tbuckley/cabot-search huggingface dataset:
Abstract P2-02-17: T-DM1 in HER2-negative metastatic breast cancer patients with HER2-amplified circulating tumor cells: Current status of the CirCe T-DM1 phase II trial
Authors: F-C Bidard, G Romieu, W Jacot, P Cottu, V Dieras, F Lerebours, V Servent, E Luporsi, A Lortholary, N Tubiana-Mathieu, M Espie, M Bollet, H Bourgeois, N Renaud, S Pelissier, S Armanet, K Baeten, J-Y Pierga
Journal: Cancer Research (2016)

Abstract Background: Liquid biopsy can reassess key therapeutic targets in metastatic breast cancer. Several studies showed that a low albeit significant rate of metastatic breast cancer initially considered as HER2-negative can be reclassified as HER2-positive by systematic biopsy procedures. We report here the current status of the CirCe T-DM1 trial [NCT01975142] which aims to demonstrate the clinical utility of HER2 status reassessment on circulating tumor cells (CTCs). Methods: The first step of the trial consists in CTC count and HER2/CEP17 FISH on detected CTCs (CellSearch, Janssen Diagnostics) in patients (pts) with measurable disease progressing after the second line of chemotherapy. Pts with amplified CTCs (HER2/CEP17 ratio equal or higher than 2.2) are eligible to the treatment step of the study in two distinct cohorts: low CTC count (1 or 2 HER2-amplified CTCs) and high CTC count (3 and more HER2-amplified CTCs). In the treatment step has a Simon's two stage design, the anti-HER2 antibody-drug conjugate T-DM1 being administered until tumor progression. The primary objective of the trial is the confirmed response rate (RECIST). This trial is supported by Roche. Results: CirCe T-DM1 has been initiated in 10 centers in France. As of June 2015, 105 metastatic breast cancers pts considered as HER2-negative were screened. 29 pts (27%) had no CTC detected, 68 pts (65%) had at least 1 CTC detected with no HER2 amplification, and 8 pts (8%) exhibited HER2-amplified CTCs. Among the 8 pts, 1 pt had 5 HER2-amplified CTC, 2 pts had 2 HER2-amplified CTC and 5 pts had 1 HER2-amplified CTC. HER2/CEP17 ratios among HER2-amplified CTCs ranged from 2.5 to 7. Five of the 8 pts were treated by T-DM1. One objective confirmed partial tumor response has been observed (20%). Conclusion: The accrual is ongoing; the first efficacy assessment will occur after having treated 14 pts. This innovative trial highlights the promise and the complexity of liquid biopsy-based programs in the era of precision medicine: scarcity of the target, reliability and reproducibility of the target assessment, major efficacy when the target is matched to the appropriate drug. Citation Format: Bidard F-C, Romieu G, Jacot W, Cottu P, Dieras V, Lerebours F, Servent V, Luporsi E, Lortholary A, Tubiana-Mathieu N, Espie M, Bollet M, Bourgeois H, Renaud N, Pelissier S, Armanet S, Baeten K, Pierga J-Y. T-DM1 in HER2-negative metastatic breast cancer patients with HER2-amplified circulating tumor cells: Current status of the CirCe T-DM1 phase II trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-02-17.
Abstract P2-05-05: Expression profiling of in vivo DCIS progression models identified BCL9 as a molecular driver of invasive progression
Authors: F Behbod, H Elsarraj, Y Hong, K Valdez, J Chien, A Godwin, T Fields
Journal: Cancer Research (2016)

Abstract Introduction: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. At present, it is not clear why some DCIS remain non-invasive for decades while others become invasive. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of DCIS patients. To identify factors that promote DCIS invasion, we have profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using two in vivo models, MIND (mouse-intraductal) and DCIS/IDC tandem lesions. These studies led to the identification of B cell lymphoma-9 as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However its role in breast cancer progression had not been recognized. Methods: Microarray and RNA sequencing were utilized to characterize the sequential and temporal changes in mRNA expression during DCIS invasive transition. BCL9 shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, EMT and canonical Wnt signaling. Immunofluorescence of 28 patient DCIS samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. TCGA data was analyzed to assess the status of BCL9 gene alterations in 959 human breast cancers. Results: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: ER and PR negative, high nuclear grade, and high HER2. In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of epithelial-mesenchymal transition (EMT). Analysis of the TCGA data showed BCL9 gene to be altered in 26% of breast cancers. This is a significant alteration when compared to ERBB2 (19%) and ESR1 (8%). A significantly higher proportion of basal like invasive breast cancers showed BCL9 amplification. Conclusion: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC. Citation Format: Behbod F, Elsarraj H, Hong Y, Valdez K, Chien J, Godwin A, Fields T. Expression profiling of in vivo DCIS progression models identified BCL9 as a molecular driver of invasive progression. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-05.
MMPI delineation of a subgroup of depressed patients refractory to lithium carbonate therapy
Authors: K M House, R L Martin
Journal: American Journal of Psychiatry (1975)

