Biomedical subjects

Toshiaki Kawai

Publications and source records attributed to Toshiaki Kawai.

At least 19 recordsLinked to original sources

PubMed2007

Telomere length and telomerase expression in atypical adenomatous hyperplasia and small bronchioloalveolar carcinoma of the lung.

Telomeres are located at the ends of every human chromosome and are subject to shortening at each cycle of cell division in cell senescence and early carcinogenesis. We examined the expression of telomeric DNA in 21 atypical adenomatous hyperplasias (AAHs) and 40 bronchioloalveolar carcinomas (BACs) measuring 2 cm or less in greatest diameter using fluorescent in situ hybridization and the expression of human telomerase reverse transcriptase (hTERT) messenger RNA (mRNA) in 35 AAHs and 37 BACs. The mean numbers of telomeric signals per nucleus were 5.0 in AAH and 7.4 in BAC, each significantly less than for normal cells (14.7; P < .0001), but the mean number of telomeric signals for AAH and BAC was not statistically different (P = .22). In "benign" lung samples, the pattern of expression of hTERT mRNA was barely detected in the nonciliated cells of the bronchioles and alveolar type II cells. Positive expression of hTERT mRNA was recognized in 66% of AAHs and 97% of BACs. Our results demonstrate telomere shortening, indicating its presence in the earliest phase of pulmonary carcinogenesis. Telomere length and telomerase may be involved in carcinogenesis in the lung.

Adenocarcinoma↗

PubMed2006

Telomere length, telomerase activity, and expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA in pulmonary neuroendocrine tumors.

BACKGROUND: Telomeres are important for chromosome structure and function, protecting them against degradation. However, few studies have examined telomeres in pulmonary neuroendocrine (NE) tumors. METHODS: We investigated deparaffinized sections obtained from 70 primary NE lung tumors [34 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 16 large cell neuroendocrine carcinoma (LCNECs) and 10 small cell lung carcinomas (SCLCs)]. RESULTS: Positive expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA were recognized, respectively, in 58% and 74% of TCs, and in 100% and 100% of ACs, LCNECs and SCLCs. Alteration of telomere length was greater in both LCNECs and SCLCs than in TCs. Telomerase activity was detected in LCNECs, but not in TCs. By the reverse-transcriptase polymerase chain reaction (RT-PCR), hTERC mRNA was detected in 100% of LCNECs and TCs examined, while hTERT mRNA was detected in 67% of LCNECs, but not at all in TCs. CONCLUSIONS: These results suggest that alterations in telomere length, telomerase activity, and the expression of hTERT mRNA may (i) play roles in pathogenesis in pulmonary neuroendocrine tumors, and (ii) be a useful tool for differential diagnosis between TCs and LCNECs.

Carcinoma, Neuroendocrine↗

PubMed2006

Mre11 expression in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

CONTEXT: The Mre11-Rad50-NBS1 complex plays an important role in telomere maintenance. Recently, it has been proposed that alterations in Mre11 function may be contributing factors in the development of some tumors. Moreover, mutations of Mre11 have been demonstrated to cause reduced Mre11 immunostaining. OBJECTIVE: To investigate Mre11 in atypical adenomatous hyperplasia (AAH) and nonmucinous bronchioloalveolar carcinoma (NMBAC), an issue not previously explored. DESIGN: We examined (1) the expression of Mre11 protein in 27 AAHs (9 lesions interpreted as low-grade AAH and 18 as high-grade AAH) and 40 NMBACs (using immunohistochemistry) and (2) Mre11 mRNA expression in 1 high-grade AAH and 6 NMBACs (using reverse transcription polymerase chain reaction). For the analysis of immunoreactivity, the intensity and extent of staining were each scored from 0 to 3. These 2 scores were summed to give in each case a final score of 0 to 6. RESULTS: Scores for Mre11 expression were 5.0 +/- 2.1 for low-grade AAH, 5.4 +/- 1.2 for high-grade AAH, and 5.5 +/- 0.9 for NMBAC, and there was no statistically significant difference among these 3 types of lesions. In the reverse transcription polymerase chain reaction for Mre11 mRNA, polymerase chain reaction products were detected in all samples. CONCLUSIONS: On this basis, we suggest that the part played by Mre11 in telomere maintenance may not be important for the progression of the adenoma-carcinoma (AAH-NMBAC) sequence in the lung, although some role for it in carcinogenesis cannot be completely ruled out.

