Serum proteolytic activity during the growth of C6 astrocytoma

✓ Tumor growth is dependent on the ability of neoplastic cells to induce angiogenesis. Blood-vessel remodeling requires the reconstruction of the nonfibrous proteins and type IV collagen components of the basement membrane. This study has assessed the influence of the growth of C6 astrocytoma cells in the rat spheroid implantation model on serum general protease and type IV collagenase activity. The results demonstrate that general protease activity increased in serum, reaching maximum values on Day 6 and Day 13 following spheroid implantation, and that type IV collagenase activity increased in serum, obtaining maximum values on Day 8 and Day 15. The measurement of serum proteolytic activity may be of value in the detection of recurrent tumors.

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Release of collagen type IV degrading activity from C6 astrocytoma cells and cell density

Journal of Neurosurgery ◽

10.3171/jns.1996.84.6.1013 ◽

1996 ◽

Vol 84 (6) ◽

pp. 1013-1019 ◽

Cited By ~ 8

Author(s):

Masashi Tamaki ◽

Warren McDonald ◽

Rolando F. Del Maestro

Keyword(s):

Cell Density ◽

Collagen Type ◽

Cell Communication ◽

Collagen Type Iv ◽

Major Protein ◽

Content Type ◽

Type Iv ◽

Astrocytoma Cells ◽

C6 Astrocytoma

✓ Type IV collagen is a major protein component of the vascular basement membrane and its degradation is crucial to the initiation of tumor-associated angiogenesis. The authors have investigated the influence of cell density on the release of collagen type IV degrading activity by C6 astrocytoma cells in monolayer culture. The release of collagen type IV degrading activity was assessed biochemically, immunocytochemically, and by Western blot analysis. The results demonstrate that increasing plating density and increasing cell density are associated with decreased collagen type IV degrading activity released per tumor cell. These findings indicate the existence of regulatory mechanisms dependent on cell—cell communication, which modulate release of collagen type IV degrading activity. The extrapolation of these results to the in vivo tumor microenvironment would suggest that individual and/or small groups of invading tumor cells, distant from the main tumor mass, would release substantial collagen type IV degrading activity, which may be crucial to their continued invasion and to angiogenesis.

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Histopathology of arteriovenous malformations after gamma knife radiosurgery

Journal of Neurosurgery ◽

10.3171/jns.1997.87.3.0352 ◽

1997 ◽

Vol 87 (3) ◽

pp. 352-357 ◽

Cited By ~ 215

Author(s):

Bernard F. Schneider ◽

David A. Eberhard ◽

Ladislau E. Steiner

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Gamma Knife ◽

Arteriovenous Malformations ◽

Type Iv Collagen ◽

Gamma Knife Radiosurgery ◽

Histopathological Changes ◽

Content Type ◽

Type Iv ◽

Fine Print

✓ Stereotactic radiosurgery effectively obliterates many arteriovenous malformations (AVMs). Hemodynamic changes in AVMs after radiosurgery have been illustrated using magnetic resonance imaging and angiography, but there have been no detailed reports describing the underlying histopathological changes. This study examines AVMs at various times after gamma knife radiosurgery (GKRS) and describes the histopathological changes that lead to vessel occlusion. The authors examined nine AVM specimens obtained 10 months to more than 5 years after GKRS, by using routine histopathological stains as well as immunohistochemical techniques to detect smooth-muscle actin, factor VIII, and type IV collagen. Blood vessels within the AVMs showed progressive changes leading to narrowing or obliteration of the lumen. The earliest changes after gamma knife irradiation appear to be damage to endothelial cells, followed by progressive thickening of the intimal layer caused by proliferation of smooth-muscle cells that elaborate an extracellular matrix that includes type IV collagen. Finally, cellular degeneration and hyaline transformation occur. For statistical correlation analyses, the specimens were graded according to the degree of histopathological change and the relative number of vessels showing such changes. Both of these parameters were significantly correlated with time after GKRS and with AVM size reduction shown on follow-up imaging studies. Gamma knife radiosurgery of AVMs causes endothelial damage, which induces the proliferation of smooth-muscle cells and the elaboration of extracellular collagen by these cells, which leads to progressive stenosis and obliteration of the AVM nidus. This series of pathological changes in AVMs after GKRS is essentially similar to the response-to-injury model of atherosclerosis.

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Type IV Collagen, Type IV Collagenase Activity and Ability of Cell Proliferation in Human Thyroid Tumours

Asian Journal of Surgery ◽

10.1016/s1015-9584(09)60196-2 ◽

2002 ◽

Vol 25 (4) ◽

pp. 304-308 ◽

Cited By ~ 4

Author(s):

Takeshi Kusunoki ◽

Shozo Nishida ◽

Saori Kimoto-Kinoshita ◽

Kiyotaka Murata ◽

Takao Satou ◽

...

