Abstract:
:BRCA2-associated pancreatic ductal adenocarcinoma (PDAC) may be sensitive to agents that target homology-directed DNA repair, such as DNA crosslinking agents (DCLs) and PARP inhibitors (PARPis). Here, we assessed the sensitivities of BRCA2-deficient (Capan-1) and BRCA2-proficient (MIA PaCa-2) PDAC cell lines to a panel of DCLs and PARPis. Compared to MIA PaCa-2, Capan-1 was significantly more sensitive to all tested DCLs and PARPis, with similar increased sensitivities to cisplatin and the PARPi BMN 673 compared to other DCLs and the PARPi veliparib. We provide further support for this observation by showing that shRNA-mediated BRCA2 knockdown in PANC-1, a BRCA2-proficient cell line, induces sensitization to cisplatin and BMN 673 but not to veliparib. These findings were validated in a PDAC murine xenograft model derived from a patient with bi-allelic BRCA2 mutations. We found 64% and 61% tumor growth inhibition of this xenograft with cisplatin and BMN 673 treatments, respectively. Cisplatin and BMN 673 treatments reduced cellular proliferation and induced apoptosis. Our findings support a personalized treatment approach for BRCA2-associated PDAC.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Andrei AZ,Hall A,Smith AL,Bascuñana C,Malina A,Connor A,Altinel-Omeroglu G,Huang S,Pelletier J,Huntsman D,Gallinger S,Omeroglu A,Metrakos P,Zogopoulos Gdoi
10.1016/j.canlet.2015.04.003subject
Has Abstractpub_date
2015-08-01 00:00:00pages
8-16issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(15)00261-Xjournal_volume
364pub_type
杂志文章相关文献
CANCER LETTERS文献大全abstract::In our joint project in the search for anti-tumor promoters from natural plant sources, we carried out a primary screening of 12 phenylpropanoids isolated from Boronia pinnata Sm. (Rutaceae) by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradeca...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(99)00147-0
更新日期:1999-07-19 00:00:00
abstract::The accumulation of the inducible hsp72 (72-kDa heat shock protein) after hyperthermia and/or cisplatin treatment in human glioblastoma cell line (A-172) was studied by Western blot analysis. The level of hsp72 increased to eight-fold 10 h after hyperthermia alone (44 degrees C for 20 min, D50) and to three-fold 10 h ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(96)04508-9
更新日期:1996-12-20 00:00:00
abstract::Vascular mimicry (VM) describes the phenomenon that tumor cells but not endothelial cells form vascular-like channels, which provide blood perfusion for tumor tissues. VM is associated with tumor growth, metastasis and worse survival of different cancers. The mechanisms of VM formation remain largely unknown. We showe...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2016.09.012
更新日期:2016-12-01 00:00:00
abstract::To clarify the roles of Bmi-1 in colorectal carcinoma, we examined the expression of Bmi-1 in 41 samples out of 46 colorectal carcinomas by reverse transcription-PCR, whereas all 46 were analyzed by immunostaining. In addition, we analyzed the expression patterns of Bmi-1 in association with p16INK4a and p14ARF (in mo...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2003.07.009
更新日期:2004-01-20 00:00:00
abstract::Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2011.06.038
更新日期:2011-12-01 00:00:00
abstract::Samples of human endometrial carcinomas of ranging degree of histological differentiation, and normal endometrial tissues were screened for the presence of single site DNA mutations at codon 12 of the C-K-ras gene using oligonucleotide hybridisation of DNA amplified by the polymerase chain reaction (PCR). Two instance...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(90)90223-k
更新日期:1990-05-15 00:00:00
abstract::Membrane glycoprotein synthesis was studied in non-tumorigenic and tumor cells treated with the lymphokine hormone, lymphotoxin, to define the biochemical mechanisms by which lymphotoxin prevents carcinogenesis and inhibits growth of tumor cells. Syrian hamster lymphotoxin increased the synthesis of high molecular wei...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(83)90096-4
更新日期:1983-07-01 00:00:00
abstract::Helicobacter pylori infection is the most important risk factor in the development of non-cardia gastric adenocarcinoma; host genetic variability and dietary co-factors also modulate risk. Because most H. pylori infections do not cause cancer, H. pylori heterogeneity has been investigated to identify possible virulenc...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2008.11.016
