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V Tse

Publications and source records attributed to V Tse.

18 recordsLinked to original sources

Hematopoietic stem cells give rise to perivascular endothelial-like cells during brain tumor angiogenesis.

Bone marrow (BM) cells have recently been shown to give rise to skeletal, hepatic, cardiac, neural, and vascular endothelial tissues. However, it has been shown that this is the result of cell fusion rather than transdifferentiation of hematopoietic stem cells (HSC). For this study, we established a mouse model of brain tumor growth to investigate the differentiation potential of HSC into endothelial cells during brain tumor-induced angiogenesis. Nontransgenic (GFP(neg)) recipient mice were lethally irradiated, and their hematopoietic cells were subsequently repopulated by transplantation of a single green fluorescent protein (GFP)-expressing HSC. Rat glioma (RT-2/RAG) cells were then injected into the striatum of the chimeric mice 6-8 weeks post-transplantation. The animals were sacrificed 3-9 days after tumor implantation, and the mobilization, temporal-spatial distribution, and lineage-specific marker expression profile of the GFP(+) cells within the growing tumor were analyzed. We saw that GFP(+) cells gave rise to elongated, CD34(+)/Flk-1(+) cells that incorporated into the endothelium of tumor blood vessels. However, all GFP(+) cells were also CD45(+), and the presence of CD45 on the HSC-derived endothelial-like cells supports the hypothesis that the hematopoietic cells were recruited into the tumor milieu. The fact that we failed to demonstrate the expression of von Willebrand factor in these cells argues against a true endothelial identity. Nevertheless, the recruitment of HSC-derived endothelial-like cells was an extremely rare event in normal brain parenchyma, and, thus, the permissive influence afforded by the growing tumor appeared to enhance the perivascular tropism and acquisition of an endothelial phenotypes by a population of HSC-derived cells.

Animals↗

Differential expression of angiopoietin-1 and angiopoietin-2 may enhance recruitment of bone-marrow-derived endothelial precursor cells into brain tumors.

OBJECTIVES: Angiogenesis is necessary for sustained neoplastic development. The angiopoietins Ang-1 and Ang-2 have been implicated in the regulation of this process; recent reports have suggested that a net gain in Ang-2 activity may be an initiating factor for tumor angiogenesis. We examined the recruitment of bone marrow-derived endothelial precursor cells into developing tumor neovasculature, and the spatial relationship between these cells and angiopoietin (Ang-1 and Ang-2) expression. METHODS: For this study T-cell depleted knockout mice (RAG-2/KO-5.2) were lethally irradiated and their bone marrow was reconstituted by bone marrow cells (BMCs) from transgenic mice (C57BL/Ka-Thy1.1) expressing green fluorescent protein (GFP). Rat glioma cells (RT-2/RAG) were then injected into the transplanted animals to form solid brain tumors. The animals were killed and their brains were analysed using immunohistochemistry and fluorescence-activated cell sorting. RESULTS: We found that BMCs migrated preferentially into the tumor when compared to adjacent healthy brain parenchyma. Furthermore, GFP+/CD34+ cells represented up to 8% of endothelial-like cells within the walls of tumor blood vessels. In the tumor, significant colocalization of Ang-2 with GFP+/CD34+ cells was noted (>80%), but colocalization with Ang-1 never exceeded 20%. In normal tissue directly surrounding the tumor, GFP+/CD34+ cells colocalized strongly with both angiopoietins (>75% and >70% for Ang-1 and Ang-2, respectively). DISCUSSION: The relative increase in angiopoietin-2 activity in brain tumors may result in the creation of a pro-angiogenic environment that enhances the recruitment of putative bone marrow-derived endothelial precursor cells into the tumor's developing vascular tree.

Angiopoietin-1↗

Comparisons of tumor suppressor p53, p21, and p16 gene therapy effects on glioblastoma tumorigenicity in situ.

