Bcl-2 expression and glucocorticoid-induced apoptosis of leukemic and lymphoma cells.

The lytic response of lymphoid cells to glucocorticoid hormones (GC) is prototypical of the induction of apoptosis: a special form of cellular demise for the removal of unwanted or redundant cells. Initiation and execution of a death programme are therefore major checkpoints in GC-sensitivity. Although Bcl-2 protein can prevent or delay apoptosis of lymphoma and leukemia cells, exposed to multiple cytotoxic agents, its antagonism of GC-induced apoptosis appears most critical in conferring resistance to corticosteroids.

Quantification of organ motion during conformal radiotherapy of the prostate by three dimensional image registration.

Purpose: Knowledge about the mobility of organs relative to the bony anatomy is of great importance when preparing and verifying conformal radiotherapy. The conventional technique for measuring the motion of an organ is to locate landmarks on the organ and the bony anatomy and to compare the distance between these landmarks on subsequent computerized tomography (CT) scans. The first purpose of this study is to investigate the use of a three dimensional (3D) image registration method based on chamfer matching for measurement of the location and orientation of the whole organ relative to the bony anatomy.

Variation in volumes, dose-volume histograms, and estimated normal tissue complication probabilities of rectum and bladder during conformal radiotherapy of T3 prostate cancer.

Purpose: To determine the pattern of changes of rectum and bladder structures during conformal therapy of T3 prostate cancer and the impact of these changes on the accuracy of the dose-volume histograms (DVHs) and normal tissue complication probabilities (NTCPs) of these organs, based on the planning computed tomography (CT) scan only.

Methods And Materials: For 11 T3 prostate cancer patients treated with conformal therapy, three repeat CT scans were made in Weeks 2, 4, and 6 of the treatment. The bony anatomy was aligned with the planning CT scan, using three dimensional (3D) chamfer matching.

Influence of shape on the accuracy of grid-based volume computations.

The influence of the shape of a region of interest (ROI) on the uncertainty in the sampled volume of the ROI is investigated for computations with regular Cartesian grids. Both mathematically defined volumes and clinically relevant ROIs were studied. The sampling uncertainty is shown to depend on the compactness of the ROI and on effects of grid matching and translational symmetry.

Formation of DNA adducts by the anticancer drug carboplatin: different nucleotide sequence preferences in vitro and in cells.

We have studied the formation of adducts upon carboplatin treatment of isolated DNA and in cells. The major adduct formed in vitro, determined with atomic absorption spectroscopy and enzyme-linked immunosorbent assay, was the intrastrand cross-link cis-Pt(NH3)2d(pGpG)(Pt-GG) (58%). cis-Pt-(NH3)2d(pApG) (Pt-AG) (11%), cis-Pt(NH3)2d(GMP)2 (G-Pt-G) (9%), and monofunctionally bound platinum (cis-Pt(NH3)3dGMP (Pt-G), 22%) were formed in smaller amounts.

Estimation of overall pulmonary function after irradiation using dose-effect relations for local functional injury.

Purpose: To predict the pulmonary function 3-4 months after irradiation for malignant lymphoma from the three-dimensional (3-D) dose distribution.

Methods: Dose-effect relations for the relative reduction of local perfusion (Q) and local ventilation (V), were calculated in 25 patients, using correlated SPECT (Single Photon Emission Computed Tomography) and CT data. By combining the 3-D dose distribution of an individual patient with the dose-effect relations averaged over all patients, the average reduction of local Q and V (i.

Optimization of automatic portal image analysis.

The purpose of this study is to quantify and optimize the performance of an automatic portal image analysis procedure under clinical conditions and to compare the performance with that of human operators. A new method, based on analysis of variance, is introduced to quantify the clinical performance of portal image analysis tools in terms of systematic and random variations. The automatic portal image analysis procedure is based on chamfer matching.

Amelioration of radiation nephropathy by acetylsalicylic acid.