Keyword(s):

Cell Proliferation ◽

Type Iv Collagen ◽

Collagen Type ◽

Human Thyroid ◽

Collagen Type Iv ◽

Collagenase Activity ◽

Type Iv Collagenase ◽

Type Iv

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The effects of dexamethasone on C6 astrocytoma radiosensitivity

Journal of Neurosurgery ◽

10.3171/jns.1989.70.5.0767 ◽

1989 ◽

Vol 70 (5) ◽

pp. 767-773 ◽

Cited By ~ 7

Author(s):

Carl D. Lordo ◽

Eric C. Stroude ◽

Rolando F. Del Maestro

Keyword(s):

Three Dimensional ◽

Inhibitory Effect ◽

Plating Efficiency ◽

Dexamethasone Treatment ◽

Content Type ◽

Astrocytoma Cells ◽

C6 Astrocytoma ◽

Radiation Induced ◽

Fine Print

✓ Brain-tumor patients often undergo radiation therapy while receiving corticosteroids for the treatment of cerebral edema. Studies have demonstrated that dexamethasone is radioprotective in a number of cell lines. The C6 astrocytoma cell line is well established in vitro and is modulated by dexamethasone treatment. It has therefore been hypothesized that dexamethasone-treated C6 astrocytoma cells would be more resistant to radiation-induced damage. The present study was carried out to assess this hypothesis using both the in vitro C6 astrocytoma monolayer and three-dimensional multicellular spheroid models. Dexamethasone was inhibitory to the C6 astrocytoma cells in the monolayer preparation, increasing their doubling time by 13%. In the spheroid cultures, dexamethasone treatment decreased the number of cells per spheroid by 46%. Dexamethasone did not affect the plating efficiency of either the cells from the monolayer experiment or those dissociated from spheroids, however, suggesting that the inhibitory effect was not tumoricidal. At a clinical concentration (1.94 × 10−5 M), dexamethasone did not significantly influence plating efficiency of irradiated C6 astrocytoma cells in monolayer or three-dimensional spheroid cultures.

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Proteolytic Activity During the Growth of C6 Astrocytoma in the Murine Spheroid Implantation Model

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100042487 ◽

1992 ◽

Vol 19 (1) ◽

pp. 17-22 ◽

Cited By ~ 10

Author(s):

Indrasen S. Vaithilingam ◽

Warren McDonald ◽

Eric C. Stroude ◽

Robert A. Cook ◽

Rolando F. Del Maestro

Keyword(s):

Proteolytic Activity ◽

Tumor Tissue ◽

Maximal Activity ◽

Vascular Basement Membrane ◽

Astrocytoma Cells ◽

Maximum Value ◽

C6 Astrocytoma ◽

Cerebral Cortex Tissue ◽

Collagenase Iv ◽

Implantation Model

ABSTRACT:General protease and collagenase IV activity are involved in the remodelling of the vascular basement membrane that occurs during tumor-induced angiogenesis. This study has assessed the level of these enzymes in tumor, peritumoral or contralateral cerebral cortex tissue during the growth of C6 astrocytoma in the rat spheroid implantation model. General proteolytic activity was increased in tumor tissue beginning on day 8 following spheroid implantation, then increased to a maximum value on day 11 and decreased to control values on day 18. A similar pattern was seen for collagenase IV activity but maximal activity occurred on day 13. The peritumor and tumor patterns of activity were similar. General protease activity was increased in the hemisphere contralateral to the tumor suggesting that the growth of C6 astrocytoma in rat brain was influencing biochemical events distant from the tumor. C6 astrocytoma cells orchestrate a cascade of proteolytic events which may play a crucial role in angiogenesis associated with tumor growth in the model system studied.

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Detection of type IV collagenase activity in malignant ascites

World Journal of Gastroenterology ◽

10.3748/wjg.v9.i11.2592 ◽

2003 ◽

Vol 9 (11) ◽

pp. 2592 ◽

Cited By ~ 15

Author(s):

Xiao-Min Sun ◽

Wei-Guo Dong ◽

Bao-Ping Yu ◽

He-Sheng Luo ◽

Jie-Ping Yu

Keyword(s):

Malignant Ascites ◽

Collagenase Activity ◽

Type Iv Collagenase ◽

Type Iv

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Burkholderia cenocepacia ZmpB Is a Broad-Specificity Zinc Metalloprotease Involved in Virulence

