tbuckley/cabot-search huggingface dataset:
Abstract 610: Short peptides for targeted apoptosis in cancer cells: development &amp; evaluation of therapeutic applications.
Authors: Oleksandr Boyko, Karl T. Riabowol
Journal: Cancer Research (2013)

Abstract The ING proteins are type II tumor suppressors that are involved in the regulation of gene transcription, DNA repair, cellular senescence, tumorigenesis and apoptosis. Inactivation of apoptosis pathways is frequently observed in cancer cells, and it leads to a drastic decrease in the efficiency of available cancer treatments. Inactivation of INGs during the suppression of apoptosis tumors and greater sensitivity of cancer versus normal cells to the elevation of ING1 levels suggest that the INGs could serve as viable targets for cancer therapy. In this study we expand our previous observations that all ING proteins share a conserved sequence domain, the Lamin Interacting Domain (LID), which is unique to INGs in the human proteome. The overexpression of a recombinant peptide containing multiple fragments of the LID domain was previously shown to induce apoptosis in a rapid and efficient way in several cancer cell line models. Together, rather limited knowledge of the molecular mechanisms that mediated these apoptosis-inducing effects and the large size of the recombinant LID peptide precluded use of the LID for therapeutic purposes. Here we define the minimal portion of the LID domain that is capable of efficiently inducing apoptosis, and devise approaches to efficiently introduce it into cancer cells where we predict it will show a good therapeutic index by virtue of inducing apoptosis in cancer cells much more efficiently than in normal surrounding cells. Our preliminary in silico analysis of the LID protein structure indicated that LID peptides could interfere with several “master regulators” of cell cycle control and apoptosis, including Retinoblastoma and SMAC proteins. Overexpression of LID peptides could also interfere with the formation of functional ING1-HDAC chromatin modifying protein complexes by disrupting ING1-Lamin A interactions, thus leading to the loss of HDAC targeting and apoptosis. Our ongoing studies should help to identify the molecular mechanism(s) of LID-mediated apoptosis induction and identify the minimal required sequence of LID peptide that still displays potent apoptosis-inducing activity against tumor cells. Our long term goal is to further expand current understanding of apoptosis pathways and develop LID-based therapeutic for the selective induction of apoptosis in cancer cells. Citation Format: Oleksandr Boyko, Karl T. Riabowol. Short peptides for targeted apoptosis in cancer cells: development &amp; evaluation of therapeutic applications. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 610. doi:10.1158/1538-7445.AM2013-610
Hyperinsulinemia in a Population at High Risk for Non-Insulin-Dependent Diabetes Mellitus
Authors: Steven M. Haffner, Michael P. Stern, Helen P. Haztjda, Jacqueline A. Pugh, Judith K. Patterson
Journal: New England Journal of Medicine (1986)

