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K Kawakami

Publications and source records attributed to K Kawakami.

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

Development of co-culture system of hepatocytes with bone marrow cells for expression and maintenance of hepatic functions.

In this study, a co-culture system of hepatocytes and bone marrow cells (BMCs) was developed and characterized for the expression and maintenance of ammonia metabolism and albumin secretion activities. A culture medium supplemented with epidermal growth factor, insulin, L-proline, hydrocortisone and 20% (v/v) heat-inactivated fetal bovine serum was developed. In addition to adhesive bone marrow cells, the co-existence of non-adhesive bone marrow cells was effective in expressing liver-specific functions for at least 3 weeks. On the other hand, experiments with Transwell in which cultured cells were separated by a semi-permeable membrane, suggested that soluble factors secreted by BMCs are the key components in the functional enhancement of cells. Furthermore, direct contact between hepatocytes and BMCs enhanced the formation of spheroids and the expression of liver specific functions. These results indicate that this co-culture system is promising in, for example, bioartificial liver, regenerative medicine, and liver function simulator applications.

Animals↗
PubMed2004

[An experimental study of the therapeutic effect of interleukin-2 and interleukin-12 with and without amphotericin B on pulmonary fungal infection].

OBJECTIVE: To study the therapeutic effect of interleukin-2 (IL-2) and interleukin-12 (IL-12) with and without amphotericin B on pulmonary fungal infection of mice. METHODS: A mouse model of pulmonary invasive aspergillus fumigatus (IPA) infection was established and the mice were divided into different groups, treated with IL-2 and IL-12 with and without amphotericin B. The survival number of mice in 15 days and the colony count of lung tissue in the different groups were observed. RESULTS: IL-2, IL-12 and amphotericin B showed synergistic effect in prolonging the survival of the infected mice and reducing the colony count in the lung tissue. CONCLUSION: IL-2 and IL-12 are effective adjuvant therapeutic agents in the immunosuppressed hosts.

Amphotericin B↗
PubMed2004

Regulatory expectations during product development for tumour vaccines.

Among various approaches for the treatment of cancer, tumour vaccines stimulate the host immune response against cancer and produce local inflammation that may result in the regression of existing tumour in the body. Therapeutic tumour vaccines may generally be grouped into cellular vaccines, synthetic peptides, purified or recombinant proteins, and multi-antigen preparations including shed, or secreted antigens or cell lysates. While no tumour vaccines have been licensed by the U.S. Food and Drug Administration (FDA), a large number of products and approaches are being developed and numerous clinical trials are currently ongoing. In this article, we summarize regulatory issues associated with different types of tumour vaccines. The step-wise approach to regulatory requirements including current good manufacturing practices (cGMPs) and characterization of these vaccines at various stages of product development is discussed.

Cancer Vaccines↗
PubMed2004

[Perioperative targeting brachytherapy for lung cancer invading the chest wall].

We evaluated the efficacy of perioperative targeting brachytherapy for lung cancer invading the chest wall. Between 1998 and 2003, 7 patients underwent perioperative targeting brachytherapy for lung cancer invading the chest wall. There were 5 male and 2 female patients. The mean age was 63.3 years, with a range of 45 to 77 years. All patients underwent complete resection including the chest wall combined resection. During the operation, plastic afterloading catheters fixed on the Vicryl mesh at interval of 1 cm were placed on the site of chest wall resection. From the third to sixth day after the operation, 15 to 32 Gy of radiation was delivered over 3 or 4 days using a high dose rate remote afterloading system. The area targeted for brachytherapy was determined by a computed tomography (CT) scanner translator with a computer program for radiation planning. The median postoperative hospital stay was 35 days. Local recurrences were observed in 2 patients, but there was no evidence of recurrence in the margin of the resected chest wall. We believe that this short period of treatment and the low side effects enhances the quality of the patients. Prevention of local recurrence was achieved in short term follow-up.

Aged↗
PubMed2003

Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors engineered to express IL-13 receptor alpha2 chain in vivo.

