tbuckley/cabot-search huggingface dataset:
Abstract 3908: A multifunctional peptide for targeted imaging, localization of transformed cell and chemotherapy for nasopharyngeal carcinoma and other cancers
Authors: Chin-Tarng Lin, Jong-Kai Hsiao, Hon-Man Liu, Hang-Chung Wu, Alice Yu
Journal: Cancer Research (2016)

Abstract Introduction: In treating cancer with chemotherapy, the ultimate goal is to deliver sufficient amounts of the drug to tumor cells while minimizing the damage of normal tissue. To achieve this purpose, using a phage-displayed random peptide library to screen the nasopharyngeal carcinoma (NPC)-TW01 cell line, we identified a specific peptide (L-peptide), which binds specifically to NPC tumor cells but not normal cells. To investigate whether this L- peptide can also bind to other cancer cell lines, be used for cancer tissue binding, targeted imaging and chemotherapy, we have performed this experiment. Methods: A fluorescein-labelled L-peptide was used to perform FACScan for 7 cancer cell lines. The L-peptide was linked to dextran coated iron oxide (L-P-Fe3O4) nanoparticles and a biotin labeled modified L-peptide (biotin-mL-P) were also used to localize L-peptide targeted protein (X-protein) in NPC and breast cancer surgical specimens. This conjugate was also injected intravenously to SCID mice bearing NPC and breast cancer xenografts for magnetic resonance imaging (MRI) analysis. Furthermore, L-peptide-linked liposomal doxorubicin (L-P-Lipo-Dox) was used to observe the efficacy of peptide-targeted chemotherapy in both cancers. Results and Conclusions: FACscan revealed specific binding of L-peptide to NPC, breast cancer, lung cancer, and neuroblastoma. The X-protein in both cancer specimens localized by biotin-mL-P was seen in many NPC and breast cancer tumor cells with some unstained tumor cells, but not or very weak in normal tissue; the X-protein in formalin-fixed paraffin-embedded section could be localized by L-P-Fe3O4 histochemistry in both cancer specimens. MRI analysis of both cancer xenograft bearing mice after injection of L-P-Fe3O4 revealed significant change in the MR signal intensity. A high efficacy of L-P-Lipo-Dox treatment for both cancers with minimal adverse effect was obtained. This multifunctional L-peptide seems able to be used for localization of its binding protein in each cancer cell type, molecular MRI analysis and targeted chemotherapy with minimal adverse effect in different cancer types. Citation Format: Chin-Tarng Lin, Jong-Kai Hsiao, Hon-Man Liu, Hang-Chung Wu, Alice Yu. A multifunctional peptide for targeted imaging, localization of transformed cell and chemotherapy for nasopharyngeal carcinoma and other cancers. [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 3908.
Genomics- and Transcriptomics-Based Patient Selection for Cancer Treatment With Immune Checkpoint Inhibitors
Authors: Krijn K. Dijkstra, Paula Voabil, Ton N. Schumacher, Emile E. Voest
Journal: JAMA Oncology (2016)

Checkpoint blockade therapy targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathways (PD-1/PD-L1) have achieved success in treating a number of malignancies. However, only a subset of patients responds to these therapies, and optimization of patient selection for treatment is imperative to avoid adverse effects without clinical benefit and keep costs manageable.The past few years have witnessed checkpoint inhibition becoming a first-line treatment option with US Food and Drug Administration approvals for various tumor types. Genomic analyses (whole genome, exome, and transcriptome) have been instrumental in identifying a genetic profile associated with sensitivity to checkpoint inhibitors. Therapy outcome is determined at various levels: (1) the degree of tumor "foreignness," as reflected by mutational burden and expression of viral genes, (2) the composition and activity of a preexisting immune infiltrate, and (3) mechanisms of tumor escape from immune surveillance. In addition, there are opportunities for genomic analyses of genetic polymorphisms and the gut microbiome that may be associated with clinical response to therapy.Genomics provides powerful tools for the identification of biomarkers for response to immune checkpoint blockade, given their potential to analyze multiple parameters simultaneously in an unbiased manner. This offers the opportunity for genomics- and transcriptomics-based selection of patients for rationally designed therapy with immune checkpoint inhibitors.
Gemcitabine-related pneumonitis: Elucidation of risk factors.
Authors: Ibrahim Halil Sahin, Alexander Geyer, Daniel Kelly, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2014)

