[Clinical study of 15 cases of primary non-immunodeficient central nervous system lymphoma in children].

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

A risk model based on the tumor microenvironment to predict survival and immunotherapy efficacy for ovarian cancer.

OBJECTIVE: Based on the interactions between immune components in the tumor microenvironment and ovarian cancer (OC) cells, immunotherapies have been demonstrated to be effective in dramatically increasing survival rates. This study aimed to identify landmark genes, develop a prognostic risk model, and explore its relevance to the efficacy of immunotherapy. MATERIALS AND METHODS: A risk model was built based on the immune- and stromal-related genes, which were extracted from the OC gene expression data of "The Cancer Genome Atlas" (TCGA) database. Survival analysis and receiver operating characteristic (ROC) analysis were then conducted through the model's risk score pattern, which was established depending on the TCGA training cohort and verified based on the internal TCGA cohort and external "Gene Expression Omnibus" (GEO) datasets. Furthermore, the immune-related characteristics and prognostic values of the risk model were evaluated. RESULTS: The prognostic risk model for ovarian cancer demonstrated excellent performance in predicting survival rates, as validated in both the TCGA and GEO databases. The model showed significant associations with 17 functional immune cells, 17 immune checkpoints, PD-1, and several immune pathways, suggesting its potential to enhance the efficacy of immunotherapy in OC. CONCLUSIONS: The risk model developed in this study has the potential to serve as a prognostic marker for OC, enabling the development of personalized immunotherapy protocols and providing a theoretical basis for novel combinations of immunotherapeutic approaches.

Effects of lncRNA MALAT1 and lncRNA NKILA on proliferation, invasion and apoptosis of retinoblastoma.

OBJECTIVE: To assess the expression of LncRNA NKILA and MALAT1 in retinoblastoma and its related mechanisms. PATIENTS AND METHODS: Tixty-eight cases of retinoblastoma patients admitted to our hospital from February 2017 to February 2019 were collected as a research group, while 70 healthy people who came to our hospital for checkup at the same time were chosen as a control group. Both retinoblastoma and human colorectal mucosa cells were purchased, expression and clinical value of NKILA and MALAT1 in serum of Rb patients were tested, and sh-NKILA, si-NKILA, NC, sh-MALAT1 and si-MALAT1 were transfected into Weri-Rb1 and Y79 cells. qRT-PCR was adopted to detect the NKILA and MALAT1 levels in samples, and WB was adopted to detect the cle-caspase-3, cle-caspase-9, Bax, Cyclin B1, CDC2 and p-CDC2 protein levels in cells. Cell proliferation was conducted via MTT assay, invasion was carried out through transwell assay, and apoptosis was confirmed by flow cytometry assay. RESULTS: NKILA and MALAT1 were low expressed in retinoblastoma, and AUC of LncRNA NKILA and MALAT1 was over 0.8. LncRNA NKILA and MALAT1 were associated with tumor size, classification and clinical grading in children with retinoblastoma. Over-expression of NKILA and MALAT1 could promote apoptosis, inhibit cell growth and Bcl-2 protein, and promote upregulation of the expression levels of clecaspase-3, clecaspase-9 and Bax. CONCLUSIONS: By regulating MALAT1 and NKILA, we controlled the growth and apoptosis of Rb cells, which was expected to be a potential clinical therapeutic target for Rb.

Characteristics and molecular basis of celecoxib modulation on K(v)7 potassium channels.

BACKGROUND AND PURPOSE: Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used for the treatment of pain and inflammation. Emerging and accumulating evidence suggests that celecoxib can affect cellular targets other than COX, such as ion channels. In this study, we characterized the effects of celecoxib on K(v)7 K(+) channels and compared its effects with the well-established K(v)7 channel opener retigabine. EXPERIMENTAL APPROACH: A perforated whole-cell patch technique was used to record K(v)7currents expressed in HEK 293 cells and M-type currents from rat superior cervical ganglion neurons. KEY RESULTS: Celecoxib enhanced K(v)7.2-7.4, K(v)7.2/7.3 and K(v)7.3/7.5 currents but inhibited K(v)7.1 and K(v)7.1/KCNE1 currents and these effects were concentration dependent. The IC(50) value for inhibition of K(v)7.1 channels was approximately 4 µM and the EC(50) values for activation of K(v)7.2-7.4, K(v)7.2/K(v)7.3 and K(v)7.3/K(v)7.5 channels were approximately 2-5 µM. The effects of celecoxib were manifested by increasing current amplitudes, shifting the voltage-dependent activation curve in a more negative direction and slowing the deactivation of K(v)7 currents. 2,5-Dimethyl-celecoxib, a celecoxib analogue devoid of COX inhibition activity, has similar but greater effects on K(v)7currents. K(v)7.2(A235T) and K(v) 7.2(W236L) mutant channels, which have greatly attenuated responses to retigabine, showed a reversed response to celecoxib, from activation to inhibition. CONCLUSIONS AND IMPLICATIONS: These results suggest that K(v)7 channels are targets of celecoxib action and provide new mechanistic evidence for understanding the effects of celecoxib. They also provide a new approach to developing K(v)7 modulators and for studying the structure-function relationship of K(v)7 channels.

[Antagonistic effects of melatonin on glutamate-induced neurotoxicity in rat hippocampal neurons].

The effects of glutamate (Glu) and melatonin (MEL) on the evoked populaion spike (PS) following stimulation of the schaffer collateral fiber were studied by extracellular recording technique in perfused slices of rat hippocampus: 5.0 mmol/L Glu decreased the PS peak values to 4.1% of control. This effect of Glu (5.0 mmol/L) on PS peak values was changed to 14.7%, 105.2% and 24.3% of control by 0.4, 0.5, 0.6 mumol/L of MEL. But when the interaction between MEL (0.5 mumol/L) and Glu (5.0 mmol/L) was entirely suppressed by CDP (0.5 mumol/L), the PS values reduced to zero. These results suggest that the inhibitory action of MEL on Glu-induced neurotoxicity may be mediated by 5-HT receptors.