tbuckley/cabot-search huggingface dataset:
Abstract P5-07-01: Granulin, a novel STAT3-interacting protein, promotes breast cancer tumorigenicity
Authors: Jennifer E Yeh, Simion Kreimer, Sarah R Walker, Andrea Richardson, Alexander R Ivanov, David A Frank
Journal: Cancer Research (2015)

Abstract Since the neoplastic phenotype of a cell is largely driven by its gene expression patterns, increasing attention is focused on transcription factors that regulate critical mediators of tumor formation and metastatic progression like the oncogenic transcription factor, signal transducer and activator of transcription 3 (STAT3). Whereas normal cells have transient activation of STAT3 due to tight control by negative regulators, cancer cells frequently have inappropriate constitutive activation of STAT3 which drives increased expression of genes involved in tumorigenesis. However, little is known about proteins that interact with STAT3 to modulate its function. To identify novel STAT3-interacting proteins, we performed liquid chromatography tandem mass spectrometry-based profiling of STAT3-containing complexes immunoprecipitated from the triple-negative breast cancer cell lines MDA-MB-468 and SUM159PT, which have constitutively active STAT3. We identified granulin (GRN) as a novel STAT3-interacting protein and validated the STAT3-GRN interaction in breast cancer cells by co-immunoprecipitation. To investigate the functional effect of GRN on STAT3 activity, we silenced GRN using small interfering RNA. We found that GRN was necessary for constitutive and maximal cytokine-induced STAT3 transcriptional activity in breast cancer cells. GRN modulated cytokine-induced STAT3 function by enhancing STAT3 DNA binding and increasing the time-integrated amount of STAT3 activation and nuclear translocation. Silencing GRN mirrored the effect of silencing STAT3 on reducing the viability, clonogenesis, and migratory capacity of triple-negative breast cancer cells. Furthermore, GRN mRNA levels were significantly and positively correlated with STAT3 gene expression signatures indicative of STAT3 activation as well as with reduced overall survival in breast cancer patients. These studies used a proteomics approach to identify GRN as a novel STAT3 interacting protein that may serve as an important prognostic biomarker and potential therapeutic target in breast cancer. Citation Format: Jennifer E Yeh, Simion Kreimer, Sarah R Walker, Andrea Richardson, Alexander R Ivanov, David A Frank. Granulin, a novel STAT3-interacting protein, promotes breast cancer tumorigenicity [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 P5-07-01.
Imprime PGG, an innate immunomodulator for cancer immunotherapy has the potential to modulate macrophages in the tumor and the spleen to an anti-tumor M1-like phenotype
Authors: Kathryn Fraser, Nadine Ottoson, Xiahong Qiu, Annisa SH Chan, Adria Jonas, Takashi Kangas, Jeremy Graff, Nandita Bose
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Imprime PGG (Imprime) in combination with anti-VEGF monoclonal antibody, bevacizumab has shown promising clinical efficacy in randomized Phase II clinical trials in non-small cell lung cancer (NSCLC) patients. Imprime, a soluble, yeast β-glucan acts as a pathogen associated
METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS
Authors: B.D. Cookson, M. Farrington, M. Webster, I. Phillips, Bartholomew Walsh, Maurice Salzmann, Nicholas Gaunt, David Seal, Robert Wall, Hillas Smith, A.G. Rivett, M.J. Newman, P.H.J. Van Keulen, H.C. Zanen, P.C.M. Van Den Berg
Journal: The Lancet (1985)
An Optimized, Ex Vivo Log-Scale Expansion of UCB-Derived Myeloid Dcs, Towards Efficient Cancer Immunotherapy
Authors: Eleni Gounari, Anastasia Papadopoulou, Minas Yiangou, Angeliki E Xagorari, Achilles Anagnostopoulos, Evangelia Yannaki, Panayotis Kaloyannidis
Journal: Blood (2014)
Normalization of Visceral Fat and Complete Reversal of Cardiovascular Remodeling Accompany Gastric Bypass, not Banding
Authors: Jennifer J. Rayner, Rajarshi Banerjee, Jane M. Francis, Ravi Shah, Venkatesh L. Murthy, James Byrne, Stefan Neubauer, Oliver J. Rider
Journal: Journal of the American College of Cardiology (2015)
Phase 1 dose-escalation study of EBC-46 given by intratumoral injection to patients with refractory cutaneous and subcutaneous tumors.
Authors: Jason D. Lickliter, Benedict Panizza, Christos Stelios Karapetis, Victoria A Gordon, Paul W Reddell, Kate T Lingard, Rodney M Cusack, Paul De Souza
Journal: Journal of Clinical Oncology (2015)

