tbuckley/cabot-search huggingface dataset:
Abstract 19803: TMEM88: A Novel Regulator of Cardiac Development Identified Through Chromatin Dynamics
Authors: Nathan Palpant, Cristi Stoick-Cooper, Lil Pabon, Randall Moon, Charles Murry
Journal: Circulation (2012)

Cardiac development is dependent on the biphasic activities of Wnt/β-catenin signaling where it is required for mesoderm development but must be blocked to specify the cardiogenic mesoderm. The mechanism mediating this inhibition of Wnt/β-catenin signaling in cardiac progenitor cells is not known. Methods and Results. RNA seq was used to analyze genes most highly induced in the cardiac progenitor cell during cardiac differentiation of human ES cells. Transmembrane protein 88 (TMEM88) was identified for further study. In line with previous work showing TMEM88 binds Disheveled by a C-terminal PDZ binding motif, we used transgenic hES cells to show that TMEM88 blocks Wnt/β-catenin signaling during cardiac differentiation. Chromatin dynamics showed marked suppression (H3K27me3) of this locus in the transition through mesoderm with a switch to an activated state (H3K4me3) in the cardiac progenitor; a signature resembling other genes involved in mediating cell fate changes such as transcription factors. By qPCR, TMEM88 is highly up-regulated prior to Nkx2.5 and Isl1 expression. In situ hybridization of developing zebrafish embryos showed expression of TMEM88 specifically in the cardiogenic ventro-lateral mesoderm overlapping the expression profile of cardiac transcription factors such as Nkx2.5 and MEF2c. Short hairpin RNA targeting the TMEM88 transcript was used to determine its requirement for cardiac differentiation of hES cells. Suppression of TMEM88 resulted in a failure to specify the cardiac lineage based on significantly reduced Nkx2.5, Tbx5, and cTnT expression. Linear regression analysis revealed a dose dependent effect of increased TMEM88 significantly correlating with higher cTnT expression. In vivo, morpholino knockdown of TMEM88 in zebrafish markedly alters heart development with some embryos failing to generate a heart. Phylogenetic analysis of TMEM88 orthologs identifies the expression of this gene only in vertebrate chordates. Conclusion. These data show that TMEM88 is required for cardiac development in vitro and in vivo acting mechanistically in a cell autonomous manner to inhibit Wnt/β-catenin signaling during the specification of the cardiac lineage in progenitor cells of the primordial heart.
Phase II study of sunitinib in patients (pts) with relapsed or refractory urothelial carcinoma (UC)
Authors: D. J. Gallagher, M. I. Milowsky, S. R. Gerst, A. Iasonos, J. Riches, M. G. Boyle, D. F. Bajorin
Journal: Journal of Clinical Oncology (2007)

5080 Background: Second-line chemotherapy has limited activity in advanced UC. Pre-clinical evidence demonstrates an important role for angiogenesis in UC biology, thus supporting this study of the novel VEGF targeted agent, sunitinib, in pts with UC. Methods: The primary objectives of this single institution phase II trial of sunitinib in pts with UC who have failed prior chemotherapy are: 1) to determine the response rate (RECIST); and 2) to evaluate toxicity. Prior therapy is restricted to = 4 chemotherapy drugs. Pts receive sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks off (one cycle). Response is assessed after each of the initial 4 cycles and every other cycle thereafter. The Simon 2-stage design requires = 2 responses in the first 21 pts to proceed to maximal accrual of 41 evaluable pts. Results: 21 pts (19 male, 2 female) with median age of 64 yrs (39–76) and median KPS of 80 (70–90) were enrolled between 9/15/06 and 1/4/07. Primary tumor sites include bladder (14 pts), ureter/renal pelvis (6 pts) and urethra (1). Prior therapy included 10 pts with 2 drugs, 9 with 3 and 2 with 4. 14 pts have metastatic visceral disease [lung (11), liver (8) and bone (1)], and 7 pts have only lymph node metastases. To date, 15 pts are evaluable for radiographic response after completing at least one cycle of therapy; 6 pts are too early for response assessment. One pt experienced a treatment-related death. Responses include: 1 PR seen after cycle 1 and confirmed after cycle 2, 8 with SD (range -29% to +16% change compared to baseline) and 6 with POD. Radiographic regression has been observed in liver, lung, soft tissue and lymph node metastases. Clinically significant toxicity (Grade 3/4) includes: hematuria (n= 1 pt, 2 events in a bladder primary), mucositis (2 pts), thrombocytopenia (2 pts), infection (1), stomatitis (1), fatigue (1), rash (1), diarrhea (1), and abdominal pain (1). Conclusions: Sunitinib has clinical activity in pts with advanced UC. Accrual is ongoing to define further the level of activity, the duration of response, and the time to progression. [Table: see text]
Phase I evaluation of paclitaxel poliglumex (PPX) administered weekly for patients with advanced cancer
Authors: C. H. Takimoto, G. Schwartz, O. Romero, A. Patnaik, A. Tolcher, M. Garrison, F. B. Oldham, A. Bernareggi, E. Rowinsky
Journal: Journal of Clinical Oncology (2005)

