tbuckley/cabot-search huggingface dataset:
Relationship of angiogenesis biomarkers and clinical response to bevacizumab (Bev) in persistent or recurrent epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC) patients treated in a Phase II Gynecologic Oncology Group study
Authors: E. S. Han, R. A. Burger, L. Randall-Whitis, B. Parmakhtiar, K. Darcy, M. Sill, P. Connelly, B. J. Monk, J. P. Fruehauf
Journal: Journal of Clinical Oncology (2007)

21021 Background: Angiogenesis promotes tumor growth and is associated with poor outcomes in ovarian cancer. Currently, there are no markers to predict or determine response to anti-angiogenesis therapies. Methods: Persistent or recurrent EOC/PPC patients (1–2 prior cytotoxic regimens, measurable disease, and GOG performance status = 2) were treated with Bev (15mg/kg IV q21days) until progression. Tissue biopsies, serum samples and dynamic contrast enhanced MRIs (DC-MRI) were obtained prior to initiation (PT01) and 4 th cycle (PT02) of Bev therapy. Tumor vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP-1), and mutant p53 were determined by immunohistochemistry (IHC) and scored using histoscore (HS) analysis ([1 + staining score (0 to 4)] x % positive). Microvessel density (MVD) was determined by counting CD31 IHC hot spots. Serum VEGF levels were obtained by ELISA. Variables were considered as continuous or discontinuous in this training set to establish appropriate cut points to be applied to an ongoing phase III trial (GOG218). Results: From 4/02 to 8/04, 62 eligible patients were enrolled. A 17.7% response rate with 40% of patients with no evidence of disease progression for at least 6 months was previously reported (ASCO 2005). 44 tissue samples from PT01 and 27 from PT02 were evaluable for IHC biomarker levels. Based on current analysis, VEGF HS average was 92 at low MVD counts, while at high MVD counts, VEGF HS average was higher at 159 (p=0.06). In addition, 77% of TSP-1 negative tissues were VEGF positive, while 52% of TSP-1 positive tissues were VEGF positive. Analysis of serum VEGF levels (from 56 PT01 and 39 PT02 specimens) and DCMRIs (49 PT01 and 42 PT02 MRIs) are ongoing. Conclusions: Higher tumorVEGF was associated with increased angiogenesis and lower TSP-1 tissue levels. Results from the biomarkers tested await correlation to the mature survival data which should be available by June 2007. We plan to determine whether an angiogenesis biomarker profile is associated with patient response to Bev therapy. No significant financial relationships to disclose.
Leukemic blasts fail to differentiate into mature antigen presenting cells, and may hinder dendritic cell maturation in vitro and in vivo
Authors: J. Rosenblatt, R. Stone, C. Lenahan, Z. Wu, B. Vasir, A. Bissonnette, I. Galinsky, K. Miller, J. D. Levine, R. Joyce, D. Avigan
Journal: Journal of Clinical Oncology (2007)

10556 Background: Dendritic cells (DC) play a key role in the development of tumor specific immune responses. Dendritic cells differentiated from leukemic blasts (LDC) are being explored as a tumor vaccine in AML. We examined the phenotypic and functional characteristics of LDC, the phenotypic characteristics of native DC in AML patients, and the effect of leukemic blasts on the phenotype of DC generated from normal donors. Methods: Leukemia blasts were isolated from peripheral blood of 24 patients with AML. LDC were generated by culturing blasts in the presence of GM-CSF, IL-4 and TNFa for 7 days. The phenotype of circulating DC1 (CD11C+/lin-) and DC2 (CD123+/ lin-) in AML patients was assessed by multichannel FACS analysis. To assess the effect of blasts on DC maturation, adherent mononuclear cells were isolated from normal donors, combined with leukemia cells in a 10:1 ratio, and cultured with GM-CSF, IL-4, and TNFa. Results: LDC demonstrate only modest expression of the costimulatory molecules CD80 and CD86 (mean expression 10% and 32%) and poorly express the maturation marker CD83 (mean expression 4%). Interferon gamma production by autologous T cells was not higher after stimulation with LDC than with blasts. LDC stimlation resulted in a 2 fold increase in both CD4+/CD25+/CD69+ (activated) and CD4+/CD25+/FOXP3+ (regulatory) T cells. Given the inability of leukemia progenitors to differentiate into phenotypically mature DC, we assessed whether leukemia cells directly inhibit differentiation of DC from normal progenitors. Expression of costimulatory molecules was decreased in DC differentiated in the presence of blasts. Mean expression of CD80, CD83, and CD86 was 16%, 2%, 83% and 49%, 10%, 99% for DCs generated in the presence or absence blasts respectively. Phenotypic characteristics of native DC in patients with AML were examined. In 3 experiments, a predominance of DC2 was seen (ratio DC2/DC1 5), and both DC1 and DC2 poorly expressed CD83 (mean expression 9% DC1, 0.9% DC2). Conclusions: LDC have phenotypic and functional deficiencies, limiting their efficacy as a tumor vaccine. Contact with leukemic blasts may inhibit DC maturation in vitro and in vivo, which may contribute to the lack of effective antitumor immunity in AML patients. No significant financial relationships to disclose.
Breast cancer patients' risk perceptions and treatment values following surgical consult.
Authors: Karen Kaiser, Kenzie A. Cameron, Melinda Stolley, Kevin P. Bethke, Nora M. Hansen, Jacqueline Sara Jeruss, Marla L. Clayman, Seema Ahsan Khan
Journal: Journal of Clinical Oncology (2013)

