tbuckley/cabot-search huggingface dataset:
Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: L. Stefan Lohmander, Scarlett Hellot, Don Dreher, Eduard F. W. Krantz, Dawie S. Kruger, Ali Guermazi, Felix Eckstein
Journal: Arthritis & Rheumatology (2014)

Objective To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA). Methods The study was a randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial. Intraarticular sprifermin was evaluated at doses of 10 μg, 30 μg, and 100 μg. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment‐emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results One hundred ninety‐two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose‐dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100‐μg dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment‐emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups. Conclusion No statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dose‐dependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns.
Final Analysis of Overall Survival Per Subgroups of Hcc Patients in the Prospective, Non-Interventional Insight Study Treated with Sorafenib
Authors: T.M. Ganten, R. Stauber, E. Schott, P. Malfertheiner, R. Buder, P.R. Galle, T. Goehler, I. Bernard, G. Gerken
Journal: Annals of Oncology (2014)
Trinitrophenyl modification of H-2k and H-2b spleen cells results in enhanced serological detection of Kk-like determinants.
Authors: R B Levy, S K Dower, G M Shearer, D M Segal
Journal: The Journal of Experimental Medicine (1984)

Several anti-H-2Kk but not anti-H-2Dd monoclonal antibodies (mAb) exhibited enhanced binding to B10.A murine spleen cells after modification of the cells with trinitrobenzene sulfonate (TNBS). The number of antibody molecules bound to TNP-modified B10.A spleen cells increased by a factor of two or more. The same anti-2Kk mAb that exhibited enhanced binding to modified B10.A cells did not bind to unmodified C57BL/10 spleen cells, as expected, but did bind to TNP-modified C57BL/10 spleen cells. This TNP-dependent binding was not a result of cross-reactions with cell surface TNP groups nor with Fc receptors. TNP modification of a variant cell line that does not express class I H-2 products did not result in enhanced binding by these mAb. These findings can account for preferential recognition of TNP-Kk by B10.A and B10.BR CTL, and also for cross-reactive lysis by C57BL/10 CTL stimulated by C57BL/10-TNP against unmodified H-2Kk targets.
Drug Transporters and Imatinib Treatment: Implications for Clinical Practice
Authors: Karel Eechoute, Alex Sparreboom, Herman Burger, Ryan M. Franke, Gaia Schiavon, Jaap Verweij, Walter J. Loos, Erik A.C. Wiemer, Ron H.J. Mathijssen
Journal: Clinical Cancer Research (2010)

Abstract Imatinib mesylate is approved for the treatment of chronic myeloid leukemia (CML) and advanced gastrointestinal stromal tumors (GIST). Unfortunately, in the course of treatment, disease progression occurs in the majority of patients with GIST. Lowered plasma trough levels of imatinib over time potentially cause disease progression, a phenomenon known as “acquired pharmacokinetic drug resistance.” This outcome may be the result of an altered expression pattern or activity of drug transporters. To date, the role of both efflux transporters (ATP-binding cassette transporters, such as ABCB1 and ABCG2) and uptake transporters [solute carriers such as organic cation transporter 1 (OCT1) and organic anion transporting polypeptide 1A2 (OATP1A2)] in imatinib pharmacokinetics and pharmacodynamics has been studied. In vitro experiments show a significant role of ABCB1 and ABCG2 in cellular uptake and retention of imatinib, although pharmacokinetic and pharmacogenetic data are still scarce and contradictory. ABCB1 and ABCC1 expression was shown in GIST, whereas ABCB1, ABCG2, and OCT1 were found in mononuclear cells in CML patients. Several studies have reported a clinical relevance of tumor expression or activity of OCT1 in CML patients. Further (clinical) studies are required to quantify drug transporter expression over time in organs involved in imatinib metabolism, as well as in tumor tissue. In addition, more pharmacogenetic studies will be needed to validate associations. Clin Cancer Res; 17(3); 406–15. ©2010 AACR.
ON THE RELATION OF THE CATALYTIC ACTIVITY OF THE BLOOD TO THE NUMBER OF RED BLOOD CELLS IN HEALTH, AND TO THE NUMBER OF WHITE BLOOD CELLS AND THE BODY TEMPERATURE IN PERITONITIS
Authors: M. C. Winternitz, J. P. Pratt
Journal: The Journal of Experimental Medicine (1910)

