tbuckley/cabot-search huggingface dataset:
A phase II study of Halichondrin B analog eribulin mesylate (E7389) as second-line therapy for patients with advanced pancreatic cancer
Authors: M. J. Moore, P. Tang, D. Renouf, P. Major, D. Hedley, V. Paterson, L. Wang, B. Dhesy-Thind, B. Southwood, L. Doyle
Journal: Journal of Clinical Oncology (2009)

e15634 Background: Eribulin mesylate is a halichondrin B analog that inhibits microtubule dynamics by a mechanism that is distinct from other tubulin-targeted agents. Preclinical studies suggest that Eribulin may be effective in pancreatic cancer. The primary objective of this study was to determine the objective response rate (complete and partial) to Eribulin in patients with advanced, pancreatic adenocarcinoma that had progressed after gemcitabine based therapy. Methods: Eligibility criteria included histologically confirmed pancreatic adenocarcinoma; measurable locally advanced, or metastatic disease; disease progression after gemcitabine; and ECOG performance status 0–2. Patients (pts) received Eribulin mesylate 1.4 mg/m2 IV on days 1 and 8. Treatment was repeated every 3 weeks in the absence of disease progression or unacceptable toxicity. Response was assessed by CT scans every 6 weeks while on treatment. Initially 12 pts were to be accrued, if 1 or more pt(s) had an objective response the accrual would increase to a total of 37. Results: 15 pts were accrued,14 received treatment and 12 were evaluable for response. Median age 61; M:F = 8:7; ECOG 1:2 = 11:4; Median number of cycles 2 (1–15). Grade 3+ adverse events included neutropenia (29%), fatigue (14%), peripheral neuropathy (7%) and thrombosis (7%). There were no complete or partial responses, and therefore the study was closed at the first accrual cut off. The best response was stable disease (SD) in 5/12 (42%) pts. Of these 5 pts, 3 (42%) had SD for 12 cycles or greater. Survival data is pending. Conclusions: Eribulin was well tolerated and did not result in any objective responses in refractory pancreatic cancer. However, 42% of pts had stable disease and for 3 pts this was maintained for more than 9 months. Further studies of eribulin in pancreatic cancer may be warranted. No significant financial relationships to disclose.
Paclitaxel/carboplatin (TC) vs. paclitaxel/carboplatin followed by topotecan (TOP) in first-line treatment of advanced ovarian cancer. Mature results of a Gynecologic Cancer Intergroup phase III trial of the AGO OVAR and GINECO
Authors: J. Pfisterer, B. Weber, A. Du Bois, A. Lortholary, C. Schade-Brittinger, U. Wagner, H. Bourgeois, C. Jackisch, V. Moebus, F. Mayer
Journal: Journal of Clinical Oncology (2005)

LBA5007 Background: A randomized phase III trial was performed in patients (pts) with advanced ovarian cancer (OC) to determine the role of Top in first line treatment. The sequential manner was chosen to incorporate Top as a non cross resistant third drug to TC by avoiding the toxicity of a simultaneous triple drug regimen. Methods: Between 12/1999 and 03/2002 1,308 pts with previously untreated OC with FIGO stages IIb-IV were randomized to receive 6 cycles of Paclitaxel (175 mg/m2 3h iv) and Carboplatin (AUC 5, Calvert formula) (TC) followed by either no further therapy (n=650) or 4 cycles of Topotecan (1.25 mg/m2 iv d1–5) (Top) (n=658) on a 3 weekly schedule. The primary endpoint was overall survival (OS). This study was designed to show an increase in 3 year survival of 8% with a power of 0.8 using a log-rank test with alpha set to 0.05. Therefore 541 events are necessary. Results: Overall, 9417 treatment cycles were administered, 5535 in the TC-Top arm and 3882 in the TC arm. During treatment with TC, there was no significant difference in Grade (G) 3/4 hematologic and non-hematologic toxicity between both study arms. The median doses of TC were given as scheduled, as were the median intervals between therapy courses. 78% of pts who were randomized for Top received Top. The median number of Top courses was 4.0. Median Top dose/course/day for all courses was 1.25 mg/m2. Top myelotoxicity resulted in treatment delays of at least 7 days in 10.6% of courses. G 3/4 anemia occured in 6.4% of all Top courses, thrombocytopenia in 10.6% and neutropenia in 57.0%. However, this was of minimal clinical relevance in terms of febrile neutropenia (1.0%) or infections (0.9%). Response data were available from 141 and 143 pts with measurable disease in the TC and TC-Top arm. There was no statistically significant difference in CR and PR between treatment arms (76.2% for TC vs. 68.1% for TC-Top, p= n.s). Conclusions: The necessary events for OS are awaited within the next couple of weeks. The final efficacy analysis reporting on OS will be done in February 2005. Results will be submitted as late breaking abstract. No significant financial relationships to disclose.
Study of the BRCA1 and BRCA2 gene mutations and a large rearrangement in high-risk hereditary breast/ovarian cancer patients from Bahia, Brazil.
Authors: I. O. Nascimento, T. B. Machado, B. Toralles, B. Garicochea, C. Abe-Sandes, C. O. Azevedo, L. Meyer, M. Romeo, R. Meyer, K. Abe-Sandes
Journal: Journal of Clinical Oncology (2010)

