Birkwebster9960
nd octacosanoic acid may be biomarkers for peritoneal metastasis of gastric cancer.Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is a specific subtype of peripheral T cell lymphoma (PTCL) with a poor prognosis. To date, there exist no standard therapeutic regimens for relapsed/refractory (R/R) ENKTL. More potent treatment strategies are urgently needed to improve the survival of these patients with R/R ENKTL. Herein, we present three R/R ENKTL patients who failed prior therapies (L-asparaginase containing chemotherapy, radiotherapy or biological-cell therapy, etc.) benefited from the combination regimen comprised of anti-programmed-death-1 (PD-1) antibody toripalimab, chidamide, etoposide, and thalidomide. They received the treatment regimen continuously until the disease progression occurs. As of data collection, two patients achieved complete remission (CR) after 4, 6 cycles of treatment, respectively, and another patient was evaluated as partial remission (PR) after 2 cycles. Treatment-related adverse events (AEs) mainly presented grade 2~3 leukocytopenia and anemia, which were controllable. It follows that PD-1 antibody, chidamide, etoposide, and thalidomide (PCET) regimen may be a promising choice for patients with R/R ENKTL and warrants further investigation.
Although molecular-targeted agents are still the first choice for advanced hepatocellular carcinoma (HCC) treatment, the therapeutic efficacy of these agents is not satisfactory. Recently, the mammalian target of rapamycin (mTOR) is considered to be a promising molecular target that can enhance the sensitivity of HCC cells to antitumor therapy. However, the reported mTOR inhibitors have some shortcomings, and novel mTOR inhibitors need to be developed to enhance the antitumor effect of molecularly targeted agents on advanced HCC.
In this study, five small-molecular compounds that could serve as potential mTOR-specific inhibitors were identified by virtual screening. The activity of tert-butyl (4-(9-(2-(1,3-dioxolan-2-yl)ethyl)-6-morpholino-9H-purin-2-yl)phenyl)carbamate (compound
) was measured by enzyme test and Western blot, and its antitumor effect on HCC was examined in nude mice subcutaneous tumor model.
The results showed that
is the most effective one in inhibiting the activation of mTOR kinase (mTOR IC
= 17.52±3.67 nmol/L) among the five lead compounds. Further research in this study indicated that treatment with
enhanced the sensitivity of HCC cells to the molecular-targeted agents, such as sorafenib, regorafenib, lenvatinib, anlotinib, and apatinib. In addition, this research indicated that mTOR was correlated with the poor prognosis in patients with advanced HCC who received sorafenib.
Our study identified a new type of small-molecular inhibitors of mTOR and confirmed their ability to enhance the antitumor effect of molecular-targeted agents on advanced HCC.
Our study identified a new type of small-molecular inhibitors of mTOR and confirmed their ability to enhance the antitumor effect of molecular-targeted agents on advanced HCC.
This study aims to reveal the mechanism underlying baicalin-suppressing ovarian cancer stemness.
OVCAR-3 and the primary ovarian cancer cells were used for cell model. The ovarian cancer stem cells were isolated by suspension culture. Cell viability and clonogenicity were examined by CCK-8 assay and colony formation assay. The self-renewal of the cells was evaluated by the determination of sphere-forming capacity and the frequency of in vitro sphere-forming and in vivo tumor-initiating cells. The mRNA and protein levels were relatively quantified by qRT-PCR and Western blot. The transcription regulation of target genes was tested by luciferase reporter assay and a modified nuclear rn-on qRT-PCR assay.
Treatment with a non-toxic dose of baicalin significantly inhibited the spherogenicity of ovarian cancer cells. Moreover, a non-toxic dose of baicalin treatment suppressed the frequency of sphere-forming and tumor-initiating ovarian cancer cells. Furthermore, the expression of ovarian cancer stem cell markers (CD133 and ALDH1A1) was inhibited by a non-toxic dose of baicalin treatment. Baicalin inhibits YAP activity and suppresses RASSF6, a positive regulator of YAP, at the transcriptional level. Overexpression of both YAP and RASSF6 abolished the inhibitory effect of baicalin on the proliferation and stemness of ovarian cancer cells.
The results in this study demonstrated that baicalin suppresses the stemness of ovarian cancer cells by attenuating YAP activity via inhibiting RASSF6 at the transcriptional level. This finding revealed baicalin as a novel YAP inhibitor that could serve as an anti-cancer drug for eradicating ovarian cancer stem cells.
The results in this study demonstrated that baicalin suppresses the stemness of ovarian cancer cells by attenuating YAP activity via inhibiting RASSF6 at the transcriptional level. This finding revealed baicalin as a novel YAP inhibitor that could serve as an anti-cancer drug for eradicating ovarian cancer stem cells.
The function of LINC00501, a long-non-coding RNA (lncRNA), is unclear at present. According to the Cancer Genome Atlas (TCGA), LINC00501 is highly expressed in lung cancer (LC), but whether it can be adopted as a potential therapy target for LC still needs further research.
The expression of LINC00501 in LC was analyzed based on the TCGA, and a real-time fluorescent quantitative PCR assay was carried out to quantify LINC00501 in non-small-cell lung cancer (NSCLC). Additionally, bioinformatics analysis, luciferase reporter gene technique, and RNA immunoprecipitation (RIP) were employed to analyze the direct interaction between LINC00501 and miR-129-5p, and CCK-8 and Transwell assays and flow cytometry were employed to analyze the effects of LINC00501 on cell proliferation, invasion, and apoptosis. Furthermore, a Western blot assay was carried out to determine the protein level of HMGB1.