TPS2616 Background: EBC-46 is a novel protein kinase C (PKC) activator being developed for intratumoral treatment of cutaneous and subcutaneous tumors. Studies in syngeneic and xenograft mouse models showed that intratumoral injection of EBC-46 into subcutaneous tumors resulted in PKC-dependent hemorrhagic necrosis within 24 hours and complete loss of viable tumor cells. Immunostaining of tumor tissue for the endothelial marker CD31 showed marked vascular disruption at 24 hours after treatment (Boyle GM, et al. PLoS ONE 2014; 9: e108887). EBC-46 is also being studied in veterinary clinical trials in companion animals as an intratumoral treatment for spontaneous skin tumors. Notably, EBC-46 therapy leads to rapid healing at treated sites in animals and the mechanism of this is currently under investigation (Campbell J, et al. Proc ETRS 2014). Methods: This is a phase 1 first-in-human dose-escalation trial of intratumoral injection of EBC-46 in patients with cutaneous and subcutaneous tumors refractory to standard therapies. Other key eligibility criteria include an ECOG score of 0-2, adequate organ function, no involvement of major blood vessels by the tumor and no therapeutic anticoagulation or major abnormality of hemostasis. The starting dose of EBC-46 is 0.06 mg/m2, which is prepared as a 0.25 mg/mL solution and infiltrated into a tumour volume 2-fold greater than the EBC-46 volume. Initial dose escalations are based on increasing the concentration of the EBC-46 solution until a maximum concentration is reached. Subsequent dose levels will inject higher volumes of EBC-46 solution into a correspondingly greater target tumour volume. Patients who tolerate the first dose, and who are deemed to be benefiting from treatment, will continue intratumoral injections in an extension protocol. Study endpoints include safety and tolerability parameters (local and systemic), pharmacokinetics of EBC-46 and preliminary efficacy assessments. Blood samples will be evaluated for biomarkers of vascular disruption and inflammation, and optional tumor biopsies will be performed pre- and post-treatment. Enrolment into the first dose level commenced in January 2015. Clinical trial information: ACTRN12614000685617.
Pre-clinical evidence for an anti-tumor activity of defibrotide, a DNA-based, endothelium stabilizing drug
Authors: C. Echart, M. Iacobelli, P. Richardson, C. Mitsiades, T. Ignoni, L. Ferro, G. Eissner
Journal: Journal of Clinical Oncology (2007)

14144 Background: Defibrotide (DF) is a mixture of polydeoxyribonucleotides with anti-thrombotic activity. Next to endothelium stabilization, recent data suggest anti-neoplastic properties of DF modulating interactions of tumor cells with their microenvironment. We investigated whether DF regulates expression and activity of heparanase, an enzyme critically involved in breaking down extracellular barriers and releasing growth factors linked to tumor invasion and angiogenesis. Methods: Heparanase expression was tested by RT-PCR and flow cytometry with multiple myeloma (MM) and microvascular endothelial cells. Heparanase activity was measured in cellular extracts with a heparan-degrading enzymatic assay. Serum degradation products of DF were identified by SEC-HPLC. The anti-angiogenic potential of DF was tested in vitro using a kit with human microvascular endothelial cells forming tubes across a layer of fibroblasts. In vivo, DF was tested in the dorsal skin-fold chamber assay in mice after inoculation of human gastric cancer cells. Proliferation was assessed by trypan blue exclusion. Results: We demonstrate a striking downregulation of expression and enzymatic activity of heparanase in endothelial as well as MM cells. In contrast, the degradation products of DF failed to exert any biological activity, suggesting that the intact mixture of deoxyoligonucleotides is responsible for the anti-tumor effect. We could also show that DF prevents (tumor) angiogenesis in vitro and in vivo. Western blots suggest that DF reduces phosphorylation-activation of p70S6 kinase, a key target in the mTOR pathway linked to angiogenesis. In addition, DF does not influence proliferation of vascular or tumor cells, rather acts via selective inhibition of tube formation of endothelial cells. Conclusion: In the present report we provide evidence for an anti-tumor activity of DF. DF inhibits (tumor) vessel formation and heparanase activity, and thus should be considered as an anti-cancer agent. [Table: see text]
Abstract 19039: Higher Burden of Sudden Cardiac Death in African Americans: A Prospective, Community-Based Study
Authors: Kyndaron Reinier
Journal: Circulation (2013)

