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Biomedical subjects

A J Cochran

Publications and source records attributed to A J Cochran.

At least 109 records · Page 6Linked to original sources

Establishment of an ascitic human melanoma cell line that metastasizes to lung and liver in nude mice.

UCLA-SO-M14, a human melanoma cell line, was cultured for ten passages in vitro. The line was converted to an ascitic form, M14-A, by transplanting M14 into CD-1 nude mice and back into tissue culture. The minimum number of M14-A cells that formed ascites in all mice (within 10-21 days) was 5 X 10(5), and over 80% of such mice developed macroscopic liver metastases. M14-A inoculated subcutaneously formed tumor at the site of injection, but rarely led to the development of metastases. However, when M14-A was inoculated subcutaneously in young mice (1-14 days old), more than 50% developed lung (but not liver) metastases. The reproducibility of the formation of ascites and metastases was confirmed by testing M14-A at various passages. M14-A may be useful as a model for the metastatic process in human melanoma.

Animals↗

Spitz's nevus in a "black" child of mixed ancestry.

The clinical and histologic features of a Spitz's nevus in a "black" child of mixed ancestry are described. The significance and rarity of this condition in phenotypically black individuals is commented upon.

Black People↗

Metastatic cancer to the larynx. Diagnosis and management.

A case of metastatic tumor in the larynx following successful treatment of a breast carcinoma and a colon carcinoma is presented. The lesion was visible by indirect laryngoscopy, and computed tomography of the larynx assisted in delineating the extent of the disease. The separation of primary adenocarcinoma of the larynx from metastases is discussed, as is the identification of the origin of a metastasis where two separate primaries have existed. Other reports of cancer metastatsizing to the larynx are reviewed. Tumor spread to the larynx may be asymptomatic or may result in hoarseness, stridor and/or airway obstruction.

Adenocarcinoma↗

Incidence and type of tumors induced by DMBA carcinogenesis in H-2 congenic strains on a B10 background.

Five congenic strains on B10 background (B10, B10.S, B10.G, B10.BR and B10.A) were investigated for their susceptibility to tumor induction by 9,10 dimethyl-1,2 benzanthracene (DMBA). The DMBA was administered via a stomach tube five times at weekly intervals (total 5 mg). Two types of malignancies predominated: diffuse lymphocytic lymphomas with or without thymic involvement, and epidermal tumors. B10 (H-2b) was the most resistant strain when total tumor incidences were compared. B10.S (H-2s) had the highest incidence of both lymphomas and epithelial tumors and B10.G was significantly more susceptible to thymic lymphomas than B10. In B10.S mice thymic lymphomas were more frequent in males than in females, the reverse being true for tumors of epithelial origin. No correlation between tumor incidence and in vitro NK activity was demonstrated.

9,10-Dimethyl-1,2-benzanthracene↗

Detection of cytoplasmic S-100 protein in primary and metastatic intraocular melanomas.

The authors sought S-100 protein in sections cut from formalin- or glutaraldehyde-fixed, paraffin-embedded tumors from the eye and other sites by an immunoperoxidase technique, using rabbit antibovine S-100 protein antiserum, swine antirabbit serum, a peroxidase-antiperoxidase preparation, and amino-ethylcarbizole as developer. Tissue from 26 intraocular tumors was examined, the pathologic diagnosis being unknown to the investigators at that time that the tests were performed. Thirteen of 16 malignant melanomas of the choroid contained S-100 protein (81%), while only one of seven retinoblastomas contained S-100 protein (14%). One cutaneous malignant melanoma metastatic to the eye contained S-100 protein, while none of three metastatic nonmelanocytic, nonneural tumors contained the protein. These results are similar to our findings with nonocular tumors, in which 56 of 56 cutaneous melanomas contained S-100 protein (100%) and only 1 of 51 nonneural, nonmelanocytic tumors contained S-100 protein (2%). S-100 protein may be useful as a marker for ocular malignant melanoma.

Eye Neoplasms↗

Cloning of human solid tumors in soft agar.

