tbuckley/cabot-search huggingface dataset:
Mucin-1 protein and mRNA expression in breast cancer: Predictive value for therapy response and survival after neoadjuvant chemotherapy.
Authors: Bruno Valentin Sinn, Gunter Von Minckwitz, Carsten Denkert, Holger Eidtmann, Silvia Darb-Esfahani, Antje Belau, Ralf Kronenwett, Hans-Juergen Holzhausen, Keyur Mehta, Sibylle Loibl
Journal: Journal of Clinical Oncology (2012)

522 Background: Mucin-1 (MUC1) is expressed in normal epithelial cells and in breast cancer. Immunotherapeutic agents targeting MUC1 are currently tested in clinical trials. Methods: We evaluated the frequency of MUC1 expression by immunohistochemistry (IHC; n = 691) and quantitative RT-PCR (qRT-PCR; n = 286) in formalin-fixed paraffin-embedded (FFPE) pre-treatment biopsies from patients of the GeparTrio trial (NCT 00544765). mRNA levels were analyzed as a continuous variable, a distribution-based cut-off was chosen for IHC data. The predictive value for therapy response and survival after neoadjuvant anthracycline/taxane-based chemotherapy (CTX) was evaluated. Results: MUC1 was detectable by IHC in 95%. qRT-PCR covered a dynamic range of 3 orders of magnitude. IHC and mRNA data were correlated (p &lt; 0.001). MUC1 was detected in higher quantities in HR+ tumors (p &lt; 0.001), the lowest levels were found in HR-/HER2- tumors (p &lt; 0.001). High MUC1 protein and mRNA expression were associated with lower probability of pathologic complete response (pCR) in the overall population (p &lt; 0.001) and in HR+ (p = 0.004 and &lt; 0.001), HER2- (p &lt; 0.001) and HR+/HER2- tumors (p &lt; 0.001). In multivariable logistic regression, MUC1 was independently predictive (high MUC1 protein: odds ratio (OR) 0.464, 95% CI 0.300 – 0.719, p = 0.001; MUC1 mRNA (per 20-dCT unit): OR 0.673, CI 0.546 – 0.829, p &lt; 0.001). MUC1 protein and mRNA expression were associated with longer patient survival in the overall population (p = 0.03 and &lt; 0.001) and in HER2- tumors (p = 0.005 and &lt; 0.001). MUC1 mRNA was also prognostic in HR+ (p &lt; 0.001) and HR+/HER2- tumors (p = 0.001). In multivariable analysis, protein and mRNA expression were independently prognostic (high MUC1 protein: hazard ratio (HR) 0.388, CI 0.166 – 0.907, p = 0.029; MUC1 mRNA per 20-dCT unit: HR 0.763, CI 0.595 – 0.909, p = 0.005). Conclusions: MUC1 is frequently expressed in breast cancer and detectable by IHC and qRT-PCR from FFPE tissue. Despite its association with HR+ status, it provides independent predictive information for therapy response and survival after neoadjuvant CTX. In clinical immunotherapy trials, MUC1 expression may serve as a predictive marker.
Natural History of Non-Infectious, Ibrutinib-Attributable Adverse Events Leading to Alternative BTK Inhibitor Use in CLL
Authors: Polina Shindiapina, Soun Khountham, Kerry A. Rogers, Jeffrey Jones, Leslie Andritsos, Kami J. Maddocks, Joseph M. Flynn, Jennifer A. Woyach, John C. Byrd, Farrukh T. Awan
Journal: Blood (2016)
RANKL coordinates multiple osteoclastogenic pathways by regulating expression of ubiquitin ligase RNF146
Authors: Yoshinori Matsumoto, Jose Larose, Oliver A. Kent, Melissa Lim, Adele Changoor, Lucia Zhang, Yaryna Storozhuk, Xiaohong Mao, Marc D. Grynpas, Feng Cong, Robert Rottapel
Journal: Journal of Clinical Investigation (2017)

