The protein profile of acetazolamide-treated sera in mice bearing Lewis neoplasm

Xiang, Yu‐Tao; Ma, Bing; Yu, Huidong; Li, Xuejun

doi:10.1016/j.lfs.2003.12.032

Cited by 11 publications

(7 citation statements)

References 10 publications

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“…Recent drug developments have produced a number of compounds with efficient CA inhibition profiles, 3 and it has been shown that some of these can markedly reduce the invasive capacity of cancer cells 3,17,18 and may also disturb neoangiogenesis, thus reducing tumor growth. 19 The present findings suggest that it could be worth testing the effect of some potent and well-tolerated CA inhibitors such as acetazolamide and topiramate on brain tumor angiogenesis. Because of the extremely high mortality rate associated with glial tumors, urgent efforts should be made to discover novel treatment strategies that might prolong the survival time of patients.…”

Section: Discussionmentioning

confidence: 68%

Carbonic anhydrase II in the endothelium of glial tumors: A potential target for therapy

Haapasalo

Nordfors²,

Järvelä³

et al. 2007

Neuro-Oncology

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Carbonic anhydrase isozyme II (CA II) is a cytosolic enzyme that is highly expressed in most organs, including the brain, where it is mainly located in the oligodendrocytes. Recent studies have shown that its expression is induced in the endothelium of neovessels in melanoma and esophageal, renal, and lung cancer. Immunological studies further indicate that CA II represents a major target antigen stimulating an autoantibody response in melanoma patients. These results prompted us to investigate endothelial CA II expression in two types of brain cancer: oligodendrogliomas and astrocytomas. A series of 255 astrocytoma and 71 oligodendroglial tumor specimens was immunostained for CA II. The staining results were correlated with a number of different clinicopathological factors and survival data. CA II showed weak or no expression in low-grade tumors, while grade 3 mixed oligoastrocytoma and glioblastoma multiforme were the most positively stained tumor types. Survival analysis indicated that endothelial CA II staining is significantly associated with a poor prognosis in patients with astrocytomas. About 17% of patients with CA II-negative tumors (weak or no endothelial signal) were still alive at the end of the follow-up period of five years. The presence of CA II in the tumor endothelium suggests that it may play an important functional role in tumor metabolism. From a clinical perspective, the results also open new avenues for selecting tumor types for dendritic cell therapy trials.

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Section: Discussionmentioning

confidence: 68%

Carbonic anhydrase II in the endothelium of glial tumors: A potential target for therapy

Haapasalo

Nordfors²,

Järvelä³

et al. 2007

Neuro-Oncology

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“…To determine whether combination treatment with acetazolamide and NaHCO 3 could reduce the number of lung metastasis synergistically, we compared the effect of two medications. Data that was collected from the treatment with acetazolamide alone were previously reported in Life Sciences [ 24 ]. We found that acetazolamide treatment alone could sharply reduce the number of lung metastasis and primary tumor growth.…”

Section: Resultsmentioning

confidence: 99%

Effects of Acetazolamide Combined with or without NaHCO3 on Suppressing Neoplasm Growth, Metastasis and Aquaporin-1 (AQP1) Protein Expression

Xiang

et al. 2007

IJMS

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This study was made to explore the effects of acetazolamide on tumor growth, metastasis and the possible mechanisms. The mice bearing with Lewis lung carcinomas were taken as the animal model. The effects of acetazolamide were compared with the combination treatment of NaHCO 3 on tumor growth, metastasis and carbonic anhydrase activity in lung and tumor tissues using imidazole-Tris technique. And also the possible role of AQP1 in tumor tissues was investigated by Western blot and immuno-histochemical analysis. Results showed that acetazolamide alone could sharply reduce the number of lung metastasis and primary tumor growth, and appeared in a dose-dependent manner. Acetazolamide significantly inhibited carbonic anhydrase activity in tumor tissue. After the addition of NaHCO 3 , the suppression of acetazolamide on tumor growth, number of metastasis and carbonic anhydrase activity in primary tumor tissue could not be altered significantly, but the inhibitory rate of metastasis in lung and carbonic anhydrase activity in lung tissue appeared to show a reversal trend in the dose dependency from the acetazolamide treatment alone. The exactly mechanisms need to be clarified in future. Western blot and immunohistochemical analysis demonstrated that AQP1 expression in the tumor tissue was higher than both tissue of normal and treated with acetazolamide treatment alone. Combination with NaHCO 3 could not synergistically inhibit the expression of AQP1 with acetazolamide. The results suggested that the mechanism of acetazolamide on anti-tumor Int. J. Mol. Sci. 2007, 8 230 especially on its anti-metastasis actions might partly involve either inhibiting the carbonic anhydrase activity or reducing AQP1 water channel protein expression, whatever if treated with or without NaHCO 3 .

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“…Recent drug developments have already pointed out a number of different compounds as CA inhibitors with high efficiency [5,40]. Some of the drugs may inhibit and disturb the neoangiogenesis while reducing the tumor growth [42], and some compounds can also decrease the invasion capacity of tumor cells [43,44].…”

Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Bootorabi¹,

Haapasalo²,

Smith³

et al. 2011

Health

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Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII expression in a cohort of human diffuse astrocytomas, mixed oligoastrocytomas and oligodendrogliomas. CA VII immunostaining was correlated to clinicopathologic findings, survival data, and expression of other molecular factors, including Ki-67, p53 protein and epidermal growth factor receptor. CA VII-positive staining was observed in 94% of astrocytomas and 85% of oligodendrogliomas. In the tumor specimens, strong positive areas were often located in close proximity to necrosis. The CA VII immunoreactivity showed positive correlation with tumor malignancy grades of astrocytomas (p = 0.02, chi-square test). In all tumor categories, CA VII-positive staining was often seen in the endothelial cells of neovessels in addition to the tumor cells. CA VII intensity showed no significant association with p53 nor did it correlate with the amplification of epidermal growth factor receptor (analyzed only in astrocytomas) or cell proliferation. Our present results show that CA VII may act as a useful biomarker in histopathologic diagnostics of gliomas. The high expression of CA VII in the tumor cells and endothelium suggests important roles for the enzyme in tumor metabolism. The results also led us to conclude that CA VII might serve as a marker of poor prognosis in diffuse astrocytomas.

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The protein profile of acetazolamide-treated sera in mice bearing Lewis neoplasm

Cited by 11 publications

References 10 publications

Carbonic anhydrase II in the endothelium of glial tumors: A potential target for therapy

Carbonic anhydrase II in the endothelium of glial tumors: A potential target for therapy

Effects of Acetazolamide Combined with or without NaHCO3 on Suppressing Neoplasm Growth, Metastasis and Aquaporin-1 (AQP1) Protein Expression

Carbonic anhydrase VII–a potential prognostic marker in gliomas

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