The mutation and/or deletion of tumor suppressor genes have been postulated to play a major role in the genesis and the progression of gliomas. In this study, the functional expression and efficacy in tumor suppression of 3 tumor suppressor genes (p53, p21, and p16) were tested and compared in a rat GBM cell line (RT-2) after retrovirus mediated gene delivery in vitro and in vivo. Significant reductions in tumor cell growth rate were found in p16 and p21 infected cells (60 +/- 12% vs 66 +/- 15%) compared to p53 (35 +/- 9%). In vitro colony formation assay also showed significant reductions after p16 and p21 gene delivery (98 +/- 5% vs 91 +/- 10%) compared to p53 (50 +/- 18%). In addition, the tumor suppression efficacy were investigated and compared in vivo. Retroviral mediated p16 and p21 gene deliveries in glioblastomas resulted in more than 90% reductions in tumor growth (92 +/- 26% vs 90 +/- 22%) compared to p53 (62 +/- 18%). Tumor suppressor gene insertions in situ further prolonged animal survival. Overall p16 and p21 genes showed more powerful tumor suppressor effects than p53. The results were not surprising, as p16 and p21 are more downstream in the cell cycle regulatory pathway compared to p53. Moreover, the mechanism involved in each of their suppressor effects is different. This study demonstrates the feasibility of using tumor suppressor genes in regulating the growth of glioma in vitro and in situ.

Animals↗

Sonic hedgehog promotes proliferation and tyrosine hydroxylase induction of postnatal sympathetic cells in vitro.

The role of Sonic hedgehog (shh) in neural crest development was initially suggested by its involvement in patterning of the neural tube. While largely implicated in cell fate determination during development, its recently discovered role in the development of neurons postnatally prompted the possibility that neural crest derivatives of the sympathoadrenal lineage may respond to Shh postnatally. In the present study, we show that Shh promotes proliferation of postnatal sympathetic cells in culture. While it has been previously found to induce tyrosine hydroxylase (TH) production in the developing midbrain, we also demonstrated that Shh is capable of promoting TH induction of mature sympathetic neurons in vitro. This duality in Shh can be inhibited by activation of protein kinase A. These findings suggest that cell response to Shh is conserved in sympathetic ganglia derived from the neural crest, and further supports the notion that Shh can function postnatally in a dose-dependent manner to mediate neuronal cell fate.

Animals↗

Expression of p16(INK4A) induces dominant suppression of glioblastoma growth in situ through necrosis and cell cycle arrest.

Tumor suppressor genes may represent an important new therapeutic modality in the treatment of human glioblastoma (GBM). p16(INK4A) is a tumor suppressor gene with mutation and/or deletion found in many human tumors, including glioblastomas, melanoma, and leukemias. RT-2 rat GBM cell line was used to investigate if the p16 gene induces dominant suppression of glioblastoma growth. Close to 100% of tumor cells were infected by high titer pCL retrovirus encoding the full-length human p16 cDNA at 5 m.o.i. Infected cells showed a 98% reduction in colony forming assay and a 60% reduction in growth curves in vitro compared to vector control. Exogenous overexpression of p16 induced hypophosphorylation of Rb protein by Western blot analysis. Intracranial injection of p16-infected tumor cells into syngeneic rats resulted in a 95% reduction in tumor volume compared to the controls. Intratumoral injection of p16 retrovirus resulted in tumor necrosis and prominent human p16 transgene expressions. Proliferation marker PCNA was not detected in these human p16-expressed RT-2 tumor cells, suggesting the cells were unable to enter into S phase after p16 expression. In addition, direct repeat intracranial injections of p16 retrovirus prolonged animal survival 3.2-fold compared to the controls (48.4 +/- 13.4 vs 15.0 +/- 2.1 days, p < 0.001). Two out of ten rats were found with dormant tumors at day 60 after p16 retrovirus injection. These results showed that p16 is effective in inhibiting GBM growth in situ. The mechanisms of tumor growth reduction and necrosis in vivo might be due to G1 arrest triggered by p16 expression.

Animals↗

The application of ultrastructural studies in the diagnosis of bladder dysfunction in a clinical setting.