Infection and Immunity ◽

10.1128/iai.00297-06 ◽

2006 ◽

Vol 74 (7) ◽

pp. 4083-4093 ◽

Cited By ~ 58

Author(s):

C. Kooi ◽

B. Subsin ◽

R. Chen ◽

B. Pohorelic ◽

P. A. Sokol

Keyword(s):

Proteolytic Activity ◽

Proteinase Inhibitor ◽

Chronic Infection ◽

Type Iv Collagen ◽

Expression System ◽

Burkholderia Cenocepacia ◽

Infection Model ◽

Type Iv ◽

Zinc Metalloprotease ◽

Sensing Systems

ABSTRACT In previous studies we characterized the Burkholderia cenocepacia ZmpA zinc metalloprotease. In this study, we determined that B. cenocepacia has an additional metalloprotease, which we designated ZmpB. The zmpB gene is present in the same species as zmpA and was detected in B. cepacia, B. cenocepacia, B. stabilis, B. ambifaria, and B. pyrrocinia but was absent from B. multivorans, B. vietnamiensis, B. dolosa, and B. anthina. The zmpB gene was expressed, and ZmpB was purified from Escherichia coli by using the pPROEXHTa His6 Tag expression system. ZmpB has a predicted preproenzyme structure typical of thermolysin-like proteases and is distantly related to Bacillus cereus bacillolysin. ZmpB was expressed as a 63-kDa preproenzyme precursor that was autocatalytically cleaved into mature ZmpB (35 kDa) and a 27-kDa prepropeptide. EDTA, 1,10-phenanthroline, and Zn2+ cations inhibited ZmpB enzyme activity, indicating that it is a metalloprotease. ZmpB had proteolytic activity against α-1 proteinase inhibitor, α2-macrogobulin, type IV collagen, fibronectin, lactoferrin, transferrin, and immunoglobulins. B. cenocepacia zmpB and zmpA zmpB mutants had no proteolytic activity against casein and were less virulent in a rat agar bead chronic infection model, indicating that zmpB is involved in B. cenocepacia virulence. Expression of zmpB was regulated by both the CepIR and CciIR quorum-sensing systems.

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Increased type IV collagenase activity in rectal mucosa during pelvic radiation therapy

Gastroenterology ◽

10.1016/s0016-5085(00)80310-8 ◽

2000 ◽

Vol 118 (4) ◽

pp. A1126

Author(s):

Nils Hovdenak ◽

Ching-Ching Sung ◽

Tom J. Kelly ◽

Martin Hauer-Jensen

Keyword(s):

Radiation Therapy ◽

Rectal Mucosa ◽

Collagenase Activity ◽

Type Iv Collagenase ◽

Pelvic Radiation ◽

Type Iv

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Therapeutic alternatives for vein of Galen vascular malformations

Journal of Neurosurgery ◽

10.3171/jns.1993.78.3.0438 ◽

1993 ◽

Vol 78 (3) ◽

pp. 438-445 ◽

Cited By ~ 70

Author(s):

Pedro Lylyk ◽

Fernando Viñuela ◽

Jacques E. Dion ◽

Gary Duckwiler ◽

Guido Guglielmi ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Vascular Malformations ◽

Clinical Status ◽

Severe Congestive Heart Failure ◽

Type I ◽

Vein Of Galen ◽

Content Type ◽

Type Iv ◽

Fine Print

✓ From September, 1986, to March, 1990, the authors treated 28 children harboring a vein of Galen vascular malformation. Eleven (39.3%) of the patients were neonates, 13 (46.4%) were 1 to 2 years old, and four (14.3%) were more than 2 years old. Fifteen patients (53.6%) presented with severe congestive heart failure, six (21.4%) had seizures, four (14.3%) had hydrocephalus, and three (10.7%) presented with intraventricular hemorrhage. Based on the Yaşargil classification of malformations, 10 lesions (35.7%) were Type I, seven (25%) were Type II, eight (28.6%) were Type III, and three (10.7%) were Type IV. In 11 patients (39.3%), a combined transfemoral, transarterial, and transvenous embolization of the vein of Galen malformation was performed. A pure transtorcular approach was utilized in eight patients (28.6%), and postembolization surgical clipping of arterial feeders was performed in two cases with intractable congestive heart failure. Complete anatomical occlusion of the galenic malformation was achieved in 13 patients (46.4%). An immediate postembolization improvement in the patient's clinical status was obtained in 23 (82.1%) of 28 patients and a good long-term clinical outcome was seen in 17 patients (60.7%). Five deaths (17.9%) occurred in this series of 28 patients; three (10.7%) were related to a transtorcular embolization and two (7.1%) to the unchanged natural history of the disease.

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