This investigation was carried out to assess the amelioration by two antithrombotic drugs of radiation nephropathy in mice. Mouse kidneys were given split-dose irradiation to total doses between 17 and 22 Gy. A first group of animals was given acetylsalicylic acid (ASA) in drinking water, a second received daltroban, a thromboxane A2/prostaglandin H2 receptor antagonist, and a third received normal tap water, serving as a control.

Detection of platinum-DNA adducts by 32P-postlabelling.

We developed a sensitive 32P-postlabeling method for the detection of bifunctional intrastrand crosslinks d(Pt-GpG) and d(Pt-ApG) in DNA in vitro and in vivo. After enzymatic digestion of DNA the positively charged platinum adducts were purified from unplatinated products, using strong cation exchange chromatography. Subsequently the samples were deplatinated with cyanide, because platinated dinucleotides are very poor substrates for polynucleotide kinase.

Comparative analysis of p53 gene mutations and protein accumulation in human non-small-cell lung cancer.

A series of 54 resected primary non-small-cell lung carcinomas was analyzed for p53 gene mutations and for p53 protein accumulation and the findings were correlated with clinical parameters. Mutations in exons 5 through 8 of the p53 gene were identified by a denaturing gradient gel electrophoresis (DGGE) assay and cycle sequencing, whereas p53 protein accumulation was detected in paraffin-embedded tissue by immunostaining using 2 different murine monoclonal antibodies (MAbs) (BP53-12 and DO7). A p53 gene mutation and/or p53 protein accumulation was found in 37 of 54 tumors.

Prognostic factors in NSCLC. Recent experiences.

In recent years, a group of new prognostic factors have been added to the list of well-known clinical prognostic factors of non-small cell lung cancer. Among these are mutations in the K-ras oncogene, abnormalities in p53, the presence of N-CAM expression as measured by Mab immunostaining and elevated serum levels of NSE. These factors have provided important clinical insights into the biology of lung cancer and prospective studies using these biomarkers are now warranted to provide further important clues about their potential significance in treatment selection of patients.

Long-term morbidity after regional isolated perfusion with melphalan for melanoma of the limbs. The influence of acute regional toxic reactions.

Objective: To determine the influence of acute regional toxic reactions on the incidence and characteristics of long-term morbidity after regional isolated perfusion with melphalan.

Design: Retrospective study.

Setting: The Amsterdam and Rotterdam perfusion centers, the Netherlands.

Effect of N-acetylcysteïne on Photofrin-induced skin photosensitivity in patients.

Background And Objective: One of the major side effects of photodynamic therapy (PDT) employing Photofrin as the sensitizer is enhanced photosensitivity of the skin. The basic mechanism in PDT damage is believed to be the formation of singlet oxygen and radical species. N-acetylcysteïne (NAC) increases glutathione levels and is known to prevent pathology elicited by radicals and reactive species.

Long-term neuropathy after regional isolated perfusion with melphalan for melanoma of the limbs.

The incidence of long-term (> or = 3 months) neuropathy in 350 melanoma patients treated with single normothermic or 'mild' hyperthermic perfusion with melphalan in the period 1978 to 1990 was studied. Long-term neuropathy was encountered in 14 patients; in 10/51 patients (20%) after perfusion at the axillary level and in 4/247 patients (2%) after perfusion at the iliac level. After brachial and femoro-popliteal perfusions no long-term neuropathy was observed.

Carcinoma arising in thyroglossal remnants.

Three patients with a papillary carcinoma arising in a thyroglossal duct cyst are presented and the literature is reviewed. This rare malignancy is seen mostly in women between the ages of 20 and 50 years. The distribution of carcinoma subtypes differs from that of thyroid carcinomas and thyroglossal duct carcinoma is recognized as a primary tumour.

Radiation reduces cyclooxygenase activity in cultured human endothelial cells at low doses.

