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Biomedical subjects

A Nanashima

Publications and source records attributed to A Nanashima.

At least 55 records · Page 3Linked to original sources

Expression of multidrug resistance protein in metastatic colorectal carcinomas.

To clarify the relationship between multidrug resistance protein (MRP) and clinicopathologic features, the influence of adjuvant chemotherapy, and prognosis of patients who underwent resection of metastatic liver carcinomas originating from colorectal carcinomas, we examined the expression of MRP in tumor tissues by immunostaining. Specimens of 38 primary colorectal tumors and 44 metastatic liver tumors of colorectal origin were examined (metastatic group). We also examined 28 nonmetastatic colorectal carcinomas. The percentages of nonmetastatic tumors and of primary and metastatic tumors of the metastasis group that expressed MRP were similar. MRP expression in primary and metastatic tumors did not correlate with any clinicopathologic features. The use of adjuvant chemotherapy after operation for primary colorectal carcinomas was associated with increased MRP expression among metastatic liver tumors. Expression of MRP in the tumor did not influence the prognosis or survival rate after resection of primary or metastatic tumors. Our data suggest that MRP expression in metachronous liver metastases from colorectal carcinomas may be induced by administration of anticancer drugs but is not associated with clinicopathologic features of the tumor, liver metastasis, or prognosis.

ATP-Binding Cassette Transporters↗

Proliferation of hepatic metastases of colorectal carcinoma: relationship to primary tumours and prognosis after hepatic resection.

In this study, we determined the proliferation indices of liver metastatic tumours originating from colorectal carcinomas using Ki67 and argyrophil nucleolar organizer region associated proteins (AgNOR) stain. We examined the primary and metastatic tumours in 27 patients with liver metastasis and eight cases with non-metastatic colorectal carcinoma as a control.The number of AgNOR dots in metastatic tumours was significantly higher than in the respective primary tumours of the metastasis group or in non-metastatic colorectal carcinomas. The Ki67 labelling index was similar in all groups. The Ki67 labelling index and AgNOR counts did not correlate with each other. There was no significant relationship between proliferation indices and the duration of the disease-free period following hepatic resection for metastases or with prognosis after hepatectomy. We conclude that Ki67 and AgNOR are not useful indicators of prognosis in patients who undergo operation for liver metastasis of colorectal carcinomas.

Adult↗

Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: relationship to primary tumours and prognosis after hepatic resection.

BACKGROUND: Adhesion molecules are closely involved in the development and growth of metastatic tumours. METHODS: We examined the expression of two adhesion molecules in liver metastatic tumours originating from colorectal carcinomas and correlated the expression of E-cadherin (EC) and CD44 variant exon 6 (v6) in these tumours with prognosis after hepatic resection. We examined 39 primary colorectal and 44 liver metastatic tumours obtained from 39 patients and 30 non-metastatic colorectal carcinomas as controls. The expression of EC in primary colorectal carcinomas of the metastasis group was significantly lower than in the non-metastasis group (P < 0.05). The expression of EC was low in metastatic liver tumours. RESULTS: The expression of CD44v6 in primary colorectal carcinomas of the metastasis group was significantly higher than in the non-metastasis group (P < 0.01). Expression of CD44v6 was high in metastatic liver tumours. However, there was no correlation between the expression of EC and CD44v6 or between each of these molecules and clinicopathological features of primary and metastatic tumours. Negative expression of EC and CD44v6 was a poor prognostic factor for survival after hepatic resection. CONCLUSIONS: Our results indicate that the lack of expression of EC and CD44v6 in liver metastases of colorectal cancer is associated with poor survival after surgery.

Aged↗

Development of hepatocellular carcinoma in a patient with chronic hepatitis C after 6 years of a sustained and complete response to IFN-alpha.

The authors report a rare case of hepatocellular carcinoma (HCC) that developed 6 years after a sustained and complete response to interferon (IFN) therapy for chronic hepatitis C. A 61-year-old Japanese man presented with a mass in the liver that was diagnosed as HCC. Six years earlier he was treated with IFN-alpha and responded successfully to therapy, with sustained normalization of serum aminotransferases and eradication of serum hepatitis C virus (HCV)-ribonucleic acid (RNA). HCV-RNA was also not detected in the resected tumorous and nontumorous liver tissues. The findings suggest that all patients with chronic HCV infection should be followed closely for as long as possible for the potential development of HCC even after a complete and sustained response to IFN treatment.

Carcinoma, Hepatocellular↗

Physiologic stress responses to laparoscopic cholecystectomy. A comparison of the gasless and pneumoperitoneal procedures.

