Atrial adipofibrosis in a dog.
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Adipose Tissue↗
Biomedical subjects
Y Une
Publications and source records attributed to Y Une.
Hepatocyte growth factor enhances the invasion activity of human hepatocellular carcinoma cell lines.
We investigated whether hepatocyte growth factor (HGF) enhances the invasion activity of three human HCC cell lines, HLF, HLE, and HC-4, in vitro. The analysis of the invasiveness consisted of the production of u-PA and the chemotaxis for fibronectin. Invasion activity of all cell lines was enhanced by the addition of recombinant human hepatocyte growth factor (rhHGF) to the medium. HGF stimulated the production of u-PA in HLF cells. HGF accelerated the chemotaxis of HC-4 and HLE. These data suggest that HGF increase the invasion activity of human HCC cell lines by affecting the production of u-PA or the chemotaxis for fibronectin.
Carcinoma, Hepatocellular↗
[Comparison of crossing-over between 30-minute drip infusion vs 30-second injection of granisetron for nausea and vomitting with cisplatin].
Recently, Granisetron (KYT) was proved to have a strong effect for cisplatin (CDDP)-induced emesis. We compared the effect of KYT for CDDP-induced emesis between two different administration schedules. Forty micrograms/kg of KYT was administered either by 30-minute drip infusion with 100 ml of saline (Group A) or 30-second injection with 10 ml of saline (Group B). We investigated the therapeutic effect of KYT in both group A and Group B by the crossing-over method. After the patients who had a malignant tumor and were going to receive CDDP (over 50 mg/m2) in two courses were selected, KYT was administered by the method of Group A or Group B in a double-blind comparison. The clinical efficacy was at least "effective" in 70% (7/10) of Group A and Group B. The study treatment was considered "useful" in 80% (8/10) of Group A, 90% (9/10) of Group B, and "safe" in 100% of Group A and B. There was no difference between two groups in this respect. The results showed that the slow intravenous injection of KYT also has an excellent antiemetic effect on CDDP-induced emesis and a high degree of safety.
Adult↗
Involvement of macrophage migration inhibitory factor (MIF) in the mechanism of tumor cell growth.
BACKGROUND: Macrophage migration inhibitory factor (MIF) was recently rediscovered as a cytokine, pituitary hormone, and glucocorticoid-induced immunomodulator. MIF is constitutively expressed in various cells and enhances production of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, and interferon gamma. Recently, it was reported that MIF mRNA was overexpressed in prostatic tumors, which suggests that MIF is a protein involved in tumor cell growth beyond inflammatory and immune responses. MATERIALS AND METHODS: We examined the expression of MIF in the murine colon carcinoma cell line colon 26 by Western and Northern blot analyses and immunohistochemistry. Next, we investigated the effects of transforming growth factor (TGF) beta, basic fibroblast growth factor (b-FGF), and platelet-derived growth factor (PDGF) on the expression of MIF mRNA. Furthermore, we examined whether MIF is involved in tumor cell proliferation, using an MIF anti-sense plasmid transfection technique. RESULTS: We demonstrated that MIF protein and its mRNA were highly expressed in colon 26 cells, using Western and Northern blot analyses, respectively. By immunohistochemical analysis, we found that MIF was localized largely in the cytoplasm of the tumor cells. In response to TGF-beta, b-FGF, and PDGF, MIF mRNA expression was significantly up-regulated. Following this, we transfected the cells with an anti-sense MIF plasmid, which revealed that this treatment induced significant suppression of cell proliferation. CONCLUSION: Although MIF plays multifunctional roles in a broad spectrum of pathophysiological states, little has been done to investigate the role of this protein in association with tumor growth. The current results suggest the possibility that MIF induces tumor cell growth in concert with other growth factors, which encouraged us to investigate a novel approach for tumor therapy using an anti-MIF antibody and an MIF anti-sense plasmid transfection technique.
Animals↗
Association of reduced cell adhesion regulator messenger RNA expression with tumor progression in human hepatocellular carcinoma.
