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Biomedical subjects

A Dritschilo

Publications and source records attributed to A Dritschilo.

140 records · Page 8Linked to original sources

Interaction between radiation and drug damage in mammalian cells. III. The effect of adriamycin and actinomycin-D on the repair of potentially lethal radiation damage.

We have studied the effects of actinomycin-D (AMD) and Adriamycin (ADRM) on the repair of radiation damage in Chinese hamster cells (V79) in plateau phase growth. Suppression of potentially lethal damage repair (PLDR) was observed in the presence of non-toxic levels of AMD and minimally toxic levels of ADRM. The suppression of PLDR by AMD persisted as long as the drug was present. Removal of AMD was followed by prompt repair of potentially lethal injury suggesting that suppression of PLDR by AMD was not accompanied by fixation of injury to a non-repairable state. On the other hand, irradiated cells exposed to ADRM eventually repair potentially lethal injury in the presence of drug after an initial delay. AMD, but not ADRM, inhibited repair of sublethal radiation damage.

Animals↗

The role of radiation therapy in the treatment of soft tissue sarcomas of childhood.

The treatment of soft tissue sarcomas in children at the Joint Center for Radiation Therapy, Children's Hospital Medical Center, and the Sidney Farber Cancer Institute from 1970 to 1976 has been reviewed. Twenty-seven patients were diagnosed with rhabdomyosarcoma, and twenty patients were diagnosed with soft tissue sarcomas of other histologies. An aggressive, combined modality therapeutic approach was applied in the treatment of all patients with emphasis placed on conservation of function. Of irradiated patients, local control was achieved in 96% of those with rhabdomyosarcoma and 85% in other sarcomas. Cumulative relapse-free survival (actuarial) at 5 years is projected at 65% for the rhabdomyosarcoma patients and at 63% for the other sarcoma patients. Although there were differences in chemotherapy regimens (vincristine, actinomycin-D and cyclophosphamide for rhabdomyosarcoma and adriamycin and DTIC for other soft tissue sarcomas), the surgical and radiation therapeutic approaches are similar for both groups. The high probability of local control using function-conserving surgery and high dose radiation therapy supports this emerging approach. Improvements in survival will require better control of metastatic disease.

Adolescent↗

The complication probability factor: a method for selection of radiation treatment plans.

The problem of selecting the best radiation treatment plan from several that may offer subtle differences has been considered. A method is introduced in which the concept of a complication probability factor (CPF) can be used to quantify the relative merits of such treatment plans. The CPF is a variant of integral dose and consists of a weighted volume of irradiated normal tissue which may relate to radiation-related complications. Treatment plans for irradiation of a pelvic tumour volume using parallel opposed, 360 deg rotational and four-field techniques with X-ray beams of 4, 8, 22, and 45 MV have been analyzed to demonstrate the utility of the method. This analysis suggests that complex radiation delivery techniques may offer a substantial improvement in dose distribution characteristics, while higher beam energies are relatively less advantageous.

Dose-Response Relationship, Radiation↗

The role of irradiation in central nervous system treatment and prophylaxis for acute lymphoblastic leukemia.

The results of central nervous system (CNS) treatment with craniocervical irradiation and intrathecal methotrexate in 117 children with ALL achieved at the Joint Center for Radiation Therapy. The Children's Hospital Medical Center, and The Sidney Farber Cancer Center are presented. A classification related to meningeal disease which correlated with prognosis is presented and the patients are analyzed within these groups. Of 80 patients classified in the most favorable groups (I and II), no child has suffered primary CNS relapse. Of the remaining 37 patients in less favorable groups (III, IV, and V), eight patients have experienced CNS relapse, five following or in conjunction with bone marrow relapse. The technical features of irradiation are reviewed and related to success of the treatment.

Adolescent↗

Thromboembolic disorders in pregnancy: pathophysiology, diagnosis, and treatment, with emphasis on heparin.

Newer concepts of blood coagulation and the pathophysiology of phlebitis and pulmonary emboli with particular reference to pregnancy are examined. New as well as established diagnostic procedures are considered. The historical development, pharmacologic effects, and clinical indications for oral anticoagulants and heparin are reviewed. Finally our own data are presented regarding 19 patients with thromboembolic disorders occurring during pregnancy who were tested with heparin as the sole anticoagulant. Because of the favorable outcome, with excellent fetal salvage, we make a plea for the use of heparin as the anticoagulant of choice during pregnancy.

Anticoagulants↗

Protein changes associated with ionizing radiation-induced apoptosis in human prostate epithelial tumor cells.

Ionizing radiation (IR) is an important component in the therapy of localized prostate cancer. Identification of protein alterations during IR-induced apoptosis prostate cancer cells is an important step toward understanding the new metabolic status of the dying cell. In the present study, we report changes in protein profile that define the execution phase of the apoptotic response in the in vitro model of tumorigenic radiation-transformed SV40-immortalized human prostate epithelial cells (267B1-XR), induced to undergo programmed cell death by IR. We employed an approach that involves use of analytical two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) coupled with Western blotting with specific antisera. Our results point out that apoptotic cells experience significant reduction in the levels of the intermediate filament proteins, keratins-18, 19, vimentin and the associated 14-3-3 adapter proteins. At the same time, molecular chaperones such as glucose-regulated protein 94, calreticulin, calnexin, and protein disulfide isomerase exhibit marked accumulation in these dying cells. The present data indicate that apoptosis-associated processes in prostate epithelial cells include solubilization of the rigid intermediate filament network by specific proteolysis as well as increased levels of endoplasmic reticulum (ER) proteins with chaperone functions.

