tbuckley/cabot-search huggingface dataset:
Abstract #3776: Development of a tumor-endothelium coculture model for pharmacodynamic study of chemotherapeutic agent
Authors: Ahmed Al-Abd, Namho Kim, Kwang-Suck Kim, Hye-Mi Lee, Soo-Yeon Kim, Hyo-Jeong Kuh
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Solid tumors often develop an angiogenic phenotype that promotes the establishment of an expanding vascular network for delivery of oxygen and other nutrients. The tumor vasculature is an established target for the therapy of solid tumor. Agents designed to prevent new vessel formation as antiangiogenic agent, or to damage existing vessels, as vascular disrupting agent(VDA), have been developed and have shown efficacy in preclinical model, and in clinical studies. For pharmacodynamic study of vascular inhibitor and dual action-chemotherapeutic agent in vitro culture model, recapitulating interaction between tumor cell and endothelial cell, is better in terms of clinical relevancy. In this study, we developed a tumor-endothelium coculture model using human colorectal, cervix and head & neck cancer cells (HT-29, DLD-1, SiHa, HeLa and PCI-1) and HUVECs. HUVECs were cultured for 1day to confirm tube formation and stained with a cell tracker(CMFDA) before coculturing with tumor cells for 1 day. Cells were stained with PI after drug treatment and viability was accessed by dual-fluorescence microscopy and image analysis. Three dimensional cocultures were well established with DLD-1 and HT-29 cells with preserved tube formation of HUVECs. SiHa and HeLa cells were incompatible with HUVECs, resulting in cell death of HUVECs. PCI-1 cells did not suppress the growth of HUVECs, however, tube formation was not sustained. We also evaluated the pharmacodynamics of chemotherapeutic agents including paclitaxel, CPT-11 and arsenic compounds. Paclitaxel and CTP-11 showed inhibition on only tumor cells but arsenic compounds affected on both cell types. The dual action of arsenic compound showed 10 fold different level of cytotoxicity between tube formation of HUVECs and growth of tumor cells (0.1\#956;M vs 1\#956;M). The IC50 of arsenic compounds in the HUVECs increased 35 fold under co-culture condition and when cultured in condition media of HT-29 increased.These results indicate that HUVECs can be cocultured into 3-dimention structure with specific solid tumor cell lines. This in vitro coculture model, of endothelial cells and tumor cells, can be successfully used for investigation of pharmacodynamic study of vascular targeting and dual-action chemotherapeutic agents.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3776.
38 GALECTIN-3 REGULATES HEPATIC PROGENITOR CELL EXPANSION DURING LIVER INJURY
Authors: A.C. Mackinnon, W.-C. Hsieh, L. Boulter, D. Wojtacha, W.-Y. Lu, T.G. Bird, D. Hay, J. Jung, T. Sethi, J.P. Iredale, S.J. Forbes
Journal: Journal of Hepatology (2013)
Pharmacodynamic assessment of the anti-angiogenic and anti-vascular properties of bevacizumab by magnetic resonance imaging in metastatic colorectal carcinoma (CRC)
Authors: A. R. Clamp, J. P. O'Connor, C. L. Mitchell, G. J. Parker, A. Jackson, L. Hope, P. Thornton, Y. Watson, O. del Puerto, G. C. Jayson
Journal: Journal of Clinical Oncology (2008)

