[Clinical phenotype and genetic analysis of a child featuring short stature and multiple skeletal dysplasia].

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a child featuring familial short stature. METHODS: A child who was admitted to Huzhou Maternal and Child Health Care Hospital on October 7, 2021 for growth retardation and pectus carinatum was selected as the study subject. Physical exam and medical imaging was performed. The child was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 1-year-old male, had manifested with slightly short stature (Z = -2.03), midfacial dysplasia, and multiple skeletal dysplasia such as pectus carinatum, irregular vertebral morphology, and defect of lumbar anterior bones. His mother, maternal grandmother and great-maternal grandfather also had short stature. WES revealed that the child has harbored a heterozygous c.2858dupA (p.Asp953GlufsTer476) frameshifting variant of the ACAN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2858dup (p.Sp953Glufster476) variant was classified as likely pathogenic (PVS1+PM2_Supporting). The patient has shown marked improved height after receiving 11 months of treatment with human recombinant growth hormone (supplemental dose) starting from 20 months of age. CONCLUSION: The ACAN: c.2858dup (p.Asp953GlufsTer476) variant probably underlay the pathogenesis of short stature in this child.

Mayer-Rokitansky-Küster-Hauser syndrome with idiopathic central precocious puberty: a case report.

Background: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is mainly characterized by congenital aplasia of the uterus and the upper two-thirds of the vagina in females with normal secondary sex characteristics and female karyotype (46,XX). MRKH syndrome is typically diagnosed due to primary amenorrhea in adolescence and is very difficult to diagnose in childhood. MRKH syndrome combined with central precocious puberty (CPP) is extremely rare. In this article, we report a case of MRKH syndrome with idiopathic CPP (ICPP). Case Description: A 7-year-old girl was presented with development of bilateral breasts for 1 year and relatively low body height. Based on her age, clinical signs, and laboratory findings, she was initially diagnosed with ICPP and treated with sustained-release gonadotropin-releasing hormone analog (GnRHa) therapy, and recombinant human growth hormone (rhGH) therapy from the 6th month onwards. During the follow-up, ultrasound and magnetic resonance imaging showed no uterus or uterine neck, an unclear vaginal structure, and normal ovaries. Her chromosome karyotype was 46,XX. A pediatric gynecological examination showed colpatresia. She was finally diagnosed with MRKH syndrome combined with CPP. After the GnRHa and rhGH treatment, her height became normal compared to her peers, and her bone age development was delayed. Conclusions: The present case suggests the possibility of concomitant CPP in patients with MRKH syndrome. The gonads and sexual organs of children with precocious puberty should be carefully monitored and assessed to exclude any sexual organ disorders.

CircKIF5B Promotes Hepatocellular Carcinoma Progression by Regulating the miR-192 Family/XIAP Axis.

Background: The long-term prognosis of HCC (hepatocellular carcinoma) with metastasis remains extremely poor. CircRNAs are promising as critical biological markers in identifying disease mechanisms and developing new effective treatments. However, the role of the aberrant expression of circRNAs in HCC progression remains largely unknown. Methods: CircKIF5B location was investigated by RNA fluorescence in situ hybridization (RNA-FISH). For circRNA determination, RNase R treatment and Real-Time Quantitative RT-PCR (qRT-PCR) were performed. Transwell chamber assays examined the chemotactic migration and invasion of liver cancer cells. Results: This study identified the circRNA circKIF5B originating from exons 1, 2, and 3 of the KIF5B gene. Importantly, we found that circKIF5B circRNA, rather than KIF5B linear mRNA, was notably upregulated in liver cancer cell lines and tissues. Moreover, we found that silencing circKIF5B markedly reduced the proliferation, invasion, and metastasis of liver cancer cells by sponging the miR-192 family, thus decreasing the expression of X-linked inhibitor of apoptosis (XIAP). Conclusion: Our data demonstrate that circKIF5B can regulate XIAP expression by sponging miR-192 and miR-215 competing for the ceRNA mechanism, indicating that circKIF5B may act as an essential upstream regulator and providing mechanistic evidence to support the view that circKIF5B/miR-192s/XIAP is a promising therapeutic target for treating liver cancer.

Clinical Trials of Liposomes in Children's Anticancer Therapy: A Comprehensive Analysis of Trials Registered on ClinicalTrials.gov.

