tbuckley/cabot-search huggingface dataset:
Disruption of Her-2 at subdomains I and III interaction promotes an overactivation of erbB receptor family and resistance to chemotherapeutical drugs.
Authors: Anatilde Gonzalez-Guerrico, Ingrid Espinoza, Ruth Lupu
Journal: Clinical Cancer Research (2007)

B51   Breast cancer growth is regulated by coordinated actions of the estrogen receptor (ER) and various growth factor receptor signaling pathways. ER, in response to E2, can interact with growth factor tyrosine kinase receptors such us HER2 and IGFR and activate their cascades. Therapies to target HER2 or ER have been developed and are currently being used successfully in many cases. However, a large population of breast cancer patients that are HER2 and ER positives are refractory to trastuzumab (used to target HER2) or to the antiestrogen tamoxifen (used to target ER positive tumors). Once the ER is blocked, cells take advantage of the Her-2 pathway and vice versa. The mechanism of how ER positive tumors that overexpress Her-2 become more aggressive and resistant to treatment is not very well understood. In this study we investigated if an extracellular domain (ECD) site in HER2 receptor, which is involved in the dimerization of the receptor, plays a role in tumor progression, resistance to antiestrogens and Her-2 therapy. We developed a deletion mutant of the sub-domain III of Her-2 ECD (Her-2 mutant). That domain contributes to most of the determinants involved in ligand binding and signal transduction. Stable BT474 cell lines overexpressing the empty vector (pLXSN) and Her-2 mutant were generated using retroviral vector. In these cell lines, first we investigated if Her-2 mutant promotes anchorage-independent growth advantage in response to E2. Her-2 mutant cells formed more colonies of a larger size than control cells, in the presence and in the absence of E2, indicating that cells that overexpress Her-2-mutant are estrogen independent and acquired a higher E2 sensitivity. However, Her-2 mutant showed to be antiestrogen sensitive as did the control cells. We did not observe differences in ERE-luciferase promoter activity between Her-2 mutant and control cells, suggesting that the growth advantage of Her-2 mutant depends on non-genomic ER activity. In addition, Her-2 mutant was resistant to Trastuzumab in anchorage-independent growth. By western blot analysis we observed that Trastuzumab treatment for 24 h causes downregulation on Her-2 levels only in the control cells. Moreover, we found that the Her-2 mutant has higher basic levels of activation of EGFR, Her-2 and Her-3, and other tyrosine kinase receptors and Akt. These results suggest that the deletion of the ECD site in the Her-2 receptor promotes elevated activation of erbB receptors, most probably by stabilization of Her-2 heterodimers with EGFR and Her-3. All together, these results suggest that there is a crosstalk between ER and erbB-family receptor that provides cell growth advantage, resistance to Her-2 therapy and estrogen independence.
A phase 1b/2 study of CD30-specific chimeric antigen receptor T-cell (CAR-T) therapy in combination with bendamustine in patients with CD30+ Hodgkin and non-Hodgkin lymphoma.
Authors: Steven I. Park, Jonathan Stuart Serody, Thomas C. Shea, Natalie Sophia Grover, Anastasia Ivanova, Kaitlin Morrison, Paul Eldridge, Katie Mckay, Catherine J Cheng, Deborah Covington, Kimberly Wehner, Gianpietro Dotti, Barbara Savoldo
Journal: Journal of Clinical Oncology (2017)

