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Biomedical subjects

T Kusumoto

Publications and source records attributed to T Kusumoto.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic significance of stromal versican expression in human endometrial cancer.

BACKGROUND: Versican expression may enhance tumor invasion and metastasis. However, the expression of versican in human endometrial cancer has seldom been characterized. The aim of this study was to investigate versican expression in endometrial cancers. PATIENTS AND METHODS: We immunohistochemically investigated the expression of versican protein in 167 endometrial cancers and analyzed the correlation with various observed clinicopathological features, including patient outcome. RESULTS: Stromal versican expression was significantly higher in the advanced-stage (P = 0.010) and high-grade (P = 0.049) cancers, lymph node metastasis (P = 0.012), and ovarian metastasis (P = 0.024). Epithelial versican expression was significantly higher in patients with lymph node metastasis (P = 0.014) and lymph-vascular space involvement (P = 0.014). The disease-free survival (DFS) and overall survival (OS) rates of patients exhibiting high stromal versican expression were significantly lower than those of patients exhibiting low stromal versican expression (P < 0.0001). Multivariate analysis showed that high stromal versican expression was an independent prognostic factor for DFS and OS. CONCLUSIONS: Versican enrichment of the stroma may be associated with tumor progression in endometrial cancer. Stromal versican expression can serve as an indicator of poor prognosis for patients with endometrial cancer.

Adenocarcinoma↗
PubMed2006

Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer.

BACKGROUND: The chemokine receptors CXCR4 and CCR7 have been suggested to play an important role in cancer invasion and metastasis. The expression of these receptors in human cervical cancer, however, has seldom been characterized. PATIENTS AND METHODS: We investigated the expression of CXCR4 and CCR7 in cervical cancer specimens and determined the association between their expression and the clinicopathological features observed, including patient outcome. RESULTS: CXCR4 expression was significantly higher in elderly patients (P=0.025); it was also significantly increased in patients with cancers displaying large tumor size (P=0.010), deep stromal invasion (P=0.0004), lymph-vascular space involvement (P=0.0002), or lymph node metastasis (P<0.0001). CCR7 expression was significantly higher in cases of squamous cell carcinomas (P=0.010) and in patients with cancers showing large tumor size (P<0.0001), deep stromal invasion (P<0.0001), vaginal invasion (P=0.047), lymph-vascular space involvement (P=0.012), or lymph node metastasis (P<0.0001). Logistic regression analysis revealed that deep stromal invasion (P=0.017) and CXCR4 (P=0.016) and CCR7 (P=0.022) expression were independent factors that influenced pelvic lymph node metastasis. The disease-free survival and overall survival (OS) rates of patients exhibiting both CXCR4 and CCR7 expression were significantly reduced (P<0.0001). In addition, the expression of both CXCR4 and CCR7 was an independent prognostic factor for OS (95% confidence interval=1.03-17.86; P=0.046). CONCLUSIONS: CXCR4 and CCR7 expression may be associated with lymph node metastasis; moreover, the expression of these receptors can serve as an indicator of poor prognosis in patients with cervical cancer.

Adult↗
PubMed2005

Prognostic significance of syndecan-1 expression in human endometrial cancer.

BACKGROUND: Syndecan-1 binds to various extracellular matrix components via its heparan sulfate glycosaminoglycans. The aim of this study was to investigate syndecan-1 expression in endometrial cancers. PATIENTS AND METHODS: We investigated the expression of the syndecan-1 core protein by immunohistochemistry in 109 endometrial cancers, and analyzed correlation with various clinicopathological features, including patient outcome. RESULTS: Epithelial syndecan-1 expression was significantly lower in advanced stage, high grade, deep myometrial invasion, cervical involvement, lymph node metastasis, lymph vascular space involvement and positive peritoneal cytology. Stromal syndecan-1 expression was significantly higher in high-grade tumors. The disease-free and overall survival rates of patients exhibiting both low epithelial and high stromal syndecan-1 expression was poor. Multivariate analysis showed that high stromal syndecan-1 expression was an independent prognostic factor for both disease-free and overall survival. Low epithelial syndecan-1 expression was a prognostic factor only in the univariate analysis. CONCLUSIONS: Loss of epithelial syndecan-1 and induction of stromal syndecan-1 expression may be associated with tumor progression. Stromal syndecan-1 expression can serve as an indicator of poor prognosis in patients with endometrial cancer.