e12012 Background: About 80% of the hereditary breast cancer patients have BRCA1 or BRCA2 genes mutations. Forty percent these are large rearrangements in the BRCA1 but only few large rearrangements in the BRCA2 have been described. Alu insertion c. 156_157 in BRCA2 is considered a founder mutation of Portuguese origin. Bahia was the capital of Brazil during the colonial period (XVI to XIX centuries) receiving a large number of Portuguese emigrees. Also, it has been for a long time the main trading port for slaves coming from Africa. During the centuries the inbreeding of these ethnic groups, Portuguese and Bantu-Yoruba, created a unique reservoir of different gene polymorphisms, including cancer gene mutations. So, besides to BRCA analysis the c. 156_157insAlu have been searched in high risk of hereditary breast/ovarian cancer patients from Bahia/Brazil. Methods: High-risk hereditary breast/ovarian patients attended at the Oncogenetic Service of the Federal University of Bahia were recruited to participate in the study. All study participants were provided with genetic counseling and gave informed consent prior to blood drawing in accordance with the protocol approved by the local Ethical Comitee. Genomic DNA was extracted from 5mL of peripheral venous blood and storage at -20°C. PCR followed by SSCP were used to mutation screening in BRCA1 and BRCA2. BRCA1 and 2 sequencing analysis was performed. BRCA2 c.156_157insAlu was screened using PCR procedure. Results: From 110 families provided with genetic counseling 77 patients were considered to be high risk hereditary breast/ovarian cancer. BRCA1 exons 2,11 and 20 and BRCA2 exon11 and all the altered SSCP were submmitted to sequencing analysis. Fourteen BRCA1 and 7 BRCA2 mutations were found. All the patients were negative for the BRCA2 exon 3 c.156_157insAlu. Conclusions: In this study, two patients presented BRCA deleterious mutations. Although historically the Portuguese have contributed to the genetic background of the people from Bahia, Brazil, until now the Portuguese founder mutation c.156_157insAlu in the BRCA2 gene has not be found among this population sample probably due the founder effect. No significant financial relationships to disclose.
Improved Outcome With T-Cell–Depleted Bone Marrow Transplantation for Acute Leukemia
Authors: Franco Aversa, Adelmo Terenzi, Alessandra Carotti, Rita Felicini, Roberta Jacucci, Tiziana Zei, Paolo Latini, Cynthia Aristei, Antonella Santucci, Maria Paola Martelli, Isabel Cunningham, Yair Reisner, Massimo F. Martelli
Journal: Journal of Clinical Oncology (1999)

To eliminate the risk of rejection and lower the risk of relapse after T-cell-depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation.Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis.Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status.Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell-depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.
Biological characteristics in triple negative high risk breast cancer and their clinical implications
Authors: A. Herr, O. Gluz, E. Ting, S. Mohrmann, F. Werner, G. Schuett, R. Schmutzler, C. Poremba, U. Nitz, R. Danebrock
Journal: Journal of Clinical Oncology (2006)