The catalytic activity of the blood of normal rabbits varies almost directly with the volume and number of red blood cells. This explains to a certain extent at least why animals of the same general degree of nutrition, and of the same litter, should have about the same activity since they are likely to have the same number of red blood cells, and why healthy large animals should read high while small poorly nourished ones should read low. Accompanying the hyperpyrexia resulting from puncture of the corpus striatum of a rabbit's brain, there is no change in either the catalytic activity of the blood or the white blood count. In experimentally produced peritonitis, the catalytic activity of the blood always rises, and is, therefore, absolutely independent of body temperature and white blood cells since one or both of these may rise, fall or remain stationary while the catalytic action increases.
Ring Finger Protein 43 as a New Target for Cancer Immunotherapy
Authors: Naotaka Uchida, Takuya Tsunoda, Satoshi Wada, Yoichi Furukawa, Yusuke Nakamura, Hideaki Tahara
Journal: Clinical Cancer Research (2004)

We have performed genome-wide exploration by using cDNA microarray profiling, and successfully identified a new tumor-associated antigen (TAA) that can induce potent cytotoxic T lymphocytes (CTLs) specific to tumor cells. In our preceding study, we identified multiple new genes by using gene expression profiling with a genome-wide cDNA microarray containing 23,040 genes. Among them, we selected RNF43 (ring finger protein 43) as a promising candidate for a TAA expressed by colon cancer cells. In this study, we examined whether the RNF43 protein contains antigenic epitope peptides restricted to HLA-A*0201 or HLA-A*2402. The CTL clones were successfully induced with stimulation by using the peptides binding to HLA-A*0201 (ALWPWLLMA and ALWPWLLMAT) and HLA-A*2402 (NSQPVWLCL), and these CTL clones showed the cytotoxic activity specific to not only the peptide-pulsed targets but also the tumor cells expressing RNF43 and respective HLAs. Lytic activities mediated by two HLA-A2-restricted epitopes were marginal, whereas tumor lysis mediated by the HLA-A24 epitope was clearly better. These findings might be caused by the poor natural presentation of RNF43-11(IX) and RNF43-11(X) by tumors or poor T-cell receptor avidity for these specific epitopes. These results strongly suggest that RNF43 is a new TAA of colon cancer. Furthermore, these results also suggest that our strategy might be a promising one to efficiently discover clinically useful TAAs.
Skin imaging modalities quantify progression and stage of infantile haemangiomas
Authors: S.A. Burkes, D.M. Adams, A.M. Hammill, C. Chute, K.P. Eaton, J.A. Welge, R.R. Wickett, M.O. Visscher
Journal: British Journal of Dermatology (2015)

Journal Article Skin imaging modalities quantify progression and stage of infantile haemangiomas Get access S.A. Burkes, S.A. Burkes Skin Sciences Program Division of Plastic Surgery Cincinnati Children's Hospital Medical Center Cincinnati OH U.S.AJames L. Winkle College of Pharmacy University of Cincinnati Cincinnati OH U.S.A Search for other works by this author on: Oxford Academic Google Scholar D.M. Adams, D.M. Adams Hemangioma and Vascular Malformation Center Cincinnati Children's Hospital Medical Center Cincinnati OH U.S.A Search for other works by this author on: Oxford Academic Google Scholar A.M. Hammill, A.M. Hammill Hemangioma and Vascular Malformation Center Cincinnati Children's Hospital Medical Center Cincinnati OH U.S.A Search for other works by this author on: Oxford Academic Google Scholar C. Chute, C. Chute Hemangioma and Vascular Malformation Center Cincinnati Children's Hospital Medical Center Cincinnati OH U.S.A Search for other works by this author on: Oxford Academic Google Scholar K.P. Eaton, K.P. Eaton Imaging Research Center Cincinnati Children's Hospital Medical Center Cincinnati OH U.S.A Search for other works by this author on: Oxford Academic Google Scholar J.A. Welge, J.A. Welge Psychiatry and Behavioral Neuroscience University of Cincinnati Cincinnati OH U.S.A Search for other works by this author on: Oxford Academic Google Scholar R.R. Wickett, R.R. Wickett James L. Winkle College of Pharmacy University of Cincinnati Cincinnati OH U.S.A Search for other works by this author on: Oxford Academic Google Scholar M.O. Visscher M.O. Visscher Skin Sciences Program Division of Plastic Surgery Cincinnati Children's Hospital Medical Center Cincinnati OH U.S.A Correspondence: Marty O. Visscher. E‐mail: marty.visscher@gmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 3, 1 September 2015, Pages 838–841, https://doi.org/10.1111/bjd.13905 Published: 01 September 2015
Duration of Chemotherapy for Metastatic Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Alessandra Gennari, Martin Stockler, Matteo Puntoni, Mariapia Sormani, Oriana Nanni, Dino Amadori, Nicholas Wilcken, Mauro D'Amico, Andrea DeCensi, Paolo Bruzzi
Journal: Journal of Clinical Oncology (2011)

