The influence of meteorological factors and total malignant tumor health risk in Wuhu city in the context of climate change.

With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014-2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.

Helicobacter pylori infection as a potential favorable factor for immune checkpoint inhibitor therapy for gastric cancer.

Gastric cancer (GC) has the third highest rate of cancer incidence and mortality worldwide. First-line immune checkpoint inhibitor (ICI) therapy for advanced GC led to landmark breakthroughs, but which GC patients are most likely to benefit from ICI therapy needs to be investigated in depth and identified via valuable biomarkers. In this letter, we describe superior outcomes in Asian patients than in North American and European patients treated with ICI therapy, and we speculate that positive H. pylori status may be a beneficial prognostic factor for ICI therapy in patients with GC. Many studies have revealed that H. pylori-activated immune responses improve prognosis in patients with GC via increased PD-L1 expression and CD3+ T cells. We propose that H. pylori status should be emphasized in ongoing or forthcoming ICI therapy trials to maximize the benefits of treatment for patients with advanced GC. Further research is required to better understand the mechanisms of inflammation and cancer progression.

A retrospective study on the efficacy and safety of Envafolimab, a PD-L1 inhibitor, in the treatment of advanced malignant solid tumors.

Envafolimab, a PD-L1 inhibitor, has demonstrated potential in treating advanced malignant solid tumors (AMST). To study its' efficacy and safety in AMST, our retrospective study recruited 64 patients with various AMST, and treated with Envafolimab (400 mg every 3 weeks). We divided the patients into two cohorts: Cohort 1 (25 patients) receiving Envafolimab as first-line therapy, and Cohort 2 (39 patients) receiving it as second-line or subsequent therapy. Our analysis focused on Envafolimab's efficacy and safety. Over a median follow-up of 7.1 months, Cohort I reported a Disease Control Rate (DCR) of 72.0% and an Objective response rate (ORR) of 12.0%, while Cohort II had a DCR of 51.3% and an ORR of 5.1%. Notably, patients with more than four treatment cycles showed higher DCR and longer Progression-Free Survival (PFS) than those with fewer cycles. Adverse events were observed in 68.8% of patients, with severe events (CTCAE grade 3/4) in 14.1%. Most adverse events were mild, leading to treatment discontinuation in only 3.1% of patients, with no life-threatening events reported. In summary, Envafolimab is a safe and effective treatment for AMST, in both initial and later therapy stages, particularly with extended treatment duration, meriting further clinical trials.

Prognostic value of inflammatory markers and clinical features for survival in advanced or metastatic esophageal squamous cell carcinoma patients receiving anti-programmed death 1 treatment.

Purpose: This study aims to assess the prognostic value of inflammatory markers and clinical features in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients receiving anti-programmed death 1 (PD-1) treatment. Methods: Based on receiver operating characteristic curve (ROC) analysis, Youden's indexes were applied to determine the cut-off values for inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocye ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Wilcoxon test was conducted to evaluate the changes in above inflammatory markers. Kaplan-Meier method was utilized to estimate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used to compare the different survival between groups. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of inflammatory markers and clinical features. Results: 162 advanced or metastatic ESCC patients receiving anti-PD-1 treatment were enrolled in this retrospective study. The cut-off values of NLR, dNLR, MLR, PLR, and SII were 4.748, 2.214, 0.309, 250.505, and 887.895, respectively. NLR, dNLR, PLR, and SII declined significantly among the partial response (PR) (P<0.001, P<0.001, P=0.036, P<0.001), objective response rate (ORR) (P<0.001, P<0.001, P=0.036, P<0.001), and disease control rate (DCR) (P<0.001, P<0.001, P=0.038, P<0.001) groups, respectively. Significant increases were found in NLR (P<0.001), dNLR (P<0.001), MLR (P=0.001), and SII (P=0.024) when anti-PD-1 treatment failed. Multivariate Cox regression analysis indicated that NLR (P<0.001, P=0.002), lymph node metastasis (P=0.013, P=0.001), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (P=0.008, P=0.002), and treatment lines (P=0.037, P=0.048) were significant prognostic indicators of PFS and OS. Additionally, SII (P=0.016) was also significantly related to OS in ESCC patients. The risk score model showed that low risk patients prolonged PFS and OS than those with middle or high risk (P<0.001, P<0.001). Conclusion: Inflammatory markers can reflect short-term outcomes of anti-PD-1 treatment for ESCC patients. NLR, lymph node metastases, ECOG PS, and treatment lines are significant prognostic indicators for PFS and OS. And the risk score model constructed based on the above factors has favourable prognostic predictive value.

