bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential Intraperitoneal Topotecan and Oral Etoposide Chemotherapy in Recurrent Platinum-Resistant Ovarian Carcinoma
Authors: Sood Anil K. , Lush Richard , Geisler John P. , Shahin Mark S. , Sanders Linda , Sullivan Dan , Buller Richard E. , Sorosky Joel I. 
Published: September 2005

Abstract
Purpose: The purpose is to investigate the safety and efficacy of i.p. topotecan and oral etoposide as salvage treatment for patients with platinum-resistant ovarian or primary peritoneal cancer.
Experimental Design: Patients were treated with i.p. topotecan initial dose, 1 mg/m2 on days 1 to 5, followed by oral etoposide 100 mg on days 6 to 9 of a 28-day cycle for six cycles. Dose reduction of topotecan was used for severe bone marrow suppression. Peritoneal (topotecan) and plasma (topotecan and etoposide) levels were assessed at multiple time points using high-pressure liquid chromatography.
Results: Twenty-two patients (mean age, 61 years) with a median of 1.5 prior treatments were enrolled. Etoposide peak plasma concentrations ranged from 1.9 to 6.9 μg/mL (mean, 3.6 μg/mL). Topotecan plasma levels rose with increasing peritoneal concentration and were detectable within 1 hour but tended to decrease rapidly to below detectable levels within 24 hours. The peak plasma concentration of topotecan was 12.82 ± 8.55 μg/mL with a plasma half-life of 6.17 ± 2.75 hours. A total of 104 cycles was administered; 14 patients (64%) completed all six planned cycles. All patients were evaluable for toxicity, and 21 patients were evaluable for response. The most common grade 4 toxicities were neutropenia and thrombocytopenia in eight and four patients (36 and 18%), respectively. There were no treatment-related deaths. The overall response rate was 38% [complete response, three (14%); partial response, five (24%)]. Seven patients had stable disease and six progressed while on treatment.
Conclusions: The combination of i.p. topotecan and oral etoposide is an active and well-tolerated regimen in platinum-resistant ovarian carcinoma. Additional studies investigating topotecan in combination with etoposide are warranted.
Low-Dose Suramin Enhanced Paclitaxel Activity in Chemotherapy-Naïve and Paclitaxel-Pretreated Human Breast Xenograft Tumors
Authors: Song SaeHeum , Yu Bei , Wei Yong , Wientjes M. Guillaume , Au Jessie L.-S. 
Published: September 2005

AbstractWe reported induction of broad-spectrum chemoresistance by acidic and basic fibroblast growth factors and chemosensitization by their nonspecific inhibitor suramin at nontoxic and subtherapeutic doses. This study evaluated whether low-dose suramin enhances paclitaxel activity in chemotherapy-naïve and paclitaxel-pretreated human MCF7 breast xenograft tumors in mice. Suramin, 10 mg/kg, and/or paclitaxel, 15 mg/kg, were administered intravenously, twice weekly for 2 to 3 weeks. In addition to conventional end points [tumor size change, median survival time (MST)], we also used clinically relevant end points [partial (PR) and complete response rates (CR); progressive disease (PD); stable disease (SD); time to tumor progression (TTP)]. In chemotherapy-naïve mice, the control and suramin groups showed identical TTP (3 days) and MST (21 days). Single-agent paclitaxel produced 47% PR and 24% CR, and prolonged both TTP and MST to 73 days. The addition of suramin further improved the total response rate to 100% with a dramatically greater 63% CR, shortened the time to attain PR and CR, and prolonged TTP and MST to ≥136 days. In the paclitaxel-pretreated group, single-agent paclitaxel resulted in 67% SD and 33% PD, whereas the combination produced 50% PR and 50% SD. Suramin also significantly enhanced the apoptotic effect of paclitaxel in tumors. In conclusion, suramin improved the activity of paclitaxel in both chemotherapy-naïve and paclitaxel-pretreated animals, without enhancing host toxicity (≤10% body weight loss in all groups). These data have led to the initiation of phase I/II trials of paclitaxel and low-dose suramin combination in advanced metastatic breast cancer patients.
Boosting T Cell-Mediated Immunity to Tyrosinase by Vaccinia Virus-Transduced, CD34+-Derived Dendritic Cell Vaccination
Authors: Di Nicola Massimo , Carlo-Stella Carmelo , Mortarini Roberta , Baldassari Paola , Guidetti Anna , Gallino Gian Francesco , Del Vecchio Michele , Ravagnani Fernando , Magni Michele , Chaplin Paul , Cascinelli Natale , Parmiani Giorgio , Gianni Alessandro M. , Anichini Andrea 
Published: September 2005

