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Biomedical subjects

Kazuya Suzuki

Publications and source records attributed to Kazuya Suzuki.

At least 19 recordsLinked to original sources

Association between the dihydrotestosterone level in the prostate and prostate cancer aggressiveness using the Gleason score.

PURPOSE: To our knowledge the association between dihydrotestosterone in the prostate and prostate cancer aggressiveness has not yet been elucidated. We analyzed dihydrotestosterone levels in the prostate and Gleason score in patients diagnosed with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 81 patients with suspected prostate cancer underwent prostate biopsy. Serum samples were collected before biopsy. Dihydrotestosterone levels in prostatic tissue and serum were analyzed using liquid chromatography/electrospray ionization-mass spectrometry after polar derivatization. RESULTS: A total of 47 patients were diagnosed with stages T1 to T3N0M0 prostate cancer and 34 were diagnosed with no malignancy. Of the 47 patients 32 had a Gleason score of 6 or less and 15 had a score of 7 to 10. Dihydrotestosterone in prostatic tissue in patients with Gleason score 7 to 10 disease was significantly lower than in those with Gleason score 6 or less disease (p = 0.025). Gleason score correlated with the testosterone-to-serum dihydrotestosterone ratio (rs = 0.329, p = 0.038). CONCLUSIONS: Patients with Gleason score 7 to 10 prostate cancer have low dihydrotestosterone in the prostate, although there were no significant differences between patients with Gleason score 7 to 10 vs 6 or less prostate cancer with respect to serum androgens. Low dihydrotestosterone in cases of aggressive prostate cancer is probably sufficient to activate androgen receptor expression and propagate tumor growth.

Aged↗

Role of connective tissue growth factor in fibronectin synthesis in cultured human prostate stromal cells.

OBJECTIVES: To clarify the correlation of connective tissue growth factor (CTGF) expression and fibronectin (FN) synthesis after transforming growth factor-beta-1 (TGF-beta1) stimulation in human prostate stromal cells. METHODS: Primary cultures of human prostate stromal cells were established from nine normal prostates by the explant method. The gene and protein expressions of CTGF and FN after TGF-beta1 treatment were examined. We also investigated the effect of CTGF blockade on TGF-beta1-induced FN synthesis by CTGF antisense oligodeoxynucleotide treatment. RESULTS: CTGF expression was detected in all nine prostate stromal cells by reverse transcriptase-polymerase chain reaction and immunoblotting. In prostatic tissues, CTGF expression was observed more strongly in epithelial cells than in the stromal area by immunohistochemistry. The upregulation of both CTGF and FN protein by TGF-beta1 treatment was demonstrated in a dose-dependent manner. CTGF antisense oligodeoxynucleotide inhibited TGF-beta1-stimulated FN synthesis. CONCLUSIONS: CTGF plays a crucial role in extracellular matrix production as a TGF-beta1 downstream mediator in human prostate stromal cells, suggesting that CTGF blockade is likely to be a therapeutic target against benign prostatic hyperplasia.

Cells, Cultured↗

Stepping-stones to the further advancement of androgen-deprivation therapy for prostate cancer.

Androgen-deprivation therapy has remained the critical therapeutic option for patients with advanced prostate cancer for over 60 years. Patients with poorly differentiated prostate cancer have low dihydrotestosterone levels in the prostate. After androgen-deprivation therapy, dihydrotestosterone levels in the prostate remain at approximately 25% of the level measured before therapy. The addition of a nonsteroidal anti-androgen to luteinizing hormone-releasing hormone analog or surgical castration significantly reduces the risk of all causes of death by 8%, which translates into a small, but significant, improvement in the 5-year survival of 2.9% over castration alone. The biologically aggressive prostate cancer cells may have an androgen receptor with heightened sensitivity to low dihydrotestosterone levels from the early stage of androgen-dependent disease. It is necessary to consider the androgen environment and the status of the androgen receptor in the prostate in order to improve the clinical efficacy of androgen-deprivation therapy and the quality of life of patients.

Androgen Antagonists↗

The critical role of disulfide bond formation in protein sorting in the endosperm of rice.

Many seed storage proteins, including monomeric 2S albumin and polymeric prolamin, contain conserved sequences in three separate regions, termed A, B, and C, which contain the consensus motifs LxxC, CCxQL, and PxxC, respectively. Protein-sorting mechanisms in rice (Oryza sativa) endosperm were studied with a green fluorescent protein (GFP) fused to different segments of rice alpha-globulin, a monomeric, ABC-containing storage protein. The whole ABC region together with GFP was efficiently transported to protein storage vacuoles (type II protein bodies [PB-II]) in the endosperm cells and sequestered in the matrix that surrounds the crystalloids. Peptide Gln-23 to Ser-43 in the A region was sufficient to guide GFP to PB-II. However, GFP fused with the AB or B region accumulated in prolamin protein bodies. Substitution mutations in the CCxQL motif in the B region significantly altered protein localization in the endosperm cells. Furthermore, protein extracts containing these substituted proteins had increased amounts of the endoplasmic reticulum (ER) chaperons BiP (for binding protein), protein disulfide isomerase, and calnexin as a part of protein complexes that were insoluble in a detergent buffer. These results suggest that the ER chaperons and disulfide bonds formed at the dicysteine residues in CCxQL play critical roles in sorting fused proteins in the endosperm cells.

