tbuckley/cabot-search huggingface dataset:
Splenic Fibrosis and Sarcomas in F344 Rats Fed Diets Containing Aniline Hydrochloride, &lt;italic&gt;p&lt;/italic&gt;-Chloroaniline, Azobenzene, &lt;italic&gt;o&lt;/italic&gt;-Toluidine Hydrochloride, 4,4′-Sulfonyldianiline, or D &amp;amp; C Red No. 9&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D. G. Goodman, J. M. Ward
 5, W. D. Reichardt
Journal: JNCI Journal of the National Cancer Institute (1984)

In six carcinogenicity bioassays, male and female F344 rats were fed diets containing aniline hydrochloride (CAS: 142-04-1; hydrochloride benzenamide), p-chloroaniline (CAS: 106-47-8), azobenzene (CAS: 103-33-3), o-toluidine hydrochloride (CAS: 636-21-5), dapsone (CAS: 80-08-0; 4,4'-sulfonyldianiline), or D & C red No. 9 [CAS: D85500000; 5-chloro-2-[2-hydroxy-1-naphthalenyl)azo)-4-methylbenzenesulfon ic acid, barium salt]. The rats, from 6 weeks to 2 years old, were given the compounds at two dose levels, the estimated maximum tolerated dose and one-half that dose. In all six bioassays, dose-dependent incidences of splenic sarcomas and fibrosis were seen, with the highest incidences in male rats. Fibrosis occurred in the splenic parenchyma and/or the capsule. Fatty infiltration also was seen in the spleen. Sarcomas appeared to arise in the splenic red pulp or splenic capsule, usually in association with areas of parenchymal and capsular fibrosis and pigmentation. Larger tumors metastasized to the peritoneal cavity and abdominal organs. In some rats there was marked osseous metaplasia when the primary tumor metastasized to peritoneal surfaces. Other, less common, splenic neoplasms included hemangiosarcoma and hemangiopericytoma. Some rats had such extensive peritoneal involvement that the site of origin of their sarcoma was difficult to determine.
HER2-positivity rates in advanced gastric cancer (GC): Results from a large international phase III trial
Authors: Y. Bang, H. Chung, A. Sawaki, J. Xu, L. Shen, O. Lipatov, S. R. Park, V. P. Gangadharan, S. H. Advani, Y. K. Kang
Journal: Journal of Clinical Oncology (2008)

4526 Background: Several studies have shown that HER2 is a negative prognostic factor in GC; however, the incidence of this disease has not been reliably established. Reported HER2-positivity rates vary widely (6–35%) due to small sample sizes and methodological differences between studies. The international, Phase III ToGA trial, which is evaluating trastuzumab (herceptin) + fluoropyrimidine (5-FU or capecitabine) + cisplatin vs chemotherapy alone in advanced HER2-positive GC, is the first prospective large-scale study to comprehensively assess HER2 positivity in GC. A total of 2484 patients (pts) have been evaluated, representing the largest dataset to describe the extent of HER2-positive disease in advanced GC. Methods: Formalin-fixed, paraffin-embedded GC samples were centrally assayed by both IHC (modified HercepTest™; Hofmann et al. ASCO Gastrointestinal Cancers Symposium 2006; abs. 24) and FISH (pharmDx) in parallel. Results: Of the 2,484 GC samples screened to date, 544 were HER2 positive and 1,940 HER2 negative, giving an overall HER2-positivity rate of 21.9%. IHC and FISH results were available for 2,218 samples, with 87.3% concordance. The HER2-positivity rate was similar for tumour tissue obtained during surgery and via biopsy (p=0.13). However, HER2 positivity was significantly associated with tumour location (19.9% stomach vs 32.2% gastro-oesophageal junction; p=0.02) and differentiation type (32.5% intestinal vs 6.0% diffuse; p<0.001). Interestingly, the average HER2-positivity rate for European countries was similar to that observed in Asian countries. Conclusions: ToGA is the largest prospective study to assess HER2 status in pts with advanced GC using a validated methodology. A high rate of HER2 positivity was observed (21.9%) in the 2484 samples assayed, similar to the HER2-positivity rate in breast cancer. Additionally, HER2-positivity rates varied significantly according to site of primary tumour and histological subtype but not according to the geographical region (Europe or Asia). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche Roche
Screening for HIV infection
Authors: Jason S Haukoos, Sarah E Rowan
Journal: BMJ (2016)

