tbuckley/cabot-search huggingface dataset:
Comparison of Interleukin-2, Interferon-alpha, 5-fluorouracyl combination and Interferon-alpha, vinblastin treatment in metastatic renal cell cancer
Authors: F. Gyergyay, E. Rathonyi, K. Biro, K. Nagyivanyi, I. Bodrogi
Journal: Journal of Clinical Oncology (2005)

4690 Background: Patients with metastatic renal cell cancer were treated with the combination of recombinant Interleukin-2 (rIL-2), 18 MIU/day every second day alternating with Interferon-alpha (IFN) 9 MIU/day, weeks 1–4 followed by IFN 18 MIU/day three time a week and weakly 5-Fluorouracyl (5-FU) 1000 mg/m2, weeks 5–8 (rIL-2+IFN+5-FU) or IFN 9 MIU/day three times a week and Vinblastin (VBL) 5mg/m2 every 3rd week (IFN+VBL). Methods and Results: 72 patients received the combination of rIL-2+IFN+5-FU: 7 patients achieved complete responses (9.7%) and 10 partial responses (13.8%), for an objective response rate of 23.6%. The median response duration was 9 months (range: 3–96+ months). Four patients in complete remission are still alive: +84, +70, +96 and +38 months. The range of survival was: 1–84+ months, with a median of 18 months. The most common toxicities were fatigue, nausea/vomiting, anorexia, skin reaction, diarrhea, fever, dyspnea, weight loss and liver enzyme elevations. Twenty percent of the patients experienced central nervous system toxicity. Twenty-four patients had dose reduction or delay of the treatment, 5 patients refused to continue the treatment because of side effect and one toxicity related death occurred. 68 patients were treated with the IFN+VBL combination. Demographic data in the two groups were comparable. Five patients achieved complete responses (7.3%) and 11 partial responses (16.1%), for an objective response rate of 23.5%. The range of survival was 3–100 months, with the median of 15 months. Side effects were mild and fairly manageable (fever, anorexia, chills) Conclusions: Although rIL-2+IFN+5-FU treatment is more expensive and more toxic, patients in complete remission are more likely to have a long relapse free survival. No significant financial relationships to disclose.
Expression of erythropoietin and its receptor in neuroblastomas
Authors: H. Sartelet, M. Fabre, M. Castaing, J. Bosq, I. Racu, E. Lagonotte, V. Scott, S. Michiels, C. Patte, G. Vassal
Journal: Journal of Clinical Oncology (2006)

9054 Background: Children with neuroblastomas (NB) may potentially benefit from treatment with recombinant human erythropoietin (Epo). Epo is a specific stimulator of erythropoiesis, acting via its specific receptor (EpoR). The aim of this study was to evaluate the expression of Epo and EpoR in NB and in normal tissues and their action in the proliferation of tumor cells. Methods: A tissue microarrays study was performed on 101 patients with NB from 3 hospitals (16 stage I; 7, II; 22, III; 48, IV and 8, IVS). Four blocks were constructed and contained 101 primary tumors, 39 paired metastases (35 lymph nodes), 56 paired control normal tissues and 6 cell lines of NB. Immunohistochemical staining was performed on sections using antibodies against Epo and EpoR. Immunostaining intensity was evaluated by a semi-quantitative score based on the percentage of positive cells. The wilcoxon signed rank test was applied for the comparison of paired data. For overall survival analysis, the expression was dichotomized at the median value and cox regression models were used stratified by hospital. An in vitro study of cell proliferation in presence of recombinant Epo was carried out with two of the 6 cell lines, one expressing EpoR, the other not. Results: Median follow-up was 64 months. The expression of EpoR was significantly higher in tumors than in paired control tissues (p&lt;0.0001) but not for Epo (p=0.06). When restricted to the lymph nodes metastases, the level of expression of EpoR was significantly more expressed in the metastases than in primary tumors (p=0.02), contrary to Epo (p=0.99). Survival analysis showed that patients who expressed more EpoR had a statistically significant better overall survival than those who did not (p=0.03). Furthermore, the expression of EpoR was an independent prognostic factor from induction chemotherapy, tumor stage and age (p=0.02). No significant differences were found in Epo analyses. EpoR was expressed in only three cell lines and Epo not in any of them. In the in vitro study, recombinant Epo did not modify the proliferation of both cell lines. Conclusions: Epo and EpoR were expressed in NB but did not modify cells proliferation. The use of Epo in children with NB could be proposed but its benefit should be confirmed in a clinical trials. No significant financial relationships to disclose.
XPA and XRCC3 gene polymorphisms and survival in esophageal cancer patients receiving neoadjuvant radiochemotherapy with cisplatin (CDDP), docetaxel (DTX), and 5-fluorouracil (FU)
Authors: M. Gusella, G. De Manzoni, R. Marinelli, S. Bruscagin, A. Bononi, L. Stievano, E. Ferrazzi, A. Zanoni, C. Cordiano, F. Pasini
Journal: Journal of Clinical Oncology (2009)

