tbuckley/cabot-search huggingface dataset:
Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear
Authors: Naila El Kechai, Elisabeth Mamelle, Yann Nguyen, Nicolas Huang, Valérie Nicolas, Pierre Chaminade, Stéphanie Yen-Nicolaÿ, Claire Gueutin, Benjamin Granger, Evelyne Ferrary, Florence Agnely, Amélie Bochot
Journal: Journal of Controlled Release (2016)
A Retinoic Acid Receptor-α (RARα) Selective Agonist Modulates Procoagulant Activity of Acute Promyelocytic Cells and Induces Their Differentiation Into Neutrophils
Authors: Misako Shibakura, Takatoshi Koyama, Mai Ohsawa, Ryuichi Kamiyama, Shinsaku Hirosawa
Journal: Blood (1998)
Phase I dose escalation study of the oral multi-CDK inhibitor PHA-848125
Authors: R. Tibes, A. Jimeno, D. D. Von Hoff, R. Walker, M. A. Pacciarini, A. Scaburri, F. Fiorentini, M. J. Borad, G. S. Jameson, M. Hidalgo
Journal: Journal of Clinical Oncology (2008)

3531 Background: PHA-848125 is a novel CDK2, CDK1, CDK4 and TRKA oral inhibitor in a first in human study. PHA-848125 showed significant antitumor activity in several tumor models (including prostate, pancreas and lung). More than additive effect was observed in combination with docetaxel and bevacizumab. Methods: Phase I dose escalation study of PHA-848125 administered orally once daily for 7 days in a 2-week cycle (cy) to investigate safety and pharmacokinetics in advanced/metastatic solid tumor patients (pts). Cohorts of 3–6 pts received PHA-848125 at doses of 50 (3 pts),100 (6 pts),150 (6 pts), 200 (6 pts), 300 (1 pt) mg/day. Results: A total of 93 cys were administered to 22 pts (15 male, 7 female). The median number of cys per pt was 3 (range 1–12), with 5 pts receiving 6 cys or more. Side effects were mainly nausea/vomiting/diarrhea (max grade [gr] 2), tremors (max gr 3 at 200 mg/day) and ataxia (gr 3 in the 3 pts at 200 mg/day and gr 4 for the pt at 300 mg/day). Onset of ataxia was around day 4–7 of a cy and reversible in 7–8 days. Occasional mild hematological toxicity at 100 and 200 mg/day was observed and 1 pt had prolonged transaminitis at 200 mg/day. The recommended phase II dose (RP2D) was identified at 150 mg/day. At the RP2D, 6 pts received a total of 35 cys. Toxicity (mild tremors, cold sensitivity in feet/thigh/buttocks, lightheadedness, intermittent orthostatic hypotension, fatigue, neutropenia, nausea) was mild/moderate, reversible and easily manageable. PK data indicate an achievement of maximal plasma concentration at 4h (median), with a half-life of 30–40 hours. Cmax and AUC increased with the dose, with a limited variability among pts. Day 7/day 1 AUC (0–24h) ratio was ≈3. At RP2D, day 7 AUC (0–24h) was 25 μM·h (CV: 34%) and Cmax 1.47 μM. Conclusions: Overall PHA-848125 is well tolerated and tremors and ataxia are dose-limiting. The RP2D is 150 mg/day. To increase the dose and control neurotoxicity, a second schedule of 4 days on/3 days off x 3w q4w is being tested starting from 150 mg/day. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Nerviano Medical Sciences Nerviano Medical Sciences Nerviano Medical Sciences Nerviano Medical Sciences
Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33.
Authors: S Welt, C R Divgi, F X Real, S D Yeh, P Garin-Chesa, C L Finstad, J Sakamoto, A Cohen, E R Sigurdson, N Kemeny
Journal: Journal of Clinical Oncology (1990)

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.
Antidepressants and Pediatric Depression — The Risk of Doing Nothing
Authors: David A Brent
Journal: New England Journal of Medicine (2004)

