tbuckley/cabot-search huggingface dataset:
Circulating methylated DNA in serum predicts melanoma patients response to biochemotherapy
Authors: T. Mori, S. J. O’day, N. Umetani, C. Kuo, M. Kitago, L. Wilson, S. R. Martinez, T.-L. Takeshima, R. Milford, D. S. Hoon
Journal: Journal of Clinical Oncology (2005)

7521 Background: There are no validated blood-based assays to accurately predict response to adjuvant therapy or outcome in melanoma patients. Recently, we demonstrated that CpG island hypermethylation of several tumor suppressor genes (TSG) was present in melanoma and increased with tumor progression. We hypothesized that methylation of specific TSG detected in circulating serum DNA could be used to predict biochemotherapy (BC) treatment response and disease outcome in melanoma patients. Methods: Fifty AJCC stage IV melanoma patients treated with a concurrent BC regimen (dacarbazine, cisplatin, vinblastin, Interferon α-2b, IL-2) were assessed. Blood was drawn immediately prior to administration of BC, and DNA extracted from serum. Patients were divided into responders and non-responders, with a follow-up of 79 months. Responders (n=26) showed complete response (CR) (n = 13), partial response (PR) (n = 10) or stable disease (SD) (n = 3). Patients with progressive disease were deemed non-responders (n = 24). CpG island hypermethylation in the promoter region of the RASSFIA and Retinoic Acid Receptor-β2 (RAR-β2) promoters was assessed by methylation-specific PCR and capillary array electrophoresis in the serum of 50 AJCC stage IV patients and 40 healthy donors. Of the 50 melanoma patients, 15 had paired paraffin-embedded metastatic tissues available for analysis. Results: Serum methylated DNA correlated with treatment response and disease outcome. The frequency of circulating RASSFIA and RAR-β2 methylated DNA for responders (3 of 26, 11.5%, p=0.024; and 2 of 26, 8%, p= 0.03) was significantly lower than non-responders (10 of 24, 42%; and 8 of 24, 33%). The incidence of at least one methylated gene was also significantly lower (4 of 26, 17%, p=0.03) in responders compared to nonresponders (11 of 24, 46%). Paired tumor tissues and serum (n=15) assessed for methylated DNA markers showed significant correlation. Patients with at least one serum methylated gene had significantly worse overall survival compared to patients with no methylated genes (Log rank, p=0.009). Conclusions: Identification of circulating methylated TSG DNA in serum has clinical utility in predicting patients’ response to BC therapy and disease outcome. No significant financial relationships to disclose.
184. PGN-503, a Herpes Simplex Virus Based Vector Expressing Neurotrophin-3, Prevents and Reverses Neuropathy in a Mouse Model of Paclitaxel-Induced Peripheral Neuropathy
Authors: James R. Goss, David Krisky, Karen Bouch, Mark O'Malley, Sarah Coghlan, James Wechuck
Journal: Molecular Therapy (2016)

Paclitaxel-induced peripheral neuropathy (PIPN) is devastating constellation of symptoms that arise as a complication in patients receiving paclitaxel chemotherapy for cancer, most notably breast cancer. It presents as a glove and stocking neuropathy characterized by numbness, tingling, and occasionally burning pain in the feet and hands. Approximately 230,000 women will be diagnosed with breast cancer this year and over half, or about 120,000 women, will develop peripheral neuropathy as a consequence of paclitaxel therapy; this neuropathy will last for 5 years or longer in a quarter of these women. The development of PIPN may result in dose reduction of the paclitaxel, a switch to less efficacious agent, or even cessation of all chemotherapy treatment. Currently there are no approved therapies for the treatment of PIPN. PGN-503 is