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IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate. OBJECTIVE: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP. DESIGN, SETTING AND PARTICIPANTS: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres. EXPOSURES: Participants self-administered 350 mg of erlotinib by mouth, one time per week for 6 months. MAIN OUTCOMES AND MEASURES: Duodenal polyp burden (sum of polyp diameters) was assessed in the proximal duodenum by esophagogastroduodenoscopy performed at baseline and 6 months, with mean per cent change defined as the primary efficacy outcome of interest. Rate of grade 2-3 AEs was evaluated as a co-primary outcome. Secondary outcomes included changes in total duodenal polyp count, along with changes in lower gastrointestinal (GI) polyp burden and count (for participants examined by optional lower endoscopy). RESULTS: Forty-six participants (mean age, 44.1 years (range, 18-68); women, 22 (48%)) were enrolled; 42 participants completed 6 months of intervention and were included in the per-protocol analysis. Duodenal polyp burden was significantly reduced after 6 months of weekly erlotinib intervention, with a mean per cent change of -29.6% (95% CI, -39.6% to -19.7%; p<0.0001). Similar results were observed in subgroup analyses defined by participants with advanced duodenal polyposis (Spigelman 3) at baseline (mean, -27%; 95% CI, -38.7% to -15.2%; p<0.0001). Post-intervention Spigelman stage was downstaged in 12% of the participants. Lower GI polyp number was also decreased after 6 months of intervention (median, -30.8%; IQR, -47.4% to 0.0%; p=0.0256). Grade 2 or 3 AEs were reported in 71.7% of subjects, with only two experiencing grade 3 toxicity at least possibly related to intervention. CONCLUSION: In this single-arm, multi-centre trial of participants with FAP, erlotinib one time per week resulted in markedly lower duodenal polyp burden, and modestly reduced lower GI polyp burden, after 6 months of intervention. While AEs were still reported by nearly three-quarters of all participants, these events were generally lower grade and well-tolerated. These findings support further investigation of erlotinib as an effective, acceptable cancer preventive agent for FAP-associated GI polyposis. TRIAL REGISTRATION NUMBER: NCT02961374.
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Poliposis Adenomatosa del Colon , Neoplasias Duodenales , Humanos , Femenino , Adulto , Clorhidrato de Erlotinib/efectos adversos , Poliposis Adenomatosa del Colon/tratamiento farmacológico , Neoplasias Duodenales/tratamiento farmacológico , Duodeno , Endoscopía GastrointestinalRESUMEN
BACKGROUND & AIMS: Familial adenomatous polyposis is an autosomal dominant disorder characterized by the development of hundreds of colorectal adenomas and eventually colorectal cancer. Oral administration of the spice curcumin has been followed by regression of polyps in patients with this disorder. We performed a double-blinded randomized trial to determine the safety and efficacy of curcumin in patients with familial adenomatous polyposis. METHODS: This study included 44 patients with familial adenomatous polyposis (18-85 years old) who had not undergone colectomy or had undergone colectomy with ileorectal anastomosis or ileal anal pouches, had at least 5 intestinal adenomatous polyps, and had enrolled in Puerto Rico or the United States from September 2011 through November 2016. Patients were randomly assigned (1:1) to groups given 100% pure curcumin (1,500 mg orally, twice per day) or identical-appearing placebo capsules for 12 months. The number and size of lower gastrointestinal tract polyps were evaluated every 4 months for 1 year. The primary outcome was the number of polyps in the curcumin and placebo groups at 12 months or at the time of withdrawal from the study according to the intention-to-treat principle. RESULTS: After 1 year of treatment, the average rate of compliance was 83% in the curcumin group and 91% in the placebo group. After 12 weeks, there was no significant difference in the mean number of polyps between the placebo group (18.6; 95% CI, 9.3-27.8) and the curcumin group (22.6; 95% CI, 12.1-33.1; P = .58). We found no significant difference in mean polyp size between the curcumin group (2.3 mm; 95% CI, 1.8-2.8) and the placebo group (2.1 mm; 95% CI, 1.5-2.7; P = .76). Adverse events were few, with no significant differences between groups. CONCLUSIONS: In a double-blinded randomized trial of patients with familial adenomatous polyposis, we found no difference in the mean number or size of lower intestinal tract adenomas between patients given curcumin 3,000 mg/day and those given placebo for 12 weeks. Clinicaltrials.gov ID NCT00641147.
