tbuckley/cabot-search huggingface dataset:
Identification of the occult tumor in cancer of unknown primary (CUP): A priority based on histology.
Authors: Chong Sung Kim, Malek Bassam Hannouf, Muriel Brackstone, Eric Winquist, Gregory S Zaric
Journal: Journal of Clinical Oncology (2013)

1605 Background: The poor prognosis of cancer of unknown primary (CUP) patients is likely to improve with knowledge of the primary site. CUP patients form a diverse clinicopathological group; however, there remains doubt as CUP may indeed represent a unique clinical classification. Methods: We used the Ontario Cancer Registry to identify all patients diagnosed with cancer from January 2000 to December 2005. We linked these patients with the Canadian Institute of Health Information Same Day Surgery and Discharge Abstract Database to identify those who were initially diagnosed with a metastatic tumour. Information on clinical and pathological characteristics including age, gender, primary tumour site, histology, and second primary were available from the Ontario Cancer Registry. We stratified results according to primary tumour site and histology. Five-year survival data were available for all patients and were obtained from the Ontario Cancer Registry. Results: Of 52,619 patients diagnosed with metastatic tumour at the time of their initial cancer diagnosis, 4,866 (9.2%) patients were diagnosed with CUP and 47,753 (90.8%) patients were diagnosed with metastasis of known primary. The 5-year Kaplan-Meier estimate of CUP overall survival (OS) differed significantly with patients diagnosed with metastasis of known primary (median OS= 1.0 versus 10.4 months, respectively, log–rank test p&lt;0.0001). In subgroup analyses, the 5-year OS of CUP patients with adenocarcinoma (n=1,389, median OS=1.83) was significantly worse when compared to metastatic adenocarcinoma of known primary (log-rank test p&lt;0.0001). An identical result was obtained with CUP patients of undifferentiated histology (n=3,230). The 5-year OS of CUP patients with squamous cell carcinoma (n=247, median OS=18.5) did not differ significantly with those of other squamous cell carcinoma groups of known primary (log-rank test p&gt;0.56). Conclusions: Although CUP patients as a whole have a poor prognosis compared to other metastatic patients of known primary, distinct subsets of CUP patients have similar prognosis. These data suggest that an intensive diagnostic approach for identification of the primary is not justified for all CUP patients.
Contents, Vol. 3, Supplement 1, 1955
Authors: Paula Elkisch, Joseph Claude Finney, E.C.M. Frijling-Schreuder, Walther D. Joël, L.N.J. Kamp, William Kaufman, Werner Kemper, James L. McCartney, Willem L. Meijering, Paul J. Reiter, Gerhard Ruffler, Raoul Schindler, Walter Schindler, Hans-Joachim Schumann, Georg Schwöbel, Paul Senft, Emilio Servadio, Berthel Sommer, L. Stein, Max M. Stern, Franz Andreas Völgyesi, Adalbert Wegeler, Edith Weigert, Walter Theodor Winkler, Benjamin Wolstein, Gerhard Adler, J. Bastiaans, Charles Baudouin, Benjamin J. Becker, M. Bergouignan, Ludwig Binswanger, Siegfried Borelli, D. Brinkmann, Madeleine Cavé, L. Chertok, Muriel Cahen, R. Le Coultre, Sidney Drobnes, Charles Durand, Pedro Folch, B.A. Finkelstein, Michael Fordham, A. Fuchs-Kamp, Gustav Hans Graber, Max Gruenthal, Heinz Häfner, Gerhard Hoffmann, H. Huebschmann, Wolfgang Kretschmer, D.A. van Krevelen, F. Kruse, G. Kühnel, S. Leclaire, Daniel M. Lipshutz, Sandor Lorand, Margaret Lowenfeld, Samuel Lowy, Ida Macalpine, Richard A. Hunter, Robert L. Moody, William Niederland, J.H.R. van der Pas, François Perrier, H. Pittrich, A.B.J. Plaut, Illis Plenge, Paul Polak, A. Poslavsky, Edmond Rochedieu, Jurgen Ruesch, F.H. Strauss, H.R. Teirich
Journal: Psychotherapy and Psychosomatics (1955)
High-Resolution Genomic Copy Number Profiling of Primary Intraocular Lymphomas Using SNP Microarrays
Authors: Ludan Wang, Aiko Sato-Otsubo, Sunao Sugita, Hiroshi Takase, Manabu Mochizuki, Yoshihiko Usui, Hiroshi Goto, Osamu Miura, Seishi Ogawa, Ayako Arai
Journal: Blood (2011)
New biweekly combination of trastuzumab, docetaxel, and gemcitabine for HER2-positive metastatic breast cancer: First early results from a phase II multicentric trial on behalf of Gruppo Oncologico Italia Meridionale
Authors: S. Cinieri, L. Orlando, V. Lorusso, G. Filippelli, E. Maiello, L. Blasi, F. Verderame, S. Barni, S. Pisconti, G. Colucci
Journal: Journal of Clinical Oncology (2009)

