tbuckley/cabot-search huggingface dataset:
Survival results with AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas: Update of phase II trial
Authors: S. P. Chawla, A. W. Tolcher, A. P. Staddon, S. Schuetze, G. Z. D'Amato, J. Y. Blay, J. Loewy, R. Kan, G. D. Demetri
Journal: Journal of Clinical Oncology (2007)

10076 Background: AP23573 is an mTOR inhibitor that has demonstrated single-agent activity in a broad range of sarcoma tumor types in phase I phase II trials. Overall survival (OS) was monitored to characterize OS in the treated population and in the subset of patients who achieved a clinical benefit response (CBR). Methods: Pts with advanced sarcomas, with no restrictions on prior therapies, were enrolled into 4 cohorts based on histologic subtype, in a phase 2, Simon's 2-stage trial. AP23573 (12.5 mg, i.v.) was administered daily × 5 every 2 wks. Efficacy was assessed using RECIST, with CBR defined as a complete or partial response or stable disease for at least 16 wks duration. OS was defined as the time from the first dose of AP23573 to the date of death from any cause. Kaplan-Meier estimates of the survival times of the population were calculated with OS time censored at the last date the pt was known to be alive when the confirmation of death is absent or unknown. Patients are continuing to be followed for OS in this ongoing trial. Results: 212 pts (105 M/107 F; median age, 50.6 yrs ([17–79 yrs]) were treated. Most pts (79%) had received =2 prior treatments, and over 90% of pts had disease progression at time of enrollment. The overall CBR rate was 29%, including 5 PRs (4 bone sarcoma, 1 MFH). The median OS was 40.1 wks for the entire study population. In the subset of patients achieving CBRs the median time to OS was 67.6 wks, suggesting that achievement of CBR, which is a measure of tumor control, correlates with extending OS. Conclusions: AP23573 exhibits single-agent activity in pts with advanced sarcomas as demonstrated by the CBR rate as a primary efficacy endpoint. The results of the OS analysis suggest that achieving a CBR in this pt population can result in prolonged survival. The consistency of this finding should be further examined with other pt factors that are also hypothesized to correlate for survival in this pt population. [Table: see text] [Table: see text]
만성C형간염 환자의 페그인터페론-리바비린 2제요법에서 치료반응에 미치는 순응도 효과 및 병합치료에 대한 순응도를 향상시키기 위한 대책
Authors: 이진우 ( Jin Woo Lee )
Journal: Clinical and Molecular Hepatology (2011)
Welfare changes could put an extra 1.5 million children into poverty
Authors: Ingrid Torjesen
Journal: BMJ (2016)

More than five million children could be growing up in poverty by 2020 as a result of the government’s proposed changes to the benefits system, a committee of MPs has said.

The All Party Parliamentary Group on Health in All Policies made the prediction as it published the findings of its inquiry into the effect on child poverty and child health of the Welfare Reform and Work Bill, being debated in parliament.1

The inquiry looked at the potential effect of seven measures in the Welfare Reform and Work Bill. It said that six measures would directly and …
Molecular basis for alpha-thalassemia associated with the structural mutant hemoglobin Suan-Dok (alpha 2 109leu----arg) [published erratum appears in Blood 1991 Mar 15;77(6):1404]
Authors: I Weiss, FE Cash, MB Coleman, A Pressley, JG Adams, T Sanguansermsri, SA Liebhaber, MH Steinberg
Journal: Blood (1990)
Abstract 13277: Abdominal Aortic Aneurysms in the Young: A Case-Control Study
Authors: Pavel J Levy, Chenchen Huang, Jeanette S Andrews, Billy G Chacko, George W Plonk, Randolph L Geary, Matthew S Edwards
Journal: Circulation (2013)