The authors found that in a sample of 26 severely depressed hospitalized patients, 5 patients with low depression and psychasthenia profiles on the Minnesota Multiphasic Personality Inventory did not show an antidepressant response to lithium carbonate. Seventeen of 21 depressed patients with high depression and psychasthenia profiles did respond to the antidepressant effects of the drug. They tentatively conclue that by using the MMPI it is possible to delineate a subgroup of depressed patients who are refractory to lithium carbonate therapy.
Impaired bortezomib binding to mutant β5 subunit of the proteasome is the underlying basis for bortezomib resistance in leukemia cells
Authors: N E Franke, D Niewerth, Y G Assaraf, J van Meerloo, K Vojtekova, C H van Zantwijk, S Zweegman, E T Chan, C J Kirk, D P Geerke, A D Schimmer, G J L Kaspers, G Jansen, J Cloos
Journal: Leukemia (2011)
Some Factors Influencing the Respiratory Toxicity of Cigarette Smoke&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: T Dalhamn
Journal: JNCI Journal of the National Cancer Institute (1972)

Some Factors Influencing the Respiratory Toxicity of Cigarette Smoke Get access T. Dalhamn, M.D. T. Dalhamn, M.D. Institute of Hygiene, University of Uppsala, Uppsala, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 6, June 1972, Pages 1821–1824, https://doi.org/10.1093/jnci/48.6.1821 Published: 01 June 1972
Prognostic correlates of psychotherapy in psychiatric outpatients
Authors: A K Shapiro, E Struening, E Shapiro, H Barten
Journal: American Journal of Psychiatry (1976)

The authors examined the follow-up data for 113 psychiatric outpatients who had been treated for up to a year in an outpatient community mental health center. Correlations between therapist and patient ratings of improvement were generally low, and anlayses were done separately for therapist and patient ratings. The strongest confirmed hypothesis was the relationship between therapist and patient ratings of improvement and therapist and patient evaluations of each other as likable, physically attractive, and either a good patient for treatment or a competent therapist. The authors discuss the advantages and disadvantages of multivariate statistics for the analysis of psychotherapy data.
Abstract B68: Erythropoietin stimulates ovarian tumor growth via EphB4.
Authors: Sunila Pradeep, Jie Huang, Edna Mora, Sherry Y. Wu, Chun Li, Gabriel Lopez-Berestein, David Jackson, Anil Sood
Journal: Clinical Cancer Research (2016)