a new investigation drug designed to prevent and/or treat PIPN. It is a herpes simplex virus type 1 based vector expressing human neurotrophin-3. Following a skin injection, PGN-503 is taken up by sensory nerves, transported back to the cell body, and directs the expression of neurotrophin-3 (NT3). NT3 is a well-studied neurotrophic factor necessary for the growth and maintenance of sensory neurons, and thus represents an ideal candidate for the treatment of primary sensory neuropathies. In a series of preclinical studies, we examined the efficacy of PGN-503 in a mouse model of PIPN. Paclitaxel, dosed at 30 mg/kg/day for 6 days over two weeks, causes a peripheral neuropathy in BALB/c mice characterized by a long-lasting decrease in evoked sensory nerve action potentials (SNAPs) and conduction velocities (SNCVs). Mice, pretreated with a single injection of PGN-503 into the plantar surface of the hind paws 3 days prior to paclitaxel dosing, were completely protected against this decrease in SNAPs and SNCVs for the length of the study (approximately 4 months). This protection was dose-dependent on the total plaque forming units of PGN-503 applied to the paws. In a separate set of animals, we determined that a single application of PGN-503 was completely protective against the development of neuropathy following a second round of paclitaxel dosing beginning at 47 days post vector injection and partially protective against a third round beginning at 99 days post vector injection. Importantly, we have also demonstrated that PGN-503, applied one week after paclitaxel dosing, is capable of reversing the peripheral neuropathy. A Phase I/II trial of PGN-503 in preventing the development of PIPN in adjuvant breast cancer treatment is currently planned to begin next year.
Liver inflammation and fibrosis
Authors: Yukinori Koyama, David A. Brenner
Journal: Journal of Clinical Investigation (2017)

Chronic liver inflammation leads to fibrosis and cirrhosis, which is the 12th leading cause of death in the United States. Hepatocyte steatosis is a component of metabolic syndrome and insulin resistance. Hepatic steatosis may be benign or progress to hepatocyte injury and the initiation of inflammation, which activates immune cells. While Kupffer cells are the resident macrophage in the liver, inflammatory cells such as infiltrating macrophages, T lymphocytes, neutrophils, and DCs all contribute to liver inflammation. The inflammatory cells activate hepatic stellate cells, which are the major source of myofibroblasts in the liver. Here we review the initiation of inflammation in the liver, the liver inflammatory cells, and their crosstalk with myofibroblasts.
Post-Thaw Colony Forming Unit (CFU) Counts and Yield Are the Most Important Predictors of Engraftment and Survival Following Unrelated Donor Cord Blood Transplantation (CBT): A COBLT Study Report.
Authors: Donna A. Wall, Elizabeth L. Wagner, Shelly L. Carter, Adam M. Mendizabal, Mitchell S. Cairo, Nancy A. Kernan, Mary Laughlin, Joanne Kurtzberg
Journal: Blood (2005)
Initial evaluation of the clinical efficacy and safety of enzalutamide in castration-resistant prostate cancer
Authors: Noriyoshi Miura, Toshio Kakuta, Terutaka Noda, Seiji Asai, Tetsuya Fukumoto, Yutaka Yanagihara, Yuki Miyauchi, Tadahiko Kikugawa, Nozomu Tanji, Masayoshi Yokoyama
Journal: Annals of Oncology (2015)
Efficacy of 5% Albumin and Fresh Frozen Plasma (AFFP) Versus Fresh Frozen Plasma (FFP) only as Replacement fluid in Plasma Exchange for Thrombotic Thrombocytopenic Purpura (TTP)
Authors: James Louie, Fouad Boctor, Jason Chiang, Zeeshan Anwar, Amanda Wittenberg, Elena Gogas
Journal: Blood (2012)
Imatinib Mesylate Induced Fatal Hepatitis B Virus (HBV) Reactivation in a Patient with CML.
