Efficacy and safety of osimertinib for patients with EGFR-mutated NSCLC: a systematic review and meta-analysis of randomized controlled studies.

BACKGROUND: Osimertinib is a recently approved third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR-T790M resistance mutations. The aim of the present meta-analysis was to investigate the efficacy and safety of osimertinib for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Databases were searched for randomized controlled studies that reported the efficacy and safety of osimertinib versus other treatments (chemotherapy, other EGFR-TKIs, etc.) in treating EGFR-mutated NSCLC. The measured effects included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), central nervous system progression-free survival (CNS-PFS), and overall survival (OS). Additional outcome was the incidence of adverse event. Relative risk (RR) for incidence and hazard ratio (HR) for survival outcomes were pooled. RESULTS: Seven studies containing 3335 participants were finally included. Osimertinib tended to improve ORR and DCR (RRs >1) as compared with other treatments. Osimertinib was also a significant protective factor for PFS, CNS-PFS, and OS (HRs <1 and p < .05). Osimertinib showed similar advantages in improving tumor response and patient survival when used as first-line, second-line, and third-line/adjuvant therapy, respectively, as compared with other treatments (RRs >1 for ORR and DCR; HRs <1 for PFS, CNS-PFS, and OS). Osimertinib also had better therapeutic effects as compared with chemotherapy, other EGFR TKIs, docetaxel + bevacizumab, and placebo, respectively. The five most common adverse events with pooled incidence > 20% were diarrhea, rash, nail effects, dry skin, and stomatitis, yet the pooled incidence of serious adverse events was less than 2%. CONCLUSIONS: This meta-analysis suggests that osimertinib has a positive effect in disease control and survival for patients with EGFR-mutated NSCLC with acceptable toxicities.

Association between long non-coding RNA H19 polymorphisms and breast cancer risk: a meta-analysis.

Common genes mutation was demonstrated associating with the risk of breast cancer (BC) recently, while the role of long non-coding RNA (lncRNA) polymorphism is still controversial. A meta-analysis was designed to discuss the association between lncRNA H19 polymorphisms and susceptibility to BC. The related databases were systematically reviewed up to April 13, 2021. Estimates were summarized as ORs and 95 percent CIs for each included study. The heterogeneity was assessed by the I2 test and subgroup analysis. Ten studies with 10354 BC patients and 11,177 control cases were included in our study. LncRNA H19 single nucleotide polymorphism (SNP) rs2839698 C/T significantly increases the susceptibility of BC (OR = 1.717 , 95 percent CI = 1.052-2.803, P = 0.031). LncRNA H19 polymorphism rs3741219 and rs217727 also increase the risk of ER-positive BC (OR = 1.128 , 95 percent CI = 1.010-1.259, P = 0.0032 for rs3741219, and OR = 1.297, 95 percent CI = 1.027-1.639, P = 0.029 for rs217727). Our results demonstrated that lncRNA H19 SNP rs2839698 C/T was significantly associated with the susceptibility of BC. LncRNA H19 SNP rs217727 and rs3741219 were associated with the risks of ER-positive BC. However, further studies are needed to reach a robust conclusion.

Expression of Nischarin negatively correlates with estrogen receptor and alters apoptosis, migration and invasion in human breast cancer.

Nischarin, a novel integrin binding protein, has been demonstrated its negative effects on cell migration and invasion. However, the biological role of Nischarin in breast cancer has not been fully elucidated yet. Our study aimed to analyze the association between Nischarin expression and clinical features of breast cancer patients, and further investigate the role of Nischarin in breast cancer cells apoptosis, migration and invasion. Results showed that Nischarin expression was significantly lower in breast cancer tissues (37.8%, 23/67) than in normal tissues (61.8%, 21/34; P < 0.05), and the expression of Nischarin significantly negatively correlated with estrogen receptor status. Similarly, Nischarin expression was highest in normal breast cell line HBL-100 while triple-negative breast cancer cell line MDA-MB-231 had the lowest expression of Nischarin. Further experiments demonstrated that overexpression of Nischarin may induce apoptosis, and inhibit cell migration and invasion. The present data confirmed that Nishcharin might be a novel tumor suppressor and plays an important role in breast cancer cell apoptosis and metastasis, which can be used as a potential therapeutic target for breast cancer treatment.