2043 Background: Weekly paclitaxel administration compared to Q3 week schedules may offer an efficacy benefit in patients with metastatic breast cancer (Proc ASCO; 2004, Abstract 512), although the benefit in NSCLC is less clear (Cancer, 97:2480, 2003; JCO 15:1, 1997). Paclitaxel poliglumex (XYOTAX) is a macromolecular drug conjugate that links paclitaxel with a biodegradable polymer, poly-L-glutamic acid. PPX is water soluble and can be administered as a 10 minute infusion. Eliminating the need for CremophorEL reduces the risk of hypersensitivity reactions, even without premedication. This study is designed to determine the MTD of PPX when administered weekly to patients (pts) with solid tumors. Methods: Escalating doses of weekly PPX are administered to pts who have received no extensive myelosuppressive regimens (defined as < 2 alkylator containing regimens) and have < grade 1 neuropathy. Each cycle consists of 6 weekly treatments with extended pharmacokinetic (PK) samples for PPX and free paclitaxel being obtained after the first and sixth dose. Toxicity and response are assessed according to NCI CTC (v2) and RECIST, respectively. Plasma samples for evaluation of the pharmacokinetics (PK) of PPX were obtained in cycle 1 and before and after the 6th dose. Results: To date, 18 pts have been treated at 20 mg/m2 (5 pts), 40 mg/m2 (4 pts), 60 mg/m2 (4 pts), and 80 mg/m2 (5 pts). Data are available for 11 pts in the 20, 40, and 60 mg/m2 dose groups. Pts were 58% female. All but 1 pt had performance status 0 or 1. PPX has been well tolerated. No pts have discontinued treatment due to adverse events. Two dose limiting toxicities (grade 3 neutropenia) occurred in the 80 mg/m2 cohort during cycle 1; however, no drug-related grade 4 toxicities have been reported. No objective responses have been seen; although 1 pt in the 20 mg/m2 cohort had stable disease for 5 months. Conclusions: PPX at doses up to 60 mg/m2 weekly shows manageable toxicity. Preliminary PK data for 9 pts in the 20 and 40 mg/m2 cohorts suggest that no significant accumulation of conjugated taxanes or unconjugated paclitaxel occurs with this dosing schedule. Enrollment continues at 70 mg/m2. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics Cell Therapeutics Cell Therapeutics
A study of 100 physician psychiatric inpatients
Authors: R E Jones
Journal: American Journal of Psychiatry (1977)

The author reviewed the case records of 100 physician inpatients in a private psychiatric hospital. He found that these physicians were more likely to have diagnoses of affective disorder and drug abuse than the general psychiatric hospital population, that their peak susceptibility occurred in their late 40s, that general practitioners and psychiatrists were overrepresented, and that female physicians were almost four times more vulnerable to suicide than male physicians. He describes some critical aspects of engaging the disabled physician in psychiatric hospitalization.
Abstract 19004: Sr-bi Deficiency is Associated with Dendritic Cell Retention in Arterial Atherosclerotic Plagues and Impaired Atherosclerotic Regression in Apoe-r61 Hypomorphic Mice
Authors: Yi Zhang, Bernardo L Trigatti
Journal: Circulation (2012)

