National Cancer Institute®
Last Modified: March 1, 2002
UI - 10433619
AU - Autier P; Dore JF; Negrier S; Lienard D; Panizzon R; Lejeune FJ;
TI - Guggisberg D; Eggermont AM Sunscreen use and duration of sun exposure: a double-blind, randomized trial.
SO - J Natl Cancer Inst 1999 Aug 4;91(15):1304-9
AD - Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. firstname.lastname@example.org
BACKGROUND: In epidemiologic studies, sunscreen use is associated with increased risk of cutaneous melanoma, basal cell skin cancer, and higher numbers of nevi. It has been proposed that sunscreens may encourage prolonged sun exposure because they delay sunburn occurrence. We examined whether, under habitual conditions of sunscreen use, the sun-protection factor (SPF) had an influence on sun-exposure duration. METHODS: Before the 1997 summer holidays, we randomly assigned 87 French and Swiss participants who were 18-24 years of age to receive an SPF 10 or an SPF 30 sunscreen. Neither medical personnel nor study participants were aware of their sunscreen assignment. Participants were asked to complete daily records of their sun exposure. To avoid influencing the recreational sun-exposure habits of the study participants, no recommendation was made about sun exposure or sun protection. Furthermore, participants were told that the trial end point was the number of pigmented skin lesions before and after the holidays. One subject was lost to follow-up. All statistical tests were two-sided. RESULTS: The SPF 10 (n = 44) and SPF 30 (n = 42) groups had equivalent mean holiday durations (19.4 days versus 20.2 days) and mean quantities of sunscreen used (72.3 g versus 71.6 g). The mean cumulative sun exposures for the two groups were 58.2 hours and 72.6 hours, respectively (P =.011). The mean daily durations of sunbathing were 2.6 and 3.1 hours, respectively (P =.0013), and, for outdoor activities, they were 3.6 and 3.8 hours, respectively (P =.62). There was no difference in sunburn experience between the two groups. CONCLUSIONS: Use of higher SPF sunscreen seems to increase the duration of recreational sun exposure of young white Europeans.
UI - 11642609
AU - Jean D; Bar-Eli M
TI - Targeting the ATF-1/CREB transcription factors by single chain Fv fragment in human melanoma: potential modality for cancer therapy.
SO - Crit Rev Immunol 2001;21(1-3):275-86
AD - Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Activating transcription factor-1 (ATF-1) and cAMP-responsive element (CRE)-binding protein (CREB) have been implicated in cAMP and Ca2+-induced transcriptional activation. The expression of the transcription factors ATF-1 and CREB is upregulated in metastatic melanoma cells. However, how overexpression of ATF-1/CREB contributes to the acquisition of the metastatic phenotype is unclear. Previously we demonstrated that quenching of CREB activity in metastatic melanoma cells by means of a dominant-negative form of CREB (KCREB) led to a decrease in their tumorigenicity and metastatic potential in nude mice. We identified two mechanisms that explain how overexpression of CREB/ATF-1 contributes to the metastatic phenotype. The first is one in which CREB/ATF-1 play an essential role in invasion by regulating the CRE-dependent expression of the metalloproteinase MMP-2 and the adhesion molecule MCAM/MUC18 genes. In the second mechanism, CREB and ATF-1 act as survival factors for human melanoma cells. Here, the effect of disrupting ATF-1 activity was investigated using intracellular expression of an inhibitory anti-ATF-1 single chain antibody fragment (ScFv). Intracellular expression of ScFv anti-ATF-1 in MeWo melanoma cells caused significant reduction in CRE-dependent promoter activation. In addition, expression of ScFv anti-ATF-1 in melanoma cells suppressed their tumorigenicity and metastatic potential in nude mice. ScFv anti-ATF-1 rendered the melanoma cells susceptible to thapsigargin-induced apoptosis in vitro and caused massive apoptosis in tumors transplanted subcutaneously into nude mice, confirming that AFT-1/CREB act as survival factors for human melanoma cells. These studies demonstrate the potential usage of ScFv anti-ATF-1 as an inhibitor of tumor growth and metastasis of solid tumors in vivo.
UI - 11857313
AU - Gutman H; Schachter J; Stopel E; Gutman R; Lahav J
TI - Impaired platelet aggregation in melanoma patients treated with interferon-alpha-2b adjuvant therapy.
