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C Y Shiau

Publications and source records attributed to C Y Shiau.

At least 19 recordsLinked to original sources
PubMed2007

Topoisomerase 2alpha plays a pivotal role in the tumor biology of stage IV thymic neoplasia.

BACKGROUND: Microsatellite studies in histologic types B3 and C thymic neoplasia detected gains on chromosome 17q, which contains the Her-2/neu and its juxtaposed topoisomerase 2alpha (T2alpha) genes. The study aimed to evaluate their impact on tumor biology and survival of advanced thymic neoplasia patients. METHODS: From 1991 to 2005, 36 consecutive stage IV thymic carcinoma patients were treated, 18 men and 18 women, aged 11 to 84 years. There were 22 thymic carcinoma, 13 type B3, and 1 type B2 thymoma. Patients received treatment consisting of surgical resection, combination chemotherapy with the CAP (cyclophosphamide, Adriamycin, cisplatin) regimen, or radiation therapy potentiated by high-dose weekly 5-fluorouracil infusion. Permutations of these 3 treatment modalities were prescribed as necessary. RESULTS: T2alpha gene amplification was detected in 4 of 14 thymic carcinoma and 1 of 15 type B3 thymoma. Three thymic carcinoma patients had Her-2/neu coamplification and these 3 patients had rapidly growing tumor and extensive disease at initial diagnosis. CAP was prescribed in 28 patients and 20 patients responded (response rate, 71.4%, 95% confidence interval [CI]: 52.8% to 85%); all responders overexpressed (> or = 10% nuclei positive) the T2alpha protein, whereas 4 nonresponders had very low expression. T2alpha overexpression predicts CAP response, and its absence predicts resistance (P = .001). Overall survival was significantly prolonged if the tumor was resectable (P = .001), of type B3 histology (P = .0039), and had no Her-2 gene amplification (P = .0081). CONCLUSION: T2alpha and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.

Adolescent↗
PubMed2001

Relationship between pattern of enhancement and local control of brain metastases after radiosurgery.

PURPOSE: A desired goal in the radiosurgery (RS) of brain metastases is improved local control. Our earlier retrospective review identified pattern of enhancement on day-of-treatment imaging as a prognostic indicator for freedom from progression (FFP) after RS in 219 brain metastases. The current study was performed to corroborate this preliminary finding. METHODS AND MATERIALS: Records and imaging studies of patients treated with RS from 1991 to 1997 were reviewed. Each metastasis was categorized as homogeneously-, heterogeneously-, or ring-enhancing. Kaplan-Meier FFP was calculated from the date of RS to the first imaging showing tumor progression. Univariate and multivariate analyses were performed using Cox proportional hazard models stratified by primary site and type of RS (alone, as a boost, or for recurrence). RESULTS: Of 682 lesions in 258 patients, 518 lesions in 193 patients were evaluable. Pattern of enhancement was homogeneous in 59%, heterogeneous in 32%, and ring-like in 8% of lesions. One-year FFP probabilities for homogeneously-, heterogeneously-, and ring-enhancing lesions were 90% (95% confidence interval, 84-93%), 76% (64-84%), and 57% (35-74%), respectively. The p-value for pattern of enhancement from the stratified multivariate analysis was 0.019 adjusting for RS dose and treatment period (1991-1994 vs. 1995-1997). Similar results were achieved adjusting for tumor volume instead of RS dose. CONCLUSION: Pattern of enhancement is confirmed as a significant prognostic factor for FFP of brain metastases treated with RS, independent of dose and volume. A possible explanation is radioresistance of hypoxic tumor cells associated with necrotic regions, suggesting future investigations with radiosensitizers, hypoxic cell sensitizers, or strategies to improve tumor oxygenation.

Adolescent↗
PubMed2001

Effect of starvation on free histidine and amino acids in white muscle of milkfish Chanos chanos.

