bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo total antioxidant capacity: comparison of two different analytical methods
Authors: Vassalle Cristina , Masini Silvano , Carpeggiani Clara , L'Abbate Antonio , Boni Claudio , CarloZucchelli Gian
Published: August 2004

Several methods to assess the total antioxidant capacity (TAC) are available. However, the final value of measured TAC in the sample depends on the procedure used in every specific assay. This makes crucial the comparison of different analytical methods. The aim of our study was to evaluate analytical characteristics and laboratory reliability of two different assays: the ferric-reducing ability (FRAP) assay and a new spectrophotometric test (OXY-adsorbent test, Diacron, Italy).

Unselected outpatients referred to the Institute of Clinical Physiology were studied (n=187, 58 females, 129 males, mean age: 65±13 years). All blood samples were maintained on ice, centrifuged within 15 minutes after blood collection and then stored at −80°C until performance of assay procedures.

OXY assay: The lower limit of sensitivity was 6 μmol HClO/ml. The assay was found to be linear up to 440 μmol HClO/ml (r=−0.99, p<0.001). Absorbance was linear over a wide concentration range with solutions containing uric acid in purified form (0–1000 μmol/l, r=−0.996, p<0.001), serum (r=−0.99, p<0.01) or plasma serially diluted (r=−0.99, p<0.01). Mean value in plasma samples accounted for 366.2±7.2 μmol HClO/ml. Mean OXY value in females (353.4±13.2 mmol HClO/ml) was not different from that detected in males (372±8.6 mmol HClO/ml). A significant difference was observed between subjects without and with hypertension in serum OXY levels (344.8±9.9 and 383.2±10 μmol HClO/ml, p<0.01, respectively).

FRAP assay: The lower limit of sensitivity was 15 μmol/l. Linearity was observed up to 1000 μmol/l (r=−0.998, p<0.001). Absorbance was linear over a wide concentration range with solutions containing uric acid in purified form (0–1000 μmol/l, r=0.997, p<0.001), serum (r=0.99, p<0.01) or plasma serially diluted (r=0.99, p<0.01). FRAP mean value in plasma samples, evaluated in 102 patients, accounted for 514.1±19.1 μmol/l. Mean FRAP in females (469±22.5 μmol/l) was not different from that detected in males (535±25.6 mmol/l).

FRAP vs. OXY: A significant direct relationship was observed when comparing FRAP with OXY levels in the whole population (r=0.22, p<0.05).

Neither of the methods are expensive and they are speedy and simple to perform. Values are reproducible and linearly correlated to the concentration of antioxidants present in the samples. For this reason, these methods may be considered practicable indicators of total antioxidant capacity, for routinely potential use in every laboratory and useful in all the studies concerning the evaluation of oxidative stress.
Evaluation of the blood gas analyzer GEM(r) PREMIER(tm) 3000
Authors: Bénéteau-Burnat Bénédicte , Bocque Marie-Chantal , Lorin Anne , Martin Catherine , Vaubourdolle Michel
Published: August 2004

During the past few decades, new technologies have allowed the fabrication of miniaturized sensors and the development of analyzers well designed for point-of-care testing (POCT). They combined the ease-of-use and portability required for POC with the accuracy and the reliability of traditional systems. Instrumentation Laboratory introduced the GEM
Application of Moire Interferometry for Mode II Testing of Stitched Composites
Authors: Chen L , Sankar BV , Ifju PG
Published: August 2004

In this paper, two experimental approaches were used to quantify the Mode II fracture toughness of stitched composites. In the End Notched Flexure (ENF) test, which is the traditional Mode II test, the delamination does not open, but slides. This makes it difficult to locate the crack-tip as the crack propagates and hence to estimate the length of crack propagation. This uncertainty introduces significant errors in the estimated value of Mode II fracture toughness, especially of stitched composite laminates. In the present study high sensitive moiré interferometry was used to obtain the full-field displacements as well as the crack tip location in ENF specimens. By using linear elastic fracture mechanics for orthotropic materials, the stress intensity factor can be determined from the relative crack surface displacements behind the crack tip. The results from the displacement matching method are compared with the conventional area method for calculating fracture toughness. It is found that stitching can increase the Mode II fracture toughness of laminated composites by a factor of 2 to 3 depending on the stitch density.
Treatment of Paraphilia in Young Adults with Leuprolide Acetate: A Preliminary Case Report Series
Authors: Saleh FM , Niel T , Fishman MJ
Published: August 2004