Abstract Background: Recombinant human erythropoietin (rhEpo) has been widely used to treat anemia in cancer patients, concerns about its adverse effects on patient survival have emerged. However the lack of correlation between expression of the canonical EpoR and rhEpo's effects on cancer cells prompted us to consider the existence of an alternative Epo receptor. Methods: We analyzed the membrane-bound portion of the proteome for candidate receptors possessing structural, regulatory, and functional features consistent with Epo binding and tumorigenic signaling. To examine the potential for EphB4 binding to Epo, we generated EpoR-/- MEFs from EpoR-/- mice. We injected A2780-shControl and-shEpoR cells, shEphB4 or -shEpoR/shEphB4 cells in nude mice to study rhEpo induced tumor progression. We also assessed potential effects of tumoral EpoR or EphB4 expression on the effects of ESA treatment in patients with ovarian (N = 175) or breast (N = 88) cancer. Results: Through systems-based approaches we identified EphB4 as an alternate Epo receptor. MST experiments with fluorophore labeled rhEpo demonstrated binding to EpoR with an apparent dissociation constant (KD,app) of 28.0 ± 14.0 nM and EphB4 with a KD,app value of 880.6 ± 128.6 nM. EphB4 and EphrinB2 bound with a KD,app value of 140.5 ± 28.3 nM. We showed that [I125]rhEpo can bind to these cells EpoR-/- MEFs cells. EphB4 triggered the downstream signaling via STAT3 and promoted rhEpo-induced tumor growth and progression. rhEpo stimulated in vivo growth of A2780-shControl (p&amp;lt;0.01) and-shEpoR cells (p&amp;lt;0.01), but not -shEphB4 or -shEpoR/shEphB4 cells. In human ovarian and breast cancer samples, expression of EphB4 rather than the canonical EpoR correlated with decreased disease-specific survival in rhEpo-treated patients. Conclusion: In this study, we identified a new mechanism that EphB4 as a critical mediator of erythropoietin signaling, which induced tumor progression in ovarian cancer patients. Altogether our study provides a novel and clinically significant dimension to the biology of erythropoietin, which was not appreciated before. Citation Format: Sunila Pradeep, Jie Huang, Edna Mora, Sherry Y. Wu, Chun Li, Gabriel Lopez-Berestein, David Jackson, Anil Sood. Erythropoietin stimulates ovarian tumor growth via EphB4. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B68.
The Architecture Of Fibrin Clots Formed From Plasma With Low Platelet Levels Are Less Altered In The Presence Of Factor-Specific Anticoagulants Compared With Unfractionated Heparin
Authors: Jorell Gantioqui, Ivan Stevic, Paul Y. Kim, Keith K. Lau, Anthony K.C. Chan, Howard H.W. Chan
Journal: Blood (2013)
Potential Usefulness of 99mTc-DMSA for Radio-Guided Surgery in Pediatric Renal Dysplasia
Authors: Demetrio Familiari, Davide Di Franco, Sebastiano Cacciaguerra, Antonella Ruggeri, Simona Russo, Maria Concetta Fornito
Journal: Clinical Nuclear Medicine (2015)

We report a case of an ectopic/hypoplastic kidney removed by radio-guided surgery. A 7-year-old girl, with a history of vaginal drainage of urine, underwent renal scintigraphy with Tc-DMSA. SPECT/CT revealed a focal uptake in the pelvis, corresponding to hypoplastic kidney as confirmed by MRI. Based on SPECT/CT findings, the patient underwent laparoscopic surgery, using Tc-DMSA scan to help the surgeon to detect the small ectopic kidney. Intraoperatory histological report confirmed the renal origin of the specimen.
Abstract IA32: Optimizing kinase inhibitors to treat cancer
Authors: Gideon Bollag
Journal: Cancer Research (2016)

Abstract Kinase inhibitors have become important therapeutic agents with at least 27 FDA-approved compounds currently available. While this success has brought important benefit to cancer patients, new challenges have been revealed. In particular, resistances to therapy and novel therapy-induced side effects have introduced rationale for optimizing next-generation treatment regimens. Two specific examples will be discussed: RAF and KIT inhibitors for BRAF- and KIT-driven cancers. Oncogenic activation of BRAF fuels cancer growth by constitutively promoting MAPK pathway signaling independent of RAS activation. Efforts to develop agents to block mutated BRAF have brought substantial therapeutic improvement in personalized treatment of metastatic melanoma. Nonetheless, many patients relapse and relapsed tumors generally display MAPK pathway re-activation. The development of these agents also revealed an unexpected consequence of these targeted therapies: stimulated growth of certain cancers. Structurally-diverse ATP-competitive RAF kinase inhibitors can either inhibit or paradoxically activate the MAPK pathway depending whether the pathway is activated by a BRAF mutation or by an upstream event, such as RAS mutation or receptor tyrosine kinase activation. We have identified next generation RAF inhibitors (dubbed “paradox breakers”) that inhibit mutant RAF cells without activating the MAPK pathway in cells containing an upstream activation event. These new inhibitors maintain efficacy in BRAF-driven cell and animal models. In addition, PLX8394 is able to overcome several known mechanisms of resistance to first generation RAF inhibitors. By dissociating MAPK pathway inhibition from pathway activation, the next generation RAF inhibitors may yield both improved safety and more durable efficacy than first generation RAF inhibitors. KIT inhibitors are now standard therapy for advanced gastrointestinal stromal tumors, and indeed comprise 1st, 2nd and 3rd line treatments reflecting both the marked dependence of these tumors on KIT and also the facile development of resistance. Even with multiple compounds approved, resistance mutations - in exon 17 in particular - still limit the durability of clinical benefit. We have discovered PLX9486 as an effective inhibitor of mutant KIT, including exon 17 mutations, with the added feature of selectivity versus the wild-type KIT kinase activity. This compound shows potent activity against exon 17 mutant tumors both in vitro and in vivo. Anticipating the obstacle of polyclonal KIT mutations in standard TKI-resistant patients, clinical development plans include a study combining PLX9486 with PLX3397, a potent KIT inhibitor addressing complementary KIT mutational profiles. Citation Format: Gideon Bollag. Optimizing kinase inhibitors to treat cancer. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA32.
Involvement of Urokinase and its Receptor in the Invasiveness of Human Prostatic Carcinoma Cell Lines
Authors: Naseema M. Hoosein, Douglas D. Boyd, William J. Hollas, Andrew Mazar, Jack Henkin, Leland W. K. Chung
Journal: Cancer Communications (1991)

