bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Protein Kinase C: New Therapeutic Opportunities Against High-Grade Malignant Gliomas?
Authors: da Rocha A. B. , Mans D.R.A. , Regner A. , Schwartsmann G. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader should be able to:
Understand protein kinase C (PKC) in signal transduction pathways. Understand protein kinase C (PKC) in tumor cell proliferation and invasion Understand protein kinase C as a potential target in experimental therapies for malignant gliomas.
Access CME test online and receive one hour category 1 credit at CME.TheOncologist.com
A large body of evidence suggests that the abnormal phenotype of neoplastic astrocytes, including their excessive proliferation rate and high propensity to invade surrounding tissues, results from mutations in critical genes involved in key cellular events. These genetic alterations can affect cell-surface-associated receptors, elements of signaling pathways, or components of the cell cycle clock, conferring a gain or a loss of relevant metabolic functions of the cells. The understanding of such phenomena may allow the development of more efficacious forms of cancer treatment. Examples are therapies specifically directed against overexpressed epidermal growth factor receptor, hyperactive Ras, excessively stimulated Raf-1, overproduced ornithine decarboxylase, or aberrantly activated cyclin-dependent kinases. The applicability of some of these approaches is now being assessed in patients suffering from primary malignant central nervous system tumors that are not amenable to current therapeutic modalities. Another potentially useful therapeutic strategy against such tumors involves the inhibition of hyperactive or overexpressed protein kinase C (PKC). This strategy is justified by the decrease in cell proliferation and invasion following inhibition of the activity of this enzyme observed in preclinical glioma models. Thus, interference with PKC activity may represent a novel form of experimental cancer treatment that may simultaneously restrain the hyperproliferative state and the invasive capacity of high-grade malignant gliomas without inducing the expected toxicity of classical cytotoxic agents. Of note, the experimental use of PKC-inhibiting agents in patients with refractory high-grade malignant gliomas has indeed led to some clinical responses. The present paper reviews the current status of the biochemistry and molecular biology of PKC, as well as the possibilities for developing novel anti-PKC-based therapies for central nervous system malignancies.
Localized Adenocarcinoma of the Pancreas: The Rationale for Preoperative Chemoradiation
Authors: Wayne Jeffrey D. , Abdalla Eddie K. , Wolff Robert A. , Crane Christopher H. , Pisters Peter W.T. , Evans Douglas B. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader should be able to:
Define the radiologic (CT) criteria that determine whether a pancreatic neoplasm is surgically resectable, locally advanced, or metastatic. Explain why it is difficult to conduct clinical trials of adjuvant or neoadjuvant therapy in resectable pancreatic cancer. Review the advantages and disadvantages of preoperative versus postoperative adjuvant therapy for patients with pancratic adenocarcinoma.
Access CME test online and receive one hour category 1 credit at CME.TheOncologist.com
Pancreatic adenocarcinoma is the fifth leading cause of cancer-related death in the U.S. In spite of advancements in surgical treatment, nearly 80% of patients thought to have localized pancreatic cancer die of recurrent or metastatic disease when treated with surgery alone. Therefore, efforts to alter the patterns of recurrence and improve survival for patients with pancreatic cancer currently focus on the delivery of systemic therapy and irradiation before or after surgery. Postoperative adjuvant therapy appears to improve median survival. However, more than one-fourth of patients do not complete planned adjuvant therapy due to surgical complications or a delay in postoperative recovery of performance status. Utilizing a preoperative (neoadjuvant) approach, overall treatment time is reduced, a greater proportion of patients receive all components of therapy, and patients with rapidly progressive disease are spared the side effects of surgery as metastatic disease may be found at restaging following chemoradiation (prior to surgery).
This paper examines the factors pertinent to clinical trial design for resectable pancreatic cancer, and carefully reviews the existing data supporting adjuvant and neoadjuvant therapy for potentially resectable disease.
Adenoviral Gene Therapy
Authors: Vorburger Stephan A. , Hunt Kelly K. 
Published: August 2004

AbstractLearning ObjectivesAfter completing this course, the reader should be able to:Understand the advantages and disadvantages of recombinant adenoviral vectors for gene delivery.Review the current biological strategies employed in clinical trials utilizing adenoviral mediated gene therapy for cancer.Understand modifications that may improve the utility of adenoviral vectors for gene therapy approaches.Access CME test online and receive one hour category 1 credit at CME.TheOncologist.comAs of May 2001, 532 gene therapy protocols had been approved for evaluation in clinical trials; however, only five of those had been evaluated in phase III clinical trials. Among the most commonly used vectors for the delivery of genetic material into human cells are the adenoviruses. Remarkable progress has been made with these vectors in the last decade, but some shortcomings continue to challenge investigators. The newly acquired knowledge of the adenoviral life cycle and the positive outcomes from phase II clinical trials have led to the application of vectors engineered to selectively target tumor tissue under controlled promoters.
The Cardiotoxic Potential of the 5-HT3 Receptor Antagonist Antiemetics: Is There Cause for Concern?
Authors: Keefe Deborah L. 
Published: August 2004

