tbuckley/cabot-search huggingface dataset:
Molecular classification for the management of melanoma patients
Authors: G. Palmieri, M. C. Sini, M. Casula, P. Baldinu, G. Palomba, M. Colombino, P. A. Ascierto, G. Botti, C. Caracò, A. Cossu, F. Tanda
Journal: Journal of Clinical Oncology (2008)

20028 Characterization of the different molecular mechanisms involved in development and progression of melanoma (referred to as melanomagenesis) could represent a potential tool to identify the molecular profiles underlying aggressiveness, clinical behavior, or response to therapy as well as to better classify the subsets of melanoma patients with different prognosis.Increasing evidence suggest that melanoma develops as a result of accumulated abnormalities in molecular pathways within the melanocytic lineage. Putting together all recent molecular findings from our group and from literature, we assessed a model of pathogenesis of melanoma, in which we could allocate the different alterations into three sequential phases of melanocytic transformation: 9p21 allelic deletions, BRAF activation, and AKT overexpression (for melanocytic proliferation); impairment of p16-RB and p14-p53 pathways, CyclinD1 overexpression, and PTEN inactivation (for melanoma development); NRAS activation, loss of p16CDKN2A, silencing of PTEN, activation of NF-kB, and MITF gene amplification (for melanoma progression). Different molecular pathways associated with the melanomagenesis may correspond to different subsets of melanoma patients, whose identification should be introduced in clinical trials. Indeed, tissue sections from each melanoma patient should be evaluated through: immunohistochemistry, using antibodies against the main candidate proteins (p16CDKN2A, p14CDKN2A, phosphoERK1/2, phosphoRB, p10, p53, CyclinD1), in order to assess any variation of their expression levels, and fluorescence in situ hybridization (FISH) analysis, in order to evaluate the existence of pathogenetic gene amplifications (for MITF, CyclinD1 or CDK4 genes). These findings along with the advancements of the biotechnologies will do provide even more reliable tools for detailed molecular analyses, allowing to better characterize new biomarkers which may predict prognosis and response to treatment in patients with melanoma. No significant financial relationships to disclose.
A multicenter study of 3 docetaxel regimens with bevacizumab as adjuvant therapy for breast cancer (BC): Preliminary results
Authors: L. L. Hart, S. Badarinath, D. M. Waterhouse, B. Daniel, D. Raimondo, H. A. Burris, D. A. Yardley
Journal: Journal of Clinical Oncology (2008)

575 Background: Docetaxel-containing early stage BC regimens have demonstrated improvements in both disease-free and overall survival in both HER2 ± patients (pts). This trial was designed to test the feasibility of administering bevacizumab with 3 adjuvant docetaxel BC regimens plus trastuzumab in HER2+ pts. The goal of this trial is to identify the cardiac safety (G3/4 congestive heart failure [CHF]) of these combinations. Methods: Phase IIb, randomized, noncomparative study. Planned accrual: 225 pts (75/arm) with previously-untreated node-positive or high-risk node-negative BC. Eligibility: invasive adenocarcinoma; known HER2 status; normal cardiac function, ≥ 4 weeks from surgery. Pts with cardiac disease or risk of cardiac disease were not eligible. Treatment: HER2 normal pts randomized to (mg/m2 unless stated otherwise) Arm A (AC-T): doxorubicin (A) 60 + cyclophosphamide (C) 600 q3w x 4 followed by docetaxel (T) 100 or Arm B (TAC): T 75 + A 50 + C 500 q3w x 6. FISH HER2+ pts received Arm C (TCH): T 75 + carboplatin AUC 6·min/mL q3w x 6 + trastuzumab (H) 6 mg/kg q3w x 52 wks. Bevacizumab (B) 15 mg/kg q3w in all arms starting Day 1 for a total of 52 wks. Granulocyte/myeloid colony-stimulating factor prophylaxis was required in all arms. Results: For the first 62 pts (Arm A = 29, Arm B = 19, Arm C = 14), safety data were analyzed with a cut-off of July 31, 2007; cardiac toxicity was analyzed for all 159 enrolled patients (A = 59, B = 61, C = 39). G3/4 toxicities (Arms A, B and C) included: neutropenia (n = 8, 5, 0), febrile neutropenia (1, 3, 0), thrombocytopenia (3, 2, 0) and fatigue (5, 0, 0). Pulmonary embolism (1, 0, 1) and jugular vein thrombosis (1, 1, 0) were each observed in 2 pts. There has been one on-study death in Arm B attributed to neutropenic enterocolitis. Documented CHF was reported in 3 pts (A = 1, B = 2); 32/159 have discontinued therapy, 24 due to toxicity. Conclusions: Preliminary data indicate an acceptable safety profile, with no unexpected toxicities, when bevacizumab was added to these docetaxel adjuvant BC regimens. Three early CHF events were observed; all events occurred in pts receiving anthracyclines. 