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Biomedical subjects

Z Fuks

Publications and source records attributed to Z Fuks.

At least 235 records · Page 13Linked to original sources
PubMed1983

Secondary leukemia following treatment of Hodgkin's disease: ultrastructural and cytogenetic data in two cases with a review of the literature.

Two cases of secondary acute nonlymphocytic leukemia developing after combined chemo-radiotherapy for Hodgkin's disease (HD) are reported. The first case was a 28-year-old woman with PSIIIsA HD, treated with total lymphoid irradiation followed by combination chemotherapy that was almost entirely ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), who developed acute monoblastic leukemia three years after the diagnosis of Hodgkin's disease. We believe this to be the first reported case of secondary leukemia associated with the combination of radiotherapy and ABVD chemotherapy. The second case was a 37-year-old man with Stage IVB Hodgkin's disease, treated with radiotherapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) who developed acute myeloblastic leukemia five years after the diagnosis of Hodgkin's disease. Both cases showed typical changes of panmyelosis demonstrated by cytochemical and ultrastructural studies. In both cases, bone marrow cells had a dominant clone with a markedly abnormal karyotype. The nature of therapy-related secondary leukemia after Hodgkin's disease and its relationship to current modes of treatment are discussed.

Adult↗
PubMed1983

Serum transcobalamin levels as an early indicator of bone marrow engraftment following transplantation.

Three B12 binding proteins, the transcobalamins TCI, TCII and TCIII, were determined serially in the serum of five patients who underwent bone marrow transplantation. The increase in TCII, followed by the increase in TCI, proved to be an early indicator of bone marrow regeneration, reaching a peak of up to twice its normal levels at least 5 d prior to the rise of the peripheral white blood cell count.

Adolescent↗
PubMed1983

The use of carcinoembryonic antigen for identification of human tumor cells in malignant effusions.

A specific anti-carcinoembryonic antigen (CEA) antiserum was used to identify CEA-positive tumor cells in peritoneal and pleural effusions obtained from patients with various malignant neoplasia. In 7 out of 10 fluids in which tumor cells were detected by cytological examinations, cytoplasmic CEA-positive cells were also detected by an indirect immunofluorescence test. In addition, out of 11 fluid samples cytologically negative for tumor cells, CEA-positive cells were found in 8 cases. When both staining for cytoplasmic CEA and soluble fluid CEA levels were considered in combination, 81% of the samples were found to be positive by either one or both of these markers, whereas only 54% were positive by using cytological criteria. The data suggest that CEA marker may be used to identify tumor cells and to assess malignancy in pleural and peritoneal effusions in patients with certain types of cancer. The CEA marker was also used for identifying tumor cells grown in tissue cultures and for separating viable CEA-positive and CEA-negative cells from a mixed cell population using the fluorescence-activated cell sorter.

Ascitic Fluid↗
PubMed1983

Prognostic significance of changes in serum transcobalamin levels in cancer patients with chemotherapy-induced granulocytopenia.

Serum transcobalamin (TC) levels were determined daily in 14 adults suffering from advanced nonhematological malignancies and hospitalized because of chemotherapy-induced leukopenia and fever. Even during the nadir leukocyte count, TCI and TCIII serum levels were normal or only slightly decreased indicating that bone marrow activity was not completely suppressed. A significant increase in serum TCII level was observed in all patients, with peak values occurring an average of 4.5 days from admission at a time when the median leukocyte count was 2,300/mm 3. Full white cell count recovery followed this peak TCII elevation within a mean of 5.5 days in all patients, coinciding with a fall in TCII levels to basal values. The rise in serum TCII level appears to be an early indicator for imminent bone marrow recovery in myelosuppressed patients.

Agranulocytosis↗
PubMed1983

Insulin binding and degradation in vascular endothelial cells: modulation by cell growth and culture organization.