Adenocarcinoma↗

PubMed2005

LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

No previous study has investigated neutral large amino acid transporter type 1 (LAT1) in normal lung cells, or in atypical adenomatous hyperplasia(s) (AAH) and nonmucinous bronchioloalveolar carcinoma(s) (NMBAC) of the lung. The authors examined: (1) the levels of LAT1 mRNA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in 41 normal lung tissues and 34 NMBAC using semiquantitative reverse transcription-polymerase chain reaction; (2) LAT1 mRNA and protein expressions in 35 normal lung tissues, 34 AAH (11 lesions were interpreted as low-grade AAH and 23 as high-grade AAH), and 43 NMBAC using in situ hybridization and immunohistochemistry; and (2) the association of the incidences of LAT1 mRNA and protein expressions with cell proliferation in these lesions. The level of LAT1 mRNA/GAPDH mRNA (1) tended to be higher in NMBAC (12.0+/-8.1) than in normal lung tissues (1.0+/-0.2), and (2) covered a much wider range (from 0 to 276) in NMBAC than in normal lung tissues (from 0 to 5.8), with six NMBAC having values higher than 7.0, while 5.8 was the highest value detected in normal lung tissues. In peripheral normal lung tissues, LAT1 mRNA and protein were detected in bronchial surface epithelial cells and alveolar macrophages (but not in nonciliated bronchiolar epithelial cells, or in alveolar type I or type II cells). In bronchial surface epithelial cells, LAT1 protein appeared to be of a nodular type, which was considered to be a nonfunctional protein pattern. The incidences of positive expressions for LAT1 mRNA and protein were 54.5 and 27.3% in low-grade AAH, 65.2 and 52.2% in high-grade AAH, and 65.1 and 79.1% in NMBAC, respectively. In the case of LAT1 protein expression, significant differences could be shown between total (low-grade plus high-grade) AAH and NMBAC, and between low-grade AAH and NMBAC. Thus, in terms of the incidence of LAT1 protein expression, high-grade AAH appeared intermediate between low-grade AAH and NMBAC. The Ki-67 labeling index (a cell proliferation score) was significantly higher in those AAH and NMBAC that were LTA1-protein-positive than in their LAT1-protein-negative counterparts. In conclusion, LAT1 expression may increase with the upregulation of metabolic activity and cell proliferation in high-grade AAH and NMBAC.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2005

Expression of hypoxia-inducible factor-1alpha protein predicts survival in patients with transitional cell carcinoma of the upper urinary tract.

Hypoxia-inducible factor-1 (HIF-1), identified as one of the transcription factors, has been found to play an essential role in oxygen homeostasis. HIF-1 is a heterodimer composed of HIF-1alpha and HIF-1beta. Increased levels of HIF-1alpha have been reported during the carcinogenesis and progress of several tumors. We investigated the prognostic importance of HIF-1alpha expression in transitional cell carcinoma of the upper urinary tract. In 127 cases of transitional cell carcinoma of the upper urinary tract, we examined its expression (using immunohistochemistry and in situ hybridization), and also its relation to the expression of p53 oncoprotein, as well as to proliferating cell nuclear antigen (PCNA) immunoreactivity, microvessel density, clinicopathologic parameters, and clinical outcome. A positive expression of HIF-1alpha protein was recognized in 55.1% of samples, the expression being apparent within the nucleus in tumor cells. HIF-1alpha protein expression correlated with grade, growth pattern, p53 oncoprotein expression, and PCNA index, but not with stage. Furthermore, a significant correlation was found between HIF-1alpha protein expression and both overall and disease-free survival rates in the univariate and multivariate analyses (in all tumors and in invasive tumors). A positive expression of HIF-1alpha mRNA was recognized in 69.6% of 125 samples which were available, the expression being apparent within the cytoplasm in tumor cells. The positive expression of HIF-1alpha mRNA by in situ hybridization correlated significantly with HIF-1alpha protein expression by immunohistochemistry. HIF-1alpha mRNA expression only correlated with pattern of growth (P = 0.0078). In conclusion, the detection of HIF-1alpha protein would seem to be of value in informing the prognosis of transitional cell carcinoma of the upper urinary tract.

