tbuckley/cabot-search huggingface dataset:
A Novel 4-anilino-3-quinolinecarbonitrile dual Src And Abl Kinase Inhibitor (SKI-606) Has In Vitro Activity On CML Ph+Blast Cells Resistant To Imatinib
Authors: Tiziana Grafone, Manuela Mancini, Emanuela Ottaviani, Matteo Renzulli, Frank Boschelli, Laura Ferraretti, Maria Alessandra Santucci, Simona Soverini, Marilina Amabile, Carolina Terragna, Angela Poerio, Gianantonio Rosti, Cristian Taccioli, Emanuela Palmerini, Michele Baccarani, Giovanni Martinelli
Journal: Cancer Research (2005)

5984  A new class of compounds, 4-anilino-3-quinolinecarbonitrile Src kinase inhibitors, has been synthesized. One member of this class, SKI606, is a dual-specificity inhibitor of both Src family and Abl kinases. To investigate the effect in vitro of SKI-606, we analyzed human cell lines from CML patients in blast crisis (K562, MK2, LAMA) and CD34+ from 8 patients in CML blast crisis using a wide range of concentrations (0.01μM-10μM) of this novel agent. In K562, MK2 and LAMA84 we observed a decrease in cell viability after treatment with SKI. The effects of this compound on cell cycle progression and on apoptotic cell death shown an accumulation of G1/S phase in our sperimental model. The antiproliferative and cytostatic effects of SKI-606 was confirmed by a general decrease of bcr-abl protein expression and a reduced protein tyrosine phosphorylation. We analyze Lyn and Hck phosphorylation in whole cell extracts from K562 cells. Blots of these samples were probed with antibody anti Hck phosphorylated and Lyn phosphorylated. Our results show an hypophosphorylation of the two tyrosine kinases .We also demonstrated an increase of Bax and a decrease of Bcl-xl expression and a subsequently activation of Caspase-9. We evaluated the effects of SKI-606 on resistant or sensitive CML patients by treating SKI606 (0.1-10 μM) alone or in combination STI571(only in some patients). In the patients resistant to STI571 with point mutation F359V, Y253H, E255V and E255K was evident a modification of cell cycle progression with an accumulation in G1phase and increment of subdiploid peak. The effect of STI571 not was relevant. Cytofluorimetric analysis of non mutated patients showed an accumulation of cells in phase G1 of cell cycle and a few increment of apoptosis when treated with 1uM of SKI. Data more significative were obtained treating the cells. In one patient with a point mutation F359V we observed a general decrease of bcr-abl protein expression and a reduced protein phosphorylation in tyr 245. In the same patient an hypophosphorylation of Hck and Lyn was observed We obtained the same results we for two patients in which we didn’t find any mutation . Our study thus showed a potential therapeutic usefulness of the drug in treatment of CML, particularly in blast crisis phase. Ongoing gene expression profiles will contribute to further understanding of the drug mechanism.
A three-arms phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and /or gemcitabine in stage IV non-small cell lung cancer (NSCLC): an european lung cancer working party study
Authors: Jean-Paul Sculier, Jean-Jacques Lafitte, Marianne Paesmans, Jean-Paul Lecomte, T. Beghmans, M.C. Florin, E. Efremidis, Constantinos Alexopoulos, Vincent Ninane, Jean Klastersky
Journal: European Respiratory Journal (2001)
Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up
Authors: M. Rosselli Del Turco
Journal: JAMA (1994)

