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G R McLeod

Publications and source records attributed to G R McLeod.

18 recordsLinked to original sources
PubMed1992

Increasing incidence of cutaneous melanoma in Queensland, Australia.

BACKGROUND: Queensland, Australia, had the world's highest incidence rates of invasive cutaneous melanoma in the 1970s. PURPOSE: The purpose of this study was to monitor trends in melanoma incidence in Queensland. METHODS: We studied two time periods in which ascertainment was comparable. RESULTS: In the 7.5 years up to 1987, the incidence of invasive melanoma in Queensland increased by more than one half in women (to 42.89 per 100,000) and more than doubled in men (to 55.81 per 100,000), with the most dramatic increase seen in men over age 50 years. This higher increase in men is a reversal of the previously higher rates in women. In Queensland, cumulative risks of total cutaneous melanoma (in persons aged 0-74 years), including preinvasive melanoma, have increased to one in 14 in men and to one in 17 in women. There were large increases in age-standardized incidence rates of thin lesions (less than 0.75 mm) in both sexes but not of in situ lesions, and there were also increases in thicker lesions, especially on the backs of males. CONCLUSIONS: Although increased awareness and earlier diagnosis appear to have accompanied increased incidence, increased exposure to solar UV radiation during the past 50 years appears to be the most likely explanation for the rise in incidence rates. IMPLICATIONS: A better understanding is needed of the causes of melanoma and of the complex relationships between constitutional factors, ambient UV radiation, and sun-exposure behavior.

Adolescent↗
PubMed1992

Exclusion of the familial melanoma locus (MLM) from the PND/D1S47 and MYCL1 regions of chromosome arm 1p in 7 Australian pedigrees.

Familial melanoma (MLM) is sometimes found associated with the dysplastic nevus syndrome (DNS). Considerable controversy exists over the possible assignment of a cutaneous malignant melanoma/dysplastic nevus gene, designated CMM, to the distal short arm of chromosome 1, linked to the PND and D1S47 loci. To date, no support for linkage of MLM alone to these markers has been found; likewise no study has been able to exclude the entire region between PND and D1S47 from linkage to MLM. We have carried out linkage studies between markers on 1p and MLM in seven Australian kindreds; three of these are the largest reported worldwide. We have been able to exclude localization of an MLM gene from a 40-cM region that spans the interval between D1S47 and PND and extends approximately 15 cM on either side of these markers. In addition, we can exclude a region of about 20 cM around the MYCL1/D1S57 loci.

Atrial Natriuretic Factor↗
PubMed1991

Treatment of advanced malignant melanoma with recombinant interferon alfa-2a in combination with DTIC: long-term follow-up of two phase II studies.

The present studies were designed to examine whether treatment of disseminated melanoma with a combination of recombinant interferon alpha (rIFN alpha-2a) and DTIC may provide better results than either agent alone. Two dose levels of rIFN alpha-2a were examined with the same dose and schedule of DTIC administration. In the first study 76 patients were treated with rIFN alpha-2a (3 x 10(6) IU days 1-3, 9 x 10(6) IU days 4-70 then 9 x 10(6) IU TIW) plus DTIC (i.v. 200 mg/m2, escalating to 800 mg/m2 each 21 d) for 6 months or longer or until failure. Responses were seen in 26% of patients overall (7CR, 13PR) with the highest responses being seen in those assessed as having a good prognosis and in patients with skin and/or lung metastases. It was notable that males showed a better response than females and that patients with metastases in lymph nodes showed low responses. Response rates in 30 patients treated with high-dose rIFN alpha-2a (18 x 10(6) IU days 7-70) were not superior to that seen at the lower dose and was accompanied by significant increase in bone marrow toxicity. The duration of responses appeared longer than expected from responses to DTIC alone and four patients remain progression free at periods in excess of 3 years. Failure in nine of the responders was due to the development of brain metastases which emphasizes the need for additional treatment approaches to treat micrometastases at this site. The results of a randomized control study comparing DTIC alone with DTIC plus 'low' dose rIFN alpha-2a are awaited with interest.

Adolescent↗
PubMed1990

Clinical evaluation of interferons in malignant melanoma.

The evaluation of interferons in the treatment of malignant melanoma has been mainly in the treatment of advanced disease using interferons as the sole agent or in combination with other agents. Studies of the value of interferons as adjuvant therapy in high-risk primary melanoma patients are necessary, but no results have been published to date. Human interferon alpha produces low response rates as a sole agent, but in combination with cimetidine, a 30% response rate has been achieved. Recombinant alpha interferons give responses of 15%-20% in advanced melanomas, and combination with cimetidine does not enhance the response rate. Recombinant alpha interferons have been used in combination with other interferons, cimetidine, monoclonal antibodies, and cytotoxics, with either no or small improvement in response rates. DTIC with recombinant interferon alpha-2a has been shown to produce objective response rates of 26%, with low toxicity and maintenance of quality of life. A randomized trial with DTIC as the sole agent, compared with combination treatment, is being conducted to determine the significance of this finding.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Desmoplastic, neural transforming and neurotropic melanoma: a review of 45 cases.

