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Biomedical subjects

J Balog

Publications and source records attributed to J Balog.

10 recordsLinked to original sources

Tomotherapy.

Tomotherapy is delivery of intensity-modulated, rotational radiation therapy using a fan-beam delivery. The NOMOS (Sewickley, PA) Peacock system is an example of sequential (or serial) tomotherapy that uses a fast-moving, actuator-driven multileaf collimator attached to a conventional C-arm gantry to modulate the beam intensity. In helical tomotherapy, the patient is continuously translated through a ring gantry as the fan beam rotates. The beam delivery geometry is similar to that of helical computed tomography (CT) and requires the use of slip rings to transmit power and data. A ring gantry provides a stable and accurate platform to perform tomographic verification using an unmodulated megavoltage beam. Moreover, megavoltage tomograms have adequate tissue contrast and resolution to provide setup verification. Assuming only translational and rotational offset errors, it is also possible to determine the offsets directly from tomographic projections, avoiding the time-consuming image reconstruction operation. The offsets can be used to modify the leaf delivery pattern to match the beam to the patient's anatomy on each day of a course of treatment. If tomographic representations of the patient are generated, this information can also be used to perform dose reconstruction. In this way, the actual dose distribution delivered can be superimposed onto the tomographic representation of the patient obtained at the time of treatment. The results can be compared with the planned isodose on the planning CT. This comparison may be used as an accurate basis for adaptive radiotherapy whereby the optimized delivery is modified before subsequent fractions. The verification afforded tomotherapy allows more precise conformal therapy. It also enables conformal avoidance radiotherapy, the complement to conformal therapy, for cases in which the tumor volume is ill-defined, but the locations of sensitive structures are adequately determined. A clinical tomotherapy unit is under construction at the University of Wisconsin.

Dose Fractionation, Radiation↗

Registration using tomographic projection files.

An algorithm has been developed and experimentally verified for tomographic registration--a patient positioning method using internal anatomy and standard external fiducial marks. This algorithm improves patient set-up and verification to an accuracy sufficient for tomotherapy. By implementation of this technique, the time-consuming reconstruction process is avoided. Instead, offsets in the x, y and z directions are determined directly from sinogram data by an algorithm that utilizes cross-correlations and Fourier transforms. To verify the efficiency and stability of the algorithm, data were collected on the University of Wisconsin's dedicated tomotherapy research workbench. The experiment indicates offset statistical errors of less than +/-0.8 mm for offsets up to 30 mm. With standard clinical techniques, initial patient offsets are expected to be less than 5 mm, so the 30 mm limitation is of no consequence. The angular resolution for the direction of patient translation is within the +/-2 degrees needed for tomotherapy.

Algorithms↗

Phase I trial of docetaxel with estramustine in androgen-independent prostate cancer.

PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a > or = 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.

Aged↗

MP2C, a plant protein phosphatase 2C, functions as a negative regulator of mitogen-activated protein kinase pathways in yeast and plants.

By interference of the yeast pheromone mitogen-activated protein kinase (MAPK) pathway with an alfalfa cDNA expression library, we have isolated the MP2C gene encoding a functional protein phosphatase type 2C. Epistasis analysis in yeast indicated that the molecular target of the MP2C phosphatase is Ste11, a MAPK kinase kinase that is a central regulator of the pheromone and osmosensing pathways. In plants, MP2C functions as a negative regulator of the stress-activated MAPK (SAMK) pathway that is activated by cold, drought, touch, and wounding. Although activation of the SAMK pathway occurs by a posttranslational mechanism, de novo transcription and translation of protein factor(s) are necessary for its inactivation. MP2C is likely to be this or one of these factors, because wound-induced activation of SAMK is followed by MP2C gene expression and recombinant glutathione S-transferase-MP2C is able to inactivate extracts containing wound-induced SAMK. Wound-induced MP2C expression is a transient event and correlates with the refractory period, i.e., the time when restimulation of the SAMK pathway is not possible by a second stimulation. These data suggest that MP2C is part of a negative feedback mechanism that is responsible for resetting the SAMK cascade in plants.

Amino Acid Sequence↗