tbuckley/cabot-search huggingface dataset:
Abstract 1631: Structural activity relationship studies of aza-podophyllotoxin derivatives on breast cancer cell line
Authors: Michael Concepcion Santana, Ajay Kumar, Vineet Kumar, Antonio E. Alegria, Sanjay V. Malhotra
Journal: Cancer Research (2014)

Abstract Podophyllotoxin is a natural precursor for the semi-synthesis of novel anticancer drugs and its an anti-tumor and antibacterial ligand derived from Podophyllum peltatum and Podophyllum emodi (Berberidaceae). Etoposide, etopophoside and tenoposide are anti-cancer drugs in pharmaceutical clinics since 1989 derived from a natural lignin podophyllotoxin. Synthesis of podophyllotoxin in a laboratory is one of the tedious and biggest challenges. In our previous work we developed a very simple method to synthesize extensively modified libraries of several novel derivatives, which were previously impossible to synthesize from podophyllotoxin (Kumar and Alegría, 2010). This method also allows us to explore the synthesis and applications of novel aza-podophyllotoxin derivatives which led to several new analogs with anti-cancer potential. Most of the compounds were found very active against Colon cancer, Melanoma, Ovarian, Renal, prostate and breast cancers at NCI upon a panel of 60 types of human cancer cell lines (Kumar, et.al. 2011). Based on structure activity relationship (SAR) of our compounds and their recent unpublished extraordinary activity especially against colon cancer (COLO 205) cell lines, we designed and synthesized novel aza-podophyllotoxin derivatives using microwave synthesis technique. We will be discussing the synthesis, SAR and biological activity of our novel 2,3-didehyropodophyllotoxin derivatives. Keywords: Pharmacology, Organic Chemistry and Toxicology Disclosure of Chemical Structure: The complete chemical structures of the compounds of the compounds used will be disclosed at the time of presentation at the meeting. Funded by INBRE-NIGMS-NIH gran #8 P20 GM 102475 and REU NSF 1262826 Citation Format: Michael Concepcion Santana, Ajay Kumar, Vineet Kumar, Antonio E. Alegria, Sanjay V. Malhotra. Structural activity relationship studies of aza-podophyllotoxin derivatives on breast cancer cell line. [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 1631. doi:10.1158/1538-7445.AM2014-1631
Genetic Clues Shed Light on Stomach Cancer Risk
Authors: Joan Stephenson
Journal: JAMA (2002)

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
ATN-224, an orally available small molecule inhibitor of SOD1, inhibits multiple signaling pathways associated with myeloma progression and has antitumor activity in a murine model of refractory myeloma growth
Authors: Richard A. Campbell, Melinda S. Gordon, Oscar Betancourt, Jose Juarez, Fernando Donate, Andrew Mazar, James R. Berenson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4859 

ATN-224 is an orally available small molecule inhibitor of the cytoplasmic enzyme superoxide dismutase 1 (SOD1) that is currently entering Phase II clinical trials in multiple cancer indications. ATN-224 has pleiotropic effects on both endothelial cells and tumor cells, leading to the inhibition of angiogenesis and the induction of tumor cell apoptosis in vitro and in vivo. ATN-224 interferes with a number of signaling pathways in parallel, including those mediated by VEGF, FGF-2 and IGF-1. These pathways have been implicated in myeloma progression, leading us to evaluate the effects of ATN-224 on myeloma cells in vitro as well as in murine models of myeloma progression in vivo. ATN-224 inhibited IGF-1 mediated activation of ERK1/2 in MM.1S cells and induced apoptosis in several myeloma cell lines including MM.1S, MM.1R (a dexamethasone resistant subclone of MM.1S) and RPMI-8226 in a dose and time-dependent manner. ATN-224 was also evaluated in SCID-hu models of myeloma. LAGκ-1B tumors, originally isolated from a patient refractory to lenalidomide, melphalan and bortezomib, were transplanted intramuscularly into SCID mice. Fourteen days post-implantation, mice were randomized based on human IgG levels and treated with ATN-224 at 5 mg/kg, 15 mg/kg, and 50 mg/kg per day via oral gavage on a Monday-Friday schedule. Mice receiving the intermediate (15 mg/kg) and high doses of ATN-224 (50 mg/kg) showed marked inhibition of tumor growth and reduction of human IgG levels while there was little effect observed in the low dose treatment group (5 mg/kg). Additionally, when a late dose of bortezomib (0.125 mg/kg) was administered with low dose ATN-224 (5 mg/kg), the combination had significantly better antitumor activity than ATN-224 or bortezomib alone, indicating that ATN-224 could re-sensitize tumors that were previously resistant to bortezomib. ATN-224 was also found to inhibit the expression of a novel myeloma growth and pro-angiogenic factor produced by myeloma cells, pleiotrophin, in a dose-dependent fashion. We have previously demonstrated that pleiotrophin expression declines in myeloma patients that respond to anti-myeloma therapy, further substantiating the anti-myeloma activity of ATN-224. These data suggest that ATN-224 may be useful in treating patients with highly refractory myeloma and provide a rationale for the clinical development of ATN-224 in this indication.
Brief Communication: Some Aspects of Host Response to Levamisole After Chemotherapy in a Murine Leukemia
Authors: K. Perk, M. A. Chirigos, F. Fuhrman, H. Pettigrew
Journal: JNCI Journal of the National Cancer Institute (1975)

