tbuckley/cabot-search huggingface dataset:
Risk of Second Primary Malignancies (SPMs) Following Bortezomib (Btz)-Based Therapy: Analysis of Four Phase 3 Randomized Controlled Trials in Previously Untreated or Relapsed Multiple Myeloma (MM)
Authors: Jesús F San Miguel, Paul G. Richardson, Robert Z. Orlowski, Hartmut Goldschmidt, Deyanira Corzo, Carol Satler, Dixie-Lee Esseltine, Rachel Neuwirth, Maria Ponsillo, Andrew Z Cakana, Jay King, William M Deraedt, Avinash Desai, Yana Lutska, Dina Gifkins, Kevin Liu, Pieter Sonneveld
Journal: Blood (2011)
155P Early recurrence after hepatectomy for colorectal liver metastases: the definition and predictive factors
Authors: K. Imai, M.-A. Allard, C. Castro Benitez, E. Vibert, A. Sa Cunha, D. Cherqui, D. Castaing, H. Bismuth, T. Beppu, H. Baba, R. Adam
Journal: Annals of Oncology (2015)
Abstract 2191: Imaging the kinetics of targeted nanoparticles to pancreatic cancer
Authors: Jonathan Moreno, Qin qin Fei, Maria P. Lambros
Journal: Cancer Research (2016)

Abstract Purpose: The purpose of this work is to image the kinetics of targeted lipid nanoparticles to an SCL transporter of pancreatic cancer using a near infrared (NIR) fluorescent dye DyLight® 747 and a mouse orthotopic model of fluorescent pancreatic cancer. Methods: Initially and before the in vivo experiments, the uptake of nanoparticles by human pancreatic cancer cells was evaluated in vitro using fluorescent microscopy and flow cytometry. A quantity of 1.5 x105 PANC-1, MIA PaCa, or BxPC-3 cells/ml was placed in each well of a six-well plate and incubated for 5 hours with different formulations of fluorescent lipid targeted and non-targeted nanoparticles encapsulation daunorubicin which has natural fluorescence. After incubation, the growth media were removed and the cells were washed with PBS. The uptake of the fluorescent lipid nanoparticles by the cancer cells was evaluated an EVOS® microscope. All the in vitro experiments were done in triplicate. For the in vivo targeting studies, nude mice (Balb/c Ola Hsd-Fox1 nu) were implanted orthotopically (in the tail of the pancreas) with 3 x106 PANC-1 cells expressing GFP. The injection volume for the implantation was 50 microliters and contained 3 x106 PANC-1-GFP cells mixed with serum free media and HC Matrigel (1:1). One month after the orthotopic implantation, the implanted pancreatic tumor was visualized in live, anesthetized animals using UVP Scientia (UVP, Upland, CA). The animals were separated into three groups (three animals in each group) and injected via the tail vein as follows: Group A, was injected with only the fluorescent dye, Dylight 747; group B was injected with fluorescent non-targeted nanoparticles; and group C was injected with fluorescent targeted nanoparticles. Results: Both the flow cytometry and fluorescence microscopy data show a significantly higher uptake of the targeted lipid nanoparticles compared to the non-targeted ones. The imaging of the fluorescent lipid nanoparticles in live mice shows that both targeted and nontargeted nanoparticles reach the pancreatic tumor. The nontargeted nanoparticles reside less than 48 hours on the tumor, whereas the targeted nanoparticles can reside for 96 hours on the tumor. The non-encapsulated fluorescent dye did not reach the tumor and was excreted in the urine. Conclusion: The results show that Dylight® 747 can be used to image the kinetics of a drug delivery system in a live animal. Furthermore while both lipid nanoparticles reach the tumor, the targeted lipid nanoparticles reside significantly longer on the tumor and this may translate to a better therapeutic outcome. Citation Format: Jonathan Moreno, Qin qin Fei, Maria P. Lambros. Imaging the kinetics of targeted nanoparticles to pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2191.
Abstract LB-253: Control of tumor growth in vivo by a synthetic multi-antigen DNA immune therapy for prostate cancer
Authors: Bernadette Ferraro, Jewell N. Walters, Emma L. Reuschel, Amritha Balakrishnan, Matthew P. Morrow, Amir S. Khan, Niranjan Y. Sardesai, Laurent M. Humeau, David B. Weiner
Journal: Cancer Research (2016)

