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Biomedical subjects

M H Greene

Publications and source records attributed to M H Greene.

At least 73 records · Page 4Linked to original sources
PubMed1983

Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU).

We evaluated the risk of acute nonlymphocytic leukemia, acute myelodysplastic syndrome, and preleukemia in 3633 patients with gastrointestinal cancer who were treated in nine randomized clinical trials. Among 2067 patients given semustine (methyl-CCNU) as adjuvant therapy, leukemic disorders developed in 14, whereas only one leukemic disorder (acute nonlymphocytic leukemia) occurred among 1566 patients given other therapies (relative risk = 12.4; 95 per cent confidence interval = 1.7 to 250). The six-year cumulative mean risk (+/- S.E.) of acquiring a leukemic disorder after treatment with semustine was 4.0 +/- 2.2 per cent; the incidence rate was 2.3 cases per 1000 persons per year. Risk increased significantly with time after treatment. The risk of leukemic disorders did not differ according to sex, race, age at treatment, or initial tumor type, nor was it enhanced by concomitant radiotherapy or immunotherapy. In addition, no excess of acute nonlymphocytic leukemia was seen in 44,370 patients treated for gastrointestinal cancer in Connecticut during the period 1935 to 1974, before the advent of nitrosourea chemotherapy. This study provides quantitative evidence that nitrosoureas are leukemogenic in human beings and confirms previous observations that adjuvant chemotherapy with alkylating agents may increase the risk of leukemia.

Acute Disease↗
PubMed1983

The familial occurrence of cutaneous melanoma, intraocular melanoma, and the dysplastic nevus syndrome.

The occurrence of cutaneous melanoma and intraocular melanoma as double primary cancers in the same patient and in different members of the same family has suggested that these two forms of melanoma are etiologically related. It is theoretically possible that the link between these two pigment cell malignancies may be the dysplastic nevus syndrome, and patients with the dysplastic nevus syndrome may have an increased risk of intraocular melanoma and cutaneous melanoma. We studied two new kindreds in which cutaneous melanoma, intraocular melanoma, and the dysplastic nevus syndrome occurred and conducted neuro-ophthalmologic examinations of 26 patients with hereditary cutaneous melanoma or the dysplastic nevus syndrome, or both. In the one family studied in detail, the cutaneous melanoma predisposition came from the paternal bloodline, whereas the intraocular melanoma occurred in the maternal bloodline. The ophthalmologic examinations disclosed neither intraocular melanoma nor suspicious or atypical choroidal nevi. Our limited data suggested that the association of intraocular melanoma with cutaneous melanoma and dysplastic nevus syndrome may be coincidental.

Adult↗
PubMed1983

Dysplastic nevi on the scalp of prepubertal children from melanoma-prone families.

Four prepubertal children, all members of melanoma-prone families, developed pigmented scalp lesions that were diagnosed as dysplastic nevi. In three cases, the scalp lesions were the only evidence that the children were affected by the dysplastic nevus syndrome, a distinctive clinicopathologic entity that identifies persons at increased risk of malignant melanoma. In general, the skin of family members with dysplastic nevus syndrome does not show characteristic lesions until just prior to or with the onset of puberty. The presence of dysplastic nevi on the scalp may permit identification of at least some high-risk family members well prior to puberty. This should facilitate the early implementation of a melanoma prevention program for susceptible individuals and help ensure that melanomas are diagnosed early in their natural history, at a time when they are surgically curable.

Child↗
PubMed1983

Familial cutaneous malignant melanoma: autosomal dominant trait possibly linked to the Rh locus.

Segregation and linkage analyses were undertaken in families with multiple cases of cutaneous malignant melanoma (CMM) and a recently-described melanoma precursor, the dysplastic nevus syndrome (DNS). Clinical and laboratory data, including 23 genetic markers, were collected on 401 members of 14 high-risk kindreds. Pedigree analysis was compatible with an autosomal dominant mode of inheritance for the familial CMM trait. Although a similar model probably applies to the DNS trait as well, segregation analysis could not confirm the presence of a major locus. However, linkage analysis suggested that an autosomal dominant model was appropriate for the DNS, and that a DNS/CMM susceptibility gene may be located on the short arm of chromosome 1, within 30 map units of the Rh locus [maximum logarithm of odds (lod) score = 2.00].

