Biomedical subjects

Tetsuya Toge

Publications and source records attributed to Tetsuya Toge.

At least 37 records · Page 2Linked to original sources

PubMed2005

[Clinical study of TS-1 for inoperative and recurrent gastric cancer and evaluation of long survival cases].

The clinical efficacy and safety of TS-1 therapy were studied retrospectively in patients with inoperable and recurrent gastric cancer. The subjects were 67 patients who were treated with TS-1 in our department between June 1999 and September 2004. The objective overall response rate was 41.0% (16/39; 95% confidence interval, CI, 25.3-56.7). By location, the response rate of peritoneal dissemination was high (57.1%), as were those of primary lesion (53.3%) and lymph nodes (42.9%). The prevalence of adverse reactions with a grade of 3 or 4 was 12.8%. The median survival rate (MST) was 276 days with 1-year and 2-year survival rates of 48.9% and 27.8%, respectively. This resulted in 6 long-term survival cases (over 2.5 years) after TS-1 therapy, and the longest survival time was 3y 5m after TS-1 therapy. PRs or long-term NCs after TS-1 therapy were likely to be important factors for long-term survival. In conclusion, TS-1 is safe and effective for patients with inoperable and recurrent gastric cancer, and is promising as a first-line treatment.

Adult↗

PubMed2005

Clinical evaluation of low-dose cisplatin and 5-fluorouracil as adjuvant chemoradiotherapy for advanced squamous cell carcinoma of the esophagus.

The aim of this retrospective study was to evaluate the effectiveness of low-dose cisplatin and 5-fluorouracil (low-dose FP) as an adjuvant chemoradiotherapy for resected advanced squamous cell carcinoma of the esophagus. From 1994 to 1999, 57 patients who showed an invasion of the tumor over the muscularis propria (T2-T4), regional lymph node metastasis (N1), and no distant metastasis (M0) were enrolled in this analysis. Postoperative chemoradiotherapy (CRT group) was performed on 14 of the patients, and they were compared to the patients who underwent surgery alone (S group) using the matched pair algorithm. In the CRT group, chemotherapy of low-dose FP was combined with concurrent radiotherapy after the esophagectomy. A side-effect of severe dysphagia (NCI-CTC Grade 3) was observed in 4 patients (28.6%) and leukocytopenia in 1 patient (7.1%) among the CRT group. The overall survival rate of the CRT group and matched S group were 35.7% and 28.5% at 5 years, respectively, with no significant difference. In the CRT group, 7 of 14 patients (50%) had a recurrence. The recurrence rate was slightly lower than in the S group (57%), with no significant difference. This combined chemoradiotherapy using low-dose FP did not improve the prognosis of patients with resected advanced esophageal carcinoma.

Aged↗

PubMed2005

CD4+CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer.

It is well known that immunosuppression may contribute to the progression and chemotherapy-resistance of cancer. Recent studies have demonstrated that lymphocytes with the phenotype of CD4+CD25+ regulatory T cells (T-regs) contribute to immune dysfunction in cancer patients, and a relative increase in CD4+CD25+ regulatory T cells is related to immunosuppression and tumor progression in patients with some malignancies. In the present study, we evaluated the prevalence of T-regs in the peripheral blood of patients with breast cancer and non-small cell lung cancer. The phenotype of lymphocyte CD4+CD25+ cells was analyzed in peripheral blood of patients with breast cancer (n=22) and non-small cell lung cancer (NSCLC) (n=17). The population of CD4+CD25+ cells in CD3+ and CD4+ cells was evaluated by flow cytometric analysis with triple-color staining. Patients with breast cancer did not have a higher percentage of CD4+CD25+ cells in the total CD3+ and CD4+ cells in their peripheral blood than healthy volunteers. In contrast, patients with recurrent NSCLC had significantly higher percentages of CD4+CD25+ cells in CD3+ (47.6%) and CD4+ (71.0%) than healthy volunteers (n=10) who had CD4+CD25+ cells in CD3+ (33.7%, p=0.02) and CD4+ (52.2%, p<0.03). The population of CD4+CD25+ T-regs in the peripheral blood of patients with non-small cell lung cancer was significantly higher than that in healthy volunteers but not in breast cancer patients. These findings suggest that the use of T-reg-targeted immunomodulatory therapy may be a more effective strategy for patients with non-small cell lung cancer than for those with breast cancer.

