Wei-Shan Chen

5-Fluorouracil: Mechanisms of Resistance and Reversal Strategies

The purpose of this work is to review the published studies on the mechanisms of action and resistance of 5-fluorouracil. The review is divided into three main sections: mechanisms of anti-tumor action, studies of the resistance to the drug, and procedures for the identification of new genes involved in resistance with microarray techniques. The details of the induction and reversal of the drug resistance are also described.

Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs

The intravertebral vacuum phenomenon (VP) is usually associated with degenerative disc disease, which could be related to the low back pain. Various theories related to the pathogenesis of VP have been proposed, but these theories have not been critically examined and remain hypothetical. In this article, we review the possible role of endplate degeneration in the pathogenesis of VP, and discuss several pathways possibly linked to them. Due to the endplate calcification and activated cytokines, the transport pathway of the nutrition for the intervertebral disc was blocked, resulting in the metabolic unbalance and decrease of the synthesis of matrix structural proteins. It could promote the matrix decomposition, causing the decrease of the quantity of matrix and the changes of stress distribution in intervertebral disc. As a result, the structure of intervertebral discs became increasingly unstable. While compression happened, the intravertebral cleft could occur and be gradually filled with gas, which may cause low back pain and aggravate the intervertebral discs degeneration. As outlined above, we hypothesize that endplate degeneration might be the origination of the vacuum phenomenon.

Possible key role of immune system in Schmorl’s nodes

Schmorls nodes (SNs) are common abnormalities in the human spine, which represent herniation of the nucleus pulposus of the intervertebral disc into the adjacent cartilaginous endplate of the vertebra. However, the principle mechanism of SNs is still not fully understood. And the relationship of SNs in the spine and their clinical significance as a source of low back pain in the general population remains unknown. It is therefore important to get better understanding of this. Here, we review the clinical and experiment evidence on inducing of the SNs and correlative back pain, and propose a possible mechanism. Studies showed that once the nucleus pulposus enters into vascular tissue, the immune system could recognize it as a foreign body, and induces the immunological reaction. Then, there would be osteoimmunology action, a crosstalk between the immune system and bone, leading to bone loss by dysregulating T-lymphocyte function, and resulting to the bone absorption. Furthermore, the cytokines are involved in the development of immunological reactions and could be responsible for the significant pathology of symptomatic SNs. Given the above background, we hypothesize that immune system could be a key role in SNs and result in the pain.

Stem Cells for the Treatment of Neurodegenerative Diseases

Neurodegenerative diseases are characterized by neurodegenerative changes or apoptosis of neurons involved in networks, leading to permanent paralysis and loss of sensation below the site of the injury. Cell replacement therapy has provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. In recent years, neurons and glial cells have successfully been generated from stem cells, and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. We review here notable previously published experimental and preclinical studies involving stem cell-based cell for neurodegenerative diseases and discuss the future prospects for stem cell therapy of neurological disorders in the clinical setting. Steady and solid progress in stem cell research in both basic and preclinical settings should support the hope for development of stem cell-based cell therapies for neurological diseases.

Posterolateral lumbar fusion versus transforaminal lumbar interbody fusion for the treatment of degenerative lumbar scoliosis

This study compares the safety and efficacy of posterolateral lumbar fusion (PLF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of degenerative lumbar scoliosis (DLS). Forty DLS patients with Cobb angles of 20-60 degrees were randomized into either the PLF or TLIF treatment group, and were followed up for 2-5 years. Operating time, intraoperative blood loss, clinical outcomes, complications and imaging were compared between the two groups. There were significant differences between the PLF and TLIF treatment groups in operative time (187.8±63.5 minutes and 253.2±57.6 minutes, respectively; p=0.002) and intraoperative blood loss (1166.7±554.1 mL and 1673.7±922.4 mL, respectively; p=0.048). The occurrence rates of early complications in the two groups were 11.1% and 26.3%. The recovery rates of the lumbar lordotic angle and spinal sagittal balance were significantly different (36.7% versus 62.5% and 44.8% versus 64.1%, respectively). In various domains of the Scoliosis Research Society-22 (SRS-22) questionnaire, the scores for pain and satisfaction with the treatment showed significant differences between PLF and TLIF group (p=0.033 and p=0.006, for pain and satisfaction respectively), and the TLIF group showed better outcomes than the PLF group. There were no significant differences in the recovery rates in the Cobb angle and the spinal coronal balance, function, self-image, or mental health scores. Although TLIF increases the surgical trauma and occurrence of complications, it helps to improve lumbar lordosis and sagittal balance and shows better clinical outcomes. For patients without significant loss of lumbar lordosis and with good spinal sagittal balance preoperatively, PLF is still an option.

