tbuckley/cabot-search huggingface dataset:
TRU-015, a novel CD20-directed biologic therapy, demonstrates significant anti-tumor activity in human tumor xenograft models
Authors: D. Barone, C. Nilsson, J. Ledbetter, M. Hayden-Ledbetter, K. Mohler
Journal: Journal of Clinical Oncology (2005)

2549 Background: Small Modular Immuno-Pharmaceuticals (SMIPs) represent a novel proprietary biologic compound class that retain Fc mediated effector functions and are smaller than monoclonal antibodies. TRU-015, a SMIP that binds to CD20, depletes B cells in vitro and in animal models. TRU-015 has potent ADCC and apoptotic activity in vitro. By design, TRU-015 has attenuated CDC activity. We have evaluated the activity of TRU-015 in established human tumor xenograft models in nude mice. Methods: Nude mice were injected sub cutaneously with either Ramos or Daudi tumor cells. When large palpable tumors (> 200 mm3) were evident, mice (N ≥ 8/group) were treated with TRU-015 or comparator molecules. Groups were evaluated for median survival time (MST), tumor volume and percentage of tumor-free animals. Results: In nude mice bearing Ramos tumors >200mm3, TRU-015 treated mice demonstrated a significant enhancement in their median survival time (MST) in comparison to control mice (MST 44.5 d vs 11 d, p < 0.0001). In a more demanding model (tumor size > 370 mm3), TRU-015 treated mice also demonstrated a significant improvement in their MST in comparison to control mice (64.5 d vs 11 d, p < 0.0001). In nude mice bearing Daudi tumors, TRU-015 treated mice also showed a significant improvement in MST (40.5 d) in comparison to both rituximab (18 d, p<0.02) and control mice (10d, p<0.02). In addition, TRU-015 treated mice had decreased mean tumor volumes and a greater percentage of complete tumor regressions as compared to the other treatment groups in these tumor models. Conclusions: TRU-015 is effective in treating large, established tumors in these human tumor xenograft models. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Trubion Trubion
Interinstitutional variations in robotic prostatectomy pathologic outcomes for a single surgeon and team
Authors: D. S. Berkman, A. Akhavan, A. W. Levinson, S. L. Rusnack, E. Goluboff, D. B. Samadi
Journal: Journal of Clinical Oncology (2008)

16035 Background: The pathology report of a prostatectomy specimen has critical prognostic significance. Given inconsistencies in processing and histological interpretations, the accuracy of pathological reports can vary between institutions. To determine main effect of institution on the review of specimens, we analyzed the robotic-assisted laparoscopic prostatectomy (RALP) outcomes of a single high volume surgeon who operated at two local institutions using the same technique and robotic team. Methods: We reviewed the pathologic outcomes of two IRB approved prospective databases for 400 consecutive RALP procedures performed by a single surgeon at two local institutions within the same 15 month period and compared the pathologic outcomes. Patients with seminal vesical invasion (pT3b), or node positive disease were excluded. Multivariate analysis was used to control for relevant preoperative oncologic risk factors. Results: Between July 2006 and September 2007, 200 RALPs were performed by a single surgeon at each of two separate institutions, for a total of 400 cases. A total of 384 patients met inclusion criteria, 191 from institution 1 (I-1) and 193 from institution 2 (I-2). Preoperative patient characteristics, including PSA, age, prostate size, and median biopsy Gleason, were similar between groups (I-1: 5.81ng/ml, 59.5y, 50.2g, 3+4; I-2: 5.96ng/ml, 58.4y, 52.4g, 3+4, respectively. There was no difference in clinical stages. Postoperatively, the overall positive margin rate for pT2 and pT3 tumors was 14% and 36%, respectively. Median pathologic gleason grade at both institutions was 4+3. However, I-1 was statistically more likely to upgrade Gleason scores than I-2 (p = 0.031). The same institution (I-1) also reported a significantly higher proportion of pT3 tumors (p = 0.01), but fewer pT3 positive margins (p < 0.001). There was no difference between the institutions in rate of pT2 positive margins (16% vs 11%, respectively, p=0.297). Conclusions: Given similar preoperative prostate sizes and PSA values, prostate cancer volumes were likely similar between the cohorts. We present a main effect of institution on pathological outcomes. Institutional differences in pathologic processing may account for some of the differences in rates of surgical margins. No significant financial relationships to disclose.
High-dose cytotoxic therapy and bone marrow transplantation for relapsed Hodgkin's disease.
Authors: R J Jones, S Piantadosi, R B Mann, R F Ambinder, E J Seifter, H M Vriesendorp, M D Abeloff, W H Burns, W S May, S D Rowley
Journal: Journal of Clinical Oncology (1990)