SO - Cancer 2002 Feb 1;94(3):780-5
AD - Department of Surgery B, Rabin Medical Center, Beilinson Campus, Petah Tiqva, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. email@example.com
BACKGROUND: High-dose interferon (INF)- alpha-2b is the only Food and Drug Administration-approved adjuvant treatment for patients with melanoma who are at high risk of recurrence. Although circumstantial evidence points to a potentially harmful effect of INF-alpha-2b on platelet function, to the authors' knowledge this has never been studied in humans. METHODS: The study group was comprised of patients who had undergone surgery for melanoma and were free of disease but at a high risk of recurrence. All patients were candidates for adjuvant INF treatment (high-dose) and were undergoing routine evaluation to which platelet aggregation was added. Aggregation was triggered in standard fashion with adenosine diphosphate, epinephrine, collagen, thrombin, arachidonic acid, and ristocetin. Blood samples were drawn immediately before treatment, during the intravenous loading phase, during the subcutaneous maintenance phase, and 3-6 weeks after cessation of treatment. Patients receiving low-dose, long-standing INF-alpha-2b treatment also were tested. All results at each phase were compared with those of normal controls. RESULTS: In those patients receiving high-dose INF-alpha-2b, ristocetin-induced aggregation did not appear to be affected. However, the response to > or = 1 of the other agonists was impaired in 5 of 6 samples during loading, 14 of 15 samples during the maintenance phase, and 8 of 13 samples after treatment, compared with only 1 of 8 samples before treatment (P = 0.025, P = 0.002, and P = 0.067, respectively). During treatment with low-dose INF, platelet function was affected to a lesser extent. CONCLUSIONS: INF treatment in melanoma patients appears to be associated with severe impairment of platelet aggregation, which appears to be dose-dependent and cumulative-dose-dependent. This is not detectable by the standard coagulation profile. This effect has significant implications in the event of accidental injury or elective surgery. The antiaggregation activity may be the mechanism by which INF delays, reduces, or prevents the formation of melanoma metastases. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10261
UI - 11565830
AU - Schwartzentruber DJ
TI - Guidelines for the safe administration of high-dose interleukin-2.
SO - J Immunother 2001 Jul-Aug;24(4):287-93
AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. firstname.lastname@example.org
High-dose interleukin-2 (IL-2) results in objective clinical regression of metastatic cancer in 15% to 17% of patients with melanoma and renal cell carcinoma. Durable complete regression of all metastases is seen in 6% to 8% of patients. Based on these findings, the U.S. Food and Drug Administration has approved the use of high-dose IL-2 for the treatment of patients with metastatic melanoma and renal cell carcinoma. Interleukin-2 administration is associated with many different side effects, and after many years of use, clinicians have learned how to safely administer high-dose IL-2. This article details practical guidelines for the safe administration of high-dose IL-2.
UI - 11565838
AU - Dudley ME; Wunderlich J; Nishimura MI; Yu D; Yang JC; Topalian SL;
TI - Schwartzentruber DJ; Hwu P; Marincola FM; Sherry R; Leitman SF; Rosenberg SA Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma.
SO - J Immunother 2001 Jul-Aug;24(4):363-73
AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA. email@example.com
This report describes a phase I study of the adoptive transfer of cloned melanoma antigen-specific T lymphocytes for therapy of patients with advanced melanoma. Clones were derived from peripheral blood lymphocytes or tumor-infiltrating lymphocytes of patients who had received prior immunization with the melanoma-associated antigen, gpl00. In response to its cognate antigen, each clone used for treatment secreted large amounts of interferon-gamma and granulocyte-macrophage colony-stimulating factor, lesser amounts of interleukin (IL)-2 and tumor necrosis factor-alpha, and little or no IL-4 and IL-10. Clones also demonstrated recognition of human leukocyte antigen-matched melanomas using cytokine secretion and lysis assays. Twelve patients received 2 cycles of cells alone; 11 patients received additional cycles of cells and were randomized between two schedules of IL-2 (125,000 IU/kg subcutaneously daily for 12 days versus 720,000 IU/kg intravenously every 8 h for 4 days). A total of 51 cycles of cells were administered, with an average of 1 x 10(10) cells per cycle. Peripheral blood samples were analyzed for persistence of transferred cells by T-cell receptor-specific polymerase chain reaction. Transferred cells reached a maximum level at 1 h after transfer but rapidly declined to undetectable levels by 2 weeks. One minor response and one mixed response were observed (both in the high-dose IL-2 arm). This report demonstrates the safety and feasibility of cloned T-cell transfer as a therapy for patients with cancer. The lack of clinical effectiveness of this protocol suggests that transfer of different or additional cell types or that modulation of the recipient host environment is required for successful therapy.
UI - 11561695
AU - Margolin K; Longmate J; Synold TW; Gandara DR; Weber J; Gonzalez R;
TI - Johansen MJ; Newman R; Baratta T; Doroshow JH Dolastatin-10 in metastatic melanoma: a phase II and pharmokinetic trial of the California Cancer Consortium.
