Assessing combinations of cytotoxic agents using leukemia cell lines.

The mainstay of clinical anti-neoplastic chemotherapy is multi-agent combinations, most of which were developed empirically. To speed research and decrease costs, there is increasing interest in moving new drugs into clinical trials in potentially active combinations based upon pre-clinical testing data. Because testing drug combinations in animals is expensive and complex, defining drug combinations initially in cell culture assays is essential.

Evaluation of a computed radiography system for megavoltage photon beam dosimetry.

Computed radiography (CR) systems have been gaining adoption as digital replacements for film for diagnostic and therapy imaging. As a result, film processors are being removed from service, leaving a void for the medical physicists who use film and processors for two-dimensional mega-voltage beam dosimetry. This is the first report to evaluate the ability of a commercial CR reader and storage phosphor plate system to accurately quantitate absolute dose and dose distributions from a 6 MV photon beam.

Assessing growth and response to therapy in murine tumor models.

Rodent models provide an important means of assessing antitumor activity vs toxicity for new cancer therapies. Tumors are often grown subcutaneously on the flank or back of animals, allowing accurate serial determination of tumor volume with calipers by measuring the tumors in three dimensions. The advantages of assessing tumor volume in subcutaneous tumors must be balanced against the potential artifacts induced by growth of tumor cells in subcutaneous tissue.

Evaluating response to antineoplastic drug combinations in tissue culture models.

The mainstay of clinical antineoplastic chemotherapy is multiagent combinations, most of which were developed empirically. Because of the desire to speed research and decrease costs, there is increasing interest in moving new drugs into clinical trials in potentially active combinations based on preclinical testing data. Different mathematical models have been proposed for evaluating drug interactions, which can be classified as synergistic (combinations demonstrating greater than the additive activity expected from each agent alone), additive, or antagonistic (drugs showing less activity in combination than expected from the sum of each agent alone).

DIMSCAN: a microcomputer fluorescence-based cytotoxicity assay for preclinical testing of combination chemotherapy.

DIMSCAN is a semiautomatic fluorescence-based digital image microscopy system that quantifies relative total (using a DNA stain) or viable (using fluorescein diacetate [FDA]) cell numbers in tissue culture multiwell plates ranging from 6 to 384 wells per plate. DIMSCAN is a rapid and efficient tool for conducting in vitro cytotoxicity assays across a 4 log dynamic range. The specificity of detecting viable cells with FDA is achieved by using digital image processing and chemical quenching of fluorescence in nonviable cells with eosin Y.

Living lobar lung transplantation.

A constant awareness of the risk to the living donors must be maintained with any live-donor organ transplantation program, and comprehensive short- and long-term follow-up should be strongly encouraged to maintain the viability of these potentially life-saving programs. There has been no perioperative or long-term mortality following lobectomy for living lobar lung transplantation, and in the authors' series the perioperative risks associated with donor lobectomy are similar to those seen with standard lung resection. These risks might increase if the procedure were offered on an occasional basis and not within a well-established program.

Stenting of the mainstem bronchus in children: a word of caution.

We present two patients with critical hemorrhage following expandable metallic stenting of the left mainstem bronchus in children. Stent migration with erosion into a bronchial artery leading to mycotic pseudoaneurysm formation and overwhelming pulmonary hemorrhage occurred in both patients. One patient died from uncontrollable hemoptysis.

Modulation of pulmonary NA+ pump gene expression during cold storage and reperfusion.

Background: Reperfusion injury with pulmonary edema continues to be a major complication after lung transplantation. Alveolar fluid homeostasis is regulated by Na+/K+-ATPase activity on the basolateral surface of alveolar epithelial cells. Intact Na+/K+-ATPase is essential to the resolution of pulmonary edema.

Sirolimus (rapamycin) potentiates cyclosporine in prevention of acute lung rejection.

Background: Cyclosporine-based immunosuppressive regimens (INN: ciclosporin) in human lung transplantation continue to result in a high incidence of acute cellular rejection. We investigated the use of sirolimus, a macrolide with structural similarity to tacrolimus, as monotherapy and in combination with cyclosporine in a rodent lung transplant model.

Methods: Orthotopic left lung transplantation was performed in Lewis recipients from Brown-Norway donor rats with syngeneic Lewis-to-Lewis controls.