Objective: Clinical trials have become essential for driving the development of medicine. However, little is known about the current status of clinical trials on liposomes in children's anticancer therapy (LCAT). This study aimed to synthesize current finding from clinical trials of LCAT in ClinicalTrials.gov. Methods: A cross-sectional descriptive study of clinical trials on LCAT was conducted, using studies registered on ClinicalTrials.gov through December 30, 2021. Results: A total of 74 eligible trials were identified, accounting for 4.8% (74/1552) of all trials on liposomes for cancer therapy. Among these trials, 70 (94.6%) were interventional trials, and the remaining 4 (5.4%) were observational trials. Of the 70 interventional trials, 63 (90.0%) were for treatment, 48.6% were involving unlabeled allocations, 30.0% were randomized, 52.9% were single group assignment, 71.4% were without masking, 28.6% were Phase 3 trials, 30.0% were Phase 1 trials, and 24.3% were Phase 2 trials. Furthermore, 17 liposomal drugs for 123 types of cancer were investigated in the interventional trials, and these were mainly focused on organic chemicals (43/70, 61.4%). Of these cancers, the highest proportion was leukemia (15.4%), followed by lymphoma (9.8%) and ovarian cancer (8.9%). Conclusion: High quality, adequately powered, masked, appropriately sized, and randomized clinical trials represent the critical priorities for conducting a high-quality clinical trial. However, most of these trials for LCAT were non-randomized, single group assignment, and non-blinded interventional trials of small scale, with various eligibility criteria and outcome measures. Our analysis highlights the need for improvement in the completeness of study designs curated on clinicalTrials.gov. We urge for decision-makers to avoid adopting entrenched positions about the study design of cancer clinical trials to avoid this problem. As such, tackling the problematic challenges related to cancer and designing efficient trials for cancer requires developing and applying new approaches and multiple strategies.

Accepting Immunotherapy After Multiline Treatment Failure: An Exploration of the Anxiety and Depression in Patients with Advanced Cancer Experience.

BACKGROUND: Tumor immunotherapy is a promising therapeutic strategy for patients with advanced cancers, and some tumors have profound and durable tumor regression. However, immunotherapy is still in the clinical trial stage with elusive long-term effects and complications as a new strategy. It is unclear whether patients possess an accurate understanding of the clinical benefits associated with these agents. OBJECTIVE: To investigate the anxiety and depression of patients with advanced cancer who received immunotherapy using programmed death-1 or programmed death-ligand 1 after multiline treatment failure, explore the influencing factors, and provide a reference for clinical medical staff and psychological support for patients. METHODS: The Hospital Anxiety and Depression Scale was used to calculate the anxiety and depression scores before and after 1, 2, and 3 courses of treatment, respectively. The patients with anxiety and depression were counted. Purposive sampling was used to conduct face-to-face semi-structured interviews with 21 patients to find out the reasons. The obtained data were analyzed and collated using Colaizzi's phenomenological method. RESULTS: One hundred and twenty-six patients with advanced cancers were included in the study. Before and after 1, 2 and 3 courses of treatment, 18.26%, 23.0%, 50% and 54% of patients suffered from anxiety and depression, respectively. The proportion of patients with anxiety and depression during immunotherapy kept increasing, mainly due to therapeutic efficacy below expectation, lack of timely information after treatment, lack of awareness of treatment and drugs, and lack of family and social support. CONCLUSION: Patients with advanced tumors after multiline treatment failure are susceptible to anxiety and depression during immunotherapy. It is necessary to test the emotional state of patients in time and carry out early intervention. Nursing staffs and medical staffs should adopt personalized measures to meet the psychological needs of patients.

Role of CXCR4 as a Prognostic Biomarker Associated With the Tumor Immune Microenvironment in Gastric Cancer.