The prevalence of non-insulin-dependent diabetes mellitus (NIDDM) is higher in Mexican Americans than in non-Hispanic white Americans, even after adjustment for the former's greater overall and more centralized adiposity. We postulated that this excess risk of NIDDM could be due to resistance to insulin. We performed oral glucose-tolerance tests with measurements of serum insulin concentrations in 225 Mexican Americans and 180 non-Hispanic whites without diabetes as part of the San Antonio Heart Study, a population-based study of risk factors for diabetes. Changes in serum insulin concentrations in response to the glucose challenge were quantified by the area under the serum insulin curve. Overall adiposity was characterized by body-mass index, and regional body-fat distribution by the ratio of subscapular to triceps skinfolds and the ratio of waist to hip circumference. After adjustment for these indicators of adiposity and also for differences in glucose tolerance, Mexican Americans were found to have significantly greater areas under the serum insulin curve than non-Hispanic whites. These data suggest that, like other populations at high risk for NIDDM such as Pima Indians and Micronesians, Mexican Americans have more hyperinsulinemia than can be accounted for by their adiposity. (N Engl J Med 1986; 315:220–4.)
FRI0015 B-cell depletion modulates T-helper cell balance in patients with primary sjÖgren’s syndrome
Authors: W.H. Abdulahad, F. Kroese, M. Huitema, P. Meiners, A. Vissink, H. Bootsma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> B-cell depletion therapy with a chimeric anti-human CD20 antibody (rituximab; RTX) is an effective treatment modality for patients with primary Sjögren’s syndrome (pSS)<sup>1</sup>. However, the mechanisms through which RTX exerts its effects on the disease process have not been fully elucidated. Alterations in T-helper (Th) cell homeostasis may contribute to the therapeutic effect of RTX in pSS patients as Th cell subset imbalances are involved in the emergence of autoimmune diseases. <h3>Objectives</h3> This study assessed the influence of RTX on Th1/Th2/Th17 balance in peripheral blood of pSS patients. <h3>Methods</h3> Twenty-eight patients with pSS were treated on days 1 and 15 with RTX (1000 mg i.v.). The frequencies and absolute numbers of circulating Th1/Th2/Th17 cell subsets were examined in fresh blood samples by 6-color flow cytometry at baseline and at 5, 16, 24, 48 and 60 weeks after treatment. The expression pattern of chemokine receptors CXCR3+CRTh2–CCR4–CCR6–, CXCR3–CRTh2+CCR4+CCR6– and CXCR3–CRTh2–CCR4+CCR6+ were used for distinction between Th1, Th2 and Th17, respectively. Sixteen age- and sex-matched healthy individuals were studied in parallel as controls (HCs). <h3>Results</h3> At baseline, compared to HCs, pSS patients showed a significant decrease in frequencies and numbers of circulating Th1-cells, and a significant increase in Th17-cells. In contrast, no differences were seen in percentages and numbers of Th2 cells between HCs and pSS patients. Following RTX treatment, frequencies and numbers of Th-cell subsets in pSS patients at 5, 16, and 24 weeks were comparable to pSS baseline values. In contrast, the frequencies and numbers of Th1 cells were significantly increased, whereas frequencies and numbers of Th17 cells were significantly decreased in RTX-patients at 48 and 60 weeks post-treatment, as compared to baseline. Th2 cells remained unchanged at these time points. Importantly, frequencies and numbers of Th1- and Th17 cells in pSS patients at week 60 post-treatment were similar to those in HCs. <h3>Conclusions</h3> These data strongly indicate that RTX treatment has profound effects on the distribution of Th cell subsets in pSS patients. Reduction in pro-inflammatory Th17 responses may contribute to the observed clinical outcome of RTX treatment in pSS patients. <h3>References</h3> Effectiveness of rituximab treatment in primary Sjögren’s syndrome: a randomized, double-blind, placebo-controlled trial. Meijer JM et al. Arthritis Rheum. 2010 Apr;62(4):960-8. <h3>Disclosure of Interest</h3> None Declared
Abstract 2985: Predicting the impact of mutations in cancer using an integrated pathway approach
Authors: Sam Ng, Janita Thusberg, Stephen Benz, Charles Vaske, Kyle Ellrott, Jing Zhu, Christina Yau, Eric Collisson, Sean Mooney, Christopher Benz, David Haussler, Joshua Stuart
Journal: Cancer Research (2012)

