bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexuality and Cancer: Conversation Comfort Zone
Authors: Penson Richard T. , Gallagher Joan , Gioiella Marie Elena , Wallace Maria , Borden Karen , Duska Linda A. , Talcott James A. , McGovern Frank J. , Appleman Leonard J. , Chabner Bruce A. , Lynch Thomas J. 
Published: August 2004

AbstractShortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages 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.Psychosocial issues profoundly affect patients with cancer. Of the many complexities that make up the psychosocial dynamic, perhaps the medical profession is most uncomfortable with sexuality. Many elements of sexual behavior remain high-profile taboos. A number of diseases and treatments significantly affect sexual function. Male and female sexuality were discussed in two separate rounds with an emphasis on how to begin a dialogue about sexuality without jeopardizing other aspects of the relationship with patients. Three cases were presented. A patient with prostate cancer considering treatment options for early-stage disease and two patients with gynecologic malignancies; one with a colostomy following cytoreductive surgery for ovarian cancer and the other with a failed vaginal reconstruction for recurrent squamous cell carcinoma of the vagina. Staff discussed the wide diversity of response to sexual dysfunction and the difficulties that patients face. A sensitive and informed approach to discussing sexuality can provide effective support. The elements of successful dialogue are presented in the PLISSIT model.
Molecular Abnormalities in Chronic Myeloid Leukemia: Deregulation of Cell Growth and Apoptosis
Authors: Di Bacco Alessandra , Keeshan Karen , McKenna Sharon L. , Cotter Thomas G. 
Published: August 2004

AbstractChronic myeloid leukemia (CML) is a disease of the hematopoietic system, characterized by the presence of the Bcr-Abl oncoprotein. The main characteristics of this disease include adhesion independence, growth factor independence, and resistance to apoptosis. Loss or mutation of the tumor suppressor gene, p53, is one of the most frequent secondary mutations in CML blast crisis. The transition between chronic phase and blast crisis is associated with increased resistance to apoptosis correlating with poor prognosis. This review focuses on the involvement of these two oncoproteins in the development and progression of the apoptotic-resistant phenotype in CML.
Current Status of Isolated Hepatic Perfusion With or Without Tumor Necrosis Factor for the Treatment of Unresectable Cancers Confined to Liver
Authors: Alexander H. Richard , Bartlett David L. , Libutti Steven K. 
Published: August 2004

Abstract
Metastatic or primary unresectable cancers confined to the liver are the sole or life-limiting component of disease for many patients with colorectal cancer, ocular melanoma, neuroendocrine tumors or primary colangio- or hepatocellular carcinomas. A number of regional treatment strategies including infusional chemotherapy and local ablative therapy are under clinical development and attest to the difficulty in adequately treating this condition. Isolated hepatic perfusion (IHP) was first clinically applied over 40 years ago, but because of its technical complexity, the attendant potential morbidity, and the lack of documented efficacy, it has not gained widespread application. In light of the remarkable antitumor activity with isolated limb perfusion with tumor necrosis factor (TNF) and melphalan in patients with unresectable extremity sarcoma or in transit melanoma, this regimen has been administered via IHP at several centers worldwide for unresectable liver cancers. IHP with TNF and melphalan can result in significant regression of advanced refractory cancers confined to the liver and, with additional clinical development, will most likely be a more routinely considered option for patients with this condition.
Nonmyeloablative Allogeneic Stem Cell Transplantation: Early Promise and Limitations
Authors: McCarthy Nicole J. , Bishop Michael R. 
Published: August 2004

