tbuckley/cabot-search huggingface dataset:
MicroRNA expression to classify breast cancer and predict relapse.
Authors: J. De La Cruz, V. Scott, C. Richon, P. Dessen, S. Delaloge, M. Mathieu, A. Goubar, S. Vagner, V. Lazar, F. Andre
Journal: Journal of Clinical Oncology (2010)

646 Background: To describe microRNA expression in breast cancer and identifies whether they could contribute to prognosis assessment. Methods: MicroRNA expression was assessed in 178 patients with early breast cancer using MIR array (miRNA 8×16K Agilent Human v3 G4470C). Patients were selected for having been treated with local treatment alone ± 2 years tamoxifen. The RNA extraction was made by trizol, and quality control was assessed by byoanalyser (RNA 6000 nanothief Agilent technologies). Molecular classification was generated by unsupervised clustering. In addition, a supervised analysis was done in order to identify MIR that could predict relapse. MIR candidates were validated in mouse models. Results: 178 patients were included in the present study. The median age at diagnosis was 57 years, the median tumor size was 18 mm and 86.51% patients had negative axillary nodes. 115 patients (64.6%) had positive estrogen receptors, and 76 patients received hormonotherapy. Unsupervised clustering identifies one cluster of 13 (7%) ER-positive breast cancer that presents a highly specific profile of MIR expression (Clusterlog2(Int) 10-20×8) as compared to the main cluster of 165 patients, and to a cluster of 6 normal tissues. Supervised analyses identified 5 microRNAs (27b, 23b, 27a, 24.1*, 199a-5p) associated with higher risk of metastatic relapse (p < 10-4). Interestingly, these 5 MIRs were located in two DNA clusters (chr19p13.13, chr 9q22.32). These MIRs were associated with higher likelihood of lymphatic spreading in mice models. Conclusions: This study suggests that MIR expression could contribute to molecular portrait of breast cancer and identifies 2 clusters of MIRs that could improve outcome prediction. A validation study (n = 100) is ongoing to evaluate the performance of the 5 MIRs to predict risk of relapse. No significant financial relationships to disclose.
Balancing Legitimate Critical-Care Interests: Setting Defensible Care Limits Through Policy Development
Authors: Jeffrey Kirby
Journal: The American Journal of Bioethics (2016)

Critical-care decision making is highly complex, given the need for health care providers and organizations to consider, and constructively respond to, the diverse interests and perspectives of a variety of legitimate stakeholders. Insights derived from an identified set of ethics-related considerations have the potential to meaningfully inform inclusive and deliberative policy development that aims to optimally balance the competing obligations that arise in this challenging, clinical decision-making domain. A potential, constructive outcome of such policy engagement is the collaborative development of an as-fair-as-possible dispute resolution process that incorporates an appropriated-justified, defensible critical-care obligation threshold.
Differential survival after prostate cancer by race: Role of NCI-designated comprehensive cancer centers
Authors: C. Sun, S. Kurian, G. Washington, K. Nielsen-Menicucci, T. Wilson, L. Crocitto, S. Donald, C. Hanby, W. Landier, S. Smith, S. Bhatia
Journal: Journal of Clinical Oncology (2009)

