Response to trastuzumab and investigation of expression profiles of matrix metalloproteinase-related proteins in primary breast cancer stem cells.

Breast cancer (BC) is the leading cause of cancer deaths in women. One of the reasons for the failure of BC treatment is reportedly the ineffectiveness of chemotherapeutic drugs against breast cancer stem-like cells (BCSCs). HER2 receptors have an important role in the self-renewal of BCSCs. Matrix metalloproteinase (MMP) and cytokine levels were found to be higher in BCSCs, which demonstrates their potential metastatic capacity. Therefore, the aim of this study was to evaluate the response of BCSCs to trastuzumab and to investigate the MMP levels in primary breast cancer cells and HER2+ BCSCs. Tumour tissue samples were obtained during surgical intervention from ten breast cancer patients, and primary culture cells were established from these tissues. Four major molecular subgroups were sorted from the primary culture: HER2+ BCSCs (CD44+CD24-HER2+), HER2- BCSCs (CD44+CD24-HER2-), HER2- primary culture cells (CD44+CD24+HER2-) and triple positive primary culture cells (CD44+CD24+HER2+). These cells were cultured and treated with trastuzumab, paclitaxel, carboplatin, and the combination of those three drugs for 96 h. Cellular responses to these drugs were determined by XTT cytotoxicity test. MMPs and cytokine array analysis showed that MMPs and TIMP-1, TIMP-2 proteins were expressed more in HER2+ BCSCs than in primary culture. HER2- BCSCs were more resistant to drugs than HER2+ BCSCs. Our findings suggest that the presence of HER2- BCSCs may be responsible for primary trastuzumab resistance in HER2+ BC cell population. Further studies investigating the function of MMPs are needed for drug targeting of BCSCs.

Survivin and cycline D1 expressions are associated with malignant potential in mucinous ovarian neoplasms.

The most prevalent malignant ovarian neoplasms are epithelial ovarian cancers which is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of survivin and cycline D1 biomarkers in mucinous ovarian neoplasms and their correlations with clinicopathological variables in mucinous ovarian cancers. We analyzed pathological specimens of 98 patients with benign (n = 34), borderline (n = 22) and malignant (n = 42) mucinous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Immunohistochemical analysis revealed that survivin and cyclin D1 expressions were located primarily in the nucleus of ovarian tumor cells and relatively weaker cytoplasmic staining. Survivin expression was significantly higher in malignant tumors (88.1 %) than those found in borderline (18.2 %) and benign tumors (8.8 %) (p < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (100 %) compared to borderline (36.4 %) and benign tumors (5.9 %) (p < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant mucinous tumors. In terms of clinicopathological variables, tumor grade, FIGO stage and lymph node methastasis were associated with the expression of both biomarkers. Whereas age exhibited no different correlations in mucinous ovarian cancers. The expressions of survivin and cycline D1 are positively correlated with the malignant potential of mucinous ovarian neoplasms.

The expression of HER-2/neu (c-erbB2), survivin and cycline D1 in serous ovarian neoplasms: their correlation with clinicopathological variables.

Ovarian cancer is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of HER-2/neu (c-erbB2), survivin and cycline D1 biomarkers in serous ovarian neoplasms and their correlations with clinicopathological variables in serous ovarian cancers. We analyzed pathological specimens of 62 patients with benign (n = 25), borderline (n = 14) and malignant (n = 23) serous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Significantly more immunoreactivity with HER-2/neu was detected in malignant tumors (100 %) compared to borderline (78.6 %) and benign tumors (48 %) (P < 0.01). Survivin expression was significantly higher in malignant tumors (91.3 %) than those found in borderline (71.4 %) and benign tumors (24 %) (P < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (95.6 %) compared to borderline (85.7 %) and benign tumors (48 %) (P < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant serous tumors. In terms of clinicopathological variables, only tumor grade was associated with the expression of all biomarkers others exhibited different correlations in serous ovarian cancers. The expressions of HER-2/neu (c-erbB2), survivin and cycline D1 are positively correlated with the malignant potential of serous ovarian neoplasms.

