PubMed Health⌕ Search

Biomedical subjects

V Israel

Publications and source records attributed to V Israel.

15 recordsLinked to original sources
PubMed2001

Twice-weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non-small-cell lung cancer: a California Cancer Consortium phase II trial.

PURPOSE: Recent studies have suggested the superiority of concurrent chemoradiotherapy and the efficacy of paclitaxel/carboplatin in advanced non-small-cell lung cancer (NSCLC). In view of those results, we sought to examine the safety and efficacy of administration of radiosensitizing paclitaxel twice weekly and carboplatin weekly with concurrent thoracic radiation therapy (XRT) followed by consolidation paclitaxel and carboplatin for stage III NSCLC in a multi-institutional phase II trial. PATIENTS AND METHODS: Induction chemoradiotherapy consisted of paclitaxel 30 mg/m2 delivered intravenously (IV) for 1 hour twice weekly for 6 weeks, carboplatin at a dose based on an area under the concentration-time curve (AUC) of 1.5 mg/mL x min, given IV once weekly for 6 weeks, and concomitant XRT of 1.8 to 2.0 Gy daily for a total of 61 Gy. Patients who achieved a complete response, partial response, or stable disease received two 21-day cycles of consolidation chemotherapy consisting of paclitaxel 200 mg/m2 IV for 3 hours and carboplatin at a dose based on an AUC of 6 mg/mL x min. RESULTS: Thirty-four patients were eligible. Their median age was 62 years (range, 39 to 73 years), 59% were female, 41% were male, 94% had a performance status of 0 or 1, 38% had stage IIIA NSCLC, and 62% had stage IIIB NSCLC. Common grade III and IV toxicities during the induction chemoradiation phase included esophagitis (38%) and neutropenia (12%). The most common adverse reaction during consolidation chemotherapy was grade III neutropenia in five patients (15%). The overall response rate was 71%, which was achieved in the induction phase. The median follow-up was 20 months, the median survival was 17 months, and 2-year actuarial survival rate was 40% (95% confidence interval, 20% to 65%). CONCLUSION: This regimen is tolerable and results are promising. We recommend further evaluation of this regimen in a phase III trial.

Adult↗
PubMed2001

Activity of high-dose toremifene plus cisplatin in platinum-treated non-small-cell lung cancer: a phase II California Cancer Consortium Trial.

PURPOSE: Although cisplatin is an important agent in non-small-cell lung cancer (NSCLC), de novo resistance is common and acquired resistance emerges rapidly during therapy. Proposed mediators of platinum resistance include the protein kinase C (PKC) signal transduction pathway and associated c-FOS overexpression. While estrogen administration has been reported to upregulate PKC and c-FOS expression, the triphenylethylenes tamoxifen and toremifene potentiate platinum cytotoxicity by inhibition of PKC. Downregulation of c-FOS expression has been reported to result from PKC inhibition. In view of these findings, we hypothesized that toremifene would reverse platinum resistance and that this interaction would be influenced by tumor estrogen receptor (ER) status. MATERIALS AND METHODS: A phase II trial of high-dose toremifene (600 mg orally daily on days 1-7) plus cisplatin (50 mg/m2 intravenously on days 4 and 11) every 28 days in NSCLC patients was conducted. A group of 30 patients with metastatic NSCLC who had been previously treated with platinum-based therapy were enrolled. RESULTS: All of the 30 patients were assessable for toxicity and 28 for tumor response. Therapy was well tolerated with minimal hematologic and non-hematologic toxicity. Common toxicity criteria grade 3 hematologic toxicity was seen in only three patients. Five patients achieved a partial response for an overall response rate of 18% (95% CI 6-37). Median overall survival was 8.1 months (95% CI 5.4-17). To assess PKC, ER, and c-Fos expression by immunohistochemistry, 12 informative pretreatment patient tumor specimens were obtained. Four patient tumor specimens were positive for one or both PKC isoforms (alpha and epsilon) while c-Fos was overexpressed in three. None of the responding patient tumors exhibited c-FOS or PKC-epsilon overexpression. ER expression was found to be infrequent (8%), contrasting with previous reports in this tumor type. CONCLUSION: While this phase II study indicates that high-dose toremifene plus cisplatin is feasible, active, and well tolerated in NSCLC patients previously treated with platinum compounds, the mechanism of action remains unclear. Further study of this regimen is warranted.

Adult↗
PubMed1999

MDR1 gene expression in primary and advanced breast cancer.