Adult↗

PubMed2005

Expression of endothelin-1 in the brain and lung of rats exposed to permanent hypobaric hypoxia.

High-altitude hypoxia causes pulmonary hypertension in humans and animals. Endothelin-1 (ET-1) is a novel and long-lasting vasoconstrictor. However, no study has dealt with the effects of a hypobaric hypoxic environment (HHE) on ET-1 activity in the brain. We examined 134 male rats permanently exposed to the equivalent of 5500 m altitude for 1 to 8 weeks. In these HHE rats, the mean pulmonary arterial pressure was significantly raised. The level of ET-1 protein, measured by enzyme immunoassay, increased rapidly in the lungs on exposure to HHE, but decreased in the brain. The level of ET-1 mRNA, measured by semiquantitative RT-PCR, was raised at 1, 4, and 6 weeks' exposure in the lungs and at 4 or more weeks' exposure in 3 of 8 brain regions. By in situ hybridization and immunohistochemistry of brain sections, ET-1 mRNA and protein were detected in the endothelial cells, neurons, and astrocyte-like cells in control rats. In HHE rats, the immunoreactive intensity for ET-1 protein decreased rapidly with time in these cells within the brain, although a few weakly ET-1 protein-positive cells were detected until 8 weeks' exposure to HHE. Only a few weakly ET-1 mRNA-positive endothelial cells were detected in any HHE rats. Although the reactivity for ET-1 mRNA had decreased significantly in neurons and astrocyte-like cells at 1 and 2 weeks' exposure to HHE, it was again strong in both types of cells at 4 weeks' exposure to HHE. These results raise the possibility that during exposure to HHE, ET-1 production in the lung may play a role in the development of pulmonary hypertension, while a decrease in ET-1 production within the brain may help to protect neurons by preventing or limiting the constriction of cerebral microvessels during the hypoxia induced by HHE.

Altitude Sickness↗

PubMed2005

Compact monochromatic flash x-ray generator utilizing a disk-cathode molybdenum tube.

The high-voltage condensers in a polarity-inversion two-stage Marx surge generator are charged from -50 to -70 kV by a power supply, and the electric charges in the condensers are discharged to an x-ray tube after closing gap switches in the surge generator with a trigger device. The x-ray tube is a demountable diode, and the turbo molecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Clean molybdenum Kalpha lines are produced using a 20 microm-thick zirconium filter, since the tube utilizes a disk cathode and a rod target, and bremsstrahlung rays are not emitted in the opposite direction to that of electron acceleration. At a charging voltage of -70 kV, the instantaneous tube voltage and current were 120 kV and 1.0 kA, respectively. The x-ray pulse widths were approximately 70 ns, and the generator produced instantaneous number of Kalpha photons was approximately 3 x 10(7) photons/cm2 per pulse at 0.5 m from the source of 3.0 mm in diameter.

Animals↗

PubMed2004

Expressions of adrenomedullin mRNA and protein in rats with hypobaric hypoxia-induced pulmonary hypertension.

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Adrenomedullin (AM) has diuretic, natriuretic, and hypotensive effects. To study the possible effects of HHE on the AM synthesis system, 150 male Wistar rats were housed in a chamber at the equivalent of a 5,500-m altitude level for 21 days. After 14 days of exposure to HHE, pulmonary arterial pressure (PAP) was significantly increased (compared with control rats). The plasma AM protein level was significantly increased on day 21 of exposure to HHE. In the right ventricle (RV), right atrium, and left atrium of the heart, the expressions of AM mRNA and protein were increased in the middle to late phase (5-21 days) of HHE, whereas in the brain and lung they were increased much earlier (0.5-5 days). In situ hybridization and immunohistochemistry showed AM mRNA and protein staining to be more intense in the RV in animals in the middle to late phase of HHE exposure than in the controls. During HHE, these changes in AM synthesis, which occurred strongly in the RV, occurred alongside the increase in PAP. Conceivably, AM may play a role in modulating pulmonary hypertension in HHE.

