tbuckley/cabot-search huggingface dataset:
Molecular characterization of temsirolimus-induced response in human renal and bladder cancer cell lines.
Authors: Axel S. Merseburger, Mario W. Kramer, Hossein Tezval, Markus Kuczyk, Juergen Serth
Journal: Journal of Clinical Oncology (2012)

295 Background: Targeted therapies like mTOR inhibition is a clinically esthablished treatment modality for advanced renal cell cancer (RCC). We hypothesize that common elements of molecular signalling exists in RCC and transitional cell carcinoma of the bladder (TCC) that could provide a rational of the usage of this novel compound in human TCC. Therefore the goal of this investigation was to measure the in vivo and in vitro effect of temsirolimus/CCI-779 on human RCC and TCC cell lines on the molecular level. Methods: For in vivo experiments 3 RCC (786-O, A498, ACHN) cell lines and 7 TCC (T24, 5637, RT112, EJ-28, CLS-439, HB-CLS-1, HB-CLS-2) cell lines were compared. Effect of temsirolimus/CCI-779 was measured by real time impedance analysis (XCelligence, Roche). Following mRNA isolation microarray based mRNA expression analysis with 45.015 oligoprobes (G4112F, Agilent Technologies) was performed for molecular comparison of RCC and TCC cell lines. Expression patterns of 15 pathways were analyzed using the statistical software R (2.12.0) and the LIMMA package. Results: RCC and TCC cell lines demonstrated dose dependent inhibition of cellular growth with IC50 values of 10-20nM of temsirolimus/CCI-779 as measured by quantitative real time impedance analysis. Furthermore six out of 15 pathways including the mTOR and VEGF signalling were found with similar expression patterns following treatment with CCI-779 in both tumor entities. Conclusions: In vivo and in vitro analysis of temsirolimus mTOR inhitibtion on human bladder cancer cell lines support the hypothesis that a common molecular architectur exists in both tumor entities suggesting inhibition of mTOR in TCC as a possible target for further experimental therapeutic studies.
Phase III AXIS trial for second-line metastatic renal cell carcinoma (mRCC): Effect of prior first-line treatment duration and axitinib dose titration on axitinib efficacy.
Authors: Brian I. Rini, Bernard J. Escudier, M Dror Michaelson, Sylvie Negrier, Martin Eric Gore, Stephane Oudard, Joseph Clark, Jamal Christo Tarazi, Brad Rosbrook, Sinil Kim, Robert John Motzer
Journal: Journal of Clinical Oncology (2012)

354 Background: Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. In the phase 3 AXIS trial of axitinib vs sorafenib for second-line mRCC, axitinib significantly prolonged median progression-free survival (mPFS) (6.7 vs 4.7 months; hazard ratio 0.665; P&lt;0.0001). Here, we evaluated the effect of prior sunitinib treatment duration and axitinib dose titration on subsequent axitinib efficacy. Methods: Eligible patients had clear-cell mRCC; measurable RECIST-defined progressive disease after 1 prior first-line systemic therapy; and Eastern Cooperative Oncology performance status (PS) 0/1. Patients were stratified by PS and prior therapy, and randomized 1:1 to either axitinib, at a starting dose of 5 mg twice daily (BID), or sorafenib, 400 mg BID. Patients without toxicity &gt;grade 2 and BP &lt;150/90 mmHg without antihypertensive medication for &gt;2 weeks were eligible to increase axitinib dose to 7 mg BID and then to 10 mg BID. Results: The mPFS for patients receiving at least one total daily axitinib dose &gt;10 mg (dose-titrated group; n=132) was 6.6 months [95% CI 4.7–8.3] and 8.3 months [95% CI 6.0–10.2] for patients receiving axitinib ≤10 mg (n=227). A total of 194 patients (53.7%) in the axitinib arm and 195 patients (53.9%) in the sorafenib arm had prior sunitinib treatment. The mPFS for patients with duration of prior sunitinib treatment ≥6 months and &lt;6 months were 4.8 months [95% CI 4.5–6.5] and 4.6 months [95% CI 2.8–8.3] for axitinib patients; and 4.6 months [95% CI 2.9–4.9] and 2.9 months [95% CI 2.8–4.6), for sorafenib patients. The mPFS for duration of prior sunitinib ≥9 months and &lt;9 months were 6.3 months [95% CI 4.6–6.7] and 4.5 months [95% CI 2.8–6.4] for axitinib patients; and 4.6 months [95% CI 2.8–4.9] and 2.9 months [95% CI 2.8–4.7]) for sorafenib patients. Conclusions: Duration of prior sunitinib ≥9 months may be associated with a longer PFS on second-line VEGFR tyrosine kinase inhibitors. Both axitinib dose-increased and non-increased patients had longer PFS compared with the sorafenib arm.