更新日期:2009-09-08 00:00:00
abstract::Detection of novel tumor-related antigens and autoantibodies in cancer patients is expected to facilitate the diagnosis of early-stage malignant tumor and establish effective new immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (T...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2008.01.013
更新日期:2008-05-18 00:00:00
abstract::The aim of this study was to clarify candidate peptides for peptide-based specific immunotherapy of patients with oral squamous cell carcinoma (SCC). Thirteen peptides were examined for in vitro induction of peptide-specific CD8(+) T lymphocyte (CD8(+)TL) activity in peripheral blood mononuclear cells from 35 patients...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2012.02.016
更新日期:2012-09-01 00:00:00
abstract::The family of cyclin-dependent kinase complexes (Cdks) are well known for their role in the cell division cycle. What is less well known, however, is that Cdks also participate in a subset of apoptosis programs. Evidence for the role of Cdks in apoptosis comes from a variety of experimental approaches, including studi...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2004.08.005
更新日期:2005-01-20 00:00:00
abstract::The effect of bile acids on the formation of azoxymethane induced aberrant crypt foci (ACF) was investigated using the fecal stream-excluded colons of colostomized F344 rats. The excluded colon was irrigated with saline or bile acids (1 mg/0.5 ml per day, 5 days/week) for 4 weeks. The mean numbers of ACF per colon in ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(01)00525-0
更新日期:2001-08-28 00:00:00
abstract::Metastasis is a characteristic and fatal feature of human malignancies. Its regulation is therefore of the utmost significance to clinicians. The present study was undertaken to determine whether a legume-derived protease inhibitor (PI) of trypsin/chymotrypsin, the field bean PI (FBPI), also has plasmin inhibitory act...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(98)00090-1
更新日期:1998-07-03 00:00:00
abstract::We describe here the establishment of a new synovial sarcoma cell line, SYO-1, derived from a biphasic synovial sarcoma that developed in the groin of a 19-year-old female. The cell line was maintained for more than 70 passages (more than 24 months) in vitro. The SYO-1 cells in monolayer culture exhibited a spindle sh...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2003.09.031
更新日期:2004-02-10 00:00:00
abstract::Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma and some other solid tumors. However, the direct functional mechanisms of tumor lethality mediated by apatinib have not yet been fully characterized, and the precise mechanis...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2018.05.046
更新日期:2018-09-01 00:00:00
abstract::The vectors PAI2, C595 and Herceptin target the membrane-bound uPA, MUC1 and HER2 antigens expressed by cancer cells, respectively. The expression of these receptors was tested in the ovarian cancer cell line OVCAR-3; MUC-1 was strongly expressed (3+), uPA moderately expressed (2+), but HER2 was negative (-). The alph...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2005.03.060
更新日期:2006-03-28 00:00:00
abstract::Interstitial fluid pressure was measured by the wick-in-needle technique in DMBA-induced rat mammary tumours during resting conditions and during noradrenaline infusion. The rate of infusion was chosen to increase the systemic blood pressure by 30-40 mmHg, known to result in a markedly increased vascular resistance of...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(85)90181-8
更新日期:1985-07-01 00:00:00
abstract::We evaluated the association between the XPD exon 10 Asp(312)Asn and exon 23 Lys(751)Gln polymorphisms and the risk of pancreatic cancer in a hospital-based study of 344 patients and 386 controls frequency matched by age, gender, and race. Stratified analyses showed ever smokers carrying the Asn(312)Asn genotype had a...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2005.12.026
更新日期:2007-01-08 00:00:00
abstract::Imatinib has revolutionized treatment strategies for chronic myeloid leukemia patients: long-term overall survival was reported to be up to 80% at 8 years of follow-up in respondent patients. Despite the straightforward results obtained, it has been estimated a failure rate per year of 2-4%. Several attempts to improv...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2012.03.021
更新日期:2012-09-28 00:00:00
