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Biomedical subjects

S M Chang

Publications and source records attributed to S M Chang.

At least 91 records · Page 5Linked to original sources
PubMed1996

Reirradiation of primary CNS tumors.

PURPOSE: Primary central nervous system (CNS) tumors are seldom reirradiated due to toxicity concerns and sparse clinical data regarding efficacy. METHODS AND MATERIALS: We retrospectively reviewed 34 patients with primary brain tumors retreated with fractionated external beam irradiation at the University of California, San Francisco from 1977-1993. Tumors included 15 medulloblastomas, 10 high-grade gliomas, 7 low-grade gliomas, and 2 meningiomas. RESULTS: Initial course of radiation was radical in intent for all patients. Median age at initial diagnosis was 19.8 years (range: 3.6-67). Median interval between radiation courses was 16.3 months (range: 3.8-166). Median Karnofsky Performance Status (KPS) prior to reirradiation was 80 (range: 40-100). Reirradiation volumes overlapped previous treatment in 30 patients and were nonoverlapping in 4 patients. Fractionation schemes used were hyperfractionated in 17, conventionally fractionated in 9, and hypofractionated in 8. Cumulative maximum overlap dose within the CNS ranged from 43.2-111 Gy (median: 79.7 Gy). Retreatment was completed as planned in 27 out of 34 patients and modified or aborted in 7 (four tumor progression on retreatment, three patient request). As measured from the time of retreatment median progression free and overall survival was 3.3 and 8.3 months. Clinical and radiographic indices were stabilized or improved in about half of patients evaluable at a median of 3 months postretreatment. Complications (early or late) potentially attributable to retreatment were noted in 10 of 34 (29%) of patients. Overt necrosis was noted in 3 of 34 (9%) of patients and the actuarial risk of necrosis was 22% at 1 year following retreatment. CONCLUSIONS: Reirradiation of primary central nervous system tumors was associated with only modest palliative and survival benefits in this retrospective review. Difficulties separating toxicity due to retreatment vs. tumor progression and limited patient survival following retreatment preclude definite conclusions regarding the safety of this practice.

Adolescent↗
PubMed1996

Microbial cyanide sensor for monitoring river water.

A microbial cyanide sensor using Saccharomyces cerevisiae for monitoring a river water is described. This sensor is based on the inhibition of S. cerevisiae's respiration by cyanide. This sensor is a reactor type flow system and composed of two oxygen electrodes and a reactor which contains S. cerevisiae immobilized beads. The S. cerevisiae's respiration activity is measured using the oxygen electrodes. The sensor showed a linear response in the range from 0 to 15 microM and maintained stable response for 9 days at ambient temperature. The sensor was optimized for the monitoring of river water and was applied to river water analysis.

Biosensing Techniques↗
PubMed1996

Suramin-induced decrease in prostate-specific antigen expression with no effect on tumor growth in the LNCaP model of human prostate cancer.

