Exploring patterns of recurrent melanoma in Northeast Scotland to inform the introduction a digital self-examination intervention

Peer reviewedPublisher PD

Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)

Background: Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNα-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. Patients and methods: In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 μg peg-IFNα-2b s.c. per week and oral TMZ 200 mg/m2 (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. Results: In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. Conclusions: The efficacy of TMZ plus peg-IFNα-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNα-2b seems to be similar to non-peg-IFN when combined with TM

Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Background: This randomized phase III trial was designed to demonstrate the superiority of autologous peptide-loaded dendritic cell (DC) vaccination over standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients. Patients and methods: DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC vaccines loaded with MHC class I and II-restricted peptides were applied subcutaneously at 2-week intervals for the first five vaccinations and every 4 weeks thereafter. The primary study end point was objective response (OR); secondary end points were toxicity, overall (OS) and progression-free survival (PFS). Results: At the time of the first interim analysis 55 patients had been enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC: 3.8%), but not significantly different in the two arms. The Data Safety & Monitoring Board recommended closure of the study. Unscheduled subset analyses revealed that patients with normal serum LDH and/or stage M1a/b survived longer in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC-arm did those patients with (i) an initial unimpaired general health status (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44− haplotype survive significantly longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated patients). Conclusions: DC vaccination could not be demonstrated to be more effective than DTIC chemotherapy in stage IV melanoma patients. The observed association of overall performance status and HLA haplotype with overall survival for patients treated by DC vaccination should be tested in future trials employing DC vaccine

Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression

Online supplemental material is available at http://www.jem.org/cgi/content/full/jem.20111487/DC1.The development of cancer-specific therapeutics has been limited because most healthy cells and cancer cells depend on common pathways. Pyruvate kinase (PK) exists in M1 (PKM1) and M2 (PKM2) isoforms. PKM2, whose expression in cancer cells results in aerobic glycolysis and is suggested to bestow a selective growth advantage, is a promising target. Because many oncogenes impart a common alteration in cell metabolism, inhibition of the M2 isoform might be of broad applicability. We show that several small interfering (si) RNAs designed to target mismatches between the M2 and M1 isoforms confer specific knockdown of the former, resulting in decreased viability and increased apoptosis in multiple cancer cell lines but less so in normal fibroblasts or endothelial cells. In vivo delivery of siPKM2 additionally causes substantial tumor regression of established xenografts. Our results suggest that the inherent nucleotide-level specificity of siRNA can be harnessed to develop therapeutics that target isoform-specific exons in genes exhibiting differential splicing patterns in various cell types.MIT-Harvard Center for Cancer Nanotechnology ExcellenceNational Cancer Institute (U.S.) (Grant U54 CA151884)Marie D. and Pierre Casimir-Lambert FundNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051

Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease

Cataloged from PDF version of article.Efforts for the identification of diagnostic autoantibodies for neuro-Behcet's disease (NBD) have failed. Screening of NBD patients' sera with protein macroarray identified mitochondrial carrier homolog 1 (Mtch1), an apoptosis-related protein, as a potential autoantigen. ELISA studies showed serum Mtch1 antibodies in 68 of 144 BD patients with or without neurological involvement and in 4 of 168 controls corresponding to a sensitivity of 47.2% and specificity of 97.6%. Mtch1 antibody positive NBD patients had more attacks, increased disability and lower serum nucleosome levels. Mtch1 antibody might be involved in pathogenic mechanisms of NBD rather than being a coincidental byproduct of autoinflammation. © 2013 Elsevier B.V

Cisplatin, gemcitabine, and treosulfan in relapsed stage IV cutaneous malignant melanoma patients

