[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.

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.

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.

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.

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.

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.

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.

The efficacy and roles of combining temozolomide with whole brain radiotherapy in protection neurocognitive function and improvement quality of life of non-small-cell lung cancer patients with brain metastases.

BACKGROUND: Brain metastasis (BM) is a poor prognostic factor for non-small-cell lung cancer (NSCLC). The efficacy and roles of combining temozolomide (TMZ) with whole brain radiotherapy (WBRT) in protection neurocognitive function (NCF) and improvement quality of life (QOL) were investigated and compared with WBRT alone in the treatment of NSCLC patients with BM. METHODS: A total of 238 NSCLC patients with BM were reviewed and categorized into WBRT plus TMZ (RCT) arm and WBRT alone (RT), respectively. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. NCF was assessed by using revised Hopkins Verbal Learning Test (HVLT-R), Controlled Oral Word Association (COWA) test and Trail-making Test (TMT). QOL was assessed by the Functional Assessment of Cancer Treatment-Lung (FACT-L) Chinese version 4.0 questionnaire. RESULTS: The average intracranial objective response (ORR) and disease control rate (DCR) for all the patients were 26.9 and 95.8%, respectively. The intracranial ORR and DCR for RCT and RT arm were 34.9% vs. 20.2% (p = 0.01) and 98.4% vs. 92.7% (p = 0.03), respectively. The median intracranial progression-free survival (PFS) and overall survival (OS) of NSCLC patients with BM were 5.2 and 7.3 months, respectively. The median PFS of RCT arm was significantly longer than that of RT arm (5.9 vs. 4.9 months, p = 0.002). The median OS of the RCT arm was also slightly longer than that of the RT arm (8.5 vs. 5.9 months), but without statistical significance (p = 0.11). Multivariate analysis indicated that TMZ was a significant factor for PFS. Statistically significant differences on NCF and QOL were observed between CRT and RT arms at 5 months. RCT showed a trend of toxicities increase compared with RT, however, the toxicities were tolerable and manageable. CONCLUSIONS: Adding TMZ to WBRT in the treatment of NSCLC patients with BM could improve the intracranial ORR, DCR, and median PFS compared with WBRT alone. Although no remarkable difference on median OS was found, adding TMZ could prevent NCF and QOL from worsening. The side effects increased by adding TMZ, but the difference was not statistical significance and toxicities were well tolerated.

Polyphyllin VII increases sensitivity to gefitinib by modulating the elevation of P21 in acquired gefitinib resistant non-small cell lung cancer.

Blockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is considered the frontline strategy for advanced NSCLC with EGFR mutations. However, acquired resistance to EGFR-TKI has been observed, resulting in disease progression and limited clinical benefit. Polyphyllin VII is the main member of polyphyllin family, which has been demonstrated to show strong anticancer activity against carcinomas. The sensitizing effect and underlying mechanism of Polyphyllin VII against acquired EGFR-TKI resistant NSCLC are still unexplored. In the present study, we aim to examined the sensitizing effect of Polyphyllin VII to gefitinib by modulating P21 signaling pathway in gefitinib acquired resistant NSCLC in vitro and in vivo. Gefitinib sensitive PC-9 cells and gefitinib acquired resistant H1975 cells were used. Cell proliferation and Clonogenic assay, Cell cycle analysis, Western blotting analysis and xenograft treatment were carried out. Polyphyllin VII enhanced the anti-proliferative effects of gefitinib and gefitinib-induced G1 phase arrest by modulation of P21 signaling pathway in acquired gefitinib resistant cells in vitro and in vivo. Polyphyllin VII elevated sensitization of gefitinib acquired resistant NSCLC cells to gefitinib through G1 phase arrest and modulation of P21 signaling pathway. It provides a potential new strategy to overcome gefitinib acquired resistance for EGFR-TKI resistant NSCLC.

MR Lymphangiography for Focal Disruption of the Thoracic Duct in Chylothorax of an Infant: a Case Report and Literature Review.