BACKGROUND: Suramin, a polysulfonated naphthylurea and a recognized antitrypanosomal agent, has shown some promise in phase II clinical trials in the management of hormone-refractory human prostate cancer. Reduction of serum prostate-specific antigen (PSA) levels has been proposed as an end point for evaluating the antitumor efficacy of treatments for hormone-refractory prostate cancer. PURPOSE: We examined the antitumor effect of suramin in an in vivo mouse model of hormone-refractory human prostate cancer to determine whether a decrease in PSA levels reflects a reduction in tumor growth (volume). The tumors were induced in castrated, athymic nude mice by use of the androgen-independent, tumorigenic human prostate cancer cell line C4-2, which is a subline of the androgen-dependent, parental nontumorigenic cell line LNCaP. We also evaluated the effects of suramin in vitro on cell growth and the expression of PSA messenger RNA (mRNA) in both LNCaP and C4-2 cells. METHODS: For the in vivo studies, 24 mice were given a subcutaneous injection of 5 x 10(6) C4-2 cells at each of four sites. Animals (n = 20) with tumor volumes greater than 1 mm3 or less than 5 mm3 were divided equally into two groups. Drug treatment was initiated in one group by administration of 1 mg suramin intraperitoneally, followed by 0.1 mg suramin at 10-day intervals to maintain constant serum levels. Tumor growth and PSA expression levels were monitored. For the in vitro studies, both LNCaP and C4-2 cells were exposed to 100-400 microgram/mL suramin, and cell growth was monitored by a quantitative crystal violet assay. PSA mRNA expression was assessed by northern blot analysis in cells treated with either 250 microgram/mL suramin, 400 ng/mL dihydrotestosterone (DHT) (positive control), or 0.5-75 microgram/mL hydrocortisone (to mimic the clinical use of hydrocortisone during suramin treatment to compensate for the loss of adrenocortical function). In some studies, the combined effect of DHT and suramin on PSA mRNA expression was also evaluated. A two-way analysis of variance was performed to evaluate the treatment differences, and P values were obtained from two-sided tests for statistical significance. RESULTS: In vivo, suramin did not significantly affect the growth of androgen-independent C4-2 tumors (relative to the growth of tumors in 5% glucose-treated control animals; P = .76). However, suramin significantly decreased the ratio of PSA level to tumor volume (ng/mL PSA per mm(3) of tumor) (P<.001). Mice developed bone metastases in both treatment arms. Suramin affected the in vitro growth of LNCaP cells but not of C4-2 cells. Suramin diminished PSA mRNA expression in both LNCaP and C4-2 cells grown in vitro. Hydrocortisone had no effect on PSA mRNA levels. CONCLUSIONS: Although suramin inhibited the growth of androgen-dependent LNCaP cells, it did not inhibit the growth of androgen-independent C4-2 cells either in vitro or in vivo. Suramin significantly decreased PSA mRNA expression in both cell lines in vitro and depressed serum PSA levels in mice bearing androgen-independent C4-2 tumors. IMPLICATIONS: PSA level should be used with caution as an end point in clinical trials using suramin therapy for hormone-refractory prostate cancer.

Analysis of Variance↗
PubMed1996

Necrosis as a prognostic factor in glioblastoma multiforme.

BACKGROUND: Many pathologists require the presence of tumor necrosis within an astrocytic neoplasm to establish the diagnosis of glioblastoma multiforme (GM). Two new grading systems for astrocytic neoplasms allow a tumor to be diagnosed at the highest level of anaplasia without requiring the presence of tumor necrosis. METHODS: To determine whether GMs without necrosis had biologic behavior most compatible with a diagnosis of GM or of anaplastic astrocytoma (AA), we examined the survival of 299 patients whose tumors were diagnosed as GM because they contained endothelial proliferation and who were treated according to prospective clinical protocols. Multivariate proportional-hazards survival analysis was used to assess the importance of tumor necrosis after adjustment for other prognostic factors. RESULTS: Of 275 patients with GMs containing endothelial proliferation, 88% had tumor necrosis. Absence of necrosis was associated with younger age and with less extensive surgical resection. The absence of necrosis predicted longer survival in univariate analysis (P = 0.02) and after adjustment for age, Karnofsky performance score, and extent of resection in a multivariate analysis (P = 0.04). However, the magnitude of the survival difference was not clinically important: patients without tumor necrosis had a median survival of 12.5 months, and those with tumor necrosis had a median survival of 10.9 months. Kaplan-Meier survival rates two years after diagnosis were 13.0% for patients with necrosis and 27.1% for patients without necrosis; the difference in 2-year survival was not statistically significant (difference in survival rates = 14.1%, 95% confidence interval -2.2% to 30.4%). CONCLUSIONS: The survival of patients with astrocytic neoplasms containing endothelial proliferation and no necrosis conforms best to the pattern expected for patients with GM rather than AA. This supports the classification of these tumors as GM in the revised World Health Organization grading system and as grade 4 astrocytomas in the St. Anne-Mayo grading system.

Adolescent↗
PubMed1996

Bromodeoxyuridine labeling index in glioblastoma multiforme: relation to radiation response, age, and survival.

