tbuckley/cabot-search huggingface dataset:
Salvage chemotherapy with irinotecan and nedaplatin for cisplatin refractory germ cell tumors
Authors: T. Nakamura, N. Nonomura, K. Mikami, T. Shiraishi, N. Takaha, A. Okuyama, T. Miki
Journal: Journal of Clinical Oncology (2009)

e16022 Background: Only 20 - 30 % of patients with cisplatin (CDDP) refractory germ cell tumor (GCT) will remain continuously disease-free with salvage chemotherapy. The present study investigated the combination chemotherapy with irinotecan (Ir) and nedaplatin (CDGP), the second generation derivative of CDDP developed in Japan, as salvage chemotherapy for CDDP-refractory GCT. Methods: Between June 1998 and December 2007, 39 CDDP refractory GCT patients treated with irinotecan and CDGP (IrN therapy) were assessed retrospectively. IrN therapy consisted of Ir: 100–150 mg/m 2 on day 1, 15 or 200–300 mg/m 2 on day 2, CDGP: 100 mg/m 2 on day 1 every four weeks with oral administration of Chinese-herb ‘Hange-shashinto’ and sodium bicarbonate for diarrhea. After tumor marker normalization, residual masses were resected and chemotherapy was continued in the case of without marker normalization. Results: The median age was 31 years old (range; 17–48). The median number of cycles of prior chemotherapy was 6 (range; 2–30). The median number of cycles of IrN therapy was 3 (range: 1–9). The response rate was 30.8% ( CR: 0%, PR m− : 15.4%, PR m+ : 15.4% ) and the outcome was no evidence of disease (NED) 46.2%, alive with disease (AWD) 25.6% and dead 28.2%, respectively. Twenty-five patients with IrN therapy as 2nd (17 cases) and 3rd (8 cases) line salvage therapy showed that the response rate was 48% (CR: 0%, PR m− : 16.0%, PR m+ : 16.0, NC m− : 16.0%) and the outcome was as follows; NED 64%, AWD 16% and dead 20%, respectively. On the other hand, 14 pts who had the treatment as fourth-line or more showed less response rate (PR: 28.5%) and worse outcome (NED 14.2%). Major adverse events more than grade 3 were neutropenia and thrombocytopenia. These adverse events were manageable. Grade 4 diarrhea which was major adverse event of CPT-11 was observed in only one case and there was no treatment related death. Conclusions: This study demonstrates that combination chemotherapy with CPT-11 and CDGP showed significant anticancer activity for patients with CDDP-refractory GCT without severe adverse events. These findings suggest that salvage IrN therapy may be one of the options as second- or third-line therapy. No significant financial relationships to disclose.
Impact of adverse effects of bevacizumab on survival outcomes of patients with recurrent glioblastoma.
Authors: Mohamed Ali Hamza, Carlos Kamiya Matsuoka, John Frederick De Groot
Journal: Journal of Clinical Oncology (2014)