e14571 Background: The aim of the study was to evaluate if genetic polymorphism of DNA repair genes may predict pathological response and survival in patients affected by locally advanced esophageal cancer, treated with a neoadjuvant schedule including weekly DTX (35 mg/mq) and CDDP (25mg/mq), protracted venous infusion of FU (150 mg/mq/die) and concomitant radiotherapy for 8 weeks followed by surgery. Methods: Fifty-seven patients were enrolled, aged 60±7 years old. Median follow-up was 27 months. Genomic DNA was extracted from peripheral blood lymphocytes and XPA, XPD, XRCC1, ERCC1 and XRCC3 were genotyped through RFLP analysis. Associations between gene polymorphisms and pathological response and survival were analysed through Chi square test and Log rank test respectively. Results: Thirty-two patients presented complete remission (pCR) and 10 patients microfocal residual disease (pMRD); the remaining 15 patients were considered stable or non-responders (pS-NR). The event free(EFS) and overall (OS) median survival times have not yet reached; significantly better 3-year survival rates were observed after pCR than in case of pMRD and pS-NR (EFS: 87% vs 42.8%, p=0.0004; OS: 86% vs 56%, p=0.02, respectively). No association was found between pathological response or survival with XRCC1, ERCC1 and XPD polymorphisms. On the contrary, the XPA 23AA genotype showed an increased risk of recurrence (HR=3.5; 95% CI 1.3 to 43.7, p=0.02) and death (HR=4.4, 95% CI 1.9 to 78.2, p=0.009); there was a trend for reduced risk of negative pathological response with decreasing number of allele 23A : MRD and S-NR were found in 71%, 45% and 35% cases for AA, AG and GG genotypes, respectively. The XRCC3 241MetMet variant was significantly associated with increased risk of death (HR= 6.0, 95% CI 3.0 to 40.0, p=0.008); a trend toward a higher recurrence (p=0.07) and worse response (60% vs 43%) was found. Conclusions: XPA and XRCC3 gene defective variants were significantly associated with worse outcome and could predict OS in esophageal cancer patients treated with a neo-adjuvant intensive radio-chemotherapy protocol. Founded by CARIPARO, Italy No significant financial relationships to disclose.
Abstract 14910: Novel Nanocrystalline Diamond Coating of Coronary Stents Reduces Neointimal Hyperplasia in Pig Model
Authors: Viktor Kocka, Toma Jirasek, Andy Taylor, Frantiek Fendrych, Bohuslav Rezek, Zuzana imnkova, Iveta Mrazkova, Petr Touek, Jan Mistrik, Milo Nesladek
Journal: Circulation (2012)