Knowledge of testicular cancer and screening acceptance: Results from a prospective study.
Authors: R. Kedzeriewicz, C. Chargari, S. Le Moulec, N. Jacques Ferrandes, A. Houlgatte, L. Vedrine
Journal: Journal of Clinical Oncology (2011)

231 Background: A delayed diagnosis of testicular cancer is associated with both greater morbidity and poorer prognosis. We conducted a prospective study in the French Armed Forces to assess whether a short medical education could increase the degree of acceptance of the routine clinical screening for testicular cancer. Methods: We enrolled 415 consecutive military patients aged 18-45 years and consulting their army general practitioner. The degree of knowledge on the testicular cancer was assessed using a self-questionnaire, which also served as short medical education. We compared the degree of acceptance for testicular palpation before and after the education delivery. Results: Only 26.8% of patients (n = 107) assumed that they had previously received general information on testicular cancer and 31 patients (7.8%) reported that they were informed on the risk factors of testicular cancer (CI95: 5.5-10.8). In the population, 16.3% of patients (n = 65) had been informed on the usefulness of self-palpation of testes. Wilcoxon tests show significant differences between baseline acceptance level before any intervention and after information delivery (p&lt;0.000001). In details, acceptance of testicular palpation after responding the questionnaire did not change in 82.25%, increased in 15%, and decreased in 2.75%. Conclusions: Young males in military environment are poorly aware of testicular cancer, but there is a demand on medical education regarding this disease. The time of annual medical visit for aptitude is probably the optimal time for this education. No significant financial relationships to disclose.
A Prospective Study of Thyomosin α1 and Intravenous Immunoglobulin Role to Prevent the Infectious Pneumonia Related to Rituximab Based Immuno-Chemotherapy for B Cell Lymphoma
Authors: Tongyu Lin, Raj Shrestha Prem, He Huang, Xueying Li, Huangming Hong, Mengping Zhang, Xiaojie Fang, Zhao Wang, Chengcheng Guo, Zhongjun Xia
Journal: Blood (2016)
Histone Deacetylase-6 (HDAC6) Modulates Akt and STAT3 Activity Via Heat Shock Protein (Hsp) 90 in Human Multiple Myeloma (MM) Cells.
Authors: Teru Hideshima, James E. Bradner, Hiroshi Yasui, Noopur Raje, Dharminder Chauhan, Klaus Podar, Yu-Tzu Tai, Constantine Mitsiades, Paul G. Richardson, Ralph Mazitschek, Stuart L. Schreiber, Kenneth C. Anderson
Journal: Blood (2006)
Growth Factor Independence 1 (Gfi1) Is Required for Initiation, Maintenance, Progression, and Transplantability of Lymphoma.
Authors: Cyrus Khandanpour, Ehssan Sharif-Askari, Khashayar Afshar, Marie-Claude Gaudreau, Jinfang Zhu, William Paul, Paul Jolicoeur, Ulrich Duhrsen, Tarik Moroy
Journal: Blood (2009)
Genome-Wide DNA Methylation Profile of CLL with 17p del Allowed Identification of Multiple Epigenetically Inactivated Molecular Pathways with Prognostic Value in Human Leukemia.