e11572 Background: Contralateral breast cancer (CBC) is the most common second primary cancer in breast cancer patients. The 10-year risk of CBC for patients with locally invasive or intraductal disease is approximately 6%. However, a recent study reported that prior to surgical consult newly diagnosed breast cancer patients without a BRCA mutation estimated their 10-year CBC risk to be 31.4%. We sought to evaluate breast cancer patients’ perceived risk of future cancer and their treatment values following surgical consult. Methods: Women diagnosed with ductal carcinoma in-situ or stage I-III invasive breast cancer were interviewed in the period between surgical consult and surgical treatment. Participants completed the Perceived Risk Questionnaire (PRQ) and the Values Scale. The PRQ contains 5 questions to assess perceived likelihood of future cancer on a 5-point scale (1=not at all likely, 5=very likely). For each question, women also estimate the likelihood of cancer in the next 10 years as a percentage from 0 to 100. The Values Scale measures the importance of 11 treatment-related values (e.g., How important is it to you to keep your breast?) on a 10-point scale (1=not at all important, 10=very important). Results: Interviews were completed with 20 patients (mean age 54.7 years) without a known BRCA mutation. On the Values Scale, women identified minimizing the chance of cancer elsewhere in the body (mean=9.2), in the other breast (mean=9.1), and in the same breast (mean=8.8) as most important. Patients estimated their 10-year risk to be 13.6% for CBC, 14.2% for breast cancer appearing in the same breast, and 19.6% for cancer appearing elsewhere in the body. One-fourth of participants believed they faced at least a 50% chance of encountering breast cancer again in the next 10 years. Conclusions: Women in this study reported lower perceived risk of CBC than in a prior study of perceived risk prior to surgical consult, thus suggesting that the surgical consult may lead to a reduction in perceived risk. Nonetheless, participants’ estimated their 10-year risk of CBC to be twice the actual estimated risk. Our findings indicate a need for additional patient education about CBC risk.
Immunophenotype of regionally recurrent melanoma of the extremity in patients before isolated limb infusion (ILI)
Authors: M. S. Brady, S. Gnjatic, G. Ritter, A. A. Jungbluth
Journal: Journal of Clinical Oncology (2006)