Objective: Diamond is known as a biocompatible material which at the same time offers possibility of additional functionalisation by simple covalent carbon chemistry. Our aim was to study performan...
Optimal Timing of Peripheral Blood Stem Cell Mobilisation in Patients with Hematological Malignancies Treated with the Hyper-CVAD Chemotherapy Regimen.
Authors: Anthony K. Mills, Simon Gibbs, Colm Keane, Peter Mollee, Karen Grimmett, Rosita Van Kuilenburg, Russell Saal, Devinder Gill, H. Miles Prince, John F. Seymour, Paula Marlton
Journal: Blood (2004)
Pregnancy following Renal Transplantation
Authors: V Parsons, M Bewick, J Elias, S A Snowden, M J Weston, C H Rodeck
Journal: Journal of the Royal Society of Medicine (1979)

A series of 7 renal transplant patients with 9 pregnancies is reported. A spontaneous abortion at 10 weeks was the only major problem. Of the other 8 pregnancies, 6 were delivered per vaginam and 2 by elective caesarean section, all after 34 weeks. The birthweights were slightly under the mean for the patients’ age but had been made up to normal by three months. Only one rejection episode occurred during pregnancy. Mild rejection episodes occurred in 4 patients within two months following delivery.
Long-term results of concurrent gemcitabine (G) and radiotherapy (GRT) for locally advanced (LA) or high-risk resected (R) pancreatic cancer
Authors: C. Townsley, A. M. Brade, C. Brezden-Masley, D. Hedley, S. Gallinger, G. R. Pond, A. M. Oza, J. Brierley, M. J. Moore
Journal: Journal of Clinical Oncology (2006)

4101 Background: G is active against pancreatic carcinoma and is a potent radiosensitizer. We present extended follow up data from a phase I/II study of patients treated with combination GRT. Methods: Eligible patients had either LA or high-risk resected [R] pancreatic cancer [positive nodes or positive margin]. 28 were enrolled in a Phase I study of increasing doses of radiotherapy (35 Gy [n = 7]/43.75 Gy [n = 11]/52.5 Gy [n = 10] given over 4, 5 or 6 weeks, respectively in 1.75 Gy fractions) concurrently with 40 mg/m 2 gemcitabine biweekly. Subsequently 35 were treated with induction gemcitabine (G) 1000 mg/m 2 7/8 weeks followed by concurrent bi-weekly gemcitabine (40 mg/m 2 ) with 52.5 Gy (30 fractions of 1.75 Gy over 6 weeks). In total there were 63 patients (31 LA and 32 R) treated between March 1999–July 2001. Results: In the LA population the best response observed was CR - 1, PR - 2, SD - 10, PD - 10. GRT was not delivered to 8 patients due to progression on G alone (n = 5) or patient request (n = 3). By intent to treat analysis, the median survival in LA disease was 15.1 months and the 2 year survival was 19%. In the resected population the median time to progression was 14.3 months, the median survival was 17.9 months and the 5 year survival was 19%. The treatment was generally well tolerated during both the induction G and the GRT ( Table ). Conclusion: Survival for both LA and HR patients with this concurrent gemcitabine radiotherapy regimen is promising and warrants further investigation. [Table: see text] No significant financial relationships to disclose.
Molecular predictors of patients with localized upper gastrointestinal cancers after chemoradiation
Authors: A. T. Phan, A. Rashid, R. Luthra, E. Lopez-Alvarez, S. Swisher, R. Komaki, R. Bresalier, J. A. Ajani
Journal: Journal of Clinical Oncology (2004)