AbstractPurpose: Six American Joint Committee on Cancer stage IV melanoma patients were enrolled into a Phase I study of vaccination with autologous CD34+-derived dendritic cells transduced with a modified vaccinia Ankara virus encoding human tyrosinase gene (MVA-hTyr).Experimental Design: Patients received a first intravenous injection of 1 × 108 MVA-hTyr–transduced dendritic cells, followed by three s.c. injections at a 14-day interval.Results: Treatment was well tolerated, except for low-grade fever (three of six patients), mild erythema at injection site (five of six), and vitiligo (two of six). A partial response, involving shrinkage of an s.c. nodule, later surgically removed, was observed in 1 patient, who then remained disease-free (&gt;850 days). By human lymphocyte antigen tetramer analysis, significant and often long-lasting increases in frequency of T cells directed to tyrosinase368–376 but not to gp100209–217 were documented in periphery of 4 of 5 HLA-A*0201+ patients, a few days after vaccine administration. In addition, maturation phenotype of tyrosinase-specific T cell shifted toward the T effector memory/T terminally differentiate stages (CCR7−CD45RA−/+) in synchrony with the T-cell frequency peaks. By enzyme-linked immunospot in peripheral blood of five HLA-A*0201+ patients, we found that the vaccine could induce interferon γ-releasing effector cells directed to HLA-A*0201/tyrosinase368–376 and to vaccinia virus HLA-A*0201/H3L184–192 epitopes. Moreover, an interferon γ response after vaccination was elicited even against the HLA-DRB1–1501/tyrosinase386–406 epitope in one out of two HLA-A* DRB1–01501+ patients.Conclusions: These results indicate that vaccination with MVA-hTyr–transduced dendritic cells is well tolerated, can possibly produce clinical responses, and activates tyrosinase- and vaccinia virus-specific T cells in vivo. These data suggest a broad utility of the MVA vector for targeting tumor-associated antigens to dendritic cells for tumor immunotherapy.
Monitoring the Response of Orthotopic Bladder Tumors to Granulocyte Macrophage Colony-Stimulating Factor Therapy Using the
Prostate-Specific Antigen
Gene as a Reporter
Authors: Wu Qinghui , Esuvaranathan Kesavan , Mahendran Ratha 
Published: September 2005

Abstract
Purpose: Although orthotopic animal models of cancer best reflect the disease in humans, a major drawback of these models is the inability to monitor tumor growth accurately. Our aims were to produce a bladder tumor cell line (MB49) that secreted human prostate-specific antigen (PSA), analyze the feasibility and accuracy of PSA as a biomarker for monitoring orthotopic bladder tumor growth, and evaluate the effectiveness of granulocyte macrophage colony-stimulating factor (GM-CSF) gene therapy using this model.
Experimental Design: PSA secretion was assessed after both s.c. and orthotopic implantation of MB49-PSA cells in C57BL/6 mice. PSA levels in mouse serum and urine samples were monitored at 2- to 3-day intervals by ELISA. Using the orthotopic model, mice with confirmed tumors were given liposome-mediated GM-CSF gene therapy twice a week for 3 weeks intravesically and PSA levels monitored.
Results: The MB49-PSA cells behaved similarly as the parental cell line and produced high levels of PSA both in vitro and in vivo. In the s.c. model, the level of PSA produced correlated with tumor volume (r = 0.96). In the orthotopic model, PSA could be detected in serum and urine on the fourth day after implantation. PSA levels over the treatment period indicated that tumor growth was inhibited by GM-CSF gene therapy. Up to 50% of the treated mice were cured. Cytokine array analysis revealed that GM-CSF gene therapy induced the production of other cytokines and chemokines.
Conclusions: MB49 cells modified to secrete PSA are a reliable method to evaluate therapeutic modalities for bladder cancer.
Circulating Nucleosomes Predict the Response to Chemotherapy in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Holdenrieder Stefan , Stieber Petra , von Pawel Joachim , Raith Hannelore , Nagel Dorothea , Feldmann Knut , Seidel Dietrich 
Published: September 2005

