tbuckley/cabot-search huggingface dataset:
Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer
Authors: Anil K. D’Cruz, Richa Vaish, Neeti Kapre, Mitali Dandekar, Sudeep Gupta, Rohini Hawaldar, Jai Prakash Agarwal, Gouri Pantvaidya, Devendra Chaukar, Anuja Deshmukh, Shubhada Kane, Supreeta Arya, Sarbani Ghosh-Laskar, Pankaj Chaturvedi, Prathamesh Pai, Sudhir Nair, Deepa Nair, Rajendra Badwe
Journal: New England Journal of Medicine (2015)

Whether patients with early-stage oral cancers should be treated with elective neck dissection at the time of the primary surgery or with therapeutic neck dissection after nodal relapse has been a matter of debate.In this prospective, randomized, controlled trial, we evaluated the effect on survival of elective node dissection (ipsilateral neck dissection at the time of the primary surgery) versus therapeutic node dissection (watchful waiting followed by neck dissection for nodal relapse) in patients with lateralized stage T1 or T2 oral squamous-cell carcinomas. Primary and secondary end points were overall survival and disease-free survival, respectively.Between 2004 and 2014, a total of 596 patients were enrolled. As prespecified by the data and safety monitoring committee, this report summarizes results for the first 500 patients (245 in the elective-surgery group and 255 in the therapeutic-surgery group), with a median follow-up of 39 months. There were 81 recurrences and 50 deaths in the elective-surgery group and 146 recurrences and 79 deaths in the therapeutic-surgery group. At 3 years, elective node dissection resulted in an improved rate of overall survival (80.0%; 95% confidence interval [CI], 74.1 to 85.8), as compared with therapeutic dissection (67.5%; 95% CI, 61.0 to 73.9), for a hazard ratio for death of 0.64 in the elective-surgery group (95% CI, 0.45 to 0.92; P=0.01 by the log-rank test). At that time, patients in the elective-surgery group also had a higher rate of disease-free survival than those in the therapeutic-surgery group (69.5% vs. 45.9%, P<0.001). Elective node dissection was superior in most subgroups without significant interactions. Rates of adverse events were 6.6% and 3.6% in the elective-surgery group and the therapeutic-surgery group, respectively.Among patients with early-stage oral squamous-cell cancer, elective neck dissection resulted in higher rates of overall and disease-free survival than did therapeutic neck dissection. (Funded by the Tata Memorial Centre; ClinicalTrials.gov number, NCT00193765.).
Phase II trial of talampanel in conjunction with standard radiation (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM)
Authors: S. A. Grossman, X. Ye, M. C. Chamberlain, T. Mikkelsen, T. T. Batchelor, S. Desideri, S. Piantadosi, H. A. Fine
Journal: Journal of Clinical Oncology (2008)

2014 Background: Recent findings suggest that Ca2+-permeable AMPA receptors play a crucial role in the proliferation and mobility of GBM cells perhaps via activation of Akt. Talampanel is a well-tolerated, oral AMPA receptor inhibitor with good CNS penetration that has been studied in patients with refractory seizures and ALS. Methods: This NABTT CNS Consortium study was designed to estimate survival in adults with newly diagnosed GBM when talampanel was added to standard RT and TMZ and to estimate talampanel toxicity in this setting. RT and TMZ were administered as per the EORTC trial reported in 2005. Talampanel was initiated on the first day of RT, escalated from 35 to 75 mg tid in patients receiving enzyme inducing antiseizure drugs (+EIASD) and from 25 to 50 mg tid in -EIASD patients, and discontinued for toxicity or disease progression. Results: Seventy-two patients with newly diagnosed GBM were enrolled from 12/05 to 7/06. 17% were >70 years old, the median age was 60 (37–85), median KPS was 90 (70–100), and 23% had only a biopsy. Talampanel was well tolerated. Grade 3–4 potentially related toxicities included fatigue in 3 patients and febrile neutropenia, hypoxia, mucositis and rash each in 1 patient. Hematologic toxicity from TMZ (8 pts with neutropenia, 15 with thrombocytopenia) was split between + and - EIAED groups. To date, 42 of 72 pts (58%) have died. The median survival is 17.9 months (lower 95% confidence interval =14.5 months, upper yet undefined) with a minimum follow-up time of 18 months. The average time on talampanel was 5 months and 7 patients remain on talampanel for >19 months. Conclusions: Talampanel can be added to standard RT and TMZ without apparent added toxicity. The 17.9 month median survival in this 72 patient, multicenter study which contained elderly patients suggests that blocking AMPA receptors may be a useful strategy in GBM. Updated survival data and a prognostic factor comparison with the EORTC study (median survival 14.6 months) will be presented. No significant financial relationships to disclose.
Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes
Authors: Kristine R. Broglio, Melanie Quintana, Margaret Foster, Melissa Olinger, Anna McGlothlin, Scott M. Berry, Jean-François Boileau, Christine Brezden-Masley, Stephen Chia, Susan Dent, Karen Gelmon, Alexander Paterson, Daniel Rayson, Donald A. Berry
Journal: JAMA Oncology (2016)