4015 Background: Survival of patients with gastric/gastroesophageal carcinoma (G/GEJC) after an R0 resection after pre-operative chemoradiation remains poor. We evaluated the impact of p53, bcl-2, her2/neu, VEGF, and Ki-67 expression on overall survival (OS). Methods: Pre-treatment biopsies were analyzed by immunohistochemical assay (IHC) for p53, bcl-2, her2/neu, VEGF, and Ki-67 protein expressions. The immunostains were analyzed without knowledge of the clinical outcome. The Cox proportional hazards model was used to determine the individual association between the expression of each marker and OS with clinical stage as co-variate. A categorical factor for the protein expression of each marker was used. P53 protein expression was defined as nuclear staining of ≥ 50% of tumor cells. Bcl-2 expression defined as either present or not. Her2/neu and VEGF defined as intense ( ≥ +2/3) staining, and Ki-67 as number of cells per high power field. Results: 39 patients treated for localized G/GEJC at M. D. Anderson Cancer Center are included in the present analysis. These clinically staged II/III patients were treated similarly and followed for at least 5 years. Independent of clinical stage, expression of her2/neu, bcl-2 and p53 were significant as a predictor of survival by hazard ratio (HR) (HR=3.73, p=0.014; HR=2.91, p=0.050; and HR 3.18, p=0.009, respectively). VEGF and Ki-67 demonstrated trends for worse survival. However, VEGF and Ki-67 correlated significantly with OS in stage III patients. Conclusion: The preliminary data suggest that some of the molecular markers correlated with OS and could become effective targets for treatment of patients with G/GEJC. Results on full cohort will be presented. No significant financial relationships to disclose.
New Insights into the Mechanism of Dominant Anemia Caused By Zinc Finger Mutations in KLF1
Authors: Andrew C Perkins, Kevin R Gillinder, Graham Magor, Mathieu Lajoie, Timothy L Bailey, Michael R Tallack, Melissa Ilsley, Michael Landsberg, Joel P Mackay, James J. Bieker, Luanne L. Peters
Journal: Blood (2014)
Efficacy and safety study of docetaxel as salvage chemotherapy in metastatic gastric cancer failing fluoropyrimidine and platinum combination chemotherapy
Authors: J.-L. Lee, M.-H. Ryu, H. J. Kang, H. M. Chang, T.-W. Kim, J. S. Lee, Y.-K. Kang
Journal: Journal of Clinical Oncology (2005)

4220 Background: Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the 1st line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease; overall response rates (RR) were 17∼25% when used as single agent in the 1st line setting. The action mechanism of D is also different from F or P. We investigated the efficacy of D monotherapy as salvage treatment in AGC failing F and P combination chemotherapy. Methods: Twenty-eight patients with measurable and documented progression within 4 months after F and P containing regimens were included in this study. D was given at a dose of 75 mg/m2 IV every 3 weeks. Patients characteristics are as follows; Male/female 24/4, median age 53(31∼70), median ECOG PS 1(1∼2), peritoneal seeding 36%, liver metastases 54%, elevated ALP level 45%, prior exposure to capecitabine + CDDP 13, 5-FU+CDDP 10, doxifluridine+CDDP 3, S1+CDDP 1, and 5-FU+heptaplatin 1. Median treatment free interval was 42 days (21∼158), and 75% of patients had had progression while receiving F+P and 25% had had progression within 4 months after withdrawal of F+P chemotherapy. Results: At the time of analysis, 24 patients were evaluable for response (refusal after 1st cycle 1, docetaxel anaphylaxis 1, too early to evaluate 2) and 26 patients for safety with 8 patients continuing D treatment. A total of 95 cycles of D were administered with a median of 3 (1∼8) cycles. We observed 5 partial responses (PR) without any complete response for an overall RR of 21% (95% CI, 5∼37). Nine patients showed stable disease and 10 patients progressed. The median time to progression was 2.6 months (95% CI, 1.9∼3.3). The duration of objective PRs were 1.8+, 2.5, 2.3+, 3.2+, and 4.0+ months, respectively. Grade 3/4 febrile neutropenia occurred in 11%. The incidence of grade 2 or worse nonhematologic toxicities are as follows; Mucositis 19%, asthenia 33%, neuropathy 10%, and nail change 14%. Conclusions: Docetaxel monotherapy is active for 2nd line salvage chemotherapy after prior exposure to F and P combination chemotherapy in AGC; The RR is comparable to that achieved in previously untreated patients. No significant financial relationships to disclose.
Long-term follow-up of efficacy of irinotecan-based chemotherapy in poor-risk patients suffering from metastatic colorectal cancer.
Authors: A. Krzyszton, M. Magon, J. Omyla-Staszewska, A. Asendrych-Wozniak, A. Deptala
Journal: Journal of Clinical Oncology (2010)

