Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyestradiol phosphate is a polymeric ester of estradiol -17 beta and phosphoric acid. The large molecule has very weak estrogenic properties but is a strong inhibitor of several enzymes, e.g. acid and alkaline phosphatases and hyaluronidase. Given by injection it acts as a depot estrogen slowly releasing estradiol during several months. Given to male patients with prostatic carcinoma, it acts as weak inhibitor of gonadotrophins and testicular hormone production. For the treatment of prostatic carcinoma in 105 patients it gave good palliation and over-all survival 38% after five years. In a new series of 126 patients, polyestradiol phosphate was combined with ethinylestradiol. Over-all survival at five years in this group was 62%. It is suggested that polyestradiol phosphate is as effective as other estrogen therapy for prostatic carcinoma and that the combination with ethinylestradiol is superior to the single drug therapy.
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PMID:Polyestradiol phosphate and ethinyl estradiol in treatment of prostatic carcinoma. 693 44

Six cases of localized benign papillary mesothelioma of peritoneum were retrieved from laboratory files over a 20-year period. One presented because of pain following torsion and the remaining five were incidental findings at operation. Light microscopy showed a delicate papillary stroma covered by a single layer of mesothelial cells. The mesothelial cells often showed punctate periodic acid-Schiff staining of cytoplasm. The brush border and stroma showed alcian blue positive staining which was abrogated by prior incubation with hyaluronidase. Electron microscopy revealed typical features of mesothelial cells with long microvilli, rough endoplasmic reticulum in relation to mitochondria, bundles of microfilaments, and tight junctions. Between cells there was a series of intercommunicating channels containing occasional lymphocytes and debris. These features are compared with nodular mesothelial hyperplasia, malignant mesothelioma and adenomatoid tumours of the genital tract. The necessity to distinguish benign papillary mesothelioma from metastatic carcinoma is stressed and relies on the recognition of their mesothelial origin.
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PMID:Benign papillary mesothelioma of peritoneum: a histological, histochemical and ultrastructural study of six cases. 721 74

Sixteen cases of malignant mesothelioma (13 pleural and 3 peritoneal) are reported. Fifteen cases were autopsied; in one case only biopsy material was available which are studied by electron microscopy. Among the autopsy cases, 12 had had previous biopsies, one had undergone multiple cytological examinations and 2 cases only one cytological examination. It was concluded that clinical signs and symptoms of mesothelioma were not specific and did not allow the diagnosis. For differential diagnosis as between mesothelioma and metastatic carcinoma, biopsy seemed to be more reliable that exfoliative cytology. Alcian blue stain after hyaluronidase digestion is a reliable test in the diagnosis of mesothelioma only when alcian blue is positive initially. However, in half of our mesothelioma cases this stain remained negative. Electron microscopic study appeared to be a satisfactory method of differentiating between malignant mesothelioma and metastatic carcinoma.
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PMID:[Malignant mesothelioma. Retrospective study of 16 cases]. 722 10

An 18-year-old woman underwent exenteration of the right orbit for tumor recurrence 3 years subsequent to external-beam irradiation for a lacrimal gland tumor diagnosed as an "adenocarcinoma." Light microscopy of the exenteration specimen revealed an acinic cell carcinoma of the lacrimal gland, with a predominant microcystic (latticelike) pattern of growth. Cytoplasmic vacuoles and the secretion within the microcysts stained positive with periodic acid-Schiff with and without alpha-amylase, alcian blue (at a pH of 2.5), mucicarmine, and colloidal iron with and without hyaluronidase. This histochemical staining for epithelial mucins supports the theory that the lacrimal gland, although serous in type, may also function as a modified mucus gland. There was cytoplasmic immunopositivity for keratin (CAM 5.2, KAE 1-3); immunostaining for vasoactive intestinal polypeptide was negative. Electron microscopy disclosed undifferentiated features of intercalated duct cells. We speculate that the lack of immunoreactivity for vasoactive intestinal polypeptide may be correlated with the predominantly undifferentiated intercalated duct cell features observed ultrastructurally.
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PMID:Acinic cell carcinoma of the lacrimal gland. 754 Mar 87

