RESUMEN
Background: Minimally invasive hemorrhoid surgeries like Doppler-Guided Hemorrhoidal Artery Ligation (DGHAL) and Stapled Hemorrhoidopexy (PPH) offer benefits over traditional methods. This study investigated public perceptions and attitudes towards these surgeries, exploring awareness, preferences, and influencing factors. Methods: A detailed questionnaire was disseminated to 2011 participants from various regions of Taiwan in December 2023, gathering data on demographics, understanding of minimally invasive surgery, and attitudes towards hemorrhoid surgery. Chi-square tests were used for analysis (p < 0.05). Results: Hemorrhoid prevalence was similar across sexes and age groups. About 70 % preferred medical centers or district hospitals for surgery. Postoperative complications were a primary concern, with significant sex differences. Approximately 70 % preferred minimally invasive surgery if costs were below NT$50,000. Medical personnel showed higher awareness of minimally invasive surgery benefits. Most participants relied on personal networks and medical social media for information. Conclusions: The study revealed generally positive perceptions of minimally invasive hemorrhoid surgery, with cost being a significant factor. Knowledge gaps exist, particularly among non-medical personnel. Future initiatives should aim to enhance public awareness of minimally invasive surgery benefits, and policy considerations should address financial aspects of healthcare decisions.
RESUMEN
BACKGROUND: With its minimally invasive approach, laparoscopic surgery has transformed the medical landscape. As the demand for these procedures escalates, there is a pressing need for adept surgeons trained in laparoscopic techniques. However, current training often falls short of catering to medical school education. This study evaluates the impact of a custom-designed laparoscopic training workshop on medical students' surgical skills and career aspirations. METHODS: This prospective experimental study was conducted at the E-Da hospital in Kaohsiung City, Taiwan. Medical students from Taiwanese medical schools undergoing Clerk 5, Clerk 6, and Postgraduate Year 1 and 2 were invited to participate. Medical students (n = 44) underwent an endoscopic skill training workshop consisting of lectures, box training, and live tissue training. The trainees performed multiple tasks before and after training using our objective evaluation system. The primary outcome was assessed before and after training through a questionnaire assessing the influence of training on students' interest in surgery as a career. The secondary outcome measured improvement in skill acquisition, comparing the task completion time pre- and post-workshop. For the primary outcome, descriptive statistics were used to summarize the questionnaire responses, and paired t-tests were performed to determine significant changes in interest levels post-workshop. For the secondary outcome, paired t-tests were used to compare the time recorded pre- and post-training. RESULTS: Post-training, participants exhibited significant proficiency gains, with task completion times reducing notably: 97 s (p = 0.0015) for Precision Beads Placement, 88.5 s (p < 0.0001) for Beads Transfer Exercise, 95 s (p < 0.0001) for Precision Balloon Cutting, and 137.8 s (p < 0.0001) for Intracorporeal Suture. The primary outcome showcased an increased mean score from 8.15 pre-workshop to 9.3 post-workshop, indicating a bolstered interest in surgery as a career. Additionally, post-training sentiment analysis underscored a predominant inclination toward surgery among 88% of participants. CONCLUSION: The custom-designed laparoscopic workshop significantly improved technical skills and positively influenced students' career aspirations toward surgery. Such hands-on training workshops can play a crucial role in medical education, bridging the gap between theoretical knowledge and practical skills and potentially shaping the future of budding medical professionals.
