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Biomedical subjects

S Retsas

Publications and source records attributed to S Retsas.

At least 19 recordsLinked to original sources
PubMed2002

Prognostic factors of cutaneous melanoma and a new staging system proposed by the American Joint Committee on Cancer (AJCC): validation in a cohort of 1284 patients.

This study, involving a cohort of 1284 evaluable patients, validates the American Joint Committee on Cancer (AJCC) proposal for the introduction of ulceration of primary cutaneous melanoma as an independent prognostic factor of survival. In univariate analyses, ulceration (Hazard Ratio (HR) 1.983; P<0.0001; 95% Confidence Intervals (CI) 1.692-2.325) was a predictor of worse overall survival. In multivariate analyses, ulceration (HR 1.302; P=0.022; (95% CI: 1.039-1.633) retained its prognostic significance for survival independent of tumour thickness (HR 1.101; P<0.0001; 95% CI: 1.055-1.150); mitotic activity (HR 1.039; P=0.005; 95% CI: 1.012-1.067); and age (HR 1.009; P=0.006; 95% CI: 1.003-1.016). Ulceration lost its significance in a subgroup analysis of 256 patients with clinically apparent regional lymph node metastases to the number of lymph nodes involved (HR 1.15; P=0.004; 95% CI:1.047-1.263). Ulceration is prognostically significant in the tumour but not the nodal classification of melanoma, with mitotic activity the second most important prognostic factor after tumour thickness.

Adolescent↗
PubMed2002

Overexpression of HER-2 in thick melanoma.

In this study we evaluated the overexpression status of HER-2 and its prognostic significance on survival in patients with thick cutaneous malignant melanoma. The immuno-alkaline phosphatase antigen detection technique was applied to archival diagnostic material from 51 patients with primary lesions measuring >or= 10 mm in Breslow thickness. Eleven additional patients with primary lesions measuring <or= 1 mm were also studied. HER-2 overexpression was evaluated using conventional light microscopy and an automated cellular imaging system (Chromavision Medical System). Fifteen (29.4%) out of 51 patients with thick lesions showed HER-2 overexpression. In contrast, no overexpression was seen in any of the thin lesions. Overexpression of HER-2 in this group of patients was of no prognostic significance for freedom from recurrence or survival when studied using univariate and multivariate analyses. Whilst the incidence of HER-2 overexpression in patients with thick cutaneous primary melanoma is similar to that reported in breast cancer, it was of no prognostic significance for survival in this study. However, further evaluation in larger numbers of patients with the full spectrum of Breslow thickness is clearly indicated.

Alkaline Phosphatase↗
PubMed2002

The CDKN2A tumour suppressor gene: no mutations detected in patients with melanoma and additional unrelated cancers.

Germ-line mutations of the CDKN2A tumour suppressor gene have been reported in association with familial melanoma, sporadic melanoma with multiple primary lesions and also pancreatic cancer. We studied the hypothesis that patients with melanoma and additional unrelated cancers may harbour mutations in the CDKN2A gene. Twenty seven patients with histologically confirmed melanoma who also had additional cancers such as breast, colorectal, lymphoma and other neoplasms were studied. We also examined 17 additional patients, 13 of whom had a first-degree relative with melanoma and four who had two or more primary melanomas. Some patients belonged to more than one of these categories. No mutations of the CDKN2A tumour suppressor gene were detected among patients with melanoma and additional cancers. The previously described Met53Ile CDKN2A mutation located in exon 2 was detected in a female patient with melanoma metastatic to the regional lymph nodes, multiple primary cutaneous lesions, atypical naevi and a first-degree relative with melanoma. The studied cohort is too small for firm conclusions. However, it would appear that melanoma and additional, apparently unrelated, cancers developing in the same individual are likely to be related to a combination of low-risk susceptibility genes and environmental factors.

Adult↗
PubMed2001

Adjuvant therapy of malignant melanoma: is there a choice?

The methodological differences, data interpretation and conclusions of recent studies of adjuvant therapy in high-risk malignant melanoma, are discussed in detail in this communication. Two observations emerge from this analysis:There is as yet no adjuvant treatment that has conclusively been shown to influence overall survival for high-grade primary lesions with or without clinically occult microscopic metastases in regional lymph nodes. With currently available drugs, meaningful benefit is more likely, if adjuvant treatment is administered on development of clinically apparent regional lymph nodes metastases. The paradox of adjuvant therapy being apparently more effective in more advanced stages of the disease is not unique to melanoma and has been observed in other cancers. This paradox can be explained by the notion that currently available treatments will not eradicate the last malignant phenotype. They may, however, anticipate and frustrate the clinical expression of the next episode of disease activity, in a defined period of time.

Antineoplastic Agents↗
PubMed2001

What is the optimal therapy of brain metastases?

