tbuckley/cabot-search huggingface dataset:
A phase II, pharmacokinetic (PK), and pharmacodynamic (PD) study of weekly docetaxel (DOC) in patients with platinum-resistant ovarian cancer
Authors: K. Odunsi, S. Ghamande, M. Macfee, A. Yin Chieh Yu, S. B. Lele, K. J. Rodabaugh, B. Thomas, W. C. Zamboni
Journal: Journal of Clinical Oncology (2009)

e16531 Background: DOC at 30 mg/m 2 q wk for 3 wks q 4 wks was modestly active and minimized toxicity in patients (pts) with platinum resistant epithelial ovarian cancer compared to historical data of DOC at 75 to100 mg/m 2 q 21 days (Berkenblit, Gynecologic Oncology 2004). However, the optimal schedule of weekly DOC in pts with ovarian cancer has not been determined. Our study assessed the activity and safety of weekly DOC at 36 mg/m 2 q wk for 6 wks q 8 wks in platinum and paclitaxel resistant ovarian cancer. PK and PD studies of DOC were performed on wks 1 and 6. Methods: Pts (n = 25) with platinum and paclitaxel resistant ovarian cancer with up to 3 previous treatments were eligible. DOC was administered at 36 mg/m 2 IV over 30 min q wk for 6 wks repeated q 8 wks until complete response or disease progression. Plasma samples were obtained from 0 to 24 h after administration of DOC on wks 1 and 6 of cycle 1. DOC plasma conc were determined by liquid chromatography mass spectrometry (LC-MS). Non-compartmental analysis of area under the plasma conc versus time curves (AUC) was calculated by WonNonLin. Results: Of the 25 pts, 6 pts (24%) had a partial response (PR) and 4 pts (16%) had stable disease using GCIG criteria or NCI RECIST criteria. Median duration of response in these 10 pts (40%) was 16.5 wks. Median survival was 32.5 wks with 4 out of 10 pts alive with disease. Hematological toxicity was mild with 20% grade 3 anemia and 20% grade 3/4 neutropenia. Mean ± SD DOC AUC on wks 1 and 6 were 2,520 ± 1,017 and 2,808 ± 1,247 ng/mL·h, respectively. Mean ± SD ratio of DOC AUC on wk 6 to wk 1 for each pt was 1.11 ± 1.23. Conclusions: DOC at 36 mg/m 2 q wk for 6 wks q 8 wks was active and well tolerated, and offered meaningful palliation in pts with platinum and paclitaxel ovarian cancer. Significant reduction in hematological toxicity over standard DOC schedule was observed. There is high inter-patient and low intra-patient variability in the PK of DOC from wk 1 to wk 6. No significant financial relationships to disclose.
流感疫苗在65岁以上人群中的应用——虽然目前对流感疫苗的效果还存质疑，但其益处可能很大
Authors: Rachel, Jordan, Jeremy, Hawker, 王翠娣
Journal: BMJ (2009)