We have investigated the role of urokinase (UK) and its cell-surface receptor in determining the invasiveness of prostate cancer cells. Three human cell lines, DU-145, PC-3 and LNCaP, that differ in androgen-responsiveness and growth characteristics, were tested. Analysis of the conditioned medium by an enzyme-linked immunosorbent assay showed secretion of UK by DU-145 (63 ng/mL/10(6) cells/48 hr) and PC-3 (682 ng/mL/10(6) cells/48 hr), but absence of secretion by LNCaP cells. Western blot analysis and enzyme activity assay of the conditioned medium confirmed these results. Scatchard analysis of radioligand binding with acid pretreated cells showed the presence of a single population of high affinity UK receptors on DU-145 cells (93,000 sites/cell, Kd = 0.9 nM) and PC-3 cells (25,000 sites/cell, Kd = 1.0 nM) but not on LNCaP cells. DU-145 and PC-3 cells were found to be highly invasive in in vitro invasion assays: 4.5 +/- 0.5% and 6.5 +/- 0.5%, respectively, of total tumor cells (approximately 2 x 10(5)) had penetrated reconstituted basement membrane (Matrigel) in a 72 hr incubation in serum-free growth medium. Under similar conditions, less than 0.25% LNCaP cells invaded Matrigel. The data indicate that androgen unresponsive, aggressive prostate tumor cells of high metastatic potential, DU-145 and PC-3, secrete UK and display cell-surface UK receptors, fully charged with the protease. Conversely, relatively indolent LNCaP cells of low metastatic potential do not secrete UK nor do they possess its binding sites. UK receptor antagonists, UK 12-32 and UK 6-135, which compete with labeled UK for binding to prostatic cells but do not inhibit cellular proliferation or UK secretion, markedly reduced DU-145 and PC-3 cell invasion (80-85% inhibition), thereby suggesting an important role of receptor-bound UK in prostate tumor cell invasion.
Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (<i>MC4R</i>) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study
Authors: Amélie Bonnefond, Ramsi Keller, David Meyre, Fanny Stutzmann, Dorothée Thuillier, Dimitre G. Stefanov, Philippe Froguel, Fritz F. Horber, John G. Kral
Journal: Diabetes Care (2016)

Data on the effects of eating behavior and genetics on outcomes of gastrointestinal surgery for diabesity have been sparse, often flawed, and controversial. We aimed to assess long-term outcomes of bariatric operations in patients characterized for eating behavior and rare mutations in the melanocortin-4 receptor (MC4R) gene, which is strongly implicated in energy balance.Between 1996 and 2005, 1,264 severely obese Swiss patients underwent current laparoscopic adjustable gastric banding, gastroduodenal bypass, or a hybrid operation. Of these, 872 patients were followed for a minimum of 6 years and were screened for MC4R mutations. Using regression models, we studied relationships between eating behavior and MC4R mutations and postoperative weight loss, complications, and reoperations after 6 years.At baseline, rare functional MC4R mutation carriers exhibited a significantly higher prevalence of binge eating disorder (BED) or loss-of-control eating independent of age, sex, and BMI. Six years after bariatric surgery, the mutation carriers had more major complications than wild-type subjects independent of age, baseline BMI, sex, operation type, and weight loss. Furthermore, high baseline BMI, male sex, BED, and functional MC4R mutations were independent predictors of higher reoperation rates.Sequencing of MC4R and eating typology, combined with stratification for sex and baseline BMI, might significantly improve patient allocation to banding or bypass operations for diabesity as well as reduce both complication and reoperation rates.
Anencephalic Newborns
Authors: R D Truog, J C Fletcher
Journal: New England Journal of Medicine (1989)

