tbuckley/cabot-search huggingface dataset:
Gelatinase targeted peptidoliposomes suppress the growth of human ovarian tumor xenografts in nude mice
Authors: Sami Kaukinen, Heli Valtanen, Ying Zhu, Marja Tähtinen, Oula Penate Medina, Kalevi Kairemo
Journal: Cancer Research (2004)

4586   A specific peptide inhibitor CTTHWGFTLC (CTT1) of gelatinases (MMP-2 and MMP-9) has been isolated from phage display peptide libraries (Koivunen  et al . 1999, Nature Biotechnology 17, 768-774). This cyclic decapeptide was shown to prevent tumor growth and to improve survival of nude mice bearing human tumors. We have designed a more hydrophilic derivative of CTT1-peptide. Here, we have studied the pharmacokinetics of this novel CTT2-peptide and shown that CTT2 exhibits lower liver accumulation than the original phage display derived peptide. CTT2 accumulation was then screened in 12 different gelatinase expressing human xenograft tumors. High accumulation of CTT2 was seen in ovarian xenografts, and the highest accumulation was observed in serous type ovarian carcinoma where tumor/muscle ratio was 35 at 180 min after peptide injection. The peptide did not accumulate significantly in any other tissues studied. To generate tumor targeted liposomes (CTT2-SL), the CTT2-peptide was coupled covalently on the surface of doxorubicin loaded liposomes (SL). After single i.v. dose the CTT2-SL showed pharmacokinetics that were indistinguishable from that of SL in xenograft mice. Furthermore, CTT2-SL retains non-immunogenicity of SL. A biodistribution study showed that tumor AUC of doxorubicin encapsulated inside CTT2-SL is 40% greater than that of doxorubicin encapsulated inside SL. Finally, therapeutic efficacy of CTT2-SL was compared to that of SL. Mice were inoculated with ovarian carcinoma cells that were shown to be sensitive to doxorubicin in  in vitro  assay. Afterwards, the mice were treated systemically three times in three day intervals with CTT2-SL or SL (9mg/kg doxorubicin equivalents). The life span of mice treated with CTT2-SL increased 35% when compared to SL treated mice. We conclude that CTT-liposomes represent a promising technology to treat gelatinase expressing solid tumors. Based on these results, the development of CTT-SL peptidoliposomes toward clinical trials is underway.
Warning on AbbokinaseCelecoxib for ArthritisCerebyx Labels ChangedWarning on AbbokinaseCelecoxib for ArthritisCerebyx Labels Changed
Authors: Stuart L. Nightingale
Journal: JAMA (1999)

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
STAT3 activation is essential for t(8;21) RUNX1-ETO leukemogenesis.
Authors: Namiko Yamashita, Motomi Osato, Xinmin Cao, Yoshiaki Ito
Journal: Clinical Cancer Research (2007)

C68  Two genetic alterations do not always result in positive augmentative effect in tumorgenesis. A negative consequence such as a clonal disappearance by apoptosis or senescence occurs occasionally. Investigation of such positive and negative combinations in a certain tumor identifies an essential mechanistic basis for the tumorgenesis. In the screening of additional genetic changes in t(8;21) leukemia, one of the most frequent types of human leukemia and generating RUNX1-ETO chimeric gene, we and others found that FLT3 is rarely mutated, while c-Kit is frequently mutated, despite the fact that FLT3 is functionally equal to c-Kit since both belong to type III receptor type tyrosine kinase (RTK). To examine these cooperations between RUNX1-ETO and RTK mutation, we carried out experiments using murine immature hematopoietic cell line, 32Dcl3 cell. Transfection of FLT3 mutant alone inhibited differentiation and accelerated proliferation, whereas transfection of the FLT3 mutant along with RUNX1-ETO led to rapid apoptosis in 32D cells. In clear contrast, c-Kit mutant showed a cooperative role with RUNX1-ETO for continued growth, in agreement with human leukemia cases. This synergism was further confirmed in vivo. The mice transplanted with 32D cells carrying RUNX1-ETO and c-Kit mutation developed leukemia, while those carrying RUNX1-ETO and FLT3 mutation did not. Interestingly, this positive cooperation between RUNX1-ETO and c-Kit coincided with phosphorylation of Stat3, whereas the negative combination between RUNX1-ETO and FLT3 mutant resulted in a complete loss of Stat3 activation, although the FLT3 mutant alone retained phosphorylation of Stat3. Therefore, Stat3 activation appears to be essential for RUNX1-ETO leukemogenesis.
Bacterial colonization in patients with bronchiectasis
Authors: Maria João Oliveira, Daniel Coutinho, Daniel Vaz, Margarida Dias, Maria do Céu Brito
Journal: European Respiratory Journal (2014)

Introduction: In patients admitted with acute exacerbation of bronchiectasis, the presence of colonization by microorganisms is an important risk factor for morbidity and mortality.

