tbuckley/cabot-search huggingface dataset:
Abstract 2756: Combination therapy of doxorubicin and the acid-sensitive albumin-binding prodrug of doxorubicin INNO-206 induces complete regressions in a xenograft pancreatic carcinoma model demonstrating excellent tolerability
Authors: Felix Kratz, Samar S E E A Azab, Rainer Zeisig, Iduna Fichtner, Andre Warnecke
Journal: Cancer Research (2012)

Abstract Combination therapy of macromolecular prodrugs with clinically established low-molecular weight anticancer drugs is a field of research that has been insufficiently explored to date. Recently, we investigated the anticancer effect of a combination of doxorubicin with the clinically assessed albumin-binding prodrug INNO-206, the (6-maleimidocaproyl)hydrazone of doxorubicin, in an ovarian carcinoma xenograft model (A2780). The combination achieved complete remissions as did therapy with INNO-206 alone, but was far better tolerated. Due to these encouraging results, we extended our combination trials to a more chemoresistant tumor indication, i.e. pancreatic cancer. Thus, we compared the following weekly schedules against the MiaPaca-2 xenograft model (i.v. administration): 3 x 6 mg doxorubicin (MTD), 3 x 24 mg/kg INNO-206 (doxorubicin equivalents, MTD), 3 x 3 mg/kg doxorubicin followed 6 h later by 3 x 12 mg/kg INNO-206, and 3 x 12 mg/kg INNO-206 followed 6 h later by 3 x 3 mg/kg doxorubicin. Whereas therapy with doxorubicin only produced a moderate tumor inhibition, all other therapy arms induced complete long-term remissions until the end of the experiment on day 44. However, there were significant differences in the tolerability as assessed by the body weight changes: whereas therapy at the MTD of INNO-206 (3 x 24 mg/kg) produced a body weight loss of −16 %, therapy with 3 x 12 mg/kg INNO-206 followed 6 h later by 3 x 3 mg/kg doxorubicin produced −7 % body weight loss, but 3 x 3 mg/kg doxorubicin followed 6 h later by 3 x 12 mg/kg INNO-206 produced a body weight gain of + 2 % as a clear indication of minimal systemic toxicity. This animal study is to best of our knowledge the first investigation demonstrating that a combination of an albumin-binding prodrug with its free parent drug not only has clear therapeutic advantages over the free drug but that the time-dependent schedule has a critical influence on the overall tolerability and results in its best case in a 100 % cure rate without causing any body weight loss. The current working hypothesis to explain this surprising effect is that the combination of doxorubicin with an albumin-binding prodrug of doxorubicin with acid-sensitive properties enables a more homogenous distribution of the drugs in the tumor due to different uptake mechanisms in a heterogeneous solid tumor (EPR effect for INNO-206 and free diffusion into the tumor interstitium for doxorubicin). 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 2756. doi:1538-7445.AM2012-2756
Abstract 1567: mTERT genetic vaccine chemotherapy combination augment antigen-specific immune response and confer tumor protection in time dependent fashion
Authors: Stefano Ugel, John Facciaponte, Elisa Scarselli, Carmela Mennuni, Nicla La Monica, George Coukos, Andrea Facciabene
Journal: Cancer Research (2012)

Abstract Successful cancer chemotherapy relies on the comprehensive elimination of tumor cells. However, at clinically tolerated doses, chemotherapeutic drugs usually fail to kill all tumor cells in vivo. Theoretically, to achieve complete eradication, partial tumor killing by chemotherapy should be accompanied by a “bystander effect” in which the immune system recognizes, attacks, and eradicates residual tumor cells. Doxorubicin) is an anthracycline antibiotic that intercalates with DNA, inhibiting its replication. It has been shown that treatment of dendritic cells with Doxorubicin increases their ability to present antigen to Ag-specific T cells in vitro and it is accompanied by upregulation of the Ag-processing machinery (APM) proteins and costimulatory molecules. The telomerase reverse transcriptase, TERT, is an attractive target antigen for cancer vaccine because its expression is reactivated in a conspicuous fraction of human tumors. Critical to the success of combination therapy using TERT vaccine and chemotherapy drugs is a positive (synergistic) interaction between chemotherapy drugs and immune effectors mechanisms. Indeed, activation of antitumor immune responses by vaccine could be antagonized by chemotherapy, if the selected drug exerts immune antagonistic effects. Understanding the dose and the schedule of administration of Doxil (pegylated Doxorubicin) is critical for the design of rational combinations of vaccine and chemotherapy. To test the interactions between TERT vaccine and Doxil we performed a series of experiment using six different therapeutic schedules of Doxil/TERT administration. Interestingly, only two of the Doxil/TERT vaccine combinations resulted in a significant tumor growth inhibition delay which was also accompanied by increase in anti-TERT T cell response. This data unveil new facets of “Chemo immune adjuvancy” of Doxorubicin, and demonstrate how the in vivo efficacy of this combination is impacted by the dosing schedule 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 1567. doi:1538-7445.AM2012-1567
Abstract 4965: The epithelial-specific ETS transcription factor ESE1 links inflammation with prostate cancer transformation and progression
Authors: Nicole Longoni, Erica Ortelli, Paolo Kunderfranco, Davide Genini, Maurizia Mello Grand, Giovanna Chiorino, Anastasia Malek, Carlo V. Catapano, Giuseppina M. Carbone
Journal: Cancer Research (2010)