Levamisole (LMS), when used with an effective remission-inducing drug in leukemic mice, resulted in a high percentage of long-term survivors. Histologic examination of spleens from treated leukemic mice showed that LMS caused an earlier return of lymphoid cells in the splenic lymphoid follicles and lymphoid elements in the red pulp.
Antiretroviral Preexposure Prophylaxis for HIV Prevention
Authors: Michael C Thigpen, Charles E Rose, Lynn A Paxton
Journal: New England Journal of Medicine (2013)

n engl j med 368;1 nejm.org january 3, 2013 82 To the Editor: Thigpen et al. (Aug. 2 issue)1 report that persons who are seronegative for the human immunodeficiency virus (HIV) and who are receiving tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) for preexposure prophylaxis had decreased bone mineral density at 24 months, as compared with those receiving placebo. In HIV-infected cohorts, TDF causes an initial loss of bone density over a period of 6 to 12 months, but there is stable bone density subsequently.2,3 These findings are consistent with other studies that have shown short-term loss of bone density in patients initiating antiretroviral treatment but stable bone density in those already receiving antiretroviral treatment.4 In contrast, Thigpen et al. found the opposite pattern: participants receiving TDF–FTC had relatively stable bone density for 12 months and then lost bone density between 12 and 24 months. The bone-density substudy had a high withdrawal rate, with only 40% of the participants having a bone-density measurement at 12 months and 26% at 24 months. This pattern could occur if participants with either normal bone density on the initial measurement or stable bone density on early serial measurements were more likely to withdraw. Can the authors report the baseline bone-density results and the changes over time among participants who withdrew, as compared with those who completed the study?
The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis
Authors: None Caproni, None Rolfo, None Bernacchi, None Bianchi, None Brazzini, None Fabbri
Journal: British Journal of Dermatology (1999)

Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions of LAD may be the consequence of the IgA deposits at the BMZ and also of the release of these cytokines together with tissue damage enzymes derived from neutrophils or eosinophils.
Bone scintigraphy in testicular tumors.
Authors: FRANCISCO JOSE H. N. BRAGA, MARCOS ABDO ARBEX, JORGE HADDAD, ALEX MAES
Journal: Clinical Nuclear Medicine (2001)

Testicular tumors do not occur frequently. Primary treatment is surgical, and radiotherapy and chemotherapy can play important roles in cases of metastatic disease. Bone scintigraphy is used largely for early detection of skeletal metastases from several tumors, and conventional radiographic studies are less sensitive than the nuclear technique for such a purpose. The aim of this study was to identify the role of bone scintigraphy in cases of testicular tumors, regardless of the grade.The authors examined 28 patients (8 to 52 years old) with proved testicular tumors using Tc-99m MDP (750 MBq; 20 mCi) injected intravenously. Whole-body images were obtained 2 hours later, at 500,000 counts per image. Radiographic studies were obtained to investigate abnormal areas noted on scintigraphy.The results of bone scintigraphy were abnormal in seven cases, consisting of variable but diffuse uptake in the iliac bone on the same side as the affected testicle. MDP uptake was substantial in five of these patients (four seminomas, one nonseminoma; only two radiographic studies were abnormal), and the two other patients had moderate uptake of the radiopharmaceutical (two seminomas; radiographic studies were normal). Metastases were confirmed by biopsy in three cases.Early metastases from seminomas can occur through the lymphatic drainage toward the iliac lymph node chain. This could explain these findings. The scintigraphic aspects of the affected iliac bones seem characteristic.Early detection of metastases is very important to ensure the efficacy of radiotherapy and chemotherapy. Bone scintigraphy may play an important role in such cases and seems to be more sensitive than conventional radiography. Testicular tumor metastases should be considered when iliac involvement is observed. Paget's disease should be included in a differential diagnosis.
Monkeypox Outbreak a Reminder of Emerging Infections Vulnerabilities
Authors: Joan Stephenson
Journal: JAMA (2003)

