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Gastric cancer (GC) is a leading cause of death, and this pathology often receives a diagnosis in an advanced stage. The development of a less invasive and cost-effective test for detection is essential for decreasing the mortality rate and increasing the life expectancy of GC patients. We evaluated the potential targeting of CD54/ICAM1, a marker of gastric cancer stem cells, with miRNAs to detect GC in blood samples. The analyses included 79 blood samples, 38 from GC patients and 41 from healthy donors, who attended INCan, México City. The total RNA was obtained from the blood plasma, and RT-PCR and qPCR were performed to obtain the relative expression of each miRNA. Hsa-miR-335-5p was detected in the plasma of GC patients and healthy donors at the same levels. The ROC curve analyses indicated that this miRNA was not a candidate for the molecular diagnosis of GC. We did not observe a correlation between the expression of hsa-miR-335-5p and clinical variables; however, the Kaplan-Meier analyses indicated that, in patients who survived more than 12 months, a lower expression of hsa-miR-335-5p was correlated with a better prognosis. It would be convenient to evaluate a larger panel of miRNAs, including miRNAs expressed in a limited number of cell types or with a low number targets, to obtain more specific candidates for developing a robust test for the diagnosis/prognosis of GC.
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BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience a considerable disease burden, evident in symptomatic and psychological spheres. Advanced cancer represents a complex scenario for patients and the healthcare team. Early palliative care (EPC) has been proven as a clinically meaningful strategy in this context by several randomized trials but not in a resource-limited setting. This study aimed to evaluate the effect of EPC compared with standard oncological care (SOC) in patients with metastatic NSCLC in Mexico. MATERIALS AND METHODS: A prospective, randomized clinical trial was conducted at Instituto Nacional de Cancerologia in Mexico. All patients had histologically confirmed metastatic NSCLC without previous treatment. Patients were randomly assigned (1:1) to receive SOC or SOCâ +â EPC. The EPC group was introduced to the palliative care team at baseline after randomization, which was integrated by psychologists, bachelor's in nutrition, specialized nurses, and physicians. Patients randomized to this arm had programmed visits to meet with the team at baseline and through the 2nd, 4th-, and 6th cycles thereafter. The primary endpoint was overall survival (OS); secondary outcomes included quality of life (QoL), anxiety and depression, and symptom intensity. They were assessed using the instruments EORTC QLQ-C30 questionnaire, Edmonton Symptom Assessment Scale (ESAS), and the Hospital Anxiety and Depression Scale (HADS) (clinicaltrials.gov [NCT01631565]). Questionnaires were completed at baseline, at 2nd, 4th, and 6th cycles of treatment. RESULTS: Between March 2012 and June 2015, 201 patients were assessed for eligibility and 146 were enrolled and allocated to receive EPC (73) or SOC (73). Median OS for patients in the EPC vs SOC arm was 18.1 months (95% CI, 7.9-28.4) and 10.5 months (95% CI, 4.7-16.2) (Pâ =â .029). Having a poor performance status (HR 1.7 [1.2-2.5]; Pâ =â .004) and allocation to the control group (HR 1.5 [1.03-2.3]; Pâ =â .034) were independently associated with a worse OS. Those patients with a global QoLâ >â 70 at baseline had a better OS if they were In the EPC arm (38.7 months (95% CI, 9.9-67.6) vs SOC 21.4 months (95% CI, 12.4-30.3)). Mean QoL had a numerical improvement in patients allocated to EPC after 6 cycles of follow-up, nonetheless this difference was not statistically significant (55.1â ±â 23.7 vs 56.9â ±â 25.3; Pâ =â .753). There were no significant differences in anxiety and depression at all study points. CONCLUSIONS: EPC is associated with a significant improvement in OS, although, we observed that the greatest benefit of providing EPC was observed in those with a global QoLâ >â 70 at baseline. This study did not identify significant changes in terms of QoL or symptom burden between the study groups after follow-up. Evidence robustly suggests that EPC should be considered part of the multidisciplinary treatment of metastatic NSCLC patients since diagnosis. According to our study, EPC can be implemented in low- or middle-income countries (LMIC).
