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Biomedical subjects

Yasuyuki Sugiyama

Publications and source records attributed to Yasuyuki Sugiyama.

At least 19 recordsLinked to original sources

Vascular endothelial growth factor protects hepatoma cells against oxidative stress-induced cell death.

BACKGROUND: The aim of the present study was to examine coordination of the vascular endothelial growth factor (VEGF) and VEGF receptor (Flk-1) system and to study control of VEGF expression by oxidative stress, which is considered a model for chronic liver disease. METHODS: Cell viability was determined by test method with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-dephenyl tetrazolium bromide (MTT). Expressions of cellular proteins were evaluated by western blot analysis. RESULTS: The c-Met tyrosine phosphorylation in PLC/PRF/5 hepatoma cells was increased by treatment with 20 ng/mL hepatocyte growth factor (HGF), and extracellular signal-regulated kinase (ERK) was also activated. Although Flk-1 was phosphorylated in response to VEGF (>50 ng/mL), phosphorylated ERK was not detected at these concentrations. A total of 5.0 and 10 micromol/L hydrogen peroxide (H(2)O(2)) caused cell death in a dose-dependent manner after 24 h. On western blot analysis at 1 h with H(2)O(2), rapid phosphorylation of both ERK1/2 and c-Jun NH(2)-terminal kinase (JNK) was observed. In the first 6 h, H(2)O(2) induced cell death for 58.4 +/- 6.8%, whereas the presence of 100 ng/mL VEGF improved the survival rate to 77.2 +/- 4.2%. The VEGF significantly decreased H(2)O(2)-induced cell death after 12 h, whereas HGF (20 ng/mL) did not have a similar effect. When cells were incubated with 5 micromol/L H(2)O(2), expression of VEGF protein was detected. Furthermore, H(2)O(2)-induced phosphorylation of ERK and JNK was also reduced by VEGF (100 ng/mL). In contrast, HGF did not induce phosphorylation of ERK and JNK. CONCLUSION: Hepatoma cells might be able to survive under continuous oxidative stress through expression of VEGF.

Carcinoma, Hepatocellular↗

Expression of vascular endothelial growth factor receptors is closely related to the histological grade of hepatocellular carcinoma.

Angiogenesis is important for tumor growth, and is regulated by angiogenetic factors such as vascular endothelial growth factor (VEGF). In the present study, we investigated whether or not expression of VEGF receptors (VEGFRs) is related to the proliferation of tumor cells in hepatocellular carcinoma (HCC). We simultaneously stained proliferation marker Ki-67 antigen and either VEGFR1 (Flt-1) or VEGFR2 (Flk-1) on paraffin-embedded tissue sections from 50 cases of surgically resected human HCC. Based on the staining pattern of VEGFRs, we classified the cases into 4 categories; receptor double-negative, Flt-1 single-positive, Flk-1 single-positive, receptor double-positive. Interestingly, the Ki-67 index was significantly lower in receptor double-negative cases in comparison to that in either Flt-1 single-positive or Flk-1 single-positive cases (P = 0.0491, P = 0.0196, respectively). Moreover, the index was also significantly lower in receptor double-positive cases in comparison to either Flt-1 single-positive or Flk-1 single-positive cases (P = 0.0026, P < 0.0001, respectively). We further investigated 35 cases showing a Ki67 index > 10% to determine the expression of VEGFRs on Ki-67 antigen-positive proliferating cells. Surprisingly, the histological grade of HCC and the expression pattern of VEGFRs showed a characteristic relation; the well-differentiated HCC cases were all distributed in the Flk-1-positive group (7/7), moderately differentiated HCC cases were distributed in either the Flt-1 or Flk-1 single-positive group (20/21), and poorly differentiated HCC cases were predominantly distributed in either the receptor double-negative or double-positive group (6/7). These findings suggest that the expression pattern of VEGFRs influences the histological differentiation of HCC.

Aged↗

Adenocarcinoma in bladder diverticulum, metastatic from gastric cancer.

BACKGROUND: Metastasis to the urinary bladder from gastric cancer is rare. Metastasis to a diverticulum of the bladder from gastric cancer is extremely rare. We report a case of isolated bladder metastasis from gastric cancer and invasion localized to the muscularis propria of the primary site (stomach). CASE PRESENTATION: A 90-year-old female presented with nausea and vomiting that was diagnosed as gastric cancer, the patient also had intermittent hematuria. Pelvic computed tomography identified an abnormally thickened area in the bladder wall that was diagnosed as a diverticulum of the bladder. A biopsy of the bladder wall revealed well differentiated tubular adenocarcinoma metastatic from gastric carcinoma. CONCLUSION: Almost all cases of bladder metastasis from gastric cancer had peritoneal dissemination. This particular presentation of bladder metastasis from gastric cancer, to the best of our knowledge, has not been previously reported.