Some juveniles who engage in sexual offenses may have a paraphilia, a psychiatric disorder characterized by a pervasive pattern of deviant and impairing sexual fantasies, thoughts, and/or behaviors. Though there is no known cure for these conditions, paraphilias can be effectively managed using a multimodal treatment approach. This may include the use of psychotherapeutic and pharmacological treatment interventions, including antiandrogen medications. One such agent, leuprolide acetate (leuprolide), a luteinizing hormone-releasing-hormone agonist, has been shown to be effective in reducing paraphilic symptoms in adult patients. To date, however, there is no published data on its use and effectiveness in adolescent and young adult paraphilic patients. This study consists of a case report series of six young adult patients treated with leuprolide. All subjects had been diagnosed with at least one paraphilia (i.e., Pedophilia, Sexual Sadism, Frotteurism, and Paraphilia Not Otherwise Specified). All subjects had been refractory to treatment in a residential program for adolescent sex offenders prior to initiation of leuprolide. All six subjects reported a reduction in sexually deviant symptoms following treatment with leuprolide. Clinicians rated four as much improved and two as moderately improved. The treatment was well tolerated in all six subjects. This preliminary case series supports the conclusion that leuprolide deserves further examination as a potentially safe and effective component in the treatment of young adult patients with paraphilia.
The Reactivity of Gamma-hydroxybutyric acid (GHB) and Gamma-butyrolactone (GBL) in Alcoholic Solutions
Authors: Hennessy S A , Moane S M , McDermott S D
Published: August 2004

In this work the stability of GBL (gamma-butyrolactone) and GHB (gamma-hydroxybutyric acid) in alcoholic media was studied. Under acidic conditions the GBL will react with ethanol or methanol to give the corresponding ethyl and methyl esters of GHB. It can be seen that ester formation is dependent on the type of alcohol, the alcohol content of the solution, and the pH of the solution. Under the same conditions it was shown that GHB does not give rise directly to the corresponding ester when merely in the presence of an alcohol; however the ester will be formed if the conditions are present for conversion of GHB to GBL followed by subsequent reaction with alcohol. In alcoholic beverage samples spiked with GBL the expected conversion to GHB occurred, and the formation of the ethyl ester of GHB was also seen in some samples. Wine samples were analyzed for the presence of the ethyl ester of GHB, and the effect of adding GHB/GBL to hot beverages was studied.
Manipulation of Human Pluripotent Embryonal Carcinoma Stem Cells and the Development of Neural Subtypes
Authors: Stewart Rebecca , Christie Victoria Buyers , Przyborski Stefan Alexander
Published: August 2004

There are few reliable cell systems available to study the process of human neural development. Embryonal carcinoma (EC) cells are pluripotent stem cells derived from teratocarcinomas and offer a robust culture system to research cell differentiation in a manner pertinent to embryogenesis. Here, we describe the recent development of a series of culture procedures that together can be used to induce the differentiation of human EC stem cells, resulting in the formation of either pure populations of differentiated neurons, populations of differentiated astrocytes, or populations of immature neuronal cell types. Cell-type-specific markers were used to examine the induction of EC stem cell differentiation by retinoic acid. In direct response to manipulation of the culture environment, the expression of cell type markers correlated with the differentiation and appearance of distinct neural cell types, including neurons and astrocytes. These experiments demonstrate that cultured human EC stem cells provide a robust model cell system capable of reproducibly forming neural subtypes for research purposes.
Human Embryonic Stem Cell Lines Derived from Discarded Embryos
Authors: Mitalipova Maisam , Calhoun John , Shin Soojung , Wininger David , Schulz Thomas , Noggle Scott , Venable Alison , Lyons Ian , Robins Allan , Stice Steven
Published: August 2004