PURPOSE: We examine the ultrastructural changes reported to be present in dysfunctional bladders and determine whether they can be used as a predictor of urodynamic diagnosis in a clinical setting. MATERIALS AND METHODS: Subjects who required urodynamic diagnosis and cystoscopy as part of clinical management were recruited for this study. After urodynamic diagnosis cases were classified into 1 of 5 dysfunction groups as normal bladder outflow obstruction, idiopathic sensory urgency, obstruction with detrusor instability and pure detrusor instability. A detrusor muscle biopsy was taken from the lateral wall of the bladder at cystoscopy for subsequent electron microscopy. RESULTS: Of the 27 cases 6 were normal, 9 had bladder outflow obstruction and detrusor instability, 8 had pure detrusor instability and 4 had idiopathic sensory urgency. The obstructed group showed the myohypertrophy pattern previously reported. In contrast to previous reports, abnormal junctions were found in all patients. For each patient the ratios of abnormal-to-normal junctions were calculated. Mean and standard error ratios were 1.1+/-0.1, 2.7+/-0.2, 6.1+/-1.2, 13.3+/-4.4 for normal, idiopathic sensory urgency, obstruction with detrusor instability and pure detrusor instability, respectively (p = 0.0003, 0.0042 and 0.04). CONCLUSIONS: There are distinct morphological changes in the detrusor associated with bladder dysfunction. The ratio of abnormal-to-normal junctions is a novel measurement and can be used to predict urodynamic dysfunction. Ultrastructural studies may be useful as an adjunct in the diagnosis of bladder dysfunction.

Aged↗

Melanotic craniopharyngioma: a report of two cases.

We report a 74-year-old woman and a 50-year-old woman with similar histories of headache and visual disturbance who were found to have adamantinomatous craniopharyngiomas which contained melanin pigment. This finding was confirmed by the Masson Fontana method and ultrastructural studies. These are only the second and third cases reported describing melanin pigment within a craniopharyngioma. The finding of melanin in craniopharyngiomas attests to their similarities with odontogenic tumors of the jaw, which can also contain melanin pigment and also supports the hypothesis that the histogenesis of these neoplasms derives from the vestiges of Rathke's pouch epithelium.

Aged↗

Radiation exposure during fluoroscopy: should we be protecting our thyroids?

BACKGROUND: Recent reports on thyroid cancer among Australian orthopaedic surgeons prompted the present study which sought to evaluate the effectiveness of lead shielding in reducing radiation exposure (RE) to the thyroid region during endo-urological procedures. METHODS: Radiation exposure to the thyroid region of the surgeon and scrubbed nurse was monitored for 20 consecutive operations over a 6-week period by thermoluminescent dosimeters (TLD). A TLD was placed over and underneath a thyroid shield of 0.5 min lead equivalent thickness to monitor the effect of shielding. RESULTS: Eight percutaneous nephrolithotomies, seven retrograde pyelograms and ureteric stentings and five ureteroscopies for calculous disease were monitored. Total exposure time was 63.1 min. For the surgeon, the total cumulative RE over and under the lead shield was 0.46 and 0.02 mSv, respectively, equating to a 23-times reduction in RE if shielding was used. This effectively reduced RE to almost background levels, which was represented by the control TLD exposure (0.01 mSv). CONCLUSION: Although RE without thyroid shields did not exceed current standards set by radiation safety authorities, no threshold level has been set below which thyroid carcinogenesis is unlikely to occur. Because lead shields are easy to wear and can effectively reduce RE to the thyroid region to near-background levels, they should be made easily available and used by all surgeons to avoid the harmful effects of radiation on the thyroid.

Fluoroscopy↗

An improved stereotactic technique for cyst cannulation.

