Multidisciplinary management of pediatric malignant rhabdoid tumor based on 5 years of experience at a tertiary care center.

OBJECTIVE: Malignant rhabdoid tumor (MRT) is a highly aggressive tumor that occurs mostly in young children with extremely poor prognosis. Standardized and effective treatment strategies for MRT have yet to be established because of its rarity. Here, we report our single-institutional experience involving MRT treatment. METHODS: Patients with newly diagnosed MRT between March 2016 and October 2021 were included. The clinical characteristic, treatment-related toxicities, clinical outcomes, and prognostic factor were retrospectively analyzed. RESULTS: A total of 18 patients with MRT were enrolled during the 5 years. The median age was 42.8 months (range 10 to 82 years). Among the 18 patients, 9 patients died after a median of follow-up 26 months (range 3 to 42 months). The 1-year event-free survival (EFS) and 3-year overall survival (OS) rates of the entire cohort were 63% (95% CI 46% to 74%) and 67% (95% CI 49% to 82%), respectively. Univariate analysis of patients who underwent gross or total resection followed by adjuvant chemotherapy and radiotherapy demonstrated an improvement in 1-year EFS. However, only gross resection and total resection predicted a better 3-year OS. CONCLUSIONS: Surgical excision is still the mainstream treatment for MRT. Postoperative adjuvant treatments including chemotherapy and radiotherapy contribute to improved disease control rate. Our single-institute experience may provide insights into the multimodal treatment of MRT.

STAT3-induced upregulation of lncRNA CASC11 promotes the cell migration, invasion and epithelial-mesenchymal transition in hepatocellular carcinoma by epigenetically silencing PTEN and activating PI3K/AKT signaling pathway.

Accumulating evidence suggest that long noncoding RNAs (lncRNAs) are dysregulated in various tumors and serve as crucial regulators in biological processes. Based on The Cancer Genome Atlas (TCGA) database, upregulation of CASC11 was associated with the low overall survival rate of patients with Hepatocellular carcinoma (HCC). However, the function and mechanism of lncRNA CASC11 in the progression of HCC remain unclear. Therefore, we further analyzed the expression pattern and biological role of CASC11 in HCC. CASC11 was found to be overexpressed in HCC tissues and cell lines and predicted a poor prognosis. Loss of CASC11 function efficiently suppressed cell migration, invasion and epithelial-mesenchymal transition (EMT). The mechanism which led to the upregulation of CASC11 was investigated. CASC11 was found to be activated by the transcription factor STAT3. Mechanically, the enhancer of zeste homolog 2 (EZH2) was found to be a binding partner of CASC11. Moreover, CASC11 epigenetically silenced PTEN by binding with EZH2. Finally, rescue assays were conducted to make confirmation. The present results revealed that CASC11 may be potential therapeutic target in HCC.

Serum microRNA-181a Expression Level in Patients with Acute Liver Failure and Its Correlation with Prognosis.

Objective: This paper examined miR-181a expression in the serum of patients with acute liver failure (ALF) and investigated the impact of its expression in the prognosis of ALF patients. Methods: A total of 112 ALF patients (ALF group) and 100 healthy controls during the same period (control group) were recruited as study subjects, and ALF patients were separated into the survival group and the death group. Serum ALT, AST, SCr, TBil, PTA, and International Normalized Ratio (INR) indices as well as serum miR-181a expression were assessed by using a fully automated biochemistry analyzer and RT-qPCR. Patients in the ALF group were evaluated using the Model for End-Stage Liver Disease (MELD) score. Correlation between serum miR-181a expression and MELD scores of ALF patients was processed by Pearson correlation analysis, and the diagnostic value of miR-181a level for the occurrence of ALF was estimated by ROC curve analysis. Multivariate logistic regression analysis was executed to assess the factors influencing the occurrence of death in ALF patients. Results: ALF patients had higher levels of ALT, AST, TBiL, SCr, INR and miR-181a and lower PTA levels in comparison to healthy controls. Serum miR-181a expression level in ALF patients revealed a significant positive correlation with MELD score. Multivariate logistic regression analysis unveiled that TBil, INR, SCr, and miR-181a were the independent risk factors for the occurrence of death in ALF patients, and that PTA was an independent protective factor for the prognosis of ALF patients. miR-181a exhibited a favorable diagnostic value in ALF and its prognosis. Conclusion: miR-181a expression is upregulated in the serum of ALF patients, and it can be utilized as an indicator for ALF diagnostic and prognostic assessment.

