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Biomedical subjects

W C Lin

Publications and source records attributed to W C Lin.

At least 55 records · Page 3Linked to original sources

Combination chemotherapy with tamoxifen, ifosfamide, epirubicin and cisplatin in extensive-disease small-cell lung cancer.

BACKGROUND: A study of tamoxifen, ifosfamide, epirubicin and cisplatin (TIEP) chemotherapy was conducted in patients with extensive-disease, small-cell lung cancer (SCLC) to assess response and toxicity. METHODS: From November, 1997, to February, 1999, 11 patients were treated, including six chemo-naïve patients and five patients previously treated with cisplatin plus etoposide (EP). The treatment regimen included tamoxifen 60 mg twice daily orally on days 1 to 3, ifosfamide 3 g/m2 intravenous (i.v.) infusion for 60 minutes with mesna on day 2, epirubicin 50 mg/m2 i.v. bolus on day 2 and cisplatin 60 mg/m2 i.v. for 60 minutes on day 2, every 4 weeks for up to six cycles. RESULTS: All patients were evaluated for toxicity and response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 leukopenia or neutropenia occurred in all patients during treatment. Two patients (18.2%) experienced fever in association with the neutropenia, one of whom died of sepsis. Grade 3 anemia occurred in two patients (18.2%) during treatment. Toxicities other than neutropenia and anemia were limited. After two cycles of treatment, five of six chemo-naïve patients (83%), and one of five previously treated patients (20%) attained a partial response (overall 54.5%, 95% confidence interval 25%-83.9%). Median survival time was 8.5 and 6 months in chemo-naïve and previously EP-treated patients, respectively. The response rate and median survival time in chemo-naïve patients did not improve compared with a previous study of ifosfamide plus etoposide undertaken 4 years earlier. CONCLUSIONS: Although TIEP is an active combination regimen with an acceptable toxicity profile in Chinese patients with extensive-disease SCLC, it showed no remarkable benefit compared with other regimens used in chemo-naïve patients. The 20% response rate and median survival of 6 months in EP-treated patients deserve further study.

Adolescent↗

Familial breast cancer in southern Taiwan.

The purpose of this study is to evaluate whether there are pathobiologic differences and differences in overall rates survival between familial and non-familial breast cancer patients in Taiwan. A retrospective study was performed evaluating 76 familial breast cancer patients in 69 families, which included two BRCA1 related cases and six BRCA2 related cases. Patients were compared with 425 non-familial sporadic cases. Familial breast cancer patients had similar ages and stages as non-familial patients (mean, 46.6 years vs 48.9 years, p = 0.306). However, the familial breast cancer patients with BRCA1 and BRCA2 related cases presented at lower stages (p = 0.034) and younger ages than non-familial patients (mean, 45.1 years vs 48.9 years P = 0.042). The occurrence of infiltrating ductal carcinoma and lobular carcinoma in situ was not significantly different in the two groups. Mucinous carcinoma was represented with 6.7% (4/76) and 1.3% (1/76) medullary carcinoma. The overall grade of familial breast cancer, including BRCA1 and BRCA2 related cases in 8 infiltrating ductal carcinoma, was significantly higher than that of controls. The mean follow up was 4.5 years for familial breast cancers. Five- and 10-year overall survival rates were 69% and 61% for those with a family history, compared with 86% and 64% for those in the control group (p = 0.644). There were no statistically significant differences in disease-free survival rates between the two groups at 5 or 10 years (69% vs 78% in 5 years; 48% vs 58% in 10 years) (p = 0.862). Despite the younger ages and earlier stages at presentation in familial breast cancer patients with BRCA1 and BRCA2 related cases, the familial breast cancer patients had higher grade patholobiologic characteristics, but similar prognoses when compared with sporadic breast cancer patients. Owing to the limited number of familial cases in this study, more cases and longer follow up are needed.

BRCA2 Protein↗

Fractal geometry in urodynamics of lower urinary tract.

The physiological signals are usually extremely complicated and difficult to analyze. Recently, investigators have tried the fractal dimension that can characterize roughness and self-similarity of them. It turns out that it is also suitable for obtaining the modalities of lower urinary tract during normal micturition. In this investigation, the external urethral sphincter electromyogram (EUS EMG) and the cystometrogram (CMG) of the Wistar rats under both room temperature and cold water stimulation of the bladder are studied. The modified relative differential box-counting (RDBC) method is used to calculate the fractal dimensions of EMG and CMG time series. According to the experimental results, the modalities of micturition for the Wistar rats can be characterized as normal if both the fractal dimensions of EMG and CMG are of low values during voiding. Furthermore, the technique is validated in identifying the dyssynergia of the bladder and EUS under cold water stimulation.

Animals↗

The status of the do-not-resuscitate order in Chinese clinical trial patients in a cancer centre.