Stereotactic techniques for cannulation of cystic structures, within the brain, are well known. Superimposed structures (vessels, ventricles, etc.) may make this problematic as does the need to approach the cystic structure perpendicular to its tangent plane (rather than "glancing") as with a craniopharyngioma cyst. To facilitate a three-dimensional visualization of the trajectory, we have employed digital holography. Transparent holographic images of cystic structures, ventricles, and sulci are rendered from T2-weighted MR data. Holographic images of vascular structures are rendered from CT or MR angiographic data. Vascular holograms are superimposed over the brain holograms, demonstrating the spatial relationships of these structures with regard to each other. Holographic images of the skull are rendered from CT slices. A Laitinen stereotactic frame (Sandstrom) is placed on the patient prior to obtaining the CT. The skull, pre-existing shunt catheters, and the stereotactic frame are all readily visible. The brain and vascular holograms are superimposed on these. The resulting image clearly demonstrates cystic structures, ventricles, vessels, pre-existing catheters, all within the skull and stereotactic frame. Using this holographic image as a "phantom", the actual Laitinen stereotactic frame is placed within its holographic image. The optical trajectory is then chosen, and the articulated arm of the stereotactic device is so adjusted. Subsequently, the frame is used to effect stereotactic placement of the cannula, in the usual manner. The major advantages of this technique are twofold. The first advantage lies with the fact that the surgeon can readily visualize the entire trajectory of the needle, and easily appreciate all structures which may be encountered by the needle on its passage from the skull to the target. Presumably, the surgeon's knowledge of anatomy would unable such knowledge to be apparent, but in complex cases the "safe" corridor may be rather small, and its limits may not be intuitively obvious. This is all the more the case, when obstacles along the pathway are pathologically distorted, or when they are not of tissue origin (shunt catheters, etc.). Employing this technique, we have successfully cannulated cystic structures in six patients, three of which presented with complex trajectory problems.

Brain Diseases↗

Functional expression of human p21(WAF1/CIP1) gene in rat glioma cells suppresses tumor growth in vivo and induces radiosensitivity.

This study reports the successful growth suppression of a rat glioblastoma model (RT-2) both in vitro and in vivo by the insertion of p21(WAF1/CIP1), a negative cell cycle regulatory gene, into the tumor cells. Greater than 95% of the tumor cells expressed p21 protein after being infected with pCL based p21 retrovirus at 4x M.O.I. (multiplicity of infection). The p21-infected cells showed a 91% reduction in colony forming efficiency and a 66% reduction in growth rate. More prominent p21 staining was found in cells exhibiting histologic evidence of senescence. Intracranial implantation of the infected cells showed complete disappearance of the p21-infected cells at day 10 and long-term survival of the animals compared to controls. Injection of pCLp21 virus into tumor established in situ showed tumor necrosis and gene expression. In a clonogenic radiation survival assay, a 93% reduction of surviving colonies of p21-infected cells was seen in comparison to vector-infected control cells and to p53-infected cells after exposure to 8 Gy (800 rads).

Animals↗

Intracavitary liposome-mediated p53 gene transfer into glioblastoma with endogenous wild-type p53 in vivo results in tumor suppression and long-term survival.

A cavitary glioblastoma model was created by injection of RT-2 cells, which express endogenous wild type p53, into the peritoneal cavity of nude mice. This model developed multiple layers of tumor cells invading the peritoneal surface and was used to mimic the postoperative surgical cavity remaining after glioblastoma (GBM) excision in patients. Rhodamine labeled DMRIE/DOPE + DNA complexes were found to penetrate at least 20 tumor cell layers. Injection of p53 gene/liposome complexes into the intraperitoneal cavity after the tumor was established resulted in massive tumor necrosis. Prominent staining of human p53 protein using the DO-1 antibody was found in tumor cells near the necrotic lesions. Tumor explants expressed human p53 protein and showed a 54% growth reduction in an in vitro growth assay. Further, DMRIE/DOPE mediated p53 gene transfection significantly increased the mean survival time of tumor bearing mice compared to vector control. These results demonstrate the efficiency of using exogenous wild type p53 to suppress glioblastoma cell with endogenous wild type p53 in vivo through liposome mediated transfection method.

Animals↗

Nephrogenic adenoma of the bladder in renal transplant and non-renal transplant patients: a review of 22 cases.