Adrenomedullin↗

PubMed2004

Telomere length, telomerase activity, and expression of human telomerase reverse transcriptase mRNA in growth plate of epiphyseal articular cartilage in femoral head during normal human development and in thanatophoric dysplasia.

Telomeres are important in chromosome structure and function, protecting against their degradation. However, few studies have examined telomeres in growth plates within articular cartilage during normal development. We investigated frozen sections that were obtained from 57 reference autopsy cases (aged from 16 weeks of gestation to 91 years) and from 2 patients with thanatophoric dysplasia. In the reference cases, telomere length was significantly longer in growth plates obtained from the 10 cases that were aged from 16 weeks of gestation to 10 years than in those from 47 of the adult cases (aged 20 to 91 years). In fetal, neonatal, and child cases, telomerase activity was significantly higher in the hypertrophied zone (HZ) in growth plates than in the other 3 zones. The hTERT mRNA staining intensity (staining area) was stronger (larger) in HZ and the proliferating zone than in the calcified zone and resting zone. In thanatophoric dysplasia, telomere length and telomerase activity were short and low, respectively, compared with those of normal growth plates at an equivalent age, and expression of hTERT mRNA was negative or weakly positive in all 4 zones within growth plates. These results suggest that telomere length and telomerase activity have significant effects in the growth plates of articular cartilage, particularly at developmental ages from fetus to child. We speculate that short telomere length and low telomerase activity may be important for chondrocyte differentiation in rhizomeric shortening of the limbs in thanatophoric dysplasia.

Adolescent↗

PubMed2004

Abnormalities in chromosome 17 and p53 in lung carcinoma cells detected by fluorescence in situ hybridization.

The value of fluorescence in situ hybridization (FISH) as an aid to deciding the prognosis for lung carcinoma patients, comparing quantitatively the signal from the p53 gene (17p13.1) on chromosome 17, was studied. A dual-labeling technique was used, using probes for the centromeric region of chromosome 17 and for the p53 gene locus. FISH was used on frozen sections of 68 surgically resected lung carcinoma (20 adenocarcinoma; 37 squamous cell carcinoma; 11 large, small, and other cell carcinoma). Hybridization signals were counted for 100-200 interphase nuclei per specimen using a Zeiss confocal laser scanning microscope (Carl Zeiss, Oberkochen, Germany) equipped with a bandpass filter for diaminophenolindole and a longpass filter for rhodamine. Clinicopathologic data were evaluated using the Statistical Analysis System. Chromosome 17 polysomy (three or more signals) was greater in poorly differentiated than in well-differentiated lung carcinoma (P < 0.05). p53 deletion correlated with p53 immunostaining (P < 0.05). Thus, analysis by FISH using DNA probes for chromosome 17 and p53 may be of some, albeit limited, value in determination of prognosis.

Carcinoma↗

PubMed2004

Demonstration of enhanced K-edge angiography using a cerium target x-ray generator.

The cerium target x-ray generator is useful in order to perform enhanced K-edge angiography using a cone beam because K-series characteristic x rays from the cerium target are absorbed effectively by iodine-based contrast mediums. The x-ray generator consists of a main controller, a unit with a Cockcroft-Walton circuit and a fixed anode x-ray tube, and a personal computer. The tube is a glass-enclosed diode with a cerium target and a 0.5-mm-thick beryllium window. The maximum tube voltage and current were 65 kV and 0.4 mA, respectively, and the focal-spot sizes were 1.0 x 1.3 mm. Cerium Kalpha lines were left using a barium sulfate filter, and the x-ray intensity was 0.48 microC/kg at 1.0 m from the source with a tube voltage of 60 kV, a current of 0.40 mA, and an exposure time of 1.0 s. Angiography was performed with a computed radiography system using iodine-based microspheres. In coronary angiography of nonliving animals, we observed fine blood vessels of approximately 100 microm with high contrasts.

Angiography↗

PubMed2004

Monochromatic polycapillary imaging utilizing a computed radiography system.

