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Biomedical subjects

T Peretz

Publications and source records attributed to T Peretz.

88 records · Page 5Linked to original sources

Mediastinal lymph node metastases from gastrointestinal carcinoma.

Mediastinal and hilar lymphadenopathy secondary to gastrointestinal metastases rarely have been reported and have been considered to occur only in conjunction with lymphangitic lung spread. The current report is of 15 cases of hilar and mediastinal metastases secondary to pancreatic, gastric, and colonic primary tumors. In only three of these cases was lymphangitic lung involvement noted. Possible pathways of spread of these tumors to the mediastinal lymph nodes are discussed.

Autopsy↗

Cord compression as the presenting symptom of extradural malignant lymphoma.

Six patients with spinal cord compression as the presenting symptom of malignant lymphoma are described. These patients suffered from back pain for several months and were diagnosed after sudden paraparesis appeared. Five patients were treated by operative decompression followed by local irradiation, and all regained their motor function. A sixth patient presented with a more insidious paraparesis. A bone marrow aspiration established the diagnosis of malignant lymphoma, and this patient recovered with radiation and steroids alone. Thus, we recommend considering malignant lymphoma as a possible cause of acute cord compression, attempting to establish the diagnosis on an emergency basis within several hours, and attempting to achieve decompression with local radiotherapy and intravenous dexamethasone.

Adult↗

Elevation of erythrocyte zinc- and free protoporphyrins with metastatic spread in cancer patients.

A sensitive fluorometric method for the evaluation of erythrocyte levels of zinc-protoporphyrin (ZPP) and free-protoporphyrin (FPP) in diluted whole blood was used to survey patients with carcinomas in different stages o metastatic dissemination. ZPP levels in patients with primary tumor or with no evidence of metastatic disease were not different from those of normal donors. However, significantly higher ZPP levels were found in patients with carcinomas in correlation with evidence of metastatic disease, irrespective of the histological origin of the tumor. FPP levels were elevated in all stages of malignancy but were found 4 times higher than the normal levels in patients with metastatic malignancies. Similar increases in ZPP and FPP were detected in patients with inflammatory processes, suggesting a common effector of erythropoiesis in these pathological conditions and in metastatic diseases. Simultaneous detection of higher than normal ZPP and FPP levels in the blood of cancer patients may serve as an additional marker of metastatic dissemination in patients without clinical evidence of infectious or autoimmune diseases.

Adult↗

Direct fluorometric determination of erythrocyte free and zinc protoporphyrins in health and disease.

Precise estimation of erythrocyte non-iron fluorescent protoporphyrins in conditions where small variations in their level are involved is experimentally difficult. We used a highly sensitive fluorometric procedure which provided, in a single direct measurement, the differential estimation of the levels of free (FPP) or zinc (ZPP) protoporphyrins relative to the hemoglobin (Hgb) concentration in diluted blood samples. With use of an internal calibration procedure, the levels of ZPP and FPP in normal healthy donors were found to be 2.7 +/- 0.9 and 0.20 +/- 0.08 micrograms/g Hgb, respectively. In blood samples taken from patients suffering from acute inflammatory processes the mean ZPP level was twofold higher, and the mean FPP was four times higher, than the normal level, suggesting better sensitivity of the FPP measurement for the detection of minor influences on the hemopoietic system. In a variety of non-inflammatory diseases FPP was less but still significantly above normal level. No significant correlation was found between the levels of both protoporphyrins and Hgb concentrations in all the groups of normal donors and patients examined.

Adolescent↗

Psychological intervention in cancer patients: a randomized study.

We examined the long-term effects of a behavioral intervention on the psychological distress of patients recently diagnosed with localized cancer, who were being treated at Hadassah University Hospital. All 116 patients who met the inclusion criteria (49 men and 67 women) were randomized into an intervention group and a control group on a 3:1 basis. The intervention chosen was Progressive Muscle Relaxation with Guided Imagery, which is intended to decrease psychological distress and increase the patient's sense of internal control. The Brief Symptom Inventory (BSI) and the Impact of Events Scale (IES) were used to assess psychological distress within 1 month of diagnosis, 3 months later (shortly before starting intervention), and 6 months after the end of the intervention. At the final assessment, the effect of the behavioral intervention on psychological distress was positive. The effect was relatively modest but statistically significant when assessed in terms of the Global Severity Index (GSI) (a decrease of 2.3 points in the GSI of the treatment group as compared to an increase of 1.2 points in the GSI of the control group P=.005). Despite these moderately positive findings, we suggest that the results might be more meaningful if cancer patients are first screened for psychological distress to exclude those with a low distress level that does not justify intervention, and only then randomized for participation in the study.

Adaptation, Psychological↗

Prognostic value of CYFRA 21-1, TPS and CEA in different histologic types of non-small cell lung cancer.