Expression changes of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer and its clinical significance.

Objective: To explore the altered expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and cell proliferation index (Ki-67) in primary and metastatic breast cancer lesions and the correlation between the primary tumor size, lymph node metastasis, Tumor Node Metastasis (TNM) stage, molecular typing, and disease-free survival (DFS) and their clinical significance. Methods: A retrospective analysis was conducted on the clinical data of 130 patients with metastatic breast cancer biopsy admitted to the Cancer Center of the Second Affiliated Hospital of Anhui Medical University in Hefei, China, from 2014-2019. The altered expression of ER, PR, HER2, and Ki-67 in primary and metastatic lesions of breast cancer was analyzed with respect to the site of metastasis, size of the primary tumor, lymph node metastasis, disease progression, and prognosis. Results: The inconsistent expression rates of ER, PR, HER2, and Ki-67 in primary and metastatic lesions were 47.69%, 51.54%, 28.10%, and 29.23%, respectively. The size of the primary lesion was not, but that accompanied by lymph node metastasis was related to the altered receptor expression. Patients with positive ER and PR expression in both primary and metastatic lesions had the longest DFS, while those with negative expression had the shortest DFS. Also, changes in HER2 expression in primary and metastatic lesions were not associated with DFS. Patients with low expression of Ki-67 in both primary and metastatic lesions had the longest DFS, while patients with high expression had the shortest DFS. Conclusion: Heterogeneity was detected in the expression levels of ER, PR, HER2, and Ki-67 in the primary and metastatic breast cancer lesions, which has a guiding significance for the treatment and prognosis of patients.

Knowledge mapping of early-onset colorectal cancer from 2000 to 2022: A bibliometric analysis.

The incidence of early-onset colorectal cancer (EO-CRC), diagnosed in patients younger than 50 years, has increased in incidence alarmingly over the past few decades, while overall incidence and mortality of colorectal cancer are stabilizing or declining in many high-income countries. These unfavorable changes have raised significant concerns and led to extensive research, resulting in a surge in studies on EO-CRC. Our aim was to obtain a more comprehensive understanding of the current state of this field and to identify prospective research directions by performing a bibliometric analysis of EO-CRC. A total of 1952 papers on EO-CRC published from 2000 to 2022 were identified after a thorough search of the Web of Science Core Collection. The United States dominated this field, with Harvard University contributing the greatest number of papers, while the journal Familial Cancer (n = 52) published the most articles. Cooperation network analysis revealed close internal cooperation among countries, institutions and authors. Based on reference and keyword analysis, high-frequency keywords showed several popular research directions, including epidemiology (incidence, young patients, age of onset, etc.), risk factors (obesity, family history, lynch syndrome, etc.) and molecular characterization (germline mutation, genome wide association, MLH1, etc.). Overall, our research provides an overview of the current status in this field, which we hope will give researchers a comprehensive perspective on the present trends within this domain.

Effectiveness and safety of camrelizumab combined with chemotherapy in nonsquamous nonsmall cell lung cancer as the second-line therapy: A retrospective analysis.

