tbuckley/cabot-search huggingface dataset:
Abstract 641: Effects of an mTOR inhibitor on immune subpopulations
Authors: Barbara Seliger, Corrina Giersberg, Franziska Leich
Journal: Cancer Research (2011)

Abstract Immune suppression is frequently detected in renal cell carcinoma (RCC) and might contribute to tumor progression. Recently, receptor tyrosine kinase inhibitors have been shown to revert the frequency of the myeloid-derived suppressor cell (MDSC)-mediated immune suppression, the development of regulatory T cells (Treg), increase the number of NK cells and prevent tumor-specific T cell anergy. The mTOR inhibitors exhibit a unique target profile resulting in both anti-tumor and anti-angiogenic activity. It has been shown that everolimus can induce apoptosis in various cancers of distinct origin. However, the role of everolimus on immune cell subpopulations have not yet been studied in detail. Therefore peripheral blood mononuclear cells as well as human CD3+ T cells obtained from healthy blood donors were either left untreated or stimulated with antibodies or PHA and subjected to multicolour flow cytometry using a large set of antibodies. We here show that everolimus exerts different effects on peripheral blood mononuclear cells regarding the composition of immune cell subpopulations, their proliferation, activation, cytokine production and degranulation. Upon everolimus treatment the number of stimulated CD3+, CD4+ and CD8+ and CD4+/FoxP3* T cells decreased, whereas the number of NK cells, CD4+/CD8+ CD45RO T cells increased. Furthermore, the T cell proliferation was reduced upon mTOR inhibitor treatment. These data suggest that everolimus modulates the composition of immune cells, their activation and growth properties, which is important for the design of combinatorial therapies. 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 641. doi:10.1158/1538-7445.AM2011-641
Abstract 777: Rosehip (Rosa canina) extracts prevent Akt-mediated cell proliferation in glioblastoma cells
Authors: Patrice McNair, Ipek Goktepe, Patrick M. Martin
Journal: Cancer Research (2010)

Abstract Glioblastoma multiforme (GBM) are aggressive malignant tumors that develop in the brain. GBMs demonstrate increased rates of cell proliferation, a lack of apoptosis as well the propensity to migrate to distal sites in the brain. The clinical management of glioblastoma consists of surgical resection followed by radiotherapy and chemotherapy. However, this treatment regimen is not very effective and more effective therapies need to be developed. Activation of several signaling pathways has been associated with the increased proliferative capacity of GBM cells. Activity of the Akt/mTOR pathway is exceptionally high in GBMs and may regulate sensitivity to chemotherapy and radiotherapy. Akt and its downstream effector p70S6 kinase (p70S6K) demonstrate a high amount of activity in GBMs. Inactivation of Akt and p70S6K attenuate GBM cell growth and may inhibit GBM cell proliferation. Therefore, we investigated the antiproliferative capacity of extracts from the Rosehip (Rosa canina) plant. Rosehip extracts have been used as dietary supplements to relieve symptoms associated with diarrhea, gastritis and rheumatoid arthritis. U-1242MG, a human GBM cell line, treated with Rosehip extracts (250 µg/ml) demonstrated a decrease in cell proliferation. The Rosehip extract-mediated decrease in cell proliferation was equal to the decrease of cell proliferation observed when LY294002 (20 µM),a known Akt inhibitor was utilized. Additionally, pretreatment of the U-1242 MG cells with these Rosehip extracts (250 µg/ml) decreased p70S6K phosphorylation, suggesting these extracts prevent GBM cell proliferation by blocking Akt/mTOR signaling mechanisms. Taken together these data suggest that p70S6K positively regulates GBM cell proliferation, and Rosehip extracts may serve as an alternative or supplement to current therapeutic regimens for GBMs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 777.
Early Prediction by 18F-FDG PET/CT for Progression-Free Survival and Overall Survival in Patients With Metastatic Colorectal Cancer Receiving Third-Line Cetuximab-Based Therapy
Authors: Feng-Yuan Liu, Tzu-Chen Yen, Jeng-Yi Wang, Tsai-Sheng Yang
Journal: Clinical Nuclear Medicine (2015)

