Radiotherapy Metastatic Prostate Cancer Cell Lines Treated with Gold Nanorods Modulate miRNA Signatures.

MicroRNA (miRNA) modulation has been identified as a promising strategy for improving the response of human prostate cancer (PCa) to radiotherapy (RT). Studies have shown that mimics or inhibitors of miRNAs could modulate the sensitivity of PCa cells to RT. In addition, pegylated gold nanoparticles have been studied as a therapeutic approach to treat PCa cells and/or vehicles for carrying miRNAs to the inside of cells. Therefore, we evaluated the capacity of hypofractionated RT and pegylated gold nanorods (AuNPr-PEG) to modulate the miRNA signature on PCa cells. Thus, RT-qPCR was used to analyze miRNA-95, miRNA-106-5p, miRNA-145-5p, and miRNA-541-3p on three human metastatic prostate cell lines (PC3, DU145, and LNCaP) and one human prostate epithelial cell line (HprEpiC, a non-tumor cell line) with and without treatment. Our results showed that miRNA expression levels depend on cell type and the treatment combination applied using RT and AuNPr-PEG. In addition, cells pre-treated with AuNPr-PEG and submitted to 2.5 Gy per day for 3 days decreased the expression levels of miRNA-95, miRNA-106, miRNA-145, and miRNA-541-3p. In conclusion, PCa patients submitted to hypofractionated RT could receive personalized treatment based on their metastatic cellular miRNA signature, and AuNPr-PEG could be used to increase metastatic cell radiosensitivity.

Application of Gold Nanoparticles as Radiosensitizer for Metastatic Prostate Cancer Cell Lines.

More than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.

Results of Surgery in Lung Cancer - A Retrospective Study of a Single Center Experience.

OBJECTIVES: Surgery provides the best chance for cure in patients with non-small-cell lung cancer stage I or II, but only a small portion of all new cases diagnosed are eventually suitable for surgical resection. Our goal was to appraise the surgical outcomes including survival and progression rates in patientswith histological diagnosis of lung cancer. METHODS: Between 1st August 2012 and 30th June 2018, the patients with histological lung cancer diagnosis that underwent surgical resection with a curative intent at the department of Cardiothoracic Surgery of Centro Hospitalar Univer- sitário de São João were included. RESULTS: The majority of patients were pathological stage I and the most performed surgery was a lobectomy (90.6%). The hospitality mortality was 1,3% and the rate of complication was 26,1%. Patients with forced expiratory volume in 1 second (FEV1) less than 80% had higher (statistically significant difference) frequency of complications. Active smokers, Eastern Co- operative Oncology Group Performance Status (ECOG PS)value different than 0 and FEV1 inferior to 80% had a higher mean length of drainage and higher mean length of stay (statistically significant difference). The overall survival was 92,6% at 1 year, 87,7 % in 2 years and 79,1% in 5 years. The overall survival according to pathological stages were similar when compared with the literature. CONCLUSIONS: Ours results are similar to international centers and we should be more alert to preoperative assessment.

C-Reactive Protein as Predictive Biomarker for Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Retrospective Study.

The standard of care for the treatment of locally advanced rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by surgery, but complete response rates are reduced. To find predictive biomarkers of response to therapy, we conducted a retrospective study evaluating blood biomarkers before nCRT. Hemoglobin (Hg), C-reactive protein (CRP), platelets, carcinoembryonic antigen, carbohydrate antigen 19.9 levels, and neutrophil/lymphocyte ratio were obtained from 171 rectal cancer patients before nCRT. Patients were classified as responders (Ryan 0-1; ycT0N0), 59.6% (n = 102), or nonresponders (Ryan 2-3), 40.3% (n = 69), in accordance with the Ryan classification. A logistic regression using prognostic pretreatment factors identified CRP ≤ 3.5 (OR = 0.05; 95%CI: 0.01-0.21) as a strong independent predictor of response to treatment. Multivariate analysis showed that CRP was an independent predictor of disease-free survival (DFS) (HR = 5.48; 95%CI: 1.54-19.48) and overall survival (HR = 6.10; 95%CI 1.27-29.33) in patients treated with nCRT. Platelets were an independent predictor of DFS (HR = 3.068; 95%CI: 1.29-7.30) and OS (HR= 4.65; 95%CI: 1.66-13.05) and Hg was revealed to be an independent predictor of DFS (HR = 0.37; 95%CI: 0.15-0.90) in rectal cancer patients treated with nCRT. The lower expression of CRP is independently associated with an improved response to nCRT, DFS, and OS.