Adult↗

PubMed2005

Intractable gastrointestinal bleeding from angiodysplasia in a patient of Bernard-Soulier syndrome--report of a case--.

We herein report a case of gastrointestinal bleeding induced by angiodysplasia of the cecum in a case of Bernard-Soulier syndrome with recurrent breast cancer. In spite of endoscopic hemostatic therapy and interventional embolization, she had repeated massive bleeding from the cecal lesion. In addition, she had chronic hepatitis C and progressive liver tumors metastasized from breast cancer, and she finally died of hepatic failure. There are four case reports in the literature describing Bernard-Soulier syndrome with gastrointestinal bleeding angiodysplasia. The reported cases benefited from hormonal, endoscopical hemostasis and surgical therapy. In our case, because of her terminal metastatic breast cancer, only conservative treatments were administered after the third bleed. Both the endoscopic hemostatic method and interventional embolization showed only a temporary effect. Surgical treatment should be considered if the general condition can tolerate a surgical procedure.

Angiodysplasia↗

PubMed2004

Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy.

Bcl-2 protein plays a critical role in inhibiting anticancer drug-induced apoptosis, which is mediated by a mitochondria-dependent pathway that controls the release of cytochrome c from mitochondria through anion channels. Constitutive overexpression of Bcl-2 or unchanged expression after treatment with anticancer drugs confers drug resistance not only to hematologic malignancies but also to solid tumors. The down-regulation of Bcl-2 protein by the antisense (AS) Bcl-2 (oblimesen sodium) may be a useful method for targeting the antiapoptotic protein and thereby increasing the chemotherapeutic effect of anticancer drugs. Several randomized, controlled, Phase III trials have compared standard chemotherapy with a combination of AS Bcl-2 and standard chemotherapy for the treatment of patients with chronic lymphocytic leukemia, multiple myeloma, malignant melanoma, and nonsmall cell lung carcinoma. Nonrandomized clinical trials and preclinical evaluations of AS Bcl-2 also are underway for patients with other malignancies. Here, the authors review the current clinical and preclinical evaluations of AS Bcl-2 and discuss its potential to act as a chemosensitizer and to enhance the therapeutic effect of cancer chemotherapy.

Antineoplastic Agents↗

PubMed2004

Preclinical evaluation of antisense bcl-2 as a chemosensitizer for patients with gastric carcinoma.

BACKGROUND: Because bcl-2 is a critical factor for anticancer drug-induced apoptosis, the authors conducted a preclinical evaluation of antisense (AS) bcl-2 as an enhancer of the chemotherapeutic effect in the treatment of patietns with gastric carcinoma. METHODS: AS bcl-2 was used with 18-mer phosphorothiated oligonucleotides in the MKN-45 gastric carcinoma cell line. Drug sensitivity in vitro was evaluated using the methyl-thiazoldiphenyl tetrazolium assay, and antitumor effects in vivo were evaluated using the nude mouse xenograft. Apoptosis was determined with the terminal deoxyuridine triphosphate nick-end labeling assay. AS bcl-2 in vitro was treated with lipofectin, whereas it was administered intraperitoneally for 6 consecutive days twice every 2 weeks in vivo. Anticancer drugs were administered intraperitoneally four times per week. RESULTS: bcl-2 was down-regulated to 60% of its initial value after treatment with 1.0 muM AS bcl-2 compared with the controls of random and mismatched oligonucleotides. Drug sensitivity to doxorubicin, cisplatin, and paclitaxel (TXL) was increased 3-4-fold when used in combination with AS bcl-2, which was determined with 50% inhibitory concentration values, compared with the control group. Increased drug sensitivity was associated with apoptosis, which increased in Bax and poly-adenosine diphosphate (ADP-ribose) polymerase and decreased in phosphorylated Akt (pAkt). The antitumor effect of cisplatin and TXL in vivo was enhanced significantly in combination with AS bcl-2. Down-regulation of bcl-2 was observed on Day 4 after the treatment with AS bcl-2. CONCLUSIONS: Combination treatment with AS bcl-2 and anticancer drugs, including cisplatin and TXL, may be a new strategy for enhancing chemotherapeutic effects in the treatment of gastric carcinoma.

Animals↗

PubMed2004

Concise prediction models of anticancer efficacy of 8 drugs using expression data from 12 selected genes.

