bluuebunny/crossref_metadata_2025 huggingface dataset:
A corner of a foreign field that is forever Spielberg’s: understanding the moral landscapes of the site of the former KL Płaszow, Krakoow, Poland
Authors: Charlesworth Andrew
Published: June 2004

This essay represents the records of three different encounters with the site of the former concentration camp at Płaszow in the suburbs of the city of Krakoow in southern Poland, all written between 1993 and 1996. As the first account suggests, before the making of the film Schindler’s list by Steven Spielberg in and around Krakoow in 1993 and the subsequent worldwide success of the film, not much notice had been paid to this place among the welter of other martyrology sites linked to the German occupation of 1939-45 scattered across Poland. As the third account indicates, locals had been using this virtually anonymous place for nearly 50 years as open space in a crowded urban landscape. The second account reveals the power of Spielberg’s moral vision to appropriate that place and the Holocaust itself. The paper sets out to consider other moral landscapes that are to be found at this place, and how the various appropriations of this landscape now sit uneasily together. As Smith implies, it is not that easy to put oneself in the place of others.
Bicalutamide Monotherapy Versus Leuprolide Monotherapy for Prostate Cancer: Effects on Bone Mineral Density and Body Composition
Authors: Smith Matthew R. , Goode Melissa , Zietman Anthony L. , McGovern Francis J. , Lee Hang , Finkelstein Joel S.
Published: June 2004

Purpose

Gonadotropin-releasing hormone agonists decrease bone mineral density, lean mass, and muscle size and increase fat mass in men with prostate cancer. Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition.

Patients and Methods

In a 12-month, open-label study, we randomly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide (150 mg by mouth daily). Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography.

Results

Mean (± standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% ± 0.5% in the leuprolide group and increased by 2.5 ± 0.5 in the bicalutamide group from baseline to 12 months (P < .001). Mean changes in bone mineral density of the total body, total hip, femoral neck, and trabecular bone of the lumbar spine also differed significantly between groups (P ≤ .003 for each comparison). Fat mass increased by 11.1% ± 1.3% in the leuprolide group and by 6.4% ± 1.1% in the bicalutamide group (P = .01). Changes in lean mass, muscle size, and muscle strength were similar between the groups. Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group. Fatigue, loss of sexual interest, and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group.

Conclusion

In men with prostate cancer, bicalutamide monotherapy increases bone mineral density, lessens fat accumulation, and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist.
Randomized, Controlled Trial Investigating Short-Term Health-Related Quality of Life With Doxorubicin and Paclitaxel Versus Doxorubicin and Cyclophosphamide As First-Line Chemotherapy in Patients With Metastatic Breast Cancer: European Organization for Research and Treatment of Cancer Breast Cancer Group, Investigational Drug Branch for Breast Cancer and the New Drug Development Group Study
Authors: Bottomley Andrew , Biganzoli Laura , Cufer Tanja , Coleman Robert E. , Coens Corneel , Efficace Fabio , Calvert Hilary Allan , Gamucci Teresa , Twelves Chris , Fargeot Pierre , Piccart Martine
Published: June 2004

Purpose

To compare health-related quality of life (HRQOL) in patients with metastatic breast cancer receiving the combination of doxorubicin and paclitaxel (AT) or doxorubicin and cyclophosphamide (AC) as first-line chemotherapy treatment.

Patients and Methods

Eligible patients (n = 275) with anthracycline-naive measurable metastatic breast cancer were randomly assigned to AT (doxorubicin 60 mg/m2 as an intravenous bolus plus paclitaxel 175 mg/m2 as a 3-hour infusion) or AC (doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2) every 3 weeks for a maximum of six cycles. Dose escalation of paclitaxel (200 mg/m2) and cyclophosphamide (750 mg/m2) was planned at cycle 2 to reach equivalent myelosuppression in the two groups. HRQOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the EORTC Breast Module at baseline and the start of cycles 2, 4, and 6, and 3 months after the last cycle.

Results

Seventy-nine percent of the patients (n = 219) completed a baseline measure. However, there were no statistically significant differences in HRQOL between the two treatment groups. In both groups, selected aspects of HRQOL were impaired over time, with increased fatigue, although some clinically significant improvements in emotional functioning were seen, as well as a reduction in pain over time. Overall, global quality of life was maintained in both treatment groups.

Conclusion

This information is important when advising women patients of the expected HRQOL consequences of treatment regimens and should help clinicians and their patients make informed treatment decisions.
Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Factorial Study
Authors: Kwong Dora L.W. , Sham Jonathan S.T. , Au Gordon K.H. , Chua Daniel T.T. , Kwong Philip W.K. , Cheng Ashley C.K. , Wu P.M. , Law Martin W.M. , Kwok Carol C.H. , Yau C.C. , Wan K.Y. , Chan Raymond T.T. , Choy Damon D.K.
Published: June 2004

Purpose

To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC).

Patients and Methods

Patients with Ho's stage T3 or N2/N3 NPC or neck node ≥ 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B.