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BACKGROUND: Information on hook-wire guided (HWG) surgery for non-palpable thyroid carcinoma (TC), locoregional-recurrent disease (LRRD) is scarce. We analyze the results of HWG resection compared with the traditional procedure. METHODS: Cohort study performed between January 2016 and December 2020. Patients with TC and non-palpable LRRD were included. A "Standard cohort", patients with non-HWG resection and "HWG cohort", with HWG resection of LRRD were defined. Surgical morbidity, re-recurrent/progressive disease (RRD), and re-recurrence-free survival (RRFS) were defined. RESULTS: 43 and 23 patients were assigned to the Standard or HWG cohorts, respectively. Complications occurred in 28 % and 17.3 % of cases, in control or HWG cohorts, respectively. HWG cohort, size of primary TC, 131I dose >150 mCi, and thyroglobulin level >1 ng/ml at detection of LRRD were associated with RRD. HWG cohort, thyroglobulin level at LRRD, 131I treatment, and dose were associated with RRFS. CONCLUSIONS: HWG surgery of non-palpable TC LRRD had improved results regarding surgical morbidity, RRD, and RRFS.
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Tiroglobulina , Neoplasias de la Tiroides , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Tiroidectomía/métodos , Recurrencia Local de Neoplasia/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patologíaRESUMEN
BACKGROUND: Cancer-related cachexia (CRC) has a profound impact on health-related quality of life (HRQL), and both were reported to be associated with overall survival (OS). We hypothesize that HRQL and CRC are associated with OS. This study analyzed the impact of CRC on HRQL and its prognostic value in women with cervical cancer (CC). METHODS: A cohort study including consecutive women with CC treated from October 2020 to October 2021 in a cancer center. Cox's model defined the associations of immune, biochemical and nutritional parameters, clinical cachexia classifications and HRQL with OS. RESULTS: Two hundred forty-four consecutive women with CC were included. Cachexia classifications and several scales of the QLQ-C30 were associated with OS by bivariate but not by multivariate analysis. QLQ-CX24 scales were not associated with OS. The prognostic nutritional index (PNI) (hazard ratio (HR) 0.828; 95% confidence interval (CI) 0.766-0.896), Food aversion (HR 0.95; 95% CI 0.924-0.976), Eating difficulties (HR 1.041; 95% CI 1.013-1.071), Loss of control (HR 4.131; 95% CI 1.317-12.963), Forced self to eat (1.024; 95% CI 1.004-1.044) and Indigestion (HR 0.348; 95% CI 0.131-0.928) scales of the QLQ-CAX24 were independently associated with OS by multivariate analysis (p = 1.9×10-11). CONCLUSION: This model permitted a clear stratification of prognostic subgroups. The PNI and several QLQ-CAX24 scales were associated with OS in women with CC. CRC, defined by several cachexia classifications, was not an independent prognostic factor. These findings require confirmation because of their possible diagnostic, therapeutic and prognostic implications.The prognostic nutritional index and several QLQ-CAX24 scales were associated with overall survival in women with cervical cancer. Cancer-related cachexia, defined by several cachexia classifications, was not an independent prognostic factor, neither The International Federation of Gynecology and Obstetrics (FIGO) stage classifications.
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Calidad de Vida , Neoplasias del Cuello Uterino , Humanos , Femenino , Caquexia/etiología , Neoplasias del Cuello Uterino/complicaciones , Estudios de Cohortes , PronósticoRESUMEN
Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.
