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Biomedical subjects

Masaki Kitajima

Publications and source records attributed to Masaki Kitajima.

At least 19 recordsLinked to original sources
PubMed2002

B7/CTLA4 pathway is essential for generating regulatory cells after intratracheal delivery of alloantigen in mice.

BACKGROUND: The mechanism of hyporesponsiveness induced by intratracheal (IT) delivery of alloantigen was examined and its effect on cardiac graft survival was assessed in studies in mice. METHODS: In CBA (H2 ) mice, donor splenocytes were given by IT delivery 7 days before transplantation of a C57BL/10 (H2 ) heart. To determine whether regulatory cells were involved in hyporesponsiveness, splenocytes from mice given IT delivery of alloantigen and antibodies for B7-1, B7-2, or CTLA4 were adoptively transferred to naïve secondary recipients 7 days after delivery; those recipients underwent heart transplantation the same day. Effects on cell proliferation and cytokine production of splenocytes from mice given IT delivery of alloantigen were examined in mixed leukocyte cultures (MLC). RESULTS: Cardiac graft survival was significantly prolonged in mice given IT delivery of alloantigen (median survival time [MST], 81 days); those given syngeneic splenocytes rejected grafts acutely (MST, 7 days; P<0.05). Adoptive transfer of splenocytes also significantly prolonged survival of cardiac grafts in secondary recipients (MST, 62 days). When B7-1, B7-2, or CTLA4 antibody was combined with IT delivery of alloantigen in the first recipient, all grafts were rejected within 14 days in second recipients after adoptive transfer. In mixed leukocyte cultures, splenocytes from these mice did not respond to alloantigen and production of interleukin-4 and interleukin-10 was increased. CONCLUSIONS: Donor splenocytes delivered IT induced hyporesponsiveness and regulatory cells in our animal model, and such induction was dependent on B7-1, B7-2, and CTLA4 signals.

Abatacept↗
PubMed2002

Intraportal infusion therapy as a novel approach to adult ABO-incompatible liver transplantation.

BACKGROUND: ABO-incompatible liver transplantation is associated with an extremely complicated postoperative course, especially when the recipients are adults. METHODS: Two adult patients underwent living-donor liver transplantation from ABO-incompatible donors. The antirejection therapy included multiple perioperative plasmapheresis, splenectomy, systemic triple immunosuppressive regimen with tacrolimus, methylprednisolone, and cyclophophamide, or azathioprine. In addition to these conventional approaches, we performed intraportal infusion therapy after transplantation with methylprednisolone, prostaglandin E1, and gabexate mesilate. RESULTS: With our protocol, antidonor blood group antibody titers in both cases remained low without any evidence of rejection or vascular complications throughout the postoperative course. Biliary complications were transient and resolved completely. The patients have now survived 30 and 12 months posttransplantation and have regained normal life activity with good liver function. CONCLUSIONS: Our experience has shown the feasibility of controlling rejection and other complications in adult ABO-incompatible liver transplantation under intraportal infusion therapy.

ABO Blood-Group System↗
PubMed2002

One-stage surgical management of concomitant abdominal aortic aneurysm and gastric or colorectal cancer.

One-stage surgical management of concomitant abdominal aortic aneurysm (AAA) and gastric or colorectal cancer should provide certain benefits. We reviewed the records of 21 patients with both AAA and gastric or colorectal cancer who underwent one-stage surgical management. Four had distal gastrectomy, 2 had total gastrectomy, and 5 had abdominoperineal rectal resection transperitoneally; 3 had total gastrectomy transperitoneally and AAA repair extraperitoneally. Two underwent right hemicolectomy and thromboexclusion of the AAA. Two had creation of a temporary ileostomy and implantation of an interposition graft. Two underwent left hemicolectomy, creation of a temporary transversostomy, and implantation of an interposition graft. One had a Hartmann's procedure and implantation of a bifurcated prosthetic interposition graft for AAA. There were no operative deaths or serious postoperative complications. One patient had colorectal ischemia that resolved with conservative treatment. Eighteen of the 21 patients (85.7%) were alive 10 months to 14 years postoperatively. In conclusion, one-stage surgical treatment of concomitant AAA and gastric or colorectal cancer is well tolerated and can avoid the time, financial costs, and patient anxiety involved in a second operation.

Aged↗
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

Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences.

Restriction landmark genomic scanning (RLGS) was utilized to identify novel genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples were examined by RLGS. Two high intensity spots were common to several RLGS profiles of different HCCs. Nucleotide sequencing and homology search analysis showed that these spots represented repetitive sequences, Human tandem repeat sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These intensified signals were attributable to the occurrence of demethylated areas in the recognition sequence of the NotI site of the corresponding fragments. The intensity of these spots in the RLGS profile reflects their degree of demethylation, which was significantly correlated with postoperative recurrence, even in patients regarded as belonging to the good prognosis group by conventional prognostic factors. Multivariate analysis showed that the intensities of the two spots retained independent prognostic value. This is a new type of predictive factor for HCC based on epigenetic changes in hepatocarcinogenesis, and in the future it is expected to be of great value in making preoperative diagnosis and selecting postoperative therapy.

