tbuckley/cabot-search huggingface dataset:
Serum iron levels potential biomarker in FOLFOX/FOLFIRI with or without molecularly targeted drug therapy.
Authors: Takumi Ochiai, Kazuhiko Nishimura, Tomoo Watanabe, Masayuki Kitajima, Akinori Nakatani, Tsuyoshi Sato, Kennji Kishine, Satoshi Okubo, Shunji Futagawa, Isao Nagaoka
Journal: Journal of Clinical Oncology (2013)

e14651 Background: We reported an increase in serum iron levels during therapy with FOLFOX or FOLFIRI ± molecularly targeted drugs and a correlation between prognosis and transition of those levels in advanced colorectal cancer (CRC) patients (ASCO; 2009: #e15110, 2011: #e14141, 2012: #e14004). The aims of this prospective cohort study were to establish serum iron levels as a new biomarker in advanced CRC patients undergoing therapy based on this correlation and investigate the mechanism of this increase in serum iron levels. Methods: Eighty-one advanced CRC patients were treated; all died between Dec. 2005 and Nov. 2012; none received radiotherapy; 9 of these patients were undergoing treatment between Sep. 2012 and Nov. 2012. Serum iron levels were measured at before and 48 hr after treatment. Taking the median rate of increase in serum iron levels as the cut-off value in each therapy, the patients were categorized into cohort I (increase rate over cut-off value in at least one therapy) or cohort II (increase rate under cut-off value in all therapies). Prognosis was evaluated between the two. Hepcidin (Hepc), Interleukin-6 (IL-6) and soluble transferrin receptor (sTfR) were measured at before and 48 hr after treatment. Results: No significant bias in patient characteristics (including in frequency or type of regimen) was observed between the two cohorts. Serum iron levels transiently increased after treatment (p&lt;0.001), then returning to baseline within 2 weeks. Median survival time (MST) in cohort I (n: 50) and cohort II (n: 31) was 437 and 378 days, respectively, with MST significantly better in cohort I (p=0.0417). Multivariate analysis identified Dukes’ stage, recurrence type, and serum iron level as independent risk factors for overall survival (OS). Hepc significantly increased after treatment (p&lt;0.001), with no significant change in IL-6 or sTfR. Conclusions: Serum iron levels offer potential as an extremely useful and convenient biomarker for OS in CRC patients. While Hepc significantly increased, no significant decrease was observed in sTfR after treatment. This suggests that serum iron levels increased as a result of a treatment-induced reduction in iron consumption by bone marrow.
MHC II+ resident peritoneal and pleural macrophages rely on IRF4 for development from circulating monocytes
Authors: Ki-Wook Kim, Jesse W. Williams, Ya-Ting Wang, Stoyan Ivanov, Susan Gilfillan, Marco Colonna, Herbert W. Virgin, Emmanuel L. Gautier, Gwendalyn J. Randolph
Journal: The Journal of Experimental Medicine (2016)

Peritoneal and pleural resident macrophages in the mouse share common features and in each compartment exist as two distinct subpopulations: F4/80(+) macrophages and MHC II(+) CD11c(+) macrophages. F4/80(+) macrophages derive from embryonic precursors, and their maintenance is controlled by Gata6. However, the origin and regulatory factors that maintain MHC II(+) macrophages remain unknown. Here, we show that the MHC II(+) macrophages arise postnatally from CCR2-dependent precursors that resemble monocytes. Monocytes continuously replenish this subset through adulthood. Gene expression analysis identified distinct surface markers like CD226 and revealed that the transcription factor IRF4 was selectively expressed in these macrophages relative to other organs. Monocytes first entered peritoneal or pleural cavities to become MHC II(+) cells that up-regulated CD226 and CD11c later as they continued to mature. In the absence of IRF4 or after administration of oral antibiotics, MHC II(+)CD226(-)CD11c(-) monocyte-derived cells accumulated in peritoneal and pleural cavities, but CD11c(+) CD226(+) macrophages were lost. Thus, MHC II(+) resident peritoneal and pleural macrophages are continuously replenished by blood monocytes recruited to the peritoneal and pleural cavities constitutively, starting after birth, where they require IRF4 and signals likely derived from the microbiome to fully differentiate.
Genetics and the Evaluation of the Febrile Child
Authors: Howard Bauchner
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
No ‘cure’ within 12 years of diagnosis among breast cancer patients who are diagnosed via mammographic screening: women diagnosed in the West Midlands region of England 1989–2011
Authors: L.M. Woods, M. Morris, B. Rachet
Journal: Annals of Oncology (2016)