Interleukin-13 receptor (IL-13R) alpha2 chain plays a key role in ligand binding and internalization. We have recently demonstrated that this cytokine receptor chain has unique characteristics in tumor biology: it inhibits tumorigenicity of breast and pancreatic cancer in animal models. In this study, we have exploited IL-13Ralpha2 chain and established a novel approach for pancreatic cancer therapy. For this, a plasmid encoding the IL-13Ralpha2 chain gene was mixed with liposomes and injected into subcutaneously or orthotopically xenografted human pancreatic tumors in immunodeficient mice, followed by systemic or local therapy by a recombinant IL-13 cytotoxin. Only tumors forced to express IL-13Ralpha2 chain acquired extreme susceptibility to the antitumor effect of IL-13 cytotoxin. There was a dominant infiltration of cells including macrophages and natural killer cells in the regressing tumors. Since macrophages were found to produce nitric oxide, IL-13Ralpha2-targeted cancer therapy involved not only a direct tumor cell killing by IL-13 cytotoxin but also activation of innate immune response at the tumor site. Therefore, this approach may be a new powerful tool for pancreatic cancer or other localized cancer therapy.

Animals↗
PubMed2003

[Successful emergent replacement of ruptured aortic arch aneurysm in an inpatient waiting for surgery: report of a case].

A 71-year-old male was admitted to our hospital for examination of mediastinal abnormal shadow, which was diagnosed aortic arch aneurysm. Once he was discharged and stayed at home for 2 weeks, and then re-admitted for surgery. On the 3rd day of 2nd admission, he suddenly fainted away in the ward and was in shock by hemorrhagic cardiac tamponade. He was transferred to operation room within an hour from onset of rupture. Emergent aortic arch replacement was performed under circulatory arrest with deep hypothermia and retrograde cerebral perfusion. His postoperative course was uneventful without any neurological deficits. Prompt diagnosis and surgery may contribute to improvement of surgical result in patients with ruptured aortic arch aneurysms.

Aged↗
PubMed2003

[Hemodynamic collapse during off-pump coronary artery bypass grafting and optimization].

The present study addressed the incidence of unpredicted hemodynamic collapse in off-pump coronary artery bypass grafting (OPCAB). Since 1999, OPCAB was attempted in 114 patients without preoperative hemodynamic collapse to date. 95% patients of OPCAB were completed without percutaneous cardiopulmonary support (PCPS) and all patients were discharged. In this study, patients are divided into a prophase of 60 patients and an anaphase of 50 patients, in consideration of learning curve. As for the trouble in procedures, 12 patients of ventricular fibrillation, 6 patients of conversion to PCPS, 19 patients of bradycardia which were evaded in temporary pacing were observed. Patients with conversion to PCPS decreased in 5 patients (8%) in prophase and 1 patient (1.8%) in anaphase. Avoidance of hemodynamic collapse were prevention of ischemia by positive use of coronary perfusion, prophylactic intra-aortic balloon pumping (IABP) use for decrease of blood pressure, apical evacuation heart positioner for visual field security.

Adult↗
PubMed2002

Malignant germ cell tumors: clinical characteristics, treatment, and outcome. A report from the study group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

PURPOSE: This study aims to assess the prognostic factors and optimal treatments for malignant germ cell tumors (MGCT) in childhood. METHODS: Among 117 MGCT, the clinical features were analyzed. Regarding the histology, there were 89 embryonal carcinomas, 13 dysgerminomas, 4 choriocarcinomas, and 11 others. The prognostic factors and treatments were assessed based on the 5-year survival rate. RESULTS: (1) Stage: 100% for stage I (n = 54), 75.0% for stage II (n = 4), 67.3% for stage III (n = 14), and 54.8% for stage IV (n = 33); Unknown: n = 12. (2) Primary site: 93.4% for the testis (n = 52), 86.7% for the ovary (n = 31), 56.9% for the sacrococcygeal (n = 21), and 60.6% for others (n = 12); unknown: n = 1. (3) Surgical intervention for primary tumor: 100% for stage I with a complete resection (n = 53), 78.4% for stage III, IV with a complete resection (n = 26), and 33.3% for stage III, IV with an incomplete resection (n = 21). (4) Type of chemotherapy for the stage III and IV: 83.9% for the PVB (cisplatin, vinblastin, bleomycin; n = 13), 66.7% for the VAC (vincristine, actinomycin D, cyclophosphamide; n = 6), and 47.1% for other regimens (n = 25). CONCLUSIONS: An early stage, a diagnosis under 1 year of age and a primary site in the gonads were favorable prognosis factors, whereas histologic findings of choriocarcinoma and liver or lung metastasis were unfavorable. Radical complete resection alone is a sufficient treatment for localized MGCT. The PVB regimen is optimal chemotherapy for advanced MGCT; however, high-risk cases still may require more aggressive treatment.