Adult↗
PubMed2002

Gastrointestinal cancer and sentinel node navigation surgery.

In the twentieth century, lymph node dissection based on metastatic distribution has developed as the standard procedure for surgical management of gastrointestinal cancer [1]. The fear that invisible micrometastases might be present has encouraged aggressive resection with lymphadenectomy to control the disease. However, the prognostic benefits of extensive surgery are still unknown and the universal application of radical surgery may affect surgical morbidity, mortality, and quality of life after surgery, particularly in patients without lymphatic spread. In the twenty-first century, a novel technology to detect micrometastases without extensive surgical resection is required to establish an individualized surgical management approach to gastrointestinal cancer. Lymphatic mapping techniques are now used in the control of superficial malignancies, such as malignant melanoma and breast cancer, providing a novel tool that may also be of use for gastrointestinal cancers.

Esophageal Neoplasms↗
PubMed2002

The role of neoadjuvant chemotherapy for breast cancer treatment.

Neoadjuvant chemotherapy has become popular, especially for patients with advanced breast cancer. The pros and cons of neoadjuvant chemotherapy for treating breast cancer patients are reviewed. The advantages of neoadjuvant chemotherapy are 1) overall survival and recurrence-free survival rate are the same as post-operative chemotherapy, 2) serves as an in vivo sensitivity test, 3) increases the rate of breast conserving therapy, 4) facilitates the study of cancer biology. On the other hand, the disadvantages of neoadjuvant chemotherapy are 1) it modifies the stage, 2) treatment delay of PD cases, 3) residual intraductal component may be left behind after breast conserving surgery, 4) there are some cases of over-treatment. Combination chemotherapy is one possible way to increase the pathological CR rate, although the optimal order and cycles have not been determined. To avoid residual cancer cells after breast conserving surgery, the shrinkage pattern should be evaluated by MRI. Core needle biopsy should be performed before neoadjuvant chemotherapy to avoid over-treatment. It is essential to develop more effective regimens and stratify patients based on predictive factors.

Antineoplastic Agents↗
PubMed2002

UCN-01 (7-hydroxystaurosporine) inhibits the growth of human breast cancer xenografts through disruption of signal transduction.

BACKGROUND: 7-Hydroxystaurosporine (UCN-01), originally isolated as a phospholipid-dependent protein kinase C inhibitor, has been shown to have antitumor activity against several human cancer cell lines. UCN-01 inhibits cell cycle progression from the G1 to S phase by inhibition of cyclin-dependent kinase (CDK) activity and induction of intrinsic CDK inhibitor protein, leading to dephosphorylation of retinoblastoma (Rb) protein. MATERIALS AND METHODS: The antitumor activity of UCN-01 has been investigated against three human breast carcinoma strains serially transplanted into nude mice, including estrogen-dependent MCF-7, Br-10, and estrogen-independent MX-1. When the inoculated tumors started growing exponentially, UCN-01 (7.5 mg/kg) was administered intraperitoneally on five consecutive days a week for 2 weeks. The antitumor effect was evaluated as the lowest T/C ratio (%) during the experiments, where T was the relative mean tumor weight of the treated group and C was that of the control group. At the end of UCN-01 administration expression of p21, a protein of the CDK inhibitor family, and phosphorylated and dephosphorylated Rb protein was detected by Western blotting using treated and control tumors. RESULTS: UCN-01 had activity against MCF-7 and Br-10, with the lowest T/C ratios of 25.0% and 27.0%, respectively, while MX-1 was resistant to UCN-01 with a T/C ratio of 65.9%. The antitumor spectrum of UCN-01 was different from that of other conventional agents such as doxorubicin and cyclophosphamide which were ineffective against Br-10 but were active against MX-1. Although p21 was induced in three tested strains by UCN-01, little dephosphorylated Rb protein was expressed in MX-1 compared with Br-10 and MCF-7 (in vitro). CONCLUSION: UCN-01 appeared to be a promising agent for the treatment of breast cancer, with a different mode of action and antitumor spectrum from other currently available antitumor drugs.

Alkaloids↗
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

Rare case of early mucosal gastric cancer presenting with metastasis to the bulbar conjunctiva.