Asunto(s)
Selección de Profesión , Competencia Clínica , Laparoscopía , Estudiantes de Medicina , Humanos , Laparoscopía/educación , Estudios Prospectivos , Femenino , Taiwán , Masculino , Educación de Pregrado en Medicina/métodos , Adulto Joven , AdultoRESUMEN
BACKGROUND: The incidence of early-onset colorectal cancer (CRC) is increasing. Many guidelines recommend initiating screening at 45 years. This study investigated the detection rate of advanced colorectal neoplasm (ACRN) by using fecal immunochemical tests (FITs) in individuals aged 40-49 years. METHODS: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2022. The primary outcomes were the detection rates and positive predictive values of FITs for ACRN and CRC in people aged 40-49 (younger age group) and ≥50 years (average risk group). RESULTS: Ten studies with 664,159 FITs were included. The FIT positivity rate was 4.9% and 7.3% for the younger age and average risk groups, respectively. Younger individuals with positive FIT results had significantly higher risks of ACRN (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.79-3.73) or CRC (OR 2.86, 95% CI 1.59-5.13) than did individuals in the average-risk group, regardless of FIT results. Individuals aged 45-49 years with positive FIT results had a similar risk of ACRN (OR 0.80, 95% CI 0.49-1.29) to that of people aged 50-59 years with positive FIT results, although significant heterogeneity was observed. The positive predictive values of the FIT were 10-28.1% for ACRN and 2.7-6.8% for CRC in the younger age group. CONCLUSION: The detection rate of ACRN and CRC based on FITs in individuals aged 40-49 years is acceptable, and the yield of ACRN might be similar between individuals aged 45-49 and 50-59 years. Further prospective cohort and cost-effective analysis are warranted.
RESUMEN
According to the Health Promotion Administration in the Ministry of Health and Welfare statistics in Taiwan, over ten thousand women have breast cancer every year. Mammography is widely used to detect breast cancer. However, it is limited by the operator's technique, the cooperation of the subjects, and the subjective interpretation by the physician. It results in inconsistent identification. Therefore, this study explores the use of a deep neural network algorithm for the classification of mammography images. In the experimental design, a retrospective study was used to collect imaging data from actual clinical cases. The mammography images were collected and classified according to the breast image reporting and data-analyzing system (BI-RADS). In terms of model building, a fully convolutional dense connection network (FC-DCN) is used for the network backbone. All the images were obtained through image preprocessing, a data augmentation method, and transfer learning technology to build a mammography image classification model. The research results show the model's accuracy, sensitivity, and specificity were 86.37%, 100%, and 72.73%, respectively. Based on the FC-DCN model framework, it can effectively reduce the number of training parameters and successfully obtain a reasonable image classification model for mammography.
RESUMEN
Clerodane diterpene, a class of bicyclic diterpenoids, is found in hundreds of plant species. 16-hydroxycleroda-3,13-dien-15,16-olide (CD) can be isolated from the plant Polyalthia longifolia and has been applied against oral cancer and glioma by xenograft model. In this study, we aim to explore its antitumour action by examining its histone deacetylase (HDAC) activity and integrin-associated intracellular signalling pathway on T24 human bladder cancer (BC) cells. Our results revealed that CD-inhibited colony formation, HDAC activity, HDAC (1, 2 and 3) mRNA and cell spreading on fibronectin-coated surfaces in a concentration-dependent manner. Furthermore, decreased cFLIP and increased caspase-8 cleavage accompanied CD-induced cell death. At non-toxic concentrations, CD blocked the migration and invasion of T24 cells. CD hindered migration and invasion by the downregulation of fibronectin, integrin α5ß1, ß-catenin, FAK, vinculin and Rho A, as well as by reduction of phosphorylated glycogen synthase kinase 3ß (pGSK3ß), pSrc, pstat3 and pNFκB. We observed that the MMP9 gene was closely linked with prognosis of patients with bladder cancer. MMP9 protein levels and activity were largely attenuated by CD in a concentration-dependent manner. In conclusion, CD-induced caspase-8-dependent apoptosis and suppressed migration and invasion by blocking several intracellular signalling pathways, including downregulation of HDAC activity and integrin-FAK and MMP9 pathways.