We developed concise, accurate prediction models of the in vitro activity for 8 anticancer drugs (5-FU, CDDP, MMC, DOX, CPT-11, SN-38, TXL and TXT), along with individual clinical responses to 5-FU using expression data of 12 genes. We first performed cDNA microarray analysis and MTT assay of 19 human cancer cell lines to sort out genes which were correlative in expression levels with cytotoxicities of the 8 drugs; we selected 13 genes with proven functional significance to drug sensitivity from a huge number of potent prediction marker genes. The correlation significance of each was confirmed using expression data quantified by real-time RT-PCR, and finally 12 genes (ABCB1, ABCG2, CYP2C8, CYP3A4, DPYD, GSTP1, MGMT, NQO1, POR, TOP2A, TUBB and TYMS) were selected as more reliable predictors of drug response. Using multiple regression analysis, we fixed 8 prediction formulae which embraced the variable expressions of the 12 genes and arranged them in order, to predict the efficacy of the drugs by referring to the value of Akaike's information criterion for each sample. These formulae appeared to accurately predict the in vitro efficacy of the drugs. For the first clinical application model, we fixed prediction formulae for individual clinical response to 5-FU in the same way using 41 clinical samples obtained from 30 gastric cancer patients and found to be of predictive value in terms of survival, time to treatment failure and tumor growth. None of the 12 selected genes alone could predict such clinical responses.

Antimetabolites, Antineoplastic↗

PubMed2004

The role of Fas ligand and transforming growth factor beta in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy.

Despite the fact that expression of Fas ligand (FasL) in cytotoxic T lymphocytes (CTLs) and in natural killer (NK) cells plays an important role in Fas-mediated tumor killing, During tumor progression FasL-expressing tumor cells are involved in counterattacking to kill tumor-infiltrating lymphocytes (TILs). Soluble FasL levels also increase with tumor progression in solid tumors, and this increase inhibits Fas-mediated tumor killing by CTLs and NK cells. The increased expression of FasL in tumor cells is associated with decreased expression of Fas; and the promoter region of the FASL gene is regulated by transcription factors, such as neuronal factor kappaB (NF-kappaB) and AP-1, in the tumor microenvironment. Although the ratio of FasL expression to Fas expression in tumor cells is not strongly related to the induction of apoptosis in TILs, increased expression of FasL is associated with decreased Fas levels in tumor cells that can escape immune surveillance and facilitate tumor progression and metastasis. Transforming growth factor beta (TGF-beta) is a potent growth inhibitor and has tumor-suppressing activity in the early phases of carcinogenesis. During subsequent tumor progression, the increased secretion of TGF-beta by both tumor cells and, in a paracrine fashion, stromal cells, is involved in the enhancement of tumor invasion and metastasis accompanied by immunosuppression. Herein, the authors review the clinical significance of FasL and TGF-beta expression patterns as features of immune privilege accompanying tumor progression in the tumor microenvironment. Potential strategies for identifying which molecules can serve as targets for effective antitumor therapy also are discussed.

Apoptosis↗

PubMed2004

A single nucleotide polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer.

PURPOSE: Matrix metalloproteinase-1 (MMP-1) plays a key role in cancer invasion and metastasis by degradation of extracellular matrix (ECM) and basement membrane barriers. The 1G/2G single nucleotide polymorphism (SNP) in the MMP-1 promoter at position -1607 bp has been reported to affect the transcriptional activity. In the light of these findings, we investigated whether this SNP in the MMP-1 promoter is associated with the development, differentiation, and progression of gastric cancer. METHODS: The 215 gastric cancer patients and 166 controls were used in this study. The SNP of the MMP-1 promoter was analyzed by PCR-RFLP and sequencing. The genotype frequency was compared between cases and controls, and the association with clinicopathological parameters among cases was studied. RESULTS: The frequency of 1G/2G genotypes in gastric cancer patients was similar to those in controls (p=0.57). The degree of tumor invasion, the presence of lymph node metastasis, and clinical stage showed no significant association with the SNP. On the other hand, we found a significant association with histological differentiation and gender among gastric cancer patients (p<0.05, respectively). CONCLUSIONS: The presence of 2G allele in the MMP-1 promoter did not enhance the risk of gastric cancer; however, it may be involved in differentiation of gastric cancer.

Aged↗

PubMed2004

Changes in therapy for solid tumors: potential for overcoming drug resistance in vivo with molecular targeting agents.