Background: Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, accounting for high rates of morbidity and mortality in the population. The tumor microenvironment (TME), which plays a crucial role in GC progression, may serve as an optimal prognostic predictor of GC. In this study, we identified CXC motif chemokine receptor 4 (CXCR4) as a TME-related gene among thousands of differentially expressed genes (DEGs). We showed that CXCR4 can be used to predict the effect of immunotherapy in patients with GC. Methods: GC samples obtained from The Cancer Genome Atlas (TCGA) were analyzed for the presence of stroma (stromal score), the infiltration of immune cells (immune score) in tumor tissues, and the tumor purity (estimate score) using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm. DEGs were sorted based on differences in the values of the three scores. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological processes and pathways enriched in these DEGs. The correlations of scores with clinicopathological features and overall survival (OS) of patients with GC were assessed by the Kaplan-Meier survival and Cox regression analyses. Through subsequent protein-protein interaction (PPI) network and univariate Cox regression analyses, CXCR4 was identified as a TME-related gene. Gene Set Enrichment Analysis (GSEA) was performed to assess the role of CXCR4 in the TME of GC. The CIBERSORT algorithm was used to further explore the correlation between tumor-infiltrating immune cells (TIICs) and CXCR4. Finally, the TISIDB database was used to predict the efficacy of immunotherapy in patients with GC. Results: We extracted 1231 TME-related DEGs and by an overlapping screening of PPI network and univariate Cox regression, CXCR4 was identified as a biomarker of TME, which deeply engaged in immune-related biological processes of gastric cancer and have close association with several immunocompetent cells. Conclusion: CXCR4 may be a useful biomarker of prognosis and an indicator of the TME in GC.

Prognostic Significance of Red Cell Distribution Width in Advanced Non-Small Cell Lung Cancer Patients.

BACKGROUND: Red blood cell distribution width (RDW) is a parameter reported in blood routine examination, and has been reported as an inflammatory biomarker. The objective of this study was to investigate the significance of RDW in NSCLC patients with EGFR mutations. METHODS: The clinical data of 102 patients with NSCLC who underwent radical resection surgery in the First Affiliated Hospital of Wenzhou Medical University from December 2012 to November 2017 were collected. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. RESULTS: The RDW levels were divided into two groups: high RDW (≥ 13.1%), n = 47 vs. low RDW, n = 55 (< 13.1%). Univariate analysis showed that there were significant associations of high RDW values with smoking history and brain metastasis. Forty-seven patients with elevated RDW levels had shorter progression-free survival (PFS) than 55 patients with normal RDW levels (264 vs. 310 days, p = 0.039). CONCLUSIONS: RDW is associated with several factors that reflect inflammation and malnutrition in lung cancer patients. Moreover, high levels of RDW are associated with poor survival.

Establishment of a Novel Risk Score System of Immune Genes Associated With Prognosis in Esophageal Carcinoma.

BACKGROUND: Few studies have addressed the role of immune-related genes in the survival and prognosis of different esophageal cancer (EC) sub-types. We established two new prognostic model indexes by bioinformatics analysis to select patients with esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) who may benefit from immunotherapy. METHODS: Based on TCGA and ImmPort data sets, we screened immune genes differentially expressed between tumor and normal tissues in ESCC and EAC and analyzed the relationship between these genes and patient survival outcomes. We established the risk score models of immune-related genes in ESCC and EAC by multivariate COX regression analysis. RESULTS: We identified 12 and 11 immune-related differentially expressed genes associated with the clinical prognosis of ESCC and EAC respectively, based on which two prognostic risk score models of the two EC sub-types were constructed. It was found that the survival probability of patients with high scores was significantly lower than that of patients with low scores (p < 0.001). BMP1, EGFR, S100A12, HLA-B, TNFSF18, IL1B, MAPT and OXTR were significantly related to sex, TNM stage or survival outcomes of ESCC or EAC patients (p < 0.05). In addition, the risk score of ESCC was significantly correlated with the level of B cell infiltration in immune cells (p < 0.05). CONCLUSIONS: The prognosis-related immune gene model indexes described herein prove to be useful prognostic biomarkers of the two EC sub-types in that they may provide a reference direction for looking for the beneficiaries of immunotherapy for EC patients.

High Mean Corpuscular Volume as a Predictor of Poor Overall Survival in Patients with Esophageal Cancer Receiving Concurrent Chemoradiotherapy.