Endometrial Neoplasms↗
PubMed2005

Loss of basement membrane heparan sulfate expression is associated with tumor progression in endometrial cancer.

Perlecan is a major heparan sulfate proteoglycan (HPSG) of the basement membrane (BM) and binds to various cytokines and growth factors via its heparan sulfate glycosaminoglycan (HS-GAG) chains. The aim of this study was to investigate BM HS-GAG expression in endometrial cancers. We investigated the expression of BM HS-GAG by immunohistochemistry in 109 endometrial cancers and analyzed correlations with various clinicopathological features. The HS-GAG expression index was significantly lower in cases of advanced stage, high-grade, deep myometrial invasion, positive peritoneal cytology, lymph vascular space invasion and lymph node metastasis. There was no association between HS-GAG expression status and patient outcome. Decreased HS-GAG expression of BM is associated with tumor progression, but is not be a useful prognostic factor in patients presenting with endometrial cancer.

Adult↗
PubMed2001

Visual enantiomeric recognition using chiral phenolphthalein derivatives.

[structure: see text] Optically active artificial host molecules 2-5 based on a phenolphthalein skeleton have been prepared for visual enantiomeric recognition of alanine derivatives 8 and 9. The receptor 3 discriminates (R)-8 and (R)-9 from (S)-8 and (S)-9, respectively, to develop a purple color.

Journal Article↗
PubMed2000

Induction and maintenance of immune effector cells in the gastric tissue of mice orally immunized to Helicobacter pylori requires salivary glands.

BACKGROUND & AIMS: Helicobactor pylori mostly colonizes the gastric mucus that contains salivary antibodies. We studied the role of saliva in the induction and maintenance of gastric immunity conferred by oral vaccination against H. pylori. METHODS: C57BL/6 mice underwent a sialoadenectomy before and after intragastric immunization using whole-cell sonicates of H. pylori and cholera toxin as an adjuvant. At 1 and 6 months after oral inoculation, we assessed the density of the H. pylori colonizing the stomach, specific antibodies in gastric secretion and sera, and the constituents of cellular infiltrates in the tissue. RESULTS: A sialoadenectomy before, but not after, immunization abrogated protection by the vaccination at 1 month after inoculation. Protected mice had more neutrophils, plasma cells, and lymphocytes, but fewer eosinophils, in the gastric tissue than nonprotected mice. Protected mice had a greater increase of immunoglobulin (Ig) G1 specific to H. pylori than IgG2a in sera. At 6 months after inoculation, oral immunization was less effective in mice who had a sialoadenectomy than in control immunized mice. The antibody titers in both gastric secretion and in sera did not correlate with the density of bacteria colonizing the stomach. CONCLUSIONS: It is suggested that, in intragastric immunization against H. pylori, saliva is necessary for both the induction and maintenance of optimal immunity in the stomach. Effective immunity was associated with an increased number of neutrophils and lymphocytes in gastric tissue.

Administration, Oral↗
PubMed1999

The p53 tumor suppressor gene in anticancer agent-induced apoptosis and chemosensitivity of human gastrointestinal cancer cell lines.