159 patients have been enrolled as of 1/7/08; updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
A Phase Ib/Ii Study of Second-Line Therapy with Panitumumab, Irinotecan and Everolimus (Pie) in Metastatic Colorectal Cancer (Mcrc) with Kras Wild Type (Wt)
Authors: A. Townsend, N. Tebbutt, C.S. Karapetis, P. Cooper, N. Singhal, S. Yeend, L. Pirc, T.J. Price
Journal: Annals of Oncology (2014)
Final results from a phase I trial of ixabepilone in patients with advanced malignancies and lymphoma
Authors: C. Aghajanian, O. O’Connor, M. Cohen, R. Peck, H. Burris
Journal: Journal of Clinical Oncology (2006)

2039 Background: Ixabepilone is the first analog in a new class of antineoplastic agents, the epothilones, which stabilizes microtubules and induces apoptosis. Ixabepilone has shown clinical activity in a broad range of tumors. Methods: This Phase I trial was designed to establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), efficacy, safety, pharmacokinetics and pharmacodynamics of ixabepilone when administered as a 1-hour infusion every 3 weeks to patients with advanced solid tumors or lymphoma. Eligible patients were aged ≥18 years with histologically/cytologically confirmed non-hematologic cancer, or a pathologic diagnosis of relapsed/primary refractory non-Hodgkin’s lymphoma (NHL) or relapsed/primary refractory mantle cell lymphoma, with ≤CTC Grade 1 neuropathy. Ixabepilone doses ranged from 7.5–65 mg/m 2 . Response was assessed every 6 weeks using RECIST. DLT was defined as Grade 4 neutropenia and/or febrile neutropenia, thrombocytopenia, ≥Grade 3 nausea/vomiting and non-hematologic toxicity, or treatment delay of &gt;2 weeks due to delayed recovery. Results: Of 61 patients (median age 58, range 18–81), 75% had solid tumors; 25% had lymphoma. 98% and 67% of patients had received one or ≥ two prior chemotherapy regimens, respectively. The MTD of ixabepilone as a 1-hour infusion every 3 weeks was established as 50 mg/m 2 . The most common DLTs were neutropenia, myalgia, arthralgia and stomatitis/pharyngitis. A total of eight patients (13%) achieved a durable objective response. Complete responses were achieved in two patients with primary peritoneal cancer and NHL. A partial response was seen in six patients. The most common Grade 3/4 treatment-related adverse events (only observed at doses ≥40 mg/m 2 ) were sensory neuropathy (13%), fatigue (13%), myalgia (10%), arthralgia (7%), nausea (5%), febrile neutropenia (5%) and neutropenia (5%). Recovery to baseline or ≤Grade 1 neuropathy occurred in some patients. Conclusions: The recommended dose of ixabepilone for the initiation of Phase II studies based on this study is 50 mg/m 2 over 1 hour every 3 weeks. Ixabepilone demonstrates promising safety in patients with solid tumors or lymphoma who have failed standard therapy. Encouraging activity was reported in several tumor types. [Table: see text]
Biopsy Proven Polymyositis in Victoria 1982–1987: Analysis of Prognostic Factors
Authors: Helen Lilley, Xenia Dennett, Edward Byrne
Journal: Journal of the Royal Society of Medicine (1994)

