tbuckley/cabot-search huggingface dataset:
Amplitude of Response, Early Mobilization (M) and Pre-Autologous Transplant (ASCT) Use of Bortezomib (V) and/or Thalidomide (T) Are Predictors of Longer Progression Free (PFS) and/or Overall Survival (OS) in Myeloma.
Authors: Meral Beksac, Ender Soydan, Vildan Ozkocaman, Pervin Topcuoglu, Berna Evranos, Merih Kizil, Aynur U. Bilgin, Mutlu Arat, Muhit Ozcan, Onder Arslan, Gunhan Gurman, Osman Ilhan
Journal: Blood (2007)
Effect of the combination of mTOR inhibitor ridaforolimus and HDAC inhibitor vorinostat on in vitro synergism in synovial sarcoma, osteosarcoma, and a range of other tumor subtypes.
Authors: S. S. Morgan, L. D. Cranmer
Journal: Journal of Clinical Oncology (2011)

10080 Background: Curative treatments for patients with metastatic synovial sarcoma (SS) do not exist, and such patients have a poor prognosis. We explored combinations of molecularly-targeted and cytotoxic agents to identify synergistic treatment combinations in SS cells. Methods: Two SS cell lines (HS-SY-II and SYO-I) were treated with single agents or combinations of molecularly targeted therapies (HDAC inhibitor, vorinostat; mTOR inhibitor, ridaforolimus) and cytotoxic agents. After 72 hours, cell viability was measured using the cell proliferation assay (MTS). Combination Indices (CI) were calculated to determine whether each combination was synergistic, additive, or antagonistic. The most active combination was selected for further confirmation in other tumor subtypes. Results: Ridaforolimus IC50 was 10.9nM in HS-SY-II and 23.1nM in SYO-I, vorinostat IC50 was 440nM in HS-SY-II and 561nM in SYO-I, doxorubicin IC50 was 9.4nM in HS-SY-II and 7.4nM in SYO-I, and melphalan IC50 was 687nM in HS-SY-II and 859nM in SYO-I. Synergism was observed in cells treated with ridaforolimus/vorinostat: CI was 0.28 and 0.63 in HS-SY-II and SYO-I, respectively. Both ridaforolimus/doxorubicin and ridaforolimus/melphalan exhibited synergism: CI ranged from 0.50 to 0.59 in HS-SY-II and SYO-I. Additive effects were observed when vorinostat was combined with doxorubicin or melphalan. Given its strong synergism, the ridaforolimus/vorinostat combination was assessed in osteosarcoma (U2OS), metastatic melanoma (Stew1 and Stew2), pancreatic cancer (Panc1 and BxPC3), and lung cancer (A549). The combination was synergistic in all cell lines: CI ranged from 0.37 to 0.77, except in Panc1, where it was additive (CI of 0.92). Conclusions: The combination of ridaforolimus and vorinostat is synergistic in vitro in SS as well as in a variety of tumor types, including osteosarcoma, melanoma, pancreatic cancer, non-small cell lung cancer. In anticipation of human studies, further in vitro studies are planned to assess the activity of this combination in other sarcomas subtypes and in vivo. Studies to assess the molecular basis for this synergism are also planned.
An Evaluation of the Effectiveness of Darbepoetin alfa 300 mcg Every 3 Weeks (Q3W) on Clinical Outcomesin Cancer Patients with Chemotherapy-Induced Anemia.
Authors: Ralph Vincent Boccia, Delong Liu, Peter Silberstein, Simon Tchekmedyian, Dianne Tomita, Greg Rossi, Greg Otterson
Journal: Blood (2004)
Early Results of a Clinical Trial Using Targeted Oncolytic Virotherapy in Kaposi Sarcoma Herpes Virus (KSHV) Associated Multicentric Castleman’s Disease (MCD).
Authors: Deirdre O’Mahony, Wendy Bernstein, Kathy Wyvill, Karen Aleman, Denise Whitby, Seth Steinberg, Giovanna Tosato, Stefania Pittaluga, Elaine S. Jaffe, Robert Yarchoan, Richard F. Little
Journal: Blood (2007)
Combined Therapy with Alemtuzumab and Pentostatin Is Feasible and Effective in T- Lymphoprolifertive Disorders.
Authors: Farhad Ravandi-Kashani, Hagop Kantarjian, Srdan Verstovsek, Alessandra Ferrajoli, William Wierda, Shirley Odinga, Xueling Huang, Sherry Pierce, Stefan Faderl, Francis Giles, Susan O’Brien, Michael Keating
Journal: Blood (2005)
Chromosomal deletions, tumor phenotype, and prognosis in prostate cancer.
