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Reply and safety of whole-brain radiotherapy additionally temozolomide with regard to individuals using brain metastases regarding non-small-cell united states: A meta-analysis.
Retroperitoneal liposarcoma (RLPS) is a rare tumor with high recurrence rate. Ribonucleotide reductase small subunit M2 (RRM2) protein is essential for DNA synthesis and replication. Our previous study has demonstrated that RRM2 downregulation inhibited the proliferation of RLPS cells, but further association between RRM2 and RLPS and relevant mechanisms remains to be explored.

RRM2 expression was evaluated in RLPS tumor tissues and cell lines by using real-time PCR and immunohistochemical analysis. The effect of RRM2 downregulation on cell proliferation, apoptosis, cell cycle, cell migration and invasion was tested by lentivirus. The effect of RRM2 inhibition on tumor growth in vivo was assessed by using patient-derived tumor xenograft (PDX) of RLPS and RRM2 inhibitor. The underlying mechanisms of RRM2 in RLPS were explored by protein microarray and Western blotting.

The results showed that RRM2 mRNA expression was higher in RLPS tissues than in normal fatty tissues (P<0.001). RRM2 expression was hiexpressed in RLPS tissues, and downregulation of RRM2 could inhibit RLPS progression. In addition, suppression of RRM2 is expected to be a promising treatment for RLPS patients.
Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) is associated with favourable outcomes of patients with triple-negative breast cancer (TNBC). However, a proportion of TNBC patients with the residual disease do not relapse and achieve long-term survival. The aim of this study was to identify biomarkers that predict clinical outcomes in these patients.

A retrospective series of 10 TNBC patients who displayed non-pCR to NACT were included in the discovery cohort. Total RNA from pre-NACT core biopsies and paired surgical specimens were subjected to the Affymetrix Human Transcriptome Array. Gene set enrichment analysis (GSEA) was used to identify signal pathways and gene signatures associated with metastasis. The Cox proportional hazard model and Kaplan-Meier survival curves were employed to assess the prognostic value of the identified signature in two independent TNBC datasets included in Gene Expression Omnibus (GEO).

The epithelial-mesenchymal transition (EMT) pathway was markedlyT and for patients treated with surgery in combination with adjuvant therapy.
Resistance is one of the main limitations of successful platinum treatment in non-small-cell lung cancer (NSCLC) patients. In this study, we aimed to identify somatic mutations associated with platinum response.

A total of 57 patients who received platinum-based chemotherapy only and 13 patients who received neoadjuvant chemotherapy (NAC) were enrolled. Somatic mutations were obtained from targeted and whole exome sequencing (WES).

Somatic mutations in a total of 225 genes were observed. Nonsynonymous variants in EGFR, TTN, TP53 and KRAS, and copy number variations (SCNVs) in chromosome 8q24.3 and 22q11.21 were identified to be associated with platinum response. Based on these mutations, the mutational signature associated with the failure of DNA double-strand break and calcium signaling pathways were identified to be associated with platinum response. Besides, we observed a decrease in tumor mutational burden after chemotherapy. We also evaluated the mutation spectrum consistency between cell-free DNA (cfDNA) and tissue DNA. Somatic mutations detected in cfDNA were consistent with that in tDNA, which indicated that plasma might be used for somatic mutation detection.

These results support that somatic mutations can affect platinum drug response and provide potential clinical biomarkers for NSCLC treatment.
These results support that somatic mutations can affect platinum drug response and provide potential clinical biomarkers for NSCLC treatment.
Immune therapy has shown good results in small-cell lung cancer (SCLC), but the impact of immune microenvironment of the disease is unclear. In this work, we detected expression of programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and other immune biomarkers of cancer. We also analyzed the correlations between these markers and survival in SCLC.

Protein expression of PD-1, PD-L1, PD-L2, CD3, CD4, CD8, and FOXP3 was analyzed in surgical tissues from 102 SCLC patients by immunohistochemistry.

Positive expression of PD-1 on tumor-infiltrating lymphocytes (TILs) was found in 40.2% of patients; 37.3% of patients showed positive expression of PD-L1 on TILs; and 3.9% showed positive expression of PD-L1 on tumor cells. PD-L2 protein was not expressed on tumor cells or TILs. Survival analysis showed that positive expression of PD-L1 on TILs was correlated with longer relapse-free survival (RFS) (p=0.004). Positive expression of PD-1 combined with a high ratio of lymphocytes (CD3, p=0.004; CD4, p=0.011; CD8, p=0.009; FOXP3, p=0.009) was associated with significantly better RFS than negative expression of PD-1 combined with a lower ratio of lymphocytes. Positive expression of PD-L1 combined with a high ratio of lymphocytes (CD3, p<0.001; CD4, p=0.001; CD8, p=0.002; FOXP3, p=0.001) was associated with significantly better RFS than negative expression of PD-L1 combined with a lower ratio of lymphocytes. All patients' stage were between I and III.

PD-1 and PD-L1 expression might be good prognostic factors in SCLC.
PD-1 and PD-L1 expression might be good prognostic factors in SCLC.
Liposarcoma was considered as a soft tissue kind of sarcoma with one-fifth in the sarcoma cases of adults. The aim of this study was to explore the role and the potential mechanisms of miR-195 in liposarcoma.

Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of microRNA-195 (miR-195) and oxysterol-binding protein (OSBP) in liposarcoma. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell migration was measured by wound healing and transwell assays. Cell cycle phases and apoptosis were examined using flow cytometry analysis. Caspase-3 activity was detected by commercial kit. Binding sites between miR-195 and OSBP were predicted through bioinformatics analysis and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Western blot was used to analyze OSBP level. Xenograft tumor assays were performed to observe the effect of miR-195 overexpression on tumor growth in vivo.

miR-195 expression was decreased, whereas OSBP was increased in liposarcoma tissues and cells. Besides, miR-195 upregulation suppressed the proliferative and migrative abilities and induced inhibition on cell growth and promotion on apoptosis in SW872 and 93T449 cells. Mechanically, miR-195 functioned as a suppressor by regulating OSBP expression. Furthermore, OSBP overexpression inverted the effects of miR-195 on cell growth, migration and apoptosis in SW872 and 93T449 cells. miR-195 overexpression also suppressed tumor growth in vivo.

miR-195 suppressed cell growth, migration and elevated cell apoptosis via OSBP in liposarcoma.
miR-195 suppressed cell growth, migration and elevated cell apoptosis via OSBP in liposarcoma.
LRRC59 (leucine-rich repeat-containing protein 59) is a ribosome-binding protein that also interacts with fibroblast growth factors. Limited investigations revealed a possible role of LRRC59 in the aggressive phenotype of breast cancer. However, whether LRRC59 contributes to the progression of lung cancer remains unclear.

In this study, an online TCGA-based survival analysis software (GEPIA2) was used to estimate the prognostic value of LRRC59 mRNA expression level for lung cancer. Cell Counting Kit-8 assay, colony-forming assay, cell cycle analysis, and transwell assay were used to assess the biological functions of LRRC59 in lung cancer cells. Then, 94 lung adenocarcinoma (LUAD) patient tissues were collected to examine the expression level of LRRC59 by the tissue microarray (TMA)-based immunohistochemistry staining (IHC). Univariate Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the prognostic value of LRRC59 protein expression in LUAD.

Higher mRNA level of LRRC59 was significantly associated with worse survival for lung adenocarcinoma, but not for lung squamous cell carcinoma. Knockdown of LRRC59 by shRNA apparently inhibited cell proliferation and colony formation in both H1299 and A549 cells. The G1/S phase arrest induced by LRRC59 depletion was observed in A549 and H1299 cells. Besides, the silencing of LRRC59 decreased cell migrative and invasive abilities. Moreover, TMA-based IHC showed that LRRC59 was highly expressed in LUAD tissues and closely associated with lymph node metastasis (P<0.001), TNM stage (P<0.001), and histological differentiation (P=0.007). Blasticidin S solubility dmso Further multivariate analysis suggested that LRRC59 overexpression was an independent prognostic factor in LUAD.

LRRC59 may serve as a novel biomarkers and therapeutic target for LUAD clinical practice.
LRRC59 may serve as a novel biomarkers and therapeutic target for LUAD clinical practice.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. However, up to 40-50% of GISTs develop secondary resistance after an average of 24 months of imatinib treatment. It has been reported that autophagy can promote the survival of GIST cells and induce drug resistance. Presently, the specific mechanism of autophagy in GISTs with imatinib resistance is not clear.

The cell-counting kit (CCK)-8 method and flow cytometry were used for in vitro drug sensitivity testing and autophagy level detection. Detection of the apoptosis level was by flow cytometry with the annexin V Kit. Western blotting was used to analyze the role of autophagy and apoptosis in GIST cells with CQ alone, imatinib alone, or in combination, and to analyze MAPK pathway expression. In vitro results were confirmed by in vivo experiments using the mice model. Hematoxylin and eosin and immunohistochemical staining were used to detect the pathological characteristics and immunophenotype autophagy inhibitor with imatinib may be a potential valuable strategy in overcoming acquired resistance in GIST patients.Invasive micropapillary carcinoma (IMPC) is a novel type of breast cancer which is potentially very aggressive and may show early lymphatic infiltration. Monosomy of chromosome 17 (m17) is rare in breast cancer, and according to the 2018 guidelines of the American Society of Clinical Oncology/College of American Pathologists, the decision to administer trastuzumab treatment should be made based on positive human epidermal growth factor receptor 2 results by immunohistochemistry. Here, we report a rare case of bilateral local advanced IMPC involving m17. A 33-year-old woman found a mass measuring 30 mm on the left breast that increased to 100 mm over 3 months. A diagnosis of IMPC was made based on the findings of core needle biopsies of bilateral breast masses and left axillary lymph node, and m17 was detected by fluorescence in situ hybridization (FISH). The patient underwent 6 cycles of neoadjuvant chemotherapy (docetaxel, epirubicin, and cyclophosphamide) and left-side modified radical mastectomy, left axillary lymph node dissection, right breast-conserving surgery, and right sentinel lymph node biopsy. Postoperative pathologic analysis of both breasts revealed IMPC, and m17 was confirmed by FISH. The patient received radiotherapy and endocrine therapy but rejected trastuzumab treatment. The patient was still alive at the 30-month follow-up, without recurrence or metastasis. Our findings suggest that loss of chromosome 17 may influence prognosis or therapeutic response, which needs to be further confirmed.
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