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Biomedical subjects

Z Fuks

Publications and source records attributed to Z Fuks.

At least 307 records · Page 17Linked to original sources
PubMedDate not supplied

Esthesioneuroblastoma: is there a role for elective neck treatment?

A retrospective review of the Memorial Sloan Kettering Cancer Center experience (MSKCC) with esthesioneuroblastoma was performed. From 1975 to 1985 14 cases were identified. Overall 5- and 10-year survival was 86% and 70%, respectively. Four local failures were observed and 4 neck failures were observed. A review of the literature since 1966 revealed an unexpectedly high incidence of neck failure, and of the 21 of 110 patients with neck failures that were identified through the literature, there were 6 subsequent deaths.

Adult↗
PubMedDate not supplied

Biotransformations and plasma-level curves of chiral 1,4-benzodiazepine-2-ones.

Biotransformations of chiral 1,4-benzodiazepine-2-ones, (S)- and (R)-1 (7-chloro-1,3-dihydro-3 (S and R)-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) in untreated and phenobarbital-pretreated rats were investigated. In urine, a 4'-oxygenated metabolite (compound 2) was identified as the biotransformation product from both enantiomers, (S)-2 being present in much higher amounts than (R)-2. Unchanged parent compounds were not found in urine. In plasma, 3'- and 4'-oxygenated metabolites were identified after administration of (S)-1 and (R)-1, respectively. The metabolite possessing an R-configuration was present in much lower amounts. The maximum concentrations of (R)-1 in plasma, following a single dose, was about 6 time as high as the maximum plasma concentration of (S)-1. Faster biotransformation and elimination of (S)-1 is assumed to be the explanation of these findings.

Animals↗
PubMedDate not supplied

Activated T lymphocytes produce a matrix-degrading heparan sulphate endoglycosidase.

We have previously found that lines of activated T lymphocytes specifically autosensitized to the basic protein of myelin (BP), on intravenous inoculation into syngeneic rats, were able to penetrate blood vessels, accumulate in the nervous system and cause experimental autoimmune encephalomyelitis (EAE). An important question is how effector T cells reach such targets outside the walls of blood vessels. To investigate this we have studied in vitro the interaction of anti-BP effector T lymphocytes with the basement membrane-like extracellular matrix produced by vascular endothelial cells. We now report that activated but not resting T lymphocytes produce an endoglycosidase capable of degrading heparan sulphate side chains of the proteoglycan scaffold of the extracellular matrix. Moreover, the anti-BP T lymphocytes respond to BP presented by extracellular matrix by markedly enhanced elaboration of the endoglycosidase. These results suggest that tissue-specific antigens on blood vessel walls could direct lymphocyte homing by activating enzymes that facilitate penetration of the subendothelial basal lamina. They also suggest that effector T lymphocytes can recognize antigen which is not associated with a major histocompatibility complex signal.

Animals↗
PubMedDate not supplied

Clinically relevant optimization of 3-D conformal treatments.

In this paper a method of computer-aided optimization of 3-D conformal treatment plans is presented which incorporates models to predict the clinical consequences of resulting dose distributions. Even though these models are simplistic, it is submitted that their intelligent use leads to treatment plans which indicate lower normal tissue complications and higher tumor control. Dose distribution data, biological models, and observed normal tissue and tumor response data are used to compute tumor control and normal tissue complication probabilities for each of the critical normal structures encountered in a treatment plan. These quantities are combined into a single score using an objective function which incorporates the importance of each end point as assessed by the physician. Using the "simulated annealing" method of optimization, the beam weights are adjusted to maximize the score. Additional constraints are applied to ensure consistency of the results of optimization with the judgment of the physician. These optimization methods have been applied to conformal treatment plans consisting of multiple fixed fields with conformal field shaping. The results indicate that the methods presented have considerable potential.

Aged↗
PubMedDate not supplied

The sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor, Fas, and ionizing radiation.

Recent evidence suggests that tumor necrosis factor alpha, Fas, and ionizing radiation employ the sphingomyelin pathway to trigger apoptosis. The sphingomyelin pathway is initiated by hydrolysis of plasma membrane sphingomyelin to generate ceramide via a sphingomyelinase. Ceramide serves as a second messenger stimulating a cascade of kinases and transcription factors that activate a final common pathway of programmed cell death. The extent to which this signaling system is used in apoptosis induced by other toxic modalities is not known, but accumulating evidence suggests that it is a commonly employed pathway that could be exploited therapeutically.

