overexpression of Wnt target genes. In addition, it was demonstrated that E6 and E6*I bind to the TCF-4 (T cell factor 4) and ß-catenin, impacting TCF-4 stabilization. We found that both E6 and E6*I proteins interact with the promoter of Sp5, in vitro and in vivo. Moreover, although differences in TCF-4 transcriptional activation were found among E6 intratype variants, no changes were observed in the levels of regulated genes. Furthermore, our data support that E6 proteins cooperate with ß-catenin to promote cell proliferation.

Aberrant expression of interleukin-10 in rheumatoid arthritis: Relationship with IL10 haplotypes and autoantibodies.

Interleukin 10 (IL-10) is an immunomodulatory cytokinethat plays a central rolein the pathogenesis of autoimmune diseases. Different studies consistently show increased IL-10 serum levels in rheumatoid arthritis (RA) and it appears to be caused by genetic variants. Three polymorphisms situated at positions -1082, -819 and -592 of IL10 gene and its major haplotypes have been associated with regulating IL10 promoter activity. In this study, we evaluated whether IL10 haplotypes are associated with mRNA expression and IL-10 serum levels as well as susceptibility to RA in a Western Mexican population. A total of 240 RA patients and 240 control subjects (CS) were included. Genotyping of IL10 polymorphisms was performed by PCR and PCR-RFLP, respectively. IL10 mRNA expression was determined by real-time PCR and IL-10 serum levels were measured using an ELISA kit. IL10 mRNA expression was 50-fold higher in RA patients than CS (p<0.001), while IL-10 serum levels did not show differences between groups. However, high IL-10 serum levels were positively related to a higherseropositivityfor rheumatoid factor (FR) and anti-CCP antibodies (p<0.05). No significant differences between the distribution of haplotype frequencies were observed between both study groups, but GCC haplotype was associated with higher IL-10 serum levels compared with the ACC and ATA haplotypes in RA patients (p<0.05). In addition, patients carrying ATA and GCC haplotypes showed higher mRNA expression than ACC (5.4-fold and 8.8-fold, respectively) and surprisingly, this trend was reversed in the controls, although it was not significant. In conclusion, our findings suggest that IL10 (GCC, ACC, and ATA) haplotypes may not be a susceptibility marker for RA in a population from Western Mexico. Nevertheless, independently of the presence of these variants, there is an aberrant overexpression of IL10 gene in RA, and it may play an important role in the pathogenesis of RA.

Mucosal immunization of BALB/c mice with DNA vaccines encoding the SEN1002 and SEN1395 open reading frames of Salmonella enterica serovar Enteritidis induces protective immunity.

Salmonella Enteritidis is the main cause of foodborne salmonellosis worldwide. The limited effectiveness of current interventions against this pathogen has been the main incentive to develop new methods for the efficient control of this infection. To investigate the use of DNA vaccines against S. Enteritidis in humans, immune responses stimulated by two plasmids containing the genes designated SEN1002, located in the pathogenicity island SPI-19 and encoding a Hcp protein involved in transport mechanisms, and SEN1395, located in the genomic island ΦSE14 and encoding a protein of a new superfamily of lysozymes, were evaluated. Humoral and cellular responses following intranasal immunization of two groups of BALB/c mice with the plasmids pV1002 and pV1395 plus adjuvant were evaluated and it was observed that the IgG2a/IgG1 ratios were sixfold higher than control groups. Both plasmids stimulated specific secretory IgA production. Increased proliferation of lymphocytes and IFN-γ production were detected in both experimental groups. DNA-vaccinated mice developed protective immunity against a virulent strain of S. Enteritidis, with nearly 2 logs of protection level compared to the negative control values in the spleen. Therefore, DNA vaccines are efficient at stimulating cellular and humoral immune responses at systemic and mucosal levels.

MHC2TA and FCRL3 genes are not associated with rheumatoid arthritis in Mexican patients.

Rheumatoid arthritis (RA) is a multifactorial disease. A combination of genetic and environmental risk factors contributes to its etiology. Several genes have been reported to be associated with susceptibility to the development of RA. The MHC2TA and FCRL3 genes have been associated previously with RA in Swedish and Japanese populations, respectively. In two recent reports, we show an association between FCRL3 and juvenile rheumatoid arthritis (JRA), and MHC2TA and acute coronary syndrome (ACS) in Mexican population. We assessed the association between three single nucleotide polymorphisms (SNPs) of the MHC2TA (-168G/A; rs3087456, and +16G/C; rs4774) and FCRL3 (-169T/C; rs7528684) genes and rheumatoid arthritis in Mexican population through a genotyping method using allelic discrimination assays with TaqMan probes. Our case-control study included 249 patients with RA and 314 controls. We found no evidence of an association between the MHC2TA -168G/A and +1614G/C or FCRL3 -169T/C polymorphisms and RA in this Mexican population. In this cohort of Mexican patients with RA, we observed no association between the MHC2TA or FCRL3 genes and this autoimmune disease.