Purpose: Evaluation of bacterial colonization in patients hospitalized with acute exacerbation of bronchiectasis.

Methods: Were retrospectively analyzed patients admitted between 31/03/2010 and 31/03/2013, diagnosed with acute exacerbation of bronchiectasis (non-cystic fibrosis). The data collected included sociodemographic variables, smoking history, comorbidities, functional respiratory study, bronchiectasis characteristics, microbiological isolation in sputum and the presence of bacterial colonization of patients.

Results: Were evaluated 253 admissions, a total of 78 patients (75.5 % male), mean age 66 years. The mean duration of hospitalization was 11.6 days. 64.4% had smoking history, chronic obstructive pulmonary disease 72.3% and 50.2% cardiovascular risk factors. The mean FEV1 was 39.4%. The bronchiectasis were: cylindrical in 43.8%, cystic in 16.2%, varicose in 8.7% and in 31.2% coexisted various types. 81.8% had bilateral distribution. Was microbiological isolation in sputum culture in 41.5% of patients (57.1% P. aeruginosa, 14.3% A. baumannii, 14.3% H. influenzae and 14.3% other). 17.4% of patients were colonized (63.6% Pseudomonas aeruginosa, 22.7% Acinetobacter baumannii, 13.7% others).

Conclusion: P. aeruginosa is the most common pathogenic microorganism in acute exacerbations of bronchiectasis. Bronchiectasis patients had a high percentage of colonization, being P. aeruginosa the most frequent colonizer. The treatment, either of infection or colonization with P. aeruginosa assume a priority to improve the prognosis of these patients.
Abstract 2742: The PARP inhibitor niraparib demonstrates robust activity in a subset of patient-derived triple-negative breast cancer xenograft models
Authors: Yan Wang, Stefano Cairo, Delphine Nicolle, Razvan Cristescu, Andrey Loboda, Michael Nebozhyn, Theresa Zhang, Jean-Gabriel Judde, Keith Wilcoxen
Journal: Cancer Research (2014)

Abstract Triple negative breast cancer (TNBC), which comprises 15% of all breast cancers, has a poor prognosis and currently lacks effective treatment. TNBCs are highly proliferative, genomically unstable and share molecular characteristics with BRCA1-/- breast cancer. Poly(ADP-ribose) polymerase-1 (PARP) is a key DNA repair enzyme that mediates single strand break (SSB) repair through the base excision repair (BER) pathway. PARP inhibitors have been demonstrated to selectively kill tumor cells that harbor BRCA1 and BRCA2 mutations. In addition, pre-clinical and preliminary clinical data suggest that PARP inhibitors are selectively cytotoxic for tumors with homologous recombination repair deficiency caused by mutations in genes other than BRCA1 or BRCA2. Niraparib is a potent, orally active PARP inhibitor that is being evaluated in Phase 3 clinical studies for ovarian cancer and BRCA related breast cancer. In exploring additional tumor indications that may be sensitive to niraparib, we investigated niraparib monotherapy activity in a panel of 17 basal breast cancer (BBC) patient-derived xenograft (PDX) models. Thirteen of the seventeen BBC models are TNBC models. Niraparib was administered po at a dose of 50 mg/kg once per day for 28 consecutive days, and tumor volume and body weight were measured twice weekly. Niraparib was well tolerated in nude mice bearing human TNBC PDXs growing subcutaneously, as there was no indication of body weight loss or decreased body weight gain relative to the vehicle control. Niraparib exhibited robust efficacy in five of the seventeen models tested. All five responsive models were TNBC. To understand the selectivity observed, a comprehensive analysis of the tumors was conducted which included analysis of gene mutation, gene copy number, gene expression and miRNA expression. A number of individual biomarkers and gene expression signatures were identified consistent with niraparib sensitivity across the 17 PDX models and will be discussed. In conclusion, in vivo activity of niraparib in TNBC was demonstrated in a panel of breast cancer PDX models, and several potential markers of niraparib sensitivity have been identified. Collectively this data supports the clinical investigation of niraparib in a subset of TNBC patients. Citation Format: Yan Wang, Stefano Cairo, Delphine Nicolle, Razvan Cristescu, Andrey Loboda, Michael Nebozhyn, Theresa Zhang, Jean-Gabriel Judde, Keith Wilcoxen. The PARP inhibitor niraparib demonstrates robust activity in a subset of patient-derived triple-negative breast cancer xenograft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2742. doi:10.1158/1538-7445.AM2014-2742
THE IRON CONTENT OF THE SKIN IN HEMOCHROMATOSIS
Authors: Harold J. Magnuson, B. O. Raulston
Journal: Annals of Internal Medicine (1942)

