Long noncoding RNA lnc-LOC645166 promotes adriamycin resistance via NF-κB/GATA3 axis in breast cancer.

Chemoresistance remains a significant obstacle for effective adriamycin (ADR) treatment in breast cancer. Recent efforts have revealed that long noncoding RNAs (lncRNAs) play a crucial role in cancer biology, including chemoresistance. We identified the lncRNA LOC645166 was upregulated in adriamycin resistant-breast cancer cells by Microarray analysis, which was further confirmed in the tissues of nonresponsive patients by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical assays. Downregulation of lncRNA LOC645166 increased cell sensitivity to adriamycin both in vitro and in vivo. In contrast, upregulation of lncRNA LOC645166 strengthened the tolerance of breast cancer cells to adriamycin. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. Together, the present study suggested that lncRNA LOC645166 mediated adriamycin chemoresistance in breast cancer by regulating GATA3 via NF-κB.

Ginsenoside Rg3 attenuates the osimertinib resistance by reducing the stemness of non-small cell lung cancer cells.

In the present study, we found that Ginsenoside Rg3 attenuated the stemness of non-small cell lung cancer (NSCLC) cells, evident by decreasing spheroid formation ability, ALDH1 activity and stemness marker expression. Furthermore, osimertinib-resistant NSCLC cells displayed a stronger stemness than the parental cells. Ginsenoside Rg3 reduced the stemness and osimertinib resistance of osimertinib-resistant cells. RNA-sequencing revealed that Hippo signaling was shown on the top of the most upregulated pathways regulated by Ginsenoside Rg3 in NSCLC cells, and YAP/TAZ expression was suppressed by Ginsenoside Rg3. Notably, the inhibitor of Hippo signaling attenuated the effects of Ginsenoside Rg3 on the stemness of NSCLC cells. Therefore, Ginsenoside Rg3 attenuates the osimertinib resistance of NSCLC cells via suppressing the stemness, which is dependent on Hippo pathway.

Identification of the BRAF V600E mutation in a patient with sclerosing pneumocytoma: A case report.

OBJECTIVES: Sclerosing pneumocytoma (sclerosing hemangioma, SP) is a rare benign tumor of the lung with a low risk of recurrence. The genomic profile of SP is not well-known. Here we report gene mutation findings in a 17-year-old girl with SP. MATERIALS AND METHODS: Immunohistochemistry (IHC), next-generation sequencing (NGS), and sanger sequencing were performed on the tumor tissue of this patient for pathological diagnosis and gene mutation analysis. RESULTS AND CONCLUSION: Two mutations were identified in the tumor tissue by NGS and sanger sequencing: AKT1 E17K and BRAF (B-Raf proto-oncogene, serine/threonine kinase) V600E. This is the first case report of a BRAF V600E mutation in a patient with SP. This discovery extends our understanding of the pathogenesis of SP, and suggests the need for future testing of BRAF V600E in this rare tumor type.

Long non-coding RNA XIST inhibited breast cancer cell growth, migration, and invasion via miR-155/CDX1 axis.

Long non-coding RNA (lncRNA) is an important member of non-coding RNA family and emerging evidence has indicated that it plays a pivotal role in many physiological and pathological processes. The lncRNA X inactive specific transcript (XIST) is a potential tumour suppressor in some types of cancers. However, the expression and function of XIST in breast cancer remain largely unclear. The objective of this study was to evaluate the expression and biological role of XIST in breast cancer. The results showed that XIST was significantly down-regulated in breast cancer tissues and cell lines. Further functional analysis indicated that overexpression of XIST remarkably inhibited breast cancer cell growth, migration, and invasion. The results of luciferase reporter assays verified that miR-155 was a direct target of XIST in breast cancer. Moreover, caudal-type homeobox 1 (CDX1) was identified as a direct target of miR-155 and miR-155/CDX1 rescued the effects of XIST in breast cancer cells. Taken together, our results suggest that XIST is down-regulated in breast cancer and suppresses breast cancer cell growth, migration, and invasion via the miR-155/CDX1 axis.

Curcumin enhances the antitumor effect of ABT-737 via activation of the ROS-ASK1-JNK pathway in hepatocellular carcinoma cells.