Of 1,014 human solid tumors of various histologic types, 690 (68%) showed evidence of colony formation within 2 to 4 weeks. Tumors which grew particularly well were colon carcinoma (104/175), melanoma (134/155), lung carcinoma (62/85), breast cancer (100/140), ovarian carcinoma (50/67), and sarcoma (72/122). Histologic examination indicated that the colony-forming cells retained functional and morphologic features similar to those of the original tumor. Plating efficiencies varied between 0.01% and 0.2%, and the numbers of colonies observed formed a direct linear correlation with the number of cells plated. Recovery of viable tumor cells was increased when enzymatic tumor dissociation was used rather than a mechanical method. A simplified, supplemented medium resulted in improved cloning efficiencies when compared to previously reported methods (Hamburger and Salmon, 1977 b).

Clone Cells↗

Detection of S-100 protein as an aid to the identification of melanocytic tumors.

We sought S-100 protein in sections prepared from formalin-fixed paraffin-embedded tumor and normal tissues by an immunoperoxidase technique with a rabbit anti-bovine S-100 protein antiserum as first antibody and aminoethyl carbazole as developer. S-100 protein was demonstrated in 56 of 56 cutaneous melanomas, regardless of their primary or metastatic status, and in 35 of 35 nevocytic nevi. The amount of S-100 protein was independent of the degree of melanization of the tumors. Only 1 of 51 non-neural non-melanocytic tumors tested contained S-100 protein. The technique is valuable in confirming the melanocytic nature of primary or metastatic tumors and in detecting small foci of metastatic melanoma in lymph nodes and other tissues. It also seems applicable to research on melanocytic anomalies.

Humans↗

Reaction of the leukocytes of melanoma patients and control donors, including pregnant women, with melanoma- and fetus-derived materials.

Using a one-stage capillary leukocyte migration inhibition assay, we examined peripheral blood leukocytes from 97 patients with malignant melanoma, 194 pregnant women, and 123 non-pregnant donors for their reactivity with materials from fetal and melanomatous tissues. As in previous studies, we found melanoma extracts selectively to inhibit melanoma patients' leukocytes. First-trimester fetal extracts also selectively inhibited melanoma patients' leukocytes, suggesting their cross-reactivity with melanoma-derived antigens. We could not localize the source of the inhibitory materials within the fetuses. We found no evidence that pregnant women were selectively immunized to fetal or melanoma extracts, regardless of their parity or the stage of their pregnancy.

Cell Migration Inhibition↗

Establishment and characterization of human neuroblastoma and ganglioneuroblastoma cell lines.

The establishment in culture and characterization of 4 human neuroblastoma (NB) cell lines and 1 human ganglioneuroblastoma cell line are described. Each cell line fulfilled at least 2 of 4 criteria for malignant or transformed cells: viz., subcultured more than 70 times, high saturation density with absence of contact inhibition, population-doubling time within a range of 10-40 h, and tumour formation in nu/nu mice. Each cell line also fulfilled at least 2 of 3 criteria for neuroblastoma cells: viz., humoral and cell-mediated immune reactivity toward NB-associated cell-surface antigen, intracellular storage and extra-cellular secretion of catecholamines, and characteristic neuroblast and ganglion-cell morphology.

Animals↗

Factors prognostic for survival in patients with malignant melanoma spread to the regional lymph nodes.

To establish clinical and histologic determinants of survival, records of all UCLA patients with resectable melanoma metastatic to the lymph nodes during the years 1954-1976 were reviewed. These 150 patients were treated first with wide excision, lymphadenectomy, and with radiation/chemotherapy and/or additional surgery only if further recurrences developed. None received adjuvant immunotherapy or chemotherapy. In 97 of 139 patients with identified primary tumors, slides of the primary lesion were reviewed. Putative prognostic factors included age, sex, parity, site of primary tumor, presence of satellitosis, clinical status of nodes, histologic characteristics of primary lesion (Clark's level, thickness of tumor, presence/width of ulceration, and number of mitoses/HPF), time from biopsy of primary tumor to lymphadenectomy, and number of positive nodes. kaplan-Meier estimates of survival for the entire group at one, two, five, and ten years were 73, 55, 37, and 33%, respectively. Median follow-up period of survivors was four years. Univariate analyses using the log-rank test showed that thickness of the primary lesion (p less than 0.001), width of ulceration (p = 0.003), absence of ulceration (p = 0.024), and number of positive nodes (p = 0,.033) were prognostic for survival. In multivariate analysis by the Cox procedure, thickness of the primary (p = 0.001) and number of melanoma-containing nodes (p = 0.043) were prognostic for survival. Location of the primary tumor became marginally significant (p = 0.12) in the multrivariate model. These findings demonstrate the prognostic importance of characteristics of both the primary lesion and extent of regional dissemination. Future prospective randomized trials for (adjuvant) therapy of Stage II melanoma should be stratified by these variables.