Pseudoaneurysm originating from left ventricle aneurysm: an autopsy case and review of literature.

Rupture of the free wall of the left ventricle is a catastrophic complication of acute myocardial infarction. Rarely, free wall rupture is contained by overlying adherent pericardium, producing a pseudoaneurysm of the left ventricle. In this report, a case of a left ventricular pseudoaneurysm due to a previous myocardial infarction is described. A 55-year-old woman had a severe chest pain 11 months prior to death. No cardiac investigation was performed. Three days prior to death, she suffered from fatigue and weakness, and had a witnessed sudden cardiac death. At autopsy, a 8.5 × 10 × 8 cm pseudoaneurysm of the left ventricle was found. There was severe coronary artery atherosclerosis. There were extensive adhesions between pericardium and pseudoaneurysm wall. The cause of death was attributed to heart failure and resulting arrhythmia. The case illustrates the rare event of left ventricular pseudoaneurysm first diagnosed at forensic autopsy.

Malignant Brenner tumor of the ovary: analysis of 13 cases.

OBJECTIVE: Most Brenner tumors are benign, with only 1% being malignant. In this study we report on 13 cases with malignant Brenner tumor of the ovary and discuss the clinical, demographic and histologic features. METHOD: Thirteen patients with malignant Brenner tumor of the ovary who were treated at Selçuk University Gynecology Department over a 6-year period from January 2004 to December 2010 were retrospectively analysed from hospital electronic medical records. Clinical and pathologic findings were reported. RESULTS: The median age of the study population was 55.69 ± 11.81 years (range 43-79 years). Most of the patients presented with abdominal pain (6/13, 46.2%). The mean size of the ovarian tumors was 9.19 ± 1.34 cm (range 4-16.5 cm). Six patients (46.2%) were in stage III, five (38.5%) in stage I, and two (15.4%) in stage IV. Ten patients (76.9%) received chemotherapy. The mean follow-up was 38.38 ± 23.25 months (range 5-84 months). During follow-up, recurrence was detected in 7 patients (53.8%). The mean recurrence time was 23.8 ± 14.46 months (range 11-48 months). CONCLUSION: In our study, we found that diagnosis was at an advanced stage, and recurrence rate was high. The mainstay of treatment is surgical resection, but the exact regimen and benefit of adjuvant therapy remain unknown.

Cotyledonoid dissecting leiomyoma of the uterus with intravascular growth in postmenopausal woman: a case presentation.

Cotyledonoid dissecting leiomyoma ("Sternberg tumor") is an unusual type of a benign uterine smooth-muscle tumor with a distinctive gross appearance. A 57-year-old woman (gravida 7, para 6), in menopause for 3 years, presented with a 3-4-year history of increased pelvic pain. The transvaginal ultrasound scan showed a 2.5 cm sized heterogenic mass in the uterus cavity and 4 × 5 cm sized irregular contoured mass in the right lateral aspect of the uterus. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed with removal of the pelvic tumor extension. Definite pathologic examination result was cotyledonoid dissecting leiomyoma of the uterus with intravascular growth. The patient is receiving follow-up care every 6 months, and she has no evidence of disease after 22 months of follow-up. The worrying appearance of the gross specimen is often mistaken for malignant or non-uterine lesions that may result in overtreatment. It is important to be aware of this entity to prevent overly aggressive treatment for this benign smooth-muscle neoplasm.

Uterine smooth muscle tumors of uncertain malignant potential: a case presentation.

A 42-year-old virgin woman was admitted to our clinic with increasing menorrhagia and dysmenorrhea for several months. A pelvic ultrasound scan showed a 9 × 7 cm heterogeneous mass in the uterine cavity. Pelvic magnetic resonance imaging showed a large non-homogeneous tumor mass measuring 97 × 56 mm in the uterine cavity. After intravenous contrast material, cystic necrotic areas with marked contrast enhancement were observed in the solid lesion. Tumor markers were all within normal ranges. The patient underwent laparotomy, and total hysterectomy and bilateral salpingo-oophorectomy were performed. Our case was diagnosed as uterine smooth muscle tumor of uncertain malignant potential (STUMP). The patient was put on a close clinical follow-up schedule, and is doing well without recurrence in 2 years later. Patients with STUMP should be counseled regarding the potential for recurrence as leiomyosarcoma, and may require closer surveillance than a yearly examination and may need a consultation with a gynecologic oncologist.

