tbuckley/cabot-search huggingface dataset:
Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer.
Authors: M Markman, T Hakes, B Reichman, J L Lewis, S Rubin, W Jones, L Almadrones, W Hoskins
Journal: Journal of Clinical Oncology (1991)

Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation).
Pleural tuberculous: A study of 46 cases
Authors: Besma Hamdi, Chiraz Aichaouia, Sameh Fereh, Samira Mhamdi, Zied Moatamri, Salsabil Daboussi, Ghaya Laaribi, Mohsen Khadhraoui, Rzaieg Cheikh
Journal: European Respiratory Journal (2011)

Pleural tuberculous (TB) remains a diagnostic challenge. It is the most frequent extra pulmonary localization.  To focus on clinical, radiological, biochemical and histopathological characteristics of pleural TB and the sensitivity of the various diagnostic tests. We study retrospectively 46 patients in whom pleural TB were diagnosed in our military department. The mean age was 29,8 year (12 to 78 year). 78,2% were male. A past medical history of TB was found in 21% of cases. We noticed a huge delay between onset of symptoms and hospitalization (35 days). Among these symptoms, the most frequent are: chest pain, cough and constitutional symptoms. The TB effusions were all exudative with a mean lymphocyte fraction of 76,5% (range: 30–100%). Tuberculin skin test was positive in 41,3% of cases. In 10,8% of cases, the diagnostic of pleural TB was made by detection of acid fast bacilli in sputum. Pleural fluid, sputum and bronchial wash culture had a poor yield for TB of 8,6% each. Diagnosis was confirmed by closed pleural biopsy in 73,9% of cases and by thoracoscopy in 21,7% of cases. 4,4% of cases was histologically non diagnostic. Dissemination of TB in other sites was detected in 19,5% of cases (pulmonary, pericardia, peritoneal, lymph node). Treatment included anti-TB drugs, thoracentisis and physiotherapy. The outcome was favourable in all cases. 45,6% of patients develop pleural thickening 6-12 months after bigining of treatement. TB, whatever its localization, is an infectious disease which can be totally cured by combining anti-TB drugs. Physical therapy and pleural rehabilitation should be implemented early after confirmation of diagnosis of pleural TB in order to limit sequelae.
The Oligodendrocyte Lineage Transcription Factor 2 (OLIG2) Is Epigenetically Regulated in AML and Suppresses Leukemia Cell Growth
Authors: Arzu Yalcin, Marlon Kovarbasic, Mahmoud Abdelkarim, Gregor Klaus, Julius Wehrle, Verena I. Gaidzik, Heike L Pahl, Konstanze Doehner, Lars Bullinger, Michael Lübbert, Björn Hackanson
Journal: Blood (2014)
Clinical effects of prior anthracycline or taxane use on eribulin as first-line treatment for HER+/- locally recurrent or metastatic breast cancer (BC): Results from 2 phase 2, multicenter, single-arm studies.
Authors: Stefan Gluck, Joyce O'Shaughnessy, Kristi McIntyre, Lee Steven Schwartzberg, Sharon Wilks, Shannon Leigh Huggins-Puhalla, Erhan Berrak, James X. Song, David Cox, Linda T. Vahdat
Journal: Journal of Clinical Oncology (2014)