Results

Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P = .14 and .06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P = .026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P = .39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P = .83 and .69; n = 111 v 108). DMR and LRFR were not reduced with AC (P = .34 and .15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P = .009).

Conclusion

An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.
Prophylactic Urokinase in the Management of Long-Term Venous Access Devices in Children: A Children's Oncology Group Study
Authors: Dillon Peter W. , Jones Gary R. , Bagnall-Reeb Holly A. , Buckley Jonathon D. , Wiener Eugene S. , Haase Gerald M.
Published: June 2004

Purpose

Infection and thrombosis are serious complications of long-term vascular access devices in children undergoing chemotherapy. Since routine fibrinolytic therapy may decrease these complications, the purpose of this study was to compare the efficacy of an every-2-week administration of urokinase with standard heparin flushes in reducing the incidence of device-related infections and occlusions.

Materials and Methods

This study was a prospective, randomized phase III multicenter trial conducted by the Children's Cancer Group, in which patients with implantable ports or tunneled catheters received either urokinase or heparin every 2 weeks for 12 months. Study end points were time to first occlusion or time to first device-related infection.

Results

Five hundred seventy-seven patients from 29 institutions were enrolled, of whom 51% had external catheters and 49% had ports. Urokinase administration resulted in fewer occlusive events than heparin (23% v 31%; P = .02), a longer time to first occlusive event (log-rank analysis, P = .006), and a 1.6-fold difference in the rate of occlusive events (Poisson regression, P = .003). Similar results were noted when comparing ports and tunneled catheters. The urokinase group also had a 1.4-fold difference in the rate of infection (Poisson regression, P = .05) and longer time to first infection (log-rank, P = .07), but the difference was significant only in tunneled catheters.

Conclusion

Urokinase administration every 2 weeks significantly affects the rate of occlusive events in ports and tunneled catheters and of infectious events in external catheters compared with heparin administration.
Coamplification of DDX1 Correlates With an Improved Survival Probability in Children With MYCN-Amplified Human Neuroblastoma
Authors: Weber Axel , Imisch Patricia , Bergmann Eckhard , Christiansen Holger
Published: June 2004

Purpose

Amplification of the MYCN oncogene at chromosome 2p24-25 identifies an aggressive subtype of human neuroblastoma with a poor clinical outcome. Differences in amplicon structure and coamplification of genes telomeric and centromeric to the MYCN oncogene have previously been described. A relevant role of gene coamplification for neuroblastoma pathogenesis remains elusive.

Patients and Methods

We analyzed 98 primary neuroblastoma tumors with MYCN amplification for coamplification of seven additional genes at chromosome 2p24-25 (DDX1, NAG, NSE1, LPIN1, EST- AA581763 , SMC6, and SDC1). Two semiquantitative multiplex polymerase chain reactions were used to obtain the amplification status of the target genes in relation to a reference gene on chromosome 2q (Inhibin-beta-b). Furthermore, mRNA expression pattern of coamplified genes in a subset of tumors was analyzed.

Results

Our results show that the frequency of gene coamplification on 2p24-25 in neuroblastoma is correlated directly to the physical distance to MYCN. Coamplification is correlated to an upregulated gene expression for DDX1 and NAG. Coamplification of the DDX1 gene within 400kb telomeric to MYCN identifies a subgroup of advanced stage neuroblastoma tumors with a more favorable outcome (P = .027, log-rank test). A high expression level of DDX1 is associated with a trend towards a better survival probability (P = .058, log-rank test).

Conclusion

Our results indicate that DDX1 coamplification correlates with a better prognosis and improved patient survival in MYCN-amplified neurobastoma.
Randomized Comparison of Combination Chemotherapy With Etoposide, Bleomycin, and Either High-Dose or Standard-Dose Cisplatin in Children and Adolescents With High-Risk Malignant Germ Cell Tumors: A Pediatric Intergroup Study—Pediatric Oncology Group 9049 and Children's Cancer Group 8882
Authors: Cushing Barbara , Giller Roger , Cullen John W. , Marina Neyssa M. , Lauer Stephen J. , Olson Thomas A. , Rogers Paul C. , Colombani Paul , Rescorla Frederick , Billmire Deborah F. , Vinocur Charles D. , Hawkins Edith P. , Davis Mary Margaret , Perlman Elizabeth J. , London Wendy B. , Castleberry Robert P.
Published: June 2004

Purpose

To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity.

Patients and Methods

Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5, and either high-dose cisplatin 40 mg/m2 on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m2 on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen.

Results

One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate ± SE (89.6% ± 3.6% v 80.5% ± 4.8% for PEB; P = .0284). There was no significant difference in OS (HDPEB 91.7% ± 3.3% v PEB 86.0% ± 4.1%). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB.

Conclusion

Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.
Small-Cell Carcinomas of the Gastrointestinal Tract: A Review
Authors: Brenner Baruch , Tang Laura H. , Klimstra David S. , Kelsen David P.
Published: June 2004

Purpose

To improve our understanding of the entity of small-cell carcinoma (SmCC) of the gastrointestinal (GI) tract.