TPS3095 Background: CAR-T therapy has emerged as one of the most promising therapeutic approaches for lymphoma. CD30 antigen is expressed on virtually all Hodgkin (HL) and various subtypes of non-Hodgkin lymphoma (NHL). HL and NHL are both sensitive to the cellular immune response and antibody-directed therapy, which makes CD30 an excellent target for CAR-Ts. In the “first-in-human” clinical trial of CD30.CAR-Ts, the dose of 2 × 10 8 CD30.CAR-Ts/m 2 was found to be safe; however, no conditioning therapy was given prior to CD30.CAR-T infusion and the expansion of CAR-Ts was thus limited. In the current study, we have further developed the CD30.CAR-T-based therapy by combining it with bendamustine. We hypothesized that bendamustine may improve therapeutic efficacy of CD30.CAR-Ts by causing sufficient depletion of endogenous immune cells to facilitate the expansion and persistence of CAR-Ts in vivo. Methods: In this phase 1b/2 clinical study, patients with CD30+ HL or NHL receive bendamustine followed by CD30.CAR-Ts (NCT02690545). The primary objective is to establish the safety of CD30.CAR-Ts in combination with bendamustine. Secondary objectives include estimation of 2-year overall and progression-free survival rates. Patients receive bendamustine (90 mg/m 2 on days 1 and 2) followed by CD30.CAR-Ts within 1 to 4 days of lymphodepletion. The maximal tolerated dose is determined based on 3 + 3 design for dose escalation starting at 1 × 10 8 CD30.CAR-Ts/m 2 . If the first 3 enrolled subjects do not experience a DLT within 6 weeks of the cell infusion, the number of cells for the infusion is increased to 2 x 10 8 /m 2 . Once the number of cells for infusion is established, up to 25 subjects will be enrolled in the Phase 2 portion of the study to further establish the safety and efficacy of this treatment regimen. Response will be assessed at 6 weeks after CD30.CAR-Ts infusion, and a second CD30.CAR-Ts infusion equal to or lower than the dose may be administered to patients with partial response or stable disease. Patient’s peripheral blood samples will be evaluated at various time points to monitor safety, function, and persistence of transduced T-cells. Clinical trial information: NCT02690545.
Papillary Muscle Dysfunction Attenuates Ischemic Mitral Regurgitation in Patients With Localized Basal Inferior Left Ventricular Remodeling
Authors: Takeshi Uemura, Yutaka Otsuji, Kenichi Nakashiki, Shiro Yoshifuku, Yuko Maki, Bo Yu, Naoko Mizukami, Eiji Kuwahara, Shuichi Hamasaki, Sadatoshi Biro, Akira Kisanuki, Shinichi Minagoe, Robert A. Levine, Chuwa Tei
Journal: Journal of the American College of Cardiology (2005)
Autologous Bone Marrow Transplantation Workshop&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: Luz D. Hammershaimb, M.D., Gary B. Witman, M.D., Silvia Marsoni, M.D., John Y. Killen, M.D.
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Autologous Bone Marrow Transplantation Workshop Get access Luz D. Hammershaimb, M.D., Luz D. Hammershaimb, M.D. Division of Cancer Treatment National Cancer Institute, Bethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar Gary B. Witman, M.D., Gary B. Witman, M.D. Division of Cancer Treatment National Cancer Institute, Bethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar Silvia Marsoni, M.D., Silvia Marsoni, M.D. Division of Cancer Treatment National Cancer Institute, Bethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar John Y. Killen, M.D. John Y. Killen, M.D. Division of Cancer Treatment National Cancer Institute, Bethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 67, Issue 1, July 1981, Pages 223–224, https://doi.org/10.1093/jnci/67.1.223 Published: 01 July 1981
Phenotypic Heterogeneity of Circulating Tumor Cells Informs Clinical Decisions between AR Signaling Inhibitors and Taxanes in Metastatic Prostate Cancer
Authors: Howard I. Scher, Ryon P. Graf, Nicole A. Schreiber, Brigit McLaughlin, Adam Jendrisak, Yipeng Wang, Jerry Lee, Stephanie Greene, Rachel Krupa, David Lu, Pascal Bamford, Jessica E. Louw, Lyndsey Dugan, Hebert A. Vargas, Martin Fleisher, Mark Landers, Glenn Heller, Ryan Dittamore
Journal: Cancer Research (2017)

Abstract The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a College of American Pathologists–accredited and Clinical Laboratory Improvement Amendments–certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTC) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified on the basis of the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of the second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients. Cancer Res; 77(20); 5687–98. ©2017 AACR.
Degradation of Cystine Peptides by Tissues. II. Distribution of Exocystine Desulfurase and Dehydropeptidase in Tissue Extracts of Various Species&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Jesse P. Greenstein, Florence M. Leuthardt
Journal: JNCI Journal of the National Cancer Institute (1944)

Journal Article Degradation of Cystine Peptides by Tissues. II. Distribution of Exocystine Desulfurase and Dehydropeptidase in Tissue Extracts of Various Species Get access Jesse P. Greenstein, Jesse P. Greenstein senior biochemist National Cancer Institute, National Institution of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Florence M. Leuthardt Florence M. Leuthardt laboratory technician National Cancer Institute, National Institution of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 3, December 1944, Pages 223–225, https://doi.org/10.1093/jnci/5.3.223 Published: 01 December 1944
Abstract P119: S100A6 Regulates Endothelial Cell Physiology
Authors: Shumei Ren, Karsten Peppel, Patrick Most
Journal: Circulation Research (2011)

