Uterine cervical adenocarcinoma typically is an aggressive neoplasm with a propensity for early invasion and dissemination; however, the regulatory mechanism of invasive activity of cervical adenocarcinoma cells has not been fully understood. In this study, biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on invasion and proteinase expression of human cervical adenocarcinoma OMC-4 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into the reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. Their effects on tumor cell migration were also confirmed by wound assay. The zymography of tumor-conditioned medium showed that the treatment of OMC-4 cells with EGF and TGF-alpha resulted in the increase of matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (uPA). Matrilysin (MMP-7), also secreted by OMC-4 cells, was not affected by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion of cervical adenocarcinoma cells, which may be associated with their stimulatory effects on tumor cell motility and the induction of type IV collagenase and uPA secreted by tumor cells.

Adenocarcinoma↗

PubMedDate not supplied

Successful treatment of patients with rheumatic disorders and acquired factor VIII inhibitors with cyclophosphamide and prednisolone combination therapy: two case reports.

Acquired haemophilia associated with autoimmune disorders can be fatal and has been reported to be refractory to steroid therapy alone. We report two cases of female patients, aged 24 years and 54 years, with acquired haemophilia caused by factor VIII inhibitors. Underlying diseases were systemic lupus erythematosus in the 24-year-old patient and rheumatoid arthritis in the 54-year-old patient. Both conditions were nearly quiescent when the patients manifested haemorrhagic diathesis. In response to combination therapy with prednisolone and cyclophosphamide, coagulation abnormalities were resolved together with complete elimination of factor VIII inhibitors in both patients. Thus, combination therapy with alkylating agents may be recommended as initial therapy for the management of autoimmune patients with factor VIII inhibitors.

Adult↗

PubMedDate not supplied

Plasma levels of myeloperoxidase and elastase are differentially regulated by hemodialysis membranes and anticoagulants.

To examine effects of dialyzer membranes and anticoagulants on hemodialysis (HD)-triggered neutrophil degranulation. We measured plasma myeloperoxidase (MPO) and elastase (ELT) by an enzyme-linked immunoabsorbent assay. During routine HD with a cuprophane membrane and high molecular weight (HMW) heparin, plasma MPO was rapidly upregulated to maximal levels within 15 min after starting extracorporeal circulation. In contrast, the level of plasma ELT gradually increased such that the highest level was achieved at the end of the procedure. When polysulfone and polymethylmethacrylate membranes were substituted for cuprophane, the rise in ELT was markedly suppressed. Polysulfone was also capable of reducing the MPO response, although the effect was less prominent than that for ELT. As for anticoagulants, nafamostat mesylate (NM) completely suppressed the rise in plasma MPO during HD with cuprophane. Low molecular weight (LMW) heparin also partially inhibited this response. In sharp contrast, there was no significant difference in the ELT response between nafamostat, HMW, and LMW heparins. Thus, NM maximally suppressed the rise of plasma MPO but had no effect on the ELT response. Our results suggest that neutrophil degranulation of MPO and ELT is differentially regulated during HD. Polysulfone and NM appear to maximally reduce excessive neutrophil activation.

Adult↗

PubMedDate not supplied

[Proceedings: 342. Further study on the structural development of the lateral eye of the Japanese horseshoe crab (author's transl)].

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Animals↗

PubMedDate not supplied

Cavernous angioma of the middle fossa: a case report and characteristic MRI findings.

Cavernous angioma of the middle fossa is a rare lesion that is considered to originate from the cavernous sinus. Because of its profuse bleeding during surgery, it is crucial to make the correct diagnosis before an operation is performed. We report here a case of cavernous angioma occurring in the right middle fossa. MRI demonstrated an extracerebral mass extending from the middle cranial fossa into the cavernous sinus which showed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Right carotid angiography demonstrated a faint vascular stain supplied by the meningohypophysial trunk. These findings suggested an extradural cavernous angioma originating from the cavernous sinus and extending into the middle-fossa.

Brain Neoplasms↗

PubMedDate not supplied

Retrovirus-mediated gene therapy of experimental brain neoplasms using the herpes simplex virus-thymidine kinase/ganciclovir paradigm.

Recent results in experimental brain tumors indicate that transfer of sensitizing genes to tumor cells in vivo with subsequent drug treatment can reduce tumor masses and prolong the survival of rodents. In the present study, the 9L rat gliosarcoma model was used to evaluate the therapeutic effectiveness of the herpes simplex virus-thymidine kinase (HSV-tk) gene, delivered by a retrovirus vector, against tumor cells in the rat brain after systemic application of the nucleoside analogue ganciclovir (GCV). The HSV-tk gene was inserted into a retroviral vector (pMFG), which was produced using the amphotropic packaging cell line CRIP-MFG-S-HSV-TK. Packaging cells were implanted into established 9L tumors in the brains of syngeneic rats to effect gene delivery to tumor cells, followed by intraperitoneal GCV injections. Treated animals survived significantly longer (more than twice as long) than did the control groups. Brains from GCV-treated and nontreated animals were examined immunohistochemically at different time intervals after grafting of CRIP-MFG-S-HSV-TK cells and GCV treatment. Tumors in GCV-treated animals were significantly smaller as compared with nontreated animals at all time points. Sections stained immunohistochemically for HSV-TK confirmed gene transfer to tumor cells, which could be distinguished from packaging cells by different morphology and immunohistochemical staining for the retroviral envelope protein gp70. Approximately 45% of the cells in tumors implanted with CRIP-MFG-S-HSV-TK cells, but not treated with GCV, showed immunocytochemical staining for HSV-TK, demonstrating a high-efficiency of retrovirus-mediated gene transfer. Tumors in rats treated with packaging cells and GCV showed only 9% HSV-TK-positive cells after treatment, indicating that most cells expressing the HSV-tk gene were killed. The success of this therapeutic modality in experimental animals depends in large parts on the high efficiency of gene delivery and on the immune response against tumor cells.

Animals↗