2075 Background: Bevacizumab (bev) is widely used for treatment of patients with recurrent glioblastoma (GB). Adverse effects (AEs) to bev or bev-containing regimens can cause discontinuation of treatment. The effects of these adverse effects on survival outcomes are not well defined. Methods: In this retrospective chart review, we identified patients with recurrent GB, who were treated with BEV alone or BEV-containing regimens between 2006 and 2011, and who discontinued bev treatment either because of AEs (bleeding, stroke, hypertension, renal disease or low blood counts) or because of physician’s decision. We excluded those who had disease progression before discontinuation. Data was analyzed to determine overall survival (OS) and progression free survival (PFS). Results: A total of 65 patients were identified, of whom 39 patients who discontinued bev because of AEs and 26 patients who discontinued bev because of physician’s decision. There were no significant differences in age, performance status, extent of resection, number of lesions, time from diagnosis to first recurrence, time from diagnosis to start of bev, number of recurrences before bev start, and duration of bev treatment between the two groups. Patients who discontinued bev because of AEs progressed earlier after bev discontinuation (3.9 months vs 5.7 months, P= 0.02), had significantly lower PFS (10.4 months vs 14.2 months, p = 0.01) and had significantly lower OS from bev start (13.9 months vs 32.5 months, P = 0.009) and lower OS from diagnosis (20 months vs 49.3 months, p=0.007) when compared to patients who discontinued bev because of physician’s decision. Conclusions: In patients with recurrent GB who were treated with bev, discontinuation of bev because of AEs is associated with earlier progression and shorter OS when compared with patients who discontinued bev because of physician’s decision. These results indicate that AEs to bev or bev-containing regimens are associated with unfavorable glioma-related outcomes in patients with recurrent GB.
Secondary Leukemia (Sl)/Myelodysplasia (MDS) and Bone Marrow (BM) Chromosomal Aberrations after Dose-Intensive Chemotherapy for Neuroblastoma (NB).
Authors: Brian H. Kushner, Kim Kramer, Shakeel Modak, Suresh C. Jhanwar, Nai-Kong V. Cheung
Journal: Blood (2004)
Preliminary phase III efficacy and safety of alemtuzumab vs chlorambucil as front-line therapy for patients with progressive B-cell chronic lymphocytic leukemia (BCLL)
Authors: P. Hillmen, A. Skotnicki, T. Robak, B. Jaksic, A. Dmoszynska, C. Sirard, J. Mayer
Journal: Journal of Clinical Oncology (2006)

6511 Background: Phase 3, open-label, randomized comparative trial, enrolled Rai stage I-IV BCLL patients with previously untreated, progressive disease requiring treatment. Objectives: Compare efficacy and safety of alemtuzumab (CAMPATH [(CAM]) to chlorambucil (CHLO) as front-line therapy. Methods:Patients were randomized 1:1 to CAM 30 mg IV 3x/week for a maximum of 12 weeks (wks) or CHLO 40 mg/m 2 PO once every 28 days, to a maximum of 12 cycles. All CAM patients received prophylactic antibiotic (trimethoprim/sulfamethoxazole DS) and antiviral (famciclovir) treatment during therapy and until CD4 + counts were ≥200 cells/μL. The primary endpoint was progression free survival; secondary endpoints included safety, response rate and overall survival. Results: Accrual completed in July 2004 with 297 patients enrolled (213 males, 84 females; median age 60 years); CAM n=149 and CHLO n=148. Treatment arms were balanced for key prognostic factors analyzed to date. Most patients had performance status 0–1 (96%) and maximum lymph nodes &lt;5cm (70%). Median length of treatment with CAM = 11.7 wks, CHLO = 24.4 wks. The design provided for investigator assessment and an independent review of response (IRR). Preliminary data from the IRR are presented. Response rate for CHLO was consistent with historical data. Safety data indicate 34.7% of CAM patients and 19.7% of CHLO patients experienced a serious adverse event, with 21.1% and 4.1% considered drug related, respectively. The incidence of grade 3/4 thrombocytopenia and anemia were comparable in both treatment arms. Grade 3/4 neutropenia (42.2% vs 23.1%), infections (excluding CMV) (14.3% vs 6.8%), and CMV infections (6.8% vs 0%) were more frequent in the CAM arm. One treatment related death occurred in the CHLO arm. Conclusions: Preliminary efficacy and safety data confirm therapy naïve BCLL patients treated with single agent CAM have an excellent response rate with a manageable toxicity profile. [Table: see text] [Table: see text]
CBIO-03. XAF1, AS A NOVEL SUPPRESSOR, HAS A CRITICAL ROLE FOR TEMOZOLAMIDE-INDUCED AMPK-MEDIATED CELL DEATH IN HUMAN GLIOBLASTOMA
Authors: Shin-Hyuk Kang, Min-Goo Lee, Mi Ok Yu, Hyungsin Kim, Kyung-Jae Park, Yong-Gu Chung, Sung-Gil Chi
Journal: Neuro-Oncology (2016)