PURPOSE: While the target of many anticancer agents has been identified, the processes leading to killing of the cancer cells and the molecular basis of resistance to the drugs are not well understood. We used human gastrointestinal cancer cell lines and examined how anticancer agents induced cell killing and how the chemosensitivity of these lines was determined. METHODS: Twelve gastrointestinal cancer cell lines were examined for the presence of either a wild-type or mutant p53 gene by direct sequencing. We also determined whether or not cell killing would occur when the cell lines were exposed to anticancer drugs. The sensitivity to the anticancer agents was determined based on colony formation. RESULTS: All 12 gastrointestinal cancer cell lines carried either a wild-type or mutant p53 gene. Three lines, MKN45, MKN74 and COLO320, carried the wild-type p53 gene, and nine carried the mutant p53 gene. When three lines were exposed to the anticancer agents etoposide, doxorubicin (DXR) or 5-fluorouracil (5-FU), cell death ensued. In these cells, the population of cells in G1 phase increased after exposure to high-dose anticancer agents, but cells in G2 phase increased when exposed to low-dose anticancer agents. Our observations support the concept that cells carrying the wild-type p53 gene tend to be sensitive to etoposide and DXR and, in particular, deletion of the p53 function results in a greater resistance to anticancer agents. CONCLUSION: Based on our findings, human gastrointestinal cancer-related cell death apparently occurs via a p53-dependent pathway. A relationship was observed between the induction of cell death and chemosensitivity.

Antineoplastic Agents↗
PubMed1997

[Pharmacokinetic and clinical evaluation of cefozopran in newborn patients].

Pharmacokinetic and clinical evaluation of an injectable cephem antibiotics, cefozopran (SCE-2787, CZOP), was conducted in newborn patients and the following results were obtained: 1. Clinical results The clinical efficacy of CZOP was evaluated in one each patient with intrauterine infection and suspected septicemia. The efficacy was "excellent" in both patients. No clinically serious adverse drug reactions of signs and symptoms and abnormal alterations of the laboratory test values were recognized. 2. Pharmacokinetics CZOP was intravenously given to newborn patients at doses of 25.0, 20.0, and 18.75 mg/kg. The blood CZOP concentrations were 44.7 +/- 7.0 micrograms/ml (n = 3), 48.3 micrograms/ml and 48.2 micrograms/ml at one hour after administration, respectively. The elimination half life (T 1/2) was 4.22 +/- 1.17 hours (n = 3) in the patients given 25.0 mg/kg and 2.74 hours in the patient given 20.0 mg/kg. The urinary drug excretion rate was 44.5 +/- 8.7% and 31.3 +/- 9.7% of dose within 8 hours after administration of 25.0 mg/kg and 20.0 mg/kg, respectively.

Bacterial Infections↗
PubMed1996

Expression of multidrug-resistance-associated protein (MRP) and chemosensitivity in human gastric cancer.

Evidence has accumulated that, in addition to the MDR1 gene-coded P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP) also mediates the multidrug resistance (MDR) of various human tumors. In the case of gastric cancer, there is little or no involvement of P-glycoprotein, and the mechanisms of MDR remain to be understood. To search for a possible relationship between expression of MRP and sensitivity to anti-cancer agents in gastric cancer, 4 gastric cancer cell lines, 43 human gastric carcinomas and 17 adjacent normal gastric tissue samples were analyzed. Expression of MRP mRNA was evaluated using reverse transcription PCR (RT-PCR) and Southern hybridization. Sensitivity of the test samples to the anti-cancer drugs cisplatin (CDDP), doxorubicin (DXR) and etoposide (VP-16) was examined using the MTT¿3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl [2H]-tetrazolium bromide¿ assay. Immunohistochemical staining with the use of the MRP antibody (MRPr1) was done to confirm the findings regarding the expression of mRNA levels. The MRP expression evaluated with RT-PCR and Southern hybridization as well as with immunohistochemical staining revealed that 23 of 43 gastric-cancer tissues (53.5%), 15 of 17 normal gastric tissues (88%) and 3 of 4 gastric-cancer cell lines (75%) were positive. The MTT assay showed that DXR was significantly more sensitive (p < 0.01) in gastric carcinoma tissues lacking MRP expression than in those with positive expression. The same tendency was seen with the other agents used. Of the cell lines, one which showed no MRP expression also had a higher sensitivity to CDDP, DXR and VP-16 than the other positive cases. These results show that MRP expression is involved in MDR of human gastric cancer and is inversely related to the chemosensitivity of tumor cells against some anticancer drugs.