To evaluate the efficacy of cisplatin, gemcitabine, and treosulfan (CGT) in 91 patients with pretreated relapsed AJCC stage IV cutaneous malignant melanoma. Patients in relapse after first-, second-, or third-line therapy received 40 mg m−2 intravenous (i.v.) cisplatin, 1000 mg m−2 i.v. gemcitabine, and 2500 mg m−2 i.v. treosulfan on days 1 and 8. Cisplatin, gemcitabine, and treosulfan therapy was repeated every 5 weeks until progression of disease occurred. A maximum of 11 CGT cycles (mean, two cycles) was administered per patient. Four patients (4%) showed a partial response; 15 (17%) patients had stable disease; and 72 (79%) patients progressed upon first re-evaluation. Overall survival of all 91 patients was 6 months (2-year survival rate, 7%). Patients with partial remission or stable disease exhibited a median overall survival of 11 months (2-year survival rate, 36%), while patients with disease progression upon first re-evaluation had a median overall survival of 5 months (2-year survival rate, 0%). Treatment with CGT was efficient in one-fifth of the pretreated relapsed stage IV melanoma patients achieving disease stabilisation or partial remission with prolonged but limited survival

BRAFV600E mutations in malignant melanoma are associated with increased expressions of BAALC

<p>Abstract</p> <p>Bachground</p> <p>Activating <it>BRAF </it>mutations are present in approximately 50% of melanomas. Although different downstream target genes of the most common mutant V600E have been identified, the contribution of activating <it>BRAF </it>mutations to malignant transformation needs further clarification.</p> <p>Methods</p> <p>Microarray gene analysis was performed for human melanoma cell lines harboring BRAF^V600Emutations in comparison to cell lines without this mutation.</p> <p>Results</p> <p>This analysis revealed a more than two fold down-regulation of 43 and an increase of 39 gene products. <it>BAALC </it>(<it>Brain and acute Leukaemia, cytoplasmatic</it>) was most prominently regulated, since it was up-regulated in mutated cell lines by a mean of 11.45. Real time PCR analyses with RNA from melanoma cell lines (n = 30) confirmed the <it>BRAF</it>-activation dependent up-regulation of <it>BAALC</it>.</p> <p>Conclusion</p> <p><it>BAALC</it>, which has been associated with cell dedifferentiation and migration, may function as a downstream effector of activating <it>BRAF </it>mutations during melanomagenesis.</p

S1-Guideline Cutaneous Angiosarcomas - Update 2021

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Dacarbazine and interferon α with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG)

In several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon α (IFN-α) only to that of therapy with DTIC and IFN-α with the addition of interleukin 2 (IL-2) in terms of the overall survival time and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m2every 28 days) plus IFN-α2a/b (3 MIU/m2, twice on day 1, once daily from days 2 to 5; 5 MIU/m23 times a week from week 2 to 4) with or without IL-2 (4.5 MIU/m2for 3 hours i.v. on day 3; 9.0 MIU/m2i.v. day 3/4; 4.5 MIU/m2s.c. days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of therapy) for every patient. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treated according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-α as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-α and IL-2. Treatment cessation due to adverse reactions was significantly more common in patients receiving IL-2 (13.9%) than in patients receiving DTIC/IFN-α only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous schedule used for this study, was added to DTIC and IFN-α. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III trials with continuous infusion and higher dosages must be performed before any final conclusions can be drawn on the potential usefulness of IL-2 in biochemotherapy of advanced melanoma. © 2001 Cancer Research Campaign http://www.bjcancer.co

Serologic and immunohistochemical prognostic biomarkers of cutaneous malignancies

Biomarkers are important tools in clinical diagnosis and prognostic classification of various cutaneous malignancies. Besides clinical and histopathological aspects (e.g. anatomic site and type of the primary tumour, tumour size and invasion depth, ulceration, vascular invasion), an increasing variety of molecular markers have been identified, providing the possibility of a more detailed diagnostic and prognostic subgrouping of tumour entities, up to even changing existing classification systems. Recently published gene expression or proteomic profiling data relate to new marker molecules involved in skin cancer pathogenesis, which may, after validation by suitable studies, represent future prognostic or predictive biomarkers in cutaneous malignancies. We, here, give an overview on currently known serologic and newer immunohistochemical biomarker molecules in the most common cutaneous malignancies, malignant melanoma, squamous cell carcinoma and cutaneous lymphoma, particularly emphasizing their prognostic and predictive significance