tbuckley/cabot-search huggingface dataset:
High KI67 expression is associated, in a multi-variate model, with lower risk of biochemical recurrence in prostate cancer patients following radical prostatectomy
Authors: P. O. Gannon, I. H. Koumakpayi, C. Le Page, M. Alam Fahmy, A. Mes-Masson, F. Saad
Journal: Journal of Clinical Oncology (2007)

21112 Background: The prediction of disease progression in prostate cancer patients following radical prostatectomy (RP) remains problematic. The use of molecular markers could offer a better stratification of patients more at risk of progression. As such, we recently reported that nuclear ErbB3 was associated with Gleason score and hormone-refractory status. The objective of this study was to evaluate whether ErbB3 could predict overall biochemical recurrence (BCR). In addition, we evaluated if three nuclear markers known to be associated with progression (Cyclin D1, Ki67 and androgen receptor) were more significant predictors of BCR than ErbB3 alone or in combination. Methods: Using immunohistochemistry, we analyzed a tissue microarray containing 373 cores from 63 RP specimens. No patient had received hormone therapy prior to surgery and prior to BCR. The quantitative analysis of nuclear staining was measured by two independent observers (ErbB3, Cyclin D1 and AR) or with the ImagePro Plus softwareTM (Ki67). Marker expressions were categorized as either positive or negative according to the median expression. Results: Of the four markers analyzed, Ki67 alone was the strongest predictor of overall BCR. In a multi-variate Cox regression model (backward conditional), while controlling for the pre-operative PSA, Gleason score and lymph node invasion at time of surgery, KI67 was found to be an independent predictor of BCR with a KI67+ patients having lower risk of BCR (HR=-2.51, p=0.015, CI 95%: 1.19–5.29). We then analyzed if different marker combinations could predict BCR. Patients positive for nuclear AR or AR+/Cyclin D1+ double positive were found to have lower risk of BCR (Kaplan-Meier, p=0.047 and p=0.026, respectively). However, in the multi- variate model, the combinations of Cyclin D1+/AR+ (HR=-2.28, p=0.053, CI 95%: 0.94–5.49), ErbB3+/Ki67+ (HR=-2.43, p=0.034, CI 95%: 1.07- 5.52) and AR+/Ki67+ (HR=-2.32, p=0.049, CI 95%: 1.01–5.35) could not improve on the predictive value of KI67 alone. Conclusions: The major new finding of the study is that patients positive for KI67 expression were at a lower risk of developing BCR, which contrast previously published results, and warrants further investigations. No significant financial relationships to disclose.
Cetuximab as first-line monotherapy in patients with skin unresectable squamous cell carcinoma: Final results of a phase II multicenter study.
Authors: E. Maubec, P. Petrow, P. Duvillard, C. Laouenan, X. Duval, L. Lacroix, M. Bagot, S. J. Faivre, F. Mentre, M. Avril
Journal: Journal of Clinical Oncology (2010)