Abstract Prostate cancer (PCa) is one of the leading causes of cancer deaths among men with limited treatment options. Accordingly, new approaches, such as immunotherapy, may represent important approaches for PCa treatment. Electroporation (EP) delivered DNA vaccines has recently shown promising results for therapeutic immunotherapy strategies has been limited to single antigen and epitope targets with limited success. We hypothesized that a broader collection of antigens adjuvanted by plasmid encoded IL-12 would bypass immune tolerance and improve the breadth and effectiveness of a PCa immunotherapy approach. We tested this hypothesis in NHP for immune tolerance effects as well as in the highly relevant TRAMP-C2 challenge model. We developed highly optimized DNA vectors encoding consensus antigens for important PCa targets prostate-specific antigen (SynCon PSA), prostate-specific membrane antigen (SynCon PSMA), and human six-transmembrane epithelial antigen of the prostate (STEAP). In mice the vaccines demonstrated potent IFNγ production by ELISpot (2740 SFU) and robust immune responses in the CD4+ (0.53%) and CD8+ (3.0%) T cell compartments. Further, sera from immunized mice reacted in ELISA with relevant targets and specifically stained LNCaP cells, a human PCa cell line, as well as human PCa tumor sections, supporting that the vaccine antigens induced relevant antibody responses. Vaccination of Rhesus Macaques, which share greater than 98% identity with humans, showed robust anti-PSA, PSMA and STEAP IFNγ production (612 SFU), potential for cytotoxic T cell function, and antigen specific seroconversion supporting the ability of these constructs to break tolerance. The therapeutic potential of PSMA, STEAP, and the combination of PSMA and STEAP, alone or with the molecular adjuvant IL-12, was evaluated in mice in the TRAMP-C2 tumor model. Alone, PSMA, STEAP or PSMA+STEAP demonstrated prolonged survival and a modest impact on tumor growth. However, the combination of synthetic vaccine antigens with IL-12 resulted in 100% efficacy in treatment and clearance of tumors resulting in 100% survival. These data support further study of this novel immune therapy of PCa. Citation Format: Bernadette Ferraro, Jewell N. Walters, Emma L. Reuschel, Amritha Balakrishnan, Matthew P. Morrow, Amir S. Khan, Niranjan Y. Sardesai, Laurent M. Humeau, David B. Weiner. Control of tumor growth in vivo by a synthetic multi-antigen DNA immune therapy for prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-253.
Epidémiologie descriptive des exanthèmes dans la région de Rotterdam, janvier 1997 à juin 1998
Authors: O Ronveaux, A Bosman, R Reintjes, M A E Conyn-Van Spaendonck
Journal: Eurosurveillance (1998)

Le Conseil Europeen sur la Vaccination a emis des recommandations visant a l’elimination de la rougeole en Europe d’ici 2007 (1), objectif approuve par les directeurs des programmes nationaux de vaccination de la region Europe de l’Organisation Mondiale de la Sante (OMS). Dans ce contexte, l'etude de l’epidemiologie des exanthemes (rougeurs/eruptions cutanees associees a de la fievre) est importante. La rougeole, autrefois la forme la plus courante d’exantheme chez les enfants en Europe, est de plus en plus rare avec l’augmentation de la couverture vaccinale.
Adjuvant chemo-radiotherapy (CRT) versus radiotherapy (RT) alone for locally advanced salivary gland carcinoma among older population: SEER-Medicare analysis.
Authors: Tawee Tanvetyanon, Kate Fisher, Tapan Padhya, Kristen J Otto, Jimmy J. Caudell, Andy Trotti
Journal: Journal of Clinical Oncology (2015)