PURPOSE: Various measures of the rate of tumor cell proliferation have been found to predict survival in patients with intracerebral gliomas. We correlated the bromodeoxyuridine labeling index (BrdUrd LI) with the response to radiation therapy, survival, and known prognostic factors in a series of patients with glioblastoma multiforme (GM) to test its utility as a prognostic factor. METHODS AND MATERIALS: The BrdUrd LI was determined in 200 newly diagnosed intracranial GMs. Age and sex were known for all patients. The response to radiation therapy was determined in 116 patients by comparing neuroimaging studies obtained before and after external beam radiation therapy. Survival was analyzed in 64 patients who were treated according to two consecutive prospective clinical protocols. RESULTS: The median BrdUrd LI was 6.5% (mean, 7.2%; range, 1.1-25.4%). The BrdUrd LI did not correlate significantly with age, sex, radiation response, or survival. Age and Karnofsky performance score were independent prognostic factors in our cohort. CONCLUSION: The proliferative rate as measured by BrdUrd LI was not a prognostic factor in our GM cohort. The BrdUrd LI did not correlate significantly with known prognostic factors in GM. There was no significant relationship between BrdUrd LI and radiation response.

Adolescent↗
PubMed1996

Transfected neu oncogene induces human prostate cancer metastasis.

c-erb B2/neu has been demonstrated to be a transforming oncogene in both rodent and human prostatic epithelial cells. To understand the potential role of neu in human prostatic cancer progression, we used a transfer procedure to determine whether neu amplification/overexpression leads to increased tumor growth and metastasis. We chose an androgen-independent human prostatic epithelial cell line, PC-3, as the target for gene transfer. PC-3 cells were cotransfected with pSVneu-T (a point-mutated rat neu oncogene construct) and pSV2neo, and single-cell cloned. Fifty cell clones were isolated and characterized, of which two neu-transfected clones (N17 and N35) and a neo control clone (C32) were studied extensively with respect to neu gene integration, levels of neu mRNA and protein expression, anchorage-independent growth, and tumorigenic and metastatic potential. Results showed that: 1) Clone N35 contained 70 copies of the neu oncogene and a high level of neu mRNA transcripts. It acquired increased anchorage-independent growth potential in vitro and increased tumorigenicity in vivo. 2) Clone N17 contained 10 copies of the neu oncogene and a low level of neu mRNA transcripts. It did not acquire additional capability for anchorage-independent growth and tumorigenic potential as compared to the controls. 3) Despite an increased level of neu mRNA transcripts present in clone N35, there was no corresponding increase of the steady-state levels of neu protein in this particular clone. 4) When administered subcutaneously, none of the cell clones tested, including the control neomycin-resistant clone, acquired metastatic potential. However, clone N35 exhibited marked metastatic potential when administered orthotopically; this cell clone was found to disseminate widely to the lymph nodes, kidney, skeletal muscle, lung, liver, and bone. 5) When neu-transfected cell subclones from N35-induced primary and metastatic lymph node, kidney, and bone tumors were analyzed for cytoskeletal, extracellular matrix, and cell adhesion protein expression, the bone metastatic subclone exhibited increased levels of vimentin and collagen IV and decreased levels of cytokeratin and ICAM-1. These results, taken together, suggest that neu transfection induces secondary changes, which, rather than neu protein per se, are responsible for the acquisition of tumorigenic and metastatic potential of prostate cancer cells when an appropriate host microenvironment is present.

Animals↗
PubMed1996

Oxytocin receptors in bovine cervix during pregnancy and parturition: gene expression and cellular localization.

OBJECTIVES: Our purpose was to determine the expression of transcripts encoding the oxytocin receptor protein in bovine cervix during pregnancy and parturition, the cellular localization of immunoreactive oxytocin receptors, and oxytocin receptors concentrations in the same tissues. STUDY DESIGN: Ribonuclease protection assay for oxytocin receptor messenger ribonucleic acid was used to determine gene expression in bovine cervical tissues obtained from 20 cows throughout pregnancy and parturition, cellular localization of oxytocin receptors was determined by immunohistochemistry, and tritiated oxytocin binding was measured in each tissue. RESULTS: Oxytocin receptor gene expression and tritiated oxytocin binding were well correlated in each instance. During pregnancy the level of oxytocin receptor messenger ribonucleic acid was very low; it was increased at term with a further, marked increase at parturition. Tritiated oxytocin binding also increased dramatically at parturition and was most abundant in the mucosal layer. Strong oxytocin receptor immunoreactivity was present in mucosal epithelial cells, and scattered muscle cells in the muscular part showed the signal. CONCLUSIONS: Our results, together with the previous finding that oxytocin stimulates prostaglandin E2 release from cervical tissue in vitro, indicate that cervical mucosal epithelial cells are targets for oxytocin at parturition and may mediate release of prostaglandin E2.