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Adenoma/tratamiento farmacológico , Poliposis Adenomatosa del Colon/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Curcumina/administración & dosificación , Adenoma/etiología , Poliposis Adenomatosa del Colon/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/etiología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism and its polymorphisms are possibly implicated in the etiology of ischemic cerebrovascular disease (CVD). The aim of this work was to determine the association of the of D9N, N291S, and T495G polymorphisms of the LPL gene as a risk factor for the development of CVD. METHODS: A case-control study was conducted that included 100 patients with CVD and 120 healthy controls. All the subjects were genotyped for the D9N, N291S, and T495G polymorphisms of the LPL gene through polymerase chain reaction-restriction fragment length polymorphism, and the results were analyzed for their association with CVD. RESULTS: The D9N genotype was not significantly correlated with CVD; the odds ratio (OR) between the control subjects and CVD patients was .29 (95% confidence interval [CI], .03-2.66; P = .27). The N291S polymorphism was not significantly correlated with CVD either; the OR between the control subjects and CVD patients was 1.2 (95% CI, .07-19.46; P = .89). And the T495G mutation was not significantly correlated with CVD; the OR between the control subjects and the CVD patients was 1.21 (95% CI, .7-2.08; P = .48). CONCLUSIONS: In the present study, the D9N, N291S, and T495G polymorphisms of the LPL gene were not risk factors for the development of CVD.
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Infarto Cerebral/genética , Predisposición Genética a la Enfermedad/genética , Lipoproteína Lipasa/genética , Polimorfismo Genético/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Obesity is associated with neoplasia, possibly via insulin-mediated cell pathways that affect cell proliferation. Metformin has been proposed to protect against obesity-associated cancers by decreasing serum insulin. We conducted a randomized, double-blind, placebo-controlled, phase 2 study of patients with Barrett's esophagus (BE) to assess the effect of metformin on phosphorylated S6 kinase (pS6K1), a biomarker of insulin pathway activation. METHODS: Seventy-four subjects with BE (mean age, 58.7 years; 58 men [78%; 52 with BE >2 cm [70%]) were recruited through 8 participating organizations of the Cancer Prevention Network. Participants were randomly assigned to groups given metformin daily (increasing to 2000 mg/day by week 4, n = 38) or placebo (n = 36) for 12 weeks. Biopsy specimens were collected at baseline and at week 12 via esophagogastroduodenoscopy. We calculated and compared percent changes in median levels of pS6K1 between subjects given metformin vs placebo as the primary end point. RESULTS: The percent change in median level of pS6K1 did not differ significantly between groups (1.4% among subjects given metformin vs -14.7% among subjects given placebo; 1-sided P = .80). Metformin was associated with an almost significant reduction in serum levels of insulin (median -4.7% among subjects given metformin vs 23.6% increase among those given placebo, P = .08) as well as in homeostatic model assessments of insulin resistance (median -7.2% among subjects given metformin vs 38% increase among those given placebo, P = .06). Metformin had no effects on cell proliferation (on the basis of assays for KI67) or apoptosis (on the basis of levels of caspase 3). CONCLUSIONS: In a chemoprevention trial of patients with BE, daily administration of metformin for 12 weeks, compared with placebo, did not cause major reductions in esophageal levels of pS6K1. Although metformin reduced serum levels of insulin and insulin resistance, it did not discernibly alter epithelial proliferation or apoptosis in esophageal tissues. These findings do not support metformin as a chemopreventive agent for BE-associated carcinogenesis. ClinicalTrials.gov number, NCT01447927.
