tbuckley/cabot-search huggingface dataset:
Mediation of HER2 expression-dependent antiproliferative and pro-apoptotic effect of pan-HER2-specific TKIs on breast cancer cells through STAT5 and JNK.
Authors: Daphne Gschwantler-Kaulich
Journal: Journal of Clinical Oncology (2013)

e11606 Background: HER-targeted tyrosine kinase inhibitors (TKIs) have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood. Methods: Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP and immunolabeling for active caspase 3, respectively. Results: All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines, irrespective of their sensitivity against the HER-TKIs. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively. Conclusions: We have shown that HER-TKIs exert a HER2 expression-dependent effect on proliferation and apoptosis in cancer cell lines in vitro, which is at least partially mediated by blockade of JNK and STAT5A/B. Despite slight differences in their specificity towards individual members of the HER family all three inhibitors had comparable antiproliferative and proapoptotic effects in vitro.
Long-term tolerability of fentanyl effervescent buccal tablets: Interim analysis in patients with cancer-related breakthrough pain
Authors: N. Slatkin, V. Charu, G. Niebler, R. Rauck
Journal: Journal of Clinical Oncology (2006)

8567 Background: Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the rate and efficiency of fentanyl absorption through the buccal mucosa. Results reported here represent a pre-specified interim analysis of an open-label safety and efficacy study of FEBT in opioid-tolerant patients with cancer-related breakthrough pain (BTP). Methods: Patients with cancer-related BTP receiving around-the-clock and supplemental opioids were eligible to enroll. Patients who had participated in a previous dose-titration study of FEBT enrolled directly into the 1-year phase; new patients entered a titration phase to determine an effective FEBT dose before entering the 1-year phase. An effective FEBT dose was defined as the dose needed to provide adequate analgesia for BTP. By October 3, 2005, 170 patients (aged 24 to 95 years) received FEBT (100–800 μg) and had documented safety data. Results: Of the 112 new patients, 70.5% identified an effective FEBT dose and were eligible for enrollment. In the long-term phase, patients received FEBT for a mean of 109.8 days; 8% at 100 μg, 15% at 200 μg, 23% at 400 μg, 25% at 600 μg, and 29% at 800 μg. The FEBT dose remained reasonably stable during the long-term phase, but 43 patients had a dose increase and 6 had a dose decrease at the discretion of the investigator. Only 2 patients required a change in the FEBT dose because of tolerability. The most common adverse events (AEs) are given in the table. The incidence of AEs did not correlate with the effective FEBT dose. The 42 patient deaths that occurred were all attributed to cancer-related pathology or the progression of cancer. Conclusions: Overall, FEBT was well tolerated in opioid-tolerant patients with cancer-related BTP. [Table: see text] [Table: see text]
Abnormalities in cancer patients' coagulation system.
Authors: Hector Alirio Gonzalez Florez, M. Rojas, J. Quiroz, Y. Mancera
Journal: Journal of Clinical Oncology (2013)

e22207 Background: It is well known cancer patients may present both hemorrhagic and thrombotic abnormalities and these phenomena are difficult to diagnose and treat. Thrombotic phenomena are developed clinicly in 15% in cancer patients and it’s higher in adenocarcinomas and myeloprolipherative disorders. These complications can be the consequence of coagulations factor direct activation or chronic DIC, because of the acquired capacity of neoplastic cells for starting coagulation cascade. Methods: In this study an untreated cancer patients group were compared with another healthy controls group, older than 14 years. Patients before treatment and controls were laboratory tested. A t – test for independent samples was employed. Results: Number: patients group: 66, control group: 73. Median age: patients: 50 (17-78). Controls: 52 (18 -93). Sex: Patients: men: 35%, women: 65%. Controls: men: 52%, women: 48%. Malignancies: breast cancer 9.7%; gastric carcinoma 8.1%; cervical carcinoma 6.5%; NH lymphomas 6.5%, unknown origen metastatic carcinoma 4.8%; oral carcinoma 4.8%. Clinical stages: I: 6.3%; II: 6.3%; III: 22.9%; IV: 62.5% (metastatic) 47.9%. Thrombotic antecedents in patients group: 19.7%. There were significant differences in: Platelets count: patients: 281121, controls: 307745 (p&lt;0.001). Protein C: 0.87 and 3.81 UI/mL, respectively (p &lt; 0.001). Antithrombin III: 97 and 101% (p&lt;0.001). Plasminogen: 92.9 and 101.1% (p &lt; 0.001). Lupus anticoagulant (RVV time): 27 and 25.6” (p&lt;0.001). There were no significant differences in PT: 18.3 and 16.9” and PTT: 31 and 34”. The same significant differences were got when the patients of every clinical stage were compared with control patients. There were no differences when the patients of every clinical stage were compared among themselves, nor between sex. Conclusions: This study shows cancer patients may have many coagulation abnormalities: anticoagulant system defects and fibrinolytic system hipoactivity, demonstrated by the significant differences found in antithrombin III, protein C and plasminogen levels between patients and controls groups. It is suggested to practice these tests to cancer patients, even without clinical coagulation disorders, to stablish prophylactic measures.
Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer xenografts
Authors: Ali Shokoohmand, Jiongyu Ren, Jeremy Baldwin, Anthony Atack, Abbas Shafiee, Christina Theodoropoulos, Marie-Luise Wille, Phong A. Tran, Laura J. Bray, Deborah Smith, Naven Chetty, Pamela M. Pollock, Dietmar W. Hutmacher, Judith A. Clements, Elizabeth D. Williams, Nathalie Bock
Journal: Biomaterials (2019)
Financial burdens (FB), quality of life, and psychological distress among advanced cancer patients (ACP) in phase I trials and their spousal caregivers (SC).
Authors: Fay J. Hlubocky, David Cella, Tamara G. Sher, Mark J. Ratain, Christopher Daugherty
Journal: Journal of Clinical Oncology (2012)

