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Biomedical subjects

Shuji Takiguchi

Publications and source records attributed to Shuji Takiguchi.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Cases of postoperative hepatic metastasis from gastric cancer in which hepatic arterial infusion chemotherapy with 5-FU, adriamycin and cisplatin was performed after TS-1 chemotherapy].

The prognosis of patients with hepatic metastasis of gastric cancer is poor, and standard therapies for patients are not established. Here we present two cases of hepatic metastasis from gastric cancer. In both cases, no other organ metastasis except the liver was confirmed, in which hepatic arterial infusion chemotherapy with 5-FU, adriamycin and cisplatin (FAP) were performed because TS-1 chemotherapy was not an effective chemotherapy. Case 1: An 80-year-old man had distal gastrectomy for type 2 gastric cancer (Stage II) in January 2001. A liver S8 metastatic recurrence was discovered in the 18th month post operation. After chemotherapy with TS-1 for 5 courses, a hepatic arterial infusion treatment was performed for 7 courses. The effect was PR, but the treatment was canceled because of a catheter obstruction. The patient is living without recurrence. Case 2: This case was a 73-year-old man who had distal gastrectomy for type 0 IIc gastric cancer (Stage IA) in May 1999. Multiple hepatic metastases recurred in the 32nd month post operation. After chemotherapy with TS-1 for 2 courses, a hepatic arterial infusion treatment was performed for 10 courses. The effect was CR, but a peritoneal recurrence was discovered, and a systemic chemotherapy was performed. The patient is living without recrudescence of hepatic metastasis. The hepatic arterial infusion chemotherapy with FAP was effective for gastric cancer patients with liver metastasis because TS-1 chemotherapy was not an effective chemotherapy. It is necessary to consider combined chemotherapy in addition to systemic chemotherapy.

Aged↗
PubMed2004

[Two cases of advanced and recurrent gastric cancer treated with the combination of chemotherapy and radiation].

Recently, new promising anti-tumor agents such as TS-1, taxanes, and CPT-11 have been approved for gastric cancer treatment. These agents showed a better response and may contribute to a patient's survival and quality of life. However, there are cases with advanced and recurrent gastric cancer that are resistive or tolerant to these agents. We report two cases in which the patients had suffered symptomatic local recurrence during the chemotherapy. Consequently, they had been treated with radiotherapy in order to improve their clinical status. We also discuss the significance of radiotherapy in gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Differential regulation of apoptosis in the corpus luteum of pregnancy and newly formed corpus luteum after parturition in rats.

Apoptosis contributes to luteal regression in many species. In the postpartum rat, there are two different types of corpora lutea (CL) in the ovary: CL of pregnancy (CLP) and newly formed CL (NCL). To investigate the regulation of apoptosis in the two different types of CL during luteal regression, apoptosis and caspase-3 activity were examined in the CL obtained on Days 7, 15, and 21 of pregnancy and Days 0, 1, 3, 5, 7, and 9 postpartum. Furthermore, the effect of lactation on apoptosis in the CL was examined in two groups of postpartum rats: lactating rats that nurse more than 10 pups, and nonlactating rats that nurse no pups. Apoptotic cells were detected after Day 21 of pregnancy. In the CLP, remarkable increases in the number of apoptotic cells on Days 5 and 9 postpartum were observed in nonlactating rats (P < 0.01), but not in lactating rats. Changes in caspase-3 activity in the CLP were not consistent with those in number of apoptotic cells. In the NCL, an increase in apoptosis was found only on Day 5 postpartum in nonlactating rats (P < 0.01), but not in lactating rats. Changes in caspase-3 activity in the NCL were consistent with those in number of apoptotic cells. In conclusion, apoptosis is, at least in part, involved in luteal regression after parturition, and lactation appears to inhibit apoptosis. This study also suggests the presence of a caspase-3-independent mechanism for apoptosis in CLP regression in the rat.

Animals↗
PubMed2003

Expression level of valosin-containing protein is strongly associated with progression and prognosis of gastric carcinoma.

PURPOSE: Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined. PATIENTS AND METHODS: VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. RESULTS: Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P <.0001), undifferentiated histologic subtype (P <.05), presence of vascular and lymphatic invasion (P <.0001 for both), presence of lymph node metastasis (P <.0001), deep tumor invasion (P <.0001), and poorer disease-free and overall survivals (P <.0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1; P <.01 and P <.05, respectively) and advanced (pT2-4; P <.05 for both) group of pathologic tumor-node-metastasis system classification. CONCLUSION: The prognostic significance of VCP expression level in GC was demonstrated.

