bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1742: Suppression of Akt activity selectively induced apoptosis of Ara-C resistant AML cells
Authors: Lee Chansu , Oh Jeong In , Kwon Jung Hye , Kim Byoung Kook , Ahn Kwang-Sung , Yoon Sung-Soo 
Published: July 2012

Abstract
Treatment outcome of acute myeloid leukemia (AML), intensive Ara-C chemotherapy, remains unsatisfactory. It has been shown that the frequency of relapse is high and only 20 to 30% rate of the overall five year survival. Ara-C resistance could be one of major factors in decreasing the efficacy of intensive Ara-C chemotherapy. In this study, we established in vitro Ara-C resistant AML cell lines (KG1 and ML-1) and examined to ascertain the cause of Ara-C resistance. The expression levels of CDA in Ara-C resistant cell lines were higher than in parental cell line. However, the expression of other genes was not significantly different. Besides, PI3K/AKT was persistantly activated in Ara-C resistant cell lines. Also, mTOR, downstream of AKT, was highly expressed in AML resistant cell lines. MTT assay showed that PI3K specific inhbitor, LY29002, and mTOR inhibitor, rapamycin, inhibited the growth of AML cells and there was no different among AML cells. A synergic effect of Ara-C induced apoptosis was not detected in AML cells co-treated with rapamycin. Nevertheless, LY29002 and rapamycin was more effective to induce apoptosis in Ara-C resistant AML cell lines. Our data indicated that persistent activation of Akt in AML cells contributed to becoming resistant to Arc-C treatments. Inhibition of Akt activation would be a potential target to overcome Ara-C resistance in AML.
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 1742. doi:10.1158/1538-7445.AM2011-1742
Abstract 1747: Biochanin A overcomes gemcitabine resistance in pancreatic cancer cells
Authors: Bhardwaj Vikas , Lai James C.K. , Bhushan Alok 
Published: July 2012

Abstract
Drug resistance is one of the major reasons for failure of chemotherapy and high mortality rate in pancreatic cancer. Gemcitabine (GEM) and 5-fluorouracil are two drugs which have shown to improve the survival of pancreatic cancer patients but intrinsic or acquired characteristics make this cancer resistant to these drugs. Previously, we have observed that biochanin A (bioA) effectively reduces the survival, signaling and progression of pancreatic cancer cells. In this study, we aim at determining the effect of bioA on drug resistant pancreatic cancer cells. To test our hypothesis, first we compared three pancreatic cancer cells line: Panc1, MiaPaCa2 and AsPC1 for their sensitivity to gemcitabine and protein expressions. We found that Panc1 cells are highly resistant to GEM with IC50 of 75µM while the same for MiaPaCa2 and AsPC1 cells was 0.04µM. Our western blot data show that the levels of NFkappaB, EGFR and CD133 were higher in Panc1 cells compared to other two cell lines suggesting the role of these factors in imparting drug resistant characteristics to pancreatic cancer cells. Our cell survival studies show that bioA is more effective in reducing the survival of Panc1 cells compared to the other two cell lines. Next, we selected GEM resistant cells (AsPC/G) by continuously exposing AsPC1 cells with increasing concentration of GEM. We generated a GEM resistant cell line that was 20-fold resistant to GEM compared to the parent cell line. AsPC/G cells had higher colony formation ability and in vivo tumorigenicity compared to the parent cells. Also, the expression of p-EGFR, NFκB, p-Akt and EMT markers were upregulated in AsPC/G cell compared to AsPC1 cells. We found that bioA was more cytotoxic to AsPC/G cells compared to AsPC1 cells suggesting that bioA affects the molecular mechanisms which impart drug resistant characteristics. To further understand this phenomenon, we analyzed the molecular mechanisms affected by bioA. We observed that bioA reduces the levels of p-EGFR, p-Akt and NFκB in AsPC1 cells. Upregulation of these proteins is known to impart drug resistant characteristics to pancreatic cancer cells; therefore, by inhibiting them, bioA reduces the survival of GEM resistant pancreatic cancer cells. Our study concludes that bioA reduces the survival of GEM resistant pancreatic cancer cells and a treatment regimen with bioA may improve the outcome of chemotherapy in pancreatic cancer patients.
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 1747. doi:10.1158/1538-7445.AM2011-1747
Abstract 1748: Metformin overcomes cisplatin-resistance in triple negative breast cancer
Authors: Lau Ying Ka Ingar , Shaw Jacquelyn M. , Campbell Julie L. , Maurer Matthew A. 
Published: July 2012