Endothelial cell dysfunction is central to the development of cardiovascular pathologies. While Calcium cycling is of recognized importance to myocyte physiology and cardiac perfomance, the role of Ca2+ signaling in endothelial cell (EC) physiology remains relatively unexplored. In this study we investigated the role of S100A6 (calcyclin), an EF-hand type Ca2+ -binding protein that modulates target protein function dependent upon intracellular Ca2+ signaling. S100A6 displays cytoplasmic distribution in quiescent, confluent HUVEC, but translocates to the nucleus upon serum stimulation. Oxidative stress, induced by incubation of HUVEC with H¬2O2 (150 uM) leads to redistribution of nuclear S100A6 to the cytosol and cell cycle arrest. Knockdown of S100A6 by siRNA transfection reduced S100A6 levels by over 70% and diminished DNA synthesis by more than 75% (±12%, n=9, p&lt;0.01), as well as expression of the proliferation markers PCNA and KI-67 (by more than 70% (±15%, n=9, p&lt;0.01). Reduced S100A6 levels in HUVEC lead to an increase in cellular senescence, as measured by the expression of senescence associated β-galactosidase expression (by more than 6-fold, n=4, p&lt;0.01) and a reduction of EC tube formation on matrigel matrix (by more than 90%, n=3, p&lt;0.01). Reduction of S100A6 increased the expression of the cell cycle control and DNA repair-associated gene BRCA2, but did not change in the expression of BRCA1, cyclins or p53 (by RT-PCR array). We conclude that Ca2+ regulation by S100A6 is essential for multiple aspects of EC physiology.
Patients are positive about accessing their records
Authors: Richard Fitton
Journal: BMJ (2017)

Millenson discusses patient centred care.1 With North Derbyshire Family Health Services Authority, patients helped me to plan, design, and manage a purpose built, patient centred medical centre in Derbyshire from 1993 to 2006. The practice had an information room with a touch screen information booth, a library, patient volunteers, and four or five specialist patient training groups, including a computer group. Patients sat on the …
Development and Validation of a Tool to Identify Patients With Type 2 Diabetes at High Risk of Hypoglycemia-Related Emergency Department or Hospital Use
Authors: Andrew J. Karter, E. Margaret Warton, Kasia J. Lipska, James D. Ralston, Howard H. Moffet, Geoffrey G. Jackson, Elbert S. Huang, Donald R. Miller
Journal: JAMA Internal Medicine (2017)

Hypoglycemia-related emergency department (ED) or hospital use among patients with type 2 diabetes (T2D) is clinically significant and possibly preventable.To develop and validate a tool to categorize risk of hypoglycemic-related utilization in patients with T2D.Using recursive partitioning with a split-sample design, we created a classification tree based on potential predictors of hypoglycemia-related ED or hospital use. The resulting model was transcribed into a tool for practical application and tested in 1 internal and 2 fully independent, external samples. Development and internal testing was conducted in a split sample of 206 435 patients with T2D from Kaiser Permanente Northern California (KPNC), an integrated health care system. The tool was externally tested in 1 335 966 Veterans Health Administration and 14 972 Group Health Cooperative patients with T2D.Based on a literature review, we identified 156 candidate predictor variables (prebaseline exposures) using data collected from electronic medical records.Hypoglycemia-related ED or hospital use during 12 months of follow-up.The derivation sample (n = 165 148) had a mean (SD) age of 63.9 (13.0) years and included 78 576 (47.6%) women. The crude annual rate of at least 1 hypoglycemia-related ED or hospital encounter in the KPNC derivation sample was 0.49%. The resulting hypoglycemia risk stratification tool required 6 patient-specific inputs: number of prior episodes of hypoglycemia-related utilization, insulin use, sulfonylurea use, prior year ED use, chronic kidney disease stage, and age. We categorized the predicted 12-month risk of any hypoglycemia-related utilization as high (>5%), intermediate (1%-5%), or low (<1%). In the internal validation sample, 2.0%, 10.7%, and 87.3% were categorized as high, intermediate, and low risk, respectively, with observed 12-month hypoglycemia-related utilization rates of 6.7%, 1.4%, and 0.2%, respectively. There was good discrimination in the internal validation KPNC sample (C statistic = 0.83) and both external validation samples (Veterans Health Administration: C statistic = 0.81; Group Health Cooperative: C statistic = 0.79).This hypoglycemia risk stratification tool categorizes the 12-month risk of hypoglycemia-related utilization in patients with T2D using only 6 inputs. This tool could facilitate targeted population management interventions, potentially reducing hypoglycemia risk and improving patient safety and quality of life.
Association of Serum Ferritin with Diabetes and Alcohol in Patients with Non-Viral Liver Disease-Related Hepatocellular Carcinoma
Authors: Rohan C. Siriwardana, Madunil A. Niriella, Anuradha Dassanayake, Dileepa Ediriweera, Bhagya Gunetilleke, Thenuka Sivasundaram, Janaka de Silva
Journal: Liver Cancer (2017)