We have previously reported that there is little evidence of population 'cure' among two populations of women diagnosed with invasive breast cancer. 'Cure' has not yet been examined in the context of screen-detection.
Deep Sequencing Reveals a Novel miR-22 Regulatory Network with Therapeutic Potential in Rhabdomyosarcoma
Authors: Francesca Bersani, Marcello Francesco Lingua, Deborah Morena, Valentina Foglizzo, Silvia Miretti, Letizia Lanzetti, Giovanna Carrà, Alessandro Morotti, Ugo Ala, Paolo Provero, Roberto Chiarle, Samuel Singer, Marc Ladanyi, Thomas Tuschl, Carola Ponzetto, Riccardo Taulli
Journal: Cancer Research (2016)

Current therapeutic options for the pediatric cancer rhabdomyosarcoma have not improved significantly, especially for metastatic rhabdomyosarcoma. In the current work, we performed a deep miRNA profiling of the three major human rhabdomyosarcoma subtypes, along with cell lines and normal muscle, to identify novel molecular circuits with therapeutic potential. The signature we determined could discriminate rhabdomyosarcoma from muscle, revealing a subset of muscle-enriched miRNA (myomiR), including miR-22, which was strongly underexpressed in tumors. miR-22 was physiologically induced during normal myogenic differentiation and was transcriptionally regulated by MyoD, confirming its identity as a myomiR. Once introduced into rhabdomyosarcoma cells, miR-22 decreased cell proliferation, anchorage-independent growth, invasiveness, and promoted apoptosis. Moreover, restoring miR-22 expression blocked tumor growth and prevented tumor dissemination in vivo Gene expression profiling analysis of miR-22-expressing cells suggested TACC1 and RAB5B as possible direct miR-22 targets. Accordingly, loss- and gain-of-function experiments defined the biological relevance of these genes in rhabdomyosarcoma pathogenesis. Finally, we demonstrated the ability of miR-22 to intercept and overcome the intrinsic resistance to MEK inhibition based on ERBB3 upregulation. Overall, our results identified a novel miR-22 regulatory network with critical therapeutic implications in rhabdomyosarcoma. Cancer Res; 76(20); 6095-106. ©2016 AACR.
A phase I trial of [(1- 4)- linked b-D-mannopyranose]17 - [(1- 6)-linked-a-D- galactopyranose]10 (DAVANAT) co-administered with 5-fluorouracil, in patients with refractory solid tumors
Authors: J. Fuloria, Y. Abubakr, R. Perez, M. Pike, M. Zalupski
Journal: Journal of Clinical Oncology (2005)