SO - Invest New Drugs 2001;19(4):335-40
AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA. firstname.lastname@example.org
Dolastatin-10 is a novel pentapeptide agent originally isolated from the marine mollusk Dolabella auricularia with a mechanism of antitumor activity that involves the inhibition of microtubule assembly. We performed a Phase II trial of Dolastatin-10, 400 microg/m2 in patients with advanced melanoma who had received no prior chemotherapy. Dolastatin-10 pharmokinetics were evaluated in a subset of patients following courses 1 and 2. Twelve patients were treated with a median of 2 cycles of Dolastatin-10, and no patient experienced an objective response. The only grade >2 toxicities were grade 3 neutropenia uncomplicated by infection, occurring in 4 patients following the first treatment cycle. The total systemic clearance and volume of distribution at steady-state were 2.61 +/- 1.9 L/h/m2 and 28.4 +/- 13 L/m2, respectively. Due to prolonged terminal elimination. Dolastatin-10 plasma concentrations of greater than 1 nM were sustained for 24 h in all patients studied. Dolastatin-10 is unlikely to have substantial activity in the treatment of melanoma.
UI - 11870502
AU - Atzpodien J; Neuber K; Kamanabrou D; Fluck M; Brocker EB; Neumann C;
TI - Runger TM; Schuler G; von den Driesch P; Muller I; Paul E; Patzelt T; Reitz M Combination chemotherapy with or without s.c. IL-2 and IFN-alpha: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM).
SO - Br J Cancer 2002 Jan 21;86(2):179-84
AD - European Institute for Tumor Immunology and Prevention (EUTIP), Gotenstr. 152, 53175 Bonn, Germany. SekrProfAtzpodien@yahoo.de
The purpose of this randomized trial was to evaluate the efficacy of combination chemoimmunotherapy compared with chemotherapy alone. A total of 124 patients were randomized to receive intravenous cisplatin (35 mg m(-2), days 1-3), carmustine (150 mg m(-2), day 1, cycles 1 and 3 only), dacarbacine (220 mg m(-2), days 1-3) and oral tamoxifen (20 mg m(-2), daily) in combination with (n=64) or without (n=60) sequential subcutaneous IL-2 and IFN-alpha. In those patients who received sequential immunotherapy, each cycle of chemotherapy was followed by outpatient s.c. IL-2 (10 x 10(6) IU m(-2), days 3-5, week 4; 5 x 10(6) IU m(-2), days 1, 3, 5, week 5) and s.c. IFN-alpha (5 x 10(6) IU m(-2), day 1, week 4; days 1, 3, 5, week 5). The overall response rate of patients treated with the combination of chemotherapy and IL-2/IFN-alpha was 34.3% with seven complete responses (10.9%) and 15 partial responses (23.4%). In patients treated with chemotherapy, only, the overall response rate was 29.9% with eight complete responses (13.3%) and 10 partial responses (16.6%). There was no significant difference in median progression free survival (0 months vs 4 months) and in median overall survival (12 months vs 13 months) for combined chemoimmunotherapy and for chemotherapy, respectively. Copyright 2002 The Cancer Research Campaign
UI - 11841361
AU - Roberts DL; Anstey AV; Barlow RJ; Cox NH; Newton Bishop JA; Corrie PG;
TI - Evans J; Gore ME; Hall PN; Kirkham N; The British Association of Dermatologists; The Melanoma Study Group U.K. guidelines for the management of cutaneous melanoma.
SO - Br J Dermatol 2002 Jan;146(1):7-17
AD - Singleton Hospital, Swansea SA2 8QA, UK.
These guidelines for management of cutaneous melanoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the U.K., they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery.
UI - 11786569
AU - Bafaloukos D; Gogas H; Georgoulias V; Briassoulis E; Fountzilas G;
TI - Samantas E; Kalofonos Ch; Skarlos D; Karabelis A; Kosmidis P Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group.
SO - J Clin Oncol 2002 Jan 15;20(2):420-5
AD - Metaxa's Cancer Hospital, Piraeus, Greece. email@example.com
PURPOSE: Temozolomide is a novel oral alkylating agent that is effective against melanoma. Moreover, temozolomide readily crosses the blood-brain barrier and may consequently be effective in patients with brain metastases. This phase II study was performed to assess the efficacy and safety of the combination regimen of temozolomide and docetaxel in patients with advanced metastatic melanoma. PATIENTS AND METHODS: Sixty-five patients with metastatic melanoma were enrolled. Treatment consisted of intravenous docetaxel (80 mg/m(2)) on day 1 and oral temozolomide (150 mg/m(2)) on days 1 to 5, every 4 weeks, for a maximum of six cycles. RESULTS: Sixty-two patients were eligible for the efficacy and safety analysis. Seventeen patients (27%) achieved an objective response, including five complete (8%) and 12 partial responses (19%). Median response duration was 9.5 months. Among responders, median time to progression (TTP) was 11.2 months and median overall survival (OS) was 16 months. For all treated patients, the median TTP was 4 months and median OS was 11 months. Three (38%) of eight patients who presented with brain metastases had a partial response for 5, 6, and 12 months. Of 52 patients who did not have brain involvement at presentation, only four (8%) developed brain metastases at a median follow-up of 14 months. Myelosuppression was the primary toxicity. CONCLUSION: The combination of temozolomide and docetaxel was effective and well tolerated as first-line treatment for patients with advanced metastatic melanoma and demonstrated encouraging antitumor activity against brain metastases.
