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Wei-Ying Yue, Su-Huan Yu, Shi-Guang Zhao and Zhong-Ping Chen

Object

Astrocytoma may progress rapidly or remain stable for many years. To clarify whether molecular characteristics could be prognostic factors, several cell cycling–associated molecular alterations in the diffuse astrocytoma have been investigated.

Methods

Thirty-three patients in whom WHO Grade II astrocytoma had been initially diagnosed were assigned to 1 of 3 groups. Group 1 consisted of 10 patients with malignant progression; the tumor had recurred within 5 years and histological analysis had confirmed that the tumor progressed to Grade III or IV. Group 2 consisted of 10 patients in whom there was no malignant progression; the tumor recurred within 5 years, but histological analysis confirmed that the tumor remained at Grade II. Group 3 consisted of 13 patients who did not experience recurrence within 5 years. Expression of Ki 67, TP53, p27, and p21 was examined using immunohistochemical analysis for the tumor samples obtained during the first and second (in recurrent cases) surgeries. Exons 5, 7, and 8 of TP53 were scanned by DNA sequencing.

Results

The Ki 67 labeling index expression was significantly higher in Group 1 (even though it was similar between initial and recurrent tumors) than that of Group 3 (p < 0.05). However, there was no difference between Group 2 (both initial and recurrent tumors) and Group 3. The TP53 protein accumulation was also higher in Group 1 than in Group 2 or 3 (p < 0.05); a difference in TP53 expression was not found between Groups 2 and 3. The p27 and p21 was expressed in all cases, but no predictive values were found. The p53 mutation was found only in 6 cases in Group 1.

Conclusions

Overexpression of TP53, TP53 mutation, and Ki 67 labeling index could be molecular markers in astrocytomas predicting malignant progression.

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Zhong-Ping Chen, Daniel Yarosh, Yesenia Garcia, Donatella Tampieri, Gérard Mohr, Adrian Langleben and Lawrence C. Panasci

Adjuvant nitrosourea chemotherapy fails to prolong patient survival significantly as many tumors demonstrate resistance to these drugs. It has been documented in cell lines that O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in chloroethylnitrosourea (CENU) drug resistance.

The authors evaluated MGMT expression in 22 glioma specimens by using an immunofluorescence assay and compared the results with clinical response of the patients to CENU-based chemotherapy.

The patients were treated with CENU after evidence of progressive disease following surgery and radiotherapy. Eight tumor samples had no detectable MGMT, whereas other samples had from 9989 to 982,401 molecules/nucleus. In one group (12 patients), the tumor decreased in size or was stable (effective group), whereas in the other group (10 patients), the tumor demonstrated continuous growth during chemotherapy (progressive group). The median time to progression (TTP) was 6.7 months with a median survival of 13 months. The Mer patients (MGMT < 60,000 molecules/nucleus) appeared to have more chance of stable disease or response to CENU therapy than the Mer+ patients (MGMT > 60,000 molecules/nucleus) (chi-square = 4.791, p = 0.0286). In patients with glioblastomas multiforme (GBMs), the TTP of Mer+ patients was shorter than that of Mer patients (t = 2.04, p = 0.049). As a corollary, the MGMT levels were significantly higher in GBM tumors from the progressive group than those from the effective group (t = -2.26, p = 0.029). The TTP and survival time in the effective GBM group were also longer than those in the progressive GBM group. However, there was no significant correlation between MGMT levels and either the survival time (r = 0.04, p = 0.8595) or TTP (r = 0.107, p = 0.6444).

Results from this study suggested that MGMT positivity is indicative of more aggressive disease that progresses more rapidly when exposed to CENU therapy. However, MGMT-negative tumors are not always sensitive to CENU agents, suggesting that other factors may also be important.

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Hong-Qi Zhang, Tong Chen, Shao-Shuai Wu, Liang-Hong Teng, Yong-Zhong Li, Li-Yong Sun, Zhi-Ping Zhang, De-Yu Guo, De-Hong Lu and Feng Ling

Object

The authors undertook this study to establish an animal model to investigate the pathophysiological changes of venous hypertensive myelopathy (VHM).

