Abstract:
BACKGROUND/AIM:The success of proteasome inhibitors in therapy of multiple myeloma has led to their use for other malignancies. For the proteasome inhibitor bortezomib, combination therapies with histone deacetylase inhibitors, which up-regulate ubiquitin-proteasome system (UPS)-related enzymes, produce a beneficial effect. However, the mechanisms underlying the effect of bortezomib are not completely understood. We hypothesized that bortezomib causes excessive accumulation of aberrant proteins, which augments endoplasmic reticulum (ER) stress, leading to death of malignant cells. MATERIALS AND METHODS:The NB4 cell line established from a patient with acute promyelocytic leukemia (APL) expressing the promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) fusion protein was used to assess changes in cell viability and apoptosis caused by bortezomib, as well as alterations in PML-RARA and UPS-related enzymes via western blotting and immunoprecipitation assays. RESULTS:Bortezomib time- and dose-dependently reduced cell viability and induced apoptosis. Bortezomib significantly increased the abundance of ubiquitinated-PML-RARA (Ub-PML-RARA), ubiquitin-conjugating human enzyme 8 (UbcH8), and Ub-UbcH8, indicating that UbcH8 is the E2 ubiquitin-conjugating enzyme for PML-RARA. Moreover, UbcH8 abundance was dose-dependently increased in the culture supernatant of bortezomib-treated cells. CONCLUSION:UbcH8 may have a utility as a biomarker of treatment response to bortezomib in patients with APL. Furthermore, bortezomib impairs the UPS that controls normal protein homeostasis by causing excessive accumulation of PML-RARA augmenting ER stress and leading to APL cell death. The study provides a rationale for incorporating proteasome inhibitors in the treatment of diseases expressing aberrant proteins. Furthermore, monitoring of UPS-related enzymes might have use in predicting the treatment response to proteasome inhibitors and in assessing their therapeutic effects.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Takenokuchi M,Miyamoto K,Saigo K,Taniguchi Tsubject
Has Abstractpub_date
2015-06-01 00:00:00pages
3307-16issue
6eissn
0250-7005issn
1791-7530pii
35/6/3307journal_volume
35pub_type
杂志文章abstract::Megakaryocyte polyploidization responds to platelet demand and results from the lack of cytoplasmic separation while the nucleus keeps dividing. In normal telophase, the plane of the actin constriction ring is determined by the tubulin spindle. In order to investigate the role of tubulin in the megakaryocyte polyploid...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND:Prostate cancer metastases to bone are associated with significant morbidity and mortality. Presently, there is little known about the biological interaction between prostate cancer cells and bone. Development of an animal model using adult human bone will enhance our ability to study the biology of prostate...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::Metals and metal compounds have been used in medicine for several thousands of years. In this review we summarized the anti-cancer activities of the ten most active metals: arsenic, antimony, bismuth, gold, vanadium, iron, rhodium, titanium, gallium and platinum. The first reviewed metal, arsenic, presents the anomaly...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:Docetaxel is a well tolerated chemotherapy for non-small cell lung cancer (NSCLC). However, few studies have investigated interstitial lung disease (ILD) associated with docetaxel. The purpose is to describe the incidence of this complication by using NSCLC patients. PATIENTS AND METHODS:Between September 2...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND/AIM:Atrophic gastritis (AG) is the most important risk condition for gastric cancer (GC). A panel of stomach-specific serum biomarkers: pepsinogen (PG) I, pepsinogen (PG) II, gastrin-17 (G-17), and IgG antibodies to H. pylori (HP-Ab) detects the extent and grade of AG. The aim of the present study was to ass...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND/AIM:The Aspartate aminotransaminase/Alanine aminotransaminase ratio (AST/ALT ratio) has been identified as a prognostic marker for several malignancies. In this study, we evaluated the prognostic value of the AST/ALT ratio in a large cohort of non-metastatic colorectal cancer patients (CRC). PATIENTS AND ME...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.14792
更新日期:2021-01-01 00:00:00
abstract:AIM:To investigate whether there is a difference in selenium levels before and after radiotherapy (RT) and to study the effects of serum selenium levels on RT-related toxicity in patients undergoing RT for head and neck cancer. PATIENTS AND METHODS:A population of 47 consecutive patients was enrolled in the study. RT ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-08-01 00:00:00
abstract::B-1 F is a cell line established from estrogen-responsive murine Leydig cell tumor and maintained in vitro. We investigated the effects of steroid hormones on the growth of tumors produced by the inoculation of B-1 F cells into mice. When tumor tissues were transplanted into castrated male mice, injections of estradio...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::The multifactorial process of carcinogenesis in the digestive system involves mutations in oncogenes or tumor suppressor genes, as well as influence of environmental etiological factors. In recent years, common DNA polymorphisms in low penetrance genes emerged as genetic factors that seem to modulate an individual's s...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:2007-09-01 00:00:00
abstract::Within the brain, dissemination of glioma cells follows myelinated fiber tracts and extracellular matrix containing structures such as the basement membranes of blood vessels. These patterns represent the two major routes of invasion frequently observed in clinical disease. Previously, we have characterized the substr...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::We report a case of mucoepidermoid carcinoma of the trachea in a 23-year-old pregnant female in her 39th week. The patient had cough and wheezing in the early morning for 9 months before admission. No abnormalities were detected on a chest roentgenogram. At Caesarean section, fiberscopy revealed a polypoid lesion narr...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::Several studies have reported that high F18-fluorodeoxyglucose (FDG) uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. While these studies evaluated the prognostic value for cases with high FDG uptake, they did not elucidate the meaning of FDG negativity in primary breast c...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2016-06-01 00:00:00
abstract::Dedifferentiated liposarcoma (DDLS) is a malignant adipocytic tumor showing transition from an atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLS) to a non-lipogenic sarcoma of variable histological grades. We present the immunohistochemical, cytogenetic, and molecular cytogenetic findings of DDLS a...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2015-01-01 00:00:00
abstract:AIM:Maximal cytoreduction to minimal residual tumor is the most important determinant of prognosis in patients with advanced stage epithelial ovarian cancer (EOC). Preoperative prediction of suboptimal cytoreduction, defined as residual tumor >1 cm, could guide treatment decisions and improve counseling. The objective ...