Animals↗
PubMed1996

Early childhood supplementation does not benefit the long-term growth of stunted children in Jamaica.

The long-term benefits of early childhood supplementation and the extent to which catch-up growth occurs following linear growth retardation remain controversial. Stunted children (height-for-age < -2 SD of NCHS references, n = 122) recruited from a survey of poor neighborhoods in Kingston, Jamaica, participated in a 2-yr randomized, controlled trial of supplementation beginning at ages 9-24 mo. A group of 32 non-stunted children from the same neighborhoods was also followed. Four years after the intervention ended, when children were 7 to 8 y old, there were no effects of supplementation on any anthropometric measure. From the end of the trial until follow-up, the children who had been supplemented gained 1.2 cm less (P < 0.05) than the non-supplemented children, approximately the same amount as they had gained during the trial compared with the non-supplemented children. After adjustment for regression to the mean, the height-for-age of stunted children (supplemented and non-supplemented combined) increased from enrollment to follow-up by 0.31 Z-score (95% CI 0.17, 0.46). The height-for-age of the non-stunted children also increased (0.96 Z-score; 95% CI 0.70, 1.22). Our results suggest that some catch-up growth is possible even when children remain in poor environments. Long-term benefits of supplementation to growth may not be achieved when intervention begins after age 12 mo in children who have already become undernourished.

Anthropometry↗
PubMed1996

Oxytocin receptors in bovine cervix: distribution and gene expression during the estrous cycle.

Oxytocin (OT) receptor (OTR) concentrations were determined in the cervix of nonpregnant cows on cycle Days 0, 3, 7-8, 17, and 19 (n = 3-4 cows each day); [3H]OT was used as the labeled ligand. Mucosal and muscle layers of the cervix were also analyzed separately for both ligand binding and expression of the OTR gene using a newly developed RNase protection assay (RAP). Cellular localization of OTR protein was determined by immunohistochemistry. All regions of cervix from cows at estrus had high concentrations of OTR; in the luteal phase, all were sharply down-regulated. At estrus the mucosal layer had about 30-fold higher concentrations than the muscle layer. OTR mRNA was readily detected by RAP in the mucosa from estrous cows, while much weaker signals were found in the muscle. On Days 7-17, the OTR mRNA signals in both mucosa and muscle were very faint or nondetectable. Thus, there was a good correlation between ligand binding and mRNA expression, which suggests that OTR concentrations are mainly regulated at the transcriptional level. The epithelial cells at the luminal surface of the mucosa were the principal site of immunoreactive OTR; muscle cells showed significantly weaker signals. Previously, OT was found to stimulate prostaglandin (PG) E2 output in vitro in bovine cervical tissues. Since PGE2 is capable of softening the cervix, our findings suggest that OT may have a novel physiological function to cause softening of the bovine cervix mediated by the release of PGE2.

Animals↗
PubMed1996

Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer.

Several DNA-based Sindbis virus vectors were constructed to investigate the feasibility and potential applications for initiating the virus life cycle in cells transfected directly with plasmid DNA. These vectors, when transfected into mammalian cells, have been used to produce virus, to express heterologous genes, and to produce infectious vector particles. This approach involved the conversion of a self-replicating vector RNA (replicon) into a layered DNA-based expression system. The first layer includes a eukaryotic RNA polymerase II expression cassette that initiates nuclear transcription of an RNA which corresponds to the Sindbis virus vector replicon. Following transport of this RNA from the nucleus to the cytoplasm, the second layer, autocatalytic amplification of the vector, proceeds according to the Sindbis virus replication cycle and results in expression of the heterologous gene. The Sindbis virus DNA vectors expressed reporter genes in transfected cells at levels that were comparable to those of in vitro-transcribed RNA replicons and were approximately 10-fold higher than the levels produced by conventional RNA polymerase II-dependent plasmids in which the promoter and reporter gene were linked directly. Reporter gene expression was also observed in rodent muscle following injection with Sindbis virus DNA vectors. In a second application, packaged vector particles were produced in cells cotransfected with complementing replicon and defective helper DNAs. The Sindbis virus-derived DNA vectors described here increase the utility of alphavirus-based vector systems in general and also provide a vector with broad potential applications for genetic immunization.