3546 Background: Addition of bevacizumab to FOLFOX-4 prolongs progression free and overall survival in patients with metastatic CRC. Bevacizumab reduces tumor blood flow, so may impair delivery of subsequent cytotoxic chemotherapy. We present the first data that describe in detail the temporal anti-angiogenic and anti-vascular effects of bevacizumab. Methods: DCE-MRI and volumetrics were used to evaluate tumor pharmacodynamics and growth inhibition in ten patients with newly diagnosed CRC liver metastases. Patients were imaged at baseline (twice), 4 hours after single agent 10mg/kg bevacizumab, and at days 3, 8, and 12. An extended Tofts model was applied to allow calculation of plasma volume (vp) and Ktrans. Results: 34 tumors were identified. Significant reductions in Ktrans and vp were detected within 4 hours, were maximal at day 3 and persisted until day 8 (all p<0.001). The proportion of enhancing voxels was also reduced within 4 hrs (p=0.007) and persisted to day 12 (p<0.001). Mean tumor volume exhibited gradual reduction that reached significance by day 12 (p<0.001), when 12/34 tumors exhibited >25% volume reduction (beyond 95% CI for volume reproducibility). Conclusions: These data provide evidence that administration of anti- VEGF antibody causes rapid reduction in blood flow and vascular shutdown. This implies that cytotoxic chemotherapy may be most effective if given before bevacizumab, rather than sequentially. In addition, we provide evidence that volumetric MRI is sensitive at detecting individual and group change in tumor size following one cycle of VEGF inhibition. This study indicates that ‘vascular normalization’ is not relevant in this clinical setting and has critical implications for the scheduling of chemotherapy with bevacizumab and for the development of new anti-angiogenic agents. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Products Ltd Roche Products Ltd
RTOG 0417: A phase II study of bevacizumab in combination with definitive radiotherapy and cisplatin chemotherapy in untreated patients with locally advanced cervical carcinoma.
Authors: T. E. Schefter, J. Moughan, J. S. Kwon, K. Stuhr, M. Rotman, B. P. Yaremko, W. Small, D. K. Gaffney
Journal: Journal of Clinical Oncology (2010)

5006 Background: Concurrent cisplatin-based chemoradiotherapy is the standard treatment for locally advanced cervical cancer. RTOG 0417 was a phase II studying exploring the safety and efficacy of the addition of bevacizumab to chemoradiotherapy. Methods: Eligible patients with bulky IB-IIIB disease were treated with once-weekly cisplatin (40 mg/m2) chemotherapy and standard pelvic radiotherapy and brachytherapy. Bevacizumab was administered at 10 mg/kg IV Q2 weeks for 3 cycles during chemoradiation. Treatment-related serious and other adverse event (SAE/AE) rates within the first 90 days from treatment start were determined. Treatment- related SAEs were defined as any grade ≥ 4 vaginal bleeding or thrombotic event or grade ≥ 3 arterial event, GI bleeding or bowel/bladder perforation or any grade 5 treatment-related death. Treatment-related AEs included all SAEs and grade 3 or 4 GI toxicity persistent for > 2 weeks despite medical intervention, grade 4 neutropenia or leucopenia persisting for > 7 days, febrile neutropenia, grade 3 or 4 other hematologic toxicity and grade 3 or 4 GI, renal, cardiac, pulmonary, hepatic or neurologic AEs. All adverse events were scored using the CTCAE v 3.0 criteria (MedDRA version 6.0). Results: 60 patients from 25 institutions were enrolled between 2006 and 2009 and 49 patients were evaluable (10 ineligible and 1 received no protocol treatment). The median follow-up was 10 months (min-max: 3.4-31.4 months). The median age was 45 (min-max: 22-80). Most patients were FIGO IIB (63%) and had Zubrod performance status of 0 (67%). 80% were squamous. There were no treatment-related SAEs. There were 15 (31%) protocol specified treatment-related AEs, most common were hematologic (12/15 = 80%). Conclusions: Bevacizumab in addition to standard pelvic chemoradiotherapy for locally advanced cervical cancer is feasible and safe with respect to the protocol-specified SAEs and AEs. This project was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the NCI. This publication's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
First-in-human phase I trial of a cyclodextrin-containing polymer-camptothecin nanoparticle in patients with solid tumors
Authors: Y. Yen, T. Synold, T. Schluep, J. Hwang, J. Oliver, M. E. Davis
Journal: Journal of Clinical Oncology (2007)

