bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1695: Relationship between expression of ATP-binding cassette (ABC) transporters (ABCB1, ABCC1, ABCG2) and breast cancer subtypes
Authors: Yamada Akimitsu , Ishikawa Takashi , Kimura Mariko , Shimizu Daisuke , Tanabe Mikiko , Chishima Takashi , Kondo Keiichi , Sasaki Takeshi , Endo Itaru 
Published: June 2012

Abstract
Background: Response to chemotherapy differs between intrinsic subtypes, luminal A, luminal B, HER2-enriched, and basal-like type. However, mechanisms of the difference are not known. Several ATP-binding cassette (ABC) transporters including ABCB1 (MDR/P-gp), ABCC1 (MRP) and ABCG2 (BCRP) have been reported to be associated with chemosensitivity.
Aim: The expression of the ABC transporters was comprehensively analyzed with respective to breast cancer subtypes.
Patients and methods: Tissue microarray (TMA) was constructed by acquiring 5.0mm cores from representative area of surgical specimens of 219 breast cancer cases. Immunohistochemistry was performed with anti ABCB1 (C219), ABCC1 (MRPr1), and ABCG2 (BXP-21), and also estrogen receptor (ER) and progesterone receptor (PgR) and Human Epidermal Receptor Growth Factor 2 (HER2).
Results: TMA revealed that 219 cases were divided into Luminal A 152(69.4%), Luminal B 13 (6.0%), HER2 18(8.2%), Triple negative 36 (16.4%). ABCB1 expression was detected in 32.4% (71/219) of the patients, and was detected 36.8%, 30.8%, 27.8%, and 16.7% in Luminal A, Luminal B, HER2, Triple negative subtypes, respectively (Luminal A vs Triple negative, p=0.03). ABCC1 (MRP) expression was detected in 23.9% (52/219) of the patients and was detected 18.7%,45.5%,14.3%, and 47.8 %, in Luminal A, Luminal B, HER2, Triple negative subtypes, respectively (n.s).
Conclusion: The expression of ABCB1 was higher in Luminal A type than in HER2 type and Triple negative breast cancer. Although further investigation is needed, the expressions of ABC transporters may, at least in part, explain the differences of chemosensitivity among subtypes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1695. doi:10.1158/1538-7445.AM2011-1695
Abstract 1702: S-adenosyl-L-methionine induces P-glycoprotein overexpression and drug resistance in human cancer cells
Authors: Tsang Tsun Yee , Yeung Chi Lam Au , Yau Pak Lun , Kwok Tim Tak 
Published: June 2012

Abstract
P-glycoprotein (Pgp) overexpression is frequently associated with multidrug resistance in cancer cells. Pgp is an efflux pump and is encoded by human mdr1 gene. The expression of mdr1 may be regulated by promoter methylation catalyzed by DNA methyltransferases (DNMTs). S-adenosyl-L-methionine (SAMe) is an important cofactor of DNMTs. Although SAMe has been shown to regulate promoter methylation of various genes, the effect of SAMe on Pgp expression and chemosensitivity of cancer cells are however not known. The aim of the present study is to examine the role of SAMe in the regulation of Pgp expression and drug sensitivity of human cancer cells. By qRT-PCR and Western blot analyses, incubation with 1mg/ml SAMe for 24h was found to increase mdr1 mRNA and Pgp protein levels in human hepatocellular carcinoma HepG2 cells, human colorectal adenocarcinoma CaCO-2 cells and human leukemia Jurkat-T cells. Methylation specific PCR and bisulfite DNA sequencing analyses revealed that the SAMe treatment induces hypomethylation of mdr1 promoter. Moreover, SAMe decreased intracellular doxorubicin accumulation and increased doxorubicin resistance in human cancer cells as assessed by doxorubicin accumulation assay and MTT assay. Furthermore, in human colorectal carcinoma HCT-116 parent cells and DNMTs knock-out sublines, SAMe induced Pgp expression in HCT-116 parent and DNMT3b knock-out subline but not in DNMT1 and DNMT1/DNMT3b double knockout sublines. The results from the present study therefore suggest that SAMe induces hypomethylation of mdr1 promoter, Pgp expression, and thus drug resistance in human cancer cells. Furthermore, DNMT1 appeared to be important in the effect of SAMe on mdr1.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1702. doi:10.1158/1538-7445.AM2011-1702
Abstract 1706: Microarray analysis of gene expression reveals that several mTOR related genes are upregulated in cisplatin resistant ovarian cancer cells
Authors: Valiyeva Fatma , Suarez Erick , Gaibi Ashla , Lopez Julio , Sebastian Moises , Flores Josean , Vivas-Mejía Pablo E. 
Published: June 2012

