Abstract:
PURPOSE:Although important for apoptosis, the signaling pathway involving MOAP-1(Modulator of Apoptosis 1), RASSF1A (RAS association domain family 1A), and Bax (Bcl-2 associated X protein) is likely to be dysfunctional in many types of human cancers due to mechanisms associated with gene mutation and DNA hyper-methylation. The purpose of the present study was to assess the potential impact of generating physiologically relevant signaling pathway mediated by MOAP-1, Bax, and RASSF1A (MBR) in cancer cells and chemo-drug resistant cancer cells. METHODS:The tricistronic expression construct that encodes MOAP-1, Bax, and RASSF1A (MBR) or its mutant, MOAP-1∆BH3L, Bax and RASSF1A (MBRX) was expressed from an IRES (Internal Ribosome Entry Site)-based tricistronic expression vector in human breast cancer cells, including MCF-7, MCF-7-CR (cisplatin resistant) and triple negative breast cancer cells, BMET05, for functional characterization through in vitro and in vivo models. RESULTS:Transient expression of MBR potently promoted dose-dependent apoptotic signaling and chemo-sensitization in the cancer cells, as evidenced by loss of cell viability, nuclei condensation and Annexin-V positive staining while stable expression of MBR in MCF-7 cells significantly reduced the number of MBR stable clone by 86% and the stable clone exhibited robust chemo-drug sensitivity. In contrast, MBRX stable clone exhibited chemo-drug resistance while transiently over-expressed MOAP-1ΔBH3L inhibited the apoptotic activity of MBR. Moreover, the spheroids derived from the MBR stable clone displayed enhanced chemo-sensitivity and apoptotic activity. In mouse xenograft model, the tumors derived from MBR stable clone showed relatively high level of tumor growth retardation associated with the increase in apoptotic activity, leading to the decreases in both tumor weight and volume. CONCLUSIONS:Expression of MBR in cancer cells induces apoptotic cell death with enhanced chemo-sensitization requiring the BH3L domain of MOAP-1. In animal model, the expression of MBR significantly reduces the growth of tumors, suggesting that MBR is a potent apoptotic sensitizer with potential therapeutic benefits for cancer treatment.
journal_name
J Cancer Res Clin Oncoljournal_title
Journal of cancer research and clinical oncologyauthors
Lee YH,Pang SW,Revai Lechtich E,Shah K,Simon SE,Ponnusamy S,Narayanan R,Poh CL,Tan KOdoi
10.1007/s00432-020-03231-9subject
Has Abstractpub_date
2020-07-01 00:00:00pages
1751-1764issue
7eissn
0171-5216issn
1432-1335pii
10.1007/s00432-020-03231-9journal_volume
146pub_type
杂志文章abstract:PURPOSE:Melanoma antigen gene A3 (MAGE-A3) is aberrantly expressed in a number of cancer types. Because of its high specificity, MAGE-A3 has shown to be a promising candidate for cancer immunotherapy. Dendritic cells (DCs) have emerged as the natural agents for antigen delivery. DCs transduced with antigen may increase...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-013-1552-8
更新日期:2014-02-01 00:00:00
abstract:PURPOSE:Our primary goal was to determine whether increased expression of the transmembrane carbonic anhydrase (CA) isozymes in renal cell carcinoma (RCC) is regulated by the von Hippel-Lindau (VHL) gene. METHODS:We studied mRNA expression of all three transmembrane CAs - CA IX, XII, and XIV - in 17 RCC cell lines, tr...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-002-0374-x
更新日期:2002-10-01 00:00:00
abstract::The long-term prognosis of surgery for hepatocellular carcinoma (HCC) is not yet satisfactory, the main reason being the high recurrence rate. The authors report the results of a long-term follow-up of 308 patients with HCC who became alpha-fetoprotein-(AFP)-negative after resection between 1975 and 1991. By March 199...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01247463
更新日期:1994-01-01 00:00:00
abstract::The dihydropyridine, dexniguldipine hydrochloride (B859-35), has shown therapeutic activity in experimentally induced neuroendocrine hamster lung tumors and demonstrated antiproliferative effects in a mammary cancer cell line via inhibition of Ca2+ calmodulin. Studies in NIH 3T3 fibroblasts have provided evidence that...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01247460
更新日期:1994-01-01 00:00:00
abstract::The formation of foci with loss of ATPase and emergence of gamma-GTase was studied histochemically in livers of male and female Wistar and Sprague-Dawley rats of 3--4 and 6--7 weeks of age, respectively, after application of diethylnitrosamine. A single dose of 8 mg/kg body weight induced a considerable island formati...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00403362
更新日期:1981-01-01 00:00:00
abstract::The primary objective of this study was to determine the response rate of patients with metastatic colorectal cancer to combined therapy with 5-fluorouracil (5-FU), leucovorin, and intravenous azidothymidine (AZT), a thymidine nucleoside analog. By itself, AZT has limited antineoplastic efficacy. However, experimental...