Patients with Hodgkin's disease who have failed two or more chemotherapy regimens or who have relapsed after an initial chemotherapy-induced remission of less than 12 months are seldom cured with conventional salvage therapies. We studied the effect of high-dose cytoreductive therapy followed by bone marrow transplantation in 50 such patients with relapsed Hodgkin's disease. Twenty-one patients with histocompatibility locus antigen (HLA)-matched donors had allogeneic marrow transplants, one patient received marrow from an identical twin, and 28 patients without a matched donor received autologous grafts purged with 4-hydroperoxycyclophosphamide. Busulfan plus cyclophosphamide was the preparative regimen for the 25 patients who had received extensive prior irradiation, and the other 25 patients received cyclophosphamide plus total body irradiation. The overall actuarial probability of event-free survival at 3 years was 30%, with a median follow-up of 26 months. The event-free survival following transplantation was influenced by the number of chemotherapy failures and the patient's response to conventional salvage therapy prior to transplant. The 16 patients who were transplanted at first relapse, while still responsive to standard therapy, had a 64% actuarial probability of event-free survival at 3 years. Age, presence of extranodal disease, preparative regimen, and type of graft (autologous v allogeneic) were not significant prognostic factors. The majority of transplant-related deaths were from interstitial pneumonitis; inadequate pulmonary function, multiple prior chemotherapy regimens, and prior chest irradiation all appeared to increase the transplant-related mortality. These results suggest a role for marrow transplantation in a subset of patients with relapsed Hodgkin's disease who are unlikely to be otherwise cured but are still responsive to conventional-dose cytoreductive therapy.
Rates of psychiatric illness in patients with cancer: An analysis of a psycho-oncology service
Authors: P. Devitt, O. Breathnach, L. Grogan, D. Cotter, S. MacHale
Journal: Journal of Clinical Oncology (2009)

e20731 Background: The diagnosis of cancer represents a major physical and psychological challenge for patients and their families. Psycho-oncology services are limited throughout the country. We assess the service profile of patients assessed between 1/2003 and 6/2008 to determine how the needs of patients have changed. Methods: Case notes from all patients referred by medical oncologists, clinical nurse specialists and/or social workers to the psycho-oncology service were reviewed for the period 7/07 to 6/08. Demographic details, cancer diagnosis and stage, time since diagnosis, psychiatric diagnosis (past/current), and need for psychiatric intervention were collected. This data was compared to a similar review performed from 1/03 to 12/03. Results: 106 patients were psychiatrically assessed during the period 07/08 compared with 63 from 2003, representing a 68% increase in activity. All major cancers were represented. There was a 30% increase in patients assessed with lung cancer (14% in 07/08 vs. 11% in 2003). More patients were referred with localised disease in 07/08 than in 2003 (37.5% vs .19%, p=0.012).Patients with a past history of psychiatric disorder were more likely to be referred in 07/08 compared to 2003 (54% vs. 32% p=0.005). There was a significant decrease in the numbers diagnosed with depression in 07/08 (29% vs. 51%, p= 0.004) with a corresponding increase in the diagnosis of adjustment disorder (26% vs. 6%). Conclusions: Psycho-oncology services remain an important component of care for patients with cancer. The increased rate of referrals may reflect an increased awareness amongst oncology staff of psychological distress in this vulnerable population. No significant financial relationships to disclose.
Optimizing engineered TCR T cell therapy for synovial sarcoma
Authors: Sandra D'Angelo, Melinda Merchant, Luca Melchiori, Hua Zhang, Lini Pandite, Tom Holdich, Gwendolyn Binder-Scholl, William Tap, Marylene Fortin, Yoav Peretz, Matthew Wright, Paul Meyers, Rafael Amado, Bent Jakobsen, Crystal Mackall
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Relapsed or metastatic synovial sarcoma remains a significant unmet medical need. NY-ESO-1 is an attractive target for sarcoma, since it is expressed in approximately 70% of synovial sarcomas but not on vital tissues. We generated NY-ESOc259, a human-derived affinity-enhanced T-
Abstract 17520: Renal Sympathetic Denervation for the Management of Chronic Hypertension (RELIEF): 40 Patient Analysis
Authors: Humera Ahmed, Petr Neuzil, Marcela Schejbalova, Michal Bejr, Stepan Kralovec, Vivek Y Reddy
Journal: Circulation (2012)