Milkfish (Chanos chanos) decreased their body weight from 47 to 28 g over the 60-day period of starvation. Starvation also resulted in the reduction of muscle lipid and protein, and hepatosomatic index. The predominant free amino acid (FAA) in white muscle of milkfish was histidine, followed by taurine and glycine. In the first 25 days of starvation, no significant change in histidine was found. After 40 days of starvation, however, the histidine concentration was significantly decreased by 46%, and remained unchanged thereafter. As compared to control group fish, the 60-day-starved fish possessed only half the amount of histidine. Taurine and glycine, on the other hand, showed no significant changes throughout starvation. Taurine became the most predominant in the FAA pool after 40 days of starvation, and the concentration of 60-day-starved fish was two times higher than that of control group fish without starvation. The ratios of histidine, taurine, and glycine to total FAAs remained approximately the same although the individual contributions varied considerably to the total FAAs during starvation. The results of this study suggested that a good strategy would be to keep taurine and glycine in milkfish muscle at relatively high levels for physiological function as histidine decreased drastically for energy source under conditions of food deprivation.

Amino Acids↗
PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗
PubMed2000

Treatment of non-small-cell lung cancer: the Chinese experience in a general teaching hospital.

BACKGROUND: It has been reported that combination chemotherapy and radiotherapy prolongs locally advanced stage IIIB non-small-cell lung cancer (NSCLC) patient survival and cisplatin-based chemotherapy prolongs survival in stage IV disease. This study was aimed at investigating whether this conclusion also applies to Chinese patients. METHODS: We retrospectively reviewed the medical records of NSCLC patients diagnosed at the Taipei Veterans General Hospital covering a period from 1990 to 1996 to examine the effect of treatment regimen on survival. RESULTS: There were 3,925 cases of NSCLC diagnosed during this period. The stage at diagnosis was stage III or IV in the majority (76.6%) of cases. Surgery followed by chemotherapy with or without radiotherapy conferred a survival benefit of more than two years in stage IIIA patients. For stage IIIB patients, chemotherapy in combination with radiotherapy yielded a median survival of 13 months, compared to only seven months for radiotherapy alone. For stage IV patients, cisplatin-based chemotherapy prolonged median survival for more than two months compared with palliative radiotherapy alone or supportive care only. Survival was improved in stage IV patients who received chemotherapy during 1990 to 1996 compared with those who received chemotherapy during 1985 to 1989. This improvement was most likely due to improvements in supportive care because the treatment regimen was constant during the study period. CONCLUSIONS: Cisplatin-based chemotherapy prolonged survival of Chinese patients with metastatic NSCLC. Combination chemotherapy and radiotherapy also prolonged survival of Chinese patients with locally advanced NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Salvage surgery for recurrent nasopharyngeal carcinoma in anterior marginal miss after radiotherapy.

Nasopharyngeal carcinoma (NPC) is treated primarily by radiotherapy. Marginal miss after radiotherapy is a potential cause for treatment failure in NPC. Anterior marginal miss after irradiation results in recurrent tumors in the nasal cavity outside the nasopharynx. From 1991 to January 1997, 6 recurrent NPCs arising in the anterior marginal miss zone after radiotherapy were confirmed by pathologic and radiologic evaluation. One patient had infiltrating growth of the original NPC tumor into the anterior part of nasal septum, and the other 5 had microscopic extensions from the original NPC tumors into the nasal cavity that were beyond detection by endoscopy or CT scan. In some cases the tumors extended further to include the hard palate or the lacrimal sac. Medial maxillectomy and partial maxillectomy with or without resection of the hard palate were necessary to encompass the extent of the tumors. Surgical margins were free of cancer cells in 5 patients. No further treatment was given in these 5 patients. Another patient with tumor extending to the lacrimal sac received postoperative radiotherapy. Five of the 6 patients survived with no evidence of disease for 8 to 65 months. One patient had distant metastasis 14 months after surgery but was free from tumor at the primary site. Radical surgery can result in good and sustained local control for anterior marginal miss of NPC after radiotherapy.

Adult↗
PubMed1998

The significance of soluble interleukin-2 receptor in monitoring disease relapse in patients with nasopharyngeal cancer.