Alpha-Globulins↗

Right upper lobe venous drainage posterior to the bronchus intermedius: preoperative identification by computed tomography.

BACKGROUND: Anatomical variations of the pulmonary vessels relevant to pulmonary surgery are of concern to thoracic surgeons. Among such variations, the right upper lobe vein posterior to the bronchus intermedius (UVPBI) has received little attention thus far. METHODS: Chest computed tomographic images and medical records of 725 patients were retrospectively reviewed. The frequency, drainage pattern, diameter, and associated anatomical characteristics of the UVPBI were assessed, and our right thoracotomy cases with the UVPBI were examined. RESULTS: The UVPBI was found in 41 (5.7%) of 725 computed tomography cases, and in 9 (3.9%) of 230 right thoracotomy cases. Three UVPBI drainage sites were observed: (1) the superior pulmonary vein group, 55%; (2) the inferior pulmonary vein group, 41%; and (3) the superior segmental vein group, 4%. The diameter of the UVPBI at the level of the bronchus intermedius ranged from 1 to 7 mm (4.1 +/- 1.6 mm). The diameter of the UVPBI in the superior pulmonary vein group was significantly greater than that in the inferior pulmonary vein group (p < 0.01). The prevalence of a central vein was 43.9% for all UVPBI cases and 15.8% for large UVPBI cases (> or = 5 mm in diameter). Of the 9 right thoracotomy patients, 1 suffered UVPBI injury; this patient's UVPBI was not identified either preoperatively or intraoperatively. CONCLUSIONS: The UVPBI is not as rare as was previously believed. It can be a main drainage route of the right upper lobe. Preoperative identification of this venous variation by computed tomography is useful for safe and accurate surgical procedures.

Adult↗

Pitfalls in lymph node staging with positron emission tomography in non-small cell lung cancer patients.

BACKGROUND: The evidence of clinical value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in lymph node (LN) staging in non-small cell lung cancer (NSCLC) has been shown in numerous papers. However, few studies have assessed its limitations. The aim of the present study is to clarify clinico-pathologic factors responsible for false PET results. METHODS: From July 2000 through December 2001, 71 NSCLC patients underwent both FDG PET and surgical intervention at the National Cancer Center Hospital East, Chiba. Clinical records, computed tomographic (CT) scan findings, PET findings, and histologic findings were retrospectively reviewed. RESULTS: Sensitivity, specificity, accuracy in nodal staging for CT were 29, 83, and 65% and for PET were 39, 79, and 66%, respectively. There were 10 (14%) false-positive PET scans and 14 (20%) false-negative PET scans. The causative factors for false-positive PET scan were: (1) inflammatory conditions in seven patients; (2) PET mis-localization of an interlobar LN as a mediastinal LN in one patient; (3) inability to distinguish the endobronchial polypoid growth of a primary tumor from a lobar LN in one patient; (4) unknown in one patient. All false-positive LNs due to inflammatory conditions showed reactive lymphoid hyperplasia histologically. The causative factors for false-negative PET scan were: (1) limitation of spatial resolution of the PET scanner in 12 patients (maximum tumor focus dimensions in false-negative LNs ranging from 1 to 7.5 mm, with an average of 3.4 mm); (2) PET mis-localization of a mediastinal LN as a hilar LN in one patient; (3) weak FDG uptake by microscopic tumor foci due to necrosis with massive bleeding in a metastatic LN in one patient. CONCLUSIONS: Inflammatory conditions were most responsible for false-positive PET scans, and spatial resolution limitation of FDG PET was the causative factor of false-negative PET scans. Recognizing these factors in advance would be clinically helpful in accurate nodal staging with FDG PET.

Adult↗

Plasminogen activator inhibitor type 1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin via alpha(v)beta(5) integrin.