Abstract Altered expression of ETS transcription factors by chromosomal translocation is a frequent event in prostate cancers. However, deregulated expression of other oncogenic ETS factors can be important for the pathogenesis of this disease. By analyzing the expression of multiple ETS genes in prostate cancer and normal prostate by genomic profiling and quantitative real-time PCR we found that the epithelial-specific ETS factor ESE1 was highly expressed (&amp;gt;4 fold) in 44% of prostate tumors compared to normal prostate. ESE1 has been previously shown to be induced by pro-inflammatory stimuli and to regulate the expression of genes involved in inflammation. Treatment of immortalized prostate epithelial cells (LHS) and prostate cancer cells 22RV1 with the pro-inflammatory cytokine IL-1beta induced ESE1 at RNA and protein levels. Concomitantly we observed that cells acquired ability to grow in poly-hema coated plates and an EMT phenotype. To define the role of ESE1 in prostate cancer progression we established 22RV1 prostate cancer cells stably expressing ESE1 (22RV1-ESE1). ESE1 expressing cells were capable to grow in poly-hema coated plates and when injected in nude mice formed larger subcutaneous tumors compared to control cells. Global gene expression profiles indicate robust changes with many genes differentially expressed in 22RV1-ESE1 cells compared to control cells, including key genes involved in cell invasion and metastasis such as COX2 and MMP-10. Consistently, 22RV1-ESE1 cells had greater ability to migrate compared to parental cells in Boyden Chamber and wound-healing assays. Furthermore, when implanted in mice via tail vein injection, 22RV1-ESE1 cells displayed greater ability to form lung metastasis compared to control cells. These results suggest that ESE1 contribute to the acquisition of transforming properties such as the ability to invade and metastasize. Induction of ESE1 during chronic inflammation could be an essential step for prostate cancer initiation and may co-operate with other ETS alterations for prostate cancer progression. 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 4965.
INTENSIVE CARE UNIT AMONG MEDICARE PATIENTS WITH NON-ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Alexander C. Fanaroff, Eric Peterson, Anita Chen, Laine Thomas, Jacob Doll, Christopher Fordyce, L. Kristin Newby, Mikhail Kosiborod, Ezra Amsterdam, James de Lemos, Tracy Wang
Journal: Journal of the American College of Cardiology (2016)
CORRELACIÓN DE HALLAZGOS DE LESIONES QUÍSTICAS PANCREÁTICAS MEDIANTE MICROSCOPIA CONFOCAL Y DEMAS PROCEDIMIENTOS DIAGNÓSTICOS (RESULTADOS PARCIALES)
Authors: M Abu-Suboh, J Colán Hernández, J Dot, J Armengol Bertroli, M Masachs Peracaula, A Benages, MD Castillo Cejas, JC Salord Osas, N Tallada, JR Armengol Miró
Journal: Endoscopy (2013)