e15243 Background: Gemcitabine (G) is a key component of therapy for pancreatic adenocarcinoma (PC). Pulmonary injury is an infrequent but not rare adverse effect of varying manifestation and is observed in approximately 8% of pts treated with G (Tamiya et al, Pancreas 2009). In this study we investigated potential risk factors for G-related pneumonitis (GRP) in PC. Methods: Patients (pts) with PC diagnosed between 01/04 and 12/13 were retrospectively screened for GRP who received therapy at Memorial Sloan-Kettering Cancer Center. ICD and Billing codes were queried for pts with a diagnosis of PC, G, pneumonia, and G-related adverse drug reaction. Eligible pts and demographics were confirmed by chart review. Results: Sixteen pts were identified to have GRP. Median age: 74 years, range 46- 88 years. Five pts (31.2%) had resectable disease, N= 4 pts (25%) had locally advanced disease, and N= 7 pts (43.8 %) had metastatic disease at the time of GRP. Six of 16 pts (37.5%) developed pneumonitis during treatment with single-agent G while N= 10 pts (62.5%) received a G-based combination (oxaliplatin, capecatabine, erlotinib, docetaxel). Fourteen of 16 pts (87.5%) had either a history of cigarette or alcohol consumption. Ten (62.5%) pts had a smoking history: N= 2 of 10 pts (20%) were active smokers and N= 7 of 10 pts (70%) had a prior smoking history. One pt had significant second-hand smoking. Eight pts (55.6%) were active alcohol users of whom 6 were a social drinker. Two pts (11.1%) had previous lung disease, one with interstitial lung disease and the other had COPD. Prior chest radiation was observed in 2 pts (11.1%). Conclusions: A history of smoking and alcohol use along with underlying lung disease and chest radiation and multiple drugs may confer increased risk for GRP. Smoking and alcohol cessation are recommended and patients at risk may benefit from early referral to pulmonologists. *Detailed updated analysis will be presented.
Case 55-1965
Authors: Homayoun Kazemi, Benjamin Castleman
Journal: New England Journal of Medicine (1965)

Presentation of CaseA sixty-four-year-old man was admitted to the hospital because of gangrene of the feet.Two weeks before admission he entered another hospital because of severe dyspnea; plethora and cyanosis were observed. During the next two weeks the cyanosis became more severe, and edema developed in both lower extremities, accompanied by coldness, hypesthesia and the appearance of vesicles that progressed to large, tense bullae. Adrenocorticotrophic hormone, prednisone, triamterene and heparin were given, without improvement. He had taken no medication before admission to the other hospital.Since the age of twenty years the patient had had a nonproductive cough . . .
Use of a Population Pharmacokinetic Model of ADVATE In Pediatric and Adult Patients with Hemophilia A Permits Limited Blood Sampling for Individual Dose Tailoring.
Authors: MyungShin Oh, Sven Björkman, Phillip Schroth, Sandor Fritsch, Peter W Collins, Kathelijn Fischer, Victor S. Blanchette, Kathleen M. Casey, Gerald Spotts, Bruce M. Ewenstein
Journal: Blood (2010)
Abstract 3764: Trabectedin activity in patient-derived mesothelioma xenografts
Authors: Simonetta Andrea Licandro, Roberta Frapolli, Ezia Bello, Roberta Libener, Sara Orecchia, Federica Grosso, Maurizio D’Incalci
Journal: Cancer Research (2016)