Authors: Wei-Gang Tong, William G. Wierda, Neby Bekele, Shao-Qing Kuang, Michael J. Keating, Guillermo Garcia-Manero
Journal: Blood (2007)
Abstract 1121: Analysis of gene expression changes as a function of PBRM1, BAP1, and SETD2 mutation status clear cell renal cell carcinoma in TCGA tumors
Authors: Philip H. Abbosh, Ilsiya Ibragimova, Michael Slifker, Paul Cairns
Journal: Cancer Research (2015)

Abstract In addition to VHL, the most commonly mutated clear cell renal cell carcinoma (ccRCC)genes are the chromatin modifiers PBRM1, BAP1, and SETD2. Mutations in these genes predict loss-of-function and presumably exert cancer-related functions through changes in chromatin context and gene expression. Mining publicly available data from The Cancer Genome Anatomy (TCGA) allowed us to correlate mutation status and gene expression profiles, potentially suggesting roles for these mutations in ccRCC. Gene set enrichment analysis (GSEA)reveals that specific signaling and metabolic changes are common for each tumor mutation and may reveal the biologic mechanism of tumor-associated mutations. Work is underway to functionally validate the effect of loss-of-function ccRCC mutations in epigenetic modifiers. Citation Format: Philip H. Abbosh, Ilsiya Ibragimova, Michael Slifker, Paul Cairns. Analysis of gene expression changes as a function of PBRM1, BAP1, and SETD2 mutation status clear cell renal cell carcinoma in TCGA tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1121. doi:10.1158/1538-7445.AM2015-1121
Corticosteroids Impair Granulocyte Transfusion Therapy By Targeting NET Formation and Neutrophil Antifungal Functions Via ROS/Dectin1 Pathways
Authors: Natarajaswamy Kalleda, Jorge Amich, Spoorthi Poreddy, Berkan Arslan, Mike Friedrich, Zeinab Mokhtari, Katja Ottmüller, Ana-Laura Jordán-Garrote, Hermann Einsele, Matthias Brock, Katrin G Heinze, Andreas Beilhack
Journal: Blood (2016)
Contralateral risk-reducing (prophylactic) mastectomy (RRM) in patients (pts) with breast cancer (BC): Experience at Mastologica Lomas Breast Center in Mexico City.
Authors: E. R. Sanchez-Forgach, C. Sanchez Basurto, P. Zabalaga
Journal: Journal of Clinical Oncology (2011)

236 Background: Contralateral RRM has increased in frequency due to patient (pt) and/or physician preference. We explore efficacy and satisfaction of procedure at our institution. Methods: A retrospective review of RRM performed from 2002 to 2010. Age, stage, BC subtype, timing of procedure, RRM pathology, reconstruction technique, complications, delay in systemic therapy, satisfaction index, and pt status were compared to pts. who did not undergo RRM. Results: 27 pts with BC had a contralateral RRM. Mean age was 34 (range 24-61). High-risk factors in 11 (40.75%) pts. Histology of BC breasts included 18 (66.66%) invasive ductal, 5 (18.52%) invasive lobular, 4 (14.81) in situ ductal carcinoma, and 1 (3.70%) tubular carcinoma. RRM was a synchronous contralateral procedure in 12 (44.44%) pts. Breast reconstruction technique for RRM: 22 (81.48%) subpectoralis implants, 2 (7.41%) tissue expanders and secondary implants, 1 (3.7%) latissimus dorsi flap with implant. RRM complications: seroma in 8 (29.63%) cases (2 required evacuation of implant), 5 (18.52%) diverse degrees of nipple-areola complex necrosis, total breast necrosis in one pt. These cases were performed earlier in the series, with a decrease in complications in the latter stages of the analysis. Pathology of RRM specimens: one (3.7%) case of ductal in situ BC in a stage IIa pt. and 4 (14.81%) atypical ductal hyperplasia. Surgical time increased a mean of 75 minutes; systemic therapy was delayed in only 2 (7.41%) pts. Recurrence presented in one pt in index breast after stage 0 BC at 13 months (7 mm invasive ductal), in reconstructed breast (3 mm invasive ductal), both treated with a total mastectomy and sentinel node biopsy. All pts are alive. Two have developed systemic metastases (brain, bone). Satisfaction results (medical and pt) were excellent or good in the RRM in 23 (85.19%), regular in 2 (7.41%), and bad in 2. Conclusions: RRM after BC is increasing in frequency, specially in young age pts. Experience at our institution has made it a safe and commonplace procedure, specially in the younger aged pts. with high risk for a contralateral BC. Longer follow-up is needed to determine efficacy.