journal_title:Journal of cancer research and clinical oncology
pub_type: 临床试验,杂志文章
doi:10.1007/BF01213552
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:Her-2/neu and the insulin-like growth factor-1 receptor (IGF-1R) share common postreceptor-signaling pathways, and pre-clinical models have implicated IGF-1R-signaling in resistance to treatment with the anti-Her-2/neu antibody trastuzumab. The present analysis was performed to evaluate the clinical relevance o...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-005-0038-8
更新日期:2006-01-01 00:00:00
abstract::The influence of infusion time and dose on the anticancer efficacy of 5-fluoro-2'-deoxyuridine (FdUrd) was investigated using a locoregional therapy model: Novikoff hepatoma transplanted i.m. into the thigh of Wistar rats and FdUrd infusion via a catheter implanted in the femoral artery. In experiment A the FdUrd dose...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01630711
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:The functional relationship between promoter hypermethylation and gene inactivation has been demonstrated for few genes only. We examined the promoter methylation status of two important tumor suppressor genes APAF-1 and DAPK-1 in bladder cancer as well as the mRNA expression pattern of these two genes for poss...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-006-0174-9
更新日期:2007-06-01 00:00:00
abstract:PURPOSE:We compared laparoscopic approach with the conventional laparotomy approach for the treatment of patients with endometrial carcinoma in developing country. METHODS:Two hundred and seventy-two patients with endometrial carcinoma were enrolled in a prospective randomized trial and treated with laparoscopic or la...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00432-013-1504-3
更新日期:2013-11-01 00:00:00
abstract::Leukaemic and lymphomatous infiltration of the appendix is rare and even rarer is acute appendicitis as the initial manifestation. From our routine biopsy material we collected four cases of haematological malignancies presenting as acute appendicitis or acute abdomen, caused or accompanied by tumoral infiltration of ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s004320050105
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:Mutations in the tumor suppressor gene TP53 are associated with a variety of cancers. Therefore, it is important to know the occurrence and prognostic effects of TP53 mutations in certain cancers. METHODS:Over 29,000 cases from the April 2016 release of the International Agency for Research on Cancer (IARC) TP...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-018-2817-z
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:Riproximin, a type II ribosome-inactivating protein (RIP), has shown significant cytotoxic effects in diverse types of cancer cells. To better understand its therapeutic potential, elaborated investigations on the mechanistic aspects of riproximin deem crucial. In this study, we focused on riproximin-mediate...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-015-2013-3
更新日期:2016-01-01 00:00:00
abstract::Gastric cancer is a major health issue and a leading cause of death worldwide. The results of standard therapy remain unsatisfactory mainly because of diagnosis at the late stage of disease. Innovative strategies such as neoadjuvant chemotherapy in locally advanced cancer have improved the outcome even in operable cas...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-008-0425-z
更新日期:2009-01-01 00:00:00
abstract:PURPOSE:PIK3CA mutation appears to predict a lack of response to anti-EGFR monoclonal antibody (mAb) treatment in patients with metastatic colorectal cancer (mCRC). However, the predictive value of PIK3CA mutations for survival remains inconclusive. Here, we pooled the data from published studies to estimate the associ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,meta分析
doi:10.1007/s00432-013-1400-x
更新日期:2013-05-01 00:00:00
abstract::Unstimulated and interferon (IFN)-stimulated natural killer cell (NK) activity was investigated in patients with malignant melanoma prior to the removal of the primary melanoma (stage I disease) or in patients with melanoma metastases. Unstimulated as well as IFN-stimulated NK activities, directed against the primaril...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00400969
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:B-cell translocation gene 3 (BTG3) has been identified as a candidate driver gene for various cancers, but its specific role in colorectal cancer (CRC) is poorly understood. We aimed to investigate the relationship between expression of BTG3 and clinicopathological features and prognosis, as well as to explore ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-017-2561-9
更新日期:2018-02-01 00:00:00
abstract::Metastatic interstitial cell tumor of the testis is one of the rarest human neoplasms. This is the nineteenth case to be reported. While most of these tumors are combined with hormonal dysfunction, the present tumor, apart from its uncommon hormonal profile, is remarkable because of its capacity of producing and secre...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00419291