Background: Abdominal aortic aneurysms (AAA) in the young are rare. Previous studies of premature lower extremity atherosclerosis (PLEA) demonstrated frequent severe aorto-iliac occlusive disease (...
Thalamic Influences on the Gamma Motor System
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
Randomized, open-label, phase III study of pemetrexed plus carboplatin (PemC) followed by maintenance pemetrexed versus paclitaxel/carboplatin/bevacizumab (PCB) followed by maintenance bevacizumab in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).
Authors: Ralph Zinner, Helen J. Ross, Robert Weaver, Ramaswamy Govindan, Viran R. Holden, Naveed Mahfooz Chowhan, J. Thaddeus Beck, David Michael Waterhouse, Manuel Modiano, Vijay Phooshkooru Rao, Jingyi Liu, Andrew Koustenis, Symantha Melemed, Susan C. Guba, Waldo Feliu Ortuzar, Durisala Desaiah, David R. Spigel, Coleman K. Obasaju
Journal: Journal of Clinical Oncology (2013)

LBA8003 Background: PemC and PCB are regimens used for first-line treatment of advanced NS-NSCLC. The primary objective was to compare progression-free survival without Grade 4 toxicity (G4PFS) between two vs three drug regimen arms. Methods: Patients ≥18 years, Stage IV NS NSCLC, AJCC (v7.0), and ECOG PS 0/1 were enrolled. Patients were randomized (1:1); received 4 cycles of induction (PemC: Pem, 500 mg/m 2 and C, AUC = 6; PCB: P, 200 mg/m 2 , C, AUC = 6, and B, 15 mg/kg) followed by Pem (PemC Arm) or B (PCB Arm) maintenance therapy in the absence of progressive disease or discontinuation. Secondary endpoints were PFS, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). The study was powered for G4PFS; assuming hazard ratio (HR) of 0.75; there was 80% power to detect superiority of PemC over PCB with a 2-sided type I error of 0.10. Efficacy data were analyzed by intent-to-treat principle using the log-rank test for time-to-event variables, and an exact test for ORR and DCR. Safety data were evaluated using CTCAE v3 for patients who received ≥1 dose of study treatment. Results: Patients were randomized to PemC (N = 182) or PCB (N = 179). Baseline factors were balanced between arms: median age 66/66 years; % female 42/42; % PS=0, 47/47; % stage IV M1a 29/30; for PemC vs PCB, median G4PFS (months) was 3.91/2.86 (HR = 0.85, 90% CI 0.7, 1.04, p = 0.176); PFS and OS had HR = 1.06 (95% CI 0.84, 1.35), p = 0.610, and HR = 1.07 (95% CI 0.83, 1.36), p = 0.616, respectively. The ORR (%) 23.6/ 27.4 and DCR (%) 59.9/57.0 were for PemC vs PCB, respectively. Significantly more drug-related grade 3/4 anemia (18.7% vs 5.4%), and thrombocytopenia (24.0% vs 9.6%) were seen on PemC; significantly more grade 3/4 neutropenia (48.8% vs 24.6%) and grade 1/2 alopecia (28.3 % vs 8.2%) were seen on PCB. Conclusions: PemC was not superior to PCB in G4PFS; no difference in PFS or OS was observed for the two- vs three-drug regimens. There were no unexpected toxicities; the toxicity profiles demonstrated distinctions by arm, and both regimens demonstrated tolerability. Clinical trial information: NCT00948675.
The Deletion of Kynurenine Hydroxylase Activity During Hepatocarcinogenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Donald E. Kizer, Boyd A. Howell
Journal: JNCI Journal of the National Cancer Institute (1963)