A phase II study of sunitinib (SU) for maintenance therapy in metastatic castration-resistant prostate cancer (mCRPC) after response to docetaxel (D).
Authors: B. J. Eigl, M. G. Trudeau, E. Winquist, K. N. Chi, M. Eliasziw, S. North
Journal: Journal of Clinical Oncology (2011)

151 Background: After treatment with D based chemotherapy, there is currently no standard therapy although new options are emerging. Due to its mechanism of action, acceptable toxicity profile and simple administration, SU has potential for therapeutic activity in the setting of maintenance therapy for patients with mCRPC who have responded to D based chemotherapy. Methods: Patients with mCRPC who had evidence of responding or stable disease at completion of D treatment were enrolled in this phase II multicentre trial. Patients received 50mg of SU daily on 4 week on/2 week off cycles. The primary endpoint was effect of SU maintenance on PFS. Because of potential effects of SU on PSA kinetics, clinical progression was defined independent of PSA. PSA response rate was a secondary endpoint. PSA-progression (PSA-P) was defined as a 25% PSA increase over baseline. Results: Thirteen patients have been enrolled and treated to date. Mean age was 63 years (47-76). ECOG scores of 0, 1, and 2 were reported for 4, 8 and 1 patients respectively. Mean number of prior cycles of D given was 9.5. A total of 28 cycles of SU were administered. A total of 291 adverse events (AEs) were recorded, of which 66%, 27%, and 7% were classified as Grades 1, 2, and 3, respectively. No Grade 4 AEs were seen. AEs were of a type and severity expected for SU. The most frequent grade 3 AEs were fatigue (n=3) and hand foot syndrome (n=3). No PSA responses have been documented. Most patients had immediate PSA increases without evidence of clinical progression. The mean PSAs increased by 159%, 396%, and 853% in Cycles 1, 2, and 3, respectively, corresponding to p-values of 0.18, 0.03, and 0.01 when compared to the PSA-P threshold of 25%. The trial will continue to complete its planned accrual of 26 evaluable patients and updated results, along with PFS, will be presented at the meeting. Conclusions: SU is well tolerated as maintenance therapy after D in men with mCRPC, with a predictable side-effect profile. PSA values after treatment with SU may not reflect progression in patients with mCRPCas significant increases were observed as early as Cycle 2 without clinical evidence of worsening disease. [Table: see text]
The role of circumferential resection margin in esophageal cancer: Does it influence local recurrence and survival?