1096 Background: The clinical activity of the combination of chemotherapy plus trastuzumab in HER-2 overexpressing metastatic breast cancer has been well documentated. We report the first results in terms of efficacy and safety of a phase II trial on biweekly combination of trastuzumab plus docetaxel and gemcitabine as first line therapy in HER-2-positive metastatic breast cancer patients. Methods: Patients at first relapse or with synchronous metastasis, were treated with trastuzumab (4 mg/kg, loading dose 6 mg/kg) plus gemcitabine (1000 mg/m2) plus docetaxel (50 mg/m2) as biweekly schedule. Primary end-point was overall response rate (ORR), secondary end-point time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks), and tolerability. Based on previous data, an ORR greater than 60% was considered to indicate clinical activity in this two stage design trial. Results: A total of 26 patients with histologically confirmed, measurable MBC, tumors scored as +3 positive for HER-2 by immuno-histochemistry or FISH +, no pretreated with chemotherapy or trastuzumab for metastatic disease have been enrolled, 22 actually evaluable for response and toxicity. Median age was 49 years (range 34–66), visceral metastases were present in most patients (73%). Median number of cycles was 8 (range 3–12). The ORR was 86% (95% CI, 80–91%), with two CR (9 %) and 17 PR (77%). 3 patients had SD, 1 prolonged (14%). The CBR was 91% (95% CI, 87%-94%). No progression of disease was observed. Median TTP was 7 months (range 5- 9+ months). The worst toxicity was WHO grade 2 neutropenia and grade 2 gastric pain. Conclusions: In this phase II study, the biweekly combination of trastuzumab, gemcitabine, and docetaxel in HER-2-positive breast cancer is very active. The toxicity observed was manageable and did not lead to treatment discontinuation. Thus, the patients accrual is ongoing to the preset target of 50 patients. No significant financial relationships to disclose.
A Retrospective Study on the Incidence of Rituximab-Related Interstitial Pneumonitis In Patients Undergoing Immunochemotherapy for Non-Hodgkin Lymphoma
Authors: Giselle Salmasi, Michael Li, Vithika Sivabalasundaram, Richard Tsang, Vishal Kukreti, Michael Crump, John Kuruvilla
Journal: Blood (2010)
Twist-1 Expression Represents a Novel Prognostic Factor in Chronic Myelogenous Leukemia.
Authors: Franck Emmanuel Nicolini, Erika Cosset, Ghassan Hamdan, Sandrine Jeanpierre, Charles Dumontet, Thibault Voeltzel, Alain Puisieux, Véronique Maguer-Satta
Journal: Blood (2009)
Abstract B46: Inhibition of STAT3 enhances the radiosensitizing effect of Temozolomide in vitro and in vivo: Validation using patient-derived glioblastoma model
Authors: Tae Jin Han, Eun Jung Choi, Bong Jun Cho, Sang Hyuk Song, Sun Ha Paek, In Ah Kim
Journal: Clinical Cancer Research (2016)

Abstract Background and purpose: Despite aggressive treatment with radiation therapy plus temozolomide (TMZ), the prognosis for glioblastoma remains poor. We investigated the potential of targeting signal transducer and activator of transcription-3 (STAT3) to improve the therapeutic outcome of glioblastoma. Material and methods: We evaluated the preclinical potential of a STAT3 inhibitor, Cpd188 combined with temozolomide and radiation in vitro assays using two established glioblastoma cell lines (U251, U87) and two patients-derived glioblastoma cell lines (GBL12, GBL28) and in vivo studies using nude mice bearing intracranial U251 xenografts. Results: Cpd188 potentiated the radiosensitizing effect of TMZ in U251 cell which has high levels of p-STAT3 expression. Increased radiosensitizing effects of TMZ were associated with impaired DNA damage repair, apoptosis and the reversion of epithelial-mesenchymal transition (EMT). Cpd188 delayed in vivo tumor growth both alone and in combination with radiation and TMZ. We also confirmed the radiosensitizing effect of Cpd188 of GBL28 cell which was originated from a patient with high level of STAT3 expression and unmethylated MGMT. Conclusion: Targeting STAT3 using Cpd188 could be a viable therapeutic approach to improve the outcome of current standard therapy for glioblastoma patients having high p-STAT3 expression regardless of MGMT methylation status. *Work supported by the grant (#2013R1A1A2074531) from the Ministry of Science, ICT &amp; Future Planning to In Ah Kim Citation Format: Tae Jin Han, Eun Jung Choi, Bong Jun Cho, Sang Hyuk Song, Sun Ha Paek, In Ah Kim{Authors}. Inhibition of STAT3 enhances the radiosensitizing effect of Temozolomide in vitro and in vivo: Validation using patient-derived glioblastoma model. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B46.