Abstract
Allogeneic stem cell transplantation is used to treat a variety of malignant and nonmalignant hematologic diseases. Conventionally, high-dose chemoradiotherapy-based preparative regimens were considered essential both for tumor eradication and facilitation of donor stem cell engraftment. It is now apparent that an immune-mediated graft-versus-tumor effect has a pivotal role in the curative potential of allogeneic stem cell transplantation. This has prompted the development of less toxic, nonmyeloablative but profoundly immunosuppressive preparative regimens, often fludarabine- or radiation-based. Full donor engraftment can be achieved; however, a significant number of patients achieve a mixed chimeric state. Mixed hematopoietic chimerism provides a platform for the use of adoptive immunotherapy using donor lymphocyte infusions to maximize the immune-mediated antitumor effect, but the optimal usage has yet to be determined. Immediate procedure-related mortality with nonmyeloablative regimens has been low, but graft-versus-host disease remains a major clinical concern and treatment challenge. Major tumor responses have been seen in many hematologic malignancies primarily including patients with highly chemorefractory disease. Follow-up data have been short and additional time is needed to determine the efficacy and toxicities of this immunotherapy. This approach has potential for widespread clinical application including HLA mismatched and matched unrelated donor transplantation, exploration of a graft-versus-solid tumor effect, and correction of phenotypic expression in nonmalignant disorders.
Uncovering Functionally Relevant Signaling Pathways Using Microarray-Based Expression Profiling
Authors: Harkin D. Paul 
Published: August 2004

Abstract
The introduction of microarray technology to the scientific and medical communities has fundamentally altered the way in which we now address basic biomedical questions. Microarrays technology facilitates a more complete and inclusive experimental approach where alterations in the transcript level of entire genomes can be simultaneously assayed in response to a variety of stimuli. Conceptually different approaches to the development of microarray technology have resulted in the generation of two different array formats: oligonucleotide arrays and cDNA arrays.
The application of microarray and related technologies to identify specific targets of defined genes that have clearly been implicated in cancer progression requires a specific experimental approach. The objective of this approach is to define changes in transcriptional profile that occur in response to modulating the expression level of the gene to be studied. The resulting altered expression profile can then be viewed as a blueprint by which that gene effects its cellular function.
We have used oligonucleotide array-based expression profiling in collaboration with Affymetrix to identify downstream transcriptional targets of the BRCA1 tumor-suppressor gene as a means of defining its function. BRCA1 has been implicated in at least three functional pathways, namely, mediating the cellular response to DNA damage, as a cell cycle checkpoint protein and in the regulation of transcription. The physiological significance of these properties and their implications for the function of BRCA1 as a tumor-suppressor gene remain to be defined.
The Role of Capecitabine, an Oral, Enzymatically Activated Fluoropyrimidine, in the Treatment of Metastatic Breast Cancer
Authors: Blum Joanne L. 
Published: August 2004

Abstract
Capecitabine is an oral fluoropyrimidine that mimics continuous infusion 5-fluorouracil and generates 5-fluorouracil preferentially at the tumor site. It is activated via a three-step enzymatic pathway, the final step of which requires thymidine phosphorylase, an enzyme that is significantly more active in tumor than normal tissue. As an oral agent, capecitabine is more convenient for patients and medical personnel, and avoids the complications associated with venous access. This paper reviews the development and clinical experience of capecitabine in breast cancer treatment. Clinical trials have established the efficacy and tolerability of capecitabine in anthracycline- and taxane-pretreated metastatic breast cancer, showing that capecitabine is an effective therapy for patients who have exhausted all established treatment options. Moreover, randomized, phase II studies have demonstrated that capecitabine is effective in anthracycline-pretreated patients and as first-line therapy for metastatic breast cancer. In addition to its confirmed efficacy, the favorable safety profile of capecitabine, particularly the low myelosuppression rate, makes it an attractive agent for incorporation into combination regimens. Therefore numerous trials have assessed the feasibility of capecitabine-containing regimens, and have shown promising results. Capecitabine is an important new treatment option for breast cancer patients, and ongoing clinical trials should further define its role in a range of settings.
Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy
Authors: Briasoulis Evangelos , Pavlidis Nicholas 
Published: August 2004