A deficiency in SR-BI, a major HDL receptor, results in accelerated arterial plaque development in ApoE-R61 hypomorphic mice, however the effect of a lack of SR-BI on atherosclerotic plaque regression is unknown. In SR-BI-knockout/ApoE hypomorphic (KO-H ) mice fed a high fat diet, aortic atherosclerosis developed much faster than in the SR-BI+/+ ApoE hypomorphic (control) mice. When these mice were switched from the atherogenic diet back to a normal diet, atherosclerotic plaques regressed over the course of 11 weeks in the control mice, but not in KO-H mice, in which the plaques continued to develop. Dendritic cells (DC's) have been found to be involved in atherosclerosis development and regression. Immunohistofluorescence analysis revealed a large number of CD11c-positive DC’s which persisted within atherosclerotic lesions of KO-H mice, even 11 weeks after the diet switching. These CD11c-positive cells exhibited apparently attenuated expression of CCR7, a major chemoattractant receptor in DCs. To determine if SR-BI in macrophages or DC’s themselves might be required for plaque regression, bone marrow (BM) was transplanted from either KO-H or control donors into irradiated ApoE-hypomorphic recipients. Plaque regression was decreased in the mice transplanted with BM from KO-H donors, confirming a role for SR-BI in BM-derived cells in plaque regression. In cultured human DC's derived from THP-1 cells, HDL dose-dependently stimulated migration. HDL-stimulated migration of DC's was abolished by a SR-BI blocking antibody, PI 3-kinase inhibitors or using BM-derived DC's from SR-BI or PDZK1 KO mice, suggesting the involvement of an HDL-triggered PI3K signaling pathway emanating from SR-BI and its cytosolic adaptor protein PDZK1. Cholesterol loading of DCs impaired migration in response to HDL or CCL19, a ligand for CCR7; this was reversed by overnight incubation with HDL. Furthermore, incubation with HDL for 24 h induced a remarkable increase in expression of CCR7 and SR-BI in DC's. Taken together, the results suggest that SR-BI may mediate the migration of DC's facilitated by HDL, and is required for atherosclerotic plaque regression.
Changing trends of dowenstaging, sphincter preservation, and complete pathologic response over 8 years in locally advanced rectal cancer patients.
Authors: H. A. El Taani, S. A. Hashem, A. F. Al-Rashdan, A. Badheeb, A. Nour, W. Shelpai, H. Haddad, B. Morcos, S. Y. Abbasi
Journal: Journal of Clinical Oncology (2010)

e14133 Background: Based on the reported results of neoadjvant chemoradition (CT/RT), our institution adopted this regimen as the standard of care for patients (pts) with locally advanced rectal cancer. We have previously reported our 4 year experience (Ann Oncol 2008) in 34 pts. The results were comparable to those reported in the literature. Nevertheless, the continuity of maintaining similar rates and improved outcome after a longer period of time was still questionable. Methods: Retrospective chart review of 109 pts with histologically confirmed rectal cancer, who had been diagnosed with locally advanced disease and treated with the Neoadjuvant CT/RT regimen from January 2002 to July 2009, at KHCC. Results: A total of 109 pts were eligible. Median age was 53 years. Male to female ratio was 1.8:1. in 98% of cases the histology was adenocarcinoma and in 54% the tumors was located ≤ 5 cm from the anal verge. Following CT/RT, 34 pts (45%) were downstaged, and 81 pts (75%) had sphincter preserving surgery, only 7% achieved complete pathological response (CpR). The rate of R0 surgery was 80%. At the date of evaluation (July 2009) 93 pts (85%) were alive, 10% had disease progression after a median time of 10.4 months (range from 1-58 months), and 16.5% had metastatsis after a median time of 16.4 moths (range from 6-59 months). The most common sites for metastasis were the lungs 31%, liver 26% and bone 21%. In comparison with our previously reported 4 year experience, the rate of downstaging was slightly decreased from 59% to 45%, while sphincter preservation increased from 66% to 75%, but what was surprisingly disappointing is that the CpR rate was notably worse, it decreased from 26% to 7%. Conclusions: We demonstrated here that downstaging and sphincter preservation rates after 8 years continued to be comparable with those reported in the literature. The decline in the CpR rates is misleading and deceptive, since the number of pts in our previous report was not powered enough to reflect the true incidents; therefore, the current rate of the CpR may represent the actual one. No significant financial relationships to disclose.
Postsurgical drainage and the risk of breast cancer recurrence in Chinese breast cancer patients
Authors: Y. Lin, W. Yin, L. Zhou, T. Yan, J. Lu, G. Di, J. Wu, K. Shen, Z. Shao
Journal: Journal of Clinical Oncology (2009)