XIAP-associated factor 1 (XAF1) is a proapoptotic tumor suppressor that is originally identified as an antagonist of the caspase-inhibiting activity of XIAP. To explore the XAF1’s candidacy for a suppressor in the pathogenesis of glioblastoma, its expression status and function were investigated in glioblastoma cell lines and tissues. XAF1 expression was easily detectable in normal tissues, but undetectable or very low in 86% (6 of 7) of glioma cell lines and 75% (12 of 16) of primary glioma tissues. XAF1 downregulation was significantly more common in high grade tumors versus low grade tumors, and its expression was re-activated in tumor cells following treatment with the demethylating agent 5-aza-dC. Hypermethylation at 7 CpG sites in the 5’ proximal region of the XAF1promoter was highly prevalent in cancers versus normal tissues and tightly associated with reduced gene expression. Intriguingly, XAF1 expression was strongly up-regulated by temozolomide and its induction was crucial for temozolamide-induced AMPK activation. In addition, XAF1 expression suppressed tumor cell growth and enhanced cellular response to apoptotic stresses in a XIAP-independent manner while knockdown of its expression protected cells from the stresses. Furthermore, it was also found that XAF1 increases the stability of phosphorylated AMPK. As predicted, XAF1 elevation was tightly associated with enhanced tumor cell sensitivity to temozolomide while XAF1 depletion greatly attenuated the growth inhibition effect of temozolomide. Collectively, this study demonstrates that epigenetic alteration of XAF1 may contribute to the malignant progression of human glioblastoma by rendering tumor cells a survival advantage partially through the attenuation of AMPK signaling.
479P The impact of initial symptoms on survival time in advanced non-small cell lung cancer
Authors: T. Miyawaki, S. Yagishita, R. Ko, Y. Suzuki, N. Matsumoto, M. Hara, N. Iwakami, M. Fujii, S.-I. Iwakami, K. Takahashi
Journal: Annals of Oncology (2016)
Notes on the Epidemiology of Enteric Fevers in the Federated Malay States.
Journal: JAMA (1928)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The influence of nodal status on progression outcomes in patients with prostate cancer: Data from the Early Prostate Cancer program at 7.4 years
Authors: P. Iversen, M. P. Wirth, W. A. See, D. G. McLeod, T. Morris, J. Armstrong
Journal: Journal of Clinical Oncology (2006)

4628 Background: The Early Prostate Cancer (EPC) program is an ongoing study of the effect of adding bicalutamide (CASODEX) 150 mg to standard care (radiotherapy [RT], radical prostatectomy [RP], or watchful waiting [WW]) for men with localized or locally advanced prostate cancer. At a median 7.4 years’ follow-up, bicalutamide significantly improved objective progression-free survival (PFS) in men with locally advanced disease, irrespective of standard care, and improved overall survival in the RT setting. There was no PFS benefit in patients with localized disease. Lymph-node involvement is an established risk factor for progression, so we conducted an exploratory analysis among patients with locally advanced disease to assess the influence of this risk factor on PFS. Methods: The EPC program (n = 8113) comprises 3 randomized trials designed for combined analysis. Patients with localized (T1–2, N0/Nx) or locally advanced (T3–4, any N; or any T, N+) non-metastatic prostate cancer received bicalutamide (n = 4052) or placebo (n = 4061) once daily plus standard care. This subanalysis studied the effect of nodal status (N−, N+, Nx) in locally advanced disease. Results: In patients with locally advanced disease, PFS improvements were irrespective of nodal status. The treatment effect increased as the risk of progression increased from N− to Nx to N+ disease. The greatest reduction in risk was seen in RP patients with N+ disease. Conclusions: The reduction in risk of progression with bicalutamide was seen irrespective of nodal status. The most significant reduction in risk of progression was in RP patients with N+ disease; survival data by nodal status for these patients will be presented. [Table: see text] [Table: see text]
Biofabrication: Single Cell Microgel Based Modular Bioinks for Uncoupled Cellular Micro- and Macroenvironments (Adv. Healthcare Mater. 3/2017)
Authors: Tom Kamperman, Sieger Henke, Albert van den Berg, Su Ryon Shin, Ali Tamayol, Ali Khademhosseini, Marcel Karperien, Jeroen Leijten
Journal: Advanced Healthcare Materials (2017)