6028 Background: Salivary gland carcinoma is an uncommon malignancy. For locally advanced or high risk disease, current standard of care consists of surgery followed by adjuvant RT. Limited data on the efficacy of adjuvant CRT exists. We sought to compare the effectiveness of adjuvant CRT vs. RT alone among older patients in real world setting. Methods: SEER-Medicare database (1992-2009) was searched for beneficiaries 66 years of age or older with Medicare coverage ≥ 1 year following a diagnosis of locally advanced (T3-4 and/or N1-3, M0) major or minor salivary gland carcinoma. Patients must have had definitive surgery within 4 months from diagnosis and adjuvant RT or CRT within 6 months from diagnosis. Results: Analyses included 741 patients: 100 received CRT and 641 received RT. The most common concurrent chemotherapy agents used were Cisplatin or Carboplatin (37%), Carboplatin plus Taxane (19%) and Cetuximab (18%). Patients in CRT group were younger (median age 74.2 vs. 76.8 years, p= 0.01), with greater node positive disease (73% vs. 64%, p= 0.05) than RT group. The median overall survival was 24.0 months with CRT vs. 41.0 months with RT, p= 0.012. Multivariable analysis adjusting for patient-, tumor- and treatment-related factors still showed that CRT increased mortality over RT alone: HR 1.40 (95% CI: 1.08, 1.81). Hospitalization with treatment-related toxicity was more frequent in the CRT group, 27.0% vs. 11.5%, p< 0.01. An effect modification (p-interaction= 0.02) between histology and CRT was present such that an increase in mortality from CRT was observed only among adenoidcystic, mucoepidermoid or acinic cell carcinoma, but not adenocarcinoma or squamous cell carcinoma. Sensitivity analysis performed by changing the adjuvant definition to within 4 months from diagnosis or restricting analytic cohort to those receiving RT within 2 months post-surgery showed results robust. Conclusions: In this older, population-base cohort, there existed a wide variation in the practice of adjuvant CRT. Adjuvant CRT, when compared with adjuvant RT alone, was associated with an increased risk of mortality and hospitalization with treatment-related toxicity.
IDH-1/2mutations and associated oncometabolite 2-hydroxyglutarate (2-HG) in solid tumors.
Authors: Nazanin Fallah-Rad, Philippe L. Bedard, Lillian L. Siu, Stefano Serra, Suzanne Kamel-Reid, Marcus O. Butler, Anthony M. Joshua, Celeste Yu, Helen Chow, Zhang Weijiang, Jennifer J. Knox, Monika K. Krzyzanowska, Geoffrey Liu, Raymond Woo-Jun Jang, Albiruni Ryan Abdul Razak, Eric Xueyu Chen
Journal: Journal of Clinical Oncology (2016)

e23210 Background: IDH-1 mutations are common in AML, gliomas, and intrahepatic cholangiocarcinoma. Relatively few cases of IDH-1/2 mutation have been reported in other solid tumors. The enzymatic product of the IDH-1 R132 variant preferentially catalyzes the NADPH-dependent reduction of alpha-ketoglutarate to R-2-Hydroxyglutarate (R-2HG), resulting in accumulation of R-2HG, relative to its enantiomer, S-2HG. Elevated plasma levels of 2-HG and/or higher ratios of R/S have been observed in AML and intrahepatic cholangiocarinoma. We investigated plasma levels of 2-HG and relative ratios of R/S in other solid tumor patients harboring IDH-1/2 mutations. Methods: Between 2012-2015, 2556 patients (pts) with advanced solid tumors were molecularly profiled through the COMPACT and IMPACT programs at Princess Margaret Cancer Centre. Tumor DNA for each patient was isolated from an FFPE archived sample and genotyped using customized Sequenom or Miseq targeted sequencing panels in a CLIA-certified laboratory. Plasma samples from pts harboring IDH-1/2 mutations and tumor type, gender, and matched controls were analyzed for R-2HG and S-2HG using HPLC tandem mass spectrometry coupled with a CHIROBIOTIC R column. Results: IDH-1/2 mutations were identified in 11 pts (0.43%), (4 colorectal, 2 lung, 1 endometrial, 1 prostate, 1 unknown primary (not consented for 2-HG analysis), and 2 cholangiocarcinomas). In 8 non-biliary cancer pts, total 2-HG levels were significantly higher in those with IDH-1/2 mutations (300.1±90.0 ng/ml vs 195.4±59.4 ng/ml, p < 0.01). In 2 biliary cancer pts, 2-HG levels were 750.8±722.95 vs 195.6±26.07 respectively. R/S ratios were 1.2±0.7 vs 0.8±0.4 for non-biliary pts, and 11.4±2.9 vs 0.6±1.0 for biliary pts respectively. Conclusions: IDH-1/2 mutations are rare in solid tumors other than cholangiocarcinomas. Patients with IDH-1/2 mutations have higher levels of oncometabolite 2-HG compared with matched controls with no difference in R/S ratio. In these solid tumor pts, both total 2-HG levels and R/S ratios are lower than those reported for those pts with AML.
Abstract 4245: BLZ-100 provides optical contrast in animal models of breast cancer
Authors: Stacey Hansen, Janean Fidel, Katie Kennedy, William Dernell, Boel Fransson, Josh Ramsay, Valorie Wiss, Mark Stroud, Julia E. Parrish-Novak
Journal: Cancer Research (2016)