Abstract The major mechanism by which cancer arises is through somatic mutations. These mutations can lead to alterations in gene regulation as well as changes in protein structure and function. Individual tumors can contain hundreds to thousands of mutations. It is critical to distinguish mutations that have an important role defining the cancer - driver mutations - from mutations that are unimportant to the tumor - passenger mutations. Differentiating driver and passenger events is essential for understanding cancer disease mechanisms, which can help guide treatment decisions as well as identify novel targets for treatment. Genomic probing with technologies such as expression arrays and high-throughput RNA sequencing provide insight into changes in gene regulation in cancer, but determining the tumorigenic role of a coding mutation is less clear. Genomic data coupled with pathway information may provide insight into the functional impact of a mutation to particular genes. We are developing a mutation prediction method based on integrated pathway analysis to discriminate loss-of-function, neutral, and gain-of-function mutations. Utilizing the set of regulatory interactions annotated for a given gene, we can detect a discrepancy in the downstream effects of an altered gene compared to what is expected from its upstream influences. We show that a score based on this discrepancy is highly predictive of the presence of a mutation and that the directionality of this discrepancy also reflects the gain- or loss-of-function in a gene. Application of our method to a set of known driver mutations reveals that there is a significantly strong signal for loss- and gain- of functional mutations in the surrounding network, demonstrating the sensitivity of this approach. In addition, when applied to the negative control of passenger mutations, the method predicts little pathway impact, indicating this approach also has high specificity. Application of this approach to all recurrent mutations in ovarian and glioblastoma multiforme cancers from the TCGA project identifies several important driver mutations across these cohorts. We also highlight the novel utility of this specific approach by comparison to earlier published approaches including MutSig, CHASM, and MutPred. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2985. doi:1538-7445.AM2012-2985
Abstract 5088: In vitro induction of a more aggressive prostate cancer phenotype by exposure to obese sera
Authors: Ramona Salcedo, David Cavazos, Stephen Hursting, Rebecca De Angel, Linda deGraffenried, Muralidhar Beeram
Journal: Cancer Research (2010)

Abstract Prostate cancer continues to be the second-leading cause of cancer related deaths for men in the United States. Obesity is a known risk factor for the progression of prostate cancer. Studies have shown an association between obesity and chronic inflammation. Inflammation may contribute to prostate growth by promoting benign prostatic hyperplasia or inducing neoplastic changes. The mechanism(s) by which obesity promotes an aggressive prostate cancer is not fully understood. Investigating these mechanisms has been hampered by the lack of appropriate in vitro and in vivo model systems. Our main hypothesis is that obesity-induced chronic inflammation promotes metastatic prostate cancer through modulation of key signaling pathways, including NF-[[Unable to Display Character: &amp;#312;]]B. Our first objective was to develop an appropriate in vitro model system to recapitulate the molecular events associated with obesity. In this current study, we obtained sera from obese and non-obese mice. Using an adipokine protein array 3 independent profiles were identified in obese mice sera that are consistent with metabolic obesity: metabolic syndrome, pro-metastatic and pro-inflammatory profile. We treated LNCaP prostate cancer cells with sera from obese and non-obese mice to determine physiological responses associated with an aggressive phenotype. We observed obese sera promoting invasion and increasing cell motility while having no effect on proliferation. In addition, obese mouse sera induced an EMT phenotype, evidenced by cytoplasmic dispersion of e-cadherin from cell-cell junctions and an increase in vimentin, which corresponded in greater tumor invasion. This study suggests that we can use an in vitro system to mimic the physiological changes in tumor biology induced by exposure to obese sera to investigate the molecular changes that induce a more aggressive phenotype. 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 5088.
Selective Binding Sites for the Transfer of Ferritin Into Erythroblasts. I. Preliminary Report23
Authors: Oliver P. Jones
Journal: JNCI Journal of the National Cancer Institute (1965)

