tbuckley/cabot-search huggingface dataset:
Abstract LB-429: Synergistic effects of low-fat diet combined with IGF-I receptor blockade on 22RV1 prostate cancer xenografts
Authors: Ramdev Konijeti, Colette Galet, Bingrong Liu, Ashley Gray, R. James Barnard, Jonathan Said, Brandon Castor, Satomi Koyama, David Hwang, Pedro Beltran, Franck Calzone, Pinchas Cohen, William J. Aronson
Journal: Cancer Research (2010)

Abstract Introduction: IGF-I receptor (IGF-1R) blockade has previously been shown to slow prostate cancer xenograft growth. Dietary fat reduction also inhibits xenograft growth, possibly by modulation of the IGF axis. We hypothesized that a low-fat (LF) diet combined with IGF-I receptor blockade would cause additive retardation of prostate cancer growth and offset the possible untoward metabolic effects of IGF-1R antibody therapy. Methods: Fifty severe combined immunodeficient mice were injected subcutaneously with 22RV1 cells (suppressible with IGF-1R blockade in vitro) and were randomized to four groups: 1) high-fat (HF) diet with intraperitoneal saline, 2) high-fat diet with intraperitoneal IGF-I receptor blocking antibody from Amgen: AMG479, (HFAb), 3) low-fat diet with intraperitoneal saline (LF), 4) low-fat diet with intraperitoneal AMG479, (LFAb). Treatment with either antibody or saline was initiated 10 days after tumor injection and given twice weekly, tumors were measured serially. The animals were euthanized at 19 days of treatment. Tumors were then weighed and stained for Ki67, TUNEL, and CD31. Serum levels of insulin, resistin, murine IGF-I, murine IGFBP-3, and TNF-alpha were measured. Results: Mean tumor weights were significantly lower (by ∼ 40%) in the HFAb and LFAb group relative to the HF group. There was no difference in mean tumor weight between the HFAb and LFAb groups. Ki67 expression (% positive cells) was significantly decreased in the LFAb group compared to the HFAb group (62 + 29 vs. 94 + 4.3, p&amp;lt;0.001). IGF-1R antibody caused a significant increase in serum insulin levels compared to the LF and HF group, but combining the LF diet with the IGF-1R antibody significantly reduced serum insulin levels by 40% relative to the HFAb group. Likewise, combining a LF diet with the IGF-1R antibody also reduced serum TNF-alpha levels relative to the HF group. Conclusion: IGF-1R antibody therapy inhibited xenograft growth in mice on HF and LF diets. Whereas combining a LF diet with IGF-1R antibody did not have additive growth inhibitory effects on tumor size, there was evidence of decreased tumor cell proliferation, reduced serum insulin levels and reduced pro-inflammatory cytokine levels. Further pre-clinical and clinical trials are warranted to evaluate the role of dietary interventions to enhance anti-tumor effects and offset the metabolic consequences of IGF-1R antibody therapy. Aknowledgements: This work was supported by the NCI grant # P50CA92131 and “The Ruby Family Foundation”. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-429.
Survival with nonmelanoma skin cancer in Germany
Authors: N. Eisemann, L. Jansen, F.A. Castro, T. Chen, A. Eberle, A. Nennecke, S.R. Zeissig, H. Brenner, A. Katalinic
Journal: British Journal of Dermatology (2015)

Nonmelanoma skin cancer (NMSC) is the most common cancer in Germany, but detailed information on survival is lacking.To provide survival estimates for female and male patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sarcoma, adenocarcinoma and Merkel cell carcinoma. Further subgroup analyses were carried out by age, tumour stage and body site.In total 459 640 patients diagnosed with NMSC in 1997-2011 were included from population-based cancer registers, covering a population of 33 million inhabitants. Age-standardized absolute and relative 5-year and 10-year survival were calculated using period analysis.The absolute and relative 5-year survival were 87·1% and 102·9% for BCC, 77·6% and 93·6% for SCC, 82·1% and 96·0% for sarcoma, 71·4% and 85·7% for adenocarcinoma and 60·0% and 70·7% for Merkel cell carcinoma, respectively. Higher age, female sex and advanced stage were associated with lower survival.A comprehensive overview of NMSC survival in Germany is provided. The differences between the NMSC subtypes require a more differentiated consideration of patient survival. The survival advantage of patients with BCC may be related to health-promoting factors related to the BCC diagnosis, such as changes to a healthier lifestyle.
Abstract 3468: Aldo-keto reductases protect lung epithelial cells from polycyclic aromatic hydrocarbons at the expense of increased oxidative stress
Authors: Zahidur Abedin, Sushmita Sen, Jeffrey Field
Journal: Cancer Research (2010)

