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S M Chang

Publications and source records attributed to S M Chang.

At least 19 recordsLinked to original sources
PubMed2000

LNCaP progression model of human prostate cancer: androgen-independence and osseous metastasis.

BACKGROUND: Clinically, the lethal phenotypes of human prostate cancer are characterized by their progression to androgen-independence and their propensity to form osseous metastases. We reported previously on the establishment of androgen-independent (AI) human prostate cancer cell lines derived from androgen-dependent (AD) LNCaP cells, with androgen independence defined as the capability of prostate cancer cells to grow in castrated hosts. One of the sublines, C4-2, was found to be AI, highly tumorigenic, and metastatic, having a proclivity for metastasis to the bone. METHODS: We established the AI and bone metastatic cell sublines B2, B3, B4, and B5 from the parental C4-2 subline, using a previously established coinoculating procedure. We determined the biologic behavior of the parental and derivative LNCaP sublines in vivo and in vitro, as well as their molecular and cytogenetic characteristics. RESULTS: Unlike other human prostate cancer models, the LNCaP progression model shares remarkable similarities with human prostate cancer. We observed a comparable pattern of metastasis from the primary to the lymph node and to the axial skeleton, with a predominant phenotype of osteoblastic reaction; 25-37.5% of the animals developed paraplegia. Cytogenetic and biochemical characterizations of LNCaP sublines also indicate close similarities between human prostate cancer and the LNCaP progression model. Additional chromosomal changes were detected in B2-B5 sublines derived from C4-2 bone metastases. These LNCaP sublines were found to grow faster under anchorage-dependent but not -independent conditions. The in vitro invasion and in vivo metastatic potential of these LNCaP sublines surprisingly correlated with anchorage-dependent and not -independent growth. The derivative LNCaP sublines when cultured in vitro produced a substantially higher (20-30-fold) amount of basal steady-state concentrations of PSA than that of the parental LNCaP cells. PSA production was high initially, but was markedly reduced when the derivative cell lines were inoculated and allowed to grow long-term in vivo for the establishment of tumors and metastasis, suggesting that unknown host factors derived either from the prostate or the bone can effectively downregulate PSA expression by prostate tumor epithelium. CONCLUSIONS: The LNCaP model of human prostate cancer progression will help improve our understanding of the mechanisms of androgen-independence and osseous metastasis, and tumor-host determinants of PSA expression.

Animals↗
PubMed2000

Solid-phase microextraction for determining the distribution of sixteen US Environmental Protection Agency polycyclic aromatic hydrocarbons in water samples.

A solid-phase microextraction (SPME) procedure has been developed for the determination of 16 US Environmental Protection Agency promulgated polycyclic aromatic hydrocarbons (PAHs). Five kinds of SPME fibers were used and compared in this study. The extracted sample was analyzed by gas chromatography with flame ionization detection or mass spectrometry. Parameters affecting the sorption of analyte into the fibers, including sampling time, thickness of the fiber coating, and the effect of temperature, have been examined. Moreover, the feasibility of headspace SPME with different working temperatures was evaluated. The method was also applied to real samples. The 85-microm polyacrylate (PA) and 100-microm poly(dimethylsiloxane) (PDMS) fibers were shown to have the highest affinities for the selected PAHs. The PA fiber was more suitable than the PDMS fiber for the determination of low-ring PAHs while high sensitivity of high-ring PAHs was observed when a 100-microm PDMS fiber was used. The method showed good linearity between 0.1 and 100 ng/ml with regression coefficients ranging from 0.94 to 0.999. The reproducibility of the measurements between fibers was found to be very good. The precisions of PA and PDMS fibers were from 3 to 24% and from 3 to 14%, respectively. Headspace SPME is a valid alternative for the determination of two- to five-ring PAHs. A working temperature of 60 degrees C provides significant enhancement in sensitivity of two- to five-ring PAHs having low vapor pressures (>10(-6) mmHg at 25 degrees C) (1 mmHg = 133.3 Pa) and low Henry's constants (>10 atm ml/mol) (1 atm = 1.01 x 10(5) Pa).

Chromatography, Gas↗
PubMed2000

Relationship between electron donor and microorganism on the dechlorination of carbon tetrachloride by an anaerobic enrichment culture.