Methods

A MEDLINE search was done, using the terms “small cell carcinoma” or “oat cell carcinoma” combined with “gastrointestinal” or with any of the GI sites, for the period 1970 to 2003. The 138 eligible reports identified in this way were reviewed for clinical data.

Results

To date, approximately 544 cases of GI SmCC have been reported. The disease represents 0.1% to 1% of all GI malignancies, with the esophagus being the most common primary site. A majority of patients present with overt distant metastases. Systemic symptoms are common; ectopic hormonal secretion may occur. By light microscopy, GI SmCCs are essentially indistinguishable from primary pulmonary SmCC. The presence of non-SmCC components is common. Data from molecular analysis of the disease has identified some similarities to pulmonary SmCC. Chemotherapy represents the main treatment option, with modest impact on survival. In locoregional disease, the literature suggests that treatment be initiated using chemoradiotherapy and then, if metastatic disease is still excluded, surgical resection be considered. The disease is highly aggressive, and survival is in the range of several weeks for untreated patients and of 6 to 12 months for those receiving therapy.

Conclusion

SmCC of the GI tract is a rare and lethal disease. Although there are many similarities to pulmonary SmCC, some differences between the two entities are suggested. While chemotherapy can achieve significant palliation, surgery may have a potential impact on long-term survival of patients with locoregional disease.
Comparison of the Informed Consent Process for Randomized Clinical Trials in Pediatric and Adult Oncology
Authors: Simon Christian M. , Siminoff Laura A. , Kodish Eric D. , Burant Christopher
Published: June 2004

Purpose

To compare the informed consent processes for phase III pediatric and adult oncology clinical trials in view of the critical importance of human subjects protection in both pediatric and adult cancer care. Findings are discussed in terms of the opportunities for improving pediatric and adult oncology informed consent.

Patients and Methods

A total of 219 subjects are reported on. Adult oncology patients made up 36.1% (n = 79) of the sample. Pediatric surrogates made up the remaining 63.9% (n = 140). Subjects in both studies were observed and audiotaped in conversation with their oncologists, and interviewed afterwards. Comparisons between the adult and pediatric subjects were done using χ2 statistics and t tests.

Results

Differences between the pediatric and adult informed consent processes were found. Adult oncology decision makers were, on average, more fully informed and more actively engaged by their oncologists. Pediatric decision makers were, however, given more information about survival/cure, randomization, and voluntariness. Comprehension difficulties were more frequent among pediatric decision makers. Suggestions for improvement are made in view of the differences between adult and pediatric oncology research environments.

Conclusion

Ongoing efforts to improve the ethical framework of clinical cancer research need to take into account the key differences between pediatric and adult oncology informed consent. More research needs to be done to explore the differences between adult and pediatric informed consent processes in oncology.
Combined-Modality Therapy With Gemcitabine and Radiotherapy As a Bladder Preservation Strategy: Results of a Phase I Trial
Authors: Kent Elizabeth , Sandler Howard , Montie James , Lee Cheryl , Herman Joseph , Esper Peg , Fardig Judith , Smith David C.
Published: June 2004

Purpose

We conducted a phase I trial of gemcitabine given twice weekly with concurrent radiotherapy in patients with muscle-invasive bladder cancer.

Patients and Methods

Eligible patients underwent maximal transurethral resection of their bladder tumors followed by twice-weekly infusion of gemcitabine with 2 Gy/d concurrent radiotherapy to the bladder, for a total of 60 Gy over 6 weeks. The starting dose of gemcitabine was 10 mg/m2 with subsequent dose levels of 20, 27, 30, and 33 mg/m2. The primary end point was the determination of the maximum-tolerated dose (MTD) of twice weekly gemcitabine with concurrent radiotherapy. Secondary end points included assessment of toxicity associated with combined-modality therapy and initial assessment of the rate of bladder preservation.

Results

Twenty-four patients were enrolled and 23 were assessable for toxicity and response. No significant toxicity was demonstrated at the 10 or 20 mg/m2 twice-weekly doses. Dose-limiting toxicity (DLT) occurred in two of three patients treated at 33 mg/m2. Intermediate dose levels of 27 and 30 mg/m2 were then evaluated. The MTD of gemcitabine was 27 mg/m2. The DLT was systemic, manifested as an elevation in liver function tests, malaise, and edema. Fifteen of 23 patients (65%) are alive with bladders intact and no evidence of recurrent disease at a median follow-up of 43 months.

Conclusion

Twice-weekly gemcitabine with concurrent radiotherapy at 2 Gy/d to a total dose of 60 Gy is well-tolerated. The MTD of gemcitabine is 27 mg/m2. There is a high rate of bladder preservation in this selected group of patients.
Liposome-Encapsulated Doxorubicin in Combination With Standard Agents (cyclophosphamide, vincristine, prednisone) in Patients With Newly Diagnosed AIDS-Related Non-Hodgkin's Lymphoma: Results of Therapy and Correlates of Response
Authors: Levine Alexandra M. , Tulpule Anil , Espina Byron , Sherrod Andy , Boswell William D. , Lieberman Robert D. , Nathwani Bharat N. , Welles Lauri
Published: June 2004

Purpose

To evaluate the safety and efficacy of liposomal doxorubicin (Myocet; Medeus Pharma Ltd, Herts,UK) when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Secondary objectives were to assess the impact of HIV viral control on response and survival, and to correlate MDR-1 expression with outcome.

