Effects of hyperthermia on multidrug-resistant human hepatocellular-carcinoma.

The effects of hyperthermia (HT) on multidrug-resistant human hepatocellular carcinoma (HCC) were evaluated experimentally. This tumor, an AFP-producing human HCC, in which MDR1 mRNA and P-glycoprotein were overexpressed, was transplanted subsequently on nude mice. Ten days after the inoculation of the tumor into the rear section of the nude mice, either or both an intra-peritoneal injection of 8 mg/kg of adriamycin (ADR) was administered or hyperthermia (HT) was induced. HT was performed immediately by immersing the mice into a water bath at a temperature of 42-degrees-C for a period of 30 minutes. Hyperthermic therapy combined with ADR significantly inhibited the tumor growth compared with ADR or HT alone. Using ADR in combination with HT, the ADR concentration in the tumor remained at a significantly higher level for a prolonged period compared with ADR alone. The results indicate that HT enhanced the anti-tumor effect of chemotherapy even for multidrug-resistant HCC.

Relationship between mdr-1 messenger-RNA expression and anticancer drug-sensitivity in human hepatocellular-carcinoma cell-lines.

We examined the relationship between chemosensitivity and the expression of mdr-1 and P-gp in ten human HCC cell lines. Expression of P-gp was detected immunohistochemically and the expression of mdr-1 mRNA by the reverse transcriptase polymerase chain reaction (RT-PCR). Chemosensitivity was determined by the MTT assay. P-gp was positive in nine of the ten lines. mdr-1 mRNA expression was found in five. All cells lines positive for mdr-1 mRNA expression expressed P-gp. We could not demonstrate a correlation between mdr-1 or P-gp expression and drug resistance. We conclude that drug-resistance in HCC cells depends not only on mdr-1 but also on other factor(s).

Different chemosensitivity of pre and postmenopausal breast-cancer cells.

In order to refine our adjuvant chemotherapy against locally advanced breast cancer, an anticancer drug sensitivity test, using the MTT assay was conducted with biopsy specimens of human breast cancer obtained prior to therapy. Dose-dependent sensitivity was observed with all tested agents: cisplatinum, mitomycin C, methotrexate and doxorubicin. The sensitivity of the premenopausal specimens to the effects of mitomycin C and doxorubicin varied widely. When selecting chemotherapeutic agents to combat breast cancer, this variation in drug sensitivity based on menopausal status and patient age should be considered.

Effects of tnp-470 (agm-1470) on tumor-growth, angiogenesis and serum copper levels in liver-cancer bearing rats.

Administration of TNP-470 (AGM-1470), a newly developed angiogenesis inhibitor, elevated serum copper concentrations (SCu) in a dose-dependent manner in normal rats as well as tumor-bearing rats. After discontinuation of TNP-470, SCu returned to the normal range in normal rats. In tumor-bearing rats, however, SCu decreased and then became elevated in relation to the tumor growth and capillary density in this hepatic tumor. The mechanisms leading to serum copper elevation may reflect a specific pharmacologic action of TNP-470, though it may also be related to tumor growth and reactivation of tumor angiogenesis after cessation of TNP-470.

Streamline phenomena in liver metastasis of gastrointestinal tumor - an experimental-study using rats.

The establishment of liver metastasis from gastrointestinal tumor is mainly considered to be via the portal vein, but its precise mechanism is still unknown. The purpose of this study is to evaluate the significance-of 'streamline' phenomena in liver metastasis of gastrointestinal tumor by means of an experimental model. An animal model for the metastatic liver tumor was made in the Donryu rat. Five million cells of AH-66 strain, alpha-fetoprotein (AFP) producing hepatoma cells maintained as an ascites type strain, were administered via portal vein. The superior mesenteric vein (group A), the inferior mesenteric vein (group B) and the splenic vein (group C) were used as the sites of injection. In every group, serum AFP levels were elevated after administration of AH-66 cells and no significant differences were revealed between each group. In the pathological specimens of the liver taken after 7 days, many tumorous lesions were seen microscopically with islet formations, but no definitive difference was seen in each lobe. The serum AFP concentration in group A was significantly higher than that in group C. The tissue AFP concentrations of the right lobe were significantly higher than those of the left in groups A and B, but significantly lower than those of the left lobe in group C. The results indicate that the distribution and proliferation of tumor cells administered via portal vein differed depending upon the site of tumor injection in accordance with the 'streamline' phenomena.

Anesthetic management of a patient with myasthenia gravis during hypothermic cardiopulmonary bypass.

The anesthetic management of a patient with myasthenia gravis (MG) who underwent cardiac surgery with hypothermic cardiopulmonary bypass (CPB) is described. Using total intravenous anesthesia with propofol and a moderate dose fentanyl, the variations of neuromuscular function and serum anti-acetylcholine receptor antibody concentration were examined in relation to hypothermic CPB in the absence of muscle relaxants. The anesthetic technique used may have helped to avoid the risks incidental to muscle relaxants in this patient with MG undergoing hypothermic CPB.

[Chemosensitivity test for thyroid cancer by in vitro MTT assay].