Enhanced expression of long non-coding RNA NEAT1 is associated with the progression of gastric adenocarcinomas.

BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as new players in the cancer. The aim of this study was to examine the abnormalities of NEAT1 (nuclear paraspeckle assembly transcript 1, also known as MENε/ß) in gastric adenocarcinomas (GACs). METHODS: One hundred thirty-one GAC tissues and matched adjacent normal tissues (ANTs) were collected from patients who undergone surgery. Differences in of NEAT1 expression were examined via quantitative reverse transcriptase PCR (qRT-PCR). WST-1 assay and transwell assay were carried out in vitro to investigate the proliferation and migration of GAC cells with alteration in NEAT1 long non-coding RNA (lncRNA) expression. RESULTS: The expression levels of lncRNA NEAT1 were significantly elevated in GAC tissues (P<0.001) compared with ANTs. There was also a statistical difference in NEAT1 expression between early and advanced GACs (P=0.0111). GACs with lymph node metastasis (LNM) expressed higher levels of NEAT1 lncRNA compared with those without LNM (P=0.004). In the in vitro experiments, the proliferation but not migration of GAC cells was attenuated after NEAT1 knockdown by RNA interference. CONCLUSIONS: Expression of NEAT1 lncRNA was enhanced in GACs; and NEAT1 may influence GAC progression by promoting tumor growth.

Litchi Seed Aqueous Extracts play a role in suppression of epithelial-mesenchymal transition, invasion and migration in breast cancer cells.

We carried out this study to unravel the function of Litchi Seed Aqueous Extracts (LSAE) on biological functions of breast cancer (BC) cells. MTT assay was adopted to measure proliferation of BC cells (MCF7, BT474 and MDA-MB-231) and normal mammary cells (MCF10A) under different time points (24, 48 and 72 h) and different concentrations (50, 100, 200 and 400 µg/mL). MCF-7 cells were selected for subsequent experiments and were grouped into blank group, negative control (NC) group, low-, medium- and high-dose LSAE (L-LSAE, M-LSAE, H-LSAE) groups. Cell viability, invasion, migration and apoptosis were measured by functional assays. Low dosage of LSAE (50 and 100 µg/mL) enhanced proliferation of MCF10A cells, while high dosage of LSAE (200 and 400 µg/mL) suppressed proliferation of MCF10A cells. The proliferation inhibition rate in BT474 and MDA-MB-231cells was increased relative to that in MCF7 cells. MCF-7 cells in the L-LSAE, M-LSAE and H-LSAE groups were rounded and epithelial-like, in which cell survival rate, epithelial-mesenchymal transition (EMT), invasion and migration abilities were reduced versus the blank and NC groups. The tendency in the H-LSAE group was substantially obvious than those in the L-LSAE and M-LSAE groups (both P < 0.05). We found that LSAE is able to inhibit EMT, invasion and migration in BC cells based on concentration and time.

MicroRNA-598 inhibits the growth and maintenance of gastric cancer stem-like cells by down-regulating RRS1.

Emerging evidence has identified the critical role of microRNAs in gastric cancer (GC). Herein, this study intends to characterize the tumor suppressive role of microRNA-598 (miR-598) in GC stem-like cells, with the involvement of RRS1. The CD133+ GC stem-like cells were sorted by flow cytometry, after which immunofluorescence assay was used to determine the co-localization of CD133 and CD44v8-10. The miR-598 expression was examined in the CD133+ and CD133- cells. Subsequently, the CD133+ cells were subjected to miR-598 mimics, miR-598 inhibitors or RRS1 siRNA to validate the effect of miR-598 on GC stem-like cell proliferation, colony formation, apoptosis, migration and invasion capacities. Besides, the effect of miR-598 on the expression of key factors (OCT4, SOX2 and NANOG) associated with stem cell characteristics was measured. The obtained results indicated that the sphere forming capacity was higher in CD133+ cells. CD133+ MKN-45 cells expressed CD133 and CD44v8-10, and were expressed on the cell membrane. MiR-598 was poorly expressed in CD133+ cells. Notably, miR-598 negatively regulated RRS1. In response to miR-598 mimics and RRS1 siRNA, the MKN-45 cells displayed inhibited proliferation, colony formation, migration and invasion, accompanied by elevated apoptosis. Besides, the miR-598 inhibitors reversed the situation. This study highlights that miR-598 a tumor suppressor in GC stem-like cells by inhibiting RRS1, whereby miR-598 represses MKN-45 cell growth and invasion by attenuating self-renewal of GC stem-like cells.