Dynamic Evolution of Land Use/Land Cover and Its Socioeconomic Driving Forces in Wuhan, China.

Human activities are considered as the main driving forces of land use/land cover (LULC) variation at city scales. Monitoring the dynamic variation of LULC and its socioeconomic driving forces helps to reveal the response of LULC change to human activities and land use policies. However, this issue remains poorly understood. In this study, the spatiotemporal transitions among different LULC types during nearly three decades in Wuhan, China, were modeled in detail using the transfer matrix method. Ten socioeconomic factors indicating the population level, economic condition and social development were selected to quantitatively explain LULC variation. Some typical policies were discussed for the LULC transitions. The results showed that construction land was detected to continuously increase, with the fastest change rate of 560.48% during the 29-year period. Farmland area significantly declined by 1855 km2, decreasing by 31.21%, contributing to 86.14% of the area increase in construction lands. To some extent, the net area increase in construction land was at the expense of farmland area. All 10 indicators considered in this study were positively correlated with the construction land area (R2 of 0.783~0.970) and negatively correlated with farmland area (R2 of 0.861~0.979). In general, social and economic development contributed considerably to urban expansion and cultivated land loss. The largest contributors were non-agricultural population and economic conditions (secondary industry output, primary industry output and local revenues). Governmental guidance and behavior were considered the original impetus for LULC transition, while the impact of land use policies and human activities on LULC transitions varied across the subperiods. These findings provide decision-making support for appropriate urban planning and efficient land use management.

Treatment of infantile fibrosarcoma: A tertiary care center experience.

Objective: Infantile fibrosarcoma (IFS) is a highly locally aggressive nonrhabdomyosarcomatous soft tissue sarcoma that most commonly occurs in young infants. There exists no standard treatment this lesion due to its rarity. We shared our treatment experience for IFS in this study. Methods: Patients' record between January 2013 and December 2018 were reviewed and patients with newly diagnosed IFS were included. The clinical characteristics, treatment strategy, treatment-related toxicities and clinical outcome were retrospectively analyzed. Results: Eleven patients were admitted in our center, including 4 girls and 7 boys, and the median age at diagnosis was 5 months (range 1-23 months). Ten patients achieved complete remission (CR) after the completion of initial treatment. The main short-term adverse effects was myelosuppression. Three patients experienced relapse, including two patients with local progression and one patient with distant metastasis. After a median follow-up of 3.5 years (range 1.5-7 years), 9 patients were alive and 2 patients died. The 3-year overall survival (OS) rate was 93.5% (95% CI 83.7-98.2). Conclusion: We formulated the treatment strategy according to group grade and the experience from previous studies, which may be effective and feasible for the treatment of IFS.

Treatment of Pediatric Inflammatory Myofibroblastic Tumor: The Experience from China Children's Medical Center.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor with intermediate malignancy that tends to affect children primarily. To date, no standardized therapies exist for the treatment of IMT. This study aimed to share experience from China Children's Medical Center for the explorative treatment of IMT. METHODS: Patients with newly diagnosed IMT between January 2013 and December 2018 were included. Patients were grouped according to surgical margins and Intergroup Rhabdomyosarcoma Study Group (IRSG) staging. The clinical characteristic, therapeutic schedules, treatment response and clinical outcome were described. RESULTS: Six patients were enrolled in this study, including two boys and four girls, with a median age of 57 months (range 10-148 months). Among them, five patients were anaplastic lymphoma kinase positive. Four patients achieved complete remission and two patients attained partial remission after treatment with this protocol. All patients were alive after a median follow-up of 4 years (range 3-7 years). The most common treatment-related adverse reaction was myelosuppression. CONCLUSION: In this study, we demonstrated that IMT has a good prognosis and the treatment selected according to risk stratification was effective and feasible.

