tbuckley/cabot-search huggingface dataset:
Predicting metastasis in uveal melanoma: Identification of a prognostic classifier by genomic profiling using array-CGH of 78 ocular tumors (OT) and 66 liver metastases (LM)
Authors: J. Couturier, J. Trolet, P. Hupe, L. Desjardins, P. Mariani, X. Sastre-Garau, B. Asselain, E. Barillot, S. Saule, S. Piperno-Neumann
Journal: Journal of Clinical Oncology (2008)

9041 Background: Despite improvements in PT treatment, more than 50% of patients develop metastases usually in the liver, with a median time of 2.4 years from ocular diagnosis, and a median survival of 6 months. Apart from complete resection of liver metastases, no treatment has yet improved overall survival. Moreover, there is no effective adjuvant treatment. Beside clinical and pathologic features, cytogenetic alterations, particularly monosomy 3, are strongly associated with metastasis. We report here the array-CGH analysis of 78 PT and 66 LM in order to identify an accurate prognosis classifier for targeting high risk patients who may benefit from adjuvant systemic therapy. Methods: PT samples were obtained from enucleated eyes of 78 patients (median follow-up 54 months, range: 24–96), LM from 66 patients by complete surgical resection. Tumor DNAs were co-hybridized with reference DNA on a genome-wide BAC/PAC DNA microarray with a 1 Mbase average resolution. After normalization of data, minimal regions of gain and loss were identified, and hierarchical clusterings were performed for PT and LM. Correlations were looked for between genomic profiles of tumors and metastatic status of patients, and a prognostic classifier was built. Results: Status of chromosome 3 defines two groups of genomic profiles in PT and LM: group 1 with disomy 3, and group 2 with monosomy 3. Seven PT show a partial loss of chromosome 3, with a minimal deletion of 8.9 Mbase, distal to 3p25.3. Hierarchical clustering lead to define 5 subgroups (see table). A prognostic classifier including monosomy 3, gains of 6p and of whole 8q, and losses of 8p and 16q, leads to the best prediction performance in this sample (83%). Conclusions: Genomic profiling by array-CGH should be a robust and reliable approach for identifying high-risk patients eligible for liver metastases screening and adjuvant systemic therapy.Genomic subgroups and their frequencies in PT and LM. Chromosome 3 status PT (%) LM (%) Group 1 : 3 normal 30 19 Group 2 : -3 70 81 Genomic subgroups 1a : +6p 1b : +6p, -6q, +distal 8q 46 54 17 83 2a : -3 2b : -3, -8p, +8q, -16q 2c : -3, -8p, +8q, -16q, -1p 20 45 35 4 55 41 No significant financial relationships to disclose.
Immune and Gene Therapy as an Emerging Cancer Treatment
Authors: Kenzaburo Tani, Yasuki Hijikata, Mutsunori Murahashi, Shohei Miyamoto, Hiroyuki Inoue, Yoshihiro Tanaka, Shinichi Kobayashi, Toshihisa Tsuruta, Kazunari Yamada, Toshihiko Okazaki
Journal: Annals of Oncology (2014)
Abstract 054: The Use of Administrative Data and Natural Language Processing to Estimate the Incidence of Statin-related Rhabdomyolysis
Authors: James S Floyd, Susan R Heckbert, Noel S Weiss, David S Carrell, Bruce M Psaty
Journal: Circulation (2012)

