Search PubMed⌕ Search

Biomedical subjects

Hirotoshi Hasegawa

Publications and source records attributed to Hirotoshi Hasegawa.

At least 19 recordsLinked to original sources
PubMed2005

TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis.

A number of receptor tyrosine kinases (RTKs) are involved in angiogenesis. TSU-68 (SU-6668) was developed as an inhibitor of RTKs involved in VEGF, bFGF and PDGF signaling, which then inhibits endothelial cell proliferation. We investigated the antitumor effects of TSU-68 against human colon cancer xenografts in male SCID mice and its anti-angiogenic activity using a dorsal air-sac (DAS) assay. TSU-68 was administered orally at a dose of 200 mg/kg twice daily. Mice bearing human colon carcinoma, HT-29, or WiDr xenografts were treated for 16 days. To determine the effect on hepatic metastasis, cell suspensions of HT-29 or WAV-I were injected into the spleen of mice on day 0, and mice treated for 28 days starting from day 1. For the DAS assay, HT-29, WiDr or WAV-I cells suspended in PBS at 2 x 10(7) cells/Millipore chamber were implanted subcutaneously into SCID mice, which were then treated from day 0 to 5, On day 6, the anti-angiogenic effects were assessed. Results indicated that TSU-68 significantly inhibited the growth of subcutaneous tumors. In the hepatic metastasis model, liver weights of the TSU-68-treated group were significantly reduced, compared to those of control mice. In the DAS assay, the angiogenic indices of the treated groups were significantly decreased for HT-29, WiDr and WAV-I tumors, with T/C ratios of 13.4, 50 and 35.3%, respectively. As TSU-68 significantly inhibited tumor growth and liver metastasis formation of human colon cancer xenografts, probably through anti-angiogenic activity, this agent may be useful for the treatment of colon cancer.

Administration, Oral↗
PubMed2005

[A case of colorectal cancer effectively treated with UFT/LV].

5-FU/LV therapy has been standard chemotherapy for advanced and recurrent colorectal cancer. Several studies reported that a new alternative chemotherapy, UFT/LV, had anti-cancer effects the same as with conventional 5-FU/LV therapy. We report a patient who had advanced and recurrent colorectal cancer treated with UFT/ LV. This 70-year-old male was admitted to our hospital because of a right lower abdominal mass, which was diagnosed as a peritoneal recurrence of transverse colon cancer by abdominal CT. UFT/LV therapy was started on an outpatient basis. After one course of chemotherapy, the intra-abdominal mass disappeared, and this therapy was continued for three courses. He did not suffer from any adverse effect during chemotherapy. Although this therapy was resumed because of the recurrence at the same site after nine months, it was refractory to chemotherapy. Thereafter, surgical resection was performed, and it was diagnosed as lymph node metastasis of previous surgery.

Adenocarcinoma↗
PubMed2004

Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer.

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.

Esophageal Neoplasms↗
PubMed2004

A clinical overview of familial adenomatous polyposis derived from the database of the Polyposis Registry of Japan.

The clinical situation of familial adenomatous polyposis (FAP) in Japan has changed in the period since the last analysis of data of the Japanese Polyposis Center. To reevaluate our data and elucidate the changes we analyzed the records of the 1390 FAP patients in 900 families registered with the Polyposis Committee of the Japanese Society for Cancer of the Colon and Rectum. In the 13-year period 1990-2003, clinical differences between men and women with FAP diminished. The postoperative prognosis was substantially better in patients without advanced colorectal cancer (stage > or = T2) than in those with early cancer or no cancer. Mean age at death improved from 42.5 years in the period before 1990 to 46.0 years, and it was a result of a decreased proportion of deaths from colorectal cancer. The distribution of colorectal cancer in FAP patients was similar to that in the general population. Desmoid tumors accounted for about 10% of deaths in the recent 13 years (1990-2003). The cumulative risk of rectal cancer in the preserved rectum was 12% at 10 years and 23% at 15 years. The registry system in Japan revealed a new clinical situation in FAP patients, and the findings of this study will be useful to improve the prognosis of patients with FAP.

Adenoma↗
PubMed2004

[Current status on laparoscopic surgery for colorectal cancer].