Introducción: Numerosas lesiones quísticas páncreáticas quedan sin diagnosticar a pesar de las técnicas disponibles actualmente. Recientemente ha surgido la Microscopía confocal (MC) que permite obtener imágenes microscópicas en tiempo real. Objetivo: La MC puede tener correlación precisa y rendimiento diagnóstico similar al obtenido por las técnicas habituales. El objetivo es evaluar los datos diagnósticos obtenidos mediante ésta técnica para el estudio de lesiones quísticas pancreáticas. Material y Método: Estudio descriptivo, prospectivo, monocéntrico, no controlado, comparando diagnósticos de quistes pancreáticos obtenidos mediante MC, radiología, USE y citología. Período de recolección de Marzo a Septiembre 2013 planteando incluir 12 pacientes. Se utilizaron, Ecoendoscopio lineal (Olympus UCT-140®), agujas EchoTip 3Cook® 19G y sonda AQ-Flex ™19 (Cellvizio; Mauna Kea Technologies) para la obtención de imágenes previa inyección de Fluoresceína. Interpretación de éstas por especialista de anatomía patológica. Resultados: Se han incluido 6 pacientes (Media 75.5 años, 4 mujeres, 2 hombres). Tamaño de lesiones 26,4 ± 7,17 mm por prueba de imagen previa y 23,83 ± 10,65 mm por USE (Media ± DE), localizados 50% en cola, 33,33% cabeza y 16,66% cuerpo pancreático. Diagnóstico previo 50% Cistoadenoma, 33,33% Tumor papilar mucinoso intraductal (TPMI) y 16,66% Quiste simple, confirmándose similar diagnóstico por USE en 66,66% de los casos. Los diagnósticos por citología han sido 3 Quiste benigno, 1 TPMI, 1 Cistoadenoma y 1 Adenocarcinoma mucosecretor. Se han identificado por MC, en 1 caso estructuras filiformes brillantes sugestivas de vasos sanguíneos, y en 2 estructuras vellosas que parecen correlacionarse con papilas, no pudiendo obtener imágenes para interpretación en 3 casos por dificultades técnicas. Conclusiones: Diagnósticos sugeridos por USE y MC son similares a los obtenidos por citología en un porcentaje considerable. La MC se puede proponer como técnica complementaria al USE y citología para el estudio de lesiones quísticas pancreáticas. Dificultades se asocian a ésta técnica
Abstract B64: Telomeric DNA sequence determines the mechanism of dysfunctional telomere fusion in human cancer cells
Authors: Bradley A. Stohr, Lifeng Xu, Elizabeth H. Blackburn
Journal: Cancer Research (2009)

Abstract Cancer cells rely on the ribonucleoprotein enzyme telomerase to maintain their telomeres, which consist of tandem DNA repeats bound to protective protein factors collectively termed shelterin. Experimentally-induced telomere dysfunction in cancer cells, either through critical telomere shortening or disruption of shelterin binding, typically leads to telomere fusions, ultimately resulting in genome instability and cell death. For reasons that are not well understood, the mechanism of telomere fusion varies depending on the cause of telomere dysfunction. We have investigated telomere fusions caused by overexpression of mutant telomerases that add mutated telomeric repeats, thereby disrupting shelterin binding and inhibiting cancer cell proliferation. We previously showed that the effect of one such telomerase in human cancer cells is ATM dependent (Stohr BA and Blackburn EH, Cancer Research 68:5309–5317, 2008). Here, we have tested additional mutant telomerases that add either palindromic or non-palindromic telomeric repeats. We show that while all mutant telomeric sequences tested induce heterodicentric chromosome fusions, only palindromic telomeric repeats induce ATM-independent sister chromatid and isodicentric chromosome fusions in human cancer cells. Thus, the telomeric sequence itself influences the fate of telomeres that have become dysfunctional. These results implicate DNA strand annealing in an alternative telomere fusion pathway in human cells. The need to avoid genome instability caused by such fusions is one explanation for the characteristic lack of self-complementarity in naturally-occurring telomeric sequences. Finally, our results have significant implications for the translational application of mutant telomerases as a cancer therapeutic strategy. Citation Information: Cancer Res 2009;69(23 Suppl):B64.
ET-17 * TRANSIENT FASTING ENHANCES REPLICATION AND THERAPEUTIC ACTIVITY OF ONCOLYTIC HSV IN GLIOBLASTOMA THERAPY
Authors: S. Esaki, S. D. Rabkin, R. L. Martuza, H. Wakimoto
Journal: Neuro-Oncology (2014)

