The inositol polyphosphate kinase (IPK) family member ITPKA (inositol 1,4,5-trisphosphate 3-kinase) regulates the levels of many inositol polyphosphates which are important in cellular signaling. Several recent studies reported the aberrant expression of ITPKA in malignancy disease and usually made cancer more aggressive. However, the contribution of the inositol polyphosphate kinase ITPKA to lung cancer development remains unclear.Here we report that ITPKA is overexpressed in lung adenocarcinoma (LUAD) and positively correlated with advanced clinical parameters. ITPKA contributes to the malignant phenotypes in-vitro. Mechanistically, ITPKA executed its action through the inducting of epithelial-mesenchymal transition (EMT) and interacting with Drebrin 1 (which is related to cancer metastasis). Moreover, the hyper-expression of ITPKA in LUAD is transcriptionally activated by the transcription factor TFAP2A. In survival analysis by using tissue microarray (TMA), we indicate that ITPKA is hyper-expressed in LUAD tissues compared to adjacent normal tissues, and increased expression of ITPKA is associated with poor prognosis. Collectively, this study indicates that TFAP2A induced ITPKA hyperexpression promotes LUAD via interacting with Drebrin 1 and activating epithelial-mesenchymal transition (EMT). ITPKA might represent a potent candidate for the treatment and prognostic prediction of LUAD.
Background:Fibroblasts were the main seed cells in the studies of tissue engineering of the pelvic floor ligament. Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) were widely studied but at various concentrations. This study aimed to optimize the concentrations of combined bFGF and EGF by evaluating their effects on proliferation and collagen secretion of fibroblasts.Methods:Fibroblasts were differentiated from rat adipose mesenchymal stem cells (ADSCs). Flow cytometry and immunohistochemistry were used for cell identification. The growth factors were applied at concentrations of 0, 1, 10, and 100 ng/ml as three groups: (1) bFGF alone, (2) EGF alone, and (3) bFGF mixed with EGF. Cell proliferation was evaluated by Cell Counting Kit-8 assays. Expression of Type I and III collagen (Col-I and Col-III) mRNAs was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. Statistical analysis was performed with SPSS software and GraphPad Prism using one-way analysis of variance and multiple t-test.Results:ADSCs were successfully isolated from rat adipose tissue as identified by expression of typical surface markers CD29, CD44, CD90, and CD45 in flow cytometry. Fibroblasts induced from ADSC, compared with ADSCs, were with higher mRNA expression levels of Col I and Col III (F = 1.29, P = 0.0390). bFGF, EGF, and the mixture of bFGF with EGF can enhanced fibroblasts proliferation, and the concentration of 10 ng/ml of the mixture of bFGF with EGF displayed most effectively (all P < 0.05). The expression levels of Col-I and Col-III mRNAs in fibroblasts displayed significant increases in the 10 ng/ml bFGF combined with EGF group (all P < 0.05).Conclusions:The optimal concentration of both bFGF and EGF to promote cell proliferation and collagen expression in fibroblasts was 10 ng/ml at which fibroblasts grew faster and secreted more Type I and III collagens into the extracellular matrix, which might contribute to the stability of the pelvic floor microenvironment.
Objective To study the efficacy and adverse reactions of lobaplatin combined with other chemotherapy drugs in the treatment of metastatic breast cancer. Methods This retrospective analysis enrolled 114 patients who were diagnosed with advanced breast cancer from January 2010 to December 2015. Lobaplatin and another chemotherapeutic agent were given to patients. The efficacy and side effects were evaluated after at least two cycles of chemotherapy. Results Therapeutic efficacy and adverse reactions could be evaluated in 112 patients with 2 complete response (CR) patients, 31 cases of partial response (PR), 52 cases of stable disease (SD) and 27 cases of progressive disease (PD). The overall response rate (ORR) was 29.5% and the disease control rate (DCR) was 75.9%. The median time to progression (TTP) was 7.7 months, and the median overall survival (OS) was expected to be 28.0 months. The main side effects were myelosuppression. Twenty five patients (21.9%) had grade 3/4 neutrophil suppression, 18 patients (15.8%) had grade 3/4 thrombocytopenia. Other toxicities included gastrointestinal reaction, peripheral neuropathy, stomatitis, hepatic dysfunction, fatigue and skin rashes, which were alleviated by symptomatic treatment. Conclusion Lobaplatin-based regimen chemotherapy for advanced metastatic breast cancer patients is effective and well tolerated.
Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows for the analysis of diagnostic tissue specimens from various regions. For pancreatic tumors, especially un-resectable ones, how to obtain pathological confirmation is important for determining sub-sequent treatment. The purpose of this study is to investigate the clinical utility of EUS-FNA in patients who failed to obtain a pathological diagnosis in surgical exploration.Methods: Patients who underwent EUS-FNA due to unsuccessful biopsy in surgical exploration in our center were retrospectively reviewed. All of the patients were diagnosed with resectable disease before surgery but were found to be unresectable during surgery. The positive rate of pathological diagnosis of EUS-FNA was analyzed.Results: A total of 11 patients were included in this study, among which 8 were males and 3 were females.The median age of the patients was 55 years (range, 48 to 73 years). The median lesion size was 34 mm (range, 25 to 44 mm). The median number of needle passes was 3 (range, 1 to 3). Two patients underwent biliary stent implantation while 3 patients underwent gastrojejunostomy before EUS-FNA. The technical success rate of EUS-FNA was 100% (11/11); 10 (90.9%, 10/11) samples were positive and 1 was negative (being inadequate).Conclusions: Intraoperative biopsy is the first choice diagnostic modality for unresectable pancreatic neoplasms. However, for patients who fail to obtain a pathological diagnosis in surgical exploration, EUS-FNA is still worth an attempt.
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