Article1 April 1942THE IRON CONTENT OF THE SKIN IN HEMOCHROMATOSISHAROLD J. MAGNUSON, M.D., B. O. RAULSTON, M.D., F.A.C.P.HAROLD J. MAGNUSON, M.D.Search for more papers by this author, B. O. RAULSTON, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-16-4-687 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptQuantitative estimations of the iron content of skin taken from patients who have hemochromatosis have been and are exceedingly rare. Sheldon1in his review of world literature in 1935 was able to find only two such analyses, and the results of these were at great variance with each other. Muir and Shaw Dunn2found an iron content of 0.188 per cent of the dry weight of the skin, while Loeper, Ravier, and Lesure3reported 1.15 per cent of the dry weight as iron. In view of these discrepancies the following report is considered to be of sufficient interest and importance...Bibliography1. SHELDON JH: Haemochromatosis, 1935, Oxford University Press, London. Google Scholar2. MUIRSHAW DUNN RJ: The iron content of the organs in bronzed diabetes, Jr. Path. and Bact., 1914, xix, 226-238. Google Scholar3. LOEPERRAVIERLESURE MJA: Les deux pigments du diabète bronze, Progrès méd., 1928, lv, 1461-1462. Google Scholar4. CHOLAKSTORY JRV: Spectroscopic analysis of biological material, Ind. and Eng. Chem., 1938, x, 619-622. Google Scholar5. HORSTERS H: Uber den Eisengehalt der Organe bei Ikterus, Arch. f. exper. Path. u. Pharmakol., 1930, clii, 198-209. CrossrefGoogle Scholar6. MONTGOMERYO'LEARY HPA: Pigmentation of the skin in Addison's disease, acanthosis nigricans, and haemochromatosis, Arch. Dermat. and Syph., 1930, xxi, 970-984. CrossrefGoogle Scholar7. JOHNS HJ: Haemochromatosis without pigmentation of the skin: resistance to protamine zinc insulin, Jr. Am. Med. Assoc., 1939, cxii, 2272-2273. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Los Angeles, California*Received for publication October 28, 1940.From the Department of Medicine, University of Southern California School of Medicine, and the Los Angeles County Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEpidermal iron metabolism for iron salvageIron in Skin of Mice with Three Etiologies of Systemic Iron OverloadIron in skin biopsiesAblagerungskrankheiten körpereigener StoffwechselproduktePHLEBOTOMY FOR HÆMOCHROMATOSIS EFFECT OF REMOVING 52 PINTS OF BLOOD IN SIXTEEN MONTHS 1 April 1942Volume 16, Issue 4Page: 687-693KeywordsAutopsyBiopsyHemochromatosisHospital medicine ePublished: 1 December 2008 Issue Published: 1 April 1942 PDF downloadLoading ...
Standard care impact on angioedema because of hereditary C1 inhibitor deficiency: a 21-month prospective study in a cohort of 103 patients
Authors: A. Zanichelli, R. Vacchini, M. Badini, V. Penna, M. Cicardi
Journal: Allergy (2010)