Abstract Tobacco exposure stimulates genes that are likely to be involved in the metabolism of tobacco and its combustion products. Four induced genes are aldo-keto reductases (AKR), a family of enzymes that reduce aldehydes and ketones to alcohols. AKRs act on a range of substrates including polycyclic aromatic hydrocarbons (PAH). AKRs convert PAH to form o-quinones. Alternatively, PAHs are metabolized to (+)-anti-benzo[α]pyrene diol epoxide ((+)-anti-BPDE)) by the combined action of P4501A1/1B1 and epoxide hydrolase. (+)-anti-BPDE forms DNA adducts directly, while PAH o-quinones cause oxidative stress through a futile redox cycle. To address the role of AKRs in PAH toxicity, we compared the toxicities of PAH metabolites and the effects of overexpressing AKR 1A1 in lung cells. We find that anti-BPDE and BP,-7,8-diol, an intermediate product, are toxic to A549 cells at concentrations with an IC50 of ∼2 µM. In addition, both anti-BPDE and BP 7,8-diol induce p53 expression in 6 hrs post-treatment at concentrations as low as 1 µM consistent with extensive DNA damage. In contrast, we found that the PAH o-quinone B[a]P-7,8-dione was about 10-fold less toxic to A549 cells with an IC 50 &amp;gt; 20 µM. B[a]P-7,8-dione treatment also did not induce p53 expression in 24 hrs at 20 µM. However, B[a]P-7,8-dione treatment generated reactive oxygen species (ROS) in A549 cells as previously reported. We also observed that overexpression of AKR 1A1 in H358 cells, which otherwise have low levels of AKR expression, protected cells 2-10 fold from the toxic effects of BP, 7,8-diol. These data suggest that overexpression of AKRs may protect lung cancer cells from the acute toxic effects of PAH at the expense of increasing the burden oxidative stress Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3468.
Case 10-2012
Authors: Cassandra M. Kelleher, David G. Forcione, Michael S. Gee, Mari Mino-Kenudson
Journal: New England Journal of Medicine (2012)

A 16-year-old boy was admitted to this hospital because of abdominal pain for 2 days. On examination, there was epigastric tenderness with guarding. Imaging revealed a posterior mediastinal cystic mass. Diagnostic procedures were performed.
Advances in pancreas transplantation
Authors: Shamik Dholakia, Youssof Oskrochi, Graham Easton, Vassilios Papalois
Journal: Journal of the Royal Society of Medicine (2016)

The potential to reverse diabetes has to be balanced against the morbidity of long-term immunosuppression associated with transplantation. For a patient with renal failure, the treatment of choice is often a simultaneous transplant of the pancreas and kidney or pancreas after kidney. For a patient with glycaemic instability, choices between a solid organ or islet transplant have to be weighed against benefits and risks of remaining on insulin. Results of simultaneous transplant of the pancreas and kidney transplantation are comparable to other solid-organ transplants, and there is evidence of improved quality of life and life expectancy. There is some evidence of benefit with respect to the progression of secondary diabetic complications in patients with functioning transplants for several years.
Mutation of Antitrypsin to Antithrombin
Authors: Maurice C. Owen, Stephen O. Brennan, Jessica H. Lewis, Robin W. Carrell
Journal: New England Journal of Medicine (1983)

Our previous studies predicted a functional relationship between the plasma proteins alpha 1-antitrypsin and antithrombin III. To elucidate this relationship we investigated the plasma of a 14-year-old boy who had died from an episodic bleeding disorder. A variant alpha 1-antitrypsin was identified in which the methionine at position 358 had been replaced by an arginine. This had converted the alpha 1-antitrypsin from its normal function as an inhibitor of elastase to that of an inhibitor of thrombin. This finding indicates that the reactive center of alpha 1-antitrypsin is methionine 358, which acts as a bait for elastase, just as the normal reactive center of antithrombin III is arginine 393, which acts as a bait for thrombin. The independence of the new thrombin inhibitor from heparin control explains the bleeding disorder; it also indicates that heparin normally acts directly on antithrombin III, revealing its inherent inhibitory activity. The episodic nature of the bleeding was a consequence of the mutant protein's being an acute-phase reactant, the level of which increased several-fold after trauma.
CARDIAC DETERMINANTS OF RIGHT VENTRICULAR PRESSURE-FLOW FESPONSE TO EXERCISE IN HEART FAILURE: A STUDY BY COMBINING CARDIOPULMONARY EXERCISE TESTING AND EXERCISE ECHOCARDIOGRAPHY
Authors: Greta Generati, Francesco Bandera, Marta Pellegrino, Valentina Labate, Valeria Donghi, Vincenzo Tufaro, Eleonora Alfonzetti, Marco Guazzi
Journal: Journal of the American College of Cardiology (2016)
Tracking Alternative Flame Retardants: Hand-to-Mouth Exposures in Adults
Authors: Kellyn S. Betts
Journal: Environmental Health Perspectives (2015)