Introduction: Sudden cardiac death (SCD) is a major contributor to mortality in the US, but there is limited data on SCD in non-white minorities. Hypothesis: Incidence rates and clinical profile of SCD vary significantly by race. Methods: All SCD cases in a large northwest US community (pop. 679,348; 2002 - 2005) were identified prospectively using multi-source ascertainment. Race and ethnicity were obtained for 98% of 1174 total cases from medical records or death certificate and categorized as White, African American (AA), Asian (all non-Hispanic); and Hispanic (regardless of race). Age-specific incidence rates were calculated using US census 2003 county population estimates. Age-adjusted rates were calculated using the US standard 2000 population. Results: In this predominantly white community, 971 (84.5%) of SCA cases were white, 106 (9.2%) were AA, 34 were Asian (3.0%), and 22 (1.9%) were Hispanic. Age-adjusted rates were highest among AA (122/100,000), 59/100,000 in Whites, 52/100,000 in Hispanics, and lowest among Asians (36/100,000). Age-specific rates showed AA had higher rates across all age categories (Figure). No race/ethnic differences were observed (p≥0.28) by sex, history of MI or CAD, or circumstances of SCD (cardiac arrest location, response time, percent with resuscitation attempted, initial rhythm, witnessed SCD, return of spontaneous circulation, or survival to hospital discharge). AA were younger than whites at the time of SCD (63.8 ± 18.7 vs. 69.8 ± 15.3, p=0.007). A higher proportion of AA were diabetic (50% vs. ≤33% in other groups; p=0.0001); and there was a trend toward higher comorbidity burden (35% AA with Charlson Index ≥4 vs. ≤25% in other groups; p=0.06). Conclusions: In this US Community, African Americans had more than double the incidence of SCD compared to other race/ethnic groups, suffered SCD at a younger age, and with higher rates of diabetes.
Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report.
Authors: J R Quesada, D A Swanson, J U Gutterman
Journal: Journal of Clinical Oncology (1985)

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.
Voriconazole (VRCZ) Versus Itraconazole (ITCZ) As Antifungal Prophylaxis For Acute Myelogenus Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) Patients In Induction Therapy, Prospective Randomized Study
Authors: Kouhei Kyo, Mitsuhiro Itagaki, Taiichi Kyo, Takeshi Okatani, Tetsuro Ochi, Yuta Katayama, Ryouta Imanaka, Kouji Iwato, Hideki Asaoku
Journal: Blood (2013)
Ultrasound is similar to mammography in detecting breast cancer, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Ultrasonography achieves similar rates of detection of breast cancer as mammography does when it is used as a primary screening test, shows a US study. The study found that ultrasonography detected a higher proportion of invasive and node negative cancers but was also associated with a higher rate of false positive results.

The study, reported in the Journal of the National Cancer Institute , included 2662 women who had three annual screening tests for breast cancer with ultrasonography (a total of 7473 examinations) and with mammography, either film screen (with results …
Ablation of Stable VTs Versus Substrate Ablation in Ischemic Cardiomyopathy
Authors: Luigi Di Biase, J. David Burkhardt, Dhanujaya Lakkireddy, Corrado Carbucicchio, Sanghamitra Mohanty, Prasant Mohanty, Chintan Trivedi, Pasquale Santangeli, Rong Bai, Giovanni Forleo, Rodney Horton, Shane Bailey, Javier Sanchez, Amin Al-Ahmad, Patrick Hranitzky, G. Joseph Gallinghouse, Gemma Pelargonio, Richard H. Hongo, Salwa Beheiry, Steven C. Hao, Madhu Reddy, Antonio Rossillo, Sakis Themistoclakis, Antonio Dello Russo, Michela Casella, Claudio Tondo, Andrea Natale
Journal: Journal of the American College of Cardiology (2015)
A randomized pilot study comparing safety and efficacy of irinotecan plus S-1 plus bevacizumab (IRIS+BV) and modified FOLFIRI plus BV (mFOLFIRI+BV) in patients (pts) with metastatic colorectal cancer (mCRC): The result of efficacy report of T-CORE0702.
Authors: H. Andoh, S. Kato, M. Gamoh, T. Yamaguchi, M. Sakayori, Y. Sasaki, T. Mori, H. Ohori, T. Yoshioka, C. Ishioka
Journal: Journal of Clinical Oncology (2011)