Authors: S. Minner, A. Krohn, L. Burkhardt, P. Tennstedt, R. Simon, H. Sirma, H. Huland, G. Sauter, T. Schlomm
Journal: Journal of Clinical Oncology (2011)

37 Background: Chromosomal deletions are frequent in prostate cancer (PCa) but target genes and potential clinical significance are often unknown. This project aimed at the identification of frequent and new deletions in PCa and to study their association with tumor phenotype and PSA recurrence. Methods: Array CGH was performed on 77 advanced PCa. Deletions of interest were subsequently analyzed on a tissue microarray containing more than 2000 PCa with clinical follow-up data using fluorescence in situ hybridization (FISH). The FISH probes used included a break-apart probe for TMPRSS2-ERG and dual-labeling probes for centromere 10/PTEN and centromere 3/3p14. Results: The most frequent circumscribed deletions found by array CGH were 3p14 (including FOXP1) in 18%, 5q31 in 16%, 5q21 in 14%, 6q13 in 21%, 6q21 in 19%, 6q26 in 14%, 8p11 in 17%, 10q23 (including PTEN) in 18%, 12p13 in 14%, 13q14 in 14%, 16q24 in 22% and 21q (representing TMPRSS2-ERG fusion) in 18%. TMPRSS2-ERG fusions, PTEN and FOXP1 deletions were selected for FISH analysis. A TMPRSS2-ERG fusion was observed in 394 of 947 interpretable cases (41.6%). TMPRSS2-ERG fusion was unrelated to tumor stage, Gleason grade, and PSA recurrence. PTEN deletions were observed in 8.9% of 1844 interpretable cases and were associated with advanced tumor stage (p&lt;0.0001), high Gleason grade (p&lt;0.0001), and early biochemical recurrence (p&lt;0.0001). FOXP1 deletions were seen in 5.0% of 619 cases. FOXP1 deletions were not significantly linked to tumor phenotype and outcome. Both PTEN and FOXP1 deletions were strongly linked to TMPRSS2-ERG fusions. TMPRSS2-ERG fusion positive tumors had PTEN deletions in 15.4% and FOXP1 deletions in 10.7%, while TMPRSS2-ERG fusion negative cancers had PTEN deletions in only 5.8% and FOXP1 deletions in only 2.0% of cases (p&lt;0.0001 each). Conclusions: The TMPRSS2-ERG fusion determines a genetically distinct subgroup of prostate cancers. Our data provide no evidence for a particular clinical behaviour of TMPRSS2-ERG fusion positive cancers in radically operated patients. PTEN and FOXP1 alterations are preferentially found in TMPRSS2-ERG fusion positive cancers. Both genes may potentially be involved in pathway dysregulation in these cancers. No significant financial relationships to disclose.
An Essential Role of <i>Maspin</i> in Embryogenesis and Tumor Suppression
Authors: Sijana H. Dzinic, M. Margarida Bernardo, Xiaohua Li, Rodrigo Fernandez-Valdivia, Ye-Shih Ho, Qing-Sheng Mi, Sudeshna Bandyopadhyay, Fulvio Lonardo, Semir Vranic, Daniel S.M. Oliveira, R. Daniel Bonfil, Gregory Dyson, Kang Chen, Almasa Omerovic, Xiujie Sheng, Xiang Han, Dinghong Wu, Xinling Bi, Dzenana Cabaravdic, Una Jakupovic, Marian Wahba, Aaron Pang, Deanna Harajli, Wael A. Sakr, Shijie Sheng
Journal: Cancer Research (2016)

Abstract Maspin (SerpinB5) is an epithelial-specific tumor suppressor gene product that displays context-dependent cellular functions. Maspin-deficient mouse models created to date have not definitively established maspin functions critical for cancer suppression. In this study, we generated a mouse strain in which exon 4 of the Maspin gene was deleted, confirming its essential role in development but also enabling a breeding scheme to bypass embryonic lethality. Phenotypic characterization of this viable strain established that maspin deficiency was associated with a reduction in maximum body weight and a variety of context-dependent epithelial abnormalities. Specifically, maspin-deficient mice exhibited pulmonary adenocarcinoma, myoepithelial hyperplasia of the mammary gland, hyperplasia of luminal cells of dorsolateral and anterior prostate, and atrophy of luminal cells of ventral prostate and stratum spinosum of epidermis. These cancer phenotypes were accompanied by increased inflammatory stroma. These mice also displayed the autoimmune disorder alopecia aerate. Overall, our findings defined context-specific tumor suppressor roles for maspin in a clinically relevant model to study maspin functions in cancer and other pathologies. Cancer Res; 77(4); 886–96. ©2017 AACR.