Early gastric cancer has an excellent outcome following surgical treatment. In particular, mucosal gastric cancer (m-cancer) very rarely results in metastatic dissemination and may be successfully treated by local surgical resection. We report a 64-year-old Japanese woman who presented with a recurrent cystic lesion on the left bulbar conjunctiva, with a biopsy specimen revealing metastatic signet-ring cell carcinoma. Gastrointestinal investigations revealed an early gastric cancer in the lesser curvature of the stomach. Biopsy specimen of the gastric lesion indicated poorly differentiated adenocarcinoma, which was identical to findings in the lesion in the bulbar conjunctiva. She underwent a distal gastrectomy and made an uneventful recovery. Histopathological analysis indicated a gastric signet-ring cell carcinoma that was limited to the mucosal layer, without evidence of lymphatic spread. Although the exact mechanism of metastatic dissemination to the bulbar conjunctiva is unclear, this case is very unusual, because ocular metastases almost invariably occur in the context of documented and established malignant disease. This is, to our knowledge, the first reported case of a patient with gastric mucosal cancer who presented with a conjunctival metastatic deposit and who subsequently received curative surgical treatment for both conditions.

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

Prognostic significance of laminin-5 gamma2 chain expression in colorectal carcinoma: immunohistochemical analysis of 103 cases.

PURPOSE: The laminin-5 gamma2 chain plays an important role in cell migration during tumor invasion and tissue remodeling. Although this chain has been reported to be expressed in tumor-stroma interface of colorectal carcinoma, prognostic significance of its expression has not been elucidated in these tumors, so we investigated the clinicopathologic significance of Laminin-5 gamma2 chain expression in colorectal carcinoma. METHODS: Laminin-5 gamma2 chain expression was investigated immunohistochemically in 103 colorectal carcinoma patients with Stage II, III, and IV disease. The patients were categorized into three groups according to the number of immunopositive tumor cells in the sections containing the maximum diameter of the tumor as follows: +, less than 20 tumor cells were positive; ++, 20 to 500 tumor cells were positive; +++, more than 500 tumor cells were positive. RESULTS: Laminin-5 gamma2 chain expression was observed in cytoplasm of tumor cells, especially those in the invasive front of the tumor penetration. Eighteen (17 percent) of tumors showed +, 60 (58 percent) showed ++, and 25 (24 percent) showed +++. The increased number of immunopositive tumor cells was significantly associated with synchronous liver metastasis (P = 0.048). The univariate (P = 0.036) and multivariate (P = 0.001) analysis of the patients' survival revealed that the prognosis became significantly poorer in patients with the increased number of immunopositive tumor cells. CONCLUSIONS: Increased laminin-5 gamma2 chain immunoreactivity, suggesting a high invasive potential of tumor cells, was a significant poor prognostic indicator for the patients with colorectal carcinoma.

Adenocarcinoma↗
PubMed2002

Clinical significance of telomerase activity in peripheral blood of patients with esophageal squamous cell carcinoma.

BACKGROUND: The presence of tumor cells in the blood stream is considered evidence of a high risk of distant organ metastasis. We examined the usefulness of telomerase activity in peripheral blood polymorphonuclear cells as an indicator of distant metastasis in patients with esophageal squamous cell carcinoma. METHODS: Telomerase activity was measured in the peripheral blood mononuclear cell and polymorphonuclear cell fractions obtained from blood samples of healthy volunteers mixed with squamous cell carcinoma cell lines, and cell distribution was analyzed by flow cytometry. Then telomerase activity of forty-two polymorphonuclear cell fractions obtained from esophageal squamous cell carcinoma patients was measured. RESULTS: Telomerase activity was detected in polymorphonuclear cell fractions and cell distribution analysis revealed the presence of esophageal squamous cell carcinoma cells. Organ metastasis was detected in 7 (78%) of the 9 patients with telomerase-positive polymorphonuclear cell fractions as opposed to only five (15%) of the 33 with telomerase-negative cases, and there was a significant positive correlation between telomerase activity and organ metastasis (p < 0.0008). CONCLUSIONS: Measurement of telomerase activity in the polymorphonuclear cell fractions is useful for identifying a high risk group for distant organ metastasis in patients with esophageal squamous cell carcinoma.

Aged↗
PubMed2002

Intratracheal delivery of a single major histocompatibility complex class I peptide induced prolonged survival of fully allogeneic cardiac grafts and generated regulatory cells.

We have previously reported that intratracheal delivery of donor splenocytes in mice induces hyporesponsiveness to fully allogeneic cardiac grafts and generates regulatory cells. Here, we examined whether an allopeptide would produce the same results. A 15-mer (54-68) peptide corresponding to a hypervariable region of the K(b) molecule was given intratracheally or intravenously to CBA (H2(k)) mice 7 days before transplantation of a C57BL/10 (H2(b)) or BALB/c (H2(d)) heart and was also used in adoptive transfer experiments. Cardiac grafts in recipients given K(b) peptide intratracheally experienced a median survival time (MST) of 56 days, whereas those in recipients given the peptide intravenously were rejected acutely (MST=7.5 days). Adoptive transfer of splenocytes from mice pretreated intratracheally with K(b) peptide to naïve secondary recipients prolonged survival of cardiac grafts (MST = 35 days). Intratracheal delivery of a single major histocompatibility complex class I peptide induced hyporesponsiveness to allogeneic cardiac grafts and generated regulatory cells.

Adoptive Transfer↗