Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression.

Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types of cancer worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is associated with a better prognosis. This reaction generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells that form a part of the tumor microenvironment. CAFs are directly involved in tumorigenesis through different mechanisms. However, their role in immunosuppression in CRC is not well understood, and the precise role of signal transducers and activators of transcription (STATs) in mediating CAF activity in CRC remains unclear. Among the myriad chemical and biological factors that affect CAFs, different cytokines mediate their function by activating STAT signaling pathways. Thus, the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors. Here, we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

Cultivable Microbiome Approach Applied to Cervical Cancer Exploration.

Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role.

Immunity and COVID-19 vaccines. Revisiting the bases.

The COVID-19 pandemic is one of the challenges of the 21st century; science and technology were put to the test for the development vaccines, diagnostic techniques and treatments in record time. However, misinformation and misinterpretation have made the safety and efficacy of COVID-19 vaccines a subject of debate. This review addresses concepts on immunization mechanisms and vaccination, as well as evidence supporting that COVID-19 vaccines are immunogenic, efficacious and safe.

La pandemia de COVID-19 es uno de los retos del siglo XXI; la ciencia y la tecnología se pusieron a prueba para desarrollar vacunas, técnicas diagnósticas y tratamientos en tiempo récord. No obstante, la desinformación y mala interpretación han hecho que la seguridad y eficacia de las vacunas contra COVID-19 sean un tema de debate. En esta revisión se abordan conceptos sobre los mecanismos de la inmunización y la vacunación; así como la evidencia que sostiene que las vacunas contra COVID-19 son inmunogénicas, eficaces y seguras.

HPV infection profile in cervical lesions.

INTRODUCTION: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region. OBJECTIVE: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology. METHODS: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays. RESULTS: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, and 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples. CONCLUSIONS: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs.

INTRODUCCIÓN: La prevalencia de los diferentes genotipos de virus del papiloma humano (VPH) varía dependiendo de la severidad de la lesión y región geográfica. OBJETIVO: Identificar infecciones múltiples de VPH en lesiones cervicales de bajo y alto grado en un grupo de mujeres del Bajío mexicano referidas con citología no concluyente. MÉTODOS: Estudio piloto de mujeres referidas de unidades del primer nivel de atención de Guanajuato, México, por citología sugerente de lesión cervical. Los raspados cervicales fueron sujetos a extracción de ADN y genotipificación del VPH mediante microarreglos. RESULTADOS: Se colectaron 100 casos consecutivos y fueron analizados 90; se observó 26 % de positividad a VPH en mujeres sanas y 62 % presentó algún grado de lesión. Los genotipos de VPH más frecuentes fueron 59, 31, 16 y 51. En la mayoría de las muestras se encontró infección múltiple. CONCLUSIONES: Se identificó heterogeneidad de VPH en las muestras de la población estudiada en contraste con los reportes internacionales; además, son comunes las infecciones múltiples en lesiones precursoras y disminuyen en las lesiones de alto grado. Estos datos podrían influir en los actuales programas de vacunación anti-VPH.

Inmunidad y vacunas contra la COVID-19. Revisando las bases / Immunity and COVID-19 vaccines. Revisiting the bases

Resumen La pandemia de COVID-19 es uno de los retos del siglo XXI; la ciencia y la tecnología se pusieron a prueba para desarrollar vacunas, técnicas diagnósticas y tratamientos en tiempo récord. No obstante, la desinformación y mala interpretación han hecho que la seguridad y eficacia de las vacunas contra COVID-19 sean un tema de debate. En esta revisión se abordan conceptos sobre los mecanismos de la inmunización y la vacunación; así como la evidencia que sostiene que las vacunas contra COVID-19 son inmunogénicas, eficaces y seguras.