BACKGROUND: Increasing numbers of recent studies have demonstrated that high mean corpuscular volume (MCV) is a predictor of poor overall survival (OS) and therapeutic response in patients with solid tumors. The aim of the present study was to explore the association between high MCV and OS in patients with advanced esophageal cancer (EC) undergoing concurrent chemoradiotherapy. PATIENTS AND METHODS: Enrolled in this study were 249 patients with advanced EC who underwent concurrent chemoradiotherapy. Pre-treatment MCV values were collected in all patients and their correlations with OS and pathophysiological characteristics were analyzed. The chi-square test was used to explore the correlation between MCV and various clinical pathophysiological characteristics, and the prognostic significance of high MCV using Kaplan-Meier curves and the Cox proportional hazards model. All P-values were two-tailed and a P-value <0.05 was considered statistically significant. RESULTS: According to ROC curve analysis, the optimal cut-off value of MCV was 93.6 fL. The mean OS was 14.7 months in all 249 EC patients, 10.9 months in patients with MCV >93.6 fL, and 18.8 months in patients with MCV <93.6 fL; the difference is statistically significant (P<0.05). Chi-square test showed that the MCV value was correlated with the N stage of the tumor and the therapeutic effect, indicating that the higher the MCV was, the higher the T stage of the tumor and the worse the therapeutic effect would be (p=0.012 and p <0.01). Multivariate analysis showed that MCV (OR = 1.864, 95% CI: 1.439-2.415) was an independent prognostic factor for OS in EC patients. CONCLUSION: High MCV is a poor predictor of OS in patients with advanced EC receiving concurrent chemoradiotherapy.

Predictive value of neuron-specific enolase, neutrophil-to-lymphocyte-ratio and lymph node metastasis for distant metastasis in small cell lung cancer.

OBJECTIVE: To investigate the value of neuron-specific enolase (NSE), neutrophil-to-lymphocyte ratio (NLR) and lymph node metastasis in predicating distant metastasis in patients with limited-stage small cell lung cancer (LD-SCLC). METHODS: Clinical pathological data of LD-SCLC patients in the First Affiliated Hospital of Wenzhou Medical University between August 2009 and October 2017 were retrospectively analyzed. The age, gender, smoking, TNM, NSE, NLR, chemotherapy cycle, radiotherapy, surgery and new metastasis of lymph nodes of 47 cases with distant metastasis and 47 cases without distant metastasis in 1 year were compared. Finally, factors influencing distant metastasis were determined as the predictors. The receiver operating characteristic (ROC) curve model was established based on logistic regression analysis of the factors obtained. RESULTS: Distant metastasis mainly involved brain (17/47), liver (17/47) and bone (17/47). Univariate analysis showed that patients with new lymph node metastasis, high NSE, pretreatment hilar lymph node metastasis and NLR were more prone to have distant metastasis. Multivariate analysis showed that new lymph node metastasis, high NSE, NLR and pretreatment hilar lymph node metastasis were independent predictors. The predictive model established using these predictors had an AUC of 0.872 (95%CI: 0.803-0.941), a sensitivity of 76.60% and a speciality of 80.85%. CONCLUSION: The new lymph node metastasis, NLR and NSE are predictors of distant metastasis, and thus, may have a profound impact on treatment decision making. Patients with lower NLR and NSE expression levels and less new metastasis of lymph nodes have a lower distant metastasis rate.

Ginsenoside Rg3 suppresses the growth of gemcitabine-resistant pancreatic cancer cells by upregulating lncRNA-CASC2 and activating PTEN signaling.

Pancreatic cancer is one of the most fatal malignancies with high mortality. Gemcitabine (GEM)-based chemotherapy is the most important treatment. However, the development of GEM resistance leads to chemotherapy failure. Previous studies demonstrated the anticancer activity of ginsenoside Rg3 in a variety of carcinomas through modulating multiple signaling pathways. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, colony formation assay, flow cytometry apoptosis assay, Western blotting assay, xenograft experiment, and immunohistochemistry assay were performed in GEM-resistant pancreatic cancer cell lines. Ginsenoside Rg3 inhibited the viability of GEM-resistant pancreatic cancer cells in a time-dependent and concentration-dependent manner through induction of apoptosis. The level of long noncoding RNA cancer susceptibility candidate 2 (CASC2) and PTEN expression was upregulated by the ginsenoside Rg3 treatment, and CASC2/PTEN signaling was involved in the ginsenoside Rg3-induced cell growth suppression and apoptosis in GEM-resistant pancreatic cancer cells. Ginsenoside Rg3 could be an effective anticancer agent for chemoresistant pancreatic cancer.