In metastatic colorectal cancer (mCRC) with wild-type K-ras, cetuximab-based regimen is an option for third-line therapy. The objective of this study was to assess if early response evaluation by 18F-FDG PET/CT can predict progression-free survival (PFS) and overall survival (OS) in these patients.Patients with mCRC going to receive third-line cetuximab-based therapy were enrolled. 18F-FDG PET/CT studies were arranged at baseline and at the ends of the first and fourth weeks of therapy. Treatment response was evaluated with 2 methods: method 1 based on PET response criteria in solid tumors 1.0 and method 2 based on the assumption that an increase in peak tumor metabolism implies nonresponse. Progression-free survival was counted to tumor progression based on the Response Evaluation Criteria in Solid Tumors 1.1 or death. The predictive powers for PFS and OS were analyzed using the Kaplan-Meier method and the log-rank test.Twenty-seven patients were eligible with a median PFS of 5.8 months and a median OS of 9.1 months. Method 2 predicts PFS (P = 0.001) and OS (P < 0.001) at the end of the first week, whereas method 1 does not. Both methods predict PFS and OS at the end of the fourth week.Early response evaluation by 18F-FDG PET/CT predicts PFS and OS in patients with mCRC receiving third-line cetuximab-based therapy. Early therapeutic change may be possible for nonresponsive patients after 1 week of treatment.
FDG Positron Emission Tomographic Imaging of Pseudo-pseudo Tumor
Authors: MADHUSUDHAN P. REDDY, YUSUF MENDA, JOSEPH FLORESCA, JUWEID MALIK, MICHAEL M. GRAHAM
Journal: Clinical Nuclear Medicine (2002)

REDDY, MADHUSUDHAN P. M.D.; MENDA, YUSUF M.D.; FLORESCA, JOSEPH M.D.; MALIK, JUWEID M.D.; GRAHAM, MICHAEL M. Ph.D., M.D. Author Information
Replacement Dose, Metabolism, and Bioavailability of Levothyroxine in the Treatment of Hypothyroidism
Authors: Lisa H. Fish, Harold L. Schwartz, John Cavanaugh, Michael W. Steffes, John P. Bantle, Jack H. Oppenheimer
Journal: New England Journal of Medicine (1987)