Patients and Methods

Liposomal doxorubicin at doses of 40, 50, 60, and 80 mg/m2 was given with fixed doses of cyclophosphamide, vincristine, and prednisone every 21 days. All patients received concurrent highly active antiretroviral therapy. NHL tissues were evaluated for multidrug resistance (MDR-1) expression.

Results

Twenty-four patients were accrued. 67% had high or high-intermediate International Prognostic Index scores; the median CD4 lymphocyte count was 112/mm3 (range, 19/mm3 to 791/mm3). No dose-limiting toxicities were observed at any level, with myelosuppression being the most frequent toxicity. Overall response rate was 88%, with 75% complete responses (CRs), and 13% partial responses. The median duration of CR was 15.6+ months (range, 1.7 to 43.5+ months). Effective HIV viral control during chemotherapy was associated with significantly improved survival (P = .027), but CRs were attained independent of HIV viral control. MDR-1 expression did not correlate with response, suggesting that the liposomal doxorubicin may evade this resistance mechanism.

Conclusion

Liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is active in AIDS-NHL, with complete remissions achieved in 75% independent of HIV viral control or tissue MDR-1 expression. HIV viral control is associated with a significant improvement in survival. Additional studies are warranted.
Colorectal Cancer Screening Knowledge, Attitudes, and Beliefs Among Veterans: Does Literacy Make a Difference?
Authors: Dolan Nancy C. , Ferreira M. Rosario , Davis Terry C. , Fitzgibbon Marian L. , Rademaker Alfred , Liu Dachao , Schmitt Brian P. , Gorby Nicolle , Wolf Michael , Bennett Charles L.
Published: June 2004

Purpose

To evaluate whether lower literacy is associated with poorer knowledge and more negative attitudes and beliefs toward colorectal cancer screening among veterans without recent colorectal cancer screening.

Patients and Methods

Three hundred seventy-seven male veterans, age 50 years and older, who had not undergone recent colorectal cancer screening, were surveyed about their knowledge, attitudes, and beliefs regarding colorectal cancer screening. Patients' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine, an individually administered screening test for reading.

Results

Thirty-six percent of the 377 men had an eighth grade literacy level or higher. Men with lower literacy were 3.5 times as likely not to have heard about colorectal cancer (8.8% v 2.5%; P = .006), 1.5 times as likely not to know about screening tests (58.4% v 40.9%; P = .0001), and were more likely to have negative attitudes about fecal occult blood testing (FOBT), but not about flexible sigmoidoscopy. Specifically, men with lower literacy skills were two times as likely to be worried that FOBT was messy (26.7% v 13.3%; P = .008), 1.5 times as likely to feel that FOBT was inconvenient (28.7% v 18%; P = .05), and four times as likely to state they would not use an FOBT kit even if their physician recommended it (17.9% v 4.0%; P = .02).

Conclusion

Limited literacy may be an overlooked barrier in colorectal cancer screening among veterans.
Outcomes of a Randomized Trial of Hyperfractionated Cranial Radiation Therapy for Treatment of High-Risk Acute Lymphoblastic Leukemia: Therapeutic Efficacy and Neurotoxicity
Authors: Waber Deborah P. , Silverman Lewis B. , Catania Lori , Mautz William , Rue Montse , Gelber Richard D. , Levy Donna E. , Goldwasser Meredith A. , Adams Heather , Dufresne Annie , Metzger Victoria , Romero Ivonne , Tarbell Nancy J. , Dalton Virginia Kimball , Sallan Stephen E.
Published: June 2004

Purpose

We evaluated 8-year survival and late neuropsychologic toxicity in children with acute lymphoblastic leukemia treated in a randomized clinical trial to test whether hyperfractionated (twice daily) cranial radiation therapy (CRT) can reduce incidence and severity of late toxicities associated with 18 Gy of CRT.

Patients and Methods

Between 1987 and 1995, 369 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for high-risk acute lymphoblastic leukemia were randomly assigned to conventionally fractionated CRT (CFX) or hyperfractionated CRT (HFX) to a total dose of 18 Gy. Neuropsychologic testing was completed for 125 of 287 children in continuous complete remission. Event-free and overall survival, as well as neuropsychologic function, were compared for the two arms of the protocol.

Results

Eight-year event-free survival (± SE) was 80% ± 3% for children randomly assigned to CFX and 72% ± 3% for HFX (P = .06). Overall survival was 85% ± 3% for CFX and 78% ± 3% for HFX (P = .06). CNS relapses occurred in 2.8% of patients receiving CFX and 2.7% receiving HFX (P = .99). Cognitive function for both groups was solidly in the average range, with no group differences in intelligence, academic achievement, visuospatial reasoning, or verbal learning. Children on the HFX arm exhibited a modest advantage for visual memory (P < .05).