e14102 Background: Irinotecan (CPT11)-based chemotherapy has provided a significant advancement in the management of patients with metastatic colorectal cancer (MCRC). However, some previous data indicated that patients with poor PS, prior adjuvant chemotherapy and high tumor burden at diagnosis might not benefit from longer survival with CPT11-based chemotherapy. To evaluate whether CPT11-based chemotherapy could be suitable for poor-risk MCRC, we performed a retrospective analysis. Methods: Out of 197 CRC patients treated in our department between 2002-2009, 53 poor risk MCRC patients (poor-risk group was defined as ≥ 2 criteria being fulfilled, i.e. PS > 1, and/or elevated serum LDH, and/or > 1 metastatic site, and/or prior adjuvant chemotherapy) were chosen for the analysis and the results were compared (retrospectively) to respective standard risk MCRC cases. The poor-risk arm included 17 females and 36 males, age between 40- 81 (median 64.7). All the patients were treated with first-line irinotecan-based chemotherapy, according to either de Gramont or AIO regimen. Results: In the analyzed poor-risk group the confirmed RR (CR + PR) was 21.3% what was lower than in the standard-risk group (RR = 50%, p < 0.05). The poor risk group median TTP was 7.1 months, median PFS was 7.3 months, and median OS 15 months. The standard-risk group median TTP, PFS and OS were not statistically different from the poor-risk group (9.3 mts, 9.9 mts, and 16 mts respectively). All the patients received second-line chemotherapy, including biologic agents. CPT11-based chemotherapy was safe. No grade (G) 4 toxicity was observed. The most common adverse events (AE) were diarrhea (28.3% – 15 pts) and neutropenia (11.3% – 6 pts), but G3 AE were noted only in three and two persons respectively. Conclusions: Our analysis showed, that irinotecan-based chemotherapy was an effective and safe treatment option even for poor-risk patients suffering from MCRC. Although the RR was lower in comparison to standard-risk cases it did not translate into significantly shorter TTP and PFS. Subsequent lines of chemotherapy affected the overall survival. Thus, poor-risk status did not preclude irinotecan-based chemotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Pfizer, Roche, sanofi-aventis
Expression of EGFR, HER-2 and p53 predictive of prognosis in muscle-invasive bladder cancer
Authors: W. Sakr, S. Marur, M. Che, L. Heilbrun, D. Smith, I. Powell, E. Pontes, M. Cher, U. Vaishampayan
Journal: Journal of Clinical Oncology (2007)