BACKGROUND AND OBJECTIVE: Short term fasting has been shown to enhance efficacy of chemotherapy by sensitizing tumor cells and protecting normal cells in a variety of cancer models including glioblastoma (GBM). Malignant cells, unlike normal cells, respond to fasting by promoting oncogenic signaling and protein synthesis, which could in turn sensitize them to anti-cancer agents, broadening therapeutic window. We hypothesize that fasting increases replication of oncolytic herpes simplex virus (oHSV) and its oncolytic activity in glioblastoma. MATERIALS AND METHODS: Patient-derived GBM cell lines, MGG8F and MGG29F, were subjected to transient fasting by switching culture medium [DMEM (4.5 g/L of glucose) supplemented with 10% fetal calf serum (FCS)] to DMEM with low glucose (0.5 g/L) and 1% FCS. oHSV G47Δ [ϒ34.5(-), ICP6 (-), LacZ (+), α47 (-)], currently tested in a phase I/II trial for recurrent GBM, and its derivative G47Δ-US11fluc, expressing firefly luciferase driven by the late US11 promoter, were used to investigate the impacts of short term fasting on late HSV gene expression, virus yields and tumor cell killing. RESULTS: 24-hour fasting followed by 24-hour recovery with regular medium increased luciferase expression after G47Δ-US11fluc infection of MGG8F and MGG29F cells. Transient fasting mediated 2-3-fold increase in G47Δ yields in both GBM cells, but not in normal human astrocytes. Although transient fasting alone did not alter cell growth, it significantly enhanced G47Δ killing of GBM cells in vitro. In vivo, 48-hour food restriction doubled luciferase activity and caused no toxicity when G47Δ-US11fluc was intratumorally injected in orthotopic MGG8F xenografts. CONCLUSION: Transient fasting increased viral replication of G47Δ and strengthened its oncolytic activity in GBM cells. These results suggest that transient fasting may be effectively combined to enhance oncolytic HSV therapy of GBM.
Abstract 2906: Towards breast cancer drug repurposing based on a pathway modeling approach.
Authors: Sara Ibrahim
Journal: Cancer Research (2013)

Abstract Molecular connectivity maps between drugs and proteins in specific disease contexts, especially breast cancer, can be particularly valuable, offering an opportunity to gain global perspectives on both the therapeutic and toxicological profiles of drugs. To assess drug pharmacological effects, we assume that “ideal” drugs for a patient can treat or prevent disease by modulating gene expression profiles of the patient to the similar level with those in healthy people. Starting from this hypothesis, we build comprehensive disease-gene-drug connectivity relationships with drug-protein directionality (inhibit/activate) information based on a computational connectivity maps (CMaps) platform. In this work, we develop a novel approach based on integrative pathway modeling using breast cancer as a case study. We identify and rank breast cancer related drugs/compounds with their overall drug-protein “connectivity map” profile. First, we retrieve breast cancer associated proteins through the CMaps platform by using breast cancer as a query term. Second, we retrieve breast cancer related pathways by using breast cancer associated proteins as input and searching in the Human Pathway Database (HPD), PAGED, and the PubMed. Third, we integrate the breast cancer related pathways into unified pathway models, from which we categorize the pharmaceutical effects of candidate drugs on all breast cancer associated proteins as either “therapeutic” or “toxic”. Expression values are given to all relevant proteins on the pathway. Potential drugs and targets are retrieved from C-Map, DrugBank, and MetaDrug. Finally, we transform the integrated pathway into network models and rank drugs based on the network topological features of drug targets, drug-affecting genes/proteins, and curated disease-associated proteins. The case studies correlated very well with the known pharmacological profiles of cancer drugs, highlighting the significance of the platform that we developed. Ongoing research can potentially change future drug discovery practices. Citation Format: Sara Ibrahim. Towards breast cancer drug repurposing based on a pathway modeling approach. [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 2906. doi:10.1158/1538-7445.AM2013-2906
ENDOSCOPIC SUBMUCOSAL DISSECTION USING IT-KNIFE NANO
Authors: F Baldaque-Silva, M Marques, F Vilas Boas, E Duarte, J Lopes, F Carneiro, G Macedo
Journal: Endoscopy (2013)

Introduction: Recently a shorter and slimmer IT-knife, IT-nano, was developed for endoscopic submucosal dissection (ESD). To our best knowledge, there are no descriptions of prospective studies evaluating this device. Aims & Methods: We evaluated prospectively, the efficacy and safety of IT-nano. Consecutive patients with esophageal or colorectal lesions prone for ESD were invited to participate and gave written inform consent. Follow-up endoscopies were performed 2 months after ESD and subsequently planned for each 6 – 12 months, according to pathology. Results: Seventeen patients (10 female) were included, with median age of 67 years (range 49 – 89). Lesions were located in the esophagus (n = 1), ascending colon (n = 3), transverse colon (n = 1), sigmoid colon (n = 6), and rectum (n = 6). Macroscopically, 2 lesions were type Ip, 4 Is, 8 IIa, 1 IIab, 1 IIa-c. There was no visible lesion in a case of Barrett's esophagus with previous resected adenocarcinoma and dysplasia on follow-up. En bloc resection and R0 resection were achieved in 15 and 14 cases, respectively. Resected tumor size ranged between 22 – 77 mm (median 40 ± 15 mm). Pathologicaly, 2 lesions corresponded to invasive denaocarcinoma (1 with < 500 µm submucosal invasion), 1 to intramucosal adenocarcinoma, 6 to high-grade dysplasia and 8 to low-grade dysplasia. There were no cases of perforation or major bleeding. Fourteen procedures were performed in an outpatient setting. The remaining patients were discharged within 7 days. Two patients needed surgery after the ESD: 1 due to poor central lifting with incomplete resection and the other because of deep submucosal invasion (R0). One patient developed esophageal stricture that was treated conservatively. There were no cases of recurrence in the short term follow-up. Conclusión: IT-nano enabled accurate and safe ESD even in large lesions and in organs more difficult and prone to complications, such as esophagus and colon. Larger studies are needed to evaluate the definitive role of IT-nano on ESD.
Brainstem auditory evoked response and subcortical abnormalities in autism
Authors: J Thivierge, C Bédard, R Côté, M Maziade
Journal: American Journal of Psychiatry (1990)