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
Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative
Authors: C. G. Tischer, C. Hohmann, E. Thiering, O. Herbarth, A. Müller, J. Henderson, R. Granell, M. P. Fantini, L. Luciano, A. Bergström, I. Kull, E. Link, A. von Berg, C. E. Kuehni, M.-P. F. Strippoli, U. Gehring, A. Wijga, E. Eller, C. Bindslev-Jensen, T. Keil, J. Heinrich
Journal: Allergy (2011)

To cite this article: Tischer CG, Hohmann C, Thiering E, Herbarth O, Müller A, Henderson J, Granell R, Fantini MP, Luciano L, Bergström A, Kull I, Link E, von Berg A, Kuehni CE, Strippoli M-PF, Gehring U, Wijga A, Eller E, Bindslev-Jensen C, Keil T, Heinrich J & as part of the ENRIECO consortium. Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative. Allergy 2011; 66: 1570–1579. Background: Several cross-sectional studies during the past 10 years have observed an increased risk of allergic outcomes for children living in damp or mouldy environments. Objective: The objective of this study was to investigate whether reported mould or dampness exposure in early life is associated with the development of allergic disorders in children from eight European birth cohorts. Methods: We analysed data from 31 742 children from eight ongoing European birth cohorts. Exposure to mould and allergic health outcomes were assessed by parental questionnaires at different time points. Meta-analyses with fixed- and random-effect models were applied. The number of the studies included in each analysis varied based on the outcome data available for each cohort. Results: Exposure to visible mould and/or dampness during first 2 years of life was associated with an increased risk of developing asthma: there was a significant association with early asthma symptoms in meta-analyses of four cohorts [0–2 years: adjusted odds ratios (aOR), 1.39 (95%CI, 1.05–1.84)] and with asthma later in childhood in six cohorts [6–8 years: aOR, 1.09(95%CI, 0.90–1.32) and 3–10 years: aOR, 1.10 (95%CI, 0.90–1.34)]. A statistically significant association was observed in six cohorts with symptoms of allergic rhinitis at school age [6–8 years: aOR, 1.12 (1.02–1.23)] and at any time point between 3 and 10 years [aOR, 1.18 (1.09–1.28)]. Conclusion: These findings suggest that a mouldy home environment in early life is associated with an increased risk of asthma particularly in young children and allergic rhinitis symptoms in school-age children.
Suicide
Authors: L. D. Hankoff
Journal: JAMA (2006)

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
Abstract 16394: Aspirin for the Prevention of Cardiovascular Events in Patients without Clinical Cardiovascular Disease: a Meta-Analysis of Randomized Trials
Authors: Anuradha Lala, Mori J Krantz, Gizelle S Baker, William R Hiatt, Jeffrey S Berger
Journal: Circulation (2010)

Background: The benefit of aspirin to prevent cardiovascular events in subjects without clinical cardiovascular disease (CVD) relative to the increased risk of bleeding is uncertain. Our aim was to investigate the benefit and risk of aspirin in patients without clinical CVD. Methods: A meta-analysis of randomized trials of aspirin versus placebo/control to assess the effect of aspirin on major cardiovascular events (MCE) consisting of non-fatal myocardial infarction (MI), non-fatal stroke, or cardiovascular death, all MI, all stroke, all-cause mortality, stroke subtype, and major bleeding. Nine trials involving a total of 102,621 patients were included, 52,145 patients allocated to aspirin and 50,476 to placebo or control. Results: Over a mean-follow-up of 6.9 years, aspirin was associated with a reduction in MCE (risk ratio [RR] 0.90, 95% confidence interval [CI] 0.85–0.96, P<0.001). There was no significant reduction for MI, stroke, ischemic stroke, or all-cause mortality. Aspirin was associated with he...
Elevated serum monoclonal and polyclonal free light chains and interferon inducible protein‐10 predicts inferior prognosis in untreated diffuse large B‐cell lymphoma
Authors: Thomas E. Witzig, Matthew J. Maurer, Mary J. Stenson, Cristine Allmer, William Macon, Brian Link, Jerry A. Katzmann, Mamta Gupta
Journal: American Journal of Hematology (2014)