BACKGROUND: Soluble interleukin-2 receptor alpha (sIL-2R alpha) is a well-known indicator of T-cell activation noted to be increasing in nasopharyngeal cancer. However, the significance of sIL-2R alpha in monitoring disease relapse is unclear. This study was initiated to address this issue. METHODS: Serum of 56 patients with NPC, which underwent either primary, salvage, or palliative treatments, from 1992 to 1993 at the Cancer Center, Veterans General Hospital-Taipei, were collected from our serum bank. According to their disease status at the time of study, at least two years after last treatments, the 56 patients were divided into four groups. The remission group represented those in remission at the time of study (n = 24). The metastasis group represented those with distant metastasis present at the time of study (n = 17). The recurrence group represented those with locoregional recurrence present at the time of study (n = 11). The combined group represented those with locoregional recurrence as well as distant metastasis (n = 4). The seral sIL-2R alpha concentrations of the 56 NPC patients were determined with enzyme-linked immunoabsorbent assay. The combined group was excluded in our statistical analysis. We performed statistical analysis on the differences of paired serum sIL-2R alpha concentrations between different periods of the diseases. The first analysis was on the differences of sIL-2R alpha concentrations between diagnosis and post-radiotherapy periods for 13 out of 24 patients in the remission group and 7 out of 11 patients in the recurrence group. The second analysis was on the differences of sIL-2R alpha concentration between follow-up before detection-of-relapse and after detection-of-relapse for 5 out of 17 patients in the metastasis group and six out of 11 patients in the recurrence group. RESULTS: The first statistical analysis revealed no significant differences of sIL-2R alpha concentrations for the remission group (P = 0.946) and the recurrence group (P = 0.156) between diagnosis and post-radiotherapy periods. The second statistical analysis revealed no significant differences of sIL-2R alpha concentrations between before and after detection-of-relapse for the recurrence group, neither (P = 0.438). The results for the metastasis group were different. The sIL-2R alpha concentrations were shown to increase after the detection of metastasis for the 5 paired samples from the metastasis group, although the Wilcoxon signed ranks test on the differences only showed borderline significance (P = 0.063). CONCLUSIONS: Our findings show that sIL-2R alpha would be of no value in monitoring the development of locoregional recurrence but might be useful in monitoring distant metastasis. Although our current limited data did not provide strong support for the role of sIL-2R alpha in monitoring metastasis, it might be delineated in the future by collecting more data.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas.

BACKGROUND: A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. METHODS: From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. RESULTS: Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n = 7), radiotherapy alone (n = 10) and radiotherapy with adjuvant chemotherapy (n = 5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P = 0.017 and 0.036). A trend of better outcome with radiation dose > 6600 cGy and the hyperfractionation scheme was also noted in our study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme was also noted in our study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P = 0.0355). Survival was not significantly affected by age, gender or method of diagnosis. CONCLUSION: Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival.

Brain Neoplasms↗
PubMed1998

The effectiveness and factors related to treatment results of gamma knife radiosurgery for meningiomas.

