Expression of matrix metalloproteinase matrilysin (mmp-7) was induced by activated ki-ras via ap-1 activation in sw1417 colon cancer cells

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metallo-proteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.     

Epirubicin is equivalent to adriamycin in vitro against many cancer cells but more effective against gastric cancer cells.

We compared the cytotoxic effects of two anthracycline derivatives, epirubicin (EPI) and adriamycin (ADM), against human tumor cells in vitro. Various tumor specimens, obtained at surgery, included 57 liver, 19 lung, 16 gastric, 10 colorectal and 7 breast cancer specimens. These tumor cells were exposed to the same concentration of EPI or ADM for 3 days. The chemosensitivity of each tumor cell type to each drug was then assayed using the in vitro succinate dehydrogenase inhibition (SDI) test. Sensitivity to the treatment was defined as a 50% or greater reduction in the succinate dehydrogenase (SD) activity of the tumor cells, relative to that of the control (untreated) cells. Each cell type, except for gastric cancer cells, was equally sensitive to EPI and ADM. Gastric cancer cells were more sensitive to EPI than to ADM (P less than 0.05). The rate of coincidence, the sum of the co-sensitive and co-resistant rates of all the tumors, was quite high (90.8%). Thus, these findings indicate that EPI and ADM are equally cytotoxic to each tumor cell type, but EPI is more cytotoxic than ADM to gastric cancer cells. Since EPI is reported to be less cardiotoxic than ADM, EPI may replace ADM in cancer chemotherapy.     

Disposition Characteristics of Macromolecules in Tumor-Bearing Mice

As part of the strategy for the design of macromolecular carriers for drug targeting, the disposition characteristics of macromolecules were studied in mice bearing tumors that served as target tissues. Eight kinds of macromolecules including four polysaccharides and four proteins with different molecular weights and electric charges were used; tissue distribution and tumor localization after intravenous injection were studied. Pharmacokinetic analysis revealed that the tissue radioactivity uptake rate index calculated in terms of clearance was different among the tested compounds; especially, the urinary radioactivity excretion clearances and the total hepatic radioactivity uptake clearances varied widely. Compounds with low molecular weights (approximately 10 kD) or positive charges showed lower tumor radioactivity accumulation; radioactivity was rapidly eliminated from the plasma via rapid urinary excretion or extensive hepatic uptake, respectively. On the other hand, large and negatively charged compounds, carboxymethyl dextran, bovine serum albumin, and mouse immunoglobulin G, showed higher radioactivity accumulation in the tumor (calculated total amounts were 15.6, 10.8, and 20.8% of the dose, respectively) and prolonged retention in the circulation. These results demonstrated that the total systemic exposure rather than the uptake rate index was correlated with total tumor uptake. Molecular weight and electric charge of the macromolecules significantly affected their disposition characteristics and, consequently, determined radioactivity accumulation in the tumor. It was concluded that a drug–carrier complex designed for systemic tumor targeting should be polyanionic in nature and larger than 70,000 in molecular weight.     

Use of latissimus dorsi flap for reconstruction with prostheses after tumor resection

Five latissimus dorsi musculocutaneous flaps (LD flap) were used for reconstruction with prostheses after resection of tumors between 1984 and 1991 in our hospital. Bony structures were reconstructed with prostheses and in three cases autoclaved autobone grafts were also needed. The prostheses and adjacent grafts were then wrapped by the LD flaps. Tumor sites included one humerus, two thighs, and two knees. All but one case healed primarily. The sole case of infection was successfully treated with debridement and irrigation. Due to the LD flaps' plentiful blood supply, we believe infection of the prosthetics can be avoided and good clinical results can be achieved using the flap with autoclaved autograft prosthetic composite reconstruction. © 1994 Wiley-Liss, Inc.     

A Case of a Patient with a Rectal Ulcer Who Had an Unusual Defecation Habit

Abstract: This case report describes a patient with a rectal ulcer who had an unusual defecation habit. Complete healing was recognized colonoscopically after the patient was instructed to break this habit. A polyp of the ascending colon was detected by a barium enema in a 37-year-old man complaining of anal bleeding. He was admitted to our division to undergo a polypectomy. At the time of the polypectomy, a round ulcer, measuring 1 cm in diameter, was detected on the right wall of the rectum 3 cm from the anal verge. A diagnosis of mucosal prolapse syndrome of the rectum could not be made because the patient did not exhibit the characteristic habit of excessive “straining” mentioned by patients with this syndrome, and no characteristic finding of fibromuscular obliteration was found on histological examination of biopsied specimens taken endoscopically from the lesion. Repeated history taking, however, revealed that the patient had the unusual habit of inserting his finger into his rectum after defecation. He broke this habit following instruction to do so. As a result, on colonoscopic examination 15 month later, the ulcer was found to have become a scar:     

Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation.

We used the Gorog Thrombosis Test to analyze the factors influencing the occlusion time, which represents platelet activation and subsequent occlusive thrombus formation, in 132 healthy Japanese volunteers (116 men, 16 women; mean age, 45.0 +/- 12.0 years). The Gorog Thrombosis Test was designed to evaluate platelet aggregation and thrombolytic activity under a high shear stress condition (175 dynes/cm) in a native blood sample in vitro. The mean +/- SD occlusion time was 154.8 +/- 64.7 s (men, 153.4 +/- 64.2 s and women, 165.4 +/- 56.5 s). The occlusion time was inversely correlated with von Willebrand factor ristocetin cofactor activity (VWF:Rco) (r = -0.242, P = 0.0055) and von Willebrand factor antigen (r = -0.230, P = 0.0080). The mean occlusion time in the group with VWF:Rco of at least 170% (137 s) was significantly shorter than that in the group with VWF:Rco less than 170% (156 s, P < 0.05). Platelet counts, other coagulation markers and smoking showed no significant correlations with occlusion time. Red blood cells (r = -0.177, P = 0.0365), hemoglobin (r = -0.191, P = 0.0245) and hematocrit (r = -0.182, P = 0.0329) also showed inverse correlations with the occlusion time. This report is the first to clearly demonstrate the role of von Willebrand factor in the formation of occlusive thrombi in the Gorog Thrombosis Test.     

The relationship between histopathological findings in oral squamous cell carcinoma and FDG uptake on PET

Objectives It is known that, in fluorine-18 fluorodeoxyglucose Positron Emission Tomography (FDG PET) for the diagnosis of oral cancer, FDG uptake may vary even among different cases of the same squamous cell carcinoma. However, the details of this phenomenon have not yet been elucidated. In this study, we analyzed the relationship between histopathological findings in oral squamous cell cancer and PET findings on FDG uptake. Methods We examined 45 patients with oral squamous cell carcinoma who had undergone FDG PET before treatment. FDG uptake was assessed by a standardized uptake value (SUV) calculated according to the PET-measured tissue concentration of FDG, the administered dose of radionuclide, and the body weight of the patient. The relationship between the mean SUV and each of the following parameters was examined: histological grade of malignancy, degree of cell differentiation, size and/or local extent of the primary lesion, and cell density of the tumor. Results The mean SUV of FDG uptake did not depend on the histological grade of malignancy or on the degree of cell differentiation, but tended to be greater the larger the primary lesion. SUV also depended on cell density, increasing with the percentage of tumor parenchyma. Conclusions It is concluded that cancer cell density greatly influences the SUV of FDG, in that a tumor with fewer cellular elements in cancer tissue tends to become a false negative.