A fundamental study on quasi-parallel radiography using a polycapillary plate and a copper-target x-ray tube is described. In the experiments, the tube voltage was regulated from 12 to 22 kV, and the tube current was regulated within 3.0 mA by the filament temperature. The exposure time was controlled in order to obtain optimum x-ray intensity, and the maximum focal spot dimensions were approximately 2.0 x 1.5 mm. The thickness and the inner capillary tube diameter of the polycapillary were 1.0 mm and 25 microm, respectively. Monochromatic x-rays were produced using a 10 microm-thick nickel filter with a tube voltage of 17 kV, and these rays were formed into quasi-parallel beams by the polycapillary. The radiogram was taken using a computed radiography system utilizing imaging plates. In the measurement of image resolution, the spatial resolution hardly varied according to increases in the distance between the resolution-test chart and imaging plate using a polycapillary. A 50 microm tungsten wire could be observed, and fine blood vessels of approximately 100 microm were visible in angiography.

Angiography↗

PubMed2003

Expressions of human telomerase mRNA component (hTERC) and telomerase reverse transcriptase (hTERT) mRNA in effusion cytology.

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto chromosomal ends. Its activity has been reported to be a novel diagnostic marker of malignant potential. However, no study has investigated the diagnostic importance of the expressions of human telomerase mRNA component (hTERC) and telomerase reverse transcriptase (hTERT) mRNA in effusion cytology. We investigated the expressions of hTERC and hTERT using in situ hybridization in 20 malignant cytologic specimens from 20 patients with adenocarcinomas disseminating into the pleura or peritoneum, and 16 benign cytologic specimens in pleural or peritoneal fluid (including reactive mesothelial cells) from 16 patients with non-neoplastic diseases. Expressions of hTERC and hTERT mRNA were detected in 95% and 90% of the 20 malignant cytology specimens, respectively, and were apparent within the cytoplasm of malignant cells. However, no expression was detected in reactive mesothelial cells in the 16 benign cytologic specimens. The expressions of hTERC and hTERT mRNA would appear to be a useful addition to cytology examination for diagnosis based on effusion cytology.

Adenocarcinoma↗

PubMed2003

Survivin expression in atypical adenomatous hyperplasia of the lung.

Few studies have investigated apoptosis-related factors in atypical adenomatous hyperplasia (AAH) and nonmucinous bronchioloalveolar carcinoma. We studied the expression of survivin, bcl-2, and p53 in 29 AAH lesions (low-grade, 11; high-grade, 18) and 40 nonmucinous BACs using immunohistochemical analysis and of survivin messenger RNA in 6 nonmucinous BACs using reverse transcription-polymerase chain reaction (RT-PCR). The incidence of positive survivin expression was 9% (1/11) in low-grade AAH, 89% (16/18) in high-grade AAH, and 100% (40/40) in nonmucinous BAC. Statistically significant differences were found between low-grade and high-grade AAH and between high-grade AAH and nonmucinous BAC. The percentages obtained for positive bcl-2 and p53 expression were 18% (2/11) and 0% (0/11) in low-grade AAH, respectively, and 28% (5/18) for both in high-grade AAH and 48% (19/40) for both in nonmucinous BAC. In RT-PCR, the intensity of survivin messenger RNA expression was stronger in nonmucinous BACs than in normal lung tissue samples. Thus, the expression of the 3 antibodies in high-grade AAH was intermediate between low-grade AAH and nonmucinous BAC. High-grade AAH may be closely related to nonmucinous BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2003

Expression of mRNAs for telomeric repeat binding factor (TRF)-1 and TRF2 in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

PURPOSE AND EXPERIMENTAL DESIGN: It has been suggested that atypical adenomatous hyperplasia (AAH) may be a precursor of peripheral adenocarcinoma of the lung. Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto chromosomal ends. Its activity is thought to participate in the development of most human cancers. Telomere-specific DNA-binding proteins, such as telomeric repeat binding factor 1 and telomeric repeat binding factor 2, also control telomere length in a complex interplay with telomerase. Here we investigated the expressions of the mRNAs encoded by the TERF1 and TERF2 genes using in situ hybridization in surgically resected specimens [28 AAHs (11 lesions were interpreted as low-grade AAH, and 17 were interpreted as high-grade AAH) and 40 peripherally located bronchioloalveolar carcinoma (BAC). RESULTS: A clear overexpression of these mRNAs was recognized in low- and high-grade AAH and BAC samples (as compared with normal tissues) using in situ hybridization and these mRNAs were detected in normal AAH and BAC samples using reverse transcription-PCR. The expressions of TERF1 and TERF2 mRNA detected by in situ hybridization were scored positive in 36% and 82% of low-grade AAH, 65% and 83% of high-grade AAH, and 88% and 88% of BAC, respectively. Statistically significant differences in TERF1 mRNA expression could be shown between low-grade AAH and BAC and between high-grade AAH and BAC. There was no statistical difference in the positive expressions of TERF2 mRNA among low-grade AAH, high-grade AAH, and BAC. CONCLUSIONS: These results are consistent with (but are not enough to confirm) the idea that high-grade AAH is closely related to BAC.

