T RAIL, also known as Apo-2 ligand, is a pro-apoptotic cytokine that constitutes a family of ligands that transduce death signals through death domain-containing receptors.(1-3) TRAIL is a transmenbrane protein that functions by binding to two closely related receptors, DR4 and DR5. Both receptors are expressed on a high proportion of tumor cell lines, contain intracytoplasmic death domains, and on ligation mediate apoptosis. TRAIL is capable of inducing apoptosis in a wide variety of cancer cells in culture and in tumor implants in mice. (4,5) However, its pro-apoptotic effects are minimal in normal cells. (6,7) Despite the ubiquitous expression of TRAIL receptors, some cancer cell lines show either partial or complete resistance to the pro-apoptotic effects of TRAIL. The reason for the TRAIL resistance is unknown, but it is not regulated solely by the differential expression of the known TRAIL receptors DR4 and DR5. Instead, it appears to be more likely that intracellular inhibitors acting downstream of TRAIL receptors render some cells insensitive to TRAIL, as the resistance of many types of cancer cells to TRAIL can be reversed by treatment with protein synthesis inhibitors (8,9) or chemotherapeutic agents.(5) The binding of TRAIL to its receptors DR4 and DR5 leads to the cleavage and activation of caspase-8, which in turn activates downstream effector caspases such as caspase-3. Activation of caspase-8 by TRAIL might also cleave BID, a Bcl-2 inhibitory protein, which triggers mitochondrial depolarization. (10,11) The study of the intracellular mechanisms that control TRAIL resistance might enhance our knowledge of death receptor-mediated signaling and help to develop TRAIL-based approaches for cancer treatment.In fact, there are many survival factors operating intracellularly in response to survival signals. Among the cellular signaling pathways that promote cell survival, Akt is one of the important survival factors that contributes resistance to apoptotic signals. (12) Akt is a Ser/Thr protein kinase implicated in mediating a variety of biological responses, which includes the inhibition of apoptosis and the stimulation of cellular growth. Activation of PI3K/Akt pathway generates phosphatidylinositol-3,4,5-triphosphate, which in turn binds to the pleckstrin homology domain of Ser/ Thr kinase Akt, resulting in recruitment of Akt to the menbrane. Previous studies have shown that Akt plays an important role in survival when cells are exposed to various kinds of apoptotic stimuli. Moreover, it was found to be overexpressed in some gastric adenocarcinomas and in breast, ovarian, prostate, and pancreatic cancers. (13,14) The purpose of this study was to investigate the role of the PI3K/Akt pathway in TRAIL-induced apoptosis in human bladder cancer cells. We showed that TRAIL induces apoptosis with variable responses in RT4 cells, whereas UM-UC-3 and T24 cells are highly resistant to TRAIL. Interestingly, UM-UC-3 and T24 cells highly express a constitutively active Akt that is inversely correlated with TRAIL sen...
Objectives:To compare perioperative outcome of transperitoneal and retroperitoneal approaches during laparoscopic radical nephrectomy (LRN) and to identify selection criteria for each approach. Methods: Over a 7-year period , 100 consecutive patients (median age 62 years, range 20-80) underwent LRN for a renal tumor with clinical stage T1a-T3a. The first choice approach was retroperitoneal. The transperitoneal approach was chosen in selected cases based on tumor characteristics. Thirty-three patients underwent the transperitoneal approach, and 67 had the retroperitoneal approach. Perioperative parameters including operative time, blood loss and complications and pathology data were retrospectively analyzed. Results: Overall, 33 transperitoneal laparoscopic radical nephrectomies (TLRN) and 67 retroperitoneal laparoscopic radical nephrectomies (RLRN) were carried out. There was a statistically significant difference between the two groups in terms of size (5.3 vs 3.0 cm, P < 0.0001) and clinical T stage (higher in the TLRN group, P < 0.0001) of the tumors. Intraoperative complications included bradycardia, pneumothorax, renal vein injury, and renal artery injury in the TLRN group, and pneumothorax in the RLRN group. There were no differences in terms of operative time, blood loss and tumor grade between the two groups. Conclusions: Retroperitoneal and transperitoneal approaches yielded excellent surgical outcomes. The transperitoneal approach should be chosen based on tumor size and location to minimize vascular injury.
The authors wish to correct an error in the Results section of this paper, when words 'fertile' and 'infertile' were inadvertently swapped.The corrected sentence should read: 'Whereas the LH level was not significantly different between infertile and fertile married exposed men (5.8 ± 2.4 U ⁄ L vs. 6.5 ± 3.2 U ⁄ L), the testosterone level was significantly higher in the fertile compared with that of infertile married exposed men (5.9 ± 1.9 ng ⁄ mL vs. 4.1 ± 0.78 ng ⁄ mL; p < 0.001)'.The authors and editors apologize to the readers.
Adrenal myelolipoma is a rare benign tumor, occasionally reported in association with endocrine disorders. We report herein a case of bilateral adrenal myelolipoma associated with adrenogenital syndrome caused by 21-hydroxylase deficiency. A diagnosis of 21-hydroxylase deficiency was confirmed by mutation analysis of the CYP21 gene. Our case represents only the second case of bilateral adrenal myelolipoma associated with adrenogenital syndrome caused by 21-hydroxylase deficiency.
The accumulating effects of exposure to electromagnetic radiation emitted by a conventional mobile phone (standby position) on the testicular function and structure are not yet fully investigated. To study these effects longitudinally, a total of 24 adult male rabbits were randomly and equally divided into three groups. Rabbits in the first (phone) group were exposed, in specially designed cages, to radio frequency emitted from the mobile phone (800 MHz) in a standby position opposite to that of testes for 8 h daily for 12 weeks. The second group consisted of the stress controls which were kept in the same kind of cages to appreciate any cage-induced anxiety. The third group included the ordinary controls which were kept in the conventional roomy cages. Semen analysis and sperm function tests (viability, hypo-osmotic swelling and acridine orange) were conducted weekly. Histological testicular sections and serum total testosterone were also evaluated. A drop in the sperm concentration appeared in the phone group at week 6. This became statistically significant at week 8, compared with the two control (stress and ordinary) groups (133, 339 and 356 x 106/mL, respectively) and to the initial sperm count (341 x 106/mL) of this group. Motile sperm population showed similarity amongst the three study groups until week 10 when it declined significantly, and thereafter in the phone and stress control groups, with more significant decline in the phone animals (50, 61 and 72.4%, respectively). Histological examination showed also a significant decrease in the diameter of seminiferous tubules in the phone group vs. the stress and ordinary controls (191 microm vs. 206 and 226 microm, respectively). The other study points did not show any difference. In conclusion, low intensity pulsed radio frequency emitted by a conventional mobile phone kept in the standby position could affect the testicular function and structure in the adult rabbit.
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