MicroRNA-1275 induces radiosensitization in oesophageal cancer by regulating epithelial-to-mesenchymal transition via Wnt/ß-catenin pathway.

Acquired radioresistance is one of the main obstacles for the anti-tumour efficacy of radiotherapy in oesophageal cancer (EC). Recent studies have proposed microRNAs (miRNAs) as important participators in the development of radioresistance in various cancers. Here, we investigated the role of miR-1275 in acquired radioresistance and epithelial-mesenchymal transition (EMT) in EC. Firstly, a radioresistant cell line KYSE-150R was established, with an interesting discovery was observed that miR-1275 was down-regulated in KYSE-150R cells compared to the parental cells. Functionally, miR-1275 inhibition elevated radioresistance in KYSE-150 cells via promoting EMT, whereas enforced expression of miR-1275 increased radiosensitivity in KYSE-150R cells by inhibiting EMT. Mechanically, we demonstrated that miR-1275 directly targeted WNT1 and therefore inactivated Wnt/ß-catenin signalling pathway in EC cells. Furthermore, WNT1 depletion countervailed the promoting effect of miR-1275 suppression on KYSE-150 cell radioresistance through hampering EMT, whereas WNT1 overexpression rescued miR-1275 up-regulation-impaired EMT to reduce the sensitivity of KYSE-150R cells to radiation. Collectively, our findings suggested that miR-1275 suppressed EMT to encourage radiosensitivity in EC cells via targeting WNT1-activated Wnt/ß-catenin signalling, providing a new therapeutic outlet for overcoming radioresistance of patients with EC.

Endoplasmic reticulum Ca2+ release causes Rieske iron-sulfur protein-mediated mitochondrial ROS generation in pulmonary artery smooth muscle cells.

Mitochondrial reactive oxygen species (ROS) cause Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptors (RyRs) in pulmonary artery smooth muscle cells (PASMCs), playing an essential role in hypoxic pulmonary vasoconstriction (HPV). Here we tested a novel hypothesis that hypoxia-induced RyR-mediated Ca2+ release may, in turn, promote mitochondrial ROS generation contributing to hypoxic cellular responses in PASMCs. Our data reveal that application of caffeine to elevate intracellular Ca2+ concentration ([Ca2+]i) by activating RyRs results in a significant increase in ROS production in cytosol and mitochondria of PASMCs. Norepinephrine to increase [Ca2+]i due to the opening of inositol 1,4,5-triphosphate receptors (IP3Rs) produces similar effects. Exogenous Ca2+ significantly increases mitochondrial-derived ROS generation as well. Ru360 also inhibits the hypoxic ROS production. The RyR antagonist tetracaine or RyR2 gene knockout (KO) suppresses hypoxia-induced responses as well. Inhibition of mitochondrial Ca2+ uptake with Ru360 eliminates N- and Ca2+-induced responses. RISP KD abolishes the hypoxia-induced ROS production in mitochondria of PASMCs. Rieske iron-sulfur protein (RISP) gene knockdown (KD) blocks caffeine- or NE-induced ROS production. Taken together, these findings have further demonstrated that ER Ca2+ release causes mitochondrial Ca2+ uptake and RISP-mediated ROS production; this novel local ER/mitochondrion communication-elicited, Ca2+-mediated, RISP-dependent ROS production may play a significant role in hypoxic cellular responses in PASMCs.

Polydatin inhibits proliferation and promotes apoptosis of doxorubicin-resistant osteosarcoma through LncRNA TUG1 mediated suppression of Akt signaling.

BACKGROUND: Development of doxorubicin-resistance is the main difficulty for osteosarcoma treatment. LncRNA Taurine upregulated gene 1 (TUG1) has been identified as oncogenic lncRNA in different types of carcinomas and was involved in chemoresistance. We aim to evaluate the anti-proliferative effects and the underlying molecular mechanism of Polydatin in doxorubicin-resistant osteosarcoma. METHODS: Doxorubicin-resistant osteosarcoma cell lines were established. MTT, colony formation, apoptosis assay, qRT-PCR and Western blotting analysis, immunohistochemistry and animal study were carried out. RESULTS: It has been showed Polydatin (50-250 µM) inhibited the cell proliferation in a dose- and time-dependent manner at 24 h, 48 h, and 72 h. Polydatin promoted the cell apoptosis significantly with the highest apoptosis rate >50%. Polydatin down-regulated TUG1 expression and TUG1/Akt signaling suppression was involved in Polydatin treated doxorubicin-resistant osteosarcoma cells. The in vivo study further confirmed the anti-cancer effect of Polydatin and related mechanisms. CONCLUSIONS: Polydatin may be a novel therapeutic agent for doxorubicin-resistant osteosarcoma treatment and TUG1 would be a potential molecular target.