140 Background: Eribulin mesylate, a nontaxane microtubule dynamics inhibitor, has demonstrated an overall survival benefit relative to other commonly used agents in patients (pts) with at least 2 prior MBC cytotoxic therapies. Primary data presented from 2 phase 2 trials, Study 206 (eribulin in HER2- BC pts) and Study 208 (combination eribulin + trastuzumab [TRAS] in HER2+ BC pts), showed clinical activity and acceptable tolerability profiles as first-line cytotoxic therapy (tx). Here we present prespecified efficacy data for both trials based on prior anthracycline (A) and taxane (T) use. Methods: In both studies, pts received eribulin mesylate 1.4 mg/m 2 IV on days 1 and 8 of each 21-day cycle. Pts in Study 208 (HER2+) also received initial TRAS (8 mg/kg IV/Day 1), followed by 6 mg/kg/day 1 of each subsequent cycle. Objective response rate (ORR), progression-free survival (PFS), and tolerability were assessed. Results: In Study 206 (N=56), 48% and 46% received prior A and T, and in Study 208 (N=52), 21% and 44% received prior A and T, respectively. ORR, the primary endpoint, was similar in pts, regardless of prior A or T, except in pts w/o prior T in Study 208 whose ORR trended higher (table). Clinical benefit rate (CBR), PFS, and duration of response (DOR) were either similar or trended higher in pts w/o prior A or T. PFS was higher in HER2+ BC patients receiving eribulin + TRAS who had not received prior A or T compared with those who had. Grade (G) 3-5 adverse event rates were similar or lower in pts who had not received prior A or T. Conclusions: As first-line therapy, eribulin in HER2- BC pts and eribulin + TRAS in HER2+ BC pts were effective and well tolerated, regardless of prior A or T tx. However, in HER2+ BC pts receiving eribulin + TRAS, the lack of prior A or T tx may be a lead to longer median PFS. Clinical trial information: NCT01268150/NCT01269346. [Table: see text]
Bendamustine in the Treatment of Chronic Lymphocytic Leukemia -Consistent Superiority Over Chlorambucil in Elderly Patients and Across Clinically Defined Risk Groups.
Authors: Wolfgang Ulrich Knauf, Toshko Lissitchkov, Ali Aldaoud, Anna Liberati, Javier Loscertales, Raoul Herbrecht, Gunnar Juliusson, Gerhard Postner, Liana Gercheva, Stefan Goranov, Martin Becker, Hans-Joerg Fricke, Francoise Huguet, Ilaria Del Giudice, Peter Klein, Karlheinz Merkle, Marco Montillo
Journal: Blood (2009)
Effects of “passive tear gas exposure”
Authors: Eda Uslu, Gulcihan Ozkan, Fatih Torlak, Peri Arbak, Elif Dagli
Journal: European Respiratory Journal (2014)

Introduction: Tear gas has been used as crowd control agent as direct exposure is believed to have an immediate reaction on the target group. However, there is little information about the health effects of environmental exposure on the individuals in vicinity.

Aim: The study aims to investigate the effect of tear gas on the residents neighboring the demonstration site who have been involuntarily exposed frequently in a duration of one month.

Methods: The respiratory symptoms and lung functions of 105 volunteers, who lived close to “Taksim Gezi Park” where protests took place in June 2013 in Istanbul, Turkey, were investigated.

Results: The average age of the subjects was 36 years and 51 % was female, 70% smokers, 28 % had a chronic disease and 31% complained breathlessness after the gas exposure. 30% was exposed to gas outdoors in close proximity, 38% indoors. Breathlessness were reported by 76%, cough 89%, sputum 44%, chest pain 41%, bloody sputum 4%, nasal discharge 76%, eye redness 84%, skin irritation 46%. Cough symptom was significantly higher in the ones who were exposed to the gas indoors. (95%vs 74% p=0,007). Sputum production was a more common complaint with indoor exposure compared with outdoor distant exposure ( 50%vs18% P=0,002).

Lung function measurements were on average FVC 100,5 % FEV 96,4 %, FEV1/FVC 99,4 %, MMFR 88,1% predicted. MMFR were found less than 65% predicted in 19% of the subjects showing isolated small airway obstruction.

Conclusion: The results of the study has shown that tear gas has environmental health effects. Repeated use of tear gas during a protest with a long duration may harm respiratory health of the people living and working in the district. Tear gas must be controlled legally like tobacco smoke.
Circulating apoptosis-related proteins in long-term disease free breast cancer survivors
Authors: P. J. Perik, E. G. E. De Vries, D. J. Van Veldhuisen, W. T. A. Van der Graaf, D. T. H. Sleijfer, J. A. Gietema
Journal: Journal of Clinical Oncology (2004)