The prognostic value of the tumor markers CYFRA 21-1, tissue polypeptide specific antigen (TPS) and carcinoembryonic antigen (CEA) was investigated in three histologic subtypes of non-small cell lung cancer. Pretreatment serum marker levels were measured in 38 patients with adenocarcinoma (AC), in 43 patients with squamous cell carcinoma (SQC) and in 35 patients with large cell carcinoma (LCC). Univariate analysis in AC showed significant lower survival of patients with elevated levels of TPS, CYFRA 21-1 and CEA. In LCC, elevated levels of TPS and CEA were found to predict lower survival, while in SQC--only TPS was a predictor. A multivariate analysis of survival identified CEA (Relative Risk-5.5; p = 0.004), CYFRA 21-1 (RR-3.4; p = 0.008) and TPS (RR-3.0; p = 0.02) as independent prognostic factors in AC. In SQC, only TPS (RR-2.3; p = 0.03) was such a factor whereas in LC--none of the markers studied retained statistical significance. Thereafter, the combinations of the two strongest prognostic factors in the AC group--CEA and CYFRA 21-1 were explored to divide this group into subsets with different prognosis. In cases where both markers were positive, the relative risk of death was 10.5 times higher as compared to cases where both markers were negative (p = 0.002).

Adenocarcinoma↗

New endoscopic palliative treatments in gastrointestinal malignancies.

Many gastrointestinal cancers are diagnosed when no curative approach is possible. Patients with these malignancies frequently have dysphagia, jaundice, intestinal obstruction and other severe symptoms which significantly impair their quality of life. We present our experience with two new endoscopic techniques for palliative treatment in these patients: placement of biliary endoprostheses to alleviate malignant obstructive jaundice and destruction of neoplastic tissue by phototherapy with laser rays.

Cholestasis↗

Treatment of primary and metastatic liver cancer using an implantable chemoinfusion pump.

Twenty evaluable patients with primary or secondary neoplastic liver involvement received FUDR (0.2 to 0.3 mg/kg per day) by continuous infusion to the hepatic artery for 14 days, every 4 weeks, through a surgically implanted Infusaid (USA) pump. In addition to FUDR, MMC (15 mg/m2 every 6 to 8 weeks) was given to 14 patients with colorectal cancer and one patient with breast cancer, and ADR, (40 mg/m2 every 4 to 6 weeks) was given to 5 patients with hepatocellular carcinoma. MMC and ADR were given as a bolus injection, through the pump sideport. Radiation therapy to the liver (2,000 rads in fractions of 180 to 200 rads each) was given to eight patients with colorectal carcinoma. In total, the 20 patients received 218 months of treatment and 580 injections. The overall remission rate (complete, partial and minor response) was 55%; one patient with a colorectal carcinoma achieved a CR and seven patients (35%) a PR; three patients (15%) had a MR, and in eight patients (40%) stabilization of disease was observed. Overall median survival was 12 months: 15.5 months for colorectal cancer patients and 7.5 months for patients with hepatocellular carcinoma. Toxicity consisted mainly of chemical hepatitis, mild to severe peptic disease and sclerosing cholangitis. Hematological toxicity was not observed. These data suggest that chemotherapy through the hepatic artery, while still experimental, may be considered for selected patients with tumor confined to the liver.

Adult↗

Chemotherapy induction, consolidation radiotherapy and maintenance alternating chemotherapy in small cell carcinoma of the lung.

Forty-four evaluable, previously untreated patients with small cell lung cancer were treated with two courses of induction chemotherapy consisting of POCC. Subsequently, all limited-disease patients and extensive-disease patients in CR received 4,000 to 5,000 cGy irradiation over 4 to 5 weeks (or the equivalent) to the primary tumor, mediastinum and supraclavicular areas and 3,000 cGy prophylactic cranial irradiation during 2 weeks. All patients received maintenance chemotherapy for a full year after CR or until disease progression. Eleven continued POCC while 33 received vinblastine, cyclophosphamide, and either adriamycin or methotrexate on an alternating schedule (VCMA). For the 20 limited-disease patients, the CR rate was 70% and the PR rate was 20%. Median survival was 22 months, local control was 62%, 2-year DFS was 35% and 3-year DFS was 20%. Of the 24 extensive-disease patients only 21% achieved CR and 54% achieved PR. Median survival was only 8 months and there were no disease-free survivors at 2 years. Toxicity was moderate with nausea and vomiting in all patients, and there were two deaths from myelosuppression in the group that received POCC maintenance therapy; there were no drug-related deaths in the VCMA group. Since these results are similar to those obtained with simpler regimes, we cannot recommend our regimen for the treatment of small cell lung cancer. The optimal treatment for this disease has yet to be elucidated.

Adult↗

Inhibition of tumor metastasis by heparanase inhibiting species of heparin.