A change in the formulation of the levothyroxine preparation Synthroid (Flint) in 1982 prompted us to reevaluate the replacement dose of this drug in 19 patients with hypothyroidism. The dose was titrated monthly until thyrotropin levels became normal. The mean replacement dose (±SD) was 112±19 μg per day, significantly less (P<0.001) than the dose of an earlier formulation—169±66 μg per day — used in a similar study (Stock JM, et al. N Engl J Med 1974; 290:529–33). The fractional gastrointestinal absorption of a tablet of the current formulation is 81 percent, considerably higher than the earlier estimate of 48 percent. Using high-performance liquid Chromatographic analysis, we found that the current tablet contains the amount of thyroxine stated by the manufacturer. By measuring the bioavailability of the earlier type of tablet in five patients, we inferred that the strength of the previous tablet had been overestimated. In the present study, the thyrotropin levels of patients on replacement therapy returned to normal when serum triiodothyronine concentrations were not significantly different from those of controls (122 vs. 115 ng per deciliter [1.87 vs. 1.77 nmol per liter]), but when serum thyroxine levels were significantly above those of controls (11.3 vs. 8.7 μg per deciliter [145 vs. 112 nmol per liter], P<0.001). These findings suggest the possibility that in humans, serum triiodothyronine may play a more important part than serum thyroxine in regulating the serum thyrotropin concentration. (N Engl J Med 1987; 316:764–70.)
THU0060 Application of the ASAS Criteria for Spondyloarthritis to Patients with Fibromyalgia
Authors: A. Khan, A. Georgiou, E. Roussou
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Aiming to assess the ASAS criteria for Spondyloarthritis (SpAs) in patients with Fibromyalgia (FM) we applied all items of the ASAS criteria (for both axial and peripheral disease) to 84 patients with FM. <h3>Methods</h3> Patients with FM attending regular out patients clinics were assessed clinically by physician and given questionnaire with FM indices. Routine blood tests obtained and radiographic evaluation to exclude other diseases. individual item of Inflammatory back pain (IBP) criteria and of the ASAS criteria were also applied. Sensitivity and specificity tests have been calculated. <h3>Results</h3> A total of 84 patients (M:F = 5:79) were assessed. They had a mean age of 47.3 years (y) (sd ± 11.2), mean age of symptom onset of 33 y (± 11.8) and mean age of diagnosis 41.9 (±10). The mean CRP of the group was 6.7 (sd ± 4). FM patients fulfilled both 1990 (tender point evaluation) and 2011 criteria. When items from the ASAS criteria were applied to the patients with FM, 6 patients (all females) had more than 1 of the items seen in the ASAS criteria (7.1%). More specifically, 6 patients had back pain onset below the age of 45 y of age and lasting for more than 3 months. Five out of 6 were positive for IBP criteria, 3 patients were HLAB27 (+), 3 patients had good response to NSAIDs, 3 patients had positive Fx of SpA (2 of Psoriasis, 1 of Crohn9s disease) 2 patients had elevated CRP and 2 patients had confirmed enthesitis by ultrasound. From those patients fulfilling the ASAS criteria for SpAs, 3 patients fulfilled criteria for axial disease, 3 fulfilled criteria for peripheral disease and 1 patient fulfilled the criteria for both axial and peripheral disease. Upon scrutinized the history and clinical evaluation 2 patients have subsequently classified as SpA while the other 4 although they could be classified as SpA they still remained under the FM umbrella requiring follow up evaluation. The specificity and sensitivity for the ASAS criteria among FM patients have been calculated which showed a sensitivity of 2% and a specificity of 91.7% for the ASAS criteria. The positive predictive value showed to be 25% while the negative predictive value was 48%. <h3>Conclusions</h3> Although IBP is commonly seen in patients with FM the ASAS criteria for SpAs showed low sensitivity and high specificity among FM patients which supports their discriminatory capacity among patients with these diseases. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6081
Abstract P2-09-01: Serial [18F] FDG-PET after the 2nd Cycle of Preoperative Chemotherapy Is Predictive for Pathological Complete Response in Stage II/III Breast Cancer
Authors: S-Y Jung, S-K Kim, Y Kwon, E-A Kim, KL Ko, IH Park, KS Lee, KW Kang, D-Y Noh, SH Shin, JS Jeong, S Lee, SW Kim, H-S Kang, J. Ro
Journal: Cancer Research (2010)

Abstract Purpose: One of substudies of the prospective trials aimed to evaluate the usefulness of serial [18F] 2-fluoro-2-deoxy-D-glucose-positron emission tomography ([18F] FDG-PET) for predicting pathological complete response (pCR) in stage II/III breast cancer with preoperative chemotherapy (PST). Methods: Serial PET was undertaken in 57 breast cancer patients enrolled in three different neoadjuvant trials: 35 patients from a phase II study with paclitaxel/gemcitabine/trastuzumab with ClinicalTrial.gov NCT 00532857, 9 patients from a phase Ib study with paclitaxel/gemcitabine/lapatinib with ClinicalTrial.gov NCT 01133912, and 13 patients from a phase Ib with paclitaxel/gemcitabine/sunitinib with ClinicalTrial.gov NCT0 1070706. All patients received 6 cycles of PST followed by surgery and radiotherapy. We assessed the peak standardized uptake value (SUVp) in the primary tumor at the baseline and after the 2nd cycle (37 patients) or after completion (20 patients) of 6 cycles of PST, and calculated the reduction rate (RR) of the SUVp. Pathological response was classified into pCR and non-pCR. To compare the mean of SUVp and RR of SUVp between different response groups, two-way tables and chi-square tests were used Results: Fifteen (40.6%) of 37 patients who took repeat PET after the 2nd PST and 15 (75%) of 20 patients after completion of PST achieved a pCR with overall pCR rate of 52.6% in the primary tumor. In patients with repeat PET after the 2nd PST, post-treatment SUVp and RR of the SUVp in primary tumors were significantly different by the pathological response (post-treatment SUVp, 1.54 ± 0.63 in pCR vs 2.54 ± 1.06 in non-pCR, P=0.002; RR of the SUVp, 79.2% ± 11.9% in pCR vs 68.9% ± 15.4% in non-pCR, P=0.03). However, in patients with repeat PET after completion of PST, there were no statistical differences of these values (post-treatment SUVp, 1.09 ± 0.63 in pCR vs 1.29 ± 0.36 in non-pCR, P=0.42; RR of the SUVp, 83.7% ± 14.0% in pCR vs 67.5% ± 21.1% in non-pCR, P=0.17) Conclusions: This study demonstrated that repeat PET after the 2nd cycle of PST, not after completion of PST could predict pCR in stage II/III breast cancer with preoperative chemotherapy. Acknowledgement NCC Grant #0910320. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-01.
IV 5-FU administration for 10 days after curative colorectal surgery, followed by oral HCFU for one year as adjuvant chemotherapy
Authors: K. Ito, H. Takagi, N. Ito, A. Koike, K. Kondo, S. Saji, T. Kato, H. Suzuki, Y. Nimura, A. Yamaguchi
Journal: Journal of Clinical Oncology (2004)