Adenocarcinoma↗

PubMed2003

Irradiation of intense characteristic x-rays from weakly ionized linear molybdenum plasma.

In the plasma flash x-ray generator, a high-voltage main condenser of approximately 200 nF is charged up to 55 kV by a power supply, and electric charges in the condenser are discharged to an x-ray tube after triggering the cathode electrode. The flash x-rays are then produced. The x-ray tube is a demountable triode that is connected to a turbo molecular pump with a pressure of approximately 1 mPa. As electron flows from the cathode electrode are roughly converged to a rod molybdenum target of 2.0 mm in diameter by the electric field in the x-ray tube, weakly ionized linear plasma, which consists of molybdenum ions and electrons, forms by target evaporation. At a charging voltage of 55 kV, the maximum tube voltage was almost equal to the charging voltage of the main condenser, and the peak current was about 20 kA. When the charging voltage was increased, the linear plasma formed, and the K-series characteristic x-ray intensities increased. The K lines were quite sharp and intense, and hardly any bremsstrahlung rays were detected. The x-ray pulse widths were approximately 700 ns, and the time-integrated x-ray intensity had a value of approximately 35 micro C/kg at 1.0 m from the x-ray source with a charging voltage of 50 kV.

Electrodes↗

PubMed2002

Expression of survivin does not predict survival in patients with transitional cell carcinoma of the upper urinary tract.

The members of the IAP (inhibitors of apoptosis) family, which includes survivin, have recently emerged as modulators of an evolutionarily conserved step in apoptosis. Survivin is present during embryonic and fetal development, but it is downregulated in normal adult tissues. However, it becomes re-expressed in a variety of cancers. We investigated the prognostic importance of the expression of survivin in transitional cell carcinoma of the upper urinary tract (TCC-UUT). In 126 cases of TCC-UUT, we examined its expression (using immunohistochemistry), and also its relationship with the expressions of bcl-2 oncoprotein, p53 oncoprotein, and proliferating cell nuclear antigen (PCNA) immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of survivin was recognized in 12.7% of samples, a granular pattern being apparent within the cytoplasm of tumor cells. Survivin expression did not correlate with clinicopathologic findings, bcl-2 oncoprotein expression, p53 oncoprotein expression, PCNA index, or prognosis. In the normal urothelium, its expression was not detected. In conclusion, the expression of survivin does not predict prognosis in TCC-UUT.

Adult↗

PubMed2002

Angiotensin II type I antagonist prevents pulmonary metastasis of murine renal cancer by inhibiting tumor angiogenesis.

Angiotensin II (AII) is a potent vasoconstrictor peptide from the renin-angiotensin system in the kidney. The AII type 1 receptor (AT1R) is reportedly expressed in several tumors including renal cell carcinoma, and AII is involved in tumor angiogenesis. We p.o. administered the long-acting AT1R antagonist, candesartan (10 mg/kg), to the 16 days mouse renal cancer lung metastasis model to test the preventive effects in tumor metastasis. Pulmonary metastases of renal cancer showed prominent AT1R expression in both mice and humans, and candesartan treatment dramatically prevented lung metastatic nodules (14.9 +/- 1.8; P < 0.0001; n = 12) in mice along with the inhibition of neovascularization and vascular endothelial growth factor expression, compared with control metastatic mice (123.3 +/- 8.6; n = 13). Candesartan is widely used clinically, so it seems to be a reasonable therapy for patients with lung metastases of renal cell carcinoma.

Adult↗