Human pluripotent embryonic stem (ES) cells have important potential in regenerative medicine and as models for human preimplantation development; however, debate continues over whether embryos should be destroyed to produce human ES cells. We have derived four ES cell lines on mouse embryonic fibroblast cells in medium supplemented with basic fibroblast growth factor, human recombinant leukemia inhibitory factor, and fetal bovine serum. The source of these cell lines was poor-quality embryos that in the course of routine clinical practice would have been discarded. After continuous proliferation in vitro for more than 12 months, these ES cell lines maintained their developmental potential to form trophoblast and somatic cells, including cardiac muscle and neuronal tissue.
The Role of Intraoperative Radiation Therapy (IORT) in the Treatment of Locally Advanced Gynecologic Malignancies
Authors: Carmen Marcela G. , McIntyre James F. , Goodman Annekathryn
Published: August 2004

The prognosis in women with locally advanced primary or recurrent gynecologic malignancies is rather poor. Doses of external beam radiation necessary to treat gross or microscopic recurrence among patients surgically treated or previously irradiated exceed what is tolerated by normal structures. In this group of patients, intraoperative radiation therapy (IORT) can be utilized to maximize local tumor control, minimizing the radiation exposure of dose-limiting surrounding structures. Review of the available literature indicates that IORT may improve long-term local control and overall survival in women with pelvic sidewall and/or para-aortic nodal recurrence. The most encouraging results have been reported in the cases of microscopic residual disease, following surgical debulking.
Oral Granisetron for the Prevention of Acute Late Onset Nausea and Vomiting in Patients Treated with Moderately Emetogenic Chemotherapy
Authors: Friedman Carl J. , Burris Howard A. , Yocom Karen , Blackburn Linda M. , Gruben David
Published: August 2004

Purpose. To demonstrate the efficacy of oral granisetron 1 mg twice daily for the prevention of late onset nausea and vomiting after moderately emetogenic chemotherapy that includes cyclophosphamide, carboplatin, or doxorubicin.

Methods. Prior to chemotherapy, patients were stratified by gender and randomized to receive oral granisetron (1 mg tablet twice daily) or prochlorperazine (10 mg sustained release capsule twice daily). Study agents were administered 1 h prior to and 12 h after chemotherapy. Antiemetics were administered for seven consecutive days. Efficacy variables were assessed 48 and 72 h after administration of chemotherapy, and included no emesis, no nausea, no moderate or severe nausea, and no antiemetic rescue. Safety analysis included all patients who received medication.

Results. A total of 230 patients were included in the intent-to-treat analysis; 119 patients received granisetron and 111 patients received prochlorperazine. Females, and all patients combined, who received granisetron had significantly higher no-emesis rates at 48 h (p = .010 and p = .016, respectively) than patients who received prochlorperazine. No-nausea rates at 48 h were numerically higher for all patients combined and females who received granisetron rather than prochlorperazine. Response rates for no nausea or mild nausea were also numerically higher in females treated with granisetron, compared to prochlorperazine, at 48 h. Significantly more patients (p < .001) and females (p < .001) in the granisetron group than in the prochlorperazine group did not require rescue antiemetics at 48 h. At 72 h, efficacy results were comparable for granisetron and prochlorperazine.

Conclusion. Oral granisetron is well tolerated and more effective than prochlorperazine in preventing nausea and vomiting for up to 48 h following treatment with moderately emetogenic chemotherapy.
Development of GnRH Antagonists for Prostate Cancer: New Approaches to Treatment
Authors: Cook Terry , Sheridan William P.
Published: August 2004

Prostate cancer has become the most common cancer among American men and is second only to lung cancer as a cause of male cancer-related death.

Several treatment options exist for different stages of prostate cancer including observation, prostatectomy, radiation therapy, chemotherapy, and hormone therapy. Hormone therapy has evolved from the use of estrogens to gonadotropin-releasing hormone (GnRH) agonists and recently, investigational GnRH antagonists.

GnRH receptor agonists such as leuprolide, bruserelin and goserelin have been used for the treatment of prostate cancer. These agonists eventually cause the inhibition of lutenizing hormone production, which in turn causes a suppression of testosterone and dihydrotestosterone, on which continued growth of prostate cancer cells depend.

Several comparative studies of leuprorelin administered as daily injections or monthly depot injections have been reported. Disease progression was prevented in more than 72% of men administered daily leuprorelin, and in 82% to 89% of those receiving monthly depots. Another synthetic GnRH analog, goserelin, has been studied in a similar population of men with daily injections producing partial responses in 60% to 80% of men with previously untreated prostate cancer. Abarelix, a peptide antagonist of GnRH receptor, is also being studied for the treatment of prostate cancer.