Abstract
Purpose: We investigated the potential of circulating, nucleosomal DNA for the early prediction of the efficacy of chemotherapy in patients with advanced lung cancer.
Experimental Design: In serum of 212 patients with newly diagnosed non–small cell lung cancer (stages III and IV) undergoing chemotherapy, nucleosomes (ELISA, Roche) were measured at days 1, 3, 5, and 8 of the first cycle and before each new therapeutic cycle. Additionally, carcinoembryonic antigen and cytokeratin 19 fragments (CYFRA 21–1; Elecsys, Roche) were determined before each cycle. The therapeutic success was classified by computed tomography before start of the third cycle according to the World Health Organization criteria.
Results: In univariate analysis, responders (patients with remission) showed significantly (P &lt; 0.05) lower values for the area under the curve of days 1 to 8 (AUC 1–8) of nucleosomes, the pretherapeutic baseline values of cycle 2 (BV2) and cycle 3 (BV3) of nucleosomes, and higher decreases of the baseline values from cycle 1 to 2 (BV1–2) and from cycle 1 to 3 (BV1–3) compared with nonresponders (patients with stable or progressive disease). Additionally, CYFRA 21–1 (BV1, BV2, BV3, BV1–2, BV1–3) and carcinoembryonic antigen (BV1–2) discriminated significantly between both groups.
In multivariate analysis including all parameters available until end of the first therapeutic cycle, nucleosomes (AUC 1–8), CYFRA 21–1 (BV1), stage, and age were independent predictors of therapy response with nucleosomes (AUC 1–8) having the strongest impact.
Conclusion: Circulating nucleosomes in combination with oncological biomarkers are valuable for the early estimation of the efficacy of chemotherapy in patients with lung cancer.
Phase II Study of Feasibility of Dose-Dense FEC Followed by Alternating Weekly Taxanes in High-Risk, Four or More Node-Positive Breast Cancer
Authors: Dang Chau T. , D’Andrea Gabriella M. , Moynahan Mary E. , Dickler Maura N. , Seidman Andrew D. , Fornier Monica , Robson Mark E. , Theodoulou Maria , Lake Diana , Currie Violante E. , Hurria Arti , Panageas Katherine S. , Norton Larry , Hudis Clifford A. 
Published: September 2005