The conclusions of a symposium held in London in October 1999 and devoted to the optimal management of brain metastatic disease were: 1. Prognostic factors are: size and number of metastases (and the presence of mass effect); the status of the systemic cancer outside the central nervous system; performance/neurological status; the age of the patient; and the type of cancer. 2. Surgical management of the single, superficially located brain metastasis with symptomatic mass effect is recommended in good performance status patients. Many would follow this routinely by whole brain radiotherapy. 3. Whole brain radiotherapy is often not followed by durable control of the disease and carries morbidity; better management plans are required. In poor prognosis patients the delivery of radiotherapy may not always be indicated. 4. The current literature demonstrates that stereotactic radiosurgery can enhance the likelihood of sterilizing individual brain metastases compared with whole brain radiotherapy alone. 5. The results of questionnaire showed that the histological diagnosis and latency to onset made little difference to the opinion of neuroscience clinicians, who generally favoured stereotactic radiation therapy over whole brain radiotherapy (with or without a conventionally delivered boost) for all patients with less than four metastases. The opinions of oncologists differed. For bronchial and breast cancer patients, whole brain radiotherapy, with or without a boost, was favoured by the majority, particularly in oat cell cancer. However, with a long latency to 'isolated' brain metastasis, oncologists favoured focal radiation therapy. There was a strong preference amongst oncology experts to reserve stereotactic radiation therapy for apparently isolated brain metastasis; this opinion applied to bronchus and breast cancer, and also to melanoma. 6. Whole brain radiotherapy followed by positron emission tomography scanning to determine what viable metastatic disease remained (and potentially treatable by stereotactic/focal technology) was favoured by most of delegates who answered this question.

Brain Neoplasms↗
PubMed2001

Serum S100beta protein as a marker of disease activity in patients with malignant melanoma.

The purpose of the study was to evaluate serum S100beta protein as a marker of disease activity in patients with malignant melanoma (MM) and compare it with serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). One hundred sixty-four patients with MM, stages I-IV according to the American Joint Committee on Cancer (AJCC), were studied. Recurrent disease was categorized as active (AD) if metastases were evident clinically or with imaging investigations and inactive (ID) if no metastases were apparent at the time of sample collection. The sensitivity and specificity of S100beta, LDH, and ALP for discrimination between AD and ID were calculated using receiver-operating characteristic curve (ROC) analysis. Serum S100beta, LDH, and ALP concentrations were significantly higher in AD compared to ID. Serum S100beta protein was the best discriminator between AD and ID, the areas under the ROC curve being 0.89, 0.71, and 0.70 for S100beta, LDH, and ALP, respectively. Serum S100beta and LDH levels (both p < 0.0001) and serum ALP levels (p = 0.0014) corresponded with the number of metastatic sites involved. Using a cutoff point of 0.20 microg/L for serum S100beta protein, a specificity of 93% with a sensitivity of 68% was obtained for AD in MM. In stage IV disease, S100 was an independent predictor of survival in univariate (p = 0.001; hazard ratio = 1.0156) and multivariate (p = 0.038; hazard ratio = 1.0108) analyses. Serum S100beta protein is a better indicator of disease activity in MM than LDH or ALP and is an independent predictor of survival in stage IV disease.

Adult↗
PubMed2000

In vitro cytotoxicity of norviburtinal and isopinnatal from Kigelia pinnata against cancer cell lines.

Crude dichloromethane extracts of Kigelia pinnata stem bark and fruit showed cytotoxic activity in vitro against cultured melanoma and other cancer cell lines using the Sulphorhodamine B assay, which was used for bioassay-guided fractionation. Thin layer chromatography (TLC) examination of the most active fractions of both stem bark and fruits showed the presence of the same major components which were found to be norviburtinal and beta-sitosterol. Norviburtinal was found to be the most active compound but had little selectivity for melanoma cell lines whilst isopinnatal also showed some cytotoxic activity. beta-Sitosterol was found to be comparatively inactive. HPLC analysis of the crude extract showed that the amount of norviburtinal present in the plant material did not account for all of the activity of the total extracts.

Anthraquinones↗
PubMed2000

Oxaliplatin is active in vitro against human melanoma cell lines: comparison with cisplatin and carboplatin.

We have previously confirmed the in vitro activity of cisplatin and carboplatin against human melanoma cell lines. Both drugs are important components in the chemotherapy used in our service for advanced metastatic melanoma. In this communication we report the in vitro activity of oxaliplatin against human melanoma cell lines in comparison with cisplatin and carboplatin. Oxaliplatin was found to be active against C32 and G361 cell lines with IC50 values of 49.48 and 9.07 microM (1 h exposure), 9.47 and 1.30 microM (4 h exposure), and 0.98 and 0.14 microM (24 h exposure), respectively. The cytotoxic activity of oxaliplatin in this in vitro system appears to be significantly superior to that of carboplatin. Its activity becomes comparatively closer to that of cisplatin as exposure time increases. Indeed at a 24 h exposure oxaliplatin appears to be significantly more active than cisplatin against the G361 cell line (p=0.0343). Oxaliplatin merits evaluation in the clinic both as a single agent and in combination with other drugs active against melanoma.

Antineoplastic Agents↗
PubMed2000

Melanoma and additional primary cancers.