Abstract
Background: Triple negative breast cancers (TNBC) account for approximately 15% of breast cancer but 30% of deaths. The majority of TNBC are basal breast cancers that have higher rate of relapses as compared with other breast cancer subtypes, indicating there exists a sub-population of tumor cells that are highly resistant to chemotherapies. Platinum-based agents and PARP inhibitors have shown efficacy in basal breast cancers with BRCA1/2 mutation background. In this study, we expand the analysis to basal breast cancer lines without BRCA1/2 mutations.
Results and Methods: We treated a panel of basal breast cancer lines (HCC70, MDA-MB-468, BT549, HCC1143) with cisplatin and observed that 6 µM of cisplatin were able to kill &gt;99% of a confluent plate of these cell lines. The cisplatin-resistant population, however, behaved very differently in these lines. Cisplatin-resistant MDA-MB-468 cells had similar phenotype as cisplatin-sensitive cells and they repopulated the whole plate in a short time. Cisplatin-resistant cells in the other 3 TNBC lines had a different phenotype than the cisplatin-sensitive cells and remained quiescent for 2-3 weeks before proliferating in a vertical fashion. The vertical string of cells eventually detached from the plate and kept expanding as clusters of cells in suspension. Screening through various drugs, we observed that 2 mM of metformin as a combined treatment with cisplatin was able to irradicate these cisplatin-resistant cells in both MDA-MB-468 and BT549 cell lines. Additionally, we demonstrated that using aminoimidazole carboxamide ribonucleotide (AICAR), an AMP kinase (AMPK) activator, and Rapamycin, an mTORC1 inhibitor had the same effect as metformin indicating the AMPK-mTOR axis might be important for the survival of cisplatin-resistant cells.
Conclusions: TNBC without BRCA1/2 mutation are sensitive to cisplatin treatment but possess a sub-population of resistant cells. We demonstrated that cisplatin-resistant cells in TNBC lines behaved differently after cisplatin treatment and that combined treatment of metformin and cisplatin may be able to overcome this resistance. Future experiments include comparing this combination with the combined treatment of cisplatin and PARP inhibitor, which might have effect in cisplatin-sensitive cells but not in cisplatin-resistant cells.
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 1748. doi:10.1158/1538-7445.AM2011-1748
Abstract 1882: Short- and long-term risk of adenoma recurrence with cigarette smoking: An analysis of the Polyp Prevention Trial and Continued Follow-Up Study
Authors: Laiyemo Adeyinka O. , Doubeni Chyke , Williams Carla D. , McDonald-Pinkett Shelly , Schoen Robert E. , Marcus Pamela M. , Lanza Elaine , Schatzkin Arthur , Smoot Duane T. , Cross Amanda J. 
Published: July 2012

Abstract
Background: Prospective studies have evaluated the association between cigarette smoking and colorectal adenoma recurrence within 4 years of follow-up, a relatively short duration. We sought to examine short- and long-term risk of adenoma recurrence in association with cigarette smoking among participants in the Polyp Prevention Trial (PPT), a multicenter, randomized controlled trial that evaluated the effect of a low fat, high fiber, fruits and vegetable diet on the risk of colorectal adenoma recurrence.
Methods: A cohort of 774 participants with colorectal adenoma completed a baseline questionnaire including tobacco use and completed the 4-year trial during which they underwent colonoscopy at 1 year and 4 years after enrollment. After the trial was completed, these participants consented to passive follow-up in the Continued Follow-up Study (CFS) during which the colonoscopy reports subsequent to the trial were collected and analyzed. We defined adenoma recurrence as any adenoma detected after the baseline colonoscopy. We used Poisson regression models to evaluate risk of adenoma recurrence up to 4 years (short-term) and up to 12 years of follow-up (long-term).
Results: At baseline, 461 (59.6%) participants had a history of smoking: 379 (49.0%) former smokers and 82 (10.6%) current smokers. Mean age of the patients was 59.6 years and 66.2% were males. The mean total duration of follow-up was 8.4 years (range 4.9 – 12.4 years). When compared with never smokers, there was no association between cigarette smoking and adenoma recurrence with either short- or long-term follow-up (Table).
Conclusions: Cigarette smoking is not associated with adenoma recurrence in the short- or the long-term.
Table: Relative Risk (RR) and 95% confidence interval (CI) for adenoma recurrence during short-term and long-term follow-up according to baseline smoking status