Although binding of peanut agglutinin (PNA) to keratinocytes is often used as a marker of terminal differentiation, the identity of the PNA-binding glycoproteins has been unclear. We now show that an antiserum raised against the glycoproteins recognises isoforms of CD44, the most abundant of which could be labelled with [35S]sulphate, indicating the presence of glycosaminoglycan side chains. RT-PCR analysis showed that keratinocytes expressed at least 5 forms of CD44 containing different numbers of exons from the variable region of the extracellular domain and also expressed the standard 'haemopoietic' form of CD44 which lacks the variable exons. Standard and variant isoforms of CD44 were expressed both by proliferating keratinocytes and cells undergoing terminal differentiation, although the level of CD44 mRNAs decreased when keratinocytes were placed in suspension to induce differentiation. The role of CD44 in intercellular adhesion was investigated by plating keratinocytes onto a rat pancreatic carcinoma line transfected with different CD44 isoforms. Keratinocyte adhesion to transfectants expressing variant exons 4-7 was greater than to cells expressing standard CD44 and could be inhibited with hyaluronan or digestion with hyaluronidase. These observations confirm earlier predictions that the PNA-binding glycoproteins of keratinocytes play a role in intercellular adhesion.
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PMID:CD44 is the major peanut lectin-binding glycoprotein of human epidermal keratinocytes and plays a role in intercellular adhesion. 754 99

Four cases are described of a distinctive morphologic variant of thymic carcinoid that was characterized by abundant stromal mucin admixed with the neuroendocrine elements resulting in a histologic picture reminiscent of metastatic mucin-secreting carcinoma. The patients were three men and a woman, aged 22 to 43 years. The tumors presented with symptoms of chest discomfort, cough, and dyspnea and were described as large anterior mediastinal masses on chest radiographs and computerized scans. Histologically, all cases showed nests and strands of tumor cells embedded in an abundant lightly eosinophilic, mucinous stroma with small cellular clusters as well as scattered single tumor cells seen floating in the mucin. The mucinous matrix was negative for periodic acid Schiff's and mucicarmine stains; alcian blue stains at pH 2.5 showed strong positivity of the mucinous material; this reaction was abolished by treatment with hyaluronidase, indicating the presence of nonepithelial stromal mucosubstances. Immunohistochemical stains showed strong positivity of the tumor cells with CAM 5.2, chromogranin, synaptophysin, and neuron-specific enolase, and negative staining with carcinoembyronic antigen and epithelial membrane antigen. Electron microscopy done in one case showed abundant dense-core cytoplasmic neurosecretory granules; there was no evidence of glandular secretory activity by the tumor cells. The tumors in two patients behaved in a highly aggressive fashion, with invasion of the chest wall, recurrence, and metastases to the lungs, pleura, and axillary, retroperitoneal, and mesenteric lymph nodes. Thymic carcinoid should be considered in the differential diagnosis of mediastinal neoplasms displaying prominent mucinous features. Application of immunostains and electron microscopy will be of value for establishing the correct diagnosis in this setting.
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PMID:Thymic carcinoid with prominent mucinous stroma. Report of a distinctive morphologic variant of thymic neuroendocrine neoplasm. 757 90

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

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

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

From a total of 62,858 autopsy files kept over a 30-year period (1961-1990), all cases that met the following criteria were extracted: (a) main tumor masses in the peritoneum with no evidence of origin from any adjacent organ; (b) histologic features suggestive of serous ovarian carcinoma; (c) ovaries definitely recognizable as having either no tumorous involvement or tumor confined to the surface and cortex of the ovaries; and (d) in patients with a history of abdominal operations, availability of slides and reports. From 670 stages III and IV serous carcinomas of the ovary, we retrieved 57 cases (8%) of serous surface papillary carcinoma (SSPC) of the peritoneum. All SSPCs occurred in women with an age range from 47 to 84 years (median 66 years). Eight cases (14%) were grade I, 36 (63%) were grade II, and 13 (23%) were grade III. Histologically, four cases (7%) resembled malignant epithelial mesothelioma in major parts of the tumor, and in one case endometrioid differentiation of the tumor was conspicuous. Additional histochemical and immunohistochemical examinations were performed in 30 cases of SSPC. In 14 cases (47%) neutral mucosubstances were identified by periodic acid-Schiff positivity after diastase predigestion, and in 16 cases (53%) acid mucosubstances were identified by alcian blue staining. In one of these cases the alcian blue-positive substances were abolished under predigestion by testicular hyaluronidase. Tumor cells stained positive for cytokeratin (100% of the cases), B72.3 (90%), Ber-EP4 (83%), CD 15 (57%), placental alkaline phosphatase (53%), CA 125 (43%), vimentin (23%), and carcinoembryonic antigen (10%). The survival rates at 1 year for SSPC (0%) were significantly shorter (p = 0.03) in comparison with stages III and IV ovarian carcinomas (34%). Problems of definition and differential diagnosis of SSPC are discussed.
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PMID:Varieties of serous surface papillary carcinoma of the peritoneum in northern Germany: a thirty-year autopsy study. 859 33


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