e22234 Background: Clinical investigations suggest that while primary breast cancer surgical removal favorably modifiers the natural history of breast cancer. Postoperative drainage, a surgery-derived discharge after breast cancer surgery, reflecting some biological features of surgical stimulation, was assessed and explored its relationship with breast cancer recurrence in this study. Methods: A total of 1445 women undergoing surgery between Jan 1, 2000 and Dec31, 2002 in Cancer Hospital of Fudan University, Shanghai, China was retrospectively studied. Survival curves were performed with Kaplan-Meier method and the predictive value of postsurgical drainage was estimated using proportional Cox regression model. Conclusions: The larger drainage volume POD 1 is a useful marker, suggesting a greater stimulation to surgical treatment compared to the lower ones. Awareness of the relationship between early surgery-stimulated effects and harmful wound healing response might help to explore new strategies to block or deplete these harmful effects, resulting in improving patients' survival. No significant financial relationships to disclose.
The prognostic value of FDG-PET measured by standardized uptake value in patients with melanoma stage III evaluated in a prospective study
Authors: E. Bastiaannet, J. R. De Jong, A. H. Brouwers, A. J. Suurmeijer, H. J. Hoekstra
Journal: Journal of Clinical Oncology (2009)

e20000 Background: FDG-PET is a sensitive modality to detect melanoma metastases; melanomas are typically FDG-avid and melanoma shows an unpredictable pattern of spread. Furthermore, FDG-PET is able to quantify FDG uptake and the amount of FDG uptake, measured by the standardized uptake value (SUV), might be important for the prediction of disease specific survival (DSS) or disease free survival (DFS). Therefore, aim of this study was to perform a prospective analysis to determine whether SUV is of prognostic value in the DFS and DSS of melanoma patients with palpable lymph node metastases. Methods: From July 2002 until December 2007, all consecutive patients with palpable, histology or cytology proven lymph node metastases of melanoma referred to the University Medical Centre Groningen for examination with FDG-PET were prospectively included. The SUVmean (70% isocontour) and SUVmax in the lymph node metastasis were calculated for patients who showed no distant metastases on chest X-Ray, FDG-PET and CT. Univariate and multivariate survival analysis was performed to determine whether SUV was associated with DFS and DSS (Cox Proportional Hazard analysis). Results: Overall, 70 patients were eligible. High SUV values were present in axillary metastases (p=0.118), in patients who had more than 15 nodes removed (p=0.061) and in patients with a large tumor size in the lymph node (p=0.0001). Patients with a low SUVmean had a 3-years DFS of 54.3% as compared to 28.1% for patients with a high SUVmean (HR 2.02;p=0.051). In multivariate analysis SUVmean seems to be associated with DFS (p=0.063). DSS for patients with a high SUV was decreased, however not statistically significant (HR 1.71; p=0.182). Conclusions: The SUV in the lymph node metastasis seems to be associated with disease-free survival for melanoma patients clinically stage III. No significant financial relationships to disclose.
P0084 : Oxidative stress reduction by nanoparticles of cerium oxide (CeO2NPS) partially reverts the activation of portal endothelial cells from cirrhotic rats
Authors: J. Rodríguez Vita, J. Ribera, G. Casals, D. Oró, S. Marfà, B. Morales, T. Yudina, V. Puntes, W Jiménez, M. Morales-Ruiz
Journal: Journal of Hepatology (2015)
Effect of Vincristine on the Fine Structure of HeLa Cells During Mitosis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: George, Phillip, Journey, L. J., Goldstein, Milton N.
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Effect of Vincristine on the Fine Structure of HeLa Cells During Mitosis Get access Phillip George, Phillip George Cell Biology Laboratory, St. Jude Hospital, and Departments of Pediatrics and Anatomy, University of Tennessee Medical Units, Memphis, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar L. J. Journey, L. J. Journey Cell Biology Laboratory, St. Jude Hospital, and Departments of Pediatrics and Anatomy, University of Tennessee Medical Units, Memphis, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar Milton N. Goldstein Milton N. Goldstein Cell Biology Laboratory, St. Jude Hospital, and Departments of Pediatrics and Anatomy, University of Tennessee Medical Units, Memphis, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 35, Issue 2, August 1965, Pages 355–375, https://doi.org/10.1093/jnci/35.2.355 Published: 01 August 1965 Article history Received: 24 November 1964 Published: 01 August 1965
Mature Survival (Os) Data of a Randomised International Phase Ii Trial (Jasint1): Vinflunine (Vfl)-Gemcitabine (Gem) Vs. Vfl-Cbdca in Cddp-Unfit Patients (Pts) with Advanced Urothelial Carcinoma (Uc)
Authors: M. De Santis, P.J. Wiechno, C. Lucas, C. Lin, W. Su, J. Bellmunt, K. Legrand, R. Fougeray, S. Culine
Journal: Annals of Oncology (2014)
Effect of Regional Hospital Competition and Hospital Financial Status on the Use of Robotic-Assisted Surgery
Authors: Jason D. Wright, Ana I. Tergas, June Y. Hou, William M. Burke, Ling Chen, Jim C. Hu, Alfred I. Neugut, Cande V. Ananth, Dawn L. Hershman
Journal: JAMA Surgery (2016)