8510 Background: Patients (pts) with advanced skin squamous cell carcinoma (SSCC) have a poor prognosis. The objective of the study was to evaluate single agent cetuximab (C) as first-line therapy for unresectable SCCS. Methods: Pts with advanced or metastatic EGFR expressing SCCS, ECOG PS ≤ 2 were eligible. No prior chemotherapy was allowed. C was kindly provided by Merck KGaA and administered iv weekly (400 mg/m2 initial dose followed by 250 mg/m2). Disease was evaluated by MRI or CT every 6 wks and independently assessed. Endpoints were disease control rate (DCR) at 6 wks, best objective response rate (ORR) (RECIST criteria) and toxicity, along with determination of KRAS mutations and FcγR genotypes. Statistical analyses were carried out both in the intent to treat (ITT) and per protocol (PP) populations. Results: Between Oct 2005 and Apr 2008, 36 pts were recruited: 58% were males, median age was 79 yrs (range 32-95), median PS was 1 (47%) and 72% of SCCS were AJCC stage 3; 31 pts were evaluable for tumor response and 36 for toxicity. DCR at 6 wks was 69% in the ITT population and 81% in the PP population (21 SD, 3 PR and 1 CR). Best ORR and DCR were 32% and 81% respectively in PP (15 SD, 8PR and 2 CR). Fourteen pts died: 6 due to disease progression; 4 were consideredas NOS and 3 sudden deaths were of unknown causes. Grade ¾ events were noted in 23 pts: infections (22%), nausea/vomiting (3%), anemia (4%), tumor bleeding (8%) and 4 C-related adverse events (2 grade 4 infusion reactions, 1 grade 3 interstitial pneumopathy and 1 grade 3 paronychia). Grade ½ acneiform rash occurred in 78% of pts. No KRAS mutation was identified in the 28 studied pts. In pts with FcγRIIa-131H/H and/or FcγRIIIa-158V/V genotypes, the PFS was similar in 131R and 158F carriers (5.4 vs. 3.5 mths; p = 0.34). Conclusions: Single agent C achieves 69% disease control rate as first-line treatment in pts with unresectable SCCS, therefore representing an interesting therapeutic option, especially in elderly pts. No significant financial relationships to disclose.
Gene expression in giant cell tumors
Authors: K. M. Skubitz, E. Y. Cheng, D. R. Clohisy, R. C. Thompson, A. P. N. Skubitz
Journal: Journal of Clinical Oncology (2004)

9050 Background: Malignant transformation is thought to be associated with changes in the expression of a number of genes, and this alteration in gene expression is felt to be critical to the development of the malignant phenotype. Giant cell tumor (GCT) is a primary bone tumor in which monocytic and multinucleated osteoclast-like cells infiltrate the tumor. The etiology of GCT is unknown. Methods: In this study, gene expression in 8 samples of GCT, as well as reparative bone from degenerative joint disease, and a variety of normal tissues was determined at Gene Logic Inc. (Gaithersburg, MD) using Affymetrix GeneChip, U 133 arrays containing approximately 40,000 known genes and ESTs. Gene expression analysis was performed with the Gene Logic Gene Express, Software System. Differences in gene expression were quantified as the fold change in gene expression between the various sample sets. Results: Differences in gene expression between GCTs and reparative bone were observed. In addition, genes expressed uniquely in GCTs among these and 519 samples from 20 other tissue types were identified. Some of the genes over-expressed in GCTs, such as tartrate resistant acid phosphatase and the lysosomal H+ transporting-ATPase, are also expressed by osteoclasts. Osteoprotegrin ligand (OPGL) was also selectively over-expressed in GCTs. Conclusions: The genes over-expressed in GCTs appear to reflect the genetic profile of osteoclast lineage cells and also the genetic profile of an osteoclastogenic environment. The genes identified in this study may play a role in the pathogenesis of giant cell tumors. They confirm the likely importance of OPGL in GCT pathogenesis, and may indicate other possible targets to which anti-tumor therapy could potentially be directed. No significant financial relationships to disclose.
A phase I trial of intraperitoneal EGEN-001, a novel IL-12 gene therapeutic, administered alone or in combination with chemotherapy in patients with recurrent ovarian cancer
Authors: J. E. Kendrick, K. S. Matthews, J. M. Straughn, M. N. Barnes, J. Fewell, K. Anwer, R. D. Alvarez
Journal: Journal of Clinical Oncology (2008)

