Biomedical subjects

Futoshi Miyazono

Publications and source records attributed to Futoshi Miyazono.

23 records · Page 2Linked to original sources

PubMedDate not supplied

Tumor-associated macrophage (TAM) infiltration in gastric cancer.

BACKGROUND: Tumor-associated macrophages (TAMs) are defined as macrophages that migrate into the tumor stroma. TAMs are known to directly or indirectly affect immune suppression. TAMs have not previously been reported in gastric cancer. MATERIALS AND METHODS: Using anti-CD68 antibodies, we immunohistochemically evaluated TAM infiltration in 97 gastric cancer patients who underwent tumor resection. Furthermore, CD3-zeta chain expression of tumor infiltrating lymphocytes (TILs) from the same section was also examined. According to the degree of TAM infiltration, 97 patients were divided into two groups (high TAM group, more than 200 positive cells; low TAM group, less than 200 positive cells). Clarification of the clinicopathological features of TAM-positive gastric cancer was attempted. RESULTS: TAM infiltration in the tumor nest ranged from 0 to 621 cells (average 187). The degree of infiltration positively correlated with depth of invasion, nodal status and clinical stage. Patients in the high TAM group had lower CD3-zeta expression by TILs than patients in the low TAM group. CD3-zeta expression by TILs negatively correlated with infiltration of TAMs (p < 0.01). Patients with a high TAM count had poorer surgical outcomes than those with a low TAM count. CONCLUSION: From the results of the current study, TAM infiltration may be used as a prognostic marker in gastric cancer. Negative correlation between TAM infiltration and CD3-zeta expression by TILs suggests that TAMs may be responsible for the immunological inactivity of T cells in gastric cancer.

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PubMedDate not supplied

Clinical merit of subdividing gastric cancer according to invasion of the muscularis propria.

BACKGROUND/AIMS: In TNM classification, carcinoma that has invaded the muscularis propria (mp) and cancer that has invaded the subserosa are both categorized as T2 cancer. However, some mp gastric cancer patients have a good postoperative course, similar to that of early gastric cancer patients. We performed a retrospective analysis of 74 patients with mp gastric cancer, based on the depth of mp invasion. METHODOLOGY: The clinicopathologic features of 74 cases of gastric cancer invading the mp (but no further) were subdivided according to depth of invasion, retrospectively reviewed and compared with surgical features of 165 patients with gastric cancer invading the submucosa (sm gastric cancer). For each tumor, we evaluated the degree of tumor invasion in the mp layer at a magnification of x100, using the section that showed the greatest extent of invasion. The patients were classified into 2 groups: mp1, tumor was limited to the first of the 3 mp layers; mp2, tumor had expanded beyond the first layer. RESULTS: Of the 74 mp gastric cancer patients, 30 were classified as mp1 and 44 were classified as mp2. Patients with mp1 gastric cancer had significantly more macroscopic signs of early gastric cancer, a lower frequency of lymph node metastasis, and a higher rate of operative cure than patients with mp2 gastric cancer. The incidence of lymph node metastasis among mp1 gastric cancer patients was almost equal to that of the 165 sm gastric cancer patients. The 5-year survival rate of mp1 patients was significantly better than that of mp2 patients (p<0.05), but was similar to that of the 165 sm gastric cancer patients (84%) (p<0.05). CONCLUSIONS: There were clear differences in clinical features between the mp1 and mp2 gastric cancer patients. Subdivision of mp gastric cancer according to depth of invasion may enable more precise prognosis and treatment of mp gastric cancer patients. The clinicopathological findings and surgical outcome of the mp1 patients were similar to those of the sm gastric cancer patients. Thus, mp1 patients may require treatment that is similar to treatment administered to patients with early gastric cancer.

Adult↗

PubMedDate not supplied

CD3 zeta expression of regional lymph node and peripheral blood lymphocytes in gastric cancer.