ATP-Binding Cassette Transporters↗
PubMed1996

Transforming growth factor-beta 1 induces apoptosis in gastric cancer cells through a p53-independent pathway.

BACKGROUND: Apoptosis is induced by various anticancer agents or radiation through the tumor suppressor gene p53-dependent pathway and is also induced by other factors, including transforming growth factor-beta 1 (TGF-beta 1). In this study, the authors investigated whether TGF-beta 1 would induce apoptosis in gastrointestinal cancer cells, and its relation to the status of the p53 gene. METHODS: The induction of apoptosis by TGF-beta 1 was determined in 12 gastrointestinal cancer cell lines using DNA ladder formation. Status of the p53 gene was examined by sequencing of cDNA from p53 mRNA and expressions of TGF-beta 1 mRNA and TGF receptors I and II mRNAs were determined by Northern blot analysis and the reverse transcriptase-polymerase chain reaction analysis, respectively. RESULTS: Of 12 cell lines, wild-type p53 was present in 3 lines, point mutation was detected in 7 lines, and p53 mRNA was absent in 2 lines. TGF-beta 1 was expressed in all 12 lines, but both TGF receptors I and II were expressed in only 6 lines. Addition of TGF-beta 1 induced DNA ladder formation only in KATOIII cells, with deleted p53 mRNA, but expressed TGF receptors I and II. CONCLUSIONS: These findings show that TGF-beta 1 induces apoptosis in gastric cancer cells through TGF-beta receptors I and II and a p53-independent pathway.

Antineoplastic Agents↗
PubMed1996

Multidrug resistance-associated protein expression in clinical gastric carcinoma.

BACKGROUND: We examined the relationship between the expression of a multi-drug resistance-associated protein (MRP) and the biologic factors regarding invasion and metastasis of human gastric cancer. METHODS: In 75 patients with gastric cancer, the expression of MRP was immunohistochemically investigated and the expression of MRP mRNA was also detected using reverse transcription PCR (RT-PCR). Sensitivity to the anticancer agents, cisplatin (CDDP), doxorubicin (DXR), etoposide (VP-16), and mitomycin C (MMC) was examined using the MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl[2H]-tetra-zolium bromide} assay. The relation between MRP expression and development, invasion, and metastasis of cancer was analyzed, and overexpression of the tumor suppressor gene p53 was investigated, immunohistochemically. RESULTS: Immunohistochemically detected MRP positive tumors were noted in 34 of 75 excised tumors (45%), and confirmed by RT-PCR. There was no significant relation between MRP expression and clinicopathologic features or prognosis. Positive p53 staining was evident in 16 of 34 MRP positive tumors (47%) and 18 of 41 negative ones (44%), and there was no significant correlation between MRP and abnormal p53 expression. The MTT assay showed that MRP positive gastric cancer tissue was less sensitive to CDDP, DXR, and MMC compared with MRP negative ones. A similar tendency was noted with VP-16. CONCLUSIONS: MRP expression relates to the chemosensitivity of tumor cells against some anticancer drugs and is independent of known factors related to the development, invasion, and metastasis of human gastric cancers.

ATP-Binding Cassette Transporters↗
PubMed1996

Cytokeratin-positive cells in bone marrow for identifying distant micrometastasis of gastric cancer.