Recent advances in molecular biology have led to the development of selective molecular targeting agents for genes involved in cell proliferation, apoptosis, and angiogenesis in cancer cells. The current success of molecular targeting therapy is shown by: imatinib mesylate (STI571, Gleevec), targeted to the Bcr/Abl fusion protein derived from a translocation between chromosomes 9 and 22 in chronic myelogenous leukemia; rituximab (Rituxan), a monoclonal antibody to CD20 used in non-Hodgkin's lymphoma; trastuzumab (Herceptin), a chimeric monoclonal antibody to HER-2 used in breast cancer; and gefinitib (ZD1839, Irresa), a tyrosine kinase inhibitor of the epidermal growth factor receptor used in non-small cell lung cancer. The superior therapeutic efficacy of these molecular targeting agents over traditional chemotherapy has been shown by the survival benefit achieved for patients with advanced or recurrent cancers. Although the precise molecular mechanisms by which these agents produce or enhance an antitumor effect, alone or in combination with anticancer drugs, are not known, the specific inhibition of target genes critically involved in tumor progression and metastasis by the agent is clear. However, further studies to determine which patient groups and anticancer drugs are appropriate for combination therapy with these molecular targeting agents are needed. Herein, we discuss the current status and potential for overcoming drug resistance in solid tumors and focus on the differential features of the tumor microenvironment in solid and hematologic malignancies.

Animals↗

PubMed2004

Multidisciplinary approach to cancer treatment: a model for breast cancer treatment at the M.D. Anderson Cancer Center.

Despite that fact that a multidisciplinary approach is important for cancer treatment, this approach is not widely used in Japan. The M.D. Anderson Cancer Center (MDACC) is one of the most well-established cancer institutes in the world, and has implemented a unique multidisciplinary team management approach for the treatment of breast cancer. The efforts of MDACC to eliminate cancer have been ongoing for more than 60 years. Here, we describe the multidisciplinary approach used at MDACC for the treatment for breast cancer. We focus on the background of the institute, in terms of establishing its treatment model and educational system, and compare its multidisciplinary approach with the current approach used in Japan, in the hopes of influencing future directions in cancer therapy in Japan.

Breast Neoplasms↗

PubMed2004

Expression of hypoxia-inducible factor (HIF)-1alpha is associated with vascular endothelial growth factor expression and tumour angiogenesis in human oesophageal squamous cell carcinoma.

The purpose of this study was to examine the relationship between hypoxia inducible factor (HIF)-1alpha expression, vascular endothelial growth factor (VEGF) expression, and tumour vascularity in squamous cell carcinoma of the oesophagus. Expression of HIF-1alpha and VEGF was examined in two oesophageal squamous cell carcinoma cell lines (TE2, TE3) and 82 archival surgical specimens of human oesophageal squamous cell carcinoma tissue. In both cell lines, the levels of HIF-1alpha protein and VEGF mRNA were increased under hypoxic conditions. Thirty-two of the 82 (39%) tumour specimens showed high levels of HIF-1alpha immunoreactivity in the nuclei and/or cytoplasm of cancer cells. HIF-1alpha expression correlated significantly with venous invasion, VEGF expression, and microvessel density. Among the 47 patients who did not receive pre-operative chemotherapy, the outcome of those with high HIF-1alpha-expressing tumours was significantly poorer than that of those with low HIF-1alpha-expressing tumours. These results suggest that HIF-1alpha and VEGF expression are important determinants of survival in squamous cell carcinoma of the oesophagus.

Blotting, Western↗

PubMed2004

A randomized phase II clinical trial of tailored CPT-11 + S-1 vs S-1 in patients with advanced or recurrent gastric carcinoma as the first line chemotherapy.

A randomized phase II clinical trial has been designed and started in the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) to select the better regimen between tailored CPT-11 + S-1 and the standard S-1 treatment for advanced or recurrent gastric cancer as the first line chemotherapy. Selection of the better treatment for general clinical practice in this clinical trial will lead to a more precise assignment of a promising regimen for a future phase III randomized trial, placing continuous 5-FU infusion as the reference arm. In this trial, subsidiary pharmacokinetic analysis for the tailored dose arm is also proposed. In order to continue chemotherapy for a long time and to obtain longer survival, our study design for the tailored therapy could be exploited, especially in the field of general clinical practice.

Antimetabolites, Antineoplastic↗

PubMed2004

Establishment of two cell lines from human gastric scirrhous carcinoma that possess the potential to metastasize spontaneously in nude mice.