Detection of Microbial Substitution in the Oral Cavity of Patients Undergoing Hematopoietic Stem Cell Transplantation with Vitek MSTM, a MALDI-TOF Mass Spectrometry System
Authors: Luna Osakabe, Bungo Saito, Nana Arai, Yukiko Kawaguchi, Kouji Yanagisawa, Norimichi Hattori, Akemi Utsumi, Kunihiko Fukuchi, Tsuyoshi Nakamaki, Shouji Hironaka
Journal: Blood (2016)
The effect of tumor subtype on survival and the graded prognostic assessment (GPA) for patients with breast cancer and brain metastases.
Authors: P. W. Sperduto, N. Kased, D. Roberge, R. Shanley, S. T. Chao, A. K. Bhatt, P. D. Brown, H. A. Shih, J. Kirkpatrick, L. E. Gaspar
Journal: Journal of Clinical Oncology (2011)

238 Background: The Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast GPA by analyzing a larger cohort and tumor subtype. Methods: A multi-institutional retrospective database of 400 breast cancer patients treated for newly-diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression (MCR) and recursive partitioning analysis (RPA). Factors were weighted by magnitude of their regression coefficients to define the GPA index. A GPA score of 4.0 represents the best prognosis, 0.0, the worst. Results: Significant prognostic factors by MCR and RPA were Karnofsky Performance Status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60-80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0-1.0, 1.5-2.0, 2.5-3.0 and 3.5-4.0 was 3.4 (n=23), 7.7 (n=104), 15.1 (n=140) and 25.3 (n=133) months, respectively (p &lt; 0.0001). See table. Among HER2-negative patients, being ER/PR-positive improved MST from 6.4 to 9.7 months whereas in HER2-positive patients, being ER/PR-positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA versus 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision-making and stratification of clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone. [Table: see text]
Angiogenic and Vasculogenic Effects of Sonic Hedgehog Gene Therapy In An Experimental Model of Peripheral Limb Ischemia
Authors: Mariangela Palladino, Ilaria Gatto, Valentina Neri, Marcy Silver, Stefania Straino, Roy C Smith, Filippo Crea, Alessandra Tritarelli, Maurizio Capogrossi, Roberto Pola, Giuseppe Leone
Journal: Blood (2010)
3,4-Diarylmaleimides Effectively Inhibit Proliferation of FLT3-ITD-Positive Leukemic Cells, Induce Apoptosis and Show Additive Effects in Combination with Chemotherapeutic Drugs.
Authors: Florian H. Heidel, Daniel B. Lipka, Fian K. Mirea, Boyka Markova, Christian Peifer, Jan-Peter Kramp, Stanislav Plutizki, Christoph Huber, Gerd Dannhardt, Thomas Fischer
Journal: Blood (2007)
Effect of probiotics in prevention of atopic dermatitis is dependent on the intrinsic microbiota at early infancy
Authors: Ekaterina Avershina, Raul Cabrera Rubio, Krister Lundgård, Gaspar Perez Martinez, Maria Carmen Collado, Ola Storrø, Torbjørn Øien, Christian Kvikne Dotterud, Roar Johnsen, Knut Rudi
Journal: Journal of Allergy and Clinical Immunology (2016)
What is the best treatment option for second line in long responders to the first-line TKI in metastatic renal cell carcinoma (mRCC) patients (pts): TKI-TKI or TKI-mTORi? A European retrospective study.