Journal Article↗

Evaluation of extracellular signal regulated kinase expression and its relation to treatment of hepatocellular carcinoma.

BACKGROUND: The aim of this study was to evaluate hepatocellular carcinoma (HCC) using a combination of extracellular signal regulated kinase (ERK) and other markers related to hepatocyte growth factor (HGF) in tumor tissue. STUDY DESIGN: Using specimens from 30 hepatocellular carcinoma patients operated on in our department from 2002 to 2003, we evaluated expression levels of HGF, c-Met, ERK, and cyclin D1 by Western blot. RESULTS: Expression levels of ERK and cyclin D1 proteins were significantly higher in patients with less well-differentiated type tumors by histologic examination or the presence of intrahepatic metastasis (IM). ERK expression in tumor tissue significantly correlated with both tumor size (p=0.0017, R(2)=0.355) and serum levels of HGF (p=0.0247, R(2)=0.218). Nontumor tissue level of cyclin D1 was significantly higher in patients with poor liver function (p=0.047). In patients with higher expression of ERK in tumor tissue compared with nontumor tissue, the histologic finding was more progressed; but a similar tendency was not observed for cyclin D1. In patients with overexpression of HGF and c-Met, the expression level of ERK was significantly higher, but cyclin D1 expression was not. The detected level of cyclin D1 was significantly higher in patients with overexpressed ERK in tumor tissue. Values of ERK and c-Met were correlated, and IM presence was detected more frequently in patients with high expression of ERK and c-Met protein. Even after complete removal of visible IM tumor, recurrence tumors were detected within 6 months in 7 patients with high expressions of both ERK and c-Met protein. CONCLUSIONS: Combination study of tumor expression of ERK might be useful to estimate the properties of hepatocellular carcinoma, especially for the presence of IM.

Aged↗

Identification of an immune tolerance reaction in response to pretreatment with frozen pancreatic tissue in islet cell transplantation in rats.

OBJECTIVES: Whereas transplantation of insulin-secreting pancreatic islets may provide long-term control of glucose metabolism in patients with diabetes mellitus, transplant rejection remains a problem. In this study, we tried pretreatment with frozen pancreatic tissue in a rat model of islet cell transplantation to determine whether induction of immune tolerance is feasible. METHODS: Isolated islet cells from Wistar rats were transplanted into the spleen of recipient rats that were sensitized and rats that were not sensitized with frozen pancreatic tissue. Spleens were analyzed histologically and then examined immunohistochemically for expression of insulin, a pancreas-specific gene. With the use of cDNA primers for proinsulin, RT-PCR was performed to detect islet cells in the spleen. RESULTS: Although islet cells were present in spleens at posttransplantation day (PTD) 1, islet cell clusters in recipients without pretreatment were markedly destroyed on PTD 14 on histologic examination. In contrast, islet cell clusters in recipients sensitized with frozen pancreatic tissue appeared similar to those at PTD 1 even at PTD 14. Proinsulin gene expression was found to be specific to pancreatic tissue. In recipients sensitized with frozen pancreatic tissue, proinsulin gene expression was identified in recipient spleens, even at PTD 14, whereas it was undetected in the absence of pretreatment. In recipients transplanted with islet cells and treated simultaneously with frozen pancreatic tissue, proinsulin gene expression was completely eliminated. The immunohistologic study also showed the presence of insulin-producing islet cells in the spleens of rats sensitized with frozen pancreatic tissue. CONCLUSIONS: Inhibition of the immune reaction in transplant rejection may be mediated by pretreatment with frozen donor tissue.

Animals↗

Apoptosis induced by 5-fluorouracil, cisplatin and paclitaxel are associated with p53 gene status in gastric cancer cell lines.