P-glycoprotein (Pgp)-associated multidrug resistance (MDR) is related to intrinsic and acquired cross resistance to anthracyclines, vinca alkaloids, and other antineoplastic antibiotics. Expression of MDR1 is widely considered to play an important role in conferring resistance to adjuvant chemotherapy in women with breast tumor cells in women with disseminated disease, although data supporting this view is, at best, conflicting. The expression of MDR1 gene and its gene product, P-glycoprotein, was investigated in primary and advanced breast cancers (both previously untreated and previously treated on specific treatment protocols) to assess the role of P-glycoprotein in determining responsiveness to adjuvant chemotherapy. Expression was assessed by immunohistochemistry, reverse transcription-PCR (RT-PCR), Northern Blot and Western Blot. MDR1 mRNA was detected in 40% of the breast cancers tested by RT-PCR with 40 cycles of PCR amplification. When reducing the PCR amplification cycles to 28, the MDR1 gene expression signal disappeared from breast cancers of the highest expressers; however, known MDR1 positive control normal tissues, such as adrenal, kidney, and liver continued to show an expression product. Western and Northern blots failed to demonstrate the MDR1 gene product, P-glycoprotein, in these breast cancers. In contrast, physiologic levels of P-glycoprotein was clearly detected in normal adrenal, kidney, and liver by these techniques. Immunohistochemistry confirmed that breast carcinoma cells lacked P-glycoprotein expression; however, interstitial mononuclear cells, morphologically consistent with lymphocytes or macrophages did show immunostaining in some of these breast tumors. MDR1 gene expression identified by RT-PCR was not correlated either with response to paclitaxel therapy (29 patients able to be evaluated, p = 0.34, Fisher Exact Test) or overall survival (32 breast cancer patients with clinical follow-up information, p = 0.336, log rank). In conclusion, P-glycoprotein was not expressed in breast carcinoma cells at significant levels, although it was expressed in stomal lymphocytes or macrophages. These results suggest that P-glycoprotein does not play a significant role in multidrug resistance of breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 3-hour infusion was combined with carboplatin in a phase I/II study directed to patients with non-small cell lung cancer. Carboplatin was given at a fixed target area under the concentration-time curve of 6.0 by the Calvert formula, whereas paclitaxel was escalated in patient cohorts from 150 mg/m2 (dose level I) to 175, 200, 225, and 250 mg/m2. The 225 mg/m2 level was expanded for the phase II study since the highest level achieved (250 mg/m2) required modification because of nonhematologic toxicities (arthralgia and sensory neuropathy). Therapeutic effects were noted at all dose levels, with objective responses in 17 (two complete and 15 partial regressions) of 41 previously untreated patients. Toxicities were compared with a cohort of patients in a phase I trial of paclitaxel alone at identical dose levels. Carboplatin did not appear to add to the hematologic toxicities observed, and the paclitaxel/carboplatin combination could be dosed every 3 weeks.

Adult↗
PubMed1980

Uterine and renal renin release after ligation of the uterine arteries in the pregnant rabbit.

Uteroplacental ischemia is associated with uterine renin release in pregnant nephrectomized rabbits. In the present study, uterine and renal renin release after uteroplacental ischemia were investigated in 10 Australian white rabbits at 24 to 28 days' gestation. Pentobarbital was administered, and both uterine arteries were ligated close to their origins. Blood samples were taken for plasma renin activity (PRA) determinations from the femoral artery, uterine vein, and right renal vein before ligation and at 30 and 60 minutes after ligation. Mean arterial blood pressure (MAP) was monitored throughout. In five additional pregnant rabbits renal blood flow (RBF) was measured with an electromagnetic flowmeter. The preligation uterine vein-artery PRA difference was not significant (1.9 +/- 1.1 ng/ml/hr). Postligation uterine vein-artery PRA was 11.4 +/- 3.2 at 30 minutes and 6.6 +/- 1.9 ng/ml/hr at 90 minutes (p less than 0.02). Preligation renal vein-artery PRA was 32.3 +/- 10.5 ng/ml/hr (p less than 0.02) and did not change significantly after ligation. MAP remained stable and RBF was unchanged after uterine artery ligation. These observations confirm the finding that the kidney is the primary source of renin in the normal pregnant rabbit and demonstrate that following acute uteroplacental ischemia there is significant uterine renin release even when the kidneys are intact.