To determine whether hepatomas retained the enzymatic capability to convert kynurenine to 3-hydroxykynurenine, kynurenine hydroxylase activity was measured in a spectrum of transplanted tumors carried in both rats and mice; in primary hepatomas induced with 4-dimethylaminoazobenzene (DAB), 3′methyl-DAB (3′Me-DAB), and 4′fluoro-DAB (4′F-DAB); and in the livers of animals fed diets containing 3′Me-DAB or the relatively weak carcinogen 4′methyl-DAB (4′Me-DAB). The enzyme activities of both normal and malignant tissues were assayed in mitochondria isolated by differential centrifugation and disrupted by treatment with digitonin. No kynurenine hydroxylase activity was detected in 4 transplanted rat hepatomas, in 2 transplanted mouse hepatomas, or in primary hepatomas induced in rat liver. The absence of activity in hepatomas was not associated with endogenous inhibitors or with the absence of essential activators in whole or soluble fraction mitochondria isolated from normal liver. Also ineffective were several compounds which were possible activators or co-factors for kynurenine hydroxylase. The kynurenine hydroxylase activity of animals maintained on a basal riboflavine-deficient diet, or this diet plus 0.06 percent 3′Me-DAB, or basal diet with 0.06 percent 4′Me-DAB, was determined at 4-week intervals throughout 12 weeks. All 3 groups sustained losses, which were heaviest in the group fed 3′Me-DAB and less severe in the group fed 4′Me-DAB. Hydroxylase activity changed least in the group maintained on the riboflavine-deficient basal diet. We concluded that factors in addition to those associated with malignant transformation altered the kynurenine hydroxylase activity of precancerous liver.—J Nat Cancer Inst 30: 675–686, 1963.
Prospective evaluation of meningeal involvement in primary CNS lymphoma (PCNSL)
Authors: A. Korfel, L. Fischer, P. Martus, M. Weller, H. Klasen, B. Rohden, A. Röth, B. Storek, M. Hummel, E. Thiel
Journal: Journal of Clinical Oncology (2008)

2029 Background: The prognostic impact of meningeal dissemination (MD) in PCNSL is still debated, and the reported incidence varies. Sensitive methods like polymerase chain reaction (PCR) might enhance the diagnostic accuracy to detect clonal cells in the cerebrospinal fluid (CSF). We prospectively evaluated the diagnostic value of PCR in comparison with CSF cytomorphology and cerebral magnetic resonance imaging (MRI) for diagnosing MD in PCNSL. Methods: A total of 282 patients from a multicenter therapy trial for PCNSL were evaluated for the presence of MD: 217 with cranial MRI, 205 with CSF cytomorphology and 171 with PCR of the rearranged immunoglobulin heavy-chain CDRIII region genes in CSF. A CSF protein ≥45mg/dl and a CSF cell count > 5/μl were denoted as abnormal. Results: MD was found in 33 of 205 patients (16%) by cytomorphologic examination, in 19 of 171 (11%) patients evaluated by PCR and in eight of 216 patients (4%) by MRI. Considering all methods, the incidence of MD was 17.4% (49 of 282 patients). PCR was monoclonal in six of 19 samples (32%) with positive, in one of 13 samples (7.7%) with suspicious, and in ten of 105 (9.5%) samples with negative cytology. In 11 samples with positive and 12 with suspicious cytology PCR was polyclonal. Of the eight MRI positive patients, CSF cytology was positive in five (two patients not evaluated), and a monoclonal PCR product was found in two (six patients not evaluated). MD was more probable in cases with CSF pleocytosis with an odds ratio of 2.48 (95% CI: 1.15 - 5.34, p=0.018), whereas CSF protein had no predictive value for MD detection. Pleocytosis correlated significantly with a positive cytology (23% vs. 5%, p=0.001) but not with MD detection by PCR. Conclusions: A low incidence of MD in PCNSL was found in this large prospective study, despite the use of PCR. The diagnostic accuracy was enhanced by PCR, however, discordant PCR and cytologic results were frequent. CSF pleocytosis had predictive value for MD detection. No significant financial relationships to disclose.
发热-肝、脾、淋巴结肿大
Authors: 李超, 吴东, 冯瑞娥, 卢朝辉, 陈嘉林
Journal: BMJ (2010)