The interaction of insulin with the vascular endothelium and its modulation by cell growth and culture organization was studied using bovine aortic endothelial cells in monolayer cultures. Three types of cultures were investigated: 1) confluent nondividing cultures, organized and differentiated as the in vivo tissue; 2) subconfluent, not yet organized cell cultures, representing proliferating endothelium; and 3) endothelial cell cultures modified to lose their property of contact inhibition, growing in multiple layers. All three types of cultures exhibited specific binding of 125I-insulin to high and low affinity cell surface receptor sites, and were capable of degrading 125I-insulin. Preexposure of the cultures to insulin resulted in a time dependent reduction in the availability of cell surface receptors (down-regulation). Insulin binding per cell was 2.4-fold and 10-fold higher in the subconfluent and modified cultures, respectively, as compared to the contact-inhibited confluent cultures. Similarly, the rate of insulin degradation was higher in the subconfluent and modified cultures (2.3-fold and 20-fold, respectively). Subconfluent cultures were more sensitive than confluent cultures to the down-regulatory effect of insulin. They exhibited a 60% decrease in insulin binding as compared to a 40% decrease in confluent cultures after preexposure to 50 ng/ml insulin. The increase in insulin binding and degradation in growing endothelial cells suggests a role for the hormone in the regulation of endothelial cell growth, e.g. in response to injury. This was further supported by the observation of a dose-dependent stimulation of [3H]thymidine incorporation into sparse, serum-starved endothelial cells by physiological concentrations of the hormone.

Animals↗
PubMed1983

Successful chemotherapy of recurrent intracranial germinoma with spinal metastases.

A recurrent CNS germinoma with subependymal and spinal metastases was treated by combination of cis-platinum, bleomycin, and vinblastine, resulting in disappearance of intracranial and spinal tumor. Second intracranial relapse responded again to the same combination chemotherapy. Response of spinal metastases to this combination chemotherapy has not been reported previously.

Adult↗
PubMed1983

Thyrotrophin and growth hormone secretion and cell morphology in hypothyroid pituitary cells cultured on a natural extracellular matrix.

Hypothyroid rat pituitary cells were cultured on an extracellular matrix (ECM) produced by corneal endothelial cells. ECM markedly affected the following parameters. 1) Cell attachment, spreading and proliferation were improved, resulting in a more rapid formation of confluent cell monolayers. 2) In the presence of ECM the production of both thyrotrophin (TSH) and growth hormone (GH) was larger than in its absence. Immunofluorescence studies revealed that 20% of the cells in these monolayers were thyrotrophs; consequently, TSH content was higher while GH level was lower than in control cultures of euthyroid pituitaries. These data suggest that the in vivo physiological differences are maintained by the conditions of the culture. 3) ECM enabled the response of both the somatotrophs and the thyrotrophs to thyrotrophin releasing hormone (TRH) and the cells remained responsive for at least 10 days. Maximal stimulation (1.3- to 6-fold) was obtained with 14 nM of TRH. In the absence of ECM the cells failed to respond to TRH. 4) Cell morphology was examined by scanning electron microscopy (SEM). Cells grown on ECM were characteristically epithelial, whereas those cultured on plastic plates had a fibroblast-like appearance. Four types of cells were identified in the epithelial cell monolayers by the appearance of their surface. TRH induced a 2-fold increase in the number of cells covered with microvilli and a corresponding decrease in the number of smooth surfaced cells. This suggests that hormone secretion is associated with the formation of microvilli.

Animals↗
PubMed1983

Treatment of febrile granuloycytopenic cancer patients receiving antineoplastic therapy with a combination of carbenicillin, cefazolin and gentamicin.

A three drug regimen of carbenicillin, cefazolin and gentamicin was used for the treatment of patients with solid tumors, who developed fever while granulocytopenic following chemotherapy. Thirty-five (8%) of 426 cancer patients receiving various combinations of antineoplastic chemotherapy qualified for the antibiotic treatment. Nine patients (26%) had bacteriologically confirmed infections, all with gram negative microorganisms. Twenty-four patients (69%) recovered and eleven (31%) died. All deaths occurred within five days of antibiotic therapy; in patients who recovered, the fever subsided within six days. Mortality was not influenced by the presence of a positive bacterial culture, age, or the cytotoxic agents used. It was, however, strongly related to metastatic spread: nine out of 14 patients with liver metastases (64%) died from the infection, while only two of 11 patients (18%) with other metastatic sites failed to respond to the antibacterial therapy. No death occurred in 10 patients who had local disease or received adjuvant therapy. This combined antibiotic therapy was as effective as reported for other combinations, with no serious side effects.