20032 Background: Hormone receptor and Her2neu negative breast cancer (triple negative, TN) presents an aggressive biological subtype with decreased survival. Basal-like BC identified by gene expression arrays (Perou CM, et al. Nature 2000) may be associated with TN breast cancer. Several studies defined the origin of TN or BBC breast cancer in a progenitor epithelial cell that is undifferentiated. Other studies investigated the association of TN with EGFR expression or BRCA1 mutations. The aim of our study was to analyze the expression of stem cell or basal markers in TN high risk breast cancer. Methods: We examined 236 patients from central tumour bank from high risk breast cancer patients (&gt;9 positive LN), who were randomized to the WSG AM-01 trial (phase III tandem HDC versus DD CT). The following markers were profiled by IHC in TMA for all patients: ER, PR, Her2neu, MIB-1, EGFR, p53, Ck 5/6, CK17, c-kit, p63, Vimentin, ABCA3, and BCRP. Their correlation with survival was studied. Results: 65 patients (30%) of 218 patients assessable for hormone receptor and Her2neu staining, were identified as TN, surprisingly not indicating any higher incidence of TN tumors in this selected high risk collective, when compared to other more heterogeneous populations. This phenotype was significantly more frequent in premenopausal women, and was significantly associated with G3, MIB1 and EGFR, CK5/6 and 17, c-kit, vimentin, p53 and BCRP expression. No association with p63 and ABCA3 was found. Poor grading, MIB1+, CK5/6 and 17, c-kit, vimentin and BCRP+ strongly correlated with relapse. Patients with TN tumors had significantly worse overall survival (p = 0.002) in comparison to the remaining group. Conclusions: The triple negative BC-type is frequent in patients with multiple positive lymph nodes and has a poor prognosis. Its association with age and basal and progenitor cell molecular markers suggests correlation with BRCA1 mutations as a potential marker for resistance to alkylating agents (Sorlie, PNAS 2003). Modern experimental (chemo)-therapy designs in this subgroup should take into account the higher incidence of EGFR and basal stem cell marker expression, p53 mutations, the poor differentiation, the expression of chemoresistance markers and the high proliferative activity. No significant financial relationships to disclose.
Phase II trial of nab-paclitaxel and bevacizumab as first-line therapy in patients with unresectable melanoma.
Authors: P. D. Boasberg, R. W. Weber, S. Cruickshank, O. Hamid, S. O'Day, L. E. Spitler
Journal: Journal of Clinical Oncology (2011)

8543 Background: We reported preliminary results of a trial investigating the safety and efficacy of nab-paclitaxel and bevacizumab as first line therapy in patients with unresectable melanoma at ASCO, 2009. Accrual has been completed and the median duration of follow-up is 31.5 months. This constitutes the final analysis of this trial. Methods: Eligible were chemotherapy-naive patients with unresectable melanoma, no central nervous system metastases, ECOG performance status of 0-1, and adequate organ function. The treatment was given in a 28 day cycle in which nab-paclitaxel 150mg/m2 was administered on days 1, 8, 15 and bevacizumab 10mg/kg on days 1 and 15. Treatment was continued until disease progression or dose limiting toxicity. Results: Fifty patients were enrolled, 66% with stage IV M1c disease, 40% with elevated LDH. The median survival is 15.6 months (95%CI 11.5, 20.7). The 1-year survival is 63% (95%CI 50%, 77%). The 2-year survival is 31% (95%CI 17%,44%). Fourteen patients remain alive. Additional outcome measures will be presented including the 4-month progression-free survival. Dose modifying toxicities consisted of proteinuria, neutropenia, neuropathy, and mucositis. Conclusions: In this multi-center study, the doublet of nab-paclitaxel and bevacizumab has activity in patients with metastatic melanoma, is well tolerated, and offers efficacy comparable or superior to alternative treatment options. A randomized Phase II or a Phase III trial with this doublet would be required to compare efficacy with alternative approaches.
Does serum VEGF predict prognosis in metastatic colorectal carcinoma patients treated with XELIRI?
Authors: H. S. Bozcuk, M. Artac, S. Akcan, D. K. Korgun, T. Ozben, M. Ozdogan, M. Samur, H. Mutlu, A. Kargi, B. Savas
Journal: Journal of Clinical Oncology (2006)

