A novel angiogenesis inhibitor bevacizumab induces apoptosis in the rat endometriosis model.

Our aim was to investigate the effects of anti-vascular endothelial growth factor (anti-VEGF) antibody Bevacizumab on endometrial explants and on apoptotic gene expression levels in the rat endometriosis model. Endometriotic implants were surgically formed, and rats treated with (i) 1 mg/kg single subcutaneous injection of depot leuprolide acetate; (ii) 2.5 mg/kg of single intaperitoneal injection of bevacizumab; (iii) intraperitoneal injection of saline. Histopathologic scores and adhesion scores of endometriotic foci and levels of Bcl-2-associated X protein (Bax), Cytochrome c (Cyt-c), B-cell lymphoma/leukemia 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) mRNA gene expressions of endometriotic foci. Bevacizumab treatment decreased the endometriotic explant size compared with control. Bevacizumab-treated rats had lower total adhesion scores when compared with the control group. Semi-quantitative evaluation of the persistence of endometrial epithelial cells in the explants showed a lower score in gonadotropin-releasing hormone (GnRH) agonist-treated rats compared with control rats. In Bevacizumab increased expression of Bax 3.1-fold, Cyt-c 1.3-fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold compared with the control group. The GnRH agonist increased expression of Bax 3.0 fold, Cyt-c 1.3 fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold, compared with the control group. This study suggests that a novel angiogenesis inhibitor, anti-VEGF antibody bevacizumab is as effective as GnRH agonist in the regression of the endometriotic lesions in rat endometriosis model. One possible mechanism of this effect is the induction of apoptosis.

Multigene methylation analysis of conventional renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common malignancy of the kidney. Since RCC is curable when it is confined to the renal capsule, early diagnosis is extremely important. Promoter hypermethylation is the most common mechanism for the inactivation of the tumor suppressor genes (TSG) in the development of human cancer. This study aimed to investigate the methylation profiles of 7 TSG (RASSF1A, ECAD, TIMP3, APC, MGMT, p16 and RARbeta2) in 3 different tissue samples (normal, premalign, malign) of patients with RCC. Twenty-one patients diagnosed with RCC were included in the study. Methylation-specific polymerase chain reaction was performed to detect the methylation patterns of the 7 TSG. High methylation rates for the genes RASSF1A (76%), p16 (80%), ECAD (42%), TIMP3 (33%) and MGMT (33%) were observed in the patients with RCC. The APC (14%) and RARbeta2 (19%) genes showed low methylation rates. In conclusion, 5 TSG (RASSF1A, ECAD, TIMP3, MGMT and p16) showed high methylation rates in RCC patients. A methylation-based gene test including these genes may be useful in the early detection of RCC.

Small cell neuroendocrine carcinoma of the endometrium and laparoscopic staging: a clinicopathologic study of a case and a brief review of the literature.

Small cell neuroendocrine (NE) carcinoma is one of the most aggressive tumors that arise in the female genital tract. Small cell carcinoma of the endometrium (SCCE) is an extremely rare disease. Because of its rarity, the only clinical reports are limited to case studies, and therefore, clinical behavior and optimal treatment modalities are not well defined. To the best of our knowledge, we present the first case of SCCE staged by laparoscopic approach. A 54-year-old parous woman admitted with intermittent vaginal spotting. On physical examination, she had a 4- x 3-cm mass fungating out of the cervical os. Magnetic resonance imaging showed an endometrial mass of 25 x 30 x 50 mm in dimensions, invading less than 50% of the depth of the myometrium at the uterine fundus. Pathologic examination revealed undifferentiated malign NE tumor of endometrium of small cell type. The patient underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and laparoscopic pelvic and para-aortic lymphadenectomy. The disease was surgically staged as IB. Histologically, tumor cells were monotone, with scanty, ill-defined cytoplasm and hyperchromatic nuclei. Immunohistochemically, tumor showed positive immunoreactivity for P16, neuron-specific enolase, and synaptophysin. She underwent pelvic external radiation and brachytherapy postoperatively. Patient has no evidence of disease after 26 months of follow-up. Small cell NE carcinoma of the endometrium is an extremely rare and aggressive disease. With the availability of skilled endoscopic surgeons, laparoscopic management of women, even with SCCE in early stage, can be a feasible option.

Premalignant lesions of the kidney share the same genetics changes as conventional renal cell carcinoma.