6117 Background: FBs have been identified as a significant predictor of stress for cancer patients and their caregivers/partners. FBs may indirectly affect the quality of life and psychological distress of clinical trial subjects, particularly those with advanced disease on Phase I trials. Methods: A convenience sample of ACP enrolling in phase I trials was assessed at baseline (T1) and one month (T2) using several measures including: depression (CES-D), state-trait anxiety (STAI-S/T), quality of life/qol (FACIT-Pal), and global health (SF-36). Data on FB were obtained via the questions of Ell (2008), querying subjects on: employment status, unexpected medical costs, concerns regarding wages (e.g. termination, use of sick time), and financial stress. Results: 104 subjects (52 Phase I ACPs and 52 SC) were separately interviewed at T1 and T2. For the total population: median age 61 (28-78y); 50% male; 100% married; 87% Ca; 67%&gt; HS educ; 55% GI dx; 53% income &lt;$65,000 yr, with45% ACPs employed full/part-time; 55% retired; 66% SC employed full/part-time with 34% retired. At T1, 82% of ACP reported medical cost concerns and 79% reported financial stress. For SC at T1, 69% reported medical costs concerns; 83% employed SC reported wage concerns; and 81% reported financial stress. For both ACP and SC, rates remained consistent with the exception of increased self-report re medical cost concerns at 85% and 72% respectively at T2. At T2, ACP who reported unexpected medical costs had higher STAI-S (31 ± 10 v 29 ±12, p=0.02) and CES-D scores (12 ± 11 v 10 ± 9, p=0.04). SC with self-reported financial stress had higher STAI-S anxiety (39 ± 17 v 35 ± 13, p=0.03) at T2. In regression analyses, ACP with medical costs concerns had poorer FACIT-Pal QOL over time. Also, SC with medical cost concerns at T2 was negatively associated with SF-36 scores. ACP and SC qualitative responses re FBs revealed salient themes: insurance coverage, unexpected costs associated with research study participation, Medicare, bankruptcy, and worry re financial stability after ACP death. Conclusions: FBs are negatively associated with quality of life among clinical trial subjects and SC in phase I trials.
In silico identification of an epithelial core signature in human tumors.
Authors: Chirayu Pankaj Goswami, Oscar D. Cano, Yesim Gokmen-Polar, Sunil S. Badve
Journal: Journal of Clinical Oncology (2012)