An investigation involving the supplement of different concentrations of substrates and microorganisms was carried out under anaerobic condition to assess the feasibility of bioremediation of carbon tetrachloride (CCl4) with the amendment of low concentrations of auxiliary substrate and microorganisms. The concentrations of substrate and microorganisms ranged from 10 to 100 mg/l and from 3.7 x 10(4) to 3.7 x 10(6) cell/ml, respectively. The biotransformation rate of CCl4 increased progressively with the increase in the concentrations of the substrate and microorganisms. In the low biomass-amended system (3.7 x 10(4) cells/ml), 28-71% and 57-96% of CCl4 removals were exhibited when 10-100 mg/l of acetate or glucose was supplemented, respectively, whereas nearly complete degradation of CCl4 was observed in the heavily inoculated systems (3.7 x 10(6) cells/ml). An addition of electron donor in the low microbial activity batches enhanced greater efficiency in dechlorination than in the high microbial activity batches. The second-order rate constants ranged from 0.0059 to 0.0092 l/mg/day in high biomass input system, while a two- to four-fold increase in rate constant was obtained in the low microbial activity system. This study indicates that biomass was the more important environmental parameter than substrate affecting the fate of CCl4. The addition of auxiliary substrates was effective only in low biomass-amended batches (0.56 mg-VSS/l) and diminished inversely with the increase of microbial concentration.

Acetates↗
PubMed2000

Effects of growth restriction in early childhood on growth, IQ, and cognition at age 11 to 12 years and the benefits of nutritional supplementation and psychosocial stimulation.

OBJECTIVES: (1) To determine whether benefits to growth and cognition remain after intervention in growth-restricted children who received psychosocial stimulation and nutritional supplementation in early childhood. (2) To investigate the extent of the differences in IQ and cognition at age 11 to 12 years between growth-restricted and non-growth-restricted children. STUDY DESIGN: Growth-restricted and non-growth-restricted children were identified at age 9 to 24 months, at which time the growth-restricted children participated in a 2-year randomized trial of nutritional supplementation and psychosocial stimulation. Eight years after the interventions ended, the children's growth, IQ, and cognitive functions were measured. RESULTS: There were no significant benefits from supplementation to growth or cognition. Children who had received stimulation had higher scores on the Weschler Intelligence Scales for Children-Revised full-scale (IQ) and verbal scale and tests of vocabulary and reasoning (all P <.05). The growth-restricted children had significantly lower scores than the non-growth-restricted children on 10 of 11 cognitive tests. CONCLUSIONS: Psychosocial stimulation had small but significant long-term benefits on cognition in growth-restricted children. Growth-restricted children had significantly poorer performance than non-growth-restricted children on a wide range of cognitive tests, supporting the conclusion that growth restriction has long-term functional consequences.

Child↗
PubMed2000

Comparison of relative cerebral blood volume and proton spectroscopy in patients with treated gliomas.

BACKGROUND AND PURPOSE: Elevated relative regional cerebral blood volume (rCBV) reflects the increased microvascularity that is associated with brain tumors. The purpose of this study was to investigate the potential role of rCBV in the determination of recurrent/residual disease in patients with treated gliomas. METHODS: Thirty-one rCBV studies were performed in 19 patients with treated gliomas. All patients also had proton MR spectroscopy and conventional MR imaging. Regions of abnormality were identified on conventional MR images by two neuroradiologists and compared with rCBV and MR spectroscopic data. Metabolites and rCBV were quantified and compared in abnormal regions. RESULTS: In high-grade tumors, rCBV values were proportional to choline in regions of tumor and nonviable tissue. Although the presence of residual/recurrent disease was often ambiguous on conventional MR images, the rCBV maps indicated regions of elevated vascularity in all low-grade tumors and in 12 of 17 grade IV lesions. Regions of elevated and low rCBV corresponded well with spectra, indicating tumor and nonviable tissue, respectively. CONCLUSION: This study suggests that rCBV maps and MR spectroscopy are complementary techniques that may improve the detection of residual/recurrent tumor in patients with treated gliomas. Compared with the spectra, the rCBV maps may better reflect the heterogeneity of the tumor regions because of their higher resolution. The multiple markers of MR spectroscopy enable better discrimination between normal and abnormal tissue than do the rCBV maps.

Adult↗
PubMed1999

Stable alphavirus packaging cell lines for Sindbis virus and Semliki Forest virus-derived vectors.

