SEMA3G, downregulated by ncRNAs, correlates with favorable prognosis and tumor immune infiltration in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC), relatively aggressive subtype of renal cell carcinoma, lacks of effective targets and promising biomarkers. Recently, although the function and immune correlation of semaphorin 3G (SEMA3G) in cancer draw more and more attention, its specific role and mechanism in KIRC are still not fully understood. In this work, we firstly conducted pan-cancer expression and survival bioinformatic analysis for SEMA3G and showed that SMEA3G might be a potential tumor suppressor and favorable prognostic biomarker in KIRC. Next, upstream noncoding RNA (ncRNA) regulatory mechanism of SEMA3G in KIRC was explored. By performing a series of in silico analyses, we identified that TBX2-AS1-miR-146a/b-5p axis was partially responsible for SEMA3G downregulation in KIRC. Furthermore, we also confirmed significant correlation of SEMA3G expression with tumor immune infiltration levels, expression of biomarkers of immune cells or immune checkpoints in KIRC. Taken together, the current data elucidated that ncRNA-caused downregulation of SEMA3G markedly linked to favorable prognosis and tumor immune infiltration in KIRC.

Continuous intravenous infusion of recombinant human endostatin using infusion pump plus chemotherapy in non-small cell lung cancer.

BACKGROUND: Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of primary lung cancer. However, efficacy and safety of the current regimens for NSCLC is unsatisfactory. Therefore, there has been an increasing urgency for development of potential therapeutic therapies for NSCLC. AIM: To investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin (Rh-endostain) using an infusion pump in retreated advanced NSCLC. METHODS: Patients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited. These patients received continuous intravenous infusion of Rh-endostain using an infusion pump. Objective response rate (ORR), clinical benefit rate (CBR), median progression-free survival (mPFS), and incidences of adverse events (AEs) were analyzed after treatment. RESULTS: A total of 45 patients with retreated advanced NSCLC were included, and all of them were evaluated. In these patients, ORR was 22.2%, CBR was 84.4%, and mPFS was 5.3 mo. The following AEs were observed, decreased hemoglobin (34 cases, 75.6%), nausea/vomiting (32 cases, 71.1%), elevated transaminase (24 cases, 53.3%), leukopenia (16 cases, 35.6%), thrombocytopenia (14 cases, 31.1%), and constipation (1 case, 3.4%). None of the patients had leukopenia, nausea /vomiting, and constipation of grade III and above. CONCLUSION: The patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump. Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.

Long Intergenic Non-Coding RNA 01121 Promotes Breast Cancer Cell Proliferation, Migration, and Invasion via the miR-150-5p/HMGA2 Axis.

PURPOSE: Long intergenic noncoding RNA 01121 (LINC01121) has been reported to be aberrantly expressed and acts as an oncogene in pancreatic cancer. However, the detailed molecular mechanism of LINC01121 in breast cancer remains largely unclear. In this study, we aimed to investigate the expression and biological function of LINC01121 in breast cancer. METHODS: LINC01121 and miR-150-5p expression were measured in breast cancer cell lines using quantitative reverse transcription PCR. MTS and flow cytometry assays were performed to determine cell proliferation, the cell cycle, and apoptosis. Cell migration and invasion were assessed by transwell assay. The protein expression of HMGA2 in breast cancer cell lines was measured by Western blotting. A luciferase reporter assay was used to assess the binding of LINC01121 and miR-150-5p. RESULTS: We found that LINC01121 was markedly up-regulated in breast cancer cell lines compared with normal breast epithelial cells. LINC01121 down-regulation markedly suppressed cell proliferation, cell cycle progression, migration, and invasion and promoted apoptosis in breast cancer cells. Further investigation showed that LINC01121 could serve as a molecular sponge for miR-150-5p and indirectly modulate the expression of its target, HMGA2. Moreover, miR-150-5p knockdown rescued the effects of LINC01121 down-regulation on HMGA2 protein expression, cell proliferation, cell cycle progression, apoptosis, migration, and invasion in breast cancer cells. CONCLUSION: Knockdown LINC01121 inhibited breast cancer cell proliferation, migration, and invasion via the miR-150-5p/HMGA2 axis.