Abstract
The mTOR pathway plays a central role in regulating protein synthesis, ribosomal protein translation, and cap-dependent translation. Recently, also mTOR signaling has been implicated not only in tumor development, but also in drug resistance against chemotherapy and radiotherapy. The mTOR pathway has emerged as an important cancer therapeutic target, principally with rapamycin and its derivatives. However the use of these mTOR inhibitors has been hampered because many cancer cells are resistant to these compounds. Cisplatin has been the most active drug for the treatment of ovarian cancer for almost 40 years. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy the majority will develop disease that becomes resistant to cisplatin. The exact mechanism of cisplatin resistance is presently unknown. We performed growth inhibition experiments and found that the A2780CP20 human ovarian cancer cell line, which is resistant to cisplatin was also resistant to rapamycin and its analogs. Opposite, the cisplatin-sensitive counterpart, A2780PAR cell line was very sensitive to these compounds. Short-term treatment (4-hr) of A2780PAR cells with temsirolimus also induced long-term growth inhibitory effects as observed with a colony formation assay. Microarray analysis of gene expression showed that several survival related genes are up-regulated in A2780CP20 compared with the A2780PAR ovarian cancer cells. Current studies with small interference RNA (siRNA) will determine whether silencing of some candidate genes will sensitize cisplatin resistant ovarian cancer cells to rapamycin treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1706. doi:10.1158/1538-7445.AM2011-1706
Abstract 1707: Establishment and characterization of pemetrexed-resistant lung cancer cell lines
Authors: Zhang Dan , Ochi Nobuaki , Takigawa Nagio , Chen Yanyan , Tanimoto Yasushi , Ichihara Eiki , Hotta Katsuyuki , Tabata Masahiro , Tanimoto Mitsune , Kiura Katsuyuki 
Published: June 2012

Abstract
Purpose: Pemetrexed (PEM), a multitargeted antifolate with manageable toxicity, is a most active drug against non-squamous non-small cell lung cancer (NSCLC); however, a majority of patients acquired the resistance to PEM eventually. To elucidate the mechanisms of acquired resistance to PEM, we established eight PEM-resistant NSCLC cell lines.
Method: PC-9 and A549 cells (adenocarcinoma of the lung) were treated with step-wise increasing concentrations of PEM. Sublines, which were able to grow in the presence of low and high concentrations of PEM, were cloned with limiting dilutions and designated PC-9/PEML and PC-9/PEMH, respectively; A549/PEML and A549/PEMH, respectively. Growth inhibition was defined by MTT assay. Thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT) and multidrug resistance-associated protein 4 (MRP4) gene expressions and protein expressions were analyzed by quantitative reverse transcriptase PCR and immunoblotting.
Result:Characteristics of PEM-resistant sublines are shown in the Table. All resistant sublines showed cross-resistant to cisplatin but not to docetaxel, vinorelbine, 5-fluorouracil and the active metabolite of irinotecan (SN-38). TS mRNA expression was significantly increased in all resistant sublines compared to the parent cells. TS mRNA expression was paralleled to the increment of TS protein. DHFR was significantly increased in the PEM-resistant A549 sublines. GARFT was not correlated with resistance to PEM. MRP4 was increased in PC-9/PEMH and A549/PEMH sublines.
Conclusions: PEM-resistant NSCLC may be still sensitive to docetaxel, vinorelbine, 5-fluorouracil and irinotecan. High TS expression seems to be the primary resistant mechanism to PEM. MRP4 and DHFR expression might be elevated at higher resistance to PEM.

Relative resistance (R.R.) was defined as the ratio of 50% inhibitory concentration (IC50) of resistant cells to IC50 of parent cells; *p&lt;0.05; **p&lt;0.01.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1707. doi:10.1158/1538-7445.AM2011-1707
Abstract 1711: Establishment and characterization of docetaxel resistant prostate cancer cell lines
Authors: Puhr Martin , Oh Su Jung , Erb Holger , Cavarretta Ilaria T. , Hobisch Alfred , Culig Zoran 
Published: June 2012