UI - 11824246
AU - Meyer T; Gohl J
TI - [Regional chemotherapy--perfusion of the extremities]
SO - Kongressbd Dtsch Ges Chir Kongr 2001;118():200-4
AD - Chirurgische Universitatsklinik Erlangen, Krankenhausstrasse 12, 91054 Erlangen.
Hyperthermic isolated limb perfusion with cytostatic drugs (HILP) is indicated in locoregional recurrences of malignant melanoma of the limbs. As a neoadjuvant treatment it is also used for non-curatively resectable soft tissue sarcoma or their recurrences on the extremities. Up to now, melphalan is still the standard drug in HILP for malignant melanoma. With melphalan, complete response can be achieved in 65-80% for clinically detectable in transit metastases (+/- regional lymph node metastases). The combination of tumor necrosis factor (TNF) alpha with melphalan has considerably improved response rates of HILP in sarcoma. In more than 80% of the patients the otherwise necessary amputation of the limb can be avoided. The combination of TNF with other drugs than melphalan could possibly further improve results of HILP in sarcoma patients. The high rate of local recurrences of malignant melanoma after HILP poses an unsolved problem yet.
UI - 11869699
AU - Guadagni S; Russo F; Rossi CR; Pilati PL; Miotto D; Fiorentini G; Deraco
TI - M; Santinami M; Palumbo G; Valenti M; Amicucci G Deliberate hypoxic pelvic and limb chemoperfusion in the treatment of recurrent melanoma.
SO - Am J Surg 2002 Jan;183(1):28-36
AD - Department of Surgical Sciences, University of L'Aquila, 67010 L'Aquila, Italy. firstname.lastname@example.org
BACKGROUND: The treatment of patients with advanced or recurrent pelvic melanoma, which are often associated with lesions in the lower limbs, is still unsatisfactory and controversial. A simplified hypoxic pelvic and limb perfusion has been recently recommended to provide therapeutic options for palliation and possibly cure. METHODS: A nonrandomized and noncontrolled phase II experimental study was performed in 11 patients with symptomatic unresectable recurrent melanoma of the pelvis and limb. Patients were submitted to hypoxic pelvic and limb perfusion with 25 mg/m(2) of melphalan, 50 mg/m(2) of cisplatin, 300 mg/m(2) of dacarbazine, and 75 mg/m(2) of epirubicin by means of a simplified balloon occlusion technique. Response rate and time to disease progression were the primary endpoints; overall survival was the secondary endpoint. RESULTS: During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery or in the postoperative period. Response rate was 82% (95% confidence interval, 58% to 100%). Median time to disease progression was 12 months (range 9 to 30 months). Three-year overall survival was 34%. CONCLUSIONS: Hypoxic pelvic and limb perfusion is a safe and good palliative treatment for patients with unresectable recurrent melanoma. Further studies are necessary to to confirm these data and to establish if refinements can be made with acceptable toxicity.
UI - 11870551
AU - Prasmickaite L; Hogset A; Selbo PK; Engesaeter BO; Hellum M; Berg K
TI - Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy.
SO - Br J Cancer 2002 Feb 12;86(4):652-7
AD - Department of Biophysics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. email@example.com
The development of methods for specific delivery of drugs is an important issue for many cancer therapy approaches. Most of macromolecular drugs are taken into the cell through endocytosis and, being unable to escape from endocytic vesicles, eventually are degraded there, which hinders their therapeutic usefulness. We have developed a method, called photochemical internalization, based on light-induced photochemical reactions, disrupting endocytic vesicles specifically within illuminated sites e.g. tumours. Here we present a new drug delivery concept based on photochemical internalization-principle -- photochemical disruption of endocytic vesicles before delivery of macromolecules, leading to an instant endosomal release instead of detrimental stay of the molecules in endocytic vesicles. Previously we have shown that illumination applied after the treatment with macromolecules substantially improved their biological effect both in vitro and in vivo. Here we demonstrate that exposure to light before delivery of protein toxin gelonin improves gelonin effect in vitro much more than light after. However, in vitro transfection with reporter genes delivered by non-viral and adenoviral vectors is increased more than 10- and six-fold, respectively, by both photochemical internalization strategies. The possible cellular mechanisms involved, and the potential of this new method for practical application of photochemical internalization concept in cancer therapy are discussed.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.