In studies of rat and human fetal livers, pinocytosis occurred on any part of the plasma membrane of early erythroblasts and it was not more frequent adjacent to a hepatic or Kupffer cell. This cell surface activity was observed both extravascularly and intravascularly. Formation of pinocytotic vesicles was more than just the internalization of parts of the plasma membrane of early erythroblasts. There was more electron scattering at the site where pinocytosis was being induced. Laminae of the unit membrane condensed to form a single electron-opaque membrane. At higher magnifications, even shallow invaginations were composed of 3 layers: an external amorphous layer with ferritin and other granules adherent to the membrane, the condensed plasma membrane, and an internal layer of relatively electron-opaque granules—presumably ribonucleoprotein. The resulting vesicles, with ferritin molecules and plasma inside, were bounded by a three-layered wall. These studies were extended to bone marrow from patients with pernicious anemia after therapy, acquired hemolytic anemia, erythremic myelosis, and sickle cell anemia. Some erythroblasts had areas of pinocytotic activity involving reticulum cells which Policard and Bessis (1958) called rhopheocytosis, a term Sorenson (1960) used similarly for areas involving developing hepatic cells, but these situations are not essential for the incorporation of ferritin. During embryonic hemopoiesis and adult erythropoiesis under pathologic conditions, ferritin molecules were attached to selective binding sites. Pinocytotic activity decreased with the maturation of erythroblasts.
Diagnosis of Hepatic Hydrothorax by Tc-99m Sulfur Colloid Peritoneal Scintigraphy
Authors: ANSHU RAJNISH, PUSPALATHA SUDHAKAR
Journal: Clinical Nuclear Medicine (2001)

RAJNISH, ANSHU D.N.B., D.R.M., M.N.A.M.S.; SUDHAKAR, PUSPALATHA D.N.B. Author Information
Abstract 1331: BMP-6 induce IL-1β expression levels in macrophage cells
Authors: Yeon Suk Jung, Geun Taek Lee, Jae-Ho Lee, Seokjoo Kwon, Isaac Yi Kim
Journal: Cancer Research (2010)

Abstract Prostate cancer is the most 2ND leading cause of cancer death among men in United States. In metastatic prostate cancer patients, androgen ablation leads to symptomatic improvement and a decrease in serum prostate-specific antigen (PSA), but in almost patients the disease will eventually become refractory to hormone ablation. Previously, it has been published that IL-1β from macrophage regulates AR dependent signal transduction. In the prostate cancer, Bone morphogenetic protein-6 (BMP-6) levels are elevated than normal prostate. BMPs are members of TGF-β super family that regulates bone formation, hematopoiesis and development. BMP-6 is a pleiotropic growth factor with frequently increased levels of expression in the context of loss of its cognate receptors in prostate cancer cells. In this study, we demonstrated that BMP-6 secretion in CaP affects on macrophage cell line, RAW 264.7. Results showed that BMP-6 increased IL-1β levels in the macrophage and the induction is concentration and time dependent. In association with these observations, it is demonstrated that IL-1β expression by BMP-6 is mediated through ALK3, BMPRII and Smad1/4. Taken together, ERK inhibitor and JNK inhibitor may block IL-1β induction by BMP-6 completely in RAW264.7, macrophage cell line. 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 1331.
Top Cancer-Related News Stories Focus on Breast, Prostate, and Colon Cancers
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Top Cancer-Related News Stories Focus on Breast, Prostate, and Colon Cancers Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 1, 5 January 1994, Pages 10–12, https://doi.org/10.1093/jnci/86.1.10 Published: 05 January 1994
THU0462 Increased Oxidative Stress and Macrophage Migration Inhibitory Factor in Patients with Familial Mediterranean Fever
Authors: I. Sari, Y. Savran, D. L. Kozaci, N. Gunay, F. Onen, S. Akar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean fever (FMF) is an autoinflammatory disorder characterized by recurrent, inflammatory, self-limited episodes of fever and serositis. Neutrophils are one of the key players in the pathophysiology of FMF. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine involved in several inflammatory processes including innate and adaptive immune responses. In addition, MIF has been shown to regulate trafficking of inflammatory cells including neutrophils to the sites of inflammation. Because its association with innate immunity, leukocyte trafficking, and inflammation MIF may be considered as an attractive cytokine in the pathogenesis of FMF. In recent years, increasing attention has been focused on the role of oxidative stress in the pathogenesis of inflammatory rheumatic diseases. As neutrophils are one of the major sources for free radicals some researchers studied oxidative stress in FMF. <h3>Objectives</h3> In this study we aimed to investigate MIF levels and its relationship with oxidative stress and M694V mutations in patients with FMF. <h3>Methods</h3> Fifty one unrelated attack free FMF patients (14 M and 27 F, 32.8±8.7 years) and 30 healthy controls (16 M and 14 F, 32.7±7 years) were included in the study. Serum MIF were studied and allele frequency of M694V was calculated. Serum total oxidant status (TOS) and total anti-oxidant status (TAS) were also studied. <h3>Results</h3> Age, sex distribution, anthropometrical indices, smoking status, serum lipids and TAS were similar between patients and controls. However; CRP, ESR, MIF, and TOS were significantly higher in the patients' group. Comparison of patients with and without M694V mutation revealed that MIF and TOS levels were not different between the groups. Regression analysis showed that none of the variables including disease duration, CRP, ESR, TOS, TAS and BMI were predicting MIF concentrations (P &gt; 0.05) <h3>Conclusions</h3> We found increased concentrations of MIF and oxidative stress in patients with FMF. Increased MIF levels were significantly correlated with oxidative stress and its levels were independent from the inflammatory activity. M694V mutations seem no effect on MIF and oxidative stress. <h3>Disclosure of Interest</h3> None Declared
P644Mechanisms of myocardial nitroso redox imbalance following elective cardiac surgery on cardiopulmonary bypass
Authors: R Jayaram, N Goodfellow, K Nahar, MH Zhang, S Reilly, MJ Crabtree, R De Silva, R Sayeed, B Casadei
Journal: Cardiovascular Research (2014)