The discovery and development of GnRH antagonists may provide an important advance for patients with prostate cancer. Clearly the studies described herein, as well as many others, outline an exciting era of research to define the optimal use of hormonal therapy in prostate cancer.
Oral Chemotherapeutic Agents for Colorectal Cancer
Authors: Sharma Sunil , Saltz Leonard B.
Published: August 2004

A number of novel oral chemotherapeutic agents are entering practice or are under development in the United States. Many of these agents display significant clinical activity against colorectal cancer. Many classes of compounds, including fluoropyrimidine analogs, dihydropyrimidine dehydrogenase (DPD) inhibitors, topoisomerase inhibitors, farnesyl transferase inhibitors, and others, are being developed for oral administration. This manuscript describes the progress of clinical development of these agents and also explores the relative merits and challenges of these approaches. Economic issues, patient preference, and patient selection issues surrounding oral chemotherapy for colorectal cancer will also be discussed.
Primary Mediastinal Malignancies in Children: Report of 22 Patients and Comparison to 197 Adults
Authors: Temes Roy , Allen Nechol , Chavez Theresa , Crowell Richard , Key Charles , Wernly Jorge
Published: August 2004

Purpose. Examine a contemporary series of patients with primary pediatric malignant mediastinal tumors and determine epidemiology, histology, treatment, and survival.

Patients and Methods. All malignancies diagnosed between January 1, 1973 and December 31, 1995 were analyzed.

Results. Twenty-two patients, age 18 years or less, with pediatric primary mediastinal malignancies were identified from a database of 110,284 patients with primary malignancies. During the same period, 197 adult patients with primary mediastinal malignancies were identified. Fifty-nine percent of the pediatric patients were male. Median age was 11 years. Lymphoma was present in 55%, neurogenic malignancies in 23%, malignant germ cell tumors in 18%, and sarcoma in 5%. Neurogenic tumors presented in infants and lymphomas and germ cell tumors presented in teens (p = 0.005). In treated children, surgery was used more often in neurogenic tumors and germ cell tumors than in lymphomas (p = 0.002). Five-year survival was 74% for lymphomas, 67% for neurogenic tumors, 25% for germ cell tumors, and 61% overall (p = 0.23). Compared to adults, children had more neurogenic tumors (p < 0.001) and fewer thymomas (p = 0.0499). There were no significant differences in staging or survival between children and adults.

Conclusions. Pediatric mediastinal malignancies occurred with a frequency of 1/5,013 patients with malignant tumors. Lymphoma, neurogenic tumors, and germ cell tumors predominated. Compared to adults, children had more neurogenic tumors and fewer thymomas. Within the pediatric group, differences were found in age of presentation between histologic groups. These differences between adults and children, and between infants and teens, should be considered when evaluating a patient suspected of having mediastinal malignancy.
Nonmyeloablative Allogeneic Stem Cell Transplant Strategies and the Role of Mixed Chimerism
Authors: Spitzer Thomas R.
Published: August 2004

Experimental and clinical experiences have demonstrated successsful donor engraftment following nonmyeloablative preparative regimens. These less toxic conditioning strategies may be better tolerated with diminished transplant-related morbidity and mortality. Importantly, the intentional induction of mixed chimerism can be established following nonmyeloablative conditioning. This approach has the potential advantages of inhibiting graft-versus-host disease, presumably secondary to the persistence of host immunoregulatory cells, and providing a platform for the delivery of adoptive cellular immunotherapy with donor leukocyte infusions for patients with an underlying malignancy. This review will describe the preclinical evolution of nonmyeloablative transplant strategies, the rationale for considering these approaches, and the preliminary clinical experience with this novel allogeneic stem cell therapy.
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

Shortly 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

Chronic 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

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

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

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

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

Noncardiogenic 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

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

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

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

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

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

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

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

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.
The Use of Chemotherapy in Soft-Tissue Sarcomas
Authors: Spira Alexander I. , Ettinger David S.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Identify the role of doxorubicin and ifosfamide in soft tissue sarcomas.Identify the role of newer agents in soft tissue sarcomas.Appreciate the role of adjuvant therapy in the management of soft tissue sarcomas.Appreciate the role of neoadjuvant chemotherapy and radiotherapy in the management of soft tissue sarcomas.