Osteoporosis as a potential contributor to the bone metastases

Bone metastasis is a serious complication of patients with tumor, and most primary tumors can metastasize to bone. And the main threat and the reason for most cancer deaths are not the primary neoplasias, but secondary tumors, the metastases. To minimize the morbidity and economic expenditure associated with bone metastases, it is important to decrease the etiological factors of bone metastasis. Although current evidence suggested that the therapies to the underlying malignancy bone metastasis might result in bone loss leading to osteoporosis, no studies have shown direct evidence the successful seeding of bone metastases of cancer cells is the part played by osteoporosis. In the state of osteoporosis, for the enhancement of the osteolysis, the increased inflammatory factors could make blood vessels leakier, resulting in the easier hematogenous metastasis to bone and bone marrow. Moreover, leptin, which was positive correlation with osteoporosis, has been showed to exert angiogenic effects and could regulate VEGF expression, promoting the proliferation of the cancer blood vessel. In addition, the increased growth factors in osteoporosis could enrich the local microenvironment, promoting the growth of the metastasis mass. Given the above background, we hypothesize that osteoporosis may be a potential contributor to the bone metastases.

Moderate alcohol consumption may decrease risk of intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a serious health problem worldwide. Unfortunately, efforts to control IDD are largely unsuccessful. It is therefore important to get better understanding of risks. Various evidences indicate that moderate alcohol consumption has protective effect on IDD. Here, we review the clinical evidence on alcohol consumption and IDD, and propose a possible mechanism. There is increasing evidence indicating that moderate alcohol consumption keeps the feeding arteries smooth. Furthermore, strong evidence indicates that some inflammatory factors are very important in the pathophysiology of IDD, while moderate alcohol consumption can decrease the expression of these inflammatory factors. Moreover, experimental studies show that alcohol exposure could increase the type II collagen and aggrecan, the major constituents of nucleus pulposus matrix. Given the above background, we hypothesize that moderate alcohol consumption may reduce the risk of IDD.

An unusual high-pressure injection injury involving the cervical spinal cord

High-pressure injection injuries occur infrequently but are usually work-related and involve the non-dominant hand. The neck is a very rare site for such an injury. We describe the management of a 36-year-old man with a high-pressure grease-gun injection injury to his neck causing a cervical spinal cord injury. He developed severe motor and sensory changes which were relieved by surgical removal of the grease through anterior and posterior approaches.

Computer simulation of two-level pedicle subtraction osteotomy for severe thoracolumbar kyphosis in ankylosing spondylitis

Background: Advanced ankylosing spondylitis is often associated with thoracolumbar kyphosis, resulting in an abnormal spinopelvic balance and pelvic morphology. Different osteotomy techniques have been used to correct AS deformities, unfortunnaly, not all AS patients can gain spinal sagittal balance and good horizontal vision after osteotomy. Materials and Methods: Fourteen consecutive AS patients with severe thoracolumbar kyphosis who were treated with two-level PSO were studied retrospectively. All were male with a mean age of 34.9 ± 9.6 years. The followup ranged from 1–5 years. Preoperative computer simulations using the Surgimap Spinal software were performed for all patients, and the osteotomy level and angle determined from the computer simulation were used surgically. Spinal sagittal parameters were measured preoperatively, after the computer simulation, and postoperatively and included thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence, pelvic tilt (PT), and sacral slope (SS). The level of correlation between the computer simulation and postoperative parameters was evaluated, and the differences between preoperative and postoperative parameters were compared. The visual analog scale (VAS) for back pain and clinical outcome was also assessed. Results: Six cases underwent PSO at L1 and L3, five cases at L2 and T12, and three cases at L3 and T12. TK was corrected from 57.8 ± 15.2° preoperatively to 45.3 ± 7.7° postoperatively (P < 0.05), LL from 9.3 ± 17.5° to −52.3 ± 3.9° (P < 0.001), SVA from 154.5 ± 36.7 to 37.8 ± 8.4 mm (P < 0.001), PT from 43.3 ± 6.1° to 18.0 ± 0.9° (P < 0.001), and SS from 0.8 ± 7.0° to 26.5 ± 10.6° (P < 0.001). The LL, VAS, and PT of the simulated two-level PSO were highly consistent with, or almost the same as, the postoperative parameters. The correlations between the computer simulations and postoperative parameters were significant. The VAS decreased significantly from 6.1 ± 1.9 to 2.0 ± 1.1 (P < 0.001). In terms of clinical outcome, 10 cases were graded “excellent” and 4 cases were graded “good.” Conclusion: Two-level PSO using a preoperative computer simulation is a feasible, safe, and effective technique for the treatment of severe thoracolumbar kyphosis in AS patients with normal cervical motion.