Conclusion

HFX provides no benefit in terms of cognitive late effects and may compromise antileukemic efficacy. HFX should not be substituted for conventionally dosed CRT in children who require radiation therapy for treatment of acute lymphoblastic leukemia.
Docetaxel Versus Docetaxel Plus Cisplatin As Front-Line Treatment of Patients With Advanced Non—Small-Cell Lung Cancer: A Randomized, Multicenter Phase III Trial
Authors: Georgoulias Vassilis , Ardavanis Alexandros , Agelidou Athina , Agelidou Maria , Chandrinos Vassilis , Tsaroucha Emilia , Toumbis Michael , Kouroussis Charalambos , Syrigos Konstantinos , Polyzos Aristidis , Samaras Nikolaos , Papakotoulas Pavlos , Christofilakis Charalambos , Ziras Nicolaos , Alegakis Athanasios
Published: June 2004

Purpose

To compare the overall survival (OS) of patients with advanced non–small-cell lung cancer (NSCLC) treated with docetaxel plus cisplatin (DC) or docetaxel (D) alone.

Patients and Methods

Chemotherapy-naïve patients with advanced/metastatic NSCLC were randomly assigned to receive either DC (n = 167; docetaxel 100 mg/m2 on day 1, cisplatin 80 mg/m2 on day 2, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) 150 μg/m2/d on days 3 to 9) or D (n = 152; 100 mg/m2 on day 1 without rhG-CSF) every 3 weeks.

Results

The overall response rates were 36.5% for DC (three complete responses and 58 partial responses) and 21.7% for D (one complete response and 32 partial responses; P = .004). The median OS was 10.5 months (range, 0.5 to 41 months) and 8.0 months (range, 0.5 to 41 months) for DC and D, respectively (P = .200). The 1- and 2-year survival rates were 44% and 19% for DC and 43% and 15% for D, respectively. Median times to tumor progression were 4.0 and 2.5 months for DC and D, respectively (P = .580). Grade 2/3 anemia was significantly higher with DC than with D (33% v 16%; P = .0001). Fifteen (9%) DC and 12 (8%) D patients developed febrile neutropenia. Grade 3/4 nausea/vomiting (P = .0001), diarrhea (P = .007), neurotoxicity (P = .017), and nephroroxicity (P = .006) were significantly more common with DC than with D. There were five treatment-related deaths in the DC group and one in the D (P = .098).

Conclusion

DC regimen resulted in a higher response rate but without improvement in median time to tumor progession or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.
Tumor Karyotype Predicts Clinical Outcome in Colorectal Cancer Patients
Authors: Bardi Georgia , Fenger Claus , Johansson Bertil , Mitelman Felix , Heim Sverre
Published: June 2004

Purpose

To investigate the prognostic value of the overall karyotypic features and specific chromosome aberrations in colorectal cancer (CRC).

Patients and Methods

Cytogenetic features of 150 primary CRCs investigated at the time of surgery were correlated with patient survival by univariate and multivariate analyses, using classical clinicopathologic parameters as covariates.

Results

In univariate analysis, in addition to tumor grade and clinical stage, structural aberrations as well as rearrangements of chromosomes 8 and 16 were significantly correlated with shorter overall survival. Karyotypic complexity, rearrangements of chromosomes 8 and 16, and loss of chromosome 4 were significantly correlated with shorter disease-free survival. In multivariate analysis, in addition to tumor grade, the type of chromosome aberrations (structural or numerical), ploidy, and loss of chromosome 18 came across as independent prognostic factors in the group of all patients. In the subset of patients with stage I and II carcinomas, none of the clinicopathologic variables could independently predict patient survival, whereas the presence of structural chromosomal aberrations was the only independent predictor of poor prognosis. In the subset of patients with stage III carcinomas, the presence of structural changes of chromosome 8 was a stronger independent predictor of prognosis than was tumor grade.

Conclusion

Cytogenetic tumor features are valuable predictors of prognosis in CRC patients. The tumor karyotype should therefore be taken into account in the clinical management of patients with this disease, especially for patients having cancers of the early or intermediate stages I, II, and III.
Tree-Based Model for Breast Cancer Prognostication
Authors: Banerjee Mousumi , George Julie , Song Eun Young , Roy Anuradha , Hryniuk William
Published: June 2004

Purpose

To define prognostic groups for recurrence-free survival in breast cancer, assess relative effects of prognostic factors, and examine the influence of treatment variations on recurrence-free survival in patients with similar prognostic-factor profiles.

Patients and Methods

We analyzed 1,055 patients diagnosed with stage I-III breast cancer between 1990 and 1996. Variables studied included socioeconomic factors, tumor characteristics, concurrent medical conditions, and treatment. The primary end point was recurrence-free survival (RFS). Multivariable analyses were performed using recursive partitioning and Cox proportional hazards regression.

