Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormalities of chromosome 1 have been reported in a number of solid tumors and hematologic malignancies, indicating that this is a frequent event in neoplasia. Here we report our observations on aberrations of chromosome 1 in malignancies of the uterine cervix. Tumor material obtained from 148 patients with invasive carcinoma of the cervix and two cases of carcinoma in situ (CIS) was analyzed on direct preparations by G-banding. The results showed abnormalities of chromosome 1 to be one of the most common karyotypic changes, with 95% of the patients showing rearrangements of this chromosome. These changes were never seen as the sole abnormality but were always found in association with other chromosomal aberrations. Numerical rearrangements were present in 54% of the cases, with losses of unaltered chromosome 1 predominating. Consistent marker chromosomes included deletions of chromosome 1 at bands q32, p34, q42, p32, and p22, isochromosomes of both the "p" and "q" arms and translocations, particularly on the long arm. Specific regions on both arms of chromosome 1 (1p11-p13 and 1q21-q32) were preferentially overrepresented in changes involving this chromosome. Certain breakpoints were nonrandomly involved in the structural changes, particularly band 1q32 breaks occurring at this site in 88 instances. The presence of chromosome 1 aberrations in the two cases of CIS suggests that rearrangements of this chromosome are not always a secondary change contributing to the progression of the cancer, but also may represent an early cytogenetic event as in neuroblastoma, some leukemias, and myeloproliferative disorders.
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PMID:Chromosome 1 abnormalities in cervical carcinoma. 341 74

In vivo delivery of immunomodulatory genes is a promising strategy for solid tumor vaccination. A drawback is that it necessitates induction of a large effect from transgene expression in a small percentage of tumor cells. Although the B7 family is known to be the most potent of the costimulatory molecules, gene transduction of B7 alone has not been effective in inducing antitumor immunity in nonimmunogenic tumors by ex vivo methods, much less in vivo. We have developed a novel approach where a gene encoding soluble B7-1, a fusion protein of the extracellular domain of murine B7-1 and the Fc portion of human IgG1, is delivered to tumor cells in vivo in the context of an oncolytic replication-competent herpes simplex virus, and the gene product is secreted by tumor cells rather than expressed on the cell surface. Defective herpes simplex virus vectors containing the B7-1-immunoglobulin (B7-1-Ig) fusion transgene (dvB7Ig) were generated using G207 as a helper virus and tested in the poorly immunogenic murine neuroblastoma, Neuro2a, in syngeneic A/J mice. Intraneoplastic inoculation of dvB7Ig/G207 at a low titer successfully inhibited the growth of established s.c. tumors, despite the expression of B7-1-Ig being detected in only 1% or fewer of tumor cells at the inoculation site, and prolonged the survival of mice bearing intracerebral tumors. Immunohistochemistry of dvB7Ig/G207-inoculated tumors revealed a significant increase in CD4+ and CD8+ T-cell infiltration compared with control tumors inoculated with defective vector expressing alkaline phosphatase (dvAP/G207). The antitumor effect of dvB7Ig/G207 was not manifested in athymic mice. In vivo depletion of immune cell subsets in A/J mice further revealed that CD8+ T cells, but not CD4+ T cells, were required. Animals cured of their tumors by dvB7Ig/G207 treatment were protected against rechallenge with a lethal dose of Neuro2a cells but not SaI/N cells. The results demonstrate that the use of soluble B7-1 for immune gene therapy is a potent and clinically applicable means of in situ cancer vaccination.
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PMID:In situ expression of soluble B7-1 in the context of oncolytic herpes simplex virus induces potent antitumor immunity. 1119 54