8052 Background: ILI is an effective, though palliative, treatment for patients with regionally recurrent melanoma of the extremity. Tumor-associated antigens such as the Cancer Testis (CT) antigens and melanocyte differentiation antigens (MDAs) have been used successfully as targets for vaccine-based immunotherapy trials in patients with recurrent melanoma. Little is known about expression of these antigens in patients with regional disease. Methods: Samples of regionally recurrent melanoma were obtained from patients prior to ILI as part of an ongoing clinical trial. 22 available samples were formalin-fixed, paraffin-embedded and analyzed by IHC for the following antigens (using the following monoclonal antibodies): CT antigens (MAGE-A1 [MA454], MAGE-A3 [M3H67], MAGE-A4 [57B], NY-ESO-1 [E978], CT7/MAGE-C1 [CT-33], GAGE) and MDAs (gp100 [HMB45], Melan-A/MART-1 [A103], tyrosinase [T311]). The presence of antibodies to CT antigens was analyzed by ELISA. Results: The antigen expression profile was as follows (positive/total): MAGE-A1 9/22 (41%); MAGE-A3 13/22 (59%), MAGE-A4 11/22 (50%), CT7 14/22 (64%), NY-ESO-1 8/22 (36%), GAGE 12/22 (55%), Melan-A 20/22 (91%), tyrosinase 20/22 (91%), gp100 19/22 (86%). The expression pattern was homogeneous for the vast majority of MDAs and for most CT antigens. No serologic response to any of the tested CT antigens was found in any of the patients. Conclusions: Regionally recurrent melanoma exhibits a homogeneous expression of melanocyte differentiation and CT antigens indicating expression similar to distant metastases. Despite the often prolonged course of patients with regionally recurrent disease, there is no evidence of an effective immune response to CT antigens. No significant financial relationships to disclose.
Physician-Assisted Death in Canada
Authors: Harvey Max Chochinov
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Sidecut radius and kinetic energy: equipment designed to reduce risk of severe traumatic knee injuries in alpine giant slalom ski racing
Authors: Josef Kröll, Jörg Spörri, Matthias Gilgien, Hermann Schwameder, Erich Müller
Journal: British Journal of Sports Medicine (2015)

Background Kinetic energy (E kin ) increases with speed by the power of 2 and is considered a major risk factor for injuries in alpine ski racing. There is no empirical knowledge about the effect of ski geometry on E kin . Consequently, the aim of this study was to investigate the influence of sidecut radius on the progress of E kin while skiing through a multigate section in giant slalom (GS). Methods 5 European-Cup level athletes skied on three different pairs of GS skis varying in sidecut radii (30, 35 and 40 m). Each athlete's position over time within a six gate section (including flat and steep terrain) was captured by the use of a differential Global Navigational Satellite System. E kin , speed, time and path length were analysed for each pair of skis used. Results When using skis with greater sidecut radius, average E kin was significantly lower over the entire six gate section, but not locally at every turn cycle. Particular decreases of E kin were observed for both turns on the flat terrain, as well as for the turn at the terrain transition and the first turn on the steep terrain. The observed decreases in E kin were found to be primarily explainable by increases in turn time. Conclusions With respect to typical sport mechanisms that cause severe knee injuries, using skis with greater sidecut radius potentially provides additional injury preventative gain, particularly in specific areas within a run. However, this injury preventative gain during falls in GS should not be overestimated.
Carfilzomib (K) Vs Low-Dose Corticosteroids and Optional Cyclophosphamide (Cy) in Patients (Pts) with Relapsed and Refractory Multiple Myeloma (Rrmm): Results from a Phase 3 Study (Focus)
Authors: H. Ludwig, T. Masszi, M.T. Petrucci, A. Palumbo, L. Rosiñol, A. Nagler, K.L. Yong, J. Minarik, M.A. Dimopoulos, V. Maisnar, D. Rossi, H. Kasparu, D. Ben-Yehuda, I. Hardan, M. Jenner, K. Rajangam, J.F. San Miguel, R. Hájek
Journal: Annals of Oncology (2014)
Transient Infectivity and Heterokaryon Formation in Hamster Cell Cultures Inoculated With Cell-Associated Stocks of Marek's Disease Virus and Herpesvirus of Turkeysl
Authors: R L Witter, J M Sharma
Journal: JNCI Journal of the National Cancer Institute (1974)

Virus infectivity persisted for up to 10 serial passages in primary hamster kidney (HK) cultures inoculated with cell-associated Marek's disease virus (MDV) or herpesvirus of turkeys (HVT). However, the direct correlation of infectivity with the persistence of at least 106 inoculum cells/culture, the ablation of infectivity by treatment with cytotoxic anti-avian cell antibody, and the failure to infect HK cultures with high doses of cell-free MDV or HVT strongly indicated that infection was solely associated with inoculum-derived avian cells. Heterokaryons containing avian and hamster nuclei as well as viral antigens were observed in HK cultures inoculated with virus-infected avian cells, but the function of these heterokaryons in viral replication was uncertain. It was concluded that HK cells did not support persistent infection with, and were probably refractory to, the strains of MDV and HVT used.
Proteasome inhibitor bortezomib &amp; re-irradiation (rRT) with scheduled treatment break in patients (pts) with head/neck squamous carcinoma (HNSCC)
Authors: B. A. Conley, E. Donovan, C. Muir, J. Morris, A. D. Colevas, D. Gius, E. Trehu, E. Sausville, J. Wright, C. Vanwaes
Journal: Journal of Clinical Oncology (2005)