Bone undergoes continuous remodeling due to balanced bone formation and resorption mediated by osteoblasts and osteoclasts, respectively. Osteoclasts arise from the macrophage lineage, and their differentiation is dependent on RANKL, a member of the TNF family of cytokines. Here, we have provided evidence that RANKL controls the expression of 3BP2, an adapter protein that is required for activation of SRC tyrosine kinase and simultaneously coordinates the attenuation of β-catenin, both of which are required to execute the osteoclast developmental program. We found that RANKL represses the transcription of the E3 ubiquitin ligase RNF146 through an NF-κB-related inhibitory element in the RNF146 promoter. RANKL-mediated suppression of RNF146 results in the stabilization of its substrates, 3BP2 and AXIN1, which consequently triggers the activation of SRC and attenuates the expression of β-catenin, respectively. Depletion of RNF146 caused hypersensitivity to LPS-induced TNF-α production in vivo. RNF146 thus acts as an inhibitory switch to control osteoclastogenesis and cytokine production and may be a control point underlying the pathogenesis of chronic inflammatory diseases.
A Novel Orally Active Small Molecule Potently Induces G1 Arrest in Primary Myeloma Cells and Prevents Tumor Growth by Specific Inhibition of Cdk4/6.
Authors: Linda B. Baughn, Maurizio Di Liberto, Kaida Wu, Peter Toogood, Tracey Louie, Rachel Gottschalk, Ruben Niesvizky, Hearn J. Cho, Scott Ely, Malcolm A.S. Moore, Selina Chen-Kiang
Journal: Blood (2006)
Abstract P5-11-16: Do patients and nurses outside clinical trial prefer subcutaneous trastuzumab over conventional intravenous infusion? Instituto Oncologico Nacional experience
Authors: O Castillo-Fernandez, A Cabreja, E Arauz, D Bellido, M Lim, R Lopez, L Montano
Journal: Cancer Research (2017)

Abstract Background In the PrefHer study, subcutaneous administration of trastuzumab was preferred over intravenous administration (iv). In 2014 our hospital approved subcutaneous (sc) trastuzumab for use in patients with early or metastatic Her 2 positive breast cancer. The aim of this study was to evaluate patients (pts) and nurses´s preferences in our institution. Methods Patients with Her2 postive breast cancer and nurses who had received or administered both sc and iv trastuzumab were interviewed to evaluate their preference. Preference for sc was compared with a linear chi squared test. Results 55 pts were interviewed. Median age was 53 years (30-83). 30 patients in adjuvant/neoad setting and 25 pts in the palliative setting. 41 pts (74.5%) preferred sc 95% CI (63-86) , 3 pts (5.5%) preferred iv 95% CI (-0.5-11.5) and 11 pts (20%) did not have preference 95% CI (9.4-20%) p&amp;lt; 0.0001. 72% of pts considered that sc trastuzumab was more convenient (p&amp;lt;0.0001). 11 nurses experienced with both iv and sc trastuzumab administration answered the questionnaire. Median age 41 years (30-55). 10/11 nurses preferred sc administration, 1/10 indicated no preference. All nurses considered that sc was the most convenient administration method for the patients and is highly recommended. The main reason for patients and nurses preference was that sc administration saved time. Conclusion Patients and nurses prefer s.c over iv trastuzumab. Our results are consistent with PrefHer study. Incorporation of sc trastuzumab could improve quality of care in patients with Breast Cancer Her 2 positive. Citation Format: Castillo-Fernandez O, Cabreja A, Arauz E, Bellido D, Lim M, Lopez R, Montano L. Do patients and nurses outside clinical trial prefer subcutaneous trastuzumab over conventional intravenous infusion? Instituto Oncologico Nacional experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-16.
Tumor response rate as a function of number of prior therapies in phase II and III trials of topotecan (T) and eniluracil/5FU (EU)
Authors: P. T. Ho, R. A. Fleming, L. Pandite, T. A. Lampkin, A. A. Flynn
Journal: Journal of Clinical Oncology (2007)