Abstract
Purpose: To develop a potentially superior adjuvant chemotherapy regimen, we conducted a pilot study of dose-dense 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by weekly alternating taxanes. The primary objective was to determine the feasibility of the regimen; the secondary objective was to estimate the disease-free and overall survival.
Experimental Design: Patients with ≥4 node-positive breast cancer were studied. Treatment consisted of FEC at 500/100/500 mg/m2, respectively, ×6 at two-week intervals with granulocyte colony-stimulating factor, followed by weekly paclitaxel (80 mg/m2) alternating with docetaxel (35 mg/m2) ×18.
Results: Between November 2001 and January 2003, 44 patients were enrolled. Median age was 46 years (range, 26–63 years), median number of positive nodes was 9 (range, 4–32), and median tumor size was 2.5 cm (range, 0.6–11.0 cm). Because of unexpected toxicities, the study was stopped when 17 (39%) had fully completed all of the planned treatment. Two of 17 (12%) developed grade 4 pericardial/grade 3 bilateral pleural effusions at treatment completion; both required pericardial window. The remaining patients were treated with taxanes using one of several standard dose and schedule combinations. Furthermore, 4 of 44 (9%) developed pneumonitis attributed to the FEC regimen. Hospital admissions were required for 12 of 44 (27%); 3 of 44 (7%) required blood transfusions. There were no treatment related deaths. Median disease-free and overall survival will not be estimatable because of early closure of study.
Conclusion: FEC ×6 at 2-week intervals followed by 18 weeks of alternating taxanes is not feasible at the doses tested. Other strategies are needed to improve adjuvant systemic chemotherapy.
Cyclophosphamide Dose Intensification during Induction Therapy for Intermediate-Risk Pediatric Rhabdomyosarcoma Is Feasible but Does Not Improve Outcome
Authors: Spunt Sheri L. , Smith Lynette M. , Ruymann Frederick B. , Qualman Stephen J. , Donaldson Sarah S. , Rodeberg David A. , Anderson James R. , Crist William M. , Link Michael P. 
Published: September 2005

Abstract
Purpose: More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome.
Experimental Design: This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages &lt; 21 years with intermediate-risk rhabdomyosarcoma. Induction therapy comprised four 3-week cycles of VAC: vincristine (V) 1.5 mg/m2 on days 0, 7, and 14; actinomycin D (A) 1.35 mg/m2 on day 0; and dose-intensified cyclophosphamide (C) on days 0, 1, and 2. The three cyclophosphamide dose levels tested were as follows: (a) 1.2 g/m2/dose; (b) 1.5 g/m2/dose; and (c) 1.8 g/m2/dose. Continuation therapy comprised nine additional cycles of VAC with 2.2 g/m2/cycle of C. Radiotherapy was administered at week 0 (parameningeal tumors with intracranial extension) or week 12 or 15 (all others).
Results: Between October 1996 and August 1999, 115 eligible patients were enrolled. Three of 15 patients treated at dose level 2 experienced life-threatening dose-limiting toxicity (typhlitis ± other severe toxicity). Dose level 1 was the maximum-tolerated dose, and 91 evaluable patients were treated at this level. The 3-year failure-free and overall survival estimates for patients treated at the maximum-tolerated dose were 52% (95% confidence interval, 41–64%) and 67% (95% confidence interval, 56–77%), respectively, at a median follow-up of 3 years.
Conclusions: A 64% increase in the standard cyclophosphamide dosage during induction (to 3.6 g/m2/cycle) was tolerated. However, outcomes were similar to those observed at lower dosages, suggesting that alkylator dose intensification does not benefit patients with intermediate-risk rhabdomyosarcoma.
A Phase I Study of Topical Tempol for the Prevention of Alopecia Induced by Whole Brain Radiotherapy
Authors: Metz James M. , Smith Debbie , Mick Rosemarie , Lustig Robert , Mitchell James , Cherakuri Murali , Glatstein Eli , Hahn Stephen M. 
Published: September 2005