The expense and lengthy follow-up periods for randomized clinical trials (RCTs) of adjuvant systemic therapy in breast cancer make them impractical and even impossible to conduct. Randomized clinical trials of neoadjuvant systemic therapy for breast cancer may help resolve this dilemma.To assess the utility of pathologic complete response (pCR) for neoadjuvant drug development in human epidermal growth factor receptor 2 (HER2 [also referred to as ERBB2])-positive breast cancer.We searched MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), and Northern Light Life Sciences Conference Abstracts (Ovid) in December 2014. Searches combined terms for "breast cancer" and "neoadjuvant therapy," with no limit on publication date.Cohort studies and RCTs were selected that met following criteria: stages I to III HER2-positive breast cancer, neoadjuvant therapy, and reports of both pCR and an event-free survival (EFS)-type outcome. The initial search identified 2614 publications, of which 38 studies met the selection criteria.Two authors independently screened each study for inclusion and extracted the data. Data were analyzed using Bayesian hierarchical models.Event-free survival and overall survival (OS) hazard ratios (HRs) for pCR vs non-pCR. For RCTs, main outcome measures were treatment benefits in pCR and the corresponding treatment HRs for EFS and OS.A total of 36 studies with EFS by pCR status representing 5768 patients with HER2-positive breast cancer were included in the patient-level analysis. Overall, the improvement in EFS for pCR vs non-pCR was substantial: HR, 0.37 (95% probability interval [PI], 0.32-0.43). This association was greater for patients with hormone receptor-negative disease (HR, 0.29 [95% PI, 0.24-0.36]) than hormone receptor-positive disease (HR, 0.52 [95% PI, 0.40-0.66]). In RCTs, the R2 correlations between odds ratios for pCR and HRs were 0.63 for EFS and 0.29 for OS. Based on absolute treatment improvements in pCR rate, predicted HRs for EFS for RCTs were concordant with observed HRs.Pathologic complete response in HER2-positive breast cancer is associated with substantially longer times to recurrence and death. This relationship is maintained in RCTs. For any particular new therapy the relationship between pCR and survival may differ. Quantifying the importance of pCR is necessary for designing efficient clinical trials, which should adapt to the relationship between pCR and survival for the therapy under investigation.
18F-2-deoxy-2-fluoro-D-glucose as a tracer in the positron emission tomographic study of senile dementia
Authors: T Farkas, S H Ferris, A P Wolf, M J De Leon, D R Christman, B Reisberg, A Alavi, J S Fowler, A E George, M Reivich
Journal: American Journal of Psychiatry (1982)

Using /sup 18/F-2-deoxy-2-fluoro-D-glucose as a tracer, the authors obtained positron emission tomographic scans of 11 patients with senile dementia and 6 age-matched controls. The rate of glucose metabolism was significantly lower in the patients with senile dementia and significantly correlated with the degree of cognitive impairment.
IMPACT OF NITINOL SELF-EXPANDING STENT ON THE PATENCY OF SUBINTIMAL ANGIOPLASTY FOR BELOW-THE-KNEE OCCLUSIONS WITH CRITICAL LIMB ISCHEMIA (NEXSIA-BTK): MULTICENTER, PROSPECTIVE REGISTRY
Authors: Jaewon Oh, Young-Guk Ko, Seung Woon Rha, Ki-Chang Kim, Sang-Ho Park, Donghoon Choi
Journal: Journal of the American College of Cardiology (2016)
MTR-02MGMT-INHIBITOR IN COMBINATION WITH TGF-β KINASE OR CDK 4/6 INHIBITOR INCREASES TEMOZOLOMIDE SENSITIVITY OF TEMOZOLOMIDE RESISTANT GLIOBLASTOMA CELLS
Authors: Arabinda Das, Megan L.T. Hilbert, Pierre Giglio, Scott M. Lindhorst, Michele L. Decandio, William A. Vadergrift, Naren L. Banik, Abhay K. Varma, Jeffery J. Raizer, Sunil J. Patel
Journal: Neuro-Oncology (2015)