Abstract P2-15-02: Attitudes towards tissue donation for rapid autopsy among community and academic oncologists
Authors: PS Rajagopal, A Lee, SL Puhalla
Journal: Cancer Research (2017)

Abstract Rapid autopsy (RA) refers to the recently developed practice of obtaining research tissue within 2-6 hours following the death of a patient. Such tissue can offer insights into the genomic and proteomic evolution of metastatic disease and possible novel therapeutic targets. Although patients generally have positive attitudes towards RA, RA programs have not been widely established by oncologists at healthcare centers with these capabilities. To identify barriers to our adoption of an RA program, we conducted a 21-item web-based survey of academic and community oncologists in a single institution with regard to knowledge, attitudes and concerns about RA. Twenty-six physicians completed the study out of a possible 98 respondents, with 50% in academic practice and 50% in community practice. 46% were not aware of RA prior to the survey. None of the community physicians had experience with patient tissue donations of any kind. In completing the survey, 85% were willing to ask future patients about participating in RA. 58% of oncologists cited lack of awareness as their primary barrier to participation, while 31% reported discomfort in discussing rapid autopsy with patients or concern about the doctor-patient relationship. A minority of physicians had ethical concerns about the practice. The most popular strategies for increasing awareness of the RA program included distributing informational pamphlets to patients, using a third-party advocate or a discussion with the patient's primary oncologist or NP. 92% of those surveyed stated that being aware of patient interest would make them much more likely to recommend RA to patients. Our study is among the first to clarify barriers among oncologists, particularly community oncologists, to establishing RA programs and suggests that increased information alone with clarification of patient perceptions could provide substantial progress in developing RA programs at tertiary healthcare centers and recruiting patients to these programs. Citation Format: Rajagopal PS, Lee A, Puhalla SL. Attitudes towards tissue donation for rapid autopsy among community and academic oncologists [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-15-02.
Increased acetylation of Peroxiredoxin1 by HDAC6 inhibition leads to recovery of Aβ-induced impaired axonal transport
Authors: Heesun Choi, Haeng Jun Kim, Jisoo Kim, Soohyun Kim, Jinhee Yang, Wonik Lee, Yeonju Park, Seung Jae Hyeon, Dong-Sup Lee, Hoon Ryu, Junho Chung, Inhee Mook-Jung
Journal: Molecular Neurodegeneration (2017)

Reduction or inhibition of histone deacetylase 6 (HDAC6) has been shown to rescue memory in mouse models of Alzheimer's disease (AD) and is recently being considered a possible therapeutic strategy. However, the restoring mechanism of HDAC6 inhibition has not been fully understood. Here, we found that an anti-oxidant protein Peroxdiredoxin1 (Prx1), a substrate of HDAC6, malfunctions in Aβ treated cells, the brains of 5xFAD AD model mice and AD patients. Malfunctioning Prx1, caused by reduced Prx1 acetylation levels, was recovered by HDAC6 inhibition. Increasing acetylation levels of Prx1 by HDAC6 inhibition recovered elevated reactive oxygen species (ROS) levels, elevated Ca2+ levels and impaired mitochondrial axonal transport, sequentially, even in the presence of Aβ. Prx1 mutant studies on the K197 site for an acetylation mimic or silencing mutation support the results showing that HDAC6 inhibitor restores Aβ-induced disruption of ROS, Ca2+ and axonal transport. Taken together, increasing acetylation of Prx1 by HDAC6 inhibition has several beneficial effects in AD pathology. Here, we present the novel mechanism by which elevated acetylation of Prx1 rescues mitochondrial axonal transport impaired by Aβ. Therefore, our results suggest that modulation of Prx1 acetylation by HDAC6 inhibition has great therapeutic potential for AD and has further therapeutic possibilities for other neurodegenerative diseases as well.