10628 Background: Gene expression analysis is performed on grossly selected specimens often without any microscopic analysis of tumor content. In studies where histological analyses have been performed, cases having 80% or more tumor content are used for microarray analysis. The variability in amount of epithelial and stromal cells may generate to misleading differential expression analysis and selection for wrong targets for therapeutics. It is also often unclear, whether the genes identified are stromal or epithelial in origin. The goal of this study was to identify genes that define core epithelial phenotype; these genes could provide means of normalization of expression data. Methods: The CABIG GSK microarray (HG-U133_plus_2) data consisting of 950 cell lines from carcinoma (n=562), non-carcinoma (n=385) and normal tissue (n=3) was analyzed to identify epithelial specific genes. 10 carcinomas each from 11 sites (n=110) and an equal number of non-carcinomas were randomly selected. In silico analyses were performed by 1) identifying genes differentially expressed between carcinoma and non-carcinoma samples using a one way ANOVA; 2) identifying gene signature associated with carcinoma using Predictive Analysis of Microarrays (PAM) and 3) a weighted gene coexpression network analysis (WGCNA) was performed to identify co-expression modules. A similar analysis was also performed on tissue samples (E-GEOD-12360) from carcinomas and non-carcinomas. Venn-diagram was generated to identify intersecting set. Results: Comparison of the carcinoma and non-carcinoma samples using ANOVA identified 1455 differential expressed gene probes in cell lines and 540 gene probes in tissues (FDR=1E-10). The cell lines analysis identified 5 modules and a 65-gene signature (43 core and 22 accessory set) that was specific for epithelial cells. In the tissue analysis a 188-gene signature was similarly identified. Cross-comparison identified a smaller 31 gene intersecting set; this was not associated with loss of discriminatory power. Conclusions: A 31 geneset which can be used to determine the epithelial content of heterogeneous tumors, was identified. This study has the potential to significantly impact the use of microarray based gene expression data.
Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis
Authors: Robert C. Wirka, Dhananjay Wagh, David T. Paik, Milos Pjanic, Trieu Nguyen, Clint L. Miller, Ramen Kundu, Manabu Nagao, John Coller, Tiffany K. Koyano, Robyn Fong, Y. Joseph Woo, Boxiang Liu, Stephen B. Montgomery, Joseph C. Wu, Kuixi Zhu, Rui Chang, Melissa Alamprese, Michelle D. Tallquist, Juyong B. Kim, Thomas Quertermous
Journal: Nature Medicine (2019)
Comparative Accuracy of Focused Cardiac Ultrasonography and Clinical Examination for Left Ventricular Dysfunction and Valvular Heart Disease
Authors: Jeffrey A. Marbach, Aws Almufleh, Pietro Di Santo, Richard Jung, Trevor Simard, Matthew McInnes, Jean-Paul Salameh, Trevor A. McGrath, Scott J. Millington, Gretchen Diemer, Frances Mae West, Marie-Cecile Domecq, Benjamin Hibbert
Journal: Annals of Internal Medicine (2019)

Incorporating focused cardiac ultrasonography (FoCUS) into clinical examination could improve the diagnostic yield of bedside patient evaluation.To compare the accuracy of FoCUS-assisted clinical assessment versus clinical assessment alone for diagnosing left ventricular dysfunction or valvular disease in adults having cardiovascular evaluation.English-language searches of MEDLINE, Embase, and Web of Science from 1 January 1990 to 23 May 2019 and review of reference citations.Eligible studies were done in patients having cardiovascular evaluation; compared FoCUS-assisted clinical assessment versus clinical assessment alone for the diagnosis of left ventricular systolic dysfunction, aortic or mitral valve disease, or pericardial effusion; and used transthoracic echocardiography as the reference standard.Three study investigators independently abstracted data and assessed study quality.Nine studies were included in the meta-analysis. The sensitivity of clinical assessment for diagnosing left ventricular dysfunction (left ventricular ejection fraction <50%) was 43% (95% CI, 33% to 54%), whereas that of FoCUS-assisted examination was 84% (CI, 74% to 91%). The specificity of clinical assessment was 81% (CI, 65% to 90%), and that of FoCUS-assisted examination was 89% (CI, 85% to 91%). The sensitivities of clinical assessment and FoCUS-assisted examination for diagnosing aortic or mitral valve disease (of at least moderate severity) were 46% (CI, 35% to 58%) and 71% (CI, 63% to 79%), respectively. Both the clinical assessment and the FoCUS-assisted examination had a specificity of 94% (CI, 91% to 96%).Evidence was scant, persons doing ultrasonography had variable skill levels, and most studies had unclear or high risk of bias.Clinical examination assisted by FoCUS has greater sensitivity, but not greater specificity, than clinical assessment alone for identifying left ventricular dysfunction and aortic or mitral valve disease; FoCUS-assisted examination may help rule out cardiovascular pathology in some patients, but it may not be sufficient for definitive confirmation of cardiovascular disease suspected on physical examination.None. (PROSPERO: CRD42019124318).
Comparison of allogeneic stem cell transplantations in chronic myeloid leukemia before and after the era of tyrosine kinase inhibitors.
Authors: Muhit Ozcan, Bengi Ozturk, Mehmet Ozen, Pervin Topcuoglu, Mutlu Arat, Onder Arslan, Osman Ilhan, Hamdi Akan, Meral Beksac, Nahide Konuk, Gunhan Gurman
Journal: Journal of Clinical Oncology (2013)