6520 Background: A significant gap exists between Caucasians and African-Americans (AAs) in prostate cancer mortality, possibly due to sociodemographics, disease biology, or treatment. Furthermore, differential access to care at NCI-designated Comprehensive Cancer Centers (NCICCCs) conceivably contributes to this difference. Methods: Using data from the Los Angeles Cancer Surveillance Program, we studied the underlying causes of differences in mortality in 18,790 men (AAs: 4,211; Caucasians: 14,579) diagnosed with prostate cancer between 1998 and 2003, and followed until 2006. Three NCICCCs serve this area: USC-Norris, UCLA-Jonsson, and City of Hope. Results: Median age at diagnosis was 67.5 yrs; AAs were significantly more likely to have lower SES; carry no insurance; have distant disease; and be managed with “watchful waiting.” The overall and prostate-specific survival was significantly superior for patients treated at NCICCCs, and for Caucasians (Table). Multivariate analysis, after adjustment for sociodemographics, race, insurance, tumor-related factors, and treatment-modality, revealed that treatment at NCICCCs was associated with lower overall (HR=0.74, 95% CI=0.6–0.9) and prostate-specific mortality (HR=0.69, 95% CI=0.5–0.97). AAs were less likely to utilize NCICCCs (OR=0.42, 95%CI=0.4–0.5). Finally, adjustment for sociodemographic, tumor/treatment-related factors, and treatment site abrogated the racial difference in overall (HR=1.08, 95%CI=0.99–1.2) and prostate-specific (HR=1.11, 95%CI=0.9–1.3) mortality. Conclusions: Patients treated at NCICCCs have lower mortality compared with other facilities. AAs are less likely to utilize NCICCCs for prostate cancer. AAs and Caucasians have comparable overall and prostate-specific survival, after adjustment for sociodemographic, tumor/treatment-related factors, and treatment site. Future studies are needed to understand barriers and facilitators to utilization of NCICCCs for management of prostate cancer. [Table: see text] No significant financial relationships to disclose.
Abstract 15610: The Infusion of Mesenchymal Stromal Cells Post Myocardial Infarction Increases Myocardial S100A6, Attenuates Myocyte Hypertrophy, Reduces Myocyte Apoptosis and Improves Cardiac Function
Authors: James Tsoporis, Shehla Izhar, Jean-Francois Desjardins, Gerald Proteau, Gustavo Yannarelli, Armand Keating, Thomas G Parker
Journal: Circulation (2014)

The beneficial effects originally attributed to the ability of bone-marrow derived mesenchymal stromal cells (BM-MSCs) to differentiate into cardiomyocytes have been questioned due to the transient presence of donor cells at injury site following myocardial infarction (MI) suggesting that the MSC-induced improvement in hemodynamic function may be attributable to paracrine effects. We showed that S100A6, a 20 kDa EF-hand calcium-binding dimer, is upregulated and secreted following MI and forced expression post-MI was beneficial to the preservation of cardiac function. The aim of this study was to determine whether the beneficial effects of infused BM-MSCs may be related to the autocrine secretion of S100A6. Balb/c murine cultured green fluorescence protein (GFP)-marked BM-MSCs express S100A6 at baseline and in response to hypoxia (5%C02/95% N2) for 1 hr increase S100A6 mRNA and protein (2-3 fold, and release S100A6 (1 nM) in the culture media, responses inhibited in BM-MSCs transfected with S100A6 siRNA. Treatment of neonatal Balb/c cardiac myocytes with human recombinant S100A6 (1nM) for 1-24 hrs attenuated baseline apoptosis (30 per cent decrease in BAX/BCL2 ratio), induced cyclin-dependent kinase 1(CDK1) mRNA 1.5 fold, miR199a 2 fold and myocyte proliferation 2.5 fold, the latter inhibited by anti-miR 199a. In 12 week old Balb/c mice, saline or GFP-marked BM-MSCs transfected with either a scrambled or S100A6 siRNA were infused intravenously 3-4 hrs post coronary artery ligation. After 3-4 days the GFP-marked cells were confined to ischemic areas and represented approximately 10% of total cellularity and co-expressed collagen type IV and myosin heavy chain, characteristic of MSCs and cardiomyocytes, respectively, and were CD45(-). Despite the absence of donor cells in the infarcted myocardium 21 days after infusion, mice that have received MSCs alone compared to MSCs transfected with an S100A6 siRNA or saline alone showed a 6-fold increase in S100A6 mRNA and protein, 3-fold increase in miR199a in peri-infarcted myocardium, attenuated myocyte hypertrophy, decreased fibrosis and apoptosis, and preservation of cardiac function. In conclusion, the secretion of S100A6 by infused BM-MSCs may contribute in limiting adverse LV remodeling post-MI.
Biologic effects of recombinant human interleukin-3 in vivo.
Authors: A Lindemann, A Ganser, F Herrmann, J Frisch, G Seipelt, G Schulz, D Hoelzer, R Mertelsmann
Journal: Journal of Clinical Oncology (1991)