To evaluate the effect of different first-line chemotherapy durations in patients with metastatic breast cancer (MBC) on overall survival (OS) and progression-free survival (PFS).We searched literature databases to identify randomized controlled trials that compared different chemotherapy durations in the first-line treatment of MBC. Only trials with unconfounded comparisons of additional cycles of chemotherapy were included. The main outcome measures for this analysis were OS and PFS. Published data from retrieved studies were analyzed according to standard meta-analytic techniques.We found 11 randomized clinical trials including 2,269 patients. Longer first-line chemotherapy duration resulted into a significantly improved OS (hazard ratio [HR], 0.91; 95% CI, 0.84 to 0.99; P = .046) and PFS (HR, 0.64; 95% CI, 0.55 to 0.76; P < .001). There were no differences in effects on either OS or PFS between subgroups defined by time of random assignment, study design, number of chemotherapy cycles in the control arm or concomitant endocrine therapy.Longer first-line chemotherapy duration is associated with marginally longer OS and a substantially longer PFS.
Characterization of a highly conserved sequence related to mutator transposable elements in maize.
Authors: L E Talbert, V L Chandler
Journal: Molecular Biology and Evolution (1988)

Mutator stocks of maize exhibit a high mutation rate correlated with the activity of a family of transposable elements. Mu1 and, to a lesser extent, the closely related Mu1.7 elements are responsible for most mutator-induced mutations that have been characterized. These elements are found in 10-60 copies in mutator stocks, and zero to a few intact elements exist in nonmutator maize stocks. Additionally, the component parts of Mu elements exist separately in the maize genome. The Mu terminal inverted repeats are found in multiple copies in all maize lines and related Zea species tested, and Mu internal sequences exist unassociated with Mu termini. In the present paper, we describe the structure and genomic distribution of one Mu-homologous sequence termed MRS-A (for Mu-related sequence). DNA sequencing shows that MRS-A is closely related to the internal region of Mu1 and Mu1.7 elements. However, it has no Mu termini and does not have the structure of a transposable element. This sequence is present in one or two copies in all maize lines and is highly conserved in the genus Zea. A similar sequence exists in a species within the genus most closely related to Zea, Tripsacum dactyloides, although the T. dactyloides genome does not contain any Mu termini or intact Mu elements. Furthermore, an RNA transcript homologous to MRS-A and its flanking DNA is found in both mutator and nonmutator maize plants. These results suggest that MRS-A represents a stable, functional region of the maize genome, and we speculate that a similar sequence was encompassed by Mu termini to generate a Mu transposable element.
Molecular basis of complement C3 deficiency in guinea pigs.
Authors: H S Auerbach, R Burger, A Dodds, H R Colten
Journal: Journal of Clinical Investigation (1990)

In experiments to ascertain the biochemical basis of a genetically determined deficiency of the third component of complement (C3) in guinea pigs, we found that C3-deficient liver and peritoneal macrophages contain C3 messenger RNA of normal size (approximately 5 kb) and amounts, that this mRNA programs synthesis of pro-C3 in oocytes primed with liver RNA and in primary macrophage cultures. In each instance, heterodimeric native C3 protein was secreted with normal kinetics but the C3 protein product of the deficient cells failed to undergo autolytic cleavage and was unusually susceptible to proteolysis. These data and a selective failure of C3 in plasma of deficient animals to incorporate [14C]methylamine suggested either a mutation in primary structure of the C3 protein or a selective defect in co- or postsynthetic processing affecting the thiolester bridge, a structure important for C3 function. A mutation in the primary structure of C3 was ruled out by comparison of direct sequence analysis of C3 cDNA generated from two C3 deficient and two C3 sufficient guinea pig liver libraries. Three base pair differences, none resulting in derived amino acid sequence differences were identified. Finally, restriction fragment length polymorphisms were identified in the C3 gene that are independent of the deficiency phenotype. This marker of the C3 gene permits testing of these hypotheses using molecular biological and classical genetic methods.
Towards an understanding of the biological basis of response to cisplatin-based chemotherapy in germ-cell tumors
Authors: F. Mayer, F. Honecker, L.H.J. Looijenga, C. Bokemeyer
Journal: Annals of Oncology (2003)

Chemotherapy is far more successful in young male patients with germ-cell tumors than in adults suffering from almost any other solid tumor. Various attempts have been made to understand the sensitivity of these tumors towards cisplatin-based chemotherapy; however, to date no explanation has been generally accepted. Recent data underline the need to seek further explanations, other than the previously postulated highintrinsic level of wild-type P53 protein, for the exquisite curability of germ-cell tumors. In this regard, the DNA repair pathways, in particular the DNA mismatch repair and nucleotide excision repair pathways, have received attention. This review summarizes the data currently available on the cellular basis for chemotherapy response in these tumors by systematically following cisplatin—presumably the most active drug in the treatment of this disease—on its course from entering the cell to the execution of apoptosis. The emerging picture points towards a multifactorial explanation for the unique chemosensitivity of germ-cell tumors, including a lack of export pumps, an inability to detoxify cisplatin and repair the respective DNA damage, and an intact apoptotic cascade not disturbed by anti-apoptotic stimuli. Even though no uniform pattern of relevant resistance factors has been identified in patients suffering from refractory disease, a significant number of these cases may be caused by defects in the DNA mismatch repair pathway.
Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG
Authors: C Prantera
Journal: Gut (2002)

