Pancreatic ductal adenocarcinoma (PDAC), generally known as pancreatic cancer (PC), ranks the fourth leading cause of cancer-related deaths in the western world. While the incidence of pancreatic cancer is displaying a rising tendency every year, the mortality rate has not decreased significantly because of late diagnosis, early metastasis, and limited reaction to chemotherapy or radiotherapy. Adjuvant chemotherapy after surgical resection is typically the preferred option to treat early pancreatic cancer. Although 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel can profoundly improve the prognosis of advanced pancreatic cancer, the development of chemoresistance still leads to poor clinical outcomes. Chemoresistance is multifactorial as a result of the interaction among pancreatic cancer cells, cancer stem cells, and the tumor microenvironment. Nevertheless, more pancreatic cancer patients will benefit from precision treatment and targeted drugs. Therefore, we outline new perspectives for enhancing the efficacy of gemcitabine after reviewing the related factors of gemcitabine metabolism, mechanism of action, and chemoresistance.

https://www.mdpi.com/1422-0067/20/18/4504/pdf

Chemoresistance in Pancreatic Cancer.

Background Neutrophil-to-lymphocyte ratio (NLR) has been used to predict the prognosis of patients with sepsis with inconsistent results. This meta-analysis aimed to clarify the prognostic value of NLR in patients with sepsis. Methods A comprehensive literature search for relevant studies, published prior to March 2019, was conducted using PubMed, Web of Science, and the China National Knowledge. Infrastructure database. Standard mean differences (SMDs) with 95% confidence intervals (CI) were used to evaluate the NLR of patients with sepsis retrospectively. Hazard ratios (HRs) with 95% CIs were used to evaluate the prognostic value of NLR in patients with sepsis. Results Patients from 14 studies (n = 11,564) were selected for evaluation. Nine studies (1371 patients) analyzed the NLR in these patients. The pooled results showed significantly higher NLR in non-survivors than in survivors (random-effects model: SMD = 1.18, 95% CI; 0.42–1.94). Nine studies (10,685 patients) evaluated the prognostic value of NLR for sepsis; the pooled results showed that higher NLR was associated with poor prognosis in patients with sepsis (fixed-effects model: HR = 1.75, 95% CI; 1.56–1.97). Subgroup analysis revealed that study design, cut-off NLR, or primary outcome did not affect the prognostic value of NLR in patients with sepsis. Conclusion This meta-analysis indicates that NLR may be a helpful prognostic biomarker of patients with sepsis and that higher NLR values may indicate unfavorable prognoses in these patients.

Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis.

Rationale: Some patients with coronavirus disease 2019 (COVID-19) rapidly develop respiratory failure or even die, underscoring the need for early identification of patients at elevated risk of severe illness. This study aims to quantify pneumonia lesions by computed tomography (CT) in the early days to predict progression to severe illness in a cohort of COVID-19 patients. Methods: This retrospective cohort study included confirmed COVID-19 patients. Three quantitative CT features of pneumonia lesions were automatically calculated using artificial intelligence algorithms, representing the percentages of ground-glass opacity volume (PGV), semi-consolidation volume (PSV), and consolidation volume (PCV) in both lungs. CT features, acute physiology and chronic health evaluation II (APACHE-II) score, neutrophil-to-lymphocyte ratio (NLR), and d-dimer, on day 0 (hospital admission) and day 4, were collected to predict the occurrence of severe illness within a 28-day follow-up using both logistic regression and Cox proportional hazard models. Results: We included 134 patients, of whom 19 (14.2%) developed any severe illness. CT features on day 0 and day 4, as well as their changes from day 0 to day 4, showed predictive capability. Changes in CT features from day 0 to day 4 performed the best in the prediction (area under the receiver operating characteristic curve = 0.93, 95% confidence interval [CI] 0.87~0.99; C-index=0.88, 95% CI 0.81~0.95). The hazard ratios of PGV and PCV were 1.39 (95% CI 1.05~1.84, P=0.023) and 1.67 (95% CI 1.17~2.38, P=0.005), respectively. CT features, adjusted for age and gender, on day 4 and in terms of changes from day 0 to day 4 outperformed APACHE-II, NLR, and d-dimer. Conclusions: CT quantification of pneumonia lesions can early and non-invasively predict the progression to severe illness, providing a promising prognostic indicator for clinical management of COVID-19.