LINC00501 was highly expressed in LC according to the database, and it was found that LINC00501 was upregulated in NSCLC specimens and cells, and the up-regulation indicated an unfavorable prognosis. Besides, knockdown of LINC00501 hindered the proliferation and invasion of NSCLC cells and intensified their apoptosis, and LINC00501 could be adopted as competitive endogenous RNA to regulate HMGB1 and tumorigenesis through miR-129-5p.
LINC00501 is overexpressed in LC and the overexpression indicates poor prognosis of patients. In addition, LINC00501 can inhibit the invasion and migration of LC by mediating miR-129-5p/HMGB1.
LINC00501 is overexpressed in LC and the overexpression indicates poor prognosis of patients. In addition, LINC00501 can inhibit the invasion and migration of LC by mediating miR-129-5p/HMGB1.
Long non-coding RNAs (lncRNAs) were confirmed to play important roles in human cancers. In this study, we explored the functional role of lncRNA double homeobox A pseudogene 8 (DUXAP8) in non-small-cell lung cancer (NSCLC).
Real-time quantitative PCR (RT-qPCR) was used to detect DUXAP8 and microRNA-409-3p (miR-409-3p) expression. CCK-8, cell colony formation assay, and Transwell migration assay were performed to measure cell growth and migration, respectively. The expression of the relative proteins was detected by Western blot. Cell glycolysis was determined by glucose uptake, adenosine triphosphate (ATP) concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. Bioinformatics analysis and dual-luciferase reporter assay were used to measure the interaction among DUXAP8, miR-409-3p, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). In vivo, subcutaneous tumor formation assay was performed in the nude mice.
DUXAP8 was highly expressed in NSCLC, while miR-409-3p was downregulated. High expression of DUXAP8 was positively related to the grade division and negatively associated with the 5-year survival rate of NSCLC patients. Downregulated DUXAP8 significantly suppressed cell growth, metastasis and glycolysis. Besides, DUXAP8 sponged miR-409-3p to promote HK2 and LDHA expression. DUXAP8 promoted cell viability, migration and glycolysis by regulating miR-409-3p/HK2/LDHA axis. Moreover, DUXAP8 downregulation markedly inhibited tumor growth in vivo.
Our findings demonstrated that DUXAP8 served as an oncogene in the progression of NSCLC.
Our findings demonstrated that DUXAP8 served as an oncogene in the progression of NSCLC.
Reliable diagnostic approaches to detect ALK rearrangement are critical for selecting patients eligible for crizotinib therapy. This study aimed to compare next-generation sequencing (NGS) and Ventana immunohistochemistry (IHC) in evaluating ALK rearrangements and evaluate their impact on first-line crizotinib efficacy.
A total of 472 NSCLC patients were identified as ALK-positive by NGS and/or IHC between March 2014 and February 2020. The concordance of ALK detection, overall response rate (ORR), and progression-free survival (PFS) were analyzed for 319 patients who received front-line crizotinib.
First-line crizotinib (n=319) significantly prolonged PFS in comparison with chemotherapy (n=46; 12.0 vs 6.8 months; p<0.0001). Of the 76 crizotinib-treated patients whose ALK status was assessed by both NGS and IHC, 78.9% of the patients had concordant ALK status (NGS-positive/IHC-positive), 18.4% patients were NGS-positive but IHC-negative, and 2 patients were IHC-positive but NGS-negative. Different detection assays confer no statistical difference in ORR and PFS with first-line crizotinib. The ORR in NGS only, IHC only, and both NGS and IHC was 84.3%, 90.1%, and 88.1%, respectively, while PFS was 11.4, 13.0, and 11.0 months, respectively. selleckchem The ORR in NGS-positive/IHC-positive and NGS-positive/IHC-negative patients was 85.4% and 92.8%, respectively. Compared to NGS-positive/IHC-positive patients, those with NGS-positive/IHC-negative results had a trend of shorter PFS but statistical significance was not reached (mPFS, 5.9 months vs 11.5 months, p=0.43).
Our results demonstrate that ALK status detected by NGS and/or IHC is reliable in identifying patients with ALK-positive NSCLC who will benefit from ALK inhibitor therapy.
Our results demonstrate that ALK status detected by NGS and/or IHC is reliable in identifying patients with ALK-positive NSCLC who will benefit from ALK inhibitor therapy.
Bladder tumor is the fifth most prevalent tumor in men, yet its pathogenesis remains to be fully identified. Albeit a host of long noncoding RNAs (lncRNA) are emerging as new players involved in bladder tumor, the functions of many lncRNAs are still enigmatic. Reports on the deluge of studies on lncRNA
have been convincingly associated with various tumors, but without mention of its roles in bladder tumor. Therefore, the roles of
in bladder tumor cells were explored in our study.
Quantitative real-time PCR assays and bioinformatic tools were applied in bladder tumor cells to identify the
and
expression. Western blot assays were performed to obtain the protein levels of bladder tumor related key molecules. CCK8, clonogenic assay, scratch wound healing, and transwell assays were separately applied to identify the functional roles of
on proliferation, migration, and invasion in bladder tumor cells.
First,
downregulation in bladder tumor cells was identified. Overexpression and knockdown experiments showed that
expression was positively related to
, which is in accordance with the results from GEO database.