Methods

This study was a randomized control animal study with blinded evaluation. The VHM model was developed in 24 adult New Zealand white rabbits by means of renal artery and vein anastomosis and trapping of the posterior vena cava; 12 rabbits were subjected to sham surgery. The rabbits were investigated by spinal function evaluation, abdominal aortic angiography, spinal MRI, and pathological examination of the spinal cord at different follow-up stages.

Results

Twenty-two (91.67%) of 24 model rabbits survived the surgery and postoperative period. The patency rate of the arteriovenous fistula was 95.45% in these 22 animals. The model rabbits had significantly decreased motor and sensory hindlimb function as well as abnormalities at the corresponding segments of the spinal cord. Pathological examination showed dilation and hyalinization of the small blood vessels, perivascular and intraparenchymal lymphocyte infiltration, proliferation of glial cells, and neuronal degeneration. Electron microscopic examination showed loose lamellar structure of the myelin sheath, increased numbers of mitochondria in the thin myelinated fibers, and pyknotic neurons.

Conclusions

This model of VHM is stable and repeatable. Exploration of the sequential changes in spinal cord and blood vessels has provided improved understanding of this pathology, and the model may have potential for improving therapeutic results.

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Guo-Bao Wang, Ai-Ping Yu, Chye Yew Ng, Gao-Wei Lei, Xiao-Min Wang, Yan-Qun Qiu, Jun-Tao Feng, Tie Li, Qing-Zhong Chen, Qian-Ru He, Fei Ding, Shu-Sen Cui, Yu-Dong Gu, Jian-Guang Xu, Su Jiang and Wen-Dong Xu

OBJECTIVE

Contralateral C7 (CC7) nerve root has been used as a donor nerve for targeted neurotization in the treatment of total brachial plexus palsy (TBPP). The authors aimed to study the contribution of C7 to the innervation of specific upper-limb muscles and to explore the utility of C7 nerve root as a recipient nerve in the management of TBPP.

METHODS

This was a 2-part investigation. 1) Anatomical study: the C7 nerve root was dissected and its individual branches were traced to the muscles in 5 embalmed adult cadavers bilaterally. 2) Clinical series: 6 patients with TBPP underwent CC7 nerve transfer to the middle trunk of the injured side. Outcomes were evaluated with the modified Medical Research Council scale and electromyography studies.

RESULTS

In the anatomical study there were consistent and predominantly C7-derived nerve fibers in the lateral pectoral, thoracodorsal, and radial nerves. There was a minor contribution from C7 to the long thoracic nerve. The average distance from the C7 nerve root to the lateral pectoral nerve entry point of the pectoralis major was the shortest, at 10.3 ± 1.4 cm. In the clinical series the patients had been followed for a mean time of 30.8 ± 5.3 months postoperatively. At the latest follow-up, 5 of 6 patients regained M3 or higher power for shoulder adduction and elbow extension. Two patients regained M3 wrist extension. All regained some wrist and finger extension, but muscle strength was poor. Compound muscle action potentials were recorded from the pectoralis major at a mean follow-up of 6.7 ± 0.8 months; from the latissimus dorsi at 9.3 ± 1.4 months; from the triceps at 11.5 ± 1.4 months; from the wrist extensors at 17.2 ± 1.5 months; from the flexor carpi radialis at 17.0 ± 1.1 months; and from the digital extensors at 22.8 ± 2.0 months. The average sensory recovery of the index finger was S2. Transient paresthesia in the hand on the donor side, which resolved within 6 months postoperatively, was reported by all patients.

CONCLUSIONS

The C7 nerve root contributes consistently to the lateral pectoral nerve, the thoracodorsal nerve, and long head of the triceps branch of the radial nerve. CC7 to C7 nerve transfer is a reconstructive option in the overall management plan for TBPP. It was safe and effective in restoring shoulder adduction and elbow extension in this patient series. However, recoveries of wrist and finger extensions are poor.