Adenosine Triphosphatases↗
PubMed2003

Totally laparoscopic distal gastrectomy using the hand-sewn Billroth-I anastomotic technique: report of a case.

The development of more sophisticated instruments has enabled advanced laparoscopic surgery. We recently devised a totally laparoscopic method of performing Billroth-I hand-sewn anastomosis and established this technique in an animal training model. This report presents the case of a 50-year-old man in whom totally laparoscopic distal gastrectomy was successfully performed for gastric cancer, using the hand-sewn Billroth-I anastomotic technique. The patient was admitted with gastric cancer in the angle of the stomach and underwent laparoscopic distal gastrectomy with radical lymph node dissection. After the resected specimen was extracted through the small incision, a Billroth-I anastomosis was performed laparoscopically by the hand-sewn technique using the Albert-Leinbert method. The patient was discharged on the seventh postoperative day without any intra- or postoperative complications. Laparoscopic hand-sewn anastomosis was performed safely and allowed for quick recovery and good cosmesis in this patient.

Anastomosis, Surgical↗
PubMed2003

Experimental study to evaluate the usefulness of S-1 in a model of peritoneal dissemination of gastric cancer.

BACKGROUND: Favorable results have been reported for the novel oral anticancer agent S-1 (TS-1) in clinical studies of advanced gastric cancer with peritoneal dissemination. In the present study we assessed its pharmacokinetics, inhibitory effects, and effect on survival time in an animal model. METHODS: A model of peritoneal dissemination was created by intraperitoneally implanting 4-week-old female BALBc nu/nu mice with the human gastric cancer cell line MKN-45 after transfection with a fluorescent protein-expressing vector. Pharmacokinetics were investigated by measuring intratumor, peritoneal lining, and blood concentrations after the administration of S-1 and fluorouracil (5-FU). The effect of S-1 on survival time was also assessed, by administration once daily to seven animals per group, starting on day 7 after implantation, and survival time was compared with that of an untreated control group. The inhibitory effect of S-1 on peritoneal dissemination was evaluated by killing mice at the start of administration, and 1 and 3 weeks after the start of administration, and examining them for the presence of peritoneal dissemination under a fluorescence stereomicroscope. RESULTS: Maintenance of high 5-FU concentrations in the intraperitoneal tumors was confirmed in the S-1 group, and survival time was prolonged without any decrease in oral food intake or body weight. CONCLUSION: Assessment in a model of peritoneal dissemination of gastric cancer showed that the novel oral anticancer agent S-1 was effective against peritoneal dissemination, and that it improved the survival rate.

Animals↗
PubMed2003

Absence of beta-tubulin gene mutation in gastric carcinoma.

BACKGROUND: Effective chemotherapy for advanced gastric cancer is yet to be established. Taxanes, novel anticancer drugs which bind to beta-tubulin and prevent disruption of microtubules, are newly approved and promising agents for advanced and recurrent gastric cancer. To predict the chemoresistance to a taxan in gastric cancer, we examined the genetic mutations of the beta-tubulin gene. METHODS: Fifty pairs of gastric tumor and normal mucosa tissues were obtained from operations and the genomic DNA was extracted from each specimen. The four exons of the beta-tubulin gene were amplified for DNA mutations by single-strand conformation polymorphism (SSCP) methods and sequencing analysis. RESULTS: Nine (18%) of 50 patients with gastric cancer had two kinds of silent variations of the beta-tubulin gene in exon 4. Three kinds of intronic variations were detected in exons 1, 2, and 3. However, no genetic alterations that would change the beta-tubulin protein structure were detected in any of the 50 gastric tumors. CONCLUSION: Our findings indicate that mutations of the beta-tubulin gene, which might be a contraindication for chemotherapy based on taxans, were very rare events in gastric cancer.

Aged↗
PubMed2003

Endoscopic thyroid surgery through the axillo-bilateral-breast approach.

We developed a new endoscopic thyroid surgery by the axillo-bilateral-breast approach (ABBA) method, which is different from the previously described breast approach (BA) in that the port sites are modified to obtain a better view and to prevent the interference of surgical instruments. This modification also improves cosmetic results by eliminating the parasternal incision, which results in hypertrophic scar in a significant number of cases treated with BA. Twelve patients with benign thyroid tumors successfully underwent endoscopic thyroid surgery by ABBA, and their clinical outcomes were compared with those of four patients treated with BA. The mean operation time was significantly shorter in the ABBA group than in the BA group (188 minutes vs. 270 minutes; P < 0.01). Furthermore, the mean blood loss in the ABBA group (53 mL) was half of that in the BA group (108 mL). Neither conversion to open surgery nor significant intraoperative complications were experienced. The operative scars by ABBA became inconspicuous in a few weeks. These results seem to indicate that ABBA is a better method than BA and can be a feasible option, particularly for young patients who opt for the better cosmetic outcome.