Introduction RSDN using a specialized solid-tip RFA catheter has recently been demonstrated to offer safe and sustained systemic blood pressure lowering in patients with refractory hypertension. Fo...
Carcinogenicity of Halogenated Olefinic and Aliphatic Hydrocarbons in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B L Van Duuren, B M Goldschmidt, G Loewengart, A C Smith, S Melchionne, I Seldman, D Roth
Journal: JNCI Journal of the National Cancer Institute (1979)

A series of 15 halogenated hydrocarbons of industrial and environmental importance were tested for carcinogenicity by chronic administration by one or more routes in Ha:ICR Swiss mice. Not all compounds were tested by the four routes of administration used. Allyl chloride, 1,2-dibromo-3-chloropropane, and vinylidene chloride were active as skin tumor initiators in the two-stage carcinogenesis assays; phorbol myristate acetate was used as a promoter. 1,2-Dibromoethane was the only compound that induced a significant incidence (p less than 0.05) of skin papillomas, skin carcinomas, and lung tumors by repeated skin application. 1,2-Dichloroethane, 1,1,2,2-tetrabromoethane, and 1,2-dibromo-3-chloropropane induced lung and/or stomach tumors by repeated skin application. Two compounds showed sarcomagenic activity by sc injection; they were cis-1,3-dichloropropene and 2-chloropropanal. By intragastric intubation, 1-chloropropene and 2-chloropropanal induced significant numbers of stomach tumors. Vehicle, no-treatment, and positive control groups were included in these tests. The following compounds were also tested by one or more of the four routes but were inactive by the criteria used; i.e., they showed P = 0.05 or greater than 0.05: trichloroethylene, tetrachloroethylene, hexachlorobutadiene, chloroacetaldehyde, 1-chloropropene oxide (cis and trans), and trichloroethylene oxide.
Increased Sensitivity of Human Leukemic Granulocytes to Heterophil Antibody in Normal Rabbit Sera&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Robert Bases, Frances Mendez, Joseph Clark, Asher Rosenberg, David Milstein
Journal: JNCI Journal of the National Cancer Institute (1970)

Heterophil antibodies in normal rabbit sera sensitized granulocytes from 6 chronic granulocytic leukemic patients to complement lysis but failed to sensitize the leukocytes from 11 normal donors. Sensitization due to heterophil antibodies in the normal rabbit sera was measured by the detection of leakage of 51Cr from sensitized labeled cells undergoing complement lysis. The difference in sensitivity to normal rabbit sera of normal and leukemic cells was highly significant (P<0.001). Since adsorption of normal rabbit sera by leukemic granulocytes or by normal leukocytes reduced the ability of these sera to sensitize leukemic granulocytes equally well, our results indicate significant differences in the response of the normal and leukemic granulocyte cell membranes to antibody and complement. It is not yet known how these differences are ultimately determined or if they reflect immaturity or the neoplastic origin of leukemic granulocytes.
Understanding how out-of-pocket expenses, treatment value, and patient characteristics influence treatment choices
Authors: Y. Wong, O. Hamilton, B. Egleston, K. Salador, C. Murphy, N. J. Meropol
Journal: Journal of Clinical Oncology (2009)