Hand-to-Mouth Exposures in AdultsSince polybrominated diphenyl ether (PBDE) flame retardants were withdrawn from use in polyurethane foam padding, alternatives including tris(1,3-dichloropropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) are now used in consumer goods including furniture, automobiles, carpet padding, and baby products. 1,2,3,4Like PBDEs, these replacement compounds have been widely found in dust samples from homes, offices, and vehicle interiors. 2,3,4A new study in this issue of EHP examines whether they also resemble PBDEs in another way: the routes by which people are exposed. 5TDCIPP and TPHP are members of the family of organophosphate flame retardants (PFRs).TDCIPP is listed as a human carcinogen under California's Proposition 65, 6 and a small human study found evidence that exposure to both TDCIPP and TPHP was associated with altered levels of some hormones and lower sperm concentration. 2 In vitro and animal data have linked TDCIPP to neurotoxicity and both TDCIPP and TPHP to endocrine disruption. 7,8,9,10,11he new study focused on home exposures.The study included 53 men and women who provided hand-wipe and urine samples.Most (92%) of these volunteers also provided a dust sample from their home.The two PFRs were found in all the dust samples at widely varying levels.There was a 200-fold increase from the lowest to highest dust concentration of TDCIPP and a 400-fold increase from the lowest to highest TPHP concentration. 5etabolites of the PFRs were detected in most of the urine samples.The primary metabolite of TPHP (DPHP) was found in 91% of samples, and the primary metabolite of TDCIPP (BDCIPP) was found in 83% of samples. 5Women had urinary levels of DPHP nearly twice those of men. 5 "This is a very unusual finding.We haven't seen that before [for flame retardants], which suggests to us that there is likely exposure through a personal care product," says corresponding author
Abstract 4516: A new class of MDM2 inhibitors cause growth inhibition and stabilize wt p53 in lymphoma cells but do not interfere with MDM2 E3 ligase activity
Authors: Angela M. Sosin, Angelika M. Burger, Dajun Yang, Ramzi M. Mohammad, Ayad Al-Katib
Journal: Cancer Research (2010)

Abstract The p53 tumor suppressor protein function is impaired in over 50% of all cancers via inactivating mutations. However, the frequency of p53 mutations is much lower in hematological malignancies. Most lymphomas have wild-type (wt) p53, mutant (mt) p53 is found in less than 30% of all cases. The ubiquitin E3 ligase MDM2 plays a central role in cancer development and progression and is typically overexpressed in lymphomas. MDM2 expression destabilizes functional wt p53 by causing its polyubiquitination and subsequent degradation in the proteasome. Small-molecule inhibitors (SMI) that can block the MDM2-p53 protein-protein interaction and restore p53 function are a promising therapeutic strategy for the treatment of cancers retaining wt p53 that is degraded by overexpression of MDM2. By utilizing two wt p53 and two mt p53 lymphoma cell lines whose p53 status was confirmed by DNA sequencing, we studied the growth inhibitory potential of two different classes of MDM2 SMIs: Nutlin-3, a cis-imidazoline, and MI-219, a new spiro-oxindole MDM2 SMI. Both trypan blue exclusion and MTT assays demonstrated IC50s between 2 and 4 µM in wt p53 cells in vitro. Mutant p53 cells displayed IC50s greater than 10 µM. Growth inhibition was time- and dose-dependent. Additional flow cytometric analyses empolying Annexin V and propidium iodide staining illustrated increasing apoptosis with cells decreasing in G2/M and S phase that also showed time- and dose-dependency. The MDM2 SMI MI-219 showed a much more prominent cell cycle arrest compared to Nutlin-3. Western blotting demonstrated a stabilization of wt p53 and proapoptotic proteins such as p21, Bcl-2, and Bax. In order to determine whether MDM2 SMIs affect the E3 ligase RING-finger domain of MDM2, in vitro autoubiquitination assays were performed using recombinant MDM2 with various concentration of drug. MDM2 autoubiquitination was not affected, even at a concentration as high as 50 µM. These results show that MDM2 autoubiquitination and thus, its degradation remains unaffected in the presence of MDM2 inhibitors that interfere with the p53-MDM2 binding site. This feature of MDM2 SMI is attractive since inhibition of MDM2 autoubiquitination would lead to its stabilization and could negate effects on p53. Our data suggest that MI-219 would be a useful treatment for lymphomas expressing wt p53 and that this should be explored in further preclinical and future clinical studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4516.
Endoscopic ultrasound-guided antegrade diathermic dilation followed by self-expandable metal stent placement for malignant distal biliary stricture
Authors: Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Taiki Kudo, Yoko Abe, Kimitoshi Kubo, Yoshimasa Kubota, Naoya Sakamoto
Journal: Endoscopy (2014)