The current status of laparoscopic surgery and its indications for colorectal cancer are described. According to multi-institutional registry by the Japanese Society of Endoscopic Surgeons, the number of laparoscopic surgeries for advanced colorectal cancer has been increasing during the last couple years. The short- and long-term results of laparoscopic surgery for pT1 or pT2 colon cancer are favourable, and laparoscopic surgery could be a standard procedure for such cases. However, the indications for pT3/T4 cancer remain controversial due to limited length of follow-up. A multi-centre randomised controlled trial (RCT) comparing open with laparoscopic surgery for advanced (T3/T4) cancer is to start in autumn this year. Laparoscopic surgery for such cases should be confined to trial cases. Laparoscopic surgery for rectal cancer is feasible; however, it is associated with higher anastomotic leak rates. Issues on education and medical costs need to be resolved.

Colonic Neoplasms↗
PubMed2003

Chemosensitivity testing--present and future in Japan.

Radical surgery with extended lymph node dissection is the first and only curative treatment of gastrointestinal cancer. Although the combined cancer chemotherapy has achieved 30%-50% response rates, a controversy still remains over the significance of the adjuvant cancer chemotherapy after surgery. To break through this limitation, we have introduced the chemosensitivity test to evaluate the appropriate adjuvant cancer chemotherapy for advanced gastrointestinal cancer. Our plural studies indicated that the chemosensitivity test would be useful in evaluating the appropriated adjuvant chemotherapy by increasing survival in the sensitive group. Recently, the molecular targets have been clarified for the conventionally available antitumor agents, e.g., thymidylate synthetase for 5-fluorouracil, ATP-binding cassette transporters for anthracyclines, glutathione-related detoxification for platins, and topoisomerase I for CPT-11, which will be applied for dinical use in evaluating the appropriate cancer chemotherapy. The chemosensitivity test is approved as "advanced clinical medicine" by the Japanese Ministry of Health, Welfare, and Labor in five institutes at present. Because complete dissection and chemosensitivity test-guided adjuvant chemotherapy will result in a survival benefit for patients with advanced gastrointestinal cancer, this test should be approved as "social insurance" for further wide clinical application.

Antineoplastic Agents↗
PubMed2003

Diffuse cavernous hemangioma of the rectum: report of a case.

Cavernous hemangioma of the rectum (CHR) is an uncommon benign vascular lesion, which mainly affects young adults. The rectosigmoid area is the most common site of cavernous hemangioma in the gastrointestinal tract. CHR is often misdiagnosed due to a lack of knowledge of the clinical features. We report a case of CHR, focusing on the clinical features, diagnostic procedures used, and treatments given. This patient was finally treated effectively with abdominoperineal resection. Thorough preoperative imaging is necessary to confirm the diagnosis and evaluate both the site and extent of the hemangioma. Magnetic resonance imaging (MRI) provides information about the dimensions of the tumor and involvement of the adjacent structures with its high resolution and multiplanar capability, without the use of contrast medium. Moreover, endorectal surface coil MRI depicts the five separate layers of the bowel wall and internal and external sphincter more clearly than the conventional body coil MRI.

Female↗
PubMed2003

Short-term surgical outcomes of laparoscopic colonic surgery in octogenarians: a matched case-control study.

This study was undertaken to evaluate the short-term surgical outcomes of laparoscopic surgery for colonic carcinoma in octogenarians and compare them with those for a younger group of patients who underwent the same surgical procedures. This matched case-control study involved 17 octogenarian patients with colonic carcinoma who underwent laparoscopic surgery between 1996 and 2001. The results were compared with those for 34 matched patients aged 60 years or less who underwent the same surgical procedures during the same period. Both groups were well matched for clinical characteristics. However, the American Society of Anesthesiology status was significantly higher in the octogenarian group (P = 0.001). There were no significant differences between the two groups in terms of the incidence of complications, the interval before resumption of liquid or solid food intake, or length of hospitalization. There were no deaths in either group. Advanced age should not be regarded as a contraindication for laparoscopic colonic surgery.

Adult↗
PubMed2003

Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray.

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cyclooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer.

Antineoplastic Agents↗
PubMed2003

Gene expression in colorectal cancer and in vitro chemosensitivity to 5-fluorouracil: a study of 88 surgical specimens.