Introduction: Despite the problem of misclassification, many studies of adverse drug reactions (ADRs) rely on administrative data rather than events validated by medical record review. Hypothesis: We evaluated the new ICD-9 code for rhabdomyolysis (728.88) and natural language processing (NLP) as methods to identify cases of statin-related rhabdomyolysis, and estimated the incidence with various statins and doses. Methods: We conducted a population-based study of statin users in a health maintenance organization in Washington State from 2006-2010. Trained abstractors reviewed the medical records of selected statin users to identify cases of statin-related rhabdomyolysis and myopathy, defined as muscle injury with a peak creatine kinase level ≥ 10x and 5-10x the upper limit of normal, in the absence of other likely etiologies. Results: The review of medical records for 361 statin users with an administrative code for rhabdomyolysis or related codes yielded 24 cases of statin-related rhabdomyolysis and 12 of myopathy. NLP methods identified another 5 cases of rhabdomyolysis and 6 of myopathy. The positive predictive value of the rhabdomyolysis ICD-9 code in statin users was only 7.5%. Incidence rates appear in the Table . The incidence rate ratio (IRR) of statin-related rhabdomyolysis for simvastatin compared with other statins was 2.61 (95% CI, 1.03-7.84), and the IRR for the 80mg dose of simvastatin compared with 20mg was 12.2 (95% CI, 3.6-52.3). In an analysis of administrative diagnostic data alone, the IRR for simvastatin compared with other statins was 1.03 (95% CI 0.80-1.34), and for 80 mg dose of simvastatin compared with 20 mg it was 1.77 (95% CI 1.05-2.88). Conclusions: Use of the administrative diagnostic code for rhabdomyolysis was highly nonspecific for this ADR and resulted in weaker associations than methods that verified ADRs with medical record review. These findings raise questions about the use of administrative data alone in studies of other medication ADRs when those events have other possible etiologies. Incidence rates for statin-related rhabdomyolysis and myopathy. Cases Incidence rates (95% CI) * Statin Person-years of exposure Statin-related rhabdomyolysis Statin-related myopathy Statin-related rhabdomyolysis Statin-related myopathy Simvastatin 170,605 23 10 13.2 (8.6-20.2) 5.9 (2.8-10.8) &lt;20mg/day 21,832 0 0 0 (0-16.9) 0 (0-16.9) 20-39mg/day 75,082 4 2 5.3 (1.5-13.6) 2.7 (0.3-9.6) 40-79mg/day 56,703 8 4 14.1 (6.1-27.8) 7.1 (1.9-18.1) ≥80mg/day 16,876 11 4 64.8 (32.3-116.9) 23.6 (6.4-60.3) Other statins 116,154 6 8 5.2 (1.9-11.2) 6.9 (3.0-13.6) All statins 286,758 29 18 10.1 (7.8-14.5) 6.3 (3.7-9.9) * Cases per 100,000 person-years of statin use
High-dose treatment (HDT) and autologous stem cell transplant (ASCT) in Waldenstrom’s macroglobulinemia (WM) patients (pts): A single center experience
Authors: A. Fassas, B. Barlogie, S. Ward, E. Rasmussen, F. van Rhee, M. Zangari, C.-K. Lee, G. Talamo, R. Thertulien, M. Fox, G. Tricot
Journal: Journal of Clinical Oncology (2005)

6661 Background: An algorithm for treating WM pts (upfront or at relapse) and the optimal integration of new, active agents remain to be defined. HDT/ASCT has been used infrequently, mainly for relapsing pts. We report our HDT experience in WM pts. Patients/Results: Twenty-two pts with symptomatic WM received HDT/ASCT between 1995–2004. There were 15 men and 7 women [median age: 54 (41–75) years] with IgMκ (15), IgMλ (6) and IgAλ (1). Fifteen pts received HDT as first-line treatment at a median of 6 (3–15) months post-diagnosis. Induction treatment was DT-PACE followed by Rituxan/DT-PACE (10) and pulsed dexamethasone x1–3 followed by cyclophosphamide or CDEP (5). Eleven pts collected >10x106 CD34+ cells/Kg; 4 pts collected 7–10 x106 CD34+ cells/Kg (2 attempts). The remaining seven pts received HDT for progressive disease (PD) at a median of 5 (3–14) years post-diagnosis. Three pts collected >10x106; 2 pts collected <5x106 after 2–3 attempts. Various regimens were used for SC collection. Conditioning regimen was melphalan 140–200mg/m2 (20) and BEAM (2). Six pts received 2 transplants. There was no peri-transplant mortality. Median time to ANC>500/μl and platelet>20k was 11 and 12 days, respectively. HDT induced CR/nCR (10), PR (9) and <PR (2) (1 too early to evaluate). In the newly diagnosed patient group, HDT induced CR/nCR (9), PR (5) and <PR (1). One patient died of lung cancer 28 months post-ASCT. In the PD patient group, HDT induced CR (1), PR (4) and <PR (1). Three pts died; 2 of PD and 1 of sepsis 13, 36 and 3 months post-ASCT, respectively. With a median follow-up of 32 months, 18 pts remain alive (16 progression-free). Rituxan/DT-PACE used in 11 pts led to 100% PR (2 CR/nCR). Conclusions: Despite the limited follow-up, the quality of responses supports using Rituxan /DT-PACE as induction treatment followed by HDT in newly diagnosed WM pts. Integration of 2-cda following SC collection (to avoid the potential genotoxic effect of purine analogues) and Rituxan maintenance are included in our current protocol for these pts. No significant financial relationships to disclose.
Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia
Authors: Cristina Fernandez-Arias, Juan Rivera-Correa, Julio Gallego-Delgado, Rachel Rudlaff, Clemente Fernandez, Camille Roussel, Anton Götz, Sandra Gonzalez, Akshaya Mohanty, Sanjib Mohanty, Samuel Wassmer, Pierre Buffet, Papa Alioune Ndour, Ana Rodriguez
Journal: Cell Host & Microbe (2016)
Tumorigenesis by Millipore Filters in Mice: Histology and Ultrastructure of Tissue Reactions as Related to Pore Size2
Authors: Richard D. Karp, Kenneth H. Johnson, Lance C. Buoen, H. K. G. Ghobrial, Inge Brand, K. Gerhard Brand
Journal: JNCI Journal of the National Cancer Institute (1973)