Chromosomes, Human↗
PubMed1983

Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma.

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). A putative role of host-environmental interactions in the etiology of hereditary melanoma has been strengthened by the recent finding that fibroblasts derived from HCMM/DNS patients demonstrated enhanced sensitivity to u.v.-irradiation in vitro. We report here an extension of these studies in which we have examined the in vitro responses to a model environmental carcinogen, 4-nitroquinoline 1-oxide (4NQO), of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. Three of the six HCMM/DNS strains showed enhanced cell killing with sensitivities greater than that of a xeroderma pigmentosum (XP) variant strain but less than those of ataxia telangiectasia and XP Group D cell strains. The inhibition and recovery of de novo DNA synthesis, together with the expression of repair synthesis, following 4NQO exposure appeared to be normal in HCMM/DNS strains, irrespective of their subsequent clonogenic potential. Our data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients.

4-Nitroquinoline-1-oxide↗
PubMed1983

Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin.

A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis.

Adenocarcinoma↗
PubMed1983

Evidence of a treatment dose response in acute nonlymphocytic leukemias which occur after therapy of non-Hodgkin's lymphoma.

We evaluated the occurrence of second cancers among 517 patients with non-Hodgkin's lymphoma (NHL) treated at the National Cancer Institute. Nine cases of acute nonlymphocytic leukemia (ANL) were observed compared to 0.08 cases expected (ratio of observed to expected cases, 105; 95% confidence limits, 48; 199). The excess risk of ANL was 4.1 cases per 1000 patients per year; the cumulative risk of ANL at 10 years was 7.9 +/- 3.2% (S.E.). A case-control study within the NHL cohort revealed that patients treated with both radiation and chemotherapy were at greater risk of ANL than were patients who received single-modality therapy (relative risk, 6.0; p less than 0.05), especially if the therapy included total-body or hemibody radiation. A positive correlation between cumulative radiation dose to the bone marrow and risk of ANL was demonstrated, independent of chemotherapy duration. A similar correlation between chemotherapy dose and risk of ANL was suggested but could not be proven with the available data. An apparent association between ANL risk and indolent NHL histological subtypes was due to the significantly larger amounts of potentially leukemogenic therapy to which these patients were repeatedly exposed. Only one case of ANL occurred among NHL patients whose initial therapy produced a durable complete remission. Our data are compatible with a multistep model of leukemogenesis and also underscore the need for curative NHL treatment regimens which minimize the duration and quantity of therapy required for optimum patient management.

Adult↗
PubMed1982

Acute nonlymphocytic leukemia after therapy with alkylating agents for ovarian cancer: a study of five randomized clinical trials.

We evaluated the occurrence of acute nonlymphocytic leukemia (ANL) among 1399 women with ovarian cancer who were treated in five randomized clinical trials. Of the 1399 women, 998 had been treated with alkylating agents, and among these, 12 cases of ANL were observed; the expected number was 0.11. Ten patients with ANL had received melphalan, and two chlorambucil. ANL was not observed in 401 women who had been treated with surgery or radiation or both, without alkylating agents. The excess risk of ANL that was associated with alkylating-agent therapy was 5.8 cases per 1000 women per year, and the cumulative seven-year risk of ANL among patients who were treated with chemotherapy alone was indistinguishable from that observed in patients receiving both radiation and chemotherapy. A positive correlation between initial drug dose and the risk of ANL was suggested. These data underscore the need to assess other cytotoxic agents and regimens of drug administration to identify those that do not have harmful late effects.

Acute Disease↗
PubMed1982

Intra-abdominal carcinomatosis after prophylactic oophorectomy in ovarian-cancer-prone families.

Prophylactic oophorectomy was performed in 28 female members of 16 families at high risk of ovarian carcinoma. 3 of these women subsequently developed disseminated intra-abdominal malignancy; there was uncertainty about the primary site despite extensive investigation. These tumours were indistinguishable histopathologically from ovarian carcinoma. It would seem that in cancer-prone families the susceptible tissue is not limited to the ovary, but includes other derivatives of the coelomic epithelium, from which primary peritoneal neoplasms may arise.

Abdominal Neoplasms↗
PubMed1982

Abnormal sensitivity to UV-radiation in cultured skin fibroblasts from patients with hereditary cutaneous malignant melanoma and dysplastic nevus syndrome.