The biologic in vivo effects of recombinant human interleukin-3 (rhIL-3) were assessed in a phase I clinical study of 30 patients with advanced malignancy. On day 1 rhIL-3 was administered by a single intravenous (IV) bolus injection, followed by subcutaneous (SC) injections once daily from day 2 to 15; at least three patients were treated at each dose level (60, 125, 250, and 500 micrograms/m2). A transient decrease of eosinophil and monocyte counts was observed immediately after IV injection of rhIL-3, whereas the neutrophil count remained unaffected. Total WBC counts and neutrophil counts increased dose dependently up to threefold, whereas a 10-fold to 50-fold rise was observed in levels of circulating eosinophils and basophils. Platelet counts increased up to twofold. Patients developed moderate increases of serum levels of soluble interleukin-2 receptors, beta 2-microglobin, and immunoglobulin M (IgM), and of the acute phase reactants, C-reactive protein (CRP), fibrinogen, and haptoglobin. An increase in interleukin-6 (IL-6) serum levels was detected in patients treated by IV bolus rhIL-3. The serum half-life of IV injected rhIL-3 was 20 +/- 3 minutes; after SC administration, 210 +/- 15 minutes. Administration of rhIL-3 was generally well tolerated, with mild fever, headache, and local reactions at the injection site being the most frequent side effects. The primary course of the underlying malignant diseases was not significantly altered by administration of rhIL-3. The results indicate that rhIL-3 acts in vivo as a multilineage hematopoietic growth factor and a weak inflammatory mediator that may be used successfully to improve states of hematopoietic failure.
Pathologic Changes in Irradiated Monkeys Treated With Bone Marrow&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M de VRIES, B G CROUCH, L van PUTTEN, D van BEKKUM
Journal: JNCI Journal of the National Cancer Institute (1961)

Autopsy was performed on 27 irradiated monkeys. The 7 irradiated nontreated animals died on the bone marrow syndrome. Intestinnal radiation death occurred in one treated with autologous bone marrow; bone marrow regeneration was delayed in the other animal that died with anemia and hemorrhagic pulmonary edema. In 3 animals treated with homologous bone marrow, there was no apparent regeneration but it occurred in the 14 others treated with homologous bone marrow cells. The pathologic changes closely resembled those found in mouse, rabbit, and human radiation chimeras suffering from secondary disease, which in the primate radiation chimera seems more severe than usually occurs in irradiated mice treated with foreign bone marrow. Since many lesions found in monkeys are more pronounced than those in rodents, this study has been illuminating in the pathogenesis of secondary disease. Cell loss, possibly a direct effect of an immunological reaction of the foreign bone marrow graft agaiast the tissues of the host, was the primary lesion, amounting to severe necrosis and atrophy in many organs. In lesions of the intestinal tract, degenerative chsmges prevailed over regenerative while the reverse was true for early skin lesions. Although infectious disease occurred less frequently than in mouse chimeras impairmentmore » of the immunological defense system may have promoted invasion by commensal parasites or activation of latent infections. Mortality in animals treated with foreign bone marrow probably was caused by widespread denudation of ileum and colon and sometimes by massive liver necrosis or infectious disease. (auth)« less
Abstract 15679: Escalating Doses of {beta}-Estradiol Fail to Improve Resuscitation Outcomes in a Rat Model of Ventricular Fibrillation and Closed Chest Resuscitation
Authors: Yang Miao, Sathya Velmurugan, Vesna Borovnik Lesjak, Jeejabai Radhakrishnan, Raul J Gazmuri
Journal: Circulation (2012)
Pulmonary Involvement in Polyarteritis
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A national registry for the off-label use of targeted therapies in patients (pts) with malignant mesenchymal tumors: A retrospective study from the GSF-GETO.
Authors: J. Bay, A. Le Cesne, A. Cioffi, N. Penel, F. Duffaud, D. Cupissol, S. Piperno-Neumann, C. Cropet, L. Bouclier, I. Ray-Coquard
Journal: Journal of Clinical Oncology (2010)