This study investigated the frequency of allelic imbalance (AI) in particular loci in conventional renal cell carcinoma tissue and premalignant lesions of the kidney. DNA from the tumor tissue, premalignant lesions and normal kidney tissue of radical nephrectomy specimens from 33 patients was obtained. It was amplified with a set of eight microsatellite markers, which are located on chromosomes 2, 3, 5, 8, 9, 11, 16, 17. AI in DNA samples was determined by analysis of the alteration in (CA)n repeats. The rates of AI in tumor tissue were found to be between 22.2% and 53.3% and in premalignant lesions between 11.1% and 40.0%. Premalignant lesions and tumor tissues in conventional renal cell carcinoma have the same genotypic changes in 50.0-87.8% (informative cases). These results suggest that the progressive accumulation of AI in areas of premalignant lesions may contribute to the development of renal cell carcinoma, representing an important molecular event in the multistep renal carcinogenesis cascade.

Recovery period of the bladder after exposure to soluble virulence factor produced by Escherichia coli.

OBJECTIVES: This study was designed to determine the time interval required for the recovery of the bladder after exposure to soluble virulence factor (SVF) in an animal model. In addition, we aimed to determine the changes in the epithelium during the recovery period. METHODS: A total of 46 male New Zealand rabbits were used in this study. Sterile human urine was infected with Escherichia coli type O6 to obtain supernatant, which would contain SVF, but no bacteria. Rabbits were assigned to one of three groups comprising the supernatant urine group (SUG) and controls, respectively. Sterile human urine and supernatant urine were instilled to controls and SUG, respectively. Bacterial inoculation with E. coli was performed 1, 24 and 72 h after initial instillation. Histopathologic and microbiologic analyses were performed on these animals. RESULTS: In SUG bacterial colonization was significantly higher than in controls 1 and 24 h after exposure to supernatant. Histopathologic analysis confirmed this finding. Histologic changes were most pronounced 1 hour after instillation of supernatant. A moderate degree of recovery was noted at 24 h, and complete recovery was seen at 72 h. CONCLUSION: Bacterial growth is potentiated by SVF-induced impaired bladder mucosa until the repairing process has been completed. During this time interval, SVF enables the colonization and growth of E. coli and other bacterium species that may result in sustained bacterial presence and recurrent infection.

May cathepsin D immunoreactivity be used as a prognostic factor in endometrial carcinomas? A comparative immunohistochemical study.

OBJECTIVE: To investigate the prognostic value of immunohistochemical detection of cathepsin D and the association between cathepsin D and established prognostic factors in endometrial carcinoma. METHODS: Cathepsin D immunoreactivity was determined by an immunohistochemical technique in a series of 79 patients with surgical stage I-III primary endometrial carcinoma. RESULTS: Of 79 tissue specimens, 48 (61%) showed a positive reaction for cathepsin D. A significant correlation between cathepsin D and histological grade was found (P < 0.05). The other established clinicopathological prognostic factors were not associated with cathepsin D. There was not any significant difference in prognosis between the positive cases and negative cases for cathepsin D (P > 0.05). In the univariate analysis cathepsin D immunoreactivity did not show significant prognostic value for overall survival (P > 0.05). The multivariate analysis also showed that cathepsin D was not related to patient outcome (P = 0.24, relative risk = 0.34, 95% confidence interval = 0.05-2.09). CONCLUSIONS: Our results suggest that cathepsin D immunoreactivity may not be of prognostic value but more studies are needed to evaluate the relationship between its immunoreactivity in tumor cells and in other cells.

Epithelioid angiomyolipoma: a case report.

Epithelioid angiomyolipoma is a recently recognized tumor entity. We report a case of epithelioid angiomyolipoma of the kidney that occurred in a 70-year-old female. The patient presented with massive abdominal hemorrhage and shock. There was no history of tuberous sclerosis complex. The tumor consisted of smooth muscle, adipocytes, small-to-medium-sized hyalinized blood vessels and numerous pleomorphic epithelioid cells with clear to eosinophilic cytoplasm. Mitosis was exceptional and no glandular pattern was recognizable. Immunohistochemically the epithelioid cells were strongly positive for HMB45 and CD68, focally positive for S-100, actin and vimentin, and negative for epithelial markers including epithelial membrane antigen and cytokeratins. Previous reports in the English literature suggest that epithelioid angiomyolipoma may have malignant potential. In our case, at six months from surgery the patient is alive and well without evidence of relapse or metastasis.

A rare tumor of craniofacial bones in children: a pediatric chondroblastic osteosarcoma case with diagnostic and therapeutic problems.