Heparanase activity correlates with the metastatic potential of lymphoma, melanoma and mammary adenocarcinoma cell lines. We investigated the ability of various modified species of heparin and size-homogeneous oligosaccharides derived from depolymerized heparin to inhibit (1) heparanase-mediated degradation of heparan sulfate in a naturally produced subendothelial extracellular matrix (ECM), and (2) lung colonization of B16-BL6 melanoma cells in C57BL mice. Inhibition of heparanase was best achieved by heparin species containing 16 or more sugar units and having sulfate groups at both the N and O positions. Low-sulfate oligosaccharides were less effective heparanase inhibitors than medium- and high-sulfate fractions of the same-size saccharide. While O-desulfation abolished the heparanase-inhibiting effect of heparin, O-sulfated, N-substituted (e.g. N-acetyl or N-hexanoyl) species of heparin retained high inhibitory activity. Potent inhibitors of heparanase activity were also efficient inhibitors of tumor invasion and lung colonization. Heparin fractions with high and low anticoagulant activity expressed similar high antiheparanase and antimetastatic activities. Structural requirement for the inhibition of melanoma cell heparanase and lung colonization by species of heparin were different from those identified for (1) release of ECM-bound basic fibroblast growth factor (b-FGF) and (2) stimulation of b-FGF receptor binding and mitogenic activity. These results indicate that various nonanticoagulant species of heparin and other polyanionic molecules differing in size, sulfation and substituted groups can be designed to elicit specific effects resulting in the inhibition of cell invasion in tumor metastasis and autoimmunity, or stimulation of neovascularization and wound healing.

Adenocarcinoma↗

The involvement of thrombin RGD in metastasis: characterization of a cryptic adhesive site.

Adhesive interactions between cells and the subendothelial extracellular matrix take place at several stages during tumor progression and metastasis. We have previously demonstrated that thrombin possesses an active yet cryptic Arg-Gly-Asp (RGD) site which can be exposed in the presence of low concentrations of plasmin and cell-associated heparan sulfate proteoglycan. Thus, thrombin may act as a matrix-adhesive molecule via activation of the alpha v beta 3 integrin. We have now identified a 31 amino acid fragment as the minimal thrombin-generated cleavage product, which contains an active RGD site, following gel filtration analysis on FPLC Superdex 75 column. The role of membrane-associated heparan sulfate in thrombin conversion to an adhesive protein was demonstrated by using CHO cell mutants defective in various aspects of glycosaminoglycan synthesis. Incubation of both thrombin and a low concentration of plasmin on the surface of wild type CHO cells resulted in a typical digestion cleavage profile upon gel filtration. No cleavage products were observed when thrombin and a suboptimal plasmin concentration were incubated on monolayers of CHO cell mutants lacking heparan sulfate. Next, we examined the possible role of the thrombin RGD site during the progression of tumor development and metastasis. Toward this, we tested murine melanoma cells expressing low (B16-F1 cells) and high (B16-BL6 cells) lung colonization potentials in cell adhesion assays in vitro. Differential adherence capability of the cells was observed: while high attachment levels of B16-BL6 cells were obtained, the low metastatic B16-F1 cells did not adhere to thrombin RGD. Antibodies raised against the RGD site in thrombin specifically recognized thrombin digested with plasmin, but were unable to interact with native thrombin or prothrombin and inhibited potently B16-BL6 melanoma cell adhesion. Furthermore, the antibodies failed to recognize RGD in other adhesive plasma proteins such as vitronectin, fibrinogen, or fibronectin. Provided that the RGD-containing fragments of thrombin are widely distributed throughout the vascular system, they may have a significant role during tumor progression and dislodgement of metastatic cells. The development of RGD mimetics and/or specific antibodies might thus be applied to inhibit a critical step in metastatic spread.

Amino Acid Sequence↗

Sub-additive effect of the combination of radiation and cisplatin in cultured murine and human cell lines.

The use of cisplatin (CDDP) as a potential radiosensitizer in tumors is controversial. Reports about CDDP interaction with radiation range from high radiosensitization to a clear sub-additive effect. We examined the effect of the combination of different concentrations of CDDP with radiation in murine mammary adenocarcinoma (EMT-6) and human ovarian carcinoma (OV-1063) cell lines. CDDP was given in the dose range of 0.01-3.0 micrograms/ml and radiation in the dose range of 1-6 Gy. A methylene blue assay of cell density was used for the evaluation of cell survival and rate of proliferation in 96-microwell plates. The validity of this assay for evaluation of cell survival was verified by colony-forming assay and radiolabeled thymidine uptake. The dose response to CDDP for both OV-1063 and EMT-6 cells lines was examined; the ID50 was 0.06 and 0.9 micrograms/ml respectively. A sub-additive effect of the combination of radiation with CDDP was clearly observed in the two cell lines tested; the increase in dose of each modality resulted in a decrease of the relative contribution on the effect of the other. These findings question the rationale of combining CDDP with radiation for the enhancement of tumor response, since with the increase in the dose of either modality the additional effect of the other decreases.

Adenocarcinoma↗