14078 Background: IT-101 is a de novo designed experimental therapeutic comprised of linear, cyclodextrin(CD)-containing polymer conjugates of camptothecin(CPT) that assemble into ca. 40 nm diameter nanoparticles via polymer-polymer interactions that involve inclusion complex formation between the CPT and the CD. Particle size, near neutral surface charge and CPT release rate were specifically designed into IT-101. Published pre-clinical animal studies show extended circulation times (t 1/2 of ca. 20 h in rodents), tumor accumulation, slow release of the CPT and anti-tumor efficacy that directly correlate to the properties of the nanoparticle. Release of CPT can disassemble the nanoparticle into individual polymer chains that have size ca. 10 nm that are capable of renal clearance (t 1/2 of several minutes in rodents). Methods: Patients with relapsed or refractory cancer were evaluated every two cycles of therapy (90 minute IV infusions of IT- 101 in D5W on days 1, 8 and 15 of a 28 day cycle). Three dose levels of 6, 12 and 18 mg CPT eq./m 2 have been tested. Results: At the time of this interim analysis, eight patients have been enrolled and five evaluated. In general, IT-101 is well tolerated and pancytopenia is the DLT. The expected MTD is 12 mg/ m 2 .Three out of five patients demonstrated stable disease on CT scan evaluation. One pancreatic cancer patient remains stable for 6 months. PK data are available from the first 5 patients. Total and free CPT display biphasic elimination from plasma with mean terminal elimination half lives of 38±3.7 and 61±43 hours, respectively. The mean Vd and CLsys of total CPT are 6.1±1.4 L and 0.1±0.03 L/h and are unrelated to dose over the range tested, with a mean total-to-free AUC ratio of 10.7±3.7. Conclusions: These first in human PK data for IT-101 confirm that 40 nm particles with near neutral surface charge provide favorable PK properties. The stable disease rate, although not yet conclusive, is consistent with promising efficacy. The preliminary results of this phase I study warrant continued enrollment that is ongoing. No significant financial relationships to disclose.
Is utility of D-Dimer test undermined because of overuse in routine clinical practise?
Authors: Gautam Marwah, Helen Taylor, Selva Selvaraj, Stephen Murphy
Journal: European Respiratory Journal (2011)

Introduction: In suspected VTE a low pre-test probability and negative D-Dimer is associated with risk of VTE < 2%. However d-dimer is raised in many conditions and utility depends on VTE prevalence in population tested (9.5-19% in validation studies). Purpose of study was to assess utility of d-dimer testing in routine practise.

Methods: Case records of patients d-dimer tested in A&E or on admission to hospital were reviewed. Data included: clinical features, admission diagnosis and pre-test probability if recorded. Investigators estimated VTE-risk, calculated post-test probability of VTE and impact on imaging

Results: 96 cases included; 52% female, mean (SD) age 61yrs. Symptoms: chest pain 44.5%; leg pain/swelling 28%; dyspnea 17%, syncope 7.5%, other 3%. Admission diagnosis: VTE likely 10%, VTE possible 57%, other diagnosis 33%. Pre-test probability done in 23%. Investigator pre-test VTE-risk: High (H) 9%, Moderate (M) 20%, Low (L) 33%, Very Low (V) 38%. D-dimer positive 43% (H 100%, M 64%, L 44%, V 41%; p<0.05). p=0.001. VTE-Imaging if d-dimer +ve (VTE-risk M, L, V): 41% v 11.5% OR 5.1 (1.8-15) p=0.001. Prevalence of VTE was 2.3% (sensitivity 1.0, specificity 0.58; negative likelihood ratio 0.0-1.1). Pre and post-test probability of VTE if negative d-dimer: VTE-risk M-H pre-8%, post-<1%; VTE-risk V-L pre-<2%, post-<1%.