BACKGROUND: Differences in the physiological stress response to pneumoperitoneal (PP) and gasless abdominal wall-lifting (AWL) procedures used for laparoscopic cholecystectomy have not been properly evaluated. METHODS: We compared leukocyte count, interleukin-6 (IL-6) levels, arterial blood gases, creatinine clearance, plasma renin activity, cardiothoracic ratio, and clinical outcome in 27 patients without systemic complications who underwent laparoscopic cholecystectomy, including 11 by AWL and 16 by PP. RESULTS: Transient leukocytosis and high IL-6 levels were observed at POD 1 (postoperative day) in both groups, but both values returned to baseline by POD 2. IL-6 levels correlated significantly with operation time (p < 0.01). Changes in blood gases, creatinine clearance, plasma renin activity, and cardiothoracic ratio were not different for the two groups. The clinical outcome was similar for both groups. CONCLUSIONS: Our results indicate that both PP and AWL are appropriate for patients without serious complications.

Adult↗

Chromosome instability evaluated by fluorescence in situ hybridization in hereditary non-polyposis colorectal cancer.

Numerical aberrations of chromosome 17 and nuclear DNA content were compared in patients with hereditary non-polyposis colorectal cancer (HNPCC) and those with sporadic colorectal cancer (SCRC). During a period of 22 years, 30 cases (3.2%) from 28 families satisfied the Japanese clinical criteria of HNPCC. Using freshly frozen tissue samples, we investigated chromosomal aberration with fluorescence in situ hybridization with alpha satellite DNA probe for chromosome 17. Flow cytometric quantification of nuclear DNA content showed DNA aneuploidy in 9 of 15 patients (60.0%) with HNPCC and in 160 of 234 patients (68.4%) with SCRC, there was no significant difference between HNPCC and SCRC. The mean proportion of nuclei with aneusomy 17 (numerical chromosome aberration index: NCAI) in 14 patients with HNPCC was significantly higher than that in 42 patients with SCRC (46.8 +/- 5.0% vs 39.0 +/- 10.3%, P < 0.01). NCAI increased in proportion with the progression of the disease in SCRC (26.1% in stage I, 33.3% in stage II, 38.8% in stage IIIa, 42.7% in stage IIIb, and 46.2% in stage IV, P < 0.01), whereas NCAI in HNPCC was high in all stages (43.5%-49.2%). The proportion of patients with multiple numerical aberration of chromosome 17 was significantly higher in HNPCC (9/14) than among SCRC (11/42). Our data suggest that chromosome 17 is present in an unstable condition in HNPCC.

Adenocarcinoma↗

Importance of cytogenetic markers for multiple primary carcinomas in colorectal cancer: chromosome 17 and p53 locus translocation.

The incidence of non-familial multiple primary cancer in colorectal cancer patients has increased in recent years in Japan. To clarify the characteristic genetic aberrations in such multiple cancers, we examined structural chromosomal aberrations by fluorescence in situ hybridization, using chromosome 17-specific and p53 cosmid DNA probes. We established short-term cultures of 78 surgical specimens and were able to obtain observable metaphase spreads in 23 single colorectal cancer specimens and in 6 colorectal cancer specimens from patients with double primary cancers. The frequency of chromosome 17 and/or p53 locus translocation was significantly greater in tumors with double cancer than in single colorectal cancers (P < 0.05 and P < 0.01, respectively). These aberrations in double cancers frequently appeared even at an early Dukes' stage (A and B) of colorectal carcinoma. Our results suggest that translocation of chromosome 17 and the p53 locus may be specific genetic events probably associated with carcinogenesis of multiple primary cancers in colorectal cancer.

Biomarkers, Tumor↗

Significance of angiogenic factors in liver metastatic tumors originating from colorectal cancers.

We examined the expression of vascular endothelial growth factor (VEGF) and microvessel counts expressed by CD34 staining in 39 patients with primary and 44 patients with metastatic liver tumors of metastatic colorectal carcinoma, and 29 patients with nonmetastatic colorectal carcinoma as control in order to determine their value in the evaluation of prognosis and recurrence after hepatectomy. Microvessel counts in primary colorectal carcinomas of the metastatic group were significantly higher than those in control (P<0.05). Neither factor correlated with any clinicopathological feature of primary or metastatic liver carcinomas. Higher microvessel counts in metastatic liver tumors tended to be associated with a shorter disease-free interval to second recurrence in the remaining liver (P = 0.069) and were significantly associated with poor prognosis after hepatectomy (P<0.05). We conclude that microvessel count is an important marker of liver metastasis and prognosis in patients with colorectal carcinoma treated with hepatectomy.

Adult↗

Immunohistochemical expression of ABH/Lewis-related antigens in primary breast carcinomas and metastatic lymph node lesions.