Authors: Tatsuyuki Kai, Kazuhiko Ikeda, Yutaka Shiga, Hideo Kimura, Hideyoshi Noji, Kazuei Ogawa, Kunihiko Takeyama, Yukio Maruyama
Journal: Blood (2004)
Abstract 1418: Screening and identification of key surface markers of mesenchymal stem cell osteogenic differentiation and osteosarcoma development
Authors: Tingting Ren, Sajida Piperdi, Amy Y. Park, Richard Gorlick
Journal: Cancer Research (2015)

Abstract Introduction: Osteosarcoma (OS) is the most common primary malignant tumor of bone in children and young adults. Knowledge about its cell of origin is limited, making new treatments difficult to develop. Our aim is to screen and identify the key surface markers of mesenchymal stem cell (MSC) to osteogenic differentiation and OS malignant transformation. Methods: A list of differentially expressed genes with a statistically significant p-value &amp;lt;0.05 was obtained by microarray analysis from MSCs and osteoblasts (OB). MSCs were differentiated into osteoblasts, adipocytes and chondrocytes and confirmed by alizarin red staining, oil red O staining and collagen II immunohistchemistry, respectively. Western blots were then performed to identify the expression of selected surface markers during the MSC differentiation and compared to those of OS cells. Results: Nine genes were obtained with a p-value &amp;lt;0.02, which are differentially expressed between MSC and OB. Four of them were correlated with cell adhesion and metastasis. The expression profile of CD49b was distinct, where it was down regulated only during MSC osteogenic differentiation and over expressed in OS cell lines. Conclusions: Cell adhesion may have an important role during MSC differentiation. CD49b is a unique marker during MSC osteogenic differentiation and may play a significant role in osteoasarcoma malignant transformation. In the future we plan to determine the function and mechanism of CD49b during MSCs osteogenic differentiation and osteosarcoma malignant transformation in vitro. We will define the clinical significance of CD49b in osteosarcoma through immunohistochemistry of patient samples and functional analyses. Citation Format: Tingting Ren, Sajida Piperdi, Amy Y. Park, Richard Gorlick. Screening and identification of key surface markers of mesenchymal stem cell osteogenic differentiation and osteosarcoma development. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1418. doi:10.1158/1538-7445.AM2015-1418
545. Syngeneic AAV Pseudo-Vectors Potentiates Full Vector Transduction
Authors: Qizhao Wang, Biao Dong, Katie A. Pokiniewski, Jenni Firrman, Zhongren Wu, Mario P.s. Chin, Yong Diao, Ruian Xu, Weidong Xiao
Journal: Molecular Therapy (2016)

An excessive amount of empty capsids are generated during regular AAV vector production process. These pseudo-vectors often remain in final vectors used for animal studies or clinical trials. The potential effects of these pseudo-vectors on AAV transduction have been a major concern. In the current study, we systemically examined how the AAV pseudo-vectors interact with the full AAV vectors in the transduction processes. Three different types of AAV pseudo-vectors were used: syngeneic AAV pseudo-vector (sAAV, purified from the full AAV vector preparation with the same reporter gene), null AAV pseudo-vector (nAAV, produced by using AAV packaging plasmid and adenoviral helper plasmid), and allogeneic AAV pseudo-vector (aAAV, purified from the AAV vector preparation with a genome different to reporter gene). All three AAV2 pseudo-vectors exhibited inhibition effects on full AAV2 vectors particle transduction in a dose dependent manner in vitro. AAV2 pseudo-vectors not only inhibited full AAV2 vector transduction but also decreased gene expression from full AAV8 vectors. However, sAAV2 pseudo-vectors exhibited less inhibition effects on the transduction efficiency of full AAV2 or AAV8 vectors compared with nAAV2 or aAAV2 pseudo-vectors in vitro. In contrast, all three kinds of AAV8 pseudo-vectors did not show such inhibition effects on full AAV8 and AAV2 vectors in vitro or in vivo. Moreover, the sAAV8 pseudo-vector enhanced its full AAV8 vector transduction while nAAV8 and aAAV8 pseudo-vector did not have similar effects. Nine fold sAAV8 pseudo-vectors increased AAV8-TTR-hF8-X5 transduction by 2~5-fold in two different hemophilia A mouse models as measured the coagulation activity of factor VIII by aPTT assays and antigen levels by Elisa. Further characterization showed that sAAV8 and aAAV8 pseudo-vectors contain DNAs of varying sizes. In general, these DNAs still have AAV ITR sequences and partial vector genomes near ITRs. It is likely that such partial genome could anneal to the full AAV genomes and facilitate the second strand DNA synthesis thus increasing full AAV transduction.
