Biomedical subjects

L Titus-Ernstoff

Publications and source records attributed to L Titus-Ernstoff.

45 records · Page 3Linked to original sources

PubMed1992

Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial.

Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B-lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) gamma and rIFN alpha in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5'-oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5'-oligoadenylate synthetase and dosage of rIFN gamma and rIFN alpha, respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN gamma and rIFN alpha can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN alpha and rIFN gamma might influence T-cell mediated antitumor activity.

2',5'-Oligoadenylate Synthetase↗

PubMed1992

Comparison of nonfamilial and familial melanoma.

There has been concern that individuals with nonfamilial melanoma and dysplastic melanocytic nevi (DMN) are not directly comparable to patients with hereditary melanoma and DMN. Because we have conducted a comprehensive study of nonfamilial melanoma over the past several years, we have addressed the above issue by directly comparing the characteristics of 145 nonfamilial patients, 6 patients with familial melanoma and the information available for familial melanoma in the literature. All 6 patients with familial melanoma had at least one first-degree blood relative with cutaneous melanoma. A large number of clinical and histologic variables were compared for both groups. Some pertinent variables included mean age at melanoma diagnosis 46.7 versus 52.3 years, mean Breslow thickness 2.11 versus 1.54 mm, mean total body nevi per patient 20.6 versus 18.3, mean total clinically atypical nevi per patient 2.0 versus 1.7 and total histologically confirmed DMN per group 22 (18.3%) versus 2 (33%), for patients with nonfamilial versus familial melanoma, respectively. No substantial differences were observed between the two groups. A review of the medical literature failed to reveal any quantitative data for melanocytic nevi, either clinical or histologic, at present that would allow distinction of patients with sporadic versus familial melanoma. We conclude that studies concerning the clinical characteristics of patients with DMN and nonfamilial melanoma are relevant to other persons with DMN including familial melanoma.

Adult↗

PubMed1991

Quantitative DNA analysis of small renal cortical neoplasms.

DNA aneuploidy is common in large renal cortical neoplasms (RCNs), but the incidence in small RCNs is not known. This study was undertaken to investigate whether the traditional 3.0-cm size distinction between small (benign) and large (malignant) tumors might have an objective correlate in the form of abnormal DNA content. Quantitative DNA analysis was performed retrospectively, by image analysis, on 59 RCNs measuring 5.0 cm or less from 30 nephrectomy specimens with solitary tumors and 17 with multiple tumors. DNA indices and the proportion of cells with DNA content greater than that of the G0/G1 population were evaluated with respect to tumor size, stage, and histologic parameters. There was a relationship between the presence of detectable nondiploid stem lines (NDSLs) and tumor size, stage, nuclear grade, and proportion of non-G0/G1 cells, but not histologic pattern. The relationship of NDSLs to tumor size was more apparent in the solitary tumor group, while the relationship of a high proportion of non-G0/G1 cells to tumor size was stronger in the multiple tumor group. Our results show that the incidence of NDSLs increases with tumor size and nuclear grade, and suggest that as RCNs enlarge, the emergence of NDSLs heralds potential biologic aggressiveness. Further, solitary tumors and multiple synchronous tumors may be biologically different in terms of etiologic factors and growth potential.

Adenoma↗

PubMed1991

A relation between childhood sun exposure and dysplastic nevus syndrome among patients with nonfamilial melanoma.

We studied 117 patients with nonfamilial melanoma to determine whether melanoma patients with dysplastic nevus syndrome might be distinguished, on the basis of solar exposure, from melanoma patients without dysplastic nevus syndrome. Study participants were interviewed and received a skin examination, which included a total count of nevi, a standardized assessment of clinically atypical nevi, and the excision of each patient's clinically most atypical nevus. Based on the histologic review of the clinically most atypical nevus, each patient was classified as to whether dysplastic nevus syndrome was present or absent. Childhood sunburn with blistering and childhood recreational sun exposure were found to be associated with dysplastic nevus syndrome. The results suggest that childhood sun exposure increases risk of melanoma by initiating the melanoma precursor syndrome.

Adult↗

PubMed1990

Immunohistochemical phenotyping of malignant melanoma. A procedure whose time has come in pathology practice.