MTR-02. MGMT-INHIBITOR IN COMBINATION WITH TGF-b KINASE OR CDK 4/6 INHIBITOR INCREASES TEMOZOLOMIDE SENSITIVITY OF TEMOZOLOMIDE RESISTANT GLIOBLASTOMA CELLS Arabinda Das1, Megan L.T. Hilbert1, Pierre Giglio1,2, Scott M. Lindhorst1, Michele L. Decandio1, William A. Vadergrift, III1, Naren L. Banik1, Abhay K. Varma1, Jeffery J. Raizer3, and Sunil J. Patel1; Department of Neurosurgery, Medical University of South Carolina,, Charleston, SC, USA; Department of Neurological Surgery, Ohio State University Wexner Medical College, Columbus, OH, USA; Department of Neurology and Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Northwestern UniversityFeinbergSchool of Medicine,, Chicago, Illinois, USA Glioblastoma is the most common and aggressive form of brain cancer and demonstrates one of the worst five year survival rates of any cancer (3-8%). Implicated in this survival rate are cells that acquire resistance to Temozolomide (TMZ)-based therapy, the standard of care. Resistance to this drug is modulated by the DNA repair enzyme methylguanine-DNA methyltransferase (MGMT). Clinical studies have shown that some TMZ-resistant tumorshaveelevatedMGMTprotein levelsor lackofMGMTpromotormethylation. This study used drug combinations in order to overcome this acquired resistance. Drugs included: MGMT inhibitors, LY2157299 (TGF-bkinase inhibitor), LY2835219 (CDK4/6 inhibitor) and Temozolomide in various combinations. The LY compounds were developed by Lilly USA and are currently undergoing clinical trials testing safety and efficacy in treating several forms of cancer. Our in vitro data clearly demonstrate that TGF-b Kinase or CDK 4/6 inhibitors enhance O6-Benzylguanine + Temozolomide activity via disruption of TGF-b-dependent signaling and transcription or abrogation of the S and G(2) checkpoints. CDK 4/6 inhibitor has additional effects on cell cycling, including induction of an RB-associated G(1) arrest. The interaction between the drugs was assessed. These studies indicate that timing of drug treatments strongly influences response to O6-Benzylguanine +Temozolomide plus TGF-b Kinase or CDK 4/6 inhibitor in MGMT+ glioblastoma cells. This is highly related to the TGFb signaling or cell cyclemodulatory effects of these agents. Furthermore, this combination was more effective in cell lines with dysfunctional MGMT. These findings support the novel combination of these drugs with currently available chemotherapies (e.g. temozolomide) as an alternative therapeutic strategy to potentiate the anti-tumor effects on temozolomide-resistant glioblastoma cells. Neuro-Oncology 17:v124–v129, 2015. doi:10.1093/neuonc/nov219.2 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.
Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses
Authors: Colleen M. Lau, Simone A. Nish, Nir Yogev, Ari Waisman, Steven L. Reiner, Boris Reizis
Journal: The Journal of Experimental Medicine (2016)