Usefulness of Functional Image Analysis Using Positron Emission Tomography for the Discrimination between Hypoplastic Myelodysplastic Syndromes and Aplastic Anemia.
Authors: Masaaki Takatoku, Toshihiko Sato, Kaoru Hatano, Ken Omine, Masaki Mori, Kazuo Muroi, Tadashi Nagai, Keiya Ozawa
Journal: Blood (2005)
Abstract P212: Circulating Homocysteine, Aldosterone and Brain Natriuretic Peptide Levels Predict the Development of Metabolic Syndrome and Longitudinal Changes in Metabolic Syndrome Components: Findings from fhe Jackson Heart Study
Authors: Solomon K Musani, Ramachandran S Vasan, Aurelian Bidulescu, Jiankang Liu, Herman A Taylor, Ervin R Fox
Journal: Circulation (2012)

Background: The relative contribution of selected circulatory biomarkers that represent distinct biological pathways to the incidence of metabolic syndrome (MetS) in African Americans is not well elucidated despite the greater prevalence of cardiovascular diseases in this ethnic group. Thus, we aimed to assess the relative contribution of a panel of representative cardiometabolic biomarkers with the hypothesis that they are predictors of incident MetS and longitudinal changes in MetS components. Materials and Methods: At the end of the second JHS examination cycle (average 4.7 years from baseline), 178 participants of the total 1055 without prevalent MetS at baseline had developed MetS. We selected informative markers from a panel of 7 representing inflammation (C - reactive protein and leptin), neurohormonal activity (aldosterone, BNP, cortisol), and endothelial function (endothelin and homocysteine) that were significantly associated with incident metabolic syndrome (MetS). Biomarker selection was performed using stepwise selection in multivariable logistic regression models. We adjusted for baseline age, gender, systolic and diastolic BP, log triglycerides, fasting glucose and HDL cholesterol, and waist circumference measurements. Results: Serum homocysteine, aldosterone and B-natriuretic peptide (BNP) concentration were retained as significantly associated with incident MetS, with p-values 0.037, 0.008 and 0.022, respectively. The multivariable adjusted OR (95%CI) were 1.28 (1.02 to 1.62) for homocysteine; 1.33 (1.08 to 1.65) for aldosterone, and 2.47 (1.31 to 4.66) for 2nd BNP quartile compared to the first quartile. In multivariable analyses evaluating longitudinal change in MetS components (analyzed as continuous variables); homocysteine was significantly and positively associated with diastolic BP. Serum aldosterone was associated with all MetS risk factors, while higher levels of plasma circulating BNP were associated with all risk factors except sex-standardized waist circumference. Discussion and Conclusions: Higher circulating homocysteine and aldosterone levels were directly associated with the development of MetS and with longitudinal change of its components except HDL cholesterol and sex standardized waist circumference, which were negatively associated with aldosterone. The second and fourth quartiles of circulating plasma BNP concentration were significantly associated with greater odds of developing MetS than the first quartile. Further, higher concentration of BNP was associated with positive changes in all risk components except for HDL cholesterol and waist circumference. These results suggest that the biomarkers and their related pathways are essential in mediating metabolic risk in African Americans.
Predicting prognosis of patients with advanced hepatocellular carcinoma treated with antiangiogenic therapy using the CUPI and CLIP staging systems.