Experience has shown that markers created in research laboratories can be adapted to everyday surgical pathology practice for malignant melanomas. These studies are feasible and readily conducted on frozen tissue as is routinely done in typing of lymphoma. The demonstration of heterogeneity using this monoclonal antibody panel, and other antibodies yet to come, may be important for prognostication. Tumor cell heterogeneity of surface antigens reflects disruption of the tumor cell's patterned gene expression. This should be regarded as an indication of different clones of cells (subsets) with a tumor, whether primary or secondary. It is entirely possible that autologous immune cells can kill or at least restrict the growth of subsets of melanoma cells having certain surface antigenic phenotypes while they are incompetent to handle other subsets. This would enable a particular phenotype within a primary melanoma to survive and escape the immunologic regression known to occur in 3 to 6 percent of these tumors. Such patients may present years later with metastases in the brain, liver, gastrointestinal (GI) tract, or lymph nodes. There are also implications in chemotherapy and chemoimmunotherapy for melanoma in this regard. It could be theorized that these agents may dispose of or restrict the growth of some phenotypes, leaving others in a resistant state. Perhaps the MDR gene is activated. Alternatively a tumor suppressor gene(s) could be absent or inactivated, as in neuroblastoma and carcinoma of the breast and lung. Markers present at the cell membrane surfaces and in the membranes themselves constitute an important field for study in the understanding of tumorigenesis. Many of these markers are present in embryos as early as the 4-to-8-cell stage and in blastocysts. Embryonic antigens in the intercell mass of blastocysts are stage-specific embryonic antigens. They are signals for organ development and the differentiation of cells. At various stages of this development, these markers disappear, especially upon differentiation into tissue types and specific organs. These cell signals are therefore organogenesis markers. Detecting a given antigen is not simple because it may be present but not immunohistochemically detectable because glycosylation, acetylation, phosphorylation, or sulfation have not taken place, or have resulted in a structural conformation not recognized by monoclonal antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Neoplasm↗

PubMed1989

Central values and variation of measured nuclear DNA content in imprints of normal tissues determined by image analysis.

A total of 109 slides derived from 37 normal tissues were analyzed for nuclear DNA content using the Cell Analysis Systems (CAS) model 100 image analysis system with the Quantitative DNA Analysis (QDA) software module in order to determine the central values of DNA content and define normal limits. Analysis of the 109 slides revealed an overall mean measured DNA index of 0.997 with a standard deviation of 0.04. Analysis of replicate samples was essentially constant. There were no differences between samples obtained from autopsy and surgical specimens. Small variations were detected among stain batches, individual patients, and tissue types. These results indicate a high degree of accuracy and reproducibility of DNA content determinations using this system.

Cell Nucleus↗

PubMed1989

Usefulness of frequent skin examination for the early detection of second primary cutaneous melanoma.

This report describes the efficacy of skin examination for the early detection of second primary cutaneous melanomas among patients with nonfamilial melanoma. A series of 121 patients with newly diagnosed first primary cutaneous melanomas participated in a study of melanoma and dysplastic nevi. Of the 121 study participants, six patients were subsequently diagnosed with a second primary melanoma. For five of these patients, frequent skin examinations resulted in the detection of second primaries that were shallower in depth than was the first primary melanoma. In four cases, the second primaries were identified in low-risk growth phases (less than 0.76 mm); three of these low-risk tumors were melanoma in situ.

Humans↗

PubMed1988

Dysplastic nevi in association with multiple primary melanoma.

Risk factors for multiple primary cutaneous melanoma were evaluated in a case-control study. Eight cases of multiple primary melanoma were matched on sex, age, and education to 24 first primary melanoma controls. Risk factors examined in the analysis included pigmentary characteristics, history of sun exposure, and nevi. The importance of histologically dysplastic nevi (DN) and clinically atypical nevi was of particular interest. Single-factor conditional logistic regression analysis showed that first primary melanoma patients with histological DN are at increased risk for a second primary (odds ratio, 6.2; 95% confidence interval, 1.2-33.4). Patients with two or more clinically atypical nevi also have elevated risk for a second primary (odds ratio, 8.8; 95% confidence interval, 1.0-80.7). Two-factor logistic models were used to evaluate the effect of histological DN while controlling singly for all other variables as potential confounders. Odds ratios for the association of histological DN varied from 6.1 to 10.4 when adjusting singly for pigmentary and sun exposure variables. In the two-factor model that included histological and clinical DN, both variables retained marginally significant statistical association with multiple primary melanoma. These results suggest that DN is a marker of increased risk for multiple primary melanoma and suggest that melanoma patients with evidence of DN should be followed closely for the development of additional primaries.

Dysplastic Nevus Syndrome↗

PubMedDate not supplied

Dysplastic nevi in relation to superficial spreading melanoma.

The aim of the present study was to evaluate the frequency with which histologically confirmed dysplastic nevi are observed among patients with superficial spreading melanoma compared to patients with nodular melanoma. A pathology review of 117 new cases of first primary nonfamilial cutaneous melanoma identified 61 patients with superficial spreading melanoma and 19 with nodular melanoma. Study participants received a physician-conducted skin examination which included enumeration of clinically benign and atypical nevi and the surgical excision of the clinically most atypical nevus. Patients' dysplastic nevus status was established by histological review of the clinically most atypical nevus. A comparison based on the tumor subtypes showed that dysplastic nevi occur nearly four times more frequently among patients with a prior diagnosis of superficial spreading melanoma relative to nodular melanoma (odds ratio = 3.6; P = 0.03).

Dysplastic Nevus Syndrome↗