e14001 Background: We conducted a randomized pilot study to compare the safety and efficacy of IRIS+BV and mFOLFIRI+BV against Japanese mCRC (T-CORE0702) and reported that IRIS+BV is a safe regimen with low hemtotoxicity and GI toxicity compared with mFOLFIRI+BV (ASCO GI 2011, abstract #496, S Kato et al.). This is the efficacy report of T-CORE0702. Methods: From July 2007 to March 2010, 60 pts with mCRC were randomized to compare 30 pts for IRIS+BV (CPT-11 150 mg/m2 infusion on day 1, S-1 80 mg/m2 orally on day 3-16, q3w) with 30 pts for mFOLFIRI+BV (CPT-11 150mg/m2). Tumor assessments were performed by every 6weeks. Tumor responses were assessed using RECIST 1.0 criteria by institutional evaluation and confirmed by blinded central monitoring. Results: Background of pts was well balanced among two arms. Among G3/4 nonhematological AEs, gastrointestinal toxicities were lower in IRIS+BV arm than mFOLFIRI+BV arm (anorexia: 3.5% vs. 17.9%, nausea: 0% vs. 7.1%, diarrhea: 6.9% vs. 14.3%, stomatitis: 0% vs. 3.6%). Nausea, vomiting and hair loss were significantly lower in IRIS+BV arm than mFOLFIRI+BV arm (p<0.05). Fifty-one pts (IRIS arm 25, mFOLFIRI arm 26) had measurable lesion defined by RECIST criteria (ver1.0). Background of pts was well balanced among two arms. RRs (central monitoring) were 72.0 % in IRIS (CR 2, PR 16, SD 5, and PD 2) and 61.5 % in mFOLFIRI arm (CR 0, PR 16, SD 8, and PD 2). Median progression free survival was 345 days versus 324 days with IRIS+BV versus mFOLFIRI+BV, respectively. Conclusions: The efficacy of our IRIS+BV regimen is comparable with mFOLFIRI regimen.
Effect of nausea vs. vomiting on patients’ quality of life during chemotherapy
Authors: J. T. Hickok, J. A. Roscoe, G. R. Morrow, J. K. Giguere, L. K. Colman, A. Malcolm
Journal: Journal of Clinical Oncology (2006)

8514 Background: Antiemetic guidelines are based largely on the presumption that vomiting is of greater concern to cancer patients, and impacts their quality of life (QOL) more strongly, than nausea. We examined the relative influence of chemotherapy-induced nausea and emesis on patients’ overall QOL and on the specific domains of social, emotional, physical and functional well-being. Methods: 667 patients enrolled in a three-arm, randomized, controlled Phase III study that detected no difference in the ability of a serotonin receptor antagonist vs. prochlorperazine (given regularly three times daily or taken only as needed for symptoms) to control the severity of nausea, completed the FACT-G before treatment and on the third day following their first infusion of anti-cancer chemotherapy containing doxorubicin (Day 4 of cycle 1). 93% were female, and 90% had breast cancer. Results: There was a significant reduction in overall QOL and in physical and functional well-being, but no significant change in emotional or social well-being, over the four day period. In a stepwise linear regression analysis predicting change in overall QOL, average nausea severity entered first and accounted for 24% of the variance in reduced QOL (p &lt; 0.001). Occurrence of vomiting (yes, no) accounted for a non-significant less than 1% of additional variance (p = 0.240). No other factors (gender, age, the degree to which patients expected to experience nausea or vomiting, whether or not nausea or vomiting occurred, and maximum nausea severity over the four days) were significant predictors of the reduction in QOL. Similar results were obtained when the relative influence of nausea and vomiting on physical and functional decline were studied. Conclusions: Severity of nausea, not the occurrence of vomiting, was the key factor in patients’ perceived decline in quality of life in the days immediately following chemotherapy infusion. Nausea severity should be a primary outcome measure in studies evaluating antiemetic efficacy. Supported in part by NCI Public Health Service grant U10 CA37420 and ACS grant RSG-01–071-PBP No significant financial relationships to disclose.
Buteyko technique (BT) as an adjunct in pulmonary rehabilitation (PR) in patients with asthma and dysfunctional breathing - First results of an ongoing prospective controlled study
Authors: Thomas Schmid, Alois Wastlhuber, Oliver Göhl, Dragan Stojanovic, Konrad Schultz
Journal: European Respiratory Journal (2012)