Both urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1) are associated with a poor prognosis in cancer patients. We demonstrate that PAI-1 inhibits human fibrosarcoma cell (HT-1080) adhesion to vitronectin (Vn) via alpha (v)beta (5) integrin, and stimulates cell migration from Vn toward collagen type IV (Col). The cells attached more strongly to Vn and Col than to fibronectin (Fn), whereas PAI-1 interfered with cell attachment to Vn only. An integrin antagonist, RGD peptide, and anti-alpha (v)beta (5) integrin antibodies, which similarly inhibited cell attachment to Vn, also stimulated cell migration from Vn toward Col. u-PA did not modify cell attachment directly, but reversed the PAI-1-mediated inhibitory effect on cell adhesion to Vn, and its stimulatory effect on cell migration from Vn toward Col. Thus HT-1080 cell migration appears to be modified by u-PA and PAI-1, altering cell adhesion to Vn via alpha (v)beta (5) integrin. This may be related to their tumor-promoting effect.

Cell Adhesion↗

Transforming growth factor-beta1 regulates cell growth and causes downregulation of SMemb/non-muscle myosin heavy chain B mRNA in human prostate stromal cells.

OBJECTIVES: SMemb/non-muscle myosin heavy chain B (SMemb/NMMHC-B) is most abundantly expressed in proliferating smooth muscle cells and correlates with phenotypic changes from a contractive to a proliferative type. The stromal cells of the prostate play a crucial role in the regulation of prostatic growth and function. The aim of this study was to investigate the effects of the multifunctional cytokine transforming growth factor-beta1 (TGF-beta1) on SMemb/NMMHC-B mRNA expression and stromal cell growth. The expression of the SM2 isoform of smooth muscle myosin heavy chain (SMMHC) mRNA was also examined. MATERIAL AND METHODS: Primary cultures of prostate stromal cells were established by means of an explant method from eight normal prostates. The effects of TGF-beta1 on stromal cell growth were determined by means of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion assay. SMemb/NMMHC-B and SM2 mRNA expression were analyzed quantitatively by means of real-time polymerase chain reaction. RESULTS: In the absence of TGF-beta1, cells expressed alpha-smooth muscle actin and vimentin. After TGF-beta1 treatment, the expression of alpha-smooth muscle actin increased and cells also expressed desmin. TGF-beta1 at concentrations of 1.0, 5.0 and 10 ng/ml suppressed cell growth by 72%, 62% and 56%, respectively, downregulated SMemb/NMMHC-B mRNA expression by 71%, 52% and 38%, respectively and upregulated SM2 mRNA expression 2.1-, 3.0- and 5.3-fold, respectively. CONCLUSIONS: These results demonstrate that TGF-beta1 modulates the smooth muscle cell phenotype from a proliferative to a contractile type and that the inhibitory effects of TGF-beta1 on stromal cell growth correlate with downregulation of the SMemb/NMMHC-B gene.

Cell Count↗

Full-thickness chest wall reconstruction using autologous tissue grafts after resection of recurrent desmoid tumor.

We report the case of a 62-year-old woman with a recurrent desmoid tumor of the chest wall who successfully underwent a full-thickness chest wall resection as well as skeletal and soft tissue reconstruction. In chest wall reconstruction, we used various kinds of autologous tissue grafts, i.e. rib, fascia lata and the transverse rectus abdominis myocutaneous flap. Judging from the reconstructed wall's strength, shape and flexibility, as well as wound healing, it is possible to conclude that this combined procedure is feasible because benefits of the procedure outweigh the disadvantage of additional operations for harvests.

Fascia Lata↗

Combined operation for myasthenia gravis and coronary artery disease.

A 57-year-old man with ocular myasthenia gravis was admitted to our hospital because of acute respiratory insufficiency associated with myasthenic crisis. He had a history of unstable angina indicated percutaneous coronary artery angioplasty. He was diagnosed with generalized nonthymomatous myasthenia gravis and a triple vessel coronary artery disease. We conducted a simultaneous surgical intervention, including extended thymectomy and coronary artery bypass grafting, using a standard cardiopulmonary bypass via median sternotomy. The patient had already been immunocompromised at surgery for having diabetes, and postoperative long-term steroid therapy. In this rare and special condition, a meticulous overall therapeutic strategy was needed in order to avoid myasthenic crisis and prepare for the worst case scenario of mediastinitis.

Cardiopulmonary Bypass↗

Prognosis and histologic features of small pulmonary adenocarcinoma based on serum carcinoembryonic antigen level and computed tomographic findings.