<h3>Objective.</h3> —To evaluate the effectiveness of early detection of intrathoracic and bone metastases in reducing mortality in breast cancer patients. <h3>Design.</h3> —Randomized clinical trial allocating breast cancer patients to two alternative follow-up protocols (intensive vs clinical) for at least 5 years. <h3>Setting.</h3> —Twelve breast clinics (referral centers) in different areas in Italy. <h3>Patients.</h3> —A total of 1243 consecutive patients (either premenopausal or postmenopausal) surgically treated for unilateral invasive breast carcinoma with no evidence of metastases. The two study groups were well balanced in terms of clinical and prognostic characteristics. <h3>Intervention.</h3> —Patients in both treatment groups had physical examination and mammography, while patients of the intensive follow-up group had, in addition, chest roentgenography and bone scan every 6 months. <h3>Main Outcome Measures.</h3> —Vital status at 5 years was the main outcome; information was available for all except five patients (0.4%). Relapse-free survival was also analyzed. <h3>Results.</h3> —Overall, 393 recurrences (104 local and 289 distant) were observed during the study. Increased detection of isolated intrathoracic and bone metastases was evident in the intensive follow-up group compared with the clinical follow-up group (112 vs 71 cases), while no difference was observed for other sites and for local and/or regional recurrences. The 5-year relapse-free survival rate was significantly higher for the clinical follow-up group, with patients in the intensive follow-up group showing earlier detection of recurrences. No difference in 5-year overall mortality (18.6% vs 19.5%) was observed between the two follow-up groups. <h3>Conclusions.</h3> —Periodic chest roentgenography and bone scan allow earlier detection of distant metastases, but anticipated diagnosis appears to be the only effect of intensive follow-up, and no impact on prognosis is evident after 5 years. Periodic intensive follow-up with chest roentgenography and bone scan should not be recommended as a routine policy. (<i>JAMA</i>. 1994;271:1593-1597)
Abstract #LB-159: MIS416: A second generation microparticle-based immune response modifier has broad spectrum anti-neoplastic activity in several pre-clinical mouse models
Authors: Gill Webster, William McBride, Frank Gelder
Journal: Cancer Research (2009)

Immune response modifiers (IRM) are agents that target the body\#8217;s immune system to combat disease by the mobilization and expansion of a broad range of intrinsic host defense mechanisms. To date, IRM developed for oncology applications comprise single agents such as Toll-like receptor agonists (TLR) or interferon-\#945;, each which have a limited spectrum of bioactivity and lack the ability to treat a broad range of malignant diseases. Virionyx Corporation has developed a second generation, multi-modal IRM, MIS416, comprising a microparticulate formulation of naturally occurring, non-immunogenic, cytosolicaly active TLR-9 and NOD-2 agonists. Signaling pathways activated by these ligands act synergistically to activate a broad range of innate immune cell subsets that are central to the development of innate and adaptive anti-tumor responses. Incorporation of these ligands as a microparticulate suspension restricts uptake to the reticulo-endothelial system and reactogencity is avoided due to the absence of cell surface immune reactivity. These design features contribute substantially to the excellent safety profile established in animal GLP single and multi-dose toxicological studies. Pre-clinical studies using a range of well established immunocompetant murine tumor models have been undertaken to evaluate the clinical utility of MIS416 as a stand alone anti-neoplastic agent or as an adjunct to local tumor radiotherapy. Single bolus i.v administration of MIS416 at various time points following tumor inoculation has been shown to significantly inhibit the formation of lung metastases in Lewis lung and 4T1 mammary tumor cancer models (P=   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-159.
Abstract P2-08-03: The association between primary breast cancer and thyroid cancer: A meta-analysis
Authors: Kyle R Joseph, Senarath Edirimanne, Guy Eslick
Journal: Cancer Research (2015)

Abstract Background: Previous studies have suggested an aetiological link between breast cancer and thyroid cancer, however, there has never been a formal meta-analysis which collates the existing evidence supporting the hypothesis that breast cancer or thyroid cancer predispose an individual to developing the other. Method: A systematic search was carried out using the electronic databases Pubmed and Medline. We searched for articles containing epidemiological evidence of breast cancer following thyroid cancer and vice versa. Additionally, we searched for articles that included epidemiological data involving the incidence of all second primary malignancies following both breast cancer and thyroid cancer, and compared the data sets. Results: The meta-analysis performed in a total of 18 studies, showed that there is a significantly increased risk of developing thyroid cancer as a second primary malignancy of breast cancer (RR=1.59, 95% CI: 1.28-1.99; I2=79.99, p&amp;lt;0.001). Additionally, there was marginally increased risk of developing breast cancer as a second primary malignancy of thyroid cancer (RR=1.24, 95% CI: 1.18-1.30; I2=24.67, p=0.18), compared to the general risk of developing a second primary malignancy following thyroid cancer. Conclusion: The findings of this meta-analysis suggest that there is less likely to be a common aetiological factor of the two cancers, but rather a specific aspect of the pathophysiology of breast cancer which pre-disposes individuals to develop thyroid cancer. Elucidation of the common mechanisms between breast cancer and thyroid cancer will have important implications in both diagnostic and therapeutic management of these cancers. Benefit of thyroid ultrasound screening after breast cancer surgery needs to be assessed. Citation Format: Kyle R Joseph, Senarath Edirimanne, Guy Eslick. The association between primary breast cancer and thyroid cancer: A meta-analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-08-03.
Chromosomal and genomic patterns of VLA-4 integrin-mediated adhesion competent and incompetent human melanoma cells
Authors: Ana Belén De La Hoz, Fernando Vidal-Vanaclocha
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4209 