The expression of blood group antigens A, B, and H, as well as sialylated and nonsialylated forms of Lewis(a) and Lewis(x), was studied using immunohistochemical methods in normal and tumor tissues in the following cohort of patients: 51 patients with primary breast carcinoma, 13 with metastatic lymph node lesions, and 16 with benign tumors of the breast. As a control, normal tissue was obtained from a similar group of 22 patients with breast cancer. The noncancerous tissues expressed the same A/B/H antigens as the patients' red blood cells and also usually expressed Lewis-related antigens. Seventy-six percent of primary carcinomas failed to express the appropriate A/B/H antigens, and in one blood group A patient the tumor tissue expressed B antigen. In the metastatic lesions, Lewis(a)/sialyl Lewis(a) expression was reduced when compared with the primary tumors, but Lewis(x)/sialyl Lewis(x) antigens were still expressed. These results suggest a possible relationship between the metastatic behavior of the tumor and expression of the blood group antigens.

Antigens, Tumor-Associated, Carbohydrate↗

Differences in spatial localization and chromatin pattern during different phases of cell cycle between normal and cancer cells.

We studied differences in chromatin patterns and the spatial localization of centromeres of chromosome 11 during the cell cycle between normal peripheral blood lymphocytes (PBL) and human promyelocytic leukemia cells (HL-60) using fluorescence in situ hybridization. The pericentromeres in both cells were located at the periphery during Gq (quiescent) phase, but moved towards the nuclear center in G1 and mid-S phase. During G2, the pericentromeres of PBL continued to move towards the nuclear center whereas those of HL-60 returned to the periphery. The angle defining the spatial location of two pericentromeres, in reference to the center of the nucleus, increased in PBL cells from a mean of 67 degrees during Gq phase to 106 degrees during G1 phase (P < 0.01), and the two pericentromeres remained wide apart throughout the entire cell cycle. In HL-60, the angle also increased during G1, but then decreased during mid-S and G2 phases. Both cells exhibited pericentromeric signals during Gq that were round and compact, and the entire chromatin was loosely condensed. The signal became more loose and dispersed during the G1 and mid-S phases. The pericentromere signal varied during G2 and was generally rod-like or bipartite with condensation of the entire chromatin or chromosome-like. Our results suggest that subtle but important differences in spatial localization of pericentromeres are present during the interphase between normal PBL and HL-60 cells.

Cell Cycle↗

Different expressions of sialyl Tn antigen between polypoid and flat-type early colorectal cancers.

PURPOSE: Sialyl Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. We compared the proportion of specimens of flat-type colorectal cancers expressing STn with that of polypoid cancers, by examining the immunohistochemical reactivity of STn in various morphologic types of early and advanced colorectal cancers. METHODS: A total of 111 biopsies from the colorectal area were examined for STn expression, including 11 adenomas, 58 early cancers, and 42 advanced cancers. Each section was stained immunohistochemically for STn antigen. In each section, we examined STn expression in the cancer area, adjacent mucosa, and normal epithelium. RESULTS: STn expression was detected in 90.9 percent of adenomas, 36.2 percent of early cancers (T1), 64.3 percent of advanced cancers (>T1), and 52 percent of mucosa adjacent to cancer. The morphology of cancer tissue did not influence the number of specimens exhibiting STn antigen expression in mucosa adjacent to cancer cells. STn antigen was rarely expressed in flat or depressed-type early cancers (T1; 7.1 percent), and the expression was higher in moderately than in well-differentiated adenocarcinomas. In advanced cancers (>T1), a similar proportion of protruding and small ulcerative cancers expressed STn. CONCLUSION: Our results suggest that the low expression of STn antigen in flat-type cancers may be the result of different mechanisms of cellular transformation during carcinogenesis from the usual adenoma-carcinoma sequence in colorectal neoplasms.

Adenocarcinoma↗

Analysis of p53 gene deletions in colorectal cancers using fluorescence in situ hybridization.

To examine the relationship between the incidence of p53 gene deletion in each nucleus and the clinicopathological features in colorectal cancers, we performed a cytogenetic study using fluorescence in situ hybridization (FISH). FISH was performed on 5 adenomas and 38 colorectal cancers that had been resected surgically. The nucleus, in which the copy number of the p53 signal was lower than that of chromosome 17, was determined as a deletion of the p53 gene. The mean frequency of the deletion of p53 in adenomas and cancers were 7.8% +/- 3.0% and 57.0% +/- 19.0%, respectively. Numerical aberrations of chromosome 17 or a deletion of p53 were also detected in DNA diploidy. The mean frequency of the deletion of p53 in 32 cases with aneusomy of chromosome 17 (65.7% +/- 14.5%) was significantly higher than that in cases of disomy (51.1% +/- 19.3%, P < 0.05). Even though this frequency was high in the early stage, it was not associated with any specific histopathological features. This frequency was also higher in double primary cancers (70.4% +/- 16.7%) compared with single colorectal cancers (53.4% +/- 18.1%) (P < 0.05). Using FISH, our results demonstrated that the clonal deletion of the p53 locus is an early genetic event of colorectal cancers and that a high incidence of p53 deletion may influence the occurrence of double primary cancers.