Abstract
Purpose: Complete alopecia is a universal complication of whole brain radiation therapy which contributes to patient anxiety over treatment. Tempol, a nitroxide radioprotector, has been shown to protect against radiation-induced alopecia in an animal model. This phase Ib study was designed to evaluate the safety and side effect profile of topical Tempol in patients with brain metastases being treated with whole brain radiotherapy.
Experimental Design: Twelve patients with metastatic cancer to the brain were enrolled in the study between October 2000 and February 2003. Tempol (70 mg/ml concentration solution) was applied topically to the scalp 15 minutes before and washed off immediately after the completion of each of 10 fractions of whole brain radiation. Pharmacokinetic studies to evaluate the systemic absorption of Tempol were performed. Patients were assessed for toxicity before, during, and after Tempol administration. A secondary end point of the study, hair retention, was also scored.
Results: Eleven patients were treated with topical Tempol. Adverse events that were considered possibly, probably, or definitely related to Tempol, included asymptomatic grade 2 (two patients) and grade 1 (one patient) hypoglycemia, grade 1 forehead skin redness (one patient), grade 1 dry scalp (one patient), and grade 1 tingling sensation on the scalp (one patient). Tempol was not detected in blood samples from more than 50% of the patients. Mean maximum Tempol levels for individual patients at any time point varied from 0.4 to 3.1 μmol/L. Hair retention was localized to the base of the scalp where the Tempol solution pooled after application in the first four patients on the study. Subsequently, full scalp hair retention was seen in three of final five evaluable patients after gauze had been wrapped around the head to hold the solution against the scalp.
Conclusions: This study demonstrates that topical application of Tempol to the scalp before whole brain radiation is safe and well tolerated. Evidence of protection against radiation-induced alopecia was observed. A phase II study that uses a gel formulation to increase the exposure of scalp to Tempol has been initiated.
Heparanase Expression at the Invasion Front of Human Head and Neck Cancers and Correlation with Poor Prognosis
Authors: Beckhove Philipp , Helmke Burkhard M. , Ziouta Yvonne , Bucur Mariana , Dörner Wolfgang , Mogler Carolin , Dyckhoff Gerhard , Herold-Mende Christel 
Published: September 2005

Abstract
Purpose: Head and neck squamous cell carcinomas (HNSCC) are characterized by a poor prognosis due to aggressive, recurrent tumor growth. Expression of the extracellular matrix–degrading enzyme heparanase was associated with poorer prognosis in several cancers. We analyzed the presence of heparanase in HNSCC tissues and tumor cells and its potential prognostic significance.
Experimental Design: We analyzed the expression of the active form of heparanase in HNSCC tissues in corresponding tumor cell cultures and after xenotransplantation of tumor cell cultures into NOD/Scid mice by immunohistochemistry, Western blot analysis, and reverse transcription-PCR in altogether 25 patients and did a comparison with clinicopathologic data of the patients.
Results: Heparanase expression in situ was detected in all tumor biopsies in the tumor stroma and in tumor cells from 13 of 19 primary tumors and 9 of 12 lymph node metastases. Heparanase was localized in disseminated tumor cells, in tumor cell clusters invading adjacent stromal tissues, and in tumor cells at the tumor invasion front. Lymph node metastases expressed higher levels of heparanase compared with corresponding primary tumors. In contrast to a heterogeneous expression pattern in tumor tissues, all corresponding HNSCC tumor cell cultures showed a rather homogeneous heparanase expression on the mRNA and protein levels. Comparison of heparanase expression in situ and in corresponding tumor cell cultures in vitro or after xenotransplantation into NOD/Scid mice revealed that heparanase expression was regulated in vivo. Lack of heparanase in tumor cells from primary tumors or lymph node metastases was correlated with prolonged disease-free survival and overall survival.
Conclusion: Heparanase expression seems to be involved in the invasiveness and aggressiveness of HNSCC.
Steroid 5α-Reductase Isozymes I and II in Recurrent Prostate Cancer
Authors: Titus Mark A. , Gregory Christopher W. , Ford O. Harris , Schell Michael J. , Maygarden Susan J. , Mohler James L. 
Published: September 2005