Authors: Reza-Thierry Elaidi, Benoit Beuselinck, Agnes Maj-HES, Delphine Carmier, Aristotelis Bamias, Philip R. Debruyne, Camillo Porta, Sophie Roca, Stephane Oudard
Journal: Journal of Clinical Oncology (2012)

375 Background: The question regarding the benefit of a TKI rechallenge versus switch to an mTOR inhibitor (mTORi) in mRCC pts who responded to a previous line of TKI remains unanswered and is a common dilemma in clinical practice. We report results of a retrospective study to address this question. Methods: This study retrospectively investigated Duration of Treatment (DT), best radiological response (OR) and predictive factors in pts treated with either TKI-TKI or TKI-mTORi sequences for clear-cell mRCC. Eligibility criteria: 1 TKI in 1 st line (L1) followed by another TKI or mTORi as 2 nd line (L2). Prior immunotherapy was allowed but not intermediate lines with other drugs. Pts characteristics and Heng’s prognostic factors were collected at each line initiation. Response (resp) was classified with regard to DT and OR using 2 different definitions: def1 = Non Responders (NR): &lt; 4months (m) + PD; Short-Term responders (STR): [4–6]m + SD/PR, Long-term Responders (LTR): &gt;6m + SD/PR, and def2 = NR: &lt; 4m + PD, STR: [4–12]m + SD/PR, LTR: &gt;12m + SD/PR. Results: 127 pts from 7 European centers were retrospectively analyzed. Based on def1, resp to L1 was: LTR=93, STR=20, NR=14; among LTR pts, 54 received a L2=TKI and 39 a L2=mTORi. Based on def2, resp to L1 was: LTR=59, STR=53, NR=15; among LTR pts, 35 received a L2=TKI and 24 a L2=mTORi. Whether def1 or def2, resp (L1 and L2) was never related to Heng’s score. Among LTR pts at L1, 26 out of 54 were LTR after L2=TKI vs 18 out of 39 after L2=mTORi (p=0.85, Z-test) for def1 and 9 out of 35 were LTR after L2=TKI vs 6 out of 24 after L2=mTORi (p=0.95) for def2 (see table). For both def1 and def2, median DT was 7.2m and 6.9m for L2=TKI and L2=mTORi, respectively (p=0.86 and p=0.95, Log-Rank). Conclusions: Results suggest that long-term responders on 1 st line TKI could benefit both from TKI and mTORi as 2 nd line and there is no evidence to favor one sequence over the other. [Table: see text]
Glioblastoma Therapy Can Be Augmented by Targeting IDH1-Mediated NADPH Biosynthesis
Authors: Daniel R. Wahl, Joseph Dresser, Kari Wilder-Romans, Joshua D. Parsels, Shuang G. Zhao, Mary Davis, Lili Zhao, Maureen Kachman, Stefanie Wernisch, Charles F. Burant, Meredith A. Morgan, Felix Y. Feng, Corey Speers, Costas A. Lyssiotis, Theodore S. Lawrence
Journal: Cancer Research (2016)

Abstract NADPH is a critical reductant needed in cancer cells to fuel the biosynthesis of deoxynucleotides and antioxidants and to sustain stress-survival responses after radiation-induced DNA damage. Thus, one rational strategy to attack cancer cells is to target their heavy reliance on NADPH. Here, we report that the isocitrate dehydrogenase IDH1 is the most strongly upregulated NADPH-producing enzyme in glioblastoma (GBM). IDH1 silencing in GBM cells reduced levels of NADPH, deoxynucleotides, and glutathione and increased their sensitivity to radiation-induced senescence. Rescuing these metabolic restrictions was sufficient to reverse IDH1-mediated radiosensitization. In a murine xenograft model of human GBM, we found that IDH1 silencing significantly improved therapeutic responses to fractionated radiotherapy, when compared with either treatment alone. In summary, our work offers a mechanistic rationale for IDH1 inhibition as a metabolic strategy to improve the response of GBM to radiotherapy. Cancer Res; 77(4); 960–70. ©2016 AACR.
Intravesical (IVe) valrubicin for treatment of carcinoma in situ (CIS) of the bladder: Use in clinical practice.