How you ask is a critical part of the process

Worldwide, approximately 37 million people are infected with HIV and approximately 46% of infections remain undiagnosed.1 The proportion of undiagnosed cases is lower in industrialized countries, although the burden of people living with undiagnosed infection remains substantial. For example, approximately 13% of the 1.2 million people living with HIV in the United States do not have a diagnosis.2 Moreover, people without a diagnosis contribute disproportionately to transmission of the virus, accounting for about 30% of HIV transmissions.3

Testing for HIV infection remains a critical first step in a series of interventions aimed at controlling the epidemic.4 People who test positive for HIV can then engage in care and attain viral suppression, which dramatically limits the possibility of forward transmission.5 Besides knowing who should be offered HIV testing, maximizing acceptance when HIV testing is offered is a vital piece of the process and may significantly …
Screening for Prediabetes and Type 2 Diabetes Mellitus
Authors: Neda Laiteerapong, Adam S. Cifu
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
A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of MN-029, a novel vascular disrupting agent (VDA), in patients (pts) with advanced solid tumors
Authors: A. D. Ricart, M. Cooney, J. Sarantopoulos, J. Brell, K. W. Locke, R. E. Gammans, G. Medina, A. Zambito, A. W. Tolcher, S. C. Remick
Journal: Journal of Clinical Oncology (2006)

3096 Background: MN-029 is a novel VDA that binds reversibly to the colchicine-binding site on tubulin and inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor endothelial cells (EC). Disruption of the tumor EC cytoskeleton ultimately leads to a temporary reduction in tumor blood flow. Methods: MN-029 is administered IV as a 10–20 min infusion, at 3-wk intervals in pts with advanced cancer. The study has followed an accelerated titration design, with intrapatient dose escalation. PD effects on tumor blood flow are evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: 28 pts were enrolled (13M/15F), median age 56 (range 35 - 76) and tumor types: colorectal (5), renal (5), hepatocellular (3), ovarian (2), melanoma (2), soft tissue sarcoma (2), carcinoid (2) and others (7). A total of 110 cycles of MN-029 were given, median 3/pt (range 1–20), over 9 dose levels (4, 8, 16, 24, 36, 54, 80, 120 and 180 mg/m 2 ). Escalation proceeded until an initial dose-limiting toxicity (DLT) was observed in 1 pt in the 180 mg/m 2 cohort, consisting of a reversible episode (3 hours post dose) of acute coronary ischemia (without sequelae and with preservation of myocardial function) probably due to coronary vasospasm. Therefore, this cohort was expanded to 6 pts, with no further DLTs observed. Common mild to moderate toxicities included nausea, vomiting (which appears dose-related), hypotension, fatigue and diarrhea. There was no significant myelotoxicity, stomatitis or alopecia. Seven pts had stable disease after 3 cycles, including 2 pts with carcinoid tumor (+21 cycles and +17 cycles). PK data generally indicated dose-related increases in C max and AUC values, although substantial inter-patient variability was observed. Tumor blood flow reduction assessed by DCE-MRI was recorded at 120 and 180 mg/m 2 , but not at 80 mg/m 2 . Conclusions: MN-029 produced reductions in tumor blood flow at doses that were well tolerated. Accrual continues at 225 mg/m 2 . [Supported in part by grants from MediciNova, Inc. and M01 RR-000080] [Table: see text]
Vaccine effectiveness in preventing laboratory-confirmed influenza in primary care patients in a season of co-circulation of influenza A(H1N1)pdm09, B and drifted A(H3N2), I-MOVE Multicentre Case–Control Study, Europe 2014/15
Authors: Marta Valenciano, Esther Kissling, Annicka Reuss, Caterina Rizzo, Alin Gherasim, Judit Krisztina Horváth, Lisa Domegan, Daniela Pitigoi, Ausenda Machado, Iwona Anna Paradowska-Stankiewicz, Antonino Bella, Amparo Larrauri, Annamária Ferenczi
Journal: Eurosurveillance (2016)

Binary file ES_Abstracts_Final_ECDC.txt matches
Phase Ib study of PTC299, a novel oral inhibitor of tumor VEGF expression, in patients with advanced cancer.
Authors: G. K. Schwartz, M. A. Dickson, L. A. Callahan, C. H. Darby, M. Llorente, Y. Cao, H. J. Dials, L. L. Miller, H. H. Miao
Journal: Journal of Clinical Oncology (2010)

