tbuckley/cabot-search huggingface dataset:
ACNU‐ETOP‐CBDCA‐CPM併用化学療法後の難治性高悪性度非ホジキンリンパ腫における自家造血幹細胞移植
Authors: Asai O, Kato A, Yano S, Watanabe H, Katori M, Nagamine M, Yahagi E, Kobayashi T, Usui N, Yamazaki H, Dobashi N, Yamaguchi Y, Hoshi Y, Kuraishi Y
Journal: Blood (1999)
In Infant ALL with t(4;11)/MLL-AF4 Multiple and Phenotypically Distinct CD19+ BM Subsets Initiate Leukemia in NOD/SCID Mice..
Authors: Michela Bardini, Lilian Wittmann, Lilia Corral, Luca Lo Nigro, Zhi Ma, Rakesh Singh, Giuseppe Basso, Giulio De Rossi, Mel Greaves, Andrea Biondi, Giovanni Cazzaniga, Sten Eirik Jacobsen
Journal: Blood (2009)
Human Primary Mensenchymal Stromal Progenitor Cells Are Highly Enriched in Both, the CD271+/CD146+ and CD271+/CD146− Bone Marrow Population with the Latter Acquiring CD146 Expression upon Culture in-Vitro
Authors: Ariane Tormin, Jan Claas Brune, Stuart Walsh, Johan Richter, Xiaolong Fan, Stefan Scheding
Journal: Blood (2008)
Cystatin C Strengthens the Association of Kidney Function with Mortality and End-Stage Renal Disease
Authors: Michael G. Shlipak, Kunihiro Matsushita, Johan Ärnlöv, Lesley A. Inker, Ronit Katz, Kevan Polkinghorne, Dietrich Rothenbacher, Mark I. Sarnak, Brad C. Astor, Josef Coresh, Andrew S. Levey, Ron T. Gansevoort
Journal: Circulation (2013)

Cystatin C Strengthens the Association of Kidney Function with Mortality and End-Stage Renal Disease
Implementation of a high-quality biospecimen program to support molecular medicine.
Authors: Susanne Morrill, Daniza Mandich, Richard Cartun, Andrew L. Salner
Journal: Journal of Clinical Oncology (2013)

200 Background: The successful implementation of a tumor genomics program relies heavily upon the collection of high quality tumor tissue samples. Although there has been an evolution towards utilizing formalin-fixed paraffin embedded (FFPE) tissue, many research centers continue to rely upon frozen fresh tissue for these types of analyses. A comprehensive effort is required to supply high-volume and high-quality tissue for research. Most community hospitals, even with superb pathology departments, are not well suited to deliver consistent tissue samples without a concerted programmatic effort. As part of the NCI Community Cancer Centers Program (NCCCP), we undertook the development of such capability at our hospital. In addition, as a member of H. Lee Moffitt Cancer Center’s Total Cancer Care program, we received grant funding to help support this comprehensive effort. Our patients and clinicians expressed a strong desire to participate in this type of translational research. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. Methods: We developed a comprehensive staffing model to implement this program, including a program coordinator, consenters, pathology assistant, lab aide, and data manager. We developed superb relationships with surgeons, interventional radiologists, pathologists and staffs to assure appropriate referrals and processes, and implemented quality checks as a standard. We developed relationships with Moffitt, The Cancer Genome Atlas, and other research efforts, which help provide funding. Results: We successfully implemented a program which resulted in high levels of patient and provider satisfaction, high numbers of fresh frozen and FFPE tissues (nearly 3,000 over 3 years), high quality pass rates, low ischemia time, and high satisfaction on the part of our research partners. We have incorporated best practices in our tissue handling protocols. Conclusions: We successfully implemented a comprehensive cancer genomics bio-specimen program utilizing dedicated staff, working with patients and clinicians closely, and assuring careful coordination of all efforts.