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Carcinoma , Neoplasias del Colon , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias del Colon/cirugía , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Carcinoma/patología , Estadificación de NeoplasiasRESUMEN
Chemoresistance to standard neoadjuvant treatment commonly occurs in locally advanced breast cancer, particularly in the luminal subtype, which is hormone receptor-positive and represents the most common subtype of breast cancer associated with the worst outcomes. Identifying the genes associated with chemoresistance is crucial for understanding the underlying mechanisms and discovering effective treatments. In this study, we aimed to identify genes linked to neoadjuvant chemotherapy resistance in 62 retrospectively included patients with luminal breast cancer. Whole RNA sequencing of 12 patient biopsies revealed 269 differentially expressed genes in chemoresistant patients. We further validated eight highly correlated genes associated with resistance. Among these, solute carrier family 12 member 1 (SLC12A1) and glutamate ionotropic AMPA type subunit 4 (GRIA4), both implicated in ion transport, showed the strongest association with chemoresistance. Notably, SLC12A1 expression was downregulated, while protein levels of glutamate receptor 4 (GLUR4), encoded by GRIA4, were elevated in patients with a worse prognosis. Our results suggest a potential link between SLC12A1 gene expression and GLUR4 protein levels with chemoresistance in luminal breast cancer. In particular, GLUR4 protein could serve as a potential target for drug intervention to overcome chemoresistance.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos/genética , Proteínas de Transporte de Membrana , Terapia Neoadyuvante , Estudios Retrospectivos , Miembro 1 de la Familia de Transportadores de Soluto 12RESUMEN
ABSTRACT Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.
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Dihydrosphingolipids are lipids biosynthetically related to ceramides. An increase in ceramides is associated with enhanced fat storage in the liver, and inhibition of their synthesis is reported to prevent the appearance of steatosis in animal models. However, the precise association of dihydrosphingolipids with non-alcoholic fatty liver disease (NAFLD) is yet to be established. We employed a diet induced NAFLD mouse model to study the association between this class of compounds and disease progression. Mice fed a high-fat diet were sacrificed at 22, 30 and 40 weeks to reproduce the full spectrum of histological damage found in human disease, steatosis (NAFL) and steatohepatitis (NASH) with and without significant fibrosis. Blood and liver tissue samples were obtained from patients whose NAFLD severity was assessed histologically. To demonstrate the effect of dihydroceramides over NAFLD progression we treated mice with fenretinide an inhibitor of dihydroceramide desaturase-1 (DEGS1). Lipidomic analyses were performed using liquid chromatography-tandem mass spectrometry. Triglycerides, cholesteryl esters and dihydrosphingolipids were increased in the liver of model mice in association with the degree of steatosis and fibrosis. Dihydroceramides increased with the histological severity observed in liver samples of mice (0.024 ± 0.003 nmol/mg vs 0.049 ± 0.005 nmol/mg, non-NAFLD vs NASH-fibrosis, p < 0.0001) and patients (0.105 ± 0.011 nmol/mg vs 0.165 ± 0.021 nmol/mg, p = 0.0221). Inhibition of DEGS1 induce a four-fold increase in dihydroceramides improving steatosis but increasing the inflammatory activity and fibrosis. In conclusion, the degree of histological damage in NAFLD correlate with dihydroceramide and dihydrosphingolipid accumulation. LAY SUMMARY: Accumulation of triglyceride and cholesteryl ester lipids is the hallmark of non-alcoholic fatty liver disease. Using lipidomics, we examined the role of dihydrosphingolipids in NAFLD progression. Our results demonstrate that de novo dihydrosphingolipid synthesis is an early event in NAFLD and the concentrations of these lipids are correlated with histological severity in both mouse and human disease.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/patología , Fibrosis , Triglicéridos , CeramidasRESUMEN
BACKGROUND: The burden of having neurologic symptoms (NS) in cancer patients has scantly been studied; therefore, we performed a study whose purpose was to measure the impact of having clinically active (NS) on the quality of life (QoL) of non-primary CNS cancer patients. METHODS: Patients with systemic cancer (non-primary CNS cancer) sent for neurological evaluation at a single cancer center (INCAN) were prospectively invited to respond the EORTC-QLQ-C30 and BN20 questionnaires. Associations of the questionnairés items were blindly measured for the following groups: NS+ or not (NS-) and having active cancer (AC+) or not (AC-). RESULTS: Of 205 patients aged 55.4 ± 15.4 years, 122 (60%) had NS+ and 107 (52%) AC +. The NS+ group (compared with the NS-) showed a significant worse perception in the following scales/items of the EORTC QLQ-C30: physical functioning (median 86 vs. 92, P = 0.012), role functioning (66 vs. 100, P < 0.001), emotional functioning (75 vs. 83, P = 0.005), cognitive functioning (66 vs. 83, P < 0.001), fatigue (33 vs. 22, P < 0.001), nausea and vomiting (P = 0.021), pain (33 vs. 16, P < 0.001), insomnia (33 vs. 0, P = 0.011), appetite loss (P = 0.021), and global health (66 vs. 75, P = 0.001). CONCLUSION: In patients with systemic (non-CNS) cancer, the QoL is significantly worse for patients with active neurologic symptoms.