13548 Background: Serum vascular endothelial growth factor (sVEGF) levels have been shown to possess prognostic value in different solid tumors. However, there is no solid information on the prognostic use of sVEGF in metastatic colorectal carcinoma (MCRC) patients treated with a standard regimen. Methods: 37 consecutive MCRC patients were given XELIRI chemotherapy as the 1 st line treatment (irinotecan 250 mg/m 2 on day one, and Capecitabine 2000 mg/m 2 /day, for 14 days starting on day1, repeated in every 3 weeks). Serum VEGF levels prior to the 1st cycle of chemotherapy was measured by ELISA. Kaplan-Meier survival curves and Cox regression analyses to adjust for basic clinical features were used for the survival analysis. Binary logistic regression analysis was employed to determine correlates of objective response (CR+PR). Results: Best objective response was CR+PR in 20/33(61%) cases (3 CR; 9% + 17 PR; 52%). In 4 patients, response assessment was not possible. Median sVEGF was 650(107–1865) pg/ml. Median OAS and PFS was 16.2 and 5.9 months, respectively. Increased age turned out to be the only predictor of better OAS with borderline significance (P=0.09). After adjustment for performance status (0, 1 versus 2) and disease extent (single vs. multiple metastatic sites), age was statistically significant (P=0.042, HR=0.95(0.90–0.99)). For PFS, again age (P=0.038) was the only correlate. After controlling for performance status and disease extent, age (P=0.014, HR=0.95(0.92–0.99)) and performance status (P=0.036, HR=3.27(1.08–9.88)) were significant. No factor was associated with the likelihood of objective response. Conclusion: In this study, we failed to determine any prognostic value for sVEGF in MCRC. However, older age and good performance status appear to have a borderline positive prognostic value for MCRC patients treated with XELIRI. No significant financial relationships to disclose.
Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels
Authors: FC van Gils, ME van Teeffelen, KJ Neelis, J Hendrikx, H Burger, RW van Leen, E Knol, G Wagemaker, AW Wognum
Journal: Blood (1995)
Abstract 9873: Inhibition of IL-1{beta} Signaling Prevents Aneurysm Formation in a Novel Model of Thoracic Aortic Aneurysm
Authors: William F Johnston, Morgan Salmon, Gang Su, Matthew L Stone, Nicolas H Pope, Guanyi Lu, Gilbert R Upchurch, Gorav Ailawadi
Journal: Circulation (2013)

Objective: To determine the role of IL-1β signaling in a novel model of thoracic aortic aneurysms (TAAs). Methods: To develop a TAA model, 8-10 week old male C57Bl/6 wild type mice (WT) underwent t...
Comparative diagnostic accuracy of magnetic resonance imaging and immunoscintigraphy for detection of bone marrow involvement in patients with malignant lymphoma.
Authors: C Altehoefer, U Blum, J Bathmann, C Wüstenberg, P Uhrmeister, J Laubenberger, W Lange, J Schwarzkopf, E Moser, M Langer
Journal: Journal of Clinical Oncology (1997)

PURPOSE To compare the diagnostic accuracy of magnetic resonance imaging (MRI) and immunoscintigraphy (IS) for detection of bone marrow infiltration in malignant lymphoma. PATIENTS AND METHODS In 32 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), MRI of the axial skeleton and whole-body IS using technetium-99m (99mTc)-labeled monoclonal antibodies were reviewed and compared with iliac crest biopsies. Criterion for marrow infiltration was a positive biopsy or concordant positive results of MRI and IS. RESULTS In 16 patients (50%), MRI, IS, and iliac crest biopsies were negative for marrow infiltration. Iliac crest biopsy showed infiltration in only four patients (13%). Infiltration was missed in two of 32 patients with IS and in one patient with MRI. In one additional patient, MRI was false-positive because of pelvic hematopoietic hyperplasia. A subset of nine patients (28%) with negative biopsies had bone marrow involvement according to MRI and IS with identical location and pattern of infiltration. In eight of these nine patients, diagnostic imaging indicated marrow involvement only in noncrest marrow. Subsequent biopsy confirmed infiltration in five patients. The clinical course suggested true-positive imaging results in the remaining four patients. Two patients (6%) remained equivocal. Overall concordance of MRI and IS for marrow infiltration was 88% (28 of 32 patients). CONCLUSION Diagnostic imaging is essential for optimal staging in malignant lymphoma, as blind biopsies appear to have low sensitivity for bone marrow infiltration because of frequent involvement in noncrest marrow. both imaging modalities show a high rate of detection of bone marrow infiltration.
Research on the detection of the gene clusters associated with pulmonary embolism by oligo microarray
Authors: Kebin Cheng, Lemin Wang, Hengjun Gao, Jinfu Xu
Journal: European Respiratory Journal (2013)