Use of partial liver resection according to carcinologic procedures as an alternative to liver transplantation for HCC
Authors: A. Herrero, C. Pulitano, F. Dondero, S. Dokmak, B. Aussilhou, A. Sauvanet, O. Farges, S. Faivre, J. Belghiti
Journal: Journal of Clinical Oncology (2009)

e15628 Background: There are some arguments showing that anatomic resection, anterior approach and preoperative transarterial chemoembolization (TACE) with portal vein embolization (PVE) before major resection improves long term survival after partial liver resection for HCC. This oncologic approach could compete with liver transplantation (LT) which remains poorly accessible in western countries and inaccessible in the greatest part of the world.The aim of this study was to evaluate in patients with good liver function.the result of partial liver resection with an intended carcinologic approach. Methods: Between 1998 and 2007, among 210 patients resected for HCC, we selected a subgroup of 36 patients with single and small HCC (&lt; 6 cm) developed on chronic liver disease (CLD) who underwent anatomic partial resection and anterior approach and TACE and PVE in case of major resection. Results: These 36 patients aged 37 to 76 years included 26 males (72%). Underlying CLD included hepatitis C in 16 (44%); hepatitis B in 8 (22%); alcohol in 9 (25%) and other in 3 ( 8%). The mean size of the tumor was 5.2 cm and 86% (n=31) had major resection. Operative mortality was 2.7% (n=1) and the overall 1-, 3- and 5-year survival rate were 92%,85%,73% while the disease free 1-, 3-, 5-year survival was 80%, 74%, 58%. Tumor recurrence occurred in 16 cases( 44%) after a mean delay of 21 months (ranging from 5 to 58 months). Recurrence was located out of the resected location in 6 cases. Conclusions: Partial liver resection for small tumors in patients with good liver function according to carcinologic procedures allow an excellent overall and disease free survival which can challenge LT. In the case of single HCC &lt;6cm on chronic liver disease, this surgical approach may therefore be considered as a valuable alternative to LT within a curative intent. No significant financial relationships to disclose.
Pretreatment normalization of mild anemia with epoetin alfa predicts long-term outcome for women with epithelial ovarian cancer
Authors: M. Marinaccio, E. Mele, S. Poma, C. Cantinieri, M. Cocca, T. Latiano
Journal: Journal of Clinical Oncology (2004)

5132 Background: In a previous study (Marinaccio et al. Proc.ASCO 2003;Abstr1952) we assumed that pretreatment normalization of mild anemia with epoetin alfa could improve the outcome in patients with epithelial ovarian cancer. The aim of this larger trial was to understand better the influence of recombinant human erythropoietin (rHuEPO) on the outcome of ovarian cancer patients showing anemia before undergoing surgery and chemotherapy. Methods: Between 1999 and 2003, 42 patients with mild anemia (Hgb 10.6–11.9 g/dL) secondary to advanced epithelial ovarian cancer were randomized to receive epoetin alfa (21 pts.) or not (21 pts.) before primary surgery. All patients were without past or present second malignancy and aged less than 76 years. FIGO stage at diagnosis was as follows: IC 13/42; II 5/42; III 19/42; IV 5/42. After surgery all patients underwent adjuvant chemotherapy with paclitaxel (175mg/mq) plus carboplatin (AUC5). Patients in the treatment group were administered rHuEPO, 10.000 IU, three times a week subcutaneously for 4–6 weeks. The patients receiving rHuEPO had a significantly greater increase in hematocrit and Hgb compared with the control group (p<0.01). Survival curves were described by Kaplan-Meier method. The relationship of Hgb to survival was determined by Cox Regression analysis after adjusting for the effect of known prognostic variables including FIGO stage, tumor grade and residual tumor. Results: The mean age of patients was 54.1 years. The median duration of follow-up was 30 months. The median relapse-free survival time was found to be 26 months in patients treated with rHuEPO and 18 months in the control arm; the evaluation of median survival time is in progress, however Kaplan-Meier 12-month estimates of survival were 65% for the rHuEPO arm and 50 % for the control arm, revealing a trend in overall survival favoring normalization of pre-treatment anemia with rHuEPO (Kaplan-Meier analysis p=0.12, Cox regression analysis p=0.044). Conclusions: Pretreatment of mild anemia with epoetin alfa in patients with epithelial ovarian cancer offers an excellent possibility of improving the outcome. No significant financial relationships to disclose.
