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Evapotranspiration is a key component of the hydrological cycle. It is important to understand the features of the variation of potential evapotranspiration and the impacts of its drivers to estimate regional water consumption. The Huang–Huai–Hai (HHH) River Basin is comprised of three major rivers (the Yellow, Huai and Hai) and has been threatened by water shortages and huge consumption of water for agricultural and industrial development. In this study of the Huang–Huai–Hai (HHH) River Basin, potential evapotranspiration (E 0) across the basin was calculated using the Penman–Monteith model, and their changing characteristics were detected by using the Mann–Kendall test. The test was based on the daily climatic variables from 1965 to 2014 at 175 meteorological gauges. In addition, the influential effect of net radiation (R n), relative humidity (RHU), wind speed (WIN), mean, maximum and minimum air temperature (T a, T max and T min) on E 0 were analyzed by using the climate elasticity method, with their relative contribution to the changes of E 0 quantitatively revealed by using the multiple linear regression method. The results showed that R n, WIN, RHU and T a are the predominant climatic predictors that are more influential to E 0 while T max and T min have the least impact. The increase in annual E 0 in the period of 1985–2014 in the HHH River Basin was mainly attributed to the significantly increasing T a, which may greatly offset the effect of decreasing WIN and R n. The decrease of annual E 0 in the period of 1965–2014 in the middle area of the basin was mainly attributed to the falling WIN and R n.

Cyclin D/cyclin-dependent kinase 4/6 (CDK4/6) complex inhibitors have recently been proven effective when combined with endocrine therapy in clinical trials. However, the clinical benefit from CDK4/6 inhibitor varied from different patients. In order to optimize the clinical application of CDK4/6 inhibitors, this review focuses on the potential biomarkers applicable to identify patients who will benefit the most from CDK4/6 inhibition. We have summarized the clinical trials about addition of CDK4/6 inhibitors to endocrine therapy and reviewed literature currently available on the potential biomarkers in predicting efficacy of CDK4/6 inhibitors. The primary objective was to determine the predictors. The secondary objective was to optimize the combination therapeutics for patients with estrogen receptor (ER)-positive breast cancer. We reviewed clinical trials on antiestrogen agents combined with the CDK4/6 inhibitor (Palbociclib, Ribociclib, or Abemaciclib) in ER-positive breast cancer. It was confirmed that the addition of CDK4/6 inhibitors was associated with an improved efficacy. More importantly, we discussed potential biomarkers for identifying the subpopulations of breast cancer patients who would derive the greatest benefit from CDK4/6 inhibitors. We have found that although CDK4/6 inhibitors combined with endocrine therapy were potent, the toxicity and financial burden also increased. To maximize the effect of the combinations and select patients that best response to such combinations, further experiments and trials are expected to confirm these molecules as reliable biomarkers.

Breast cancers have been increasingly recognized as malignancies displaying frequent inter- and intra-tumor heterogeneity. This heterogeneity is represented by diverse subtypes and complexity within tumors, and impinges on response to therapy, metastasis, and prognosis. Cancer stem cells (CSCs), a subpopulation of cancer cells endowed with self-renewal and differentiation capacity, have been suggested to contribute to tumor heterogeneity. The CSC concept posits a hierarchical organization of tumors, at the apex of which are stem cells that drive tumor initiation, progression, and recurrence. In breast cancer, CSCs have been proposed to contribute to malignant progression, suggesting that targeting breast cancer stem cells (BCSCs) may improve treatment efficacy. Currently, several markers have been reported to identify BCSCs. However, there is objective variability with respect to the frequency and phenotype of BCSCs among different breast cancer cell lines and patients, and the regulatory mechanisms of BCSCs remain unclear. In this review, we summarize current literature about the diversity of BCSC markers, the roles of BCSCs in tumor development, and the regulatory mechanisms of BCSCs. We also highlight the most recent advances in BCSC targeting therapies and the challenges in translating the knowledge into clinical practice.

The selective estrogen receptor modulator tamoxifen is the most commonly used treatment for patients with ER-positive breast cancer. However, tumor cells often develop resistance to tamoxifen therapy, which is a major obstacle limiting the success of breast cancer treatment. miRNAs, as oncogenic or tumor suppressor genes, regulate the expression and function of their related target genes to affect the biological behaviors of cancer cells, including cancer initiation, progression, metastasis, and therapeutic resistance. In detail, many miRNAs associated with breast cancer tamoxifen resistance have been identified, which offer new targets for breast cancer therapy. Here, we review the miRNAs involved in regulation of tamoxifen resistance in human breast cancer and the mechanism of how the modulation of miRNAs may regulate the sensitivity of breast cancer cells to tamoxifen. We also discuss the future prospects of studies about miRNAs in regulation of tamoxifen resistance and miRNA-based therapeutics for tamoxifen resistance breast cancer patients.

Emerging evidence has shown that adding poly(ADP-ribose) polymerase (PARP) inhibitors to chemotherapy regimens is superior to the control regimens alone in BRCA1-mutated triple-negative breast cancer (TNBC) patients, but their underlying mechanisms have not been fully elucidated. In this study, using miRNA microarray analysis of two BRCA1-mutated TNBC cell lines, we found that miR-664b-5p expression was increased after adding a PARP inhibitor, olaparib, to a carboplatin (CBP) plus gemcitabine (GEM) therapy regimen. Functional assays showed miR-664b-5p overexpression inhibited proliferation, migration and invasion in BRCA1-mutated TNBC cells. CCNE2 was identified as a novel functional target of miR-664b-5p, and CCNE2 knockdown revealed effects similar to those observed with miR-664b-5p overexpression. Both CCNE2 knockdown and miR-664b-5p overexpression significantly increased the chemosensitivity of BRCA1-mutated TNBC cells. In addition, in vivo studies indicated that miR-664b-5p inhibited tumour growth compared with the control in tumour xenograft models, and we also found that CCNE2 expression was inversely correlated with miR-664b-5p expression in 90 TNBC patient samples. In conclusion, miR-664b-5p functions as a tumour suppressor and has an important role in the regulation of PARP inhibitors to increase chemosensitivity by targeting CCNE2. This may be one of the possible mechanisms by which PARP inhibitors increase chemosensitivity in BRCA1-mutated TNBC.

Breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor protein that functions to maintain genomic stability through critical roles in DNA repair, cell-cycle arrest and transcriptional control. The androgen receptor (AR) is expressed in more than 70% of breast cancers and has been implicated in breast cancer pathogenesis. However, little is known about the role of BRCA1 in AR-mediated cell proliferation in human breast cancer. Here, we report that a high expression of AR in breast cancer patients was associated with shorter overall survival (OS) using a tissue microarray with 149 non-metastatic breast cancer patient samples. We reveal that overexpression of BRCA1 significantly inhibited expression of AR through activation of SIRT1 in breast cancer cells. Meanwhile, SIRT1 induction or treatment with a SIRT1 agonist, resveratrol, inhibits AR–stimulated proliferation. Importantly, this mechanism is manifested in breast cancer patient samples and TCGA database, which showed that low SIRT1 gene expression in tumor tissues compared with normal adjacent tissues predicts poor prognosis in patients with breast cancer. Taken together, our findings suggest that BRCA1 attenuates AR-stimulated proliferation of breast cancer cells via SIRT1 mediated pathway.

The aim of our study was to assess the efficacy of regional hyperthermia combined with intrapleural chemotherapy and to evaluate the effect on the immunologic cells and vascular endothelial growth factor (VEGF) in patients with malignant pleural effusion. The 102 patients with malignant pleural effusion were included in this study: 52 patients undergoing regional hyperthermia with intrapleural chemotherapy (HICT), and 50 patients treated with intrapleural chemotherapy (ICT). Chemotherapy was administered into the thoracic cavity weekly through a tube with CDDP (dose = 40 mg/m2), and hyperthermia was performed twice a week for 60 minutes following the ICT. We evaluated the response rates and side-effects after 4 weeks. Before and after the treatment, T cell subsets and NK cells were detected by flow cytometry and VEGF was measured with ELISA kits. Compared HICT to ICT, the overall response rates of the whole group, breast cancers and lung cancers were 80.8% vs 54% (P 0.05) and 78.4% vs 52.9% (P < 0.05) respectively. The ratios of CD4+, CD4+/CD8+ and NK cells increased and the concentration of VEGF decreased more significantly after HICT. We concluded that combined regional hyperthermia with intrapleural chemotherapy could control the malignant pleural effusion effectively with mild toxicity. The levels of the T cell subset, NK cells and VEGF in both blood and effusion changed obviously.

Background Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that VEGF polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients. Methods We genotyped three potentially functional VEGF variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between VEGF variants and overall survival (OS). Results Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, P = 0.022), compared with the VEGF -460 TT genotype. Conclusions Our study suggests that VEGF -460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings.

BackgroundBoth TGF-β1 and VEGF play a critic role in the multiple-step process of tumorgenesis of gastric cancer. Single nucleotide polymorphisms (SNPs) of theTGFB1andVEGFgenes have been associated with risk and progression of many cancers. In this study, we investigated the association between potentially functional SNPs of these two genes and risk of gastric cancer in a US population.MethodsThe risk associated with genotypes and haplotypes of fourTGFB1SNPs and fourVEGFSNPs were determined by multivariate logistic regression analysis in 171 patients with gastric cancer and 353 cancer-free controls frequency-matched by age, sex and ethnicity.ResultsCompared with theVEGF-634GG genotype, the -634CG genotype and the combined -634CG+CC genotypes were associated with a significantly elevated risk of gastric cancer (adjusted OR = 1.88, 95% CI = 1.24-2.86 and adjusted OR = 1.56, 95% CI = 1.07-2.27, respectively). However, none of otherTGFB1andVEGFSNPs was associated with risk of gastric cancer.ConclusionOur data suggested that theVEGF-634G>C SNP may be a marker for susceptibility to gastric cancer, and this finding needs to be validated in larger studies.

BackgroundSomeTGFB1andVEGFpolymorphisms are believed to be functional. Given that these genes are involved in tumor growth and progression including angiogenesis, dissemination, and invasiveness, we hypothesized that these polymorphisms would be associated with survival in patients with gastric cancer.MethodsWe genotypedTGFB1-509 C>T, +1869 T>C, and +915 G>C andVEGF-1498T>C, -634G>C, and +936C>T in 167 patients with gastric cancer. Using the Kaplan and Meier method, log-rank tests, and Cox proportional hazard models, we evaluated associations amongTGFB1andVEGFvariants with overall, 1-year, and 2-year survival rates.ResultsAlthough there were no significant differences in overall survival rates among all polymorphisms tested, patients withTGFB1+915CG and CC genotypes had a poorer 2-year survival (adjusted hazard ratio (HR), 3.06; 95% confidence interval (CI), 1.09–8.62;P= 0.034) than patients with the GG genotype had. In addition, patients heterozygous forVEGF-634CG also had a poorer 1-year survival (adjusted HR, 2.08; 95% CI, 1.03–4.22;P= 0.042) than patients with the -634GG genotype.ConclusionOur study suggested thatTGFB1+915CG/CC andVEGF-634CG genotypes may be associated with short-term survival in gastric cancer patients. However, larger studies are needed to verify these findings.