Alphavirus vectors are being developed for possible human vaccine and gene therapy applications. We have sought to advance this field by devising DNA-based vectors and approaches for the production of recombinant vector particles. In this work, we generated a panel of alphavirus vector packaging cell lines (PCLs). These cell lines were stably transformed with expression cassettes that constitutively produced RNA transcripts encoding the Sindbis virus structural proteins under the regulation of their native subgenomic RNA promoter. As such, translation of the structural proteins was highly inducible and was detected only after synthesis of an authentic subgenomic mRNA by the vector-encoded replicase proteins. Efficient production of biologically active vector particles occurred after introduction of Sindbis virus vectors into the PCLs. In one configuration, the capsid and envelope glycoproteins were separated into distinct cassettes, resulting in vector packaging levels of 10(7) infectious units/ml, but reducing the generation of contaminating replication-competent virus below the limit of detection. Vector particle seed stocks could be amplified after low multiplicity of infection of PCLs, again without generating replication-competent virus, suggesting utility for production of large-scale vector preparations. Furthermore, both Sindbis virus-based and Semliki Forest virus-based vectors could be packaged with similar efficiency, indicating the possibility of developing a single PCL for use with multiple alphavirus-derived vectors.

Alphavirus↗
PubMed1999

Nongenomic steroidal modulation of high-affinity serotonin transport.

The ability of steroids to modulate high-affinity 5-HT transport was investigated using cell-based models which stably manifest all known properties of this transport system. beta-Estradiol (E2) exhibited noncompetitive, and possibly allosteric, inhibition of both radiolabeled serotonin ([3H]5-HT) transport by, and radiolabeled cocaine congener ([3H]CFT) binding to, this system. Such inhibitory effects were observed within short time courses and unlikely to result from genomic effects normally ascribed to estrogen action. Rather, such nongenomic effects on 5-HT uptake were more akin to modulatory effects of select steroid metabolites on other plasma membrane systems such as neurotransmitter receptors and ionic channels. Beyond E2, preliminary examination of other steroid metabolites and synthetic steroid receptor agonists/antagonists revealed that inhibition of 5-HT transport is additionally attributable only to estriol (E3, an E2 metabolite) and tamoxifen (a nonsteroidal, E2 receptor antagonist). These findings indicate that the present form of transport modulation is only rendered by select compounds and not a general property of steroidal and related agents. Assessments of covalent conjugates of E2 suggested that E2 interacts with the transporter protein at allosteric site(s) inaccessible from the extracellular domain. These findings collectively suggest that steroid-mediated regulation of 5-HT transport may be a physiologically relevant mechanism, and that antidepressant as well as psychostimulant effects in vivo may contain a steroidal component.

Animals↗
PubMed1999

Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: results of a Phase II study.

PURPOSE: To report the results of a Phase II study of hyperfractionated craniospinal radiation therapy, with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs) and malignant ependymomas. METHODS AND MATERIALS: Newly diagnosed PNET or malignant ependymomas were treated with hyperfractionated craniospinal radiation therapy. The primary tumor site was treated to a dose of 72 Gy, with 30 Gy given to the rest of the craniospinal axis. The fraction size was 1.0 Gy, given twice a day. Patients with poor risk factors also received adjuvant chemotherapy with CCNU, cisplatin, and vincristine. Patients had follow-up for survival, time to tumor progression, and patterns of relapse. RESULTS: A total of 39 patients (21 males/18 females) were treated between March 12, 1990 and October 29, 1992. The median age was 16 years (range 3-59 years). Tumor types included 25 medulloblastomas, 5 pineoblastomas, 5 cerebral PNETs, 1 spinal cord PNET, and 3 malignant ependymomas. Twenty cases were staged as poor-risk and received adjuvant chemotherapy following radiation. Three-year progression-free survival (PFS) was 60% and 63% for poor-risk and good-risk patients, respectively. Overall 3-year survival for these groups was 70% and 79%, respectively. For the 25 patients with medulloblastoma, there were 16 good-risk and 9 poor-risk patients. Three-year PFSs were 63% and 56%, respectively. The 5-year survival for good-risk medulloblastoma was 69% with 43.7% of these patients having failures outside the primary site. CONCLUSIONS: Survival in patients with good-risk medulloblastoma was no better than that seen in previous studies with single-fraction radiation, and the rate of failure outside the primary site is excessive. Those with poor-risk features had comparable survival to that seen in patients with good risk factors, but these patients were treated with chemotherapy, and the role that hyperfractionated radiation played in their outcome is uncertain.

Adolescent↗
PubMed1999

B-chain sequence and in situ hybridization of the rabbit placental relaxin-like gene product.