Abstract
Introduction: For treatment of castration-refractory prostate cancer (CRPC) patients a systemic chemotherapy and a second line hormone therapy have been developed in the last years. The administration of the chemotherapeutic drug docetaxel in combination with prednisone given to patients with CRPC on the basis of its improved survival, pain reduction, PSA response, and quality of life is the state of the art treatment at the moment. However, many patients do not respond to docetaxel or develop a resistance during treatment. Due to the low overall response survival of the patient is prolonged just for a few months. Until now, not much of molecular characteristics for docetaxel resistance is known in prostate cancer. Therefore, the main aim of the study was the establishment and characterization of docetaxel resistant cell lines. For this reason we generated docetaxel resistent sub cell lines of DU-145 and PC3 cells, which are considered models for an advanced disease.
Methods: PC3 and DU-145 cells were treated with increasing concentrations of docetaxel (up to 12,5nM). The resistance of the newly established sub lines was determined by testing cell viability, proliferation, apoptosis, and cell cycle regulation with MTT, [3H]thymidine incorporation assay and FACS measurement, respectively.
Results: Treatment of parental PC3 and DU-145 cells with 12,5nM docetaxel up to 4 days leads to a significant decrease in cell viability. An increase of cleaved PARP protein after 48h for DU-145 and after 72h for PC3 cells could confirm this observation. In contrast to parental cells, the newly established PC3-DR and DU-145-DR docetaxel resistant cells have a different cell morphology. Treatment with docetaxel did not result in increased cPARP levels. Moreover, we could not detect a significant difference in proliferation, basal apoptosis and cell cycle regulation in a direct comparison between parental PC3 and PC3-DR cells. DU-145-DR cells showed a slight increase in apoptosis and a significant decrease in proliferation after docetaxel treatment. However, we still observed a higher viability compared to parental DU-145 cells treated with 12.5nM docetaxel.
Conclusions: The generated sub lines are less sensitive to docetaxel compared to the parental cells. However, DU-145-DR cells are more sensitive to docetaxel than PC3-DR cells. Taken together, we report on successful establishment and characterization of docetaxel-resistant PC3 and DU-145 cells. These cells represent a promising cellular model to investigate the responsible molecular mechanism for docetaxel resistance in prostate cancer cells in vitro.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1711. doi:10.1158/1538-7445.AM2011-1711
Abstract 1714: Chemoresistance in patients with papillary serous carcinoma of the ovary
Authors: Kerr Elizabeth H. , Frederick Peter J. , Oelschlager Denise K. , Amm Hope , Sellers Jeffery , Della Manna Debbie , Buchsbaum Donald J. , Grizzle William E. , McNally Lacey R. 
Published: June 2012

Abstract
The majority of patients with ovarian carcinoma present at an advanced stage, with metastatic disease throughout the peritoneal cavity. Therefore, patients commonly undergo platinum-based chemotherapy. Even though the initial response rates can be high, the majority of patients will have recurrent disease and the 5-year survival rate is only 10-20%. The human lung resistance protein (LRP) is a multidrug resistance protein that has been shown to be overexpressed in models of chemotherapy resistance, but has not been adequately explored in platinum-resistant epithelial ovarian cancer (EOC). The primary aim of this study was to compare LRP expression in the tumor cells from ascitic fluid with tumor cells from omental metastasis in chemotherapy-naïve patients with advanced EOC. The secondary aim was to explore possible mechanisms in which LRP might cause drug resistance.
After IRB approval, patient ascites and metastatic implants were collected and evaluated for platinum sensitivity and expression of LRP, phospho-ERK, and AKT using western blots and immunohistochemistry (IHC). Both ascites and omental metastatic implants were treated with 50 uM carboplatin for 48 hours and cell viability was analyzed. LRP, phospho-ERK, and AKT were analyzed using IHC on samples treated with 50 uM carboplatin or phosphate buffered saline.
Of 20 patients who had matched ascites and omental metastatic implants adequate for analysis, 4 were platinum resistant, 3 were platinum sensitive, and 13 displayed intermediate platinum sensitivity. Overall, the malignant cells in ascites were more resistant to carboplatin than the metastatic implants (p=0.001) and the malignant cells in ascites showed higher expression of LRP than the omental metastatic implants by IHC and western blotting. IHC and western blotting also demonstrated that the malignant cells in ascites had lower expression of phospho-ERK and higher expression of AKT than the metastatic implants. After treatment with 50 uM carboplatin, the platinum resistant patients had decrease in phospho-ERK and an increase in AKT versus the platinum sensitive patients who had an increase in phopho-ERK and a decrease in AKT and LRP. High expression of LRP in the tumor cells in ascitic fluid may indicate platinum resistance prior to initiation of platinum-based chemotherapy. Also, changes in phospho-ERK and AKT following platinum based therapy may indicate the extent of response of EOC to this therapy.
Supported in part by the Kaleidoscope of Hope ovarian cancer foundation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1714. doi:10.1158/1538-7445.AM2011-1714
Abstract 1722: Multidrug resistant P-glycoprotein mediates through Src-EGFR cascade to attenuate DNA-PK-mediated DNA repair
Authors: Lee Pei-Chih , Su Tsann-Long , Lee Te-Chang 
Published: June 2012

