Discovery of Oncogenic Mediator Genes in Rectal Cancer Chemotherapy Response using Gene Expression Data from Matched Tumor and Patient-Derived Organoid.

Rectal cancer (RC) presents significant treatment challenges, particularly in the context of chemotherapy resistance. Addressing this, our study pioneers the use of matched RC tumor tissue and patient-derived organoid (PDO) models coupled with the innovative computational tool, Moonlight, to explore the gene expression landscape of RC tumors and their response to chemotherapy. We analyzed 18 tissue samples and 32 matched PDOs, ensuring a high-fidelity representation of the tumor bioloy. Our comprehensive integration strategy involved differential expression analyses (DEAs) and gene regulatory network (GRN) analyses, facilitating the identification of 5,199 genes governing at least one regulon. By using the biological processes (BPs) collected from Moonlight closely related to cancer, we pinpointed 2,118 regulator-regulon groups with potential roles in oncogenic processes. Further, through integration of Moonlight and DEA results identified 334 regulator-regulon groups significantly enriched in both tissue and PDO samples, classifying them as oncogenic mediators (OMs). Among these, four genes (NCKAP1L, LAX1, RAD51AP1, and NAT2) demonstrated an association with drug responsiveness and recurrence-free survival (RFS), offering new insights into the molecular mechanisms of chemotherapy response in RC. Our integrated approach not only underscores the translational fidelity of PDOs, but also harnesses the analytical prowess of Moonlight, setting a new benchmark for targeted therapy research in rectal cancer.

Enhancing Chemotherapy Response Prediction via Matched Colorectal Tumor-Organoid Gene Expression Analysis and Network-Based Biomarker Selection.

Colorectal cancer (CRC) poses significant challenges in chemotherapy response prediction due to its molecular heterogeneity. This study introduces an innovative methodology that leverages gene expression data generated from matched colorectal tumor and organoid samples to enhance prediction accuracy. By applying Consensus Weighted Gene Co-expression Network Analysis (WGCNA) across multiple datasets, we identify critical gene modules and hub genes that correlate with patient responses, particularly to 5-fluorouracil (5-FU). This integrative approach advances precision medicine by refining chemotherapy regimen selection based on individual tumor profiles. Our predictive model demonstrates superior accuracy over traditional methods on independent datasets, illustrating significant potential in addressing the complexities of high-dimensional genomic data for cancer biomarker research.

Watch-and-Wait Approach to Rectal Cancer: The Role of Imaging.

The diagnosis and treatment of rectal cancer have evolved dramatically over the past several decades. At the same time, its incidence has increased in younger populations. This review will inform the reader of advances in both diagnosis and treatment. These advances have led to the watch-and-wait approach, otherwise known as nonsurgical management. This review briefly outlines changes in medical and surgical treatment, advances in MRI technology and interpretation, and landmark studies or trials that have led to this exciting juncture. Herein, the authors delve into current state-of-the-art methods to assess response to treatment with MRI and endoscopy. Currently, these methods for avoiding surgery can be used to detect a complete clinical response in as many as 50% of patients with rectal cancer. Finally, the limitations of imaging and endoscopy and future challenges will be discussed.

Anorectal mucosal melanoma.

Anorectal mucosal melanoma accounts for less than 1 % of all anorectal malignant tumors and a tendency for delayed diagnosis leads to advanced disease at presentation.1,2 Due to the rarity of the disease, there are limited prospective trials exploring the optimal treatment strategies. Generally, tumors are surgically excised, with a preference for conservative management with wide local excision. In the past decade, there have been advances with immunotherapy and other targeted therapies. Multiple clinical trials continue exploring neoadjuvant/adjuvant combination treatments in the setting of advanced or unresectable disease.