3632 Background: In our two prior studies it is proved that the surgical treatment for the colorectal cancer with lymph node metastases (macroscopic Dukes C) can be improved by the additional oral adjuvant chemotherapy of HCFU + intravenous MMC in the 10 year survival rate and by the additional oral adjuvant chemotherapy of HCFU in the 5 year disease free rate. In this study it is aimed to know if intravenous 5-FU administration just after the curative resection of colorectal cancers + oral HCFU administration for one year is more effective for the disease free survival rate than that of the two studies. Methods: In 41 participating institutions, 518 primary colon cancer patients with macroscopic lymph node metastases and the depth of tumor deeper than propria musclaris( macroscopic Dukes C) were allocated into 3 groups, after curative resection. All cases are administered oral HCFU 200mg/m2 / day for 54 weeks, from 14th days after surgery. Group A(194); a daily infusion of 5-FU (5-fluorouracil)333mg/m2/24h×10 days, continuously, group B(155); MMC 2.7mg/ m2 / iv x 6/ 2 weeks, and group C(169); no intravenous chemotherapy. The efficacy of these drugs in adjuvant chemotherapy was evaluated in all entered 518 cases, 500 eligible cases, and 428 evaluable cases. Results: There were no back ground differences among the 3 groups. The total 5 year survival rate among 3 groups was not statistical difference, and the 5 year disease free rate of evaluable 428 cases, was also not statistical different among 3 groups (P<0.0662), but the 5 year disease free survival rate among 3 groups of colon cancer was statistically difference (p<0.036), Group A(n=112) 82.5%, Group C(n=100) 76.5%, Group B (n= 95) 67.1%, respectively. Side effects were minimal and mainly due to MMC.Conclusions: It was suggested that the continuous infusion of 5-FU (5-fluorouracil)333mg/m2/24h, for 10 days, just after surgery, followed by oral administration of HCFU 200mg/m2 / day for 54 weeks, from 14th days after surgery obtain the better 5 year disease free rate in colon cancer than No significant financial relationships to disclose.
Abstract 4023: ARID1A is a candidate tumor suppressor gene in breast cancer
Authors: Catherine Chabot, Aline Mamo, Luca Cavallone, Sukru Tuzmen, Saima Hassan, Henrik Edgren, Cristiano Ferrario, Olga Aleynikova, Ewa Przybytkowska, Kristin Malcolm, Olli Kallioniemi, Patricia Tonin, Spyro Mousses, Mark Basik
Journal: Cancer Research (2011)