Hydrophilic Millipore filter disks, 2.0 cm in diameter, with 8 different pore sizes ranging from 0.025 to 8.0 µm, were subcutaneously implanted into female CBA/H, CBA/H-T6, or (CBA/H × CBA/BrA)F1 mice. Sarcomas at implant sites developed after 7–27 months in 25 of 31 animals that had received filters with pore sizes of ≤0.1 µm. Filters with pore sizes of ≥0.22 µm were non-tumorigenic. Histologic and ultrastructural studies were done 1, 3, 5, and 10 months post implantation on specimens composed of implants and surrounding tissue reactions. Nontumorigenic filters induced tissue reactions characterized by a) invasion of filters by macrophages or their cytoplasmic processes and b) presence of phagolysosomes within macrophages as evidence of phagocytic activity. In tissue reactions induced by tumorigenic filters, these criteria were always missing; instead, there was more fibrosis which resulted in thicker collagenous tissue capsules. The results permitted assessment of various etiologic hypotheses relating to a) interruption of cellular contact or communication, and b) smoothness, continuity, or electric charge of foreign-body surfaces.
Bone-targeted therapy in advanced androgen-independent prostate carcinoma: A feasibility study
Authors: A. Crespo, M. Sureda, B. Vazquez, J. Rebollo, E. Calvo, F. J. Garcia-Cases, A. Brugarolas
Journal: Journal of Clinical Oncology (2005)

4793 Background: Bone metastasis is a major complication for prostate carcinoma patients, and some times the first indication of progressive disease and worsening prognosis. Various bone target radio-pharmaceuticals have shown good efficacy in relieving bone pain due to metastasis, improving morbidity, and in some studies improving survival. We have used 153-Samarium-lexidronam in advance prostate carcinoma patients with osteoblastic metastases in an attempt to improve the duration of the responses. Methods: Seven advanced androgen-independent prostate carcinoma patients with osteoblastic bone metastases were treated with 153-Sm-Lexidronam. A single dose of 37 MBq/Kg (1 mCi/Kg) was given in 4 patients, 2 doses in two and 3 doses in one (median interval in-between, 3 months). Six treatments were given as a consolidation of the previous response, one treatment as adjuvant therapy and four treatments in biochemical and/or bone progression. Results: Overall 3 out of 7 patients (pts) had a partial response −minimum of 50% reduction in serum prostate-specific antigen concentration (PSA)− that was maintained for at least 8 weeks, 2 pts had no significant changes in PSA and 2 pts had bone and/or biochemical progression. The duration of the responses were 11, 4 and 3 months (m) respectively. Finally, all the patients had a progression of their disease, with a medium time to progression of 3 m. No haematological toxicity (HT) was observed in 3 pts, HT Grade II in 1 pt and HT Grade III in 3 pts (one heavily pre-treated with radiotherapy, 2 concurrent chemo-radiotherapy). No added toxicity appeared in re-treated pts. Conclusions: Bone target therapy with 153-Sm-Lexidronam could be an effective modality of treatment to improve both duration and quality of response in advance prostate carcinoma with bone metastases when a good PSA response was previously achieved. No life-threatening toxicity was encountered, with only severe toxicity in radiation-treated patients. Re-treatment is safe. No significant financial relationships to disclose.
Anti-elastin immunity in COPD patients
Authors: Manuela Rinaldi, An Lehouck, Marc Decramer, Ghislaine Gayan-Ramirez, Wim Janssens
Journal: European Respiratory Journal (2011)

