Biomedical subjects

T Lampidis

Publications and source records attributed to T Lampidis.

5 recordsLinked to original sources

PubMed2000

Correlation of a unique 220-kDa protein with vitamin D sensitivity in glioma cells.

We have investigated the antitumor and apoptotic effects of 1, 25-dihydroxyvitamin D(3) (VD(3)) in glioma cell lines and in primary cultures derived from surgical specimens from patients. Our results showed that certain glioma cells underwent apoptosis, whereas others were resistant. In an attempt to search for parameters that dictate VD(3) sensitivity, we discovered a unique 220-kDa protein in glioma cells that were sensitive to VD(3). This protein was not a classical vitamin D receptor (VDR), but was recognized by two different anti-VDR monoclonal antibodies. Furthermore, the level of the 220-kDa protein was inversely correlated with the IC(50) of VD(3) in these glioma cells. This 220-kDa protein was also present in frozen brain tumor samples, and the level of expression appeared to correlate with their corresponding primary cultures. Thus, our findings suggest that this 220-kDa protein may play an important role in determining VD(3) sensitivity in malignant glioma.

Apoptosis↗

PubMed1997

Multidrug-resistant gene expression in small-cell lung cancer.

The development of drug resistance can contribute to treatment failure in small-cell lung cancer (SCLC). In this report, we investigate p-glycoprotein-mediated multidrug resistance (MDR) in these patients. Tumor tissue was obtained prior to treatment and at relapse if possible, short-term culture was carried out, and these tumor cells were analyzed for MDR gene expression by slot blot and reverse transcriptase polymerase chain reaction (RT-PCR) and northern blot analysis. Three cell lines were also established from short-term cultures. Twenty-four patients with MDR(-) and seven with MDR +(++) were available for survival analysis. Median survival for MDR (-) patients was 10 months, whereas for MDR +(++) patients it was 2 months. This was statistically significance (p < 0.0007). The presence of MDR1 gene expression also correlated with the lack of response to chemotherapy (p < 0.001). Increased MDR1 gene expression is usually present in patients with more tumor burden at initial diagnosis. Furthermore, loss of MDR1 gene expression can occur in intrinsically MDR(+) SCLC cells after multiple passages in drug-free media. We concluded that increased MDR1 gene expression is present in a small number of SCLC both before and after chemotherapy and usually signifies poor survival and no response to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

Phase II study of homoharringtonine in patients with recurrent primary malignant central nervous system tumors.

A phase II trial of Homoharringtonine (HHT) was performed in 15 patients with recurrent or progressive malignant glioma. The drug was administered at a initial dose of 4 mg/m2/day by continuous 5 day intravenous infusion (3 mg/m2/day x 5 days for heavily pretreated patients). Courses were repeated every 3-4 weeks upon recovery from toxicity. No objective antitumor regressions occurred. Two patients had no change in their CT brain scans for 2-3 months and one patient had stable disease for 6 months. Toxicity was tolerable and included myelosuppression and occasionally mild hypotension. Chemosensitivity testing with HHT and several other chemotherapy drugs was performed in glioma cell lines, including cell lines derived from these patients. The results suggest that HHT is an inactive drug in malignant glioma using this dose schedule.

Adult↗

PubMed1989

Membrane potential differences between adriamycin-sensitive and -resistant cells as measured by flow cytometry.

Using the fluorescent membrane potential probe, 3,3'-dihexyl-oxacarbocyanine (DiOC6(3], we found a 4-fold higher uptake in Adriamycin (ADM)-sensitive versus -resistant Friend leukemia cells (FLC). When sensitive cells were treated in the presence of high potassium (120 mM K+), there was a greater than 80% reduction of DiOC6(3) uptake. Using carbonylcyanide 4-trifluoromethoxy-phenylhydrazone (FCCP), a specific inhibitor of mitochondrial membrane potential, DiOC6(3) accumulation was reduced by less than 30% in these cells. Both results support the conclusion that a greater uptake of DiOC6(3) in ADM-sensitive than in -resistant cells indicates an increased plasma transmembrane potential. Since electronegative plasma membrane potentials are a driving force for the transport of lipophilic positively-charged compounds, differences in membrane potentials between sensitive and multiple drug resistant (MDR) tumor cells could have an important influence on drug accumulation and cytotoxicity. The drugs which our ADM-resistant FLC display multiple drug resistance to are positively charged. In MDR FLC, the calcium channel antagonist, verapamil, has been shown to block the efflux of Rhodamine 123 (Rho 123) and other positively-charged compounds. Since DiOC6(3) is also positively-charged, we used verapamil to investigate its effects on drug uptake. In MDR FLC, verapamil increased DiOC6(3) accumulation by 1.9-fold, whereas in sensitive cells it was increased 1.5-fold. In contrast, verapamil increased the levels of Rho 123 in resistant cells 7.8-fold but lowered them in sensitive cells 1.5-fold. The minimal loss of DiOC6(3) from both sensitive and MDR cells and the above results can best be interpreted as indicating that DiOC6(3) is not transported by the efflux "pump" system but that verapamil induces a plasma membrane potential increase in sensitive and resistant cells that DiOC6(3) is sensitive to. On the other hand, since Rho 123 did appear to be actively effluxed from these resistant cells, the enhancement of this compound by verapamil was more likely due to inhibition of the MDR "pump." How, or whether, plasma membrane potentials and the MDR efflux "pump" are related remains to be investigated. In the resistant cells, verapamil also induced an increase (13-fold) in the accumulation of the electrically neutral fluorescent probe for calcium, INDO-1/AM. However, verapamil had no effect on the efflux of this compound, which was equivalent in both resistant and sensitive cells. Thus, a new effect of verapamil on drug accumulation in MDR cells is identified here.

Animals↗

PubMed1971

Park-Williams number 8 strain of Corynebacterium diphtheriae.

Five clones of the Park-Williams number 8 strain of Corynebacterium diphtheriae, previously maintained in separate laboratories, were examined for their colonial and biochemical properties, for the restriction and modification system which operates to obscure their lysogeny, and for their capacity to produce large amounts of toxin under ordinary laboratory conditions. The phenotypes of their phage, P, produced in strain 603 and C7 (P.603 and P.C7) differ both as to stability to storage in the cold and to inactivation by antiphage serum. Evidence for a high degree of stability in the integration of P prophage in the PW8 genome is presented.

Animals↗