Background:  BT is recommended as an additional therapeutic module in asthmatics. So far there is inconclusive evidence of the effectiveness of BT as part of standard PR.  Method:  From November 2011 until January 2012 in our clinic 258 asthmatics underwent a 3-week inpatient PR. Of these 36% were characterised by dysfunctional breathing (Nijmegen Questionnaire, NQ≥23). Of those, the control-group patients (CG; n=21) received standard PR consisting among others of physical training, patient education, breathing therapy and psychosocial support. The intervention group (IG, n=39) additionally underwent at least 6 Buteyko sessions. The indication for enrolling patients to the BT was decided upon by the responsible physician. Primary outcome was the total score of the asthma control test (ACT), secondary outcome was the NQ-score. Statistics are based on data that resulted in complete data pairs of ACT and NQ at baseline (t0) and end of PR (t1).  Results  (mean±SD):   Discussion:  Considering all asthmatics with dysfunctional breathing, our PR program resulted in significant improvements in ACT (+4,4) and NQ (-8,8). The IG tended to reach greater improvements in ACT (especially in items 2, 3 and 4, i.e. shortness of breath, asthma symptoms at night, rescue inhaler) and NQ than the CG, but these trends weren9t significant between groups.  Conclusion:  BT could be a promising adjunct to PR.
Effect of 3-month CPAP treatment on blood pressure and serum aldosterone concentration in patients with resistant hypertension
Authors: Patricia Lloberes, Gabriel Sampol, Eugenia Espinel, Alfons Segarra, M. Ferrer, Odile Romero, Maria Jose Jurado, M. Antonia Ramon, Dolores Untoria, Miguel Angel Martinez Garcia
Journal: European Respiratory Journal (2013)

Introduction: The role of the renin-angiotensin-aldosterone system (RAAS) on the association obstructive sleep apnea (OSA) and resistant hypertension (RH) is unclear. Aim: To analyze the effect of CPAP on 24-h blood pressure monitoring (ABPM) and on serum aldosterone in RH patients. Methods: 102 patients with an OSA15 and office-RH were randomized to CPAP (n=50) or to conventional treatment (n=52) for 3 months. 24-h ABPM and serum aldosterone were measured. 78 patients completed the follow-up (36 CPAP, 42 conventional treatment). Results: 66.7% were male, aged 58.27±9.3yrs and AHI 50.1±21.6, without significant differences between both groups. Serum aldosterone and AHI correlated significantly in patients with ABPM-confirmed RH (r= 0.25, p=0.02). CPAP achieved a significant decrease in serum aldosterone and 24-h BP decreased especially in those with ABPM-confirmed RH.  Conclusion: The association between OSA and RH could be mediated at least in part by an effect on the RAAS.
Social supports in relation to physical health and symptoms of depression in the elderly
Authors: I Grant, T L Patterson, J Yager
Journal: American Journal of Psychiatry (1988)

The authors examined the relationship of social supports to physical and psychological well-being in 118 men and women 65 years old or older who were living independently in the community. Subjects with more symptoms of depression reported having fewer emotionally satisfying consistent supports from relatives, but those who had physical illnesses reported more supports from relatives. The authors conclude that although having fewer key supports may contribute to dysphoria, having a physical illness may mobilize meaningful support. They suggest that social supports and health outcomes be carefully defined so that possible differential relationships between them can be understood more specifically.