Adenoma↗
PubMed2003

Prevention of peritoneal metastasis of human gastric cancer cells in nude mice by S-1, a novel oral derivative of 5-Fluorouracil.

OBJECTIVE: Recent clinical trials have suggested that oral administration of a new anti-cancer agent, S-1, seems a promising therapy for advanced gastric cancer. In this study, we assessed the efficacy of S-1 against peritoneal dissemination of gastric cancer in a newly developed animal model and investigated the efficacy of S-1 from a pharmacokinetic angle. METHODS: Human gastric cancer cells (MKN-45) were injected into the peritoneal cavity of nude mice. The cancer cells were transduced using an enhanced green fluorescent protein (EGFP)-expressing plasmid vector, enabling micrometastatic foci to be accurately assessed with a high level of detection sensitivity. To investigate pharmacokinetics, the concentration of 5-FU was determined in tumor, peritoneum and plasma. RESULTS: Fourteen and 21 days after intraperitoneal injection, a significant difference in the number of fluorescent foci was observed between the control group and the S-1 group (p = 0.02 and p = 0.0024, respectively. The therapeutic effect of S-1 was significantly greater than that of 5-FU. Furthermore, S-1 treatment greatly improved the survival time and cachexia. The area under the curve of 5-FU in tumor was higher than in the peritoneum and plasma. CONCLUSION: Oral S-1 is a promising chemotherapy for peritoneal dissemination of gastric cancer.

Administration, Oral↗
PubMed2003

Quantitative molecular diagnosis of peritoneal lavage fluid for prediction of peritoneal recurrence in gastric cancer.

We developed a quantitative multiple-marker RT-PCR assay for sensitive detection of free cancer cells in the peritoneal cavity and examined the significance of this molecular diagnostic technique for detection and prediction of peritoneal dissemination in patients with gastric cancer. Preoperative peritoneal lavage fluid samples obtained from 129 patients with gastric cancer were subjected to RT-PCR assay with primers specific for carcinoembryonic antigen (CEA) and cytokeratin-20 (CK-20), and conventional cytological examination with Papanicolaou staining. The multi-marker RT-PCR assay was positive in 59 of 129 (46%) gastric cancer patients, whereas conventional cytology was positive in only 9 of 129 (7%) patients. Thirty-two of 129 (22%) patients suffered disease recurrence after surgery. Twenty-one of these patients were confirmed to have had peritoneal recurrence. Although conventional cytology was positive on peritoneal washes in only 9 patients, the RT-PCR assay was positive in 20 of these 21 patients. Furthermore, in cases with negative cytology, patients with PCR-positive findings in peritoneal lavage fluid had a significantly poorer prognosis than those with negative PCR, mainly because of peritoneal recurrence. Our results suggest that the multiplex RT-PCR assay for CEA and CK-20 was highly sensitive for detection and might be useful for prediction of peritoneal dissemination in gastric cancer.

Ascitic Fluid↗
PubMed2003

[Two advanced gastric cancer patients who showed malignant ileus soon after administration of combination therapy of preoperative intra-peritoneal chemotherapy and gastrectomy].

Forty-eight patients with serosa-invaded advanced gastric cancer were administered to pre-operative intra-peritoneal chemotherapy to prevent peritoneal recurrence. There were no severe adverse effects from the intra-peritoneal chemotherapy. Of these patients, 2 showed malignant ileus shortly after intra-peritoneal chemotherapy and gastrectomy, and needed laparotomy because of dilatation of duodenum stump and liver dysfunction. The intestines and mesothelium showed diffuse thickness and hardness. We report the clinicopathological features of these cases and therapeutic limitation of intra-peritoneal chemotherapy.

Adenocarcinoma, Scirrhous↗
PubMed2003

[A case of multiple advanced esophageal carcinomas with abdominal LN metastases showing complete response after chemoradiotherapy with concurrent cisplatin, 5-FU and adriamycin chemotherapy].