15637 Background: The significance of over expression of Erb-1 (epidermal growth factor receptor/ EGFR) and Erb-2 (Her-2) has been reported in various tumors. The aim of this study was to investigate the correlation of the expression of EGFR, Her-2 and p53 with relapse free survival (RFS) and over all survival (OS) in patients with muscle invasive bladder cancer Methods: All patients with muscle invasive bladder cancer diagnosed at our institution between1993and 2004 were considered for the study. Immunohistochemical staining for EGFR, Her2 and p53 performed on formalin-fixed paraffin-embedded archival tissue was evaluated as positive or negative without knowledge of clinical outcome. Survival data determined by reviewing patients medical records were correlated with the staining results. Results: Of the 46 patients who qualified for the study, 40 had slides interpretable for Her 2 and p 53 staining and 38 had slides interpretable for EGFR staining. 35 of 38 were EGFR +ve, 22/40 were Her-2 +ve and 12/40 were p53+ve. The median age of the 46 patients was 67.5 years with a male/female ratio of 60% and 40%. 83% had clinical Stage 2; of those 42%, 23%, and 35% had pathological stages T2, T3 and T4 respectively. Six of 46 (13%), received adjuvant therapy. Tumor histology was pure transitional carcinoma in 56%, or with other components (squamous or adenocarcinoma) in 44%. Median follow-up was 48.8 months for RFS and 44.9 months for OS. Patients with positive EGFR had a median RFS of 34.8 months and median OS of 59.8 months. In patients with negative EGFR, median RFS and OS were not yet reached. Her 2 positive patients had median RFS of 19.2 months compared to 63.8 months in Her-2 negative patients. Her-2 negative patients had median OS of 59.7 months while median was not reached in Her 2 positive patients. Conclusions: While the differences are not statistically significant, the trends observed warrant prospective investigation of the prognostic significance of these markers in a larger population of muscle invasive bladder cancer patients. No significant financial relationships to disclose.
Telomerase - a tumor antigen in chronic lymphocytic leukemia (CLL) induces spontaneously autologous leukemia specific cytotoxic T lymphocytes
Authors: P. Kokhaei, M. Palma, L. Hansson, A. Ã-sterborg, A. Choudhury, H. Mellstedt
Journal: Journal of Clinical Oncology (2005)

2577 Background: Human telomerase reverse transcriptase (hTERT) is the catalytic domain of the functional telomerase complex, which expression is absent and/or transient in most normal human adult cells, but high in most tumor cells. Almost 90% of human tumors display high levels of telomerase expression, implying the possibility of using hTERT as a target for cancer immunotherapy. Methods: Peripheral blood mononuclear cells (PBMC) from 26 B-CLL pts were tested for telomerase expression by RT-PCR. Monocyte-derived dendritic cells (DC) were generated from PBMC of 4 telomerase positive and 2 telomerase-negative CLL patients. DC were pulsed with a 16 mer amino acid long peptide from hTERT and with a RAS peptide as control. To assess telomerase-specific T cells, IFN-γ production (ELISPOT), 3H thymidine incorporation, MHC blocking, and cytotoxicity assays were used. Results: PCR showed that hTERT was expressed in 13 out of 26 pts. Among the 13 telomerase-positive pts, 4 were selected for hTERT-specific CTL expansion. In all 4 pts DC pulsed with hTERT peptide could generate CTL against the autologous leukemic cells upon two rounds of restimulation with a specific lysis of 58±12% (mean± SEM). The corresponding figures for Ras stimulated T cells were15±3.5% lysis (p<0.025). In two telomerase-negative pts telomerase specific CTLs recognizing the autologous leukemic B cells could not be expanded. Telomerase expanded T cells induced 1.8± 0.2% lysis of tumor B cells and the control Ras peptide 1.7 ± 1% lysis. Comparing lytic capacity of telomerase positive and negative pts was statistically significant (p<0.027). In 2 out of 4 pts a proliferative response against hTERT was noted in fresh T cells. No restimulation was done. MHC class I and MHC class II blocking revealed that the proliferative response was both MHC I and MHC II-dependent. No INF-γ production was detected in fresh isolated T cells stimulated once with the peptide. Conclusion: Our data show that CLL pts with telomerase positive leukemic cells have spontaneously occurring telomerase specific T cells able to lyse the leukemic cells. The results indicate that telomerase might be a valid target structure for vaccine development in CLL. No significant financial relationships to disclose.
Mechanisms of resistance to imatinib in chronic myeloid leukemia (CML) patients in chronic phase (CP) who achieved durable complete cytogenetic responses (CCR)
Authors: R Piazza, Magistroni, L Tornaghi, F Andreoni, S Bungaro, G Cazzaniga, A Biondi, E Pogliani, M Varella-Garcia, G Corneo, C Gambacorti Passerini
Journal: Blood (2003)