PD-L1 Induces Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma Cells Through Activation of the PI3K/AKT Pathway.

Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma of the head and neck. Cancer therapy targeting programmed cell death protein-1 (PD-1) or programmed death ligand-1 (PD-L1) is revolutionary. However, the tumorigenic mechanism of PD-L1 is not yet clear in NPC. Here we demonstrated an oncogenic role of PD-L1 via activating PI3K/AKT in NPC cells. PD-L1 overexpression was frequently detected in NPC biopsies and cell lines by qRT-PCR. PD-L1 overexpression and knockdown demonstrated that PD-L1 promoted NPC cell invasion and metastasis in vitro and in vivo. Mechanistically, PD-L1 prominently activated the epithelial-mesenchymal transition (EMT) process in a PI3K/AKT-dependent manner. Taken together, we found that PD-L1 overexpression confers NPC cell malignancy and aggressiveness via activating the downstream PI3K/AKT signaling. Thus, these results provide a basis for diagnosis and treatment of NPC.

MicroRNA­301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells.

Esophageal cancer (EC) is one of the leading causes of death among malignancies. Radiotherapy for esophageal squamous cell carcinoma (ESCC) patients is limited by resistance to ionizing radiation (IR). An increasing body of evidence has demonstrated that aberrant expression of microRNA­301a (miR­301a) contributes to cancer progression and sensitivity to radiation. The aim of the present study was to investigate the exact functions and potential mechanisms of miR­301a in ESCC radioresistance. Initially, the miR­301a­transfected radioresistant ESCC cells KYSE­150R exhibited a decreased proliferation rate, and enhanced radiosensitivity and migration, whereas downregulation of miR­301a in radiosensitive KYSE­150 cells produced the opposite results. miR­301a regulates WNT1 expression at both the mRNA and protein levels. Furthermore, dual­luciferase reporter assays revealed that WNT1 was a target gene of miR­301a. In addition, the expression of miR­301a markedly affected the expression of Wnt/ß­catenin­related proteins such as ß­catenin and cyclin D1. Finally, overexpression of miR­301a inhibited epithelial­mesenchymal transition (EMT) conversion by directly targeting Snail and vimentin in radioresistant­ESCC cell lines; however, no inhibitory effects were exerted on Twist. Collectively, these results indicated that miR­301a increased the radiosensitivity and inhibited the migration of radioresistant­ESCC cells by targeting WNT1, thereby inactivating the Wnt/ß­catenin signaling pathway and EMT reversal. Thus, miR­301a may be a potential therapeutic target for the treatment of EC radioresistance.

CXCR3 expression in colorectal cancer cells enhanced invasion through preventing CXCR4 internalization.

One of the major causes of death in colorectal cancer (CRC) is invasion and metastasis. Better understanding of the molecular mechanism of CRC invasion and metastasis is essential in developing effective cancer therapies. Cooperative effect of CXCR3 and CXCR4 plays a crucial role in regulating CRC invasion. In present study, we discovered that CRC cells expressing higher levels of CXCR3 and CXCR4 were more invasive. Additionally, CXCR3 formed heteromers with CXCR4 and retained CXCR4 on cell surface. CXCR3 knockdown reduced surface CXCR4 expression and partially inhibited CRC cell invasion. On the contrary, CXCR3 overexpression enhanced surface CXCR4 abundance and promoted CRC cell invasion. Further research indicated that CXCR3-A isoform was responsible for increased CXCR4 surface expression and CRC cell invasion. However, CXCR3-A overexpression without CXCR4 expression did not cause CRC cell invasion, which suggested that CXCR3-A indirectly affect cell invasion through regulating CXCR4. Taken together, CXCR3 enhanced CXCR4 function in CRC cell invasion through forming heteromers with CXCR4 on cell surface and prevent CXCR4 internalization. Therefore, targeting CXCR3 could be a promising strategy for clinical treatment of CRC cell invasion and metastasis.