Conclusion: Prevalence of VTE in patients D-dimer tested in clinical practise is much lower than in validation studies. Both high risk and very low risk patients with alternative diagnoses are often tested. If VTE risk is very low a negative d-dimer test makes little difference to post-test probability of VTE but positive tests lead to unnecessary imaging.
Variability in DXA Reporting and Other Challenges in Osteoporosis Evaluation
Authors: Tiffany Y. Kim, Anne L. Schafer
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study.
Authors: L Ovesen, L Allingstrup, J Hannibal, E L Mortensen, O P Hansen
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study examined the effect of frequent nutritional counseling on oral intake, body weight, response rate, survival, and quality of life in patients with cancer of the lung (small-cell), ovary, or breast undergoing cyclic chemotherapy. PATIENTS AND METHODS Of 105 assessable patients, 57 were randomized to receive nutritional counseling, and 48 to receive no nutritional counseling and consumption of an ad lib oral intake. The intervention group was counseled to achieve a daily energy and protein intake according to recommended dietary allowances. Counseling was standardized and performed by a trained dietitian, and took place twice monthly during a 5-month period from start of chemotherapy. RESULTS Dietary counseling increased daily energy intake by approximately 1 MJ and protein intake by 10 g over the entire study period. There was no change in the control group. Counseling led to an insignificant increase in body weight, but triceps skinfold measurement increased significantly after 5 months. Response rate and overall survival did not differ between the groups. Quality of life measured by the Quality-of-Life index (QL-index) increased significantly in both groups, but did not differ between groups. CONCLUSION No clinical benefit could be demonstrated despite long-term and continuous improved food intake in cancer patients with solid tumors undergoing aggressive chemotherapy.
Glioblastoma-derived cells exhibit differential responses to glycolysis inhibition under hypoxia
Authors: F. Pistollato, S. Abbadi, E. Rampazzo, G. Viola, A. Della Puppa, L. Cavallini, D. M. Panchision, G. te Kronnie, G. Basso
Journal: Journal of Clinical Oncology (2009)

e13031 It has been suggested that oxygen tension is a crucial component of the brain tumor niche, as hypoxia positively correlates with tumor aggressiveness and over-activity of hypoxia inducible factor-1α (HIF-1α) reinforces tumor progression. Furthermore, hypoxia has been implicated in the regulation of several signaling pathways (Notch, BMP), angiogenesis and importantly, glucose metabolism. Here we investigate the effects mediated by in vitro glycolysis inhibition by using 2-deoxyglucose (2-DG) in glioblastoma (GBM) derived cells maintained under two different oxygen tensions, a lowered oxygen tension (2%) versus a higher non-physiological (20%). GBM account for 50% of all gliomas and arise after age 50 in most patients and it has been seen that younger patients tend to have a better prognosis than the elderly. Our results show that adult GBM displaying a highly immature phenotype manifested the highest resistance to glucose deprivation. Furthermore, increase of multi-drug resistant cell fraction, described as side population, occurred following 2-DG treatment, but only under hypoxia. Neuronal committed precursors were selected by 2-DG, but these effects were mitigated by hypoxia. Also, hypoxia inhibits the mitochondria-controlled apoptosis induced by 2-DG, by conferring cell resistance through progressive activation of pro-survival NF-kB and induction of tumor cell autophagy. Importantly, HIF-1α level reduction and proline hydroxylase 2 (PHD2) upregulation occurred following 2-DG treatment even under hypoxia, and this may depend on reactive oxygen species reduction. These results indicate differences in tumor cells behavior that may be predictive of cell response to therapy aiming to limit glucose uptake or glucose metabolism. No significant financial relationships to disclose.
Pre-Transplant PET Status May Not Impact on Survival Following Reduced-Intensity Allogeneic Stem-Cell Transplant for Lymphoma. However, Post-Transplant Surveillance with PET May Be Important for Directing Immunotherapy.
Authors: Jonathan R Lambert, Jamshed B Bomanji, Nichola Cooper, Daniel P Hart, Karl Peggs, Kirsty Thomson, Peter J Ell, Stephen Mackinnon
Journal: Blood (2008)
Vaccine-induced tumor regression requires a multi-step cooperation between T cells and myeloid cells at the tumor site
Authors: Maxime Thoreau, Hwei Penny, Kar Tan, Fabienne Regnier, Julia Weiss, Bernett Lee, Ludger Johannes, Estelle Dransart, Agnes Le bon, Jean-Pierre Abastado, Eric Tartour, Alain Trautmann, Nadege Bercovici
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Most cancer immunotherapies under present investigation are based on the belief that cytotoxic T cells are the most important anti-tumoral immune cells, whereas intratumoral macrophages would rather play a protumoral role. We have challenged this antagonistic point of view and
Degenerative Effects of the Radiotherapy on the Cerebral Gliomas
Authors: R. D’Avanzo, M. Natale, M. Lama, F. A. Cioffi
Journal: Neuro-Oncology (1991)

