Stimulatory effects of lipoprotein(a) and low-density lipoprotein on human umbilical vein endothelial cell migration and proliferation are partially mediated by fibroblast growth factor-2.

We previously reported a transient increase in plasma lipoprotein(a) (Lp(a)) concentrations following acute myocardial infarction and surgical operations, and demonstrated Lp(a) accumulation in healing tissues. In the present study, the stimulatory effect of Lp(a) on migration and proliferation of human umbilical vein endothelial cells (HUVEC) was assessed by quantitative assay methods and compared it with that of LDL. Lp(a) stimulated both migration and proliferation of HUVEC in a dose-dependent manner and the stimulatory activities for migration and proliferation were two times higher than those of LDL in terms of moles of apoB. In addition, this stimulatory activity of Lp(a) was not affected by the difference of Lp(a) phenotype. Although each neutralizing antibody to hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and interleukin-1beta (IL-1beta) had no further effect on migration and proliferation of HUVEC treated with Lp(a), only antibody to fibroblast growth factor-2 (FGF-2) partially suppressed them. Moreover, pertussis toxin, which inhibits FGF-2-stimulated endothelial cell movement, also partially suppressed Lp(a)-induced HUVEC migration. FGF-2 concentrations in the medium of HUVEC treated with Lp(a) were constant in spite of the increase in FGF-2 mRNA levels in HUVEC. Taken together, it is suggest that Lp(a) stimulates HUVEC migration and proliferation, which is mediated, at least in part, by FGF-2 and may promote the angiogenesis during wound healing.

Morphometrical and biochemical analysis on autofluorescent granules in various tissues and cells of the rats under several nutritional conditions.

The effects of age and nutritional conditions on accumulation of autofluorescent granules in various organs and tissues of male Sprague-Dawley rats were compared morphometrically. The relative intensity of the specific fluorescence of these autofluorescent granules was similar in all tissues and cells examined. In almost all cases, there were more autofluorescent granules in the 12-month experiment than in the 4-month one. Multiple necrotic foci of myofibrils with an accumulation of autofluorescent granules were seen in striated muscles in the rats on vitamin E-deficient diets for 12 months. In splenocytes, renal proximal convoluted tubules and hepatic cells, autofluorescent granules quantitatively increased significantly with an increase of the corn oil contents in the diets. The increase was rather marked in the splenocytes and renal epithelia of vitamin E-deficient rats. In the Purkinje cells and bronchial epithelial cells, no significant differences were noted according to the difference in the vitamin E and corn oil contents in diets. The accumulation of autofluorescent granules was not merely considered to be an age-related change, but to be influenced by a relationship to the cell metabolism and functional activity in various organs.

Age changes of myofibrils of human minor pectoral muscle.

Micro- and ultramicromeasuring studies have been made on the age changes of surgically resected minor pectoral muscles in 200 Japanese females of various ages (26-80 years). With advancement of age, muscle fibers of type I decreased in number and increased in size, and the age-related increase in size is not considered to be due to an increase in number of myofibrils but seems to be due to an increase in their volume resulting from an increase in the number of myofilaments.

Age changes in size and number of muscle fibers in human minor pectoral muscle.

Micromeasuring studies have been made on the senile changes of the surgically resected minor pectoral muscles in 200 Japanese females of various ages (26-80 years). The microscopic differentiation between type I (red) and type II (white) fibers were made by the histochemically demonstrated myosin-ATPase activity with frozen sections and also by the immunohistochemical demonstration of beta-enolase in the paraffin sections with indirect antibody method. The decrease with age in weight of the muscle was not markedly observed. Muscle fibers of type I were significantly decreased in number and increased in size after 60 years of age. However, size of muscle fibers of type II decreased gradually after 40 years of age. However, size of muscle fibers of type II decreased gradually after 40 years of age. Total volume of type I muscle fibers was not changed according to age, on the contrary, that of the type II fibers decreased significantly after 60 years of age.

Inhibition of growth and invasive activity of human pancreatic cancer cells by a farnesyltransferase inhibitor, manumycin.

The effects of manumycin, a competitive farnesyltransferase (FTase) inhibitor, on pancreatic cancer cell lines with or without K-ras mutation were studied. Manumycin inhibited the growth of human pancreatic cancer cells (SUIT-2, MIA PaCa-2, AsPC-1, BxPC-3) in a dose-dependent manner. The 50% inhibitory concentration (IC50) in cell lines with a mutant K-ras gene (SUIT-2, MIA PaCa-2, AsPC-1) was lower than that in BxPC-3 with a wild-type ras. Both mitogen-activated protein kinase activity after growth stimuli and the ability for chemotactic invasion were markedly more inhibited by manumycin in SUIT-2 than in BxPC-3. These results suggest that mutated Ras is more sensitive to manumycin than the wild type. Furthermore, tumor growth and liver metastasis in nude mice inoculated with manumycin-treated SUIT-2 cells were inhibited dose dependently. Inhibition of Ras activity might be a new anticancer strategy in pancreatic cancer in which Ras plays a role.

Intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: An increasing number of intraductal papillary mucinous tumors of the pancreas have been reported in recent years. The indolent character and favorable prognosis of this neoplasm have been described. METHODS: Intraductal papillary mucinous tumors were classified into main duct type (n = 8) and branch type (n = 28) according to the dominant location of the tumor. This single-institute study examined the clinicopathological features and outcome after surgical resection in patients with intraductal papillary mucinous tumors. RESULTS: The gender, age, tumor size, and prognosis were quite similar for the main duct type and branch type groups. Branch type tumors were more frequently located in the head of the pancreas than were main duct type tumors. Histological examination revealed that 88% of main duct type tumors were adenocarcinomas; however, only 46% of branch type tumors were adenocarcinomas. Five-year survival rates for the patients with all main duct type tumors (n = 8), main duct type adenocarcinoma (n = 7), all branch type tumors (n = 28), and branch duct adenocarcinoma (n = 13) were 100%, 100%, 90.6%, and 90.9%, respectively. CONCLUSIONS: Intraductal papillary mucinous tumors had a favorable prognosis after surgical treatment. A curative pancreatectomy should be indicated for this localized malignant tumor.