Abstract
Purpose. To review and evaluate the potential cardiac effects of 5-HT3 antiemetic treatment in patients who may be predisposed to cardiac complications resulting from malignancy, cytotoxic oncologic regimens, or preexisting comorbid conditions.
Design. A literature review was conducted on the negative cardiovascular effects of chemotherapeutic agents, and, more specifically, on the cardiac interactions of the 5-HT3 receptor antagonists commonly used to treat chemotherapy-induced nausea and vomiting.
Results. Clinical studies in healthy subjects have reported electrocardiograph changes following administration of 5-HT3 receptor antagonists. However, there are limited data on the use of 5-HT3 antiemetics when administered with cardiotoxic chemotherapy. Nonetheless, the development of significant electrocardiograph changes with some agents may indicate a potential for significant cardiac effects in patients, particularly those who may be predisposed to cardiac complication.
Conclusions. As the predicted human life span increases, clinicians will be treating a larger, older oncology population. Because two of the most common major comorbidities are cardiovascular related, we need to be acutely aware of the toxic effects of chemotherapy, as well as the possible cardiac interaction of supportive agents, specifically the 5-HT3 antiemetics. Until more data are made available, the best antiemetic option for patients receiving emetogenic and cardiotoxic chemotherapy may be the agent with the fewest apparent cardiac effects.
Development of the Proteasome Inhibitor PS-341
Authors: Adams Julian 
Published: August 2004

Abstract
Over the last decade, the critical role of the proteasome in cell-cycle regulation has become increasingly apparent. The proteasome, a multicatalytic protease present in all eukaryotic cells, is the primary component of the protein degradation pathway of the cell. By degrading regulatory proteins (or their inhibitors), the proteasome serves as a central conduit for many cellular regulatory signals and, thus, is a novel target for therapeutic drugs. PS-341 is a small molecule that is a potent and selective inhibitor of the proteasome. In vitro and mouse xenograft studies of PS-341 have shown antitumor activity in a variety of tumor types, including myeloma, chronic lymphocytic leukemia, prostate cancer, pancreatic cancer, and colon cancer, among others. Although PS-341 rapidly leaves the vascular compartment, a novel pharmacodynamic assay has shown that inhibition of proteasome—the biologic target—is dose dependent and reversible. These studies provided the rationale for a twice-weekly dosing schedule employed in ongoing clinical studies. Phase I trials in a variety of tumor types have shown PS-341 to be well tolerated, and phase II trials in several hematologic malignancies and solid tumor types are now in progress. Efficacy and safety data from the most advanced of these, a phase II multicenter trial in myeloma, will be available in early 2002.
Comparable Efficacy of Epoetin Alfa for Anemic Cancer Patients Receiving Platinum- and Nonplatinum-Based Chemotherapy: A Retrospective Subanalysis of Two Large, Community-Based Trials
Authors: Glaspy John , Degos Laurent , Dicato Mario , Demetri George D. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Understand the etiology, symptoms, and impact (as reported by patients) of cancer- and chemotherapy-associated anemia. Recognize the clinical evidence supporting the efficacy of epoetin alfa in reducing transfusion requirements, increasing hemoglobin levels, and improving quality-of-life in anemic cancer patients receiving platinum- versus nonplatinum-based chemotherapy. Identify potential prognostic factors for responsiveness to epoetin alfa.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Background. Data from two large, community-based clinical trials that evaluated the efficacy of epoetin alfa in anemic cancer patients receiving chemotherapy were retrospectively analyzed to determine if clinical outcomes were different depending on whether chemotherapy was platinum- or nonplatinum-based.
Patients and Methods. Patients received epoetin alfa 150-300 IU/kg (Glaspy: Study 1; n = 2,342) or 10,000-20,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each week for 4 months. Efficacy end points were changes in transfusion requirements, hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712 patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both received chemotherapy and had available data, were eligible for this retrospective analysis.
Results. Baseline characteristics across groups were comparable with few exceptions, which were anticipated in view of the characteristics of the two different chemotherapy types. Decreases in transfusion requirements after 2, 3, and 4 months were significant, regardless of chemotherapy type. Mean increases in Hb level from baseline to final evaluation ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant, regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy type, and improvements were associated with increases in Hb. Epoetin alfa was well tolerated in both studies, regardless of chemotherapy type.
Conclusion. Treatment of anemic cancer patients with epoetin alfa results in significant reduction in transfusion requirements, increase in Hb levels, and improvements in QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based.
The Effect of Nonmalignant Systemic Disease on Tolerance to Radiation Therapy
Authors: Chon Brian H. , Loeffler Jay S. 
Published: August 2004

