Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substrate gel electrophoresis is of use for detecting minute amounts of hyaluronidase (HAase). In substrate gel electrophoresis, hyaluronan (HA) is impregnated in a gel. To determine the presence of degradation enzymes for other glycosaminoglycans (GAGs), the sizes of whose molecules are much smaller than that of HA, we have developed a technique by which chondroitin sulfate (CS) is chemically modified by introducing an allyl group at the reducing end for its immobilization in the gel. Enzymes with CS-degrading activity were detected on a CS-copolymerized gel in the presence or absence of sodium dodecyl sulfate. The smallest amount of chondroitinase ABC and HAase was found to be 8 microU and 0.35 mU, respectively. By zymography using HA-impregnated and modified CS-copolymerized gels human serum HAase has been shown to consist of at least two isoforms each with its own substrate specificity. Using this method, uterine tumor tissue has been shown to secrete a novel HAase which degrades HA at neutral pH, but not CS at any pH. This method was also confirmed applicable to other GAGs for determining individual GAG-degrading enzymes. In future research, it will be used to examine the regulation of each GAG species in tissue.
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PMID:Analysis of glycosaminoglycan-degrading enzymes by substrate gel electrophoresis (zymography). 776

Nine cases are presented of a distinctive morphologic variant of myogenic gastrointestinal stromal tumor characterized by an unusually prominent myxoid stromal background reminiscent of a neural neoplasm but lacking the immunohistochemical or ultrastructural features of peripheral nerve sheath or ganglionic differentiation. The patients included six women and three men aged 42 to 86 years (mean, 70). The lesions occurred in the stomach (seven cases) and small intestine (two cases) and ranged in size from 2.5 to 9.5 cm. They were described grossly as well circumscribed, unencapsulated, with a prominently myxoid and often cystic cut surface. Histologically, the lesions were composed of a proliferation of round, spindle, or stellate cells embedded in an abundant myxoid stroma. Histochemical stains showed strong positive reaction of the myxoid stromal background with alcian blue at pH 2.5; this staining reaction was abolished by treatment with hyaluronidase, indicating an abundance of connective tissue mucosubstances rich in hyaluronic acid. Immunohistochemical stains showed strong positivity of the tumor cells with vimentin antibodies in all cases and focal weak to moderate positive staining with muscle actin (HHF35) in eight cases and with desmin in two. Stains for keratin, S-100; epithelial membrane antigen, and collagen type IV were uniformly negative. Ultrastructural examination carried out in all cases showed features consistent with those previously described for myogenic gastrointestinal stromal tumors, namely, scattered mitochondria and prominent Golgi apparati, strands of rough endoplasmic reticulum, focal accumulation of intracytoplasmic microfilaments with occasional focal condensations, subplasmalemmal attachment plaques and immature cell junctions, focal extracellular basal lamina material, and surface-oriented micropinocytotic activity. The myxoid changes observed in these tumors may represent a secondary, nonspecific reaction pattern of the tumor cells to some noxious stimulus, or they may be a form of degenerative phenomenon such as that commonly observed in smooth-muscle tumors of the uterus and other sites. Myogenic gastrointestinal stromal tumors with prominent myxoid stroma should be distinguished from benign schwannoma of the stomach and gastrointestinal autonomic nerve tumors. Because of the differences in prognosis for these entities, immunohistochemical and ultrastructural examinations are recommended for the evaluation of gastrointestinal stromal neoplasms with prominent myxoid features.
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PMID:Gastrointestinal stromal tumors with prominent myxoid matrix. Clinicopathologic, immunohistochemical, and ultrastructural study of nine cases of a distinctive morphologic variant of myogenic stromal tumor. 750 67

Fourteen cases of "normal-sized ovary carcinoma syndrome" (diffuse metastatic malignant disease of the abdominal cavity of the female, with normal-sized ovaries, with no origin assigned definitively by intraoperative or preoperative evaluation, Feuer et al., 1989) were analyzed histologically, histochemically, immunohistochemically and ultrastructurally. Through these studies, 14 cases were divided into 11 primary peritoneal tumors (4 diffuse malignant mesotheliomas and 7 serous surface papillary carcinomas) and 3 metastatic peritoneal tumors (2 ovarian tumors and 1 appendicular tumor). To distinguish serous surface papillary carcinomas from epithelioid diffuse malignant mesotheliomas, examinations such as hyaluronidase digestion test, electron microscopy, and immunohistochemical studies using antibodies for Ber-EP4 and Vimentin were found to be useful. In order to achieve an accurate prognosis of normal-sized ovary carcinoma syndrome, it seems necessary for us to accumulate more information on this syndrome.
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PMID:[Normal-sized ovary carcinoma syndrome: histopathological analysis of 14 cases]. 784 50