An analysis of the clinicopathological features of 45 cases of desmoplastic, neural transforming and neurotropic melanoma assessed by a single pathologist are reported. The age range of 27 males and 18 females was 17-88 years. Twenty primary lesions (44%) were on the head and neck and fourteen (31%) were on the trunk. Thirty lesions (67%) were amelanotic. The initial clinical diagnosis was incorrect for 16 patients. Mean thickness was 4.5 mm. Recurrence occurred in 17 patients (38%). Local recurrence has occurred in 12 patients. This was related to a primary where: pathological diagnosis was incorrect; excision was less than 1 cm; the site was on the head and neck; Clarke level was V; and Breslow thickness was greater than 4 mm. Four patients had cranial nerve neuropathies due to recurrent neurotropic melanoma. Four patients are alive with inoperable disease and five have died from disseminated melanoma. These tumours can be difficult to recognize clinically and pathologically, with poor results if not adequately treated primarily. Therefore, the need for surgeons to be aware of this tumour and its clinicopathological features is important. Close follow-up is essential.

Adolescent↗
PubMed1987

Recombinant interferon alfa-2a in advanced malignant melanoma. A phase I-II study in combination with DTIC.

There is a rising incidence of malignant melanoma world-wide and, despite major improvements in its early diagnosis and treatment, the 10-year death rate remains at 20-25%. Evidence that the immune system has a role in the control of melanoma growth has encouraged immunological intervention. The results of phase II trials of recombinant interferon alfa-2a in advanced melanoma justified further studies. A review of trials of various interferons used as sole agents showed an overall objective response rate of 16.3%, one-third of the responses being complete responses of long duration. The use of cimetidine together with recombinant interferon alfa-2a remains controversial. Trials of both beta- and gamma-interferons are incomplete and information on their effect in advanced melanoma is not yet available. Recombinant interferon alfa-2a in combination with chemotherapy is now being used in trials and the early results are encouraging. In a combined series from Brisbane and Newcastle, Australia involving 44 patients treated with recombinant interferon alfa-2a and DTIC, 13 objective responses including 6 complete responses have been obtained. These response rates compare favourably with those of earlier trials using interferon alone. Further work is necessary to determine the best combined dosage and method of administration for optimum immunobiological effect.

Adolescent↗
PubMed1986

Adenovirus replication as an in vitro probe for drug sensitivity in human tumors.

The feasibility of using adenovirus 5 as an in vitro probe for chemosensitivity in short-term cultures of human tumors was evaluated using human melanoma cell lines and primary cultures of melanoma biopsies. A convenient immunoperoxidase method was developed for quantitating viral replication 2 days after infection. Two different approaches were explored: the host cell reactivation assay (HCR) using drug-treated virus; and the viral capacity assay using drug-treated cells. The HCR assay detected sensitivity to 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC) in Mer- (methyl excision repair deficient) cell lines as decreased ability of the cells to replicate MTIC-treated virus. This test should be applicable to DNA-damaging agents and repair-deficient tumors. Adenovirus replicated readily in nonproliferating primary cultures of melanoma biopsies; application of the HCR assays to this material identified one Mer- sample of 11 tested. Herpes viruses were not suitable for use in HCR because herpes simplex virus type 1 failed to distinguish Mer- from Mer+ melanoma cells; and nonproductive infection of MTIC-sensitive lymphoid cells with Epstein-Barr virus yielded an MTIC-resistant cell line. The second assay (viral capacity) involved determination of the inhibition of replication of untreated virus in treated cells. This approach correctly predicted sensitivity to hydroxyurea and deoxyadenosine in melanoma cell lines when compared with clonogenic survival assay. Viral capacity was also inhibited by cytosine arabinoside, fluorouracil, vincristine, adriamycin, 6-mercaptopurine and ionising radiation, and may therefore be useful for detecting sensitivity to a wide range of antitumor agents.

Adenoviridae↗
PubMedDate not supplied

Desmoplastic melanoma: patterns of recurrence.

Desmoplastic melanoma is a rare type of malignant melanoma, recognized since 1971. Other variants of desmoplastic melanoma include neural transforming melanoma and neurotropic melanoma. The pathology and clinical features of 58 patients whose tumor had the features of desmoplastic melanoma, neural transforming melanoma, and neurotropic melanoma, either separately or in combination, were examined to assess patterns of recurrent disease. The tumor was situated on the head and neck in 41% of patients and was amelanotic in 71% of patients. There was an associated superficial melanoma in 48% of patients. There was a combination of the 3 histologic patterns, commonly found in the 1 melanoma. Local recurrence occurred in 29% of patients and malignant cranial neuropathies were documented in 4 patients. Nineteen percent of patients have died from disseminated disease. Neurotropic melanomas had a lower incidence of visceral recurrence. Desmoplastic and neural transforming melanomas had similar rates of local and visceral recurrence. When this specific variant of melanoma is compared with larger series of malignant melanoma in general, they appear to be more advanced locally, with a higher incidence of local recurrence. When considered in relation to the thicker nondesmoplastic melanomas, the survival is no worse and may be more favorable. Surgeons should excise the primary tumor and local recurrences with wide margins and adopt close follow-up. On the head and neck, symptoms and signs relating to trigeminal or facial nerve innervation may herald a developing malignant cranial neuropathy.

Adolescent↗