Koji Katsuta

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

Alternative splicing of fibronectin-like type III (FNIII) repeats of tenascin-C (Tn-C) generates a number of splice variants. The distribution of large variants, typical components of provisional extracellular matrices that are up-regulated during tumor stroma remodeling, was here studied by immunoblotting and immunohistochemistry using a monoclonal antibody against the FNIII B domain (named 4C8MS) in a series of human breast cancers. Large Tn-C variants were found at only low levels in normal breast tissues, but were highly expressed at invading sites of intraductal cancers and in the stroma of invasive ductal cancers, especially at invasion fronts. There was a positive correlation between the expression of large Tn-C variants and the cell proliferation rate determined by immunolabeling of the Ki-67 antigen. Of the Tn-C recombinant fragments (all FNIII repeats or mFNIII FL, the conserved FNIII domain only, the epidermal growth factor-like domain, and the fibrinogen-like domain) which were expressed by CHO-K1 cells transfected with mouse Tn-C cDNAs, only the mFNIII FL enhanced in vitro migration and mitotic activity of mammary cancer cells derived from a Tn-C-null mouse. Addition of 4C8MS blocked the function of mFNIII FL. These findings provide strong evidence that the FNIII alternatively spliced region has important roles in tumor progression of breast cancer.

Co-expression of tenascin and fibronectin in epithelial and stromal cells of benign lesions and ductal carcinomas in the human breast

Tenascin (TN)‐C and fibronectin (FN), which are glycoproteins of the extracellular matrix (ECM), are up‐regulated in cancer tissues, including breast cancer. For assessment of their involvement in cancer invasion, it is important to know which cells are responsible for their production and secretion. The distribution of cells expressing TN and FN mRNAs in benign and malignant human breast tissues was therefore analysed by in situ hybridization, using digoxigenin‐labelled cRNA probes, in addition to demonstrating the proteins immunohistochemically. Both mRNAs were expressed in epithelial cancer as well as in stromal cells in a large fraction of the tumours, with co‐expression in individual cells. In cancers with intraductal components and/or those consisting of large nests, the mRNAs were more often expressed in the cancer than in the stromal cells. In scirrhous carcinomas, in contrast, the stromal cells were almost always positive for TN and FN mRNAs, while the cancer cells only rarely exhibited TN or FN expression. In benign lesions including adenosis, fibroadenoma and intraductal papilloma, the expression patterns also varied. These findings indicate that TN and FN co‐expressed by cancer cells and stromal cells are probably involved in the intraductal extension and early invasion of cancer cells and in the remodelling of cancer stroma.

Differential expression of tenascin-C and tenascin-X in human astrocytomas

Abstract Tenascins (TNs) are a family of extracellular matrix glycoproteins. The first member of this family to be recognized, tenascin-C (TN-C), is known to be expressed in various tumors including human astrocytomas. Tenascin-X (TN-X) is the latest member of the TN family to be reported, and its expression in tumor tissues has not yet been examined. In this study, we found expression of TN-X in glioma cell lines and human astrocytomas by immunoblot analysis using anti-mouse TN-X antibodies. We also examined the expression of TN-C and TN-X immunohistochemically in a series of 32 human astrocytomas and tissue from 5 normal brains. Expression of TN-X was up-regulated to a higher degree in low-grade astrocytomas than in high-grade astrocytomas. TN-X was mainly localized in the perivascular stroma around tumor vessels, and weakly expressed in the intercellular spaces among tumor cells. In contrast, TN-C was more strongly expressed in the intercellular spaces and in tumor vessels in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas) than in low-grade astrocytomas. In the tissues expressing both TNs, the distribution of TN-X was often reciprocal to that of TN-C. These findings indicate that the expression of TN-C and TN-X in astrocytomas is different, and that these glycoproteins could be involved in neovascularization in different manners.