2501 Background: Patients with 2 or more prior cytotoxic treatment regimens are often excluded from clinical trials because of expectations for greater tumor resistance to treatment. This retrospective cross-study analysis evaluated the relationship between tumor response rate (RR) and the number of prior therapies received. Methods: Phase II and III studies in the GSK database of topotecan (T, n=18) in patients with ovarian or small cell lung carcinoma (SCLC) and of eniluracil/5FU (EU, n=5) in patients with colorectal (CRC) or breast cancer were analyzed. This provided a total 4,220 patients consisting of 1,898 receiving T, 465 receiving various T comparator chemotherapy (paclitaxel, cyclophosphamide, doxorubicin or vincristine), 1,036 receiving EU, and 821 receiving EU comparator (5FU + leucovorin). Number of prior treatments was defined as the sum of all cytotoxic treatment regimens received. Best response was defined according to standard tumor response criteria with missing data or inevaluable assessments considered as progressive disease. Experimental (T or EU) vs. respective comparator arms were combined and an overall RR (CR + PR) in the analysis populations was assessed as a function of the number of prior treatments. Results: The overall RR for ovarian and SCLC patients receiving first-line treatment was 47%. RR declined to 17% for second-line therapy but was unchanged at 18% for those receiving third-line treatment. For all (CRC + breast cancer) patients in EU studies, there were no significant differences between first-, second-, or third-line treatment (RR=12%, 10% and 10% respectively). However, within the limited subset of breast cancer patients (n=145) in EU studies, RR was 54%, 14%, and 11% for first-, second-, and third-line treatments, respectively, suggesting no difference in RR once second-line treatment was administered. Conclusions: The presumption that a higher number of prior regimens always equates with greater treatment resistance may be incorrect. Patients in this analysis with 1 vs. 2 prior therapies exhibit equivalent RR to a broad range of cytotoxic therapies. Exclusion from clinical trials of patients with &gt;1 prior treatment regimen who otherwise meet study eligibility criteria may not be warranted. No significant financial relationships to disclose.
Intensity of palliative care and its impact on the aggressiveness of end-of-life care in patients with advanced pancreatic cancer.
Authors: Raymond Woo-Jun Jang, Monika K. Krzyzanowska, Camilla Zimmermann, Nathan Taback, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2013)

9518 Background: Quality indicators have been developed to avoid overly aggressive care in patients with advanced cancer. Specialized palliative care (PC) may reduce overly aggressive care in patients with advanced pancreatic cancer. Our objective was to examine the impact of the intensity of specialized PC (defined as a physician consultation focusing on PC needs, lasting at least 40 minutes) on (a) use of chemotherapy within 14 days of death; (b) more than one emergency department (ED) visit; (c) more than one hospitalization; and (d) at least one intensive care unit (ICU) admission, all within 30 days of death. Methods: A retrospective population-based cohort study using linked administrative databases in Ontario, Canada was conducted with patients diagnosed with advanced pancreatic cancer from Jan 1 2005 to Dec 31 2010. Multivariable logistic regression analyses were performed with the above quality indicators as the outcomes of interest and the intensity of PC visits as the exposure, adjusting for other variables (age, sex, comorbidity, rurality, and health region). Intensity of PC was defined in both absolute numbers (ie 0, 1, 2, 3+ visits) and rate of visits per month. Results: Of 6076 patients with advanced pancreatic cancer, 5381 had died at last followup. 2816 (52%) received a PC consultation, 218 (4%) received chemotherapy near death, 234 (4%) patients went to the ICU near death, 993 (18%) had multiple ED visits near death, and 447 (8%) had multiple hospitalizations near death. 2565 (48%) had 0 PC visits, 513 (10%) had 1, 555 (10%) had 2, and 1748 (32%) had 3 or more. In multivariable analyses, having had one PC consultation was associated with a lower odds of ICU admission near death (odds ratio (OR) 0.25; 95% CI 0.13-0.46), multiple ED visits near death (OR 0.44; 95% CI 0.33-0.58), and multiple hospitalizations near death (OR 0.47; 95% CI 0.33-0.69). Two PC visits were associated with a lower OR for chemotherapy near death (OR 0.26; 95% CI 0.14-0.51). Using the monthly PC visit rate, a higher rate was associated with less aggressive care for each outcome. Conclusions: In patients with advanced pancreatic cancer, more intensive PC involvement is associated with less frequent overly aggressive care.
Allogeneic Stem Cell Transplantation (allo-SCT) in 192 Acute Myeloid Leukemias (AML): A Single Center Experience From 1982 to 2010
Authors: Carmen Montes-Gaisan, Jorge Monge, Clara Martin, Zurie Diez, Johny Alberto Hinostroza, Javier Nuez, Marta Albajar, Carlos Richard, Eulogio Conde, Arturo Iriondo
Journal: Blood (2011)
Abstract P5-04-04: Activation of ERβ in triple negative breast cancer results in cell cycle arrest
Authors: JM Reese, ES Bruinsma, DG Monroe, MP Goetz, JR Hawse
Journal: Cancer Research (2017)