Modular bioinks based on single-cell-laden microgels are engineered using droplet microfluidics and leveraged to uncouple micro- and macroenvironments of biomaterials by Marcel Karperien and co-workers in article 1600913. These inks enable straightforward biofabrication of 3D constructs that recapitulate the multiscale modular design of native tissues with a single cell resolution. This approach represents a major step forward in endowing engineered constructs with the multifunctionality that underlies the behavior of native tissues.
Efficacy of Recombinant Human C1 Esterase Inhibitor (rhC1INH) Across Anatomical Locations in Acute Hereditary Angioedema (HAE) Attacks
Authors: James W. Baker, Jonathan A. Bernstein, J.R. Harper, A. Relan, Marc A. Riedl
Journal: Journal of Allergy and Clinical Immunology (2017)
NCCN Invasive Breast Cancer Clinical Practice Guidelines in Oncology
Authors: Robert W Carlson, Benjamin O Anderson, Harold J Burstein, W Bradford Carter, Stephen B Edge, William B Farrar, Lori J Goldstein, William J Gradishar, Daniel F Hayes, Clifford A Hudis, Mohammad Jahanzeb, Britt-Marie Ljung, Krystyna Kiel, Lawrence B Marks, Beryl McCormick, Lisle M Nabell, Lori J Pierce, Elizabeth C Reed, Samuel M Silver, Mary Lou Smith, George Somlo, Richard L Theriault, John H Ward, Eric P Winer, Antonio C Wolff
Journal: Journal of the National Comprehensive Cancer Network (2007)

The American Cancer Society estimates that 214,640 new cases of breast cancer will be diagnosed and 41,430 will die of the disease in the United States in 2006. Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The incidence of breast cancer has steadily increased in the United States over the past few decades, but breast cancer mortality appears to be declining, suggesting a benefit from early detection and more effective treatment. These guidelines discuss diagnosis, treatment, and follow up for invasive breast cancer. For the most recent version of the guidelines, please visit NCCN.org
Efficacy and safety of cobimetinib (cobi) and atezolizumab (atezo) in an expanded phase 1b study of microsatellite-stable (MSS) metastatic colorectal cancer (mCRC)
Authors: J. Desai, Y.S. Hong, J.E. Kim, T.W. Kim, S.W. Han, Y.-J. Bang, C.E. Chee, V.Y.M. Heong, A. McRee, L.Q. Chow, E.L. Kwak, J.R. Infante, J. Wallin, M. Das Thakur, G. Mwawasi, P. Foster, E. Cha, J.C. Bendell
Journal: Annals of Oncology (2016)
P08.08 Expression level of miRNAs on chromosome 14q32.31 region correlates with survival of glioblastoma patients
Authors: T. Shahar, A. Granit, D. Zrihan, T. Canello, H. Charbit, U. Rozovski, S. Elgavish, Z. Ram, T. Siegal, I. Lavon
Journal: Neuro-Oncology (2016)

