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.

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.

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.

A non-invasive tool for detecting cervical cancer odor by trained scent dogs.

BACKGROUND: Cervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population's quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC. METHODS: Using clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle's ability to discriminate CC from control samples. RESULTS: The beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle's success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients. CONCLUSION: Present data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.

Krüppel-like factor 5 as potential molecular marker in cervical cancer and the KLF family profile expression.

Cervical cancer (CC) as other cancer types, presents molecular deregulations, such as the alterations of transcription factors. Krüppel-like factors (KLF) are a family of transcriptional regulators. They are involved in diverse cellular processes, such as proliferation, apoptosis, and angiogenesis among others. Here, we analyzed the expression of all 17 KLF members at messenger RNA (mRNA) level, and protein expression of the two most commonly altered KLF5 and KLF6 in cervical tissues. Fifty-nine cervical tissues ranging from normal tissue to CC were evaluated for KLF1-17 mRNA expression by end-point RT-PCR and KLF5 by qRT-PCR. For KLF5 and KLF6 protein analysis, a tissue microarray was constructed containing the 59 cases and subjected for immunohistochemistry assay and KLF6 IVS1-27G>A single nucleotide polymorphism by direct DNA sequencing. KLF2-16 expressions were present in normal tissue, whereas all 17 were present in Low-Grade Squamous Intraepithelial Lesion, High-Grade-SIL and CC, unrelated to presence of human papillomavirus (HPV). KLF5 mRNA expression gradually increased throughout the subgroups and overexpressed in CC (p=0.01). KLF5 and KLF6 proteins were immunodetected in all samples. For the KLF6 SNP analysis, 80% of the CC population analyzed presented GG genotype and the remaining 20% presented GA genotype (p=0.491). Our present data show that KLFs expression could not be related to HPV presence, at least at transcriptional level, and KLF5 mRNA overexpression could represent a potential molecular marker for CC; KLF6 SNP has no relation to increased risk of CC.

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.

HPV16 E2 could act as down-regulator in cellular genes implicated in apoptosis, proliferation and cell differentiation.

BACKGROUND: Human Papillomavirus (HPV) E2 plays several important roles in the viral cycle, including the transcriptional regulation of the oncogenes E6 and E7, the regulation of the viral genome replication by its association with E1 helicase and participates in the viral genome segregation during mitosis by its association with the cellular protein Brd4. It has been shown that E2 protein can regulate negative or positively the activity of several cellular promoters, although the precise mechanism of this regulation is uncertain. In this work we constructed a recombinant adenoviral vector to overexpress HPV16 E2 and evaluated the global pattern of biological processes regulated by E2 using microarrays expression analysis. RESULTS: The gene expression profile was strongly modified in cells expressing HPV16 E2, finding 1048 down-regulated genes, and 581 up-regulated. The main cellular pathway modified was WNT since we found 28 genes down-regulated and 15 up-regulated. Interestingly, this pathway is a convergence point for regulating the expression of genes involved in several cellular processes, including apoptosis, proliferation and cell differentiation; MYCN, JAG1 and MAPK13 genes were selected to validate by RT-qPCR the microarray data as these genes in an altered level of expression, modify very important cellular processes. Additionally, we found that a large number of genes from pathways such as PDGF, angiogenesis and cytokines and chemokines mediated inflammation, were also modified in their expression. CONCLUSIONS: Our results demonstrate that HPV16 E2 has regulatory effects on cellular gene expression in HPV negative cells, independent of the other HPV proteins, and the gene profile observed indicates that these effects could be mediated by interactions with cellular proteins. The cellular processes affected suggest that E2 expression leads to the cells in to a convenient environment for a replicative cycle of the virus.

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.

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.

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.

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.

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.

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.

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.

Analysis of human serum from women affected by cervical lesions.

Cervical cancer is one of the first causes of death in Mexican women population. The plasma proteome has a wide dynamic range concentrations of different protein and their alterations reflect the physiological state of the individual's health. The aim of this study was to characterize the 2D-PAGE serum patterns from healthy women and with different levels of cervical lesions. Changes in haptoglobin, apolipoproteins, and transthyretin, when comparing the serum from healthy women and serum from patients with different levels of cervical lesion were found. The Western blot analysis showed increasing concentrations of metalloproteinases (MMP's), proteins with important biological roles in tumor development and metastasis. Protein profiles in conjunction with MS, bioinformatics, and Western blot analysis, allow us to compile information for the acquisition of results to proposed candidates biomarkers of cervical cancer among Mexican women population.

Local and circulating microchimerism is associated with hypersensitivity pneumonitis.

RATIONALE: Hypersensitivity pneumonitis (HP) is a lymphocytic alveolitis provoked by exposure to a variety of antigens. However, the disease occurs in only a subset of exposed individuals, suggesting that additional factors may be involved. Microchimerism has been implicated in the pathogenesis of autoimmune diseases, especially in those showing increased incidence after childbearing age. OBJECTIVES: To evaluate the presence of circulating and local microchimeric cells in female patients with HP. METHODS: Male microchimerism was examined in 103 patients with HP, 30 with idiopathic pulmonary fibrosis (IPF), and 43 healthy women. All of them had given birth to at least one son, with no twin siblings, blood transfusions, or transplants. Microchimerism was examined by dot blot hybridization (peripheral blood), and by fluorescence in situ hybridization in bronchoalveolar lavage cells and lungs. MEASUREMENTS AND MAIN RESULTS: Blood microchimerism was found in 33% of the patients with HP in comparison with 10% in those with IPF (p = 0.019) and 16% in healthy women (p = 0.045). Patients with HP with microchimerism showed a significant reduction of diffusing capacity of carbon monoxide (Dl(CO); 53.5 +/- 11.9% vs. 65.2 +/- 19.7%; p = 0.02) compared with patients with HP without microchimerism. In bronchoalveolar lavage cells, microchimerism was detected in 9 of 14 patients with HP compared with 2 of 10 patients with IPF (p = 0.047). Cell sorting revealed that microchimeric cells were either macrophages or CD4+ or CD8+ T cells. Male microchimeric cells were also found in the five HP lungs examined by fluorescence in situ hybridization. CONCLUSIONS: Our findings (1) demonstrate that patients with HP exhibit increased frequency of fetal microchimerism, (2) confirm the multilineage capacity of microchimeric cells, and (3) suggest that microchimeric cells may increase the severity of the disease.

pRB detection as a common event in human retinoblastomas: an immunohistochemical study.

Approximately 30% of the cases of retinoblastoma (RB), the childhood eye cancer, are inherited and are manifested by unilateral or bilateral tumor. In sporadic tumors, accounting for 70% of cases, only one eye is affected. RB has three histological features: undifferentiated anaplastic cells, retinoblast pattern, and differentiated pattern characterized by Flexner Wintersteiner rosettes (FWR). Currently, results concerning phosphoprotein RB (pRB) expression in RB tumors are contradictory. In this study we detected pRB immunohistochemically in 10 tumors from bilateral or unilateral RBs, which did not show gross chromosomal alterations in cytogenetic studies. Interestingly, pRB was undetectable in only one tumor where we found distinct histological features. Our results suggest that pRB immunopositivity may be common in these tumors. However, it does not rule out the possibility that pRB is functionally inactive in some cases. This may be due to the protein being present in phosphorylated form or being altered by point mutations not affecting its expression. Another possibility is that mechanisms other than RB1 gene changes may lead to retinoblastoma because not all cases of retinoblastoma show gene alterations. Together these findings may be useful in understanding the molecular mechanisms associated with this type of pediatric tumor.