每年的预防流感接种工作是英国最成功实施的公共卫生项目之一，据估计，70岁以上人群中应用流感疫苗约占78％，这一比例在欧洲是最高的。。该项工作的理论基础是：疫苗有效，且经济划算。尽管老年人因免疫功能减退，使接种疫苗的效果不如年轻人，但是，一项对60岁以上人群所做的高质量、随机对照试验显示老年人接种疫苗具有显效（血清学证实的流感为58％，其95％可信限区间为26％～77％；
Phase I and Pharmacokinetic Study of a Daily Times 5 Short Intravenous Infusion Schedule of 9-Aminocamptothecin in a Colloidal Dispersion Formulation in Patients With Advanced Solid Tumors
Authors: Virginie M.M. Herben, Roel van Gijn, Jan H.M. Schellens, Margaret Schot, Jan Lieverst, Michel J.X. Hillebrand, Nadja E. Schoemaker, Maria Grazia Porro, Jos H. Beijnen, Wim W. ten Bokkel Huinink
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of 9-aminocamptothecin (9-AC) in a colloidal dispersion (CD) formulation administered as a 30-minute intravenous (IV) infusion over 5 consecutive days every 3 weeks. PATIENTS AND METHODS: Patients with solid tumors refractory to standard therapy were entered onto the study. The starting dose was 0.4 mg/m 2 /d. The MTD was assessed on the first cycle and was defined as the dose at which ≥ two of three patients or ≥ two of six patients experience DLT. Pharmacokinetic measurements were performed on days 1 and 5 of the first cycle and on day 4 of subsequent cycles using high-performance liquid chromatography. RESULTS: Thirty-one patients received 104+ treatment courses at seven dose levels. The DLT was hematologic. At a dose of 1.3 mg/m 2 /d, three of six patients experienced grade 3 thrombocytopenia. Grade 4 neutropenia that lasted less than 7 days was observed in four patients. At a dose of 1.1 mg/m 2 /d, four of nine patients had grade 4 neutropenia of brief duration, which was not dose limiting. Nonhematologic toxicities were relatively mild and included nausea/vomiting, diarrhea, obstipation, mucositis, fatigue, and alopecia. Maximal plasma concentrations and area under the concentration-time curve (AUC) increased linearly with dose, but interpatient variation was wide. Lactone concentrations exceeded 10 nmol/L, the threshold for activity in preclinical tumor models, at all dose levels. Sigmoidal E max models could be fit to the relationship between AUC and the degree of hematologic toxicity. A partial response was observed in small-cell lung cancer. CONCLUSION: 9-AC CD administered as a 30-minute IV infusion daily times 5 every three weeks is safe and feasible. The recommended phase II dose is 1.1 mg/m 2 /d.
The safety of long-term bevacizumab use: Results from the BRiTE observational cohort study (OCS)
Authors: D. M. Purdie, J. D. Berlin, P. J. Flynn, A. Grothey, F. F. Kabbinavar, M. F. Kozloff, W. Dong, M. M. Sugrue
Journal: Journal of Clinical Oncology (2008)

4103
Genetic Influence of the Rs Locus on Susceptibility to Avian Tumor Viruses. II. Rous Sarcoma Virus Antibody Production After Strain RPL12 Virus Inoculation
Authors: L B Crittenden, W Okazaki
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Genetic Influence of the Rs Locus on Susceptibility to Avian Tumor Viruses. II. Rous Sarcoma Virus Antibody Production After Strain RPL12 Virus Inoculation Get access Lyman B. Crittenden, Lyman B. Crittenden U.S. Department of Agriculture, ARS, Regional Poultry Research Laboratory, East Lansing, Michigan Search for other works by this author on: Oxford Academic PubMed Google Scholar William Okazaki William Okazaki U.S. Department of Agriculture, ARS, Regional Poultry Research Laboratory, East Lansing, Michigan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 36, Issue 2, February 1966, Pages 299–303, https://doi.org/10.1093/jnci/36.2.299 Published: 01 February 1966 Article history Received: 21 June 1965 Published: 01 February 1966
Analysis of management of rectal carcinoma (RC) after the establishment of Multidisciplinary Rectal Cancer Committee (MRCC)
Authors: J. Alarcon, M. Guillot, P. Mut, P. Luna
Journal: Journal of Clinical Oncology (2008)