OBJECTIVES: To review diagnoses of nephrogenic adenoma and in particular to evaluate its association with transitional cell carcinoma (TCC) of the bladder and its relationship to renal transplantation. METHODS: A retrospective review of 22 cases of nephrogenic adenoma (NA) diagnosed between 1989 and 1996 was conducted, 7 of which were in renal transplant patients. Data collected in each case included demographic details, predisposing factors, associated urologic pathology, mode of presentation, cystoscopic finding, management, and follow-up. RESULTS: There was a 3:1 predominance of men. Mean follow-up was 21.4 months (range 3 to 50). Six patients (27%) had one or more recurrences. All 22 patients had some form of previous bladder insult or surgery, including recurrent urine infections, urinary tract instrumentation, placement of ureteric stents, cystodiathermy, and open bladder surgery. Six cases were associated with TCC of the bladder, of which 4 had NA lesions directly over or close to the site of previous fulguration. In 4 patients, there was a temporal relationship between the administration of intravesical doxorubicin hydrochloride or bacille Calmette-Guérin (BCG) and the onset of NA lesions. One case was associated with an inverted papilloma that had not been described before. In 7 renal transplant cases, 3 lesions were found contralateral to the side of the ureterovesical anastomosis. All 22 cases were benign histologically, but one NA was found within a low-grade baldder TCC. Nineteen cases were followed up regularly with no malignant transformation. Three patients were lost to follow-up. CONCLUSIONS: This study has demonstrated an association between NA and bladder cancer. Patients with NA, especially those treated with intravesical chemotherapy or BCG, should have regular cystoscopies. Fulguration or transurethral resection appear to be sufficient treatment. No renal transplant patients had vesical TCC and NA simultaneously. Neither immunosuppression nor ureterovesical anastomosis appeared to be a significant predisposing factor in the transplant patients.

Adenoma↗

Concurrent colonic adenocarcinoma and two ileal carcinoids in a 72-year-old male.

A case of synchronous rectal cancer and two small-bowel carcinoid tumours was recently encountered in a 72-year-old man. This will be presented and discussed with a literature review. It emphasizes the importance of the concept of synchronous malignancy within the gastrointestinal tract and that patients presenting with any gastrointestinal neoplasm, especially colonic cancer and carcinoids, should undergo thorough exploration of the peritoneal cavity and its organs at initial surgery.

Adenocarcinoma↗

Development and evaluation of an information system for quality assurance.

The aim of this study was to develop and evaluate an information system for monitoring impact of acute hospital care on health status of elderly patients, burden on carers, and consumer satisfaction with care. The study was undertaken on four acute care wards of an elderly care unit of a teaching hospital. We used a consensus-building process to achieve within-and-between-team convergence of policy and practice in the use of structured assessments on three wards, with parallel data collection by a research nurse on one ward. We describe the changes to our working practices, the costs of data collection, staff attitudes to the system and the assessment instruments, using 5-point Likert Scales, with additional in-depth interviews with senior staff for their attitudes to the system. We found that only nursing staff were able to change their practice. On admission, it was feasible to undertake functional assessment of activities of daily living (ADL), depression, perceived life quality and carer strain. Discharge assessment was only feasible for ADL. Other discharge assessments and follow-up assessments including consumer satisfaction interviews required audit assistant support. The total annual cost per ward was 6,225 pounds for the adopted system, or 6,455 pounds to incorporate follow-up assessments by audit assistant in a random sample of 50 patients. Staff attitudes to the system were positive, especially for use of the Relatives' Stress Scale, and for the value of follow-up interviews. We conclude that the participatory approach to the introduction of the information system produced a system which was perceived to be beneficial for patient care.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Ependyma-lined cysts.

Ependyma-lined cystic lesions of the subarachnoid space are uncommon. They form a histologically heterogeneous group and have been referred to as epithelial, ependymal, glioependymal and neuroepithelial cysts depending on their respective histological characteristics. In this report, we describe two cases of ependyma-lined cysts in the posterior fossa that support a common pathogenesis for this diverse group of lesions.

Adult↗