Results

The most significant difference in prognosis was between patients with fewer than four and those with at least four positive nodes (P < .0001). Four distinct prognostic groups (5-year RFS, 97%, 78%, 58%, and 27%) were developed, defined by the number of positive nodes, tumor size, progesterone receptor (PR) status, differentiation, race, and marital status. Patients with fewer than four positive nodes and tumor ≤ 2 cm, PR positive, and well or moderately differentiated had the best prognosis. RFS in this group was unaffected by type of adjuvant therapy (P = .38). Patients with at least four positive nodes and PR-negative tumors had the worst prognosis, and those treated with tamoxifen plus chemotherapy had the best outcome in this group (P = .0001). Among patients in the two intermediate-risk groups, those treated with tamoxifen or a combination of tamoxifen and chemotherapy had the best outcome.

Conclusion

Lymph node status, PR status, tumor size, differentiation, race, and marital status are valuable for prognostication in breast cancer. The prognostic groups derived can provide guidance for clinical trial design, patient management, and future treatment policy.
Cetuximab, a Monoclonal Antibody Targeting the Epidermal Growth Factor Receptor, in Combination With Gemcitabine for Advanced Pancreatic Cancer: A Multicenter Phase II Trial
Authors: Xiong Henry Q. , Rosenberg Arthur , LoBuglio Albert , Schmidt William , Wolff Robert A. , Deutsch John , Needle Michael , Abbruzzese James L.
Published: June 2004

Purpose

To determine the response rate, time to disease progression, survival duration and rate, and toxicity with the combination of cetuximab and gemcitabine in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer.

Patients and Methods

Patients with measurable locally advanced or metastatic pancreatic cancer who had never received chemotherapy for their advanced disease and had immunohistochemical evidence of EGFR expression were eligible for the multicenter phase II trial. Patients were treated with cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly for 7 weeks. Gemcitabine was administered at 1,000 mg/m2 for 7 weeks, followed by 1 week of rest. In subsequent cycles, cetuximab was administered weekly, and gemcitabine was administered weekly for 3 weeks every 4 weeks.

Results

Sixty-one patients were screened for EGFR expression, 58 patients (95%) had at least 1+ staining, and 41 were enrolled onto the trial. Five patients (12.2%) achieved a partial response, and 26 (63.4%) had stable disease. The median time to disease progression was 3.8 months, and the median overall survival duration was 7.1 months. One-year progression-free survival and overall survival rates were 12% and 31.7%, respectively. The most frequently reported grade 3 or 4 adverse events were neutropenia (39.0%), asthenia (22.0%), abdominal pain (22.0%), and thrombocytopenia (17.1%).

Conclusion

Cetuximab in combination with gemcitabine showed promising activity against advanced pancreatic cancer. Further clinical investigation is warranted.
Collaboration: The Social Context of Theory Development
Authors: Levine John M. , Moreland Richard L.
Published: June 2004

Collaboration plays a critical role in scientific creativity. This article draws on research involving small groups and interpersonal relationships to analyze the social processes underlying scientific collaboration. 3 stages of activity in collaborative groups are discussed: formation, performance, and dissolution. In regard to group formation, we consider the characteristics of the people who join, the conditions under which they come together and the socialization experiences they encounter In regard to group performance, we discuss idea generation, selection, and implementation, with special emphasis on how group composition (diversity) and group processes affect creativity. In regard to group dissolution, we discuss factors that lead members of collaborative groups to stop working together, including a reduced market for the group's creative products and conflict among members regarding group goals and the ownership of ideas. We next consider the role that intergroup processes play in scientific collaboration, discussing, for example, how such processes contribute to ingroup identification and increase competitive motivation. Finally, we conclude with some brief reflections on our own collaboration of some 20 years.
Dynamical Minimalism: Why Less is More in Psychology
Authors: Nowak Andrzej
Published: June 2004

The principle of parsimony, embraced in all areas of science, states that simple explanations are preferable to complex explanations in theory construction. Parsimony, however, can necessitate a trade-off with depth and richness in understanding. The approach of dynamical minimalism avoids this trade-off. The goal of this approach is to identify the simplest mechanisms and fewest variables capable of producing the phenomenon in question. A dynamical model in which change is produced by simple rules repetitively interacting with each other can exhibit unexpected and complex properties. It is thus possible to explain complex psychological and social phenomena with very simple models if these models are dynamic. In dynamical minimalist theories, then, the principle of parsimony can be followed without sacrificing depth in understanding. Computer simulations have proven especially useful for investigating the emergent properties of simple models.
Theory in Social Psychology: Seeing the Forest and the Trees
Authors: Trope Yaacov
Published: June 2004