Hereditary angioedema (HAE) due to the deficiency of C1 inhibitor (C1-INH) causes chronically recurrent cutaneous, abdominal and laryngeal angioedema that are disabling and potentially life-threatening. We designed a prospective study to quantify the residual disease in patients with HAE treated according to the existing consensus documents. Data were collected from diaries recording occurrence, duration, location and treatment of acute angioedema attacks. A total of 386 semesters properly completed were analyzed. Forty-seven of 103 patients were on prophylactic treatment, 41 with attenuated androgens and six with tranexamic acid. A total of 1532 angioedema attacks (one every 45.3 days) were registered. Peripheral attacks were the most frequent (698), followed by abdominal (503) and combined locations (232), laryngeal edema was less common (99). Patients on prophylaxis with attenuated androgens had 7.7 attacks/year lasting 1.47 days, those on tranexamic acid had 8.1 attacks/year lasting 1.59 days, and those without prophylaxis had 8.9 attacks/year lasting 1.68. Plasma-derived C1-INH was used by 44 patients to treat a total of 376 acute attacks that resolved faster (1.1 day) than those not treated (1.85 day) or treated with tranexamic acid (1.79 day). No adverse events related to C1-INH infusion were reported. Our data demonstrate that tranexamic acid is not effective in the treatment of acute attacks and indicate that under the current therapeutic approach, the HAE related disability is effectively but partially reduced. Incomplete success does not appear to depend on limited efficacy of the drugs but on their limited use that can be overcome by implementing specific treatment strategies.
c-kit Gene was not transcribed in cultured mast cells of mast cell- deficient Wsh/Wsh mice that have a normal number of erythrocytes and a normal c-kit coding region
Authors: T Tono, T Tsujimura, U Koshimizu, T Kasugai, S Adachi, K Isozaki, S Nishikawa, M Morimoto, Y Nishimune, S Nomura
Journal: Blood (1992)
Gene expression profile in patients' samples with recurrent and persistent squamous cell cancer of head and neck
Authors: Agnes N. Juhasz, Xiwei Wu, Maricela Covarrubias, Frank Yen, Stephen Shibata, Yun Yen
Journal: Clinical Cancer Research (2006)

B23  Gene expression correlation with clinical outcome was studied in samples from patients enrolled in the PH-II clinical trial. Patients had stage IV, locally recurrent, locally persistent squamous cell cancer (SCC). The intra-tumoral mRNA expression level before treatment with hydroxyurea and gemcitabine was determined using microarray analysis (Affymetrix 2.0) and real-time PCR array for DNA damage (SuperArray Inc.). The microarray analysis compared the average gene expression of 3 patients with stable (S) disease to 5 patients with progressive (P) disease. The analysis resulted in a list of 116 genes with significantly different expression levels (p 2-fold) between patients with stable and progressing disease. Genes involved in cancer cell proliferation, cellular movement, and DNA damage are on the list. The top 3 genes with the highest significance, are not well-studied (COL10A1, ADCY2, ITGBL1) and their roles in squamous cell carcinoma is not known. More studies are needed to determine the role these genes play in predicting SCC outcome. The real-time PCR array showed increased expression of the following genes in patients with stable disease (N=4) compared to progressing cases (N=6): GADD45A, GADD45G, FANCG, DDIT3, and MAPK12. The GADD45A and GADD45G expression correlates with the microarray data. Another group of genes were down-regulated in patients with stable disease: EXO1, FEN1, HUS1, IGHMBP2, MAP2K6, MSH2, RAD1, SESN1, PDCD8, PMS2, and XRCC2. These genes might be indicators of the potential outcome of the treatment. Our trial had a limited number of samples. Future studies with a larger number of cases can prove the expression of which gene acts as a potential biomarker to be used as target for therapy.
Abstract 19645: Marked Improvement of Postprandial Hypotension by Xanthine Derivatives and Preparations
Authors: Haruki Sekiguchi, Fujio Tatsumi, Yuka Manaka, Yukiko Tanaka, Makiko Kimura, Eri Watanabe, Ken Shimamoto, Masatoshi Kawana
Journal: Circulation (2014)

Introduction: Postprandial hypotension (PPH) is an important and frequent problem, particularly in the elderly. Several studies have suggested that caffeine, acarbose, DL-DOPS, Guar gum and octreotide can improve postprandial symptoms and result in reduction in postprandial blood pressure (BP). However, these treatments may not necessarily be effective in the patients with symptomatic PPH. Hypothesis: In the present study, we sought to determine whether Xanthine derivatives and preparations, an adenosine antagonist same as caffeine which block splanchnic methylxantine-sensitive adenosine receptors could be effective for PPH showing resistance to other treatments. Methods: 74-year-old man under outpatient care for hypertension was admitted to Aoyama Hospital, Tokyo Women’s Medical University, Tokyo, Japan, for the investigation and treatment of syncope after breakfast in June 2014. Ambulatory BP monitoring (ABPM) over a 24 hours period showed a decrease in systolic BP of more than 20 mmHg within 2 hours af...
(-)-Epigallocatechin-3-gallate (EGCG), green tea components, antagonize the anti-myeloma activity of proteasome inhibitor PS-341 by direct chemical interaction
Authors: Tae Young Kim, Jongmin Park, Bora Oh, Hyun Jung Min, Tae-Sook Jeong, Jae Hoon Lee, Seung Bum Park, Dong Soon Lee
Journal: Cancer Research (2008)