The recently identified cell adhesion regulator (CAR) modulates the process of integrin-mediated cell adhesion. The CAR gene is located on 16q, a locus at which high levels of allelic losses have been demonstrated in advanced human hepatocellular carcinoma (HCC). We studied the possible involvement of the CAR gene in the progression of HCC. With this aim, we determined the expression of CAR mRNA in 30 cases of HCC. Matching pair samples of tumor and adjacent nontumoral liver were analyzed by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The results were compared with the clinicopathological features of the patients. Every nontumoral liver tissue sample analyzed, expressed CAR mRNA. All tumor samples showed amounts of expression that were equal or lower, compared with those found in their matching controls. Thus, in 16 out of 30 cases (53.3%), CAR mRNA expression in tumor was diminished to less than one tenth of that observed in nontumoral tissue. This group of patients exhibited higher amounts of alpha-fetoprotein, and comprised tumors with poor histological differentiation (Edmondson-Steinert's grades III-IV), higher rates of intrahepatic metastasis and recurrence within the first postoperative year (p < 0.05, respectively). Tumors exhibiting low levels of CAR mRNA were also found to be diagnosed at more advanced TNM stages (p < 0.01). We conclude that downregulation of CAR mRNA expression may play an essential role in the progression of HCC.
ATPases Associated with Diverse Cellular Activitie↗
Intraperitoneal dissemination probably caused by needle biopsy of alveolar echinococcosis of the liver: experimental study.
Alveolar echinococcosis of the liver (AEL) is a parasitosis with a potential for malignant tumor-like behavior. The disease is diagnosed by a combination of serologic tests, diagnostic images, and the histology of needle biopsy specimens. It remains unresolved whether the biopsy induces subsequent troubles. We designed this study to investigate critical problems after needle biopsy of AEL lesions using an experimental model. Five samples were prepared from the resected lesions of AEL patients: (A) 10% suspension of trypsin digests of the minced lesion; (B) 10% suspension of mesh-filtered sediment of the minced lesion; (C) 10% sediment suspension after washing the nonminced lesion; (D) supernatant after centrifuging intracystic fluid; (E) 10% sediment suspension after centrifuging intracystic fluid. A 1-ml aliquot of each sample was injected intraperitoneally into jirds (gerbils) or cotton rats, respectively. The animals were sacrificed 12 weeks later, and intraperitoneal metacestodes were observed. All samples except D developed metacestodes, and their histologies were all lesions of typical alveolar echinococcosis. These results suggest that a needle biopsy may cause intraperitoneal dissemination or tracial implantation of the parasites along the track of the needle.
Animals↗
TNP-470 antiangiogenic therapy for advanced murine neuroblastoma.
The finding that angiogenesis plays an important role in the progression and metastasis of malignant tumors has led to the development of several antiangiogenic drugs. The authors report here an examination of the effect of the antiangiogenic agent TNP-470 on the growth, metastases, and survival of two differing murine neuroblastoma cell lines, TBJ and C1300. We found that TNP-470 significantly reduced primary tumor volumes in mice injected with either cell line. In addition, antiangiogenic therapy significantly reduced the size of axillary lymph node metastases in both groups as well as decreased the size of liver metastases in mice receiving TBJ neuroblastoma. TNP-470 treatment also improved animal survival. These data suggest that antiangiogenic therapy retards the growth of primary and metastatic murine neuroblastoma. We speculate that antiangiogenic therapy may be a useful therapeutic modality in the treatment of advanced neuroblastoma once side effects and appropriate dosage requirements are determined.
Animals↗
Efficacy and safety of preoperative percutaneous transhepatic portal embolization with absolute ethanol: a clinical study.