Abstract Malignant pleural mesothelioma (MPM) incidence is increased over the past two decades and it is predicted to increase further in the next 20 years especially in developing countries where asbestos has not yet been banned. Surgery is not an option for the majority of patients due to the diffuse growth of MPM, making chemotherapy the treatment of choice, but prognosis remains very poor with a median survival time of 10-17 months. Trabectedin (ET-743, Yondelis) is a marine alkaloid used for the 2nd line therapy of ovarian cancer (combined with pegylated doxorubicin) and soft tissue sarcomas. It binds the DNA minor groove modulating transcription of cancer cells and has an anti-inflammatory effect modifying tumor microenvironment and reducing tumor associated macrophages. The aim was to test antitumor activity of trabectedin in newly established patient derived xenografts of MPM. MPM473, MPM484 and MPM487 xenografts were obtained in athymic nude mice by s.c. injection of 107 cells isolated from the pleural effusion of MPM patients and maintained by serial passages in mice. H&amp;E staining and immunohistochemistry were performed. Mice were randomized when tumor reached about 200 mg to receive trabectedin, cisplatin, pemetrexed, gemcitabine, and imatinib. Antitumor activity was expressed as T/C% were T and C are the mean tumor weight of treated and control mice, respectively. The three xenografts reproduced the morphology and the histochemical profile of the human tumors. As reported in the table trabectedin was able to induce a 50% reduction in tumor growth in MPM473 and MPM 487 xenografts and only a marginal effect in MPM484 xenograft. TreatmentDose (mg/kg)ScheduleBest T/C% (Day)MPM473MPM484MPM487Cisplatin5i.v. q7dx361.9 (69)66.1 (69)67.3 (39)Gemcitabine100i.p. q4dx583.2 (41)67.7 (48)49.7 (56)Imatinib200p.o. qdx1568.9 (76)89.4 (55)87.1 (39)Pemetrexed250i.p. q4dx477.4 (52)76.8 (49)84.3 (39)Trabectedin0.15i.v. q7dx351.0 (73)63.6 (69)51.3 (56) In conclusion we report three new MPM xenografts able to mimic the pathological features of human MPM. Although trabectedin showed only a moderate antitumor activity in our experimental models, its efficacy is comparable or better than that of the other drugs currently used for this disease. Studies are in progress in syngenic models that are more appropriate to test also the ability of trabectedin to modulate the immune system. Citation Format: Simonetta Andrea Licandro, Roberta Frapolli, Ezia Bello, Roberta Libener, Sara Orecchia, Federica Grosso, Maurizio D’Incalci. Trabectedin activity in patient-derived mesothelioma xenografts. [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 3764.
Endothelial progenitor dysfunction associates with a type I interferon signature in primary antiphospholipid syndrome
Authors: Robert C Grenn, Srilakshmi Yalavarthi, Alex A Gandhi, Nayef M Kazzaz, Carlos Núñez-Álvarez, Diego Hernández-Ramírez, Antonio R Cabral, W Joseph McCune, Paula L Bockenstedt, Jason S Knight
Journal: Annals of the Rheumatic Diseases (2016)

Patients with antiphospholipid syndrome (APS) are at risk for subclinical endothelial injury, as well as accelerated atherosclerosis. In the related disease systemic lupus erythematosus, there is a well-established defect in circulating endothelial progenitors, which leads to an accrual of endothelial damage over time. This defect has been at least partially attributed to exaggerated expression of type I interferons (IFNs). We sought to determine whether these pathways are important in APS.We studied 68 patients with primary APS. Endothelial progenitors were assessed by flow cytometry and functional assay. Type I IFN activity was determined by a well-accepted bioassay, while peripheral blood mononuclear cells were scored for expression of IFN-responsive genes.Endothelial progenitors from patients with APS demonstrated a marked defect in the ability to differentiate into endothelial cells, a phenotype which could be mimicked by treating control progenitors with APS sera. Elevated type I IFN activity was detected in the circulation of patients with APS (a finding that was then replicated in an independent cohort). While IgG depletion from APS sera did not rescue endothelial progenitor function, the dysfunction was successfully reversed by a type I IFN receptor-neutralising antibody.We describe, for the first time to our knowledge, an IFN signature in primary APS and show that this promotes impaired endothelial progenitor function. This work opens the door to novel approaches that may mitigate vascular damage in APS, such as anti-IFN drugs.
Abstract LB-171: Repression of miR-125b-1 by epigenetic mechanisms in breast cancer cell lines
Authors: Fernanda Cisneros-Soberanis, Marco Alonso Andonegui, Clementina Castro, Luis Alonso Herrera
Journal: Cancer Research (2016)