Askin's Tumor in an Adult: Case Report and Findings on 18F-FDG PET/CT.

Primitive neuroectodermal tumor (PNET) of the chest wall or Askin's tumor is a rare neoplasm of chest wall. It most often affects children and adolescents and is a very rare tumor in adults. In this case report, we present an Askin's tumor occurred in a 73-year-old male. The patient was admitted with a history of 3-month lower back pain and cough. In computed tomography, there was a lesion with dimensions of 70 x 40 x 65 mm in the superior segment of the lower lobe of the left lung. Positron emission tomography/computed tomography with 18F-flourodeoxyglucose revealed a pleural-based tumor in the left lung with a maximum standardized uptake value of 4.36. No distant or lymph node metastases were present. The patient had gone through surgery, and wedge resection of the superior segment of left lobe and partial resection of the ipsilateral ribs were performed. Pathology report with immunocytochemistry was consistent with PNET and the patient received chemotherapy after that.

Malignant glioblastomatous transformation of a low-grade glioma in a child.

BACKGROUND: The term of low-grade glioma addresses a favorable clinical outcome with indolent histological features in general consideration; however, recent studies underline the inconsistency, which originates from the accumulation of different histologic subtypes in this terminology. The malignant transformation of a low-grade glioma is unusual but presents a poor prognosis. CASE HISTORY: We report a case of a 12-year-old boy, who was referred for complaints of recurrent seizures. His physical examination was unremarkable, but it was learned that a peripheral mass lesion located on the left posterior parietal lobe--which had been thought to be a low-grade glioma--had been detected on a magnetic resonance imaging 2 years ago at a different hospital. The patient was then treated with valproate and carbamazepine for the seizures and advised to be followed up without any additional diagnostic and therapeutic studies for his suspected low-grade glioma. A recent magnetic resonance imaging study showed enlargements of the mass and surrounding edema with additional necrosis. Surgical excision of the tumor was performed. After the diagnosis of glioblastoma multiforme, the patient received radiation therapy and chemotherapy with a good clinical recovery without any evidence of residue or recurrence at 12-month follow-up. CONCLUSION: The first line treatment modality in the management of low-grade glioma--especially in suitable patients--is clearly surgery. The gross total resection guarantees the distinguishing of the histological types of the low-grade gliomas and reflects the biologic behavior of these tumors. Observation without surgery must be reserved for selected inoperable cases.

Effects of phototherapy on the growth plate in newborn rats.

The aim of the present study was to evaluate the effect of phototherapy and oxidative stress on the growth plate of newborn rats. Forty newborn Sprague-Dawley rats were randomized into a phototherapy group and a control group. Twenty of the rats received phototherapy for 7 days. All zones of the growth plate were assessed with quantitative histomorphometric analysis. Individual zonal lengths were measured for the reserve zone (RZ), the proliferative zone (PZ), the hypertrophic zone (HZ), ossifying cartilage (OC), and total zone (TZ) of the growth plate. Levels of plasma malondialdehyde (MDA), an index of oxidative stress, were also evaluated. Compared with zonal lengths on day 7 after phototherapy between the two groups, the phototherapy group had significantly lower values than those of controls for RZ (5.13 +/- 0.36 vs. 6.4 +/- 0.85 mm x 10(-2); P < 0.001), PZ (20.6 +/- 3.0 vs. 29.25 +/- 1.68 mm x 10(-2); P < 0.001), HZ (15.4 +/- 1.44 vs. 20.87 +/- 1.12 mm x 10(-2); P < 0.001), OC (47.08 +/- 4.25 vs. 62.06 +/- 3.7 mm x 10(-2); P < 0.001), and TZ (88.15 +/- 6.56 vs. 118.48 +/- 4.50 mm x 10(-2); P < 0.001). Plasma MDA levels were correlated with the size of the PZ in the phototherapy group (r = -0.53, P = 0.01). In a multivariate regression model for all rats, being in the phototherapy group was the best predictor of the size of the TZ (beta = -0.94, P < 0.001), with the total variance explained being 88%. These results suggest that in newborn rats, receiving phototherapy is associated with early impairment of growth plate structure, and oxidative stress may be the main risk factor for growth plate injury.