Abstract Tumor suppressor genes (TSGs) have been classically defined as genes whose loss of function in tumor cells contributes to the formation and/or maintenance of the tumor phenotype. Typically but not always, tumors neutralize both alleles of TSGs by deleting one copy and mutating the other. One molecular strategy to discover potential tumor suppressor gene candidates involves the “re-expression” of RNA transcripts containing nonsense mutations by inhibition of the nonsense-mediated RNA decay (NMD) process. Combining NMD inhibition with array CGH has lead to the genome-wide identification of genes with biallelic inactivation (involving nonsense mutations on one allele and loss of the second allele) in prostate cancer cell lines and identified EphB2 as a novel candidate TSG in prostate cancer. Using such a strategy in 5 breast cancer cell lines, we identified ARID1A as a NMD target in the T47D breast cancer cell line. ARID1A encodes a human homologue of yeast SWI1, which contains a DNA-binding motif (AT-rich interactive domain, ARID) and is an integral member of the hSWI/SNF complex, an ATP-dependent chromatin-remodeling multiple-subunit enzyme. Mutations in the ARID1A gene were recently reported to be present in 50% of clear cell tumors of the ovary. We found the ARID1A gene contains a nonsense mutation in exon 9, which introduces a premature stop codon, changing Q944 to a stop codon in the T47D breast cancer cell line. Although we did not find any somatic mutations in breast tumors, we show that low ARID1A RNA expression or low ARID1A nuclear protein expression is associated with more aggressive breast cancer phenotypes in 2 independent cohorts of over 200 breast cancers each. We also found that low or absent ARID1A nuclear expression becomes more prevalent during the later stages of breast tumor progression. Finally, we found that ARID1A re-expression in the breast cancer cell line in which it is mutated results in significant inhibition of colony formation in soft agar. These results suggest that the ARID1A gene may be a candidate tumor suppressor gene in breast cancer, and that it warrants further investigation as potential diagnostic and therapeutic marker in breast 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 4023. doi:10.1158/1538-7445.AM2011-4023
Pellets in the Appendix
Authors: Ibrahim Zardawi, Eranga Siriweera
Journal: New England Journal of Medicine (2013)

An 8-year-old hyperactive boy was admitted to the hospital after having been found to have elevated blood lead levels, ranging from 17.4 to 27.4 μg per deciliter (reference range, <10). An abdominal radiograph revealed many small, hyperdense foci in the right lower quadrant.
Abstract 1281: Endothelial cells promote the cancer stem cell phenotype of human colorectal cancer cells
Authors: Jia Lu, Debashish Bose, Yunfei Zhou, Puja Gaur, Shaija Samuel, Fan Fan, Ling Xia, Xiang-Cang Ye, Eric Sceusi, Federico Tozzi, Sendurai A. Mani, Lee M. Ellis
Journal: Cancer Research (2010)

Abstract Background: Cancer stem cells (CSC), which possess the properties of self-renewal, multi-potential differentiation and tumor initiation, can arise either from normal stem cells or due to the influence of the tumor micro-environment. This study was done to determine the potential role of endothelial cell (EC) derived paracrine factors on promoting the CSC phenotype in human colorectal cancer (CRC) cells. Methods: RFP-labeled human CRC cells HCT116 were co-cultured with RF24 ECs (immortalized HUVECs) under low serum conditions. After FAC-sorting for the CRC cells, the CSC population was analyzed by 1) the Aldefluor assay, 2) sphere forming ability, and 3) Western blot analysis for the CSC markers CD133 and CD44. In addition, low serum condition media obtained from either ECs or parental CRC cells (control), was added to CRC cells to determine its effect on the CSC phenotype. In order to characterize the apoptotic effect of EC derived factors on CRC cells, we performed Annexin V staining by FACS, PARP cleavage, Caspase 3 cleavage, and Bcl2 levels by Western blotting. Using MTT assay, we determined the effect of EC derived factors on chemo-sensitivity of CRC cells exposed to 5-FU. Results: Co-culturing of CRC cells with ECs markedly increased the ALDH-positive population from 5% to 18%, and the sphere forming ability by more than 4-fold in CRC cells. In addition, CRC cells also displayed increased CD133 (6-fold) and CD44 (4-fold) protein levels. Furthermore, this effect could be mimicked simply by co-culturing CRC cells with conditioned media obtained from ECs. Similarly, treatment of CRC cells with conditioned medium from ECs significantly increased the ALDH-positive population from 4% to 8%, sphere forming ability &amp;gt;3-fold, and the expression of CD133 (7-fold) and CD44 (6-fold). Conditioned medium from ECs, concomitantly decreased spontaneous apoptosis in CRC cells as demonstrated by a 3-fold decrease in Annexin V-positive population (21% to 7%), down-regulation of cleaved PARP and Caspase 3, and up-regulation of Bcl2. CRC cells exposed to EC conditioned medium also displayed decreased sensitivity to 5-FU [&amp;gt;10-fold increase of the IC50 from 2.0 μg/ml to 22.3 μg/ml (p&amp;lt;0.05)]. Conclusions: Exposure of CRCs to ECs increased CSC properties, and decreased spontaneous apoptosis. Since, this effect can also be mimicked by the conditioned media, additional experiments to identify and validate the soluble factors that mediate this effect are in progress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1281.