5572 Background: EGEN-001 (E1), an IL-12 expressing plasmid formulated with a novel gene delivery system, stimulates natural killer cells, IFN-γ secretion, and T-helper 1 response, inhibits tumor neovascularization, and has potent antitumor activity in preclinical models of ovarian cancer. The activity of E1 was evaluated in two early phase I clinical trials. Methods: Patients with recurrent ovarian cancer were treated intraperitoneally (IP) with escalating dosages and cycles of E1 alone or in combination with intravenous docetaxel and carboplatin. Study endpoints included the identification of clinical toxicity, the MTD, and antitumor activity. Results: In the initial phase 1A study, 13 patients were treated IP with 0.6–24 mg/m2 of E1. All patients except one in the 24 mg/m2 dose cohort completed all 4 weekly E1 treatments. The most commonly experienced adverse events included pyrexia (69%) and abdominal pain (54%). Three patients experienced peritonitis; one of these patients in the 24 mg/m2 cohort experienced a possibly reagent related DLT. The MTD was not identified. The overall clinical response was 31% stable disease and 69% progressive disease. Ten evaluable patients had measurable IL-12 plasmid DNA and IFN-γ levels in their peritoneal fluid. In the first cohort of patients enrolled in the phase 1B study, three patients have been treated with 12 mg/m2 of E1 IP every 10 days for 4 cycles in combination with docetaxel (75 mg/m2) and carboplatin (AUC 5) at 3 week intervals for a planned 6 cycles. All patients completed therapy. Two patients experienced mild pyrexia during E1 administration. One patient developed G3 anemia following the 4th cycle of E1 and required transfusion. No other G3/4 toxicities were noted. All patients demonstrated a partial response by CT evaluation and reductions in CA- 125 levels following the completion of E1 and two cycles of chemotherapy. Conclusions: IP administration novel IL-12 gene therapeutic E1 is feasable and demonstrates potential antitumor activity when given alone or in combination with chemotherapy in patients with recurrent ovarian cancer. Further development of E1 as a potential therapy for ovarian cancer is warranted. No significant financial relationships to disclose.
Dactinomycin (A) and vincristine (V) with or without cyclophosphamide (C) and radiation therapy (RT) for newly diagnosed patients with low-risk embryonal/botryoid rhabdomyosarcoma (RMS). An IRS-V report from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group (STS COG)
Authors: D. O. Walterhouse, J. L. Meza, R. B. Raney, J. Anderson, E. S. Wiener, S. S. Donaldson, S. J. Qualman, W. Meyer
Journal: Journal of Clinical Oncology (2006)

9001 Background: The STS COG defines patients with low-risk RMS as those with localized tumors of embryonal histology that occur in favorable sites or occur in unfavorable sites and are grossly resected. Intergroup Rhabdomyosarcoma Studies (IRS)-III (1984–1991) and -IV (1991–1997) found that these patients had a 5-year failure-free survival (FFS) of 83% and an overall survival of 95%. Methods: Two subsets were identified for the IRS-V low-risk RMS study (D9602) (1997–2004) based on the hypothesis that they required different treatment intensities to achieve similar excellent outcomes. Patients assigned to Subset A (Stage [Sg] 1 Group [Gp] I/IIA, Sg 1 Gp III orbit, Sg 2 Gp I) received VA (cumulative doses over 1 year of treatment: V: 54 mg/m 2 , A: 24 mg/kg) ± local RT. Patients assigned to Subset B (Sg 2 Gp IIB/C, Sg 1 Gp III non-orbit, Sg 2 Gp II, Sg 3 Gp I/II) received VA + C (C: 28.6 g/m 2 ) ± RT. The RT dose was reduced to 36 Gy (instead of 41.4 Gy on IRS-IV) for Gp IIA patients and to 45 Gy (instead of 50.4 or 59.4 Gy on IRS-IV) for Gp III orbit patients. The primary endpoint was FFS. Results: Estimated 3-yr FFS was 89% (95% CI 84%, 93%) for Subset A (n=263) and 89% (95% CI 77%, 95%) for Subset B (n=79). Median follow-up was 2.9 years. Estimated 3-yr FFS was 80% (95% CI 64%, 89%; n=59) for patients with Sg 1 Gp IIA disease and 88% (95% CI 77%, 94%; n=76) for Gp III orbit disease. Conclusions: There is not evidence to suggest that outcome for these patients differs from outcomes observed in similar patients treated on IRS-III and IRS-IV. No significant financial relationships to disclose.
Palifermin Treatment in Patients Receiving High Dose Melphalan or BEAM Prior to Autologous Peripheral Blood Stem-Cell Transplantation.
Authors: Anne Sonet, G. Bries, N. Meulemans, A. Van Hoof, E. Steel, M. André, A. Ferrant, N. Straetmans, P. Zachée, V. Robin, H. Demuynck, L. Noens, A. Bosly, M. Delforge, D. Bron
Journal: Blood (2006)
Hepatic cell proliferation and outcome in alcoholic hepatitis: histology, gene expression and effect of stem cell therapy.
Authors: Nicolas Lanthier, Laura Rubbia-Brandt, Nathalie Lin-Marq, Sophie Clément, Jean-Louis Frossard, Nicolas Goossens, Laurent Spahr
Journal: Hepatology (2014)

