Chih-Jen Wang

17β-estradiol inhibits endothelin-1 production and attenuates cerebral vasospasm after experimental subarachnoid hemorrhage

Though cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) has been recognized for over half a century, it remains a major complication in patients with SAH. Clinical studies have shown that elevated levels of endothelin-1 (ET-1) are present in the cerebrospinal fluid of patients with SAH, suggesting that ET-1–mediated vasoconstriction contributes to vascular constriction after SAH. Administration of estrogen promotes vasodilation in humans and in experimental animals, in part by decreasing the production of ET-1. This study evaluated the influence of 17β-estradiol (E2) on the production of ET-1 and cerebrovasospasm in an experimental SAH 2-hemorrhage model in rat. A 30-mm Silastic tube filled with E2 in corn oil (0.3 mg/ml) was subcutaneously implanted in male rats just before SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Plasma samples collected before death were assayed for ET-1. The protective effect of E2 in attenuating vasospasm achieved statistical significance when compared with the SAH only or SAH plus vehicle groups (P < 0.01). Concentrations of ET-1 were higher in the SAH only and SAH plus vehicle groups than in controls (P < 0.001). Serum levels of ET-1 in the SAH plus E2 and E2 only groups were significantly lower than those in the SAH only and SAH plus vehicle groups (P < 0.001). There was no significant difference between ET-1 levels in the healthy control and SAH plus E2 groups. A significant correlation was found between the cross-sectional areas of basilar artery and ET-1 levels (P < 0.001). The beneficial effect of E2 in attenuating SAH-induced vasospasm may be due in part to decreasing ET-1 production after SAH. The role of E2 in the treatment of cerebral vasospasm after SAH is promising and is worthy of further investigation.

Expression of thyroid hormone receptors in human pituitary tumor cells

To understand the expression of thyroid hormone receptors (TRs) in various types of pituitary tumor cells, we performed the reverse transcription coupled to polymerase chain reaction (RT-PCR). Specimens of pituitary adenomas were obtained by transsphenoidal adenomectomies from 2 patients with acromegaly, 6 patients with prolactinoma, 3 patients with Cushings disease, 2 patients with gonadotropin-secreting tumors, one patient with a TSH-secreting tumor, and 3 patients with non-functioning adenoma with no clinical evidence of pituitary hormone overproduction. Human thyroid hormone receptors beta 1 and alpha 1, alpha 2 (h-TR beta 1, alpha 1, alpha 2) are expressed in nonfunctioning adenomas; h-TR alpha 1 and beta 1 are specific for prolactinomas; h-TR beta 1 is involved in acromegalies and FSH-secreting tumors, while h-TR alpha 1, alpha 2, and beta 1 are not expressed in TSH-secreting and ACTH-secreting tumors. The results suggest that human thyroid hormone receptors are differentially expressed in human pituitary tumor cells, and our studies have shed new light on the understanding of the role of TRs in pituitary tumors.

Low-grade astrocytoma associated with abscess formation: case report and literature review.

A rare case of low‐grade astrocytoma associated with abscess formation occurred in a 52‐year‐old man presenting with Brocas aphasia. He underwent craniotomy and tumor removal under the impression of brain tumor with necrotic cystic change. Abscess accumulation within the intra‐axial tumor was found intraoperatively. Literature related to brain abscess with brain tumor is reviewed, with an emphasis on abscesses with astrocytoma. We discuss the common brain tumors that are associated with abscess, pathogens that coexist with brain tumor, and the pathogeneses of coexisting brain abscess and tumor. It is very important to know how to differentiate between and diagnose a brain abscess and tumor, or brain abscess with tumor, preoperatively from clinical presentation and through the use of computed tomography, conventional magnetic resonance imaging, diffusion‐weighted imaging or magnetic resonance spectroscopy.

Plasma levels of transforming growth factor-beta 1 before and after removal of low- and high-grade astrocytomas.

Transforming growth factor-beta 1 (TGF-β1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-β1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-β1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-β1 before tumor removal was ≥ 2.52 ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-β1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p<0.05); there was no significant change in TGF-β1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-β1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ=0.597, p=0.002). The findings show that plasma TGF-β1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-β1 might be useful as a tumor marker for astrocytomas.

Prevention and reversal of vasospasm and ultrastructural changes in basilar artery by continuous infusion of CGS 35066 following subarachnoid hemorrhage.

Endothelin-1, a potent vasoconstrictive peptide, has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). The goal of this study was to evaluate the effect of continuous intravenous infusion of a highly selective endothelin-converting enzyme-1 inhibitor, CGS 35066, on the prevention and reversal of cerebral vasospasm following SAH. New Zealand white rabbits were subjected to SAH by injecting autologous arterial blood into the cisterna magna. Infusion of CGS 35066 at dosages of 1, 3, or 10 mg/kg/ day was initiated either 1 hr and 24 hrs later in the prevention and reversal protocols, respectively. Animals were sacrificed by perfusion-fixation 48 hrs after SAH induction. The cross-sectional areas of basilar arteries were measured using computer-assisted videomicroscopy. Ultrastructural changes in basilar arteries were determined using electron microscopy. CGS 35066 significantly prevented and reversed the arterial narrowing after SAH in all three groups. The mean cross-sectional areas of arteries from animals in both the prevention and reversal protocol groups that received 10 mg/kg/day of CGS 35066 did not differ significantly from those of the healthy controls. Histological studies of the basilar artery in the 10 mg/kg/day treatment group did not show pathomorphological changes, such as corrugation of the endothelium seen at 2 days after SAH induction or vacuole formation in the endothelial cells noted in the vehicle-treated SAH group. These findings suggest that CGS 35066 is a promising therapeutic agent for the prevention and reversal of cerebral vasospasm after SAH. It also prevents the pathological changes in vascular walls due to SAH.