The enhanced photo-thermal therapy of Surface improved photoactive cadmium sulfide (CdS) quantum dots entrenched graphene oxide nanoflakes in tumor treatment.

Cancer is one of the death causing disease is always being a public health concern due to its rapid increase in the world population. Hyperthermal therapy is an anticancer treatment mutually given with chemotherapy. In the present study, CdS/rGO nanocomposites were synthesized using simple and scalable solvothermal method and applied as an efficient material in anticancer treatment. The prepared nanocomposites were characterized from physicochemical characterization techniques. The surface morphology and the crystallographic details were obtained from TEM and XRD analyses respectively. The elemental composition was confirmed from XPS spectra. The phase purity and the functional group analysis were done using Raman and FTIR spectroscopies respectively. The morphological analysis has been displayed the spherical shaped CdS nanoparticles that are firmly attached on the rGO thin sheet matrix further confirmed the formation of CdS/rGO nanoflakes. The live-dead assay method (cancerous and normal cell lines) cytocompatibility study displayed the cell survival of the CdS/rGO nanomaterials exhibited that above 95%, which means materials highly appropriate for the cancer therapy. The temperature profile of the CdS/rGO nanoflakes has enhanced effectively under the NIR absorption property of CdS coated rGO nanoflakes, which influenced to the cancer cell death. The results shown the anticancer activity of the proposed nanocomposites could open a new avenue in biomedicine research and utilized as an efficient materials for practical applications.

Chemokine SR-PSOX/CXCL16 expression in peripheral blood of patients with acute coronary syndrome.

BACKGROUND: Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 (SR-PSOX/CXCL16) promotes foam cell formation through the tumor necrosis factor (TNF)-alpha mediated mechanism. Because chemokine CXCL16 could be expressed in atherosclerotic lesions and induce smooth muscle cell (SMC) proliferation, we presume that the monocyte SR-PSOX/CXCL16 detection in the patients' peripheral blood will be important for early diagnosis and prognosis of atherosclerosis (AS). METHODS: Enrolled in this study were 40 patients with acute coronary syndrome (ACS), including 20 patients with acute myocardial infarction (AMI) and 20 patients with unstable angina pectoris (UAP), and 20 normal controls. Monocytes in the peripheral blood were isolated, and the changes of expression of CXCL16/SR-PSOX mRNA were compared using reverse transcription-polymerase chain reaction (RT-PCR), with beta-actin as internal control. We compared the expression of CXCL16/SR-PSOX in the ACS subgroups, using Western-blot to analyze protein expression levels. Tissue sections were made from biopsy specimens taken from patients with infective endocarditis, liver cirrhosis, and lung cancer as well as normal controls. And the expression of CXCL16/SR-PSOX was analyzed with a confocal microscope. RESULTS: The expression of CXCL16/SR-PSOX mRNA and protein in the monocytes of peripheral blood was significantly higher in ACS patients than in normal controls (P < 0.05); however, there was no significant difference in CXCL16/SR-PSOX expression between UAP group and AMI group (P > 0.05). Immunofluorescence showed that there were low expression of SR-PSOX in normal vascular endothelial cells and enhanced expression in every layer of the infected vessels, while spreading from endothelial cells to surrounding tissues as infection worsens. Confocal microscopy showed that the expression of SR-PSOX was enhanced in the infiltrated lymphocytes in liver cirrhosis, and that the expression level was proportionate to the degree of inflammation in the portal hepatis and folia. CONCLUSIONS: The expression of CXCL16/SR-PSOX in the monocytes of peripheral blood was significantly higher in ACS patients than in the controls. CXCL16/SR-PSOX-mediated inflammation may contribute to the pathogenesis of ACS, and CXCL16 may play an important role in the pathogenesis and development of AS in humans.