Background: The clinical outcome of alcoholic hepatitis (AH) is partly influenced by impaired liver cell proliferation and insufficient tissue repair. The role of stem cell therapy in this setting remains unclear. We aimed to study histological features, cytokine profile and hepatic gene expression at baseline and during follow-up in patients with AH and liver failure treated with the standard of care (SOC) alone or in association with stem cell transplantation (SCT). Methods: Immunohistochemical studies for macrophage expansion, proliferative hepatocytes, total and proliferative liver progenitor cells (LPC) as well as global microarray gene expression analysis were performed on liver biopsies of 58 AH patients (28 of whom received SCT) both at baseline and after 4 weeks of follow-up. Abstinent cirrhotics (n=12) were used as controls for baseline studies. Patients were qualified as “improvers” or “non-improvers” according to the presence/absence of a decrease of at least 3 points of MELD at 3 months as compared to baseline value. Results: Compared to controls, AH patients at baseline demonstrated a significant expansion of macrophages, invasion of LPC and a higher number of proliferating hepatocytes and LPC (p<0.001). The group of improvers (n=34) were characterized at baseline by a higher number of proliferating hepatocytes (p<0.01), proliferative LPC (double CK7+Ki67+ cells, p<0.01) and liver macrophages (p<0.05) as compared to non-improvers (n=24), in spite of similar clinical and biological variables. Up-regulated genes in improvers were associated with cell cycle mitosis together with an important expression of SPINK1, an acute phase protein linked with cell proliferation. On repeat biopsy, as compared to patients on SOC alone, those who received SCT showed a more important liver macrophagic expansion (p<0.01), but transcriptome data showed no significant changes in genes related to cell cycle. Conclusions: Baseline histology and hepatic gene expression differ according to clinical outcome in patients with AH. Higher liver macrophage expansion, increased proliferative hepatocyte and LPC number as well as up-regulation of cell proliferation related genes are associated with a favourable outcome (decrease in MELD score at 3 months). Stem cell transplantation has no effect on hepatocyte proliferation.
Targeting prostate cancer progenitor cells with telomerase interference: A novel therapeutic strategy
Authors: A. Goldkorn, T. Xu
Journal: Journal of Clinical Oncology (2009)