The phenomena social psychology seeks to explain–how people think, feel, and act in response to social situations–are rich and diverse. Therefore, explanatory power, the simplicity of a model relative to its empirical scope, is an important desideratum for social psychological theories. A model achieves high explanatory power to the extent that it integrates narrower models within a unified conceptualization, reconciles conflicting findings, and makes novel predictions regarding specific phenomena. This article first relates explanatory power to the various facets of scientific inquiry (modeling, derivation, observation, evaluation, and decision) and then discusses this criterion as a guide for 2 theory-based lines of research my colleagues and I have conducted in the area of social judgment and decision making.
The Naive Epistemology of a Working Social Psychologist (Or the Working Epistemology of a Naive Social Psychologist): The Value Of Taking “Temporary Givens” Seriously
Authors: Zanna Mark P.
Published: June 2004

In this article I first describe the origin of 6 recent lines of inquiry. In describing these 6 case studies, I attempt to determine the inspirations for my ideas. I also attempt to determine (a) whether these specific inspirations (or, perhaps, strategies) have occurred in my past research and (b) whether, in conclusion, some general principle can begin to account for how I generate my ideas.
Taking the Social Origins of Human Nature Seriously: Toward a More Imperialist Social Psychology
Authors: Brewer Marilynn B.
Published: June 2004

To recognize that human beings are adapted for social living is fundamental to the science of human psychology. I argue that the development of broad social psychological theory would benefit from taking this basic premise more seriously. We need to pay more attention to the implications for personality and social psychology of recognizing that all of the building blocks of human psychology—cognition, emotion, motivation-have been shaped by the demands of social interdependence. In this article I illustrate the generative potential of this basic premise for development of more expansive social theory.
Common Sense, Intuition, and Theory in Personality and Social Psychology
Authors: Cacioppo John T.
Published: June 2004

Theoretical work in personality and social psychology benefits from a well-developed understanding of the prior empirical and theoretical work on a problem and from informed intuitions. Intuitions develop about a subject matter through years of study, investigation, and problem solving, just as chess masters develop a sophisticated set of cognitive structures that change the very appearance of the chess board. In part because the subject matter is so personal, students new to personality and social psychology arrive with many intuitions, prior beliefs, and naive theories about social processes and behavior based on unsystematic experiences and observations. These intuitions can hinder or foster theoretical progress. The role of mentors, critiques, and empirical tests in minimizing the deleterious effects of these entry biases is discussed. Refined scientific intuitions are also subject to error, however, so means of minimizing these errors are also discussed.
Tools, Toys, Truisms, and Theories: Some Thoughts on the Creative Cycle of Theory Formation
Authors: Fiedler Klaus
Published: June 2004

Theory creation underlies the basic laws of evolution, calling for both random variation (loosening) and critical selection processes (tightening). Theory construction requires support of both components. However, whereas psychology has created a refined methodology for the tightening stage, attempts to understand the loosening stage of the creative cycle are conspicuously missing. I propose that both aspects of the creative cycle of theory formation can be acquired and exercised playfully, through distinct loosening and tightening games. I outline the rules of these games and illustrate them with examples from contemporary research.
Mind the Gap: In Praise of Informal Sources of Formal Theory
Authors: Fiske Susan T.
Published: June 2004

Theory-making can be taught and learned. New theories aim to fill a gap in existing explanations. Although mathematical statements are privileged elsewhere, social psychology–s impactful theories tend to be verbal, perhaps because of the arbitrary scales of our variables. Good theories posit causal relations, attempt coherence, form a good narrative, aim for parsimony, are testable, prove fertile, and solve problems. Theories' sources can be intellectual, personal, group, or worldview. As long as the theory is stated logically, any source can be heuristic.
The Quest for the Gist: On Challenges of Going Abstract in Social and Personality Psychology
Authors: Kruglanski Arie W.
Published: June 2004

Abstraction and generalization constitute important aims of science (Kruglanski, 2001, in press), yet broad theorizing is rather rare in social and personality psychology. Some reasons for this state of affairs are examined, including the considerable staying power of insufficiently abstract theories and the broad resistance that abstract theories can incite. The trials and tribulations of abstract theorizing are considered, drawing on my own work on lay epistemics. Its problems and pitfalls notwithstanding, abstract theorizing is what our field needs more of if progress is to take place and social and personality psychology is to obtain the voice it merits in the general cultural dialogue about societal issues. To encourage such theorizing, 3 principles are offered, including the commonality focus (the horizontal voyage), the data focus (the vertical voyage), and the restructuration focus (the upstream voyage) principles.
A Role for Kisspeptins in the Regulation of Gonadotropin Secretion in the Mouse
Authors: Gottsch M. L. , Cunningham M. J. , Smith J. T. , Popa S. M. , Acohido B. V. , Crowley W. F. , Seminara S. , Clifton D. K. , Steiner R. A.
Published: June 2004