OBJECTIVES: In 2001, we proposed the criteria for combined evaluation of the serum carcinoembryonic antigen (CEA) level and the tumor shadow disappearance rate (TDR) to predict pathologic N0 (pN0) disease in pulmonary adenocarcinomas. The objective of the present study was to determine the prognosis and histologic features in small-sized pulmonary adenocarcinomas according to serum CEA level and TDR. METHODS: We reviewed clinical records of 189 consecutive patients with peripheral pulmonary adenocarcinoma 3.0 cm or smaller who underwent major lung resection and systematic lymph node dissection: 50 patients with TDR 0.8 or more and normal CEA level (group I) and 139 patients with TDR <0.8 and/or elevated CEA level (group II). Among them, we investigated histologic features of 177 adenocarcinomas according to serum CEA level and TDR. RESULTS: The 5-year survival rates were 95% for group I and 75% for group II (P = 0.002) and for pN0 patients, 97% in group I and 87% in group II (P = 0.04). In univariate analyses, TDR, preoperative serum CEA level, and the maximum tumor dimension on computed tomographic (CT) scan were significantly associated with prognosis. Multivariate analysis showed that only preoperative serum CEA level and TDR were significant independent prognostic factors, and the maximum tumor dimension was not significant. Group I patients developed no local recurrence, including lymph node metastases. In 25 group I adenocarcinomas 2.0 cm or smaller, no lymph node involvement, two lymphatic permeation, two vascular invasion, and one pleural involvement tumors were observed. These signs of local invasiveness were less frequent than the remaining adenocarcinomas. CT findings correlated well with histologic findings in small-sized adenocarcinomas. CONCLUSIONS: Combined evaluation of preoperative serum CEA level and TDR may enable us to identify minimally invasive adenocarcinomas with good prognosis. Candidates for limited lung resection without systematic lymph node dissection could be selected based on these findings.

Adenocarcinoma↗

Molecular analysis of the TSC1 gene in adenocarcinoma of the lung.

We previously reported that loss of heterozygosity (LOH) in tuberous sclerosis 1 (TSC1)-gene-associated region on chromosome 9q34, was frequently observed in adenocarcinoma (AC) of the lung and its putative precursor lesion, atypical adenomatous hyperplasia (AAH). Some novel tumor suppressor gene for AC of the lung may be present in this region, and the TSC1 gene located on chromosome 9q34 is one candidate. The aim of this study was to determine whether the TSC1 gene itself acts as a tumor suppressor gene in the pathogenesis of AC of the lung. DNA extracted from frozen tumor tissue was used to screen 47 ACs of the lung for the presence of mutations in 21 coding exons of the TSC1 gene. When using these bulk tissue specimens, three different types of mutations were detected in five ACs. These positive samples were then submitted to laser capture microdissection to selectively collect tumor cells, DNA extraction and finally analysis of LOH and mutations of the TSC1 gene. Mutations were detected in three ACs, and LOH was detected in another AC. No mutations or LOH was detected in the other AC. Loss of heterozygosity and mutations were not detected simultaneously in the same tumor. We concluded that the TSC1 gene itself does not act as a tumor suppressor gene in the pathogenesis of AC of the lung in accordance with classical Knudsen's two-hit hypothesis. However, the frequent LOH in AC and AAH shown in our previous studies indicate the following possibility in the etiology of AC of the lung: the presence of a novel tumor suppressor gene close to the TSC1 gene, aberrant promoter methylation, or haploid insufficiency of the TSC1 gene.

Adenocarcinoma↗

Laparoscopic transgastric tumor-everting resection of the gastric submucosal tumor located near the esophagogastric junction.

Local resection of the stomach is suitable for the treatment of submucosal tumors (SMT). However, it cannot be easily performed laparoscopically on tumors located near the esophagogastric junction. We have developed a new technique, which is called transgastric tumor-everting resection. To identify the location of the SMT laparoscopically without an oral endoscope, an Indiana ink mark was made prior to the operation. The SMT was everted from the gastrotomy and held by the Mini Loop Retractor II. The gastric mucosa could be observed from gastrotomy, allowing us to confirm that the staple line would not cause deformity of the esophagogastric junction. The lesion was then resected, and the gastrotomy was closed simultaneously using the Endo-GIA Universal. This technique is easy, safe, and useful for the laparoscopic resection of gastric SMTs located on the greater curvature or anterior wall of the fornix, near the esophagogastric junction.

Aged↗

[Extrapleural pneumonectomy after hyperthermo-chemotherapy for the lung cancer patients with malignant pleural effusion].

The prognosis of the lung cancer patients with malignant pleural effusion is extremely poor. Intrapleural perfusion hyperthermo-chemotherapy for the treatment of malignant pleural effusion was performed in 120 lung cancer patients and showed better prognosis than conventional treatment. After successful local control by hyperthermo-chemotherapy, extrapleural pneumonectomy was performed in 8 patients with clinical N 0 or N 1 and M 0 lung cancer. All patients survived for more than 1 year. The only 1 patient survived for more than 3 years and 3 months without recurrence. Almost all patients who died within 2 years had pathological n 2, carcinomatous pericarditis, cancer invasion beyond extrapleural space and so on. Extrapleural pneumonectomy after hyperthermo-chemotherapy can be a choice of surgical treatment if the n 2 disease, pericarditis, and extrapleural invasion of disseminated cancer cells should be excluded precisely.

Adenocarcinoma↗