Endoscopic ultrasound (EUS)-guided antegrade stenting (AGS) is established as an alternative interventional technique in patients in whom endoscopic transpapillary stenting has failed [1] [2]. Here, we present a patient who underwent EUS-AGS after diathermic dilation with placement of a self-expandable metal stent (SEMS) for a malignant distal biliary stricture.
AB1099 Obesity and fibromyalgia: Relationship between body mass index and severity of the symptoms
Authors: S. Castro, M.J. Poveda, R. Fontova, A. Castel, R. Qanneta, S. Montull, R. Periñán, I. Miralles, N. Aragonés, I. Salvat, R. Cascόn, S. Monterde, A. Padrol, C. Añez, M. Rull
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia (FM) is a prevalent musculoskeletal chronic pain condition. Obesity is frequent in patients with FM. Several studies suggests that body mass index (BMI) is related with pain intensity and quality of life. <h3>Objectives</h3> 1) To determine the prevalence of obesity in a sample of women with FM. 2) To determine the relationship between obesity and the following variables: pain intensity, functionality, psychological distress, quality of life, and sleep problems. <h3>Methods</h3> 152 women with FM according to the American College of Rheumatology criteria who participated in a multidisciplinary treatment. Patients were assessed before treatment, after treatment, and at 3-6-12 month follow-up. Measures: Body Mass Index (BMI), pain intensity (Numeric Rating Scale), functionality (FIQ), psychological distress (HADS), quality of life (COOP-WONCA), and sleep problems (Medical Outcome Study: MOS). Patients were classified according their BMI: normal weight (BMI &lt;25), overweight (BMI 25.0-29.9), obesity (BMI ≥30). <h3>Results</h3> The 30.9% (N=47) of the patients were normal weight, the 40.1% (N=61) overweight, and the remaining 28.9% (N=44) obese. Groups were homogeneous regarding to age. ANOVA analysis, with Bonferroni correction, showed no differences between groups in the assessed measures, except in pain intensity. Patients with obesity had more pain than patients with overweight (p&lt;.01). <h3>Conclusions</h3> 1) As already stated in previous studies, obesity was a frequent comorbid condition in patients with FM. 2) Patients with obesity had more pain than overweight patients. 3) Weight didn't determine differences in the other studied variables. Supported by the Foundation Maratό Grant Number 070910 <h3>Disclosure of Interest</h3> None Declared
ACR Program Accredits Nearly 800 Mammography Units
Authors: S. Kumar
Journal: JNCI Journal of the National Cancer Institute (1989)

ACR Program Accredits Nearly 800 Mammography Units Get access Seema Kumar Seema Kumar Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 16, 16 August 1989, Pages 1211–1212, https://doi.org/10.1093/jnci/81.16.1211 Published: 16 August 1989
Abstract 701: Elevated insulin-like growth factor 1 receptor provides an essential survival signal via Bcl-xL in rhabdomyosarcoma cells as an alternative to Bcl-2 overexpression
Authors: Linnia H. Mayeenuddin, Yunkai Yu, Zhigang Kang, Lee J. Helman, Liang Cao
Journal: Cancer Research (2010)