Abstract P3-04-08: The role of HER2 mutations in resistance to endocrine therapy in ER+ breast cancer
Authors: U Nayar, O Cohen, C Oh, N Wagle
Journal: Cancer Research (2017)

Abstract Resistance to endocrine therapies in estrogen receptor positive (ER+) metastatic breast cancer is widespread, and understanding the mechanisms whereby these tumors acquire resistance is a critical need. Through whole-exome sequencing of metastatic tumor biopsies from patients with endocrine resistant ER+ metastatic breast cancer, we identified 13 different HER2 mutations, including five in the kinase domain, four in the signaling domain, three in the extracellular domain, and one in the transmembrane region of the protein. Two of the kinase domain mutations (L755S and V777L) have been previously described and shown to be activating and resistant to reversible anti-HER2 targeted therapies; the remaining mutations have not been reported. In several of these patients, whole exome sequencing of a pre-treatment primary tumor did not identify the HER2 mutations seen in the corresponding metastatic tumor, suggesting that they were acquired during therapy. To examine the role of HER2 mutations in endocrine resistance, we generated ER+ breast cancer cell lines (MCF7 and T47D) stably expressing the HER2 mutants observed in our clinical data. Several mutants promoted enhanced growth in charcoal dextran-stripped media, which lacks estradiol and mimics treatment with aromatase inhibitor. In addition, several mutants conferred varying degrees of resistance to fulvestrant and tamoxifen. Taken together, these results suggest that HER2 mutations are associated with acquired resistance to endocrine therapies in patients with ER+ breast cancer. The ability of irreversible anti-HER2 agents as well as other agents that target the HER2 pathway to overcome this resistance is being tested for individual HER2 mutations in vitro. The results from these studies may provide a clinical rationale for therapeutic combination strategies in patients with refractory tumors that have acquired endocrine resistance through HER2 mutations. Citation Format: Nayar U, Cohen O, Oh C, Wagle N. The role of HER2 mutations in resistance to endocrine therapy in ER+ breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-08.
Re: Archie Fernando, James Pattison, Catherine Horsfield, David D’Cruz, Gary Cook, Tim O’Brien. [18F]-Fluorodeoxyglucose Positron Emission Tomography in the Diagnosis, Treatment Stratification, and Monitoring of Patients with Retroperitoneal Fibrosis: A Prospective Clinical Study. Eur Urol 2017;71:926–33
Authors: Liangyou Gu, Yiwen Wang, Xu Zhang
Journal: European Urology (2017)
Abstract P085: Inhibition of Akt Reverses the Isoproterenol-Enhanced Diastolic Calcium Leak in Rabbit Ventricular Myocytes
Authors: Sathya Velmurugan, Jerry Curran, Thomas Shannon
Journal: Circulation Research (2011)

Cardiac ryanodine receptor (RyR)-dependent diastolic SR Ca2+ leak is increased in heart failure and during beta-adrenergic (β-AR) stimulation. This increased SR Ca2+ leak could limit the SR [Ca2+] thereby decreasing contractility in HF and could also lead to arrhythmogenic Ca-dependent inward depolarizing current resulting in HF. It has recently been shown in our lab that this leak is dependent on calcium-calmodulin-dependent protein kinase II (CaMKII) and subsequent NOS activation, and that it is independent of either protein kinase A (PKA) activation or an increase in free Ca2+ concentration in the cytosol ([Ca2+]i). Here we investigate whether Akt is also involved in the pathway leading to increased diastolic leak during β-AR stimulation. Methods: [Ca2+]i was measured using fluo-4 in left ventricular myocytes isolated from rabbits. To vary the SR load, myocytes were field-stimulated to steady state at different frequencies. Tetracaine (1mM) was used to rapidly and reversibly block the RyR. The tetracaine-dependent shift of Ca2+ from the cytosol to the SR (decrease in [Ca2+]i and increase in SR Ca2+ content) is proportional to SR Ca2+ leak. To activate β-AR, isoproterenol (ISO; 250 nM) was added to perfuse the myocytes starting 5 min before leak assessment through the end. Results: ISO-induced increase in the SR Ca2+ leak is abolished by the treatment of myocytes with Akt inhibitor X (AIX; 5μM; 30min pre-incubation and perfusion throughout the experiment). When SR Ca2+ load was matched in each group (ISO alone: 155.22 ± 5.1 μM; ISO + AIX: 153.92 ± 3.8 μM), myocytes treated with ISO alone had significantly higher leak (12.43 ± 3.8 μM) vs. those treated with ISO and AIX (1 ± 2.2 μM) (P = 0.01, t-test). This evidence indicates that Akt activation may also be involved in the β-AR-induced SR Ca2+ leak possibly upstream from CaMKII and NOS activation.
Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia
Authors: Andreas Hochhaus, Richard A. Larson, François Guilhot, Jerald P. Radich, Susan Branford, Timothy P. Hughes, Michele Baccarani, Michael W. Deininger, Francisco Cervantes, Satoko Fujihara, Christine-Elke Ortmann, Hans D. Menssen, Hagop Kantarjian, Stephen G. O’Brien, Brian J. Druker
Journal: New England Journal of Medicine (2017)

Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy.In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events.The median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment.Almost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840 .).
Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial
Authors: Ruth Ladenstein, Ulrike Pötschger, Andrew D J Pearson, Penelope Brock, Roberto Luksch, Victoria Castel, Isaac Yaniv, Vassilios Papadakis, Geneviève Laureys, Josef Malis, Walentyna Balwierz, Ellen Ruud, Per Kogner, Henrik Schroeder, Ana Forjaz de Lacerda, Maja Beck-Popovic, Pavel Bician, Miklós Garami, Toby Trahair, Adela Canete, Peter F Ambros, Keith Holmes, Mark Gaze, Günter Schreier, Alberto Garaventa, Gilles Vassal, Jean Michon, Dominique Valteau-Couanet
Journal: The Lancet Oncology (2017)
Comparison of MRI with radiography for detecting structural lesions of the sacroiliac joint using CT as standard of reference: results from the SIMACT study
Authors: Torsten Diekhoff, Kay-Geert A Hermann, Juliane Greese, Carsten Schwenke, Denis Poddubnyy, Bernd Hamm, Joachim Sieper
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objective</h3> Radiographs of sacroiliac (SI) joints are used for the detection of structural damage in patients with axial spondyloarthritis (axSpA), but are often difficult to interpret. Here, we address the question how the T1-weighted MRI (T1w MRI) sequence compares with radiography for SI joints' structural lesions using low-dose CT as the standard of reference. <h3>Methods</h3> Radiographs, T1w MRI and low-dose CT of the SI joints from 110 patients (mean age 36.1 (19–57) years, 52% males and 48% females; 53% with axSpA, 21 non-radiographic axSpA and 32% radiographic axSpA, 47% with non-SpA) referred to the rheumatologist because of unclear chronic back pain, but possible axSpA, were scored for structural lesions (erosions, sclerosis, joint space changes and an overall impression of positivity). <h3>Results</h3> Using low-dose CT as the standard of reference, T1w MRI showed markedly better sensitivity with significantly more correct imaging findings compared with radiography for erosions (79% vs 42%; p=0.002), joint space changes (75% vs 41%; p=0.002) and overall positivity (85% vs 48%; p=0.001), respectively, while there were no differences between X-rays and MRI-T1 sequence regarding specificity (&gt;80% for all scores). Only for sclerosis, MRI-T1 was inferior to radiography (sensitivity 30% vs 70%, respectively), however, not statistically significant (p=0.663). <h3>Conclusions</h3> T1w MRI was superior to radiography in the detection of structural lesion of the SI joints in patients with axSpA. Future studies should focus on finding an agreement on the definition of MRI-T1 positivity.