10097 Background: Currently, targeted therapies are not registered in advanced STS relapsing after standard chemotherapy. Several phase II trials reports promising results for some particular couples target therapy/histological subtype. The off label use of these compounds for such tumors was explored in advanced situations within the GSF-GETO. Methods: The registry covers all consecutive pts with mesenchymal tumors, not amenable to curative treatment, with progressive disease, having exhausted standard treatment, ineligible for clinical trial and having received off label targeted treatment following multidisciplinary discussion. All pts gave oral consent on the off label use of the treatment. A retrospective evaluation of response rate and tolerability was performed by local multidisciplinary committees dedicated to sarcoma. Results: 161 pts (males 52%) with a median age of 48 years were included from Oct 2008 to Oct 2009. The median number of previous lines of treatment was 4 (range 1-10). Histotypes were leïomyosarcoma 20%, (56% of them have been treated with sorafenib –Sfb-), GIST 13% who received for 76% Sfb, chordoma 8% who received for 58% imatinib, angiosarcoma (7%) who received for 73% Sfb, PNET 6% who received for 75% Sfb or sunitinib as previously reported in previous clinical trials. Among pts with confirmed radiological assessments, the 3-month progression-free survival (PFS) rates were 65% (LMS), 68% (GIST), 36% (chordoma), 60% (angiosarcoma), and 28% (PNET) respectively. In the whole group, PFS at 6 and 12 months were 35% and 24% respectively. Overall, 2 complete responses were reported: one with sunitinib for PNET and one with temsirolimus for PEComa (3 are currently on treatment). No toxic death was reported and grade 3 and 4 toxicities were seen in 30% and 4.5% of pts, respectively. 121 (80%) patients were alive at 6months. Conclusions: In pts with malignant mesenchymal tumors, off label was commonly used in routine practice. The toxicity profile was acceptable in these selected pts. This registry may identify useful observations for the rarest tumors. No significant financial relationships to disclose.
Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study.
Authors: P Reichardt, J Tilgner, P Hohenberger, B Dörken
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the feasibility and toxicity of the combination of full-dose epirubicin (EPI) and high-dose ifosfamide (IFO) with granulocyte colony-stimulating factor (G-CSF) support and to determine the clinical efficacy in terms of response and impact on survival. PATIENTS AND METHODS Forty-six consecutive, previously untreated patients with locally advanced or metastatic high-grade soft tissue sarcomas were treated with IFO 2.5 g/m2/d as a continuous infusion on days 1 to 5 and EPI 45 mg/m2/d as a continuous infusion on days 2 and 3 every 3 weeks. G-CSF 5 microg/kg/d subcutaneously (s.c.) was given on days 6 to 15 or until recovery of leukocytes after all cycles. Response evaluation was performed every two cycles and responding patients were treated with up to six cycles. All patients were evaluated for resectability of residual local or metastatic disease and underwent surgery if possible. RESULTS All patients experienced grade 3 or 4 myelosuppression. Other toxicities were mild. The overall response rate was 52%, with a complete remission (CR) rate of 22% after chemotherapy alone. Eight additional patients were rendered free of tumor (no evidence of disease [NED]) by surgical procedures. The median overall survival of all patients is 24 months. The CR/NED patients (39%) have a significantly superior survival time compared with all other patients. Thirteen of these 18 patients (72%) are alive, nine free of tumor, with a median follow-up time of 33 months. CONCLUSION This dose-intensive combination chemotherapy is toxic but feasible and produced a high number of partial remissions (PRs) and especially CRs, which resulted in prolonged survival.
The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis
Authors: Matjaz Vogelsang, Carlos N. Martinez, Justin Rendleman, Anuj Bapodra, Karolina Malecek, Artur Romanchuk, Esther Kazlow, Richard L. Shapiro, Russell S. Berman, Michelle Krogsgaard, Iman Osman, Tomas Kirchhoff
Journal: Clinical Cancer Research (2016)