abstract::Brain metastasis is an important cause of morbidity and mortality in cancer-patients. Breast tumor cells frequently metastasize to brain and initiate severe therapeutic complications. In the present study, we evaluated the anti-metastatic effects of 2'-hydroxyflavanone (2HF) alone and in combination with RLIP targeted...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2018.09.015
更新日期:2018-12-01 00:00:00
abstract::Aquaporin 3 (AQP3) and c-Met are both overexpressed in human gastric carcinoma and highly associated with its metastasis and invasion. However, it still remains unknown whether c-Met and AQP3 correlate with each other. Herein, we demonstrated that c-Met expression in gastric cancer tissues significantly correlated wit...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2011.12.040
更新日期:2012-06-01 00:00:00
abstract::A newly found human retrovirus, adult T-cell leukemia virus (ATLV) was shown by means of membrane immunofluorescence to bind to various hematopoietic cells including T-, B- and non-T, non-B-cell lines. Partially purified viral gp46 from culture fluids of ATL virus producer lines also bound efficiently to an ATLV-negat...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(84)90004-1
更新日期:1984-01-01 00:00:00
abstract::Tumors are known to cause profound changes in host biology, but the mechanisms responsible for these changes remain unclear. Ornithine decarboxylase (ODC) is a rate-limiting enzyme that catalyzes the biosynthesis of polyamines. The purpose of this study was to examine the effects of MC-26 tumor burden on ODC activity ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(91)90039-k
更新日期:1991-06-14 00:00:00
abstract::RXRalpha is an obligatory heterodimerization partner in many signal transducing pathways. To evaluate RXRalpha expression during laryngeal carcinogenesis, immunohistochemistry was performed on laryngeal epithelial specimens of 154 patients with normal-appearing, hyperplastic, dysplastic laryngeal epithelium and squamo...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(03)00346-x
更新日期:2003-09-25 00:00:00
abstract::N-[2-(p-bromocinnamylmethylamino) ethyl]-5-isoquinolinesulfonamide (H-87), a newly synthesized inhibitor of protein kinase A, significantly decreased the drug resistance of multidrug resistant human U937/M cells, mouse FM3A/M and P388/M cells. Northern blot analysis showed MDR1 gene expression was decreased in H-87-tr...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(93)90041-7
更新日期:1993-10-15 00:00:00
abstract::EGCG [(-)epigallocatechin-3-gallate], a green tea-derived polyphenol, has been shown to suppress cancer cell proliferation, and interfere with the several signaling pathways and induce apoptosis. Practically, there is emerging evidence that EGCG has a potential to increase the efficacy of chemotherapy in patients. We ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2006.03.030
更新日期:2007-03-08 00:00:00
abstract::We examined the responsiveness of normal and neoplastic lung cells to agents which stimulate cAMP production. While their basal cAMP levels were similar, spontaneous in vitro transformant E9 cells and tumor-derived PCC4 cells produced much less cAMP in response to 1 microM isoproterenol compared to non-tumorigenic C10...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(92)90137-k
更新日期:1992-12-24 00:00:00
abstract::Retinoic acid alone has no effect on the human breast cancer cell line BT-20 but can amplify the antiproliferative action of interferon-gamma (IFN-gamma). In our system ornithine decarboxylase (ODC) activity correlates well with growth rate; it was investigated whether the antiproliferative effects of IFN-gamma and IF...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(89)90108-0
更新日期:1989-01-01 00:00:00
abstract::Tyrosine kinase inhibitor (TKI) treatment is the first-line therapy for non-small cell lung cancer (NSCLC) caused by activating mutations of epidermal growth factor receptor (EGFR). However, acquired resistance to EGFR-TKI occurs almost inevitably. Aberrant activation of proto-oncogene MET has been known to confer EGF...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2020.09.003
更新日期:2020-12-28 00:00:00
abstract::Although brain tumors are classified as if their lineage were well understood, the relationship between the molecular events that specify neural cell lineage and brain tumors remains enigmatic. Traditionally, cell surface membrane antigens have served as biomarkers that distinguish brain tumor origin and malignancy. I...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2008.01.007
更新日期:2008-05-18 00:00:00