AbstractNoncardiogenic pulmonary edema (NCPE) is a rare and less well-recognizable pulmonotoxic syndrome of anticancer therapy than pneumonitis/fibrosis. NCPE is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, and no evidence of left atrial hypertension/congestive heart failure. The diagnosis of drug-related NCPE relies upon documented exclusion of any infectious, metabolic, or cancer-related causes. The time proximity to therapy with drugs that are known to precipitate NCPE, any preceding episodes of flu-like symptoms during previous chemotherapy courses and possible response to corticosteroids may further support such a diagnosis. Cancer therapeutic agents clearly associated with NCPE are cytarabine, gemcitabine, and interleukin-2, as well as all-trans retinoic acid in acute promyelocytic leukemia patients, while a few other compounds have rarely or occasionally been implicated. The pathophysiology of lung injury in drug-induced NCPE remains unclear. There are indications suggesting that both a direct cytotoxic insult to the lung epithelial cells and induction of a cytokine-triggered inflammatory response may be involved in its pathogenesis. By distinction to drug-induced pulmonary pneumonitis that may lead to permanent pulmonary fibrosis, NCPE if not fatal, can be reversed upon prompt recognition, following immediate discontinuation of the offensive drug and start of intensive supportive treatment and intravenous corticosteroids.
Activity and Safety of Vinorelbine Combined with Doxorubicin or Fluorouracil as First-Line Therapy in Advanced Breast Cancer: A Stratified Phase II Study
Authors: Hochster Howard S. , Vogel Charles L. , Burman Susan L. , White Robin 
Published: August 2004

Abstract
Purpose. To evaluate the efficacy and safety of vinorelbine combined with doxorubicin or continuous infusion of fluorouracil as initial therapy for advanced breast cancer.
Subjects and Methods. A total of 118 women who had not received chemotherapy for advanced breast cancer were enrolled and included in the intent-to-treat analysis. Subjects were stratified into two treatment groups. If subjects were candidates for anthracycline therapy, they received doxorubicin 50 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 (n = 62). If subjects had received adjuvant anthracycline therapy or had cardiac disease, they received fluorouracil 750 mg/m2/day by continuous infusion on days 1 through 5 and vinorelbine 30 mg/m2 on days 1 and 5 (n = 56). The regimens were repeated every 21 days until evidence of progression of disease or severe toxicity.
Results. For doxorubicin and vinorelbine, the objective response rate was 55% (95% confidence interval [CI]: 42% to 68%), median time to disease progression was 34 weeks, median time to treatment failure was 32 weeks, and median survival was 92 weeks (95% CI: 72 to 128 weeks). For fluorouracil and vinorelbine, the objective response rate was 45% (95% CI: 31% to 59%), median time to disease progression was 32 weeks, median time to treatment failure was 30 weeks, and median survival was 53 weeks (95% CI: 47 to 64 weeks). The most common adverse event was grade 3 or 4 granulocytopenia, which occurred in 95% of subjects in the doxorubicin-vinorelbine group and in 88% of those in the fluorouracil-vinorelbine group. The most common nonhematologic adverse event was grade 3 or 4 stomatitis, which occurred in 9% and 32% of subjects in the two groups, respectively.
Conclusion. Both vinorelbine-containing regimens appear to offer useful options as initial therapy for advanced breast cancer. Both regimens were active, and any efficacy differences between the two may have been related to differences in prognosis for the anthracycline-pretreated group (i.e., selection for prior aggressive adjuvant therapy) and or comorbid cardiac conditions. Both regimens were associated with predictable but manageable toxicity, but a lower dose of fluorouracil (e.g., 600 mg/m2/day) should be used to reduce the risk of stomatitis.
Activity of Infusional Etoposide, Vincristine, and Doxorubicin with Bolus Cyclophosphamide (EPOCH) in Relapsed Hodgkin's Disease
Authors: Stokoe Christopher T. , Ogden Julie , Jain Vinay K. 
Published: August 2004