Prognostic factors were analysed in 77 patients with idiopathic inflammatory myopathy identified over a 5 year period. Formal statistical tests did not differentiate useful prognostic indices and a polymyositis disability score was devised in an attempt to gain some prognostic information. Partial (47%) or full (31%) recovery were seen in most cases with no recovery of strength (9%) and death (11%) being less common outcomes. Onset before the age of 50 and duration of symptoms of less than 12 months prior to presentation were favourable prognostic features, and treatment with regimes other than steroid therapy alone a probable favourable indicator. Level of creatine kinase (CK) at presentation and histopathological separation of dermatomyositis or polymyositis failed to alter prognosis. Most patients who died did so within the initial 6 months of treatment. Four of five patients &lt;50 years old with either a fatal outcome or no improvement were treated with steroids alone. Large multi-centre studies are required to provide reliable data about prognostic factors in idiopathic inflammatory myopathies and the methodology used in this study can only be regarded as providing pointers towards possible prognostic factors rather than being definitive.
Intraperitoneal Chemotherapy for Ovarian Cancer: Where Are We Now?
Authors: Pankaj Singhal, Shashikant Lele
Journal: Journal of the National Comprehensive Cancer Network (2006)

Patients with advanced epithelial ovarian cancer are conventionally treated with intravenous (IV) platinum- and taxane-based chemotherapy to try to eradicate residual disease after optimal cytoreductive surgery, resulting in a median overall survival of 49 months. The Gynecologic Oncology Group (GOG) conducted 3 large randomized, phase III clinical trials of intraperitoneal (IP) chemotherapy (GOG 104, 114, and 172) that clearly showed superior progression-free and overall survival with IP chemotherapy compared with IV chemotherapy. All 3 clinical trials investigated IP cisplatin, with the last one adding IP paclitaxel. The most recent study (GOG 172) resulted in a median survival of 66 months for patients in the IP arm versus 50 months for those in the IV arm. Fewer patients in the IP arm than in the IV arm completed all 6 treatment cycles (42% vs. 83%, respectively) because of the toxic effects of chemotherapy and IP catheter-related complications. Initially, patients in the IP arm reported significantly worse quality of life than those in the IV arm. However, at 12-month follow-up, the groups experienced no difference in quality of life, except that paresthesias were more likely to persist at moderate levels among patients in the IP arm. Based on these clinical trials, the National Cancer Institute issued a clinical announcement recommending that women with stage III ovarian cancer who undergo optimal surgical cytoreduction be considered for IP chemotherapy.
춘계학술대회 : 포스터전시 ; 방사선 치료에 반응이 없었던 간세포암의 척추전이를 CT 유도하 경피적 에탄올 주입술로 치료한 1예
Authors: 이현웅, 홍윤석, 이정민, 이석근, 이승현, 장병국, 정우진, 박경식, 조광범, 황재석, 안성훈, 권중혁
Journal: Clinical and Molecular Hepatology (2007)
A Critical Review on the Use of Support Values in Tree Viewers and Bioinformatics Toolkits
Authors: Lucas Czech, Jaime Huerta-Cepas, Alexandros Stamatakis
Journal: Molecular Biology and Evolution (2017)

Phylogenetic trees are routinely visualized to present and interpret the evolutionary relationships of species. Most empirical evolutionary data studies contain a visualization of the inferred tree with branch support values. Ambiguous semantics in tree file formats can lead to erroneous tree visualizations and therefore to incorrect interpretations of phylogenetic analyses. Here, we discuss problems that arise when displaying branch values on trees after rerooting. Branch values are typically stored as node labels in the widely-used Newick tree format. However, such values are attributes of branches. Storing them as node labels can therefore yield errors when rerooting trees. This depends on the mostly implicit semantics that tools deploy to interpret node labels. We reviewed ten tree viewers and ten bioinformatics toolkits that can display and reroot trees. We found that 14 out of 20 of these tools do not permit users to select the semantics of node labels. Thus, unaware users might obtain incorrect results when rooting trees. We illustrate such incorrect mappings for several test cases and real examples taken from the literature. This review has already led to improvements in eight tools. We suggest tools should provide options that explicitly force users to define the semantics of node labels.