Cierre de la comunicación interauricular por cateterismo intervencionista con dispositivo Amplatzer en pediatría / Atrial Septal defect closure by interventional catheterization with Amplatzer device in Pediatrics

Introducción: El cateterismo intervencionista corrige las cardiopatías complejas, donde el dispositivo Amplatzer es el más usado y está disponible en Cuba. Objetivo: Evaluar el cateterismo intervencionista con Amplatzer, en el cierre de la comunicación interauricular ostium secundum. Métodos: Estudio de evaluación, longitudinal y prospectivo en 92 pacientes. El cierre de la comunicación por cateterismo con Amplatzer, se realizó en el Cardiocentro Pediátrico William Soler (2010-2016). Se utilizaron variables demográficas, ecocardiográficas (transtorácicas y transesofágicas) antes, durante y al año del cateterismo. Se observaron las complicaciones. La evaluación clínica y ecocardiográfica se realizó al año poscateterismo. Los pacientes a quienes se les realizó el proceder en el 2016, se evaluaron a los 6 meses. Resultados: Se encontraron diferencias significativas en el sexo (p<0,05): femenino 64,1 por ciento con homogeneidad para la edad (p= 0,244): media 9,8 años ( 5 desviaciones estándar. Precateterismo: 28,3 por ciento eran desnutridos y 17,4 por ciento delgados; poscateterismo la desnutrición mejoró significativamente (p= 0,000): desnutridos 9,8 por ciento y delgados 8,7 por ciento. El diámetro medio del defecto por ecocardiografía transcateterismo fue significativo (p= 0,000). Transcateterismo: 98,9 por ciento con cierre de defecto, 16,3 por ciento con insuficiencia tricúspidea y 4,3 por ciento con insuficiencia mitral. Poscateterismo: 98,9 por ciento con Amplatzer bien colocado. Hubo complicaciones inmediatas en 8,7 por ciento (arritmias, derrame pericárdico y embolización). Al año se detectó cortocircuito residual pequeño (n= 1) e insuficiencias valvulares auriculoventriculares (n= 3). La evolución fue satisfactoria (n= 91). Conclusiones: La evolución del cierre de la comunicación interauricular ostium secundum con dispositivo Amplatzer es satisfactoria, con mejoras de la desnutrición(AU)

Introduction: The interventional catheterization corrects complex heart diseases, and the Amplatzer device is the most widely used and is available in Cuba. Objective: To assess the interventional catheterization with Amplatzer device in the ostium secundum atrial septal closure. Methods: Longitudinal and prospective evaluation study in 92 patients. The closure of the communication by Amplatzer catheterization was performed in the William Soler Pediatric Cardiocenter of (2010-2016). Demographic and echocardiographic (transthoracic and transesophageal) variables were used before, during, and at the year of the catheterization. Complications were observed. Clinical and echocardiographic assessment was made a year after catheterism. The patients who underwent the procedure in 2016 were evaluated at 6 months. Results: Significant differences were found in the sex (p< 0.05): Female 64.1 t percent with homogeneity of the age (p= 0.244): average 9.8 years ( 5 standard deviations. Pre-catheterism: 28.3 percent were malnourished and 17.4 percent thin; post-catheterism: malnutrition improved significantly (p= 0.000): 9.8 percent malnourished and 8.7 percent thin. The average diameter of the defect by transcatheter echocardiography was significant (p= 0.000). Transcatheter: 98.9 percent : with default closure, 16.3 percent with tricuspid insufficiency and 4.3 percent with mitral regurgitation. Post-catheterism: 98.9 percent with Amplatzer device correctly positioned. There were immediate complications in 8.7 percent (arrhythmia, pericardial effusion, and embolization). A year after, small residual short circuit was detected (n= 1), and atrioventricular valve regurgitation (n= 3). The evolution was satisfactory (n= 91). Conclusions: The evolution of ostium secundum atrial septal defect´s closure with Amplatzer device is satisfactory and improves malnutrition(AU)

Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis.

BACKGROUND: The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. AIM: This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. METHODS: Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2-6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. RESULTS: The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005-0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. CONCLUSION: This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.