Paget-Schroetter Syndrome: Review of Pathogenesis and Treatment of Effort Thrombosis

Effort thrombosis, or Paget-Schroetter Syndrome, refers to axillary-subclavian vein thrombosis associated with strenuous and repetitive activity of the upper extremities. Anatomical abnormalities at the thoracic outlet and repetitive trauma to the endothelium of the subclavian vein are key factors in its initiation and progression. The role of hereditary and acquired thrombophilias is unclear. The pathogenesis of effort thrombosis is thus distinct from other venous thromboembolic disorders. Doppler ultrasonography is the preferred initial test, while contrast venography remains the gold standard for diagnosis. Computed tomographic venography and magnetic resonance venography are comparable to conventional venography and are being increasingly used. Conservative management with anticoagulation alone is inadequate and leads to significant residual disability. An aggressive multimodal treatment strategy consisting of catheter-directed thrombolysis, with or without early thoracic outlet decompression, is essential for optimizing outcomes. Despite excellent insights into its pathogenesis and advances in treatment, a significant number of patients with effort thrombosis continue to be treated suboptimally. Hence, there is an urgent need for increasing physician awareness about risk factors, etiology and the management of this unique and relatively infrequent disorder

Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells.

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase androgen responsiveness

Altered antioxidant system stimulates dielectric barrier discharge plasma-induced cell death for solid tumor cell treatment.

This study reports the experimental findings and plasma delivery approach developed at the Plasma Bioscience Research Center, Korea for the assessment of antitumor activity of dielectric barrier discharge (DBD) for cancer treatment. Detailed investigation of biological effects occurring after atmospheric pressure non-thermal (APNT) plasma application during in vitro experiments revealed the role of reactive oxygen species (ROS) in modulation of the antioxidant defense system, cellular metabolic activity, and apoptosis induction in cancer cells. To understand basic cellular mechanisms, we investigated the effects of APNT DBD plasma on antioxidant defense against oxidative stress in various malignant cells as well as normal cells. T98G glioblastoma, SNU80 thyroid carcinoma, KB oral carcinoma and a non-malignant HEK293 embryonic human cell lines were treated with APNT DBD plasma and cellular effects due to reactive oxygen species were observed. Plasma significantly decreased the metabolic viability and clonogenicity of T98G, SNU80, KB and HEK293 cell lines. Enhanced ROS in the cells led to death via alteration of total antioxidant activity, and NADP+/NADPH and GSH/GSSG ratios 24 hours (h) post plasma treatment. This effect was confirmed by annexin V-FITC and propidium iodide staining. These consequences suggested that the failure of antioxidant defense machinery, with compromised redox status, might have led to sensitization of the malignant cells. These findings suggest a promising approach for solid tumor therapy by delivering a lethal dose of APNT plasma to tumor cells while sparing normal healthy tissues

Synthesis, structure and anticancer activity of copper(II) complexes of <i style="">N</i>-benzyl-2-(diethylamino)acetamide and 2-(diethylamino)-<i style="">N</i>-phenylethylacetamide

474-483The ligands N-benzyl-2-(diethylamino)acetamide, (HL1) and 2-(diethylamino)-N-phenylethylacetamide (HL2), have been used to synthesize copper(II) complexes, [Cu(HL1)2](ClO4)2 (1) and [Cu(HL2)2](ClO4)2 (2), respectively. Both complexes are well characterized by various spectral and physical methods. The crystal structure of complex (1) reveals that two bidentate ligands coordinate the Cu(II) ion via Oamide and Namine atoms in the basal plane whereas one of the ClO4- ions occupies the apical position maintaining a square–pyramidal geometry. Screening results for anti–proliferative studies against the U87 and HeLa cancerous cells indicate promising activity. The complexes enhanced growth inhibition and cell death in a concentration and time dependent manner for both U87 and HeLa cell lines. Of the two compounds, complex (2) exhibits better activity against both HeLa and U87 cells. Further, both complexes are specifically potent against U87 after 72 h of treatment. Micronucleus and apoptosis frequencies are 3 – 4 times higher in treated cells when compared with untreated control. Despite potent in vitro activity, both complexes exhibit diminished cytotoxicity against the normal human HEK cells at all effective concentrations

Analyses of the size variability of T98G and HEK293 cells.

<p>(a) and (b) show the frequency distribution of length and width, respectively, in the T98G cell population. (c) and (d) shows the frequency distribution of length and width, respectively, in the HEK293 cell population.</p

Induction of ROS in APNT DBD plasma treated cells.

<p>(a) T98G, SNU80, KB and HEK293 cells were treated with the oxidation-sensitive fluorescent probe 2,7-dichlorodihydrofluorescein diacetate (H₂DCFDA) for detection of total ROS, (b) detection of H₂O₂ level (in µM) in cells observed at 24 h after exposure. In (a) and (b), all fluorescence levels were expressed as fluorescence intensity (FL intensity). Results from four independent experiments are shown as mean ± SD, and Student’s <i>t</i>-test was performed to controls (*<i>p</i><0.05 and **<i>p</i><0.01).</p

Analysis of APNT induced cell death (apoptosis).

<p>Flow cytometry data of Annexin V and PI staining of human T98G, SNU80, KB and HEK293 cells after plasma treatment. Apoptosis of each cell was evaluated after 24± SD, and Student’s <i>t</i>-test was performed to controls (*<i>p</i><0.05 and **<i>p</i><0.01).</p

The cell counts (relative to control) showed exposure/incubation time-dependent death rate.

<p>KB cells underwent more severe loss than SNU80 and HEK293 by APNT DBD plasma treatment. Results from four independent experiments are shown as mean ± SD, and Student’s <i>t</i>-test was performed to controls (*<i>p</i><0.05 and **<i>p</i><0.01).</p

Involvement of caspase activation and loss in mitochondrial membrane potential during apoptosis.

<p>(a) APNT plasma induced activation of caspase-3/7 of human glioblastoma (T98G) and a non-malignant (HEK293) cell lines. (b) APNT plasma affects mitochondrial membrane potential of T98G, SNU80, KB and HEK293 cells. (c) Flow cytometric plot of mitochondrial membrane potential in cells, using Mito Flow rhodamine dye. Results from four independent experiments are shown as mean ± SD, and Student’s <i>t</i>-test was performed to controls (*<i>p</i><0.05 and **<i>p</i><0.01).</p