Abstract The COVID-19 pandemic is one of the challenges of the 21st century; science and technology were put to the test for the development vaccines, diagnostic techniques and treatments in record time. However, misinformation and misinterpretation have made the safety and efficacy of COVID-19 vaccines a subject of debate. This review addresses concepts on immunization mechanisms and vaccination, as well as evidence supporting that COVID-19 vaccines are immunogenic, efficacious and safe.

Perfil de infecciones por VPH en lesiones cervicales / HPV infection profile in cervical lesions

Resumen Introducción: La prevalencia de los diferentes genotipos de virus del papiloma humano (VPH) varía dependiendo de la severidad de la lesión y región geográfica. Objetivo: Identificar infecciones múltiples de VPH en lesiones cervicales de bajo y alto grado en un grupo de mujeres del Bajío mexicano referidas con citología no concluyente. Métodos: Estudio piloto de mujeres referidas de unidades del primer nivel de atención de Guanajuato, México, por citología sugerente de lesión cervical. Los raspados cervicales fueron sujetos a extracción de ADN y genotipificación del VPH mediante microarreglos. Resultados: Se colectaron 100 casos consecutivos y fueron analizados 90; se observó 26 % de positividad a VPH en mujeres sanas y 62 % presentó algún grado de lesión. Los genotipos de VPH más frecuentes fueron 59, 31, 16 y 51. En la mayoría de las muestras se encontró infección múltiple. Conclusiones: Se identificó heterogeneidad de VPH en las muestras de la población estudiada en contraste con los reportes internacionales; además, son comunes las infecciones múltiples en lesiones precursoras y disminuyen en las lesiones de alto grado. Estos datos podrían influir en los actuales programas de vacunación anti-VPH.

Abstract Introduction: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region Objective: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology. Methods: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays. Results: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples. Conclusions: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs.

RET gene mutational diagnosis and precision medicine in Mexico.

Precision medicine is a reality in some diseases; it supports the development of accurate and specific diagnostic methods, new drugs and molecules. Our research team in Mexico, made up of clinical and biomedical researchers, has been performing free RET gene mutational diagnosis for medullary thyroid cancer and multiple endocrine neoplasia (MEN) 2 and 3 for 20 years. RET pathogenic variants in the Mexican population are consistent with reported data: most common mutations are 634/NEM2 and 918/NEM3. Currently, new nanobiotechnology methods are being developed for this type of determination in order to obtain faster, simpler, more sensitive and specific results applicable in all types of laboratories.

La medicina de precisión en algunas enfermedades es una realidad; respalda el desarrollo de métodos diagnósticos certeros y específicos, de nuevas drogas y moléculas. Nuestro equipo de investigación en México, conformado por investigadores clínicos y biomédicos, desde hace 20 años realiza de forma gratuita el diagnóstico mutacional del gen RET y su relación con el cáncer medular de tiroides y la neoplasia endocrina múltiple (NEM) 2 y 3. Las variantes patogénicas de RET en la población mexicana coinciden con los datos reportados: la mayoría con 634/NEM2 y 918/NEM3. Actualmente se están desarrollando nuevos métodos de nanobiotecnología para este tipo de determinaciones, de tal forma que puedan obtenerse resultados más rápidos, simples, sensibles y específicos aplicables en todo tipo de laboratorio.

Diagnóstico mutacional del gen RET y la medicina de precisión en México / RET gene mutational diagnosis and precision medicine in Mexico

Resumen La medicina de precisión en algunas enfermedades es una realidad; respalda el desarrollo de métodos diagnósticos certeros y específicos, de nuevas drogas y moléculas. Nuestro equipo de investigación en México, conformado por investigadores clínicos y biomédicos, desde hace 20 años realiza de forma gratuita el diagnóstico mutacional del gen RET y su relación con el cáncer medular de tiroides y la neoplasia endocrina múltiple (NEM) 2 y 3. Las variantes patogénicas de RET en la población mexicana coinciden con los datos reportados: la mayoría con 634/NEM2 y 918/NEM3. Actualmente se están desarrollando nuevos métodos de nanobiotecnología para este tipo de determinaciones, de tal forma que puedan obtenerse resultados más rápidos, simples, sensibles y específicos aplicables en todo tipo de laboratorio.