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Neoplasias , Calidad de Vida , Humanos , Calidad de Vida/psicología , Neoplasias/complicaciones , Dolor/complicaciones , Náusea , Vómitos , Encuestas y CuestionariosRESUMEN
There are multiple associations between the different blood groups (ABO and RhD) and the incidence of oxidative stress-related diseases, such as certain carcinomas and COVID-19. Bioactive compounds represent an alternative to its prevention and treatment. Phycobiliproteins (PBP) are bioactive compounds present in the microalga Porphyridium cruentum and, despite its antioxidant activity, their inhibitory effect on hemolysis has not been reported. The aim of this work was to evaluate the erythroprotective potential of phycobiliproteins from P. cruentum in different blood groups. The microalga was cultured in F/2 medium under controlled laboratory conditions. Day 10 of culture was determined as the harvest point. The microalgal biomass was lyophilized and a methanolic (MetOH), Tris HCl (T-HCl), and a physiological solution (PS) ultrasound-assisted extraction were performed. Extract pigments were quantified by spectrophotometry. The antioxidant activity of the extracts was evaluated with the ABTS+â¢, DPPHâ¢, and FRAP methods, finding that the main antioxidant mechanism on the aqueous extracts was HAT (hydrogen atom transfer), while for MetOH it was SET (single electron transfer). The results of the AAPH, hypotonicity, and heat-induced hemolysis revealed a probable relationship between the different antigens (ABO and RhD) with the antihemolytic effect, highlighting the importance of bio-directed drugs.
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BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Specific and thorough identification of cancer cell subsets with higher tumorigenicity and chemoresistance, such as cancer stem cells (CSCs), could lead to the development of new and promising therapeutic targets. For better CSC identification, a complete or extended surface marker phenotype is needed to provide increased specificity for new cell targeting approaches. Our goal is to identify and characterize a putative extended phenotype for CSCs derived from patients with GC before treatment, as well as to evaluate its clinical value. In addition, we aim to ensure that cells with this phenotype have stemness and self-renewal capabilities. METHODS: This is a cohort study including 127 treatment-naïve patients with GC who attended the Instituto Nacional de Cancerología. Multiparametric flow cytometry analysis was performed to determine the extended phenotype of cells derived from gastric biopsies. The tumorigenic capability of cells identified in patients was assessed in a zebrafish model. RESULTS: CD24+CD44+CD54+EpCAM+ cells were present in all treatment-naïve patients included, with a median abundance of 1.16% (0.57-1.89%). The percentage of CD24+CD44+CD54+EpCAM+ cells was categorized as high or low using 1.19% as the cutoff for the CD24+CD44+CD54+EpCAM+ cell subset. Additionally, a higher TNM stage correlated with a higher percentage of CD24+CD44+CD54+EpCAM+ cells (Rho coefficient 0.369; p < 0.0001). We also demonstrated that a higher percentage of CD24+CD44+CD54+EpCAM+ cells was positively associated with metastasis. The metastatic potential of these cells was confirmed in a zebrafish model. Ultimately, under our conditions, we conclude that CD24+CD44+CD54+EpCAM+ cells are true gastric cancer stem cells (GCSCs). CONCLUSION: The CD24+CD44+CD54+EpCAM+ cells present in tissue samples from patients are true GCSCs. This extended phenotype results in better and more specific characterization of these highly tumorigenic cells. The relative quantification of CD24+CD44+CD54+EpCAM+ cells has potential clinical value, as these cells are associated with metastatic disease, making their presence an additional prognostic marker and possibly a target for the design of new antineoplastic treatments in the era of precision oncology. Overall, the extended CD24+CD44+CD54+EpCAM+ phenotype of GCSCs could support their isolation for the study of their stemness mechanisms, leading to the identification of better molecular targets for the development of both new therapeutic approaches such as oncoimmunotherapy and new diagnostic and clinical prognostic strategies for GC.