Triple carcinomas of the biliary tract associated with congenital choledochal dilatation and pancreaticobiliary maljunction

Abstract: We report a rare case of triple carcinomas of the biliary tract associated with congenital choledochal dilatation (CCD) and pancreaticobiliary maljunction (PBM). The patient was a 58-year-old Japanese man who complained of epigastralgia. Ultrasonography and computed tomography revealed an elevated lesion inside the markedly dilated extrahepatic bile duct, thickening of the gallbladder wall, and small polypoid lesions in the gallbladder. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed CCD and PBM. With a diagnosis of carcinoma of the bile duct and cholesterol polyps in the gallbladder, pylorus-preserving pancreaticoduodenectomy was performed. The resected specimen showed two elevated lesions in the dilated bile duct, cholesterol polyps, and an area of irregular mucosa in the gallbladder. Histopathological examination showed two carcinomas in the bile duct, an adenosquamous cell carcinoma, and a moderately differentiated tubular adenocarcinoma, and a well differentiated tubular adenocarcinoma of the gallbladder. Two years and 6 months after the operation, a solitary metastatic liver tumor was detected. Left hepatic lobectomy was performed. At present, 7 months after the second operation, the patient is doing well with no signs of recurrence. Multiple carcinomas in the biliary tract associated with CCD and PBM, including the details in the present patient, were reviewed.

Successful surgical treatment for implanted intraperitoneal metastases of ruptured small hepatocellular carcinoma: report of a case.

We report herein the case of a 53-year-old man with disseminated intraperitoneal metastases caused by the rupture of small hepatocellular carcinoma (HCC). He was admitted to our hospital in shock after suffering a trauma injury to the upper abdomen. Ultrasonography revealed a massive hemoperitoneum. At surgery, 4000 ml of blood was drained from the abdominal cavity and a ruptured tumor, 2 cm in diameter, was found in the right lobe of the liver. The tumor was resected with an adequate surgical margin and subsequent microscopic examination confirmed a diagnosis of moderately differentiated HCC without associated liver cirrhosis. The patient was readmitted 14 months later, following the development of right lower quadrant pain. Ultrasonography and computed tomography revealed extrahepatic abdominal tumors, and abdominal angiography demonstrated four intraperitoneal tumors. At surgery, four implanted metastases adhered to the greater omentum were found and resected. No other tumors were detected. Microscopically, all four tumors were confirmed as moderately differentiated hepatocellular carcinoma. Ruptured HCC may lead to implanted intraperitoneal metastasis, but rupture of small HCC is very rare. While hepatic resection is the treatment of choice for ruptured HCC, according to our review of the literature, only a few patients have survied long-term after resection of implanted metastasis.

Primary adenosquamous carcinoma of liver resected by right trisegmentectomy: Report of a case and review of the literature

A case of primary adenosquamous carcinoma of the liver in a patient with an elevated level of serum squamous cell carcinoma-related antigen is reported. A 68-year-old man was admitted to our hospital with a 10-day history of fever and jaundice. From the results of laboratory and imaging studies before surgery, a diagnosis of cholangiocellular carcinoma was made, and the patient underwent right trisegmentectomy with regional lymph node dissection. Histopathological examination of the resected specimen revealed adenocarcinoma, squamous cell carcinoma, and a transitional area containing both types of cancer cells. The number of argyrophilic nucleolar organizer regions and the labeling index of proliferating cell nuclear antigen were markedly elevated and the deoxyribonucleic acid ploidy pattern was aneuploid in the squamous component. The patient died due to liver metastases 3 months after the operation. We reviewed the 31 cases of adenosquamous carcinoma of the liver reported in the Japanese and English language literature, including the present case.

Solid cystic tumor of the pancreas in elderly men: report of a case.

