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Biomedical subjects

B Zbar

Publications and source records attributed to B Zbar.

At least 181 records · Page 10Linked to original sources
PubMed1989

Retention of chromosome 3 in extrapulmonary small cell cancer shown by molecular and cytogenetic studies.

In small cell lung carcinoma, one of the short arms of chromosome 3 is typically lost. To investigate chromosome 3 in extrapulmonary small cell carcinoma, we used DNA probes that detect restriction-fragment-length polymorphisms at loci on 3p. These probes were used to study DNA extracted from tumors and normal tissues and/or tumor cell lines from five patients with extrapulmonary small cell cancer. Tumor DNA from four of the five patients with extrapulmonary small cell cancer retained heterozygosity at loci on 3p. Cytogenetic studies of the tumor cell lines established from these four patients showed retention of both short arms of chromosome 3. We conclude that the loss of genetic material from 3p observed in small cell lung cancer is not typical in extrapulmonary small cell cancer.

Adult↗
PubMed1989

Genetic changes in human adrenocortical carcinomas.

Recent studies have suggested that loss of heterozygosity at loci on the short arm of human chromosome 11 (11p) may be important in the pathogenesis of benign and malignant adrenal cortical tumors. To test this concept, adrenocortical carcinomas from nine patients and benign adrenal cortical lesions from eight patients were tested for loss of alleles at loci on human chromosomes 11, 13, and 17. All patients with adrenocortical carcinoma whose normal somatic tissues were heterozygous for a locus on chromosome 17p had lost alleles in the tumor. Four of six patients with adrenocortical carcinoma who were heterozygous for one or more alleles on chromosome 11p in normal tissues had lost 11p alleles in the tumor. Three of six patients with adrenocortical carcinoma showed loss of 13q alleles in the tumor. Loss of alleles on chromosomes 11p, 13q, and 17p was observed in primary tumors and metastases but not in adrenocortical adenomas or hyperplastic lesions of the adrenal cortex. One patient with adrenocortical carcinoma had a somatic mutation in the HRAS1 gene in the normal adrenal gland. The consistency of the genetic changes on chromosomes 11p, 13q, and 17p suggests that they are important in the pathogenesis of adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗
PubMed1989

Improved detection of allele loss in renal cell carcinomas after removal of leukocytes by immunologic selection.

We used immunologic selection to remove contaminating leukocytes from primary renal cell carcinomas and to improve detection of chromosome 3p allele loss. Leukocytes were removed from disaggregated renal cell carcinomas by a double-antibody, magnetic bead separation technique. Before immunologic selection, the preparations contained 26% +/- 15% (SD) tumor cells (n = 7); after immunologic selection, the preparations contained 76% +/- 12% tumor cells. The recovery of tumor cells in the purified preparations was about 10%. Detection of allele deletion was facilitated by immunologic selection. This method may be useful in allele deletion analysis of other human solid tumors that are contaminated with host leukocytes and, with appropriate modification, may be applied to tumors that are contaminated with other cell types.

Alleles↗
PubMed1989

Loss of heterozygosity at the c-raf locus in small cell lung carcinoma.

The c-raf-1 oncogene is located at chromosome 3p25, near a region known to be specifically deleted in patients with renal cell carcinoma and small cell lung carcinoma (SCLC). From cytogenetic analyses of SCLC cell lines, we have estimated that one c-raf-1 allele was deleted in approximately 80% of the cases. However, c-raf-1 was generally thought to be distal to the most common deletion in SCLC, 3p14-23. Using restriction site polymorphisms (RFLPs) located within the c-raf-1 locus, we have examined DNA from 84 human lung carcinomas. In an analysis of 11 paired (normal versus tumor) SCLC DNA samples, all five informative cases showed loss of heterozygosity at this locus in the corresponding tumor sample. Analysis of 73 unpaired lung carcinoma DNAs showed that out of 31 non-SCLC samples, 19% were heterozygous for the BglI polymorphism and 25% showed heterozygosity with TaqI. However, all of the 42 SCLC samples were homozygous for both of these RFLPs. This striking loss of heterozygosity at the c-raf-1 locus in SCLC indicates that one allele of c-raf-1 is deleted in SCLC. The kinase activity of the c-raf protein appears to be constitutively activated in these cells. Whether this apparent activation results from genetic or epigenetic events is under investigation.

Carcinoma, Small Cell↗
PubMed1988

Serotherapy of cancer: cellular changes in primary rat mammary carcinomas after infusion of syngeneic sera absorbed with protein A-Sepharose.