BACKGROUND: Preoperative portal embolization has been performed by using various thrombogenic substances to increase the safety and resectability of liver surgery. We evaluated the clinical safety and efficacy of using absolute ethanol in preoperative portal embolization. METHODS: Our study included 19 patients who had undergone right hepatic lobectomy. According to our criteria for right lobectomy of the liver, seven patients were not appropriate for the operation because of a high risk in each of postoperative liver failure. Those patients received preoperative right portal embolization with 11 to 32 ml absolute ethanol. The remaining 12 patients satisfied our criteria and received no preoperative embolization. RESULTS: Although alanine aminotransferase concentrations increased dramatically after the embolization, all serologic changes reverted within 3 weeks. The mean volume of the nonembolized lobe increased from 320 cm3 to 619 cm3 and 667 cm3 2 and 4 weeks, respectively, after embolization. The mean regeneration rate of this lobe was 21.3 cm3 per day for the first 2 weeks and 11.4 cm3 per day for the first 4 weeks after embolization. All patients underwent right lobectomy of the liver and survived; none of the patients had severe complications associated with embolization or surgery. The postoperative survival periods were not statistically significant between the patients with and without preoperative portal embolization. CONCLUSIONS: According to our criteria for liver surgery, the seven patients should not have undergone major surgery, but each underwent right lobectomy of the liver and all survived, showing that portal embolization with absolute ethanol brings about compensatory hepatic hypertrophy for major surgery and that its extreme effect on liver regeneration could widen the range of patients appropriate for liver surgery.
Adult↗
Characterization of a liver metastatic variant of murine colon 26 carcinoma cells.
Intraportal vein injection of highly metastatic L5 cells consistently resulted in liver metastases (increases in the number of tumor colonies in the liver), whereas inoculation of P cells rarely did. L5 cells invaded the basement membrane Matrigel in greater numbers than did P cells, suggesting that the metastatic potential of L5 cells is partly related to enhanced invasive properties. The enhanced adhesion of L5 cells to fibronectin-, laminin- and Matrigel-coated substrates, as well as their haptotactic migration to fribronectin, may be associated with the preferential expression of VLA-2 and VLA-4 integrins on the surface of these cells detected by flow cytometry. Gelatin zymograms showed that the degradative activity of 72-kD gelatinases was greater in L5 cells than P cells. These results indicate that, in addition to adhesiveness and motility, the invasive ability of L5 cells may also be attributed to enhanced gelatinolytic activity. L5 cells grew more rapidly than P cells in vitro. Thus, an experimental model using highly metastatic colon 26 L5 cells would be useful for analyzing the molecular mechanism of liver metastasis and for evaluating the efficacy of treatment of occult micrometastases which may already have been disseminated at the time of surgery.
Adenocarcinoma↗
[Clinicopathological study on early recurrent hepatoma and its treatment].
Early Recurrence of Hepatoma: PCNA Labeling Index and DNA Ploidy Pattern Sixty-four cases of recurrent hepatocellular carcinoma (HCC) after hepatectomy were divided into two groups; E-group with recurrence within one year, and L-group with recurrence after 1 year. Clinicopathological features and surgical curability were the same in both groups. E-group had significantly higher positive rates of portal invasion, intrahepatic metastasis and rate of patients with more than 40% on PCNA labeling index. While the similar recurrence mode and the same treatment modalities were done, cumulative survival rates after recurrence in E-group had a poorer prognosis than L-group. These results suggest the possibility of lower response for the treatment on the recurrent lesion would be manifest in the E-group. New modalities for prevention of early recurrence of HCC after resection should be developed.
Aged↗
[Prognosis and preoperative imaging of patients with small hepatocellular carcinoma].
We conducted a retrospective study on the relation of the preoperative imaging patterns to the prognosis of patients with small HCC after hepatectomy. Forty patients with small HCC less than 2 cm in diameter without vascular invasion were enrolled in this study. There were no significant differences in the signal intensity of T1WI on MRI, and angiographic findings such as neo-vascularity or tumor stain. Ultrasonographical images of the internal of tumor were classified into two groups. Six cases with homogeneous pattern were significantly worse in cumulative survival rate than 28 cases with heterogeneous pattern (p = 0.0012). The same results were obtained with respect to limitation of cases treated by relative curative operation (p = 0.0041). It was concluded that histopathological grading and malignant potential of small HCC could be evaluated by classification of the pattern of internal ultrasonographical images, and complete locoregional therapy, and that intense course observation for cases with ultrasonographical homogeneous pattern would be important.
Carcinoma, Hepatocellular↗
Evaluation of surgical resection for small hepatocellular carcinomas.