Background: The role of camrelizumab combined with chemotherapy as the second-line therapy in nonsquamous nonsmall cell lung cancer (NSCLC) remains unverified. The retrospective study investigated efficacy and safety of camrelizumab combined with chemotherapy in the treatment of nonsquamous NSCLC as the second-line therapy. Subjects and Methods: Patients of nonsquamous NSCLC who were already discharged or died of the First Affiliated Hospital of Anhui Medical University between August 2019 and September 2020. According to the treatment method, the patients who received chemotherapy were denoted as the C group and those who received camrelizumab plus chemotherapy were denoted as the C&C group. Statistical Analysis Used: Patients responses were statistically analyzed. The Cox proportional hazards regression model was used in the assessment of the prognostic value of factors. Furthermore, adverse event evaluation was estimated. Results: Of the 60 patients with nonsquamous NSCLC included in the research, 29 patients received chemotherapy, and 31 patients received camrelizumab plus chemotherapy. The objective response rate was 13.79% and 32.26% for chemotherapy and camrelizumab plus chemotherapy groups, and the disease control rate was 72.41% and 80.65%. The median progression-free survival (mPFS) in camrelizumab plus chemotherapy group was obviously higher than that in the chemotherapy group (9.67 vs. 6.87 months, P = 0.01). The median overall survival of the camrelizumab plus chemotherapy was longer than the chemotherapy (10.89 vs. 7.95 months, P < 0.01). In the current treatment, radiotherapy and smoking were independent risk factors for the mPFS of patients with nonsquamous NSCLC. The occurrence of adverse events was similar between chemotherapy and camrelizumab plus chemotherapy groups. Conclusions: Camrelizumab combined with chemotherapy was an effective regimen with manageable toxicity in treating nonsquamous NSCLC as the second-line therapy.

Safety and efficacy of sintilimab combination therapy for the treatment of 48 patients with advanced malignant tumors.

Background: Sintilimab is a recombinant fully human anti-programmed death 1 (PD-1) monoclonal antibody that blocks the interaction of PD-1 with its ligand. We evaluated the safety and efficacy of sintilimab combined with chemotherapy and targeted therapy in the treatment of advanced malignant tumors. Methods: We performed a retrospective analysis of the clinical data of patients with advanced malignant tumors treated with sintilimab combined with chemotherapy and targeted therapy admitted to the Third Ward of the Department of Medical Oncology, First Affiliated Hospital of Anhui Medical University, China, from July 2019 to February 2021. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and related adverse reactions were analyzed. Results: A total of 48 patients with advanced malignant tumors treated with sintilimab combined with chemotherapy and targeted therapy. All 48 patients completed 2 courses of treatment, and the ORR and DCR were 20.83% and 81.25%. The median PFS for all patients in this study was 7 months, and the median OS was not yet reached. The median PFS for the first-line and second-line patients was 10 months, and the median OS was not yet reached. The median PFS for third-line and beyond patients was 7 months, and the median OS was 10 months. The differences in PFS and OS were both statistically significant. Adverse events occurred in 24 patients, of which 18 patients had grade I-II adverse events and 6 patients had grade III-IV adverse events. Conclusions: Sintilimab is an inexpensive PD-1 drug produced in China. Sintilimab combination therapy showed good safety in the treatment of advanced malignant tumors, with increases in the treatment efficacy and DCR for advanced tumors. Because of few adverse reactions and proven efficacy, sintilimab combination therapy can be used as an option for the treatment of advanced malignant tumors.

Anlotinib plus nab-paclitaxel/gemcitabine as first-line treatment prolongs survival in patients with unresectable or metastatic pancreatic adenocarcinoma: a retrospective cohort.

Background: The timely addition of anlotinib to the nab-paclitaxel/gemcitabine regimen may further increase the treatment efficacy for pancreatic adenocarcinoma (PDAC), which has not yet been reported. Therefore, we aimed to compare the efficacy and safety of anlotinib plus nab-paclitaxel/gemcitabine in the first-line treatment of patients with unresectable or metastatic PDAC. Methods: This was a retrospective cohort of patients with unresectable or metastatic PDAC performed in The First Affiliated Hospital of Anhui Medical University from August 17, 2019 to April 3, 2021. Patients who received anlotinib plus nab-paclitaxel/gemcitabine treatment were defined as the anlotinib plus chemotherapy group and patients who received nab-paclitaxel/gemcitabine were defined as the chemotherapy group. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and toxic side effects. Clinical data and follow-up information were mainly obtained from hospital records or by telephone. Results: A total of 33 patients were included in this study, with 17 cases in the anlotinib plus chemotherapy group and 16 cases in the chemotherapy group. The median PFS (mPFS) of the anlotinib plus chemotherapy group was 5 months while the mPFS of the chemotherapy group was 2.7 months (P=0.0220). The median OS (mOS) of the anlotinib plus chemotherapy group was 9 months while the mOS of the chemotherapy group was 6 months (P=0.0060). The 3-month and 6-month PFS, and the 6- and 12-month OS of the anlotinib plus chemotherapy group were significantly higher than those of the chemotherapy group (P<0.05). The proportion of patients with hematological toxicities in the anlotinib plus chemotherapy group was not significantly higher than that in the chemotherapy group. Conclusions: Anlotinib plus nab-paclitaxel/gemcitabine as a first-line treatment regimen is safe and may prolong survival compared with nab-paclitaxel/gemcitabine chemotherapy in patients with unresectable or metastatic PDAC. Randomized controlled trials with large sample sizes are warranted to further evaluate the treatment effects of anlotinib in PDAC. Keywords: Pancreatic adenocarcinoma (PDAC); anlotinib; nab-paclitaxel/gemcitabine; progression-free survival (PFS); overall survival (OS).