Adolescent↗
PubMed1983

Lymphoma cell-mediated degradation of sulfated proteoglycans in the subendothelial extracellular matrix: relationship to tumor cell metastasis.

Cloned lines of the methylcholanthrene-induced DBA/2 low-metastatic T-lymphoma Eb line and its highly metastatic variant ESb line were compared for the ability to degrade proteoglycans in the subendothelial extracellular matrix (ECM) produced by cultured endothelial cells. The ECM was metabolically labeled with Na2(35)SO4, and the tumor cell-mediated release of labeled degradation products was analyzed by gel filtration. More than 90% of the labeled material released upon incubation of ESb cells with the ECM, either when exposed or covered with vascular endothelial cells, was in the form of low-Mr, heparan sulfate-containing fragments (Mr approximately 10(4)) compared to high-Mr sulfated proteoglycans (mostly excluded from Sepharose 6B) released by incubation with the low-metastatic Eb cells. The same high- and low-Mr degradation products were obtained by incubation of the ECM with a serum-free medium conditioned by the low (Eb)- and high (ESb)-metastatic sublines, respectively. The high-Mr proteoglycans released by incubation of the ECM with Eb-conditioned medium was further degraded into Mr 10(4) glycosaminoglycan fragments upon a subsequent incubation with ESb-conditioned medium. These fragments were smaller than glycosaminoglycan side chains released by treatment of the ECM with papain or alkaline borohydride, suggesting an ESb-specific endoglycosidase activity. The higher ability of the ESb over the Eb cells to solubilize the glycosaminoglycan scaffolding of the sub-endothelial ECM may, among other properties, facilitate their hematogenous dissemination and extravasation.

Animals↗
PubMed1983

Lymphoma cell interaction with cultured vascular endothelial cells and with the subendothelial basal lamina: attachment, invasion and morphological appearance.

Invasion and extravasation of tumor cells through blood vessels and the capillary bed of different organs provide a major pathway for the dissemination and metastatic spread of neoplastic cells. In order to investigate this process in vitro, cloned lines of the low-metastatic methylcholanthrene-induced DBA/2 T lymphoma Eb and its highly metastatic variant line ESb were compared for their mode of interaction (attachment, invasion and morphological appearance) with a confluent monolayer of cultured vascular endothelial cells and with the subendothelial extracellular matrix (ECM). Both the Eb and ESb lymphoma cells exhibited a much faster and firmer attachment to the subendothelium than to the apical surface of the endothelial cell layer. Whereas the Eb cells mostly retained their spheroidal shape when attached to the subendothelium, the ESb cells adopted within 5-24 h a flatter morphology and 30-40% of the cells exhibited an extension of a long pseudopod. Invasion through the endothelial cell layer was faster and occurred to a higher extent with ESb than with Eb cells and was most frequently seen at the edges of an artificial wound made to locally expose the subendothelial basal lamina. Lymphoma cell invasion was most often initiated by a cytoplasmic process indenting at junctions between adjoining endothelial cells and less often traversing through intact cells. Invasion was followed by regeneration of the endothelium and sealing of the invasive cells from the exterior environment. These findings corroborate and extend previous observations on endothelial cell penetration and basement membrane attachment and degradation by various types of metastatic tumor cells. The major new observation comes from the striking contrast in morphological appearance and dynamic behavior between the high- and low-metastatic cells of this tumor system after contact with endothelial cells or their ECM. This suggests a critical role of pseudopod formation and cell motility in endothelial cell penetration and invasion, and thus in an essential step in cancer metastasis.

Animals↗
PubMed1983

Enhancement of adriamycin delivery to liver metastatic cells with increased tumoricidal effect using liposomes as drug carriers.