A retrospective analysis was conducted on 80 patients with intracranial mengiomas treated with Gamma Knife radiosurgery between 1993 and 1996. The purpose was to analyze the efficacy of the treatment and to assess appropriate treatment parameters. The results were assessed by regular MR examinations, and tumor volume was measured at 6-month intervals. Mean follow-up duration was 21 months (range 6-45 months). 63 meningiomas were at the skull base and 17 were distal from the skull base. Tumor volumes <5 ml (n=38), 5-10 ml (n=21), 10-15 ml (n=14), 15-20 ml (n=7). The patients were divided into 3 groups according to the radiation dose. The groups were high-dose (peripheral dose 17-20 Gy, n=19), medium-dose (15-16 Gy, n=33) and low-dose (12-14 Gy, n=28) groups. A statistical method (Generalized Estimation Equation) was applied to compare treatment results in these groups with different doses and tumor volumes. The volume measurement at the latest follow-up showed 74% (59/80) meningiomas decreased in volume, 17% (14/80) had no tumor enlargement and 9% (7/80) had increased in volume. The increased volume was found more frequently in the patients with a short (6-12 months) follow-up period. In this series, the tumors had 32&percnt reduction in average tumor volume at 3 years after radiosurgery. At the range of 12-20 Gy peripheral dose (PD), radiosurgery was effective to reduce tumor volume 0.7% per month (p<0.05). However, higher doses had no significant difference on tumor volume reduction (p>0.05). On the other hand, high-dose (PD>17 Gy) treatment was associated with a higher risk of temporary tumor swelling and the development of adverse radiation effects (AREs). The AREs detected on MR images occurred in (25/80) 31% patients. Only 6/25 AREs were symptomatic and 2 had neurological sequelae. Peripheral doses, tumor volumes and their locations had significant impacts on the ARE (p<0. 05). In conclusion, a peripheral dose of 15-16 Gy may be adequate for meningiomas with small volumes (<5 ml). In larger tumors (>10 ml) a lower PD is preferred (12-14 Gy). To avoid initial tumor swelling and ARE, high-dose irradiation (PD>17 Gy) is not recommended for meningiomas larger than 5 ml.

Adult↗
PubMed1998

Protection of visual pathway in gamma knife radiosurgery for craniopharyngiomas.

Craniopharyngiomas present a major challenge to Gamma Knife radiosurgery (GKRS) due to their proximity to the optic apparatus. Based on observations of the evolving tumoral change on MRI and clinical results, an optimization of the treatment strategy and dose selection is possible. From March 1993 to September 1996, 21 patients with craniopharyngiomas were treated by GKRS. Every patient received stereotactic MRI exclusively for targeting and dose planning. The tumor and adjacent structures, including optic nerves, chiasm, and tracts were carefully identified and delineated on sagittal, coronal and axial films. The tumor volume ranged from 0.3 to 28 ml (average 9 ml). We purposefully apply multiple isocenters (average 9.1 shots) to create an isodose curve that covered the tumor optimally while sparing the optic pathway. The marginal dose prescribed was 9.5 to 16 Gy (50%). The maximal dose was 19 to 32 Gy. The maximal dose to the optic apparatus was 3.2 to 12.5 Gy. After GKRS, all patients were followed up clinically every month. MR studies were conducted every six months with the same techniques on the same scanner to investigate evolution of tumor volume and any adverse radiation effect. The follow-up period ranged from 6 to 40 months (mean: 18.4, median: 19). All patients were followed more than 6 months. Nineteen out of 21 cases (90.5%) achieved tumor control; that is, 18 tumor shrinkage (volume reduction: 15-95%) and 1 stabilized tumor growth. Among these 21 patients, 7 had improved visual acuity or visual field after GKRS, and the rest remained stable. Two patients developed mild T2 change on MRI without any endocrinological disturbance or visual impairment. Protection of the visual pathway can be secured by a sophisticated delineation on 3-dimensional stereotactic images with multiple-shot dose planning. Craniopharyngiomas with tumor volume up to 25 ml were treated safely and effectively, because the dose to the optic apparatus was kept as low as possiby this strategy. Further follow-up is needed to determine the highest tolerable dose to surrounding critical structures and the long-term outcome of tumor control.

Adolescent↗
PubMed1998

Verifying complete obliteration of carotid artery-cavernous sinus fistula: role of color Doppler ultrasonography.