Adenoma↗

Aneusomy of chromosome 18 is associated with the development of colorectal carcinoma.

Specific loss of heterozygosity of chromosome 18 has been observed frequently in advanced colorectal carcinoma and is closely associated with its development. We investigated the prevalence of numerical aberrations of chromosome 18 in 44 specimens of colorectal carcinomas, using fluorescence in situ hybridization. We also examined the relationship between aneusomy of chromosome 18 and the clinicopathological features of these tumors. Aneusomy of the specimens (monosomy and polysomy) was determined when the same aneusomic population was detected in more than 15% of the nuclei. The frequency of monosomy and polysomy of chromosome 18 in colorectal carcinomas was 43% (19/44) and 29% (12/44), respectively. The prevalence of monosomy and polysomy 18 was significantly higher in cancers with invasion exceeding category T2 compared with T1 (P < 0.01), and with tumor size exceeding 20 mm in diameter compared with tumors less than 20 mm (P < 0.05). However, the prevalence of aneusomy 18 was not associated with other clinico-pathological features. The mean survival period and the 5-year survival rate after operation in patients with aneusomy 18 was not different from findings for those with disomy 18. Our results indicate that aneusomy of chromosome 18 is associated with the development of colorectal carcinoma; however, it is not a useful indicator of postoperative prognosis.

Adult↗

Gain of chromosome 20 is a frequent aberration in liver metastasis of colorectal cancers.

To investigate the characteristics of the numerical chromosome aberrations in liver metastasis of colorectal cancers, fluorescence in situ hybridization (FISH) for chromosomes 8, 18, 14/22, and 20 was performed in 18 specimens of primary regions and 18 of metastatic regions in liver metastasis of colorectal cancers compared with 15 of non-liver metastatic cancers. Among these numerical aberrations, the gain of chromosome 20, especially copy numbers exceeding three, was frequently observed in primary and metastatic cancers. Among these numerical aberrations, the gain of chromosome 20, especially copy numbers exceeding three, was frequently observed in primary and metastatic regions of liver metastasis groups compared with that of the non-liver metastasis group (P < 0.05). The incidences of gain of chromosome 20 in both regions of the liver metastasis group were higher than that of the non-liver metastasis group (P < 0.05). The gain of chromosome 20 is a frequent aberration in primary and metastatic regions in patients with liver metastatic colorectal cancers and may be available as a genetic marker for the diagnosis or prediction of liver metastasis.

Case-Control Studies↗

Deletion of chromosome 11 and development of colorectal carcinoma.

The deletion of chromosome 11q is observed frequently in tumors of the large intestine. To investigate the relationship between aberrations of chromosome 11 and histopathological features of colorectal carcinoma, we examined the frequency of chromosome aberrations using fluorescence in situ hybridization to 29 short-term cultured cells from surgical specimens. Numerical aberrations were not related to any factors. The deletion of chromosome 11 was frequently observed in larger (> or = 5 cm) and more invasive tumors (> or = T3 category) (p < 0.05). Furthermore, the incidence of aberrations tended to increase in Dukes' B. Although translocation of chromosome 11 was also found in 17% of cases, it was not associated with histopathological features. Our findings indicate that the deletion of chromosome 11 is closely related to the progression of colorectal carcinoma.

Chromosome Aberrations↗

[Numerical aberration of chromosome 17 is correlated with multiple primary cancer in colorectal carcinoma].

Numerical aberration of chromosome 17 of 14 cases of colorectal carcinoma with multiple primary cancer (: multiple cancer) was compared with that of 35 cases of colorectal carcinoma without any other cancer (: single cancer). Fluorescence in situ hybridization with p17H8 was performed on touch smear from fresh materials. The proportion of aneusomy 17 (NCAI: numerical chromosome aberration index) in multiple cancers was significantly higher than that of single cancers (37.7 +/- 10.5% VS 46.1 +/- 8.0%; p < 0.01). Although NCAI of single cancers conformed to cancer progression (26.1 +/- 4.7% in Dukes A, 33.1 +/- 7.1% in Dukes B, 39.9 +/- 6.9% in Dukes C, and 45.7 +/- 12.0% in Dukes D), that of multiple cancers was high in all stages (44.7 +/- 7.3%, 44.4 +/- 6.8%, 50.4 +/- 11.2%, and 49.6 +/- 5.6%, respectively). Furthermore, the multiple numerical aberration of chromosome 17 in multiple cancers was more often than that of single cancers (64.3% VS 22.9%; p < 0.01).

Aged↗