In vitro MTT assay was applied for examining chemosensitivity with 50 thyroid cancers; 47 papillary cancers, 1 follicular cancer, 1 anaplastic cancers, and 1 medullary cancer. Anticancer drugs examined were 5-fluorouracil (5-FU), cisplatin (CDDP), adriamycin (ADM), etoposide (VP-16) and ifosfamide (IFO) (active type). Their efficacy was as follows: 5-FU 0%, CDDP 40.9%, ADM 0%, VP-16 5.3%, IFO 48.5%. Anaplastic cancer and medullary cancer showed no sensitivity to all tested drugs. We compared the chemosensitivity between cancer tissue and normal tissue. CDDP was more effective in cancer tissue than in normal tissue. Chemosensitivity of CDDP depended on the drug concentration but 5-FU did not. CDDP and IFO might be useful against human differentiated thyroid cancer.

[Chemosensitivity test on hepatocellular carcinoma (HCC) and drug resistance].

UNLABELLED: 10 HCC cell lines and 122 surgically resected HCC were studied on chemosensitivity to 6 anticancer agents. Succinic dehydrogenase inhibition test was used for evaluating chemosensitivity of HCC. The HCC cell lines were positive in sensitivity to the most anticancer agents except 5-FU. Sensitivity of resected HCC specimens was positive in 17/42 (40.5%) to exposed to VP-16, in 21/57 (36.8%) to IFM, but also it was positive in 40/46 (87.0%) of the non-cancer tissue of the same liver exposed to VP-16 and in 33/60 (55.0%) to IFM. So VP-16 and IFM were probably considered to injure the residual liver after hepatectomy. In immunostainings of P-gp, GST-pi, MT, and P-450 of HCC cell lines, the expression of P-gp correlated with MDR1 mRNA and chemosensitivity test to ADM. Correlation between the expression of GST-pi and chemosensitivity test to ADM and CDDP were considered to be probably recognized. However, in surgically resected HCC, correlation among those factors was not observed. IN CONCLUSION: P-gp, MDR1 gene and GST-pi have probably a role in drug resistance in HCC. Selection of anticancer agents after chemosensitivity tests on both HCC and normal tissue of liver should be performed. We need more investigation for how the results of chemosensitivity test correlate with clinical effectiveness.

Differential diagnosis of vertical root fractures using reconstructed three-dimensional models of bone defects.

OBJECTIVES: The purpose of this study was to evaluate the accuracy of diagnosing vertical root fractures (VRFs) by comparing the volume of bone defects in VRFs with those in non-VRFs on reconstructed three-dimensional (3D) models (TDMs) using CBCT. METHODS: 32 maxillary pre-molars and anterior teeth with radiolucent areas were evaluated on pre-operative CBCT images. Of the 32 teeth, 16 had a fractured root (VRF group) and 16 had a non-fractured root (non-VRF group). The radiolucent area of each tooth was traced in each dimension [mesiodistal, buccolingual and horizontal (the apicoincisal aspect)] by two observers, and 3D images were reconstructed with the Amira(®) software (Visage Imaging Inc., Richmond, Australia). The volume, V, of the TDM was divided into the coronal side and the periapical side at the horizontal slice through the apical foramen, and v was defined as the volume of the coronal side. The values of v/V were calculated for all cases. The Mann-Whitney U test was used to compare values between the VRF group and the non-VRF group (p < 0.05). A receiver operating characteristic (ROC) curve was constructed to select the optimal cut-point. RESULTS: There was a statistically significant difference in the value of v/V between the two groups (p < 0.05). With a cut-point derived from the ROC curve, and the sensitivity, specificity and accuracy of predicting the VRFs were 1.00, 0.75 and 0.88, respectively. CONCLUSIONS: Lesions resulting from VRFs can be distinguished from those of non-VRFs on 3D CBCT images with a high degree of accuracy, based on their different 3D shapes.

Development of torsade de pointes caused by exacerbation of QT prolongation during clipping of cerebral artery aneurysm in a patient with subarachnoid haemorrhage.

We report the case of a 79-yr-old woman with subarachnoid haemorrhage (SAH) in whom torsade de pointes (TdP) caused by worsening the QT prolongation occurred during clipping of cerebral artery aneurysm. This patient shows a potential risk of occurrence of life-threatening tachyarrhythmia, TdP by prolonging the QT interval during surgery in patients with SAH even with no additional factors that predispose to TdP. Therefore, a proper monitoring of the QT interval is necessary as a predictor of TdP. When ventricular tachyarrhythmia occurs, recognition of TdP is important because antiarrhythmic drug therapy for TdP is different from that for ventricular tachyarrhythmias that is not TdP.

Airway management for an uncooperative patient with recessive dystrophic epidermolysis bullosa.

We describe a case of an unco-operative patient with recessive dystrophic epidermolysis bullosa in whom difficult tracheal intubation was anticipated and fibreoptic bronchoscope guided tracheal intubation was successfully achieved after induction of general anaesthesia. Other problems in airway management associated with this disorder are discussed.