Animals↗
PubMed1978

A model for the adsorption of phage P22 to Salmonella typhimurium.

A new model for the adsorption of bacteriophage P22 to its host Salmonella typhimurium is proposed. The main feature of this model is that only three of the six tail proteins found on the mature phage function during adsorption. This model explains why there is a difference in the specific endoglycosidase activity of the tail protein of mature virions as opposed to unattached tail protein. It also accounts for the cubic relationship between p.f.u. and tail protein concentration in in vitro assembly experiments.

Adsorption↗
PubMed1977

E proteins of bacteriophage P22. I. Identification and ejection from wild-type and defective particles.

Of the nine proteins found in the virion of phage P22, four are ejected into the cell after adsorption. The four ejected proteins, termed E proteins, are gp16, gp20, gp26, and gp7. This was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of radioactively labeled phage that had been adsorbed to cells and then eluted off the surface with distilled water. Phage particles that lack gp7 (7- particles) or gp20 (20- particles) successfully eject all their E proteins. The 16- particles do not eject gp7. Analysis of phage ghosts showed that they lack gp16, gp20, and gp7, but they have gp26 in close to normal quantities. Our results suggest roles for gp16 and gp26 in DNA and E protein ejection. All four E proteins are possible candidates for roles in helping the phage DNA cross the plasma membrane.

Adsorption↗
PubMed1976

Sonic fragility of the head-tail bond of bacteriophage P22.

The binding of tail parts to the head of phage P22 is normally irreversible, but after adsorption to host cells sonication releases many of the tail parts intact. This release is dependent on the power of sonication, but is independent of the length of sonication from 2 to 32 s. This phenomenon has been used to show that the upper limit of the number of P22 particles that can bind to a cell is no lower than 700.

Adsorption↗
PubMed1976

Role of the bacteriophage P22 tail in the early stages of infection.

The initial binding of phage P22 to its host, Salmonella typhimurium, is dependent in a linear fashion on the number of tail parts per phage head. (The normal head has six.) There is also a later step which depends on tail parts. This step must occur some time after hydrolysis of the O antigen has been initiated and before ejection of phage DNA from the head is complete. This step causes PFU to depend on approximately the third power of the number of tail parts per head.

Adsorption↗
PubMed1972

Binding of bacteriophage P22 tail parts to cells.

Purified base-plate parts of bacteriophage P22 can bind to the host cell, Salmonella typhimurium. Although the reaction is reversible, a stable equilibrium is not formed between bound and unbound base-plate parts. This is because the binding sites on the cell, presumably the O antigens, are destroyed. The destruction of binding sites does not kill the cells, and, in fact, the binding sites are soon regenerated. The site-destroying activity reacts with P22 heads to make active phage and with antiserum made against purified phage. Therefore site-destroying activity is a characteristic of the base-plate parts and not some contaminant of the preparation.

Adsorption↗
PubMed1972

New deoxyribonuclease activity after bacteriophage P22 infection.

Extracts from P22-infected and uninfected cultures of Salmonella typhimurium were subjected to deoxyribonucleic acid (DNA)-cellulose and diethylaminoethyl-cellulose chromatography. Comparison of the elution patterns revealed that in infected cells there is a decrease in the amount of nuclease activity specific for denatured DNA and an increase in the amount of nuclease activity specific for native DNA. The latter activity was shown to differ from a similar host enzyme in Mg(2+), Mn(2+), and pH optima. This new activity is not found after infection of a lysogen with a nonvirulent phage or after infection under nonpermissive conditions with P22ts25.1 (a mutant in gene 25 that carries out no known functions other than adsorption and injection) and thus appears to be specified by the phage genome.

Ammonium Sulfate↗
PubMed1972

Inhibitory effect of bacteriophage P22 infection on host cell deoxyribonuclease activity.

Infection of Salmonella typhimurium with phage P22 causes a decrease in the activity of host deoxyribonuclease which degrades single-stranded deoxyribonucleic acid (DNA). This decrease is reversed when the infecting phage is P22c(+); it is not reversed if the infecting phage kills the cell. The decrease does not occur in infections with P22ts25.1 (which only adsorbs and injects DNA) or in infections of a lysogen by a nonvirulent phage. It does occur, however, after infections with other phages which are blocked in phage DNA synthesis. Inhibiting protein synthesis with chloramphenicol does not in itself cause the decrease in uninfected cells, but it does prevent infected cells from showing this effect.

Chloramphenicol↗