3041 Background: PTC299 is a novel, oral investigational drug designed to inhibit tumor expression of VEGF and other angiogenic cytokines. PTC299–administered alone or in combination with taxanes–has shown antitumor activity in multiple xenograft models of human cancers. Methods: A phase Ib study comprised 3 stages, each using a classic 3+3 design. In stage 1, monotherapy was given 4 weeks on and 2 weeks off using body-weight-adjusted BID dosing. In stage 2, monotherapy was given continuously with unit BID or TID dosing. In stage 3, PTC299 was given with docetaxel, 75 mg/m2. Treatment was given until disease progression. Safety, PK, and activity were assessed. Results: The study enrolled 27 subjects (9 males, 18 females) with median [range] age 59 [31-75] years, ECOG PS 0 (n=16) or 1 (n=11), 13 tumor types, and median [range] of prior therapies of 3 [0-8] to receive PTC299 in stage 1 (n=12), stage 2 (n=6), or stage 3 (n=9). Median [range] of time on treatment has been 10 [3-61+] weeks. No MTD was observed through the highest dose levels: stage 1, 1.2 mg/kg BID; stage 2, 120 mg TID; and stage 3, 100 mg TID. Adverse events were infrequent, usually grade 1, and not generally considered PTC299-related. No hypertension was observed. PTC299 PK were generally dose proportional, with rapid appearance of drug in plasma, Tmax of ∼4 hours, and an effective t1/2 of ∼12 hours. From day 1 to day 28 (stage 1) or day 42 (stage 2), PTC299 showed a ∼2-fold accumulation when dosed continuously. Trough plasma concentrations exceeded values associated with maximal preclinical antitumor activity. Decreases in circulating angiogenic VEGF and inflammatory cytokines (IL-6) were seen. Patients with thyroid cancer (n=2), chondrosarcoma (n=1), and head and neck cancers (n=3) remain on study with stable disease for 14+, 2.8+, 8+, 5.6+, 3.7+, and 2.6+ months respectively. Patients with other advanced cancers (n=5) completed the study with stable disease for 3.5-12 months. Conclusions: PTC299 monotherapy or combination therapy with docetaxel is generally well tolerated, achieves target plasma concentrations, and shows evidence of pharmacodynamic and clinical activity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PTC Therapeutics PTC Therapeutics
The Great Blue Yonder
Authors: Mari Lloyd Williams
Journal: BMJ (2001)

Alex Shearer Macmillan, £9.99, pp 182 ISBN 0 333 96006 8 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> We all have an underlying curiosity of what it is like to be dead. What happens on the “other side” may not be the topic of most dinner party conversations but it probably occupies our subconscious for much of the time. As adults we can try to rationalise our destiny through our humanistic or our religious beliefs, but so often we get stuck—for example, in the grief of losing a loved … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Analysis of the dinucleotide repeat polymorphism in the epidermal growth factor receptor (EGFR) in tumor and normal tissue of head and neck cancer (HNC) patients
Authors: N. Magné, S. Pereira, M. C. Etienne, J. L. Formento, M. Francoual, F. Demard, O. Dassonville, G. Poissonnet, P. Szepetowski, G. Milano
Journal: Journal of Clinical Oncology (2004)