3114 Background: [(1- 4)- linked b-D-mannopyranose]17 - [(1- 6)-linked-a-D- galactopyranose]10 (DAVANAT), enhances activity of 5-Fluorouracil (5-FU) in 5-FU refractory murine colon tumor models. DAVANAT binds to surface lectins and promotes transport of 5-FU into the tumor cells. Lectins are present in large amounts on the surface of metastatic tumor cells, and may mediate cell association, apoptosis and metastasis. Method: A Phase I open-label study was initiated to evaluate the safety and tolerability of escalating doses of DAVANAT (30 mg/m2to 280 mg/m2) plus and minus 500 mg/m2 5-FU in patients with advanced solid tumors. Objectives were to determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicities (DLT) of DAVANAT alone, and with 500 mg/m2of 5-FU, establish the pharmacokinetics (PK) of 5-FU plus DAVANAT, and to study the effect of DAVANAT plus 5-FU on tumor size in patients with measurable disease. Patients received DAVANAT alone days 1–4 of cycle 1, followed by DAVANAT plus 5-FU days 1–4 of cycle 2. Cycle length was 28 days, and patients with stable or responding disease continued DAVANAT. Results: Twenty-six of 38 patients injected with DAVANAT have completed the study through 12/6/04. DAVANAT alone and in combination with 5-FU was found to be well tolerated. DLT has not been reached at the highest dose level of 280 mg/m2. Three of 26 patients had serious adverse events thought to be at least possibly related to DAVANAT: dehydration, dyspnea and thrombocytopenia. One unrelated on-study death occurred, due to unexpectedly rapid disease progression. Toxicities of DAVANAT plus 5-FU were similar to those expected for 5-FU alone at this dose and schedule. Of 24 patients with measurable disease, 13 had stable and 11 had progressive disease by RECIST criteria following cycle 2. Nine of the 13 stable patients received additional cycles of DAVANAT plus 5-FU. No dose dependent effects on 5-FU PK were noted in patients treated with DAVANAT doses analyzed thus far (30–150 mg/m2). Conclusions: The tolerability of DAVANAT co-administered with 5-FU established in this Phase I study warrants further testing in a Phase II clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pro-Pharmaceuticals
A prospective randomized trial of gemcitabine alone or gemcitabine + cisplatin in the treatment of metastatic pancreatic cancer
Authors: C. P. Li, Y. Chao
Journal: Journal of Clinical Oncology (2004)

4144 Background: To determine the efficacy and toxicity of gemcitabine alone (GEM) versus GEM + cisplatin (G + C) in the treatment of metastatic pancreatic cancer. Methods: From Jan-98 to Jun-02, 46 patients with metastatic pancreatic cancer were studied. Twenty-five patients were randomized to receive GEM (1000 mg/m2/week × 3 every 4 weeks), and 21 patients to G + C (GEM 1000 mg/m2/week and cisplatin 25 mg/m2/week × 3 every 4 weeks). The primary endpoint was patients' survival. Results: The planned accrual was 24 patients per arm. The reported accrual was 25 patients in GEM group and 21 in G + C group. The median duration of follow-up was 5.3 months. Sex, age, pre-treatment serum biochemistries, tumor size and location, and performance status were similar between both groups. Gemcitabine dose intensity was similar between GEM and G + C (684 ± 32 vs 617 ± 31 mg/m2/wk). Cisplatin dose intensity was 15.1 ± 0.9 mg/m2/wk × 9.9 ± 1.8 weeks. Median survival and median time to progression (TTP) were 4.6 months and 2.8 months for GEM and 5.6 months and 2.8 months for G + C patients (p= 0.75 and p= 0.9). Clinical benefit (including pain control, performance status, and body weight gain) was 36% for GEM and 29 % for G + C (p> 0.05). Quality-adjusted-life-months survival were 5.6 ± 0.3 months for GEM and 3.8 ± 0.2 months for G + C patients (p< 0.001). Response rates were 12% (3 PR) for GEM and 10% (2 PR) for G + C patients (p> 0.05). Grade 3–4 neutropenia (8% vs 19%), anemia (8% vs 10%) or hospitalization days per month of survival (6.8 ± 2.2 vs 6.2 ± 1.6 days) was not significantly different between GEM and G + C patients, but G + C had higher rate of thrombocytopenia than GEM patients (24% vs 4%, p = 0.012). Conclusions: GEM and G + C had comparable and modest response rates for metastatic pancreatic cancer, but GEM produced lesser toxicities than G + C. No significant financial relationships to disclose.
Phase II study of the src family kinase inhibitor saracatinib (AZD0530) in metastatic melanoma.
Authors: T. Gajewski, Y. Zha, J. Clark
Journal: Journal of Clinical Oncology (2010)