Abstract Background: Triple negative breast cancer (TNBC), which comprises approximately 20% of breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and Her-2 expression. However, we have identified that 30% of TNBC patients express estrogen receptor beta (ERβ), a nuclear hormone receptor and potential therapeutic target. Here we examine the effects of ERβ in triple negative breast cancer cell lines. Methods: Cell lines that stably express ERβ were used to perform microarray analyses following five days of estrogen treatment. Ingenuity pathway analysis was conducted on differentially expressed genes to determine alterations in biological pathways. The effects of ERβ on cell cycle progression and apoptosis was determined. Cell cycle-related expression changes were confirmed with RT-qPCR and western blotting. The impact of siRNA mediated gene silencing of CDK1 on TNBC cell proliferation was assessed as was the ability of ERβ to elicit anti-proliferative effects in the setting of CDK1 knockdown. Results: We have shown that estrogen or ERβ-specific agonist treatment causes decreased proliferation of ERβ+ TNBC cells. This inhibitory effect is not due to programmed cell death but rather a G1/S phase cell cycle arrest as indicated by flow cytometry experiments. Microarray data and ingenuity pathway analysis revealed a number of down regulated genes involved in cell-cycle progression. Specifically, estrogen treatment of ERβ positive TNBC cells was shown to result in suppression of cyclin-dependent kinase 1 (CDK1) and Cyclin B, effects that were confirmed following ERβ-specific agonist treatment at both the mRNA and protein levels via RT-qPCR and western blotting, respectively. Knockdown of CDK1 in ERβ+ TNBC cells using siRNA resulted in decreased proliferation and diminished the anti-proliferative effects observed following estrogen or ERβ-specific agonist treatment. Conclusions: Our data demonstrate that estrogen and ERβ-specific agonists cause cell cycle arrest in ERβ positive TNBC. These effects are due to ERβ-mediated suppression of multiple genes involved in cell cycle progression including CDK1 and Cyclin B. Following knockdown of CDK1, estrogen or ERβ-specific agonist treatment displayed minimal impact on cell proliferation. Therefore, ERβ's effects on proliferation may primarily be mediated by blockade of CDK1 and Cyclin B. Regardless of ERβ, our data suggest that inhibition of CDK1 activity may have therapeutic benefit in a subset of TNBC patients, an area of study that has yet to be explored. Citation Format: Reese JM, Bruinsma ES, Monroe DG, Goetz MP, Hawse JR. Activation of ERβ in triple negative breast cancer results in cell cycle arrest [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-04-04.
Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology
Authors: Hui Fang, Ki Jun Yu, Christopher Gloschat, Zijian Yang, Enming Song, Chia-Han Chiang, Jianing Zhao, Sang Min Won, Siyi Xu, Michael Trumpis, Yiding Zhong, Seung Won Han, Yeguang Xue, Dong Xu, Seo Woo Choi, Gert Cauwenberghs, Matthew Kay, Yonggang Huang, Jonathan Viventi, Igor R. Efimov, John A. Rogers
Journal: Nature Biomedical Engineering (2017)
Inhibition of Factor VIII-Specific Memory B Cell Responses by Supra-Physiological Concentrations of Factor VIII.
Authors: Christina Hausl, Rafi U. Ahmad, Maria Sasgary, Christopher B. Doering, Pete S. Lollar, Guenter Richter, Hans Peter Schwarz, Peter L. Turecek, Birgit M. Reipert
Journal: Blood (2004)
Current State of Patient Awareness and Participation in Care for Multiple Myeloma and the Psychophysical Impact of Treatment: An International Internet-Based Study
Authors: Sikander Ailawadhi, Abhisek Swaika, Pooja Advani, Michael S Katz, David O Hodge, Aneel Paulus, Nandita Khera, Shahrukh K Hashmi, Gerardo Colon-Otero, Vivek Roy, Asher Chanan-Khan
Journal: Blood (2014)
m<scp>TORC</scp>2 controls Th9 polarization and allergic airway inflammation
Authors: H. Chen, L. Zhang, P. Wang, H. Su, W. Wang, Z. Chu, L. Zhang, X. Zhang, Y. Zhao
Journal: Allergy (2017)

T helper type 9 (Th9) cells, a subpopulation of CD4+ T cells, play a critical role in the pathogenesis of allergic airway inflammation. However, it remains unknown whether mTORC2 regulates Th9 differentiation or function during allergic inflammation.T-cell-specific Rictor-deficient mice, a mouse model of allergic airway inflammation induced by ovalbumin (OVA) sensitization and a mouse model of adoptive transfer of induced Th9 cells, were used to address the roles of mTORC2 in the pathogenesis of allergic airway inflammation. The in vitro Th9 induction, multiple colors flow cytometry, real-time PCR, and Western blots were used to investigate the molecular effects of mTORC2 in Th9 induction.The differentiation of naïve CD4+ T cells into Th9 cells was significantly diminished in the absence of Rictor, the core component of mTORC2. Using a mouse model of allergic airway inflammation induced by OVA sensitization, T-cell-specific Rictor-deficient mice show much less severe allergic airway inflammation characterized by decreased pathological alterations and fibrosis of the lungs, which was accompanied with reduced Th9 differentiation and infiltration. Importantly, the isolated Rictor-deficient Th9 cells mediate less severe allergic pathogenesis upon adoptive transfer. Rictor deficiency impairs Th9 cell differentiation by reducing IRF4 expression rather than affecting Foxo1/Foxo3a transcriptional activity, which is likely due to decreased Akt and/or STAT6 activation.These findings uncover a novel role of mTORC2 in Th9 cell differentiation and may have important implications for therapeutic intervention of allergic diseases.
Evidence for the Baby-Friendly Hospital Initiative to Support Breastfeeding—Reply
Authors: Valerie Flaherman, Isabelle Von Kohorn
Journal: JAMA (2017)