Authors: Michael S. Cookson, Christine Francis Lihou, Samira Q. Harper, Zhihui Lang
Journal: Journal of Clinical Oncology (2012)

317 Background: IVe valrubicin is indicated for bacillus Calmette-Guérin (BCG)-refractory CIS when cystectomy is not an option. An ongoing retrospective clinical-practice chart review is being conducted to examine use of valrubicin since its reintroduction (Oct 2009). Methods: Records were analyzed for adults with non-muscle invasive bladder cancer (NMIBC) treated with valrubicin. Results: In this ongoing study, 62 patients received valrubicin (date range; 10/7/2009-6/10/2011). Most were male (52, 84%) and white (49, 79%); median age was 79 y (range, 49–89). 49 patients (79%) had a history of CIS + papillary tumors, 8 had CIS (13%), 4 had papillary (7%), 1 had NMIBC unspecified (1%). 57 patients (92%) received prior IVe therapy (median [range], 2 [0–11] courses); 13 patients (21%) received 1 course, 16 (26%) 2 courses, and 28 (45%) ≥3 courses. Immunotherapy (eg, BCG, unspecified) was the most common prior treatment (54 patients, 87%; median [range], 2 [0–7] courses); 17 patients (27%) received 1 course, 15 (24%) 2 courses, and 22 (35%) ≥3 courses. Prior IVe chemotherapy was less common (21 patients, 34%). 47 patients (76%) had ≥1 transurethral resection of the bladder tumor (median [range], 2 [0–9] for n=62 patients). Fewer had undergone ≥1 fulguration procedures (27, 44%). Most valrubicin courses (49/67, 73%) used the recommended 6 instillations (median [range], 6 [2–7]). Retention time (median [range], 120 [0–180] min) was recorded for 89/381 instillations (23%). Adverse events (AEs) were observed for 31 patients (50%); most AEs (102/106, 96%) were mild or moderate. 3 patients (5%) had serious AEs (treatment-relationship unknown). Median followup for all patients was 5.2 mo (range, 0–13.9). 13 patients (21%) underwent cystectomy at a median of 5.3 mo (range, 1-13) from the last valrubicin dose. 2 patients died, at 1.1 (metastatic disease) and 11.9 mo after finishing valrubicin. Conclusions: Patients treated with valrubicin in clinical practice often had concomitant papillary tumors and were heavily pretreated. One in 8 patients had no record of previous immunotherapy. Drug administration adhered closely to labeled instructions and was well tolerated. Funding: Endo Pharmaceuticals.
Methylation-specific high-resolution melting analysis (MS-HRM)-based DNA promoter profiling in paired FFPE bladder cancer samples.
Authors: Wei Meng, Arnab Chakravarti, Tim Lautenschlaeger
Journal: Journal of Clinical Oncology (2012)

315 Background: DNA methylation and histone modification are widely studied epigenetic events that can decrease gene expression levels. Promoter hypermethylation has been proposed as a potential diagnostic or prognostic biomarker in various cancers. We studied DNA promoter methylation of 5 cancer-associated genes (MRE11, APX1, ERCC1, RASSF1A and RASSF2A ) in paired FFPE bladder cancer tissues and normal adjacent tissue. The MRE11/Rad50/NBS1 complex serves as a single-strand DNA nuclease which participates in the repair of DNA double-strand breaks and replication errors. APX1 plays a key role in regulating H 2 O 2 levels and H 2 O 2 signaling. DNA repair machinery, ERCC1 protein levels in tumor tissue have been shown to predict response to platinum-based chemotherapy. RASSF1 is thought to be a tumor suppressor gene, while the function of RASSF2 is less well understood. Methods: 16 bladder cancer cases with available paraffin-embedded tumor and matched normal adjacent tissue specimens (32 tissue samples) were analyzed. DNA was extracted by Ambion RecoverAll Total Nucleic Acid Isolation kit. FFPE DNA bisulfite modification was performed using Zymo EZ DNA Methylation Kit. Methylation Specific-High Resolution Melting (MS-HRM) analysis was used to assess methylation status. MS-HRM monitors the melting behavior of PCR amplicons by using a DNA intercalating fluorescent dye. Results: MRE11 and APX1 promoters were not methylated in either cancer or normal adjacent samples. The ERCC1 gene was heavily methylated in 94% (30/32) of all cancer and wild type samples. RASSF1A and RASSF2A promoter methylation was significantly different between cancer and normal adjacent tissue. 50% (8/16) RASSF1A and 25% (4/16) RASSF2A had promoter methylation in cancer tissues, while only 6% (1/16) RASSF1A and 0% (0/16) RASSF2A had promoter methylation in normal adjacent tissues. 69% (11/16) of bladder cancer tissues were positive for RASSF1A or RASSF2A promotor methylation while only 1/16 normal adjacent tissue samples was positive for either promotor methylation. Conclusions: The results show that cancer and non-cancer tissue have different RASSF1A and RASSF2A promoter methylation patterns.
Alterations in B-cell subsets in pediatric patients with early atopic dermatitis
Authors: Tali Czarnowicki, Hitokazu Esaki, Juana Gonzalez, Yael Renert-Yuval, Patrick Brunner, Margeaux Oliva, Yeriel Estrada, Hui Xu, Xiuzhong Zheng, Sreya Talasila, Isabel Haugh, Thy Huynh, Sarah Lyon, Gary Tran, Hugh Sampson, Mayte Suárez-Fariñas, James G. Krueger, Emma Guttman-Yassky, Amy S. Paller
Journal: Journal of Allergy and Clinical Immunology (2016)
Shared Decision Making Regarding Aspirin in Primary Prevention of Cardiovascular Disease
Authors: Steven D. Stovitz, David J. Satin, Ian Shrier
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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