A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3ITD knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3ITD/ITD mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8+ cDCs and noncanonical CD8+ cDCs were expanded and showed specific alterations in their expression profiles. Flt3ITD mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner.
In wealthier countries, patients perceive worse impact of the disease although they have lower objectively assessed disease activity: results from the cross-sectional COMORA study
Authors: Polina Putrik, Sofia Ramiro, Monika Hifinger, Andras P Keszei, Ihsane Hmamouchi, Maxime Dougados, Laure Gossec, Annelies Boonen
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To investigate patterns in patient-reported and physician-reported disease outcomes in patients with rheumatoid arthritis (RA) from countries with different level of socioeconomic development. Methods Data from a cross-sectional multinational study (COMOrbidities in RA) were used. Contribution of socioeconomic welfare (gross domestic product (GDP); low vs high) of country of residence to physician-reported (tender joint count, swollen joint count (SJC), erythrocyte sedimentation rate, disease activity score based on 28 joints assessment (DAS28)-3v based on these three components and physician global assessment) and patient-reported (modified Health Assessment Questionnaire (mHAQ), patient global assessment and fatigue) disease outcomes was explored in linear regressions, adjusting for relevant confounders. Results In total, 3920 patients with RA from 17 countries (30 to 411 patients per country) were included, with mean age of 56 years (SD13) and 82% women. Mean SJC varied between 6.7 (Morocco) and 0.9 (The Netherlands), mean mHAQ ranged between 0.7 (Taiwan) and 1.5 (The Netherlands). Venezuela had the lowest (1.7) and the Netherlands the highest score on fatigue (5.0). In fully adjusted models, lower GDP was associated with worse physician-reported outcomes (1.85 and 2.84 more swollen and tender joints, respectively, and 1.0 point higher DAS28-3v), but only slightly worse performance-based patient-reported outcome (0.15 higher mHAQ), and with better evaluation-based patient-reported outcomes (0.43 and 0.97 points lower on patient global assessment and fatigue, respectively). Conclusions In patients with RA, important differences in physician-reported and patient-reported outcomes across countries were seen, with overall a paradox of worse physician-reported outcomes but better patient-reported outcomes in low-income countries, while results indicate that these outcomes in multinational studies should be interpreted with caution. Research on explanatory factors of this paradox should include non-disease driven cultural factors influencing health.
Utility Of Revised International Prognostic Scoring System (R-IPSS) To Predict Outcome Of Myelodysplastic Syndromes (MDS) Patients After Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT)
Authors: Maria Gabriela Corrales-Yepez, Teresa Field, Alan List, Claudio Anasetti, Janelle Perkins, Najla H Al Ali, Asmita Mishra, Eric Padron, Jeffrey E Lancet, Mohamed A. Kharfan-Dabaja, Rami S Komrokji
Journal: Blood (2013)
Mechanisms of Thermal Responses to 2,4-Dinitrophenol
Authors: I SHEMANO, M NICKERSON
Journal: JAMA (1963)

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
Results of a phase II study to evaluate the biological effects of intratumoral (ITu) reolysin in combination with low dose radiotherapy (RT) in patients (Pts) with advanced cancers
Authors: M. Saunders, A. Anthoney, M. Coffey, K. Mettinger, B. Thompson, A. Melcher, C. M. Nutting, K. Harrington
Journal: Journal of Clinical Oncology (2009)

e14514 Background: Reolysin, a wild type reovirus serotype 3 Dearing strain, replicates preferentially in Ras-activated cancer cells. In vitro and in vivo data have shown that combining reolysin and radiation (RT) significantly increases RT-induced cytotoxicity. A completed phase I trial of ITu reolysin and RT demonstrated that the combination was well tolerated and resulted in local and systemic responses. Methods: This open-label, single-arm, multicenter Phase 2 study combined ITu reolysin with low-dose fractionated RT. 20 Gy was given in 5 consecutive daily 4 Gy fractions combined with 2 ITu injections of reolysin (1x10 10 TCID 50 ) on days 2 &amp; 4. The primary endpoint was objective tumor response rate in treated lesions. Secondary endpoints were to evaluate: viral replication, immune response and safety. Pts with ECOG performance status ≤2, with refractory advanced or metastatic cancers were eligible. Results: 16 heavily pre-treated pts (9 male, median age 66 yrs, ECOG 0:4pts; 1:12pts) with advanced cancer: melanoma (5), colorectal (4), gastric (1), ovarian (1), pancreas (1), lung (1), cholangiocarcinoma (1), sinus (1), and thyroid (1) were enrolled since Dec 2006. Most pts had received prior chemotherapy (13 pts) or RT (5 pts). No related serious adverse effects were observed during the study. Toxicities related to treatment were Grade 1 or 2: chills, pyrexia, headache, lethargy, anorexia, vomiting, shivering, nausea, and mild injection site pain. Of 14 pts evaluable for response, 13 pts had stable disease or better in the treated target lesion. Of these, partial responses were observed in 4 pts (lung, melanoma x 2, gastric) and minor responses were observed in 2 pts (thyroid, ovarian). Antibody responses to reolysin were delayed compared to previous results with intravenous administration. Conclusions: The combination of ITu reolysin and low dose RT was well tolerated and resulted in marked responses or stabilization in the treated target lesions for most of the pts evaluated to date. Further study in the radical setting is warranted. [Table: see text]
Significance of local and circulating cancer stem cells in human liver cancer
Authors: Zhen Fan Yang, Michael N.P. Ng, David Wing-Yuen Ho, Chi Keung Lau, Chi Tat Lam, Ronnie Tung-Ping Poon, Sheung Tat Fan
Journal: Cancer Research (2008)

