Impedance spectroscopy with field-effect transistor arrays for the analysis of anti-cancer drug action on individual cells.

In this study, impedance spectroscopy measurements of silicon-based open-gate field-effect transistor (FET) devices were utilized to study the adhesion status of cancer cells at a single cell level. We developed a trans-impedance amplifier circuit for the FETs with a higher bandwidth compared to a previously described system. The new system was characterized with a fast lock-in amplifier, which enabled measuring of impedance spectra up to 50 MHz. We studied cellular activities, including cell adhesion and anti-cancer drug induced apoptosis of human embryonic kidney (HEK293) and human lung adenocarcinoma epithelial (H441) cells. A well-known chemotherapeutic drug, topotecan hydrochloride, was used to investigate the effect of this drug to tumor cells cultured on the FET devices. The presence of the drug resulted in a 20% change in the amplitude of the impedance spectra at 200 kHz as a result of the induced apoptosis process. Real-time impedance measurements were performed inside an incubator at a constant frequency. The experimental results can be interpreted with an equivalent electronic circuit to resolve the influence of the system parameters. The developed method could be applied for the analysis of the specificity and efficacy of novel anti-cancer drugs in cancer therapy research on a single cell level in parallelized measurements.

Locoregional approaches to therapy with gliomas as the paradigm.

Most malignant gliomas recur locally, despite the fact that these tumors are usually found to be diffusely infiltrating on pathologic studies. Thus, efforts have concentrated on local disease control as an initial step to improve the prognosis of these patients. This review discusses the most recent studies on locoregional approaches in therapy for this poor-prognosis neoplasm. Emphasis is placed on the radiotherapeutic and combined modality (radiotherapy and chemotherapy) approaches reported during the past year.

Mechanisms of myocardial hypercarbic acidosis during cardiac arrest.

During the global myocardial ischemia of cardiac arrest and during regional myocardial ischemia due to local impairment of coronary blood flow, intramyocardial carbon dioxide tensions (Pmco2) of ischemic myocardium increase to levels exceeding 400 Torr. The mechanism of such myocardial hypercarbic acidosis is as yet incompletely understood, specifically whether these increases in Pmco2 are due to increased oxidative metabolism, decreased CO2 removal, or buffering of metabolic acids. We therefore measured Pmco2 and the total CO2 content of rat hearts harvested before, during, and after resuscitation from cardiac arrest. Pmco2 significantly increased from an average of 63 to 209 Torr during a 4-min interval of untreated ventricular fibrillation. This was associated with concurrent decreases in intracellular pH from an average of 7.03 to 6.02 units. The total CO2 content of the myocardium simultaneously decreased from 17.0 to 16.5 mmol/kg. Accordingly, increases in Pmco2 and [H+] were observed in the absence of increases in the total CO2 content and therefore the calculated myocardial bicarbonate. These observations in the rat model implicate buffering of metabolic acids by bicarbonate rather than increases in CO2 production or decreases in CO2 removal as the predominant mechanism accounting for myocardial hypercarbia.

[Breast cancer: chemotherapy preceding locoregional treatment with extension of the indications for conservative treatment]. / Cancer du sein: chimiothérapie précédant le traitement loco-régional avec extension des indications du traitement conservateur.

About 80 per cent of patients with breast cancer ultimately die of metastatic disease in the following twenty years. Distant metastases are more important as cause of death than loco-regional relapses, it is why adjuvant chemotherapy is necessary, especially in young patients and in those with extensive disease. Initial chemotherapy preceding any locoregional treatment is justified on the basis that both surgery and anesthesia lead to immuno-depression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials of Nissen-Meyer, Bonadonna and Cooper. We have treated 145 patients, including 67 with inflammatory breast cancer (IBC), with 4 to 6 weeks of Velbe, Thiotepa, Methotrexate Fluorouracil and Prednisone with Adriblastine added for those patients with IBC or T greater than 7 cm, or N2 N3. Because of tumor regression of more than 50 per cent observed in 80 per cent of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium) and are in a complete remission in all these cases after curietherapy. Maintenance treatment with the same drugs was prescribed for 6 to 18 months depending on the initial staging. Tumor regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest one being 42 months. The overall survival at 2 years for IBC, is 90 per cent with a disease-free survival of 80 per cent. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.

Clinical activity of detorubicin: a new anthracycline derivative.

The anthracycline derivatives are intercalating drugs which are of major importance in the treatment of leukemias and in the management of solid tumors. Structural analogs have been prepared by semisynthetic modifications in an attempt to extend the spectrum of antitumor activity and to reduce toxicity (acute myelosuppression and cardiotoxicity). This report concerns our preliminary clinical experience in 111 patients who received detorubicin. Two dose schedules were used in acute leukemia patients. Sequential doses were active in acute leukemia relapses but the mucous membrane toxicity was excessive; more recently, intermittent doses proved active in acute leukemia relapses (one 6-mg/kg dose) and in a patient with resistant Burkitt's lymphoma. In non-Hodgkin's lymphomas, a complete response rate of 71% was achieved with an intermittent schedule (3 mg/kg/day X 3 weeks). A remarkable shrinkage of skin involvement was also observed. Detorubicin showed a high activity in mycosis fungoides (five regressions among six patients) and some activity in soft tissue sarcomas, osteosarcomas, and various solid tumors.