Abstract:
:The use of polyADPribose polymerase inhibitors in cancer treatment provides a unique opportunity to target DNA repair processes in cancer cells while leaving normal tissue intact. The PARP-1 enzyme repairs DNA single strand breaks (SSB). Therefore PARP-1 inhibition in BRCA1 negative cancers results in the formation of cytotoxic DNA double strand breaks (DSB) causing synthetic lethality. The use of PARP1 inhibitors is gaining momentum in the treatment of a variety of tumours with BRCA1 involvement including breast, ovarian, pancreatic and prostate cancer. Our previous work showed that the PARP-1 inhibitor Olaparib causes both hypersensitivity of BRCA1+/- cells following exposure to gamma radiation due to the persistence of DNA strand breaks in cells, measured by the DNA damage biomarker γ-H2AX. Therefore dual treatment of cancers with radiotherapy and PARP1 inhibition may lead to cases of increased normal tissue toxicity in cancer patients. In this study we exposed two normal lymphoblastoid cell lines and three heterozygous BRCA1 lymphoblastoid cell lines to the PARP-1 inhibitor Olaparib and gamma radiation and after measured BRCA1 protein expression and apoptosis levels following treatment. BRCA1 protein foci analysis was performed on cells exposed to 2 Gy radiation in the presence or absence of 5 μM Olaparib. Using immunofluorescence and imaging flow cytometry, foci were measured in untreated cells and at 0.5, 3, 5 and 24 hours post-irradiation. Exposing normal and BRCA1+/- cells to Olaparib followed by gamma radiation results in a dramatic change in BRCA1 protein foci expression, with a significant reduction in BRCA1 protein expression observed in the heterozygote cells, together with an increase in apoptosis levels in these cells. In conclusion, combining PARP1 inhibitors with radiotherapy in treating of BRCA1-related cancers has clinical relevance, however this study and our previous publications serve to highlight the potential problems of increased side effects in these scenarios.
journal_name
J Cancerjournal_title
Journal of Cancerauthors
Bourton EC,Ahorner PA,Plowman PN,Zahir SA,Al-Ali H,Parris CNdoi
10.7150/jca.21338subject
Has Abstractpub_date
2017-10-23 00:00:00pages
4048-4056issue
19issn
1837-9664pii
jcav08p4048journal_volume
8pub_type
杂志文章abstract::Objective: Liposarcoma is a mesenchymal malignant tumor characterized by adipocyte differentiation which is divided into four subtypes with different prognosis. Accurate histopathological diagnosis is essential for precise treatment. Perilipins, including PLIN1, PLIN2, PLIN3, PLIN4, PLIN5, is a family of lipid droplet...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.41736
更新日期:2020-04-07 00:00:00
abstract:BACKGROUND:Age-adjusted evaluations have explored the possible utility of (HPV test results in women with LSIL Pap. We investigated HPV test results and histopathologic follow-up results of LSIL patients from China's largest CAP-certified laboratory. METHODS:Patients with LSIL between 2011 and 2015 from the Guangzhou ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.19421
更新日期:2017-07-23 00:00:00
abstract::Yes-associated protein (YAP) is a transcriptional coactivator that promotes cell proliferation, migration, and tissue homeostasis in colorectal cancer (CRC). Here, we established 5-Fu resistant CRC cell line (SW620R) and examined the role of YAP in chemotherapy resistance. We showed that YAP promoted cell proliferatio...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.44775
更新日期:2020-07-11 00:00:00
abstract::In this short communication we report a quick, cost-free method of purification of DNA fragments from agarose gel. Unlike those procedures that involve commercial kits, this method uses glass wool or absorbent cotton to filter agarose gel during a quick spinning-down of DNA, thus significantly simplifying the routine ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.4163
更新日期:2012-01-01 00:00:00
abstract::MicroRNA-519d (miR-519d) has been reported to play important roles in tumor development and progression in multiple cancers, either as tumor suppressor or tumor promotor. However, the expression level, biological function and molecular mechanisms of miR-519d in oral squamous cell carcinoma (OSCC) remain unclear. There...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.31825
更新日期:2019-06-02 00:00:00
abstract::Distant metastasis is the primary cause of cancer-related death among patients with colorectal cancer (CRC), and the discovery of novel therapeutic targets by further exploring the molecular mechanisms of CRC metastasis is therefore urgently needed. We previously illustrated that CDC27 overexpression promoted prolifer...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.19381
更新日期:2017-08-21 00:00:00
abstract::Liver kinase B1 (LKB1) is a critical tumor suppressor that is frequently mutated in human cancers. LKB1 has serine/threonine protein kinase activity, which regulates gene expression by phosphorylation of Yes-Associated protein (YAP). The phosphorylation-dependent YAP shuttling is critically important intracellular mec...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.33237
更新日期:2019-06-09 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::Objective: Multiple reports have described the proportion of T-regulatory cells (Tregs) in peripheral blood (PB) and tissues in patients with gynecological cancers (GCs) with controversial results. Thus, the aim of this study was to investigate the proportion of Tregs and its prognostic survival role in GCs patients. ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.42472
更新日期:2020-03-05 00:00:00
abstract::Tissue-derived RNA, DNA and protein samples become more and more crucial for molecular detection in clinical research, personalized and targeted cancer therapy. This study evaluated how to biobanking colorectal tissues through examining the influences of cold ischemic time and freeze-thaw cycles on RNA, DNA and protei...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.29372
更新日期:2019-08-27 00:00:00
abstract:PURPOSE:We conducted a meta-analysis to evaluate and compare the short- and long-term results of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for colon cancer. METHODS:We searched MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trial Register for relevant papers published between Janua...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.3621
更新日期:2012-01-01 00:00:00
abstract::Background: Programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) is considered as a predictive biomarker of anti-PD-1/PD-L1 cancer therapies. However, the correlation of PD-L1 expression status between the primary and paired metastatic NSCLC is still not clear. The current study aims to a...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.34793