BACKGROUND: The surgical results for small hepatocellular carcinomas (HCCs) are not necessarily satisfactory. The resectional therapy for small HCC was evaluated to elucidate its benefits and limitations. PATIENTS AND METHODS: Data were analyzed concerning 52 patients having small HCC of <3 cm in diameter and <3 nodules, who underwent hepatic resections from 1978 to 1989. RESULTS: Cumulative and disease-free survival at 5 years after resection were 57% and 37%, respectively. Histologic features, such as differentiation of HCCs, pseudocapsular invasion, and ploidy pattern of nuclear DNA, appeared to be good prognostic indicators. The survival rate of the large-resection group (number of resected segments greater than number of tumor-occupying segments) was significantly better than that in the small-resection group (84% versus 48% at 5 years, P<0.05). CONCLUSIONS: Surgical resection of small HCCs is a safe and effective therapy. A large resection appears to provide better patient survival and tumor-free survival compared to a small resection.
Adult↗
Selective portal vein embolization with absolute ethanol induces hepatic hypertrophy and makes more extensive hepatectomy possible.
Portal vein embolization has been used recently to decrease the amount of the liver to be resected and to enhance the function of the remaining hypertrophied lobes. We have observed a strong contact destructivity of absolute ethanol and used it for portal vein embolization. The present study was performed to produce hepatic hypertrophy and to show histopathologic changes that follow ethanol embolization of rat liver. Hepatic proliferation and histopathology were studied in rats receiving low and high doses of absolute ethanol via portal vein and rats undergoing 70% hepatectomy alone. The liver weight of the unresected and unembolized lobes increased rapidly after embolization and hepatectomy. Although the increase was more rapid in the high-dose group than the low-dose group in early days, the final results were not different from each other and were almost equal to those after hepatectomy. Complete obstruction of portal venous branches and massive necrosis were the main histopathologic observations after portal vein embolization with all doses of ethanol. Because the mortality rate in the low-dose group was lower than in the high-dose group and extensive necrosis of the liver parenchyma and subsequent regeneration was sufficient, using minimum dose of ethanol was much safer. Based on the biochemical and hematologic parameters, portal vein embolization with low-dose ethanol did not impair liver function more than hepatectomy alone during the initial 14 days. Portal vein embolization with absolute ethanol makes more extensive hepatectomy possible by reducing the volume necessary to resect and preserves the function of the remaining liver.
Animals↗
A pharmacological pilot study: application of an intermittent schedule of oral uracil and ftorafur (UFT) for hepatocellular carcinoma patients.
Patients with hepatocellular carcinoma (HCC) are highly compromised by failing liver function. To retain good compliance in the administration of uracil and ftorafur (UFT) in such patients, an intermittent schedule for oral administration of UFT was expected to have the same effect as daily continuous use without affecting liver function. A pharmacological pilot study was carried out to confirm the efficacy of this schedule. Sixteen patients with HCC who underwent hepatectomy were given UFT 200 mg b.i.d. for five consecutive days. Blood samples were drawn before the last administration of UFT and at the operation (2 days after the last administration of UFT), and the tumor and adjacent liver tissue were collected. The concentration of ftorafur (FT), 5-fluorouracil (FUra) and uracil (Ura) in serum and liver tissue were measured. Oral administration of UFT 200 mg b.i.d. resulted in a trough level of FT, FUra and Ura in serum of 9.4 micrograms/ml, 13.3 ng/ml and 64.2 ng/ml, respectively. At the operation, FT and FUra in serum had decreased significantly. However, FUra in tissue was still higher than that in serum, in contrast to the results for FT and Ura. There was no difference in the concentration of FUra between the tumors and adjacent liver tissues. No side effect was noted in any of the patients. These results indicated that an intermittent schedule for the administration of oral UFT is not only tolerable but also effective because a sufficient concentration of FUra in the liver tissue is reached and maintained.
Adult↗
Hepatitis and hepatocellular carcinoma in two prairie dogs (Cynomys ludovicianus).