Abstract Precision medicine is a reality in some diseases; it supports the development of accurate and specific diagnostic methods, new drugs and molecules. Our research team in Mexico, made up of clinical and biomedical researchers, has been performing free RET gene mutational diagnosis for medullary thyroid cancer and multiple endocrine neoplasia (MEN) 2 and 3 for 20 years. RET pathogenic variants in the Mexican population are consistent with reported data: most common mutations are 634/NEM2 and 918/NEM3. Currently, new nanobiotechnology methods are being developed for this type of determination in order to obtain faster, simpler, more sensitive and specific results applicable in all types of laboratories.

Neurophysiological Mechanisms Related to Pain Management in Bone Tumors.

BACKGROUND: Primary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel therapeutic approaches in this field. AIM: This study aims to identify the neurophysiology of the mechanisms related to pain management in bone tumors. METHODS: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index to get information about the neurophysiology mechanisms related to pain management in bone tumors. RESULTS: The central and peripheral mechanisms that promote bone cancer pain are poorly understood. Studies have shown that bone cancer could be related to neurochemicals produced by tumor and inflammatory cells, coupled with peripheral sensitization due to nerve compression and injury caused by tumor growth. The activity of mesolimbic dopaminergic neurons, substance P, cysteine/ glutamate antiporter, and other neurochemical dynamics brings us putative strategies to suggest better and efficient treatments against pain in cancer patients. CONCLUSION: Cancer-induced bone pain could include neuropathic and inflammatory pain, but with different modifications to the periphery tissue, nerves and neurochemical changes in different neurological levels. In this sense, we explore opportunity areas in pharmacological and nonpharmacological pain management, according to pain-involved mechanisms in this study.

The Mechanisms of Action of Botulinum Toxin Type A in Nociceptive and Neuropathic Pathways in Cancer Pain.

BACKGROUND: Botulinum toxin type A (BoNT-A) is widely employed for cosmetic purposes and in the treatment of certain diseases such as strabismus, hemifacial spasm and focal dystonia among others. BoNT-A effect mainly acts at the muscular level by inhibiting the release of acetylcholine at presynaptic levels consequently blocking the action potential in the neuromuscular junction. Despite the great progress in approval and pharmaceutical usage, improvement in displacing BoNT-A to other pathologies has remained very limited. Patients under diagnosis of several types of cancer experience pain in a myriad of ways; it can be experienced as hyperalgesia or allodynia, and the severity of the pain depends, to some degree, on the place where the tumor is located. Pain relief in patients diagnosed with cancer is not always optimal, and as the disease progresses, transition to more aggressive drugs, like opioids is sometimes unavoidable. In recent years BoNT-A employment in cancer has been explored, as well as an antinociceptive drug; experiments in neuropathic, inflammatory and acute pain have been carried out in animal models and humans. Although its mechanism has not been fully known, evidence has shown that BoNT-A inhibits the secretion of pain mediators (substance P, Glutamate, and calcitonin gene related protein) from the nerve endings and dorsal root ganglion, impacting directly on the nociceptive transmission through the anterolateral and trigeminothalamic systems. AIM: The study aimed to collect available literature regarding molecular, physiological and neurobiological evidence of BoNT-A in cancer patients suffering from acute, neuropathic and inflammatory pain in order to identify possible mechanisms of action in which the BoNT-A could impact positively in pain treatment. CONCLUSION: BoNT-A could be an important neo-adjuvant and coadjuvant in the treatment of several types of cancer, to diminish pro-tumor activity and secondary pain.

Expression of Pregnancy Specific ß-1 Glycoprotein 1 in Cervical Cancer Cells.