Models were adjusted for age, sex, NSAIDs use, BMI and family history of colorectal cancer.
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 1882. doi:10.1158/1538-7445.AM2011-1882
Abstract 1884: Serological testing along with epidemiological data establishes a trend of pylori's association with colon polyps
Authors: Brim Hassan , Lee Edward L. , Razjouan Hadi , Smoot Duane T. , Hassanzadeh Hassan , Ashktorab Hassan 
Published: July 2012

Abstract
Background: It has become common wisdom that Helicobacter pylori (HP) infection is linked to gastric cancer. However, its involvement in colorectal cancer (CRC) is still under investigation. The trophic effects of induced hypergastrinemea on colon homeostasis as well as HP direct effects on the colon mucosa might play a role in CRC.
Methods: We previously reported that epidemiological data in African American patients (n=1262, &gt;40 years old) who underwent bidirectional gastrointestinal endoscopy show an HP association with colon polyps formation. To substantiate this linkage, we used serological testing on healthy (n=94) and colon polyp (n=95) patients for anti-HP and anti-CagA antibodies to further confirm our epidemiological findings. Microarray used to detect the Gut flora including HP using 16rDNA from stool (n=12) of healthy and colon adenomas.
Results: The healthy individuals had an average age of 63.7 (SD=9.80) while the polyp patients had an average age of 62.8 (SD=9.7). The gender distribution was 42/52 and 41/54 in the two groups for males and females, respectively. As such, the two groups were age and sex matched. In the polyp patients, 55.6% was HP-positive while there was only 48.8% positive in the control group (p=0.30 for this difference). Cag A positive samples were 73.3% in polyp patients and 67.5% in healthy individuals (p = 0.5).
Gut flora analysis using a 16S rDNA microarray from stool (n=12) samples revealed the presence of HP signals in healthy and colon adenomas analyzed samples.
Conclusion: HP seems to be associated with an increased risk of colon adenoma. However, whether HP is a colon inhabitant and participant in colon carcinogenesis or just a gastric wash-out is under investigation in normal and tumor colon biopsies’ gut flora studies. Large sample size is needed to confirm the above observed trend of a possible association of HP with 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 1884. doi:10.1158/1538-7445.AM2011-1884
Abstract 1885: Malignancies associated with immune thrombocytopenic purpura
Authors: Arnaout Karim , Khalife Mustapha , Hanbali Amr 
Published: July 2012

Abstract
Background: Cancer and Immune thrombocytopenic purpura (ITP) are two common disorders. However, the relationship between these two diseases has rarely been reported in the literature. The purpose of this retrospective study was to determine the association between cancer and ITP.
Methods: We retrospectively reviewed the charts of 307 patients diagnosed with ITP in our institution between 2005 and 2009. The diagnosis of ITP was defined by a platelet count less than 140.109/l with normal or increased number of megakaryocytes on bone marrow aspirate, after exclusion of thrombocytopenia-induced medications or disorders, and absence of splenomegaly.
Results: 32 patients (10.4 percent) were found to have cancer. Of these 32 patients, breast cancer accounted for 28.1 percent, prostate cancer for 18.8 percent, skin cancer for 15.6 percent, gastrointestinal cancer and multiple cancer history for 12.5 percent each, bladder cancer and lymphoma for 6.25 percent each. 12 patients (37.5 percent) had ITP before cancer diagnosis, and 16 patients (50 percent) after cancer diagnosis. Both diseases were concomitant in 4 patients (12.5 percent).
Conclusion: 10.4 percent of patients with ITP have cancer. Breast cancer accounted for most of the cases followed by prostate cancer. Our data suggest an association between cancer and autoimmune platelet destruction, and further investigation is warranted to understand the exact mechanism.
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 1885. doi:10.1158/1538-7445.AM2011-1885
Abstract 189: Kaempferol induces apoptosis in ovarian cancer cells through intrinsic pathway
Authors: Luo Haitao , Rankin Gary , DePriest Laura , Chen Yi C. 
Published: July 2012