e20543 Background: Cost-sharing is a method to control “over-use” of healthcare services but may have the unintended consequence of reducing utilization of necessary services among vulnerable patients (pts). It is not known if cost influences pts’ choices of cancer treatments. Methods: A survey was administered to a convenience sample of pts on surveillance for localized cancer. Domains included demographic questions as well as clinical scenarios to elicit the maximum co-payment pts would be willing to pay for hypothetical cancer treatments. Scenario A described adjuvant therapy; questions varied reductions in recurrence rates from 5–20%. Scenario B described palliative therapy; questions varied 2-year survival between 19–34%. Scenario C described palliative therapy; questions varied improvement in median life expectancy from 11–20 months. GEE fit multiple logistic regressions examined pts’ characteristics associated with willingness to pay (WTP). Pts chose from 9 co-payment levels (highest: &gt;$7,000/6 months for Scenario A; &gt;$1,000/3 weeks for Scenarios B-C), which were dichotomized (highest 5 vs lowest 4 levels). Results: 60 pts completed the survey. Demographics: Female (78%); &lt; 65 (83%), Caucasian (97%), college degree (58%). 13% reported making financial sacrifices to pay for treatment. Overall, pts showed a greater WTP for more effective treatments (p&lt;0.05 for all 3 scenarios). In Scenario B, pts who were currently working demonstrated a greater WTP (OR 12.6 95% CI 2.0 -80.4) when controlling for dichotomized efficacy. In Scenario C, pts with a college degree showed greater WTP (OR 5.0, 96% CI 1.2–20.9). In addition, pts who reported having to make previous financial sacrifices for care showed lower WTP (OR 0.2 95%CI 0.04–0.6). Conclusions: Pts may assign a higher value to treatments of greater efficacy. Even among this relatively young, affluent and educated group, demographic variables were associated with WTP. Larger studies in more diverse populations are required to further elucidate how cost may influence pts'treatment choices and contribute to health disparities. These findings may inform health policy by suggesting benefit plans that use cost sharing to optimize use of limited health care resources without compromising access to needed care. [Table: see text]
Role of bronchoscopy in lung cancer translational research: Tumor harvest for the lung cancer mutation consortium (LCMC) studies
Authors: Rex Yung, Marian Rutledge, Peter Illei, Malcolm Brock, Charles Rudin
Journal: European Respiratory Journal (2011)

Introduction:  The LCMC is a multi-institution collaboration to collect 1,000 cases of advanced (stage IIIB/IV) Adenocarcinoma for rapid analysis of multiple genes felt important in LC pathogenesis, to accelerate biomarker validation & discovery, to develop novel therapeutics.   Aim:  To address the need to harvest sufficient tumor from subjects who are often not suitable surgical candidates. To advance bronchoscopic harvest of tumor sufficient for multigene studies.   Method:  68 lung AdenocarCA pts consented (3-10 and 2-11) for sending tumor tissue to Univ Colorado for multiple molecular analysis – FISH analysis for MET gene & ALK protein fusion, gene mutations by SNaPshot testing: APC, AKT1, BRAF,CTNNB1, EGFR, FLT3, JAK2, KIT, KRAS, MAP2K1, NOTCH1, NRAS, PIK3CA, PTEN, TP53. One pathologist (P.I.) review slides for tumor cellularity and adequacy for 20 extra slides.   Results:  2 subjects ineligible (non AC, withdrew), 15 QNS, 33 with tissue successfully sent, 18 awaiting review of slides. Material deemed insufficient - 4 effusion cell block, 2 excised nodes, 9 bronch samples but 3/9 had sufficient tissue for in-house testing KRAS,EGFR,ALK, hence likely exhausted.  Of 33 successful send-out: 17 lung surgery, 5 brain mets, 2 pleural met biopsies, 2 CT core bx. 7/33 (21%) from bronchs: 3 endo & 2 each transbronchial forceps and TBNA.   Conclusion:  Of 16 bronch specimens evaluated for multiplex tumor pathway testing after local site clinical testing, 7 (44%) adequate, 6 (37%) QNS, 3 (19%) likely used up for local biomarker testing. With additional effort at tumor collection at time of diagnosis, large panel testing for tumor biomarkers should be possible in a majority of cases.
Political bias is tenacious
Authors: Peter H. Ditto, Sean P. Wojcik, Eric Evan Chen, Rebecca Hofstein Grady, Megan M. Ringel
Journal: Behavioral and Brain Sciences (2015)

Abstract Duarte et al. are right to worry about political bias in social psychology but they underestimate the ease of correcting it. Both liberals and conservatives show partisan bias that often worsens with cognitive sophistication. More non-liberals in social psychology is unlikely to speed our convergence upon the truth, although it may broaden the questions we ask and the data we collect.
Aromatase inhibitor and tamoxifen's impact on breast cancer recurrence among survivors in a large HMO.
Authors: R. Haque, J. E. Schottinger, A. H. Fisher, J. M. Shi, C. C. Avila, A. Guo, S. Zelt, V. P. Quinn
Journal: Journal of Clinical Oncology (2010)

