Small-molecule MDM2 antagonists as a new therapy concept for neuroblastoma

Circumvention of the p53 tumor suppressor barrier in neuroblastoma is rarely caused by TP53 mutation but might arise from inappropriately increased activity of its principal negative regulator MDM2. We show here that targeted disruption of the p53-MDM2 interaction by the small-molecule MDM2 antagonist nutlin-3 stabilizes p53 and selectively activates the p53 pathway in neuroblastoma cells with wild-type p53, resulting in a pronounced antiproliferative and cytotoxic effect through induction of G(1) cell cycle arrest and apoptosis. A nutlin-3 response was observed regardless of MYCN amplification status. Remarkably, surviving SK-N-SH cells adopted a senescence-like phenotype, whereas CLB-GA and NGP cells underwent neuronal differentiation. p53 dependence of these alternative outcomes of nutlin-3 treatment was evidenced by abrogation of the effects when p53 was knocked down by lentiviral-mediated short hairpin RNA interference. The diversity of cellular responses reveals pleiotropic mechanisms of nutlins to disable neuroblastoma cells and exemplifies the feasibility of exploiting, by a single targeted intervention, the multiplicity of anticancer activities exerted by a key tumor suppressor as p53. The observed treatment effects without the need of imposing a genotoxic burden suggest that selective MDM2 antagonists might be beneficial for treatment of neuroblastoma patients with and without MYCN amplification.     

Angiomyolipoma with cavoatrial extension

In this paper, we report a case of angiomyolipoma with cavoatrial extension in a 55-yr-old woman. Multislice computed tomography revealed a hypodense mass extending into the right atrium through the right renal vein and inferior vena cava without a renal mass. The patient underwent surgery, and right atrial mass was resected. Pathologic evaluation revealed a tumor consisting of mature adipose tissue, smooth muscle and vessels consistent with angiomyolipoma. Our case reminds us of the rare possibility that angiomyolipoma, which is classified as a benign tumor, may invade the inferior vena cava or right atrium.     

Analysis of L-myc gene polymorphism in patients with renal failure outcome to renal transplant

BACKGROUND: Abnormalities of cell numbers and apoptosis have been observed in renal failure. As uncontrolled expression of c-myc is known to induce apoptosis, we thought that polymorphism in the other myc gene, L-myc gene, which is structually similar to c-myc and reported to be expressed in the kidney, may have a role in the induction of apoptosis and thus have role in chronic renal failure. The aim of this study was to investigate the relationship between the distribution of L-myc genotypes and renal failure. METHODS: In the present study we examined 101 chronic renal failure patients who had either live or cadaveric renal transplants and 105 healthy individuals, for L-myc gene polymorphism by polymerase chain reactions and restriction fragment length polymorphism techniques. RESULTS: Among our patient group, the distribution of the LL, LS, and SS genotypes was 24% (n=25), 71% (n=71), and 5% (n=5), respectively, versus 41% (n=43), 47% (n=49), and 12% (n=13) in our control group. The distribution of genotypes was significantly different between our patients and the control group (chi2=12.281; P=.002). The frequency of the S allele was significantly higher in the patient group (chi2=6.122; P=.013). CONCLUSION: Our study showed that having an S allele in the L-myc gene may increase the risk of renal failure.     

Benefits of early aggressive management of empyema thoracis

BACKGROUND: The end-target of the management of thoracic empyema is to obtain early rehabilitation by re-expansion of the trapped lung resulting from intrapleural infected material. Our aim was to shorten the hospitalization time and to prevent a possible thoracotomy by using video-assisted thoracoscopy initially. METHODS: Seventy patients with parapneumonic empyema were prospectively studied between January 1997 and June 2004. The patients were randomly divided into two groups. In group I (n = 35 patients), a chest tube was inserted into the patients after pleural content was evacuated and fibrins were debrided using video-assisted thoracoscopy. In group II (n = 35 patients), tube thoracostomy was carried out without using a video-assisted thoracoscope. Both groups were compared in terms of hospitalization time, open surgery for decortication and complications. RESULTS: There was no statistically significant difference between the groups from the point of view of age and sex (P > 0.05). In group I, 17.1% of the patients underwent open decortication, whereas in group II, 37.1% of the patients underwent the same procedure (P < 0.05). Whereas average hospital stay in group I was 8.3 days (range, 7-11 days), it was 12.8 days in group II (range, 10-18 days; P < 0.05). There was one bronchopleural fistula in group I, and there was one bronchopleural fistula and one death in group II. CONCLUSION: Video-assisted thoracoscopic evacuation and chest tube insertion in situ is a new therapeutic approach for pleural empyema that shortens hospital stay and reduces the necessity of open decortication.     

Experience on semirigid ureteroscopy and pneumatic lithotripsy in children at a single center

Aim  

Ureteroscopy in children with miniaturized instruments is becoming popular with the advent of pediatric ureteroscopes and laser lithotriptors. We had been performing pediatric ureteroscopies with a 7.5 Fr. semirigid ureteroscope and pneumatic lithotriptor, used in adults as well. Herein, we present our experience in pediatric ureteroscopy with a semirigid 7.5 Fr. ureteroscope and pneumatic lithotriptor with a specific focus on changes in success and complication rates with time.     

Bilateral tonsillar adenoid cystic carcinoma

Adenoid cystic carcinoma is a malignant epithelial tumor of the salivary glands. It accounts for less than 1% of all head and neck cancers and less than 10% of all salivary gland neoplasms. It shows slow and indolent growth rate, low probability of regional nodal metastases, high propensity for perineural invasion, multiple and/or delayed recurrences and high incidence of distant metastases. It is the most frequently encountered malignant tumor of the minor salivary glands. The oral cavity and the oropharynx are the most common sites followed by the parotid, submandibular gland, paranasal sinuses, larynx, trachea, and pharynx, in frequency order. In this report an adenoid cystic carcinoma of oral cavity localized in the left palatine tonsil and right peritonsillar tissue was presented.     

Abdominal manifestations of polyarteritis nodosa demonstrated with CT

We report a rare case of polyarteritis nodosa (PAN) presenting in childhood. The child had multiple visceral aneurysms and later developed ascending colitis and jejunitis. The diagnosis was established with multidetector CT and CT angiography.     

Malignant Struma Ovarii: A Case Report

We present a case of a 40-yr-old woman diagnosed with a primary malignant struma ovarii. The patient was admitted with the complaint of pelvic pain and a large pelvic mass in the mid-portion of lower abdomen on gynecological examination. Pre-operative tumor markers and routine biochemistry were unremarkable. She was treated with total abdominal hysterectomy and right salpingo-oopherectomy. Post-operatively, she was diagnosed with a malignant struma ovarii through the usage of histopathological criteria similar to the guidelines for primary thyroid gland disease. The patient was subsequently performed left salpingo-oopherectomy and retroperitoneal pelvic lympadenectomy for re-staging. Although, left ovary and lymph nodes were histopathologically normal, she was offered thyroidectomy but she refused to accept the offer. Thyroglobulin level was monitored in the post-operative period. She is free of the disease for 18 months.