To predict the sensitivity of colorectal cancer to 5-fluorouracil (5-FU), we compared the gene expression of surgically obtained colorectal cancer specimens with chemosensitivity to 5-FU as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Eighty-eight patients with advanced and/or metastatic colorectal cancer provided written informed consent and entered the trial from September 2000 to October 2001. Fresh surgical specimens were used for the MTT assay, and sensitivity to 5-FU was evaluated at a cutoff concentration of 50 microg/ml and 48-h incubation time. Frozen samples were stored at - 80 degrees C until mRNA analysis of thymidylate synthetase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), es-nucleoside transporter (NT), and E2F1 by real-time RT-PCR. The correlations between the variables were analyzed, and the predictive value of these mRNAs was assessed statistically using a receiver operating characteristic (ROC) curve. NT and DPD, TP and DPD, and TP and NT mRNA expression levels correlated significantly, while TS and E2F1 showed no correlations. High NT expression was associated with low sensitivity to 5-FU (P < 0.013), as were high DPD and E2F1 expression (P < 0.022 for both). High TP mRNA expression correlated with low sensitivity to 5-FU (P < 0.034), although high TS mRNA expression did not. ROC curves indicated that DPD and NT mRNAs were possible predictors of sensitivity to 5-FU, with cutoff values of 0.6 and 0.4, respectively. The sensitivity of colorectal cancer to 5-FU may be regulated by DPD, the rate-limiting enzyme of catabolism, and NT, an important transmembrane transporter of nucleosides.

Antimetabolites, Antineoplastic↗
PubMed2002

Significance of transforming growth factor beta1 as a new tumor marker for colorectal cancer.

Transforming growth factor beta1 (TGF-beta1) is thought to be involved in cancer growth and progression. TGF-beta1 changes to its active form after being secreted in its latent form. Our aim was to clarify the significance of plasma concentrations of active and total TGF-beta1 of patients with colorectal cancer. Plasma concentrations of active and total TGF-beta1 in 45 patients with colorectal cancer and 23 healthy volunteers were measured using ELISA and the activation rate (ratio of active to total TGF-beta1) was determined. Plasma concentrations of active TGF-beta1 (21.9 +/- 12.8 pg/ml) were significantly higher in patients with colorectal cancer than in healthy volunteers (9.9 +/- 5.9 pg/ml; p < 0.001, Welch's t-test). Concentration of total TGF-beta1 was also significantly higher for patients with colorectal cancer (18.0 +/- 13.0 ng/ml vs. 11.1 +/- 6.4 ng/ml; p < 0.01, Welch's t-test). However, there was no significant difference in the TGF-beta1 activation rate between the 2 groups. There was a correlation between Dukes' stage and plasma concentration of active or total TGF-beta1 (p < 0.01, Spearman's rank correlation test) and on day 7 the active TGF-beta1 levels for patients recovering from curative resection were similar to those of the control group of healthy volunteers. These results suggest that active TGF-beta1 might be used as a tumor marker for colorectal cancer.

Adenocarcinoma↗
PubMed2002

Serrated adenoma developing into advanced colon cancer in 2 years.

We report the case of a 76-year-old woman with a flat elevated lesion (laterally spreading tumor; LST) in the transverse colon that had been identified 2 years before the current presentation. Pathologically, the lesion had been diagnosed as a serrated adenoma with severe dysplasia. The patient had refused endoscopic resection because she was afraid of the risk of colonic perforation; she did not come to follow-up until 2 years after the diagnosis, when she had advanced colon cancer in the transverse colon where the LST had been detected. Histopathological examination confirmed a poorly differentiated adenocarcinoma with no adenomatous component such as had been found in the LST lesion.

Adenocarcinoma↗
PubMed2002

Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer.

PURPOSE: Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer. METHODS: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome. RESULTS: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002). CONCLUSION: Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.

Aged↗
PubMed2002

Successful application of laparoscopic surgery to the treatment of Crohn's disease with fistulas.