Abstract
Introduction. A phase II study of EPOCH chemotherapy in relapsed Hodgkin's disease was performed in 14 patients in a multicenter community setting.
Patients and Methods. A total of 14 patients (9 males and 5 females) were included in the study. Ages ranged from 21-72 with a median age of 33. Eleven out of 14 patients had advanced (stage III or IV) disease, but all patients had good performance status. All 14 patients had received prior chemotherapy with ABVD, MOPP, or MOPP/ABVD hybrid.
Results. A total of 57 cycles of EPOCH were administered during this trial. Patients received a median of four cycles of chemotherapy. An overall response rate of 86% was seen among the 14 patients with one patient achieving a complete response. Following EPOCH chemotherapy, 7 of 12 patients who responded underwent high-dose chemotherapy with stem cell support. Six out of 14 patients are currently alive, and three had no evidence of disease at the time of last follow-up. Toxicity with EPOCH chemotherapy consisted mainly of myelosuppression, and most patients were managed on an outpatient basis.
Conclusion. This multicenter community study confirms the activity of EPOCH chemotherapy in the treatment of patients with relapsed Hodgkin's disease.
Broadcast Quality Teleconferencing for Oncology
Authors: McAleer James J.A. , O'Loan Desmond , Hollywood Donal P. 
Published: August 2004

Abstract
The National Cancer Institute (NCI) in Bethesda, Maryland has developed a broadcast-quality teleconferencing system known as the Telesynergy™ system to address the need to convey expert information between larger cancer centers and their remote counterparts. This system is available to “Partnerships in Science Program” partners across the U.S. Recently, it has been made available in Ireland under a “Memorandum of Understanding” among the Department of Health and Children of Ireland, the Department of Health and Social Services in Northern Ireland, and the NCI. The Telesynergy system is capable of transmitting not only broadcast-quality teleconferencing among several different sources, but also diagnostic-quality radiology and pathology images. Remote operated microscopes and video cameras allow biopsy specimens to be discussed and manipulated from several different locations. Smear preparations of blood, bone marrow, and other cytological specimens can be examined in detail by a remote operator. The system can also transmit conventional x-ray images and paper documents. The Telesynergy system ensures that each patient, regardless of location, will receive an expert assessment and be given optimal therapy. While the system is currently being developed in Ireland for use in oncology, it is hoped that other specialties can benefit from it in the future.
Contemporary Perspectives in Tobacco Cessation: What Oncologists Need to Know
Authors: Carter Cindy L. , Key Janice , Marsh Linda , Graves Kristi 
Published: August 2004

Abstract
Within the last 5 years there has been a large outgrowth of smoking cessation research, largely encouraged by the release of the 1996 Clinical Practice Guidelines for Treating Tobacco Use and Dependence. These federal guidelines published by the Agency for Healthcare Policy and Research offered comprehensive empirical evidence that tobacco cessation interventions are effective and encouraged routine implementation within medical settings. Since that time, numerous studies in tobacco cessation have augmented the state of knowledge regarding successful smoking intervention modalities. Unfortunately, approximately one-third of cancer-related deaths continue to be attributed to smoking behaviors. It is imperative that health care providers encourage and participate in the smoking cessation efforts of their patients and family members. This article provides a review of the current literature in smoking cessation and describes first-line therapies with proven effectiveness in tobacco cessation. Clinicians are encouraged to consistently screen for tobacco use and provide brief interventions utilizing behavioral counseling and pharmacotherapies to treat their patients' tobacco dependence.
Breast Cancer Prevention
Authors: Powles Trevor J. 
Published: August 2004