Abstract
Purpose: Prostate cancer recurs during androgen deprivation therapy despite reduced circulating androgens. We showed that recurrent prostate cancer tissue has testosterone levels similar to androgen-stimulated benign prostate, whereas dihydrotestosterone levels were reduced 82% to 1.45 nmol/L, sufficient for androgen receptor activation. The altered testosterone/dihydrotestosterone ratio in recurrent prostate cancer suggests loss of 5α-reducing capability. The aim of this study was to characterize steroid 5α-reductase isozymes I (S5αRI) and II (S5αRII) in prostate tissues.
Experimental Design: A tissue microarray was constructed from 22 recurrent prostate cancer specimens and matched pairs of androgen-stimulated benign prostate and androgen-stimulated prostate cancer from 23 radical prostatectomy specimens. Immunoblots were constructed from eight recurrent prostate cancers, eight androgen-stimulated benign prostate, and eight androgen-stimulated prostate cancer specimens. Isozyme expression was examined in microarray sections and immunoblots using S5αRI and S5αRII polyclonal antibodies. Isozyme activities were measured in 12 recurrent prostate cancer, 12 androgen-stimulated benign prostate, and 12 androgen-stimulated prostate cancer specimens.
Results: Nuclear immunostaining exhibited higher S5αRI expression than S5αRII in recurrent prostate cancer, androgen-stimulated benign prostate, and androgen-stimulated prostate cancers (P &lt; 0.0001); mean expression was 125, 150, and 115 for S5αRI versus 10, 29, and 37 for S5αRII, respectively. Cytoplasmic immunostaining was moderate and similar for both isozymes in the three tissue types (P &gt; 0.05). Immunoblots confirmed immunohistochemistry; S5αRI was expressed in recurrent prostate cancer specimens and S5αRII was not detected. The activity of S5αRI (114.4 pmol/mg epithelial protein/minute) was 3.7-fold higher than S5αRII (30.7 pmol/mg epithelial protein/minute) in recurrent prostate cancer specimens.
Conclusions: Expression levels and isozyme activity shifts from S5αRII toward S5αRI in recurrent prostate cancer. Dual inhibition of S5αRI and S5αRII should reduce dihydrotestosterone biosynthesis and may prevent or delay growth of recurrent prostate cancer.
Variability in the Degree of Expression of Phosphorylated IκBα in Chronic Lymphocytic Leukemia Cases With Nodal Involvement
Authors: Rodríguez Antonia , Martínez Nerea , Camacho Francisca I. , Ruíz-Ballesteros Elena , Algara Patrocinio , García Juan-Fernando , Menárguez Javier , Alvaro Tomás , Fresno Manuel F. , Solano Fernando , Mollejo Manuela , Martin Carmen , Piris Miguel A. 
Published: September 2005

AbstractPurpose: Based on previous preliminary observations, we hypothesize that the molecular and clinical variability of chronic lymphocytic leukemia (CLL) reflects differences in the degree of nuclear factor (NF)-κB activation, as determined by the expression of phosphorylated IκBα (p-IκBα).Experimental Design: The expression profile (mRNA and protein expression) was analyzed with the Centro Nacional de Investigaciones Oncológicas Oncochip, a cDNA microarray containing 6386 cancer-related genes, and a tissue microarray (TMA). The results were correlated with the IgVH mutational status, ZAP-70 expression, cytogenetic alterations, and clinical outcome.Results: We found correlations between the presence of p-IκBα, a surrogate marker of NF-κB activation, and changes in the expression profile (mRNA and protein expression) and clinical outcome in a series of CLL cases with lymph node involvement. Activation of NF-κB, as determined by the expression of p-IκBα, was associated with the expression of a set of genes comprising key genes involved in the control of B-cell receptor signaling, signal transduction, and apoptosis, including SYK, LYN, BCL2, CCR7, BTK, PIK3CD, and others. Cases with increased expression of p-IκBα showed longer overall survival than cases with lower expression. A Cox regression model was derived to estimate some parameters of prognostic interest: IgVH mutational status, ZAP-70, and p-IκBα expression. The multivariate analysis disclosed p-IκBα and ZAP-70 expression as independent prognostic factors of survival.Conclusions: A variable degree of activation of NF-κB, as determined by the expression of p-IκBα, is an identifiable event in CLL, and is correlated with changes in the expression profile and overall survival.