15108 Background: Treatment of RC was heterogeneous before MRCC. Surgery was the standard treatment for rectal carcinoma (RC) with the help of radiochemotherapy (RCT) applied either before or after the operation. Pathologic complete responses (pCR) are 9–14% with 5FU in phase III studies. Methods: A MRCC was settled at the beginning of 2006 in our institution. With a mean follow up of 17.5 months, we report data about 53 rectal cancer patients (p) admitted to our centre between 2005 and 2007. Results: Mean age was 67 years (range 46–84). Seventy percent were male. Performance status (PS) 0 in 30% and PS 1 57%. All had adenocarcinoma in histology, moderately differentiated in 43.4%. Pelvis MRI was performed in 56.6%, rectal USE in 54.7%, and both in 37.7%. Twenty four patients (45.3%) received no preoperative treatment, distributed as follows: cT2 2p; cT3 5p; cN+ 5p. Data about clinical stage were not recorded in 12p. Neoadjuvant RCT was administered in 29 patients (54.7%) distributed as follows cT3 2p; cT4 1p; cN+ 26p. RCT consisted in chemotherapy with 5-flurouracil (5-FU) 225 mg/m2/day continuous infusion IV concomitantly with radiotherapy. Mean dose of 45 Gy (45–50.4 Gy) in 1.8 Gy fractions was delivered. RCT was completed in 82.7% of patients. Patients treated preoperatively were in pathologic stages ypT0 2p; ypT1 4p; ypT2 6p; ypT3 8p; ypN+ 6p. Downstaging was seen in 76.9%. In two patients (6.9%) pCR was achieved. Significant GIII toxicities were diarrhea in 6.9%, neutropenia in 6.9% and asthenia 3.5%. Surgery group were pT1 1p; pT2 2p; pT3 8p; pN+ 12p. One metastatic relapse was seen in the neoadjuvant group, and 4 metastatic and two local relapses in the surgery group. Conclusions: Neoadjuvant 5FU continuous infusion IV with RT seems to provide downstaging and pCR and is generally well tolerated. Multidisciplinary approach is mandatory to homogenize the clinical management of RC patients. No significant financial relationships to disclose.
Recording casualties of war
Authors: Hamit Dardagan
Journal: BMJ (2015)

Analysis, doi:10.1136/bmj.h4736

Why better data are important 

The impulse to create a permanent record of a war, including those who died in it, is far from new. The Louvre’s curators believe that the museum contains the remains of the oldest known historical document, and certainly its oldest war memorial, the Stele des Vatours, so named because of its representations of vultures feasting on the corpses.1 Dating from around 2450 BC the Sumerian memorial “commemorates not the glorious dead of the victors but their victory and the sorry fate of the vanquished, who are shown on the stele lying piled one upon the other.”2

Herodotus records 192 Athenians killed in the Battle of Marathon in 490 BC, an exact number that could be verified as much as 600 years later by the ancient Greek geographer Pausanias, who saw the stele inscribed with their names at their burial mound. Tellingly, the rounded number of 6400 Persians killed, estimated by the Greek victors, remains a matter of historical debate3—even today any record of …
A Public Health Framework for Screening Mammography
Authors: Kenneth W. Lin, Lawrence O. Gostin
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Mobile Text Messaging and Adherence of Patients to Medication Prescriptions
Authors: Robby Nieuwlaat, Niraj Mistry, R. Brian Haynes
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Comparison of intrapulmonary percussive ventilation and high frequency chest wall oscillation in patients with severe COPD
Authors: Davide Russo, Christopher Romaggi, Bruna Grecchi, Antonello Nicolini
Journal: European Respiratory Journal (2014)

Background  We test the hypothesis that adding IPV or HFCWO to the best pharmacological therapy (PT) may provide additional clinical benefit over PT in patients with severe COPD.  Methods  Sixty patients were randomized to three groups ( 20 patients in each group) : a group was treated with PT and IPV, a group with PT and HFCWO and a group with PT alone.Primary outcome measures included dyspnea scale (MMRC),breathlessness, cough, and sputum scales, as well as daily life activity evaluations (CAT, BCSS). Secondary outcome measures were pulmonary function testing, arterial blood gas analysis (ABG), and hematological examinations.  Results  Both patients in the IPV group and in the HFCWO group showed a significant improvement in the tests of dyspnea and quality of life assessment (MMRC, BCSS,CAT) compared to the control group, as well as in pulmonary function tests and ABG. However, in the group comparison analysis for the same variables between IPV group and HFCWO group we observed a significant improvement in the IPV group MIP, MEP (p≤0.01) and BCSS (p≤ 0.001), CAT (p≤ 0.02).  Discussion  The two techniques improve the quality of life and lung function in patients with severe COPD. IPV demonstrated a significant greater effectiveness in improving some pulmonary function tests linked to the respiratory muscle strength and quality of life tools (BCSS,CAT) than HFCWO.
Kinetics of Cell Replication of Migration in Atypical Epithelia the Uterine of Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: C A Rubio, A Zetterberg, Y Kock, M Sveander, M Edenholm
Journal: JNCI Journal of the National Cancer Institute (1980)