In a recent study, we evaluated the efficacy and toxicity of 5-fluorouracil (5-FU), cisplatin (CDDP), and 5-FU plus CDDP (FP treatment) in gastric cancer cell lines and examined the relationship between the response to FP treatment and apoptosis. Our study indicated that there may be prognostic value in measuring p53 prior to FP treatment, and that cancers with wild-type p53 may be better candidates for FP treatment than those with mutant-type p53 in gastric cancer patients. In the present study, because cells with mutant-type p53 are suggested to be less responsive to FP chemotherapy treatment, we examined the relationship between the response to paclitaxel and apoptosis in MKN45 and MKN28 human gastric cancer cell lines by flow cytometry. In both MKN45 and MKN28 cells, paclitaxel arrested cells in the G2/M phases of the cell cycle after 24 h. Additionally, in both MKN45 and MKN28 cells, paclitaxel produced a significant rise in the number of subG1-phase cells after 72 h by the flow cytometry histogram. From these results, our previous study suggests that cells with mutant-type p53 may be less responsive to FP treatment and the present study indicates that another anti-cancer drug like paclitaxel, which might be mediated by a p53-independent pathway, should be selected. These insights may provide a new strategy for gastric cancer chemotherapy, especially second-line chemotherapy or adjuvant chemotherapy.

Antineoplastic Agents↗

The evaluation of gastric cancer sensitivity to 5-FU/CDDP in terms of induction of apoptosis: time- and p53 expression-dependency of anti-cancer drugs.

Clinical in vivo and in vitro studies have revealed pronounced gastric cancer activity using the combination of 5-fluorouracil (5-FU) and cisplatin (CDDP). In addition, the combination of 5-fluorouracil plus cisplatin (FP treatment) possesses synergistic cytotoxicity against gastric cancer. Sensitivity of two gastric cancer cell lines to anti-cancer drugs, 5-fluorouracil (5-FU) and/or cisplatinum (CDDP), was evaluated by use of either flow cytometric analysis (FACS) or morphological observation in terms of induction of apoptosis. In morphological observation, a new experimental technique was used in which cancer cells were distributed in thin collagen gel as one or two cell layers, and cultured with anti-cancer drugs. Thereafter, cells were stained with fluorescent Hoechst 33258 (Ho) and photographed, then stained with hematoxylin and eosin (H&E) and photographed again. Cell death patterns were determined by combining observations of Ho- and H&E-stained cells. While combined administration of 5-FU and CDDP did not induce apoptosis of MKN-28 (mutant-type p53), apoptotic cells were markedly observed in the case of MKN45 (wild-type p53). In addition, consecutive administration of CDDP for 3 h and 5-FU for 21 h effectively induced apoptosis of MKN45. These results indicated that the type of p53 expression in cancer cells could be a promising factor in predicting response to FP therapy and the administration of CDDP prior to 5-FU may be more effective in inducing apoptosis of gastric cancer cells with wild-type p53 expression. These data may provide evidence to support the idea that p53 expression is related to multidrug resistance (MDR) in FP therapy of gastric cancer cell lines.

Antineoplastic Agents↗

Expression of p53 protein as a predictor of the response to 5-fluorouracil and cisplatin chemotherapy in human gastrointestinal cancer cell lines evaluated with apoptosis by use of thin layer collagen gel.

Apoptosis of the target cells is an important index in the assessment of the efficacy of cancer chemotherapy. We previously established a new experimental technique in which cancer cells are distributed in thin collagen gel as one or two cell layers, and cultured with anti-cancer drugs. The cells are stained with fluorescent Hoechst 33258 (Ho) and photographed, then with hematoxylin and eosin (H&E) and again photographed. The results show that most cell death patterns can be determined by combining observations of Ho and H&E-stained cells without the necessity for judging the apoptosis by electron microscopy. 5-fluorouracil (5-FU) and cisplatin (CDDP) are important anti-cancer drugs in the treatment of a variety of cancers. 5-FU or CDDP alone have shown significant effects in the treatment of gastric and colon cancers, and in addition, it has been shown that the combination of 5-FU plus CDDP (FP) therapy produces synergism greater than 5-FU or CDDP alone in gastrointestinal cancer. In this study, we evaluated the efficacy and toxicity of FP therapy in the gastric cancer cell lines MKN45, MKN28, and KATOIII and the colon cancer cell lines HCT116 and COLO320, and examined the relationship between the response to FP therapy and apoptosis. Additionally, we performed transfection of normal p53 gene into p53 mutant MKN28 cells and analyzed the impact of the p53 gene on a sensitivity test. Wild-type p53 in MKN45, HCT116, and COLO320 cells underwent significantly (p<0.01) more apoptosis than MKN28 and KATOIII cells possessing p53 mutant- and deficient-type, respectively, in FP therapy. Transfection of p53 to MKN28 cells resulted in a significantly (p<0.01) higher apoptotic index. From these results, we conclude that the p53 pathway allows induction of apoptosis in gastrointestinal cancers in FP therapy treatment, and that identification of the p53 type of a patient's cancer can be used to predict the success of FP therapy.