Genetic changes underlying the progression of malignant melanoma is incompletely understood. In addition, specific chromosomal alterations associated with the metastatic behavior of melanoma cells are unknown. The goal of this study was to explore specific chromosomal alterations and specific genes associated with the ability of melanoma cells to develop very late antigen-4 (VLA-4)-vascular cell adhesion molecule-1 (VCAM-1) interaction-dependent metastases. Immobilized VCAM-1 substrate was used to select VLA-4 integrin-dependent adhesion competent and incompetent A375 human melanoma cells. Comparative genomic hybridization (CGH) was performed to screen and compare genomic imbalances present in melanoma cell subpopulations selected for their expression of constitutively active and inactive VLA-4, and to define those loci to be investigated for potential genes associated with metastatic behavior. Quantitative PCR and fluorescence in situ hybridization (FISH) with locus-specific probes were employed to verify the rearranged chromosomes on same cell subpopulations. A375 cell constitutively expressed VLA-4 although only 15% cells were competent for VLA-4-dependent adhesion. VLA-4-dependent adhesion competent cells, but not incompetent cells, produced VEGF and induced endothelial cell migration under oxidative stress in vitro, and produced a large metastasis number. The number of genetic alterations was significantly higher (by 6-fold increase along the whole genomic) in VLA-4-expressing A375 cells compared to non-VLA-4-expressing cells. Inactive VLA-4-expressing A375 cells had aberrations involving 1p36, 2p13-p12, 5q33-q35, 7p12, 9p21, 12q13-q14, 13q14, 15p11-p13, 15p23, 17qtel and 20q12. In contrast, a larger aberration number involving copy changes at multiple genome targets in the whole genome occurred in active VLA-4-expressing A375 cells. These included those affecting 1p34-p13, 1q31, 2ptel-p24, 2p13-p12, 2q27-q37, 3q21-q22, 4q24-q26, 5q31, 5q33-q35, 6p21, 8p22-p21, 9p21-p11, 9q22-9qtel, 12q13, trisomy of 13, 14q13-14q32, 16p13, 17p13-p11, 17q11, 17q23, 18q21, 19q12 y 20q13. These genomic alterations involved genes associated with tumorigenesis such as oncogenes, tumor suppressor genes, apoptosis genes and cell cycle control genes. The comparison of quantitative PCR and CGH array data gave good correlation. Capillary adhesion of melanoma cells via cytokine-induced VLA-4/VCAM-1 interaction regulates metastasis under experimental conditions. Chromosome regions and genomic alterations, which differ in the melanoma cell subpopulations with different capillary adhesion potential, may represent new targets to identify metastases-related chromosomal alterations and their specific genes.
Regulation of Mammary and Adipose Tissue Lipoprotein Lipase and Blood Triacylglycerol in Rats during Late Pregnancy
Authors: Peter M. Spooner, Mary M. Garrison, Robert O. Scow
Journal: Journal of Clinical Investigation (1977)

The effects of several prostaglandins on lipoprotein lipase activity of mammary gland and adipose tissue and serum triacylglycerol were studied during late pregnancy in rats. Prostaglandins were injected twice daily for 2 days before and once on the day of analysis. In rats pregnant 20 days, prostaglandin F2α (PGF2α) increased the activity of lipoprotein lipase in mammary gland fourfold, reduced the activity in adipose tissue about 60%, and decreased serum concentration of triacylglycerol 50%. PGF2α also reduced serum concentration of progesterone 90% and increased that of prolactin fivefold, but had no effect on serum concentrations of either immuno-reactive insulin or 17β-estradiol. Injections of 13,14-dihydro-15-keto PGF2α, a metabolite of PGF2α, had similar effects in rats pregnant 20 days, whereas prostaglandins E1 and E2 did not. In rats pregnant 16 days, PGF2α did not affect lipoprotein lipase activity in the tissues or the concentration of triacylglycerol and prolactin in serum, although it decreased serum progesterone 80%.
Use of erlotinib in management of advanced non-small cell lung cancer (NSCLC): The Czech Republic experience with the treatment of a non-selected population of 1735 patients (pts)
Authors: Jana Skrickova, Milos Pesek, Petr Zatloukal, Vitezslav Kolek, Frantisek Salajka, Leona Koubkova, Jana Krejci, Marcela Tomiskova, Grygarkova Ivona, Michal Hrnciarik
Journal: European Respiratory Journal (2011)

Erlotinib is the first EGFR TKI to be approved in Czech Republic for use in advanced NSCLC. This analysis presented examines data of all pts treated in Czech republic between 12/2005 and 12/2010.