Abstract Insulin-like growth factors and their receptor IGF1R play important roles in growth, development, stress response, aging, and cancer. Many antibodies targeting IGF1R are in varies stages of clinical development. It is important to understand the mechanism of the antibody-mediated cancer cell growth inhibition and death, and to identify biomarkers predictive of responses that can be implemented in clinical investigations. We previously reported that IGF1R mediated cell growth suppression of rhabdomyosarcoma (RMS) in vitro and in vivo, in which the anti-proliferative activity was correlated with IGF1R levels and AKT signaling (Cao, et al., Cancer Research 2008, 68:8039). Here, we show that in some RMS cells, treatment with a humanized IGF1R antibody results in a rapid onset of mitochondrial-dependent apoptosis, including mitochondrial depolarization, cytochrome C release, and the activation of specific caspases. The antibody-induced cell death is mediated in part via AKT-dependent pathway, and both the inhibition of AKT signaling and induction of cell death by anti-IGF1R can be rescued by the introduction of a constitutively active AKT. Further analysis reveals IGF1R antibody-induced hypophosphorylation (activation) of BAD and the activation of downstream BAX. Bcl-xL was previously shown to be a key target of activated BAD. Our data indicate that cells with the transgenic expression of Bcl-xL are completely resistant to antibody-induced cell death, while still susceptible to antibody-mediated growth inhibition. Moreover, siRNA against Bcl-xL enhances anti-IGF1R-induced apoptosis. Interestingly, the examination of RMS cell lines and tumors reveals an inverse correlation between elevated IGF1R and another pro-survival gene Bcl-2 (P=0.033). Thus, our results indicate that RMS pathogenesis may involve two strategies for cell survival: 1) increasing IGF1R expression that enhances Bcl-xL activity; or 2) up-regulating Bcl-2 expression. Our study suggests a particular subgroup of the cancer with elevated IGF1R and low Bcl-2 maybe more susceptible to anti-IGF1R treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 701.
P2-01-18: Cancer Stem-Like Cells in Breast Cancer Progression.
Authors: FAM Valejo, JM Andrade, RD Sicchieri, HMR Antonio, HRC Marana, LR Mouro, TMG Oliveira, L Benevides, JS Silva, VF Muglia, DG Tiezzi
Journal: Cancer Research (2011)

Abstract Background: increasing evidences support the presence of cancer stem-like cells (CSLCs) within breast carcinomas. A subset of cells enriched for CSLCs within the tumor can be identified by flow cytometry. It has been supposed that CSLC component is responsible for tumor resistance and metastasis. However, the analysis of such population has never been evaluated during breast cancer progression. Patients and Methods: We prospectively included 98 women with histologically proven breast carcinomas to assess the presence of CSLCs within the primary tumor. According to clinical stage (CS), five patients were CS 0 (palpable DCIS), 16 CS I, 20 CS II and negative lymph nodes (IIA-), 20 CS II and positive lymph nodes (IIA+), 6 IIIa, 17 IIIb, 1IIIc and 2 CS IV. Additionally, ten lymph node metastases from IIA+ patients were analyzed. Invasive ductal carcinoma (IDC) was observed in 79 patients. We excluded from the analysis patients with non ductal histology (n= 11). The percentage of CD44+/CD24- (n= 79), ALDH1+ (ALDEFLUOR®) (n= 29), ABCG2+ (n= 44) and CXCR4+ (n= 46) cells within ESA+ cells was determined by flow cytometry in fresh sampled tumors. The mammosphere assay was studied in 14 samples. The relationship between cytometry analyses and clinical and pathological features was analyzed. Results: The median prevalence of CD44+/CD24- cells within ESA+ population was 1.63% in stage 0, 2.39% in stage I, 0.42% in stage IIA-, 8.15% in stage IIA+, 0.52% in stage III (p=0.005). The CD44+/CD24- cell population was analyzed in 10 lymph node metastasis and, the median prevalence of this population within ESA+ cells was 4.7%. There was no variation of median prevalence of ALDH1+, CXCR4+, ABCG2+ and the median number of spheres among clinical stages (p=0.1, p=0.8, p=0.8, p=0.8, respectively). We didn't observe any association among the expression of, ABCG2+, CXCR4+ with histological grade and the expression of ER and PgR. The median percentage of CD44+/CD24- cells was higher (2.39% vs 0.41%) in ER positive tumors (p=0.003). The median percentage of ESA+/ CXCR4+ cells was higher (42,5% vs 9,7%) in HER2− tumors. There was no correlation between the studied markers and the patients’ age and clinical tumor diameter. The results are summarized in Table 1. Results of association between expression cells surface markers and ALDH1 activity (Aldefluor®) with clinical and pathological features in invasive ductal carcinomas. Discussion: We found a significant variation in CSLC population during breast cancer progression. Our data show a gradual increase in CD44+/CD24- cells within ESA+ population from stage 0 to stage IIA+ and a significant decrease in stage III tumors. This observation supports the hypothesis that a population of CSLCs could be associated with breast cancer progression. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-18.