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Esófago de Barrett/complicaciones , Esófago de Barrett/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Neoplasias Esofágicas/prevención & control , Metformina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Esófago de Barrett/patología , Método Doble Ciego , Endoscopía del Sistema Digestivo , Femenino , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Placebos/administración & dosificación , Estudios Prospectivos , Proteínas Quinasas S6 Ribosómicas/análisis , Adulto JovenRESUMEN
BACKGROUND/AIMS: Breast cancer is the most common gynecologic malignancy known worldwide. The consumption of certain foods may modify the risk for its development. Peanuts and other seeds have shown anticarcinogenic effects in vitro, but there are a few studies that evaluate the effect of their consumption on the development of breast cancer. The aim of the present study was to determine whether there is an association between the consumption of peanuts, walnuts, and almonds and the development of breast cancer. METHODS: We analyzed 97 patients presenting with breast cancer and 104 control subjects that did not have the pathology (BIRADS 1-2). An analysis of the main clinical characteristics and lifelong seed consumption was carried out. The association between the consumption of these foods and the risk for breast cancer was estimated by odds ratios and 95% confidence intervals, controlling other risk factors, using the Mantel-Haenszel analysis. RESULTS: The high consumption of peanuts, walnuts, or almonds significantly reduced the risk for breast cancer by 2-3 times. This protective effect was not found with low or moderate seed consumption when compared with null consumption. CONCLUSIONS: High consumption of peanuts, walnuts, and almonds appears to be a protective factor for the development of breast cancer.
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Arachis , Neoplasias de la Mama/prevención & control , Dieta , Juglans , Prunus dulcis , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Factores ProtectoresRESUMEN
Gastric adenocarcinoma (GAC) is the fourth-leading global cause of cancer mortality and leading infection-associated cancer. High incidence regions include Latin America and Eastern Asia. Immigrants from high incidence regions maintain their GAC risk. GAC is a major U.S. cancer disparity, incidence rates are 2-10 time higher in non-white populations. Emerging guidelines recommend 3-year surveillance endoscopy for patients with high-risk gastric premalignant conditions (GPMCs). Clinical trials of GPMC chemoprevention agents are lacking. We conducted an NCI Division of Cancer Prevention-funded, phase II placebo-controlled chemoprevention trial in patients with GPMCs (atrophic gastritis, intestinal metaplasia) with a highly bioavailable preparation of curcuminoids (Meriva®). The trial sites in Puerto Rico and rural Honduras had important characteristics: (1) representative Caribbean and Mesoamerican populations, linked to large U.S. immigrant populations; (2) high prevalence of H. pylori infection and GPMCs; (3) absence of turmeric and curcuminoids in the local diets; (4) proven bidirectional collaboration with U.S. academic institutions. H. pylori-negative GPMC patients were randomized to study drug (500 mg po bid) or placebo for 180 days (NCT02782949), with primary outcomes based upon histologic parameters. Principal study challenges included: (1) international regulatory environment; (2) research infrastructure strengthening, particularly in Central America; (3) participant recruitment in Honduras wherein only 10-15% are H. pylori negative; (4) the Covid-19 pandemic; and (5) natural disasters (3 hurricanes). There were no losses to follow-up related to the pandemic or natural disasters. In conclusion, the south-south partnership provides a model for chemoprevention and translational studies in Latino populations with prevalent cancers such as GAC.
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INTRODUCTION: The expression of plasminogen activator inhibitor type 1 (PAI-1), vascular endothelial growth factor (VEGF), and transforming growth factor ß1 (TGF-ß1) participates in the angiogenesis of several cancer types. The goal of this study was to investigate polymorphisms in genes related to angiogenesis (PAI-1-675 4G/5G, VEGF C936T, and TGF-ß1 G-800A) to evaluate the risk for developing uterine cervical cancer (UCC). METHODS: In a case-control study, 100 healthy subjects and 100 patients with UCC from Mexico were included. We determined the genetic profile of the polymorphic markers, which were evaluated by polymerase chain reaction using a sequence-specific primer. RESULTS: There was no statistical difference in the allele distribution from the intergroup comparisons of PAI-1 675 4G/5G and VEGF C936T data; however, a significant difference was observed within TGF-ß1 G-800A. The linkage disequilibrium analysis revealed that PAI-1 -675 4G and TGF-ß1 -800A pair-haplotype was in strong linkage disequilibrium with a significantly increased risk (odds ratio, 3.44; 95% confidence interval, 1.66-7.25) to UCC. CONCLUSIONS: The polymorphisms in the genes related to angiogenesis -675 4G/5G PAI-1 and G-800A TGF-ß1, segregated solely or combined, might contribute to the increased susceptibility to UCC in a Mexican population.