患者男，32岁，因“发热伴纳差、消瘦4个月”于2009年4月8日入院。青年男性，不明原因发热（FUO），有消耗症状。FUO的病因主要分为3类：感染、自身免疫病和恶性肿瘤。既往北京协和医院的资料表明，上述3类疾病分别占FUO病因构成的49．0％、16．9％和14．3％；就单病种而言，结核最为常见（21．6％），恶性肿瘤中淋巴瘤（5．4％）占重要地位。
Advanced non-small-cell lung cancer: to treat or not to treat?
Authors: H H Hansen
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.11.1711 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2824704 Advanced non-small-cell lung cancer: to treat or not to treat? H H HansenxH H HansenSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.11.1711 PDF "Advanced non-small-cell lung cancer: to treat or not to treat?." Journal of Clinical Oncology, 5(11), pp. 1711–1712© 1987 by American Society of Clinical Oncology
Analysis of expression of TGF-β1 receptor (ALK-1) in normal and tumor tissues by tissue microarrays
Authors: A. Erbersdobler, R. Simon, O. J. Hellwinkel, C. Bokemeyer, G. Sauter, D. Hu-Lowe, W. Levin, C. Gallo-Stampino, W. Fiedler
Journal: Journal of Clinical Oncology (2009)

e22044 Background: TGF-β1 is an important angiogenic factor involved in different aspects of angiogenesis and vessel maintenance. TGF-β1 receptors consist of class I, class II and accessory receptors. Activin-like kinase I (ALK-1) is a class I TGF- β1 receptor which is almost exclusively expressed on endothelial cells. Hereditary hemorrhagic telangiectasia (HHT) is caused by mutations in the ALK-1 gene. Knock-out mice for ALK-1 die during gestation due to vascular malformation. ALK-1 may thus represent an attractive target for anti-angiogenic therapy. A therapeutic monoclonal antibody (PF-03446962) against ALK-1 has been developed which is currently in phase I testing. Here we describe target validation in normal and tumor tissue using tissue micro-arrays (TMAs). Methods: Normal tissue arrays comprised of 609 individual histological samples representing 76 human tissues. Multi-tumor arrays consisted of 3923 individual tumor samples from 87 tumor types. Consecutive sections of tissue arrays were stained for ALK-1 and CD31. CD31 immunohistology (IHC) was performed to ensure presence of vessels within tissue samples. ALK-1 staining was graded 0=absent, 1=weak, 2= moderate and 3=strong by an experienced pathologist blinded to tissue type. Results: ALK-1 staining of vessels in normal tissues was generally weak (mostly grade 1 and rarely grade 2) and was detectable in lymphatic tissues including tonsil, lymph nodes, thymus and spleen, lung, the entire GI tract including parotid, submandibular and sublingual glands as well as pancreas. ALK-1 positive vessels were also found within the female genital tract including placenta, uterus and ovary. In human tumor vessels ALK-1 expression showed high variability between tumor types. The highest ALK-1 expression rate was found in lung cancer (NSCLC 49%, SCLC 83%), neuroendocrine pancreas tumor (71%), colon cancer (50%), chondrosarcoma 50%, angiosarcoma 40% and NHL (44%). Conclusions: TMAs are an excellent tool to verify target expression in normal and tumor tissues. Results may be used to predict side effects of targeted therapy and to direct phase II testing of innovative agents in patients likely to respond. [Table: see text]
Tumor-Associated Immunity in Bovine Ocular Squamous Cell Carcinoma Detected by Leukocyte Adherence Inhibition Microassay2
Authors: Philip A. Jennings, William J. Halliday, Denis Hoffmann
Journal: JNCI Journal of the National Cancer Institute (1979)

A microplate modification of the leukocyte adherence inhibition (LAI) assay was used with blood leukocytes from cattle with ocular squamous cell carcinomas (OSCC); control groups were cattle with ocular or cutaneous lesions (not carcinoma) and healthy normal cattle. For the assay, saline extracts of OSCC and skin from the same donor, lymphosarcoma, and mastocytoma (M) were used as antigens. Specific LAI reactivity to OSCC extract (but not to skin extract) was detected in 14 of 18 animals with squamous cell carcinoma. One animal with OSCC showed LAI reactivity to both OSCC and M-extracts. No control animals had LAI reactivity to OSCC extract, but 1 clinically normal cow had LAI with the M-extract. Leukocyte adherence stimulation reactions with the various antigens were seen in all groups of animals.
Free Speech and Pharmaceutical Regulation—Fishy Business
Authors: Amy Kapczynski
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
Genetic predisposition to oral absorption of imatinib: Correlation of a variant allele in ABCG2 with transport activity
Authors: E. R. Lepper, A. T. van Oosterom, E. A. de Bruijn, W. D. Figg, J. Verweij, A. Sparreboom, K. Nooter
Journal: Journal of Clinical Oncology (2005)