Abstract miR-125b-1 downregulates targets as ERBB2, BAK1 and ETS1. These targets are involved in cell proliferation, apoptosis and cell migration, respectively. Previous studies on tumor cells reveal that downregulation of miR-125b-1 is associated with poor prognosis in breast cancer patients. DNA methylation of the miR-125b-1 promoter can repress its expression, in addition, this promoter is embedded in an intermediate CpG island thus, DNA methylation and histone modifications could also affect its transcription. Repression by DNA methylation has been well characterized, but there is no information about the role of histone modifications in the regulation of miR-125b-1 promoter. We evaluated the enrichment of two histone modifications involved in gene repression, H3K9me3 and H3K27me3, on the miR-125b-1 promoter of two breast cancer cell lines, a luminal A, MCF 7, and a triple negative, MDA-MB-231, compared with a non-transformed breast cell line, MCF 10A. We found that breast cancer cell lines are enriched with H3K27me3 and H3K9me3 in MCF 7 and MDA-MB-231, respectively. Then, we focused on reactivating miR-125b-1 in MCF 7 using an EZH2 inhibitor. After the treatment with the EZH2 inhibitor, we evaluated the transcriptional levels of the pri-miR-125b-1 and the mature miR-125b by qRT-PCR. Our results suggest that transcripts, pri-miRNA and mature miRNA, increase their expression levels after the treatment in the MCF7 cell line, but not in the MDA-MB-231 and MCF 10A cell lines. Subsequently, we evaluated the BAK1 expression and protein levels to investigate whether the miR-125b-1 reactivation could affect some targets. We observed a 60% and 70% decrease in the expression and protein levels of after treatment with the EZH2 inhibitor. To determine if the H3K9me3 is involved on miR-125b-1 silencing in MDA-MB-231, we over-expressed KDM4B/JMJD2B to reactivate this miRNA. Then, we evaluated the transcript. A three-fold increase was observed compared. We conclude that the miR-125b-1 can be repressed by different epigenetic mechanisms depending on the breast cancer subtype; the miR-125b-1 reactivation by removing the repression histone modification marks affect the expression of BAK1, a pro-apoptotic target. Citation Format: Fernanda Cisneros-Soberanis, Marco Alonso Andonegui, Clementina Castro, Luis Alonso Herrera. Repression of miR-125b-1 by epigenetic mechanisms in breast cancer cell lines. [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-171.
Abstract 1281: Prostaglandin D synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPARγ
Authors: Masakazu Yashiro, Tatsunari Fukuoka, Haruhito Kinoshita, Go Masuda, Kishu Kitayama, Yuichiro Miki, Tamami Morisaki, Tsuyoshi Hasegawa, Kosei Hirakawa
Journal: Cancer Research (2016)

Abstract Background &amp; Aims: The antitumor activity of prostaglandin (PG) D2 has been demonstrated against some types of cancer, including gastric cancer. However, exogenous PGD2 is not useful from a clinical point of view because it is rapidly metabolized in vivo. The aim of this study was to clarify the antitumor efficacy of an alternative, PGD2 synthase (PGDS), on gastric cancer cells. This is the first report showing that PG synthase is a promising agent for the treatment of gastric carcinomas that express peroxisome proliferator-activated receptor γ (PPARγ). Methods: The effects of PGD2 and PGDS on the proliferation of gastric cancer were examined in vivo and in vitro for five human gastric cancer cell lines. The expression levels of PGD2 receptors and PPARγ were evaluated by RT-PCR. The effects of PGD2 and PGDS on the expression of c-myc and cyclin D1 were examined by Western blotting in the presence or absence of a PPARγ antagonist. Results: PPARγ was expressed in gastric cancer cell lines, but PGD2 receptors were not. PGD2 and PGDS significantly decreased the proliferation of gastric cancer cells that highly expressed PPARγ. PGDS increased the PGD2 production of gastric cancer cells. A PPARγ antagonist significantly suppressed the growth-inhibitory effects of PGD2 and PGDS. Expression of c-myc and cyclin D1 was significantly decreased by PGD2; this inhibitory effect was suppressed by the PPARγ antagonist. Both PGD2 and PGDS significantly decreased subcutaneous tumor growth in vivo. Tumor volume after PGDS treatment was significantly less than after PGD2 treatment. PGD2 decreased the proliferation of gastric cancer cells through PPARγ signaling. Conclusion: PGDS and PGD2 decreased the proliferation of gastric cancer via the PPARγ pathway. PGDS is a promising therapeutic agent for gastric cancer and PPARγ might be a predictive biomarker for PGDS treatment in gastric cancer. Citation Format: Masakazu Yashiro, Tatsunari Fukuoka, Haruhito Kinoshita, Go Masuda, Kishu Kitayama, Yuichiro Miki, Tamami Morisaki, Tsuyoshi Hasegawa, Kosei Hirakawa. Prostaglandin D synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPARγ. [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 1281.
Withdrawal effect after 4-year statin therapy on creactive protein is independent of LDL-cholesterol change
Authors: van der Pim Harst, FW Asselbergs, Hans Hillege, Stephan Bakker, Adriaan Voors, van Dirk Veldhuisen, van Wiekert Gilst, Prevend-It Investigators
Journal: Journal of the American College of Cardiology (2006)
A Decrease in Cardiac Energy Metabolism Precedes a Reduction in Mass and Function in the The Hypoxic Human Heart
Authors: C J Holloway, L E Cochlin, H E Montgomery, A W Johnson, I Codreanu, E Bloch, D J Tyler, D Z Levett, M P Grocott, M Fatemian, C Szmigielski, J M Francis, P Robbins, S Neubauer, K Clarke
Journal: Circulation (2010)
Abstract 2385: Understanding the dynamic interplay between genetically different cancer cell clones in glioblastoma
Authors: Min Guo, Susanne Heller, Jessie Thorslund, Lukas Orre, Janne Lehtiö, Monica Nistér, Daniel Hägerstrand
Journal: Cancer Research (2016)