Randomized, phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated, extensive-stage (ES) small cell lung cancer (SCLC)
Authors: N. H. Hanna, L. Einhorn, A. Sandler, C. Langer, S. Hariharan, R. Ansari, P. Ellis, M. Byrne, B. Wang, P. Bunn
Journal: Journal of Clinical Oncology (2005)

LBA7004 Background: EP has been standard treatment for ES SCLC. A phase III study reported improved overall survival (OS) for pts receiving IP vs. EP (Noda et al NEJM ‘02). The current trial was designed to confirm these results using a modified weekly regimen of IP vs EP, enabling improved tolerability and greater dose intensity. Methods: The 1° endpoint of this multicenter, open-label, randomized, prospective trial in chemonaive pts with ES SCLC was to compare OS of IP vs EP. Eligible pts had ECOG PS 0–1 and adequate organ function. Pts with uncontrolled brain mets were excluded. Pts were randomized 2:1 [stratified by gender, LDH (≤ ULN or > ULN), and age (<65 or ≥ 65)] to: IV cisplatin 30 mg/m2 + irinotecan 65 mg/m2, days 1,8 every 21 days (arm A); or IV cisplatin 60 mg/m2, day 1, and IV etoposide 120 mg/m2, days 1–3 every 21 days (arm B) for 4 cycles, or PD, or intolerable toxicity. A sample size of 300 (200 arm A;100 arm B) was planned to achieve 80% power to detect a 30% OS improvement (from 37%–50% at 1 yr). Primary analysis is planned after Dec 31, 2004, 18 months after the last pt enrollment. Results: Of 336 pts randomized between 12/00–6/03, 330 were treated (221/109 in arms A/B). Baseline demographics were similar in both arms: 57% male;median age 63;PS 1∼66%. In both arms, 65% of pts received ≥4 cycles. There are 278 deaths to date. Selected grade 3/4 toxicities in arms A/B were: diarrhea (21 vs 0%), neutropenia (35 vs 84%), febrile neutropenia (4 vs11%), anemia (5 vs11%), thrombocytopenia (4 vs19%). OS and response data will be presented using Kaplan-Meier methodology and Cox models. Conclusions: IP had significantly less myelosuppression, but more diarrhea than EP. The primary endpoint will be analyzed before March 25, 2005 and will be presented at the ASCO meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer, Pharmacia Pfizer Pfizer, Pharmacia
Patterns of HER-family receptor dimerization in trastuzumab susceptible and trastuzumab resistant cell lines
Authors: R. Dua, P. Nhonthachit, C. Rinehart, C. L. Arteaga, R. Nahta, F. J. Esteva, J. Winslow, M. Bates, C. Petropoulos
Journal: Journal of Clinical Oncology (2007)

2533 Background: HER2 overexpression is associated with accelerated disease progression and poor prognosis in breast cancer. Trastuzumab, a monoclonal antibody targeting the extracellular domain of HER2, is effective in the treatment of metastatic breast cancer. However, most patients treated with trastuzumab eventually develop clinical resistance. To investigate the role of HER-family receptors in trastuzumab resistance, we measured HER-family receptor expression, dimerization, and phosphorylation in trastuzumab susceptible and resistant cell lines. Methods: Cell lysates from trastuzumab susceptible and resistant BT474 and SKBR3 cell lines were obtained from the Arteaga and Esteva laboratories. Proximity-based, multiplexed assays were used to detect and quantify HER1, HER2, and HER3 expression and phosphorylation levels, as well as HER1/HER1, HER1/HER2, HER1/HER3, HER2/HER2, and HER2/HER3 dimers. Samples were incubated with a mixture of HER specific antibodies conjugated either with fluorescent reporter tags (eTags), or biotin, which binds a reporter tag releasing agent (chemical scissor). Reporter molecules are released based on proximity to the scissor in a photochemical reaction