更新日期:2020-01-01 00:00:00
abstract::Many preclinical and clinical studies are currently evaluating metformin in combination with classical therapeutic agents as anti-cancer therapy. In this study we used three distinct pancreatic cancer cell lines and evaluated cell death by trypan blue assay and Western Blots using antibodies directed against cleaved c...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.17972
更新日期:2017-07-01 00:00:00
abstract::Increasing studies indicate that long noncoding RNA (lncRNA) plays a critical role in aerobic glycolysis of various tumors. However, the contribution of lncRNA in gastric cancer (GC) cell glycolysis is still poorly understood. The objective of this research was to investigate the functional role and mechanism of lncRN...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.48365
更新日期:2020-08-27 00:00:00
abstract::Background: The purpose of this study was to examine and compare the prognostic value of different immunization-based scoring systems in patients with soft tissue sarcoma (STS). Methods: We conducted a retrospective study evaluating a cohort of 165 patients diagnosed with STS between July 2007 and July 2014. The relat...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.17356
更新日期:2017-02-25 00:00:00
abstract::Background: Most hepatocellular carcinoma (HCC) patients have undergone a progression from chronic hepatitis, then liver cirrhosis (LC), and finally to carcinoma. The objective of this study was to elucidate risk factors to predict HCC development for cirrhosis patients. Methods: Multiple methylated specific PCR (MSP)...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.24024
更新日期:2018-06-04 00:00:00
abstract::Background: Noninvasive stool-based DNA methylation testing emerges as a new approach for detecting colorectal cancer (CRC). However, its feasibility for early detection of CRC and precancerous lesions in the Chinese population remains inconclusive. Methods: In this study, we establish a possibilities screening method...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.50525
更新日期:2021-01-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is currently one of the most intractable malignancies with a typical scirrhous pattern in histology. Due to its abundant tumor stroma and scant vascularization, chemotherapeutic agents are considered inefficiently permeable to cancer nests, making it highly difficult to cure the...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.24415
更新日期:2018-07-30 00:00:00
abstract::Background: Immunotherapy including immune checkpoint blockade, cancer vaccines, and adoptive cell therapy. However, no immune therapies support ovarian cancer. It is not clear whether the neutrophils, the component of the immune system derived from umbilical cord blood play a role in inhibiting the progression of ova...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.41035
更新日期:2020-05-18 00:00:00
abstract::Ovarian cancer, cervical cancer and endometrial cancer are three relatively common malignant cancers of the female reproductive system. Despite improvements in female genital tract cancer detection and development of new therapeutic approaches, there are still poor prognoses and some do not respond to therapeutic patt...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.44727
更新日期:2020-10-21 00:00:00
abstract:PURPOSE:Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.15696
更新日期:2016-07-08 00:00:00
abstract:OBJECTIVE:The main aim of this study was to study swith of the ovarian cancer cell to a calcifying phenotype in the formation of calcification in ovarian cancer, and to offer some help for ovarian cancer's diagnosis and differentiation therapy. METHODS:The mineralization of ovarian cancer cell lines SKOV3 was induced ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.22932
更新日期:2018-02-28 00:00:00
abstract::Lung cancer is the most common malignancy in China and is associated with a poor survival rate amongst Han Chinese. The high mortality is largely attributed to late-stage diagnosis, when treatment is largely ineffective. Identification of genetic variants could potentially assist with earlier diagnosis and thus more e...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.31134
更新日期:2019-06-02 00:00:00
abstract::PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with an increased cancer risk. We evaluated the chemopreventive effect of statins against all cancers in COPD patients and identified the statin with the strongest chemopreventive effect. PATIENTS AND METHODS: All patients diagnosed with COPD at healt...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.15779
更新日期:2016-09-13 00:00:00
abstract::Objective: Chemotherapy is a major therapeutic method for bladder urothelial carcinoma (BUC), which can effectively improve the prognosis of BUC patients, but the chemoresistance often leads to chemotherapy failure. This study will research the regulatory roles and molecular mechanism of miR-101-3p in BUC chemoresista...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.33117
更新日期:2019-06-02 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:AIM:The aim of our study was to compare clinical outcomes between elderly patients aged ≥75 years (elderly group, n=66) with intermediate hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE) and younger patients aged <75 years (control group, n=84) with intermediate HCC undergoing T...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.9413
更新日期:2014-07-17 00:00:00
abstract:BACKGROUND:This study was performed to assess the impact of irradiation on the tissue penetration depth of doxorubicin delivered during Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC). METHODS:Fresh post mortem swine peritoneum was cut into 10 proportional sections. Except for 2 control samples, all received...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.14714
更新日期:2016-05-07 00:00:00
abstract::Trend analysis is the analysis using statistical models to estimate and predict potential trends over time, space or any independent continuous-variable. It has been widely used in epidemiology and public health, but much less so in clinical oncology and basic cancer research. Methodological imitations of the chosen s...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.43521
更新日期:2020-03-04 00:00:00
abstract:BACKGROUND:Heterogeneity of surgical care exists among surgeons regarding the conduct of thyroidectomy and parathyroidectomy. AIM:To identify the current patterns of technical conduct of operation amongst surgeons performing thyroidectomy or parathyroidectomy. METHODS:A survey was designed and beta-tested on five sur...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.4452
更新日期:2012-01-01 00:00:00