Abstract Over 230,000 new breast cancer cases occur in the US annually. Complete surgical removal of tumor tissue is critical to reduce the risk of local recurrence. About 24% of patients who undergo breast conservation surgery require a second surgery due to positive margins. Second surgeries can be psychologically and financially costly to patients. BLZ-100, a peptide-fluorophore conjugate, is a Tumor Paint product candidate being developed to provide real-time, high resolution, intraoperative optical contrast between tumor and normal tissue, potentially helping surgeons accomplish more complete and accurate tumor resections. Intraoperative imaging with BLZ-100 may potentially improve the percentage of breast cancer patients achieving a complete resection and negative margins at their first surgical procedure. To better define the relationship between tumor pathology and BLZ-100 fluorescence, data from mouse models and canine mammary cancer cases were evaluated. Human breast cancer was modeled in mice using cell lines and xenograft models using patient-derived tumors. Review of histopathology was also conducted for each dog case. Animals received a single IV dose of BLZ-100, and tumors were excised one day after dosing. Excised tumor and normal tissues were imaged using the Odyssey Clx (LI-COR) to determine the ratio of signal in tumor compared to normal (background) tissue (TBR). Detailed histopathology reports for the dog cases were also analyzed to determine factors potentially associated with fluorescence intensity and TBR. A significant BLZ-100 TBR was observed. Histopathologic features potentially associated with TBR in dogs included cellularity and the degree of infiltration and demarcation. The studies supported the concept that BLZ-100 might potentially serve as an intraoperative optical imaging agent for breast cancer surgery. Citation Format: Stacey Hansen, Janean Fidel, Katie Kennedy, William Dernell, Boel Fransson, Josh Ramsay, Valorie Wiss, Mark Stroud, Julia E. Parrish-Novak. BLZ-100 provides optical contrast in animal models of breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4245.
Phase I/II study of PCI-27483, a coagulation factor VIIa (FVIIa) inhibitor in patients with advanced pancreatic cancer receiving treatment with gemcitabine.
Authors: R. K. Ramanathan, V. Gressler, S. Shah, D. Loury, A. Hamdy, A. A. Khorana
Journal: Journal of Clinical Oncology (2011)

221 Background: PCI-27483 is a selective inhibitor of FVIIa, a serine protease activated by interaction with tissue factor (TF). TF upregulation in tumor cells correlates with angiogenesis and a worsened prognosis. Hydrolysis of protease activated receptors by the TF:FVIIa complex induces up-regulation of IL-8 and VEGF. PCI-27483 inhibited the growth of human pancreatic tumors in animal models at a 2.5x to 3.0x change in prothrombin time. PK/INR relationships from a phase I study in healthy volunteers were used to select initial doses of PCI-27483 for the current study. Methods: Patients (pts) with locally advanced or metastatic pancreatic cancer, ECOG performance status 0-1, and normal coagulation were enrolled. All pts in phase I and II receive gemcitabine (G) as a 30-min IV infusion at a dose of 1000 mg/m 2 on 3 out of every 4 wks. PCI-27483 is administered twice daily by SC injection. In phase I, doses of PCI-27483 were intra-patient escalated (0.8 to1.2 to1.5 mg/kg) over 4 to 8 wks. The targeted peak INR, measured 2 h postdose, was 3.0. In phase II, pts are being randomized to a control arm to receive G only or to a PCI-27483 arm to receive G plus PCI-27483. Phase I pts receiving 80% of planned doses during in first 6 wks were considered evaluable. Spiral CT scans are performed at 8-wk intervals. Study endpoints: adverse event profile, progression-free survival, venous thromboembolic events, and overall survival. Results: Phase I—8 pts enrolled, 5 pts evaluable. Highest dose of PCI- 27483 achieved was 0.8 mg/kg for 2 pts, 1.2 mg/kg for 3 pts and 1.5 mg/kg for 3 pts. Hematologic toxicity: grade 3 neutropenia (n= 1) or anemia (n = 2). Other grade 3 toxicities: elevated INR (n = 4) or elevated aPTT (n = 1). Dose-level-specific mean 2-h INR values were 2.2 at 0.8 mg/kg (CV=9%; n=7), 3.2 at 1.2 mg/kg (CV=33%; n=6) and 2.9 at 1.5 mg/kg (CV=16%; n=3). No VTEs occurred. Radiologic evaluations of 5 evaluable pts: 4 SD at 16 wks (1st pt SD for &gt;40 wks; 5th pt SD at 8 wks, 16-wk scan pending). Conclusions: PCI-27483 is well tolerated at doses up to 1.5 mg/kg bid with G 1,000 mg/m 2 . Sustained SDs occurred and INRs were generally within the expected range. The randomized phase II study is ongoing at a dose of 1.2 mg/kg bid. [Table: see text]
Abstract 1104: MicroRNA miR-31 regulates oral squamous cell carcinoma cell migration by targeting critical enzyme of peroxisomal lipid metabolism
Authors: Yi-Shiuan Lai, Hsuan Liu, Ting-Wen Chen, Shu-Jen Chen, Hua-Chien Chen, Bertrand Chin-Ming Tan
Journal: Cancer Research (2016)