Chylothorax is a rare cause of pleural effusion in children, and it is usually difficult to identify the location of chyle leakage due to the small size of the thoracic duct in children. Herein we report an infant case with chylothorax whose leakage of the thoracic duct was successfully located by magnetic resonance lymphangiography (MRL) using pre-contrast MR cholangiopancreatography (MRCP) and gadodiamide-enhanced spectral presaturation inversion recovery (SPIR) T1-weighted imaging, which demonstrate the imaging method is easy and effective for detecting the focal disruption of the thoracic duct in children with chylothorax and younger than 8 months old.

Profiling and bioinformatics analyses reveal differential circular RNA expression in radioresistant esophageal cancer cells.

BACKGROUND: Acquired radioresistance during radiotherapy is considered as the most important reason for local tumor recurrence or treatment failure. Circular RNAs (circRNAs) have recently been identified as microRNA sponges and involve in various biological processes. The purpose of this study is to investigate the role of circRNAs in the radioresistance of esophageal cancer. METHODS: Total RNA was isolated from human parental cell line KYSE-150 and self-established radioresistant esophageal cancer cell line KYSE-150R, and hybridized to Arraystar Human circRNA Array. Quantitative real-time PCR was used to confirm the circRNA expression profiles obtained from the microarray data. Bioinformatic tools including gene ontology (GO) analysis, KEGG pathway analysis and network analysis were done for further assessment. RESULTS: Among the detected candidate 3752 circRNA genes, significant upregulation of 57 circRNAs and downregulation of 17 circRNAs in human radioresistant esophageal cancer cell line KYSE-150R were observed compared with the parental cell line KYSE-150 (fold change ≥2.0 and P < 0.05). There were 9 out of these candidate circRNAs were validated by real-time PCR. GO analysis revealed that numerous target genes, including most microRNAs were involved in the biological processes. There were more than 400 target genes enrichment on Wnt signaling pathway. CircRNA_001059 and circRNA_000167 were the two largest nodes in circRNA/microRNA co-expression network. CONCLUSIONS: Our study revealed a comprehensive expression and functional profile of differentially expressed circRNAs in radioresistant esophageal cancer cells, indicating possible involvement of these dysregulated circRNAs in the development of radiation resistance.

Inhibition of cyclin D1 enhances sensitivity to radiotherapy and reverses epithelial to mesenchymal transition for esophageal cancer cells.

Acquired radioresistance during radiotherapy has significantly affected the treatment efficacy in esophageal cancer. Many of radioresistant cancer cells demonstrated epithelial-mesenchymal transition (EMT).We found in previous study that a radioresistant cell line (KYSE-150R) possessed EMT characteristic with cyclin D1 overexpression. Cyclin D1 has been demonstrated to affect the radiation sensitivity in cancer cells. To elucidate the molecular functions of cyclin D1 on EMT phenotypes and esophageal cancer radiosensitivity, we treated the radioresistant esophageal cancer cells (KYSE-150R) and parental cells (KYSE-150) with cyclin D1 small interfering RNA (siRNA). The cell proliferation rate of KYSE-150R and the radiation survival fraction were significantly decreased in cyclin D1 siRNA treatment group. Knocking down cyclin D1 resulted in G0/G1 arrest in KYSE-150R cells. The average number of irradiation-induced γ-H2AX foci increased in the cells treated with cyclin D1 siRNA, indicating impaired DNA double-strand break (DSB) repair in KYSE-150R cells. Cyclin D1 also reversed EMT phenotypes with significantly increased expression of E-cadherin in KYSE-150R cells. However, cyclin D1 siRNA have no radiosensitizing effects on KYSE-150 cells, with no obvious change in EMT marker expression .Our work showed that EMT phenotypes can be reduced and the radiosensitivity of esophageal cancer cells can be enhanced by inhibiting cyclin D1.

Upregulated expression of long non-coding RNA LINC00982 regulates cell proliferation and its clinical relevance in patients with gastric cancer.

Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker or potential therapeutic targets. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. In this study, we identified a novel lncRNA LINC00982, whose expression was downregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, decreased LINC00982 expression was negatively correlated with invasion depth (P < 0.001), advanced TNM stage (P = 0.004), and regional lymph node metastasis (P = 0.005). LINC00982 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.742; 95 % confidence interval (CI) = 0.678-0.800, P < 0.01]. Kaplan-Meier analysis demonstrated that decreased LINC00982 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that LINC00982 could be an independent prognostic marker. The levels of LINC00982 in gastric juice from gastric patients were significantly lower than those from normal subjects (P = 0.026). Furthermore, knockdown of LINC00982 expression by small interfering RNA (siRNA) could promote cell proliferation and cell cycle progression, while ectopic expression of LINC00982 inhibited cell proliferation and rendered cell cycle arrest in GC cells partly via regulating P15 and P16 protein expressions. Our findings present that decreased lncRNA LINC00982 could be identified as a poor prognostic biomarker in GC and regulate cell proliferation.

Upregulated expression of long noncoding RNA SNHG15 promotes cell proliferation and invasion through regulates MMP2/MMP9 in patients with GC.

Accumulation of data indicates that misregulated long noncoding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be served as diagnosis and prognosis biomarker or potential therapeutic targets. Identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are significant for understanding the development and progression of cancer. In this study, we identified a novel lncRNA SNHG15, whose expression was upregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, increased SNHG15 expression was positively correlated with invasion depth (P < 0.001), advanced tumor node metastasis (TNM) stage (P = 0.001), and lymph node metastasis (P = 0.019). SNHG15 levels were robust in differentiating GC tissues from controls (area under the curve (AUC) = 0.722; 95 % confidence interval (CI) = 0.657-0.782, P < 0.01). Kaplan-Meier analysis demonstrated that elevated SNHG15 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that SNHG15 could be an independent prognostic marker. Furthermore, knockdown of SNHG15 expression by siRNA could inhibit cell proliferation and invasion and induce apoptosis, while ectopic expression of SNHG15 promoted cell proliferation and invasion in GC cells partly via regulating MMP2 and MMP9 protein expression. Our findings present that elevated lncRNA SNHG15 could be identified as a poor prognostic biomarker in GC and regulate cell invasion.

Anticancer Effects of Paris Saponins by Apoptosis and PI3K/AKT Pathway in Gefitinib-Resistant Non-Small Cell Lung Cancer.

BACKGROUND Paris saponins have been studied for their anticancer effects in various cancer types, but the mechanisms underlying the cytotoxic effects, especially in EGFR-TKI-resistant cells, are still unclear. We explored the potential mechanism of the antitumor effects of PSI, II, VI, VII in EGFR-TKI-resistant cells and attempted to develop PSI, II, VI, VII as a systemic treatment strategy for EGFR-TKI-resistant lung cancer. MATERIAL AND METHODS Growth inhibition was detected by MTT assay. The apoptosis assay was detected using annexin-V/PI and Hoechst staining. The level of PI3K, pAKT, Bax, Bcl-2, caspase-3, and caspase-9 protein expression were detected using Western blot analysis. RESULTS The results revealed that PSI, II, VI, VII inhibited the proliferation of PC-9-ZD cells. Furthermore, PSI, II, VI, VII induced significant cell apoptosis. The levels of PI3K, pAKT, Bcl-2 protein decreased, while the Bax, caspase-3, and caspase-9 protein was increased by PSI, II, PSVI, PSVII treatment and resulted in increased sensitivity to gefitinib in PC-9-ZD cells. CONCLUSIONS The underlying mechanism of Paris saponins may be related to targeting the PI3K/AKT pathways to cause apoptosis. Our results suggest a therapeutic potential of Paris saponins in clinical settings for gefitinib-resistant NSCLC.

[Clinical value of prenatal MRI in the diagnosis and differential diagnosis of fetal bronchopulmonary sequestration].