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Biomarcadores de Tumor/genética , Neovascularización Patológica/genética , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo de Nucleótido Simple/genética , Factor de Crecimiento Transformador beta1/genética , Neoplasias del Cuello Uterino/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adolescente , Adulto , Estudios de Casos y Controles , Cuello del Útero/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos/genética , Humanos , Desequilibrio de Ligamiento , México/epidemiología , Reacción en Cadena de la Polimerasa , Pronóstico , Neoplasias del Cuello Uterino/epidemiología , Adulto JovenRESUMEN
Attrition is high among surgical trainees, and six of ten trainees consider leaving their programs, with two ultimately leaving before completion of training. Given known historically and systemically rooted biases, Black surgical trainees are at high risk of attrition during residency training. With only 4.5% of all surgical trainees identifying as Black, underrepresentation among their peers can lend to misclassification of failure to assimilate as clinical incompetence. Furthermore, the disproportionate impact of ongoing socioeconomic crisis (e.g., COVID-19 pandemic, police brutality etc.) on Black trainees and their families confers additional challenges that may exacerbate attrition rates. Thus, attrition is a significant threat to medical workforce diversity and health equity. There is urgent need for surgical programs to develop proactive approaches to address attrition and the threat to the surgical workforce. In this Society of Black Academic Surgeons (SBAS) white paper, we provide a framework that promotes an open and inclusive environment conducive to the retention of Black surgical trainees, and continued progress towards attainment of health equity for racial and ethnic minorities in the United States.
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COVID-19 , Internado y Residencia , Cirujanos , Humanos , Estados Unidos , Pandemias , COVID-19/epidemiología , Cirujanos/educaciónRESUMEN
PURPOSE: To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation. PATIENTS AND METHODS: Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0. RESULTS: Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9-17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P < 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60-1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15-1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events. CONCLUSIONS: An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection.
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Adenoma , Neoplasias del Colon , Neoplasias Colorrectales , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adenoma/prevención & control , Neoplasias Colorrectales/prevención & control , Inmunoglobulina G , Vacunas de SubunidadRESUMEN
The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon's design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2-37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.
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Coronavirus disease 2019 (COVID-19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID-19. A prospective, 2-arm, parallel-group, randomized, open-label, multi-center, phase I-II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20-day follow-up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro-pharyngeal detection by reverse transcription-quantitative (RT-q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03-0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01-0.42, P=0.007) and also resulted in an 18-fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29-45.09, P<0.001), compared with usual medical care alone. Overall, neutral electrolyzed saline solution was better than usual medical care alone. Of the patients analyzed, >50% were negative for the virus as detected by RT-qPCR in naso/oro-pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C-reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone-cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID-19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX-COVID19: RPCEC00000309).