Background  Pulmonary embolism (PE) has been proved to be associated with huge amounts of gene mutations, gene polymorphisms and gene differential expressions in human being.   O  bjectives  To find out gene clusters associated with PE through the detection of differential expression genes between PE patients and controls by oligo microarray, and elucidate the molecular genetics mechanism of PE.   Methods  The fresh venous blood of 9 PE patients and 33 normal controls were collected,then the total RNA was extracted and purified.We synthesized 9 PE cRNA probes labeled with cyanine 3, a standard cRNA probe labeled with cyanine 5 which was from total RNA mixture of all the controls.After that,hybridization with Agilent Whole Human Genome Oligo Microarray was performed.The image scanning and data analysis showed the differential expression, which was proved by FQ-PCR.   Results  434 differential expression genes were screened. These gene transcripts are associated with blood coagulation, immune or inflammatory response,cell proliferation, apoptosis, metabolism, cell growth/maintenance, cell-cell signaling or signal transduction, cytoskeleton or motility, transcription, DNA/RNA binding, and so on.   Conclusions  Profiling oligo microarray technology is an effective tenique in screening candidate gene clusters of PE. The impairment of the balance of blood coagulation system and fibrinolytic system are important mechanisms for PE. Our study suggests that the inflammatory response, cell proliferation/apoptosis and metabolic disturbance may play a role in the process of initiation and development with PE.
Risk of asthma, passive smoking and genetics
Authors: T J Whitfield
Journal: Thorax (2009)

There is a known association between genetic variants on chromosome 17q21 and the development of asthma. This study investigated whether specific single nucleotide polymorphisms (SNPs) on 17q21 were linked to specific phenotypes of early-onset asthma and early-onset smoking-exposed asthma.

Individuals with asthma and their first-degree relatives were selected from seven French clinical centres. …
Blocking the tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritis
Authors: Lilian N Nwosu, Paul I Mapp, Victoria Chapman, David A Walsh
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Tropomyosin receptor kinase A (TrkA) mediates nociceptor sensitisation by nerve growth factor (NGF), but it is unknown whether selective TrkA inhibition will be an effective strategy for treating osteoarthritis (OA) pain. We determined the effects of a TrkA inhibitor (AR786) on pain behaviour, synovitis and joint pathology in two rat OA models. Methods Knee OA was induced in rats by intra-articular monosodium-iodoacetate (MIA) injection or meniscal transection (MNX) and compared with saline-injected or sham-operated controls. Pain behaviour was assessed as weight-bearing asymmetry and paw withdrawal threshold to punctate stimulation. Oral doses (30 mg/kg) of AR786 or vehicle were administered twice daily in either preventive (day −1 to –27) or treatment (day 14–28) protocols. Effect maintenance was evaluated for 2 weeks after treatment discontinuation. Alterations in knee structure (cartilage, subchondral bone and synovium) were examined by macroscopic visualisation of articular surfaces and histopathology. Results Preventive AR786 treatment inhibited pain behaviour development and therapeutic treatment attenuated established pain behaviour. Weight-bearing asymmetry increased 1 week after treatment discontinuation, but remained less than in vehicle-treated arthritic rats, whereas paw withdrawal thresholds returned to levels of untreated rats within 5 days of treatment discontinuation. AR786 treatment reduced MIA-induced synovitis and did not significantly affect osteochondral pathology in either model. Conclusions Blocking NGF activity by inhibiting TrkA reduced pain behaviour in two rat models of OA. Analgesia was observed both using preventive and treatment protocols, and was sustained after treatment discontinuation. Selective inhibitors of TrkA therefore hold potential for OA pain relief.