and separated by capillary gel electrophoresis. Results: In comparison to trastuzumab susceptible parental cell lines, both SKBR3 and BT474 trastuzumab-resistant cell lines displayed upregulated HER1 expression. Resistant BT474 cell lines exhibited markedly increased levels of HER1/HER2 heterodimers. Increases in HER2 phosphorylation in the trastuzumab resistant SKBR3 cell line were observed, consistent with previous studies implicating trastuzumab in the induction of HER2 phosphorylation. Total HER2 and HER3 levels were similar in trastuzumab susceptible and resistant BT474 cell lines. Conclusions: The development of trastuzumab resistance in these cell line models correlated with HER1 expression and the appearance of HER1:HER2 dimers. Since signaling initiated by such heterodimers is ineffectively antagonized by trastuzumab, these data suggest that selection for proliferative signaling mediated by HER1:HER2 dimers may represent a mechanism of trastuzumab resistance in breast cancer. No significant financial relationships to disclose.
Phase I study of panitumumab + chemoradiotherapy (CRT) for head and neck cancer (HNC)
Authors: L. J. Wirth, M. R. Posner, R. B. Tishler, R. I. Haddad, J. R. Clark, L. Goguen, C. M. Norris, D. Annino, R. Costello, A. M. Allen
Journal: Journal of Clinical Oncology (2008)

6007 Background: Both chemotherapy and epidermal growth factor receptor (EGFR) antibody therapy improve outcomes in HNC when added to radiotherapy. This phase I study adds the fully human anti-EGFR antibody, panitumumab, to carboplatin/paclitaxel/IMRT for HNC. Methods: Nineteen treatment-naïve adults with stage III/IV HNC (1° sites: oropharynx, hypopharynx and unknown primary) with normal hematologic, renal, and liver function enrolled in a phase I study to determine the maximum tolerated dose (MTD) of paclitaxel in 2 dose levels (DLs) (15 and 30 mg/m2 wkly x 7 wks) with fixed-dose carboplatin and panitumumab (AUC of 1.5 and 2.5 mg/kg wkly, respectively) plus IMRT (70 Gy). All patients (pts) received a gastrostomy (g-) tube. Pts were enrolled in sets of 3, with an expansion cohort of 10 at the MTD. Acute toxicities were graded per Common Toxicities Criteria for Adverse Events v3.0. Chronic toxicities occurring ≥ 16 wks post treatment were graded per RTOG/EORTC Late Radiation Morbidity Scoring Scheme. Results: Three pts were treated in DL 1, and 16 in DL 2 (10 of these in the expansion cohort). All are evaluable for acute toxicities; 13 pts are evaluable for chronic toxicities. One dose-limiting toxicity (DLT) occurred in DL 2: grade (gr) 4 febrile neutropenia. One pt had a gr 4 sepsis and thromboembolic event, not considered a DLT as it occurred 3 wks after treatment. Other adverse events include gr 3 dysphagia (n=18, 95%), gr 3/4 mucositis (n=17, 89%), gr 2/3 acneiform rash (n=15, 79%), gr 3 radiation dermatitis (n=7, 37%), and gr 3 nausea (n=3, 16%). Neither dose-reduction nor radiotherapy breaks > 3 days were necessary. Chemotherapy and panitumumab were held for 1–2 wks in 3 pts in DL 2 for gr 4 mucositis (n=2) and gr 3 mucositis and nausea (n=1). There were no gr 3/4 chronic toxicities. Median duration of g-tube use was 10 wks. Of 15 pts evaluable for response, 13 (87%) had complete response, 1 had 1 positive node on neck dissection, and 1 has a residual base of tongue mass on restaging CT (further evaluation pending). Conclusions: Panitumumab added to CRT for HNC treatment is safe and feasible. The MTD is defined as the study's DL2. Early results suggest that panitumumab + CRT is a highly effective regimen for HNC. Phase II study is warranted. No significant financial relationships to disclose.