Abstract
The purpose of this study is to investigate whether and how kaempferol, a dietary flavonoid, induces apoptosis in human ovarian cancer cells.
Ovarian cancer cell lines, OVCAR-3, A2780/CP70, and A2780/wt, were treated with kaempferol for 24 hours and analyzed for cell proliferation and cytotoxicity by genomic DNA staining and LDH assay, respectively. Apoptosis of cells were detected with Caspase-Glo 3/7 Assay. Intrinsic apoptotic pathway was further confirmed by pre-treating cancer cells with caspase-9 inhibitor, and tested for caspase 3/7 levels after kaempferol treatment. Protein levels of pro-apoptosis genes including p53, Bad, and Bax, and anti-apoptosis gene, Bcl-XL, were analyzed by western blots.
Our data demonstrate that kaempferol inhibits cell proliferation but causes no necrosis in all 3 ovarian cancer cell lines. For apoptosis, caspase 3/7 levels were escalated by kaempferol treatment concentration-dependently and significantly. This effect can be diminished by pre-treatment with caspase-9 inhibitor, indicating an intrinsic apoptosis pathway involved in kaempferol-induced apoptosis in ovarian cancer cells. Western blot analysis revealed that protein levels of anti-apoptosis gene, Bcl-xL were decreased in ovarian cancer cells, while pro-apoptotic genes, p53, Bad, and Bax, were up-regulated by kaempferol treatment.
In conclusion, kaempferol induces apoptosis in ovarian cancer cells through regulating expression of both pro-apoptotic and anti-apoptotic genes within the intrinsic apoptosis pathway. As a natural flavonoid wildly distributed in fruits and vegetables, kaempferol is a good candidate for chemoprevention of ovarian cancers in humans. Further studies in animal models and clinical trials are warranted.
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 189. doi:10.1158/1538-7445.AM2011-189
Abstract 1890: Human papillomavirus serology and the risk of lung cancer
Authors: Anantharaman Devasena , Pawlita Michael , Waterboer Tim , Zaridze David , Mukeria Anush , Mates Dana , Szeszenia-Dabrowska Neonila , Rudnai Peter , Lissowska Jolanta , Bencko Vladimir , Scelo Ghislaine , Boffetta Paolo , Brennan Paul 
Published: July 2012

Abstract
A role for HPV in lung cancer has been suggested by several case series. We examined further the role of HPV and lung cancer in a case-control study involving 1633 lung cancer cases and 2729 matched controls from six central European countries. HPV infection status was ascertained for several low-risk and high-risk HPV types by bead-based multiplex serology. Unconditional logistic regression models were used to examine the risk of lung cancer associated with specific HPV types. Overall, low prevalence (&lt;5%) of antibodies for early proteins (E6 and E7) of all HPV types were observed among controls. Seropositivity for both E6 and E7 proteins (for any HPV type) was very rare (&lt;0.3%). We observed a significantly increased risk of lung cancer in the presence of antibodies to HPV6L1, HPV11L1, HPV16L1, HPV18L1, HPV11E6, HPV11E7, HPV16E7 and HPV18E7 after adjustment for potential confounders including age, gender and smoking (Table 1). Similar effects were observed for never, former and current smokers. These results indicate that HPV antibodies are substantially increased in lung cancer cases compared to controls. Whether this indicates a causal relationship is yet to be determined.

