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Biomedical subjects

V A Levin

Publications and source records attributed to V A Levin.

At least 235 records · Page 13Linked to original sources
PubMedDate not supplied

Radiosensitization of the RIF-1 murine flank tumor by desmethylmisonidazole (Ro 05 9963) during interstitial brachytherapy.

We have investigated the interaction of the nitroimidazole radiosensitizer desmethylmisonidazole (Ro 05 9963) with interstitial radiation using a clonogenic cell assay as the endpoint. Removable I-125 sources were implanted at right angles to the outer surface of globular RIF-1 tumors grown in the flanks of C3H/He mice. Desmethylmisonidazole was administered by continuous intraperitoneal infusion at a rate of 2.7 mg/gm body weight /24 hr. Tumor and serum drug levels were measured by high performance liquid chromatography. Tumor drug levels of 40--100 mugm/gm tumor tissue were achieved consistently. No appreciable cytotoxicity was produced by desmethylmisonidazole alone, but a radiosensitization effect with a dose modifying factor of 1.6 was found.

Animals↗
PubMedDate not supplied

Differentiation of cerebral radiation necrosis from tumor recurrence by [18F]FDG and 82Rb positron emission tomography.

Nine radiation-treated brain tumor patients were studied by positron emission tomography (PET) in an attempt to differentiate tumor recurrence from radiation necrosis. Rubidium-82 was used to define the region of absent or disturbed blood-brain barrier and [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) was used to evaluate the metabolic state of the brain. By comparing glucose utilization in the pathologic region with utilization in the adjacent tissue, a diagnosis of recurrent tumor (increased [18F]FDG accumulation) or necrosis (decreased FDG accumulation) was made. In the seven patients who underwent surgery the PET diagnosis was confirmed by histologic examination of resected tissue. The two patients who did not undergo surgery have had a clinical course consistent with the PET diagnosis of necrosis. Dynamic 82Rb imaging showed that the rate of 82Rb accumulation was greater in tumor than in normal brain. However, this finding alone did not differentiate tumor from necrosis, as some necrotic tissue also showed high rates of 82Rb accumulation, and washout kinetics were similarly nonspecific. The differentiation of radiation necrosis from tumor recurrence is reliably achieved by [18F]FDG PET examination and is aided by information obtained from a 82Rb PET study done immediately prior to the [18F]FDG injection.

Brain↗
PubMedDate not supplied

Characterization of cellular pathways involved in glioblastoma response to the chemotherapeutic agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by gene expression profiling.

The effectiveness of chemotherapy for human cancers is limited by pharmacokinetic parameters such as variation in metabolism and is determined by the cellular response. In this work, we aimed to gain a more holistic understanding of the molecular basis of glioma response to the DNA-alkylating agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by using a systematic approach: we investigated the expression of 588 genes with various cellular functions in a BCNU-resistant glioblastoma cell line and a BCNU-sensitive subline before and after treatment with BCNU. Our gene expression profiling revealed major differences in gene expression between these two cell lines, especially after treatment with BCNU. One striking example was that BCNU decreased the expression of six DNA-repair genes in sensitive but not in resistant cells. In sensitive cells, BCNU treatment resulted in the induction of two MAP kinase genes; this finding suggests that the specific response to BCNU in sensitive cells may involve the Jun kinase signal transduction pathway. After BCNU treatment, marked induction of tumor necrosis factor was detected only in sensitive cells, suggesting that tumor necrosis factor is a mediator of BCNU-induced cell death. Bcl-2 family members were not altered by BCNU in sensitive cells, suggesting that BCNU-induced cell death may be independent of the bcl-2 pathway. Results of the present study demonstrate that gene expression profiling may facilitate identification of cellular pathways associated with specific responses to chemotherapeutic agents and contribute to an understanding of the molecular basis of drug action.

Antineoplastic Agents, Alkylating↗
PubMedDate not supplied

Influence of acidic residues on substrate specificity of oncogene products pp60v-src and p56lck in vitro.

Substrate specificities of two protein tyrosine kinases were compared using nine undecapeptides modeled after human gastrin. Using the proto-oncogene product, p56lck, Vmax decreased with the distance between glutamate and tyrosine, whereas for the oncogene product, pp60v-src there was no relation. For pp60v-src there was a precipitous rise in Km, from 2.9 to 20 mM when glutamate was greater than three residues away from tyrosine. For p56lck, Km was a minimum when glutamate occupied either a position 3 residues, or both positions 3 and 4, N-terminal to tyrosine. An important factor in enzyme recognition of these peptides is glutamate three residues N-terminal to tyrosine.

Amino Acid Sequence↗