There is great concern that antidepressants used in children and adolescents may paradoxically increase their risk of suicidal thoughts and behavior. Is this concern valid, and if so, how should it modify our clinical approach to pediatric depression?Twenty-five years ago, long before the introduction of selective serotonin-reuptake inhibitors (SSRIs), the adolescent suicide rate was increasing rapidly, having tripled over the previous two decades, but the risk factors involved were unknown. Adolescents who committed suicide were regarded as misunderstood teenagers who had been under too much stress. There was debate about whether depression could occur in children, and the prevailing . . .
Sompas: a Prospective, Non-Interventional Study (Nis) of the Management of Symptomatic Chemotherapy (Ct)-Induced Anemia (Cia) in Patients (Pts) with Colorectal (Crc), Breast (Bc) or Lung Cancer (Lc) in Austria (At) and Switzerland (Ch)
Authors: W. Eisterer, A. Trojan, A. Galid, F. Haslbauer, G. Delmore, R. Kolb, C. Jaeger, C. Bast, I. Pezzani, M. Schmid
Journal: Annals of Oncology (2014)
PAH-specific therapies improve survival in patients with pulmonary arterial hypertension associated with connective tissue diseases: A Russian single centre experience
Authors: Alexander Volkov, Natalia Yudkina, Ekaterina Nikolaeva, Ildar Kurmukov
Journal: European Respiratory Journal (2014)

Connective tissue diseases (CTD) is one of the frequent causes of the pulmonary arterial hypertension (PAH). Patients with PAH, associated with CTD have a poorer prognosis than other forms. We analyzed effect on survival PAH-therapy, including bosentan, sildenafil, iloprost and combined therapy.  A prospective analysis of 42 patients with PAH-CTD (mean age 48(14) yrs., 35 SSc, 5 SLE and 2 MCTD) were performed. 23 patients were observed when PAH-specified therapy was not available in Russia. 70 CTD-patients without PAH were control group. Survival analyzed by Kaplan-Meier method. PAH-specific therapy was prescribed after PAH verification by RHC. Monotherapy received 25 patients (12 bosentan, 13 sildenafil) and 17 combined therapy. Pulmonary fibrosis and left heart diseases were excluded.  Overall survival from first symptoms estimates was 100%, 97% and 87% at 1, 3 and 5 years in group receiving PAH-specific therapy, and was significantly better than those in a historical cohort of SSc pts 87%, 30% and 4% respectively. Survival in control group (98%, 81% and 78% respectively) was same with CTD-PAH pts. 7 pts (17%) died after a mean follow up 72(33) months.  Conclusion: Overall survival rate was higher than in historical cohort, but 17% pts died. Our study underlines the importance of early start of treatment and importance of hemodynamic evaluation.
Abstract 18348: Hoxb13 is a Meis1 Cofactor Involved in Transcriptional Regulation of Cardiomyocyte Cell Cycle
Authors: Shalini Muralidhar, Wataru Kimura, Suwannee Thet, Hesham A Sadek
Journal: Circulation (2013)

Lower vertebrates, such as newt and zebrafish, retain a robust cardiac regenerative capacity following injury. Although adult mammals lack this cardiac regenerative potential, numerous attempts at unraveling the regenerative potential of the mammalian heart have been pursued to reawaken this process in adult humans. We recently showed that mice are capable of regenerating their hearts shortly after birth following various types of injury. This remarkable regenerative potential appears to be primarily mediated by proliferation of preexisting cardiomyocytes during a brief window of time after birth. However, following arrest of cardiomyocyte proliferation shortly after birth, the mammalian heart loses this regenerative ability. We recently identified Meis1 is a key regulator of postnatal cardiomyocyte cell cycle arrest, where Meis1 deletion in cardiomyocytes results in reactivation of myocyte proliferation in the post-natal heart. However, further the transcriptional networks involved in mediating the postnatal effect of Meis1 in cardiomyocytes remain unclear. The transcriptional activity of Meis1 is known to be tightly linked to a number of Hox genes in various tissues. Therefore, we profiled the expression patterns of entire Hox family of transcription factors by qRT-PCR in the early neonatal window. We found that the only up regulated Hox genes were Hoxa10, Hoxa11, Hoxb13 and Hoxd12, which belonged to the AbdB-like paralogue of Hox genes. Intriguingly, these four transcription factors along with Hoxa9 are the only Hox proteins (out of 37 known mammalian Hox transcription factors) known to interact with Meis1. Detailed analysis of these Hox genes revealed that Hoxb13 mirrors Meis1 expression pattern during normal post-natal development and following injury, shares common cell cycle targets with Meis1, and appears to compensate for loss of Meis1 following its knockout. These findings identify Hoxb13 as a Meis1 cofactor in cardiomyocytes, and an important transcriptional regulator of cardiomyocyte cell cycle.
Care delivery barriers to personalized medicine in breast cancer.
Authors: J. C. Schink, C. B. Weldon, J. R. Trosman, A. B. Benson, A. I. Löffler, W. J. Gradishar
Journal: Journal of Clinical Oncology (2010)