Abstract
Purpose. Some patients with nonmalignant systemic diseases, like collagen vascular disease (CVD), hypertension, diabetes mellitus, and inflammatory bowel disease (IBD), tolerate radiation therapy poorly. Although the mechanisms of each of these disease processes are different, they share a common microvessel pathology that is potentially exacerbated by radiotherapy. This article reviews and evaluates available data examining the effects of these benign disease processes on radiation tolerance.
Methods. We conducted a thorough review of the Anglo-American medical literature from 1960 to 2001 on the effects of radiotherapy on CVD, hypertension, diabetes mellitus, and IBD.
Results. Fifteen studies were identified that examined the effects of radiation therapy for cancer in patients with CVDs. Thirteen of 15 studies documented greater occurrences of acute and late toxicities (range 7%-100%). Higher rates of complications were noted especially for nonrheumatoid arthritis CVDs. Nine studies evaluated the effects of hypertension and diabetes on radiation tolerance. All nine studies documented higher rates of late toxicities than in a “control” group (range 34%-100%). When patients had both diabetes and hypertension, the risk of late toxicities was even higher. Six studies examined radiation tolerance of patients with IBD irradiated to the abdomen and pelvis. Five of these six studies showed greater occurrences of acute and late toxicities for patients with IBD, even with precautionary measures like reduced fraction size and volume and patient immobilization (13%-29%).
Conclusion. The majority of published studies documented lower radiation tolerance for patients who have CVD, diabetes mellitus, hypertension, and IBD. This may reflect a publication bias, as the majority of these studies are retrospective with small numbers of patients and use different scoring scales for complications. These factors may contribute to an overestimation of true radiation-induced morbidity. Although the paucity of data makes precise estimates difficult, a subset of patients, in particular, those with active CVD, IBD, or a combination of uncontrolled hypertension with type I diabetes, is likely to be at higher risk. Future prospective trials need to document these disease entities when reporting treatment-related complications and also must monitor toxicities associated with quiescent versus active IBD and CVD, type I versus type II diabetes, and levels of hypertension (controlled versus uncontrolled) matched for radiation-specific treatment sites, field size, fractionation, and total dose.
Osteogenic Sarcoma Presenting with Lung Metastasis
Authors: Staddon Arthur P. , Lackman Richard , Robinson Keith , Shrager Joseph B. , Warhol Michael 
Published: August 2004

AbstractLearning ObjectivesAfter completing this course, the reader will be able to:Understand the multimodality treatments needed for the best outcome in patients with osteogenic sarcoma. Understand the selection criteria for resecting pulmonary metastases. Identify the appropriate work-up and follow-up of patients with osteogenic sarcoma.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.comA patient with osteogenic sarcoma presenting with lung metastases is discussed with attention to appropriate diagnosis, staging, and treatment. Multimodality treatment options using chemotherapy, orthopedic surgery and thoracic surgery are presented. Physical medicine and rehabilitation evaluation and treatment are included. Current research options are discussed.
Between Parent and Child: Negotiating Cancer Treatment in Adolescents
Authors: Penson Richard T. , Rauch Paula K. , McAfee Steve L. , Cashavelly Barbara J. , Clair-Hayes Kathy , Dahlin Constance , Green Kara M. , Chabner Bruce A. , Lynch Thomas J. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Understand the epidemiology and paradigms of care for adolescents with cancer. Understand the impact of cancer on patient, family, and health care team. Identify appropriate responses to different developmental stages and preferences in style of care. Foster compassionate care.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit in Risk Management at CME.TheOncologist.com
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.
Cancer in adolescents presents an extra dynamic of psychosocial complexity. The case of a 19-year-old woman with acute myelocytic leukemia is discussed. Her disease was refractory to allogeneic transplantation, and she died with severe graft-versus-host disease. Ms. P and her mother established very different relationships with the team which supported them through the transitions in her care, and Ms. P was able to die at home, with hospice care. The personal connection with the team enabled a degree of positive adjustment through the nightmare of loss. The epidemiology of cancer in adolescents and paradigms of care are reviewed. Psychosocial aspects of adolescence, opportunities for personal growth and support, and the challenge of end-of-life care are discussed.
Interpreting Measures of Treatment Effect in Cancer Clinical Trials
Authors: Case L. Douglas , Kimmick Gretchen , Paskett Electra D. , Lohman Kurt , Tucker Robert 
Published: August 2004