7038 Background: In this retrospective study we aimed to evaluate the rates and the clinical outcomes of allo-HSCT in CML following the advent of TKIs. Methods: We compared the transplantations (Txs) performed prior to 2002 (old era), the first year of TKIs, with the Txs during and after 2002 (new era). Results: Between 1989 and 2012 inour Tx unit a total of 189 allo-HSCTs were performed in 185 CML patients (second Tx for 4 patients). The ratio of Tx for CML among the whole Tx group decreased from 40 % to 12 % after 2002. The ratio also dropped to less than 5 % after 2008 and increased again to 15% in 2012. Time from diagnosis to Tx was longer in the old era than in the new era (9.2 months vs 15.4 months, p&lt;.0001). The ratio of patients with advanced disease (accelerated or blastic phase) was higher in the new era. Although the progression free survival (PFS) was shorter in the new era than in the old era (median 13.8 months vs 37.1 months, p=0.09), overall survival, Tx outcomes and survival curves did not change. Conclusions: AlloHSCT rates sharply decreased after the TKIs, but a slight increase in recent years have been observed compatible with the TKI’s failure in years. Despite the fact that patients who underwent allo HSCT in the new era had more challenging disease biologically, overall survival was not affected possibly due to post-Tx interventions such as use of TKI alone or with donor lymphocyte infusion. [Table: see text]
Increasing Cases of Shingles in the Eye Raise Key Questions
Authors: Rebecca Voelker
Journal: JAMA (2019)

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
Phase II study of aflibercept (VEGF-Trap) in patients (pts) with recurrent or metastatic transitional cell carcinoma (TCC) of the urothelium: A California Cancer Consortium trial
Authors: P. Twardowski, W. M. Stadler, P. Frankel, P. N. Lara, C. Ruel, G. Chatta, E. I. Heath, D. I. Quinn, D. R. Gandara
Journal: Journal of Clinical Oncology (2009)

e16030 Background: The role and efficacy of subsequent systemic therapies for advanced TCC following failure of frontline platinum-based chemotherapy is unclear. There is evidence that vascular endothelial growth factor (VEGF) is important in the pathophysiology of TCC. Aflibercept is a recombinant fusion protein that binds and neutralizes multiple VEGF isoforms. Methods: Pts with measurable, metastatic or locally advanced urothelial TCC previously treated with one platinum-containing regimen were entered. Aflibercept was given at 4 mg/kg IV q 2 weeks. Response rate (RR) and progression free survival (PFS) were assessed in a 2-stage accrual design (22+18). A maximum of 40 pts were to be accrued to rule out a null hypothesized RR of 4% and PFS of 3 months versus alternative of 15% RR and 5.4 months PFS with α=0.12 and β=0.19. Results: 22 pts were accrued between 11/06–2/08. Pt characteristics: M/F 15/7; Median age 67 years (45–79); 18 had bladder primary. One partial response (4.5% RR) was seen in a pt with nodal metastasis. Median PFS was 3.5 months (95% CI: 1.8–4.1). Attributable grade 3 toxicities included: hypertension (2), proteinuria (1), pulmonary hemorrhage (1), back pain (1), upper GI bleed (1), hyponatremia (1), anorexia (1) and fatigue (1). There were no attributable grade 4+ toxicities Conclusions: Aflibercept was well tolerated with toxicities similar to those seen with other VEGF pathway inhibitors, however it has limited single agent activity in platinum-pretreated TCC pts. [Table: see text]
Preoperative Topical Decolonization—An Additional Strategy to Reduce Oral Antibiotic Prophylaxis for Mohs Infections?—Reply
Authors: John S. Barbieri, Jeremy R. Etzkorn, David J. Margolis
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Efficacy of a Technology-Enhanced Community Health Nursing Intervention vs Standard of Care for Female Adolescents and Young Adults With Pelvic Inflammatory Disease
Authors: Maria Trent, Jamie Perin, Charlotte A. Gaydos, Jennifer Anders, Shang-en Chung, Lisa Tabacco Saeed, Julia Rowell, Steven Huettner, Richard Rothman, Arlene Butz
Journal: JAMA Network Open (2019)

Pelvic inflammatory disease (PID) is a common reproductive health disorder that disproportionately affects female adolescents and young adults. Despite data indicating poor adherence and adverse outcomes among those who experience subsequent Neisseria gonorrhoeae and Chlamydia trachomatis infection, few trials have been designed to address this public health need.