Antineoplastic Combined Chemotherapy Protocols↗

p53 dependence and apoptosis in response to FP treatment with p53-transfected colon cancer cell lines by use of thin layer collagen gel.

The combination of 5-fluorouracil (5-FU) plus Cisplatin (CDDP) (FP treatment) possesses synergistic cytotoxicity against colon cancer. The molecular mechanisms by which chemotherapeutic agents induce apoptosis have been clarified by identifying apoptosis-related genes such p53 and bcl-2. We previously established a new experimental technique in which cancer cells are distributed in thin collagen gel as 1 or 2 cell layers. additionally, we evaluated the efficacy and toxicity of FP treatment in the gastric and colon cancer cell lines, and examined the relationship between the response to FP treatment and apoptosis. In these results we reported transfection of normal p53 gene into p53 mutant and analyzed the impact of the p53 gene in a sensitivity test. In this study, we examined induced apoptosis in colon cancer cell lines and the status of p53 expression in response to treatment of HCT116, COLO320, SW480 and DLD1 with 5-FU alone, CDDP alone and FP treatment under flow cytometric analysis. Transfection of SW480 and DLD1 cells was performed to compare the chemosensitivity of naturally occurring mutant-type p53 SW480 and DLD1 cells with neo-transfected SW480 and DLD1 cells and transfected SW480 and DLD1 cells. Appreciable apoptosis was induced in HCT116 and COLO320 (p53 wild-type) but not in SW480 and DLD1 cells (p53 mutant-type). Transfected SW480 and DLD1 cells underwent significantly more apoptosis (p<lt;0.001) than naturally occurring mutant-type p53 SW480 and DLD1 cells. p53 expression may further induce apoptosis in FP treatment. Patients with p53 wild-type may be better candidates for FP therapy than patients with p53 mutant-type in colon cancer. Therefore, we think that p53 may be also effective against colon cancer in FP therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Relationship between mammographic density and the risk of breast cancer in Japanese women: a case-control study.

BACKGROUND: The relationship between mammographic density and the risk of breast cancer was examined in Japanese women. The study was a matched case-control study comparing the mammographic densities of both breast cancer cases and healthy controls. MATERIALS AND METHODS: We selected 237 women who were diagnosed with a histologically verified breast cancer, and who underwent surgery at Gihoku General Hospital in Gifu, from January, 1998 to December, 1999. During the time of this study, 3,650 people participated in breast cancer screening with mammography and ultrasound together. We selected 742 women as a control group from the screening participants and matched them by age and the number of deliveries with the cancer patients. The same mammography machine was used for both cases and controls. For evaluation, we used a visual method (Wolfe's classification) and a computer assisted method to classify the mammograms based on mammographic density. RESULTS: (1) According to Wolfe's classification, the DY group had a significantly increased breast cancer risk compared with the N1 group (Relative risk (RR)=2.20, 95% confidence interval (95%CI) (1.02-4.77). (2) The group showing a high mammographic density had a significantly increased risk of breast cancer compared with the group with low mammographic density (RR=2.83, 95%CI=1.33-5.98) as classified by the computer assisted method. CONCLUSION: It is suggested that women with high mammographic densities, classified visually or by computer, have an elevated risk of breast cancer compared with those with low mammographic densities.

Asian People↗

Prediction of 5-fluorouracil and cisplatin synergism for advanced gastrointestinal cancers using a collagen gel droplet embedded culture.

PURPOSE: The combination effects of 5-fluorouracil (5-FU) and cisplatin (CDDP) are herein reported using a drug sensitivity assay, with a special focus on the induction of apoptosis. METHODS: The combination effects of 5-FU and CDDP were examined using in vitro chemosensitivity testing by means of the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in MKN45 and GSS cell lines, and primary gastrointestinal cancer cells ob-tained from 40 patients. Apoptosis was assayed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin neck end labeling (TUNEL) method. RESULTS: The combination of 5-FU with CDDP increased the efficacy of 5-FU 1.16-1.35-fold with the GSS cell line and 1.10-2.01-fold with primary gastric and colorectal cancers when the exposure time was 7 days. In primary tumor cells a synergistic action was noted in 15 of 40 (38%) gastric and colorectal cancers. Both 5-FU and CDDP were found to induce apoptosis in GSS and MKN45 cells, and the number of apoptotic cells increased synergistically after the combined treatment in the GSS cases and showed a correlation with the results of CD-DST. CONCLUSIONS: Our findings suggested that the efficacy of the combined treatment with 5-FU and CDDP can be predicted by the in vitro chemosensitivity test and that a synergistic effect might be associated with the induction of apoptosis.