We report the response of our new regimen of chemoradiotherapy for advanced esophageal carcinoma. The patient was a 66-year-old man who had double primary esophageal carcinomas: type o-IIc tumor of the cervical esophagus from the esophageal inlet to 23 cm from incisors and a 9 cm length type 3 tumor of the middle to lower thoracic esophagus with a 2 cm diameter cardiac lymph node metastasis. Since he completely rejected surgical treatment, new definitive chemoradiotherapy with 2 courses of FAP chemotherapy (cisplatin 50 mg/m2 and adriamycin 20 mg/m2 on day 1 and 5-FU 700 mg/day from day 1 to 5 continuously) concurrent with a split course of radiotherapy to a total dose of 60 Gy in 30 fractions was devised and administered. The treatment was completed and there was no severe toxicity except grade 3 leukocytopenia. Just after treatment, cervical tumor and cardiac lymph node reached complete response but stenosis and wall thickness remained in the thoracic tumor. Soon after, however, these findings improved and, at present 1 year later, complete response has continued. Our new regimen of chemoradiotherapy concurrent with FAP chemotherapy seems to be effective and promising for advanced esophageal carcinoma.

Aged↗
PubMed2002

Real-time rapid reverse transcriptase-polymerase chain reaction for intraoperative diagnosis of lymph node micrometastasis: clinical application for cervical lymph node dissection in esophageal cancers.

BACKGROUND: New molecular techniques have been designed to detect cancer micrometastases that are otherwise missed by conventional histologic examination. The aim of this study was to establish a sensitive and rapid genetic assay to detect lymph node micrometastasis and to assess its usefulness clinically for cervical lymphadenectomy in esophageal cancer. We have recently shown that metastasis in the lymph node chain along the recurrent laryngeal nerves (rec LNs) is a predictor of cervical node metastasis in esophageal cancer. In our retrospective study, the positive rate of cervical lymph node metastasis with rec LNs metastasis was 51.6%, and the rate without rec LNs metastasis was 11.6%. There was a significant difference in both positive rates (P =.0002). METHODS: Rec LNs obtained from 50 patients with esophageal cancer were assessed prospectively by intraoperative histopathologic examination (HE) and genetic analysis. The latter involved a real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) system with multiple markers, carcinoembryonic antigen, squamous cell carcinoma, and melanoma antigen-3, whose messenger RNAs are highly and frequently expressed in esophageal cancers. Cervical lymphadenectomy was subsequently performed in a subset of these patients. RESULTS: Ten of 50 patients (20%) were scored as node positive by HE, and 24 patients (48%) were scored positive by genetic diagnosis, including 9 HE-positive cases. Genetic diagnosis of rec LNs accurately predicted all 9 cases with cervical lymph node metastasis and 2 cases with cervical lymph node recurrence, whereas HE missed 2 cases with cervical lymph node metastasis and 2 cases with cervical lymph node recurrence. CONCLUSIONS: Our real-time rapid RT-PCR assay can improve the sensitivity of HE for detection of lymph node metastasis and might be potentially useful for intraoperative genetic diagnosis for subsequent cervical lymphadenectomy in esophageal cancer surgery.

Aged↗
PubMed2002

Different mechanisms for the induction of copper-zinc superoxide dismutase and manganese superoxide dismutase by progesterone in human endometrial stromal cells.

BACKGROUND: The present study was undertaken to investigate the cAMP-dependent regulation of copper-zinc superoxide dismutase (Cu,Zn-SOD) and manganese SOD (Mn-SOD) by ovarian steroids in human endometrial stromal cells (ESC). METHODS AND RESULTS: To examine the effect of cAMP on SOD expression, ESC were incubated with dibutyryl-cAMP (db-cAMP, 0.5 mmol/l), forskolin (25 micromol/l), or estradiol (E(2), 10(-8) mol/l) + medroxyprogesterone acetate (MPA, 10(-6) mol/l), for 18 days. E(2) + MPA significantly increased Cu,Zn-SOD activity and mRNA concentrations, whereas db-cAMP and forskolin had no effect. On the other hand, Mn-SOD activity and mRNA concentration were significantly increased by all of these treatments. Insulin-like growth factor-binding protein-1, a marker of decidualization, was clearly induced by db-cAMP, forskolin or E(2) + MPA, accompanied by morphological changes characteristic of decidualization. To study whether the increase in Mn-SOD by db-cAMP or E(2) + MPA was mediated by cAMP-dependent protein kinase A (PKA), ESC were incubated with protein kinase inhibitor (PKI) (10 microg/ml), an inhibitor of PKA, in the presence of db-cAMP or E(2) + MPA. The increase in Mn-SOD activity following db-cAMP or E(2) + MPA was completely inhibited by PKI. CONCLUSIONS: In the process of decidualization, E(2) + MPA increases Mn-SOD expression via a cAMP-dependent pathway. Cu,Zn-SOD is also up-regulated by E(2) + MPA, but via a different pathway from that involving cAMP.