845 Background: Adjuvant chemotherapy may result in cardiovascular dysfunction. We evaluated whether plasma levels of apoptotic proteins are increased in patients (pts) with long-term follow-up after adjuvant therapy, as potential markers for cardiotoxicity. Methods: In 40 long-term disease free adjuvant treated breast cancer survivors (5×FEC n=15, 4×FEC + high-dose (H-D) CTC n=20, 6×CMF-doxorubicin + H-D mitoxantrone, thiotepa n=5) with median follow-up 79 mo after chemotherapy, of which 28% (n=11) had a >10% decrease of left ventricular ejection fraction (EF) or an EF <50% at median 29 mo. Plasma tumor necrosis factor(TNF)-related protein levels (soluble (s) TNF receptor TNFR2, sFas/ -ligand (L), and sTNF-related apoptosis-inducing ligand (sTRAIL) were determined (ELISA). Factor VIII (F8), plasminogen activator (PA) inhibitor (I), tissue PA (t-PA) and fibrinogen were measured as endothelial damage markers. 12 age matched healthy women served as controls (contr). Results: Plasma sTRAIL, sTNFR2, sFas, sFasL, and fibrinogen levels were increased in pts vs controls (table). Median plasma sTRAIL, sTNFR2, sFas levels were higher in the H-D pts vs. standard dose pts. PAI, t-PA and F8 were higher in pts, but not significant. Conclusions: Apoptosis markers are increased in long-term disease free adjuvant-treated breast cancer survivors, especially if they received H-D chemotherapy. The potential pathogenetic role of the apoptosis markers in the development of cardiotoxicity deserves further study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb; Roche
Pattern of Loco-Regional Failure after Definitive Chemo Radiotherapy for NSCLC: Results from NARLAL, a Phase II Randomized Trial
Authors: Tine Schytte, Tine B Nielsen, Marianne Knap, Azza Ahmed Khalil, Christa H Nyhus, Tine McCulloch, Bente Holm, Carsten Brink, Olfred Hansen
Journal: Journal of Thoracic Oncology (2015)
Prognostic impact of bone turnover markers in multiple myeloma
Authors: O. Dizdar, I. Barista, U. Kalyoncu, O. Karadag, I. Celik, A. Kars, G. Hascelik, A. Cila, A. Pinar, G. Tekuzman
Journal: Journal of Clinical Oncology (2008)

8610 Background: Osteopontin (OPN) and macrophage inflammatory protein-1 alpha (MIP) were suggested to have a role in pathogenesis of myeloma bone disease. In this study, we aimed to investigate the prognostic value of these markers along with biochemical markers of bone turnover including C-terminal telopeptide (Ctx), deoxypyridinoline (DPD), type-I collagen propeptide (T1-Pro), bone-specific alkaline phosphatase (BALP), in multiple myeloma (MM). Methods: Twenty-five patients with MM diagnosed between 2003 and 2005 were included. Pretreatment serum levels of OPN, MIP, Ctx, DPD, BALP, and T1-Pro were measured. The effects of these parameters on survival were assessed using Kaplan-Meier method and Cox regression analysis. Results: The patients comprised 8 women and 17 men. Median age was 65. 32% of the patients were stage I, 28% were stage II and 40% were stage III according to the International Staging System. Median follow-up was 28 months. Sixty-four percent of the patients received vincristine, doxorubicin, and dexamethasone regimen as induction. Five patients had undergone autologous bone marrow transplantation. Nine patients died on follow-up. Median survival time has not been reached yet. Two-year overall survival rate was 69%. The only parameter associated with survival was OPN level in Cox regression analysis (p=0.04). No significant relationship was found between survival and other parameters (p=0.15 for Ctx, p=0.2 for T1-Pro, p=0.47 for DPD, p=0.76 for BALP). The survival of the patients with high OPN levels was significantly shorter than those with normal OPN levels (29.7 months vs. not reached, p=0.049). Multivariate analysis was not performed because of the limited number of patients. Conclusions: Osteopontin has prognostic importance in newly-diagnosed patients with MM. Higher levels of OPN were found to be associated with shorter survival. This findings should be investigated in larger patient series. No significant financial relationships to disclose.
Abstract 16303: Left Atrial Ejection Fraction is a Feasible Parameter to Predict Poor Prognosis in Patients with Heart Failure and Sinus Rhythm
Authors: Shintaro Sasaki, Harutoshi Tamura, Tetsu Watanabe, Masahiro Wanezaki, Satoshi Nishiyama, Mitsunori Ishino, Chika Sato, Takanori Arimoto, Hiroki Takahashi, Tetsuro Shishido, Takehiko Miyashita, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2012)