Protective effect of celastrol on type 2 diabetes mellitus with nonalcoholic fatty liver disease in mice.

To investigate the protective effects of celastrol on mice with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), and to explore its underlying mechanism. The levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) in serum were tested. Malondialdehyde (MDA) and superoxide dismutase (SOD), GOT, and GPT in serum were also detected. The histopathological changes of liver tissues were observed by HE staining. The apoptosis cell number of liver tissues was measured by TUNEL staining. Nrf-2 and HO-1 protein and mRNA expression were evaluated by IHC, WB, and RT-PCR assay. Celastrol had effects to depress TG, TC, LDL-C, GPT, GOT, and MDA concentration and increase HDL-C and SOD concentration (p < .05, respectively) with dose-dependent. Compared with model group, apoptosis cell number was significantly depressed in Cel-treated groups with dose-dependent (p < .05, respectively). Nrf-2 and HO-1 mRNA and protein expressions were significantly improved in Cel-treated groups with dose-dependent (p < .05, respectively). Celastrol can inhibit the oxidative stress reaction and liver cell apoptosis via regulation Nrf2/HO-1 pathway in T2DM mice with NAFLD.

MicroRNA­34a inhibits liver cancer cell growth by reprogramming glucose metabolism.

MicroRNAs (miRs) have been proposed as minimally invasive prognostic markers for various types of cancer, including liver cancer, which is one of the most common cancers worldwide. In the present study, the expression of miR­34a in human liver cancer tissues and cell lines was evaluated and the effects of miR­34a on cell proliferation, invasion and glycolysis in hepatocellular carcinoma (HCC) cells were determined. The results indicated that miR­34a was downregulated in human liver cancer tissues. Overexpression of miR­34a significantly inhibited liver cancer cell proliferation and clone formation. In terms of the underlying mechanism, miR­34a was indicated to negatively regulate the expression of lactate dehydrogenase A (LDHA), which consequently inhibited LDHA­dependent glucose uptake in the cancer cells, as well as cell proliferation and invasion. Collectively, these data suggest that miR­34a functions as a negative regulator of glucose metabolism and may serve as a novel marker for liver cancer prognosis.

LINC00261 suppresses cell proliferation, invasion and Notch signaling pathway in hepatocellular carcinoma.

BACKGROUND: Recent findings have identified thousands of long non-coding RNAs (lncRNAs) and reveal that lncRNAs play crucial roles in the regulation of tumor development and progression. However, the clinical significance and potentially functional value of LINC00261 in hepatocellular carcinoma (HCC) remain unknown. METHODS: Expression of LINC00261 was detected by qRT-PCR in HCC tissues and adjacent normal tissues. Kaplan-Meier analysis was used to assess the relationship between LINC00261 expression and the overall survival (OS) time. Cell proliferation and invasion were evaluated using MTT assay, cell colony formation assay and transwell assay. The protein expression was determined by western blot analysis. RESULTS: In present study, we confirmed that LINC00261 was frequently lower in HCC tissues compared to adjacent normal tissues. Decreased LINC00261 expression associated with lager tumor size, TNM stage (III-IV) and poor overall survival time of HCC patients. The functional assays demonstrated that overexpression of LINC00261 in HCC cells inhibited cell proliferation, cell colony formation, cell invasion and EMT process in vitro. Moreover, we also demonstrated that upregulation of LINC00261 significantly inhibited Notch signaling by downregulating Notch1 and Hes-1 expression in HCC cells. CONCLUSION: These results indicated that LINC00261 may be a potential target of HCC treatment.