Asunto(s)
Diterpenos de Tipo Clerodano , Neoplasias de la Vejiga Urinaria , Humanos , Proteína-Tirosina Quinasas de Adhesión Focal , Anoicis , Metaloproteinasa 9 de la Matriz/genética , Integrinas , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Histona Desacetilasas/genética , Caspasa 8/genética , FibronectinasRESUMEN
Objectives: Recently, molecular medicine targeting Folate Receptor Alpha (FOLR1), which mediates intracellular folate uptake and tumor cell proliferation, has been identified in several malignancies. However, the association between FOLR1 expression and rectal cancer remains unclear. Methods: Immunostaining of FOLR1 was performed on biopsy specimens from 172 rectal cancer patients undergoing preoperative chemoradiotherapy (CRT). FOLR1 expression was measured and divided into low (0+-2+) or high (3+-4+) level. Correlations between FOLR1 status and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival, and metastasis-free survival (MeFS) were analyzed, retrospectively. Results: High FOLR1 expression was significantly associated with advanced post-treatment tumor and nodal status (T3-4; N1-2, P = .001), vascular invasion (P = .042), perineural invasion (P = .012), and poor regression change after CRT (P = .001). In uni- and multi-variable survival analysis, FOLR1 overexpression remained a significant predictor of lower DSS (hazard ratio [HR], 2.328; 95% confidence interval [CI], 1.014-5.344; P = .046) and MeFS (HR, 2.177; 95% CI, 1.000-1.1286; P = .050). Conclusion: These results indicate that high FOLR1 status is associated with aggressive tumor behavior, poor response to CRT, and worse survival. Therefore, FOLR1 expression at initial biopsy may be useful in predicting outcomes and also be a target for the exploration of FOLR1-based therapeutic agents.
Asunto(s)
Receptor 1 de Folato , Neoplasias del Recto , Humanos , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Estudios Retrospectivos , Pronóstico , Biomarcadores de Tumor , Neoplasias del Recto/genética , Neoplasias del Recto/terapia , QuimioradioterapiaRESUMEN
For rectal cancer patients with stage T3-4 disease or positive lymph node, neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment, but the clinical outcomes are still far from satisfactory. Accordingly, a more precise predictive tool such as genetic biomarkers is urgently required to optimize therapy decisions. Colorectal cancer (CRC) development has been considerably correlated with cellular metabolic process involving nucleotides, but the underlying molecular mechanisms remain unclear. In this study, we employed a transcriptome dataset comprising 46 rectal adenocarcinoma patients undergoing preoperative CCRT and focused on nucleobase-containing compound metabolic process (GO: 0055134) for data mining. We identified solute carrier family 28 member 2 (SLC28A2) as the most considerably upregulated gene among rectal cancer patients with CCRT resistance. Afterwards, there were a total of 172 rectal cancer tissue blocks procuring from our biobank, and the immunointensity of SLC28A2 was appraised utilizing immunohistochemical staining. Strong SLC28A2 immunointensity was significantly linked to female patients (p = 0.032), vascular invasion (p = 0.021), and post-CCRT tumor invasion and regional lymph node involvement (p < 0.001 and p = 0.005). Notably, patients with strong SLC28A2 immunointensity had no tumor downstaging (p < 0.001). Univariate analysis revealed that high SLC28A2 immunoexpression was considerably unfavorably linked to all three endpoints: local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS) (all p ≤ 0.0333). Moreover, both high SLC28A2 immunoexpression and low tumor regression grade were independently unfavorable prognostic factors for all three endpoints (all p ≤ 0.013) in the multivariate analysis. Utilizing function prediction analysis, SLC28A2 upregulation was more likely to be linked with stem cell homeostasis in rectal cancer. In brief, we demonstrated that high SLC28A2 immunoexpression is substantially linked to an advanced stage, poor response to CCRT, and worse patient survival. Consequently, SLC28A2 expression can be a valuable predictive and prognostic marker for rectal cancer patients and be an encouraging therapeutic target for those with CCRT resistance.
Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Femenino , Pronóstico , Biomarcadores de Tumor/análisis , Neoplasias del Recto/patología , Quimioradioterapia , Supervivencia sin EnfermedadRESUMEN
Some studies showed that when distant metastasis or locally advanced tumors were observed, the participation of 2 or more operating surgeons (combined surgery) in the operation could improve the prognosis of patients. The multispecialty operative team would perform combined surgery in colon cancer patients with some complications since 2015. The goal of this study is to confirm performing combined surgery would improve the outcomes of colon cancer patients. A retrospective observational study was conducted, which involved all colon cancer patients between November 2015 and December 2019 at one would-be medical center. Patients were divided into 3 cohorts: those with complicated cases and had combined surgery (C_2S), those with complicated cases and had surgery performed by a single surgeon (C_1S), and those with uncomplicated cases and had surgery performed by a single surgeon (NC_1S). Overall survival and disease-free survival were compared among the 3 groups. A total of 296 colon cancer patients during the study period. Among them, 35 were C_2S, 87 were C_1S, and 174 were NC_1S. Patients in the NC_1S group had significantly higher 12-, 24-, and 36-month OS rates compared to those in the C_1S group (P < .01). In contrast, there was no significant difference in overall survival among patients in the NC_1S and C_2S group (P =.15). The quality of surgery must be impact the prognosis, especially in the individual who was complicated case, the survival in patients who had surgery performed by multispecialty operative team would be improved.
Asunto(s)
Neoplasias del Colon , Procedimientos Quirúrgicos del Sistema Digestivo , Neoplasias del Colon/cirugía , Humanos , Pronóstico , Estudios Retrospectivos , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Dividing liver organs or lesions depicting on computed tomography (CT) images could be applied to help tumor staging and treatment. However, most existing image segmentation technologies use manual or semi-automatic analysis, making the analysis process costly and time-consuming. OBJECTIVE: This research aims to develop and apply a deep learning network architecture to segment liver tumors automatically after fine tuning parameters. METHODS AND MATERIALS: The medical imaging is obtained from the International Symposium on Biomedical Imaging (ISBI), which includes 3D abdominal CT scans of 131 patients diagnosed with liver tumors. From these CT scans, there are 7,190 2D CT images along with the labeled binary images. The labeled binary images are regarded as gold standard for evaluation of the segmented results by FCN (Fully Convolutional Network). The backbones of FCN are extracted from Xception, InceptionresNetv2, MobileNetv2, ResNet18, ResNet50 in this study. Meanwhile, the parameters including optimizers (SGDM and ADAM), size of epoch, and size of batch are investigated. CT images are randomly divided into training and testing sets using a ratio of 9:1. Several evaluation indices including Global Accuracy, Mean Accuracy, Mean IoU (Intersection over Union), Weighted IoU and Mean BF Score are applied to evaluate tumor segmentation results in the testing images. RESULTS: The Global Accuracy, Mean Accuracy, Mean IoU, Weighted IoU, and Mean BF Scores are 0.999, 0.969, 0.954, 0.998, 0.962 using ResNet50 in FCN with optimizer SGDM, batch size 12, and epoch 9. It is important to fine tuning the parameters in FCN model. Top 20 FNC models enable to achieve higher tumor segmentation accuracy with Mean IoU over 0.900. The occurred frequency of InceptionresNetv2, MobileNetv2, ResNet18, ResNet50, and Xception are 9, 6, 3, 5, and 2 times. Therefore, the InceptionresNetv2 has higher performance than others. CONCLUSIONS: This study develop and test an automated liver tumor segmentation model based on FCN. Study results demonstrate that many deep learning models including InceptionresNetv2, MobileNetv2, ResNet18, ResNet50, and Xception have high potential to segment liver tumors from CT images with accuracy exceeding 90%. However, it is still difficult to accurately segment tiny and small size tumors by FCN models.