Data of all 1735 patients were summarised and retrospective analyses were carried out to determine if any associations were seen between specific characteristics and either mPFS or mOS.

Of the 1735 pts with advanced NSCLC 35,6% were female and 64,4% male, 21,6% non-smokers, 39,5% former smokers and 38,9% current smokers. Median age was 65 years. Erlotinib was used as 1st line therapy in 14,4%, as 2nd line in 47,3% and as 3rd line in 38,3% pts. PS 0 was in 7,6%, PS 1 in 56,3%, PS 2 in 33,5% and PS 3 in 2,6% pts. Adenocarcinoma was confirmed in 45,9%, squamous-cell carcinoma in 39,2%, large–cell carcinoma in 4,0% and non specified carcinoma in 9,4% pts. CR was confirmed in 0,6%, PR in 123 7,1% pts, SD in 44,1% of pts; 23% of pts progressed and 25,2% pts were not evaluated. Skin toxicity was in 56,7%. Median survival (95% CI) was 7,5 months, PFS (95% CI) was 2,9 months. The differences between groups of pts according to PS (0+1 vs. 2+3) were statistically significant (p < 0,001). The best median survival (17,6 month) was in the group of pts with PS 0. Statistically significantly longer (p < 0,001) was mOS and mPFS survival in patients with skin toxicity, in female pts, in non-smokers and in pts with adenocarcinoma.

Erlotinib in this non-selected group of pts with advanced NCCLC was well tolerated and the results from Czech Republic are better then the data from BR.21 study and comparable with the results of TRUST.
THE NUTRITIONAL STATUS OF JAPANESE PRISONERS OF WAR, BURMA 1945
Authors: Robert Kark, H. F. Aiton, E. D. Pease
Journal: Annals of Internal Medicine (1946)

Article1 August 1946THE NUTRITIONAL STATUS OF JAPANESE PRISONERS OF WAR, BURMA 1945ROBERT KARK, H. F. AITON, E. D. PEASEROBERT KARKSearch for more papers by this author, H. F. AITONSearch for more papers by this author, E. D. PEASESearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-25-2-266 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn May 1945, during environmental and nutritional investigations on Indian soldiers in South East Asia, an opportunity offered itself for the study of 29 Japanese prisoners of war captured near Pegu, Burma, and held in a forward divisional prisoner of war cage.It was thought that such a study would be useful as it might indicate what types of nutritional disturbance one could expect to find in Allied soldiers held captive by the Japanese in South East Asia, and their rehabilitation could be planned accordingly.METHODSEach Japanese prisoner of war was given a medical examination and stigmata of early...Bibliography1. JOHNSON RE: A field nutritional laboratory, War Med., 1945, vii, 222. Google Scholar2. KARK RM: The nutritional status of Indian soldiers, 14th Army. Report No. C6206 to the Associate Com. on Army Medical Research, N.R.C. Canada, 1945. Google Scholar3. JOHNSONSARGENTROBINSONCONSOLAZIO REFPFFC: Assessment of nutritional and metabolic condition in the field. General and clinical aspects, War Med., 1945, vii, 227. Google Scholar4. FIELDPARNALLROBINSON HCWO: Pellagra in average population of Northern States, New England Jr. Med., 1940, ccxxiii, 307. CrossrefGoogle Scholar5. KARK RM: Nutritional lesions of the eye in Indian soldiers. To be published. Google Scholar6. KARKMCCREARY RMJF: The Prince Albert winter field ration trials, 1944, Edmond Cloutier, Ottawa, Canada. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication November 9, 1945.From the Research and Development Division, Director General of Medical Services, National Defence Headquarters, Ottawa.†Officer Commanding Canadian Research Team, Allied Land Forces, South East Asia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDecreased Mortality of falciparum Malaria in Anemic Prisoners of War?Allgemeine Pathologie des exogenen quantitativen NahrungsmangelsA CLINICAL STUDY OF MALNUTRITION IN JAPANESE PRISONERS OF WAR*MAURICE A. SCHNITKER, M.D., F.A.C.P., PAUL E. MATTMAN, M.D., THEODORE L. BLISS, M.D., F.A.C.P.Vitamin Supplementation in Health and Disease 1 August 1946Volume 25, Issue 2Page: 266-269KeywordsMedical servicesNutrition ePublished: 1 December 2008 Issue Published: 1 August 1946 PDF downloadLoading ...
Androgen Receptor and Nutrient Signaling Pathways Coordinate the Demand for Increased Amino Acid Transport during Prostate Cancer Progression
Authors: Qian Wang, Charles G. Bailey, Cynthia Ng, Jessamy Tiffen, Annora Thoeng, Vineet Minhas, Melanie L. Lehman, Stephen C. Hendy, Grant Buchanan, Colleen C. Nelson, John E.J. Rasko, Jeff Holst
Journal: Cancer Research (2011)