Efficacy and mechanism of osimertinib combined with bevacizumab in the treatment of postoperative EGFR positive stage II-IIIA lung adenocarcinoma.

OBJECTIVE: To explore the efficacy and mechanism of osimertinib combined with bevacizumab in treating postoperative epidermal growth factor receptor (EGFR) positive stage II-IIIA lung adenocarcinoma. METHODS: In this retrospective study, one hundred and thirty patients with postoperative EGFR positive stage II-IIIA lung adenocarcinoma were divided into two groups according to different treatment methods. Patients treated with osimertinib alone were included in the single group (65 patients). Patients treated with bevacizumab on the basis of the single group were included in the joint group (65 patients). The short-term efficacy, side effects and survival results of the two groups were counted. The changes of serum vascular endothelial growth factor, serum tumor markers and life quality before and after the treatment were observed. RESULTS: The ORR (66.15%) and DCR (86.15%) in the joint group were significantly higher than those in the single group (47.69% and 70.77%) (both P<0.05). The serum levels of VEGFA, VEGFB, VEGFC, BFGF, HDGF, SDF-1, CEA, CA153, CYFRA21-1 and CA199 in the joint group were lower than those in the single group after the treatment (all P<0.05). No significant difference was shown in the incidence of adverse reactions such as rash, diarrhea, constipation, albuminuria, hypertension and interstitial pneumonia between the joint group and the single group (all P>0.05). After the treatment, the ZPS score of the joint group was lower than that of the single group, and the KPS score was higher than that of the single group (both P<0.05). There was no significant difference in the two-year median DFS and the one or two-year DFS rate between the joint group and the single group (all P>0.05). CONCLUSION: Osimertinib combined with bevacizumab in the treatment of postoperative EGFR positive stage II-IIIA lung adenocarcinoma has evident short-term efficacy and mild side effects, which is helpful in improving the disease control rate and life quality. The mechanism may be related to the regulation of serum CEA, CA153, CYFRA21-1, CA199 levels and inhibition of VEGFA, VEGFB, VEGFC, BFGF, HDGF, and SDF-1 levels.

miR-765 Acts as a Tumor Promoter and Indicates Poor Prognosis in Non-Small Cell Lung Cancer.

PURPOSE: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide with poor prognosis. Accumulating evidence indicates that miR-765 is an important regulator in the progression and prognosis of various cancers. In this study, the function in the progression and prognosis of NSCLC was investigated. PATIENTS AND METHODS: The expression of miR-765 in NSCLC was analyzed by qRT-PCR. The effect of miR-765 on cell proliferation, migration, and invasion of NSCLC was evaluated by CCK8 and Transwell assay. Kaplan-Meier analysis and Cox regression analysis were employed to assess the prognostic value of miR-765. RESULTS: The results demonstrated the significant upregulation of miR-765 in NSCLC tissues and cell lines relative to normal tissues and cells. High miR-765 expression was significantly correlated with the TNM stage of patients. Patients with high miR-765 expression showed a poorer prognosis than that of patients with low miR-765 expression. Cox analysis indicated that miR-765 could be considered as an independent prognostic factor for NSCLC. Additionally, the upregulation of miR-765 was revealed to promote NSCLC cell proliferation, migration, and invasion by targeting BMP6. CONCLUSION: The overexpression of miR-765 in NSCLC was associated with TNM stage and poor prognosis of patients. miR-765 served as a tumor promoter of NSCLC by regulating BMP6. These findings provide a potential biomarker and therapeutic target for the prognosis and treatment of NSCLC.