Induction chemotherapy plus concurrent chemoradiotherapy versus induction chemotherapy plus volumetric modulated arc therapy alone in the treatment of stage II-IVB nasopharyngeal carcinoma patients: a retrospective controlled study.

BACKGROUND: In the era of intensity-modulated radiotherapy (IMRT), the role of additional concurrent chemotherapy (CC) to radiotherapy (RT) after induction chemotherapy (IC) compared to IC followed by RT alone remains unclear for stage II-IVB nasopharyngeal carcinoma (NPC) patients. The aim of this study was to evaluate the efficacy and toxicities of IC/RT and IC/CCRT in the treatment of NPC with volumetric modulated arc therapy (VMAT). METHODS: From January 2012 to March 2016, a total of 217 NPC patients were retrospectively assessed. Of the 217 patients, 139 patients received IC followed by VMAT alone and 78 patients received IC plus CCRT. Overall survival (OS), progression-free survival (PFS) and toxicities were assessed. RESULTS: The 5-year OS, PFS rates were 57.5%, 41.8% and 47.8%, 38.4% for the IC/RT and IC/CCRT arms, respectively, without significant difference in survival between the two groups (both p > 0.05). Multivariate analysis indicated that treatment modality (IC/RT vs. IC/CCRT) was not an independent prognostic factor for OS or PFS. Grade 3-4 leukopenia/neutropenia (3.60% vs. 20.51%, p < 0.001), gastrointestinal disorder (nausea/vomiting/diarrhea, 2.16% vs. 41.03%, p < 0.001), mucositis (29.50% vs. 47.44%, p = 0.01) and xerostomia (34.53% vs. 48.72%, p = 0.04) were more frequent in the IC/ CCRT arm than in the IC/RT arm during VMAT. CONCLUSIONS: No significant difference in OS and PFS was observed between IC plus VMAT alone and IC/CCRT in the treatment of stage II-IVB NPC patients, however, more side effects were observed in the IC/CCRT arm.

Curcumin reverses irinotecan resistance in colon cancer cell by regulation of epithelial-mesenchymal transition.

The objective of this study was to investigate the effect and the mechanism by which curcumin reverses irinotecan-induced chemotherapy resistance in colon cancer. Construction of irinotecan-resistant colon cancer model LoVo/CPT-11R cells was performed by increasing drug concentration. The Cell Counting Kit-8 assay was used to detect inhibition of proliferation; cell morphology was observed by an optical microscope. Quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial-mesenchymal transition (EMT); drug-resistant cells were treated with curcumin at different concentrations and Cell Counting Kit-8 was reperformed to detect cell proliferation after treatments. Drug-resistant cells were then divided into four groups: control group, irinotecan group, curcumin group, and irinotecan+curcumin group; quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial-mesenchymal transition. Flow cytometry was used to detect cell apoptosis after grouping, and apoptosis-related protein was detected by western blotting. LoVo/CPT-11R cells could survive in culture medium containing irinotecan at 60 µg/ml and the drug-resistance index was 5.69; the drug-resistant cells had a larger volume than normal cells and were poorly connected to each other. E-cadherin expression was downregulated, whereas vimentin and N-cadherin expressions were upregulated. After curcumin treatment, drug-resistant cell proliferation was significantly inhibited; in the curcumin+irinotecan treatment group, E-cadherin expression was upregulated, whereas vimentin and N-cadherin expressions were downregulated. Curcumin could significantly increase cell apoptosis. EMT is involved in the development of irinotecan resistance and curcumin can reverse this drug resistance through reversion of the EMT process.

Retraction Note to: Decreased expression of the long noncoding RNA LINC00261 indicate poor prognosis in gastric cancer and suppress gastric cancer metastasis by affecting the epithelial-mesenchymal transition.

RETRACTION: The authors have retracted this article [1] because of significant overlap of text and some images with a previously published article by Xu et al. [2]. A formal investigation by the 1st Affiliated Hospital of Wenzhou Medical University has found that some panels in Fig. 6b [1] are identical with panels in Fig. 5a [2] and some images of mice lungs in Fig. 6c [1] are identical with images in Fig. 3g [2]. The data reported in this article are therefore unreliable. All authors agree to this retraction.