The AA. present two cases of malignant gliomas verified after short. latent period from radiation therapy for a low grade astrocytoma located in the controlateral hemisphere. Because these lesions did not meet the criteria for defining a neoplasm as radiation induced and for the common glial origin of both tumors, a multicentric origin was considered. The role of the radiation could be the acceleration of the natural malignant degeneration of the multicentric gliomas.
Does ovarian cancer survival differ by who gives the chemotherapy?
Authors: J. H. Silber, P. R. Rosenbaum, D. Polsky, R. N. Ross, J. S. Schwartz, O. Even-Shoshan, K. Armstrong, T. C. Randall
Journal: Journal of Clinical Oncology (2006)

6110 Background: Medical Oncologists (MOs) specialize in administering chemotherapy while Gynecologic Oncologists (GOs) specialize in the surgical management of gynecologic cancers as well as providing chemotherapy. We asked whether survival differed according to the type of specialist providing the chemotherapy after ovarian cancer surgery. Methods: Using merged SEER-Medicare clinical and administrative data from the years 1991 through 2001 we identified all patients who were diagnosed with ovarian cancer after the age of 65 and who received chemotherapy from a GO after surgery performed by any type of surgeon. Using optimal matching and a propensity score based on 35 prognostic characteristics, we identified similar patients who were operated on, and staged, by nearly identical types of surgeons but who received chemotherapy from an MO. Results: We identified 344 patients who were given chemotherapy for ovarian cancer by GOs after having undergone surgery by either GOs (76%), Gynecologists (16%), or general surgeons or other surgical specialties (8%). Patients given chemotherapy by MOs were matched to these patients. Both groups had nearly identical surgical specialists, age, year of treatment, stage, tumor grade, race and 32 other prognostic factors. There was no difference in overall survival between the GO or MO groups (P = 0.45, paired Prentice-Wilcoxon test). The 5 year survival was 35% (± 2.6%) for the GO group and 34% (± 2.6%) for the MO group. However, MOs administered chemotherapy over more weeks than did the GOs (patient mean = 16.5 Vs 12.1 weeks, P &lt; 0.0023, Wilcoxon rank sum test) and MO patients had more weeks that included at least one of the following chemotherapy associated adverse events (neutropenia, anemia, thrombocytopenia, diarrhea, dehydration or mucositis) than did the GO group (patient mean = 16.2 Vs 8.9 weeks, P &lt; 0.0001, Wilcoxon rank sum test). Conclusions: Despite differences in training, specialty emphasis, and practice style concerning the use of chemotherapy (MO patients had more weeks of chemotherapy and more weeks with chemotherapy associated adverse events than GO patients), we found no difference in survival between patients who received chemotherapy administered by gynecologic oncologists and medical oncologists. No significant financial relationships to disclose.
Abstract 13638: Impact of Cardiac Magnetic Resonance Imaging on Utilization of Invasive Cardiac Procedures
Authors: Andrew Ertel, Siddique Abbasi, Vineet Dandekar, Jaehoon Chung, Afshin Farzaneh-Far
Journal: Circulation (2012)

Background - There is growing concern from government and payers regarding rising healthcare costs related to possible overutilization of invasive cardiac procedures. Cardiac magnetic resonance ima...
Legal and Ethical Considerations in Allowing Parental Exemptions From Newborn Critical Congenital Heart Disease (CCHD) Screening
Authors: Lisa A. Hom, Tomas J. Silber, Kathleen Ennis-Durstine, Mary Anne Hilliard, Gerard R. Martin
Journal: The American Journal of Bioethics (2016)

Critical congenital heart disease (CCHD) screening is rapidly becoming the standard of care in the United States after being added to the Recommended Uniform Screening Panel (RUSP) in 2011. Newborn screens typically do not require affirmative parental consent. In fact, most states allow parents to exempt their baby from receiving the required screen on the basis of religious or personally held beliefs. There are many ethical considerations implicated with allowing parents to exempt their child from newborn screening for CCHD. Considerations include the treatment of religious exemptions in our current legal system, as well as medical and ethical principles in relation to the rights of infants. Although there are significant benefits to screening newborns for CCHD, when a parent refuses for religious or personal beliefs, in the case of CCHD screening, the parental decision should stand.