The effect of Gynostemma pentaphyllum mak (GP) on carcinogenesis of the golden hamster cheek pouch induced by DMBA]

AIM: of this study is to compare two similar groups presenting inguinal herniae, one group having laparoscopic herniography and the other having a Bassini or Fruchaud repair. METHOD: Since September 1994, in our department, patients presenting with symptoms of unilateral or bilateral inguinal herniae to our practice were offered the transperitoneal or preperitoneal approach as an alternative of open surgical repair. We considered the first 50 patients operated by laparoscopic technic (35 M and 15 F), age between 22-72 years (group A), and similar group operated by Bassini or Fruchaud technic (group B). All the patients had general anesthesia and perioperative antibiotics. In the group A we used Prolene, Mercilene or Plastex mesh. The following parameters were assessed: 1) operative time from incision to closure: 2) amount and type of analgesia required postoperatively; 3) morbidity related to the procedure; 4) interval before returning to full activity; 5) early recurrence rate; 6) hospital cost. RESULTS: The mean operative time for unilateral herniae in group A was 70 +/- 10 minutes versus 40 +/- 12 minutes in group B. Group A required to return to work was significantly shorter for the patients in group A (7 +/- 3 days) compared with group B patients (25 +/- 10 days). Although no recurrent herniae have yet been found in patients from either group; follow-up was only 2-18 months in the two groups. The cost of hospital care of group A patients exceeded that of group B by approximately 1.7 more. IN CONCLUSION: was consider that although is more expensive, the laparoscopic procedure in treatment of inguinal herniae, has more benefits for the patients.     

Interaction of [D-Pen2,D-Pen5]enkephalin and [D-Ala2,Glu4]deltorphin with delta-opioid receptor subtypes in vivo

A total of 78 patients with superficial bladder carcinoma were prospectively randomized to two groups following complete transurethral resection (TUR). Each received 12 intravesical instillations of 10(7) units interferon A or 120 mg BCG Connaught for 1 year starting 6 weeks post-TUR. After a mean observation period of 24 (13-31) months in the BCG and 25 (6-32) months in the IFN group 5/32 (15.6%) recurrences in the BCG versus 21/35 (60%) in the IFN group were observed (P = 0.0003). In the IFN group 18.4% of the patients had dysuria and 2.6% fever; in the BCG group 35% had fever, 60% cystitis, 1 patient granulomatous epididimoorchitis and 1 patient pneumonitis with granulomatous prostatitis. With our instillation regimen interferon A had few side effects but also no prophylactic effect, whereas BCG had tolerable-seldom severe--side effects and was very effective in preventing recurrences. Perhaps IFN should be given earlier after TUR and in a higher dosage.     

Phenylacetate in chemoprevention: in vitro and in vivo suppression of 5-aza-2'-deoxycytidine-induced carcinogenesis

Differentiation inducers selected for their low cytotoxic and genotoxic potential could be of major value in chemoprevention and maintenance therapy. We focus here on phenylacetate, a naturally occurring plasma component recently shown to affect the growth and differentiation of established neoplasms in experimental models. The ability of phenylacetate to prevent carcinogenesis by the chemotherapeutic hypomethylating drug 5-aza-2'-deoxycytidine (5AzadC) was tested in vitro and in mice. Transient exposure of immortalized, but poorly tumorigenic ras-transformed 4C8 fibroblasts to 5AzadC resulted in neoplastic transformation manifested by loss of contact inhibition of growth, acquired invasiveness, and increased tumorigenicity in athymic mice. The latter was associated with elevation in ras expression and a decline in collagen biosynthesis. These profound phenotypic and molecular changes were prevented by a simultaneous treatment with phenylacetate. Protection from 5AzadC carcinogenesis by phenylacetate was: (a) highly efficient despite DNA hypomethylation by both drugs, (b) free of cytotoxic and genotoxic effects, (c) stable after treatment was discontinued, and (d) reproducible in vivo. Whereas athymic mice bearing 4C8 cells developed fibrosarcomas following a single i.p. injection with 5AzadC, tumor development was significantly inhibited by systemic treatment with nontoxic doses of phenylacetate. Phenylacetate and its precursor suitable for oral administration, phenylbutyrate, may thus represent a new class of chemopreventive agents, the efficacy and safety of which should be further evaluated.     

In vitro cytotoxicity and DNA damage production in Chinese hamster ovary cells and topoisomerase II inhibition by 2-[2''-(dimethylamino)ethyl]-1, 2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with substitutions at the 6 and 7 positions (azonafides)

The p53 tumor suppressor gene encodes a phosphoprotein which when overexpressed can induce growth arrest at the G1 and G2/M phases of the cell cycle, promote differentiation and apoptosis. This paper demonstrates that p53 can associate with trk tyrosine kinase. Expression of a murine temperature-sensitive (ts) p53 mutant in PC12 cells overexpressing trk (a model system to analyse cellular differentiation and signal transduction induced by NGF) induces morphological changes in the absence of NGF stimulation at 32 degrees C but not at 37 degrees C. In cells differentiated by p53, trk, but not EGFr, was hyperphosphorylated on tyrosine. Furthermore trk was not phosphorylated when expressed in Saos-2 cells (human osteosarcoma cells that lack expression of both endogenous trk and p53) at either temperature. However, transfection of ts p53 into these cells induces trk phosphorylation at 32 degrees C in the absence of NGF stimulation. Association of trk and p53 can be detected in NIH3T3 and PC12 cells co-expressing trk and the ts p53 mutant, in NIH3T3 and PC12 cells transfected with trk alone, and in untransfected PC12 cells, showing that overexpressed and/or endogenous trk associates with endogenous, low levels of p53. These data suggest a novel function for p53 which involves the stimulation of signal transduction pathways (mediating morphological properties of cells), possibly through association with and hyperphosphorylation of trk.     

In vitro and in vivo functional characterization of bovine vitamin K-dependent gamma-carboxylase expressed in Chinese hamster ovary cells

Coagulation factor IX is a serine protease for which high-level expression of biologically active protein in heterologous cells is limited due to inefficient proteolytic removal of the propeptide as well as vitamin K-dependent carboxylation of multiple amino-terminal glutamic acid residues. We have overexpressed the vitamin K-dependent gamma-carboxylase cDNA and monitored its ability to improve factor IX processing in Chinese hamster ovary (CHO) cells. From amino acid sequence analysis of bovine liver vitamin K-dependent gamma-carboxylase, degenerate oligonucleotides were used to isolate a 3.5-kbp bovine cDNA that encoded a 758-residue open reading frame. Expression of the cDNA in COS-1 and CHO cells yielded 17- and 16-fold increases in the in vitro gamma-carboxylase activity of microsomal preparations, respectively. Anti-serum raised against a predicted peptide sequence reacted with a 94-kDa polypeptide in the partially purified bovine liver preparation as well as in stably transfected CHO cells. The amount of antibody reactivity correlated with the increased ability to carboxylate a peptide substrate in vitro. These results strongly support the conclusion that the cDNA encodes the vitamin K-dependent gamma-carboxylase. Transient transfection of the gamma-carboxylase expression vector into factor IX-expressing CHO cells did not improve the specific procoagulant activity of secreted factor IX. In contrast, transfection of an expression vector encoding the propeptide processing enzyme PACE (paired basic amino acid cleaving enzyme) did improve the specific activity of secreted factor IX by 3-fold. These results demonstrate that the ability of CHO cells to modify glutamic acid residues to gamma-carboxyglutamic acid in secreted factor IX is not limited by the expression of the vitamin K-dependent gamma-carboxylase alone.