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). Although environmental exposures, especially solar UV-irradiation, have been implicated as risk factors in sporadic melanoma, the role of such exposures in the pathogenesis of HCMM is unknown. We have studied the in vitro radiation responses of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. All six HCMM/DNS strains were found to show some degree of enhanced cell killing sensitivity, compared with normal controls, following 254 nm UV-irradiation. The abnormal survival responses appeared to relate to specific characteristics of HCMM/DNS cells since the six strains had essentially normal sensitivity to gamma-radiation. The enhanced photosensitivity was not associated with abnormal patterns in either DNA repair synthesis or UV-induced inhibition and recovery of de novo DNA synthesis. The survival results are consistent with the hypothesis that the genetically determined predisposition to malignant melanoma may directly or indirectly be the consequence of increased susceptibility to UV-induced cellular damage.

Adolescent↗
PubMed1982

Amyl nitrite may alter T lymphocytes in homosexual men.

To evaluate the recent outbreak of Kaposi's sarcoma (KS) and opportunistic infections in homosexual men, clinical, virological, and immunological data on two homosexual men with KS and on fifteen healthy homosexual volunteers were collected. Both KS patients had regularly used amyl or butyl nitrite (AN); they had low helper/suppressor (H/S) T-lymphocyte ratios before chemotherapy and high titres of antibody against cytomegalovirus (CMV). Eight of the fifteen volunteers were regular AN users; seven of the eight had low H/S ratios due to larger than normal numbers of OKT8-positive suppressor cells and smaller numbers of OKT4-positive helper cells. In all eight AN users the fluorescence profile obtained with monoclonal antibody 9.6 (which detects the sheep E-rosette receptor) was bimodal, indicating a subpopulation of T cells with increased receptor density. A similar pattern was observed when OKT8, the antibody which detects cytotoxic suppressor cells, was used. Two of the seven men who did not use AN had abnormal fluorescence with reagent 9.6, and one of these also had a low H/S ratio. CMV-antibody titres were persistently high in fourteen of the fifteen healthy men, but the titres were not related to AN use of T-cell abnormalities. The data suggest that nitrites may be immunosuppressive in the setting of repeated viral antigenic stimulation and may contribute to the high frequency of DS and opportunistic infections in homosexual men.

Adult↗
PubMed1982

Lymphomas and leukemias in the relatives of patients with mycosis fungoides.

Of 526 consecutive patients with cutaneous T-cell lymphomas, 21 had first-degree relatives with lymphoproliferative or hematopoietic malignancies. Twenty-nine such tumors occurred in the 21 kindreds. Hodgkin's disease accounted for one-third of this total, with various leukemias (11 cases), non-Hodgkin's lymphoma (five cases), and multiple myeloma (three cases) comprising the remainder. These data suggest that genetically-determined immunoregulatory abnormalities may represent a shared pathway of oncogenesis in diverse lymphoproliferative and hematopoietic malignancies.

Adolescent↗
PubMed1982

Hairy cell leukemia in three siblings: an apparent HLA-linked disease.

In a sibship of 11 adults the HLA haplotype A1, B7 occurred in four brothers, three of whom developed hairy cell leukemia (HCL) within a seven-year period. While this haplotype does not appear to occur with increased frequency in random cases of HCL, the fact that three cases of this uncommon and unique disorder occurred within one family and affected siblings with a common haplotype strongly suggests a genetic linkage.

Adult↗
PubMed1981

Malignant melanoma in renal-transplant recipients.

14 patients who developed cutaneous malignant melanoma (CMM) after renal transplantation were studied. Histological review of the primary melanomas revealed that all 10 evaluable patients had a precursor naevus from which the CMM arose, 7 of which were dysplastic, and that 13 of the 14 patients had an abnormal host response to the tumour, characterised by absence of the usual lymphocyte/ macrophage infiltrate. These observations suggest that CMM in renal-transplant recipients evolves from precursor naevi in immunosuppressed patients who are unable to mount an appropriate cellular immune response to neoplastic cells. The clinical detection of dysplastic naevi offers an opportunity to identify in advance those immunosuppressed patients who are prone to melanoma and to modify their medical management accordingly.

Adult↗