A concise review on miRNAs as regulators of colon cancer stem cells and associated signalling pathways.

Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes.

Pediatric Antibiotic Prescribing in China According to the 2019 World Health Organization Access, Watch, and Reserve (AWaRe) Antibiotic Categories.

OBJECTIVES: To assess clinical indication-specific antibiotic prescribing in pediatric practice in China based on the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) metrics and to detect potential problem areas. STUDY DESIGN: Pediatric prescription records on the 16th of each month during 2018 were sampled for all encounters at outpatient and emergency departments of 16 tertiary care hospitals via hospital information systems. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) classification. RESULTS: A total of 260 001 pediatric encounters were assessed, and antibiotics were prescribed in 94 453 (36.3%). In 35 167 encounters (37.2%), at least 1 intravenous antibiotic was administered. WHO Watch group antibiotics accounted for 82.2% (n = 84 176) of all antibiotic therapies. Azithromycin (n = 15 791; 15.4%) was the most commonly prescribed antibiotic, and third-generation cephalosporins (n = 44 387; 43.3%) were the most commonly prescribed antibiotic class. In at least 66 098 encounters (70.0%), antibiotics were prescribed for respiratory tract conditions, mainly for bronchitis/bronchiolitis (n = 25 815; 27.3%), upper respiratory tract infection (n = 25 184; 26.7%), and pneumonia (n = 13 392; 14.2%). CONCLUSIONS: Overuse and misuse of WHO Watch group antibiotics for respiratory tract conditions and viral infectious diseases is common in pediatric outpatients in China. Pediatric antimicrobial stewardship should be strengthened using WHO AWaRe metrics.

Expresión de p73 en relación con factores clínicos, patológicos y biológicos en tumores colorrectales / p73 expression in relation to factors clinical, pathological and biological colorectal tumors

Background: The p73 can inhibit cell growth and induce apoptosis, indicating that p73 is a p53-like tumour suppressor. However, studies have shown that either loss of heterozygosity (LOH) or mutation of p73 is not a common genetic event in tumour development. Material, methods and results: Western blotting was used for confirming the specificity of the p73 antibody. p73 expression was evaluated by using immunohistochemistry in 58 normal colorectal mucosa samples, 221 primary cancers and 58 lymph node metastases. PCR-restriction fragment length polymorphism was used for determining LOH in 52 primary tumours. The results showed that the frequency and the intensity of p73 immunostaining were markedly increased from normal tissue to primary tumour and to metastasis (p < 0.05). p73 overexpression predicted a worse prognosis outcome (p = 0.03), even after adjustment for patient's sex, age, tumour stage, growth pattern, and differentiation (p = 0.01). There was no LOH in primary tumours. Conclusion: The expression of p73 protein was up-regulated during the development from the normal mucosa to primary and to metastatic tumours. Furthermore, the overexpression of p73 was a predictor of poor prognosis in colorectal cancer patients. However, LOH of the gene was not an important factor in colorectal cancer development.

Antecedentes: La p73 puede inhibir el crecimiento celular e inducir apoptosis, lo cual indica que es un supresor de tumores, del tipo de p53. Sin embargo, los estudios demostraron que la pérdida de la heterocigotia (loss of heterozygosity, LOH) o la mutación de p73 no es un evento genético común en el desarrollo tumoral. Material, métodos y resultados: Para confirmar la especificidad del anticuerpo p73 se utilizó inmunotransferencia. Mediante inmunohistoquímica se evaluó la expresión de p73 en 58 muestras de mucosa colorrectal normal, en 221 muestras de cánceres primarios y en 58 muestras de ganglios linfáticos metastásicos. Se usó reacción en cadena de polimerasa y estudio de longitud de fragmentos de restricción para determinar LOH en 52 tumores primarios. Los resultados mostraron que la frecuencia y la intensidad de fijación de p73 aumentaron significativamente desde la evolución de tejido normal a tumores primarios y a metástasis (p < 0.05). La expresión exagerada de p73 predijo un pronóstico más desfavorable (p = 0.03) aun después del ajuste por sexo, edad, estadio tumoral, patrón de crecimiento y diferenciación (p = 0.01). No hubo LOH en tumores primarios. Conclusión: La expresión de la proteína p73 estuvo aumentada durante el pasaje de mucosa normal a tumores primarios y a metástasis. Más aun, la mayor expresión de p73 fue un factor predictivo de pronóstico desfavorable en pacientes con cáncer colorrectal. Sin embargo, la LOH del gen no fue un factor importante en la aparición de cáncer colorrectal.