Inferior head resection of the pancreas for intraductal papillary mucinous tumors.

BACKGROUND: Patients with intraductal papillary mucinous tumor have a favorable prognosis after surgical treatment. When this neoplasm is located in the head of the pancreas, resection has conventionally required pancreatoduodenectomy. Although pancreatoduodenectomy can now be performed with a low mortality rate, morbidity still occurs frequently. METHODS: Between November 1982 and January 1999, 38 intraductal papillary mucinous tumors of the pancreas were resected at the Chiba University Hospital. Seven patients (18%) underwent inferior head resection of the pancreas. In this preliminary study, the operative technique is presented, and its efficacy in improvement of quality of life is evaluated. RESULTS: Patients with intraductal papillary mucinous tumor underwent resection with no perioperative mortality. After discharge from hospital, 6 patients who underwent inferior head resection were still alive without recurrent disease after a median follow-up of 3 years. However, 1 patient developed peritoneal dissemination and died 18 months after inferior head resection. Patients had regained 98% of preoperative weight 1 year after inferior head resection. N-benzoyl-L-tyrosyl-p-amino-benzoic acid (BT-PABA) excretion test showed the same value before (73%) and after (73%) inferior head resection (n = 7). Pancreatic fistulas occurred more frequently after inferior head resection (38%), but the incidence of major complications was similar between inferior head resection and other types of pancreatic head resection. CONCLUSIONS: Pancreatic function was well preserved, and patients regained 98% of preoperative weight after inferior head resection of the pancreas. The authors concluded that the limited involvement of intraductal papillary mucinous tumors enables the surgeons to perform inferior head resection of the pancreas.

Gilvusmycin, a new antitumor antibiotic related to CC-1065.

A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp. QM16. The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis. Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo.

Combined therapy with radiofrequency thermal ablation and intra-arterial infusion chemotherapy for hepatic metastases from colorectal cancer.

BACKGROUND/AIMS: In this preliminary study, we investigated the efficacy of combined radiofrequency thermal ablation therapy (RFA) with hepatic arterial infusion chemotherapy (HAI) in the treatment of multiple liver metastases from colorectal cancer. METHODOLOGY: Nine patients with bilobular multiple metastases was treated. The number of nodules was 6.0 +/- 3.9 (range: 2-13), and the size was 2.1 +/- 1.0 cm (range: 0.5-4.8 cm) in diameter. RFA was performed using a RF generator operating at 460 kHz with a 15-gauge, 4-prong custom RF needle. Treatment temperature was kept at 90-110 degrees C for 5 min. 5-Fluorouracil (5-FU) was administered by weekly 750-1250 mg/body/5 h as the regimen of HAI. RESULTS: During a 15.2-month follow-up period, 6 of 9 patients survived more than 1 year. Three of the 6 survived more than 2 years. Serum CEA level in 5 patients dropped from 24.5 +/- 9.5 ng/ml to 10.3 +/- 5.5 ng/ml. Local recurrence was observed in 5 patients and new lesions in 4. Extrahepatic recurrence was observed in 5 patients. There were no serious complications but one HAI-related cerebral thrombosis. CONCLUSIONS: Combined RFA with HAI would be effective and safe. This modality provides a new option for the treatment of multiple liver metastases from colorectal cancer.

Imprint cytology of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the thymus: a case report.

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the thymus is a very rare tumor with characteristic morphologic features. We describe a case of thymic low-grade B-cell MALT lymphoma occurring in a 59-yr-old woman with Sjögren's syndrome, in whom the definite diagnosis was difficult at the time of surgery. An immunohistologic and genotypic study, however, was diagnostic of lymphoma. A review of cytologic material was undertaken, and it was felt that the cytologic features in Giemsa-stained preparations in imprint smears were present that initially should have enabled the correct cytodiagnosis and distinction from the other thymic lesions. The findings presented in this study were considered to contribute to the cytodiagnosis of a thymic lesion, which might, in the past, have been erroneously interpreted as another lymphoproliferative disorder.

Virtual pancreatoscopy of mucin-producing pancreatic tumors.

We used computer-based virtual endoscopy techniques as a novel approach to clarify the three-dimensional (3D) surgical anatomy of the pancreas and of mucin-producing pancreatic tumors. Thirteen cases (18 lesions) of mucin-producing pancreatic tumors were investigated by virtual pancreatoscopy. Virtual endoscopic images were generated with virtual endoscopy software application on UNIX workstations. We created surface-rendered virtual endoscopic images derived from a computer reconstruction of the cross-sectional magnetic resonance imaging data. Virtual endoscopy could visualize the surfaces of the pancreatic duct and the bile duct, and also demonstrated all cystic tumors. The surfaces of malignant mucin-producing pancreatic tumors were illustrated as being more irregular than those of benign lesions. The virtual endoscopic technique could demonstrate not only a surface-rendered endoscopic image of the tumors but also a 3D reconstructed image of the pancreas. The relationship to anatomic structures located outside the surfaces is continuously maintained and displayed at the same time. Virtual pancreatoscopy was useful for surgical planning of minimally invasive resection of the pancreas.