journal_title:Anticancer research
pub_type: 杂志文章,多中心研究
doi:
更新日期:2011-11-01 00:00:00
abstract::The 5-year survival of colorectal cancer patients with distant metastases is below 30%, despite the development and use of a variety of chemotherapeutic regimens. Therefore, new therapeutic strategies are warranted. Whereas radioimmunotherapy (RIT) has shown disappointing results in bulky disease, it may be a promisin...
journal_title:Anticancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND:The efficacy and toxicity of adjuvant chemo-immunotherapy using dendritic cells and activated killer cells are not clear in post-surgical primary lung cancer patients. PATIENTS AND METHODS:Pathologically diagnosed N2 lung cancer patients were selected for postsurgical adjuvant chemo-immunotherapy. The activ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2008-03-01 00:00:00
abstract:AIM:The present study aimed to examine the survival benefit of adjuvant chemotherapy for the patients with stage IB gastric cancer according to the second English edition of the Japanese Classification of Gastric Carcinoma (2nd JCGC). PATIENTS AND METHODS:In total, 201 consecutive patients who underwent curative surge...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2015-07-01 00:00:00
abstract:BACKGROUND:Lung cancer is the second leading cause of mortality among men and women in the U.S. Among different varieties of lung cancer, the non-small cell lung cancer (NSCLC) has the highest frequency comprising about 85% of cases. We evaluated 1-methyl-4-phenylpyridinium ion (MPP(+)) for cytotoxicity against human l...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:Histone acetyltransferase E1A-binding protein p300 (EP300), tumor protein p53 (TP53) and B-cell lymphoma-2-associated X protein (BAX) contribute to the regulation of the cell cycle and apoptosis, cellular processes that are often impaired in cancer cells. The aim of this study was to determine the expression...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.11646
更新日期:2017-06-01 00:00:00
abstract::In furtherance of our structure-activity relationship studies on the antitumor activity of indolo[2,3-b]quinolines, novel cytotoxic derivatives bearing methyl groups at N-5, C-11, C-2 and/or C-9, as well as methoxy-groups at C-2 and/or C-9, were synthesized by the modified Graebe-Ullmann reaction. To elucidate the met...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::During the last 50 years median survival for metastatic breast cancer has not varied and remains 2-3.5 years. To assess the clinical benefit of salvage systemic therapy a retrospective analysis of metastatic breast cancer patients all homogeneously treated with a commonly used first-line anthacycline-containing cytoto...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND/AIM:Tyrosine kinase inhibitors are important in the treatment of metastatic renal cell cancer (mRCC). The aim of the study was to evaluate the costs and effects of sunitinib in mRCC. PATIENTS AND METHODS:A total of 81 mRCC patients who received first-line sunitinib therapy between 2010 and 2014 were recruit...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.13749
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND:Circulating nucleosomes, complexes of DNA and histones, are recognized as a potential new diagnostic tool for therapy monitoring of cancer disease and as prognostic marker in other acute diseases. Because many studies are carried out retrospectively on serum samples collected earlier, we tested the stability...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2010-05-01 00:00:00
abstract::A series of poly (ADP-ribose) synthesis inhibitors was evaluated for their ability to potentiate the cytotoxicity of bleomycin compared with their inhibition of poly(ADP-ribose) synthesis in L1210 cultured cells. Theophylline, nicotinamide, 3-aminobenzamide and thymidine inhibited 70 to 80% of poly(ADP-ribose) synthes...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::The human MAGE gene products are recognized by major histocompatibility complex-restricted cytotoxic T lymphocytes. We analyzed by RT-PCR the expression of MAGE-1, MAGE-2, MAGE-3 and HLA-A2 genes in 10 human gastric cancer cell lines and 46 human stomachs removed due to advanced gastric carcinomas. All the cell lines ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::Urachal cancer is a rare malignancy and the standard treatment is surgical resection. The prognosis of recurrent and metastatic urachal cancer is extremely poor because there is no established chemotherapy regimen. Here, the response of one patient with recurrent urachal cancer to combination chemotherapy of gemcitabi...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Increasing evidence suggests that COX-2 promotes carcinogenesis but it is controversial as to whether COX-2 expression is a prognostic factor for rectal carcinoma. MATERIALS AND METHODS:Data of 62 consecutive patients with rectal carcinoma in UICC-stages I-III, which were curatively resected between 1995 an...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:Radiofrequency ablation (RFA) is one of the standard percutaneous therapies for hepatocellular carcinoma (HCC), but RFA has not been applied to treat bone metastasis from HCC. CASE:A 65-year-old male patient, who underwent hepatectomy for HCC two and a half years previously, complained of pain in his right ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Cancer is a family affair. Clinical work and research studies have shown that cancer affects the entire family and that spouses especially are often highly distressed. Breast cancer has a special importance for a couple. It is convenient to help the patient and her husband together. In the first six months especially ...
journal_title:Anticancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::We have previously reported that polaprezinc in sodium alginate suspension (P-AG) inhibited the incidence of oral mucositis induced by radiochemotherapy in patients with head and neck cancer. The present study was designed to investigate whether P-AG prevents oral mucositis in all patients (36 patients) with hematolog...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2014-12-01 00:00:00