Animals↗
PubMed1996

Phase II study of paclitaxel in patients with recurrent malignant glioma.

PURPOSE: To assess the efficacy and toxicity of paclitaxel administered as a 3-hour infusion to patients with recurrent malignant glioma. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma following radiation therapy, who had received no more than one prior chemotherapy regimen and who had a Karnofsky performance status (KPS) > or = 60, were treated with a 3-hour infusion of paclitaxel every 3 weeks. The initial dose was 210 mg/m2; dose escalation to 240 mg/m2 was allowed. Tumor response was assessed at 6-week intervals using radiographic and clinical criteria. Treatment was continued until documented tumor progression or a total of 12 paclitaxel infusions. RESULTS: Of 41 eligible patients, all were assessable for treatment toxicity and 40 (98%) were assessable for response. The response rate (disease stabilization or better) was 35%. Twenty-nine patients (71%) underwent dose escalation to 240 mg/m2 without the use of growth factors. Toxicities included alopecia (98%), nausea (22%), arthralgias (32%), CNS toxicity (24%), peripheral neuropathy (15%), cardiac toxicity (7%), and myelosuppression (10% grade 3 or 4 hematologic toxicity). No patient developed febrile neutropenia. There was one allergic reaction (2%). CONCLUSION: Paclitaxel is well tolerated at this dose schedule in patients with recurrent malignant glioma, and affords a modest response rate. Because minimal myelotoxicity was encountered in our patients, a dose-escalating phase I/II study of paclitaxel is planned to determine the maximal-tolerated dose (MTD).

Adult↗
PubMed1996

Radiation response and survival time in patients with glioblastoma multiforme.

The determine the value of radiographically assessed response to radiation therapy as a predictor of survival in patients with glioblastoma multiforme (GBM), the authors studied a cohort of 301 patients who were initially treated according to uniform clinical protocols. All patients had newly diagnosed supratentorial GBM and underwent the maximum safe resection followed by external- beam radiation treatment (60 Gy in standard daily fractions or 70.4 Gy in twice-daily fractions of 160 cGy). The radiation response and survival rates were assessable in 222 patients. The extent of resection and the immediate response to radiation therapy were highly correlated with survival, both in a univariate analysis and after correction for age and Karnofsky performance scale (KPS) score in a multivariate Cox model (p< 0.001 for radiation response and p=0.04 for extent of resection). A subgroup analysis suggested that neuroimaging obtained within 3 days after surgery served as a better baseline for assessment of radiation response than images obtained later. Imaging obtained within 3 days after completion of a course of radiation therapy also provided valid radiation response scores. The impact of the radiographically assessed radiation response on survival time was comparable to that of age or KPS score. This information is easily obtained early in the course of the disease, may be of value for individual patients, and may also have implications for the design and analysis of trials of adjuvant therapy for GBM, including volume-dependent therapies such as radiosurgery or brachytherapy.

Adolescent↗
PubMed1995

Carboplatin hypersensitivity in children. A report of five patients with brain tumors.