Decreasing left atrial (LA) systolic force was reported to be related to the occurrence of cardiac events. Recently, it was reported that decreased LA ejection fraction (LAEF) is a marker of left atrial dysfunction. However, the prognostic value of LAEF in patients with heart failure (HF) has not been fully investigated. We examined whether decreased LAEF can predict poor prognosis in patients with HF and sinus rhythm. We performed transthoracic echocardiography in 152 consecutive patients who were hospitalized for HF (88 males, 72 ± 13 years). Patients with atrial fibrillation and those with severe mitral valve diseases were excluded. LAEF was calculated by the biplane modified Simpson method from apical 4- and 2-chamber views at end systolic and diastolic phase. There were 57 cardiac events (38%) including cardiac deaths or rehospitalizations for worsening HF during a median follow-up period of 430 days (160 - 738 days). LAEF was markedly lower in patients with cardiac events than in those without. All patients were stratified into 3 groups according to tertiles for LAEF: > 38%, n=51; 29-37%, n=51;
Case-matched comparison of survival after cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion for peritoneal carcinomatosis versus liver resection for metastatic colorectal cancer
Authors: J. Franko, N. J. Gusani, M. P. Holtzman, S. A. Ahrendt, H. J. Zeh, D. L. Bartlett
Journal: Journal of Clinical Oncology (2008)

4058 Background: Cytoreductive surgery combined with peritoneal hyperthermic chemoperfusion (CS-HIPEC) is an emerging option for patients with peritoneal carcinomatosis from metastatic colorectal cancer (mCRC). Conduction of further surgical randomized trails has proven unfeasible. On the other hand, the survival benefit derived from liver resection for mCRC is well recognized. Both resection of liver metastases and CS-HIPEC are considered regional therapies. Therefore we compared the outcome of CS-HIPEC to the known benefit in patients resected for liver metastases from mCRC. Methods: All consecutive patients with peritoneal carcinomatosis from mCRC treated by CS-HIPEC at our institution in 2001–2006 were included. Hyperthemic perfusion of peritoneal cavity with 40 mg of mitomycin C for 100 minutes was performed after surgical cytoreduction. The control group was frequency matched 1:4 for age, gender and tumor grade (n=248) and consisted of patients undergoing colorectal and liver resection for mCRC. These cases were extracted from the Surveillance, Epidemiology, and End Results Program. Overall survival was the primary end-point. Results: 62 procedures were performed in 57 patients. Initial systemic chemotherapy was performed in all but one patient in the CS-HIPEC group. Median survival was 28.0 months in the control group versus 25.8 months in CS-HIPEC group (p=0.624). One, 2, and 3-year survival was 78, 53, and 36% in the controls versus 84, 55, and 39% in the CS-HIPEC group. A sensitivity analysis including CS-HIPEC cases initially presenting with synchronous peritoneal carcinomatosis (n=22) showed that survival estimator curves remained identical (p=0.793). Conclusions: Survival benefit in patients undergoing CS-HIPEC is comparable to that derived from liver resection for mCRC. This evidence further supports the role of cytoreductive surgery and hyperthermic chemoperfusion in the treatment of patients with peritoneal carcinomatosis of colorectal origin. No significant financial relationships to disclose.
Breast Cancer in Carriers of <i>BRCA1</i> and <i>BRCA2</i> Mutations: Tackling a Molecular and Clinical Conundrum
Authors: Daniel A. Haber
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.11.3367 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10550129 Breast Cancer in Carriers of BRCA1 and BRCA2 Mutations: Tackling a Molecular and Clinical Conundrum Daniel A. HaberxDaniel A. HaberSearch for articles by this author Show More Massachusetts General Hospital Cancer Center, Boston, MA https://doi.org/10.1200/JCO.1999.17.11.3367 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Use of protein pathway mapping of brain metastasis from breast and lung cancer patients to identify new therapeutic targets: A seed/soil study.
Authors: G. Improta, A. Zupa, J. Deng, H. Fillmore, M. Aieta, P. Musto, W. Broaddus, L. A. Liotta, J. D. Wulfkuhle, E. Petricoin
Journal: Journal of Clinical Oncology (2010)

