Search PubMed⌕ Search

Biomedical subjects

Masaki Kitajima

Publications and source records attributed to Masaki Kitajima.

At least 127 records · Page 7Linked to original sources
PubMed2004

Differences between scirrhous and non-scirrhous human gastric carcinomas from the aspect of proMMP-2 activation regulated by TIMP-3.

Gastric carcinomas can be classified into scirrhous carcinomas (SC), i.e. 'linitis plastica' or Borrmann 4 gastric cancer, and non-scirrhous carcinomas (NSC). SC are characterized by diffuse invasive growth patterns with marked fibrosis, frequent peritoneal dissemination and lymph-node metastases and poor prognosis, while NSC show medullary growth patterns and common hematogenous metastases. To study the differences in local expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between SC and NSC, we examined the expression of MMPs and TIMPs in human gastric carcinoma tissues by several methods including sandwich-enzyme immunoassay systems, gelatin zymography, reverse transcriptase-polymerase chain reaction (RT-PCR), real-time quantitative PCR, immunoblotting, immunohistochemistry and in situ zymography. Of the seven MMPs and two TIMPs tested, only proMMP-2 levels were remarkably higher in SC than in NSC (P < 0.01), and proMMP-2 activation ratio was significantly lower in SC than in NSC (P < 0.05). TIMP-3 mRNA levels were remarkably about 2-fold higher in SC than in NSC tissues (P < 0.01). TIMP-3 production in SC was confirmed by immunoblotting and TIMP-3 was immunolocalized to stromal fibroblasts in SC. TIMP-3 mRNA levels inversely correlated with proMMP-2 activation ratios, although the expression levels of MT1-MMP and MT2-MMP were not different in SC and NSC. By in situ zymography, gelatinolytic activity appeared to be weaker in SC than in NSC. All these data suggest that proMMP-2 activation is down-regulated by TIMP-3 expressed in scirrhous gastric carcinomas. Our findings may explain the differences in clinical behaviors of SC and NSC.

Adenocarcinoma, Scirrhous↗
PubMed2004

Lymphatic mapping for upper gastrointestinal malignancies.

Recent studies on lymphatic mapping of upper gastrointestinal (GI) malignancies have provided new insights with regard to the sentinel node (SN) concept in solid tumors. At present, the SN concept seems to be valid not only for breast cancer, but also for esophageal and gastric cancers, which have multidirectional and complicated lymphatic flows. In addition to the staging merits, individualized surgical management has been proposed for upper GI cancer based on the SN concept. Gastric cancer is now a suitable target of SN-guided surgery after breast cancer because of its anatomical situation. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Because SNs in esophageal cancer are multiple and widespread, complete sampling of SNs is not a minimally invasive procedure, as it is in breast cancer. However, selective and modified lymphadenectomy targeting SNs for clinically N0 esophageal cancer instead of three-field lymph node dissection should become not only feasible but also clinically important. When performing chemoradiotherapy as curative treatment for cT1N0 esophageal cancer, lymphoscintigrams revealing the distribution of SNs in each individual case are useful to tailor the field of irradiation to control occult micrometastases. Although there are several issues to be resolved, this novel procedure has the potential to improve quality control in upper GI cancer.

Esophageal Neoplasms↗
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

The influence of platelets on the promotion of invasion by tumor cells and inhibition by antiplatelet agents.

OBJECTIVE: Using a chemoinvasion assay, we show that platelets promote invasiveness of 5 pancreatic adenocarcinoma cell lines. METHODS: Gelatin zymography and Western blot analysis were performed to detect metalloproteinase-9 (MMP-9) secreted from tumor cells in the presence or absence of platelets. The effects of antiplatelet agents on the invasiveness of tumor cells and the secretion level of MMP-9 were evaluated. RESULTS: The number of traversed tumor cells significantly increased when incubated with platelets compared without platelets in all cell lines. The MMP-9 band was detected in all tumor cell lines, and the intensity was obviously greater in conditions of incubation with platelets than without. In the experiment of antiplatelet agents effects, it was confirmed that invasiveness of tumor cells significantly decreased following incubation with cilostazol depending on the concentration in spite of the presence of platelets. The level of MMP-9 also significantly decreased in the ELISA analysis. CONCLUSIONS: These data mean platelets activate invasiveness of tumor cells because of enhanced MMP-9 secretion. Furthermore, anti-platelet drugs may inhibit invasiveness of tumor cells due to decreased MMP-9 secretion, and this inhibition may lead to the suppression of tumor cell invasion. We propose that antiplatelet agents are applicable in clinical treatment to inhibit metastasis of malignant tumor cells.

Adenocarcinoma↗
PubMed2004

Squamous cell carcinoma of the liver originating from non-parasitic cysts after a 15 year follow-up.