The science and technology of organ transplantation have seen tremendous growth in recent years, particularly with regard to pediatric patients and smaller organs. Unfortunately, the current need for organs greatly exceeds the supply.1 One innovative approach has involved the use of organs from infants born with the fatal congenital malformation known as anencephaly.Anencephaly results in the "partial or complete absence of the cranial vault as well as absence of overlying tissues and varying degrees of malformation and destruction of the exposed brain rudiments."2 Although anencephalic infants have a slightly higher than normal incidence of anomalies in other organ systems, . . .
Quality of Care — What is It?
Authors: David Blumenthal
Journal: New England Journal of Medicine (1996)

Of the many issues now confronting medical professionals, none seems more perplexing than the debate about the quality of care. Just a few years ago, physicians could be confident that they alone had a social mandate to judge and manage the quality of care. Now, that mandate is contested daily in industrial boardrooms, legislative-hearing rooms, and even medical-consultation rooms. The very language of current discussions about the quality of care leaves many physicians tongue-tied and uncomprehending: observed and expected mortality, outcomes and process measures, SF-36, case-mix and case-severity adjustments, profiles, HEDIS measures, control charts, continuous quality improvement, total quality management, . . .
CC Chemokine Receptors, CCR-1 and CCR-3, Are Potentially Involved in Antigen-Presenting Cell Function of Human Peripheral Blood Monocyte-Derived Dendritic Cells
Authors: Katsuaki Sato, Hiroshi Kawasaki, Hitomi Nagayama, Ryo Serizawa, Junji Ikeda, Chikao Morimoto, Kunio Yasunaga, Noboru Yamaji, Kenji Tadokoro, Takeo Juji, Tsuneo A. Takahashi
Journal: Blood (1999)
Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia: retention of IRF1 on the 5q- chromosome in some patients with the 5q- syndrome
Authors: J Boultwood, C Fidler, S Lewis, A MacCarthy, H Sheridan, S Kelly, D Oscier, VJ Buckle, JS Wainscoat
Journal: Blood (1993)
Public Engagement on Social Distancing in a Pandemic: A Canadian Perspective
Authors: None Joint Centre for Bioethics Pandemic
Journal: The American Journal of Bioethics (2009)

Click to increase image sizeClick to decrease image size Acknowledgment The authors would like to thank the CanPREP and Engaging Voices team for their contributions in collecting and analyzing the data, and send thanks to the participants of our town halls and surveys. The authors would also like to acknowledge the CIHR for their generous support through our SARS grant, Engaging Voices of the Public grant, and CanPREP grant. Ross E.G. Upshur is supported by the Canada Research Chair in Primary Care Research. Contributors to the University of Toronto Joint Centre for Bioethics Pandemic Ethics Working Group Commentary are Jason X. Nie, Sachin S. Sahni, Clara E.S. Sellers, Maxwell J. Smith, A.M. Viens, Ross E.G. Upshur.
The Celestial Fire of Conscience
Authors: Wolffe Nadoolman
Journal: New England Journal of Medicine (2005)

to the editor: With regard to the Perspective article by Charo on conscience clauses, I am disappointed by the treatment of a very serious topic in medicine. The debate over conscience is an important one for both providers and patients. Charo offers distortions of the proposed Wisconsin law, as well as a very biased approach. Even the title frames the discussion in terms of the refusal of care. I urge readers to read the proposed law for themselves.1 In the included legislative analysis, it is plain that the law would leave in place current law that deems it unprofessional to fail to make a good-faith effort to refer a patient. It is also surprising that Charo does not mention the protection in the bill for nurses, medical students, and others in employee relationships who are being fired, harassed, and coerced into actions that they find morally troubling. It seems to me that she would be the “moral busybody” in forcing a medical student or nurse to violate his or her own conscience. That would be the worst “tyranny.” I hope that in the future the Journal will deal with this topic in an honest and balanced manner.