Asunto(s)
Neoplasias Hepáticas , Tomografía Computarizada por Rayos X , Abdomen/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
Background: There are no randomized control trials comparing the efficacy of trifluridine/tipiracil and regorafenib in patients with metastatic colorectal cancer (mCRC). Herein, we conducted an observational study to compare the oncologic outcomes of trifluridine/tipiracil-containing regimen (TAS-102) and regorafenib-containing regimen (REG) in patients with mCRC. Material and method: Patients who were diagnosed to have mCRC in 2015 to 2021 and treated with TAS-102-containing regimen or REG-containing regimen were recruited. Monotherapy or combination therapy were all allowed in this study. Oncologic outcomes were presented with progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Results: A total of 125 patients were enrolled into our study, accounting for 50 patients with TAS-102 and 75 patients with REG. Of these patients, 64% were treated with TAS-102 or REG monotherapy, while the remaining were treated with TAS-102 combination or REG combination. In general, the median PFS and OS were 3.7 versus 2.0 months (P = 0.006) and 9.2 versus 6.8 months (P = 0.048) in TAS-102 and REG, respectively. The ORR and DCR were 44% versus 20% (P < 0.001) and 72% versus 43% (P < 0.001) in TAS-102 and REG, respectively. As for treatment strategies, the survival were significantly longer in combination than in monotherapy, no matter in TAS-102 or REG group. Multivariate analysis showed TAS-102 and combination therapy were independent predictor associated with better survival. Conclusions: Our results suggested that TAS-102 had better oncologic outcomes than REG in patients with mCRC, especially in combination. Further prospective trials are warranted to confirm our results.
RESUMEN
We present a modified technique called noninflated intracorporeal ileocolic anastomosis, which maintains the benefits of the intracorporeal technique, but has the advantages of no requirement for laparoscopic suturing.
Asunto(s)
Colectomía , Laparoscopía , Anastomosis Quirúrgica/métodos , Colectomía/métodos , Colon/cirugía , Humanos , Íleon/cirugía , Laparoscopía/métodosRESUMEN
Insufficient lymph node harvest (< 12) may lead to incorrect classification of stage I and II disease. Many studies have indicated a poor prognosis with inadequate lymph node harvest in stages I to III, but few studies have demonstrated the relationship between low lymph node harvest and T4 disease. This study aimed to identify the influence of insufficient number of lymph nodes harvested on survival in T4N0 colorectal cancer. We enrolled patients with T4N0 colorectal cancer who underwent radical resection between 2010 and 2016. A total of 155 patients were divided into 2 groups; 142 patients hadâ ≥â 12 harvested lymph nodes, and the other 13 hadâ <â 12 lymph nodes. All patients were followed up for at least 5 years. The primary outcome was the impact of the number of lymph nodes harvested on disease-free survival and overall survival, which were investigated using Kaplan-Meier survival techniques. There were no significant differences in recurrence rate, emergent or elective surgery, laparoscopic or open surgery, or chemotherapy between the 2 groups. Kaplan-Meier analyses showed no statistical differences in 5-year disease-free survival (Pâ =â .886) and 5-year overall survival (Pâ =â .832) between the groups. There were no significant differences in disease-free survival and overall survival between patients with adequate (≥ 12) and inadequate (< 12) lymph node harvest in T4N0 colorectal cancers.
Asunto(s)
Neoplasias Colorrectales , Escisión del Ganglio Linfático , Humanos , Taiwán/epidemiología , Estadificación de Neoplasias , Estudios Retrospectivos , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Neoplasias Colorrectales/patología , PronósticoRESUMEN
Data mining of a public transcriptomic rectal cancer dataset (GSE35452) from the Gene Expression Omnibus, National Center for Biotechnology Information identified the melanophilin (MLPH) gene as the most significant intracellular protein transport-related gene (GO:0006886) associated with a poor response to preoperative chemoradiation. An MLPH immunostain was performed on biopsy specimens from 172 rectal cancer patients receiving preoperative chemoradiation; samples were divided into high- and low-expression groups by H-scores. Subsequently, the correlations between MLPH expression and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) were analyzed. MLPH expression was significantly associated with CEA level (p = 0.001), pre-treatment tumor status (p = 0.022), post-treatment tumor status (p < 0.001), post-treatment nodal status (p < 0.001), vascular invasion (p = 0.028), and tumor regression grade (p < 0.001). After uni- and multi-variable analysis of five-year survival, MLPH expression was still associated with lower DSS (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178-46.920; p = 0.003) and MeFS (HR, 5.621; 95% CI, 1.762-17.931; p = 0.004). In conclusion, identifying MLPH expression could help to predict the response to chemoradiation and survival, and aid in personal therapeutic modification.