5518 Background: EGFR plays a major role in cell proliferation. EGFR overexpression is strongly associated with poor prognosis in HNC patients. First intron of EGFR gene contains a highly polymorphic microsatellite sequence (9 to 23 CA-repeats) and in vitro transcription declines with increasing number of repeats. We analyzed EGFR gene polymorphism and EGFR expression in tumor (T) and normal mucosa (N) of HNC patients. Methods: T biopsies (initial diagnosis) were taken in 113 patients (mean age 60, 101 men, 12 women; 13 stage II, 21 stage III, 79 stage IV; 53 cancer-related deaths) along with N biopsies for 100 patients. EGFR levels were measured by ligand-binding assay. The microsatellite marker was analyzed by semi-automated fluorescent genotyping. Prognostic values of EGFR genotype and expression on specific survival were analyzed by multivariate Cox regression including performance status and node involvement. Results: Number of CA repeats varied from 13 to 22. Allelic distribution in tumor was trimodal : 49 % 16 CA, 17.5 % 20 CA, 15.5 % 18 CA. A similar pattern was observed in N samples. Heterozygosity was 60 % and 65% in T and N, respectively. In 33% of patients genotype was discordant between T and N, strongly suggesting high EGFR microsatellite instability. There was no relationship between EGFR genotype and EGFR expression (by considering either the shorter allele, the longer, homozygous samples, samples having a common allele, or classifying genotypes as short/long/intermediary defined as 2 alleles<17 vs 2 alleles[tmsnew]63[/tmsnew]17 vs others). Cox analysis confirmed the prognostic significance of T EGFR expression (p = 0.030). T EGFR genotype did not influence survival. A poorer survival was observed in patients with short repeats in normal mucosa (short/long/intermediary, p = 0.040). Patients with EGFR microsatellite instability exhibited significantly shorter survival (p = 0.013). Furthermore, EGFR microsatellite instability (p = 0.003) and T EGFR expression (p = 0.009) were independent significant survival predictors. Conclusion: These promising new findings shed a new light on EGFR implication in HNC. No significant financial relationships to disclose.
Tyrosine Kinase Inhibitor Treated CML Patients Harboring Philadelphia-Negative Cytogenetically Aberrant Clones Show Molecular Mutations In 31% Of Cases Not Present At Diagnosis: A High-Throughput Amplicon Sequencing Study Of 29 Genes
Authors: Susanne Schnittger, Sabrina Kuznia, Manja Meggendorfer, Niroshan Nadarajah, Sabine Jeromin, Tamara Alpermann, Andreas Roller, Andreia Albuquerque, Sandra Weissmann, Thomas Ernst, Christiane Eder, Frank Dicker, Wolfgang Kern, Alexander Kohlmann, Torsten Haferlach, Andreas Hochhaus, Claudia Haferlach
Journal: Blood (2013)
Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo
Authors: Susan Ashton, Young Ho Song, Jim Nolan, Elaine Cadogan, Jim Murray, Rajesh Odedra, John Foster, Peter A. Hall, Susan Low, Paula Taylor, Rebecca Ellston, Urszula M. Polanska, Joanne Wilson, Colin Howes, Aaron Smith, Richard J. A. Goodwin, John G. Swales, Nicole Strittmatter, Zoltán Takáts, Anna Nilsson, Per Andren, Dawn Trueman, Mike Walker, Corinne L. Reimer, Greg Troiano, Donald Parsons, David De Witt, Marianne Ashford, Jeff Hrkach, Stephen Zale, Philip J. Jewsbury, Simon T. Barry
Journal: Science Translational Medicine (2016)

A nanoparticle formulation of an Aurora B kinase inhibitor uses ion pairing to achieve controlled release and efficacious, nontoxic target inhibition in tumors.
Canine Transmissible Venereal Sarcoma: Transplantation Studies in Neonatal and Adult Dogs2
Authors: T. J. Yang, J. B. Jones
Journal: JNCI Journal of the National Cancer Institute (1973)

The transplantation of 2 spontaneous canine transmissible venereal sarcomas (CTVS) showed that the subcutaneous inoculation of 1 × 108 viable tumor cells consistently produced positive tumor takes in 16 days in 88% (15/17) of non-preconditioned adult mongrel dogs. After a period of rapid growth, the tumor regressed spontaneously in 2–6 months. Sixteen newborn puppies from normal mothers developed malignant neoplasms within 15 days after inoculation. These grew quickly, enlarged, ulcerated, and metastasized to other organs. In contrast, 36 of 43 puppies (84%), whose dams either failed to develop tumors or had borne tumors in our laboratory, developed tumors. Some of the 36 puppies with neoplasms had latent periods of up to 67 days, and the tumors invariably grew much more slowly than in puppies from unexposed dams. Spontaneous regression was seen in about 20% of the animals. The growth pattern of the tumor, benign or malignant, seemed to reflect the immunologic competence of the host, i.e., benign in normal adults and malignant in puppies. There appeared to be an inverse relationship between the maximum size the tumor attained and the proportion of small lymphocyte-like cells present in the viable tumor cell suspension. In contrast to previous reports, present findings on malignant behavior of experimental CTVS in normal puppies indicate the possible usefulness of this neoplasm for studies of experimental therapy.
Can gene expression microarray (GEM) provide a diagnosis in cases of carcinoma of unknown primary?
Authors: J. A. Bridgewater, A. Floore, M. O. Warmoes, L. Veer van’t
Journal: Journal of Clinical Oncology (2006)