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Prostate cancer (PCa) is the second most common non-dermatological cancer in men and is a growing public health problem. Castration-resistant disease (CRD) is the most advanced stage of the disease and is difficult to control. Patients with CRD may no longer accept conventional therapies as they are not in appropriate clinical conditions or they refuse to receive it. Given that inflammation is an essential component of CRD origin and progression, anti-inflammatory agents could be a therapeutic option with fenamates as one of the proposed choices. A prospective, randomized, double-blinded, 2-arm, parallel group, phase II-III clinical trial was performed involving 20 patients with CRD-PCa (with a prostate specific antigen level <100 ng/ml) that were undergoing androgen deprivation therapy (ADT) and did not accept any established treatment for that disease stage. In addition to ADT, 10 patients received placebo and 10 received mefenamic acid (500 mg orally every 12 h) for 6 months. The primary endpoint was the change in serum prostate-specific antigen (PSA) at 6 months. The PSA levels decreased significantly with mefenamic acid (an average 42% decrease), whereas there was an average 55% increase in the placebo group (P=0.024). In the patients treated with the placebo, 70% had biochemical disease progression (an increase of ≥25% in PSA levels), which did not occur in any of the patients treated with mefenamic acid (relative risk=0.12; 95% confidence interval, 0.01-0.85; P=0.033). There was a significant increase in quality of life (EQ-5D-5L score) and body mass index (BMI) with the experimental treatment. In conclusion, mefenamic acid administration decreased biochemical progression in patients with castration resistant PCa, improved their quality of life and increased their BMI. Future studies are required in order to strengthen the findings of the present clinical trial. Trial registration, Cuban Public Registry of Clinical Trials Database RPCEC00000248, August 2017.
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Background: Coronavirus disease (COVID-19) is currently the main public health problem worldwide. The administration of neutral electrolyzed saline, a solution that contains reactive species of chlorine and oxygen (ROS), may be an effective therapeutic alternative due to its immunomodulating characteristics, in systemic inflammation control, as well as in immune response improvement, promoting control of the viral infection. The present study evaluated the efficacy of treatment with intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care versus usual medical care alone, in ambulatory patients with COVID-19. Methods: A prospective, 2-arm, parallel group, randomized, open-label, phase I-II clinical trial included 39 patients in the control group (usual medical care alone) and 45 patients in the experimental group (usual medical care + intravenous and/or nebulized electrolyzed saline, with dose escalation). Two aspects were evaluated during the twenty-day follow-up: i) the number of patients with disease progression (hospitalization or death); and ii) the Patient Acceptable Symptom State (PASS), a single-question outcome that determines patient well-being thresholds for pain and function. Biochemical and hematologic parameters, as well as adverse effects, were evaluated in the experimental group. Results: The experimental treatment decreased the risk for hospitalization by 92% (adjusted RR=0.08, 95% CI: 0.01-0.50, P=0.007), with a 43-fold increase in the probability of achieving an acceptable symptom state on day 5 (adjusted RR= 42.96, 95% CI: 9.22-200.0, P<0.001). Intravenous + nebulized administration was better than nebulized administration alone, but nebulized administration was better than usual medical care alone. Clinical improvement correlated with a decrease in C-reactive protein, and aberrant monocytes and an increase of lymphocytes, and platelets. Cortisol and testosterone levels were also evaluated, observing a decrease in cortisol levels and an increment of testosterone-cortisol ratio, on days 2 and 4. Conclusions: The experimental treatment produced no serious adverse effects. In conclusion, intravenous and/or nebulized neutral electrolyzed saline importantly reduced the symptomatology and risk of progression (hospitalization and death), in ambulatory patients with COVID-19. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000309. Registered: 05. May 2020. https://rpcec.sld.cu/en/trials/RPCEC00000309-En.
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BACKGROUND: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity on matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism C>T transition at -1306 displayed a strong association with several cancers. Our study investigated whether or not the MMP-2 -1306C>T polymorphism contributed to the development of breast cancer (BC) in a Mexican population. METHODS: 90 patients with BC and 96 control subjects were analyzed to detect MMP-2 -1306C>T polymorphism. RESULTS: The frequency of MMP-2 CC genotype was significantly higher in BC patients when compared with the control group (OR 2.15; 95% CI 1.1-4.1). MMP-2 CC genotype frequency was more pronounced in younger subjects (< or =50 years) at diagnosis (OR 2.66; 95% CI 1.04-6.96). CONCLUSION: The data suggest that MMP-2 -1306C>T polymorphism strongly contributes to the development of BC in the population studied, especially among women 50 years old and younger.