Functionally impaired follicular helper T cells induce regulatory B cells and CD14+ human leukocyte antigen-DR- cell differentiation in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) represents one of the most common and aggressive cancers worldwide, as it typically displays irreversible progression and poor prognosis. Interaction between programmed death 1 (PD-1) and its ligand, PD-L1, plays important roles in tumor immunology. Follicular helper T (Tfh) cells have characteristically high PD-1 expression; thus, in the present study, we investigated the role of circulating Tfh cells and their correlation with disease-free survival after tumor resection in NSCLC. We found significantly higher number of Tfh cells but lower serum interleukin (IL)-21 levels in NSCLC patients, especially in those with advanced stage (III and IV), indicating that the function of Tfh cells to produce IL-21 was impaired. Further analysis showed that the increase in Tfh cells was attributable to an expansion of the PD-1+ -Tfh2 and PD-1+ -Tfh17 subtypes. Functional analysis showed that Tfh cells from NSCLC patients induced the differentiation of regulatory B cells and CD14+ human leukocyte antigen (HLA)-DR- cells. Interestingly, the number of Tfh1 subtypes in NSCLC patients was negatively correlated with disease-free survival after tumor resection. In short, the high number and abnormal function of Tfh cells could cause further immunosuppression and lead to tumor development in NSCLC. Rescuing Tfh functions therefore represents a potential therapeutic strategy in NSCLC.

Multiplex Assay for Identifying Animal Species Found in the Tibetan Area Using the Mitochondrial 12S rRNA Gene.

Southwestern China has an area with unique natural conditions located in alpine regions at altitudes from 2000 to 5000 m; this area is referred to as the Qinghai-Tibetan plateau (QTP). Unique animals, such as yaks (Bos grunniens), are found extensively on the plateau of Southwestern China due to its unique environment. In recent years, the prevalence of fake meat products such as fake jerky has increased in this area. This research was conducted as an attempt to develop a reliable multiplex polymerase chain reaction (mPCR) detection method for identifying nine animal species found in QTP. We developed the mPCR method using the specific sites found in 12S rRNA region of these nine species, which was effective in discriminating between the nine species and was successful in terms of validated reproducibility, detection limit (<6 pg total DNA), discrimination of mixed samples, and specificity (approximately 99%) using real meat samples. Our results show that the mPCR detection method can overcome the limitations of prior detection methods, such as restriction fragment length polymorphism or high-resolution melting analysis methods.

CYFRA 21-1 is an early predictor of chemotherapeutic effectiveness in advanced nonsmall cell lung cancer: An observational study.

Serum cytokeratin 19 fragment (CYFRA21-1) has been found to be a useful prognostic marker in lung cancer. Previous studies have revealed that change in CYFRA21-1 synchronously predicted therapeutic effectiveness in advanced nonsmall cell lung cancer (NSCLC) after the second cycle of chemotherapy. The objective of this study was to investigate the early predictive value of percentage change in serum CYFRA21-1 from pretreatment to completion of the first cycle of chemotherapy for chemotherapeutic effectiveness in advanced NSCLC patients.Ninety-seven advanced NSCLC patients with elevated serum CYFRA21-1 level (≥3.8 µg/L), who received 2 platinum-containing drugs, were included in this retrospective study. Serum CYFRA21-1 had been assayed before and after the first cycle of chemotherapy. To evaluate the effectiveness of chemotherapy, patients were allocated to disease control (DC) and progressive disease groups. The percentage changes of serum CYFRA21-1 concentration before and after first-cycle chemotherapy that occurred in each group were evaluated for their ability to predict achievement of radiologic DC, that is, to predict therapeutic effectiveness.The percentage change of serum CYFRA21-1 and the prevalence of ≥5% weight loss were higher in patients with progressive disease than in those with DC. The differences in other clinical and pathological variables including age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, cigarette smoking, histological type, gross type, clinical stage, and chemotherapy regimens of the 2 groups were not significant. Both multiple generalized linear model analysis and linear trend tests indicated that the percentage change of serum CYFRA21-1 concentration was independently and negatively linked to the effectiveness of chemotherapy for NSCLC (P < 0.01). The area under the receiver-operating characteristic curve of the percentage change in prediction of DC was 0.84 and the optimal cut-off value was17.5% (P < 0.001).The percentage change of serum CYFRA21-1 after completing the first cycle of chemotherapy was predictive of treatment effects and might be helpful in making early decisions to change chemotherapy regimens in patients with advanced NSCLC.