To get a long-term culture of tumor-infiltrating lymphocytes (TILs) is very difficult. The authors have investigated some suitable enzymes, their digestive conditions such as time and temperature, which may influence the viability and cytotoxicity of TILs. The results showed that collagenase II and IV could keep viability of TILs much longer than those treated with trypsin or hyaluronidase. The digestion with collagenase II or IV at 4 degrees C for 24 hours was much less damage to viability of TILs than those treated at 37 degrees C for one hour. The TILs, which digested at 4 degrees C for 24 hours, still had cytotoxicity against autologous tumor cells as long as sixty to seventy-five days.
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PMID:[Study on the influence of enzymatic digestion upon tumor-infiltrating lymphocytes]. 804 6

Doxorubicin is an anticancer agent widely used in the treatment of human cancer. The major limitation of this drug governing the cell-killing effect appears to be its poor penetration into a tumor mass. We have studied the effects of hyaluronidase on the penetration and cell-killing effect of doxorubicin using multicellular tumor spheroids (MTS). MTS approximately 500 microns in diameter were produced by a liquid-overlay culture technique from PC-10 lung and HEp-2 laryngeal squamous carcinoma cell lines. Cells in MTS and monolayer were exposed to hyaluronidase for various lengths of time; this was followed by a 1-h resting interval and a subsequent 1-h exposure to doxorubicin. MTS and monolayer cells were then trypsinized to a single-cell suspension and subjected to clonogenic assay. Hyaluronidase at a concentration of 25 U/ml or 250 U/ml was nontoxic to the monolayer cells. For PC-10 MTS, pretreatment with 25 U/ml hyaluronidase for 24 h and 72 h resulted in approximately 20% increases in Doxorubicin cell killing at the median (IC50) dose as compared to doxorubicin alone. HEp-2 MTS were more sensitive to the hyaluronidase pretreatment. Thus, a 1-h exposure to the enzyme produced a 40% increase in doxorubicin-induced cell death at the IC50 dose. A fluorescence microscopic study revealed that a 1-h exposure of MTS to doxorubicin produced doxorubicin fluorescence only in the one or two outer layers of MTS. When MTS were pretreated with hyaluronidase, there was enhanced penetration of doxorubicin fluorescence into the MTS core. Hyaluronidase-induced enhancement of Doxorubicin penetration and its cell-killing effect is dependent on the exposure time and tumor cell origin. These data suggest that anecdotal reports of hyaluronidase-enhanced activity of preclinical chemotherapy deserve a controlled trial.
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PMID:Effects of hyaluronidase on doxorubicin penetration into squamous carcinoma multicellular tumor spheroids and its cell lethality. 812 58

We report 20 cases of a peculiar fatty tumor that occurred in 16 female and four male patients who were 14-70 years old (median, 36 years). Most lesions were situated in the subcutis, superficial muscular fascia, or skeletal muscle of the limbs and limb girdles (15), trunk (3), and the head and neck (2). They were 1.5-11 cm in size (median, 4 cm) and usually described as yellow (13 of 15) and encapsulated (13 of 15). Microscopically they were well circumscribed and consisted of nests, strands, and sheets of eosinophilic and vacuolated cells, which contained glycogen and fat droplets, resembling brown fat cells, lipoblasts and chondroblasts. In all cases there was a variable background of mature adipose tissue associated with a prominent, partially fibrinous to hyalinized myxoid matrix that contained acid mucopolysaccharides usually resistant to hyaluronidase digestion. Several cases had foci of serous atrophy, perivascular fibrosis, and small thrombi; two were focally calcified. The lesions stained for S100 protein (11 of 12), vimentin (10 of 11), and CD68 antigen with KP1 (9 of 11); focal staining for keratin was also seen (4 of 11), but none stained for epithelial membrane antigen or actin or with HMB45. Follow-up in 12 cases (median, 9.5 years) revealed no local recurrences or metastases. Despite its deep location and atypical cellular features, the lesion's nonaggressive behavior suggests it is benign and neither a myxoid liposarcoma nor a myxoid chondrosarcoma, with which it is most frequently confused. The presence of glycogen in vacuolated fat cells is similar to brown fat, and the presence of sulfated stromal mucins supports focal chondroid differentiation. Although the pathogenesis remains uncertain, a lipoma with hibernomatous features, myxoid change, chondroid metaplasia, and secondary degenerative features is favored over a lipogranulomatous process.
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PMID:Chondroid lipoma. A unique tumor simulating liposarcoma and myxoid chondrosarcoma. 821 55