Traumatic lumbar spinal subdural hematoma--a case report.

A 74-year-old woman suffered from lower legs weakness after a motor vehicle accident. Magnetic resonance imaging (MRI) on the seventh posttraumatic day, revealed a lumbar spinal subdural hematoma at the level of L4-5. After surgical intervention to remove the subdural hematoma, the patient made a complete recovery.

Analysis of Surgically Treated Intraspinal Tumors in Southern Taiwan

The medical records of 117 patients with spinal tumors who underwent surgery with pathologic confirmation from January 1999 to April 2004 at Kaohsiung Medical University Hospital were reviewed. Data from this review were compared with those obtained from the same institution 10 years earlier (covering the period 1988‐1995) and from other reported series. There were 69 male and 48 female patients aged from 13 to 87 years old (mean age, 51.9). The most common pathologic findings were metastasis in 45.3% (53/117), nerve sheath tumors in 28.2% (33/117), menin‐giomas in 12% (14/117) and neuroepithelial tumors in 6% (7/117). The peak ages at diagnosis were 41‐50 years and 61–70 years. A slight male predominance was noted for all tumors, except meningiomas. Motor weakness, even paralysis, was the major clinical presentation (64–86%), followed by sensory deficits (50%) and pain (42%). The location of tumors was most often in the thoracic (50.4%; 59/117), lumbosacral (27.4%; 32/117) and cervical spine (22.2%; 26/117) segments. Among the metastatic tumors, the lung (22.6%) and breast (15.1%) were the most common primary sites of origin, followed by unknown origin, the liver (hepatocellular carcinoma), the gastrointestinal tract and the nasopharynx (nasopharyngeal cancer).

Expression of Thyroid Hormone Receptors in Intracranial Meningiomas

Thyroid hormone has a unique function in human organs. Many of its effects occur at the level of gene expression and are mediated by thyroid hormone receptors (TRs). We investigated the relationship between TRs and the prognosis of meningiomas. We investigated TR expression in human intracranial meningiomas using reverse transcription‐polymerase chain reaction. Specimens of 25 tumors were obtained by craniotomy from various intracranial meningiomas. We found that the expression of TRs was receptor subtype‐ and cell type‐dependent. Human TRα1 (hTRα1) was expressed in nine cases, hTRα2 was expressed in 14 cases, and both hTR‐alpha‐1 and hTR‐alpha‐2 were expressed in five cases; hTRβ1 was expressed in nine cases of recurrent or malignant tumors. The expression of hTRβ1 may be an indicator of recurrent or malignant meningiomas.

The alteration of plasma TGF-β1 levels in patients with brain tumors after tumor removal

Transforming growth factor (TGF) β1 may be a candidate for a serologic tumor marker. In this study, the plasma levels of TGF‐β1 in patients with brain tumors were measured using enzyme‐linked immunosorbent assay before and after tumor removal. Patients were divided into four groups, the control group and the benign, malignant, and metastatic brain tumor groups. All brain tumor groups showed significant increases in the levels of TGF‐β1 before tumor removal (6.36 ± 3.94, 17.0 ± 9.7, and 12.2 ± 10.3 ng/ml for the benign, malignant, and metastatic groups, respectively). When compared with the results obtained in the control group (1.12 ± 0.74 ng/ml), significant decreases in TGF‐β1 concentrations after total tumor removal were found in both the benign and malignant brain tumor groups (2.55 ± 2.00 and 8.93 ± 5.73 ng/ml, respectively; p = 0.0001 and p = 0.003, respectively). On the other hand, plasma TGF‐β1 levels in the metastatic brain tumor group showed a slight but significant increase (14.7 ± 9.3 ng/ml, p = 0.035) after tumor removal. In a case of low‐grade astrocytoma, plasma levels of TGF‐β1 were found to be 3.6 and 1.1 ng/ml before and after tumor removal, respectively. However, recurrent tumor was noted in this patient 7 months later, and the levels of TGF‐β1 were 26.2 and 8.4 ng/ml before and after the second operation, respectively. The data show that plasma TGF‐β1 was elevated in the circulation of patients with brain tumors and that significant decreases in TGF‐β1 levels were observed after the removal of benign and malignant tumors. The results also suggest that TGF‐β1 may be a useful serologic marker for brain tumors.

Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: A case report

A 44‐year‐old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole‐brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty‐six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patients neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.