The prognostic and therapeutic relevance of p27kip1 in Ewing's family tumors.

PURPOSE: Ewing's family tumors (EFTs) display the characteristic fusion gene EWS-Fli1. We have reported EWS-Fli1 may promote the cell cycle progression accompanied by the suppression of the expression of cyclin-dependent kinase inhibitor p27(kip1) in EFT cells. Here, we describe the prognostic and therapeutic relevance of p27 in EFTs. EXPERIMENTAL DESIGN: We examined tumor samples taken from 21 patients with primary EFTs for the expression of p27 protein immunohistochemically and evaluated its correlation with clinical outcome. We also investigated the usefulness of p27 as a therapeutic strategy in vitro and in vivo using p27 expression adenovirus. Finally, we examined the process of EWS-Fli1-mediated reduction of p27 expression. RESULTS: Immunohistochemical analysis showed that a low expression level of p27 protein was related to poor event-free survival in an univariate analysis and that the expression level of p27 correlated more significantly with patient survival than several clinical factors in a multivariate survival analysis. Overexpression of p27 with the adenoviral vector remarkably inhibited the cell growth in all EFT cells tested and further induced apoptosis in the wild-type p53 EFT cells. In vivo studies demonstrated a reduction in tumor growth of EFT xenograft in nude mice treated with the intratumoral injection of p27-expressing adenovirus. EWS-Fli1 did not significantly affect the p27 promoter activity and p27 mRNA levels. However, the challenge of the proteasome inhibitor caused accumulation of p27 protein in EFT cells. These data strongly suggest EWS-Fli1 might attenuate p27 protein level via activation of the proteasome-mediated degradation pathway. CONCLUSIONS: Our findings provide the first evidence of the prognostic relevance of p27 expression in EFTs. We propose p27 as a novel and powerful therapeutic factor for the molecular target therapy of EFTs.     

Transient Elastography for the Prediction of Oxaliplatin-Associated Liver Injury in Colon Cancer Patients : A Preliminary Analysis

Objective

The prognosis of advanced colon cancer has improved significantly over the last decade since new chemotherapy regimens including oxaliplatin have been developed. However, oxaliplatin-induced liver injury and characterized hepatic hemostatic status can occur after chemotherapy. The assessment of this type of liver injury is often difficult.

Methods

Elastography (Fibroscan?) was used to evaluate liver injury in five cases before and after 5-FU, leucovorin, and oxaliplatin combination (FOLFOX) treatment.

Results

A clear change was observed in the stiffness of liver after chemotherapy within 48 h, and the hepatic stiffness was normalized in most cases after 2 weeks. Among the five patients, one patient showed aberrant elevation after a FOLFOX treatment, and the patient showed liver injury pathologically.

Conclusion

Elastography is a good tool for evaluating hepatic injury after FOLFOX treatment.     

Clinical usefulness of fusion of 131I SPECT and CT images in patients with differentiated thyroid carcinoma.

Precise localization of the foci of (131)I uptake for management of patients with differentiated thyroid carcinoma can be difficult because of a lack of anatomic landmarks. The objective of the present study was to demonstrate the clinical usefulness of (131)I SPECT/CT fusion images in patients with differentiated thyroid carcinoma. METHODS: CT and SPECT were performed 7 d after administration of a therapeutic dose of (131)I to 17 patients with differentiated thyroid carcinoma. External markers were placed at 3 locations on the skin of the patient to adjust the sections of CT and SPECT in the same geometric plane. Fusion images were constructed by combining the digital CT and SPECT images on a computer workstation. The data from both planar and SPECT (131)I images and CT images were first separately assessed by 2 nuclear medicine physicians. (131)I SPECT/CT fusion images were then interpreted. Fusion images were considered to improve image interpretation in comparison with CT and scintigraphy separately when they provided better localization of sites of increased radiopharmaceutical uptake. RESULTS: Both CT and (131)I SPECT showed the pathologic sites in 5 of 17 patients (29%). Fusion images were considered to be of benefit in 15 of 17 patients (88%). In 4 patients, CT showed normal-sized lymph nodes, whereas (131)I SPECT showed abnormal findings. In 3 patients with bone metastasis, fusion images confirmed the precision of the localization of abnormal (131)I uptake. Five bone metastases and 1 muscle metastasis were occult and were not seen on the CT images. Finally, (131)I scintigraphy findings were abnormal for 2 patients for whom the CT findings were initially considered normal. Fusion images confirmed the precision of the localization of physiologic (131)I uptake. CONCLUSION: For registration of anatomic and functional images in fusion imaging, the method using external markers was simple and practical. (131)I SPECT/CT fusion images using this technique may improve anatomically limited interpretation of (131)I scintigraphy alone in patients with differentiated thyroid carcinoma.     