CT quantification of pneumonia lesions in early days predicts progression to severe illness in a cohort of COVID-19 patients.

Circulating miRNA analysis for cancer diagnostics and therapy.

Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention. The functional proteins or non-coding RNAs contained in exosomes secreted from tumor and stromal cells mediate drug resistance by regulating drug efflux and metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, and tumor microenvironmental remodeling. In this review, we summarize the underlying associations between exosomes and drug resistance of BC and discuss the unique biogenesis of exosomes, the change of exosome cargo, and the pattern of release by BC cells in response to drug treatment. Moreover, we propose exosome as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistance of BC.

/pdf/exosomes-and-breast-cancer-drug-resistance-4bgkcgjrlo.pdf

Exosomes and breast cancer drug resistance.

Diagnostic and prognostic role of HE4 expression in multiple carcinomas: A protocol for systematic review and meta-analysis

Conceptual, statistical and clinical interpretation of results from a systematic review and meta-analysis of prevalence of cervical HPV infection in women with SLE.

We have come across the paper titled, “Diagnostic and prognostic value of microRNA-628 for cancers”, published by Li et al. in the Journal of Cancer. The publication is of great interest to us, and we would like to put forth a few strategies and approaches in regards to the publication in the spirit of scientific inquiry.

/pdf/diagnostic-and-prognostic-value-of-micrornas-for-cancers-l3xky89ft4.pdf

Diagnostic and prognostic value of microRNAs for cancers- strategies and approaches to improve the clinical utility.

Effect of protein arginine methyltransferase-1 inhibition on hypoxia-induced vasoconstriction.

We performed a systematic review and meta-analysis to identify and underline multiple microRNAs (miRNAs) as biomarkers of disease prognosis in stage II colorectal cancer (CRC) patients. This systematic review and meta-analysis study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The required articles were collected from online bibliographic databases from January 2011 to November 2019 with multiple permutation keywords. Quantitative data synthesis was based on a meta-analysis with pooled data to observe and analyse the outcome measures and effect estimates by using the random effect model. The subgroup analysis was performed from demographic characteristics and the available data. Eighteen articles were included in this study, 16 of which were incorporated for meta-analysis to examine the stage II CRC prognosis with up- and downregulated miRNA expressions. The pooled hazard ratio (HR) for death in stage II CRC patients was 1.90 (95% confidence interval 1.63–2.211), with a significant p value. A subgroup analysis based on up- or downregulated miRNA expression individually and any deregulated miRNA was also associated with a worse prognosis. The subgroup analysis included parameters such as age, gender, stage II and III combined patients’ survival and the repetitive miRNAs (miR21, miR215, miR143-5p, miR106a and miR145) individually. MicroRNAs play a significant role in determining prognosis in stage II CRC patients, with upregulation of miR21, miR215, miR143-5p and miR106a, in particular, portending a worse prognosis. These miRNAs could be considered for further evaluation as biomarkers of prognosis and to guide the decision to administer adjuvant chemotherapy.

Chellan Kumarasamy

Papers

Diagnostic and prognostic role of HE4 expression in multiple carcinomas: A protocol for systematic review and meta-analysis

Conceptual, statistical and clinical interpretation of results from a systematic review and meta-analysis of prevalence of cervical HPV infection in women with SLE.

Diagnostic and prognostic value of microRNAs for cancers- strategies and approaches to improve the clinical utility.

Effect of protein arginine methyltransferase-1 inhibition on hypoxia-induced vasoconstriction.

Prognostic Value of MicroRNAs in Stage II Colorectal Cancer Patients: A Systematic Review and Meta-Analysis