Kisspeptins are products of the KiSS-1 gene, which bind to a G protein-coupled receptor known as GPR54. Mutations or targeted disruptions in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice, suggesting that kisspeptin signaling may be important for the regulation of gonadotropin secretion. To examine the effects of kisspeptin-54 (metastin) and kisspeptin-10 (the biologically active C-terminal decapeptide) on gonadotropin secretion in the mouse, we administered the kisspeptins directly into the lateral cerebral ventricle of the brain and demonstrated that both peptides stimulate LH secretion. Further characterization of kisspeptin-54 demonstrated that it stimulated both LH and FSH secretion, at doses as low as 1 fmol; moreover, this effect was shown to be blocked by pretreatment with acyline, a potent GnRH antagonist. To learn more about the functional anatomy of kisspeptins, we mapped the distribution of KiSS-1 mRNA in the hypothalamus. We observed that KiSS-1 mRNA is expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. We conclude that kisspeptin-GPR54 signaling may be part of the hypothalamic circuitry that governs the hypothalamic secretion of GnRH.
Pharmacokinetic modulation of irinotecan metabolites by sulphobromophthalein in rats
Authors: Itoh Tatsuya , Itagaki Shirou , Sasaki Kentaro , Hirano Takeshi , Takemoto Isao , Iseki Ken
Published: June 2004

The purpose of this study was to modulate the pharmacokinetics of irinotecan metabolites, SN-38 and SN-38-glucuronide, by possibly reducing biliary excretion, which in turn could lower irinotecan toxicity. SN-38-glucuronide is associated with severe diarrhoea that occurs after irinotecan therapy as a result of enteric injury caused by SN-38. Sulphobromophthalein is used clinically as a drug for testing liver function and is considered to be a safe drug. We investigated the effect of sulphobromophthalein on the disposition of irinotecan metabolites after CPT-11 (7-ethyl-10-[10-4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin) administration. Wistar rats were administered CPT-11 (500 μg/body) in saline as a bolus injection into the femoral vein through a catheter. The volume of drug solution injected into each animal was 1 mL. Rats were either administered CPT-11 alone or simultaneously with sulphobromophthalein (20mg/body). After administration, blood and bile samples were taken at appropriate intervals and analysed by HPLC. Co-administration of sulphobromophthalein partially inhibited the biliary excretion of SN-38-glucuronide with a concomitant increase in its area under the plasma concentration-time curve (AUC) but did not significantly alter the biliary excretion and AUC of the active metabolite SN-38. These results suggested that cotreatment of CPT-11 with sulphobromophthalein might decrease intraluminal SN-38 concentrations without altering the pharmacokinetics of SN-38.
Aqueous solubilization of furosemide by supramolecular complexation with 4-sulphonic calix[n]arenes
Authors: Yang Wenzhan , de Villiers Melgardt M
Published: June 2004

The solubilization of the practically water insoluble drug furosemide by guest:host inclusion complexation with 4-sulphonic calix[n]arenes has been reported. The 4-sulphonic calix[n]arenes are water-soluble phenolic cyclooligomers that form inclusion complexes with neutral molecules. The solubility of furosemide in acidic (pH < 4) aqueous solutions containing increasing concentrations of the calixarenes was determined at 30°C and the concentration of furosemide in solution was determined by HPLC. Results showed that the molecular size of the 4-sulphonic calix[n]arenes and the concentration of the calix[n]arenes significantly influenced the increase in the solubility of furosemide. 4-Sulphonic calix[6]arene improved the solubility of furosemide the most (± 104%) followed by 4-sulphonic calix[8]-arene (±84–102%), while 4-sulphonic calix[4]arene increased the solubility of furosemide the least (±73–81%). The increase in furosemide solubility afforded by the calixarenes was most probably the result of the incorporation of the non-polar portions of the furosemide molecule into the non-polar cavities of the calixarenes similar to furosemide:cyclodextrin complexes. The driving force for this interaction was the reduction in the non-polar-water interfacial surface area when the furosemide (guest) molecules were inserted into the 4-sulphonic calix[n]arenes (host).
Development and application of a micro-capillary rheometer for in-vitro evaluation of parenteral injectability
Authors: Allahham A , Mainwaring D , Stewart P , Marriott J
Published: June 2004

A micro-capillary rheometer was developed to determine the rheology and injectability of parenteral formulations. The rheometer consisted of a micro-capillary and a glass syringe attached to an Instron that drove the syringe plunger at predetermined speeds and measured resulting forces on the plunger. The cross-head speed and the measured force were used to calculate the shear rate and the shear stress respectively, according to the Hagen-Poiseuille equation. The resulting rheograms of several Newtonian standards showed excellent linearity over a broad range of about 10 times 103 to 160 times 103 s−1 and produced accurate and reproducible viscosity determinations over the viscosity range of about 10 times 10−3 to 100 times 10−3 Pa.s. The developed methodology focussed primarily on the minimization of errors associated with the determination of the wall frictional force using both direct measurement and linear regression to determine this parameter from the data. The effect of micro-capillary diameter, syringe cross-sectional area and micro-capillary length was explored in an effort to increase the measured force so that wall frictional force errors could be minimized. The micro-capillary rheometer gave reproducible and accurate rheograms over a range of shear rates consistent with the shear rate range used in clinical practice, and showed that Newtonian and non-Newtonian rheological behaviours could be evaluated quantitatively.