The detection of serum free light (FLC) is useful in the diagnosis of several hematological diseases. The role and biological relevance of monoclonal or polyclonal FLC elevations in predicting long-term outcome in diffuse large B-cell lymphoma (DLBCL) is unknown. We determined the relationship of the type of FLC elevations to outcome, tumor genotype, and pattern of serum cytokine elevations in 276 patients with untreated DLBCL. Elevated FLC was an adverse prognostic factor through 6 years of follow-up (monoclonal, Event free survival (EFS) HR = 3.56, 95% CI: 1.88-6.76, P <0.0001; polyclonal, EFS HR = 2.56, 95% CI: 1.50-4.38, P = 0.0006). About 73% of DLBCL tumors with monoclonal FLC elevations were activated B-cell type (ABC) versus 33% from patients with normal FLC. Only ABC-DLBCL lines secreted kappa FLC in vitro and this secretion could be inhibited by the NF-κB inhibitor bortezomib. Patients with monoclonal FLC had significantly (all P <0.001) increased serum levels of IL-12, sIL-2Rα, IL-1R, and IP-10. Patients with polyclonal elevations of FLC had higher levels of IL-6 (P = 0.033), IL-8 (P =0.025), sIL2Rα (P = 0.011), and IL-1R1 (P = 0.041). The combination of elevated FLC and a CXC superfamily chemokine IP-10 predicted a particularly inferior outcome characterized by late relapse. These increased abnormal FLC and cytokines are potentially useful biomarkers for prognosis and selecting agents for untreated DLBCL.
Abstract 17750: The Effects of Typical Levels of Consumption of Dietary Sugars on Traditional Risk Factors for Cardiovascular Disease and Triglycerides
Authors: Joshua L Lowndes, Stephanie Sinnett, James Rippe
Journal: Circulation (2014)

High levels of fructose consumption may cause metabolic disruptions that increase the risk of cardiovascular disease (CVD). The American Heart Association has recommended that women and men should not consume more than 100 or 150 kcal/day, respectively, from added sugars. However, there is a lack of evidence suggesting negative effects when fructose is consumed in typical doses or in ways more typical to the American diet, such as with glucose as high fructose corn syrup (HFCS) and Sucrose.In the present study, 267 individuals aged 20-60 years old were required to drink sugar sweetened, low fat milk every day for 10 weeks as part of their usual diet. The amount of milk consumed was individualized based on the estimated number of calories required to maintain body weight (via Miflin St Joer equation ) and random group assignment: Groups 1 and 2 - 9% estimated caloric intake from fructose (n=65) or glucose (n=77) respectively added to milk (50th percentile consumption levels of fructose). Group 3 (n=125) - ...
Endotoxin exposure protects against new onset of pollen sensitisation
Authors: Grethe Elholm, Øyvind Omland, Torben Sigsgaard, Gert Doekes, Ioannis Basinas, Charlotte Hjort, Pernille Milvang Grønager, Vivi Schlünssen
Journal: European Respiratory Journal (2011)

Background:  Farmers are exposed to a wide range of organic and microbial components. We studied the relation between farm-related endotoxin exposure and changes in atopic sensitisation over time in young adults in The Danish Farming Cohort (SUS).   Method:  The SUS cohort (n=1166) was examined twice with a 15 year follow-up period. Specific IgEs against cat, birch, grass, HDM and storage mite allergens were determined (ADVIA Centaur, ALK Abello ®). Sensitisation was defined as sIgE≥0.35 kU/L, and atopy was defined as sensitisation to one or more of the 5 allergens tested for. Personal average yearly exposure to endotoxin during the follow-up period was estimated from more than 500 personal inhalable dust measurements and a farm-specific internal job exposure matrix.   Results:  New onset atopy was negatively associated with endotoxin exposure in a dose dependent manner (Table 1). Endotoxin exposure was not seen to be related to new onset of mite sensitisation. In contrast, all levels of endotoxin exposure showed a significant and strong protective effect against new onset of pollen sensitisation.   Conclusion:  These analyses suggest endotoxin exposure to have a significant protective effect against new onset of pollen sensitisation.