BACKGROUND: Cervical Cancer (CC) is a worldwide public health concern associated with genetic alterations, among these the gain of the 19q chromosome harboring the Pregnancy Specific Glycoproteins (PSG) gene family. These proteins play a critical role in pregnancy, with participation in immunotolerance, angiogenesis, and invasion processes, which are also observed in carcinogenesis. The aim of this study was to determine the molecular alterations of PSG1 and its relationship with CC. METHODS: PSG1 Copy Number Variation (CNV) was evaluated in 31 CC and eight normal cervical tissues by qPCR. PSG1 expression was correlated with HPV detection and IL-10 and TGF-ß expression in CC samples. Finally, PSG1 protein expression was evaluated by immunofluorescence in CC cell lines, by immunohistochemistry in a tissue microarray, and by immunoblotting in the sera of women with normal cervix, pre-invasive lesions, and CC. RESULTS: PSG1 showed a gain of 25.6% in CNV and gene expression in CC. There was a lack of PSG1 expression in normal cervical epithelium and positive immunostaining in 57% of CC tissues, while all CC cell lines expressed PSG1. Finally, PSG1 was immunodetected in 90% of pre-invasive lesions and in all CC serum samples, but not in healthy women. PSG1 expression correlates with the expression of IL-10 and TGF-ß in CC tissues, but not with the presence of HPV. CONCLUSION: These data show evidence of the differential expression of PSG1 in CC that could explain its participation in tumor-biology and immunotolerance mechanisms. Further, its immunodetection could provide early detection of this cancer.

Sensorial innovation for non-invasive breast cancer detection. / La innovación sensorial para detección no invasiva del cáncer de mama.

Breast cancer represents a great challenge due to the context of gender, social and cultural aspects, as well as of the possibility of making accessible early detection methods. Currently, detection mostly relies on image tests (invasive procedures). However, due to new and numerous cases detected in young women, and detected in such advanced stages that only palliative care may be offered, there is opportunity to develop new, innovative and promising detection tests. In order to find solutions to the organizational process of tumor cells, and adapt them for early detection, biomimesis eases the development of new non-invasive approaches and innovative designs. Nowadays, the volatile organic compounds detection (also called volatolome) emitted by tumoral cells can be detected with the use of biological and/or artificial intelligent noses. This approach may represent a real opportunity for the early detection of cancer and several pathologies. There is no doubt that novel test for early detection of different diseases will be soon reality.

El cáncer de mama representa un gran reto por el contexto de género, su "look", el contexto social y cultural, así como la probabilidad de que la detección oportuna sea de fácil acceso. Si bien en la actualidad contamos con pruebas de imagen para su detección, los nuevos y numerosos casos detectados tanto en mujeres jóvenes como en etapas avanzadas de la enfermedad, cuando no hay más que ofrecer que cuidados paliativos, abren oportunidad para desarrollar nuevos y prometedores sistemas de detección. Tratando de buscar soluciones al proceso organizativo de las células tumorales y adaptarlas para su detección oportuna, la biomimesis abre la oportunidad para nuevos enfoques no invasivos y desarrollos innovadores. En la actualidad, la detección de compuestos orgánicos volátiles (llamado también volatoloma), emitidos por las células tumorales mediante narices biológicas y narices con inteligencia artificial, podrían representar una realidad para la detección oportuna del cáncer y otras enfermedades. Es posible que una prueba de detección oportuna para las enfermedades incluyendo al cáncer esté pronta.

Biology of SARS-CoV-2: Towards understanding and treating COVID-19. / Biología del SARS-CoV-2: hacia el entendimiento y tratamiento de COVID-19.

During the last two decades, three different epidemics, caused by three different coronaviruses, have affected humankind. The most recent, known as COVID-19, has caused in only five months, more than 340,000 deaths worldwide. Knowing the biology of coronavirus is key, not just to face the current pandemic, but to prepare ourselves for future epidemics. With this in mind, this article is focused on the biology of coronaviruses emphasizing SARS-CoV-2, the agent that causes COVID-19. This is a comprehensive review article, which covers different topics, from the biology and taxonomy of viruses, to the molecular biology of SARS-CoV-2, its mechanisms of action, and the immune response this virus elicits. We have also addressed clinical aspects of COVID-19, its methods of detection, treatment, and vaccines.