Tumor Microenvironment Characteristics of Pancreatic Cancer to Determine Prognosis and Immune-Related Gene Signatures.

Background: Pancreatic cancer (PC) is one of the most lethal types of cancer with extremely poor diagnosis and prognosis, and the tumor microenvironment plays a pivotal role during PC progression. Poor prognosis is closely associated with the unsatisfactory results of currently available treatments, which are largely due to the unique pancreatic tumor microenvironment (TME). Methods: In this study, a total of 177 patients with PC from The Cancer Genome Atlas (TCGA) cohort and 65 patients with PC from the GSE62452 cohort in Gene Expression Omnibus (GEO) were included. Based on the proportions of 22 types of infiltrated immune cell subpopulations calculated by cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), the TME was classified by K-means clustering and differentially expressed genes (DEGs) were determined. A combination of the elbow method and the gap statistic was used to explore the likely number of distinct clusters in the data. The ConsensusClusterPlus package was utilized to identify radiomics clusters, and the samples were divided into two subtypes. Result: Survival analysis showed that the patients with TMEscore-high phenotype had better prognosis. In addition, the TMEscore-high had better inhibitory effect on the immune checkpoint. A total of 10 miRNAs, 311 DEGs, and 68 methylation sites related to survival were obtained, which could be biomarkers to evaluate the prognosis of patients with pancreatic cancer. Conclusions: Therefore, a comprehensive description of TME characteristics of pancreatic cancer can help explain the response of pancreatic cancer to immunotherapy and provide a new strategy for cancer treatment.

m6A Methyltransferase METTL14-Mediated Upregulation of Cytidine Deaminase Promoting Gemcitabine Resistance in Pancreatic Cancer.

OBJECTIVE: Pancreatic cancer is one of the most lethal human malignancies. Gemcitabine is widely used to treat pancreatic cancer, and the resistance to chemotherapy is the major difficulty in treating the disease. N 6-methyladenosine (m6A) modification, which regulates RNA splicing, stability, translocation, and translation, plays critical roles in cancer physiological and pathological processes. METTL14, an m6A Lmethyltransferase, was found deregulated in multiple cancer types. However, its role in gemcitabine resistance in pancreatic cancer remains elusive. METHODS: The mRNA and protein level of m6A modification associated genes were assessed by QRT-PCR and western blotting. Then, gemcitabine-resistant pancreatic cancer cells were established. The growth of pancreatic cancer cells were analyzed using CCK8 assay and colony formation assay. METTL14 was depleted by using shRNA. The binding of p65 on METTL14 promoter was assessed by chromatin immunoprecipitation (ChIP) assay. Protein level of deoxycytidine kinase (DCK) and cytidine deaminase (CDA) was evaluated by western blotting. In vivo experiments were conducted to further confirm the critical role of METTL14 in gemcitabine resistance. RESULTS: We found that gemcitabine treatment significantly increased the expression of m6A methyltransferase METTL14, and METTL14 was up-regulated in gemcitabine-resistance human pancreatic cancer cells. Suppression of METTL14 obviously increased the sensitivity of gemcitabine in resistant cells. Moreover, we identified that transcriptional factor p65 targeted the promoter region of METTL14 and up-regulated its expression, which then increased the expression of cytidine deaminase (CDA), an enzyme inactivates gemcitabine. Furthermore, in vivo experiment showed that depletion of METTL14 rescue the response of resistance cell to gemcitabine in a xenograft model. CONCLUSION: Our study suggested that METTL14 is a potential target for chemotherapy resistance in pancreatic cancer.

