Small interfering RNA urokinase silencing inhibits invasion and migration of human hepatocellular carcinoma cells

The serine protease urokinase-type plasminogen activator (u-PA) is involved in a variety of physiologic and pathological processes; in particular, u-PA mRNA is up-regulated in human hepatocellular carcinoma (HCC) biopsies and its level of expression is inversely correlated with patients' survival. To determine the role of u-PA in the invasiveness properties of HCC, we successfully down-regulated u-PA by RNA interference (RNAi) technology, in an HCC-derived cell line at high level of u-PA expression. RNAi is a multistep process involving generation of small interfering RNAs (siRNA) that cause specific inhibition of the target gene. SKHep1C3 cells were transfected with a U6 promoter plasmid coding for an RNA composed of two identical 19-nucleotide sequence motifs in an inverted orientation, separated by a 9-bp spacer to form a hairpin dsRNA capable of mediating target u-PA inhibition. Stable transfectant cells showed a consistently decreased level of u-PA protein. In biological assays, siRNA u-PA-transfected cells showed a reduction of migration, invasion, and proliferation. In conclusion, u-PA down-regulation by RNAi technology decreases the invasive capability of HCC cells, demonstrating that stable expression of siRNA u-PA could potentially be an experimental approach for HCC gene therapy.     

On the mode of action of heterologous antileukemic sera. Growth of syngeneically transplanted leukemia cells on serum treated neonatally thymectomized mice (author's transl)]

A heterologous antiserum against a Nitrosomethylurea--induced mouse leukemia prevented the outgrowth of syngeneically transplanted leukemia cells in neonatally thymectomized mice. After subcutaneous challenge with 50 000 leukemia-ascites cells thymectomized CBA mice at the age of 8 weeks were given 5 intraperitoneal injections each of 0,1 ml of the heterologous serum. While the antileukemic serum protected 9 out of 11 mice all of the 11 mice treated with normal rabbit serum developed a tumor. The absence of the thymus was confirmed by macroscopic control and by the absence of antibodies against the injected rabbit serum. With regard to previous findings showing a cooperation of heterologous antibodies with host cells as responsible for the antileukemic effect this result indicates that the effector cells are thymus-independent.     

Effect of electrode cap on measured cortical motor threshold

We investigated the role of electrode cap use in the determination of the cortical motor threshold (MT), and the resulting changes in the recorded motor evoked potentials (MEPs). We also tested whether the induced changes in determined MT could be corrected via previously introduced correction method. Sixteen healthy subjects were studied. Navigated TMS was used for mapping the optimal representation area of the thenar musculature in the primary motor cortex and individual MTs were determined with and without the use of the electrode cap. A mathematical correction was utilized to compensate for the effect of electrode cap in the MTs. Individual MEPs were also measured. We observed a significant (p<0.05) increase in the determined MTs attributable to the use of the electrode cap. At the group level this difference was reduced significantly (p<0.01) by the use of the correction method. However, at the individual level the efficiency of the correction was poor. The MEP-amplitudes were not affected whether measured with or without the electrode cap. The electrode cap affects significantly the cortical MT measured as stimulation intensity making the comparison of MTs difficult with other studies not having used an electrode cap.     

Navigated transcranial magnetic stimulation and computed electric field strength reduce stimulator-dependent differences in the motor threshold

The motor threshold (MT) is a fundamental parameter for evaluating cortical excitability in transcranial magnetic stimulation (TMS) despite remarkable variation, both within, and between subjects. We intended to test whether the variation could be reduced by targeting the stimulation on-line and modeling the TMS-induced electric field on individual MR images. Navigated TMS was used to map the primary motor cortex for the representation area of the thenar muscles (abductor pollicis brevis) and to determine the MT. Thirteen healthy subjects participated in the study. To determine the between-subject variation, the MTs of nine subjects were measured with two different stimulators (comparison study). To study the individual variation, the MT measurement was repeated 20 times in four subjects always using the same stimulator (longitudinal study). In the comparison study, the MTs differed significantly between the two stimulators over all subjects (p<0.001), whereas the electric field strengths did not exhibit significant difference between the stimulators. Both, the MTs, and the electric field strengths showed similar variations, which were greater between subjects (comparison study) than within subjects (longitudinal study). In the comparison study, the distance between the locations of the two different coils on the scalp was significantly greater than the distance between the induced electric field maxima in the brain (p<0.001). We conclude that on-line navigation can be used to reduce the variation caused by different stimulator types and individual subject anatomy. In addition, cortical excitability can be evaluated by using computed electric field strength as well as stimulator-dependent MT.     

Current melanoma staging

American Joint Committee on Cancer (AJCC), TNM staging, represents the cornerstone of management for cutaneous melanoma. This staging system groups patients with similar prognoses and has important implications in optimizing management and treatment and conducting better clinical trials. T describes the extent of the primary tumor, N the extent of regional lymph node metastases, and M the extent of distant metastases. The AJCC staging system for cutaneous melanoma underwent significant revision in 2002. The revised, current AJCC staging system and the TNM classification are detailed in this review.     

Parallel input makes the brain run faster

In serial sensory processing, information flows from the thalamus via primary sensory cortices to higher-order association areas. However, association cortices also receive, albeit weak, direct thalamocortical sensory inputs of unknown function. For example, while information proceeds from primary (SI) to secondary (SII) somatosensory cortex in a serial fashion, both areas are known to receive direct thalamocortical sensory input. The present study examines the potential roles of such parallel input arrangements. The subjects were presented with median nerve somatosensory stimuli with the instruction to respond with the contralateral hand. The locations and time courses of the activated brain areas were first identified with magnetoencephalography (MEG). In a subsequent session, these brain areas were modulated with single-pulse transcranial magnetic stimulation (TMS) at 15-210 ms after the somatosensory stimulus while electroencephalography (EEG) was recorded. TMS pulses at 15-40 ms post-stimulus significantly speeded up reaction times and somatosensory-evoked responses, with largest facilitatory effects when the TMS pulse was given to contralateral SII at about 20 ms. To explain the results, we propose that the early somatosensory-evoked physiological SII activation exerts an SII-->SI influence that facilitates the reciprocal SI-->SII pathway - with TMS to SII we apparently amplified this mechanism. The results suggest that the human brain may utilize parallel inputs to facilitate long-distance cortico-cortical connections, resulting in accelerated processing and speeded reaction times. This arrangement could also allow very early top-down modulation of the bottom-up stream of sensory information.     

Can Hernia Sac to Abdominal Cavity Volume Ratio Predict Fascial Closure Rate for Large Ventral Hernia? Reliability of the Tanaka Score

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