Abstract
Epidemiological, experimental, and clinical data strongly support the possibility that breast cancer will be prevented by using anti-estrogenic interventions in healthy women. Three trials involving over 20,000 women have so far been reported using tamoxifen 20 mg/day or placebo in healthy women to chemoprevent breast cancer. The American National Surgical Adjuvant Breast and Bowel P-1 Project randomized over 13,000 women to take tamoxifen or placebo and showed a 49% reduction in the early incidence of breast cancer. This was associated with a reduction in osteoporotic fractures but increases in the risks of endometrial cancer, cataract, and thromboembolism. The Royal Marsden tamoxifen trial randomized 2,500 women, and the Italian national trial randomized 5,000 women. Interim analyses from these two trials showed no effect on the early incidence of breast cancer. These results, therefore, have not been able to clearly show an overall clinical benefit of giving tamoxifen to healthy women, nor have they shown which women are likely to benefit.
Another selective anti-estrogen (SERM), raloxifene, has been used in a clinical trial to prevent osteoporotic fractures in women with low bone mineral density. Annual mammography in this trial has shown an approximate 80% reduction in the early incidence of breast cancer, and further follow-up of this trial continues. New trials in chemoprevention of breast cancer being started or being proposed use luteinizing-hormone-releasing hormone analogues, aromatase inhibitors, and other SERMs.
Molecular Aspects of the Mammalian Cell Cycle and Cancer
Authors: Sandal T. 
Published: August 2004

Abstract
Cancer arises mainly from mutations in somatic cells. However, it is not the result of a single mutation, rather, it results from increasing genetic disarray accumulated over time. Tumorigenesis in humans is, therefore, a multistep and age-dependent process.
The multiple mechanisms and multiple players involved in this process necessitate an understanding of the molecular mechanisms, in order to distinctively classify the tumor sample and to assess the risk and treatment of the disease.
Viral Oncolysis
Authors: Mullen John T. , Tanabe Kenneth K. 
Published: August 2004

Abstract
The concept of using replicating viruses as anticancer agents is not a new one, but the ability to genetically modify these viruses into increasingly potent and tumor-specific vectors is a recent phenomenon. As more is learned about the functions of viral gene products in controlling the mammalian cell cycle and in disabling cellular defense mechanisms, specific viral functions can be augmented or eliminated to enhance antineoplastic efficacy. In this article, general mechanisms by which oncolytic viruses achieve their antitumor efficacy and specificity are reviewed. The paradoxical roles of the immune response are addressed with respect to oncolytic viral therapy, as it, on one hand, impedes the spread of viral infection, and on the other, augments tumor cell destruction through the recruitment of T cells “vaccinated” against tumor antigens. The most commonly used oncolytic viruses are each reviewed in turn, including adenoviruses, herpes simplex viruses, vaccinia viruses, reoviruses, and Newcastle disease viruses. Special attention is focused on the unique biology of each of these viruses as well as the status of several of these mutants in clinical trials.
Weekly Topotecan: An Alternative to Topotecan's Standard Daily × 5 Schedule?
Authors: Rowinsky Eric K. 
Published: August 2004

Abstract
Relapsed ovarian cancer and small cell lung cancer are frequently treated with topotecan (Hycamtin®), for which the standard dose and schedule are 1.5 mg/m2 daily for five consecutive days every 3 weeks. Clinical experience has shown that this dose and schedule may be too toxic for some patients, especially those who have been heavily pretreated with platinum-based therapeutics, and it has been suggested that starting doses of topotecan be reduced to 1.0-1.25 mg/m2/d. Recently, multiple clinical trials have begun to evaluate the feasibility and preliminary antitumor activity of an alternative schedule based on weekly administration of topotecan. The potential benefits of weekly administration include not only reduced toxicity without significant compromise of antitumor activity, but also greater patient convenience and quality of life and greater potential for developing new topotecan-containing combination therapies. This report reviews the rationale for a weekly schedule, as well as a growing base of emerging clinical data. These preliminary data suggest that weekly topotecan is active; further evaluations are planned to confirm the activity and therapeutic index and to determine optimal dosing of a weekly schedule.