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C Bais B Santomasso O Coso L Arvanitakis EG Raaka JS Gutkind AS Asch E Cesarman MC Gershengorn EA Mesri MC Gerhengorn 《Canadian Metallurgical Quarterly》1998,391(6662):86-89
The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a gamma-2 herpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL, it encodes putative oncogenes and genes that may cause Kaposi's sarcoma pathogenesis by stimulating angiogenesis. The G-protein-coupled receptor encoded by an open reading frame (ORF 74) of KSHV is expressed in Kaposi's sarcoma lesions and in PEL and stimulates signalling pathways linked to cell proliferation in a constitutive (agonist-independent) way. Here we show that signalling by this KSHV G-protein-coupled receptor leads to cell transformation and tumorigenicity, and induces a switch to an angiogenic phenotype mediated by vascular endothelial growth factor, an angiogenesis and Kaposi's-spindle-cell growth factor. We find that this receptor can activate two protein kinases, JNK/SAPK and p38MAPK, by triggering signalling cascades like those induced by inflammatory cytokines that are angiogenesis activators and mitogens for Kaposi's sarcoma cells and B cells. We conclude that the KSHV G-protein-coupled receptor is a viral oncogene that can exploit cell signalling pathways to induce transformation and angiogenesis in KSHV-mediated oncogenesis. 相似文献
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AS Lages KC Silva AL Miranda CA Fraga EJ Barreiro 《Canadian Metallurgical Quarterly》1998,8(2):183-188
OBJECTIVE: To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma. DESIGN: A randomized controlled trial. SETTING: A tertiary referral center. PATIENTS: During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months. INTERVENTION: Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment. MAIN OUTCOME MEASURES: Recurrence rate and disease-free survival. RESULTS: A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04). CONCLUSION: In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome. 相似文献
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A hypothesis on autoregulatory mechanism of reproduction of bone matrix structural changes was proposed resulting from the theoretical study based on author's own data and data documented in literature. This mechanism seems to underly osteoporosis development. All etiological factors of osteoporosis reported were united into a common pathogenetic mechanism on the basis of this conception. 相似文献
66.
AG Baranovskii TG Kanyshkova AS Mogelnitskii VA Naumov VN Buneva EI Gusev AN Boiko TA Zargarova OO Favorova GA Nevinsky 《Canadian Metallurgical Quarterly》1998,63(11):1239-1248
It is known that in the blood of patients with some autoimmune diseases catalytically active antibodies hydrolyzing proteins, DNA, and RNA may be detected. In the present work homogeneous preparations of IgG antibodies (Ab) possessing high affinity for nucleic acids (NA) were obtained for the first time from blood and cerebrospinal fluid of patients with multiple sclerosis (MS). The fraction of IgG Ab as well as its Fab fragments and isolated light chains of both kappa- and lambda-types were shown to catalyze effectively the hydrolysis of DNA and RNA. It is shown by different methods that the capability for nucleic acid hydrolysis is an intrinsic property of the polyclonal Ab. NA-hydrolyzing Ab were detected in the blood of 69 of 72 and in the cerebrospinal fluid of 5 of 5 examined MS patients, while they were not detected in the blood of any of 50 healthy donors examined. Comparison of relative rates of RNA hydrolysis and of the substrate specificity in hydrolysis of various model RNAs--cCMP, poly(U), poly(A), and poly(C)--revealed pronounced differences of MS antibodies from ribonucleases of human blood, ribonuclease A, and all earlier described abzymes. The abzymes are usually characterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS patients are the first example of autoabzymes whose specific activity in RNA hydrolysis is comparable or even higher than that of pancreatic ribonuclease A--one of the most active RNA-hydrolyzing enzymes. 相似文献
67.
A durable bond between the end of skeletal muscles and prosthetic structures could, with appropriate linkage, allow circulatory support power by synchronous and/or sequential contraction of several in situ conditioned muscles. Potential advantages relative to a myoplasty wrap involve 1) less traumatic dissection, 2) efficient linear force development, 3) selectable contraction rate, 4) greater stroke work, 5) independent control of muscle pre-load and end diastolic pressure, and 6) independent control of duration of muscle tension and ejection time. However, no existing means of tissue-prosthetic bonding appears adequate. Practicality would demand that full tension bearing capacity by the bond take no longer than muscle conditioning. A prosthesis was developed to achieve those goals. As scaled for this study, it is made of 7,200-7,800 unspun, unplaited, 22 to 26 microns diameter polyester fibers swaged into four taper needles for weaving through distal muscle. The other end is formed into a polyurethane sheathed kernmantel cord for distal fixation. Devices were implanted in six 3 to 4 kg rabbits (unilateral posterior tibial tendon replacement, random side selection with contralateral dissection/closure controls), and their tensile strength was tested at 30 days. All healed well; leg movements were normal after 1 week. Limbs were frozen at -70 degrees C between death and testing. Control failure occurred at 243 +/- 94 N and experimental at 163 +/- 44 N (p = 0.065, t-test); highest estimated requirement was 17.2 N. Interface strength was adequate by 30 days. Continued investigations, addressing other questions, are warranted. 相似文献
68.
Mutations of the p53 gene are associated with a number of non-lymphoid cancers of the dog. The present study investigates the p53 gene status within canine patients treated for primary and secondary lymphoma. Three out of eight patients exhibited p53 gene mutations. These included one patient with a germ line mutation and two patients with de novo p53 mutations associated with the secondary lymphoma. Allelic loss of the p53 gene was also observed within primary and secondary tumours of the three canine patients. The results indicate that germ line p53 mutations exist in dogs and may be involved in the known predisposition of some breeds to cancer. The presence of therapy-related p53 point mutations was found to be associated with chemoresistant secondary lymphomas. A causative role for DNA-damaging chemotherapy in de novo mutation of the p53 gene is discussed. Characterization of p53 inactivation in canine tumorigenesis may provide a valuable clinical model for assessing the efficacy and optimal therapeutic regimens of anti-cancer agents. 相似文献
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