Abstract MicroRNAs (miRNAs) are small endogenous non-coding RNAs that play important roles in a variety of cellular processes, such as growth, differentiation and metabolic homeostasis. Dysregulation of microRNA has been linked to the development of various types of human diseases, including cancer. Our previous study has identified that miR-31 is significantly up-regulated in oral squamous cell carcinoma (OSCC) tissues. Further gain- and loss-of-function analyses revealed that miR-31 promotes OSCC by enhancing the migration and invasiveness of OSCC cells but not cell proliferation. However, the exact role of miR-31 in OSCC neoplastic development, especially metastasis, has not been explored. Computational microRNA target prediction and pathway analysis showed an enrichment of putative targets in lipid metabolism pathway. In this study, we aimed to investigate the role of miR-31 in the regulation of lipid metabolism and to establish the relationship between lipid metabolism and tumor pathogenesis in OSCC cells. First, we demonstrated that ACOX1, the rate-limiting enzyme in peroxisomal β-oxidation, is the direct target of miR-31. We further analyzed publicly available mRNA and miRNA deep sequencing datasets and found that the expression levels of miR-31 inversely correlate with those of ACOX1. Furthermore, we discovered that depletion of miR-31 significantly decreased the intensity of cellular lipid droplets (LDs), and knockdown of ACOX1 conversely showed an increase of LD formation. These data suggested that miR-31 may regulate lipid metabolism by targeting ACOX1. In cultured OSCC cells, the migration capability and invasiveness were significantly increased after knockdown of ACOX1. We further confirmed that ACOX1 depletion enhances ERK1/2 expression and phosphorylation and increases the expression levels of MMP9 in OSCC cells. Collectively, our findings suggest that the elevated expression of miR-31 in OSCC cells directly contributes to the down-regulated expression of ACOX1, subsequently leading to accumulation of lipid metabolites and elevated OSCC migration and invasion through ERK pathway. Citation Format: Yi-Shiuan Lai, Hsuan Liu, Ting-Wen Chen, Shu-Jen Chen, Hua-Chien Chen, Bertrand Chin-Ming Tan. MicroRNA miR-31 regulates oral squamous cell carcinoma cell migration by targeting critical enzyme of peroxisomal lipid metabolism. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1104.
Phase I dose escalation and pharmokinetic study of a modified schedule of 14-o-phosphonooxymethyltriptolide.
Authors: Edward Greeno, Erkut Hasan Borazanci, Jon P. Gockerman, Ronald Lee Korn, Ashok Saluja, Daniel D. VonHoff
Journal: Journal of Clinical Oncology (2016)

TPS472 Background: We are conducting a phase I trial of a modified dosing schedule of 14-O-phosphonooxymethyltriptolide (Minnelide,) a water-soluble prodrug of triptolide, a diterpene derived from the thunder god vine (tripterygium wilfordii). Triptolide is a potent inhibitor of heat shock protein 70 (HSP70) and pancreatic ductal adenocarcinoma over-expresses HSP70 as a protective mechanism. We have previously shown Minnelide to be effective and well tolerated in preclinical models of pancreatic carcinoma. We have previously presented our results from the initial phase I study of 27 patients using a daily dosing schema. That study demonstrated promising clinical activity with documented reductions in HSP70 levels. The common and dose limiting toxicity was neutropenia, which though cumulative, was also rapidly reversible early in the course of therapy with brief treatment interruptions. Several patients with disease control in the highest dose cohorts (0.67 and 0.8 mg/m2) progressed after dose reductions or prolonged treatment breaks mandated by the study protocol for cytopenias. Because of these observations we have revised the treatment schedule with short, early treatment breaks to allow more sustained therapy, and describe here the new study protocol. Methods: The study uses a 3+3 dose escalation scheme, enrolling subjects with gastrointestinal malignancies refractory to standard therapies. The drug is administered as a daily, brief IV infusion for 5 of 7 days for 3 weeks of a 4 week cycle. The initial dose cohort begins at 0.67mg/m2, above the MTD defined in the prior study and one step below the highest level achieved in our previous study of 0.8 mg/m2. The primary endpoint is toxicity, in order to define the MTD for this dosing schedule. Secondary endpoints being measured include: pharmokinetics of the study drug and its active metabolite triptolide; suppression of HSP70 levels; and tumor response. Cohort 1 at 0.67mg/m2 has been completed without DLT, enrollment to cohort 2 at 0.8mg/m2 is complete without DLT to date, and cohort 3 is anticipated to begin November of 2015. Clinical trial information: NCT01927965.