Frequency distribution of interleukin-10 haplotypes (-1082 A>G, -819 C>T, and -592 C>A) in a Mexican population.

Interleukin 10 (IL-10) is an immunoregulatory cytokine with multiple roles in the immune system. Three single nucleotide polymorphisms at positions -1082 (A>G), -819 (C>T), and -592 (C>A) in the promoter region of the IL10 gene are believed to be associated with different inflammatory, infectious, and autoimmune diseases. These polymorphisms exhibit a strong linkage disequilibrium (LD) and form three principal haplotypes (GCC, ACC, and ATA). The GCC and ATA haplotypes have been associated with high and low levels of IL-10 production, respectively. The aim of this study was to establish the allele and haplotype frequencies of the IL10 polymorphisms in Mestizos from western Mexico. SNPs were analyzed in 340 healthy unrelated Mestizos from western Mexico by polymerase chain reaction-restriction fragment length polymorphism. The studied population presented significant differences, in the distribution of IL10 polymorphisms, from the Asian, African, and European populations. We also observed a strong LD within -1082 A>G, -819 C>T, and -592 C>A (100% pc = 7.735 x 10-18). The haplotypes ACC (45.4%), ATA (22.0%), GTA (14.9%), and GCC (13.9%) were most frequently observed in this population. The haplotype frequencies, however, differed from those reported previously in Mestizos from central Mexico, Asians, Africans, and European Caucasians, suggesting a differential gene flow in the Mexican Mestizo population. This could account for the genetic variability between Mexicans and populations of other ethnicities. The study of these polymorphisms and their haplotypes could help in expanding our knowledge to design future disease-risk studies on the western Mexican population.

CD40 functional gene polymorphisms and mRNA expression in rheumatoid arthritis patients from western Mexico.

The CD40 pathway is involved in the development and pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). Two single nucleotide polymorphisms (SNPs) in the CD40 gene, rs1883832 and rs4810485, are associated with susceptibility to inflammatory and autoimmune diseases and are thought to alter CD40 expression at the mRNA and protein level. This study assessed for the first time the association of these SNPs with RA and CD40 mRNA levels in a western Mexican population. A total of 278 RA patients and 318 control subjects were included. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and CD40 mRNA expression was determined by real-time quantitative PCR. No significant differences in genotype and allele frequencies were identified between the RA patients and controls. When stratified by genotype, these SNPs were not found to be associated with the presence of autoantibodies or the clinical activity of the disease. CD40 mRNA levels were elevated 1.5-fold in RA patients compared to control subjects; however, no clear tendencies were observed following stratification by genotype. These results suggest that the CD40 SNPs rs1883832 and rs4810485 are not RA susceptibility markers in the western Mexican population. Further studies are needed to clarify their roles in CD40 mRNA expression.

Students' perceptions of their learning environment at the College of Medicine, University of Ilorin, Southwest, Nigeria.

BACKGROUND: Quality of medical school graduates is influenced by cumulative effect of their learning environment. Measurement of such environment at the University of Ilorin, Nigeria was done by evaluating Students' perception using the DREEM questionnaires, with a view to improving the quality of medical education. METHODS: DREEM questionnaire was applied to second, third, fourth and fifth year medical students, for assessment of the various aspects of effective educational environment. Responses were analyzed using SPSS software version 19. RESULTS: One hundred and eighty students (66.2%) were males and 92 (33.8%) females. The mean age was 21.2 years ± 2.5 with 83 (30.5%) students in second year of study, 68 (25.0%) in third year, 80 (29.4%) in fourth year and 41 (15.1%) in fifth year. Mean global perception score was 108.4 / 200 points (54.2%) and this was not affected by sex, age and year of study. Scores for "Students' Perception of Learning" (SPL) and "Students' Academic Self Perceptions" (SASP) were 28.0/48 (58.8%) and 21.8/32 (68.1%) respectively. Three key areas are in need of attention; "Students' Perception of Course Organizers" (SPCO) (22.0/44, 50.0%), "Students' Perception of Atmosphere" (SPA) (23.8/48, 49.6%) and "Students' Social Self Perceptions" (SSSP) (12.8/28, 45.7%). The SSSP score was significantly higher in males (13.18) than in females (12.06) (p=0.02; p < 0.05), and in second (13.38) and third year (13.55) students compared to fourth year (12.16) and fifth year (11.76) (p=0.003). CONCLUSION: Improvement in some aspect of teaching, atmosphere and social factors could be of further benefit to the students.

Potential Transcript-Based Biomarkers Predicting Clinical Outcomes of HPV-Positive Head and Neck Squamous Cell Carcinoma Patients.

Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.

Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study).

Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.

Retinal age as a predictive biomarker of the diabetic retinopathy grade.