The aim of this study was to examine the occurrence of additional, unrelated primary cancers in patients with melanoma. Data from the hospital-based, melanoma registry of a specialist unit (the Melanoma Unit at Charing Cross Hospital, London, UK) were compared with the incidence rates in a population-based cancer registry (the Thames Cancer Registry). In total, 2076 patients with the histological diagnosis of melanoma established between 1960 and 1997 who were registered with the Melanoma Unit at Charing Cross Hospital, were included in the study. Patterns in time and in the tumour type of the additional cancers were analysed in the cohort. The relative risk of subsequent cancers was evaluated, the number of expected cancers being calculated by applying incidence rates in the population of south-east England to the person-years of follow-up in the cohort. Sixty-six (3%) of the 2076 evaluable patients had a history of, or developed, 69 histologically verified additional cancers, the commonest being colorectal, breast and lymphoma. Twenty-six additional cancers preceded the diagnosis of melanoma by 1-42 years, 16 were diagnosed within 12 months and 27 followed the diagnosis of melanoma, 1-28 years later. Seven cancers occurred after chemotherapy for metastatic melanoma: two colorectal, one bladder, one renal, two myelodysplasias and one acute myeloid leukaemia. The relative risk of additional cancers developing after the diagnosis of melanoma during the 8537 evaluable years-at-risk was 0.64 (95% confidence interval 0.41-0.96; P = 0.0006). Thus, the risk of additional cancers following treatment for metastatic melanoma in this cohort is small. The potential influence of other factors on the occurrence of additional cancers observed overall in this study requires further investigation.

Adolescent↗
PubMed1999

Detection of tyrosinase mRNA by RT-PCR in the peripheral blood of patients with advanced metastatic melanoma.

Detection of melanoma cells in the peripheral blood has been facilitated by the reverse transcriptase-polymerase chain reaction (RT-PCR), but their presence is of uncertain importance in the evolution of the disease. We studied the detection of melanoma cells using RT-PCR in the peripheral blood of 21 patients, four with regional lymph node metastases (American Joint Committee on Cancer [AJCC] stage III) and 17 with disseminated disease (AJCC stage IV). RNA was extracted from 10 ml of heparinized blood following density gradient centrifugation and converted into cDNA for PCR analysis. Assay sensitivity of 10 cells in 10(7) mononuclear cells and granulocytes obtained from 10 ml of peripheral blood was achieved using the G361 and C32 melanoma cell lines. Tyrosinase mRNA was not detected in control samples from healthy volunteers or patients with non-malignant disease. Six patients (one stage III, five stage IV) tested positive for tyrosinase mRNA (28.6%); with one exception, all patients were receiving chemotherapy at the time of sampling. Of the six positive results, three were from patients who initially tested negative but were subsequently positive after a 3-4 week interval. The low detection rates of melanoma cells in the peripheral blood of patients with widely disseminated disease is consistent with recent reports and correlates poorly with the clinical stage of melanoma. This may be partly explained by the clinically observed intermittent and random evolution of melanoma metastases.

Adult↗
PubMed1997

In vitro synergy of paclitaxel (Taxol) and vinorelbine (navelbine) against human melanoma cell lines.

Paclitaxel (PTXL) (Taxol), a taxane, and vinorelbine (VRB), a semisynthetic vinca alkaloid drug, have tubulin as their common intracellular target, but inhibit growth by binding to different sites. We evaluated in vitro the antiproliferative activity of these two drugs as single agents and in combination, against two human melanoma cell lines, G361 and StM111a. The SRB (sulphorhodamine B) assay was used to determine growth inhibition. Possible drug-drug interaction at the cellular level was assessed by constructing Isoboles (Isobologram analysis) and applying the concept of an 'envelope of additivity'. Both agents were active in the nanomolar range at clinically achievable concentrations. The mean IC50 for G361 was 46.6 nM (PTXL) and 19.9 nM (VRB) after a 1 h drug exposure. Mean IC50 (1 h) for StM111a was 9.7 nM (PTXL) and 26.9 nM (VRB). Isobole analysis at the isoeffect levels of 25%, 50% and 75% indicated that drug interaction was predominantly synergistic (supra-additive) when paclitaxel and VRB were added concurrently for 1 h to cultures of StM11 1a or G361. In some experiments, this synergy was observed with particularly low concentrations of paclitaxel (3 nM) and VRB (0.01 nM). A new points were located within the envelope of additivity or in the subadditive (antagonism) region of the isobole. An overall synergy was also found if the data were analysed by the median effect analysis. The effect of these agents on the cytoskeleton and ultrastructure were studied with immunofluorescence and electron microscopy, respectively. These results confirm the in vitro inhibitory activity of paclitaxel and VRB against malignant melanoma, but more importantly the two drugs appear to act synergistically at relatively low concentrations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Systemic treatment of malignant melanoma: grade is as important as stage.

The prognosis of malignant melanoma relates to the biological profile of the tumour and is independent of the magnitude of surgery on the offending primary lesion. The optimal management of this cancer throughout its evolution depends on the appraisal of its metastatic potential. With better understanding of the natural history of the disease and improvements in the therapeutic ratio of currently available drugs, systemic treatment of high risk melanoma in the adjuvant context and before dissemination is emerging as a therapeutic priority. There is now evidence from recently published, controlled studies with long follow up that this approach can prolong relapse-free and overall survival.

Aged↗