Abstract 116: Detrimental Role of Toll-Like Receptor 4 in Cardiovirus-Induced Myocarditis
Authors: Fumitaka Sato, Seiichi Omura, Nicholas E Martinez, Eiichiro Kawai, Ganta V Chaitanya, Jonathan S Alexander, Ikuo Tsunoda
Journal: Circulation Research (2012)

Picornavirus infections have been known as a leading cause of viral myocarditis in humans. Theiler’s murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, the family Picornaviridae and was reported to cause inflammation in the heart in one manuscript, while its pathomechanism is unclear. In viral myocarditis, viral replication in the heart and/or immune responses against virus as well as heart-antigen (autoimmunity) can contribute to the pathogenesis. Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that are important for recognizing pathogens as well as triggering innate immunity. Among TLRs, TLR4 has been demonstrated to play important roles in virus-mediated pathology: 1) TLR4 can contribute to viral entry in some viruses, 2) TLR4 may mediate tissue damage by anti-virus immune responses (immunopathology), 3) high levels of TLR4 expression were observed in the heart of patients with dilated cardiomyopathy following acute viral myocarditis, and 4) some viruses can bind to lipopolysaccharide (LPS), which is a TLR4 ligand. To determine the role of TLR4 in TMEV-induced myocarditis, we infected male C3H/HeJ (TLR4-deficient) and C3H/HeNtac (control TLR4+) mice with the DA strain of TMEV. We harvested the hearts and spleens on days 6 and 7 (acute phase) or days 63 and 64 (chronic phase) post-infection. Cardiac pathology was evaluated by hematoxylin and eosin staining and production of pro-inflammatory cytokines, interleukin (IL)-17A and interferon (IFN)-γ, from spleen cells was measured by an enzyme-linked immunosorbent assay (ELISA). In both mice, mild myocarditis was observed during the acute phase of TMEV infection. During the chronic phase, both mice developed severe pathology in the heart, including basophilic degeneration and calcification. However, the incidence of myocarditis was higher in control mice than TLR4-deficient mice. IL-17A and IFN-γ production was higher in control mice than in TLR4-deficient mice (control vs. TLR4-deficient mice, acute phase: IL-17A, 196 vs. 146 pg/ml; IFN-γ, 72 vs. 39 ng/ml; chronic phase: IL-17A, 290 vs. 229 pg/ml; IFN- γ, 142 vs. 88 ng/ml). These results suggest that TLR4 may be detrimental in TMEV-induced myocarditis by increasing pro-inflammatory cytokine production.
Positron emission tomography (PET) and improved survival in non-small cell lung cancer (NSCLC) patients: The Will Rogers Phenomenon revisited
Authors: K. Chee, D. V. Huynh, M. Brown, D. R. Gandara, T. Wun, P. N. Lara Jr.