<b>Background and aims:</b> Experimental studies have shown that luminal bacteria may be involved in Crohn9s disease. Probiotics are a possible alternative to antibiotics. The aim of this randomised placebo controlled study was to determine if <i>Lactobacillus</i> GG, given by mouth for one year, could prevent Crohn9s recurrent lesions after surgery or to reduce their severity. <b>Methods:</b> Patients operated on for Crohn9s disease in whom all of the diseased gut had been removed were randomly allocated to receive 12 billion colony forming units of <i>Lactobacillus</i> or identical placebo for one year. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms. Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system. <b>Results:</b> Eight of 45 patients were excluded from the trial (three for non-compliance and five for protocol violations). Clinical recurrence was ascertained in three (16.6%) patients who received <i>Lactobacillus</i> and in two (10.5%) who received placebo. Nine of 15 patients in clinical remission on <i>Lactobacillus</i> (60%) had endoscopic recurrence compared with six of 17 (35.3%) on placebo (p=0.297). There were no significant differences in the severity of the lesions between the two groups. <b>Conclusions:</b><i>Lactobacillus</i> GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions.
SCARRING DUE TO ENURESIS BLANKETS
Authors: M. W. GREAVES
Journal: British Journal of Dermatology (1969)

Journal Article SCARRING DUE TO ENURESIS BLANKETS Get access M. W. GREAVES M. W. GREAVES Univeristy Department of Dermatology, Newcastle upon Tyne, 1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 6, 1 June 1969, Pages 440–442, https://doi.org/10.1111/j.1365-2133.1969.tb14014.x Published: 01 June 1969 Article history Accepted: 16 October 1968 Published: 01 June 1969
Phase II Trial of Trastuzumab Followed by Weekly Paclitaxel/Carboplatin As First-Line Treatment for Patients With Metastatic Breast Cancer
Authors: Howard Burris, Denise Yardley, Suzanne Jones, Gerry Houston, Catherine Broome, Dana Thompson, F. Anthony Greco, Melissa White, John Hainsworth
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the response rate of trastuzumab as first-line therapy in patients with HER-2 overexpressing metastatic breast cancer. To assess the feasibility and toxicity of weekly paclitaxel/carboplatin with or without trastuzumab following initial treatment with trastuzumab. Patients and Methods Sixty-one patients received trastuzumab (8 mg/kg followed by 4 mg/kg/wk) for 8 weeks. Responding patients received 8 additional weeks of trastuzumab (4 mg/kg/wk), and then proceeded to receive trastuzumab (2 mg/kg) in combination with paclitaxel 70 mg/m 2 and carboplatin (area under the curve, 2) weekly for 6 weeks followed by 2 weeks rest. Stable patients after the initial 8 weeks of trastuzumab proceeded to treatment with trastuzumab, paclitaxel, and carboplatin. Patients with disease progression during the initial 8 weeks had the trastuzumab discontinued and were treated with weekly paclitaxel/carboplatin. Results Weekly paclitaxel/carboplatin with or without trastuzumab was well tolerated. Fifty-two patients were assessable for response and all 61 patients were assessable for survival. Seventeen (33%) of 52 patients experienced a minor/partial response to single-agent trastuzumab and received 8 additional weeks of single-agent trastuzumab. Fifteen (29%) of 52 patients had stable disease and proceeded to receive paclitaxel/carboplatin/trastuzumab. Thirty-one patients with measurable disease were assessable for response after initial single-agent trastuzumab followed by paclitaxel/carboplatin/trastuzumab. An overall response rate of 84% (eight complete responses/18 partial responses), median time to progression of 14.2 months, and median overall survival of 32.2 months was reported with the triplet combination. In the patients treated with paclitaxel/carboplatin alone after disease progression on initial single-agent trastuzumab, an overall response rate of 69% (one complete response/10 partial responses), median time to progression of 8.3 months, and median overall survival of 22.2 months was reported. Median time to progression for all 61 patients is 10 months and the median overall survival is 26.7 months. Conclusion This trial confirms the activity and tolerability of weekly paclitaxel/carboplatin alone or in combination with trastuzumab in women with HER-2 overexpressing metastatic breast cancer.