Despite the lack of efficacy data, robotic-assisted surgery has diffused rapidly into practice. Marketing to physicians, hospitals, and patients has been widespread, but how this marketing has contributed to the diffusion of the technology remains unknown.To examine the effect of regional hospital competition and hospital financial status on the use of robotic-assisted surgery for 5 commonly performed procedures.A cohort study of 221 637 patients who underwent radical prostatectomy, total nephrectomy, partial nephrectomy, hysterectomy, or oophorectomy at 1370 hospitals in the United States from January 1, 2010, to December 31, 2011, was conducted. The association between hospital competition, hospital financial status, and performance of robotic-assisted surgery was examined.The association between hospital competition was measured with the Herfindahl-Hirschman Index (HHI), hospital financial status was estimated as operating margin, and performance of robotic-assisted surgery was examined using multivariate mixed-effects regression models.We identified 221 637 patients who underwent one of the procedures of interest. The cohort included 30 345 patients who underwent radical prostatectomy; 20 802, total nephrectomy; 8060, partial nephrectomy; 134 985, hysterectomy; and 27 445, oophorectomy. Robotic-assisted operations were performed for 20 500 (67.6%) radical prostatectomies, 1405 (6.8%) total nephrectomies, 2759 (34.2%) partial nephrectomies, 14 047 (10.4%) hysterectomies, and 1782 (6.5%) oophorectomies. Use of robotic-assisted surgery increased for each procedure from January 2010 through December 2011. For all 5 operations, increased market competition (as measured by the HHI) was associated with increased use of robotic-assisted surgery. For prostatectomy, the risk ratios (95% CIs) for undergoing a robotic-assisted procedure were 2.20 (1.50-3.24) at hospitals in moderately competitive markets and 2.64 (1.84-3.78) for highly competitive markets compared with noncompetitive markets. For hysterectomy, patients at hospitals in moderately (3.75 [2.26-6.25]) and highly (5.30; [3.27-8.57]) competitive markets were more likely to undergo a robotic-assisted surgery. Increased hospital profitability was associated with use of robotic-assisted surgery only for partial nephrectomy in facilities with medium-high (1.67 [1.13-2.48]) and high (1.50 [0.98-2.29]) operating margins. With analysis limited to patients treated at a hospital that had performed robotic-assisted surgery, there was no longer an association between competition and use of robotic-assisted surgery.Patients undergoing surgery in a hospital in a competitive regional market were more likely to undergo a robotic-assisted procedure. These data imply that regional competition may influence a hospital's decision to acquire a surgical robot.
Factors in Association Between Parkinson Disease and Risk of Cancer in Taiwan—Reply
Authors: Pei-Ying Lin, Ching-Heng Lin, Pan-Chyr Yang
Journal: JAMA Oncology (2016)

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