Journal: Journal of Clinical Oncology (2008)

11038 Background: The Will Rogers phenomenon occurs when newer technology allows for more sensitive detection of tumor spread, resulting in stage migration and an apparent improvement in patient survival. We investigated whether the use of PET scanning in NSCLC has resulted in this effect. Methods: 12,395 NSCLC patients from Region 3 (Sacramento) of the California Cancer Registry were analyzed. Two distinct periods, pre-PET (1994–1998) and PET (1999–2004), were identified. Inter-period differences in staging procedures, clinical variables, and survival were evaluated. Variables included computed tomography (CT) and PET scan use, age, gender, race, stage, surgery, radiation therapy, chemotherapy, and urban/rural setting. Cox regression was used to generate hazard ratios (HR) for death adjusted for potential confounders related to PET period or use. Further covariate balance and confounder adjustment was done by the Propensity Score (PS) method. The PS (the chance of receiving a PET scan given the covariates) was obtained using logistic regression. Survival differences for each stage were compared between matched subjects who received PET or not, where the matched pairs were based on their PS. Results: There was a 5.4% decline in stage III and an 8.4% increase in stage IV disease in the PET period, corresponding with an increase in PET use from 6.3% to 20.1% (P<0.001). The odds ratio (OR) for stage IV disease compared to stage III for the PET era was 1.53 (95% confidence interval [CI]: 1.397–1.7, P<0.001). PET use was independently associated with better survival in stage III (HR 0.765, 95% CI 0.687–0.851) and stage IV disease (HR 0.638, 95% CI 0.581–0.700), but not for stage I and II. The PET period predicted better survival with an adjusted HR of 0.95 (95% CI 0.912–0.990, P=0.0151). Similar results were obtained with the PS matched pair analysis compared to the above adjusted HRs obtained from multivariate Cox regression. Conclusions: Stage migration is at least in part responsible for an apparent improvement in stage III and IV NSCLC patient survival in the modern PET scan era. The Will Rogers Phenomenon should still be considered in the interpretation of survival data in clinical trials, particularly single-arm uncontrolled studies. No significant financial relationships to disclose.
Six-year (yr) follow-up of patients (pts) with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia (CML-CP) receiving dasatinib.
Authors: Neil P. Shah, Hagop Kantarjian, Dong-Wook Kim, Andreas Hochhaus, Giuseppe Saglio, Francois Guilhot, Charles Alan Schiffer, Juan Luis Steegmann, Hesham Mohamed, David Dejardin, Diane I. Healey, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2012)

6506 Background: Dasatinib, a potent BCR-ABL inhibitor, is approved for use as 1st- and 2nd-line therapy for CML pts with newly diagnosed disease or resistance/intolerance to imatinib. This ongoing study in pts with imatinib-resistant/-intolerant CML provides the longest follow-up of a second-generation BCR-ABL inhibitor. Methods: Study design has been described (Shah, J Clin Oncol 2008). Pts with imatinib-resistant/-intolerant CML (N=670) were randomized to dasatinib 100 mg once daily (QD), 50 mg twice daily (BID), 140 mg QD, or 70 mg BID. Results: Five-yr data are reported here; 6-yr data will be presented. After a minimum of 5 yrs, 151 pts (74%) remain on QD dosing, 85 of whom (56%) are on ≥100 mg QD dosing. Overall, 205 pts (31%) remain on study therapy with 55 pts (53%) originally randomized to BID dosing having switched to QD dosing. For pts randomized to the 100 mg QD arm (n=167), progression-free survival (PFS) at 5 yrs is 57%, overall survival (OS) is 78% with an overall 5% rate of transformation to advanced disease. In exploratory analyses, 42% and 60% of pts had BCR-ABL levels ≤10% (International Scale) at 1 and 3 months (mos), respectively. In a landmark analysis, BCR-ABL ≤10% at 1 or 3 mos was associated with higher 5-yr PFS. For dasatinib 100 mg QD, nonhematologic adverse events (AEs; all grades) generally first occurred in &lt;24 mos. Cumulative rates of AEs in the 100 mg QD arm were headache (33%), diarrhea (28%), fatigue (26%), and pleural effusion (24%). For dasatinib 100 mg QD, cytopenias (grades 3/4) generally first occurred in &lt;12 mos. The most common hematologic AEs (grades 3/4) in the 100 mg QD arm were neutropenia (36%) and thrombocytopenia (24%). AEs were managed by dose/schedule modifications. Conclusions: Five-yr follow-up of pts who switched to dasatinib 100 mg QD after imatinib-resistance/intolerance shows high rates of PFS, and OS with an overall low rate of transformation. Exploratory analyses suggest that achievement of a fast and deep response (≤10% BCR-ABL) at 1 or 3 mos after initiation of dasatinib 100 mg QD may be associated with a higher PFS. Dasatinib 100 mg QD was generally well tolerated over 5 yrs. Six-yr data will be presented.