5592 Background: We & others have previously shown that bortezomib inhibits activation of NFκB & other survival effectors & has cytotoxic, radiosensitizing, & anti-tumor activity in preclinical HNSCC models. A previous NCI phase 1 study evaluating dose escalation of bortezomib with rRT established a maximum tolerable dose (MTD) of 0.6 mg/m2 twice weekly IV with daily rRT for 6.6 weeks (60–70 Gy) based on dose limiting toxicity (DLT) of grade 3 hyponatremia & hypotension in 2 pts. The current study was designed to further explore the MTD & best tolerated schedule of bortezomib with rRT by introducing a treatment break. Methods: Pts with recurrent or metastatic HNSCC in whom rRT was feasible, who were ≥ 6 months since prior RT, had PS ≤2, AST/ALT <2.5x normal, bilirubin <1.5x normal, adequate hematopoetic & renal function were enrolled. Bortezomib was administered twice weekly as an IV bolus at the 0.6 mg/m2 dose level with rRT 1.8 Gy/day to 60–72 Gy. A 2-week break in both drug & rRT was given halfway through planned rRT. Results: 5 of 6 pts enrolled are currently evaluable for toxicity (CTC v 2.0) & response. Median ECOG PS was 1 (0–1). DLT was seen in 1 pt (hyponatremia & orthostatic hypotension), who died unexpectedly less than a week after treatment completion. Other grade 3 toxicities (non-DLT) included mucositis, vomiting, hyperglycemia & pain. Four pts completed treatment at the 0.6 mg/m2 dose without DLT & are alive 3–9 months after treatment; one pt remains on treatment. Conclusions: The combination of bortezomib & rRT is feasible with this novel schedule employing a treatment interruption. Bortezomib MTD with rRT is ≤0.6 mg/m2. A future study will explore continuous rRT with 2-week midcourse bortezomib treatment break. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millenium Millenium
Seeing a cause for blindness in severe pancreatitis
Authors: A D Hopper, D Gosling, S Patwary, D Partridge, M Peterson
Journal: Gut (2015)

During a holiday on a Mediterranean island, a 63-year old woman suffered a severe attack of pancreatitis secondary to gallstones. During the hospital stay, no sepsis was noted, but she was treated with prophylactic intravenous antibiotics, intravenous fluid and analgesia intensive care support was not required. After 22 days in hospital, she travelled back to the UK and presented to our department on advice to seek further help regarding ongoing symptoms of nausea and reduced appetite. A CT scan performed on admission demonstrated a developing 13×4.5 cm acute pancreatic collection with fat necrosis, splenic vein occlusion and gastric compression. Treatment with analgesia, venous thrombosis prophylaxis and nasojejenual feeding was commenced pending …
To test or not to test: where is the truth?
Authors: M Gilseth
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.4.1406 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8648405 To test or not to test: where is the truth? M GilsethxM GilsethSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.4.1406 PDF "To test or not to test: where is the truth?." Journal of Clinical Oncology, 14(4), pp. 1406–1407© 1996 by American Society of Clinical Oncology
Estimation of the reproduction number for 2009 pandemic influenza A(H1N1) in the presence of imported cases
Authors: H Nishiura, M G Roberts
Journal: Eurosurveillance (2010)

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Abstract MP052: Lifestyle Factors and Antihypertensive Treatment on the Risks of Ischemic and Haemorrhagic Stroke
Authors: Gang Hu, Yurong Zhang, Pekka Jousilahti, Yujie Wang, Riitta Antikainen, Jaakko Tuomilehto
Journal: Circulation (2012)