Chair-Stand Exercise Improves Sarcopenia in Rehabilitation Patients after Stroke

Currently, there is a lack of evidence to show that exercise therapy improves sarcopenia in older patients in clinical practice. We therefore conducted a retrospective cohort study to clarify the effects of chair-stand exercise on improving sarcopenia among patients diagnosed with sarcopenia undergoing convalescent rehabilitation after stroke. According to the latest Asian criteria, sarcopenia was diagnosed when both skeletal muscle mass index (SMI) and handgrip strength (HGS) were low. Patients were asked to perform a repeated chair-stand exercise as whole-body resistance training, in addition to the rehabilitation program. Outcomes included sarcopenia rates, SMI, HGS, and physical function at hospital discharge. Multivariate analyses were used to examine whether the frequency of daily chair-stand exercise was independently associated with the outcomes after adjustment for potential confounders. After enrollment, 302 patients with sarcopenia (mean age: 78.6 years; 46.4% male) were analyzed. Overall, sarcopenia prevalence decreased by 21.9%, from 100% at admission to 78.1% at discharge. Multivariate analyses showed that the frequency of the exercise was significantly associated with the presence of sarcopenia (odds ratio: 0.986, p = 0.010), SMI (β = 0.181, p < 0.001), and HGS (β = 0.101, p = 0.032) at discharge, respectively. The chair-standing exercise was effective in improving sarcopenia in these patients.     

Effects of dipyridamole on Plasmodium falciparum-infected erythrocytes

This study assessed the antimalarial activity of dipyridamole, a well-known vasodilator and inhibitor of platelet aggregation. Dipyridamole was effective against all of the erythrocytic stages such as rings, trophozoites and schizonts, and induced ultrastructural changes during the transition from trophozoite to schizont in vitro. Merozoites were also inhibited from invading dipyridamole-treated erythrocytes. It seems that dipyridamole binds to the erythrocyte membrane blocking the receptors for the merozoite. The 50% inhibitory concentration (IC(50)) of dipyridamole against Plasmodium falciparum infection was 30 nM. The IC(50) of chloroquine decreased from 97.0 nM to 13.7 nM when combined with dipyridamole (0.1 nM). Therefore, we suggest that dipyridamole has antiplasmodial activity due to its ability to arrest parasite development and by inhibiting merozoite invasion of the erythrocytes. Chloroquine activity against P. falciparum is also enhanced by the addition of dipyridamole. Treatment with a combination of chloroquine and dipyridamole may lead to a more effective treatment for chloroquine-resistant strains of P. falciparum.     

Segmental pedicle screw fixation for a scoliosis patient with post-laminectomy and post-irradiation thoracic kyphoscoliosis of spinal astrocytoma

Spinal deformity is an important clinical manifestation after surgery for spinal cord tumors. One-third of patients who receive laminectomies and irradiation of the spinal column develop scoliosis, kyphosis, or kyphoscoliosis. Recent reports indicate good results after scoliosis surgery using segmental pedicle screws and a navigation system, but these reported studies have not included surgery for post-laminectomy kyphosis. Hooks and wires are ineffective in such patients who undergo laminectomy, and there are also high perioperative risks with insertion of pedicle screws because landmarks have been lost. Here, we report on the 5-year follow-up of a 13-year-old male patient with post-laminectomy and post-irradiation thoracic kyphoscoliosis after surgical treatment of spinal astrocytoma. Posterior segmental pedicle screw fixation was performed safely using a computer-assisted technique. The authors present the first case report for treatment of this condition using a navigation system.