[Incidental finding of a cardiac paraganglioma]. / Zufallsbefund eines kardialen Paraganglioms.

Cardiac paragangliomas are extremely rare neoplasms with an incidence of 1% of all cardiac tumors and can be completely asymptomatic, therefore, diagnosis is difficult. This article reports the case of an 18-year-old man with a heart murmur detected during a routine physical examination. Echocardiography revealed a heart tumor measuring 7 cm in size in the right atrium. Due to the tumor size and the threat of tricuspid valve insufficiency, tumor resection was performed. The histopathological examination revealed a cardiac paraganglioma with positive reactions of the tumor cells for chromogranin A, synaptophysin and CD56. Differentiating a primary cardiac paraganglioma from other more common cardiac tumors and particularly from metastases of neuroendocrine neoplasms from other locations is essential not only for the further clinical treatment but also for the prognosis of the patient.

Evaluation of aortic cannula jet lesions in a porcine cardiopulmonary bypass (CPB) model.

In cardiosurgery patients atherosclerotic debris displaced from the cannulation site but also from the opposite aortic wall by the "sandblast-like" effect of the high-pressure jet emanating from the cannula is a potential source of intraoperative arterial embolization and consequently postoperative neurologic dysfunction. The present study examined the extent to which shear stress exerted on the intact aortic intima by an aortic cannula jet stream can cause endothelial lesions that promote thrombogenesis and consequently thrombembolism. A single-stream, straight-tip aortic cannula was used in a porcine cardiopulmonary bypass (CPB) model. Following a 120-minute CPB pump run, a 60-minute stabilization period was allowed before sacrificing the pigs (N.=40) for histological evaluation of the ascending aorta and the brain. Opposite the cannulation site endothelial lesions (diameter: 3.81±1.3 mm; depth: 0.017±0.003 mm) were present in 22.5% (9/40) of aortic specimens. Cerebral thrombembolic lesions were not found. The present study showed that single-stream, straight-tip aortic cannulas caused jet lesions of the formerly intact aortic endothelium opposite the cannulation site in 22.5% of cases in a porcine CPB model.

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1.

Levels of the proinflammatory cytokine interleukin-6 (IL-6) are increased in therapy-resistant prostate cancer. IL-6 has been considered a positive growth factor in late-stage prostate cancer cells and a potential target for therapeutic interference. Effects of inhibition of IL-6 on cell survival were studied in LNCaP-IL6+ cells, a model system for advanced prostate cancer, which produce IL-6. We show that the autocrine IL-6 loop is responsible for resistance to apoptosis and increased cellular levels of myeloid cell leukemia-1 (Mcl-1) protein, an antiapoptotic member of the Bcl-2 family. Treatment of cells with a chimeric anti-IL-6 antibody (CNTO 328) led to the induction of apoptosis and downregulation of Mcl-1 protein levels. Specific knockdown of Mcl-1 gene expression by small interfering RNA also yielded an increase in apoptosis of LNCaP-IL-6+ cells. Vice versa, inactivation of IL-6 autocrine loop had no influence on apoptosis levels in the absence of Mcl-1, thus suggesting this molecule as a mediator of the survival action of IL-6. Mcl-1 protein regulation by the endogenous cytokine directly involved the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway. Our data support the concept of anti-IL-6 targeted therapy in therapy-resistant prostate cancer.

Cytokine-regulated expression of collagenase-2 (MMP-8) is involved in the progression of ovarian cancer.

Matrix metalloproteinases (MMPs) have been implicated in ovarian cancer progression. Among them, MMP-8 that degrades type I collagen may play a crucial role. The aim of our study was to determine MMP-8 expression and regulation in ovarian cancer and its association with other MMPs and tissue inhibitors of metalloproteinases (TIMPs). Tissue microarrays (TMAs) containing tissue cylinders from 302 patients were used for immunohistochemical studies. In addition, MMP-8 expression in vitro was analysed by a specific immunoassay and PCR-analysis. MMP-7 (81%), MMP-8 (95%), MT3-MMP (100%), TIMP-2 (100%), and TIMP-3 (96%) were expressed in all the OVCAs, but the staining intensities varied. MMP-3 (6%), MMP-9 (57%) and TIMP-1 (43%) expressions were more rarely detected. Only MMP-8 expression levels correlated with tumour grade (P<0.01), tumour stage (P<0.01), and a poor prognosis (P<0.05). MMP-8 protein and gene expression in vitro was found to be significantly upregulated by interleukin-1beta (IL-1beta, P<0.01). The data indicate that MMP-8 overexpression in OVCAs is regulated by IL-1beta and that pro-inflammatory cytokines may promote the invasive potential of ovarian cancer.