The migration of tritiated thymidine ([3H]dThd)-labeled cells toward the epithelial surface was recorded at various intervals (from 1 to 240 hr) in the normal and atypical cervical epithelial of 127 C57BL mice. Cervical atypias were induced by local application of 3,4-benzo[a]pyrene for 5 months9 This treatment was discontinued 7 days before the animals were killed. Cells were labeled by a single ip injection of 6 muCi [3H]dThd/g body weight. The disappearance of heavily labeled cells in normal animals 96 hours after the pulse and in solvent-treated controls after 144 hours suggested that the original labeled cells had been exfoliated. However, cervical atypias showed heavily labeled cells as much as 240 hours after the [3H]dThd incorporation. Universal epithelial labeling (suggesting repopulation by daughter cells) usually occurred 24--48 hours after pulse labeling in normal and control animals but occurred after 96--240 hours in animals with atypical epithelium. On the basis of these results, the pace of both cellular intraepithelium transmigration and of epithelial repopulation by atypical daughter cells is substantially retarded during the early stages of cervical carcinogenesis.
Abstract 3171: IL-25/IL-17E does not induce breast tumor cell apoptosis and both IL-17A and IL-25/IL-17E contribute to breast cancer survival and proliferation associated with generation of pro-oncogenic low molecular forms of cyclin E
Authors: Jérôme Giustiniani, Hervé Curé, Christian Garbar, Yacine Merrouche, Nathalie Bonnefoy, Jérémy Bastid, Gilles Alberici, Jean-François Eliaou, Armand Bensussan
Journal: Cancer Research (2015)

Abstract Pro-inflammatory IL-17 cytokines were initially described for their pathogenic role in chronic inflammatory diseases and subsequent accumulating evidence indicated their involvement in carcinogenesis. In the present study we focused our work on IL-17A and IL-17E which are found in the breast tumoral microenvironment. Cell proliferation and cytotoxic assays as well as Quantitative PCR and Western Blot analysis of oncogenic pathways were performed using several breast cancer cell lines and primary tumor cells. We report that IL-17A and IL-17E receptor subunits (IL17RA, RB and RC chains) are up-regulated in breast cancers versus normal samples. Moreover, IL-17E, which is undetectable in most normal breast tissues tested, is expressed at higher levels in tumors. We studied the molecular signaling following the stimulation of cell lines with IL-17A and IL-17E. We found that both cytokines induced cell proliferation and activation of pathways involved in cells survival. Accordingly, IL-17A and IL-17E promoted resistance to Docetaxel but failed to induce apoptosis as previously reported for IL-17E. Interestingly, we also revealed that both cytokines induced the generation of tumorigenic low molecular weight forms of cyclin E (LMW-E), high levels of which correlate strongly with a poor survival in breast cancer patients. These results show for the first time some of the molecular pathways activated by IL-17A and IL-17E that may participate to their pro-oncogenic activity in breast cancers. Citation Format: Jérôme Giustiniani, Hervé Curé, Christian Garbar, Yacine Merrouche, Nathalie Bonnefoy, Jérémy Bastid, Gilles Alberici, Jean-François Eliaou, Armand Bensussan. IL-25/IL-17E does not induce breast tumor cell apoptosis and both IL-17A and IL-25/IL-17E contribute to breast cancer survival and proliferation associated with generation of pro-oncogenic low molecular forms of cyclin E. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3171. doi:10.1158/1538-7445.AM2015-3171
CD4<sup>+</sup>T effector memory cell dysfunction is associated with the accumulation of granulocytic myeloid-derived suppressor cells in glioblastoma patients
Authors: Daniel Dubinski, Johannes Wölfer, Martin Hasselblatt, Tilman Schneider-Hohendorf, Ulrich Bogdahn, Walter Stummer, Heinz Wiendl, Oliver M. Grauer
Journal: Neuro-Oncology (2015)

Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of myeloid cells that are significantly expanded in cancer patients and are associated with tumor progression.Multicolor flow cytometry was used to study the frequency, phenotype, and function of MDSCs in peripheral blood and freshly resected tumors of 52 participants with primary glioblastoma (GBM).The frequency of CD14(high)CD15(pos) monocytic and CD14(low)CD15(pos) granulocytic MDSCs was significantly higher in peripheral blood of GBM participants compared with healthy donors. The majority of granulocytic MDSCs consisted of CD14(low)CD15(high) neutrophilic MDSCs with high T-cell suppressive capacities. At the tumor side, we found an increase in CD14(high)CD15(pos) monocytic MDSCs and high frequencies of CD14(low)CD15(pos) granulocytic MDSCs that displayed an activated phenotype with downregulation of CD16 and upregulation of HLA-DR molecules, which did not inhibit T-cell proliferative responses in vitro. However, a strong association between granulocytic MDSCs and CD4(+) effector memory T-cells (TEM) within the tumors was detected. Tumor-derived CD4(+) TEM expressed high levels of PD-1 when compared with their blood-derived counterparts and were functionally exhausted. The respective ligand, PD-L1, was significantly upregulated on tumor-derived MDSCs, and T-cell co-culture experiments confirmed that glioma-infiltrating MDSCs can induce PD-1 expression on CD4(+) TEM.Our findings provide a detailed characterization of different MDSC subsets in GBM patients and indicate that both granulocytic MDSCs in peripheral blood and at the tumor site play a major role in GBM-induced T-cell suppression.
Contrast Enhanced Ultrasound Sonography in Intestinal Acute Graft Versus Host Disease: Advantages of Non-Invasive Anatomic and Physiologic Measurements.
Authors: Edoardo Benedetti, Benedetto Bruno, George B. McDonald, Francesco Caracciolo, Federico Papineschi, Matteo Pelosini, Daniele Focosi, Sara Galimberti, Mario Petrini
Journal: Blood (2009)
Epothilone B analog (BMS-247550) at the recommended phase II dose (RPTD) in patients (pts) with gynecologic (gyn) and breast cancers
Authors: T. Chen, A. Molina, S. Moore, S. Goel, K. Desai, A. Hamilton, T. Griffin, A. D. Colevas, S. Mani, F. Muggia
Journal: Journal of Clinical Oncology (2004)

2115 Background & Methods: Epothilones differ from taxanes in biodistribution and mechanisms of resistance. Our prior phase I study (ASCO 2002, abstract#409) established the RPTD of BMS-247550 to be 40mg/m2 as a 1hour infusion every 3 weeks. 42 pts (21 gyn, 13 breast, 8 other) were entered at this dose level: male/female 4/38, median age 56 years (range 29–81), performance status 0–1, median # prior cytotoxic regimens 3 (range 0–8). Results: Neutropenia and neuropathy were the most frequent toxicities. Grade ≥3 neutropenia occurred in 19 pts (4 with fever on cycle(C)1 day(D)14, C5D6, C2D8, and fatal sepsis in an 81 y/o on C1D7) leading to 8 dose reductions. 10 pts (9 on prior taxanes or cisplatin) developed new onset grade ≥2 neuropathy (2 grade 3) after a median of 3 cycles (range 2–8). 1 previously untreated pt developed neuropathy after 8 cycles. All resolved to grade ≤ 1 by the next cycle, including 1 who refused further therapy. Other toxicities: thrombocytopenia, anemia, fatigue, alopecia, and gastrointestinal (e.g. nausea, vomiting, abdominal pain, diarrhea) were rarely grade 3. Hypersensitivity reaction occurred in 2 pts on cycles 2 and 3 with successful rechallenge. Pharmacokinetic/toxicity and other lab correlates (e.g. microtubule bundling) are under analysis. Median cycle # was 3 (gyn), 3 (breast), and 2.5 (other). Gyn (all taxane pretreated) partial response (PR)= 2 (1/14 ovarian, 1/3 endometrial primaries); breast (11/13 taxane pretreated) PR= 4 (all taxane pretreated). Conclusion: BMS-247550 is tolerated at 40mg/m2 every 3 weeks as a 1hr infusion, and has activity in gyn and breast cancers pretreated with taxanes. Supported in part by N01-CM17103, U01-CA76642, M01 RR00096, & P30 CA16087 No significant financial relationships to disclose.