Few experimental studies have been conducted to clarify the mechanism of development of metastasis in scirrhous carcinoma of the stomach. In the present study, we attempted to establish gastric carcinoma cell lines by incubation of cancer cells collected from the body fluids of patients with gastric cancer. At the same time, xenografting of these cells to nude mice was performed. It was found that, of the gastric carcinoma cell lines thus established, two cell lines, designated as HSC-44PE and HSC-58, formed s.c. tumors with a high infiltrative potential (often invading the lymphatics around the cancer tissue) when implanted. Metastasis to the lymph nodes and lungs was observed in 20-40% of all the animals, indicating that the two cell lines are also capable of metastasizing spontaneously. Through repeated selection, i.e., repeated cycles of removal, culture, and implantation of the HSC cancer cells from metastatic lesions, we obtained 5 subclones of HSC-44PE and HSC-58 (designated as m2509, m2615, m2792, m2917, and m2691), which, when implanted orthotopically, exhibited the following characteristics as compared to the parent cells: (1) a higher percentage take (survival), similar frequency of metastasis, shorter time to metastasis (less than 100 days), and consistent metastasizing potential; (2) a relatively high frequency of metastasis to lymph nodes, including distant metastasis to axillary lymph nodes; (3) the potential to cause occasional bloody ascites; (4) enhanced expression of dysadherin, CD44, and other molecules. This is the first report of cultured scirrhous gastric carcinoma cells showing the potential for spontaneous metastasis.

Adenocarcinoma, Scirrhous↗

PubMed2004

Potential roles of antisense therapy in the molecular targeting of genes involved in cancer (review).

Recent advances in antisense methods targeting genes involved in cell proliferation, angiogenesis, and apoptosis provide a potential anticancer effect alone as well as in combination with drugs, and antisense therapy may be useful in overcoming drug resistance and increasing survival in patients with advanced cancer including those with solid tumors. In particular, antisense to Bcl-2 comprises a most promising therapy and is being tested in combination with anticancer drugs in randomized phase III trials for chronic lymphocytic leukemia, multiple myeloma, and malignant melanoma. The targeting of apoptosis-related proteins is promising for enhancing the effect of cancer chemotherapy. The molecular mechanism by which anticancer drugs induce apoptosis has been identified as mitochondrial dysfunction mediated by the release of cytochrome c. Modulation of multiple antiapoptotic signaling pathways involving Bcl-2 and Akt, which are related to growth factor-stimulated signal transduction in cell survival, is essential for enhancement of the cytotoxic effect of anticancer drugs. Herein, we review the current status of antisense therapy and its potential for enhancing anticancer drug-induced apoptosis.

Animals↗

PubMed2004

Locoregional immunotherapy of malignant ascites from gastric cancer using DTH-oriented doses of the streptococcal preparation OK-432: Treatment of Th1 dysfunction in the ascites microenvironment.

Locoregional administration of the streptococcal preparation OK-432 is effective in treating malignant ascites from gastric cancer. In order to enhance the efficacy, we conducted a pilot study of locoregional immunotherapy for malignant ascites using host-oriented doses of OK-432. Moreover, action mechanisms of OK-432 were further explored in view of the T-helper type 1 (Th1)-Th2 concept. Gastric cancer patients with cytologically determined malignant ascites were locoregionally administered with OK-432. The dose of OK-432 was selected according to the delayed-type hypersensitivity (DTH) reaction levels to OK-432. Cytokine production profiles of ascites cells were determined using whole ascites assay by stimulation with OK-432. IL-10 mRNA expression was analyzed using RT-PCR. It was found that a positive clinical response was observed in 37 of the 51 (73%) patients with the DTH-oriented approach, showing a significantly higher efficacy than traditional dosage methods using empirical doses (31/58, 53%) (p=0.0487). The DTH-oriented administration of OK-432 produced adverse effects such as fever elevation (p<0.0001) and abdominal pain (p=0.0013) to a significantly lesser extent compared with the traditional treatment. Analysis of the action mechanism of OK-432 revealed that the DTH reaction in responders (19+/-6 mm) was stronger than that in non-responders (6+/-4 mm) (p<0.0001). Tumor necrosis factor (TNF)-alpha production of ascites cells was also higher in responders (3943+/-1247 pg/ml) than in non-responders (1217+/-939 pg/ml) (p=0.0002). There was a significant positive correlation (p=0.0085) between the levels of DTH reaction and TNF-alpha production of ascites cells, but not of blood cells. Responders appeared to polarize on the Th1 axis when clinical responses were plotted on Th1-Th2 dimensions according to the cytokine production profiles of TNF-alpha, IFN-gamma, IL-4 and IL-6 of ascites cells. In vitro culture with IL-2 of ascites cells after OK-432 administration demonstrated an almost clonal expansion of CD4+ lymphocytes, which produced TNF-alpha and IFN-gamma, but did not produce IL-4 or IL-6. IL-10 mRNA expression was detectable in ascites cells from non-responders before treatment. These results suggest that the DTH-oriented locoregional administration of OK-432 may be both effective and less toxic in treating malignant ascites from gastric cancer, showing a possibility of the tailored immunotherapy for malignant ascites. Th1 dysfunction exists in the microenvironment of malignant ascites from gastric cancer, in which IL-10 may, in part, play a role. The up-regulation of Th1 responses by OK-432 may result in positive clinical responses. The DTH reaction to OK-432 may be a useful tool not only for predicting clinical response but also for selecting the optimal dose of OK-432.