Background and Aims: The mechanisms responsible for myocardial stunning after cardiac surgery are only partially understood, although ischemia - reperfusion (IR) injury associated with cardio pulmonary bypass (CPB) may play an important role. Reactive oxygen species and nitric oxide have been implicated in both myocardial injury and cardio protection suggesting that identification of their sources may refine therapeutic strategies. Here we investigated the effect of cardioplegia, CPB and reperfusion on myocardial nitroso-­redox balance in patients after cardiac surgery.
Case 28-2008
Authors: Kevin J. Staley, Katherine B. Sims, P. Ellen Grant, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (2008)

An 8-day-old boy was admitted to this hospital because of weakness and lethargy. He had been hospitalized briefly after birth because of respiratory distress, and sensorineural deafness was noted, but his postnatal course had been otherwise normal. On the day before admission, he became lethargic and hypothermic, with grunting respirations; lumbar puncture at another facility disclosed blood in the cerebrospinal fluid, and he was transferred to this hospital. Imaging studies disclosed intracerebral hemorrhage and edema. Coma developed, and the infant died on the fifth hospital day. An autopsy was performed.
Retroperitoneal Hemangioma Demonstrated on Blood Pool Scan
Authors: Muhammad Shah, Leonard M. Freeman, Munish Chitkara, Kwang J. Chun
Journal: Clinical Nuclear Medicine (2013)

Retroperitoneal hemangioma is a rare but clinically significant condition that can be challenging to diagnose and characterize on anatomical imaging alone. We present a case of an 80-year-old woman with diabetes and hypertension, who was found to have an abdominal mass diagnosed first on CT abdomen and pelvis in March 2011 and demonstrated to be stable on subsequent MRI study performed 16 months later in July 2012. The mass was later confirmed to be a hemangioma on a 99mTc-red cell study.
Mirror mechanism and dedicated circuits are the scaffold for mirroring processes
Authors: Leonardo Fogassi
Journal: Behavioral and Brain Sciences (2014)

Abstract In the past decade many studies have demonstrated the existence of a mirror mechanism that matches the sensory representation of a biological stimulus with its somatomotor and visceromotor representation. This mechanism, likely phylogenetically very old, explains several types of mirroring behaviours, at different levels of complexity. The presence in primates of dedicated neuroanatomical pathways for specific sensorimotor integrations processes implies, at least in the primate lineage, a hard-wired mirror mechanism for social cognitive functions.