Paeonol induces antitumor effects in hepatocellular carcinoma cells through survivin via the cyclooxygenase-2/prostaglandin E2 signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most life-threatening malignancies worldwide due to the lack of significant improvement in therapeutic methods. This study aimed to unravel the effects of paeonol, the main active component of Paeonia suffruticosa, on survivin, a key molecule in tumorigenesis, and elucidate the mechanisms by which paeonol exerts antineoplastic effects in human HCC cells. METHODS: Immunohistochemistry (IHC) was used to study the expression levels of survivin and cyclooxygenase-2 (COX-2) in 57 human HCC tissue samples. Human HCC cell lines (HepG2 and SMMC-7721) were treated with prostaglandin E2 (PGE2). Subsequently, the cells were treated with paeonol and NS-398, and the expression levels of survivin, COX-2, and PGE2 were evaluated by Western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. Fluorescence-activated cell sorting (FACS) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed to analyze cell proliferation and apoptosis. RESULTS: Survivin was expressed in 47 of 57 human HCC tissue samples, as observed by IHC, and its expression was correlated with COX-2 activity. Furthermore, Western blotting showed that the expression of survivin was increased in HepG2 and SMMC-7721 cells treated with PGE2, the biosynthesis of which is mainly regulated by COX-2. Interestingly, FACS and TUNEL staining demonstrated that paeonol significantly inhibited the proliferation of HepG2 and SMMC-7721 cells and induced apoptosis, concomitant with the downregulation of survivin. The levels of COX-2 and PGE2 were also reduced by paeonol, as confirmed by Western blotting and ELISA, respectively. To determine the mechanism by which paeonol inhibited survivin in HCC cells the effects of COX-2 expression on surviving were studied. Treatment with the COX-2 selective inhibitor NS398 effectively decreased the levels of PGE2 and survivin, inducing apoptosis in a manner similar to that of paeonol. Survivin expression was increased by PGE2 treatment but was blocked by paeonol, which suggests that paeonol inhibits survivin by inhibiting the COX-2/PGE2 signaling pathway. CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate that paeonol can exert antitumor effects on HCC cells by targeting survivin via the COX-2/PGE2 signaling pathway. Paeonol could therefore be considered as a potential therapeutic candidate for HCC.

PCAT1/miR-129/ABCB1 axis confers chemoresistance in non-small cell lung cancer.

Long noncoding RNA prostate cancer-associated transcript 1 (PCAT1) is oncogenic and causes progression of non-small cell lung cancer (NSCLC). We hypothesized that PCAT1 might be involved in the acquisition of chemoresistance of NSCLC cells to treatment with cisplatin (DDP). Here, we show that PCAT1 and ATP-binding cassette sub-family B member 1 (ABCB1) are highly expressed in NSCLC tissues and cell lines, and regulate the growth and apoptosis of these cells. Compared with those in DDP-sensitive patients, PCAT1 and ABCB1 are highly expressed in the tumors of DDP-resistant patients, and such overexpression correlates with a shorter overall survival of these patients. Knockdown of PCAT1 or upregulation of miR-129 led to apoptosis and sensitized the DDP-resistant cells to DDP. The 3' UTR activity of PCAT1 and ABCB1, which was increased by PCAT1 overexpression, was shown to harbor an miR-129 binding site. DDP resistance is induced by elevated ABCB1 expression, which involves binding of miR-129 in DDP resistant cells. These findings suggest that the PCAT1/miR-129/ABCB1 axis may be a potential target for the treatment of DDP-resistant oat cell cancer.

Circular RNA circ_SETD2 represses breast cancer progression via modulating the miR-155-5p/SCUBE2 axis.