Authors: Y. Y. Shao, C. Hsu, Z. Lin, C. Hsu, A. Cheng
Journal: Journal of Clinical Oncology (2011)

e14669 Background: Antiangiogenic therapy, especially sorafenib, has become the most important treatment for advanced hepatocellular carcinoma (HCC). Staging systems that correlate best with the prognosis of this group of patients are unclear. Methods: Advanced HCC patients who had been enrolled in three prospective phase II trials of first-line anti-angiogenic therapies were analyzed. Clinicopathologic characteristics, as well as corresponding staging scores according to AJCC, BCLC, Okuda, CLIP, JIS, CUPI, Tokyo, and GETCH staging systems, were analyzed for their correlation with overall survival (OS). Results: A total of 122 patients were included; 110 (90%) were male and 91 (75%) had chronic hepatitis B virus infection. All patients were of Child-Pugh class A liver reserve. The median OS was 6.0 months (95% C.I., 4.4-7.6). In multivariate analysis of clinicopathologic characteristics for prognostic prediction, male, liver involvement over 50% or infiltrative disease, hepatitis B/C virus co-infection, ECOG 1, high AFP and high ALP were independent predictors for poorer OS. By log rank test, CLIP (p < 0.001), CUPI (p < 0.001), Okuda (p < 0.001), Tokyo (p = 0.001), and GETCH (p = 0.005) staging systems were capable of differentiating OS. GETCH, CUPI, and CLIP had the highest concordance indexes (C-indexes) (0.80, 0.78 and 0.74, respectively). When all the staging systems were examined together for prediction of OS by Cox’s proportional hazards model, CUPI and CLIP stood out in the final model as best staging systems for the prediction of OS. Conclusions: Among current staging systems of HCC, CUPI and CLIP have the best prognosis-prediction power in this patient group. This study was supported by the grants of DOH98-TD-B-111-001 and DOH99-TD-B-111-001.
Panobinostat As Salvage Treatment for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Not Eligible to High Dose Therapy: A Phase II Study of the Fondazione Italiana Linfomi (FIL)
Authors: Francesco Zaja, Stefano Volpetti, Annalisa Chiappella, Flavia Salvi, Angelo M. Carella, Adalberto Ibatici, Pier Paolo Piccaluga, Stefano A. Pileri, Davide Rossi, Pier Luigi Zinzani, Caterina Patti, Umberto Vitolo, Alfonso D'Arco, Alessandra Tucci, Silvia Franceschetti, Andrea Evangelista, Valentina Lenti, Renato Fanin, Alessandro Levis
Journal: Blood (2014)
IKZF1 Deletion Is An Independent Predictor of Outcome In Pediatric Acute Lymphoblastic Leukemia Treated According to the ALL-BFM 2000 Protocol
Authors: Petra Breithaupt, Barbara Meissner, Martin Zimmermann, Anja Möricke, André Schrauder, Jochen Harbott, Wolf-Dieter Ludwig, Rolf Köhler, Claus R Bartram, Martin Schrappe, Gunnar Cario, Martin Stanulla
Journal: Blood (2010)
Single molecule RNA sequencing of formalin-fixed paraffin-embedded tissue derived from patients with lung cancer.
Authors: A. J. Yee, T. Raz, A. Amzallag, D. Lipson, E. Giladi, H. Lopez, D. R. Borger, M. Mino-Kenudson, J. F. Thompson, A. J. Iafrate, P. Milos, D. A. Haber, S. Ramaswamy
Journal: Journal of Clinical Oncology (2011)

10550 Background: Next generation sequencing has revolutionized the study of cancer biology by providing an unprecedented view of cancer genomes. However, high throughput sequencing has conventionally utilized fresh frozen tissue collected for research prospectively. The ability to apply this tool to formalin-fixed, paraffin-embedded (FFPE) clinical specimens, where nucleic acid integrity is not optimal and where next generation sequencing has been challenging, would enable its use to improve patient care and clinical research. Methods: Total RNA was extracted from FFPE blocks of 7 lung adenocarcinomas and matching normal lung tissue for 6 of the 7 tumors. Genotype information for selected mutation alleles in EGFR, TP53, etc. was previously determined using the SNaPshot single nucleotide polymorphism genotyping platform. Ribosomal RNA was depleted using biotinylated oligos targeting 28S and 18S ribosomal subunits. cDNA was synthesized using random hexamers. Whole transcriptome sequencing was performed using the Helicos BioSciences Heliscope single molecule sequencer. Sequences were aligned to reference human transcriptome and genome as well as a reference of mutation alleles. Results: Ribosomal RNA depletion increased mRNA yield from ~20% to ~35% of RNA species sequenced. We obtained ~10 million aligned mRNA reads per sample. We re-identified clinically relevant EGFR exon 19 deletions in two samples. In another sample, we discovered an exon 20 insertion in EGFR that was not previously appreciated. In a fourth sample, we were able to detect the presence of an EML4-ALK fusion through the integration of sequence and expression information. Conclusions: This study shows that RNA sequencing from FFPE patient samples is feasible, and in cases where gene expression is sufficient, enables the determination of clinically relevant mutations. These findings represent the initial step towards leveraging the power of next generation sequencing into a comprehensive diagnostic and clinical research tool.