Improving colon cancer prognosis using Index of Metastasis: A SEER analysis
Authors: G. J. Chang, C. Hu, M. A. Rodriguez-Bigas, J. M. Skibber
Journal: Journal of Clinical Oncology (2008)

4019 Background: Survival and staging in colon cancer is related to the number of lymph nodes (LN) containing metastasis. However the total number of LN examined is variable. AJCC staging does not account for cases with few LN. Prior studies have not evaluated the index of metastasis (IM) for colon cancer using Surveillance Epidemiology and End Results (SEER) data nor the limitations of IM for prognosis. The aim of this study was to evaluate the predictive value of the IM for survival and to define the boundaries of this relationship. Methods: Patients with stage III colon cancer diagnosed 1998–2004 were identified from the SEER registry, 2007 release. 5-year cancer-related survival rates by stage at diagnosis were determined using the Kaplan-Meier method. IM was defined as # positive LN/total # LN Patients were stratified by Tstage (1–2, 3, or 4) and N-stage (1 or 2) or IM quartile according to T stage group. Log-rank analysis was used to determine the range of total LN number over which IM remained prognostic. Results: 57,410 patients were analyzed. There were 6,084 T1–2, 39,920 T3, and 11,200 T4 tumors with N1–2 disease (38,893 N1 and 18,517 N2). The median number of LN evaluated was 10 (interquartile range [IQR] 6–15) for T1–2, 12 (IQR 8–18) for T3, and 11 (IQR 7–17) for T4 tumors. The median IM differed based on T stage and was 0.182 (IQR 0.100-0.333), 0.222 (IQR 0.111-0.436), and 0.286 (IQR 0.133-0.571) for T1–2, T3, and T4 tumors, respectively. Within each T-stage group, IM more accurately predicted survival than N-stage (TABLE). Chi-square analysis demonstrated that at IM as a predictor of survival was minimally sensitive to total numbers of LN unless within the highest IM quartile with fewer than 8 total LN evaluated (X2=85.8). Conclusions: The IM is a more accurate predictor of cancer-related survival in stage III colon cancer than is AJCC N-stage. This is true even when the total number of LN recovered is low. However when the IM is high (> ∼0.5) and when the total number of LN is <8, IM may underestimate survival. 5-year actuarial survival stratified by T-stage and IM IM Quartile T1–2 T3 T4 <6 LN >15 LN All T1–2 <8 LN >18 LN All T3 <7 LN >17 LN All T4 1 85 88 86 73 79 78 58 65 61 2 82 86 84 66 70 68 45 49 48 3 81 86 82 45 63 59 33 44 38 4 67 82 76 34 50 43 14 30 22 N1 81 86 84 57 78 68 40 63 51 N2 62 78 71 32 62 48 15 45 29 Grouped by total #LN, low and hi 25% within each T-stage. IM quartiles specific to each T group. No significant financial relationships to disclose.