Aged↗

Significance of apoptosis induced by tumor necrosis factor-alpha and/or interferon-gamma against human gastric cancer cell lines and the role of the p53 gene.

PURPOSE: The expression of the p53 gene in target cells plays an important role in the induction of apoptosis by tumor necrosis factor (TNF)-Alpha and interferon (IFN)-Gamma. We herein present a study suggesting the existence of a caspase-independent pathway from p53 via insulin-like growth factor binding protein 3 (IGF-BP3) which acts as an apoptosis induction mechanism. METHODS: MKN-45 (wild-type p53) or MKN-28 (mutant-type p53) was cultured with TNF-Alpha or IFN-Gamma either alone or together. After 24 and 48 h, the apoptotic index (AI) was determined by Hoechst staining and then compared. To clarify whether the mechanism of apoptosis is induced by TNF-Alpha and/or IFN-Gamma, apoptosis-related genes were examined by a cDNA on microarray analysis and a Western blot analysis. RESULTS: (1) The AI for MKN-45 increased at 48 h in the presence of TNF-Alpha or IFN-Gamma alone. (2) In the case of combination treatment using TNF-Alpha and IFN-Gamma, the AI for MKN-45 was higher than those in the groups with a single treatment. (3) A cDNA microarray analysis showed that IGF-BP3, the TNF superfamily, and caspase 1 were all upregulated after treatment with the combination of TNF-Alpha and IFN-Gamma. (4) A Western blot analysis of MKN-45 showed a reaction with an anti-IGF-BP3 antibody. CONCLUSIONS: These results suggest that the induction mechanism underlying apoptosis induced by TNF-Alpha and IFN-Gamma might therefore involve the caspase-independent pathway via IGF-BP3.

Apoptosis↗

Antitumor effects of residual tumor after cryoablation: the combined effect of residual tumor and a protein-bound polysaccharide on multiple liver metastases in a murine model.

Cryoablation is a low-invasive surgical treatment for malignant tumors. It may induce an immunological response leading to the eradication of distant metastases or alternatively it might promote the growth of residual tumors. In this paper we confirm the occurrence of both phenomena and we describe the preventive effect of a protein-bound polysaccharide preparation. Metastatic liver tumors were produced in BALB/c mice by the intrasplenic inoculation of colon 26 cells and cryoablation was carried out using liquid nitrogen (-170 degrees C) applied by a contact method. The value of combining cryoablation with administration of the polysaccharide preparation in the prevention of growth of residual tumors was investigated. It was shown that the number of metastatic liver nodules and the size of the primary tumor at the site of inoculation in the spleen were significantly lower when the volume that was frozen was small. The production by splenocytes of the tumor necrosis factor TNF-alpha, interferon INF-gamma, and the interleukins IL-4 and IL-10 increased significantly after freezing and thawing of the tumor tissue. The polysaccharide treatment significantly reduced the production of IL-4 and IL-10 following cryoablation; the production of TNF-alpha and INF-gamma was slightly promoted; the natural killer and cytotoxic T-cell activities of splenocytes were slightly enhanced. It was concluded that the polysaccharide preparation was beneficial by suppressing IL-4 and IL-10 production and might inhibit the growth of residual tumor that is sometimes induced by large-volume cryoablation.

Animals↗

Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers.