Previous studies of the neurobiology of autism that have used the brainstem auditory evoked response have given contradictory results. The authors of this study considered two supplementary aspects; they added an ipsilateral masking procedure, and they compared the results for every subject to the values (corrected for age and sex) of a large number of normal children. Twenty autistic (according to DSM-III-R criteria) and 13 mentally retarded (nonverbal IQ less than 75) subjects were assessed. Eighty percent of the autistic subjects had abnormal interpeak latencies, compared to 15% of the mentally retarded subjects. The I-V and III-V prolonged interpeak latency values were seen only in the autistic subjects. The ipsilateral masking procedure doubled the rate of detection of higher-brainstem abnormalities in the autistic children.
Biology and prognosis by age of primary operable breast cancer.
Authors: O Brouckaert, E Camerlynck, V Van Belle, S Van Huffel, S Pintens, F Amant, K Leunen, A Smeets, P Berteloot, E Van Limbergen, C Weltens, W Van den Bogaert, R Paridaens, P Moerman, I Vergote, M Christiaens, H Wildiers, P Neven
Journal: Cancer Research (2009)

Abstract Abstract #2082 Introduction Breast cancer (BC) biology and prognosis are age dependent. We studied the effect of age on BC biology, treatment and prognosis.&amp;#x2028; Methods Data from 2059 consecutive patients, primary operated for invasive BC in UZ Leuven (01/01/00–01/06/05), were used. Patients with ≥ 3.5 yrs follow-up were included (n=1064) to study relapse in relation to age (logistic regression).&amp;#x2028; Results Early relapse in BC is age-related, decreasing 3.2% each yr for patients &amp;lt; 60 yrs at diagnosis (p=0.0132, 95% CI OR: 0.943-0.993). This relation is reversed &amp;gt;60 yrs: early relapse increases 5.5% each yr (p=0.0007, 95% CI OR: 1.021-1.082). The positive lymph node status is decreasing 3.5% each yr &amp;lt;65 yrs (p&amp;lt;0.0001, 95% CI OR: 0.950-0.980) and increasing 3.8% each yr ≥65 yrs (p=0.0259, 95% CI OR: 1.004-1.072) (Fig 1). The chance on a positive estrogen receptor (ER) increases with increasing age until 60 yrs (p=0.0071, 95% CI OR=1.009-1.059) with no significant effect &amp;gt;60 years. For the progesterone receptor (PR), this depends quadratically on the age at diagnosis (p=0.0108, 95% CI OR=0.999-1.000), decreasing &amp;lt;50 years and increasing above. With increasing age, the chance on HER-2 positivity decreased (p=0.0414, 95% CI OR: 0.970-0.999). Grade 3 tumors dropped significantly until 50 yrs (p&amp;lt;0.0001 CI OR=0.900 (0.869-0.933) whereafter we observed a non significant upward trend (Fig 2). The chance to receive any adjuvant therapy decreased with age (p=0.0023, 95% CI OR: 0.958-0.991). Above 70 yrs, systemic adjuvant therapy was absent in 12.95% of non-relapsing -, but in 28.95% of relapsing patients. Radiotherapy was not taken into account.&amp;#x2028; Conclusion Early relapse was higher with increasing/decreasing age, starting from age 60. This goes in parallel with the U-shape curve of lymph node involvement (Fig1). Increased relapse and lymph node positivity in elderly might partially be a reflection of the fact that BC is diagnosed in a later stage in elderly patients but might also be related to different biological behavior or to decreased use of adjuvant systemic treatment. HER-2 overexpression decreases with age and age related differences in ER and PR expression as well as tumor grading are observed (Fig 2).&amp;#x2028; &amp;#x2028; &amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2082.