Squamous cell carcinoma is an extremely rare primary liver tumour. A 42-year-old man presented at our hospital on 19 February 1986, with pain in the right upper quadrant of the abdomen and general fatigue, and reported an 8 year history of this complaint. Ultrasonography showed four cystic masses in the liver with a maximum diameter of 15 cm, one of which contained a solid component. A computed tomography (CT) scan confirmed a huge, predominantly cystic, mass in the liver with a small solid component and irregular wall. Calcifications were seen in the solid components. On 22 April 1986, a laparotomy was performed but the masses were too large to be removed. During 15 years of follow-up after the laparotomy, there had been no change seen in his abdominal CT scan. He subsequently arrived at our hospital again on 10 July 2001 with loss of appetite and of body weight. A CT scan showed a cyst in the liver of 25 cm in diameter with calcification that had a large solid part invading the liver. A post-mortem pathological dissection showed multiple cysts, the largest of which was 25 cm in diameter. They had large solid parts with calcification invading the liver. There were widespread metastatic lesions. Microscopic examination showed the tumour to be a well differentiated squamous cell carcinoma. To the best of our knowledge, this is the first report of a squamous cell carcinoma arising from 15 multiple non-parasitic hepatic cysts after a 15 year follow-up. Furthermore, 23 years had passed since the patient's symptoms appeared for the first time.

Adult↗
PubMed2004

Docetaxel enhances the cytotoxicity of cisplatin to gastric cancer cells by modification of intracellular platinum metabolism.

We have examined the combined anticancer effects of docetaxel (DOC) and cisplatin (CDDP) in vitro using the gastric cancer cell lines MKN-45, MKN-74, and TMK-1. Treatment of the cell lines with 30 microg/ml of DOC for 24 h followed by incubation with 3 or 10 microg/ml of CDDP for 24 h showed a clear synergistic effect. Sequence dependency of the agents was observed in these cell lines: DOC followed by CDDP (DC) showed a stronger antitumor effect than CDDP followed by DOC (CD) in all cell lines. To clarify the mechanism of action of the DC combination, total intracellular platinum (Pt) levels were evaluated after treatment with CDDP alone or combined with DC. For the MKN-45 and -74 cell lines, cells treated with DOC (10 microg/ml for 12 h) and then CDDP showed significantly increased intracellular Pt accumulation compared to cells treated with CDDP alone. We also investigated alterations in intracellular glutathione (GSH) concentration in response to DOC and CDDP. MKN-45 and -74 cells pretreated with DOC (10 microg/ml for 12 h) showed significantly increased intracellular GSH levels compared to cells administered CDDP only. To explain these findings, messenger RNA (mRNA) levels for multidrug resistance-associated protein-1 (MRP-1), the ATP-dependent pump for Pt-GSH complexes, were quantified in CDDP-treated MKN-45 cells with and without DOC pretreatment. While CDDP administration increased MRP-1 mRNA expression in MKN-45 cells, MRP-1 was not up-regulated after CDDP administration in DOC pretreated MKN-45 cells. Our results suggested that the enhanced CDDP toxicity due to DOC pretreatment may be related to the accumulation of intracellular Pt-GSH complexes, because DOC appears to suppress the MRP-1 up-regulation induced by CDDP exposure in gastric cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

[Adjuvant chemotherapy for breast cancer--a current controversy].

EBCTCG meta-analysis revealed a significant reduction in mortality in patients receiving chemotherapy irrespective of nodal status and ER status. Compared with CMF, 5-year RFS and OS favored the anthracycline-containing regimens, 57% vs 54% (p = 0.006) and 72% vs 69% (p = 0.02), respectively. No survival benefit was obtained for CMF durations greater than 6 months. Delaying radiation therapy for several months after breast-conserving surgery until the completion of adjuvant chemotherapy appears safe and may be preferable for patients at high risk of distant metastasis. No difference in disease-free survival for the 3 dose levels of doxorubicin (60, 75, and 90 mg/m2) was found. Higher doses (100 mg/m2) of epirubicin led to a high survival rate in women with poor-prognosis disease. Dose-dense therapy seems promising but still needs further investigation. Incorporation of taxanes into adjuvant chemotherapy for early breast cancer is also controversial.

Anthracyclines↗
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↗
PubMed2004

[Usefulness of weekly administration of paclitaxel for advanced or recurrent gastric cancer].

We report herein the efficacy and feasibility of weekly administration of paclitaxel for advanced/recurrent gastric cancer retrospectively. Eleven patients with advanced or recurrent gastric cancer who had received prior chemotherapy were treated with this regimen. Seventy mg of paclitaxel per m2 dissolved in 250 ml 5% glucose was administered by 1-hour intravenous infusion once a week for 3 weeks followed by 1 week rest. To avoid hypersensitivity reactions, the following short premedication was given to all the patients 1 hour before paclitaxel treatment: Dexamethasone 20 mg intravenously (i.v.), diphenhydramine 50 mg i.v., and ranitidine 50 mg i.v. Treatment cycle was 1 to 23 with an average cycle of 5.4. The response rate was 33% (2/6 with measurable lesions), the median time to progression was 104 days, and the median survival time was 160 days. Grade 3 neutropenia occurred in 27.2% of the patients. Weekly paclitaxel may be a promising regimen as a second-line chemotherapy for advanced/recurrent gastric cancer. However, special attention needs to be paid to the neutropenic adverse effect in gastric cancer patients with poor performance status than 2 (greater).