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The treatment of advanced soft-tissue sarcomas is often palliative, although a subset of patients may be cured or have a long disease-free interval. This paper reviews the historical data over 30 years of treatment that has led to the use of ifosfamide and doxorubicin as the mainstay in the treatment of metastatic disease. These treatments have a high toxicity, relative to other chemotherapeutic regimens, with median response durations on the order of months. Agents developed in the last few years, whose role in the treatment of sarcomas is still evolving, are discussed as well. Finally, we discuss the role of chemotherapy in combination with surgery and radiation in the adjuvant and neoadjuvant settings.
State-of-the-Art Treatment of Metastatic Hormone-Refractory Prostate Cancer
Authors: Goodin Susan , Rao Kamakshi V. , DiPaola Robert S.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Identify agents which have shown activity in the treatment of hormone refractory prostate cancer (HRPC).Recognize the mechanisms of resistance to chemotherapy in HRPC, including genetic alterations commonly found in advanced disease.Recognize the development of novel approaches to the treatment of HRPC.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Initial therapy for advanced prostate cancer includes androgen ablation by surgical or medical castration. Still, nearly all men with metastases will progress to hormone-refractory prostate cancer (HRPC). Current U.S. Food and Drug Administration-approved agents for the treatment of HRPC include mitoxantrone and estramustine, although the vinca alkaloids and the taxanes have shown promising activity in single-agent phase II trials. Combinations of these agents induce a biochemical response in greater than 50% of patients, but the median duration of response is approximately 6 months. Overall survival of patients treated with these combinations is approximately 18-24 months. Studies are ongoing to develop novel therapies that target specific molecular pathways or mechanisms of chemotherapy resistance. Novel agents under development include growth factor receptor inhibitors, antisense oligonucleotides, bisphosphonates, and cell differentiating agents. Evaluation and incorporation of these agents into existing treatment regimens will guide us in the development of more active regimens in the treatment of HRPC.
Impact of Tumor Hypoxia and Anemia on Radiation Therapy Outcomes
Authors: Harrison Louis B. , Chadha Manjeet , Hill Richard J. , Hu Kenneth , Shasha Daniel
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:Discuss the prognostic significance of intratumoral hypoxia and low hemoglobin levels in patients receiving curative-intent radiation for head and neck or cervical cancer.Describe the potential relationship between anemia and intratumoral hypoxia in patients with solid tumors.List possible interventions for improving intratumoral oxygenation and radiosensitivity in the radiation oncology setting.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Local recurrence remains a major obstacle to achieving cure of many locally advanced solid tumors treated with definitive radiation therapy. The microenvironment of solid tumors is hypoxic compared with normal tissue, and this hypoxia is associated with decreased radiosensitivity. Recent preclinical data also suggest that intratumoral hypoxia, particularly in conjunction with an acid microenvironment, may be directly or indirectly mutagenic. Investigations of the prognostic significance of the pretreatment oxygenation status of tumors in patients with head and neck or cervical cancer have demonstrated that increased hypoxia, typically designated in these studies as pO2 levels below 2.5-10 mm Hg, is associated with decreased local tumor control and lower rates of disease-free and overall survival. Hypoxia-directed therapies in the radiation oncology setting include treatment using hyperbaric oxygen, fluosol infusion, carbogen breathing, and electron-affinic and hypoxic-cell sensitizers. These interventions have shown the potential to increase the effectiveness of curative-intent radiation therapy, demonstrating that the strategy of overcoming hypoxia may be a viable and important approach. Anemia is common in the cancer population and is suspected to contribute to intratumoral hypoxia. A review of the literature reveals that a low hemoglobin level before or during radiation therapy is an important risk factor for poor locoregional disease control and survival, implying that a strong correlation could exist between anemia and hypoxia (ultimately predicting for a poor outcome). While having a low hemoglobin level has been shown to be detrimental, it is unclear as to exactly what the threshold for “low” should be (studies in this area have used thresholds ranging from 9-14.5 g/dl). Optimal hemoglobin and pO2 thresholds for improving outcomes may vary across and within tumor types, and this is an area that clearly requires further evaluation. Nonetheless, the correction of anemia may be a worthwhile strategy for radiation oncologists to improve local control and survival.