Abstract
We have synthesized several novel bifunctional alkylating derivatives of 3a-aza-cyclopenta[a]inden (BO-1012, BO-1005, BO-1099, and BO-1101) and demonstrated that they were more cytotoxic to multidrug resistant (MDR) cells, such as KBvin10, KBtax50, and CEM/VBL, than their parental cells. Using xenograft model, we confirmed that BO-1012 was more effective to suppress the growth of MDR KBvin10 cells in nude mice than to the parental KB cells. To explore the possible mechanism, we revealed that KBvin10 and CEM/VBL MDR cells have significantly lower repair activity than KB and CEM parental cells. Our results also showed that reduced repair activity in KBvin10 cells was likely due to the defective in translocation of DNA-PK, a component of repair machinery of non-homologous end-joining, from cytosol into nucleus. Furthermore, we found that BO-1012 could activate Src kinase and trigger nuclear transport of EGFR in parental cells but not in MDR cells. Inhibition of Src resulted in suppression of BO-1012-induced EGFR translocation and consequently sensitized the parental cells to BO-1012. On the contrary, Src activation induced by BO-1012 was revived in MDR cells by using siRNA to reduce the expression of P-glycoprotein (P-gp). Meanwhile, P-gp silencing also facilitated the EGFR translocation and DNA repair in MDR cells treated with BO-1012. Taken together, our results demonstrated that overexpression of P-gp in MDR cells mediates through inhibition of Src-EGFR pathway to attenuate the DNA-PK-mediated repair.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1722. doi:10.1158/1538-7445.AM2011-1722
Abstract 1734: MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy
Authors: Yoon Juyong , Koo Kyoung-Hwa , Choi Kang-Yell 
Published: June 2012

Abstract
EGFR monoclonal antibodies (mAbs) are used widely to treat metastatic colorectal cancer (mCRC) patients, but it is now clear that patients harboring K-ras mutation are resistant to EGFR mAbs such as cetuximab (Erbitux) and panitumumab (Vectibix). For this reason, current recommendations for patient care involve diagnosing the K-ras mutational status of patients prior to EGFR mAb therapy. In this study, we investigated the ability of two MEK inhibitors currently in clinical trials, AS703026 and AZD6244, to address the challenge posed by the resistance of K-ras mutated colorectal cancers to EGFR mAb. AS703026 and AZD6244 were tested in various cell-based assays and tumor xenograft studies, focusing on isogenic human colorectal tumor cell lines that expressed only WT or mutant K-Ras (D-WT or D-MUT). The EGFR mAb cetuximab inhibited the Ras-ERK pathway and proliferation of D-WT cells in vitro and in vivo, but it did not inhibit proliferation of D-MUT cells in either setting. In contrast, AS703026 and AZD6244 effectively inhibited the growth of D-MUT cells in vitro and in vivo by specific inhibition of the key MEK downstream target kinase ERK. Inhibition of MEK by AS703026 or AZD6244 also suppressed cetuximab-resistant colorectal cancer cells attributed to K-ras mutation both in vitro and in vivo. Our findings offer proof-of-concept for the use of MEK inhibitors as an effective therapy in K-ras mutated CRC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1734. doi:10.1158/1538-7445.AM2011-1734
Abstract 1735: Silencing survivin splice variant 2B leads to antitumor activity in taxane-resistant ovarian cancer
Authors: Rodriguez-Aguayo Cristian , Vivas-Mejia Pablo E. , Han Hee-Dong , Shahzad Mian M.K. , Valiyeva Fatma , Shibayama Mineko , Chavez-Reyes Arturo , Sood Anil K. , Lopez-Berestein Gabriel 
Published: June 2012

Abstract
Survivin, a protein highly expressed in human cancers is involved in both control of cell cycle progression and inhibition of apoptosis. Transcription of the survivin gene locus (BIRC-5) yields at least 5 alternative splice variants including survivin wild-type (WT), survivin ΔEx3, survivin 2B, survivin 3B, and survivin 2α. Here, we studied the role of survivin and its splice variants in taxane-resistant ovarian cancer. Taxane-resistant ovarian cancer cells express higher survivin mRNA levels than their taxane-sensitive counterparts. Survivin 2B expression was significantly higher in taxane-resistant compared to sensitive cells. Small-interference RNAs (siRNAs) targeting survivin were designed to silence all survivin splice variants (T-siRNA) or survivin 2B (2B-siRNA). Silencing survivin 2B induced growth inhibitory effects similar to silencing total survivin in vitro. In addition, survivin 2B siRNA incorporated into DOPC nanoliposomes resulted in significant reduction in tumor growth (p&lt;0.05) in the HeyA8.MDR and SKOV3.TR models, and these effects were similar to T-siRNA-DOPC. The anti-tumor effects were further enhanced in combination with docetaxel chemotherapy (p&lt;0.01). Finally, we found a significant association between survivin 2B expression and progression free survival in 117 epithelial ovarian cancers obtained at primary debulking surgery. These data identify survivin 2B as an important target in ovarian cancer, and provide a translational path forward for developing new therapies against this target.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1735. doi:10.1158/1538-7445.AM2011-1735