The identification of personalized germline markers with biologic relevance for the prediction of cutaneous melanoma prognosis is highly demanded but to date, it has been largely unsuccessful. As melanoma progression is controlled by host immunity, here we present a novel approach interrogating immunoregulatory pathways using the genome-wide maps of expression quantitative trait loci (eQTL) to reveal biologically relevant germline variants modulating cutaneous melanoma outcomes.Using whole genome eQTL data from a healthy population, we identified 385 variants significantly impacting the expression of 268 immune-relevant genes. The 40 most significant eQTLs were tested in a prospective cohort of 1,221 patients with cutaneous melanoma for their association with overall (OS) and recurrence-free survival using Cox regression models.We identified highly significant associations with better melanoma OS for rs6673928, impacting IL19 expression (HR, 0.56; 95% CI, 0.41-0.77; P = 0.0002) and rs6695772, controlling the expression of BATF3 (HR, 1.64; 95% CI, 1.19-2.24; P = 0.0019). Both associations map in the previously suspected melanoma prognostic locus at 1q32. Furthermore, we show that their combined effect on melanoma OS is substantially enhanced reaching the level of clinical applicability (HR, 1.92; 95% CI, 1.43-2.60; P = 2.38e-5).Our unique approach of interrogating lymphocyte-specific eQTLs reveals novel and biologically relevant immunomodulatory eQTL predictors of cutaneous melanoma prognosis that are independent of current histopathologic markers. The significantly enhanced combined effect of identified eQTLs suggests the personalized utilization of both SNPs in a clinical setting, strongly indicating the promise of the proposed design for the discovery of prognostic or risk germline markers in other cancers. Clin Cancer Res; 22(13); 3268-80. ©2016 AACR.
CD8 T cell dose impacts acute graft-versus-host disease after reduced intensity conditioning (RIC) for allogeneic stem cell transplantation
Authors: M. Mohty, C. Faucher, S. Bagatini, V.-J. Bardou, K. Bilger, C. Chabannon, P. Ladaique, N. Vey, D. Maraninchi, D. Blaise
Journal: Journal of Clinical Oncology (2004)

6633 Background: We previously reported that the incidence of acute GVHD (aGVHD) was significantly associated with the antithymocyte globulin (ATG) dose (Sangstat*) infused during RIC using fludarabine, busulfan and ATG. The impact of ATG is likely related to a dose-dependent in vivo T cell depletion. Here, we investigated whether a correlation exists between graft composition and transplant-related events. Methods: 71 consecutive pts from a single center receiving HLA-identical RIC allogeneic transplantation, were analyzed. Median age was 50 y. (18–60), diagnosis: 34 myeloid malignancies (48%) and 37 lymphoid malignancies (52%). 51 pts (72%) were high risk. 38 pts (53%) received a low ATG dose (2.5 mg/Kg), while 33 received the highest dose (7.5 or 10 mg/Kg). 40 pts (56%) received PBSC and 31 (44%) received BM. All pts received CsA alone for GVHD prophylaxis. Results: 42 pts had aGVHD [13 grade I (18%), 12 grade II (17%) and 17 grade III-IV (24%)]. Chronic GVHD (cGVHD) occurred in 36 [8 limited (11%) and 28 extensive (39%)] out of 55 evaluable pts. Univariate analysis showed that stem cell source, ATG dose, CD4+, CD8+, CD19+ and CD56+ cells infused, significantly influenced the risk of aGVHD. In multivariate analysis, CD8+ T cell dose (>69x10e6/Kg) was the only parameter significantly associated with the risk of aGVHD (P=0.0002; RR=3.5; 95%CI, 1.8–6.7). The impact of CD8+ cell dose on aGVHD could be also confirmed if restricting the analysis to PBSC recipients (P=0.02). In contrast, in multivariate analysis, the risk of cGVHD was not statistically associated with lymphoid subsets, but was associated with grade II-IV aGVHD (RR=2.5; 95%CI, 1.2–5.0) and stem cell source (PBSC; RR=2.35; 95%CI, 1.1–5.0), suggesting that other cell subtypes (e.g. dendritic cells…) might contribute to long term imune reactions. With a median FU of 31 m (5–58), 37 pts are alive with OS being significantly higher in pts experiencing aGVHD and/or cGHVD as compared to pts without GVHD (P=0.004). Conclusions: These results suggest that graft manipulation may have a significant impact on the probability of a favorable outcome after RIC transplantation. No significant financial relationships to disclose.
Triple Negative Breast Cancer: Clinicopathologic Characteristics and Fatty Acid Synthase (Fasn) Expression As a Potential Target
Authors: F. Holguin Flores, G. Vinas, G. Oliveras, A. Giro-Perafita, F. Perez-Bueno, A. Roque, J. Brunet, T. Puig
Journal: Annals of Oncology (2014)