We have investigated the tissue distribution of liposome-entrapped Adriamycin (ADM) in mice with metastatic spread to the liver and spleen after inoculation of J-6456 lymphoma cells. Sonicated phosphatidylserine:phosphatidylcholine:cholesterol liposomes were used as carriers of ADM, based on previous studies on the drug entrapment, stability, and tissue distribution of ADM-containing liposomes of various compositions (A. Gabizon, A. Dagan, D. Goren, Y. Barenholz, and Z. Fuks. Cancer Res., 42: 4734-4739, 1982). Increased hepatic and splenic levels of ADM were found in tumor-bearing mice when the drug was injected in the liposome-entrapped form. Concomitantly, decreased cardiac uptake of ADM was observed in tumor-bearing mice treated with liposome-entrapped ADM. In order to measure the concentration of ADM directly in metastatic cells, J-6456 lymphoma cells were isolated from the liver by Percoll density gradients. It was found that the ADM levels were significantly augmented in tumor cells from mice given injections of liposome-entrapped ADM as compared to those given injections of free ADM at all time intervals checked after drug injection. In addition, the in vitro and in vivo growth ability of these isolated metastatic cells was significantly more impaired when they were obtained from mice receiving liposome-entrapped ADM as compared to mice which received free ADM. The histopathological damage to the normal liver parenchyma of mice treated with liposome-entrapped ADM was mild and confined to discrete foci and was not significantly different from that observed in mice treated with free ADM. These results indicate that liposome delivery may provide an efficient means of improving the therapeutic efficiency of ADM in certain forms of metastatic liver disease, while diminishing the potential hazard of cardiotoxicity.

Animals↗
PubMed1982

Platelet interaction with the extracellular matrix produced by cultured endothelial cells: a model to study the thrombogenicity of isolated subendothelial basal lamina.

Cultured bovine endothelial cells produce an extensive underlying extracellular matrix (ECM) which closely resemble the vascular subendothelial basal lamina in its organization and chemical composition. This naturally produced ECM was used to study the interaction of platelets with the subendothelium when exposed or covered with vascular endothelial cells. Incubation of platelet rich plasma with the ECM induced a rapid and massive platelet adherence, aggregation, thromboxane formation and release reaction. These were demonstrated using phase and scanning electron microscopy, Indium-111 or (14C)-serotonin labelled platelets, and a radioimmunoassay for thromboxane B2. In contrast to the ECM no platelet activation was induced either by uncoated plastic dishes or ECM covered with a confluent endothelial cell monolayer. Aspirinized platelets failed to undergo aggregation and degranulation, when incubated with the ECM. Culture dishes coated with characteristic constituents of the basal lamina such as collagen type IV and type V or fibronectin induced a much lower platelet reactivity as compared with ECM coated dishes. Digestion of ECM components (collagen, fibronectin, hyaluronic acid, and chondroitin sulphate) by specific enzymes was not associated with a substantial decrease in its platelet reactivity. Furthermore, exposure of ECM to sodium dodecyl sulphate or sodium periodate, or freezing and thawing did not decrease its biological activity. In contrast, platelet activation was completely abolished following heat denaturation or glutaraldehyde fixation of the ECM. The availability of a naturally produced ECM provides an appropriate model to study the interaction of platelets with the subendothelium in a controlled system which is isolated from other components of the vessel wall.

Animals↗
PubMed1982

Anterior decompression of the spine for metastatic epidural cord compression: a promising avenue of therapy?

Most metastatic epidural tumors arise in a vertebral body and invade the anterior epidural space. Therefore, it is logical to decompress the spine anteriorly and not by traditional laminectomy. Surgical decompression is indicated if relapse occurs after radiotherapy and further radiation cannot be administered, if there is neurological deterioration during radiotherapy, and when histological diagnosis of the primary tumor is lacking. This pilot study consists of eleven consecutive anterior decompressions of the spine performed in nine patients. In seven instances other treatment modalities had been exhausted, and in four patients a tissue diagnosis was lacking. Before operation eight of the patients were nonambulatory, four of them paraplegic. Following decompression all but one patient became ambulatory. At operation the main bulk of the compressing tumor was found anterior or anterolateral to the cord. Spine stabilization was done when stability was a problem. Wound infection in one patient was the only postoperative complication. The encouraging outcome of our management prompts us to suggest that anterior decompression of the spine should be considered more often in metastatic compression of the cord and cauda equina.

Cauda Equina↗