AbstractBackground:The 54 miRNAs within the DLK-DIO3 genomic region on chromosome 14q32.31 (cluster 14 miRNAs) are organized into sub-clusters 14A and 14B. These miRNAs are downregulated in glioblastomas and might have a tumor suppressive role. Any association between the expression levels of cluster 14 miRNAs with overall survival (OS) is undetermined.Method:We randomly selected miR-433, belonging to subcluster 14A and miR-323a-3p and miR-369-3p, both belonging to subcluster 14B, and assessed their role in in vitro glioblastoma cell lines. We also determined the expression level of cluster 14 miRNAs in tumor samples obtain from tumor bank tissues of 28 patients with newly diagnosed glioblastoma. We analyzed the association between cluster 14 miRNAs expression level and OS.Results:Overexpression of miR-323a-3p and miR-369-3p, but not miR-433, in glioblastoma cells inhibited their proliferation and migration in in-vitro studies. Bioinformatics analysis identified 13 putative target genes of cluster 14 miRNAs, and real-time RT-PCR validated these findings. Pathway analysis of the overexpressed transcripts identified neuregulin (glial growth factor) as the most enriched pathway. The expression level of cluster 14 miRNAs correlated with the patients’ OS. The median OS was 8 months for patients with low expression levels and 32.5 months for patients with high expression levels (HR = 0.37; 95% CI 0.12–0.64, P = .005).Conclusions:The expression level of cluster 14 miRNAs correlates with OS, suggesting a role for cluster 14 miRNAs in promoting aggressive behavior of glioblastoma, possibly through neuregulin signaling.
PDTB-14. INVESTIGATING HISTONE H3 POST-TRANSLATIONAL MODIFICATIONS USING PARAFFIN-EMBEDDED PEDIATRIC GLIOMA TISSUE SAMPLES
Authors: Amanda Saratsis, Tina Huang, Andrea Piunti, Rintaro Hashizume, Elizabeth Bartom, Tadanori Tomita, C. David James, Ali Shilatifard
Journal: Neuro-Oncology (2016)

Mutant Histone H3 protein is increasingly thought to play a role in pediatric gliomagenesis. Chromatin immunoprecipitation sequencing (ChIP-Seq) is a powerful method for studying the epigenetic effects of histone protein modifications. However, analysis of rare or surgically-inaccessible tumors, such as pediatric diffuse intrinsic pontine glioma (DIPG), is often precluded by the relative paucity of fresh tissue available, while tumor primary cell lines may not accurately reflect the tumor epigenome. ChIP-Seq of formalin-fixed, paraffin-embedded (FFPE) tumor samples, derived via tumor biopsy or autopsy, could therefore provide valuable insight to tumor biology in lieu of fresh tissue. Here we present, to our best knowledge, the first successful ChIP-Seq of FFPE pediatric brain tumor tissue, as an alternative to fresh tissue analysis. Archival FFPE pediatric glioma tissue (n=8) was used to evaluate Histone H3K27M mutation status via Sanger Sequencing and genomic deposition of H3K27M, H3K4me3 and H3K27ac via ChIP-Seq. Four 20-micron FFPE sections were deparaffinized then rehydrated via ethanol incubation at decreasing concentrations. Extracted chromatins were sonicated to produce DNA fragments for subsequent ChIP-Seq analyses. ChIP-Seq libraries were prepared using the KAPA HTP Library Preparation Kit and sequenced on the Illumina NextSeq 500 Sequencing System. Successful extraction of chromatins was achieved from H3K27 wild-type FFPE Juvenille Pilocytic Astrocytoma tissue (n=1). ChIP-Seq revealed genomic enrichment of H3K4me3 and H3K27ac, consistent with known patterns of gene expression regulation in pediatric glioma. Analysis of H3K27M DIPG specimens is currently underway (n=7) for comparison to ChIP-Seq results from DIPG primary cell lines (n=2). We present the technical feasibility of FFPE pediatric glioma ChIP-Seq. Epigenetic analysis of FFPE tumor tissue, which may be more accessible than fresh tumor samples, could provide new insight into tumor biology and identify novel therapeutic targets for improved patient outcomes in rare but highly aggressive tumors, such as DIPG.
TMIC-26. EXPLORATION OF TRYPTOPHAN METABOLISM VIA THE KYNURENINE PATHWAY IN HUMAN GLIOMAS
Authors: Anthony R. Guastella, Sam Kiousis, Neil V Klinger, Sharon K Michelhaugh, Sandeep Mittal
Journal: Neuro-Oncology (2016)