Serotherapy and plasma therapy have proved to be effective in the treatment of diverse neoplasms. The mechanisms of the tumoricidal or growth-inhibitory effects are unknown. We previously reported that activation of the alternative pathway of complement in absorbed sera correlated with the presence of anti-tumor activity. Complement components generated during absorption may serve as the initial mediators of cytotoxicity; for example, C5a may function in its role as a chemo-attractant. To further investigate the anti-tumor mechanisms, we undertook a series of sequential histological studies of in vivo changes in tumors following i.v. serotherapy. We found diffuse inflammatory cellular infiltrates in the interstitial compartments of primary mammary carcinomas of rats within 3-4 hr of administration of protein A-Sepharose absorbed syngeneic serum. The number of inflammatory cells was significantly higher in tumors from treated rats: total infiltrating cells (p = 0.002), eosinophils (p = 0.001), neutrophils (p = 0.001), macrophages (p = 0.001), lymphocytes (p = 0.004) and plasma cells (p = 0.001). Also, the mitotic index of tumor cells was significantly lower 4 hr after serotherapy when compared with that of untreated rat tumor cells. C3 in tumor tissue was decreased at 4 hr following serotherapy. Fibrosis was present in tumor nodules with retarded growth 5 weeks after the start of serotherapy. Localization of the infiltrating cells to tumor interstitial compartments prevents direct contact between inflammatory cells and neoplastic cells, making it unlikely that direct cell-cell killing occurs. Indirect cell killing within the tumor bed apparently occurs through several mechanisms involving interactions between serotherapy-initiated humoral mediators and inflammatory cells. The resulting anti-tumor effects include microvascular injury leading to localized ischemia, tumor infarction, and fibroblastic reactions obstructing tumor invasion and growth.

Animals↗
PubMed1987

Tumor cells transfected with the neomycin resistance gene (neo) contain unique genetic markers useful for identification of tumor recurrence and metastasis.

Studies in tumor biology often require techniques to accurately identify tumors or tumor cell lines. Transfection of plasmid DNA into mammalian cells has been shown to introduce unique genetic markers into recipient cells. These unique genetic markers are detected by Southern transfer. To determine the usefulness of such markers for in vivo studies, a bacterial gene, neo, was transfected into mouse and guinea pig tumor cells. Inbred mice and guinea pigs were injected with syngeneic tumor lines marked with neo. DNA extracted from primary and recurrent tumors and metastases was tested for the presence of the characteristic markers. Integration of neo in cell lines was shown to be stable during tumor growth, recurrence and metastasis, and therefore to be useful for identification of tumors growing in vivo.

Animals↗
PubMed1987

Clonality of pulmonary metastases from the bladder 6 subline of the B16 melanoma studied by southern hybridization.

The possible clonal origin of pulmonary metastases from the bladder 6 subline of the B16 melanoma (B16-BL6) was evaluated with the use of the technique of Southern hybridization. Genetic markers were introduced into B16-BL6 cells by the transfection of a plasmid containing a bacterial gene. Genetic markers were detected by hybridizing DNA extracted from tumors with a 32P-labeled bacterial gene. Clones containing unique genetic markers were mixed and injected into the footpads of normal syngeneic C57BL/6 mice. Footpad tumors were amputated when they were 1 cm in diameter. Individual pulmonary metastases were harvested and expanded by implantation in nude mice. Although footpad tumors contained both genetic markers, virtually all (13/15) pulmonary metastases contained single unique genetic markers. Pulmonary metastases of both marker types were identified. Two examples of pulmonary metastases of mixed origin were detected. The Southern hybridization technique was sufficiently sensitive to detect a clone that was present at 5% of the total cell population.

Animals↗
PubMed1987

In vivo immunologic selection of class I major histocompatibility complex gene deletion variants from the B16-BL6 melanoma.

The mechanism by which tumor allografts escape host immunologic attack was investigated. B16-BL6 cells (the bladder 6 subline of the B16 melanoma) (H-2b) were transfected with a gene (Dd) encoding an allogeneic class I major histocompatibility complex antigen. Clones that expressed Dd antigen were injected into the footpads of nonimmune syngeneic mice, syngeneic immune mice, and nude mice. Under conditions of immunologic selection a clone that contained multiple copies of the transfected gene formed variants that lacked the transfected gene. Primary tumors and pulmonary metastases of immunized mice and pulmonary metastases of nonimmunized mice had lost the Dd gene and, in most cases, all of the associated plasmid. In contrast, in immunodeficient nude mice, primary tumors and pulmonary metastases retained the Dd gene and the associated plasmid. Deletion of genes encoding cell surface antigens may be one of the mechanisms by which allogeneic tumors escape immunologic attack.

Animals↗
PubMed1987

Host-clonal interactions in the generation of proviral gene deletion variants.