3026 Background: Imatinib mesylate (Gleevec, STI-571), an inhibitor of Bcr-abl tyrosine kinase, is currently being used in the treatment of chronic myeloid leukemia and gastrointestinal stromal cell tumors. Interindividual pharmacokinetic variability of imatinib in humans is very substantial, but currently unexplained. Imatinib has recently been shown to be a substrate for ABCG2, a transporter protein that is highly expressed in the intestines and liver, suggesting a major role in drug disposition. A single nucleotide polymorphism (SNP) has been identified in the ABCG2 gene resulting in a non-synonymous mutation (421C>A; Q141K) that causes impaired ability to transport substrates in vitro. Herein, we sought to determine whether patients possessing the mutation would have higher exposure to imatinib. Methods: Patients were treated with oral imatinib at a dose of 100-1000 mg/day. At steady-state, a series of blood samples were drawn to provide a full pharmacokinetic profile over one dosing interval. Imatinib concentrations in plasma were determined by liquid chromatography with tandem mass-spectrometric detection. Pharmacokinetic parameters were calculated by non-compartmental analysis using WinNonlin, and were normalized to total drug dose. Genotyping was carried out using direct sequencing. Results: Of 36 white cancer patients evaluated (23 males, 13 females; median age, 59 years), 32 were wild-type and four were heterozygous for the ABCG2 421C>A SNP (allele frequency, 0.056). No patients with the homozygous variant sequence were identified. The systemic exposure to imatinib, assessed using the area under the curve of imatinib, was approximately 3-fold higher in patients that were heterozygous for the tested SNP compared to patients with the wild-type sequence [mean (± SE), 391 ± 255 versus 136 ± 17.9 ng.h/mL; P = 0.011, t-test]. Conclusions: This pilot study indicates a genetic predisposition to the oral absorption of imatinib, suggesting that patients with low intestinal ABCG2 activity due to ABCG2 421C>A may be at an increased risk for imatinib-induced toxicity. This observation warrants confirmation in a larger patient population involving different ethnic groups. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma
Authors: Nicolas Jacquelot, David P. Enot, Caroline Flament, Nadège Vimond, Carolin Blattner, Jonathan M. Pitt, Takahiro Yamazaki, María Paula Roberti, Romain Daillère, Marie Vétizou, Vichnou Poirier-Colame, Michaëla Semeraro, Anne Caignard, Craig L. Slingluff, Federica Sallusto, Sylvie Rusakiewicz, Benjamin Weide, Aurélien Marabelle, Holbrook Kohrt, Stéphane Dalle, Andréa Cavalcanti, Guido Kroemer, Anna Maria Di Giacomo, Michele Maio, Phillip Wong, Jianda Yuan, Jedd Wolchok, Viktor Umansky, Alexander Eggermont, Laurence Zitvogel
Journal: Journal of Clinical Investigation (2016)

Melanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4+ and CD8+ T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate whether T cell CCR/CXCR expression correlates with intratumoral accumulation, metastatic progression, and/or overall survival (OS). Homing receptor expression on lymphocytes strongly correlated with MMel dissemination. Loss of CCR6 or CXCR3, but not cutaneous lymphocyte antigen (CLA), on circulating T cell subsets was associated with skin or lymph node metastases, loss of CXCR4, CXCR5, and CCR9 corresponded with lung involvement, and a rise in CCR10 or CD103 was associated with widespread dissemination. High frequencies of CD8+CCR9+ naive T cells correlated with prolonged OS, while neutralizing the CCR9/CCL25 axis in mice stimulated tumor progression. The expansion of CLA-expressing effector memory CD8+ T cells in response to a single administration of CTLA4 blockade predicted disease control at 3 months in 47 patients with MMel. Thus, specific CCR/CXCR expression patterns on circulating T lymphocytes may guide potential diagnostic and therapeutic approaches.