Abstract Glioblastoma is the most frequent and aggressive brain tumor in adults. Based on genomic data glioblastomas can be classified into at least four subclasses: proneural, neural, classical and mesenchymal. However, recent publications have shown that individual glioblastoma can be heterogeneous and contain a mixture of these four subclasses. Moreover, it has been shown in other studies that intratumoral communication between genetically distinct cancer cell subclones in glioblastomas can affect the overall tumor growth via secreted proteins. In this project we aim to investigate the difference between protein secretomes from different tumor cell clones from within genetically heterogeneous glioblastomas. For this we have used the U343 cell culture system, consisting of U343MG, U343MGa, U343MGa-31L and U343MGa-Cl2:6. These cultures were derived from a single glioblastoma, and can be divided into at least two categories based on their mutually exclusive expression patterns of FN1 and GFAP. Here we show that these different cultures display different characteristics with regard to matrigel invasion capacity, neurosphere formation capacity, and gene and protein expression. Combinatorial co-culture and conditioned media based experiments showed that the U343MG culture elicit anti-proliferative effects on U343MGa-31L via secreted factors. To identify proteins that are secreted by U343MG we have used Secretome Protein Enrichment with Click Sugars (SPECS) followed by mass spectrometry analysis. We detected 150 proteins by more than 2 peptides in U343MG conditioned media. Several of these proteins were growth factors and matrix proteins, including FN1. We are now performing a combined secretome and gene expression analysis of all U343 cultures to identify candidate secreted proteins that most likely are involved in the observed signaling effects between U343MG and U343MGa-31L. Finally, a functional genomic approach will be taken to experimentally pinpoint mediators of these inter-clonal effects. This study shows that subclones from a heterogeneous glioblastoma can display different phenotypic characters and affect each other via secreted factors. Further knowledge about cell-to-cell communication through secreted proteins in glioblastoma may provide novel therapeutic targets. Citation Format: Min Guo, Susanne Heller, Jessie Thorslund, Lukas Orre, Janne Lehtiö, Monica Nistér, Daniel Hägerstrand. Understanding the dynamic interplay between genetically different cancer cell clones in glioblastoma. [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 2385.
Abstract 3522: Cyclins and CDKs regulation and caspase cascade activation by cucurbitacin D induced cell cycle arrest and apoptosis in pancreatic tumor
Authors: Myeong-Sun Kim, Ji Hye Kim, Jin Mo Ku, Se Hyang Hong, Kangwook Lee, Hyeong Sim Choi, Sang Mi Woo, Jee Yun Chang, Tai Young Kim, Seong Gyu Ko Ko.
Journal: Cancer Research (2016)

Abstract Pancreatic cancer has a poor prognosis and very low survival rate over the world. Because pancreatic cancer probably is diagnosed at a late stage, aggressive local invasion, and poor response to chemotherapy. Gemcitabine was the standard treatment for advanced and metastatic pancreatic cancer patients, but it is associated with multiple adverse effects-fever, fatigue, nausea, and drug resistance. Whether cucurbitacin D has any efficacy against human pancreatic cancer was examined in cell culture system. In vitro, cell viability was measured by MTT assay to recognize of cell cytotoxicity. Consequently, cytotoxicity was observed at a low concentration of cucurbitacin D. Wound healing assay and clonogenic assay indicated that cucurubitacin D inhibited the growth of cell growth through cyclins and CDKs regulation, and decreased colony-forming ability. Also, this compound down-regulated expression level of anti-apoptotic protein, Bcl-2, up-regulated of pro-apoptotic molecule Bax, and activated caspase-8, caspase-3 cascade extrinsic pathway. Additionally, PARP, caspase-3 substrate, protein was cleaved by cucurbitacin D treatment. Overall, our study suggest that cucurbitacin D could be a clinical medicine for the treatment of pancreatic cancers. Citation Format: Myeong-Sun Kim, Ji Hye Kim, Jin Mo Ku, Se Hyang Hong, Kangwook Lee, Hyeong Sim Choi, Sang Mi Woo, Jee Yun Chang, Tai Young Kim, Seong Gyu Ko Ko. Cyclins and CDKs regulation and caspase cascade activation by cucurbitacin D induced cell cycle arrest and apoptosis in pancreatic tumor. [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 3522.