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Neoplasias de la Mama/genética , Metaloproteinasa 2 de la Matriz/genética , Polimorfismo Genético , Neoplasias de la Mama/etnología , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Americanos Mexicanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Regiones Promotoras GenéticasRESUMEN
Gene therapy with adenoviral vectors can eliminate neoplasic cells through selective replication and/or through pro-apoptotic, immunogenic or suicide gene expression. However, an adenoviral vector may provide anti-cancerous effects even in the absence of replication or therapeutic gene expression. The present study evaluates the therapeutic effects caused by the administration of an adenoviral vector, alone, in HPV-dependent neoplasias (HPV-N). In vivo trials were carried out in two HPV-N mouse models. One model was immunocompetent and the other was immunodeficient. In both models, the effect of intratumoral administration of saline solution (PBS) was compared with administration of an adenoviral vector that had no replicative capacity or therapeutic gene (Ad-BGal). In the immunocompetent mice, Ad-BGal adenoviral vector administration significantly reduced tumor growth, compared with PBS. No differences were observed in the immunodeficient mice. In conclusion, the present study lends support to the use of adenoviral vectors in HPV-N treatment since they are capable of generating an antitumoral effect in immunocompetent individuals, even in the absence of a therapeutic gene or viral vector replication.
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Adenoviridae , Terapia Genética , Neoplasias/terapia , Neoplasias/virología , Infecciones por Papillomavirus/terapia , Animales , Femenino , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Nevertheless its association with cervicouterine cancer, there is no information about cervical human papillomavirus infection prevalence in patients with rheumatoid arthritis. OBJECTIVE: To evaluate human papillomavirus infection prevalence through molecular biology tests, and to analyze this infection related factors in patients with rheumatoid arthritis. MATERIAL AND METHOD: Analytic, transversal study to 250 patients: 61 women with rheumatoid arthritis selected from a rheumatologic external consult of a second level hospital, and 189 healthy women, with cervical cytology, of a first level hospital. They were polled to find infection risk factors. They were exfoliated to get cervix cells to extract its DNA and detect human papillomavirus (chain reaction of polymerase with specific consensus markers), and identification of restriction enzyme in high and low risks viruses. Prevalence was calculated, and adjusted factors analysis was performed through logistic regression with odds ratio and confidence intervals of 95%. RESULTS: Prevalence of papillomavirus infection in patients with rheumatoid arthritis was 30%, and in control group was 24%, with an odds ratio of 0.8 (CI 95% 0.42-1.6, p = 0.5). Ninety-four percent of the most frequent viral types in women with rheumatoid arthritis were high risk (mainly types 16, 58, and 18). Factors associated with higher human papillomavirus adjusted to rheumatoid arthritis were: more than one sexual partner (OR = 5.8 CI 95% 1.1-31.1, p = 0.04), more than one sexual intercourse weekly (OR = 6.7, CI 95% 0.9-51.6, p = 0.06), circumcised sexual partner (OR = 9.0, CI 95% 1.2-64.4, p = 0.02). Patients and controls had same values of marital status. Seventy-four percent of controls worked, compared to 44% of women with rheumatoid arthritis (p < 0.01). CONCLUSION: One out of three women with rheumatoid arthritis has human papillomavirus infection and 94% has the high-risk viral type. Infection associated factors mainly includes sexual partner ones; due to high risk of cervical dysplasia, it is necessary the early detection of the infection and surveillance.