Heparanase-1 gene expression in normal, hyperplastic and neoplastic prostatic tissue.

Heparanase-1 (Hpa-1) has been implicated in tumour invasion and metastasis. In the present study, we evaluated the clinicopathological significance of Hpa-1 mRNA expression in prostate cancer and non-cancerous prostatic tissue by one-step polymerase chain reaction (PCR) of laser microdissected prostatic gland cells. In addition, cell type-specific expression of Hpa-1 mRNA in prostatic tissue was analysed by in situ hybridisation. Hpa-1 mRNA expression was found in 50% of normal and 40% of hyperplastic prostatic tissue. In situ hybridisation showed that Hpa-1 mRNA was strongly expressed in prostate gland cells. Of the 26 prostate carcinomas tested, 42% were positive for Hpa-1 mRNA. However, in non-cancerous prostatic tissue, Hpa-1 mRNA was significantly more often expressed than in less differentiated or more invasive prostate cancers (P<0.05). In situ hybridisation revealed only focal Hpa-1 mRNA expression in the neoplastic gland cells. Hpa-1 mRNA expression in the tumours significantly correlated with tumour differentiation and tumour stage (P<0.05). Our data indicate that Hpa-1 gene expression may be lost during dedifferentiation of prostatic gland cells.

Immunohistochemical detection of matrix metalloproteinases (MMP) 1 and 2, and tissue inhibitor of metalloproteinase 2 (TIMP 2) in stage I and II endometrial cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases which participate in the degradation of collagen and other extracellular matrix macromolecules. Expression of gelatonic MMPs, such as MMP-2 has been linked to enhanced tumor invasion and metastasis in in vitro and in vivo model systems. It was the aim of this study to determine whether the expression of MMP-1, MMP-2, and TIMP-2 correlates with survival in patients with surgically treated endometrial cancer. METHOD: A sample of 103 paraffin-embedded tumor specimens of surgical treated endometrial cancer was immunohistochemically investigated. RESULTS: MMP-1, MMP-2, and TIMP-2 were detected by immunohistochemistry in 95% (98/103), 87% (89/103), and 80% (82/103) of the tumour samples, respectively. Correlation coefficients for MMP-1/MMP-2, MMP-1/TIMP-2, MMP-2/TIMP-2 were 0.28 (p = 0.004), 0.05 (p = 0.6), and -0.03 (p = 0.73), respectively. In the univariate analysis, the expression of MMP-1 (log-rank test, p = ns), MMP-2 (log-rank test, p = ns), and TIMP-2 (log-rank test, p = ns) were not associated with overall survival. CONCLUSION: MMP-1, MMP-2, and TIMP-2, detected by immunohistochemistry are not helpful in predicting the prognosis of endometrial cancer patients.

Immunohistochemical detection of matrix metalloproteinases (MMP) 1 and 2, and tissue inhibitor of metalloproteinase 2 (TIMP 2) in stage IB cervical cancer.

OBJECTIVE: Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases which participate in the degradation of collagen and other extracellular matrix macromolecules. Expression of gelatonic MMPs, such as MMP-2 has been linked to enhanced tumor invasion and metastases in in vitro and in vivo model systems. It was the aim of this study to determine whether the expression of MMP-1, MMP-2, and TIMP-2 correlates with survival in patients with surgically treated cervical cancer stage IB. METHODS: A sample of 154 paraffin-embedded tumor specimens of surgical treated FIGO stage IB cervical cancer was immunohistochemically investigated. RESULTS: MMP-1, MMP-2, and TIMP-2 were detected by immunohistochemistry in 74% (113/154), 32% (49/154), and 80% (107/154) of the tumor samples, respectively. Correlation coefficients for MMP-1/MMP-2, MMP-1/TIMP-2, MMP-2/TIMP-2 were 0.14 (p = 0.12), 0.37 (p = 0.0001), and 0.17 (p: 0.005), respectively. A significant correlation was found between MMP-1 and lymph node status (P < 0.01) and lymphvascular space invasion (P < 0.05). The expression of MMP-1 (log-rank test, p = 0.6), MMP-2 (log-rank test, p = 0.8), and TIMP-2 (log-rank test, p = 0.15) were not correlated with overall survival. CONCLUSION: MMP-1, detected by immunohistochemistry, seems to play a role in the development of lymphvascular space invasion and lymph node metastases, but is not helpful in predicting the prognosis of cervical cancer patients.