Search PubMed⌕ Search

Biomedical subjects

R Pincus

Publications and source records attributed to R Pincus.

11 recordsLinked to original sources
PubMed2000

A phase II pilot study of KW-2189 in patients with advanced renal cell carcinoma.

BACKGROUND: KW-2189 is a semi-synthetic, water-soluble analog of duocarmycin B2, a new class of potent antitumor antibiotics produced by streptomyces, with improved in vitro antitumor potency. PATIENTS AND METHODS: Forty patients with pathologically confirmed metastatic renal cell carcinoma were treated in this multicenter, open-label phase II trial. All patients received 0.4 mg/m2 KW-2189 as an i.v. infusion for Cycle I. Cycles were repeated every 5 to 6 weeks with escalations to 0.5 mg/m2 in the absence of significant toxicity or disease progression. RESULTS: No patient had an objective response. The most common drug-related toxicity was hematological-delayed neutropenia and thrombocytopenia, with recovery by week 6. Non-hematologic toxicity consisted of mild to moderate fatigue, nausea and vomiting, and anorexia that was generally manageable. CONCLUSIONS: KW-2189 in this dose and schedule has a predictable safety profile of reversible myelosuppression. No activity in metastatic renal cell carcinoma was demonstrated.

Antibiotics, Antineoplastic↗
PubMed1990

Evidence for impaired mitoxantrone and vinblastine binding in P388 murine leukemia cells with multidrug resistance.

Multidrug resistance is associated with a P170 glycoprotein efflux pump that limits net drug accumulation in resistant cell lines. Other evidence has suggested that diminished net drug uptake in multidrug resistant (MDR) cells is due to decreased drug binding as well. To assess the contribution of binding differences to net drug accumulation and retention in MDR cells, mitoxantrone and vinblastine, two agents commonly associated with the MDR phenotype but with different mechanisms of action and intracellular binding sites, were studied in P388 murine leukemia cells. For both drugs, resistance was associated with a marked reduction in tightly bound drug which can account for the diminished net drug accumulation in this cell line; even at 1 microM vinblastine when the exchangeable component was one-half that of the sensitive cells, the nonexchangeable component was only one-seventh. For mitoxantrone, the exchangeable drug component was greater in resistant cells at low drug levels (1 microM) and similar at high drug levels (10 microM). For vinblastine, the exchangeable drug component was decreased in the resistant cells at 1 microM, but the difference compared to sensitive cells became neglible at 10 microM. The data indicate that diminished net drug uptake in the P388 MDR cell line was associated with a marked decrease in tightly bound, i.e. nonexchangeable, drug fractions for both mitoxantrone and vinblastine. Therefore, alterations in intracellular binding are in important factor in the decreased cellular uptake and retention of drugs in the multidrug resistance phenomenon. The relationship between these changes and the P170 efflux pump requires further clarification.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Membrane protein changes in an L1210 leukemia cell line with a translocation defect in the methotrexate-tetrahydrofolate cofactor transport carrier.

We report on membrane protein changes in an L1210 leukemia cell line with a highly specific defect in the function of the methotrexate (MTX)-tetrahydrofolate cofactor transport carrier. This clonal line, MTXrA, made 100-fold resistant to MTX, was derived in a single step and exhibited stable resistance over 120 generations in the absence of drug. The transport defect was associated with a 10-fold decrease in influx Vmax without a change in influx Km. There was no difference between the MTXrA and parent lines in the levels or affinities of specific cell surface binders for MTX nor in the labeling of the 44-kDa membrane protein upon treatment with the specific affinity label, N-hydroxysuccinimide ester of tritiated MTX. Consistent with impaired carrier function was the observation that trans-stimulation of MTX influx by intracellular 5-formyltetrahydrofolate observed in the parent line was not demonstrated in the MTXrA line. The transport defect was highly specific for the MTX-tetrahydrofolate cofactor transport carrier. Initial uptake rates for 5-fluoro-2'-deoxyuridine and 2-deoxyglucose were unchanged and influx and net transport of alpha-aminoisobutyric acid were, in fact, increased. There was no cross-resistance of this line to phenylalanine mustard or cytosine arabinoside, agents that utilize specific amino acid and nucleoside transport carriers, respectively. SDS-polyacrylamide gel electrophoresis of purified plasma membrane preparations stained with Coomassie Blue revealed several protein differences between the parental and MTXrA lines. Most prominent is a band at approximately 190 kDa which ran with slightly greater mobility than a lesser staining band in the parent line. [3H]Borohydride labeling of cells also identified a distinct protein peak in the MTXrA line at approximately 190 kDa eliminated by prior treatment of cells with neuraminidase. Absence of expression of protein or mRNA related to the multidrug resistance gene as well as lack of cross-resistance to daunorubicin or trimetrexate indicate that this mechanism of resistance to MTX is completely unrelated to the multidrug resistance phenomenon observed with high molecular weight heterocyclic compounds. These data represent the first demonstration of membrane protein differences in a highly resistant L1210 murine leukemia cell line with a marked unique defect in MTX transport which appears to be related to impaired mobility of the tetrahydrofolate-cofactor carrier. Further studies are now required to elucidate the possible role of one or more of these proteins in the transport defect.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1981

Salbutamol infusion for premature labour--the Australian trials experience.

Fourteen clinical trials were conducted in Australia to evaluate the safety and efficacy of salbutamol infusions in the prevention of premature labour. A total of 527 single pregnancies and 36 multiple pregnancies during which this treatment was used were reported sufficiently fully for inclusion in this report. The results suggest that significant prolongation of pregnancy can be achieved in most cases, provided that cervical dilatation is less than 3 cm and that the membranes are intact. If either of these conditions is absent, prolongation of pregnancy is still possible in some cases. The treatment is not without risks, and adequate supervision is essential.

Albuterol↗
PubMed1972

Medical ethics.

Explore the source record for details and available documents.

Australia↗
PubMedDate not supplied

The role of endoscopic sinus surgery in patients with acquired immune deficiency syndrome.

PURPOSE: Increasingly, otolaryngologists are treating patients with acquired immunodeficiency syndrome (AIDS) who suffer from associated sinusitis refractory to medical therapy. Despite this trend, few reports in the literature detail the mode of surgical therapy, pathogens, and outcome in this patient population. Our aim in this study was to describe our experience in treating these patients, with particular attention to surgical outcome and pathogens. PATIENTS AND METHODS: We reviewed our experience with performing sinus surgery in 33 AIDS patients. Endoscopic sinus procedures were performed in 24 patients, while the remaining nine patients underwent nasal antral windows and/or Caldwell-Luc operations. Follow-up information was obtained in 16 of the 24 patients who underwent endoscopic sinus surgery. RESULTS: At an average follow-up time of 16 months, 14 of the endoscopic sinus surgery patients reported improvement from their preoperative condition. Thirty-seven pathogens were identified in 23 patients. A larger percentage of nontraditional pathogens was found in these patients, which suggests a larger role for microbiologic diagnosis and treatment versus empiric therapy. CONCLUSION: Patients with AIDS and chronic sinusitis may benefit from endoscopic sinus procedures.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Hypodermic needles: an unusual tracheobronchial foreign body.

Case reports of foreign bodies in the upper aerodigestive regions and descriptions of the various methods used to retrieve them have been recorded in the medical literature since ancient times. Sharp, penetrating foreign bodies are most dangerous and may cause acute complications if they perforate the air and food passages. Recently, the authors encountered nine cases of hypodermic needles in the tracheobronchial tree. Seven of the nine needles were removed endoscopically without complications and two were expelled by the patients.

Adult↗