Hematopoietic Stem Cell Transplantation (SCT) for Hematologic Malignancy from 10/10 Matched Unrelated Donors (MUD) with a Myeloablative Once Daily IV Fludarabine (Flu)/Busulfan Based Regimen (FLUBUP) with Thymoglobulin: Outcomes According to Stem Cell Source.
Authors: James A. Russell, M. Ahsan Chaudhry, Michelle Geddes, Nizar J. Bahlis, Mary Lynn Savoie, Loree M. Larratt, Diana M. Quinlan, A. Robert Turner, Alexander Balogh, Jan Storek, Christopher Brown, Douglas A. Stewart
Journal: Blood (2006)
Survival After Early-Stage Breast Cancer of Women Previously Treated for Depression: A Nationwide Danish Cohort Study
Authors: Nis P. Suppli, Christoffer Johansen, Lars V. Kessing, Anita Toender, Niels Kroman, Marianne Ewertz, Susanne O. Dalton
Journal: Journal of Clinical Oncology (2017)

Purpose The aim of this nationwide, register-based cohort study was to determine whether women treated for depression before primary early-stage breast cancer are at increased risk for receiving treatment that is not in accordance with national guidelines and for poorer survival. Material and Methods We identified 45,325 women with early breast cancer diagnosed in Denmark from 1998 to 2011. Of these, 744 women (2%) had had a previous hospital contact (as an inpatient or outpatient) for depression and another 6,068 (13%) had been treated with antidepressants. Associations between previous treatment of depression and risk of receiving nonguideline treatment of breast cancer were assessed in multivariable logistic regression analyses. We compared the overall survival, breast cancer-specific survival, and risk of death by suicide of women who were and were not treated for depression before breast cancer in multivariable Cox regression analyses. Results Tumor stage did not indicate a delay in diagnosis of breast cancer in women previously treated for depression; however, those given antidepressants before breast cancer had a significantly increased risk of receiving nonguideline treatment (odds ratio, 1.14; 95% CI, 1.03 to 1.27) and significantly worse overall survival (hazard ratio, 1.21; 95% CI, 1.14 to 1.28) and breast cancer-specific survival (hazard ratio, 1.11; 95% CI, 1.03 to 1.20). Increased but nonsignificant estimated risks were also found for women with previous hospital contacts for depression. In subgroup analyses, the association of depression with poor survival was particularly strong among women who did not receive the indicated adjuvant systemic therapy. Conclusion Women previously treated for depression constitute a large subgroup of patients with breast cancer who are at risk for receiving nonguideline breast cancer treatment, which probably contributes to poorer overall and breast cancer-specific survival.
Chemotherapy Versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome Following Allogeneic Stem Cell Transplant: A Retrospective Review
Authors: Ibraheem H Motabi, Jingxia Liu, Camille N. Abboud, Amanda F. Cashen, Keith E. Stockler-Goldstein, Geoffrey L. Uy, Ravi Vij, Peter Westervelt, John F. DiPersio
Journal: Blood (2014)