Optimizing chemotherapy in patients with metastatic transitional-cell carcinoma: High rate of complete response with two sequential dose-dense regimens of cisplatin, gemcitabine, paclitaxel, followed by MVAC.
Authors: Rodolfo Passalacqua, Maria Olga Giganti, Matteo Brighenti, Bruno Perrucci, Maddalena Donini, Federica Negri, Gianluca Tomasello, Laura Toppo, Wanda Liguigli, Rossana Poli, Margherita Ratti, Luigi Benecchi, Andrea Prati, Roberto Arnaudi, Michele Potenzoni, Stefano Panni, Silvia Lazzarelli
Journal: Journal of Clinical Oncology (2015)

303 Background: Currently, cisplatin, gemcitabine, paclitaxel (CGP) and MVAC are the most active regimens in transitional-cell carcinoma (TCC). We tested the hypothesis that two sequential non-cross-resistant, dose-dense (DD) regimens may target different cancer cells, avoid drug resistance, and improve response rate. Methods: This is a phase II, single institutional trial, including patients (pts) with bladder, renal pelvis, or ureteral TCC. Primary end point was the rate of complete response (CR) after two sequential DD regimens. Primary analysis was carried out in the intention to treat (ITT) population.Patients with histological diagnosis of TCC, PS 0–2 (ECOG), adequate organ function and no previous systemic regimens were treated with 4 cycles of CGP DD followed by 4 cycles of M-VAC DD. All received peg-filgrastim after chemotherapy. Pts were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for 2 years and 6 months thereafter. Results: 44 consecutive pts followed in the same oncology institution were included. Males were 73%; median age was 66 years; median PS ECOG was 1; Bajorin risk factors was 0 in 36%, 1 in 48%, 2 in 16%. After the first 4 cycles of CGP DD, we observed 6.8% CR, 43.2% PR, 38.6% SD, and 11.4% PD. After the 4 sequential cycles of M-VAC DD, we observed a global 27.3% of CR, 15.9% of PR, 18.2% of SD, and 13.6% of PD. Median TTP was 9.66 months (95% CI, 6.7-13) and median OS was 18.6 months (95% CI, 12-30). Main grade 3–4 toxicity included asthenia (26%), anemia (26%), neutropenia (9.5%), febrile (7%), thrombocytopenia (12%), and neurological toxicity (5%). No toxic deaths were seen. After a median follow up of 50 months, 4 of 12 patients who obtained a complete response are free of disease since more than 3 years. Conclusions: This sequential use of these two DD regimens leads to a 4-fold increase in CR, an increase in survival, and a possible cure for some patients. A phase III trial is warranted.
Abstract 16108: Smoking-Induced Vascular Damage is Associated With Decreased Circulating MicroRNA-126 and Pesistent Elevation of Plasma Serotonin
Authors: Tomonori Sugiura, Yasuaki Dohi, Sumiyo Yamashita, Nobuyuki Ohte, Yuji Hirowatari, Shiori Ito, Soichiro Iwaki, Satoshi Fujii
Journal: Circulation (2013)
Suppressive Factors in Ascitic Fluids and Sera of Mice Bearing Ascites Tumors2
Authors: Carol J. Elleman, David Eidinger
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Suppressive Factors in Ascitic Fluids and Sera of Mice Bearing Ascites Tumors Get access Carol J. Elleman, Carol J. Elleman Search for other works by this author on: Oxford Academic PubMed Google Scholar David Eidinger David Eidinger Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 3, September 1977, Pages 925–931, https://doi.org/10.1093/jnci/59.3.925 Published: 01 September 1977 Article history Received: 11 November 1976 Accepted: 08 March 1977 Published: 01 September 1977