Breast cancer (BC) is the leading cause of cancer deaths in women worldwide. Circular RNA circ_SETD2 (circ_SETD2), also termed as hsa_circ_0065173, is reported to be abnormally expressed in BC. Nevertheless, the role and mechanism of circ_SETD2 in BC are unclear. Expression of circ_SETD2, miR-155-5p, and SCUBE2 mRNA was evaluated by quantitative real-time polymerase chain reaction. Cell cycle progression, proliferation, apoptosis, migration, and invasion were determined by flow cytometry, MTT, and transwell assays. The relationship between circ_SETD2 or SCUBE2 and miR-155-5p was verified through a dual-luciferase reporter assay. The role of circ_SETD2 in BC in vivo was confirmed by a xenograft assay. circ_SETD2 and SCUBE2 were downregulated, while miR-155-5p was upregulated in BC tissues and cells. Both circ_SETD2 and SCUBE2 elevation arrested cell cycle progression, inhibited cell proliferation, migration, and invasion, and accelerated cell apoptosis in BC cells. Moreover, circ_SETD2 upregulation repressed BC growth in vivo. Importantly, circ_SETD2 modulated SCUBE2 expression through competitively binding to miR-155-5p in BC cells. Also, the inhibitory impacts of circ_SETD2 enhancement on the malignant behavior of BC cells were restored by miR-155-5p overexpression. Besides, SCUBE2 silencing abolished miR-155-5p downregulation mediated effects on the malignant behavior of BC cells. Therefore, circ_SETD2 curbed BC progression via upregulating SCUBE2 via binding to miR-155-5p.

Incidence and detection of high microsatellite instability in colorectal cancer in a Chinese population: a meta-analysis.

BACKGROUND: The 4 most common types of DNA mutations in tumors are single-nucleotide variations, insertion-deletion, fusion, and copy number variations. This is followed by microsatellite instability (MSI), which is known to trigger the development of MSI-high (MSI-H) cancer and is responsible for 300,000 new cases of cancer per year in China. We aim to conduct a meta-analysis based on a comparison between the positive rates of the National Cancer Institute (NCI) panel (also known as 2B3D NCI panel) and mononucleotide panels for the diagnosis of MSI in the Chinese population. METHODS: In the present meta-analysis, we searched the PubMed, Embase, Web of Science, CNKI, Wanfang, CQVIP, and CBM databases. MSI diagnosis studies by PCR and capillary electrophoresis were included to compare the incidence of MSI-H in colorectal cancer obtained from panels with different microsatellite markers. Egger's bias test was used to assess risk of bias. RESULTS: Seventeen articles were included, which used the Newcastle-Ottawa Scale (NOS) scale for quality evaluation. The NOS scores of the included documents were ≥7 points, and the quality of the documents met the requirements. The incidence of MSI-H detected by the 2B3D NCI panel was 13.5% [95% confidence interval (CI): 10.8-16.4, I2=52.321%, P=0.026, n=10 studies including 2,681 participants], the incidence of MSI-H detected by the mononucleotide panels was 10.6% (95% CI: 7.1-14.7, I2=81.147%, P=0.000, n=7 studies including 3,249 participants). This indicates that, in the Chinese population, the 2B3D NCI panel can detect 27.4% more MSI-H cancers than the mononucleotide panels, 54.7% more MSI-H cancers than the panel of 6 mononucleotides, and its sensitivity is comparable to that of Promega. CONCLUSIONS: The findings of the meta-analysis demonstrated that, using the 2B3D NCI panel for MSI detection can avoid the underestimation of the incidence MSI-H in colorectal cancer and can be considered the most suitable panel for MSI detection in the Chinese population. The inclusion of only published data might be a potential source of publication bias.

Long Noncoding RNA PTPRG Antisense RNA 1 Reduces Radiosensitivity of Nonsmall Cell Lung Cancer Cells Via Regulating MiR-200c-3p/TCF4.

BACKGROUND: PTPRG antisense RNA 1 has been well-documented to exert an oncogenic role in diverse neoplasms. However, the precise role of PTPRG antisense RNA 1 in regulating radiosensitivity of nonsmall cell lung cancer cells remains largely elusive. METHODS: Expression levels of PTPRG antisense RNA 1 and miR-200c-3p in nonsmall cell lung cancer tissues and cells were detected by quantitative real-time polymerase chain reaction, while transcription factor 4 expression was examined by immunohistochemistry and Western blot. After nonsmall cell lung cancer cells were exposed to X-ray with different doses in vitro, Cell Counting Kit-8 assay and colony formation assay were conducted to determine the influence of PTPRG antisense RNA 1 on cell viability. Interaction between miR-200c-3p and PTPRG antisense RNA 1 as well as transcription factor 4 was investigated by dual luciferase reporter assay. RESULT: In nonsmall cell lung cancer tissues, the expressions of PTPRG antisense RNA 1 and transcription factor 4 were significantly upregulated, whereas the expression of miR-200c-3p was downregulated. It was also proved that PTPRG antisense RNA 1 and 3'-untranslated region of transcription factor 4 can bind to miR-200c-3p. Under X-ray irradiation, overexpressed PTPRG antisense RNA 1 could promote the viability and enhance the radioresistance of nonsmall cell lung cancer cells, and this effect was partially weakened by miR-200c-3p mimics. Transcription factor 4 was identified as a target gene of miR-200c-3p, which could be positively regulated by PTPRG antisense RNA 1. CONCLUSION: PTPRG antisense RNA 1 reduces the radiosensitivity of nonsmall cell lung cancer cells via modulating miR-200c-3p/TCF4 axis.