20117 Patients with CUP constitute approximately 5% of all malignancies and have no primary site of malignancy despite standard investigation, a poor prognosis secondary to metastatic disease and generate despondency amongst clinicians. GEM may provide an improved diagnostic tool and improve prognosis for patients through the use of more site specific chemotherapy. CupPrint is a 1900 gene custom microarray optimized for paraffin samples which uses a compiled database of 591 cancer cases to provide a statistically proven method for the discrimination of 39 different tumor types. Few data are available on the practical application of this novel technique. We have taken paraffin samples from 21 cases of “true” CUP where standard investigation failed to determine a primary site of malignancy although there were some cases were more uncertain than others. Three 4μm sections from the paraffin blocks were analysed and reviewed in the context of the histology reports, an independent histological review and the clinical history. 2 datasets were available for 1 patient and 3 datasets for another. A case by case analysis will be given but in summary, 16/21 diagnoses confirmed the clinicians suspicion. There was a clinical/CupPrint inconsistency in 4/21 patients and a pathological/CupPrint inconsistency in 1 patient. All CupPrint diagnoses were possible clinically. There was a consistency between identical samples analysed blindly by CupPrint and a consistency between different sites of tumour metastasis in the same patient. For most patients there was a consistency within the “K-Nearest Neighbors” analysis (see http://www.agendia.com). Clinical suspicion coincides with CupPrint certainty such that in those patients for whom there was no suspected site of primary, the “K-Nearest Neighbours” analysis did not match. 11/21 patients had had palliative chemotherapy with a further 4 yet to be receive treatment thus 15/21 patients could receive palliative chemotherapy. 5 patients are still alive. CupPrint is a promising analytical tool in order to more appropriately direct systemic palliative treatment in patients with CUP. These data need to be expanded to demonstrate a survival benefit of CupPrint guided treatment in a randomized clinical study. [Table: see text]
Abstract P101: Predictors of Coronary Artery Disease in Type 1 Diabetic Subjects With and Without Microalbuminuria: A 20 Year Follow Up Study
Authors: Trevor J Orchard, Georgia Pambianco
Journal: Circulation (2012)

The incidence of nephropathy, a major predictor of coronary artery disease (CAD) in type 1 diabetes (T1D), has been strongly declining over the past several years. However, CAD rates do not appear to be declining commensurately. To identify similarities and differences in the CAD risk factor profile in subjects with and without microalbuminuria or worse (MA+), 20 year follow up data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset T1D (mean baseline age 28 and duration 19 yrs) were examined. MA+ was determined by kidney disease-related death, dialysis, transplant, or AER&gt;20 μg/mL in 2 of 3 timed urine collections. CAD was defined as angina, ischemic ECG changes, revascularization, confirmed MI, or CAD death. Cox proportional hazard models, adjusted for all the significant univariate risk factors, were determined separately for subjects who developed MA+ before their incident CAD event and for those who had CAD without preceding MA (MA-). As we have previously shown that CAD risk factors to vary by sex, we performed sex specific analyses within each MA group to determine if the predictors of CAD differ by sex and MA status. The results of the sex-specific analysis are listed in the table below. MA- MA+ Men (n=15 cases/84 β (CI) Men (n=65 cases/165) β (CI) nonHDL (mg/dl) 1.02 (1.0-1.04) Diabetes Duration (years) 1.12 (1.1-1.2) WHR 3.05 (.98-9.5) AER (log) 1.34 (1.2-1.5) Women (n=20 cases/92) Women (n=56 cases/172) Diabetes Duration (years) 1.11 (1.0-1.2) Diabetes Duration (years) 1.11 (1.07-1.15) Pulse Rate (bpm) 1.06 (1.0-1.1) Hypertension 1.85 (1.0-3.2) nonHDL (mg/dl) 1.01 (1.0-1.01) In the MA+ group, diabetes duration predicted CAD in both sexes, with AER (men) and hypertension and nonHDL (women) also contributing. However, in the MA- group, duration was only predictive in women, where pulse rate (p=0.016) was also predictive, while in men nonHDL, and to a small extent WHR (p=.054) predicted CAD. In conclusion, these data suggest that further factors beyond standard risk factors and renal disease are operative in T1D, particularly pulse rate in women.