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 1890. doi:10.1158/1538-7445.AM2011-1890
Abstract 1898: The Liverpool Lung Project risk model: An independent validation and clinical utility in primary care
Authors: Field John K. , Raji Olaide Y. , Cassidy Adrian , Duffy Stephen W. , Baker Stuart G. , Christiani David C. 
Published: July 2012

Abstract
Background: The results from a recent CT screening trial for lung cancer showed evidence of mortality reduction in the screened arm of the study. The long term success of future National Screening Programme as an early diagnosis tool may be dependent upon identifying populations at sufficient risk of developing the disease such that the benefit:harm ratio of the intervention can be maximised. Risk prediction models can play an important role in risk stratification by providing an estimate of individual's risk of developing a disease at a future time, but require validation in independent populations before they can be successfully generalised. Within the Liverpool Lung Project (LLP), we have developed a risk prediction model for estimating individual's 5-year absolute risk of lung cancer. The model was based on five epidemiological risk factors namely smoking duration, prior diagnosis of pneumonia, family history of lung cancer, occupational exposure to asbestos and prior diagnosis of other cancer. We present here an independent validation and clinical utility of the model using data from two case-control studies and a cohort population from Europe and North America.
Method: The 5-year absolute risk of lung cancer was estimated for subjects in the Harvard and European Early Lung Cancer (EUELC) case-control and LLP prospective cohort studies. The model's performance was assessed through its predictive accuracy (discrimination and calibration) and clinical utility. The area under the receiver-operator characteristic curve (AUC) measures the model's discriminatory power while calibration was assessed by comparing the observed and the expected lung cancer cases in the cohort population. The clinical relevance of the model was examined using the decision and relative utility curves.
Results: There was an evidence of good discriminations in Harvard (AUC = 0.76) and LLP cohort (c-index = 0.77, 0.82) with no significant difference in discrimination by age, gender and smoking status. In general, the model calibration indicated an underestimation of absolute risk; this showed improvement with high absolute risks. The application of the model was associated with reasonably good clinical utility across the three datasets as demonstrated by its superior ‘net benefit’ against any other alternative strategy.
Conclusion: The LLP risk model demonstrates good performance and evidence of clinical usefulness in three independent settings and can serve as an adjunct tool for clinicians or used in primary care for referring patients for early detection and prevention intervention.
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 1898. doi:10.1158/1538-7445.AM2011-1898
Abstract 1899: Validation of the Spitz lung cancer risk prediction model with the Dutch-Belgian randomized lung cancer screening trial (NELSON) cohort
Authors: D'Amelio Anthony M. , Baecke Eleonora , Spitz Margaret R. , de Koning Harry J. , van Klaveren Rob J. , Etzel Carol J. 
Published: July 2012

Abstract
Background: Risk modeling has been shown to be important in detection and prevention of disease, and this is especially true for cancer research. One prominent lung cancer risk model is the Spitz Lung Cancer Risk Model, which was constructed from case-control data and incorporates clinical and epidemiologic variables (smoking status, family history and select co-morbidities). Although the Spitz model is validated using case-control data, the model has not been calibrated.
Methods: We used data from 109 lung cancer patients and 4622 controls that were a subset of a large longitudinal cohort study, the Dutch-Belgian randomized lung cancer trial (NELSON). We estimated absolute lung cancer risks from the Spitz risk model to evaluate the model's calibration, discriminatory power and clinical utility.
Results: With the 10 year absolute risk calculations, the Spitz model was well calibrated with NELSON data, with slightly weaker calibration for five year absolute risk calculations. The overall discriminatory power was 0.69 (95% CI = 0.64-0.74), with current smokers having higher discriminatory power (0.73, 95% CI = 0.67-0.79) compared to former smokers (0.61, 95% CI = 0.51-0.70). When examining clinical utility, it peaked at four lung cancer patients correctly identified by the model for every control incorrectly identified as a lung cancer patient.
Conclusions: This is the first time the Spitz model has been evaluated for calibration, with very good results except for the lowest and highest risk individuals. The calibration results also confirmed the notion by Dr. Peter Bach's group that 10 year absolute risk models are better indicators of cancer risk than five year models. The clinical utility results are very similar to those calculated by the Spitz model with Harvard data that was published in the British Journal of Cancer recently. The Spitz model showed moderate discriminatory power, especially among current smokers.
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 1899. doi:10.1158/1538-7445.AM2011-1899