Abstract l-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cells. These cells maintained levels of amino acid influx through androgen receptor–mediated regulation of LAT3 expression and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses remained intact in primary prostate cancer, as indicated by high levels of LAT3 in primary disease, and by increased levels of LAT1 after hormone ablation and in metastatic lesions. Taken together, our results show how prostate cancer cells respond to demands for increased essential amino acids by coordinately activating amino acid transporter pathways vital for tumor outgrowth. Cancer Res; 71(24); 7525–36. ©2011 AACR.
Natural History of Infarct-Related Lesions
Authors: Fernando Alfonso
Journal: Circulation (1998)

To the Editor:Moussa and colleagues report restenosis in 43 (22%) of 201 lesions and 31 (37%) of 84 patients undergoing multivessel coronary stenting at angiographic follow-up at a mean of 5.2 months. 1 Confirmation of the lesion-to-lesion independence of restenosis after balloon angioplasty or stenting has validated lesion-based restenosis analysis in patients with multivessel disease. 2 Restenosis rates for patients with multiple treated lesions can therefore be calculated and equal the sum of the independent probabilities of restenosis.Given a lesion restenosis rate of 22% after stenting, the proportion of patients with restenosis at Ն1 site for 2, 3, 4, or 5 treated lesions would be 39%, 53%, 63%, and 71%, respectively.Moussa et al treated 2 lesions in 66 patients, 3 lesions in 24 patients, 4 lesions in 5 patients, and 5 lesions in 3 patients, which gives a predicted restenosis rate by patient of 45%, slightly higher than the observed 37%.This difference may be due to chance or to clustering of restenosis in particular patients.Clustering is supported by the observation that 20 (47%) of 43 restenotic lesions occurred in 8 (10%) of 84 patients 1 (PϽ0.05by comparison of proportions).Further information on these 8 patients, including diabetic status, postprocedure lumen diameter, number of lesions treated, and number of stents used per lesion, should be provided.The existence of distinct lesion populations with differing propensities for restenosis may be of particular relevance to case selection.Patients with multivessel disease may have lesions requiring dilation that are amenable to balloon angioplasty but not to stenting.Furthermore, restenosis rates are higher after vein graft interventions.The disproportionate impact of lesion restenosis rate and the number of lesions treated on the patient's overall risk of restenosis should be underscored.On the basis of lesion restenosis rates from the STRESS, 3 BENESTENT, 4 and SAVED 5 trials, a hypothetical patient who had 1 coronary stenosis stented, a second ballooned, and stent placement for a third vein graft lesion would have a predicted overall restenosis rate of 71%.In the study by Moussa et al, 1 two thirds of the patients had only 2 lesions stented, which partly explains their good results.What do the authors believe are the implications of these observations for case selection, including the issue of left ventricular dysfunction for which completeness of revascularization may be prognostically important?Should there be a limit to the number of lesions treated?Is a more complete follow-up, including coronary angiography, advisable in these patients?
Reduction of Postoperative Pain by Encouragement and Instruction of Patients
Authors: Lawrence D. Egbert, George E. Battit, Claude E. Welch, Marshall K. Bartlett
Journal: New England Journal of Medicine (1964)

MANY reports have discussed the treatment of patients suffering after operation. Narcotics are not without danger; they also vary considerably in effectiveness. Hypnosis will reduce pain but is difficult to achieve and requires special training for the operator. Despite considerable effort the problems of treating postoperative pain remain.Janis1 has shown that patients who were told about their operations before the procedure remembered the operation and its sequelae more favorably than those who were not well informed. We have determined the effects of instruction, suggestion and encouragement upon the severity of postoperative pain.MethodWe studied 97 patients after elective . . .