Factors affecting survival after palliative radiotherapy in patients with lung cancer.

BACKGROUND: Lung cancer is the most common cancer worldwide. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to identify factors that play a major role in the survival of lung cancer patients treated with palliative radiotherapy. MATERIALS AND METHODS: We retrospectively reviewed data of 280 lung cancer patients treated with palliative radiotherapy from January 2013 to December 2017. A multivariate analysis using the proportional hazards model of Cox was conducted. Also, Kaplan Meier curves were used to describe the distribution of survival times of the patients. The level of significance was set at 0.05. RESULTS: The mean age at diagnosis was 65.6 years. About 77.5% of patients were male and 22.5% were female. In our cohort > 95% had stage 4 lung cancer. Most cases were adenocarcinomas (72.5%) and ECOG-PS 0-1 (80.4%). Different sites were submitted to palliative treatment: 120 brain metastases, 96 bone metastases, 53 lung tumour, 8 lymph nodes and 3 lung metastases. Brain as first site of palliative radiotherapy (HR: 1.553, 95% CI: 1.167-2.067, p = 0.003) and ECOG-PS 2-3 compared with ECOG-PS 0-1 (HR: 2.253, 95% CI: 1.546-3.283, p ≤ 0.001) were associated with increased likelihood of lung cancer death. Patients who received biological therapy had 70.7% (p ≤ 0.001) reduction in lung cancer death risk. CONCLUSION: Brain as the first metastatic site treated with radiotherapy and ECOG-PS 2-3 are associated with increased lung cancer death. Biological therapy was associated with decreased death risk.

Baseline anaemia increases locally advanced rectal cancer mortality in older patients undergoing preoperative chemoradiation.

PURPOSE: The median diagnosis age of rectal cancer (RC) is 70 years old. The standard of care for locally advanced RC (LARC) is preoperative chemoradiation (CRT) followed by surgery. Anaemia is a frequent condition in older patients but is not a pure consequence of ageing. METHODS: The patients aged 65 years or over, with clinical stage II/III LARC, and treated with preoperative concurrent CRT were retrospectively reviewed. Baseline haemoglobin (Hb) levels were collected. RESULTS: One hundred and seven patients enrolled in this study, but 17 were excluded in relation with treatment disruption. Fifty-seven (63.3%) males and 33 (36.7%) females completed preoperative CRT whose median age at diagnosis was 73. Twenty-five (27.8%) patients presented with anaemia at rectal cancer diagnosis, and median Hb was 13.5 g/dL (IQR = 1.45) and 11.2 g/dL (IQR = 1.35), for non-anaemic and anaemic patients, respectively. For the enrolled older population, only 2 patients reported acute grade 3 toxicity. Baseline anaemia tended to decrease the LARC-free interval and was associated with a significantly higher hazard of all-cause and LARC mortality, approximately 5 times (HR = 5.25; 95% CI 1.48-18.66) and 10 times (HR = 10.09; 95% CI 2.40-42.48), respectively. Patients older than 75 presented a significantly negative impact on overall survival (OS) and LARC-specific survival (HR = 6.20, 95% CI 2.00-19.22; and HR = 7.61, 95% CI 2.08-27.87, respectively). Conversely, no significant impact was found for age-adjusted Charlson comorbidity index on OS, LARC-specific survival and LARC-free interval. CONCLUSIONS: Overall and LARC-specific survival were significantly lower for the baseline anaemic older patients and for those aged 75 years or over.