Combined LIM kinase 1 and p21-Activated kinase 4 inhibitor treatment exhibits potent preclinical antitumor efficacy in breast cancer.

LIM kinase 1 (LIMK1) and p21-activated kinase 4 (PAK4) are often over-expressed in breast tumors, which causes aggressive cancer phenotypes and unfavorable clinical outcomes. In addition to the well-defined role in regulating cell division, proliferation and invasion, the two kinases promote activation of the MAPK pathway and cause endocrine resistance through phosphorylating estrogen receptor alpha (ERα). PAK4 specifically phosphorylates LIMK1 and its functional partners, indicating possible value of suppressing both kinases in cancers that over-express PAK4 and/or LIMK1. Here, for the first time, we assessed the impact of combining LIMK1 inhibitor LIMKi 3 and PAK4 inhibitor PF-3758309 in preclinical breast cancer models. LIMK1 and PAK4 pharmacological inhibition synergistically reduced the survival of various cancer cell lines, exhibiting specific efficacy in luminal and HER2-enriched models, and suppressed development and ERα-driven signals in a BT474 xenograft model. In silico analysis demonstrated the cell lines with reliance on LIMK1 were the most prone to be susceptible to PAK4 inhibition. Double LIMK1 and PAK4 targeting therapy can be a successful therapeutic strategy for breast cancer, with a unique efficiency in the subtypes of luminal and HER2-enriched tumors.

Clinical efficacy analysis of Osimertinib treatment for a patient with leptomeningeal metastasis of EGFR+ non-small cell lung cancer without the T790M mutation.

BACKGROUND: To find the method of therapy of leptomeningeal metastasis (LM) to non-small cell lung cancer (NSCLC) patient with EGFR mutation (EGFR+) but without T790M mutation. METHODS: A retrospective analysis was reviewed for 5 NSCLC patients with EGFR+ who develop to LM from January 2018 to February 2019 in our hospital. RESULTS: All five NSCLC cases were adenocarcinoma, four cases were verified existed EGFR mutation with 19 exon deletion in the first diagnosed by biopsy tissue, the other tissue was verified 21 exon mutation. Two cases were initially diagnosed with LM, and the other three cases were found metastasis with leptomeningeal respectively after 64, 3 and 4 months when the lung cancer was diagnosed. There were not verified to exist T790M mutation with EGFR+ when all the five cases developed to LM. The major symptom was headache and blurred vision. In the image scanning, two cases were not revealed, but other three cases show that multiple metastatic lesions with brain and meninges. All patients were identified existed adenocarcinoma cells in cerebrospinal fluid (CSF). Four cases were treated by the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and joint therapy including chemotherapy and radiotherapy, and the other case was treated by temozolomide and intrathecal chemotherapy in their earlier therapy. The curative effect was significant when they took osimertinib orally 80 mg once a day, for the disease progressing. The neurological symptoms were relieved in patient about 5-10 days after osimertinib treatment. The remission time was 10, 7, 7, 5, 4 months respectively until last following time to June 2019. The survival time was respectively 74, 7, 27, 18, and 4 months. The side effects were not increased. CONCLUSIONS: Whether EGFR+ with T790M mutation was positive or negative, osimertinib is an effective drug and can improve quality of life and prolong the survival for NSCLC patient with EGFR mutation to progress LM.