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Neoplasias Gástricas , Pez Cebra , Animales , Biomarcadores de Tumor/metabolismo , Antígeno CD24/genética , Línea Celular Tumoral , Estudios de Cohortes , Molécula de Adhesión Celular Epitelial/genética , Molécula de Adhesión Celular Epitelial/metabolismo , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Células Madre Neoplásicas/metabolismo , Medicina de Precisión , Neoplasias Gástricas/metabolismo , Pez Cebra/metabolismo , Molécula 1 de Adhesión Intercelular , HumanosRESUMEN
Cancer-related cachexia (CRC) is a common phenomenon in cervical cancer (CC), severely affecting clinical response, drug toxicity and survival. The patients' point of view should be evaluated to quantify the impact of CRC, and adequate instruments to do so are required. Thus, the study aimed to validate the Mexican-Spanish version of the QLQ-CAX24 instrument in women with CC. A cohort of women with CC answered the EORTC QLQ-C30 and QLQ-CAX24 instruments. The psychometric and clinimetric properties of the instruments were assessed. Two hundred and forty-four women were included; the mean age was 50 years (IQR: 41-60) and 188 (77%) were first diagnosed in locally advanced stages. The QLQ-CAX24 internal consistency test demonstrated adequate convergent (Spearman correlation coefficient 0.08-0.709) and divergent validity (Spearman correlation coefficient 0.006-0.471). Cronbach's alpha coefficients of the three multi-item scales were >0.5 (minimum 0.539, maximum 0.84). Patients with decreased handgrip strength, low fat-free mass, or high C-reactive protein levels had worse QLQ-CAX24 scale scores. Cachexia was diagnosed with the SCRINIO, Fearon and Evans criteria, and 31.5, 32.4 and 38.5% of women had cachexia, respectively. Patients with cachexia had the worst scores in terms of quality of life. The test re-test analysis did not show differences between visits in patients without malnutrition. The Mexican-Spanish version of the QLQ-CAX24 instrument is reliable and valid. Low handgrip strength, low fat-free mass and high C-reactive protein levels were associated with poor scale scores.
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Calidad de Vida , Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Neoplasias del Cuello Uterino/complicaciones , Caquexia/etiología , Proteína C-Reactiva , Fuerza de la Mano , Encuestas y Cuestionarios , Psicometría , Reproducibilidad de los ResultadosRESUMEN
The Hispanic population, compared with other ethnic groups, presents a more aggressive gastric cancer phenotype with higher frequency of diffuse-type gastric adenocarcinoma (GA); this could be related to the mutational landscape of GA in these patients. Using whole-exome sequencing, we sought to present the mutational landscape of GA from 50 Mexican patients who were treated at The Instituto Nacional de Cancerología from 2019 to 2020. We performed a comprehensive statistical analysis to explore the relationship of the genomic variants and clinical data such as tumor histology and presence of signet-ring cell, H. pylori, and EBV. We describe a potentially different mutational landscape between diffuse and intestinal GA in Mexican patients. Patients with intestinal-type GA tended to present a higher frequency of NOTCH1 mutations, copy number gains in cytobands 13.14, 10q23.33, and 12q25.1, and copy number losses in cytobands 7p12, 14q24.2, and 11q13.1; whereas patients with diffuse-type GA tended to present a high frequency of CDH1 mutations and CNV gains in cytobands 20q13.33 and 22q11.21. This is the first description of a mutational landscape of GA in Mexican patients to better understand tumorigenesis in Hispanic patients and lay the groundwork for discovering potential biomarkers and therapeutic targets.