Introduction:  The contribution of anti-elastin immunity in COPD is subject of intense debate. Conflicting data are reported on the presence of serum auto-antibodies against elastin fragments correlating with COPD severity. As auto-immunity is driven by antigen-specific T cells, we investigated the presence of B cell and T cell responses against elastin fragments in a large sample of COPD patients and controls.   Material and methods:  Anti-elastin antibodies were analyzed with indirect ELISA on plasma samples of 352 COPD patients (GOLD 1-4) and 168 age-matched smoking controls. In a random subgroup of 25 patients, T-cell responses against elastin fragments were further determined with ELISPOT (IFN-g and IL-2) on peripheral blood mononuclear cells (PBMC) and compared with responses of 5 non-smoking age-matched controls.   Results:  Increased titers of anti-elastin antibodies were found in 14.2% (24/168) of smoking controls compared to 12.5% (44/352) of the COPD population (p=0.07). No significant correlation was found between anti-elastin antibodies and FEV1% predicted (p=0.699), nor with the presence of emphysema on CT scan (p=0.150). Despite significant responses to control antigen, ELISPOT analysis could not detect increased T cell responses against elastin in any of the individuals.   Conclusion:  Anti-elastin antibodies are not specific for COPD patients and do not correlate with disease severity. The absence of elastin-specific T cell responses further weakens the role of anti-elastin auto-immunity in the pathogenesis of COPD.  Supported by FWO-Vlaanderen G.0687.09.
Breast Carcinomas Arising in Carriers of Mutations in <i>BRCA1</i> or <i>BRCA2</i>: Are They Prognostically Different?
Authors: Kelly-Anne Phillips, Irene L. Andrulis, Pamela J. Goodwin
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To review the preclinical and clinical studies relevant to the prognosis and prognostic associations of BRCA1- and BRCA2-associated breast carcinomas, with an emphasis on research methodology. METHODS: Reports of relevant studies obtained from a MEDLINE search, and references from these articles, were critically reviewed. RESULTS: Consistent associations with both favorable (medullary or atypical medullary carcinoma) and unfavorable (high tumor grade, hormone receptor negativity, somatic p53 mutation) prognostic characteristics have been found for BRCA1-associated breast carcinomas. Inconsistent results have been demonstrated for prognostic associations of BRCA2-associated breast tumors. Clinical studies that have directly assessed the prognosis of these tumors have not shown a clear effect of BRCA1 or BRCA2 mutation, but no study has used optimal methodology. In vitro and animal model data suggest a possible influence of these mutations on response to agents that cause double-strand DNA breaks, but clinical data are limited. CONCLUSION: The elucidation of an identifiable subgroup of breast carcinomas that result from germline mutations in BRCA1 or BRCA2 may be an important step toward genotype-based understanding of prognosis and choice of therapy in this disease. However, currently there are inadequate data to support use of BRCA1 or BRCA2 status to counsel individuals regarding their prognosis or to select treatment. Well-designed studies of population-based inception cohorts of breast cancer patients, which have adequate sample size and complete follow-up, and which use objective outcome criteria and blinding of outcome assessment, are required to optimally address this question.
Efficacy/Safety of Palonosetron Vs Ondansetron in Preventing Chemotherapy-Induced Nausea and Vomiting (Cinv) in Pediatric Patients Receiving Moderately or Highly Emetogenic Chemotherapy (Mec/Hec)
Authors: G. Kovacs, A. Wachtel, E. Basharova, T. Spinelli, P. Nicolas, E. Kabickova
Journal: Annals of Oncology (2014)
Abstract P178: Famine Exposure in the Young and the Risk of Type 2 Diabetes in Adulthood
Authors: Annet F van Abeelen, Sjoerd G Elias, Patrick M Bossuyt, Diederick E Grobbee, Yvonne T van der Schouw, Tessa J Roseboom, Cuno S Uiterwaal
Journal: Circulation (2012)

Background The developmental origins hypothesis proposes that undernutrition during early development is associated with an increased risk of type 2 diabetes mellitus (T2DM) in adulthood. We investigated the association between moderate and severe undernutrition during childhood and young adulthood and the risk of T2DM in later life. Methods We studied 7,837 women from the Prospect-EPIC cohort who were exposed at various degrees to the short but severe 1944-1945 Dutch Famine when they were between 0 and 21 years. We used Cox proportional hazard regression models to explore the effect of famine exposure on the risk of subsequent T2DM in adult life. We adjusted for potential confounders, including age at famine exposure, smoking, and level of education as a proxy for socio-economic status. Findings Famine exposure during childhood and young adulthood was associated with an increased T2DM risk in a dose-dependent manner (p for trend &lt;0·001). In those who were moderately famine exposed the T2DM hazard ratio (HR) was 1·36 (95% CI 1·09 to 1·69); in those severely famine exposed the HR was 1·64 (95% CI 1·26 to 2·13) relative to unexposed women. These effects did not materially change after adjustment for confounders (HR for moderate: 1·33, 95% CI 1·06 to 1·67; HR for severe: 1·51, 95% CI 1·16 to 1·98). Interpretation This study provides the first direct evidence, using individual famine exposure data, that a short period of moderate or severe undernutrition during postnatal development increases the risk of T2DM in adult life.
TRAIL death receptor therapy for malignant glioma
Authors: J. B. Fiveash, D. J. Buchsbaum, G. Y. Gillespie
Journal: Journal of Clinical Oncology (2005)