Osteosarcoma of the cranial facial region is uncommon and only rarely involves the ethmoid or sphenoid bones. The authors report on an unusual case of a 17-year-old male presenting with chondroblastic osteosarcoma of the maxillary, ethmoid, and sphenoid sinuses who remains well and disease-free at 46 months. He was treated with anterior craniofacial resection followed by postoperative radiotherapy to the sight of the primary tumor. He did not receive chemotherapy because of emerging hepatitis-B infection and vasculitis. The literature on extragnathic craniofacial osteosarcomas is reviewed with particular emphasis on treatment options of this rare tumor.

Omentectomy, peritoneal biopsy and appendectomy in patients with clinical stage I endometrial carcinoma.

The aim of this study was to evaluate whether omentectomy, appendectomy, and peritoneal biopsy should be a routine part of staging surgery in endometrial carcinoma. Data of 97 patients who had been diagnosed with clinical stage I endometrial carcinoma were reviewed. Associations in the data obtained, pelvic and para-aortic lymph node status, depth of myometrial invasion, grade, and histology were investigated. The chi-square (chi2) test was used for statistical analysis. Of 97 patients, six (6%) had omental metastases, which was microscopic in four. There was a statistically significant relationship between omental metastasis and tumor grade (P < 0.01). Deep myometrial invasion was significantly more common in patients with omental metastases. Tumor was found in one of 55 appendectomy specimens (2%). Omentectomy may be included in surgical staging in patients with deeply invasive or grade 3 endometrial cancer because of the possibility of omental metastasis in spite of what appears to be stage I disease in laparotomy. In other cases, omentectomy and appendectomy and biopsies from peritoneal sites should be performed in the presence of grossly suspicious disease.

Borderline phylloides tumor in an 11-year-old girl.

Phylloides tumor is an uncommon breast tumor in children. Only a few cases have been reported in the literature. A case of borderline phylloides tumor in an 11-year-old girl is described.

Subcapsular hemorrhage of adult Wilms' tumor.

Wilms' tumor is a rare malignancy of kidney in adults. It usually cannot be differentiated from other renal masses preoperatively. This is a presentation of a case of adult Wilms' tumor who developed spontaneous hemorrhage during radiological evaluation. As tumor rupture can change the stage of the tumor and alter the prognosis of the patient, urgent work-up and treatment is advised.

Circadian rhythmicity in serotonin-induced acute gastric mucosal injury in rats.

Time-dependent patterns in the susceptibility of the rat gastric mucosa to ulcerogenic stimuli involving stress or chemical injury have been described. The purpose of this study was to evaluate whether serotonin (5-HT)-induced gastric mucosal injury is produced in a circadian fashion in the rat model. In fasted Wistar rats (adapted for 3 weeks to a standard 12-h light-dark cycle), 5-HT administered subcutaneously (20 mg/kg, 4 h before autopsy) produced gastric mucosal injury. The stomachs were removed and the ulcers were scored for intensity, using a scale of 0-4. In studies performed at 4-h intervals, beginning 1 h after lights-on, most of the mucosal injury occurred at 2000 h, i.e. early in the dark phase. Likewise, serum corticosterone levels were also found to be high at the same time period. The time of 2000 h is approximately determined to be the beginning of the rats' active period. These results suggest that the extent of acute 5-HT-induced gastric mucosal injury varies with the time of day and that elevations in corticosterone concentrations might be responsible for the 5-HT-induced gastric mucosal injury.

Investigation of p53, c-erbB-2, PCNA immunoreactivity, DNA content, AgNOR and apoptosis in bladder carcinoma as prognostic parameters.

The association between known prognostic variables such as TNM stage, histological grade and mutant p53 tumor suppressor gene product, c-erbB-2 oncoprotein, DNA ploidy and cell kinetic data, including mitoses, PCNA expression, AgNOR scores and apoptosis, was investigated in 29 transitional cell carcinoma (TCC) cases. A positive correlation between the histologic grade and all the studied parameters, except for c-erbB-2 expression, and a positive correlation between the stage and histological grade, DNA ploidy, mitoses, apoptosis and p53 expression were found. The results of this study are in accordance with some of the previous studies, except for apoptosis which had been studied for the first time in TCCs. Although we found a statistically significant correlation between the apoptosis and both tumor stage and histological grade, the predictive value of apoptosis as an independent prognostic factor remains to be established in a larger series.

Prostatic carcinoma presenting with painless parotid mass.

Metastasis of prostate cancer to the parotid gland is exceedingly rare, with only 4 cases reported in the literature. We present the case of an 83-year-old white man who had a painless parotid mass that was diagnosed as metastatic prostate cancer. Immunohistochemical staining with prostate-specific antigen was positive. This is the first case of prostate cancer presenting with a painless parotid mass. Prostate cancer can be metastatic to the head and neck region, and this should be kept in mind when treating patients with this disease.