Changes of Microrna Levels in Plasma of Patients with Rectal Cancer during Chemoradiotherapy.

Since the response to chemoradiotherapy in patients with locally advanced rectal cancer is heterogeneous, valid biomarkers are needed to monitor tumor response. Circulating microRNAs are promising candidates, however analyses of circulating microRNAs in rectal cancer are still rare. 111 patients with rectal cancer and 46 age-matched normal controls were enrolled. The expression levels of 30 microRNAs were analyzed in 17 pre-treatment patients' plasma samples. Differentially regulated microRNAs were validated in 94 independent patients. For 52 of the 94 patients a paired comparison between pre-treatment and post-treatment samples was performed. miR-17, miR-18b, miR-20a, miR-31, and miR-193a_3p, were significantly downregulated in pre-treatment plasma samples of patients with rectal cancer (p < 0.05). miR-29c, miR-30c, and miR-195 showed a trend of differential regulation. After validation, miR-31 and miR-30c were significantly deregulated by a decrease of expression. In 52 patients expression analyses of the 8 microRNAs in matched pre-treatment and post-treatment samples showed a significant decrease for all microRNAs (p < 0.05) after treatment. Expression levels of miR-31 and miR-30c could serve as valid biomarkers if validated in a prospective study. Plasma microRNA expression levels do not necessarily represent miRNA expression levels in tumor tissue. Also, expression levels of microRNAs change during multimodal therapy.

Acute burn care and outcomes at the Hospital Nacional Guido Valadares (HNGV), Timor-Leste: A 7-year retrospective study.

The purpose of this study was to describe the epidemiology of patients presenting with acute burns and undergoing admission at Hospital Nacional Guido Valadares (HNGV) in Dili, Timor-Leste in the period 2013 to 2019. HNGV is the only tertiary referral hospital in Timor-Leste. This was a retrospective study involving all acute burn patients admitted to the surgical wards of HNGV from 2013 to 2019. The data was collected from patient charts and hospital medical archives. Data were reviewed and analyzed statistically in terms of age, gender, residence, cause, total body surface area (TBSA), burns depth, length of stay (LOS), and mortality. The outcomes were analyzed using logistic regression. Over the 7-year period, there were 288 acute burn patients admitted to the surgical wards of HNGV. Most patients were children (55%), male (65%) and from the capital city of Dili or surrounding areas (59%). The most common cause of burns in children was scalds and the most common cause among adults was flames. Of the admitted patients 59% had burns affecting >10% of the TBSA and 41% had full thickness burns. The median LOS was 17 days (1-143) and the average mortality for admitted burn patients in HNGV was 5.6% (annual mortality 0-17%). The odds ratio for extended LOS was 1.9 (95% confidence interval 1.1-3.2) in female compared with male patients. The odds ratio for mortality was 14.6 (95% confidence interval 2.7-80.6) in the older adults when compared with younger adults. Higher TBSA, full thickness burns, and flame burns were also significantly associated with longer LOS and higher mortality. Children and male patients were disproportionately overrepresented among patients admitted to HNGV, while female patients had longer LOS and older adults had more severe injury and a higher risk of mortality. Establishment of a national program for the prevention of burns is essential.

Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g.

BACKGROUND AND PURPOSE: Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity. MATERIAL AND METHODS: Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established. Functional relevance of selected miRNAs was established by transfecting miRNA-mimics into SW480 and SW837 cells. The prognostic value of selected miRNAs was assessed in 128 pretherapeutic patient biopsies. RESULTS: Thirty-six miRNAs were identified to significantly correlate with sensitivity to CRT (Q < 0.05) including miR-320a and other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Transfection of selected miRNAs (let-7g, miR-132, miR-224, miR-320a) each induced a shift of sensitivity. High expression of let-7 g was associated with a good prognosis in rectal cancer patients (P = 0.03). CONCLUSIONS: This is the first report of a miRNA expression signature for in vitro chemoradiosensitivity of CRC cell lines. Many of the identified miRNAs have not been linked to the response to CRT and may represent potential molecular targets to sensitize resistant cancers. If further validated, let7g expression may serve as predictive biomarker.