OBJECTIVE: To investigate the clinical value of prenatal MRI in the diagnosis and differential diagnosis of congenital bronchopulmonary sequestration (BPS). METHODS: From January 2009 to December 2014, 16 fetuses with BPS were diagnosed by fetal MRI in Huzhou Maternity and Child Care Hospital and Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine. The clinical data of these cases were analyzed retrospectively. All were singleton pregnancy, and MRI was carried out within 24-48 hours after routine prenatal ultrasound. All the neonates underwent postnatal enhanced CT scan or surgical biopsy after birth, and the results were compared to prenatal MRI diagnosis. RESULTS: (1) With prenatal MRI, 16 cases were diagnosed BPS. The lesions located in left lung in 10 cases, and right lung in 6 cases. As the scope of the lesion, 3 cases located in the whole left lung, 6 cases limited to the left lower lobe, and 1 case was subdiaphragmatic on the left side. 2 cases located in the whole right lung and 4 cases limited to the right lower lobe. One case complicated oligoamnios, and one had pleural effusion. Supplying vessels could be found in 14 cases. (2) When the postnatal results were compared with prenatal MRI, 15 cases were comfirmed as BPS (15/16), including 10 intralobar cases 5 extralobar cases. One that was diagnosed as BPS by prenatal MRI was confirmed to be congenital cystic adenomatoid malformation (CCAM) by pathology. The accuracy of prenatal MRI diagnosis of BPS was 15/16. Prenatal ultrasound missed one case and misdiagnosed two cases, as one was mistakened as CCAM and the other as cystic teratoma. CONCLUSION: Prenatal MRI has good clinical value in the diagnosis and differential diagnosis of fetal BPS.

FH535 increases the radiosensitivity and reverses epithelial-to-mesenchymal transition of radioresistant esophageal cancer cell line KYSE-150R.

BACKGROUND: Acquired radioresistance has significantly compromised the efficacy of radiotherapy for esophageal cancer. The purpose of this study is to investigate the roles of epithelial-mesenchymal transition (EMT) and the Wnt/ß-catenin signaling pathway in the acquirement of radioresistance during the radiation treatment of esophageal cancer. METHODS: We previously established a radioresistant cell line (KYSE-150R) from the KYSE-150 cell line (a human cell line model for esophageal squamous cell carcinoma) with a gradient cumulative irradiation dose. In this study, the expression of EMT phenotypes and the Wnt/ß-catenin signaling pathway proteins were examined by real-time PCR, western blot and immunofluorescence in the KYSE-150R cells. The KYSE-150R cells were then treated with a ß-Catenin/Tcf inhibitor FH535. The expressions of nuclear and cytoplasmic ß-catenin and EMT markers in KYSE-150R cells were assessed at both mRNA and protein level after FH535 treatment. The radiosensitization effect of FH535 on KYSE-150R was evaluated by CCK8 analysis and a colony forming assay. DNA repair capacities was detected by the neutral comet assays. RESULTS: KYSE-150R cell line displayed obvious radiation resistance and had a stable genetic ability. EMT phenotype was presented in the KYSE-150R cells with decreased E-cadherin and increased snail and twist expressions. The up-regulated expressions of Wnt/ß-catenin signaling pathway proteins (Wnt1, FZD1-4, GSK3ß, CTNNB1 and Cyclin D1), the increased phosphorylation of GSK3ß, and the decreased phosphorylation of ß-catenin were observed in KYSE-150R cells compared with KYSE-150 cells, implicating the activation of the Wnt pathway in KYSE-150R cells. The expression of nuclear ß-catenin and nuclear translocation of ß-catenin from the cytoplasm was decreased after FH535 treatment. FH535 also reversed EMT phenotypes by increasing E-cadherin expression. The cell proliferation rates of KYSE-150R were dose-dependent and the radiation survival fraction was significantly decreased upon FH535 treatment. Neutral comet assays indicated that FH535 impairs DNA double stranded break repair in KYSE-150R cells. CONCLUSIONS: Acquisition of radioresistance and EMT in esophageal cancer cells is associated with the activation of the Wnt/ß-catenin pathway. EMT phenotypes can be reduced and the radiosensitivity of esophageal cancer cells can be enhanced by inhibiting the Wnt/ß-catenin pathway with FH535 treatment.

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.

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.

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.