Animals↗
PubMedDate not supplied

Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer.

PURPOSE AND OBJECTIVE: Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precision radiotherapy designed to increase the tumor dose and decrease the dose to normal tissues. This study reports the final results of the first two dose levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D-CRT for the treatment of non-small cell lung cancer. PATIENTS AND METHODS: Fifty-two patients were treated with 3D-CRT without chemotherapy. The median age was 67 years (range, 39-82 years). The majority of patients had locally advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week. A radiation dose level was considered complete when 10 patients received the intended dose without unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme. RESULTS: Twenty patients were initially assigned to the 70.2-Gy level; 14 of them received the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 (fatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxicity, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible for dose escalation. Patients who had a normal tissue complication probability (NTCP) of greater than 25% received a lower dose of radiation. An additional 18 patients were entered on the modified study; 11 of them received 70.2 Gy. One patient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients developed grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75.6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity, and one patient refused treatment. The 2-year local control, disease-free survival, and overall survival rates were 37%, 12%, and 24%, respectively. The median survival time was 11 months. DISCUSSION: Treatment to 70.2 Gy and 75.6 Gy using 3D-CRT was delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouraging in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gy level of the study.

Adult↗
PubMedDate not supplied

Involvement of heparanase in tumor metastasis and angiogenesis.

The capacity of various blood-borne cells, whether normal or malignant, to extravasate was found to correlate with heparanase-mediated degradation of HS in subendothelial ECM. This degradation was stimulated by proteases or plasminogen and inhibited by native heparin and by various modified nonanticoagulant species of heparin. These heparins also induced a marked reduction in tumor cell metastasis and autoimmune diseases in experimental animals. Heparanase-mediated degradation of HS in ECM also released EC growth factors that are stored in ECM, most likely by high affinity binding to HS. Such growth factors were extracted from subendothelial ECM synthesized in vitro and from basement membranes of the cornea in vivo, and are structurally and functionally related to bFGF;bFGF binds to ECM and is readily released by incubation with either HS, heparin or low MW heparin fragments as well as by various normal and malignant cells and by heparanase-mediated degradation of ECM HS. In contrast, there was little or no release of growth-promoting activity upon incubation of ECM with hyaluronic acid, chondroitin sulfate or chondroitinase ABC. A model is proposed suggesting that regulation of capillary growth and neovascular response may result from displacement of an angiogenic protein (bFGF) from its storage sites within basement membranes.

Extracellular Matrix↗
PubMedDate not supplied

The effects of ionizing irradiation on production of thromboxane and prostacyclin by the isolated perfused rat kidney.

Exposure to whole body radiation is associated with prompt changes in urinary excretion of prostaglandins. We investigated the separate effects of radiation on rat kidney capillary and tubular system prostaglandin synthesis. Animals were irradiated to the left kidney area with a single dose of 15 Gy. One week later the rats were anesthesized, the renal artery, vein and ureter of the left kidney cannulated, and the kidney removed and perfused with Krebs-Henseleit physiological buffer at a rate of 10-12 ml/min. Effluent fluids were collected separately from the renal vein and from the ureter of irradiated and control (operated sham-irradiated animals) and were assayed by radioimmunoassays for thromboxane A2 (TXB2) and prostacyclin (6 keto PGF1 alpha). Histological examination of the irradiated kidneys showed no significant changes, and electron microscopy revealed minimal interstitial edema. In contrast to these minimal changes, TXB2 assays showed a significant increase both in the venous and ureter effluents. Following stimulation with angiotensin II in the perfusate, a further significant increase in TXB2 production was observed both by the capillary and the tubular systems. With 6 Keto PGF1 a slightly different response was seen. The basal production was increased only in the ureter effluent of the irradiated animals, while there were no changes in the release in the venous effluents. In parallel, radiation significantly increased the angiotensin II stimulated production capacity of prostacyclin by the tubular system. The response of the capillary system following irradiation may create imbalance between these two important substances and lead to the radiation effects in the renal tissue.

Animals↗
PubMedDate not supplied

Questioning current policies for the curative management of ovarian carcinoma.