CD44 is a cell-surface glycoprotein postulated to play a role in a variety of biological processes, including lymphocyte homing and tumor-cell metastasis. Several isoforms of CD44 have been identified in human cells, and the genesis of some of these isoforms has been attributed to alternative splicing. In the study presented here we amplified three novel transcript variants of CD44 from human cell lines using a reverse transcriptase-polymerase chain reaction strategy. Two of the novel isoforms differed from previously described CD44 isoforms as a result of alternative splicing that occurred at previously reported splice junctions. The third novel CD44 isoform was generated from a previously unreported alternative splice junction near the 5' end of the open reading frame. Southern blot analysis of genomic DNA revealed that these novel isoforms and all of the previously described CD44 isoforms arose from alternative splicing. The capability of cells to modify their CD44 alternative splicing pattern was demonstrated in MCF-7 cells, which altered their CD44-isoform expression pattern in response to treatment with hyaluronidase. A better understanding of mechanisms regulating CD44 alternative splicing may provide insights into diverse processes, including tumor-cell metastasis and lymphocyte homing.
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PMID:Novel variants of CD44 arising from alternative splicing: changes in the CD44 alternative splicing pattern of MCF-7 breast carcinoma cells treated with hyaluronidase. 835 81

Various tumors secrete tumor-specific substances capable of producing signs and symptoms in host organs not caused by direct tumor invasion or organ destruction. These symptoms are collectively referred to as "remote effects" or "paraneoplastic syndromes" of malignancy. Paraneoplastic syndromes are uncommon in childhood cancer. In Wilms tumor several distinct paraneoplastic syndromes have been reported: hypertension, erythrocytosis, hypercalcemia, Cushing syndrome, and acquired Von Willebrand disease. In addition some tumor-specific substances are known to be elevated in patients with a malignancy without causing specific symptoms. These so called "tumor markers" can be used to detect early recurrence in previously treated patients, or in the evaluation of patients undergoing adjuvant therapy. Five of particular interest are erythropoietin, neuron-specific enolase (NSE), hyaluronic acid (HA), hyaluronic acid-stimulating activity (HSA), and hyaluronidase.
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PMID:Serum biological markers and paraneoplastic syndromes in Wilms tumor. 838 82

The Hyal-1 locus, which we have previously described and mapped to mouse chromosome 9, influences the serum levels and molecular weight forms of hyaluronidase. We have also shown that the growth of two transplantable tumors, the 3LL carcinoma and the B16F10 melanoma, is influenced by the alleles at Hyal-1, in that the tumors develop more slowly in congenic B6.C-Hyal-1a (also called HW23) mice than in the parental Hyal-1b C57BL/6 mice. Here we present evidence that tumor development is stimulated and mortality is accelerated in B6.C-Hyal-1a mice grafted with 3LL carcinoma cells when treated with alpha/beta interferon (IFN-alpha/beta) or with IFN-beta, whereas in IFN-treated C57BL/6 mice 3LL tumor growth is inhibited. Likewise, in B6.C-Hyal-1a mice grafted with B16F10 melanoma cells, IFN-alpha/beta treatment results in stimulation of tumor growth, whereas in IFN-treated C57BL/6 mice tumor growth, whereas in IFN-treated C57BL/6 mice tumor growth is inhibited and mortality delayed. Thus, IFN-alpha/beta treatment of B6.C-Hyal-1a mice results in stimulation of tumor development and sometimes in accelerated mortality. This is the opposite of the usually described effect of IFN treatment in mice, which is inhibition of tumor development and delayed mortality, as was indeed observed in the C57BL/6 mice in the present experiments. These results provide the first indication that host genes can up- or down-regulate the antitumor activity of IFN and that, on some genetic backgrounds, IFN treatment enhances rather than inhibits tumor development. This may help to explain the apparent discordance between mouse model studies, which hitherto have consistently reported inhibition of tumor formation by IFN, and the clinical trials, in which only a limited percentage of individuals show tumor regression while others have no beneficial effect or even have progression of disease in spite of the IFN treatment.
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PMID:Accelerated tumor development in interferon-treated B6.C-Hyal-1 a mice. 851 20

Oncogene-dependent regulation and tumor relatedness of CD44 expression were investigated in Balb/c 3T3 cells and their derivatives transformed with different ras oncogenes (metastatic tumor model) or the human c-sis oncogene (non-metastatic model). Ras transformants using either the Harvey or Kirsten oncogenes expressed high levels of cell surface CD44 protein that bound fluoresceinated hyaluronan (HA). Much lower levels of CD44 were expressed in parental 3T3 cells, ras- revertants generated from Kirsten-transformed cells, or c-sis transformants, confirming the significance of the ras oncogene in this upregulation. To determine whether endogenous HA regulates these parameters, hyaluronidase treatment of ras transformants exposed more cell surface CD44 to anti-CD44 antibody and increased fluoresceinated HA binding; this did not occur with 3T3 or c-sis transformants. CD44 expression and its HA-binding function were conserved in a panel of in vivo primary and lung metastatic tumor cell lines derived from ras transformants. Ras transformants also retained the ability to downregulate CD44 protein levels in confluent cultures which occurred through a translational or post-translational mechanism (as CD44 mRNA levels were not reduced). These results taken together demonstrate that ras-dependent regulation of CD44 may correlate with tumor progression and metastasis in vivo, possibly (although not exclusively) supporting CD44's importance in metastatic progression.
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PMID:Oncogene-dependent expression of CD44 in Balb/c 3T3 derivatives: correlation with metastatic competence. 852 19


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