Gastric heterotopia together with intestinal metaplasia in the gallbladder: case report and review of literature.

Heterotopic gastric mucosa in the gallbladder is extremely unusual. In this study, we aimed to report a case of gastric heterotopia together with intestinal metaplasia in the gallbladder of a 16-year-old male patient who experienced a sudden onset of epigastric pain with nausea. He was admitted to the hospital with a prediagnosis of mild degree obstructive jaundice. Cholecystectomy and hepaticoduodenostomy were carried out. In the microscopical examination of the gallbladder, an antral and pyloric type gastric mucosa together with intestinal metaplasia were clearly evident in the gallbladder submucosa, and the adjacent gallbladder mucosa showed typical features of chronic cholecystitis.

The effects of serum estrogen levels on hypoxemia and blood nitric oxide levels in experimental hepatopulmonary syndrome.

BACKGROUND: : Hepatopulmonary syndrome (HPS) is a well-defined cause of hypoxemia in patients who have liver disease due to abnormal intrapulmonary vascular dilatation. The pulmonary symptoms of HPS are the result of oxygenation defects that occur as a result of acquired dilatations of the pulmonary blood vessels. In this study, we investigated the effects of estrogen and nitric oxide (NO) in experimental HPS, especially in intrapulmonary vascular dilatation. METHODS: : Fifty female Sprague-Dawley rats were used in this study. The animals were divided into five groups of 10. Group l (the control group): the common bile duct (CBD) was dissected but not ligated. Group 2 (the cirrhosis group): the CBD was ligated. Group 3 (the cirrhosis+oophorectomized group): the CBD was ligated and a bilateral oophorectomy performed. Group 4 (the cirrhosis+estrogen group): the CBD was ligated and exogenous estrogen (5000U/kg) given. Group 5 (the control+estrogen group): the CBD was dissected, but not ligated and exogenous estrogen (5000U/kg) given. A 5-week waiting period was observed for the development of cirrhosis and the rats' lungs and liver were taken for histopathological examination. Pulmonary vessel diameters were measured. The total bilirubin, direct bilirubin, alkaline phosphatase (ALP), estrogen and serum nitric oxide (NO) levels were measured. RESULTS: : The mean perialveolar vessel diameters were significantly higher in the cirrhotic rats (Groups 2, 3, and 4) than the control and control+estrogen administered groups. Again, when we compared the cirrhosis+oophorectomized group and the cirrhosis+estrogen group, the mean perialveolar vessel diameter was significantly lower in the cirrhosis+oophorectomized group than the cirrhosis+estrogen administered group (p=0.001). The mean perialveolar vessel diameter in the cirrhosis+oophorectomized group was significantly lower than the cirrhosis group (p=0.01). When we compared the cirrhotic rats (Groups 2, 3, and 4) and the control group, the plasma NO levels were significantly higher in the cirrhotic rats than the control group (p<0.001). Among the cirrhotic rats, the plasma NO levels were 47.2+/-0.7 and 70.9+/-1.5mumol/l in the cirrhosis+oophorectomized group and the cirrhosis+estrogen administered group, respectively (p=0.004). CONCLUSIONS: : We consider that raised levels of estrogen have a potential role in intrapulmonary vascular dilatation and hypoxemia in HPS. Also, we consider that this effect of estrogen is due to increased levels of NO. Antiestrogenic surgical therapy may decrease the serum estrogen and NO levels, and may decrease the diameter of perialveolar vessels in order to relieve hypoxia in cirrhotic cases.