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Artritis Reumatoide/complicaciones , Infecciones por Papillomavirus/epidemiología , Enfermedades del Cuello del Útero/epidemiología , Enfermedades del Cuello del Útero/virología , Adulto , Estudios Transversales , Femenino , Humanos , Infecciones por Papillomavirus/complicaciones , Prevalencia , Factores de Riesgo , Enfermedades del Cuello del Útero/complicacionesRESUMEN
OBJECTIVE: To describe and explain imaginaries about sexuality that university students have at the beginning of their professional training. METHODS: Study with a qualitative approach, for which grounded theory was used as methodology and method. 11 students enrolled in the first semester of different undergraduate programs were included. The information was collected through 25 in-depth interviews, with an average of two interviews per reporter. RESULTS: Six categories emerged from the data: socialization of sexuality in the family; socialization of sexuality in the school; socialization of sexuality in the media; socialization of sexuality with peers; traditional imaginary of sexuality; and liberal imaginary of sexuality. The grounded theory emerged based on these general categories: "Sexuality imaginaries between adaptation and resistance". DISCUSSION: The theoretical approach describes how young people internalize the symbols and views of sexuality that they learn before entering university during socialization processes with their family, the school, the media, peers and own experiences. This internalization is not completely passive, as the youth go through some confrontation processes in relation to these visions that lead them to adapt or resist.
OBJETIVO: Describir y explicar los imaginarios sobre sexualidad que tienen los estudiantes universitarios al comienzo de su formación profesional. MÉTODOS: Estudio con enfoque cualitativo, en el que se utilizó como metodología y método la teoría fundamentada; en total participaron 11 estudiantes que se encontraban matriculados en primer semestre en diferentes programas presenciales de pregrado; la recolección de la información se realizó mediante 25 entrevistas a profundidad, con un promedio de dos entrevistas por informante. RESULTADOS: A partir de los datos surgieron seis categorías: socialización de la sexualidad en la familia; socialización de la sexualidad en la escuela; socialización de la sexualidad en los medios de comunicación; socialización de la sexualidad con los pares; imaginario tradicional de sexualidad; imaginario liberal de la sexualidad. Finalmente, a partir de las categorías generales emergió la teoría sustantiva: imaginarios de sexualidad entre la adaptación y la resistencia. DISCUSIÓN: El planteamiento teórico, describe como los jóvenes van interiorizando los símbolos y visiones de la sexualidad que van aprendiendo antes de ingresar a la universidad, en los procesos de socialización en la familia, la escuela, los medios de comunicación, los pares y sus propias experiencias. Esta interiorización no es totalmente pasiva, sino que en el joven se van dando unos procesos de confrontación de estas visiones que los llevan a adaptarse o a resistirse.
Asunto(s)
Imaginación , Sexualidad/psicología , Socialización , Estudiantes/psicología , Adolescente , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pathogens affecting humans. Genetic variations in viruses are likely to be a condition for more effective evasion of the immune system and resulting in severe clinical consequences. The DENV1 NS5 gene was sequenced to establish whether during an epidemic burst there were genetic variations of the virus and whether any variant was associated (through a casecontrol design) with severe clinical behavior. A total of 31 patients positive for DENV1 were enrolled. Among the nucleotide differences between the sequences, only two generated amino acid changes. The variants 124Met/166Ser (amino acid positions according to the report GenBank AJL35015.1), were associated with a severe clinical course of the disease. Via in silico tests, it was identified that the variations generate changes in the protein probably affecting the function of type1 interferon, either at the level of its receptor or by interfering with the Janus kinasesignal transducer and activator of transcription signaling pathway.
Asunto(s)
Virus del Dengue/genética , Dengue/inmunología , Inmunidad Innata , Interferón Tipo I/inmunología , Quinasas Janus/inmunología , Factores de Transcripción STAT/inmunología , Proteínas no Estructurales Virales/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Dengue/virología , Virus del Dengue/inmunología , Femenino , Variación Genética , Humanos , Janus Quinasa 1/inmunología , Masculino , Persona de Mediana Edad , Simulación del Acoplamiento Molecular , Mutación Puntual , Transducción de Señal , Proteínas no Estructurales Virales/inmunología , Adulto JovenRESUMEN
AIM: To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pß-cateninS552 as a biomarker of recurrent dysplasia. METHODS: We examined the effects of dietary myo-inositol treatment on inflammation, pß-cateninS552 and pAkt levels by histology and western blot in IL-10-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pß-cateninS552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS: In mice, pß-cateninS552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, pß-cateninS552 staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease. CONCLUSION: Enumerating crypts with increased numbers of pß-cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.