Aged↗

PubMed2004

Neoadjuvant chemotherapy for local advanced breast cancer with stage IIIB.

In this study, we have done a retrospective evaluation of the clinical benefits of neoadjuvant chemotherapy in 25 patients with stage IIIB, locally advanced breast cancer in terms of response rate and survival benefit. Most of these patients were treated with an anthracycline-based regimen such as CAF and EC, and some were also treated sequentially with docetaxel. An overall objective response was observed in 15 patients (60%), composed of 1 patient (4%) with a complete response (CR) and 14 (56%) with a partial response (PR). No progressive disease was observed. Following neoadjuvant chemotherapy, locoregional treatment (mastectomy without partial resection) was carried out in 24 patients, 1 of whom also received radiotherapy. The rate of local recurrence in neoadjuvant chemotherapy with anthracycline-based regimens was lower than those of adjuvant chemotherapy with anthracycline-based and non-anthracycline-based regimens (10.0% versus 33.3% and 28.5%, respectively). By contrast, the rate of distant metastasis with neoadjuvant chemotherapy was higher than that seen with anthracycline-based adjuvant chemotherapy regimens (35.0% versus 11.1%, respectively), while the rate of distant metastasis in non-anthracycline-based regimens was even higher at 66.6%. The 5-year survival in the responders treated with neoadjuvant chemotherapy was better than in the non-responders (90.9% versus 50.0%; NS, P=0.28, log-rank test). The survival at 5 years in the patients treated with neoadjuvant chemotherapy was inferior to that with adjuvant anthracycline-based chemotherapy regimens (69.7% versus 77.8%), although the survival in neoadjuvant chemotherapy was better than those of non-anthracycline-based adjuvant regimen (69.7% versus 66.7%). However, at 10 years the overall survival with anthracycline-based neoadjuvant chemotherapy regimens was superior to that seen with either anthracycline or non-anthracycline-based adjuvant chemotherapy regimens. These results suggest that primary (neoadjuvant) systemic therapy with anthracycline-based regimens for locally advanced, stage IIIB, breast cancer may have a potential survival benefit when given in combination with adjuvant chemotherapy, as it will provide the best means of decreasing both local recurrence and distant metastasis.

Adult↗

PubMed2004

[Telomerase activity in gastrointestinal, bladder and breast carcinomas and their clinical applications].

Telomere ends are known to be shortened at every division of the cells. Telomerase is a ribonucleoprotein which compensate for the telomere ends and indispensable for the immortalization of the cells. It is reported that the enzyme is activated in a variety of cancer cells. In the present report, the enzyme was activated in more than 70% of gastrointestinal, bladder and breast cancer by TRAP assay. Moreover, in order to elucidate whether the enzyme activity is useful for the non-invasive detection of exfoliated cancer cells in the colon bowel washings, urine and fine needle aspirate of the breast tumors, TRAP assay was performed. In most of the cases, the positive findings were observed which support that the enzyme activity is useful for the clinical application. The expression of mRNA and protein for hTERT was detected in cancer cells, however, the assay contains the pitfall including the Taq inhibitor or telomerase inhibitor. Moreover, the activity is also detected although it is weak, in the benign or premalignant lesions. Further analysis is required for the clinical application of the method.

Adult↗