e22029 Background: We investigated whether telomerase, which is critical for benign stem cell activation, also plays a role in prostate cancer progenitor cells (PCPCs), which are thought to mediate therapy resistance and cancer progression, and we tested whether telomerase interference can effectively inhibit PCPC proliferation. Methods: A putative PCPC population was isolated from human prostatectomy specimens via collagen attachment and FACS selection for integrin α 2 β 1 and CD 44 . PCPCs were characterized for gene expression (RT-PCR), clonogenicity (colony formation), invasiveness (matrigel chamber), and telomerase activity (qPCR-TRAP). PCPC telomerase interference was accomplished by lentiviral expression of 2 constructs: telomerase RNA with an altered template region (MT-Ter) and siRNA targeting wild-type telomerase RNA (anti-Ter siRNA). The effects of these constructs were assessed by measuring PCPC viability (MTS) and apoptosis (TUNEL assay). Results: An integrin α 2 β 1 + CD 44 + putative PCPC population was isolated from 6 human prostate tumors. This population expressed high levels of “progenitor phenotype” genes (ABCG2, β-catenin, NANOG, Oct3/4) and low levels of “differentiated phenotype” genes (AR and PSA). PCPCs yielded &gt;50 colonies per 1000 cells seeded on collagen after 3 weeks vs. none from FACS - cells, and matrigel chamber assay showed 10% of the PCPC population invading over 24 hours vs. none of the FACS - population. Most importantly, PCPCs possessed at least 20- fold greater telomerase activity than FACS - cells, and induction of telomerase interference in PCPCs via MT-hTer and anti- hTer siRNA expression elicited a brisk apoptotic response (TUNEL) by day 3 in &gt;90% of cells, with concomitant near-complete growth inhibition (MTS). Conclusions: We have shown that human prostate tumors contain a subpopulation of prostate cancer progenitor cells (PCPCs) marked by an undifferentiated gene expression profile, vigorous clonogenicity and invasiveness, and high levels of telomerase activity that can be successfully exploited to neutralize these cells. Ongoing studies are investigating the in vivo effects of telomerase interference on PCPC tumorigenicity in mouse models. No significant financial relationships to disclose.
Abstract 15389: High On-Treatment Platelet Reactivity in Clopidogrel-Treated Patients Undergoing Elective Carotid Stenting: Correlation with Previous Cerebrovascular Events
Authors: MassimoLenti, ValentinaConti, PaolaDe Rango, GiuseppeGuglielmini, AlessandraManzone, ManuelaSebastiano, EmanuelaFalcinelli, AnnamariaMezzasoma, GioeleSimonte, GiuseppeGiordano, PaoloGresele
Journal: Circulation (2012)

Background: High on-treatment platelet reactivity (HPR) is an established predictor of adverse cardiovascular outcome in patients with coronary artery disease treated with clopidogrel. No data are available on the prognostic value of HPR in patients with cerebrovascular disease. Our aim was to study the response to clopidogrel in patients undergoing carotid artery stenting (CAS). Methods: Consecutive patients undergoing CAS were enrolled in a prospective study. Clopidogrel, in combination with aspirin, was started before the procedure and continued for at least one month. Platelet reactivity was assessed in 137 patients on the day of the procedure, in 122 after 24 hrs and in 91 after 30 days. Platelet reactivity was assessed by light transmission aggregometry (ADP 5 microM), VerifyNow P2Y12 assay, Multiplate and VASP-P assay. HPR was defined according to cut-off values established by the recent consensus on HPR. Results: HPR, as detected by two or more tests, was found in 29.9% of clopidogrel-treated pati...
Pre-transplant positive PET/Gallium scans predict poor outcome in relapsed/refractory Hodgkin’s lymphoma (HL)
Authors: E. Jabbour, C. Hosing, B. Pro, R. Champlin, I. Khouri, J. Romaguera, L. E. Fayad
Journal: Journal of Clinical Oncology (2005)

6509 Background: High dose chemotherapy followed by autologous stem cell transplantion (SCT) has become the standard of care in patients (pts) with relapsed or refractory HL. Chemosensitivity, assessed by conventional tomography has been correlated with better disease free-survival (DFS) and outcome. Methods: We assessed the value of functional imaging in pts with HL referred to MDACC and treated with high dose chemotherapy followed by SCT from December 1999 to May 2004. 122 pts, male 57%, median age 31 years, (range, 10–76), with nodular sclerosis type 91%, were diagnosed at stages I (2%), II (43%), III (32%), and IV (23%). 86% of the pts were treated with ABVD-based regimens, 45% received adjuvant radiation therapy. 33% of the pts were primary refractory. Most of the pts were salvaged with ESHAP chemotherapy. At the time of salvage therapy, B symptoms were present in 45% of the pts, extra-nodal disease was documented in 23%, and relapse beyond 12 months of response occurred in 65%. Response was evaluated, before SCT, by PET scan and Gallium scan in 68 and 55 pts respectively. Results: 59% of the pts were in complete response (CR) or unconfirmed complete response (CRu), 38% were in partial response (PR), and 3% were stable by CT scan. PET scan and Gallium scan were positive in 25 of 68 (37%) and 9 of 55 (16%) pts, respectively. Relapses occurred in 44 of 122 (36%) pts. At 2 years, the cumulative probability of DFS was 65% for pts with a negative PET scan versus 30% for pts with a positive PET scan (p=0.00008), and 75% for pts with a negative Gallium scan versus 37% for pts with a positive Gallium scan (p=0.046). The positive predictive value (PPV) of the PET scan and Gallium scan were 68% and 55% respectively. The negative predictive values (NPV) were 77% and 76% respectively. Conclusions: Pre-transplant functional imaging is a strong predictive factor of DFS. Investigational therapy should be considered for pts with positive functional studies. No significant financial relationships to disclose.
The impact of mechanical ventilation on the systemic inflammatory response of patients with severe acute exacerbation of COPD
Authors: Georgios Hillas, Paraskevi Katsaounou, Fotis Perlikos, Dimitris Toumpanakis, Eleni Litsiou, Sofia Nikolakopoulou, Kostas Sagris, Theodoros Vassilakopoulos
Journal: European Respiratory Journal (2014)