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Adenocarcinoma , Helicobacter pylori , Neoplasias Gástricas , Adenocarcinoma/genética , Antígenos CD/genética , Cadherinas/genética , Helicobacter pylori/genética , Humanos , Mutación , Neoplasias Gástricas/patología , Secuenciación del ExomaRESUMEN
Molecular mechanisms behind obesity and sex-related effects in adipose tissue remain elusive. During adipocyte expansion, adipocytes undergo drastic remodelling of lipid membrane compositions. Lipid flippases catalyse phospholipid translocation from exoplasmic to the cytoplasmic leaflet of membranes. The present study aimed to analyse the effect of sex, obesity, and their interactions on the gene expression of two lipid flippases-ATP8A1 and ATP8B1-and their possible microRNA (miR) modulators in visceral adipose tissue (VAT). In total, 12 normal-weight subjects (5 premenopausal women and 7 men) and 13 morbidly obese patients (7 premenopausal women and 6 men) were submitted to surgery, and VAT samples were obtained. Gene expression levels of ATP8A1, ATP8B1, miR-548b-5p, and miR-4643 were measured in VAT. Our results showed a marked influence of obesity on VAT ATP8A1 and ATP8B1, although the effects of obesity were stronger in men for ATP8A1. Both genes positively correlated with obesity and metabolic markers. Furthermore, ATP8B1 was positively associated with miR-548b-5p and negatively associated with miR-4643. Both miRs were also affected by sex. Thus, lipid flippases are altered by obesity in VAT in a sex-specific manner. Our study provides a better understanding of the sex-specific molecular mechanisms underlying obesity, which may contribute to the development of sex-based precision medicine.
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CONTEXT: The prevalence of obesity and hypertriglyceridemia is an alarming worldwide health issue. Mitochondria play a central role in these disorders as they control cell metabolism. OBJECTIVE: The aim of the present study was to characterize mitochondrial homeostasis in subcutaneous and visceral adipose tissue (SAT and VAT) in grade III obese patients with and without hypertriglyceridemia. Moreover, this study presents the evaluation of mitochondrial fitness as a marker for hypertriglyceridemia improvement. PATIENTS: Eight control and 12 hypertriglyceridemic (HTG) grade III obese subjects undergoing bariatric surgery were included. MAIN OUTCOME MEASURES: Anthropometric and biochemical data were obtained before and 3 months after surgery. Mitochondrial homeostasis was evaluated by mitochondrial DNA (mtDNA), gene expression and protein abundance in SAT and VAT. RESULTS: Mitophagy-related gene expression was increased in HTG SAT and VAT, while mitochondrial marker gene expression and mtDNA were decreased, indicating an altered mitochondrial homeostasis in HTG. Mitophagy protein abundance was increased in VAT of those subjects that did not improve their levels of triglycerides after bariatric surgery, whereas mitochondrial protein was decreased in the same tissue. Indeed, triglyceride levels positively correlated with mitophagy-related genes and negatively with mitochondrial content markers. Moreover, mitochondria content and mitophagy markers seem to be significant predictors of hypertriglyceridemia and hypertriglyceridemia remission. CONCLUSIONS: Mitochondrial homeostasis of adipose tissue is altered in hypertriglyceridemic patients. At the protein level, mitochondria content and mitophagy are potential markers of hypertriglyceridemia remission in obese patients after bariatric surgery. These results may contribute to the implementation of a clinical approach for personalized medicine.