Direct evidence of tumour seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap since it is a feature of epithelial cells that would not normally be present in bone marrow. The bone marrow of 46 patients with primary gastric cancer was examined for tumour cells, using immunocytochemical techniques and antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. The monoclonal antibody CK2 recognises a single cytokeratin polypeptide (human cytokeratin no. 18) commonly present in epithelial cells. The expression of tumour-suppressor genes p53 and RB for the primary lesion was also determined using the monoclonal antibodies PAb 1801 and 3H9 respectively, and the proliferating activity was determined by the Ki-67 antigen labelling index for MIB-1 antibody staining. Of these 46 patients, 15 (32.6%) presented with cytokeratin-positive cells at the time of primary surgery. The positive findings were related to the undifferentiated tissue type and to the prominent depth of invasion, but not to other clinicopathological factors. In 2 of 15 (13.3%) patients, the depth of invasion was limited to the mucosa. The metastatic potential to bone marrow did not relate to expressions of p53 and RB genes, or to the proliferating activity of MIB-1 staining for the primary lesion of gastric cancer. As tumour cells in bone marrow are indicative of the general disseminative capability of an individual tumour, this technique may be useful for identifying patients at high risk of metastasis from a gastric tumour.

Antibodies, Monoclonal↗
PubMed1995

A female heterozygous patient with Fabry's disease with renal accumulation of trihexosylceramide detected with a monoclonal antibody.

We describe a female patient with heterozygous Fabry's disease. The patient had persistent proteinuria and microhematuria but lacked any other diagnostic signs such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy showed the segmentally distributed enlarged glomerular epithelia. These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures under electronmicroscopic observation. Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr, n = 20). All of these findings were compatible with the diagnosis of heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens suggesting Fabry's disease be immunostained with anti-CTH antibody.

Antibodies, Monoclonal↗
PubMed1995

Correlation between sialyl Tn antigen and lymphatic metastasis in patients with Borrmann type IV gastric carcinoma.

The expression of sialyl Tn (STn) antigen in 180 patients with Borrmann type IV gastric carcinomas was examined immunohistochemically. The rate of positive STn staining was 32% (57/180) for the primary tumours, and this positive staining correlated well with tumour extension, lymph node metastasis (P < 0.05) and peritoneal dissemination (P < 0.01). One-third (5/15) of patients with positive STn-staining cancer cells had a high level of serum STn. Lesions with positive STn staining were related to a lower survival rate for the patients (P < 0.05). Proliferative activity of the tumour, as measured by proliferating nuclear antigen (PCNA) labelling percentage and argyrophilic nucleolar organiser region (AgNOR) count, was significantly higher (41.5 +/- 13.0%, 3.78 +/- 0.98) in the STn-positive group than in the STn-negative group (34.2 +/- 13.2%, 3.48 +/- 0.85) (P < 0.01, P < 0.05 respectively). Estimating STn antigen may be useful for predicting the likelihood of lymph node metastasis or peritoneal dissemination and the clinical prognosis for patients with Borrmann type IV gastric carcinoma.

Adult↗
PubMed1995

Cyclosporin A and FK506 reverse anthracycline resistance by altering the cell cycle.

We investigated the effect of cyclosporin A (CsA) or FK506 on the cytotoxicity of anthracyclines against a human laryngeal cancer cell line, KB cells, and a multi-drug resistance cell line, VJ-300 cells. CsA and FK506 enhanced the cytotoxicity of anthracyclines, especially in the VJ-300 cells. The intracellular concentrations of epirubicin (EPIR), daunomycin (DM), adriamycin (ADM) and THP-adriamycin (THP) were increased by the addition of CsA or FK506 in VJ-300, but not in KB cells. The intracellular accumulation of EPIR was most increased when CsA or FK506 was concomitantly administered with the drug. We also asked whether CsA or FK506 might influence the cycle of KB or VJ-300 cells. The population of cells in each phase of the cell cycle was little changed in both KB and VJ-300 cells when 0.3 microM ADM was administered for 24 h. Both CsA and FK506 significantly increased the ADM-induced accumulation of VJ-300 cells in G2M phase, in comparison with findings with KB cells. Thus, the reversal of MDR by CsA or FK506 is related to increased intracellular concentrations of cytotoxic drugs and, as a result, the increased G2M accumulates in MDR cells. Among of antrhacyclines, EPIR was most effective when concomitantly combined with CsA or FK506 in VJ-300 cells.

Antibiotics, Antineoplastic↗