3187 Purpose: To evaluate the in vivo efficacy of a novel proapoptotic mouse monoclonal antibody, TRA-8, which binds to death receptor 5 (TRAIL-R2). TRA-8 acts through a caspase-8 dependent mechanism. The antibody approach to death receptor therapy may be safer than TRAIL-based therapies since TRA-8 does not induce apoptosis in normal tissues. Methods: The in vivo cytotoxicity of TRA-8 alone and in combination with temozolomide (Tmz) chemotherapy and radiation therapy (RT) was evaluated in D54 glioma xenografts. Athymic nude mice were injected subq with 2x107 cells. 8 treatment groups of 7 mice each were compared: control, TRA-8 alone, RT alone, Tmz alone, RT/TRA-8, RT/Tmz, TRA-8/Tmz, and TRA-8/Tmz/RT (triple therapy). The primary endpoints of these subq experiments were tumor response and regrowth. Two additional intracranial experiments have been performed with 10–11 animals treated per group with TRA-8 alone, Tmz alone, Tmz/RT, triple therapy, or untreated control. Results: In both subq experiments, complete tumor regressions were most common in animals that received triple therapy with the TRA-8/Tmz/RT (12/15 animals) vs. those that did not (4/105 animals), p=<0.001. 3/4 complete regressions that did not receive triple therapy received TRA-8/Tmz. The addition of TRA-8 to either RT or Tmz enhanced tumor growth delay compared to either RT or Tmz alone. TRA-8 alone without Tmz or RT had limited activity in this model. In intracranial experiments, TRA-8 alone had marginal activity. In both studies, the median survivals of triple treated or chemoradiation only treated mice were significantly different from that of control or TRA-8 alone mice. While median survivals of triple-treated mice (107, 219 days) were greater in both studies than those of mice receiving chemoradiation without TRA-8 (75, 166 days), these differences were not statistically significant (p=0.10, p=0.17). Conclusions: TRA-8 significantly enhances tumor regression and growth delay in vivo in combination with RT and chemotherapy. Intracranial experiments suggest an improvement in survival with the addition of TRA-8 to chemoradiation as compared to chemoradiation alone. Future studies of local administration through CED may improve upon these Results: Supported by ABC2 and Sankyo Co., Ltd. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sankyo
High intensity focused ultrasound in the treatment of small kidney tumours— The Oxford experience
Authors: T. A. Leslie, R. O. Illing, J. E. Kennedy, M. F. Wu, G. R. Ter Haar, R. R. Phillips, A. S. Protheroe, D. W. Cranston
Journal: Journal of Clinical Oncology (2006)

14645 Background: High-intensity focused ultrasound (HIFU) provides a potential non-invasive alternative to conventional therapies. We have been using the extracorporeal ultrasound-guided Model-JC Tumor Therapy System (HAIFU Technology Company, China) in clinical trials to evaluate the safety and feasibility of treating small renal tumours. Methods: Patients with renal tumours less than 4cm diameter and unsuitable for surgery were treated with HIFU were enrolled into this phase II prospective trial. Treatment was delivered under general anaesthesia in a single session using the Model-JC Tumor Therapy System. Magnetic resonance imaging (MRI) 12 days after treatment provided an initial assessment of response (technical success). Patients are followed-up with further MR imaging at 6 months and one year to gauge technique effectiveness. A total of 14 patients will be included in the trial. Results: Eight patients with kidney tumours have been treated to date. All eight have had pre- and 12-day post-treatment MR imaging. One patient was not included in the analysis as treatment was suspended due bowel interposition in the treatment field during therapy. MRI changes suggestive of kidney tumour response have been seen in 4/7 (57%) cases. Complete ablation has been seen in two cases and partial ablation in two cases. One patient remains disease free 12 months after HIFU. Mild transient discomfort was reported by 4/8 patients (50%), and moderate discomfort in 3/8 (38%) but more severe pain needing opiate analgesia has not been encountered in this series. Minor skin toxicity (1mm blister at the treatment site) was seen in two patients. All patients were discharged the day after the procedure. There have been no adverse effects on renal, haematological or hepatic function. Conclusions: Extracorporeal HIFU has the ability to completely ablate small renal tumours. Our early clinical experience suggests that HIFU treatment of kidney tumours is safe and extremely well tolerated. The reasons for the variability in observed response remain obscure, and reliability of tumour ablation will need to improve before extracorporeal HIFU can be proposed for wider clinical use. [Table: see text]