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Hipertrigliceridemia , Obesidad , Biomarcadores/metabolismo , ADN Mitocondrial , Homeostasis , Humanos , Hipertrigliceridemia/complicaciones , Hipertrigliceridemia/genética , Hipertrigliceridemia/metabolismo , Grasa Intraabdominal/metabolismo , Mitocondrias/metabolismo , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/cirugía , Grasa Subcutánea/metabolismoRESUMEN
BACKGROUND: The expression of liver kinase B1 (LKB-1) has been associated with prognosis in squamous cell carcinoma of the oral cavity (SCCOC). This study aimed to define the prognostic role of LKB-1 expression for patients with SCCOC and the suitability of its integration into a multivariate prognostic model. METHODS: A retrospective cohort study of patients with SCCOC was conducted in a cancer center. Expression of LKB-1 was evaluated by immunohistochemistry, and multivariate analysis defined prognostic factors associated with recurrence, recurrence-free survival (RFS), and overall survival (OS). The logistic regression model was used to construct a predictive computer software program. RESULTS: Of the 201 patients in this study, 104 (51.7%) experienced recurrence of their disease. Lower expression of LKB-1, high-risk histopathology, and advanced tumor-node-metastasis (TNM) stages were independent factors via multivariate analysis associated with the increased recurrence risk, poor RFS, and poor OS. If lack of LKB-1 expression is considered the reference category, the factors independently associated with recurrence were low (odds ratio [OR], 0.157; 95% confidence interval [CI], 0.044-0.557), intermediate (OR, 0.073; 95% CI, 0.017-0.319), and intense (OR, 0.047; 95% CI, 0.007-0.304) expression of LKB-1. This model permitted construction of a computer software program capable of prediction with receiver operating characteristic analysis (area under the curve, 0.925) and led to the definition of five prognostic groups with a biologic gradient. CONCLUSION: These results suggest that LKB-1 expression in patients with SCCOC is of robust prognostic value and complements the TNM staging system. The proposed model requires external validation in prospective observational studies.
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PURPOSE: To describe our experience upon developing and implementing a hospital-based cancer registry (HBCR) in a quaternary-level of care private non-profit academic medical center in Cali, Colombia. METHODS: HBCRs capture, in a given institution, every single patient with a confirmed malignancy. In this study, all cases evaluated between 2014 and 2018 were included in the HBCR. In compliance with the International Agency for Research on Cancer recommendations, cases were classified as analytic or non-analytic. Data derived from an exhaustive selection of patients was stored in a computing platform owned by the institution, meeting the 2016 Facility Oncology Registry Data Standards recommendations. Quality control was performed by evaluating comparability, timeliness, validity, and completeness. RESULTS: A total of 24,405 new cases were registered between 2014 and 2018, from which 4253 (17.4%) died. Among all cases, based on the anatomic location, most common malignancies were breast (n = 1554), thyroid (n = 1346), hematolymphoid (n = 1251), prostatic (n = 805), and colorectal (n = 624). The behavior of the new cases was consistent with an incremental trend. CONCLUSION: Upon implementing the HBCR, major challenges were identified (i.e., a precise definition of cases, the development of processes for capturing new cases, a standardized data collection strategy, and carrying-out an appropriate patient follow-up). Based on our experience, the success of an HBCR largely relies on the interest from the institution, the engagement of stakeholders and financial support, that is, it depends on the adequate access over time to funding, technological, and staffing resources.
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Hospitales , Neoplasias , Colombia/epidemiología , Humanos , Renta , Neoplasias/epidemiología , Sistema de RegistrosRESUMEN
In this article, a series of original manuscripts and reviews published between 2015 and 2021 in the Revista de Investigación Clínica -Clinical and Translational Investigation- chosen by the Editors are presented. The articles were selected according to what the editors considered are the most outstanding contributions based on originality, and the potential impact of the information provided on translational medicine, rather than on the number of readings and citations.