Integrating microRNA and mRNA expression profiling using a novel algorithm identified a small set of unique genes upregulated in malignant pleural mesothelioma (MPM)
Authors: M. Suraokar, A. Corvalan, C. Chow, A. Gazdar, C. Moran, G. Raso, R. Mehran, A. Tsao, I. Wistuba
Journal: Journal of Clinical Oncology (2009)

e22111 Background: We employed a global profiling strategy using miRNA microarrays in MPM cell lines and archival tumor tissue. Methods: We isolated total RNA from 4 MPM cell lines, 2 control cell lines, and 16 tissue specimens from patients with resected MPM (n=8) and normal counterpart (n=8) patients as controls. Total RNA was labeled with Cyanine 3, then hybridized with Agilent human miRNA microarray v1 slides. Results: Preliminary miRNA profiles show up-regulation of 44 versus down-regulation of 29 miRNA's in MSTO-211H cancer cells compared to HCT-4012 (pleural telomerase-transformed control). Profiling of 16 tissue specimens (8 normal vs 8 MPM) revealed down-regulation of 11 miRNA's in MPM tumor tissue. To focus on relevant miRNA that regulate genes involved in carcinogenesis and progression, we identified &gt; 1000 unique genes using the online targetscan 4.2 program ( http://www.targetscan.org ), which predicts biological targets of miRNAs by identifying the presence of conserved 8-mer and 7-mer sites that match the seed region of each miRNA. We then explored a novel screening strategy, which combines mRNA expression dataset with the miRNA dataset, to narrow the list of relevant miRNA's. We conducted gene expression profiling on the cell lines and MPM tissue samples with Affymetrix U133 plus 2.0 chips. Bioinformatic analysis was conducted with MeV: MultiExperiment Viewer software, data reduction techniques (Correspondance Analysis), hierarchical clustering methods, and Serial Analysis for Microarray (SAM), and showed up-regulation of ∼300 genes in MPM compared to normal tissues. We then computed of the ∼300 mRNA's up-regulated in MPM only 32 are recognized by the 11 down-regulated miRNA's using the targetscan 4.2 algorithm. Most of the miRNA's regulate single messages while ∼20 % of the messages are regulated by more than 1 miRNA's. Some of these targets include Ets variant 1 and Protein kinase C - epsilon. Conclusions: This innovative approach of selecting highly relevant miRNA is feasible and enables discovery of novel genes based on their ability to be bound by single or multiple miRNA's. Validation of our profiling studies using real-time PCR and protein analysis methods will be presented. No significant financial relationships to disclose.
High prognostic potential of glioblastoma stem cell analysis
Authors: G. L. Banna, R. Pallini, L. Ricci-Vitiani, M. Signore, D. Lombardi, M. Martini, G. Maira, D. Giuffrida, L. M. Larocca, R. De Maria
Journal: Journal of Clinical Oncology (2007)

10580 Background: Cancer stem cells (CSCs) are a rare cell population responsible for tumor development and maintenance. Recent studies have shown that glioblastoma stem cells express the CD133 marker and are resistant to radiotherapy and chemotherapy. However, clinical data based on the study of CSCs in patients with glioblastoma are not available yet. Methods: Glioblastoma samples from 44 patients treated with complete or partial tumorectomy, followed by radiotherapy and temozolomide were prospectively analyzed. Immunohistochemistry was performed to evaluate the prognostic value of the number of CD133+ cells present in tumors. Moreover, the relationship between the ability to generate long-term culture of tumorigenic cells in vitro and the clinical outcome of glioblastoma patients was tested. Results: CD133 expression did not show an overall prognostic value. CSC cultures were obtained from 14 of the 44 tumors (32%). The generation of CSCs emerged as significant independent prognostic factor by the Cox multivariate analyses, with an adjusted hazard ratio of 2.50 (95% CI, 1.04 to 6.06; P=0.004). The median overall survival among patients with tumors generating CSCs was 8.0 months (95% CI, 4.0 to 11.5), as compared with 15 months (95% CI, 11.0 to 19.0) among those without generation of CSCs (P=0.0002). The median progression-free survival was 3.5 months (95% CI, 2.0 to 6.0) for glioblastoma generating CSCs and 9.0 months (95% CI, 7.0 to 12.0) for glioblastoma not generating CSCs (P=0.0001). A higher CD133 expression significantly associated with tumors generating CSCs (P=0.006), and correlated with a higher risk of death in patients with tumors generating CSCs in vitro (hazard ratio of 1.65, 95% CI, 1.05 to 2.60; P=0.0285). Conclusions: Generation of long-term culture of tumorigenic CSCs in vitro from glioblastoma predicts a poor clinical outcome for patients, in terms of both overall and progression-free survival. In tumors generating CSCs, CD133 expression may have a prognostic value. No significant financial relationships to disclose.