626 Background: Tamoxifen has been prescribed for the past 25 years, but the extent to which women are prescribed AIs in community settings and as frontline or extended therapy remains unknown. We examined the effectiveness of reducing subsequent breast cancer (BCa) among survivors who were treated with Tam, AIs, or both using data from an HMO that serves 3+ million Southern California residents. Methods: The cohort included 24,066 women (stage 0 to IV) diagnosed from 1996 to 2006, and followed through 12/31/2008 until subsequent BCa occurrence, health care disenrollment, or death. We collected demographic, treatment, and filled prescription data from automated files and the SEER-affiliated cancer registry. Subsequent BCa included lesions that occurred ≥6 months after the original diagnosis or were second primaries. We compared subsequent BCa among four groups: 1) Tam only, 2) AI only, 3) Switchers, and 4) Nonusers of hormone treatment (used for ≤6 months). Adjusted hazard ratios and 95% confidence intervals were estimated using Cox models with time-dependent drug use status. We adjusted for age, year, stage, menopausal status, race/ethnicity, comorbidity, tumor features, medical utilization, bisphosphonate use, and duration of medication use. Results: Nearly 7,000 (29%) women used Tam while 6,092 (25%) used AIs only or were Switchers. Adjusted HRs demonstrate the recurrence reduction was greatest among women who used AIs only or were Switchers versus Nonusers. Women who used tamoxifen also experienced a lower risk. The confidence intervals for all treatment groups overlapped. Conclusions: These preliminary analyses suggest that women who took AIs had a 56% lower risk of recurrence versus Nonusers, while tamoxifen users had a 47% reduction. Our next steps include assessing the effectiveness of these medications in relation to dose, adherence, and timing of the Tam/AI switch. Adjuvant treatment N (24,066) Person- yrs/1,000 Recurrence (N=3,046) Recurrence rate/1000 PY Adjusted HR 95% CI Tam only 6,989 48,035 839 17.47 0.53 0.49- 0.59 AI only 3,004 9,933 236 23.76 0.44 0.38- 0.51 Switchers* 3,092 10,184 147 14.43 0.44 0.37- 0.53 None 10,981 53,186 1,824 34.29 1.00 Ref * Over 90% had switched from Tam to AIs. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
Normal but Not Carcinomatous Primary Rat Mammary Epithelium: Readily Transplanted to and Maintained in the Athymic Nude Mouse&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C W Welsch, D H O'Connor, C F Aylsworth, L G Sheffield
Journal: JNCI Journal of the National Cancer Institute (1987)

Transplantation success rates of primary 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]-induced rat mammary carcinomas and normal rat mammary glandular epithelium into female athymic nude mice were compared. The rat mammary carcinomas obtained from female Sprague-Dawley rats were transplanted into host athymic mice (6–8 wk of age) as 1×1-cm slices xenografted sc (2 slices/mouse) or as enzymatically dissociated cells inoculated into the gland-free mammary fat pad. Normal rat mammary glands (No. 4 glands from 3- to 5-mo-old virgin rats) were transplanted into host athymic mice as whole, intact mammary glands sc (1 gland/mouse) or as enzymatically dissociated cells inoculated into the gland-free mammary fat pad. All (100%) of the normal rat mammary glands were readily accepted and maintained in the athymic mice when transplanted either sc as whole glands or as dispersed cells inoculated into the gland-free fat pad. In contrast, only 13–14% of the DMBA-induced rat mammary carcinomas were accepted and maintained in the athymic mice (transplanted as slices sc or as dispersed cells inoculated into the gland-free fat pad). Treatment of host athymic nude mice with an intense mammotropic hormonal stimulus (prolactin and/or ovarian steroids) markedly enhanced the developmental growth of the transplanted normal rat mammae (subcutaneous slices and fat-pad inoculates); such a hormonal stimulus did not influence the transplantation success rate of the DMBA-induced rat mammary carcinomas. Thus female athymic nude mice can readily accept and maintain transplants of normal rat mammae but not carcinogen-induced carcinomatous rat mammae; the meager acceptance rate of the carcinomatous rat mammae by the athymic nude mouse was not enhanced by providing the host mice with a potent mammotropic hormonal growth stimulant.