Authors: Asad Kutup, Tarik Ghadban, Yogesh Kumar Vashist, Dean Bogoevski, Jakob Robert Izbicki
Journal: Journal of Clinical Oncology (2012)

23 Background: Established independent prognostic factors after resection are tumor stage, tumor grade, nodal involvement, lymph node ratio and tumor infiltration of the proximal or distal resection margin in esophageal cancer. In a few series the clinical and prognostic significance of the CRM involvement have been investigated, showing conflicting results in esophageal cancer. The purpose of this study was to analyze the significance of microscopic tumor involvement of the CRM on long-term survival and local recurrence (LR) following esophagectomy in T3 esophageal cancer. Methods: Between 1993 and 2008, 146 patients, with T3 esophageal tumors had undergone potentially curative transthoracic esophagectomy (TTE) with radical lymphadenectomy of the upper abdomen and mediastinum or transhiatal esophagectomy (THE) with microscopically tumor free proximal and distal resection margins. Surgical specimen were recorded as CRM positive (CRM+) if the distance from the CRM was measured microscopically 1mm or less; otherwise it was graded as CRM negative (CRM-). None of these patients had a neoadjuvant therapy. Results: In the whole study population, median survival for CRM-- and CRM+ patients was 13 and 15 months, respectively (p=.933). LR occurred in 48 patients (32.9%). Of these, 19 (39.6%) had a positive CRM and 29 patients (60.4%) a negative CRM. Of the remaining 98 patients (67.1%) without LR, in 40 patients (40.8%) CRM was positive, while 58 patients (59.2%) had a negative CRM (p=.887). The grading and tumor localization had no significant influence on the LR (p=.181 and .163). The TTE group included 104 patients, in 68 patients (65.4%) of them CRM was negative, in 36 (34.6%) CRM was positive. The THE group included 42 patients, in 19 patients (45.2%) CRM was negative, whereas in 23 patients (54.8%) CRM was positive, respectively (p=.025). CRM involvement had no statistical significant impact on LR or metastatic relapse in either node negative tumors (p=.384) or node positive tumors (p=.653). Conclusions: After TTE a positive CRM was less seen without statistifical influence on median survival time. This study has shown that the presence of microscopic tumor of the CRM is not a significant prognostic variable.
Treatment Free Survival of Patients with MBL and Early CLL: Follow-up of 405 Patients at Mayo Clinic.
Authors: Tait Shanafelt, Neil E. Kay, Kari Rabe, Timothy G. Call, Clive S. Zent, Kami Maddocks, Diane F. Jelinek, Justin Boysen, Deborah Bowen, Susan Schwager, Gregory Jenkins, Susan L. Slager, Curtis A. Hanson
Journal: Blood (2008)
Long Term Follow-up of Hematopoietic Stem Cell Transplantation (HSCT) for Primary Plasma Cell Leukemia (pPCL): Final Results of a Prospective Study of IFM Group
Authors: Bruno Royer, Momar Diouf, Murielle Roussel, Lionel Karlin, Cyrille Hulin, Bertrand Arnulf, Margaret Macro, Sylvie Cailleres, Annie Brion, Sabine Brechignac, Karim Belhadj, Marie Lorraine Chretien, Marc Wetterwald, Carine Chaleteix, Mourad Tiab, Xavier Leleu, Laurent Frenzel, Laurent Garderet, Sylvain Choquet, jean Gabriel Fuzibet, Charles Dauriac, luc-Matthieu Fornecker, Lotfi Benboubker, Thierry Facon, Philippe Moreau, Herve Avet Loiseau, Stephane Minvielle, Jean Pierre Marolleau
Journal: Blood (2016)
Impact of PCA3 on the number of repeat prostate biopsies and sensitivity to detect high-grade cancer in the placebo cohort of the REDUCE study.