Durante las últimas dos décadas, tres epidemias de gran magnitud, causadas por tres distintos tipos de coronavirus, han impactado a la humanidad. La más reciente, conocida como COVID-19, ha provocado en tan solo cinco meses, más de 340 000 muertes en todo el mundo. Conocer la biología de los coronavirus es fundamental, tanto para enfrentar la pandemia actual, como para prepararnos para futuras epidemias. En este contexto, el presente artículo está enfocado en la biología de los coronavirus con énfasis en el SARS-CoV-2, agente causal de COVID-19. La temática que se incluye es muy amplia, abarca desde la biología general de los virus y su taxonomía, hasta aspectos muy puntuales de la biología molecular de SARS-CoV-2, así como de sus mecanismos de acción y la respuesta inmune. También presentamos distintos aspectos clínicos de COVID-19, de los métodos para su detección y algunos enfoques terapéuticos, incluyendo tratamientos antivirales y vacunas.

Revisiting the Genomic and Transcriptomic Landscapes from Female Malignancies Could Provide Molecular Markers and Targets for Precision Medicine.

AIMS: Gynaecological malignancies such as breast, ovarian and cervical cancers have become an important public health problem. Detection of molecular alterations in cancer research is fundamental since it can reveal specific pathogenic patterns and genes that could serve as markers. Our aim was to characterize common genomic and transcriptomic signatures for the three gynaecologic malignancies with the highest incidence and mortality to try to identify new molecular markers, therapeutic targets and molecular signatures. METHODS: Here we analysed a total of 723 microarray libraries corresponding to equal number of breast, ovary and cervical cancer and non-cancer patient samples. Copy number variation (CNV) was carried out using 428 libraries and transcriptomic analysis using the 295 remaining samples. RESULTS: Our results showed that breast, ovary and cervical malignancies are characterized by gain of 1q chromosome. At transcriptomic level, they share 351 coding and non-coding genes, which could represent core transcriptome of gynaecological malignancies. Pathway analysis from the resulting gene lists from CNV and expression showed participation in cell cycle, metabolism, and cell adhesion molecules among others. CONCLUSIONS: Chromosome 1q characterize the gynaecological malignancies, which could harbour a richness of genetic repertoire to mine for molecular markers and targets, particular gynaecologic expression profile, containing FANCI, FH and MIR155HG among others, could represent part of the transcriptomic core for diagnostic test and attractive therapeutic targets. It may not be long before every human cancer sample is profiled for a detections test to ascertain a molecular diagnosis and prognosis and to define an optimal and precise treatment strategy.

Vaginosis-associated bacteria and its association with HPV infection. / Bacterias relacionadas con vaginosis bacteriana y su asociación a la infección por virus del papiloma humano.

BACKGROUND AND OBJECTIVE: Cervical cancer is an important health problem in our country. It is known that there are several risk factors for this neoplasm, and it has been suggested that cervical microbiome alterations could play a role in the development and progress of cancer. Bacterial vaginosis associated bacteria such as Atopobium vaginae and Gardnerella vaginalis has been suggested as potential risk factor for cervical lesions and cervical cancer. MATERIAL AND METHODS: DNA from 177 cervical scraping samples was studied: 104 belonged to women without cytological or colposcopic alterations and 73 samples from precursor lesions with previous human papillomavirus (HPV) infection history. All samples were screened for Atopobium vaginae, Gardnerella vaginalis and HPV by PCR. RESULTS: High HPV prevalence was found in precursor samples, and 30% of samples without lesions were positive for HPV. Virtually all samples contained sequences of both bacteria, and interestingly, there was not HPV association observed; these results could suggest that these microorganisms could be part of the cervical microbiome in Mexican population. CONCLUSIONS: The results obtained indicate that the bacteria analysed could be part of normal biome in Mexican women, suggesting a potential reconsideration of the pathogen role of these microorganisms.