Despite major advances in the understanding of the natural history and mode of the spread of ovarian carcinoma, and in the development of new and effective techniques for its radiation and chemotherapy, the cure rates of this disease have not changed substantially over the last two decades. The disappointing results of treatment raise serious questions regarding the validity of some of the current strategies and policies for the management of ovarian carcinoma. This review discusses the need for a new staging classification system, the indications for initial maximal tumor reductive surgery and second-look laparotomy, the curative potentials of postoperative radiation or chemotherapy when employed as single modalities, and the causes of failure of combined modality treatment protocols. The therapeutic value of new experimental approaches, such as i.p. instillations of chemotherapy and/or monoclonal antibodies, when combined with conventional treatments, are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Continuous course of megavoltage radiotherapy for carcinoma of the prostate.

Between 1978 and 1983, 55 patients with advanced carcinoma of the prostate (38 with Stage C and 17 with Stage D) were treated with external beam MeV radiotherapy. In 29 patients radiotherapy was the first treatment modality, and 26 patients had previously received hormonal therapy. Both treatment modalities were continued simultaneously for Stage D and bulky Stage C of the disease. Severe urodynamic problems were the main treatment indications for patients with Stage D carcinoma. The treatment consisted of two courses each of 25 gray (Gy) whole pelvic irradiation, interrupted for 2 weeks to deliver a rotation field to the prostate at a dose of 20 Gy. Patients have been followed for a minimum of 36 months. For patients with Stage C disease the overall 3-year survival was 80%, with 55% disease-free survival. Palliative irradiation for Stage D prostatic carcinoma improves the quality of life and probably the survival rate. Acute minor complications were observed in 49% of the patients, and chronic complications occurred in 14% of the patients. The described MeV technique is well tolerated and effective for Stage C as well as for Stage D prostatic cancer patients.

Adenocarcinoma↗
PubMedDate not supplied

Treatment of locally advanced breast carcinoma with high-dose external beam supervoltage radiotherapy.

Between 1960 and 1978, 85 patients with locally advanced T3-4N0-3M0 carcinoma of the breast were treated with 5,000 to 8,000 rad of external beam supervoltage radiotherapy. Initial clinical eradication of the tumor was observed in 76 of 87 cases (87%), but the actuarial probability of local control at 6 yr was only 53%. Furthermore, the actuarial probability of disease-free survival was 25% at 5 year and 13% at 10 yr. Most of the patients eventually succumbed to metastatic breast carcinoma and the actuarial survival at 5 yr was 43% and at 10 yr, 16%. The addition of adjuvant low-dose chemotherapy, given to 13 patients, did not affect the rates of local control, survival or disease-free survival. The most common long-term complication was extensive and deforming radiation-induced fibrosis of the treated breast. The actuarial probability of 10-yr survival without a local recurrence and without severe fibrosis of the treated breast was only 17.5%. The role of adjuvant high-dose chemotherapy in the treatment of locally advanced breast carcinoma and the possible use of improved radiotherapy techniques to achieve a more effective long-term local control and a more desirable cosmetic end result are discussed.

Adult↗
PubMedDate not supplied

Serum transcobalamin II levels in breast carcinoma patients.

Serum levels of transcobalamin II (TCII) were determined in 139 patients with breast carcinoma. The patients were divided into two groups. Group A consisted of 74 patients with no evidence of active disease at the primary site or in complete remission. Serum levels of TCII were normal (up to 1,500 pg/ml) in 60 patients (81%) and moderatelyy elevated (up to 1,900 pg/ml) in 14 patients (19%) in this group. Group B consisted of 65 patients with active disease. Serum TCII levels were normal in 23 patients (35%) and were markedly elevated (up to 2,500 pg/ml) in 42 patients (65%). In Group B, 56 patients had widespread metastatic disease and 9 had active locoregional disease. Whether the moderately elevated TCII in the 14 patients of Group A with no evidence of disease and the normal TCII in the 23 patients of Group B with active disease is of prognostic value, will be determined by follow-up and close monitoring of the patients. Preliminary results of serial determinations of TCII indicate that changes in the TCII level generally correlate with the clinical course of the disease and the effects of therapy. These data indicate that TCII serum level may be useful as a marker for tumor activity in breast carcinoma.

Adult↗