Solid cystic tumor of the pancreas is a primary pancreatic neoplasm of unknown etiology that most commonly occurs in young women and ordinarily contains hemorrhagic tissue. We report herein the unusual case of a 75-year-old man found to have a solid cystic tumor in the body and tail of the pancreas, who is the oldest such male patient to be documented in Japan. The results of laboratory data and imaging studies indicated that the patient had a nonfunctioning islet tumor or solid cystic tumor of the pancreas, and distal pancreatectomy with splenectomy was performed. The diagnosis of solid cystic tumor was confirmed based on macroscopic and histological findings of the resected pancreatic tumor. The patient is currently in good health, without any signs of tumor recurrence 1 year, and 4 months after his operation. A total of 181 cases of solid cystic tumors, of the pancreas reported in the Japanese literature, including our case, were reviewed to evaluate the clinical differences between patients aged 50 years or over and those younger than 50 years.

Association of a cytoplasmic dynein-like protein recognizable by anti-map 1C with the mammalian mitotic spindle

A rabbit antibody to bovine brain MAP 1C was prepared. The antibody stained the mitotic spindle of PtK2 cells by immunofluorescence. On immunoblots of PtK2 cell extract the antibody reacted with polypeptides of molecular weights greater than 350 and 80 KD that resemble the subunit proteins of bovine brain MAP 1C. An additional 135 KD polypeptide in the extract was also stained. These results indicate that a cytoplasmic dynein recognizable by the anti-MAP 1C antibody is localized in the mitotic spindle.

Analysis of mammalian dynein using antibodies against A polypeptides of sea urchin sperm flagellar dynein.

Two different affinity-purified polyclonal antibodies were prepared against A polypeptides of dynein 1 extracted from sea urchin sperm. These antibodies, named AD1 and AD2, reacted exclusively with the alpha and beta heavy chains of dynein 1. Using these antibodies, we analyzed their cross-reactivity with dynein of mammalian cells. Immunohistochemically, both AD1 and AD2 stained dynein-related structures such as cilia of rabbit tracheal epithelia and flagella of rat spermatozoa. Immunoblots of the proteins extracted from mammalian cilia and flagella revealed the presence of A polypeptide-like proteins which cross-reacted with AD1 and AD2. Immunoblot analysis showed that the cross-reactive proteins were localized to the 370-kDa band of rabbit cilia and the 390- and 350-kDa bands of rat sperms. The reaction patterns showed that there were some differences between the two antibodies. On ciliary protein immunoblots, AD1 recognized about half of the broad band region which reacted with AD2, and AD1 also recognized only the 350-kDa band of the flagella extract, suggesting that the antibody reveals only a beta-like polypeptide. Immunoprecipitation studies using the ciliary proteins and AD2 confirmed that the immunoreactive protein had ATPase activity. Given these results, we have characterized mammalian dyneins previously reported by other laboratories.

Giant leiomyosarcoma of the remnant stomach: Report of a case

We describe herein the case of a 73-year-old woman who developed a giant leiomyosarcoma in the remnant stomach 4 years after undergoing a distal gastrectomy for gastric carcinoma. Abdominal ultrasonography and computed tomography revealed a huge tumor, 22 cm in maximum diameter, in the left hypochondrial region. Selective abdominal angiography showed a hypervascular tumor fed by the branches of the splenic artery and left inferior phrenic artery. The tumor arose from the posterior wall of the remnant stomach, and demonstrated marked extragastric growth and direct invasion of the pancreas, transverse colon, and diaphragm on the left side. Total resection of the remnant stomach with en bloc resection of these adjacent organs was subsequently carried out. We reviewed the Japanese literature on this extremely rare tumor and evaluated its clinical profile. In comparison with leiomyosarcoma of the unresected stomach, that of the remnant stomach more frequently showed endogastric-type growth and was accompanied by ulceration of the gastric mucosa. The prognosis of patients with leiomyosarcoma of the remnant stomach appears to be gratly affected by the presence of liver metastases and the tumor diameter, similar to that of patients with leiomyosarcoma of the unresected stomach.