PLK (polo-like kinase), the human counterpart of polo in Drosophila melanogaster and of CDC5 in Saccharomyces cerevisiae, belongs to a family of serine/threonine kinases. It is intimately involved in spindle formation and chromosome segregation during mitosis. The purpose of this study was to determine whether PLK1 is overexpressed in primary colorectal cancer specimens as compared with normal colon mucosa and to assess its relation to other kinases as a potential new tumor marker. In the present study, immunohistochemical analyses were performed of PLK1 expression in 78 primary colorectal cancers as well as 15 normal colorectal specimens. Furthermore, we examined the relationship between other kinases, Aurora-A and Aurora-C, and PLK1 expression. In normal colon mucosa, some crypt cells showed weakly positive staining for PLK1 in 13 out of 15 cases, the remaining cases being negative. Elevated expression of PLK1 was observed in 57 (73.1%) of the colorectal cancers, statistically significant associations being evident with pT (primary tumor invasion) (P=0.0006, Mann-Whitney U test), pN (regional lymph nodes) (P=0.008, chi2 test) and the Dukes' classification (P=0.0005, Mann-Whitney U test). Mean proliferating cell nuclear antigen-labeling index was 52.3%, with a range of 24.1% to 77.3%. Values for lesions with high and low PLK1 expression were 54.7+/-10.3% (mean+/-SD) and 45.9+/-11.9% (P=0.002, Student's t test). PLK1 was significantly associated with Aurora-A, but PLK1 staining was more diffuse and extensive than for Aurora-A or Aurora-C. Interestingly, PLK1 overexpression was significantly associated with p53 accumulation in colorectal cancers. Our results suggest overexpression of PLK1 might be of pathogenic, prognostic and proliferative importance, so that this kinase might have potential as a new tumor marker for colorectal cancers.

Adenocarcinoma↗

[Cryoimmunological therapy with local injection of OK-432 against advance or recurrent breast cancer].

A total of 5 breast cancer patients, 2 with far advanced primary breast tumor and 3 with local recurrent tumors on their anterior chest wall, underwent multimodal therapy in which cryosurgery was performed in combination with local injection of the non-specific immunopotentiator OK-432. This multimodal therapy was repeated as many times as possible. In addition, all patients were treated with mild chemotherapy. In every patient who underwent cryosurgery combined with locoregional immunotherapy, eradication or reduction of tumor was observed for several months. In 3 of the patients who underwent cryosurgery, locoregional immunotherapy and systemic chemotherapy, the tumor burden decreased markedly in 2 patients even though the diameter of tumor was over 5 cm in both cases. In case 1, we examined the concentration of IFN-gamma and IL-10 before and after cryosurgery. The value of IFN-gamma/IL-10 increased from 3.0 to 6.1 after treatment. All patients experienced high fever within 2 days after surgery, but no other side effects resulted from either cryosurgery or locoregional immunotherapy. All patients maintained good QOL throughout their therapy. These results indicate that cryosurgery in combination with local injection of OK-432 should be a feasible modality against unresectable breast cancer on the chest wall, and that this therapeutic effect may be augmented by mild chemotherapy.

Aged↗

[Percutaneous cryoablation therapy under local anesthesia for unresectable metastatic liver tumors].

Even though liver resection is the first choice against metastatic liver tumors, oncologists are often obliged to include other treatment modalities depending on metastatic tumor size, number of metastatic nodules, location of tumors, patient's general condition, and so on. Among others we selected cryoablation therapy against unresectable tumors and examined its usefulness clinically in 5 patients. Under local anesthesia, the cryoprobe, which was 3 mm in diameter, was introduced into the center of the tumor by use of an ultrasonographic guiding technique. In the middle of the freezing process, through ultrasonography we could clearly monitor the target tumor, which would change into an ice ball. It was noteworthy that not only the treated tumor but also untreated tumors were reduced in 2 cases. Because of extra-hepatic metastases, 3 patients died within 1 year after the therapy, while 2 patients are alive. This modality was easily repeatable and was minimally invasive with little toxic effect. In addition, it did not worsen quality of life (QOL). The above results indicate that cryoablation therapy could be a feasible modality against unresectable metastatic liver tumors.

Adenocarcinoma↗

[Relation between p53 expression of human colon cancer cell lines and induction of apoptosis by anticancer drugs].

The relation between p53 expression of human colon cancer cell lines and induction of apoptosis by anticancer drugs was examined experimentally. HCT116 had wild-type p53 expression and 5-fluorouracil (5-FU) in combination with cisplatinum (CDDP) increased both Sub G1 DNA content and the proportion of apoptotic cells. However, solitary administration of these drugs altered neither. Alternatively, for SW480 with mutant-type p53 expression, both combined administration and solitary administration of anticancer drugs showed minimal effect on Sub G1 DNA content and proportion of apoptotic cells. These results indicate that the type of p53 expression might play an important role in the determination of response to low-dose CDDP + 5-FU therapy in colon cancer patients.

Antineoplastic Agents↗