The purpose of this study was to evaluate the role of color Doppler ultrasonography in verifying obliteration of carotid artery-cavernous sinus fistula before and after therapeutic embolization or gamma knife radiosurgery. Before treatment, carotid artery-cavernous sinus fistula showed the following data on color Doppler ultrasonography: (1) increased blood flow in the common carotid artery (220 to 1264 ml/min with mean+/-SD of 728+/-378 ml/min); internal carotid artery (435 to 1097 ml/min with mean+/-SD of 834+/-216 ml/min) in fistulas of the direct type; and external carotid artery (85 to 257 ml/min with mean+/-SD of 170+/-75 ml/min) in fistulas of the indirect type in comparison to the contralateral side; (2) reverse pulsatile flow or spiculated wave form with turbulent flow in the engorged superior ophthalmic vein on the lesion side in all patients. All of the above abnormal hemodynamic changes became normal in six patients immediately after first embolization, in two patients with balloon embolization combined with subsequent direct embolization by direct puncture through the superior orbital fissure or internal carotid artery embolization, and in five patients after gamma knife radiosurgery at 4, 4, 8, 9, and 9 months, respectively. Color Doppler ultrasonography might be a good modality in long-term follow-up of carotid artery-cavernous sinus fistula after gamma knife radiosurgery and embolization.

Adolescent↗
PubMed1998

Effects of gamma knife radiosurgery for brain tumors: clinical evaluation.

BACKGROUND: Gamma knife radiosurgery is a safe and effective alternative to microsurgery in the management of selected intracranial lesions. In our initial three-year experience with gamma knife radiosurgery, 431 patients were treated using this method. This report presents the treatment results for three different types of brain tumors: benign meningiomas, malignant metastases and gliomas. METHODS: A retrospective study was performed to analyze a consecutive series of 71 meningiomas, 31 metastatic tumors and 21 gliomas treated by gamma knife radiosurgery between March 1993 and May 1996. The treatment results were investigated using regular magnetic resonance examinations and tumor volume measurement at six-month intervals to observe sequential changes of the tumors. Patients with meningiomas were further divided into three groups according to the peripheral radiation doses: high-dose (20-17 Gy, n = 18), medium-dose (16-15 Gy, n = 33) and low-dose (14-12 Gy, n = 20). The Generalized Estimation Equation was applied to compare treatment results in these three groups with different doses and tumor volumes. RESULTS: Volume measurements of the 71 meningiomas showed that 76% decreased in size, 16% stabilized and 8% increased in size. The volumes increased most frequently in the early stage (6-12 months) after treatment and subsequently regressed after the twelfth month. The tumor control rate for meningiomas in our three-year follow-up was over 90%. For meningiomas, the statistical analysis showed that both the radiation dose and tumor volume were significantly related to the development of adverse radiation effects (p < 0.05). In metastatic tumors, rapid tumor regression after radiosurgery was found in 87% of the patients. In gliomas, radiosurgery effectively inhibited tumor growth in selected patients with small, circumscribed, less infiltrative tumors. Ependymomas and low-grade astrocytomas had more favorable outcomes than other gliomas. CONCLUSIONS: Gamma knife radiosurgery is effective for controlling tumor growth in benign meningiomas for up to three years after surgery. In selected cases of malignant metastasis and gliomas, most patients appeared to benefit from the treatment with symptomatic improvement and prolonged survival. Treatment strategy and dose selection in radiosurgery should be adjusted to optimize tumor control and avoid adverse radiation effects.

Brain Neoplasms↗
PubMed1997

L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine synthetase: thioesterification of valine is not obligatory for peptide bond formation.

L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase is probably the simplest known peptide synthetase in terms of the number of reactions catalyzed. In the "thiol-template" proposal for nonribosomal peptide synthesis, a key step is transfer of aminoacyl groups derived from the substrates to enzyme-bound thiols prior to peptide bond formation. No incorporation of 18O was seen in AMP isolated from the reaction mixture when di[18O]valine was incubated with relatively large amounts of active synthetase and MgATP. We therefore utilized di[18O]valine as a substrate for the biosynthesis of the diastereomeric dipeptides L-O-(methylserinyl)-L-valine and L-O-(methylserinyl)-D-valine [Shiau, C.-Y., Baldwin, J. E., Byford, M. F., Sobey, W. J., & Schofield, C. J. (1995) FEBS Lett. 358, 97-100]. In the L-O-(methylserinyl)-L-valine product, no significant loss of 18O was observed. However, in the L-O-(methylserinyl)-D-valine product, a significant loss of one or both 18O labels was observed. Thus, both peptide bond formation and the epimerization of the valine residue can both occur before formation of any thioester bond to the valine carboxylate in the biosynthesis of these dipeptides. The usual qualitative test for thioesterification of substrates to the synthetase, lability of enzyme-bound radiolabeled amino acid to performic acid, proved inconclusive in our hands. These results require a new mechanism for the enzymic synthesis of L-O-(methylserinyl)-L-valine and L-O-(methylserinyl)-D-valine and imply that a revised mechanism for ACV synthesis is also required.