BACKGROUND: Carboplatin, which is used in the treatment of several childhood tumors, increasingly has been reported to cause hypersensitivity reactions, the majority reported in adults. Five cases of children with primary brain tumors who were treated with carboplatin and developed acute allergic reactions are presented. METHODS: The clinical history of each patient is described, as is the schedule, cumulative dose, and number of infusions of carboplatin, type of reaction, and retreatment. RESULTS: Four of the five patients had histologically proven low grade astrocytic tumors; three had juvenile pilocytic astrocytomas, and one had a mixed oligoastrocytoma. One patient with neurofibromatosis type I had radiographically-defined bilateral optic nerve gliomas. Three patients had prior chemotherapy, one with cisplatin. All five patients developed hypersensitivity reactions such as urticaria, facial erythema, and facial swelling after multiple infusions of carboplatin. Two were retreated with carboplatin after receiving antihistamines, but still developed a reaction. Carboplatin therapy was discontinued in all patients. CONCLUSION: The purpose of this report is to heighten awareness of this potentially serious complication of carboplatin in children so that potentially dangerous retreatment is avoided. As use of a weekly schedule of carboplatin in children with low grade gliomas increases, with planned therapy extending for more than 50 weeks, more hypersensitivity reactions are anticipated.

Adolescent↗
PubMed1995

In vitro transformation of rabbit cytotrophoblast cells into syncytiotrophoblast: stimulation of hormone secretion by progesterone and dibutyryl cyclic 3',5'-adenosine monophosphate.

Rabbit placenta syncytiotrophoblast cells exhibit immunostaining for the hormone relaxin. The objectives of this study were to evaluate the ability of cultured rabbit trophoblast cells to secrete immunoreactive (IR) relaxin and then to study the effects of progesterone, which is essential for maintenance of the placenta and of pregnancy in the rabbit, on that secretion. On Day 1, both treated and untreated trophoblast cell cultures consisted of 90% relaxin-negative mononuclear cells (cytotrophoblast and fibroblast) and 10% relaxin-positive multinuclear cells (syncytiotrophoblast). Media from untreated cultures, collected throughout 9 days of culture, contained low but constant levels of relaxin. Electron microscopy studies indicated that relaxin was localized in dense granules of the multinuclear cells and that these cells formed by fusion of mononuclear cytotrophoblast. Progesterone treatment (40 and 80 ng/ml) increased (p < 0.0001) media concentrations of relaxin, increased the number of desmosomes between cytotrophoblast cells (12 vs. 4 for controls on Day 5), and increased the percentage of multinuclear cells (73% of the cell population vs. 20% for controls on Day 7). Specificity of the progesterone effect was evaluated by treatment of cultures with dibutyryl cAMP (dbcAMP), insulin, hCG, estradiol-17 beta, prostaglandin E2, and prostaglandin F2 alpha. Only dbcAMP (2 mM and 4 mM) produced an increase (p < 0.0001) in media concentrations of relaxin. These results indicate that, like the intact placenta, cultured cytotrophoblast cells fuse to form syncytiotrophoblast and that the latter contain IR relaxin.

Animals↗
PubMed1995

Chemotherapy for gliomas.

Despite advances in surgical and radiation therapy techniques, the prognosis of patients with malignant gliomas remains poor. Few agents have been developed specifically for brain tumors, and the nitrosoureas remain the most active antitumor agents available. In this paper we review the chemotherapeutic and chemoradiation protocols currently being used to treat primary and recurrent gliomas in adults.

Adult↗
PubMed1995

Simultaneous differential scanning calorimetry, X-ray diffraction and FTIR spectrometry in studies of ovalbumin denaturation.

The new application of differential scanning calorimetry (DSC) and the susceptibility of ovalbumin to alpha-chymotrypsin gave a quantitative estimation of protein denaturation in solid ovalbumin. Solid ovalbumin in granules with 11% of water was heated at 100 degrees C in closed and nonclosed ampules. In order to compare effects of size and crystal structure, two proteins (bovine albumin and gamma-globulin) were examined at similar conditions for the extent of denaturation. Ovalbumin and bovine albumin showed similar extents of denaturation, but gamma-globulin, with a very different molecular mass, showed the maximal conformational changes. The enthalpy of denaturation was measured to elucidate the conformational changes in solid proteins. Its value was used for calculation of the degree of denaturation. The thermodynamic data associated with transition were calculated and the number of bonds broken during denaturation was determined. Intrinsic fluorescence was utilized in order to compare these two methods. Moreover, X-ray diffraction and FTIR spectrometry were applied to native and denatured proteins.

Calorimetry, Differential Scanning↗