6146 Background: Personalized medicine—pharmacogenomics (PGx) and molecular diagnostics (MDx)—improve outcomes by more accurately individualizing treatment to patients. The Institute of Medicine reported care delivery and coordination issues in oncology impede appropriate care. Using qualitative research, our goal was to identify care delivery and reimbursement barriers to guideline based use of PGx and MDx for breast cancer (BC) patients using examples of BRCA and gene expression profile (GEP) tests. Methods: We conducted 64 interviews with BC care participants: clinicians (n=24) from 1 NCCN and 3 community centers, BC patients (n=8), executives (n=24) from 5 insurers and staff (n=8) from 3 testing laboratories. We conducted two focus groups to further characterize the barriers identified in the interviews. The interviews and focus groups were analyzed according to the framework approach using NVivo software. Results: Theme analysis identified two barriers to the BRCA and GEP test use. (1) Poor timing and sequencing of tests relative to treatment decisions was common within and across groups (see Table). Examples: BRCA test is not ordered preoperatively due to concern that it delays definitive surgery; GEP is ordered only after the first appointment with the oncologist causing treatment delay or decisions made without use of test results. (2) Chemotherapy revenue is significant financial incentive which drives decision making and behavior. This barrier was a significant concern for all non-patient groups. Examples: GEP may inform a clinician to forgo chemotherapy resulting in a net loss of revenue to the physician; E&M codes provide inadequate reimbursement for the physician time needed to discuss test results or treatment options. Conclusions: Inadequate sequencing of breast cancer care and chemotherapy reimbursement create barriers to the use of personalized medicine tests. Processes for appropriate timing and sequencing of tests and new chemotherapy reimbursement models are needed to facilitate the appropriate use of personalized medicine. Barrier Clinicians % Patients % Payers % Labs % Total % Poor timing and sequencing 79 75 46 63 56 Chemotherapy reimbursement 88 0 67 100 71 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genomic Health
Superlatives are commonly used in news coverage of cancer drugs, study finds
Authors: Michael McCarthy
Journal: BMJ (2015)

The use of superlatives such as “breakthrough,” “revolutionary,” and “groundbreaking” are common in news articles about cancer drugs, even in stories reporting results from mouse, cell culture, or other preclinical studies, US research has found.1

The study authors used Google’s news search to identify articles about cancer drugs in which superlatives appeared from 21 to 25 June this year, three weeks after the national meeting of the …
Clinicians Embrace 3D Printers to Solve Unique Clinical Challenges
Authors: Bridget M. Kuehn
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
The stimulator of soluble guanylate cyclase riociguat protects against bleomycin-induced pulmonary fibrosis in mice
Authors: Oleg V. Evgenov, Johannes-Peter Stasch, Mari Mino-Kenudson, Eugene J. Mark, Emmanuel S. Buys, Lin Zou, Ming Zhang, Michael J. Raher, Yan Li, Yan Feng, Rosemary C. Jones, Wei Chao
Journal: European Respiratory Journal (2011)

Background: Effective therapies for pulmonary fibrosis (PF) are currently lacking. Patients with PF develop pulmonary hypertension (PH), in part due to impaired production of endogenous nitric oxide (NO) that activates soluble guanylate cyclase (sGC). We hypothesized that the NO-independent stimulation of sGC might attenuate PF.

