Critical role of the long non-coding RNAs (lncRNAs) in radiotherapy (RT)-resistance of gastrointestinal (GI) cancer: Is there a way to defeat this resistance?

Radiotherapy (RT) is a frequently used treatment for cervical cancer, effectively decreasing the likelihood of the disease returning in the same area and extending the lifespan of individuals with cervical cancer. Nevertheless, the primary reason for treatment failure in cancer patients is the cancer cells' resistance to radiation therapy (RT). Long non-coding RNAs (LncRNAs) are a subset of RNA molecules that do not code for proteins and are longer than 200 nucleotides. They have a significant impact on the regulation of gastrointestinal (GI) cancers biological processes. Recent research has shown that lncRNAs have a significant impact in controlling the responsiveness of GI cancer to radiation. This review provides a concise overview of the composition and operation of lncRNAs as well as the intricate molecular process behind radiosensitivity in GI cancer. Additionally, it compiles a comprehensive list of lncRNAs that are linked to radiosensitivity in such cancers. Furthermore, it delves into the potential practical implementation of these lncRNAs in modulating radiosensitivity in GI cancer.

MicroRNAs in the cancer cell-to-cell communication: An insight into biological vehicles.

Cell-to-cell communication networks have indispensable roles in coordinating various biological processes in cancer cells or altering metabolism activity in both cancer and non-cancer cells. Exosomes, migrasomes, ectosomes, apoptotic bodies, and exomeres belonging to the heterogeneous world of extracellular vesicles (EVs), which have gained significant attention in recent years due to their principal role in cell-to-cell communication, including Extracellular Circulating miRNAs (ECmiRNAs) as a rich cargo content. ECmiRNAs can be taken up by target cells to mediate heterotypic cell-interactions and facilitate recipient repression in neighboring cells. The complex of ECmiRNAs with EVs, proteins, and lipoproteins structures such as TLR, AGO protein complex, HDL, and LDL can be more effective as mediators between cancer cells. The mechanism of multidrug resistance and angiogenesis in cancer cells may be altered during special signaling of EVs-ECmiRNAs during cell-to-cell communication. Also, those complexes may serve as novel biomarkers in cancer prognostication.

The synergy between miR-486-5p and tamoxifen causes profound cell death of tamoxifen-resistant breast cancer cells.

Breast cancer (BC) is the most common type of malignancy in women. A subset of breast cancers show resistance to endocrine-based therapies. The estrogen receptor (ER) plays a critical role in developing hormone-dependent BC. Loss of ER contributes to resistance to tamoxifen therapy and may contribute to mortality. Thus, it is crucial to overcome this problem. Here, using luciferase reporter assays, qRT-PCR, and Western blot analyses, we demonstrate that the microRNA miR-486-5p targets HMGA1 mRNA, decreasing its mRNA and protein levels in ER-positive (ER+) BC cells. Consistently, miR-486-5p is significantly downregulated, whereas HMGA1 is considerably upregulated in ER+ BC samples. Remarkably, while both miR-486-5p and tamoxifen individually cause G2/M cell cycle arrest, combination treatment synergistically causes profound cell death, specifically in tamoxifen-resistant ER+ cells but not in tamoxifen-sensitive ER+ cells. Combined treatment with miR-486-5p and tamoxifen also additively reduces cell migration, invasion, colony formation, mammary spheroid formation and a CD24-CD44+ cell population, representing decreased cancer stemness. However, these phenomena are independent of the tamoxifen responsiveness of the ER+ BC cells. Thus, miR-486-5p and tamoxifen exhibit additive and synergistic tumor-suppressive effects, most importantly causing profound cell death specifically in tamoxifen-resistant BC cells. Therefore, our work suggests that combining miR-486-5p replacement therapy with tamoxifen treatment is a promising strategy to treat endocrine therapy-resistant BC.

Effect of sequential therapy on treatment of Helicobacter pylori infection in children.