RESUMEN
PURPOSE: This study assessed the benefits and efficacy of bariatric surgery (BS) in reducing the risk of cancer in Asians with morbid obesity. METHODS: Records for patients aged between 18 and 55 years whose diagnoses corresponded with the ICD-9 codes for obesity and BS were extracted from the National Health Insurance Research Database (NHIRD) in Taiwan between 2000 and 2015. The patients who underwent BS (BS group), those who did not undergo BS (NS group), and the general population (GP group) were propensity score matched. The outcome was newly diagnosed malignancy. Data were extracted from the Registry for Catastrophic Illness Patient Database (RCIPD) of the NHIRD. RESULTS: The BS group developed significantly less malignancy (1.18%) than the GP group (1.46%, p = 0.0364). There was no statistically significant difference in malignancy risk between the BS and GP groups (aHR =1.00, p = 0.9997). The NS group developed significantly higher malignancy (2.48%) than the GP group (1.97%, p < 0.0001). There was a significantly higher malignancy risk in the NS group (aHR =1.22, p < 0.0001) than in the GP group. In the subgroup analysis, the malignancy risks of the NS group were significantly higher in the subgroup of men aged between 18 and 35 years (aHR =1.37, p = 0.003) and women aged between 18 and 35 years (aHR = 1.62, p < 0.0001), and 35-55 years (aHR = 1.27, p < 0.0001). All the subgroup analyses between the BS and GP groups demonstrated no significant differences. CONCLUSIONS: Our study demonstrated that BS reduced the risk of malignancy in patients with morbid obesity, particularly in women and young men.
Asunto(s)
Cirugía Bariátrica , Neoplasias , Obesidad Mórbida , Adolescente , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Obesidad Mórbida/cirugía , Taiwán/epidemiología , Adulto JovenRESUMEN
Two hole-transporting materials (HTMs) based on carbohelicene cores, CH1 and CH2, are developed and used in fabricating efficient and stable perovskite solar cells (PSCs). Owing to the rigid conformation of the helicene core, both compounds possess unique CH-π interactions in the crystalline packing pattern and good phase stability, which are distinct from the π-π intermolecular interactions of conventional planar and spiro-type molecules. PSCs based on CH1 and CH2 as HTMs deliver excellent device efficiencies of 19.36 and 18.71%, respectively, outperforming the control device fabricated with spiro-OMeTAD (18.45%). Furthermore, both PSCs exhibit better ambient stability, with 90% of initial performance retained after aging with a 50-60% relative humidity at 25 °C for 500 h. Due to the low production cost of both compounds, these newly designed carbohelicene-type HTMs have the potential for the future commercialization of PSCs.
RESUMEN
Preoperative fasting aims to prevent pulmonary aspiration and improve bowel preparation, but it may induce profound systemic catabolic responses that lead to protein breakdown and insulin-resistant hyperglycemia after operation. However, the molecular mechanisms of catabolic reaction induced by prolonged preoperative fasting and surgical stress are undetermined. In this study, anesthetized rats were randomly assigned to receive a sham operation or laparotomy cecectomy. Fasting groups were restricted from food and water for 12 h before operation, while the feeding group had free access to food throughout the study period. Twenty-four hours after operation, the animals were sacrificed to collect blood samples and soleus muscles for analysis. Postoperative blood glucose level was significantly increased in the fasting group with elevated serum insulin and C-peptide. Continuous feeding reduced serum myoglobin and lactate dehydrogenase concentrations. Preoperative fasting activated inositol-requiring transmembrane kinase/endoribonuclease (IRE)-1α and c-Jun N-terminal kinase (JNK) mediated endoplasmic reticulum (ER)-stress, and reduced glucose transporter type 4 (Glut4) expression in the soleus muscle. Phospholamban phosphorylation was reduced and intracellular calcium levels were increased in the isolated skeletal muscle cells. Similar results were found in ER stress-induced C1C12 myoblasts. The expression of Glut4 was suppressed in the stressed C1C12, but was potentiated following inhibition of ER stress and chelation of intracellular free calcium. This study provides evidence demonstrating that prolonged preoperative fasting induces ER stress and generates insulin resistance in the skeletal muscle through suppression of Glut4 and inactivation of Ca2+-ATPase, leading to intracellular calcium homeostasis disruption and peripheral insulin resistance.