Methods: Male C57/BL6 mice (10-12 wks) were subjected to intratracheal bleomycin (0.5 U/kg) and gavage-feeding with the sGC stimulator riociguat (1, 3 or 10 mg/kg/day), the phosphodiesterase 5 (PDE5) inhibitor sildenafil (100 mg/kg/day), a combination of riociguat (1 mg/kg/day) and sildenafil (100 mg/kg/day), or vehicle alone for two weeks.

Results: Bleomycin-induced PH (an increase in the right ventricle systolic pressure and a decrease in the pulmonary acceleration time/ejection time ratio) and the right ventricular hypertrophy were attenuated by riociguat and the combination of riociguat and sildenafil to a greater extent than by sildenafil alone. In the vehicle-treated mice, fibrosis and inflammation diffusely involved lung parenchyma. Riociguat and its combination with sildenafil but not sildenafil alone markedly ameliorated PF and inflammation that was mainly confined to subpleural areas and/or peripheral lung in a patchy distribution. Riociguat increased plasma cGMP levels and also reduced mortality.

Conclusions: Pharmacological stimulation of sGC with riociguat attenuates PF, PH, right ventricular hypertrophy and mortality in the bleomycin-exposed mice. This therapeutic approach appears to be superior to treatment with sildenafil. Stimulation of sGC might represent a new modality for treating PF and related conditions.
Effect of lapatinib plus capecitabine (L+C) on quality of life (QOL) compared to capecitabine (C) alone in ErbB2+ metastatic breast cancer (MBC): An exploratory analysis
Authors: X. Zhou, A. Segreti, D. Cameron, C. E. Geyer, D. Cella, M. Amonkar, S. Stein, M. D. Walker
Journal: Journal of Clinical Oncology (2008)

9532 Background: In a phase III randomized open-label multicenter trial, L+C improved time to progression and progression free survival vs C alone in women with ErbB2+ MBC who had received prior therapy including trastuzumab. Per-protocol QOL analyses showed higher point estimates for QOL scores for L+C vs C suggesting no detriment to QOL for patients receiving combination therapy. Here we report exploratory QOL analyses. Materials: QOL outcomes included the Functional Assessment of Cancer Therapy-Breast (FACT-B) total, FACT-general (FACT-G), trial outcome index (TOI), EQ-5D utility, and EQ-5D visual analog scale (VAS) scores assessed at screening, every 6 weeks for the first 24 weeks, every 12 weeks thereafter and at study withdrawal. Higher scores indicate better QOL. Analyses included: comparison of proportions of patients achieving clinically important differences (CID) in QOL scores for L+C vs C with Fisher’s exact test; relationship between QOL and tumor response status using analysis of covariance adjusted for baseline score; and Pearson correlation coefficients (r) between QOL change from baseline scores and % tumor size reduction. Results: The study randomized 198 subjects to L+C and 201 subjects to C with nearly 50% completing Week 12 and 20% completing Week 24. A greater proportion of patients receiving L+C vs C achieved the CID for all 5 QOL scores (greater by 3 - 12 % points, although the differences in proportions were not statistically significant). Patients who showed a tumor response had higher adjusted mean QOL change from baseline scores compared to those showing disease progression (significant at Week 12, FACT-B total by 7.3, FACT-G 6.1, TOI 5.7, EQ-5D utility 0.11, and ED-5D VAS 10.7). Also, reductions in tumor sizes were associated with improvement in the 5 QOL scores (ranging from r = 0.15 to 0.19, p = 0.02 to 0.07). Conclusions: A greater proportion of patients receiving lapatinib in combination with capecitabine achieved clinically important improvements in QOL scores versus capecitabine alone. These QOL benefits were positively related to the clinical benefits. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Inhibitor of Differentiation-1 (Id1) and Id3 Expression Correlates with Epithelial-Mesenchymal Transition (Emt)-Related Proteins (Emtrp) in Non-Small Cell Lung Carcinoma (Nsclc)
Authors: I. Gil-Bazo, E. Castanon Alvarez, I. Lopez, M. Ponz-Sarvisé, C.D. Rolfo, M. Santisteban, J.M. Lopez-Picazo, J.P. Fusco, L. Ceniceros, J. Legaspi, A. Soltermann
Journal: Annals of Oncology (2014)
&lt;italic&gt;Trans&lt;/italic&gt; Fatty Acids in Tumor Development and the Host Survival&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A B Awad
Journal: JNCI Journal of the National Cancer Institute (1981)