Adolescent↗
PubMed2002

[Early and late survival of total aortic arch replacement in patients with dissecting or atherosclerotic aneurysm].

Forty-seven patients (pts) were underwent total aortic arch replacement (TAAR) were studied to compare the early and late results between atherosclerotic (AA) and dissecting aneurysm (DA). There were 23 pts with AA and 24 pts with 24 pts. Preoperative risk were observed with shock in 12 pts (26%), major organ ischemia in 2 pts (4%), rupture in 8 pts (17%), stroke in 8 pts (17%) and coronary artery disease in 4 pts (9%). Operative procedure was TAAR in 22 pts, TAAR with ascending aorta replacement in 14 pts, and TAA with descending aorta replacement in 11 pts. Hospital mortality was 21 pts (45%) and late mortality was a surgical death after thoracoabdominal aneurysm in 1 pts. There was no difference in early and late survival rate, however early mortality was higher in pts with ruptured AA and with DA suffered from preoperative shock. There were 19 of early death in recent pts without rupture in AA and preoperative shock in DA.

Adult↗
PubMed2001

In vivo overexpression of IL-13 receptor alpha2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice.

Interleukin 13 receptor alpha2 (IL-13R(alpha)2) chain is highly expressed on some tumor cell lines and primary cell cultures. This receptor chain plays an important role in ligand binding and internalization. To determine the functional significance of overexpression of this chain, we stably transfected IL-13R(alpha)2 chain in human breast (MDA-MB-231) and pancreatic (PANC-1) cancer cell lines that naturally do not express this chain. There was no difference in growth between vector only transfected and IL-13R(alpha)2 chain transfected cells in vitro. However, surprisingly, in immunodeficient mice, tumorigenicity was profoundly inhibited in IL-13R(alpha)2 chain overexpressing tumors. Because breast tumors that grew later showed loss of IL-13R(alpha)2 gene expression, lack of tumorigenicity correlated positively with IL-13R(alpha)2 chain expression. Inflammatory cells including neutrophils and macrophages were identified in IL-13R(alpha)2 overexpressing regressing tumors and neutrophils were found to produce IL-13. IL-13 showed a modest antitumor activity to IL-13R(alpha)2 chain overexpressing tumors in vitro and in vivo. Furthermore, IL-13R(alpha)2 chain overexpressing tumors constitutively produced IL-8 that has been shown to have antitumor effect. These results establish a novel function of a cytokine receptor chain and further suggest that the presence of this chain on tumor cells by itself may play a key role in tumorigenicity.

Animals↗
PubMed2001

Monocyte chemoattractant protein-1-dependent increase of V alpha 14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection.

To elucidate the role of NKT cells in the host defense to cryptococcal infection, we examined the proportion of these cells, identified by the expression of CD3 and NK1.1, in lungs after intratracheal infection with Cryptococcus neoformans. This population increased on day 3 after infection, reached a peak level on days 6-7, and decreased thereafter. In Valpha14 NKT cell-deficient mice, such increase was significantly attenuated. The proportion of Valpha14 NKT cells, detected by binding to alpha-galactosylceramide-loaded CD1d tetramer, and the expression of Valpha14 mRNA increased after infection with a similar kinetics. The delayed-type hypersensitivity response and differentiation of the fungus-specific Th1 cells was reduced in Valpha14 NKT cell-deficient mice, compared with control mice. Additionally, elimination of this fungal pathogen from lungs was significantly delayed in Valpha14 NKT cell-deficient mice. Production of monocyte chemoattractant protein (MCP)-1 in lungs, detected at both mRNA and protein levels, increased on day 1, reached a peak level on day 3, and decreased thereafter, which preceded the increase in NKT cells. Finally, the increase of total and Valpha14(+) subset of NKT cells after infection was significantly reduced in MCP-1-deficient mice. Our results demonstrated that NKT cells, especially Valpha14(+) subset, accumulated in a MCP-1-dependent manner in the lungs after infection with C. neoformans and played an important role in the development of Th1 response and host resistance to this fungal pathogen.