8562 Background: The Src family kinases Fyn, Yes, and Src have variably been shown to be expressed and functionally active in melanoma cell lines. Inhibition of Src kinase activity in vitro has been shown to inhibit Stat3 phosphorylation and promote apoptosis. A role for Src kinases in tumor stromal cell elements also has been suggested. The availability of the highly selective Src kinase inhibitor saracatinib (AZD0530) for clinical investigation prompted a phase II study in patients with advanced melanoma. The fact that Src kinases are also critical for T cell activation motivated assessment of T cell function in treated patients ex vivo. Methods: Patients with measurable advanced melanoma, at most one prior therapy, adequate PS and organ function, normal QTc, no brain metastases, and no severe concurrent illnesses were considered eligible. Saracatinib was administered at 175 mg po daily. CYP3A4-metabolized drugs were avoided. Cycles were 4 weeks, and tumor re- evaluation was performed every 2 cycles. RECIST criteria were used to assess response, and CTCAE 3.0 was used for cataloguing toxicity. A 2-stage trial was pursued; if 2 patients among the first 23 showed a response then an additional 17 would be enrolled. T cell function was measured by assessing IL-2 production in response to SEA, pre-treatment and during week 7 on drug. Results: 23 patients were accrued. All were Caucasian, 15 were male, and 4 had received a prior therapy for metastatic disease. There were no objective clinical responses, and only 2 patients had SD and received an additional 2 cycles of therapy. Common grade 1/2 toxicities included fatigue (n = 18), hyperglycemia (17), anemia (14), diarrhea (13), nausea (10), anorexia (10), increased LFTs (7), lymphopenia (6), and vomiting (5). Analysis of T cell function ex vivo showed significant inhibition of IL-2 production in a subset of patients and a trend for the overall cohort. Conclusions: Our results indicate that saracatinib has minimal clinical activity as a single agent in metastatic melanoma. A trend towards reduced T cell cytokine production in treated patients suggests potential immune suppression by this agent. No significant financial relationships to disclose.
Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy
Authors: Charlotte S. Lo, Sanaz Sanii, David R. Kroeger, Katy Milne, Aline Talhouk, Derek S. Chiu, Kurosh Rahimi, Patricia A. Shaw, Blaise A. Clarke, Brad H. Nelson
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Some forms of chemotherapy can enhance antitumor immunity through immunogenic cell death, resulting in increased T-cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunologic changes consistent with this possibility. Experimental Design: Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors. The prognostic significance of post-chemotherapy TIL patterns was assessed in an expanded cohort (n = 90). Results: Neoadjuvant chemotherapy was associated with increased densities of CD3+, CD8+, CD8+ TIA-1+, PD-1+ and CD20+ TIL. Other immune subsets and factors were unchanged, including CD79a+ CD138+ plasma cells, CD68+ macrophages, and MHC class I on tumor cells. Immunosuppressive cell types were also unchanged, including FoxP3+ PD-1+ cells (putative regulatory T cells), IDO-1+ cells, and PD-L1+ cells (both macrophages and tumor cells). Hierarchical clustering revealed three response patterns: (i) TILhigh tumors showed increases in multiple immune markers after chemotherapy; (ii) TILlow tumors underwent similar increases, achieving patterns indistinguishable from the first group; and (iii) TILnegative cases generally remained negative. Despite the dramatic increases seen in the first two patterns, post-chemotherapy TIL showed limited prognostic significance. Conclusions: Chemotherapy augments pre-existing TIL responses but fails to relieve major immune-suppressive mechanisms or confer significant prognostic benefit. Our findings provide rationale for multipronged approaches to immunotherapy tailored to the baseline features of the tumor microenvironment. Clin Cancer Res; 23(4); 925–34. ©2016 AACR.
The Pseudokinase MLKL and the Kinase RIPK3 Have Distinct Roles in Autoimmune Disease Caused by Loss of Death-Receptor-Induced Apoptosis
Authors: Silvia Alvarez-Diaz, Christopher P. Dillon, Najoua Lalaoui, Maria C. Tanzer, Diego A. Rodriguez, Ann Lin, Marion Lebois, Razq Hakem, Emma C. Josefsson, Lorraine A. O’Reilly, John Silke, Warren S. Alexander, Douglas R. Green, Andreas Strasser
Journal: Immunity (2016)
Smoke and Letters
Authors: Steven C. Parrish
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The Editorial by Dr Rennie<sup>1</sup>is disquieting and disheartening. Readers were exposed to lack of balance, selective use of data, and the very type of bias that Rennie accuses the tobacco industry of practicing. At face value, Rennie addresses whether to publish letters critical of a study on environmental tobacco smoke (ETS) published in<i>JAMA</i>. Reason suggests that the answer lies in the content of the letters. Rennie gives a nod to content, but focuses attention on the source and subsequent use of letters as factors in determining whether to publish them. Presuming the information offered has scientific merit, this approach—calling into question the veracity of authors, prima facie, who work with the tobacco industry and weighing subsequent potential use of letters to the editor—has no place in a medical journal. It appears that Rennie's commentary is not about selecting letters to publish. Rather, it is
Allocation of Physician Time in Ambulatory Practice: A Time and Motion Study in 4 Specialties
Authors: Christine Sinsky, Lacey Colligan, Ling Li, Mirela Prgomet, Sam Reynolds, Lindsey Goeders, Johanna Westbrook, Michael Tutty, George Blike
Journal: Annals of Internal Medicine (2016)