AbstractThe efficacy of a new cancer regimen is usually assessed by analyzing outcomes such as tumor response and overall survival. Many publications summarizing results of cancer clinical trials report measures such as odds ratios and hazard ratios, as these are the estimators of treatment effect obtained from regression models used to analyze the data. However, these measures are sometimes misinterpreted, as they are not necessarily familiar to many readers. The most common mistake is to interpret both measures as relative risks, an interpretation that can lead to an incorrect impression of the impact of the treatment on response and survival.
Carcinoma of the Anus: Strategies in Management
Authors: Esiashvili Natia , Landry Jerome , Matthews Richard H. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:Appreciate the evolution of methods of managing anal carcinomas and appropriate selection of modalities to employ in various situations at the present time.Understand methods of integrating chemotherapy and radiation to achieve desirable outcomes.Understand considerations in choice of chemotherapy agents and radiation doses.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
The management of anal cancer underwent an interesting transformation over the last two decades. Prior to this period, the standard definitive treatment for carcinoma of the anal canal was abdominal-perineal resection, which necessitated a permanent colostomy. The organ preservation concept appeared following the discovery of a high complete response rate from preoperative combined chemoradiation prior to abdominal-perineal resection.
The organ preservation method of treatment rapidly gained popularity and ultimately saved a large number of patients from undergoing abdominal-perineal resection and colostomy. Chemoradiation treatment itself subsequently went through an evolutionary process. Several studies have sought to define the optimal chemotherapeutic regimen as well as radiation treatment dose and fractionation. Ongoing studies attempt to define an optimal treatment regimen that yields a higher cure rate while minimizing toxicity. We review the etiology, epidemiology, and treatment regimens for anal cancer.
Assessing a Decade of Progress in Cancer Control
Authors: Andersen LeAnn D. , Remington Patrick , Trentham-Dietz Amy , Reeves Mathew 
Published: August 2004

Abstract
The age-adjusted death rate from cancer peaked in the U.S. in 1990, and has declined steadily since then. We assess reasons for this progress by examining trends in cancer mortality by age, gender, and cause, using underlying cause mortality data from the Centers for Disease Control. Mortality rates for 2000 were estimated using models based on 1979 through 1997 mortality data. Indirect standardization was used to calculate the expected number of cancer deaths in 2000, by age, gender, and cause, assuming that the rates in 1990 had not changed. In the U.S. in 2000, there were an estimated 500,000 deaths from cancer; 64,000 (12.7%) fewer than expected, with 51,900 fewer cancer deaths among men and 12,200 fewer deaths among women. The decline in deaths among men resulted from fewer deaths from lung cancer (20,800), colon cancer (6,700), and prostate cancer (12,900). The decline in deaths among women resulted from fewer deaths from breast cancer (11,100) and colon cancer (4,200), but there were more deaths from lung cancer (6,500). Among women over the age of 75, 5,000 more died of cancer than expected. Declines in lung, prostate, and colon cancer deaths among men and breast and colon cancer among women account for 86% of the recent decline in cancer deaths over the past decade.
A Phase II Study of Intravenous Navelbine and Doxorubicin Combination in Previously Untreated Advanced Breast Carcinoma
Authors: Pawlicki M. , Rolski J. , Zaluski J. , Siedlecki P. , Ramlau C. , Tomzak P. 
Published: August 2004

Abstract
Purpose. The combination of vinorelbine and doxorubicin, two very active drugs in metastatic breast cancer, has demonstrated impressive results in terms of efficacy, at the price of cardiac toxicity (10% grades 2-4) due to the cumulative dose of doxorubicin delivered. This study was designed to divide the dose of doxorubicin into two administrations (day 1 and 8) in order to reduce the toxicity profile, while keeping the same level of efficacy.
Patients and Methods. Thirty-eight chemotherapy-naïve metastatic breast cancer patients entered into the study and were treated with vinorelbine, 25 mg/m2, and doxorubicin, 25 mg/m2, both on days 1 and 8, every 3 weeks. Thirty-seven patients were evaluable for efficacy and 38 for tolerance; 71% of the patients presented with visceral metastases.
Results. Patients received a median of seven cycles and 94.9% of the intended dose intensity of both drugs. Grade 3-4 neutropenia was reported in 10% of cycles. Alopecia was reported in 89.5% of the patients, and grade 2 nausea/vomiting in 9.3% of the cycles. Grade 1-2 cardiac toxicity was noted in 23.7% of the patients. The objective response rate of the patients was 78.4% (nearly 81% for patients with visceral metastases); the median duration of response was 11.6 months, the median survival 21.6 months, and the 1-year survival 75.2%.
Conclusion. This schedule of vinorelbine/doxorubicin represents an active and well-tolerated combination.