PURPOSE: The role of laparoscopic surgery in patients with Crohn's disease remains to be defined, although increasingly difficult cases are being treated using minimally invasive techniques. We examined technical feasibility in 20 patients with Crohn's disease associated with fistulas. METHODS: Laparoscopic surgery was attempted in 37 patients with stricturing ileal disease or ileocolonic Crohn's disease from 1994 to 2000 after failure of strict nutritional therapy. Twenty of these patients with a total of 31 intestinal fistulas (14 ileoileal, 6 ileocolonic, 5 ileorectal, 2 ileovesical, 2 ileocutaneous, 1 gastrocolic, and 1 ileoduodenal) underwent 25 operations. Fistulas were divided intracorporeally, except for ileoileal fistulas. Fifteen patients underwent ileocecal resection; six underwent strictureplasty; six underwent partial resection of the small intestine; three underwent segmental colonic resection; and one underwent resection of anastomotic recurrence. Median follow-up was 48 (range, 5-77) months. RESULTS: Oral intake was started a median of 1 (range, 1-9) day after operation, and patients were discharged a median of 8 (range, 6-21) days after surgery. Four complications were observed in 25 operations (16 percent), including 1 intestinal obstruction/ileus, 2 wound infections, and 1 intra-abdominal abscess. There were no intraoperative or postoperative deaths. Four of the 5 operations were converted to open surgery (16 percent). Three of the 5 patients (60 percent) who required reoperation for anastomotic recurrence underwent repeated laparoscopic surgery using the same small incision. CONCLUSION: Laparoscopic treatment for Crohn's disease complicated by fistulas is feasible without high complication or conversion rates. Recurrent disease requiring reoperation can also be successfully treated using laparoscopic methods.

Adult↗
PubMed2002

Sentinel node mapping for colorectal cancer with radioactive tracer.

PURPOSE: The aim of this study was to test the feasibility and accuracy of radioactivity-guided mapping of the first lymph nodes found in draining the primary tumor site for colorectal cancer. METHODS: We enrolled 56 consecutive patients with preoperative diagnosis of curatively resectable colorectal cancer. Endoscopic injection of technetium Tc 99m-labeled tin colloid (15 MBq) was performed preoperatively, and radioactive sentinel nodes were identified intraoperatively with a gamma probe. Standard radical resection with lymph node dissection was performed in all patients, and all resected nodes were evaluated by routine histopathologic examination. RESULTS: Radioactivity-guided methods were used to detect sentinel nodes in 51 (91 percent) of 56 patients. The number of lymph nodes resected was 23.9 +/- 15.2 per case. The number of sentinel nodes was 3.5 +/- 2.1 (range, 0-8) per case. In 18 of 22 patients with lymph node metastasis, the sentinel node was positive. The incidence of metastasis in the sentinel node (22 percent) was significantly higher than that in nonsentinel nodes (3 percent, P < 0.01). Diagnostic accuracy according to sentinel node status was 92 percent (47/51). Four false-negative cases in this study were advanced cases with T3 primary tumors. The detection rate and diagnostic accuracy for patients with T1 or T2 primary tumors (29 cases) were 100 percent each. CONCLUSION: Intraoperative radioactivity-guided sentinel node mapping was accurate for patients with colorectal cancer with T1 or T2 tumors. The results suggest that sentinel node mapping and intraoperative biopsy may be a sensitive and specific diagnostic method for detecting metastasis in regional lymph nodes in patients with colorectal cancer.

Adult↗
PubMed2002

Prospective evaluation of laparoscopic surgery for rectosigmoidal and rectal carcinoma.

PURPOSE: This study was designed to examine the short-term results of laparoscopy in the treatment of curative cases of rectosigmoidal and rectal carcinoma. METHODS: A review was performed of a prospective registry of 70 patients who underwent curative laparoscopic resection for rectosigmoidal and rectal carcinoma between July 1993 and April 2001. Before 1997, only patients with early (Tis or T1) cancers located in the rectosigmoid and upper rectum that required bowel resection were candidates for laparoscopy. In 1997, we expanded the application of laparoscopy to include T2 cancers located anywhere in the rectum. Mesorectal transection was performed at least 5 cm below the tumor for rectosigmoidal and upper rectal lesions, and total mesorectal excision was performed for lower tumors. Primary anastomosis was performed by a double-stapling technique, or a handsewn coloanal anastomosis was performed. Patient demographics and outcomes were recorded prospectively. RESULTS: The median follow-up was 23 months. An anastomosis was performed in 92.9 percent of the operations. Oral intake was started on median postoperative Day 1, and the median length of hospitalization was 8 days. Two patients needed conversion to conventional open surgery. A total of 15 postoperative complications occurred in 13 patients (18.6 percent), including anastomotic leakage in 6 (8.6 percent) and bowel obstruction in 3 (4.3 percent). Reoperation was required in six patients. Two patients developed recurrence of cancer at the anastomotic site. The expected 5-year survival and disease-free survival rates were 100 and 92.1 percent, respectively. CONCLUSION: The findings of the present study demonstrate the feasibility and safety of laparoscopic surgery for selected patients with rectal carcinoma. Morbidity and mortality rates and oncologic outcome appear to be comparable with conventional surgery.

Adult↗