The kynurenine pathway (KP) is responsible for a majority of the catabolism of the essential amino acid tryptophan, and recently was implicated in the pathophysiology of human gliomas. The KP generates various active metabolites, is the main source of the essential co-factor nicotinamide adenine dinucleotide (NAD+), and plays a pivotal role in promoting anti-tumor immune suppression through depleting local tryptophan and causing T-cell growth arrest. Kynurenine, a KP metabolite, was recently discovered to be an endogenous ligand of the aryl hydrocarbon receptor (AHR), a transcription factor associated with carcinogenesis. We hypothesized that higher-grade gliomas will have a more dysregulated KP, and therefore sought to examine the potential differences in KP expression in low- versus high-grade gliomas. Active tumor tissue was acquired immediately following microsurgical resection, and the tumor was dissociated into a single-cell suspension for performance of in vitro experiments. Immunohistochemical staining of Grade II, III, and IV glioma (glioblastoma: GBM) patient tumor sections with antibodies specific for: human indoleamine 2,3-dioxygenase (IDO) 1; IDO2; tryptophan 2,3-dioxgyenase (TDO2); kynureninase; kynurenine 3-monooxygenase (KMO); and AHR. Tissue sections were scored from 0-3 based on staining intensity. Patient-derived tumor cell cultures were treated with commercially available small molecule inhibitors for IDO1 (epacadostat), IDO2 (chloroquine), TDO2 (680C91), KMO (Ro61-8048), and AHR (CH-223191) for 48-hours. GBM tissues show significantly (p<0.001, ANOVA) higher levels of KP enzymes and AHR compared to Grade II and Grade III tissues. In vitro drug treatment showed markedly diminished cell proliferation via MTT assay in response to chloroquine and CH-223191. The increased staining of KP enzymes, as well as the diminished proliferation with the inhibitors, suggests that the KP plays a role in malignant gliomas, and may offer novel therapeutic targets for a patient population with highly limited treatment options.
Metabolic Tumor Volume Influences Response to Brentuximab-Vedotin in Relapsed Refractory Hodgkin Lymphoma
Authors: Yassine Al Tabaa, Michel Meignan, Scherman Elodie, Corinne Haioun, Pauline Brice, Catherine Thieblemont, Pascal Merlet, Denis Mariano Goulart, Guillaume Cartron
Journal: Blood (2015)
Identifying the Outliers Among Gene Expression Profiling (GEP)-Defined Low-Risk Myeloma Patients Treated with Total Therapy 2 and 3 (TT2, TT3)
Authors: Frits van Rhee, Sarah Waheed, Saad Z Usmani, Joshua Epstein, Adam Rosenthal, Christoph Heuck, Jameel Muzaffar, Al-Ola Abdallah, Nathan M Petty, Clyde Bailey, Antje Hoering, Bart Barlogie
Journal: Blood (2012)
Utility of a targeted NGS oncology assay for circulating tumor DNA in a multi-histology clinical setting
Authors: T. Eerkes, A. Ademi Santiago-Walker, M. Loreen, L. Lim, J. Hernandez, C. Raymond, S. Henderson, D. Dipasquo, T. Shaffer, C. Motely, C. Moy, S. Wallace, K. Eaton, J. Karkera, M. Li
Journal: Annals of Oncology (2016)
Government should ringfence funding for national cancer strategy, urges charity
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Funding to deliver the government’s cancer strategy for England must be ringfenced if the plan is to succeed by 2020, a leading charity has said.

The five year blueprint for improving cancer outcomes was launched in 20151 after an independent task force set out six strategic priorities that included an emphasis on prevention and a renewed focus on early diagnosis.

In a report tracking progress against the plan, Macmillan Cancer Support outlined challenges and concerns which it warned could undermine progress.2

It found mixed confidence …