10620 Background: Brain metastases are the most common fatal complication of systemic cancer, especially of lung (50%-60%) and breast (15%-20%) cancers. In this era of personalized therapy, there is a critical need to uncover the critical molecular targets for brain metastases, however little is known about what signaling pathways are actually activated in the context of the brain microenvironment. Using a unique study set of brain metastases from patients with breast or lung cancer along with a separate set of primary NSCLC tumors, functional broad-scale pathway activation mapping could be performed. Methods: Epitheliumfrom 89 frozen biopsy samples (10 breast and 32 lung metastasis; 47 primary lung cancer) were collected using Laser Capture Microdissection. The phosphorylation/activation of 128 key signaling proteins involved in important molecular pathways was measured using Reverse Phase Protein Microarray technology. Results: Brain metastasis from breast and lung cancer formed distinct pathway subgroups that consisted of amongst others, c-erbb2, AKT, mTOR, EGFR, SMAD, and ERK-p38 signaling. EGFR phosphorylation did not necessarily correlate with EGFR protein expression levels. Of 128 signaling analytes measured, 30 revealed significant differences in levels of activation/phosphorylation between breast and lung metastases to the brain and 58 were differently activated between lung to brain metastases and primary lung tumors (p < 0.05). Breast cancer metastases showed significantly (p < 0.05) higher activation of many components of the c-erbB2/IGFR-AKT pathway networks compared to lung cancer metastasis whereas lung cancer metastases to the brain exhibited higher relative levels of many members of the EGFR- ERK signaling network. Conclusions: Pathway activation mapping of brain metastasis demonstrates signaling activation portraits with both “seed” and “soil” components. These distinct activation groupings reveal both the heterogeneity of signaling networks in brain metastasis that would require a prior stratification to targeted therapies as well as the requirement of direct analysis of the metastatic lesion. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Theranostics Health Theranostics Health Theranostics Health
A Novel Fusion Gene NDEL1-Pdgfrb in a Patient with JMML with a New Variant of TKI-Resistant Mutation in the Kinase Domain of PDGFRβ
Authors: Konstantin Byrgazov, Renate Kastner, Michael Dworzak, Gregor Hoermann, Oskar A. Haas, Raphael Ulreich, Christian E. Urban, Oliver D. Hantschel, Peter Valent, Thomas Lion
Journal: Blood (2014)
Prospective study of cognitive function (cog fcn) in women with early-stage breast cancer (BC): Relationship between perceived and measurable cognitive deficits.
Authors: Lara Heflin, Sally Fang, Amy N DeLuca, Michelle E. Melisko, Mark M. Moasser, John W. Park, Amy Jo Chien, Pamela N. Munster, Laura Esserman, Susan M Landau, William J Jagust, Joel H Kramer, Hope S. Rugo
Journal: Journal of Clinical Oncology (2013)

6619 Background: Cognitive complaints are common among patients (pts) receiving adjuvant therapy (Rx) for early stage BC. Longitudinal prospective data is needed to help understand the relationship between measured cog fcn, patient reported cognitive changes, and patient reported depression and fatigue. We conducted a prospective trial to evaluate the effects of chemo- (CTX) and hormone therapy (HRx) on brain and cog fcn in pts with early stage BC using multiple objective and subjective tests as well as MRI/PET imaging. Here we report relationships between objective measures and patient reported outcomes (PRO). Methods: Eligibility included female pts planning to receive adjuvant Rx for ESBC. Pts were enrolled in 3 Rx groups (grps): CTX, CTX &amp; HRx, and HRx, with a 4 th no Rx age/education matched control group. All pts underwent a battery of objective and subjective cog tests before start of rx, 1 mo after CTX or 5 mo after start of HRx (FU1), then 9 mo (FU2) and 18 mo (FU3) after CTX. Brain MRI, PET and serum estradiol were performed at baseline, FU1 and FU2. Results: 81 pts were enrolled as follows: 14 CTX, 33 CTX &amp; HRx, 22 HRx, and 12 control. 90% completed FU1, 72% FU2, and 62% FU3, with 29 pts waiting to complete testing. Demographics were similar between grps, median age was 54 (range 34-71), 78% were Caucasian. At FUP1, depression (BDI-II) and fatigue predicted poorer overall perceived cog fcn (FACT-Cog); decline in letter fluency (FAS) on cog testing also predicted poorer overall perceived cog fcn (FACT-Cog). Decline in verbal memory (CVLT-II) predicted perceived memory deficits (FACT-Cog Memory), even after controlling for depression and fatigue. Conclusions: In pts receiving adjuvant Rx for early stage BC, depression, fatigue, and decline in letter fluency predicted poorer perceived cog fcn. Decline in verbal memory independently predicted perceived memory deficits, demonstrating that PRO are related to actual deficits in cog fcn. Future intervention studies should focus on these factors. Funding: NIH R01 1AG025303-01A2. Clinical trial information: NCT00755313.