OBJECTIVE: To report and analyse the pattern of end-of-life decision making for terminal Chinese cancer patients. DESIGN: Retrospective descriptive study. SETTING: A cancer clinical trials unit in a large teaching hospital. PATIENTS: From April 1992 to August 1997, 177 consecutive deaths of cancer clinical trial patients were studied. MAIN MEASUREMENT: Basic demographic data, patient status at the time of signing a DNR consent, or at the moment of returning home to die are documented, and circumstances surrounding these events evaluated. RESULTS: DNR orders were written for 64.4% of patients. Patients in pain (odds ratio 0.45, 95% CI 0.22-0.89), especially if requiring opioid analgesia (odds ratio 0.40, 95% CI 0.21-0.77), were factors associated with a higher probability of such an order. Thirty-five patients were taken home to die, a more likely occurrence if the patient was over 75 years (odds ratio 0.12, 95% CI 0.04-0.34), had children (odds ratio 0.14, 95% CI 0.02-0.79), had Taiwanese as a first language (odds ratio 6.74, 95% CI 3.04-14.93), or was unable to intake orally (odds ratio 2.73, 95% CI 1.26-5.92). CPR was performed in 30 patients, none survived to discharge. CONCLUSIONS: DNR orders are instituted in a large proportion of dying Chinese cancer patients in a cancer centre, however, the order is seldom signed by the patient personally. This study also illustrates that as many as 20% of dying patients are taken home to die, in accordance with local custom.

Adult↗

A space-time delay neural network for motion recognition and its application to lipreading.

Motion recognition has received increasing attention in recent years owing to heightened demand for computer vision in many domains, including the surveillance system, multimodal human computer interface, and traffic control system. Most conventional approaches classify the motion recognition task into partial feature extraction and time-domain recognition subtasks. However, the information of motion resides in the space-time domain instead of the time domain or space domain independently, implying that fusing the feature extraction and classification in the space and time domains into a single framework is preferred. Based on this notion, this work presents a novel Space-Time Delay Neural Network (STDNN) capable of handling the space-time dynamic information for motion recognition. The STDNN is unified structure, in which the low-level spatiotemporal feature extraction and high-level space-time-domain recognition are fused. The proposed network possesses the spatiotemporal shift-invariant recognition ability that is inherited from the time delay neural network (TDNN) and space displacement neural network (SDNN), where TDNN and SDNN are good at temporal and spatial shift-invariant recognition, respectively. In contrast to multilayer perceptron (MLP), TDNN, and SDNN, STDNN is constructed by vector-type nodes and matrix-type links such that the spatiotemporal information can be accurately represented in a neural network. Also evaluated herein is the performance of the proposed STDNN via two experiments. The moving Arabic numerals (MAN) experiment simulates the object's free movement in the space-time domain on image sequences. According to these results, STDNN possesses a good generalization ability with respect to the spatiotemporal shift-invariant recognition. In the lipreading experiment, STDNN recognizes the lip motions based on the inputs of real image sequences. This observation confirms that STDNN yields a better performance than the existing TDNN-based system, particularly in terms of the generalization ability. In addition to the lipreading application, the STDNN can be applied to other problems since no domain-dependent knowledge is used in the experiment.

Algorithms↗

Ameliorative effect of an urinary preparation on acetaminophen and D-galactosamine induced hepatotoxicity in rats.

The effect of oral administration of a preparation of human urine (PHU) on acute liver injury was examined in rats intoxicated with acetaminophen and D-galactosamine. The results indicated that PHU protected the liver from acetaminophen and D-galactosamine-induced injury as judged by morphological and biochemical observation. An increase in lipid peroxide concentrations and decrease in protein concentrations occurred in the liver by D-galactosamine injection, PHU administration significantly prevented these changes.

Acetaminophen↗

Effect of a urinary preparation on liver injury by short-term carbon tetrachloride treatment in rats.

The hepatoprotective effect of a preparation of human urine (PHU) was assessed against short-term carbon tetrachloride (CCl4) treatment in rats. Significant prevention of liver injury by PHU was found after CCl4 treatment, judging by the changes of serum biochemical parameters, and hepatic protein and triglyceride contents. The increased liver lipid peroxidation, and decreased liver vitamin C concentrations observed after CCl4 treatment were significantly prevented by PHU administration. The increase in liver glutathione (GSH) contents observed after CCl4 treatment was further increased by PHU treatment. Liver catalase activity decreased after CCl4 treatment, while liver superoxide dismutase and GSH-peroxidase activities did not change. PHU administration further inhibited the decrease in liver catalase activity after CCl4 treatment. These results indicate that PHU administration can prevent liver injury induced by CCl4 in rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.

Animals↗

Tagged tumor cells reveal regulatory steps during earliest stages of tumor progression and micrometastasis.