2-Aminoadipic Acid↗
PubMed1997

Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control.

PURPOSE: This study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS). METHODS AND MATERIALS: All brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model. RESULTS: Of 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving > or = 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55). CONCLUSION: A minimum prescribed radiosurgical dose > or = 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a new finding in this retrospective analysis, needs to be confirmed.

Adenocarcinoma↗
PubMed1995

Delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase: isolation of L-cysteinyl-D-valine, a 'shunt' product, and implications for the order of peptide bond formation.

L-Cysteinyl-D-valine was isolated from incubations of L-glutamate, L-cysteine and L-valine with delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase and identified by 1H NMR and electrospray ionization MS. This is entirely consistent with our prior proposal (Shiau, C.-Y., Baldwin, J.E., Byford, M.F., Sobey, W.J. and Schofield, C.J. (1995) FEBS Lett. 358, 97-100) that the alpha-peptide bond between cysteine and valine is formed before the delta-peptide bond between alpha-aminoadipate and cysteine. The inclusion of L-glutamate, an analogue of L-alpha-aminoadipate, did not result in a detectable amount of tripeptide product, but did increase apparent yields of L-cysteinyl-D-valine. Conceivably, formation of the L-glutamyladenylate stimulates synthesis of the cysteinyl-valine dipeptide indirectly via a conformational change in the enzyme.

Acremonium↗
PubMed1995

delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase: the order of peptide bond formation and timing of the epimerisation reaction.

delta-L-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase catalyses the formation of the common precursor tripeptide of both the penicillin and cephalosporin antibiotics from the L-enantiomers of its constituent amino acids. Replacement of cysteine with L-O-methylserine in preparative-scale incubations led to the isolation of both L-O-methylserinyl-L-valine and L-O-methylserinyl-D-valine dipeptides. The dipeptides were characterized with the aid of authentic synthetic standards by both 1H NMR and electrospray ionization MS. A revised mechanism for ACV biosynthesis involving formation of the cysteinyl-valine peptide bond before the epimerisation of valine and subsequent condensation with the delta-carboxyl of L-alpha-aminoadipate is therefore proposed.

Amino Acid Sequence↗
PubMed1995

Early effects of Gamma Knife surgery on malignant and benign intracranial tumors.

To assess the early response of intracranial tumors to Gamma Knife surgery, we performed a prospective investigation of 42 patients treated by Gamma Knife surgery for different types of intracranial tumors. The clinical condition, tumor volume, treatment results and their temporal correlation with the irradiation were analyzed, based on MRI performed on the same MR scanner. Volume reduction in the tumors measured at the latest follow-up ranged from 0.2 to 100%. All except 1 malignant tumor showed decreasing size and improving peritumoral edema 1-7 months after radiosurgery. In 30 benign tumors, 13 showed either a decrease or no change in volume. However, an initial volume increase was observed in 17 tumors, with a maximum at 3-9 months, which subsequently regressed. In 2 meningioma patients, peritumoral edema increased and needed steroid treatment. Sequential PET-FDG imaging of the patients showed decreasing FDG uptake, indicating a decrease tumor in metabolism. The PET findings correlated well with the loss of contrast enhancement on MR images. In conclusion, intracranial tumors respond to Gamma Knife surgery from an early stage. Different tumors have different responses to radiosurgery. It is too early to offer a prognosis of long-term effects based on the limited material. However, sequential clinical, MR and PET follow-ups provide an excellent opportunity to investigate the evolving irradiation effects in vivo.

Brain Neoplasms↗