In two blacktailed prairie dogs (Cynomys ludovicianus), hepatocellular carcinoma with metastasis to the lung, co-existing chronic active hepatitis, and hyperplasia of hepatocytes in the non-neoplastic areas of the liver tissue were observed. The hyperplastic hepatocytes had many eosinophilic inclusion bodies positive for orcein stain in their cytoplasm. Electron microscopy revealed areas of a specific mail-like mesh structure in the location of the cytoplasmic inclusion bodies. Ultrastructure of inclusion bodies differed from that of the hepadna virus usually associated with hepatocellular carcinoma, and hepadna virus-like particles were not observed.
Animals↗
[Efficacy of intra-arterial chemotherapy with reservoir for patients with unresectable hepatocellular carcinoma].
Long-term results of intra-arterial chemotherapy using a reservoir (IA) for patients with unresectable hepatocellular carcinoma (HCC) were investigated. Ninety-nine patients with unresectable HCC who were treated in our department during the past 7 years were enrolled in this study. Thirty-four out of the 99 patients were treated by IA with a conventional reservoir (SR group), and 21 by IA with a double-lumen reservoir (DR group) by which IA with occlusion of hepatic arterial flow would be possible. The other 44 patients were treated by transcatheter arterial embolization (TAE group). Cumulative 1-and 2-year survival rates were 54.2 and 21.7% in DR group, respectively, and 50.8 and 35.2% in TAE group, respectively. The results of these two groups were statistically equivalent, and were more favorable than those of the SR group. Cumulative patency rate of reservoirs was maintained at 93.7% after one year and at 61.8% after two years. No difference was recognized in this rate according to the type of reservoir. We concluded that IA with a double-lumen reservoir should be taken into consideration as one of the strategies for treatment of unresectable HCC. However, maintenance of catheter-patency would be necessary for satisfactory outcome.
Antineoplastic Combined Chemotherapy Protocols↗
[DNA ploidy pattern in resected human hepatocellular carcinomas from the view point of biological malignant potential].
Nuclear DNA ploidy analysis was studied in patients with hepatocellular carcinoma (HCC) who underwent hepatic resections. These patients were classified three groups according to the following prescriptions. Group A (n = 100) was a group of patients of which excluded ones treated by absolute non-curative resection, Group B (n = 43) was patients who underwent absolute curative resection or relative curative resection, and Group C (n = 81) was patients whose tumor sizes were more than 2 cm in Group A. Aneuploid pattern was found in 59 cases (59.0%) in Group A, 22 cases (51.2%) in Group B and 54 cases (66.7%) in Group C. The rate of aneuploid pattern was significantly higher in patients with carcinomas more than 2 cm in diameter, fc-inf positive growth, Stage III + IV and PCNA LI > or = 40% in Group A, those with carcinomas more than 2 cm in diameter, fc-inf positive growth, im-positive and Stage III + IV in Group B, and those with PCNA LI > or = 40% in Group C. The postoperative prognoses of patients with aneuploid pattern in Group A and Group C were significantly poorer than those of the diploid one in cumulative survival rates and survival rates after recurrence. Patients with aneuploid pattern in Group B had a poorer prognosis than those with diploid one in cumulative survival rates and disease-free survival rates. These results suggest that nuclear DNA ploidy analysis was a useful marker of biological malignant potential in resected human HCCs.
Carcinoma, Hepatocellular↗
[A case of hepatocellular carcinoma treated by intra-arterial infusion chemotherapy using THP-adriamycin].
A 46-year-old male with unresectable hepatocellular carcinoma (HCC) comprised of severe liver dysfunction was treated by intra-arterial infusion chemotherapy through an implantable reservoir. During 39 months, a total amount of THP-ADR 420 mg, ADR 70 mg and CDDP 350 mg was infused. Through the therapy, the tumor size on the lateral segment was well controlled, and serum AFP and PIVKA-II levels were also lowered. No severe side effect was observed. The patient was treated on an outpatient basis, and a good quality of life during therapy was maintained. This case suggests that THP-ADR may play an important role in a combined intraarterial chemotherapy for advanced HCC.
Antibiotics, Antineoplastic↗