Suppression of TRPV4 channels ameliorates anti-dipsogenic effects under hypoxia in the subfornical organ of rats.

The phenomenon of water intake reduction during the 1(st) day of hypobaric hypoxia has been known for a long time. However, the reason for the same is yet unknown. The transient receptor potential vanilloid (TRPV) channels, including TRPV1 and TRPV4, are located in the subfornical organ (SFO). These are calcium permeable cationic channels gated by various stimuli such as cell swelling, low pH, and high temperature, and participate in anti-dipsogenic effects when activated. We aimed to explore the drinking behavior of rats and the mechanism of TRPVs under hypoxia. Chemical TRPV4 inhibitors (HC-067047 and Gadolinium) or TRPV4 knockout, but not TRPV1 inhibitor SB-705498, could restore the water intake under hypoxia. Hypoxia-mediated direct activation of TRPV4 may be the reason of anti-dipsogenic effects because the serum sodium, pH, and intracranial temperature are unaltered. Interestingly, we found that hypoxia immediately increased the intracellular Ca(2+) concentration ([Ca(2+)]i) in HEK293-TRPV4 cells and primary neurons from SFO region, but not in the HEK293-TRPV1 cells. Moreover, hypoxia-induced [Ca(2+)]i increase depended on the indispensable hemeoxygenase-2 (HO-2) and TRPV4. HO-2 and TRPV4 were also confirmed to form a complex in SFO neurons. These results demonstrated that SFO cells sense hypoxia and activate via the HO-2/TRPV4 multiple channels, which are associated with anti-dipsogenic effects.

RETRACTED: Aberrant frequency of IL-10-producing B cells and its association with Treg and MDSC cells in Non Small Cell Lung Carcinoma patients.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The Editor-in-Chief has retracted this article due to serious problems with copied and re-labeled images in several figures. Specifically, the problematic items are the HC and Stage I samples in figure 1D (IL-10/CD19) and figure 2B (CD127/CD25), in which the flow dot plots outside of the boxes are identical. This strongly suggests that the data was manipulated. The authors were unable to provide the raw data files to prove otherwise. This makes the overall conclusions of the paper unreliable and violates our ethical publishing policies. The corresponding author, Liannv Qiu takes full responsibility and apologizes to all co-authors in this article, and the editors and readership of Human Immunology for any negative impact this may have on the journal.

p53 codon 72 polymorphism and hematological cancer risk: an update meta-analysis.

BACKGROUND: Previous studies on the association of p53 codon 72 (Arg72Pro) polymorphism with hematological malignancies risk have produced conflicting results. The purpose of this meta-analysis is to define the effect of p53 Arg72Pro polymorphism on hematological malignancies risk. METHODOLOGY/PRINCIPAL FINDINGS: Through searching PubMed databases (or hand searching) up to April 2012 using the following MeSH terms and keywords: "p53", "codon 72" "polymorphism" and "leukemia", or "lymphoma", or "myeloma", thirteen were identified as eligible articles in this meta-analysis for p53 Arg72Pro polymorphism (2,731 cases and 7, 356 controls), including nine studies on leukemia (1,266 cases and 4, 474 controls), three studies on lymphoma (1,359 cases and 2,652 controls), and one study on myeloma. The overall results suggested that p53 Arg72Pro polymorphism was not associated with hematological malignancies risk. In stratified analyses, significantly increased non-Hodgkin lymphomas risk was found in p53 Arg72Pro polymorphism heterozygote model (Arg/Pro vs. Arg/Arg: OR = 1.18, 95%CI: 1.02-1.35) and dominant model (Arg/Pro+Pro/Pro vs. Arg/Arg: OR = 1.18, 95%CI: 1.03-1.34), but no significant association was found between leukemia risk and p53 Arg72Pro polymorphism. Further studies showed no association between leukemia risk and p53 Arg72Pro polymorphism when stratified in subtypes of leukemias, ethnicities and sources of controls. CONCLUSIONS/SIGNIFICANCE: This meta-analysis indicates that the p53 Arg72Pro polymorphism may contribute to susceptibility to non-Hodgkin lymphomas.