Introduction:  Resistive breathing due to airflow limitation is observed during the natural course of chronic obstructive pulmonary disease (COPD), especially during acute exacerbation of COPD (AECOPD) and is characterized by elevated cytokine plasma levels.   Objective:  To test the hypothesis that the respiratory muscles and/or the mechanically stressed lung contribute to the elevated cytokine plasma levels in patients with AECOPD and that these levels would be decreased after respiratory muscles relaxation due to mechanical ventilation.   Methods : 30 patients with AECOPD, that led to endotracheal intubation and mechanical ventilation (intervention group) and 7 patients with COPD in steady state, which were intubated and mechanically ventilated for elective surgery (control group) were used.  Blood samples were collected just before, 20 minutes and 6 hours after intubation (intervention group) and just before and 20 minutes after intubation (control group).  Luminex 100 IS technique was used to access the cytokine plasma levels.   Results:  IL-6, IL-8, Eotaxin and EGF plasma levels decreased statistically significantly over time, whereas IL-5, IL-8, TNF-α, INF-γ, MCP-1 and RANTES levels didn9t change significantly over time (intervention group).  Plasma levels of all measured cytokines did not change significantly over time in the control group.   Conclusions:  Application of mechanical ventilation in patients with AECOPD leads to decreased plasma levels for circulating IL-6, IL-10, Eotaxin and EGF. The respiratory muscles and especially the contracting diaphragm and/or the mechanically stressed inflammatory lung could contribute to the elevate levels of these cytokines.
Neoadjuvant paclitaxel, carboplatin and concurrent weekly paclitaxel and conventional radiotherapy for locally advanced NSCLC
Authors: A. Yöney, Ö. Kandemir, H. Akbörü, S. Altin, M. Ünsal
Journal: Journal of Clinical Oncology (2004)

7361 Background:Concurrent radiation and chemotherapy plays an important role in the treatment of locally advanced NSCLC.Methods: We performed a phase II study of chemoradiation for patients with locally advanced NSCLC.26 patients received Paclitaxel (225mg/m2 as three hours infusion) followed by Carboplatin(AUC=6) on day 1,22 and 43.Weekly Paclitaxel 60 mg/m2 before one hour starting RT every week.60 Gy of thorasic irradiation was given over six weeks beginning on day 64.Results:Twenty-six patients were entered with median age of 55 years(43 to 65) and median KPS of 80(70 to 90).All patients were male.There were 8 PR,4 MR and 10 SD.4 of the 26 pts progressed during initial chemotherapy.Of the 26 pts evaluable for acute toxicity:6 had grade II and 1 had grade III mucositis.Skin toxicity was unremarkable and 5 pts developed pneuminitis.4 pts developed radiationfibrosis in terms of late toxicity.The median survival was 14 months with a oneyear survival of 49 %. Conclusions:Carboplatin plus Paclitaxel followed by weekly paclitaxel and RT was active and reasonably well tolerated.We will conduct aphase III trial to test wheather chemotherapy timing(neoadj. vs. adj) influence the survival and local control data or not;with using the same regimen. No significant financial relationships to disclose.