The expression of transcription factor BORIS and its association with the estrogen receptor beta (ER-ß) in cervical carcinogenesis.

BORIS is a transcription factor aberrantly expressed in human cancers that can regulate the expression of estrogen receptors in endometrial cancer and breast cancer. We evaluated the expression of BORIS and the estrogen receptors alpha (ER-α) and beta (ER-ß) in ten cell lines derived from cervical cancer using RT-PCR and Western-blot. We also evaluated 54 cervical tissues: normal epithelia, low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL), and invasive squamous carcinomas (SC) using immunohistochemistry. In the cell lines, BORIS mRNA and protein expressions are associated with ER-ß expression but not with ER-α expression. In the normal cervical epithelium, ER-α and ER-ß were expressed but the BORIS protein was not detected. In the LSIL samples, BORIS, ER-α and ER-ß were expressed; however, in the HSIL samples, only the BORIS and ER-ß expressions were detected, but ER-α expression was minimal or null. In the SC, only BORIS and ER-ß were detected. In summary, the results show that the expressions of BORIS and ER-ß increase while the expression of ER-α decreases according to the severity of the lesions. These results suggest synergistic roles for BORIS and ER-ß during cervical cancer progression with a possible regulation of the estrogen receptors by BORIS in the development of cervical cancer; however, more detailed studies are needed to confirm this suggestion and to determine the precise role of BORIS in cervical cancer.

Expression of the growth hormone receptor isoforms and its correlation with the metabolic profile in morbidly obese subjects.

BACKGROUND AND AIM OF THE STUDY: Given the lipolytic effect of GH and its potential role in determining adipose tissue distribution, we evaluated the expression of the GH hormone receptor (GHR) isoforms in patients with morbid obesity seeking associations with metabolic parameters. METHODS: 262 morbidly obese subjects (mean age 42.5 ± 11 years, 75% women) underwent PCR-genotyping of the exon 3 GHR polymorphism. In 17 of these subjects, who proved to be heterozygous for the exon 3 genotype (+3/-3), subcutaneous and visceral adipose tissue was obtained during bariatric surgery; total RNA was extracted, reversely transcribed, and the different isoforms of the GHR (exon 3 containing and lacking flGHR as well as the trGHR) were PCR-amplified using specific primers. RESULTS: 27% were +3/+3 homozygous, 20% -3/-3 homozygous and 53% were +3/-3 heterozygous. Compared to subjects homozygous for the +3 genotype, homozygous and heterozygous carriers of the -3 genotype were significantly heavier and tended to have a higher HOMA 2-IR. Expression of the flGHR and trGHR mRNA was demonstrated in all evaluated samples of subcutaneous and visceral adipose tissue from the 17 patients. The exon 3+ isoform was expressed in all adipose tissue samples, whereas only six subjects expressed the 3- isoform as well. The only distinctive feature of these six patients was a higher HbA1c. CONCLUSIONS: The heterozygous GHR +3/-3 genotype is more prevalent in subjects with morbid obesity. Patients expressing the exon +3 and exon -3 isoforms in adipose tissue had a higher HbA1c, than those expressing only the exon -3 isoform.

Predicting Human miRNA-like Sequences within Human Papillomavirus Genomes.