Apoptosis↗

Protein expression changes associated with radiation-induced neoplastic progression of human prostate epithelial cells.

Carcinogenic progression in most epithelial systems is a multistep process and presents as numerous (un)stable intermediate stages prior to the development of a fully malignant phenotype. Recently, we reported the neoplastic transformation of an SV40 immortalized, neonatal human prostate epithelial cell line (267B1) by multiple exposures to X-rays [1, 2]. The parental 267B1 cells acquired anchorage-independence and exhibited morphological transformation following exposure to two consecutive doses of 2 Gy. Exposure of either the parental 267B1 cells or the anchorage-independent derivatives (F3-SAC) to a total dose of 30 Gy of X-rays yielded tumorigenic transformants (267B1-XR and 267B1-SXR, respectively). All of these radiation-treated derivatives (F3-SAC, 267B1-XR, and 267B1-SXR) were characterized by reduced cell size and poorly organized actin stress fibers [2, 3]. The present study examines the protein expression changes associated with cytoskeletal alterations during the different steps of neoplastic progression induced by X-rays in the in vitro human prostate cell system. This analysis was achieved by using the high resolving power of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) in the 267B1, F3-SAC, 267B1-XR, and 267B1-SXR cells. We report changes in the expression of gelsolin in the partially transformed, anchorage-independent, nontumorigenic (F3-SAC) cells and a progressive loss of expression of tropomyosin isoforms (TM-1 and TM-3), and myosin light chain-2 (MLC-2) in the tumorigenic (267B1-XR; 267B1-SXR) cells, respectively. In contrast, our results demonstrate that the levels of the small GTP-binding protein Rho-A, an active participant in the actin stress fiber organization, are not altered during neoplastic progression of these 267B1 cells. Thus the changes in synthesis of gelsolin, tropomyosins, and MLC-2 provide a rationale for the alterations in the actin stress fiber formation and reduction in cell size during the exposure of prostate epithelial cells to multiple doses of X-rays.

Actins↗

Radioresistant tumor cell lines derived from head and neck radiation failures.

We studied the in vitro radiobiological parameters of 16 human head and neck squamous cell carcinoma tumor cell lines cultured from patients who suffered local failure after a curative course of radiotherapy. The radiobiological parameters determined included D0, n, and D. When compared with in vitro radiobiological parameters of tumor cells cultured from head and neck cancer patients prior to radiotherapy, human sarcoma cell lines, and normal human diploid fibroblasts studied in our laboratory (as well as other human tumor cell lines reported in the literature), tumor cells derived from radiotherapy failures on average are resistant to the cytotoxic effects of ionizing radiation.

Carcinoma, Squamous Cell↗

Poly(ADP-ribosyl)ation of p53 in vitro and in vivo modulates binding to its DNA consensus sequence.

The tumor-suppressor p53 undergoes extensive poly(ADP-ribosyl)ation early during apoptosis in human osteosarcoma cells, and degradation of poly(ADP-ribose) (PAR) attached to p53 coincides with poly(ADP-ribose)polymerase-1, (PARP-1) cleavage, and expression of p53 target genes. The mechanism by which poly(ADP-ribosyl)ation may regulate p53 function has now been investigated. Purified wild-type PARP-1 catalyzed the poly(ADP-ribosyl) of full-length p53 in vitro. In gel supershift assays, poly(ADP-ribosyl)ation suppressed p53 binding to its DNA consensus sequence; however, when p53 remained unmodified in the presence of inactive mutant PARP-1, it retained sequence-specific DNA binding activity. Poly(ADP-ribosyl)ation of p53 by PARP-1 during early apoptosis in osteosarcoma cells also inhibited p53 interaction with its DNA consensus sequence; thus, poly(ADP-ribosyl)ation may represent a novel means for regulating transcriptional activation by p53 in vivo.

Apoptosis↗

Dynamic CT vs 0.5 T MR imaging in the detection of surgically proven hepatic metastases.

Seventeen patients with 52 surgically proven hepatic metastases were studied preoperatively with dynamic CT and 0.5 T magnetic resonance (MR). Dynamic CT detected 38 metastases (73%), and the combination of short echo time (T1-weighted) and T2-weighted pulse sequences detected 46 lesions (88%). Magnetic resonance was also superior at assessing potential resectability. This study suggests that MR excels in detecting and anatomically localizing individual hepatic metastases.

Humans↗

Inhibition of Raf-1 protein kinase by antisense phosphorothioate oligodeoxyribonucleotide is associated with sensitization of human laryngeal squamous carcinoma cells to gamma radiation.

BACKGROUND: Previous studies suggest a central role for Raf-1 protein kinase in mitogenic and radiation damage responsive signaling pathways. PURPOSE: Here we report that the expression and enzymatic activity of Raf-1 protein are inhibited in SQ-20B cells exposed to raf antisense oligodeoxyribonucleotide (As-ODNs) directed against the translation initiation site of human c-raf-1 cDNA. In contrast, treatment of SQ-20B cells with an equimolar concentration of raf sense oligodeoxy-ribonucleotide (S-ODNs) had no effect on the expression and activity of Raf-1. RESULTS: We have observed radiosensitization of raf As-ODNs-treated SQ-20B cells. The dose modifying factor of As-ODNs treatment was approximately 1.4. CONCLUSIONS: These studies demonstrate that raf As-ODNs is a DNA sequence-specific radiosensitizer that may have potential for use in the radiation therapy of cancers.

Base Sequence↗