Animals↗
PubMed2001

Early clinical results of endorectal surgery using a newly designed rectal tube with a side window.

BACKGROUND: Transanal endoscopic microsurgery (TEM) using the original Buess devices requires the use of a completely closed system for positive pressure gas insufflation. To simplify the setup of the system and expose the target lesion in the rectum without gas insufflation, we have developed a new operating rectal tube with a side window. METHODS: The new rectal tube is a transparent cylinder measuring 40 mm in diameter with its forward end closed and a 40-mm opening on its side. When a rectal tumor is captured within the opening, it can be clearly visualized without positive gas insufflation. Under endoscopic control, the lesion is then resected and the defect is closed by suturing. Using this new system, we performed endorectal surgery on 10 patients with rectal tumors. Our series included four benign adenomas, two carcinomas in situ, two T2 cancers, and two carcinoid tumors. RESULTS: The operation was performed successfully in all 10 cases. There were no significant operative complications and the postoperative course was excellent in all cases. Pathological analysis revealed that the surgical margins of all specimens were completely free from tumor. CONCLUSIONS: Our early clinical results suggest that the newly designed operating rectal tube with a side window simplifies the endorectal surgical procedure and facilitates the safe resection of rectal tumors < 40 mm in diameter.

Adenoma, Villous↗
PubMed2001

Interleukin-13 receptor-targeted cancer therapy in an immunodeficient animal model of human head and neck cancer.

Although interleukin-13 receptors (IL-13R) are overexpressed on several head and neck cancer cell lines, a majority of cell lines express only low levels of IL-13R. We have found that the primary interleukin-13-binding protein IL-13Ralpha2 chain plays an important role in ligand binding and internalization. We showed that the gene transfer of IL-13Ralpha2 chain into various solid tumor cell lines that express few IL-13Rs can dramatically sensitize cells to the cytotoxic effect of a recombinant chimeric protein composed of interleukin-13 and a mutated form of Pseudomonas exotoxin A, IL13-PE38QQR. Based on the expression of IL-13R, we have classified five head and neck cancer cell lines into two groups: (a) IL-13Ralpha2 chain-positive cell lines (SCC-25 and KCCT873); and (b) IL-13Ralpha2 chain-negative cell lines (A253, YCUT891, and KCCT871). By plasmid-mediated stable gene transfer, we demonstrate that not only IL-13Ralpha2 chain-positive head and neck cancer cell lines but also IL-13Ralpha2 chain-negative cell lines can dramatically increase sensitivity to IL-13 toxin by 520-1000-fold compared with mock-transfected control cells after genetic alteration to express high levels of the IL-13Ralpha2 chain. In animal studies, i.p. or intratumoral administration of IL13-PE38QQR given daily or on alternate days for 3-5 days showed dramatic tumor response with complete remission in intratumorally injected tumors in both IL-13Ralpha2 chain-positive and -negative but transfected with IL-13Ralpha2 chain head and neck tumor implanted s.c. in nude mice. These results demonstrate that by using a combination approach of gene transfer and systemic or locoregional cytotoxin therapy, the IL-13R represents a new potent target for head and neck cancer therapy.

ADP Ribose Transferases↗
PubMed2001

Clinical and biologic characteristics for recurring neuroblastoma at mass screening cases in Japan.

BACKGROUND: It is said that most cases detected by neuroblastoma mass screening at 6 months of age tend to have a favorable clinical course after a surgical resection either with or without mild chemotherapy. However, a few cases have an unfavorable outcome. In the current study, the authors analyzed the clinical and biologic characteristics for recurring neuroblastoma in mass screening cases. METHODS: In 245 cases detected through mass screening in the Kyushu area in Japan, the clinical data and biologic features (N-myc status, DNA ploidy, Shimada histology, neuron-specific enolase (NSE), ferritin) were investigated, whereas, in particular, the data for recurring cases also were analyzed. RESULTS: Of 245 cases, 28 tumors had one or more biologically unfavorable prognostic factors, and 6 patients experienced recurrence. Three of the six patients with recurring disease underwent a complete resection of the primary tumor, whereas three cases had undergone an incomplete resection of the tumor. Regarding the initial chemotherapy, three cases received mild chemotherapy, two cases received no chemotherapy, and one case had high-dose multidrug chemotherapy. Regarding biologic prognostic factors, four of six cases with recurring disease had one or more unfavorable factors, whereas two cases had no unfavorable factors. Regarding the outcome after recurrence, four cases are CR, one case has a stable residual tumor, and one case died of disease with N-myc amplification. CONCLUSIONS: Most neuroblastomas detected by mass screening at 6 months of age have biologically favorable factors. However, approximately 10% of the cases had one or more unfavorable factors and thus might have a higher risk of recurrence than the patients with no unfavorable factors. Conversely, some cases with recurring disease had no unfavorable factors; however, the reason for this is still unclear. A long-term follow-up for mass screening cases is important, and it also might be necessary to research the established biologic factors and identify other new prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor alpha 2 chain.