OBJECTIVE: To apply artificial intelligence (AI) techniques, through deep learning algorithms, for the development and optimization of a system for predicting the age of a person based on a color retinography and to study a possible relationship between the evolution of retinopathy diabetes and premature ageing of the retina. METHODS: A convolutional network was trained to calculate the age of a person based on a retinography. Said training was carried out on a set of retinographies of patients with diabetes previously divided into three subsets (training, validation and test). The difference between the chronological age of the patient and the biological age of the retina was defined as the retinal age gap. RESULTS: A set of 98,400 images was used for the training phase, 1000 images for the validation phase and 13,544 for the test phase. The retinal gap of the patients without DR was 0.609 years and that of the patients with DR was 1905 years (p < 0.001), with the distribution by degree of DR being: mild DR: 1541 years, moderate DR: 3017 years, DR severe: 3117 years and proliferative DR: 8583 years. CONCLUSIONS: The retinal age gap shows a positive mean difference between diabetics with DR versus those without DR, and it increases progressively, according to the degree of DR. These results could indicate the existence of a relationship between the evolution of the disease and premature ageing of the retina.

HPV16 E6 and E7 Oncoproteins Stimulate the Glutamine Pathway Maintaining Cell Proliferation in a SNAT1-Dependent Fashion.

Persistent high-risk human papillomavirus infection is the main risk factor for cervical cancer establishment, where the viral oncogenes E6 and E7 promote a cancerous phenotype. Metabolic reprogramming in cancer involves alterations in glutamine metabolism, also named glutaminolysis, to provide energy for supporting cancer processes including migration, proliferation, and production of reactive oxygen species, among others. The aim of this work was to analyze the effect of HPV16 E6 and E7 oncoproteins on the regulation of glutaminolysis and its contribution to cell proliferation. We found that the E6 and E7 oncoproteins exacerbate cell proliferation in a glutamine-dependent manner. Both oncoproteins increased the levels of transporter SNAT1, as well as GLS2 and GS enzymes; E6 also increased LAT1 transporter protein levels, while E7 increased ASCT2 and xCT. Some of these alterations are also regulated at a transcriptional level. Consistently, the amount of SNAT1 protein decreased in Ca Ski cells when E6 and E7 expression was knocked down. In addition, we demonstrated that cell proliferation was partially dependent on SNAT1 in the presence of glutamine. Interestingly, SNAT1 expression was higher in cervical cancer compared with normal cervical cells. The high expression of SNAT1 was associated with poor overall survival of cervical cancer patients. Our results indicate that HPV oncoproteins exacerbate glutaminolysis supporting the malignant phenotype.

RIPOR2 Expression Decreased by HPV-16 E6 and E7 Oncoproteins: An Opportunity in the Search for Prognostic Biomarkers in Cervical Cancer.

High-risk human papillomavirus (HPV) infection is the main risk factor for cervical cancer (CC) development, where the continuous expression of E6 and E7 oncoproteins maintain the malignant phenotype. In Mexico, around 70% of CC cases are diagnosed in advanced stages, impacting the survival of patients. The aim of this work was to identify biomarkers affected by HPV-16 E6 and E7 oncoproteins that impact the prognosis of CC patients. Expression profiles dependent on E6 and E7 oncoproteins, as well as their relationship with biological processes and cellular signaling pathways, were analyzed in CC cells. A comparison among expression profiles of E6- and E7-expressing cells and that from a CC cohort obtained from The Cancer Genome Atlas (TCGA) demonstrated that the expression of 13 genes impacts the overall survival (OS). A multivariate analysis revealed that the downregulated expression of RIPOR2 was strongly associated with a worse OS. RIPOR2, including its transcriptional variants, were overwhelmingly depleted in E6- and E7-expressing cells. Finally, in a Mexican cohort, it was found that in premalignant cervical lesions, RIPOR2 expression decreases as the lesions progress; meanwhile, decreased RIPOR2 expression was also associated with a worse OS in CC patients.

Mast Cell-Tumor Interactions: Molecular Mechanisms of Recruitment, Intratumoral Communication and Potential Therapeutic Targets for Tumor Growth.

Mast cells (MCs) are tissue-resident immune cells that are important players in diseases associated with chronic inflammation such as cancer. Since MCs can infiltrate solid tumors and promote or limit tumor growth, a possible polarization of MCs to pro-tumoral or anti-tumoral phenotypes has been proposed and remains as a challenging research field. Here, we review the recent evidence regarding the complex relationship between MCs and tumor cells. In particular, we consider: (1) the multifaceted role of MCs on tumor growth suggested by histological analysis of tumor biopsies and studies performed in MC-deficient animal models; (2) the signaling pathways triggered by tumor-derived chemotactic mediators and bioactive lipids that promote MC migration and modulate their function inside tumors; (3) the possible phenotypic changes on MCs triggered by prevalent conditions in the tumor microenvironment (TME) such as hypoxia; (4) the signaling pathways that specifically lead to the production of angiogenic factors, mainly VEGF; and (5) the possible role of MCs on tumor fibrosis and metastasis. Finally, we discuss the novel literature on the molecular mechanisms potentially related to phenotypic changes that MCs undergo into the TME and some therapeutic strategies targeting MC activation to limit tumor growth.

HPV Prevalence and Predictive Biomarkers for Oropharyngeal Squamous Cell Carcinoma in Mexican Patients.

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.