Adolescent↗

Lymphoid cell lines as indicators of lymphokine generation.

We investigated the migration characteristics of the cells of four human lymphoid lines, normal peripheral blood leucocytes (PBL), and normal mouse splenocytes (MSC). Two lines (QIMR-WIL and Namalwa) were actively migratory, as were the PBL and MSC. Migration was inhibited at low temperatures and reduced by inhibition of glycolysis, oxidative phosphorylation and RNA synthesis. The migration of QIMR-WIL cells, PBL and MSC but not Namalwa was inhibited by lymphokine-containing supernatants from phytohaemagglutinin-pulsed MSC or MSC stimulated by allogenic cells. The inhibitor of migration in the supernatants had properties similar to those of human leucocyte inhibition factor but distinct from those of macrophage inhibition factor. QIMR-WIL and normal human PBL were compared as indicators in an indirect leucocyte migration assay. QIMR-WIL cells were the more sensitive responder cells and are an abundant, stable, and uniform cell population for lymphokine detection.

Animals↗

Tumor-directed immunity in human neuroblastoma.

Tumor-directed immunity was assessed in 29 patients with neuroblastoma (NB). Cell-mediated and humoral immunity were assessed in vitro using the one-stage direct capillary leukocyte migration inhibition test and the indirect, membrane immunofluorescence test, respectively. Leukocytes from 83% of NB patients, 40% of normal children, and 24% of adults were inhibited by NB-derived materials. NB patients' leukocytes reacted as frequently with materials from allogeneic neuroblastomas as with autologous extracts. Sera from 50% of NB patients, 8% of child controls, and 18% of adult controls reacted with allogeneic tissue cultured neuroblastoma cells. Leukocytes from NB patients, control children, and control adults were inhibited at a similar low frequency by extracts of human melanomas and cancers of cervix, colon, and breast. Sera from NB patients and controls reacted infrequently with cultured melanoma cells.

Antibody Formation↗

Adjuvant reactivity predicts survival in patients with "high-risk" primary malignant melanoma treated with systemic BCG. EORTC Malignant Melanoma Cooperative Group Writing Committee.

We report the prognostic importance of strength of reaction to BCG, tumor histology and clinical factors in patients with previously untreated high-risk (Clark, III, IV and V) primary malignant melanoma. One hundred and one such patients receive high-dose BCG (1 x 10(8) viable units) by Heaf gun as an adjuvant to standardized primary surgery according to EORTC Protocol 18741. Univariate analysis of disease-free interval (DFI) indicates that the degree of maximum reaction to BCG (p = 0.0003), Breslow thickness (p = 0.0003) and Clark level (p = 0.002) are highly significant prognostic factors. When a multivariate model using Cox's proportional hazard regression was used for DFI, the degree of maximum reaction to BCG and Breslow thickness were by far the most significant criteria. A prognostic equation wa obtained to predict DFI from maximum BCG reaction and Breslow thickness. From analysis of the "scores" calculated in this way it appears that the two variables act independently. This technique permits the determination of values that are predictive of DFI and discriminate between subgroups of patients with different DFI characteristics (5 groups, p less than 0.0001). This exercise was repeated for survival and similar results were obtained. The degree of a patient's immune reaction to BCG administered therapeutically is of paramount importance in determining the likelihood of survival. This factor and the Breslow thickness can be integrated to produce a mathematical equation which accurately predicts survival for appropriately treated melanoma patients.

Adolescent↗