A nonproducer clone (clone A1) (from a retrovirus-infected guinea pig fibrosarcoma) has been described that under conditions of in vivo immunologic selection forms variants that lack the proviral gene. One trivial explanation for the apparent loss of the provirus from clone A1 is that clone A1 did not originate from a single cell. For evaluation of this possibility, subclones were derived from clone A1 and tested for tumor recurrence in nonimmune and virus-immune animals. Each of four subclones contained the A1 provirus and exhibited specific viral interference; tumor recurrences formed from each of these four subclones lacked the clone A1 provirus. Possible, when heterogeneous populations of retrovirus-infected cells are injected into nonimmune animals, some clones will elicit immunologic responses to retroviral antigens and subject other clones in the population to immunologic selective pressures. For testing this concept, clone A1 was injected in admixture with a producer clone (clone A4) into nonimmune Sewall Wright strain 2 guinea pigs. Tumors formed in nonimmune guinea pigs inoculated with clone A1 in admixture with clone A4 were shown to lack a detectable clone A1 provirus. The results supported the concept that a somatic mutational event (deletion of the proviral gene) occurs during growth of clone A1. When heterogeneous populations of retrovirus-infected cells are injected into animals, host-clonal interactions may occur leading to outgrowth of proviral gene deletion variants. These results supported the notion that interactions between tumor clones and the host can change the dominant clonal type of the tumor and provide a genetic basis for this change.

Animals↗
PubMed1986

In vivo immunologic selection of proviral gene deletion variants from a nonproducer clone.

The mechanism by which tumors recur at sites of injection of retrovirus-infected fibrosarcoma cell lines was investigated. Previously, it was established that tumor recurrences reflect outgrowth of rare cells that lack viral antigens and are susceptible to superinfection with the homologous retrovirus. In the present study clones isolated from a retrovirus-infected cell line were evaluated as precursors for tumor recurrence. Under conditions of in vivo immunologic selection, a clone that contained a single abbreviated copy of the provirus formed variants that lacked the proviral gene. Tumor variants lacking the proviral gene grew progressively in both nonimmune and virus-immune male Sewall Wright strain 2 guinea pigs. Tumor recurrence could be prevented by superinfection of the virus-infected fibrosarcoma cell line or by superinfection of the precursor for tumor recurrence. Cell lines infected with retroviruses varied in frequency of tumor recurrence formation. This model may be useful in analyzing gene deletion as a mechanism of tumor escape from host immunologic attack.

Animals↗
PubMed1986

Serotherapy of primary rat mammary carcinoma: inhibition by ethylenedinitrilotetraacetic acid but not by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid.

We reported inhibition of growth of primary rat mammary carcinomas after infusions of tumor-bearer plasma absorbed with Protein A-Sepharose or inactivated CNBr Sepharose. Absorbed plasmas were depleted of the third component of complement (C3) (other complement components defined similarly) and C5 but not C1, C4, or C2. These results suggested that activation of the alternative pathway of complement might be involved in the observed antitumor effects. To test this concept sera were treated with ethylenedinitrilotetraacetic acid or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid before absorption with Protein A-Sepharose. Ethylenedinitrilotetraacetic acid, by chelating calcium and magnesium, prevents activation of both the alternative and classical complement pathways. [Ethylenebis(oxyethylenenitrilo)]tetraacetic acid, by chelating calcium but not magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. Sera in the presence or absence of chelating agent were absorbed with Protein A-Sepharose twice at room temperature. After absorption calcium was added to the sera. Rats were treated by i.v. injection of sera twice a week for 2 weeks. Measurements of tumor size were made weekly for 5-7 weeks and then tumor weight was determined. Groups were compared both for size of index and total tumors. The results can be summarized as follows: tumor-bearer sera before absorption did not inhibit the growth of rat primary mammary carcinomas; tumor-bearer sera after absorption with Protein A-Sepharose showed significant consumption of C3 and did inhibit tumor growth; tumor-bearer sera absorbed in the presence of ethylenedinitrilotetraacetic acid did not show a decrease in C3 functional activity and did not inhibit tumor growth; tumor-bearer sera absorbed in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid did show a decrease in C3 functional activity and did inhibit tumor growth; sera from normal adult female rats after absorption with Protein A-Sepharose did inhibit tumor growth. The results are consistent with a role for the alternative pathway of complement in the inhibition of growth of rat primary mammary carcinomas observed after treatment with absorbed sera.

Animals↗
PubMed1985

Immunogenicity and immunosensitivity of a guinea pig B-cell leukemia subline lacking cell surface Ia antigens.

L2C is a transplantable B-cell leukemia of strain 2 guinea pigs. Transplantation protection experiments were performed with L2C sublines expressing or lacking cell surface antigens coded for by the I region of the major histocompatibility complex (Ia). A subline (BZ-L2C) that lacked cell surface Ia antigens was immunogenic but relatively resistant to immunological attack. The data suggest that rejection of this B-cell leukemia may be influenced by expression of cell surface Ia antigens.

Animals↗