Abstract:
:Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme in the de novo biosynthesis pathway of pyrimidines. Inhibition of this enzyme impedes cancer cell proliferation but the exact mechanisms of action of these inhibitors in cancer cells are poorly understood. In this study, we showed that cancer cells, namely melanoma, myeloma and lymphoma overexpressed DHODH protein and treatment with A771726 and Brequinar sodium resulted in cell cycle arrest at S-phase. Transfection with DHODH shRNA depleted DHODH protein expression and impeded the proliferation of melanoma cells. shRNA knockdown of DHODH in combination with DHODH inhibitors further reduced the cancer cell proliferation, suggesting that knockdown of DHODH had sensitized the cells to DHODH inhibitors. Cell cycle regulatory proteins, c-Myc and its transcriptional target, p21 were found down- and up-regulated, respectively, following treatment with DHODH inhibitors in melanoma, myeloma and lymphoma cells. Interestingly, knockdown of DHODH by shRNA had also similarly affected the expression of c-Myc and p21 proteins. Our findings suggest that DHODH inhibitors induce cell cycle arrest in cancer cells via additional DHODH-independent pathway that is associated with p21 up-regulation and c-Myc down-regulation. Hence, DHODH inhibitors can be explored as potential therapeutic agents in cancer therapy.
journal_name
J Cancerjournal_title
Journal of Cancerauthors
Dorasamy MS,Choudhary B,Nellore K,Subramanya H,Wong PFdoi
10.7150/jca.14835subject
Has Abstractpub_date
2017-09-05 00:00:00pages
3086-3098issue
15issn
1837-9664pii
jcav08p3086journal_volume
8pub_type
杂志文章abstract:BACKGROUND:Non-small cell lung cancer (NSCLC) accounts for approximately 85% of clinical lung cancer cases. MicroRNA-93 (miR-93) is an oncomiR in many types of human cancer, exerting pivotal effects in the development and progression of malignancies, including NSCLC. However, the mechanism underlying miR-93 involvement...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.17958
更新日期:2017-03-07 00:00:00
abstract::Objectives: Chordomas are slow-growing malignancies that commonly affect vital neurological structures. These neoplasms are highly resistant to current chemotherapeutic regimens and often recur after surgical intervention. Therefore, there is an urgent need to identify molecular targets and more robust drugs to improv...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.35426
更新日期:2020-01-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) is one of the most common types of aggressive cancer. The tumor tissue, which shows an active angiogenesis, is composed of neoplastic and stromal cells, and an abundant inflammatory infiltrate. Angiogenesis is important to support tumor growth, while infiltrating cells contribute to ...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.12286
更新日期:2015-08-07 00:00:00
abstract::Chemo- and radio-therapy suffer from certain well-recognized drawbacks for lymphoma therapy. Passive immunotherapy with monoclonal antibody has improved outcome for patients with CD20+ B cell lymphoma, but not for T cell lymphoma. Therefore, novel treatment approaches are clearly required for T cell lymphoma. To date,...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.20015
更新日期:2017-09-15 00:00:00
abstract::In this article, the use of different types of thermotherapies to treat breast cancer is reviewed. While hyperthermia is most commonly used as an adjuvant in combination with radiotherapy, chemotherapy, targeted therapy or cryotherapy to enhance the therapeutic effect of these therapies, thermoablation is usually carr...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.8693
更新日期:2014-05-29 00:00:00
abstract::Protein tyrosine kinase 6 (PTK6) is a non-receptor tyrosine kinase and works as an oncogene in various cancers. Recently, PTK6 has been used as a therapeutic target for breast cancer patients in a clinical study. However, the prognostic value of PTK6 in bladder cancer (BC) remains vague. Therefore, we retrieved 3 inde...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.21318
更新日期:2017-09-27 00:00:00
abstract::Stromal fibroblasts are suggested to be a key determinant in the malignant progression of breast cancer. To find an in vitro culture model that best mimics the in vivo tumor microenvironment so we can study the effects of stromal fibroblasts on breast cancer progression, we evaluated several three-dimensional (3D) co-...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.2.458
更新日期:2011-01-01 00:00:00
abstract::Several randomized studies have been completed in prostate cancer that show a benefit to immediate postoperative treatment in patients undergoing prostatectomy. In one of the studies, there was even a survival advantage. In spite of those positive findings, there has been some reluctance to uniformly offer adjuvant tr...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:
更新日期:2010-12-07 00:00:00
abstract::Cachexia is a common term for the wasting symptoms which may appear in almost every chronic illness, such as AIDS, tuberculosis, and cancer. Cancer cachexia (CCA) is a result of the interaction between the host and the tumor, mainly manifested in short-term wasting, malnutrition, and so on. Due to the chronic food sho...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.28246
更新日期:2019-01-01 00:00:00
abstract::Colorectal cancer (CRC) is considered to be closely associated with alteration of intestinal microorganisms. The purpose of present study was to investigate the distribution of gut microbiota in the distinction of microbiota dysbiosis between two disease syndromes called Zheng-Qi-Kui-Xu(ZQKX) and Xie-Du-Yong-Sheng (XD...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.50318
更新日期:2020-10-23 00:00:00
abstract::Ever since its discovery (1924) the Warburg effect (aerobic glycolysis) remains an unresolved puzzle: why the aggressive cancer cells "prefer" to use the energetically highly inefficient method of burning the glucose at the cellular level? While in the course of the last 90 years several hypotheses have been suggested...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.14274
更新日期:2016-04-26 00:00:00
abstract::We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiprolife...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.15690
更新日期:2016-06-23 00:00:00
abstract::Cervical cancer is a commonly diagnosed cancer among females. Polymorphisms in pre-microRNAs have been demonstrated to play critical roles in cancer. However, the roles of pre-microRNA polymorphisms in the aetiology of cervical cancer have not been well documented. We genotyped eight pre-microRNA polymorphisms in 290 ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.39636
更新日期:2020-02-03 00:00:00