Adult↗
PubMed2002

Differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase by progesterone withdrawal in human endometrial stromal cells.

The present study was undertaken to investigate the role of estrogen and progesterone in the expression of copper-zinc superoxide dismutase (Cu,Zn-SOD) and manganese SOD (Mn-SOD) in human endometrial stromal cells (ESC). ESC were incubated with estradiol (10(-8) mol/l), medroxyprogesterone acetate (MPA, 10(-6) mol/l), or estradiol + MPA for 18 days. MPA significantly increased Cu,Zn-SOD and Mn-SOD mRNA levels and enzyme activities as well as the mRNA level of insulin-like growth factor-binding protein-1 (IGFBP-1), a marker for decidualization. Estradiol only augmented the effects of MPA on Cu,Zn-SOD activity and IGFBP-1 mRNA level, and estradiol alone had no effect. To study the withdrawal of estrogen and progesterone (EP withdrawal), ESC that had been treated with estradiol + MPA for 12 days were washed and then incubated with or without estradiol + MPA for a further 11 days. Cu,Zn-SOD mRNA levels and activities declined after EP withdrawal, while they were gradually increased by the continuous treatment with estradiol + MPA. In contrast, Mn-SOD mRNA levels and activities were not affected by EP withdrawal. IGFBP-1 mRNA levels were significantly increased 4 days after EP withdrawal and decreased thereafter, whereas they were gradually increased by the continuous treatment with estradiol + MPA. In conclusion, Cu,Zn-SOD, Mn-SOD and IGFBP-1 are differently regulated by estrogen and progesterone in human ESC. The decrease in Cu,Zn-SOD after the ovarian steroid withdrawal may be involved in endometrial breakdown.

Cells, Cultured↗
PubMed2002

Nuclear factor-kappa B is required for tumor necrosis factor-alpha-induced manganese superoxide dismutase expression in human endometrial stromal cells.

We recently found that manganese superoxide dismutase (Mn-SOD) is up-regulated by TNF alpha at the transcription level in human endometrial stromal cells (ESC) and that TNF alpha-induced Mn-SOD expression is mediated by protein kinase C (PKC)-dependent phosphorylation. This study was undertaken to investigate whether nuclear factor-kappa B (NF-kappa B), a transcription factor, is involved in Mn-SOD induction by TNF alpha or PKC in human ESC. Electrophoretic mobility shift assay revealed that TNF alpha (1 ng/ml) and phorbol 12-myristate 13-acetate (TPA; 0.4 micro M), PKC activator, caused marked increases in nuclear NF-kappa B DNA binding activity. Secondly, ESC were incubated with MG132 (proteasome inhibitor) or SN50 (inhibitor of translocation of NF-kappa B into the nucleus) in the presence of TNF alpha or TPA. TNF alpha and TPA significantly increased Mn-SOD activities and Mn-SOD mRNA levels, and those effects were completely inhibited by MG132 and SN50. TNF alpha alone caused no effect on cell viability, but in the presence of MG132, TNF alpha significantly decreased cell viability. This inhibitory effect of MG132 was blocked by simultaneous addition of N-acetyl-L-cysteine, an antioxidant. In conclusion, the present study showed the involvement of NF-kappa B in Mn-SOD induction by TNF alpha or PKC in human ESC. This phenomenon could be a self-defense system of ESC against TNF alpha-mediated oxidative stress.

Antineoplastic Agents↗
PubMed2002

[The introduction of preoperative staging laparoscopy and molecular diagnosis of peritoneal lavages for the treatment of advanced gastric cancer].

In this study, intra-peritoneal chemotherapy was performed for advanced gastric cancer with serosal invasion. We assessed the efficacy of the chemotherapy using quantitative genetic diagnosis with peritoneal lavages collected before and after chemotherapy at staging laparoscopy and/or gastrectomy. Cases in which genetic diagnosis of peritoneal lavages showed negative results, or changed from positive to negative after chemotherapy, had a good prognosis. On the other hand, cases in which genetic diagnosis showed positive results after chemotherapy had worse prognosis. Intra-peritoneal chemotherapy may be indicated for patients with a positive genetic diagnosis only and cases becoming negative as a result of this therapy may have a better prognosis.

Antineoplastic Combined Chemotherapy Protocols↗