Background Although hypertension is a potential intermediate factor on the causal pathway of lifestyle factor with stroke risk, the joint relationship between healthy lifestyle and antihypertensive treatment with stroke risk is unclear. Methods We prospectively investigated the individual and joint effects of healthy lifestyle factors and antihypertensive treatment on total and type-specific stroke risk among 36,686 Finnish participants who were 25 to 74 years old and free of coronary heart disease and stroke at baseline. The Cox proportional hazards model was used to evaluate the associations between healthy lifestyle factors and hypertension subgroups with stroke risk. Results During a mean follow-up of 13.7 years, 1,478 people developed an incident stroke event (1,167 ischemic and 311 hemorrhagic). The risk of stroke was significantly decreased in people adhered to ≥3 healthy lifestyle factors (never smoking, normal weight, moderate/high level of physical activity, vegetable consumption ≥3 times/week, and light/moderate alcohol drinking) compared with those adhered to &lt;3 healthy lifestyle factors and this association was present among participants with different hypertensive status. The risk of stroke was significantly increased in all hypertensive subgroups compared with the normotensive group. Compared with hypertensive subjects who did not use antihypertensive drugs and were adhered to ≥3 healthy lifestyle factors, the multivariable-adjusted hazard ratios in hypertensive subjects who used antihypertensive drugs and were adhered to &lt;3 healthy lifestyle factors were 1.39 (95% CI 1.04-1.86) for total stroke, 1.42 (1.03-1.97) for ischemic stroke, 1.37 (0.72-2.58) for hemorrhagic stroke in men, and 2.27 (1.71-3.01) for total stroke, 2.31 (1.69-3.16) for ischemic stroke, 2.21 (1.16-4.23) for hemorrhagic stroke in women, respectively. Only hypertensive men but not women who used antihypertensive drugs and were adhered to ≥3 healthy lifestyle factors had decreased risks of total and ischemic stroke compared with those who did not use antihypertensive drugs and were adhered to &lt;3 healthy lifestyle factors. Conclusions The present study demonstrates our study demonstrates that a healthy lifestyle significantly decreases the risks of total, ischemic and hemorrhagic stroke in different hypertensive status in both men and women. A healthy lifestyle may be more effective in preventing stroke than antihypertensive treatment in hypertensive subjects.
C/EBPα expression by immunohistochemistry lacks prognostic or predictive significance in primary resected non-small cell lung cancer
Authors: D. B. Costa, P. Stephenson, O. Kocher, D. G. Tenen, R. H. Feins, S. M. Keller, J. H. Schiller, D. H. Johnson, B. Halmos
Journal: Journal of Clinical Oncology (2006)

7202 Background: The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) is down-regulated in a majority of lung cancers. We sought to determine if C/EBPα could be a prognostic or predictive factor in non-small-cell lung cancer (NSCLC). Methods: Our cohort originated from ECOG 3590/4592 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratorial study). 166 tumor samples contained material for immunohistochemical (IHC) analysis of C/EBPα expression. We used a scoring system comparing tumor staining to that of basal bronchial cells (3+). 0 or 1+ (weak) staining suggested lack of, while 2 or 3+ (strong) suggested C/EBPα expression. Our primary outcomes were differences in progression-free and overall survival between the groups with weak or strong staining. Results: Among the 166 patients analyzed for C/EBPα IHC, the median progression free and overall survival were 30.7 and 40.3 months, respectively; which do not differ from the complete E4592 cohort. 92 patient samples (55%) had 0 or 1+ staining, and the remaining 74 (45%) 2 or 3+. The median progression free survival for patients with weak and strong C/EBPα IHC expression was 31.5 and 30.2 months, respectively (p = 0.84). The median overall survival between the weak and strong groups was 47.5 and 38.3 months, respectively (p = 0.54). 10 years after enrollment, 27% (25/92) of patients were alive in the weak, and 24% (18/74) in the strong C/EBPα IHC group. No difference between our primary outcomes by C/EBPα expression was identified. There was no difference in outcome by treatment arm, tumor histology, stage, or patient’s characteristics. There was a trend towards loss of C/EBPα and less differentiated tumor samples (p = 0.07). Conclusions: C/EBPα is a novel tumor suppressor gene in lung cancer with loss of expression in over 50% of NSCLC. However, our data demonstrate that in a subset of patients with resected NSCLC, C/EBPα IHC status is neither a prognostic nor a predictive marker. Further studies are needed to establish the molecular mechanisms of C/EBPα inactivation in lung cancer and its possible role as a new therapeutic target. No significant financial relationships to disclose.