At present, the therapeutic treatment strategies for patients with hepatocellular carcinoma (HCC) remain unsatisfactory, and novel methods are urgently required to treat this disease. Members of the B cell lymphoma (Bcl)-2 family are anti­apoptotic proteins, which are commonly expressed at high levels in certain HCC tissues and positively correlate with the treatment resistance of patients with HCC. ABT-737, an inhibitor of Bcl-2 anti-apoptotic proteins, has been demonstrated to exhibit potent antitumor effects in several types of tumor, including HCC. However, treatment with ABT-737 alone also activates certain pro-survival signaling pathways, which attenuate the antitumor validity of ABT-737. Curcumin, which is obtained from Curcuma longa, is also an antitumor potentiator in multiple types of cancer. In the present study, the synergistic effect of curcumin and ABT-737 on HCC cells was investigated for the first time, to the best of our knowledge. It was found that curcumin markedly enhanced the antitumor effects of ABT-737 on HepG2 cells, which was partially dependent on the induction of apoptosis, according to western blot analysis and flow cytometric apoptosis analysis. In addition, the sustained activation of the ROS-ASK1-c-Jun N-terminal kinase pathway may be an important mediator of the synergistic effect of curcumin and ABT-737. Collectively, these results indicated that the combination of curcumin and ABT-737 can efficaciously induce the death of HCC cells, and may offer a potential treatment strategy for patients with HCC.

Role of taxane and anthracycline combination regimens in the management of advanced breast cancer: a meta-analysis of randomized trials.

The clinical benefits provided by using combined taxanes and anthracyclines in first-line chemotherapy for metastatic breast carcinoma (MBC) remain uncertain. This meta-analysis compares the benefits of using a combination of anthracyclines along with taxanes versus using single-agent-based chemotherapeutic regimens in the treatment of MBC.Relevant clinical trials as well as abstracts from articles presented at major cancer conferences were searched in various databases including PubMed, Embase, and Cochrane Library. The relevant studies had a primary endpoint of overall survival (OS) and secondary endpoints that included progression-free survival (PFS), time-to-treatment failure (TTF), time to progression (TTP), objective response rate (ORR), disease control rate (DCR), and safety. The hazard ratios of OS, PFS, TTF, and TTP, the odds ratios of ORR and DCR, and the risk ratios (RRs) for grades 1-2 and 3-4 toxicities were extracted from the retrieved studies and analyzed using various statistical methods. Meta-analytic estimates were derived from a random-effect model.Fifteen trials were included in the final meta-analysis, and the results suggest that chemotherapy with combined anthracyclines and taxanes does not significantly improve the OS of MBC patients when compared with the OS achieved using separate taxane or anthracycline-based regimens. Compared with taxane-based regimens, combined taxane along with anthracycline regimens failed to significantly improve TTP, ORR, or DCR, but did significantly improve TTP and ORR when compared with anthracycline-based regimens. Furthermore, both individual taxane-based and anthracycline-based regimens produced fewer toxic reactions compared to combined taxane along with anthracycline regimens. Taxane-based regimens had lower RRs for side effects of neutropenia, infection/febrile neutropenia, nausea, and vomiting, whereas patients receiving anthracycline-based regimens had lower RRs for neutropenia, infection/febrile neutropenia, anorexia, stomatitis/mucosal inflammation, diarrhea, and sensory neuropathy. In contrast, patients receiving taxane-based regimens were at higher RRs for hand-foot syndrome and diarrhea, whereas patients receiving anthracycline-based regimens had higher RRs for nausea and vomiting.A taxane-based treatment regimen may be a better option than a combined taxane/anthracycline regimen for managing patients with advanced breast cancer, as it produces equivalent clinical outcomes and has less toxicity compared to other similar regimens.

Primary pericardial osteosarcoma on FDG PET/CT.

We present the (18)F-FDG PET/CT images of a 38-year-old woman with primary pericardial osteosarcoma. Routine chest radiography showed an enlarged cardiac silhouette. Plain chest CT found an oval tumor with dense calcification adhered to the left back of the heart. A whole-body FDG PET/CT scan was performed to evaluate the patient's condition. The images showed heterogeneous tracer uptake in the calcified tumor. There was no other evidence of active neoplastic disease. Histopathologic analysis of the pericardial tumor showed characteristic findings of primary pericardial osteosarcoma.