Little is known about how physician time is allocated in ambulatory care.To describe how physician time is spent in ambulatory practice.Quantitative direct observational time and motion study (during office hours) and self-reported diary (after hours).U.S. ambulatory care in 4 specialties in 4 states (Illinois, New Hampshire, Virginia, and Washington).57 U.S. physicians in family medicine, internal medicine, cardiology, and orthopedics who were observed for 430 hours, 21 of whom also completed after-hours diaries.Proportions of time spent on 4 activities (direct clinical face time, electronic health record [EHR] and desk work, administrative tasks, and other tasks) and self-reported after-hours work.During the office day, physicians spent 27.0% of their total time on direct clinical face time with patients and 49.2% of their time on EHR and desk work. While in the examination room with patients, physicians spent 52.9% of the time on direct clinical face time and 37.0% on EHR and desk work. The 21 physicians who completed after-hours diaries reported 1 to 2 hours of after-hours work each night, devoted mostly to EHR tasks.Data were gathered in self-selected, high-performing practices and may not be generalizable to other settings. The descriptive study design did not support formal statistical comparisons by physician and practice characteristics.For every hour physicians provide direct clinical face time to patients, nearly 2 additional hours is spent on EHR and desk work within the clinic day. Outside office hours, physicians spend another 1 to 2 hours of personal time each night doing additional computer and other clerical work.American Medical Association.
Reduced Intensity Conditioning Based On Fludarabine, Intravenous Busulfan (2 Days) and Antithymocyte Globulins (2 Days) Results In High Disease Free Survival Without Persisting Gvhd In Patients Transplanted For Hematological Malignancies: Large Single Center Cohort With Long Follow-Up
Authors: Raynier Devillier, Sabine Furst, Roberto Crocchiolo, Samia Harbi, Luca Castagna, Jean El Cheikh, Angela Granata, Catherine Faucher, Anne Marie Stoppa, Bilal Mohty, Thomas Prebet, Diane Coso, Jerome Rey, Reda Bouabdallah, Norbert Vey, Didier Blaise
Journal: Blood (2013)
Seroepidemiology of Coxsackievirus A6, Coxsackievirus A16, and Enterovirus 71 infections in infants and children: A prospective cohort study in Jiangsu, China
Authors: Fan Gao, Qun-Ying Mao, Pan Chen, Lian-Lian Bian, Xin Yao, Jing-Xin Li, Feng-Cai Zhu, Zheng-Lun Liang
Journal: Journal of Infection (2016)
Increased Pre-Transfusion Reticulocytosis Among Chronically Transfused Sickle Cell Disease Patients Is Associated With More Severe Cerebral Vasculopathy
Authors: Megha Kaushal, Ross M. Fasano, Colleen Byrnes, Naomi L.C. Luban, Emily Riehm Meier, Jeffery L. Miller
Journal: Blood (2013)
Healthy diet could prevent gout flares, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Eating a diet high in whole grains, fruit, and vegetables and low in red meat and saturated fats may significantly reduce serum uric acid, a randomised study has shown. The authors say this may help to reduce flares in patients with gout.1

Serum uric acid is an important factor in the causative pathway for gout, and several drug development programmes are investigating how to reduce this metabolite. But, even though diet plays a major role in determining serum …
Natural Language Processing and Electronic Medical Records—Reply
Authors: Harvey J. Murff
Journal: JAMA (2011)

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