4591  Background: Cancer stem cells (CSCs) have been shown to be the source of many solid tumor types, including cell-line induced hepatocellular carcinoma (HCC). However, few studies characterize liver CSCs in the tumor specimens and blood samples from liver cancer patients. Here, we design the present study to investigate whether CSCs are present in tumor specimens and blood samples from liver cancer patients, and the characteristics of those cells, using CD90 as a potential marker. Materials and Methods: Fresh tumor specimens and blood samples were collected from normal control, patients with cirrhosis, dysplatic nodules and liver cancers, respectively. CD45-CD90+ and CD45-CD90- cells were isolated from tissue and blood samples from different sources, and injected into the liver of severe-combined immunodeficient (SCID)/Beige mice to determine tumorigenicity. CD90+ and CD90- cells were also sorted from two HCC cell lines, PLC and MHCC97L, respectively, and injected into the liver of BALB/c nude mice to determine tumorigenicity. Flow cytometry was used to evaluate the distribution of CD90+ cells in the primary tumor tissues and generated tumor xenografts. Immunohistochemical staining was used to assess the localization of CD90 expression in the tumor tissues. Results: CD45-CD90hi cells were only detectable in the tumor tissues from liver cancer patients, but not in the control tissues. In addition, CD45-CD90+ cells were detected in more than 90% of blood samples from liver cancer patients, but not from the controls. CD45-CD90+ cells from the tumor specimens and blood samples of liver cancer patients generated tumor nodules in the liver of immunodeficient mice, whereas CD45-CD90+ cells from the normal and cirrhotic livers, and CD45-CD90- cells from the tumor tissues did not. Immunohistochemical staining revealed scattered and clustered distribution of CD90+ cells in the tumor tissues, with both membrane and cytoplasmic localization. Transplantation of CD90+ cells isolated from the generated tumor xenografts into a second or subsequent a third batch of immunodeficient mice also induced tumor formation, and the proportion of CD90+ cells in the serially generated tumor xenografts remained steady. In HCC cell lines, only CD90+ cells generated tumor nodules in nude mice. Administration of anti-CD44 antibody induced CD90+ cells undergoing apoptosis in a dose dependent manner. Conclusion: The present study reveals that CD90 is a potential marker for liver CSCs. The presence of circulating CSCs reflects an aggressive characteristic of human liver cancer. The evidence that CD44 inhibition induced CSCs undergoing apoptosis suggests that CD44 could be a therapeutic target for liver CSCs.
2D Strain in the evaluation of early alteration of global and regional left ventricular function in pre-hypertension
Authors: Di Bello V, E Talini, Ml Canale, G Dell'Omo, S Affinito, Mg Delle Donne, C Palagi, C Nardi, M Mariani, M Marzilli, P Roberto
Journal: Journal of the American College of Cardiology (2008)
Treatment and Outcome(S) of a Large Cohort of Poor Risk Metastatic Renal Cell Carcinoma (Prrcc) Patients (Pts)
Authors: A. Felici, D. Santini, U. De Giorgi, S. Iacobelli, G. Facchini, M. Santoni, E. Verzoni, L. Derosa, G. Di Lorenzo, R. Ardito, G. Badalamenti, P. Marchetti, E. Cortesi, R. Cengarle, S.L. Fedeli, V. Adamo, P. Maroto, F.M. Guida, I. Sperduti, M. Milella
Journal: Annals of Oncology (2014)