Because trans fatty acids exist in the American diet and their relationship to cancer incidence has been proposed, studies were designed to investigate their possible role in the development of Ehrlich tumor cells in inbred CBA mice. Feeding elaidic acid (18:1 delta 9, trans) to Ehrlich ascites tumor-bearing animals resulted in tumors that incorporated more thymidine into their cells and into their acid-insoluble fraction as compared with those grown in animals fed the natural oleic acid (18:1 delta 3, cis)-rich diet. Elaidic acid diet feeding at 5% in the diet also resulted in a reduction in the host survival rate. This reduction ranged from 23 to 45%.
Age, tumor grade, and mitosis-karyorrhexis index (MKI) are independently predictive of outcome in neuroblastoma (NB)
Authors: W. B. London, H. Shimada, E. d'Amore, M. Peuchmar, B. Hero, A. Faldum, D. Machin, V. Mosseri, T. Iehara, A. Pearson, S. L. Cohn
Journal: Journal of Clinical Oncology (2007)

9558 Background: NB is a rare pediatric malignancy (USA incidence 1:100,000), and treatment is tailored according to risk. NB patients (pts) in the Children's Oncology Group are stratified to low, intermediate or high risk according to age at diagnosis, stage of disease, MYCN status, histopathology, and tumor cell ploidy. The International NB Pathologic Classification (INPC) uses age at diagnosis to classify tumors as Favorable or Unfavorable histology. This results in duplication of the prognostic contribution of age when both age and INPC, with other factors, are used to assign risk groups or build multivariable models of prognostic factors. To eliminate the confounding contribution of age and INPC, and determine if tumor pathology is predictive of outcome independent of age, we performed multivariable modeling using the underlying pathologic components of INPC. Methods: Using the largest cohort of NB pts ever assembled (n=11,054; 1980–2002; international), 1,860 pts with known age, INPC, diagnosis, tumor grade of differentiation, MKI, and outcome were identified. Half were selected at random (reserving the other half for validation) for analysis. A Cox multivariable model was used to perform survival tree regression to identify factors statistically significantly (p&lt;0.05) prognostic of event-free (relapse, progression, secondary malignancy, death) survival (EFS). Factors tested were age, diagnosis, grade, and MKI. Results: Age (&lt;547 v. ≥547 days) was the most significant factor (p&lt;0.0001). Within pts &lt;547 days, no factors were significantly prognostic. Within pts ≥547 days, stroma-poor NB and nodular (composite) ganglioNB was associated with significantly lower EFS than intermixed ganglioNB and ganglioneuroma, maturing (p&lt;0.0001). Pts were further stratified within the latter diagnoses by MKI (Low/Intermediate v. High) (p=0.0016). These results were validated in the other half of the cohort. Conclusions: Histologic features of NB tumors are predictive of outcome. To remove confounding of the prognostic contribution of age, the underlying histologic features of the tumor (diagnosis, MKI, grade) should be used instead of INPC class to assign pts to risk groups or identify prognostic factors with multivariable models. No significant financial relationships to disclose.
A Comparative Oncology Study of Canine and Human Genomics and Proteomics in Peripheral T-Cell Lymphoma (PTCL): Examination of Shared Oncogenic Signaling for Biomarker and Therapeutic Target Discovery
Authors: Athena Kritharis, Trent Fowler, Ravi Dashnamoorthy, Kristine E Burgess, Afshin Beheshti, Nassera Abermil, Ananda Roy, Lynn Hlatky, Monika Pilichowska, Elizabeth McNiel, Andrew M. Evens
Journal: Blood (2014)