We reported that the nucleotide sequence of a cDNA generated from rabbit placental poly(A)(+) RNA using porcine preprorelaxin primers was identical to SQ10, a product of squamous differentiated tracheal epithelial cells. However, these results did not confirm that SQ10 was the biologically active rabbit relaxin that had been isolated previously yet not sequenced. In this study, a 7-kDa protein isolated from rabbit placentas exhibited relaxin bioactivity and cross-reacted with a porcine relaxin antiserum. A partial amino acid sequence of this protein revealed a sequence identical to that of SQ10. Although the amino acid sequence of the putative relaxin receptor-binding domain found in the B chain of relaxin was modified in SQ10 from CGRDYVR to CRNDFVR, the placental protein was bioactive. These results suggest that SQ10 is the rabbit relaxin. In situ hybridization, using an SQ10 riboprobe, indicated radiolabeling in the syncytiotrophoblast cells of the rabbit placenta. The pattern of labeling corresponded with the immunohistochemical staining for relaxin observed with use of a porcine relaxin antiserum. These results indicate that the syncytiotrophoblast cells are a site of synthesis for SQ10 and that the immunostaining is not solely the result of sequestering SQ10 through receptor-mediated endocytosis. A potential role for relaxin in implantation is discussed.

Amino Acid Sequence↗
PubMed1999

Phase II study of phenylacetate in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report.

PURPOSE: To determine the response rate, time to treatment failure, and toxicity of phenylacetate in patients with recurrent malignant glioma and to identify plasma concentrations achieved during repeated continuous infusion of this agent. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma were treated with phenylacetate. The schedule consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off). A starting dose of 400 mg/kg total body weight per day of phenylacetate was initially used and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient dose escalations were allowed to a maximum of 450 mg/kg ideal body weight/d. Tumor response was assessed every 8 weeks. The National Cancer Institute common toxicity criteria were used to assess toxicity. Plasma concentrations achieved during the patients' first two 14-day infusions were assessed. RESULTS: Forty-three patients were enrolled between December 1994 and December 1996. Of these, 40 patients were assessable for toxicity and response to therapy. Reversible symptoms of fatigue and somnolence were the primary toxicities, with only mild hematologic toxicity. Thirty (75%) of the 40 patients failed treatment within 2 months, seven (17.5%) had stable disease, and three (7.5%) had a response defined as more than 50% reduction in the tumor. Median time to treatment failure was 2 months. Thirty-five patients have died, with a median survival of 8 months. Pharmacokinetic data for this dose schedule showed no difference in the mean plasma concentrations of phenylacetate between weeks 1 and 2 or between weeks 5 and 6. CONCLUSION: Phenylacetate has little activity at this dose schedule in patients with recurrent malignant glioma. Further studies with this drug would necessitate an evaluation of a different dose schedule.

Adult↗
PubMed1999

Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.

PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.

Adult↗
PubMed1999

The role of paclitaxel in the treatment of primary and metastatic brain tumors.

The rationale for the use of paclitaxel to treat brain tumors includes impressive activity in a wide array of chemotherapy-resistant solid tumors, in vitro and in vivo evidence of cytotoxicity against primary brain tumors, and a paucity of effective alternative agents. A review of published studies evaluating paclitaxel alone or in combination with other chemotherapeutic agents suggests that paclitaxel alone is not highly active against newly diagnosed or recurrent glioblastoma multiforme. However, additional prospective trials are warranted to evaluate the efficacy of paclitaxel plus conventional cranial irradiation or stereotactic radiosurgery. Single-agent paclitaxel appears to be active against gliomas with an oligodendroglial component and may prove useful both as a component of initial therapy and for recurrent disease. Activity against anaplastic gliomas and brain metastases also should be explored. With radiation, a weekly paclitaxel administration schedule is particularly appealing from pharmacologic, safety, and dose-intensity perspectives. In addition, the dose of paclitaxel must be increased in patients who are concurrently receiving medications that induce the P-450 drug metabolizing system. Primary and metastatic brain tumors constitute a very difficult problem in oncology. Future investigations should be directed at evaluating paclitaxel-based chemotherapy regimens in selected brain tumor types, combining paclitaxel with stereotactic radiosurgery, and determining the importance of other proposed mechanisms of action of paclitaxel (eg, inhibition of angiogenesis and tumor invasion).

Antineoplastic Agents, Phytogenic↗
PubMed1999

Term pregnancy in a noncommunicating rudimentary horn of an unicornuate uterus: a case report.