BACKGROUND: This study presents a prediction of putative miRNA within several Human Papillomavirus (HPV) types by using bioinformatics tools and a strategy based on sequence and structure alignment. Currently, little is known about HPV miRNAs. METHODS: Computational methods have been widely applied in the identification of novel miRNAs when analyzing genome sequences. Here, ten whole-genome sequences from HPV-6, -11, -16, -18, -31, -33, -35, -45, -52, and -58 were analyzed. Software based on local contiguous structure-sequence features and support vector machine (SVM), as well as additional bioinformatics tools, were utilized for identification and classification of real and pseudo microRNA precursors. RESULTS: An initial analysis predicted 200 putative pre-miRNAs for all the ten HPV genome variants. To derive a smaller set of pre-miRNAs candidates, stringent validation criteria was conducted by applying <‒10 ΔG value (Gibbs Free Energy). Thus, only pre-miRNAs with total scores above the cut-off points of 90% were considered as putative pre-miRNAs. As a result of this strategy, 19 pre-miRNAs were selected (hpv-pre-miRNAs). These novel pre-miRNAs were located in different clusters within HPV genomes and some of them were positioned at splice regions. Additionally, the 19 identified pre-miRNAs sequences varied between HPV genotypes. Interestingly, the newly identified miRNAs, 297, 27b, 500, 501-5, and 509-3-5p, were closely implicated in carcinogenesis participating in cellular longevity, cell cycle, metastasis, apoptosis evasion, tissue invasion and cellular growth pathways. CONCLUSIONS: The novel putative miRNAs candidates could be promising biomarkers of HPV infection and furthermore, could be targeted for potential therapeutic interventions in HPV-induced malignancies.

HPV Could be a Potential Factor of Survival in Laryngeal Cancer: a Preliminary Study in Mexican Patients

Introduction: In Head and Neck (HN) cancer, the High-Risk Human Papillomavirus (hr HPV) infection has been associated in about 40% of these tumors. The hr HPV infection is one of the etiological factors of several epithelial tumors; however, its association with the prognosis has not yet been established for patients with Laryngeal Squamous Cell Carcinoma (LSCC). On the other hand, Epidermal Growth Factor Receptor (EGFR) is a molecular marker widely studied in cancer and its overexpression has been associated with poor prognosis in some types of cancer, including the HN cancer. In the present study, we analyzed EGFR expression and HPV detection in a cohort of Mexican patients with LSCC and define their association with clinical-pathological and survival parameters. Methods: EGFR expression analysis was performed by immunohistochemistry assay. A tissue array was constructed based on 30 paraffin-embedded tissue samples. HPV detection was performed by PCR. The results were then compared with the clinical-pathological variables and outcome measures (Kaplan Meier and Cox analysis). Results: High expression of EGFR was observed in 43% of the samples and 20% of HPV detection. The statistical analyses provided evidence of disassociation between clinical-pathological parameters and EGFR expression, but there was an association with poor prognosis. Interestingly, HPV detection is slightly associated with good prognosis. Conclusion: Both, EGFR overexpression and HPV presence could be associated with an unfavorable prognosis in patients with LSCC, independently of other clinical-pathological factors.

Krüppel-Like Factor 10 participates in cervical cancer immunoediting through transcriptional regulation of Pregnancy-Specific Beta-1 Glycoproteins.

Cervical cancer (CC) is associated with alterations in immune system balance, which is primarily due to a shift from Th1 to Th2 and the unbalance of Th17/Treg cells. Using in silico DNA copy number analysis, we have demonstrated that ~20% of CC samples exhibit gain of 8q22.3 and 19q13.31; the regions of the genome that encodes the KLF10 and PSG genes, respectively. Gene expression studies demonstrated that there were no alterations in KLF10 mRNA expression, whilst the PSG2 and -5 genes were up-regulated by 1.76 and 3.97-fold respectively in CC compared to normal tissue controls. siRNA and ChIP experiments in SiHa cells have demonstrated that KLF10 participates in immune response through regulation of IL6, IL25 and PSG2 and PSG5 genes. Using cervical tissues from KLF10-/- mice, we have identified down-regulation of PSG17, -21 and -23 and IL11. These results suggest that KLF10 may regulate immune system response genes in cervical cancer among other functions. KLF10 and PSG copy number variations and alterations in mRNA expression levels could represent novel molecular markers in CC.