BACKGROUND: Helicobacter pylori infection which plays a major role in the etiology of chronic gastritis and duodenal ulcers in children and adults is one of the commonest chronic infection worldwide. Cure of the infection leads to healing of gastric inflammation and prevention of peptic ulcer. OBJECTIVE: The aim of this study was to evaluate the efficacy of the sequential therapy for treatment of Helicobacter pylori infection. MATERIALS AND METHODS: In this study, 40 children with symptoms of H. Pylori that the infection was proved by endoscopy and biopsy and rapid urease test (UBT) were enrolled, and received sequential therapy (Lansoprazol, Amoxicillin) for 5 days and (Lansoprazol, Metronidazole and Clarithromycin) for next 5 days. The eradication rate of therapy was evaluated by stool antigen test 6 weeks after completion of therapy. This study was carried out in Pediatric Gastroenterology Clinic of Shiraz University of Medical Sciences, Shiraz, Iran. This study was approved by ethic committee of Shiraz University of Medical Sciences. RESULTS: Forty children with mean age of (10.8±4 years) were evaluated. The most common symptom on first admission was epigastric pain (82.5%), with mean duration of symptoms (16±14.5 month). The most common endoscopic findings was redness and erosion of the antrum (55%) and the most pathologic findings was chronic gastritis (77.5%). The most drug adverse effect was nausea (22.5%). The eradication rate of sequential therapy was 82.5%. CONCLUSION: Eradication rate of sequential therapy was 82.5% among our cases.

Effect of sequential therapy on treatment of Helicobacter pylori infection in children / Efecto de la terapia secuencial en el tratamiento de la infección por Helicobacter pylori en niños

Background: Helicobacter pylori infection which plays a major role in the etiology of chronic gastritis and duodenal ulcers in children and adults is one of the commonest chronic infection worldwide. Cure of the infection leads to healing of gastric inflammation and prevention of peptic ulcer. Objective: The aim of this study was to evaluate the efficacy of the sequential therapy for treatment of Helicobacter pylori infection. Materials and methods: In this study, 40 children with symptoms of H. Pylori that the infection was proved by endoscopy and biopsy and rapid urease test (UBT) were enrolled, and received sequential therapy (Lansoprazol, Amoxicillin) for 5 days and (Lansoprazol, Metronidazole and Clarithromycin) for next 5 days. The eradication rate of therapy was evaluated by stool antigen test 6 weeks after completion of therapy. This study was carried out in Pediatric Gastroenterology Clinic of Shiraz University of Medical Sciences, Shiraz, Iran. This study was approved by ethic committee of Shiraz University of Medical Sciences. Results: Forty children with mean age of (10.8±4 years) were evaluated. The most common symptom on first admission was epigastric pain (82.5%), with mean duration of symptoms (16±14.5 month). The most common endoscopic findings was redness and erosion of the antrum (55%) and the most pathologic findings was chronic gastritis (77.5%). The most drug adverse effect was nausea (22.5%). The eradication rate of sequential therapy was 82.5%. Conclusion: Eradication rate of sequential therapy was 82.5% among our cases.

Antecedentes: La infección por Helicobacter pylori, que juega un rol principal en la etiología de la gastritis crónica y las úlceras duodenales en niños y adultos, es una de las infecciones crónicas más comunes en el mundo. La cura de esta infección lleva a la cura de la inflamación gástrica y a la prevención de la úlcera péptica. Objetivo: Evaluar la eficacia de la terapia secuencial en el tratamiento de la infección por Helicobacter pylori. Material y métodos: En este estudio, se enrolaron 40 niños con síntomas en los que la infección por H. pylori se demostró por endocopía con biopsia y prueba rápida de ureasa (UBT) y recibieron terapia secuencial (Lansoprazol, Amoxicilina) por 5 días y (lansoprazol, metronidazol y clarotromicina) por otros 5 días. La tasa de erradicación de la terapia se evaluó por prueba de antígeno en heces 6 semanas después de terminar la terapia. Este estudio se llevó a cabo en la Clínica de Gastroenterología Pediátrica de la Universidad de Ciencias Médicas de Shiraz, Irán. El estudio fue aprobado por el comité de ética de la Universidad de Ciencias Médicas de Shiraz. Resultados: Se evaluaron cuarenta niños con una edad media de (10,8±4 años). El síntoma más común al ingreso fue dolor epigástrico (82,5%) con una duración media de síntomas de (16±14,5 meses). El hallazgo endoscópico más común fue enrojecimiento y erosión del antro (55%) y el hallazgo patológico más común fue gastritis crónica (77,5%). El evento adverso más común fue náusea (22,5%). La tasa de erradicación de la terapia secuencial fue 82,5%. Conclusión: La tasa de erradicación de la terapia secuencial fue de 82,5% en nuestros casos.