Authors: Bertrand Tombal, Gerald L. Andriole, Louis Smets, Herman Stoevelaar
Journal: Journal of Clinical Oncology (2012)

111 Background: 10-35% of men with a negative initial biopsy (Bx) have prostate cancer (PCa) found on repeat Bx (rBx). Fear of missing significant cancer frequently results in, often negative, rBx. As Bx is associated with pain, anxiety and complications, a better individualization of the decision for rBx to reduce the number of rBx and overdiagnosis of indolent PCa is needed. Recently, we used the RAND Appropriateness Method (RAM) to develop a model for rBx patient selection, based on expert recommendations and including the PROGENSA PCA3 Assay (Tombal B, et al. World J Urol 2011;doi:10.1007/s00345-011-0721-0). PCA3 has been shown to predict the probability that a rBx will be positive and may be indicative of PCa significance (Aubin SMJ, et al. J Urol 2010;184:1947-52). In the current analysis, we tested the expert recommendations model on the placebo cohort of the REDUCE study. Methods: The RAM expert recommendations were applied to the placebo cohort of the REDUCE study in which 1073 men with a baseline PSA 2.5-10 ng/mL and a prior negative Bx had a PCA3 test before the planned 2-year and 4-year rBx 2 . For each scenario (with and without PCA3), the number of rBx and the number of missed high-grade (Gleason sum ≥ 7) cancers were assessed. Results: Data from 1024 subjects were available for analysis. In the scenario without PCA3 consideration (reflecting the experts’ recommendations using PSA, DRE, number of previous negative Bx, prostate volume and life expectancy), 267 (26%) of study-mandated rBx were considered inappropriate and the number of missed high-grade cancers was 14. The scenario including also PCA3 consideration led to a reduction of the number of rBx (656 or 64%), while the number of missed high-grade cancers was decreased to 8. The diagnostic accuracy was superior in the model with PCA3: sensitivity for high-grade cancer was 85% vs. 75%, specificity 67% vs. 26%, positive predictive value PPV 13% vs. 5%, NPV 99% vs. 95%. Conclusions: Application of RAM expert recommendations for rBx that include the PCA3 Score can reduce the number of rBx for men with an elevated PSA while maintaining the sensitivity to detect high-grade cancer.
Improvement in the quality of care for patients with locally advanced breast cancer through implementation of an integrated electronic care pathway.
Authors: S. Hogeveen, D. Han, R. L. George, M. Sweet-Goldstein, R. E. Dinniwell, D. Muradali, C. B. Brezden, R. Haq, C. E. Simmons
Journal: Journal of Clinical Oncology (2011)

207 Background: Locally advanced breast cancer (LABC) refers to the most advanced stage of non-metastatic tumours with an incidence of approximately 10% in newly diagnosed breast cancers. Currently, for optimal care, patients with LABC require a multidisciplinary approach including coordinated planning with medical, surgical and radiation oncologists. We created an interactive electronic care pathway and self populating quality assurance database at St. Michael’s Hospital (SMH) to facilitate multidisciplinary teams to track LABC patient histories and patient treatments in order to coordinate therapy effectively and expedite care (LABC E-PATH). Methods: This is an observational before-and-after cohort study of patients with LABC with a retrospective review pre-implementation and prospective collection of clinical data post-implementation. The completeness of workup and the timeliness of treatment pre- and post-implementation of the LABC E-PATH in May 2010 were assessed. Results: With the implementation of the LABC E-PATH in May 2010 at SMH, the delay between the identification of the patient as LABC and their referral to a medical oncologist for treatment for their LABC decreased from a median of 9 days pre-implementation, (range 0-780 days) to 1 day post-implementation, (range 0-52 days). The time between referral to medical oncologist and the start of their chemotherapy treatment decreased from a median of 12 days to 9 days (pre-implementation: range = 4 to 494, post-implementation: range = 0 to 39). All pre-treatment staging was completed faster post-implementation of the LABC e-path than pre-implementation, expediting time to initiation of chemotherapy. The number of referrals for LABC to the SMH program increased from &lt; 1 patient per month to 5 patients per month post-implementation. Conclusions: The LABC E-PATH at SMH has achieved its goal of expediting care for this patient population. It has also ensured timely and appropriate resource allocation. This unique system may also be applied to other disease sites where coordination of a multi-disciplinary team is critical for appropriate patient management.
An 18-year retrospective study on the outcomes of keratoacanthomas with different treatment modalities at a single academic centre
Authors: D.C. Tran, S. Li, S. Henry, D.J. Wood, A.L.S. Chang
Journal: British Journal of Dermatology (2016)

An 18-year retrospective study on the outcomes of keratoacanthomas with different treatment modalities at a single academic centre