A case of full-term pregnancy in the noncommunicating rudimentary horn of unicornuate uterus is presented. A healthy female infant weighing 2,985 g was delivered by cesarean section at 37 weeks' gestation. The diagnosis was missed by prenatal ultrasonography and was made only at laparotomy. A retrospective analysis of our ultrasound studies revealed that the echo pattern of the nongravid uterus resembled a soft pelvic mass. Color Doppler imaging revealed prominent low-impedance uterine arcuate-radial arterial blood flow surrounding the periphery of the pelvic mass, as well as multiple areas of placental implantation with a pulsatile lacunar flow pattern. A high index of suspicion of rudimentary horn pregnancy should be borne in mind whenever late-pregnancy ultrasonography shows the above-mentioned characteristic ultrasonic findings.

Adult↗
PubMed1999

The nutritional status of rural Jamaican school children.

Three thousand, eight hundred and eighty-two (3,882) children in grades 2-5, attending 16 rural primary and all-age schools in central Jamaica were weighed and their weight-for-age standard deviation scores calculated using the World Health Organization/National Center for Health Statistics (WHO/NCHS) references. Heights were also measured in a random sample of the grade 5 children (n = 793) and height-for-age and body mass index (BMI-kg/m2) calculated. Sixty-nine per cent of the total sample were of normal weight-for-age, 2% were moderately undernourished (weight-for-age > -3 Z-score, < or = -2 Z-score), and a further 24% mildly undernourished (weight-for-age > -2 Z-score, < or = -1 Z-score). Few children were overweight. The frequency distribution of weight-for-age was similar in girls and boys. In the subsample of children in whom heights were measured, 25.8% were < or = -1 Z-score height-for-age, and of these 4.9% were < -2 Z-score. Compared with a survey conducted in a similar rural area in the 1960s, the children's mean weights for age group categories were 1.1 to 3.7 kg heavier. Children who were older than appropriate for their grade were more likely to be undernourished (Odds ratio 3.94, 95% CI 3.21, 4.83), which suggests that undernourished children may be more likely to repeat a grade or start school later.

Body Constitution↗
PubMed1998

Possible existence of quaternary structure in the high-affinity serotonin transport complex.

Deletion-mutants of the cloned mouse serotonin transporter (SERT) rendered dominant negative-mutant effects upon wild-type transporter activities in heterologous expression studies; such effects were transporter-selective and did not influence the activities of co-expressed neuronal GABA transporter. Heterologous expression of linear concatenates (up to four copies) of SERT further revealed discernable uptake activities for both transporter-dimer and -tetramer, but not for the trimer. Kinetic and pharmacological analyses revealed that the monomer, dimer, and tetramer manifested comparable transport Km and potencies for known serotonin uptake inhibitors; the tetramer was distinct from the others only in manifesting notably reduced transport Vmax. Surprisingly, equivalent cocaine congener-binding activities were observed for all concatenates, including the functionally inactive trimer. These findings collectively support the existence of quaternary structure in the active 5-HT transport complex; such structure is likely to be a critical determinant of ligand transport activities, but apparently not of transporter-inhibitor interactions.

Animals↗
PubMed1998

Genetic immunization of chimpanzees chronically infected with the hepatitis B virus, using a recombinant retroviral vector encoding the hepatitis B virus core antigen.

Cytotoxic T lymphocyte (CTL) activity and CD4+ helper T cell responses to the hepatitis B virus (HBV) core antigen (HBcAg) have been implicated in clearance of acute and chronic HBV infections. We showed that intramuscular injections of a novel recombinant retroviral vector expressing an HBcAg-neomycin phosphotransferase II (HBc-NEO) fusion protein induces HBc/eAg-specific antibodies and CD4+ and CD8+ T cell responses in mice and rhesus monkeys. We have now immunized three chronically infected chimpanzees, each with 10(10) CFU of nonreplicating retroviral vector particles expressing the HBc-NEO fusion protein. Of two immunized chimpanzees examined for CTL responses, one developed HBcAg-specific CTLs and showed marginal, transient elevations of alanine aminotransferase (ALT) levels following injection. However, both chimpanzees remained positive for serum HBeAg, negative for anti-HBe antibody by conventional assays, and displayed no change in HBV viral load throughout the study. In contrast, the third chimpanzee exhibited a traditional seroconversion evidenced by a loss of serum HBeAg and the subsequent emergence of anti-HBe antibodies within 24 weeks after the first injection. Simultaneously, two transient ALT flares and a significant decrease in the serum HBV DNA levels were noted. Despite its limitations, the present study demonstrates (1) the safety of treatment with high titers of retroviral vector in chimpanzees, (2) the capability of a retroviral vector expressing HBcAg to stimulate immune responses in HBV chronic carrier chimpanzees, and (3) that retroviral vector immunization may be therapeutically beneficial in the treatment of chronic HBV infection.

Amino Acid Sequence↗