The effect of radiation on prostaglandin (PG) production was investigated in cultured human umbilical vein endothelial cells. It was found that 48 hours after irradiation the endothelial cell capacity to synthesize prostacyclin (PGI2), Prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) from exogenous arachidonic acid (AA) was strongly reduced in a radiation dose-dependent way, with 50% of the maximal inhibition at approximately 2 Gy. By incubating the endothelial cells between 24 and 48 hours after irradiation with 50 U/ml interleukin-2 (IL-2), which is known to selectively stimulate de novo synthesis of cyclooxygenase, the PGI2 synthesis from exogenous AA was nearly completely restored.

In vivo determination of the accuracy of field matching in breast cancer irradiation using an electronic portal imaging device.

The purpose of this study was to investigate the accuracy of field matching in patients treated by irradiation of the breast and adjacent lymph nodes. Field matching is performed by the radiographers during each session on a match line drawn on the patient's skin. Field edge positions were assessed in the cranial match plane of tangential breast fields and supraclavicular-axillary fields using an electronic portal imaging device and match line markers placed on the skin of the patients.

Evidence for a renovascular component in hypertensive patients with late radiation nephropathy.

Purpose: This study was undertaken to investigate whether the hypertension observed in a subgroup of patients with progressive radiation-induced nephropathy has a renovascular component.

Methods And Materials: Fifteen patients with prospectively documented renal injury after high-dose radiation treatment for various abdominal malignancies were studied, 8 of them having hypertension. 99mTc-DTPA renography and plasma renin activity measurements were performed before and after an oral dose of 50 mg captopril.

Vulvar sarcoma: clinical implications.

This is a review of the histories of 47 patients with vulvar sarcoma, consisting of leiomyosarcoma (25), malignant fibrous histiocytoma (5), epithelioid sarcoma (8), dermatofibrosarcoma protuberans (9), including 7 from our own institute. When compared to the biological behaviour of sarcomas from other anatomic sites of the body, no essential differences were found. The prognosis after the appearance of regional or distant recurrence was poor and prevention of local recurrence by wide excision was the best way to improve the prognosis of leiomyosarcoma and dermatofibrosarcoma protuberans.

Loss of reirradiation tolerance in the kidney with increasing time after single or fractionated partial tolerance doses.

The aim was to determine the influence of initial dose and dose per fractionation on retreatment tolerance of the kidney. Mouse kidney was bilaterally irradiated with various single or fractionated X-ray doses equivalent to about 12-70% of a defined response dose. The mice were retreated with a range of single doses after 2 or 26 weeks.

Potential applications of positron emission tomography in surgical oncology.

Positron emission tomography (PET) is a new nuclear medicine technique. The number of PET facilities is limited due to the high costs and complexity of this diagnostic modality. The principles of PET are explained.

Melphalan tissue concentrations in patients treated with regional isolated perfusion for melanoma of the lower limb.

In 14 consecutive patients with recurrent melanoma of the lower limb a total of 35 biopsies were taken at the end of perfusion treatment to assess melphalan tissue concentrations in tumour, skin/subcutis and muscle tissue. In tumour tissue (n = 12) the mean melphalan concentration was 6.8 micrograms g-1, which was significantly higher than that of healthy skin/subcutis (3.

Limb recurrence-free interval and survival in patients with recurrent melanoma of the extremities treated with normothermic isolated perfusion.

To date, little is known about prognostic factors for limb recurrence-free interval and survival in patients with recurrent melanoma of the limbs treated with regional isolated perfusion. Therefore, 216 such patients treated with normothermic perfusion using melphalan during the period 1978 to 1990 were analyzed for patient and tumor related variables using a Cox proportional hazard model. The five year limb recurrence-free interval was 52 percent.

Transfer errors of planning CT to simulator: a possible source of setup inaccuracies?

The purpose of this study was to analyse whether the intended patient setup, based on a CT scan, was different from the setup at the simulator. Furthermore, we investigated how these possible transfer errors between the planned patient setup and the actual simulator setup affected the resulting overall treatment setup accuracy. Two groups, of 15 prostate patients each, were studied.