BACKGROUND AND AIM: Impaired expression of the CD3 zeta chain in T cells associated with T cell anergy has been reported in cancer patients. However, few studies have investigated CD3 zeta expression in regional lymph node lymphocytes (LAL) in cancer patients. This study aims to confirm CD3 zeta expression levels by lymph node and peripheral blood lymphocytes (PBL) in gastric cancer patients and to discuss the clinical implications of intranodal or peripheral blood expression of CD3 zeta in gastric cancer. PATIENTS AND METHODS: Twenty-two gastric cancer patients were enrolled. Macroscopically non-metastatic compartment 1 LNL (C1LNL), compartment 2 LNL (C2LNL) and PBL were surgically obtained. Two-color flow cytometry was then used to quantify the levels of CD3 zeta expression in C1LNL, C2LNL and PBL. RESULTS: Impaired CD3 zeta expression was confirmed in 9.5% of C1LNL, 8.9% of C2LNL and 4.2% of PBL. There was a significant difference in CD3 zeta expression levels between C1LNL and PBL (p<0.01). CD3 zeta expression in PBL was significantly correlated with depth of invasion but not nodal involvement. Distinct differences between the respective lymph node compartments were not identified. CONCLUSION: Immunological paralysis following CD3 zeta impairment may occur more frequently in LNL than in PBL in gastric cancer. Identifying such patients during the perioperative period using flow cytometric methods will increase the efficacy of cytokine therapy aiming to normalize CD3 zeta expression levels.

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PubMedDate not supplied

HLA-G expression in gastric cancer.

BACKGROUND: Ectopic HLA-G expression in tumor cells may indicate immune escape from the host immune defense via the inhibitory receptor on natural killer (NK) cells. However, there is little information on HLA-G expression in gastric cancer. PATIENTS AND METHODS: HLA-G expression was immunohistochemically analyzed in 115 gastric cancer patients and the clinical implications of its expression in gastric cancer were assessed. Moreover, NK cell infiltration into the primary tumor was evaluated using anti-CD57 antibodies. RESULTS: The HLA-G-positive group had a more differentiated histology, less nodal invasion and earlier clinical stage than the HLA-G-negative group and these differences were significant. The 5-year survival rate in the HLA-G-positive group was 78%, which was significantly higher than that in the HLA-G-negative group (51%). NK cell infiltration into the tumor tended to be negatively correlated with HLA-G expression. CONCLUSION: Our results suggest a high frequency of HLA-G expression in early gastric cancer. However, this may not be directly related to aggressive tumor behavior via escape from the host antitumor immune defense. Further investigation is required.

Adult↗

PubMedDate not supplied

P53 and MIB-1 expression in gastrointestinal stromal tumor (GIST) of the stomach.

BACKGROUND/AIMS: Routine clinical approaches for evaluating the risk of recurrence in patients with gastrointestinal stromal tumor (GIST) of the stomach have been limited. Some biomolecular markers may yield more useful information in identifying patients having a higher risk of recurrence. In the current retrospective study, we selected MIB-1 and p53 expression as markers to detect at-risk patients. METHODOLOGY: We enrolled 31 gastric GIST patients who underwent gastrectomy at Kagoshima University Hospital. Patients were classified into two groups based on mitosis and tumor diameter. p53 and MIB-1 expression in the primary tumor were detected immunohistochemically. RESULTS: The patients were classified as having a malignant GIST (20 cases), a benign GIST (11 cases). MIB-1 labeling index (LI) varied from 1 to 32% (average 7.8%). The MIB-1 LI for malignant GISTs was 6.3 +/- 6.4%, which was significantly higher than the 3.2 +/- 2.5% observed for benign GISTs (p < 0.01). The 3 patients positive for p53 died as a result of GIST recurrence. CONCLUSIONS: In addition to routine pathological evaluation, expression of p53 and MIB-1 may provide more accurate information regarding the risk of GIST recurrence. Especially, p53 expression of the tumor may indicate patients having a high risk of recurrence.

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