更新日期:1979-07-27 00:00:00
abstract:PURPOSE:With the increasing interest in treatment decision-making based on risk prediction models, it is essential for clinicians to understand the steps in developing and interpreting such models. METHODS:A retrospective registry of 20 Dutch hospitals with data on patients treated for castration-resistant prostate ca...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-020-03286-8
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Cancer is a serious public health problem worldwide, and difficulty in early diagnosis has been the chief obstacle to improve the prognosis of patients. Recently, microRNAs (miRNAs) were widely studied to be potential biomarkers for cancer detection. miR-16 is a prevalent but sophisticated one. In the curren...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,meta分析
doi:10.1007/s00432-019-02849-8
更新日期:2019-03-01 00:00:00
abstract:PURPOSE:The aim of this study was to determine which clinicopathological factors influenced the long-term survival after potentially curative resection of colorectal cancer patients with a normal preoperative serum level of carcinoembryonic antigen (CEA). METHODS:A total of 1,732 patients who underwent curative surger...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-013-1459-4
更新日期:2013-09-01 00:00:00
abstract:PURPOSE:There was no standard treatment for hepatocellular carcinoma with portal vein tumour thrombosis (PVTT). This prospective, randomised, two-arm clinical trial aims to investigate the feasibility, safety and effectiveness of transarterial chemoembolisation (TACE) combined with the endovascular implantation of an i...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00432-013-1568-0
更新日期:2014-02-01 00:00:00
abstract:PURPOSE:To determine the incidence of hepatocellular carcinoma in cirrhosis and to examine the influence of age and sex, and the contribution of etiological factors. METHODS:967 patients with liver cirrhosis and free of hepatocellular carcinoma were enrolled in this longitudinal, retrospective and observational study....
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320050215
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:Lung cancer has become a crucial problem among individuals living with the human immunodeficiency virus (HIV) and causes high mortality in Western countries. Japan has an increasing number of newly infected HIV patients, and lung cancer is becoming a theme in this population. However, clinical factors of this p...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00432-015-1956-8
更新日期:2015-09-01 00:00:00
abstract::The effects of alpha-difluoromethylornithine (DFMO), radiation and the therapy of their combination were investigated in rats bearing G-XII glioma. DFMO treatment as well as radiation therapy prolonged the survival period when compared to the results in non-treated control rats. The combination therapy showed a greate...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01410129
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Pregnancies in women with essential thrombocythemia (ET) are at a higher risk for obstetrical complications. Acetylsalicylic acid (ASA) and low-molecular weight heparin (LMWH) are common options to prevent miscarriages and maternal complications, whereas interferon alpha (IFN) seems to be the cytoreductive ther...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-020-03430-4
更新日期:2020-11-02 00:00:00
abstract::A series of 202 breast cancer biopsy specimens were analysed immunohistochemically for collagen IV to demonstrate basement membrane (BM) structures and blood vessels within tumour tissue. Integrity of the BM was graded into four categories and the number of vascular channels per square millimetre of tumour tissue were...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01245375
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Serrated adenomas (SAs), which include a wide spectrum of lesions, can be broadly divided into two subtypes: type I, closely mimicking hyperplastic polyps (HPs), and type II, unequivocal adenomatous tumor. Our preliminary findings showed clinicopathologic differences between them. The present study was conducte...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-003-0478-y
更新日期:2003-08-01 00:00:00
abstract:PURPOSE:Acute intestinal damage induced by chemotherapeutic agent is often a dose-limiting factor in clinical cancer therapy. The aim of this study was to investigate the effect of chemokine CXCL9 on the intestinal damage after chemotherapy and explore the therapeutic potential of anti-CXCL9 agents. METHODS:In vitro c...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-014-1869-y
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:The purpose of this study was to examine breast tumors and normal breast tissues for the expression of the glycoprotein lacritin. The mRNA and protein expression of lacritin has been reported to be restricted to the lacrimal gland. METHODS:We investigated 37 human primary invasive breast tumors, seven breast c...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-003-0514-y
更新日期:2003-12-01 00:00:00