abstract::The capture of peritoneal metastatic cancer stem cell of human gastric cancer (pMCSC-hGC) is important to further understand the mechanism of peritoneal metastasis in gastric cancer patients. Previously, cancer stem cells (CSCs) of gastric and rectal cancers were captured and identified. However, the bottleneck of cap...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.21669
更新日期:2017-09-16 00:00:00
abstract::Cancer-testis (CT) genes played important roles in the progression of malignant tumors and were recognized as promising therapeutic targets. However, the roles of genetic variants in CT genes in lung cancer susceptibility have not been well depicted. This study aimed to evaluate the associations between genetic varian...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.40002
更新日期:2020-02-03 00:00:00
abstract::Background: HER2 serves as an important therapeutic target in gastroesophageal cancer. Differences in HER2 gene signal distribution patterns can be observed at the tissue level, but how it influences the HER2 amplification status has not been studied so far. Here, we investigated the link between HER2 amplification an...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.17878
更新日期:2017-06-01 00:00:00
abstract::Purpose: The aberrant of fibroblast growth factors and their receptors (FGF/FGFR) is an emerging target in the treatment of solid tumors. This study aimed to explore the landscape of FGF/FGFR alterations in a large cohort of cancer patients. Material and Methods: The formalin-fixed paraffin-embedded specimens of cance...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.49269
更新日期:2020-09-23 00:00:00
abstract::Purpose: We explored the influence of age on clinicopathologic features and survival of patients with M0 gastric cancer (GC). Methods: 16856 GC patients from Surveillance, Epidemiology and End Results (SEER) database and 1037 GC patients from Chinese multiple centers were enrolled in the U.S. and Chinese cohort, respe...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.22085
更新日期:2018-03-08 00:00:00
abstract::Endocrine resistance in hormone receptor positive breast cancer patients urges us to develop novel approaches such as inhibitors of the cyclin-dependent kinases (CDK) 4/6 to reverse its resistance. Nowadays, three selective CDK4/6 inhibitors (Palbociclib, Ribociclib and Abemaciclib) are approved by Federal Drug Admini...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.33079
更新日期:2019-10-21 00:00:00
abstract::Background: Malnutrition and systemic inflammatory response are frequently associated with prognosis in patients with several types of cancer, including renal cell carcinoma (RCC). The study is aimed to investigate the ability of preoperative serum albumin to globulin ratio (AGR) to predict the long-term mortality of ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.16525
更新日期:2017-01-15 00:00:00
abstract::Endometrial and ovarian cancers are two most common cancers affecting women in their post-menopausal years. To date, there are no simple biochemical tests to detect these cancers at early stages. Our previous study has demonstrated that the activity of total proprotein convertases (PCs) is significantly increased in u...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.16331
更新日期:2016-08-12 00:00:00
abstract::Background: Radiotherapy is a primary treatment strategy for patients with unresectable hepatocellular carcinoma (HCC); however, the prognostic factors among HCC patients who have received radiotherapy but not undergone surgery have not been systematically studied. Thus, the prognostic factors were investigated in thi...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.30365
更新日期:2019-07-25 00:00:00
abstract::Objective: Although previous studies suggest that previous pulmonary tuberculosis was associated with increased risk of lung cancer. It remains controversial whether pulmonary tuberculosis is a risk factor for lung cancer. Our study was aimed to examine the association between pulmonary tuberculosis and lung cancer ri...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.37022
更新日期:2020-01-20 00:00:00
abstract::Cancer is a genetic disease where genetic variations cause abnormally functioning genes that appear to alter expression. Proteins, the final products of gene expression, determine the phenotypes and biological processes. Therefore, detecting gene expression levels can be used for cancer diagnosis, prognosis, and treat...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.24744
更新日期:2018-06-05 00:00:00
abstract::Aims: We previously demonstrated that a loss of lean body mass loss at one month after gastrectomy was an independent risk factor for the continuation of adjuvant chemotherapy with S-1. However, it is unclear whether or not lean body mass loss after gastrectomy leads to a poor survival through poor compliance to adjuv...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.30697
更新日期:2019-05-28 00:00:00
abstract::Background: The use of PCI in early operable patients with small cell lung cancer (SCLC) is still controversial. Therefore, we conducted a systematic review with meta-analysis to investigate the effects of PCI in resected SCLC patients. Methods: Relevant studies were identified from PubMed and EMBASE databases, the po...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.21465
更新日期:2018-01-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. However, science has not yet been able to substantially improve the prognosis of lung cancer patients. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor development and metastasis....
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.16961
更新日期:2017-06-30 00:00:00
abstract::Background: Overall survival of patients with primary CNS lymphoma (PCNSL) has improved since the introduction of immunochemotherapy. However, up to 10-15% of PCNSL patients still die shortly after diagnosis. In the present study, we aimed to investigate the risk factors of early mortality (death within 60 days after ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.32467
更新日期:2019-07-05 00:00:00
abstract::Taking into account the previously reported relationship between inflammation and carcinogenesis, and the scant amount of data concerning the role of neutrophil extracellular traps (NETs) in carcinogenesis, we decided to study the process of extracellular trap formation in patients with inflammation as well as in pati...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.24238
更新日期:2018-04-30 00:00:00
abstract::Introduction: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a standard first-line treatment for advanced EGFR-mutated NSCLC patients. Factors associated with symptoms and quality of life (QOL) improvements have not been investigated. Methods: We conducted a multicenter, prospective study ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.30507
更新日期:2019-07-10 00:00:00