2272   PS-341 (also known as bortezomib, Velcade®) has a remarkable anti-myeloma acitivity and is also potential candidate for the treatment of other tumors either alone  or in combination with other chemotherapeutic agents. Investigations on the effectiveness of PS-341 in combination with other anti-neoplastic agents are currently under clinical trial. Since (-)-epigallocatechin-3-gallate (EGCG) has been reported its anti-cancer activity in various cancer types, we tried a co-treatment of PS-341 with EGCG on myeloma cells, expecting a synergistic effect. However, the anti-cancer activity of PS-341 was blocked by EGCG without any synergistic effect. At the early stage of our research, we suspected antioxidant function of EGCG is the main cause of antagonistic effect on PS-341-induced cell death. Thus we selected polyphenols showing strong antioxidant function including vitamin C. But, we did not obtain any consistant data that support the significant correlation of antioxidant function of polyphenols with antagonistic effects. Instead, the structural features of polyphenols showed striking correlations with antagonistic effect; especially the presence or absence of vicinal diol moiety on polyphenol was the key elements for the effective blocking on anti-cancer function of PS-341. We infer that vicinal diols on polyphenols interact with boronic acid of PS-341, which convert active triangular boronic acid (sp 2  character) of PS-341 to inactive tetrahedral boronate (sp 3  character) through direct chemical interaction. The equilibrium of this conversion is controlled by structures and concentration of polyphenols, and this conversion abolished the anti-myeloma activity of PS-341. We confirmed our hypothesis on direct chemical interaction of PS-341 with EGCG through  11 B NMR experiment and cell viability assay data clearly support the antagonistic interaction between PS-341 and polyphenols in multiple myeloma cell lines and primary myeloma cells from patients. Based on our researches, restriction of the intake of natural polyphenols by food or vitamin supplements should be considered during the treatment with PS-341 in MM patients.
Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity
Authors: M.C.M. Bickerstaff, M. Botto, W.L. Hutchinson, J. Herbert, G.A. Tennent, A. Bybee, D.A. Mitchell, H.T. Cook, P.J.G. Butler, M.J. Walport, M.B. Pepys
Journal: Nature Medicine (1999)
Skin culture: another diagnostic tool in chronic meningococcaemia
Authors: N. Shah, O.E. Dadzie
Journal: British Journal of Dermatology (2010)

Journal Article Skin culture: another diagnostic tool in chronic meningococcaemia Get access N. Shah, N. Shah Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar O.E. Dadzie O.E. Dadzie St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 7EH, U.K. Ophelia E. Dadzie. E‐mail: OpheliaDadzie@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 1, 1 July 2010, Pages 218–219, https://doi.org/10.1111/j.1365-2133.2010.09770.x Published: 01 July 2010
Species differences in small molecule binding to αIIbβ3 are the result of sequence differences in 2 loops of the αIIb β propeller
Authors: Ramesh B. Basani, Hua Zhu, Michael A. Thornton, Cinque S. Soto, William F. DeGrado, M. Anna Kowalska, Joel S. Bennett, Mortimer Poncz
Journal: Blood (2008)
Gastrointestinal bleeding is common
Authors: J.-R. Laporte, X. Vidal, X. Carne
Journal: BMJ (1995)

its mother so modest matemal fevers may lead to fetal temperatures approaching 40°C, which could be dangerous for the baby.2In addition, maternal raised body temperature leads to fetal tachycardia which may be misinterpreted as fetal distress, leading to intervention.2Unlike normal labour rooms (usually kept at 26-28°C), birthing pools are close to body temperature and can therefore prevent the normal loss of heat that is necessary to maintain maternal isothermia.In our unit the protocol for use of the pool originally suggested keeping the water at 37-38°C.In the light of our audit, we now recommend maintaining the temperature at 36-37°C, with hourly monitoring.Prospective research is urgently needed to determine the optimum water temperature for safe use of the birthing pool.This is particularly important in the light of the surprising length of time some women spend in the pool.