Biomedical subjects

Nobuhiko Sasaki

Publications and source records attributed to Nobuhiko Sasaki.

5 recordsLinked to original sources

PubMed2004

Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-alpha through IL-12/TNF-alpha/NF-kappaB autocrine loop.

This study focused on the question of how monocyte-derived dendritic cells (Mo-DCs) that capture dead tumor cells (Mo-DCs-Tum) secrete interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-alpha). Mo-DCs-Tum showed higher secretions of IL-12 and TNF-alpha than were shown by Mo-DCs. Enhanced nuclear factor-kappa B (NF-kappaB) activation was also induced in Mo-DCs-Tum within 6 h. The NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), suppressed both IL-12 and TNF-alpha secretions from Mo-DCs-Tum. Administration of recombinant TNF-alpha or IL-12 enhanced IL-12 or TNF-alpha secretion respectively in Mo-DCs-Tum. Addition of anti-TNF-alpha or anti-IL-12 neutralizing antibody decreased NF-kappaB activation and IL-12 or TNF-alpha secretion in Mo-DCs-Tum. These results suggest that TNF-alpha or IL-12 secretion induces NF-kappaB activation, and it stimulates further TNF-alpha and IL-12 secretions, i.e., an IL-12/TNF-alpha/NF-kappaB autocrine loop, in Mo-DCs-Tum. Thus, Mo-DCs-Tum secrete a large amount of IL-12 and TNF-alpha through accelerated NF-kappaB activation induced by the IL-12/TNF-alpha/NF-kappaB autocrine loop.

Apoptosis↗

PubMed2003

Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food.

Among ten patients who contracted sporadic acute or fulminant hepatitis E between 2001 and 2002 in Hokkaido, Japan, nine (90 %) had a history of consuming grilled or undercooked pig liver 2-8 weeks before the disease onset. We tested packages of raw pig liver sold in grocery stores as food in Hokkaido for the presence of hepatitis E virus (HEV) RNA by RT-PCR. Pig liver specimens from seven (1.9 %) of 363 packages had detectable HEV RNA. Partial sequence analyses revealed that the seven swine HEV isolates belonged to genotype III or IV. One swine HEV isolate (swJL145) from a packaged pig liver had 100 % identity with the HE-JA18 isolate recovered from an 86-year-old patient in Hokkaido. Two swine HEV isolates (swJL234 and swJL325) had 98.5-100 % identity with the HE-JA4 isolate obtained from a 44-year-old patient in Hokkaido. These results indicate that inadequately cooked pig liver may transmit HEV to humans.

Acute Disease↗

PubMedDate not supplied

Candidate host marker for peritoneal dissemination.

BACKGROUND: Mesothelial cell injury is common in peritoneal dissemination (PD) of cancer cells. The plasminogen activator system, including urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1), plays an important role in repair of the peritoneum damaged by several types of peritonitis. We investigated and compared the expression of uPA and PAI-1 in the peritoneum of cancer patients with and without PD. MATERIALS AND METHODS: Cancer cell-positive peritoneum and cancer cell-negative peritoneum specimens were obtained from 11 patients with PD, while peritoneum specimens were also obtained from 24 patients without PD. The presence or absence of cancer cells in the peritoneal tissues was confirmed by both hematoxylin-eosin staining and reverse transcriptase-polymerase chain reaction (RT-PCR) detection of carcinoembryonic antigen (CEA) mRNA. uPA and PAI-1 mRNA expression in these peritoneal tissues was determined by RT-PCR and the proteins were localized immunohistochemically. The results were compared statistically. RESULTS: uPA mRNA was expressed in the cancer cell-positive peritoneum from 9 of the 11 (81.8%) patients with PD; PAI-1 mRNA was expressed in the peritoneal tissue from 10 of (91.9%) these patients. Either uPA or PAI-1 mRNA was expressed in the cancer cell-negative peritoneum from 8 (72.7%) of the 11 patients with PD, whereas uPA mRNA was expressed in none of the peritoneal tissues from the 24 patients without PD and PAI-1 mRNA was expressed in specimens from 4 (16.7%) of these patients. Immunohistochemical analysis revealed uPA and/or PAI-1 in the mesothelial cells and submesothelial fibroblasts in cancer cell-negative peritoneum from the patients with PD but not in peritoneum from the patients without PD. CONCLUSION: uPA transcription in the peritoneum may be a host marker indicating the existence of PD.

Adult↗

PubMedDate not supplied

Nuclear factor-kappaB p65 is a prognostic indicator in gastric carcinoma.

BACKGROUND: In common with other investigators, we have reported the constitutive activation of transcription factor nuclear factor-kappaB (NF-kappaB) in a variety of carcinomas, but there is no definite information on its clinical significance. MATERIALS AND METHODS: NF-kappaB p65 activation was determined by immunohistochemical analysis of surgically resected specimens from 63 gastric carcinomas. The 63 patients were divided into a high NF-kappaB group (21 patients) and a low NF-kappaB group (42 patients). Forty-seven of the 63 patients underwent curative resection. The 47 patients consisted of 13 high NF-kappaB patients and 34 low NF-kappaB patients. RESULTS: The high NF-kappaB group demonstrated a shorter overall survival rate compared with the low NF-kappaB group (p=0.015). In the 47 patients who underwent curative resection, the high NF-kappaB group also showed a poor survival prognosis (p=0.032). Multivariate analysis indicated that NF-kappaB activation is a potential prognostic factor in gastric carcinoma. CONCLUSION: Constitutive activation of NF-kappaB p65 may be a new prognostic parameter in gastric carcinoma.

Aged↗

PubMedDate not supplied

Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression.

OBJECTIVES: Nuclear factor-kB (NF-kB) is a transcription factor that participates in the induction of several genes for cytokines and enzymes that play important functional roles in various cell types. The aim of this study was to determine NF-kB activation status in human colorectal carcinoma and its correlation to the clinicopathological characteristics of patients. MATERIALS AND METHODS: We examined the activation status of NF-kB in 28 resected colorectal carcinomas and in colonic mucosa from uninvolved portions of these specimens by electrophoretic mobility shift assay (EMSA) and immunohistochemical staining for the p65 subunit of NF-kB. RESULTS: EMSA showed much greater activation in the tumors than in normal mucosa, as did epithelial p65 immunostaining. NF-kB activation significantly increased in the more progressed cases (T3 + T4 cases or Stage II< cases). In vitro studies using lipopolysaccharide (LPS)-responsive colon carcinoma cells suggested a correlation between NF-kB activation and cell proliferation. CONCLUSION: Our findings indicated that NF-kB is constitutively activated in human colorectal carcinoma tissue and correlates with tumor progression. The regulation of this transcription factor might be therapeutically useful against these tumors.

Adenocarcinoma↗