Non-alcoholic fatty liver disease is a leading cause for hepatocellular carcinoma (HCC) in Sri Lanka. Diabetes mellitus, alcohol abuse, and liver inflammation are known to increase the risk of HCC. The present study evaluates serum ferritin levels in a cohort of patients with non-viral HCC (nvHCC).Consecutive patients with nvHCC presenting to the Colombo North Liver transplant Service, Ragama, from January 2012 to July 2013 were investigated. All were negative for hepatitis B and C. At registration, 5 mL of serum was separated into plain tubes, stored at -80°C and analysed for ferritin using an enzyme-linked immunosorbent assay. Correlation between the serum ferritin and patient risk factors, liver status, and tumour characteristics were analysed.There were 93 patients with nvHCC (median age 65 [12-82] years; 82 [88.2%] males). The median ferritin level was 246.2 μg/L, and 38 (40.86%) patients had elevated ferritin. Non-diabetics (median 363.5 mg/L, p = 0.003) and alcohol abusers (median 261.2 mg/L, p = 0.018) had higher ferritin levels. On multiple-variable analysis, being non-diabetic (p = 0.013) and alcoholic (p = 0.046) was significantly associated with high serum ferritin. No association was found with body mass index, tumour stage, size, macrovascular invasion, number of nodules, alpha-fetoprotein, bilirubin, international normalized ratio, and survival.In patients with nvHCC, serum ferritin levels are higher in non-diabetics and alcoholics.
Properties of the Mouse Mammary-Tumor Agent
Authors: Howard B. Andervont, W. Ray Bryan
Journal: JNCI Journal of the National Cancer Institute (1944)

Journal Article Properties of the Mouse Mammary-Tumor Agent Get access Howard B. Andervont, Howard B. Andervont principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Ray Bryan W. Ray Bryan biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 2, October 1944, Pages 143–149, https://doi.org/10.1093/jnci/5.2.143 Published: 01 October 1944
Acoustic Cluster Therapy(ACT)を伴う超音波穿法は膵管腺がんの皮下異種移植モデルにおいて一時的な腫瘍容積の減少をもたらした
Authors: Kotopoulis Spiros, Stigen Endre, Popa Mihaela, Safont Mireia Mayoral, Healey Andrew, Kvale Svein, Sontum Per, Gjertsen Bjorn Tore, Gilja Odd Helge, McCormack Emmet
Journal: Journal of Controlled Release (2017)
Genetic Engineering: Reprise
Journal: JAMA (1972)

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
Patient-centred health care for people with chronic skin conditions
Authors: P. Abbott
Journal: British Journal of Dermatology (2017)

Patient‐centredness is an established principle of high‐quality health care that applies to individual clinician–patient interactions as well as how patients are treated by the health system as a whole.1 Better health outcomes and greater patient satisfaction can be achieved when healthcare providers and patients find common ground and a shared commitment to care that is effective and acceptable for individuals in their context.2,3 In this issue of the BJD, Khoury and colleagues4 present their qualitative study of the experiences and expectations of people with psoriasis who were receiving care at a hospital outpatient clinic after treatment from a private dermatologist had failed. From the patients' perspectives, the clinic routines and consultations were often physician‐centred, and their individual contexts and questions were not considered adequately within often brief consultations. Patient‐centredness has been expressed as clinicians trying to see the illness through the patient's eyes.5 People with psoriasis and other chronic skin conditions can perceive that treating clinicians discount the importance of their symptoms. In particular, the psychological sequelae of such conditions can be unacknowledged and poorly managed,6 contributing to poor relationships with general practitioners and dermatologists.7 Dermatologists do recognize the need to detect and manage mental health problems in people with psoriasis, but can disagree as to the extent of their role in ensuring this happens.8 This may be related in part to concerns about dermatologists' skills and confidence in mental health management and a resulting preference for standardized screening and referral to colleagues if mental health problems are detected.8 However, openness to exploring patients' well‐being and their concerns while providing care for their chronic skin condition does not require mental health training. Rather, it can be seen as a core dimension of expert dermatological care9 and a well‐accepted expectation of quality doctor–patient interactions.
Studies in Carcinogenesis XIII. Tumors of the Spleen and Liver in Mice Following the Introduction of Hydrocarbons Into These Organs&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: M. J. Shear, Harold L. Stewart, Arnold M. Seligman
Journal: JNCI Journal of the National Cancer Institute (1940)

Journal Article Studies in Carcinogenesis XIII. Tumors of the Spleen and Liver in Mice Following the Introduction of Hydrocarbons Into These Organs Get access M. J. Shear, M. J. Shear principal biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold L. Stewart, Harold L. Stewart senior pathologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Arnold M. Seligman Arnold M. Seligman student research fellow Harvard Medical School Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 3, December 1940, Pages 291–302, https://doi.org/10.1093/jnci/1.3.291 Published: 01 December 1940