Interleukin (IL)-13 receptor alpha2 (IL-13Ralpha2) chain is an essential binding component for IL-13-mediated ligand binding. Recently, we have demonstrated that this receptor chain also plays an important role in the internalization of IL-13. To study the mechanism of IL-13 internalization, we generated mutated IL-13Ralpha2 chains that targeted trileucine residues (Leu(335), Leu(336), and Leu(337)) in the transmembrane domain and a tyrosine motif (Tyr(343)) in the intracellular domain and transfected these cDNAs in COS-7 cells. Cells that expressed a C-terminally truncated IL-13Ralpha2 chain (Delta335) did not bind IL-13, suggesting that the trileucine region modulates IL-13 binding. Truncation of IL-13Ralpha2 chain with a mutation in the trileucine region resulted in significantly decreased internalization compared with wild type IL-13Ralpha2 chain transfected cells. COS-7 cells transfected with tyrosine motif mutants exhibited a similar internalization level compared with wild type IL-13Ralpha2 chain transfected cells; however, dissociation of cell surface IL-13 was faster compared with wild type IL-13Ralpha2 transfectants. These results were further confirmed by determining the cytotoxicity of a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13-PE38QQR) to cells that expressed IL-13Ralpha2 chain mutants. We further demonstrate that the IL-13Ralpha2 chain is not ubiquitinated and that internalization of IL-13Ralpha2 did not depend on ubiquitination. Together, our findings suggest that the dileucine motif in the trileucine region and tyrosine motif participate in IL-13Ralpha2 internalization in distinct manners.

ADP Ribose Transferases↗
PubMed2001

The interleukin-13 receptor alpha2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway.

The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13Ralpha1 (also known as IL-13Ralpha') and IL-13Ralpha2 (also known as IL-13Ralpha). For a functional IL-13 receptor, the IL-13Ralpha1 chain forms a productive complex with the primary IL-4 binding protein (IL-4Ralpha also known as IL-4Rbeta). However, the function of the IL-13Ralpha2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13Ralpha2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of (125)I-IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Ralpha2 chain; (2) a recombinant chimeric fusion protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13Ralpha2-transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13Ralpha2-transfected cells. IL-13 efficiently caused activation of STAT6 protein in cells transfected with the IL-13Ralpha1 and IL-4Ralpha chains, and IL-13Ralpha2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13Ralpha2 is signal independent and that this property of IL-13Ralpha2 can be exploited for receptor-directed cancer therapy.

Animals↗
PubMed2001

Changes in the levels of glutathione after cellular and cutaneous damage induced by squalene monohydroperoxide.

Squalene monohydroperoxide (Sq-OOH), the initial product of ultraviolet-peroxidated squalene, was used to investigate the effect of peroxidative challenge upon the glutathione contents in rabbit ear skin and primary-cultured fibroblasts derived from rabbit ear skin. The cellular reduced glutathione (GSH) contents decreased during 30-minute incubations in vitro with Sq-OOH, and oxidized glutathione (GSSG) was formed concomitantly, indicating that Sq-OOH had a potential for GSH-depleting activity in vitro. When Sq-OOH was applied topically to the skin in vivo, only GSSG contents increased significantly within 30 minutes. Moreover, pretreatment with the GSH depletors, DL-buthionine sulfoximine (BSO) and diethyl maleate (DEM), could potentiate the cytotoxicity and comedogenicity induced by Sq-OOH. These findings suggest that the endogenous antioxidant, glutathione, is quite sensitive to Sq-OOH and may be an important material for protecting cells and/or tissues against the oxidative stress induced by Sq-OOH treatment.

Animals↗