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
Genomics Analysis of Freshly-Purified Human Marrow Stromal Cells (MSCs): Comparison with Hematopoietic Lineage Cells and Culture-Expanded MSCs.
Authors: Elena A. Jones, Sally E. Kinsey, Anne English, Sarah Field, Andy Rawstron, Richard A. Jones, Liz Strazsynski, Stephen Rundlett, Selina Jain, Robert Deans, Paul Emery, Frederique Ponchel, Dennis McGonagle
Journal: Blood (2006)
Polycythemia of Mice with Human Gain-of-Function EPOR (mtHEPOR) Is Transiently Corrected in Perinatal Life in Association with Low Epo and Increased Erythrocyte Phosphatidylserine Exposure
Authors: Jihyun Song, Barbora Kralova, Monika Horvathova, Donghoon Yoon, Josef T. Prchal, Vladimir Divoky
Journal: Blood (2015)
THE PRESENT ASPECT OF THE TUBERCULOSIS PROBLEM IN THE UNITED STATES.
Authors: S. A. KNOPF
Journal: JAMA (1902)

After this general comment I will take up some of the states individually. Dr. William Duffield, Phoenix, Ariz., tells me that there is no board of health in the territory. Just think of it! Arizona, the place which is perhaps more sought and visited by consumptive invalids than any other, has no board of health, and consequently no laws nor regulations concerning tuberculosis in man. No circulars nor ordinances are issued. The town of Phoenix has an anti-spitting ordinance, but the law is a dead letter and has never been enforced. There is no sanatorium or special hospital for the exclusive treatment of tuberculosis in Arizona and no society for the prevention of tuberculosis. In his letter to me, Dr. Duffield lays particular stress on the sad fact that there is not a single place in the whole territory where the poor consumptive can receive shelter and treatment, and he
Cell-free DNA copy number variations as a marker for breast cancer in a large study cohort.
Authors: Julia Beck, Ekkehard Schütz, Howard B. Urnovitz, Adel Tabchy, William M. Mitchell, Gordon B. Mills, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2013)

11013 Background: Massive parallel sequencing provides high numbers of cell-free nucleic acid serum DNA sequences (cfDNA) that can detect trace amounts of tumor derived chromosomal imbalances and copy number variations (CNVs) in patients with cancer. The aim of this study was to determine if there is a difference between the cfDNA CNVs from patients with breast cancer (BrCa) compared to healthy controls. Methods: DNA extracted from serum samples of 225 BrCa (Stage 1 to 4) and 205 gender and age-matched healthy controls (HC) was amplified using random primers, tagged with a unique molecular identifier per sample, sequenced on an Illumina HiSeq system and aligned to the human genome (Build 37). Hits were counted in sliding 1Mbp interval regions and normalized. Using a Random-Resampling procedure, a model was established to distinguish BrCa from HC using the copy number variations (CNV) and cross validated. Results: From 1,100 rounds of random resampling (50/50), a set of 31 regions was selected, based on the frequency of occurrence in the models. Using 20 random sets of a 10-fold cross validation, the selected regions were found to be highly significant discriminators between BrCa and HC (p&lt;10 -5 ). When using a final linear model with 16 regions the AUC of a diagnostic ROC curve was found to be 0.895 for all samples, for Stage I and II the AUC was 0.86 compared to 0.93 for the higher stages. The final model included three regions from chromosome 8 and 1 and two regions from chromosome 15, the remaining regions were found as one per chromosome. Conclusions: Using comparative massive parallel sequencing of cfDNA from cancer patients vs. controls, we were able to show that a 16-region model based on CNV, is useful to distinguish patients with breast cancer from matched controls. Genomic instabilities that are shed into the circulation from breast cancer may play a role in screening, monitoring or as companion diagnostic tests in breast cancer.