Asunto(s)
Ayuno/efectos adversos , Transportador de Glucosa de Tipo 4/metabolismo , Resistencia a la Insulina , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Operativos/efectos adversos , Animales , Calcio/análisis , Calcio/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Estrés del Retículo Endoplásmico , Endorribonucleasas/metabolismo , Glucosa/metabolismo , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Ratones , Complejos Multienzimáticos/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Mioblastos , Fosforilación , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/metabolismo , Complicaciones Posoperatorias/patología , Cuidados Preoperatorios/efectos adversos , Cuidados Preoperatorios/normas , Proteínas Serina-Treonina Quinasas/metabolismo , RatasRESUMEN
Rectal cancer is a heterogeneous malignancy with different clinical responses to preoperative concurrent chemoradiotherapy (CCRT). To discover the significant genes associated with CCRT response, we performed data mining of a transcriptomic dataset (GSE35452), including 46 rectal cancer patients who received preoperative CCRT and underwent standardized curative resection. We identified ARHGEF28 as the most significantly upregulated gene correlated with resistance to CCRT among the genes related to Rho guanyl-nucleotide exchange factor activity (GO:0005085). We enrolled 172 patients with rectal cancer receiving CCRT with radical surgery. The expression of ARHGEF28 encoded protein, Rho guanine nucleotide exchange factor (RGNEF), was assessed using immunohistochemistry. The results showed that upregulated RGNEF immunoexpression was considerably correlated with poor response to CCRT (p = 0.018), pre-CCRT positive nodal status (p = 0.004), and vascular invasion (p < 0.001). Furthermore, high RGNEF expression was significantly associated with worse local recurrence-free survival (p < 0.0001), metastasis-free survival (MeFS) (p = 0.0029), and disease-specific survival (DSS) (p < 0.0001). The multivariate analysis demonstrated that RGNEF immunoexpression status was an independent predictor of DSS (p < 0.001) and MeFS (p < 0.001). Using Gene Ontology enrichment analysis, we discovered that ARHGEF28 overexpression might be linked to Wnt/ß-catenin signaling in rectal cancer progression. In conclusion, high RGNEF expression was related to unfavorable pathological characteristics and independently predicted worse clinical prognosis in patients with rectal cancer undergoing CCRT, suggesting its role in risk stratification and clinical decision making.
RESUMEN
BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. This study aimed to investigate the anticancer effect of the combination treatment of Ribociclib (LEE011) and 5-Fluorouracil (5-FU) on CRC cells. MATERIALS AND METHODS: HT-29 and SW480 cells were treated with LEE011, 5-FU, or the combination of LEE011 and 5-FU. Cell viability and cycle were investigated through 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and flow cytometry. The expression of cell cycle-related proteins was determined through western blot. RESULTS: The combined treatment of LEE011 with 5-FU synergistically reduced cell viability in HT-29 and SW480 cells. Specifically, it induced cell cycle arrest at the G1 phase, down-regulated the phosphorylation of retinoblastoma protein and the expression of p53. CONCLUSION: LEE011 exhibited potential as an effective therapeutic inhibitor for the combination treatment of CRC patients.