Adult↗
PubMed2004

Inhibition of DNA methyltransferase by antisense oligodeoxynucleotide modifies cell characteristics in gastric cancer cell lines.

DNA (cytosine-5-)-methyltransferase 1 (DNMT1) plays an important role in the maintenance of DNA methylation patterns via complicated networks including signaling pathways and transcriptional factors, relating to cell differentiation or carcinogenesis. In the present study, we designed an antisense oligodeoxynucleotide of DNMT1 (AS/MT: 5'-CGGTAC GCGCCGGCATCT-3') and demonstrated successful inhibition of DNMT1 expression by AS/MT at the protein level, using gastric cancer cell lines in vitro. E-cadherin protein expression was increased, and both cyclin D1 and PCNA were decreased by AS/MT treatment. AS/MT also induced suppression of cell growth as determined by BrDU uptake incorporation, in a dose-dependent manner, suggesting specificity of AS/MT. Simultaneously, morphological alterations were observed in both TMK-1 and MKN-45 cells after 24 h incubation with 2 micro M of AS/MT. The cells changed shape from their original forms to dispersed, fibroblast-like cells with neurite-like processes, accompanied by an increased adhesive potential of the cells. An in vivo model of peritoneal dissemination using the nude mouse system showed an increased malignant potential of AS/MT treated TMK-1 cells as demonstrated by a greater number of peritoneal tumor nodules in the AS/MT as compared to the NS/MT treated group, 34.8+/-4.3 vs. 22.4+/-3.0 nodules, respectively (p=0.0039). The total wet tumor weight in the AS/MT group (350+/-47.4 g) was significantly greater than that in the NS/MT group (248+/-41.5 g) (p=0.0065). In conclusion, the inhibition of DNA methylation by DNMT1 by an antisense oligodeoxynucleotide influences cell morphology and adhesion, as well as cell growth in gastric cancer cells in vitro. Moreover, these alterations in the characteristics of cancer cells resulted in an increased ability to attach onto the peritoneum in the nude mouse system in vivo, suggesting that strict clinical guidelines will be necessary to utilize such a DNA methylation inhibitor, since it does not always mean a therapeutic antitumor strategy.

Adenocarcinoma↗
PubMed2004

[Endoscopic treatment for gastroesophageal reflux disease].

The endoscopic treatment as a minimally invasive method to gastroesophageal reflux disease (GERD) came to be tried in addition to medication and laparoscopic antireflux surgery. Clinical trials, such as the Endoluminal Gastroplication method, the Full Thickness Plicator method, the Stretta method, the Enteryx method, and the Gatekeeper method, are advancing in the United States and Europe. It is necessary to consider the efficacy, safety, durability, cost effectiveness, an indication, etc. using data from a randomized controlled trial with sufficient observation period. If the usefulness of endoscopic treatment is confirmed in the future, the new minimally invasive strategy over GERD will be established.

Endoscopy, Digestive System↗
PubMed2004

[Current status of sentinel node adenectomy and future perspectives].

Sentinel node adenectomy has rapidly been accepted in recent years. A survey performed under the auspices of the Japanese Breast Cancer Society revealed that about 40% of institutions in Japan have already introduced sentinel lymph adenectomy. Analysis of questionnaire responses from 40 institutions in Japan revealed an identification rate using the dye method alone of 87% compared with 96% using the combined method. The identification rate and the false-negative rate are about the same among various methods used such as colloidal radiotracers, injection site, use of lymphoscintigraphy, etc., provided that the surgeon has adequate experience. It is recommended that the surgeon should start to perform sentinel node adenectomy after experiencing more than 60 cases, because there is a learning curve. Some investigators are devising other methods to replace the RI method, for example, using magnetic particles instead of RI colloid and detecting them using magnetic probes. and a trial to detect lymphatic flow with CT after local injection of contrast medium is also being conducted. Sentinel node adenectomy may become a standard technique for early breast cancer patients in the near future.

Breast Neoplasms↗
PubMed2004

[Liver regeneration after resection: molecular and cellular mechanism].

It has been well established that the liver can regenerate after resection. Liver regeneration is a fundamental mechanism by which the liver responds to injury. This review article discusses molecular and cellular mechanism of liver regeneration, including growth factors and cytokines in the initiation and regulation of liver regeneration, the importance of the liver extracellular matrix and its dynamic effect on hepatocyte growth, and finally, stem cell biology in liver regeneration.

Animals↗