Histochemical marker genes were used to "tag" mouse fibrosarcoma or human neuroblastoma cells, providing a better understanding of their subsequent progression and metastasis mechanisms in nude mice. Micrometastases in the lung were initiated from clusters of 2-6 cells rather than single cells in most cases; tumor cells were also visualized binding to the endothelium of small blood vessels to initiate these micrometastases. Shortterm, these mechanisms relied heavily on fluidity of cell surface proteins, rather than nuclear events. Micrometastases in some organs were transient and never became established. Angiogenesis was visualized in both primary tumor systems via "fixation" of the animal's circulation; very small microvessels were growing toward the primary tumor as soon as 48-72 hours post-injection. Marker genes were also valuable for quantitating genetic instability of specific tumor cell populations and potential gene regulatory mechanisms operating in specific organ sites. These latter studies have direct relevance to the significance of N-myc oncogene amplification in neuroblastoma during progression and CD44 gene plasticity of expression in fibrosarcoma during metastasis. Marker gene-tagged single tumor cells can now be analyzed for gene regulatory events in virtually any organ and in combination with laser capture microdissection and other high-resolution methodologies, providing insight into the very earliest gene-regulatory events during micrometastasis.

Animals↗

Post transplant CD8+ gammadelta T-cell lymphoma associated with human herpes virus-6 infection.

Gammadelta T-cell lymphoma is a rare T-cell lymphoproliferative disorder that has been reported in both immunocompetent and immunocompromised persons. This report describes a forty eight year old patient who developed gammadelta T-cell lymphoma four years after undergoing living-related kidney transplantation. The lymphoma expressed CD2, CD3, CD7, CD8 and CD56, and the gammadelta T-cell receptor and did not express CD5, CD4 and the alphabeta T-cell receptor. In addition, HHV-6 was cultured from the patient's bone marrow, marking the first time that this virus has been associated with gammadelta T-cell lymphoma. Since all patients with gammadelta T-cell lymphoma described to date have responded poorly to standard combination chemotherapies, the patient was treated with the purine analogue 2-chlorodeoxyadenosine. While he responded transiently to treatment, long term remission was not achieved indicating that additional therapeutic approches still need to be developed, for the management of this disorder.

Antigens, CD↗

Development of adenoids: a study by measurement with MR images.

Magnetic resonance (MR) imaging, which is able to demonstrate the actual size of adenoids by differentiating them from other soft-tissue structures, can be effectively used to study the normal development of adenoids. To assess the normal development of adenoids and to understand their role in the nasopharyngeal airway compromise, the adenoids of 290 children who had MR examination for other reasons were measured by midsagittal T1-weighted spin-echo MR image. The maximal thickness of adenoids (A), anteroposterior depth of the nasopharynx (N) and the adenoid-nasopharynx (A/N) ratios were obtained using this method. The results showed that of the infants under the age of 3 months only 2 out of 11 adenoids (18%) could be identified. By 4 months of age, adenoids could be identified in 6 of 8 infants (75%). After 5 months of age, all adenoids were well demonstrated by MR imaging. The adenoids developed rapidly during infancy and reached a plateau between 2- and 14 years of age with a mean thickness ranging from 10.7 to 12.2 mm. Finally, the adenoids regressed rapidly after 15 years old. The A/N ratios, which could be used to assess the airway compromise, had a plateau between 2- and 7 years of age. After that, with the steady growth of the nasopharynx, the possible role of adenoid in airway compromise will become increasingly less significant in later childhood.

Adenoids↗

Efficacy of pelvic floor rehabilitation for treatment of genuine stress incontinence.

To assess the clinical efficacy of a pelvic floor rehabilitation (PFR) program for treatment of genuine stress incontinence (GSI), we studied 72 patients with slight to moderate (2-10 g of urine loss per hour) or severe (11-50 g of urine loss per hour) GSI who underwent PFR. Objective and subjective assessments were performed before and 3, 6, 12, 18, and 24 months after the start of treatment. The overall success rate (complete cure or marked improvement in symptoms) was 61% (44/72) at the 2-year follow-up. The number of leakages per 24 hours and urine loss in the 1-hour pad test were significantly reduced, and vaginal muscle strength was significantly increased in successfully-treated patients. Significant changes were also observed in symptoms of micturition frequency and nocturia and in volume at first desire to void during cystometry in the treatment success group. Patient compliance with the exercise program was a significant predictor of success. The success rate during the 2-year follow-up period, estimated according to patient compliance, also differed significantly among groups, with good, moderate, and poor compliance. Patients experienced no serious adverse effects. These results show that the PFR program used in this study is an effective alternative to surgical intervention for the treatment of GSI in selected patients.

Adult↗

tie-1 protein tyrosine kinase: a novel independent prognostic marker for gastric cancer.

Protein tyrosine kinases (PTKs) are a major class of proto-oncogenes that are involved in tumor progression. The purpose of this study was to establish a comprehensive PTK expression profile in gastric cancers, with the objective of identifying possible biomarkers for gastric cancer progression. We have designed degenerate primers according to the consensus catalytic motifs to amplify PTK molecules from gastric cancers by reverse transcriptase-PCR methods. The PTK expression profile was established by sequencing analysis of the cloned PCR products. We have identified 17 PTKs from a gastric adenocarcinoma. Two receptor PTKs, tie-1 and axl, were selected for in situ immunohistochemistry studies because of their higher expression level and their described roles in adhesion, invasion, and angiogenesis. Among the 97 gastric adenocarcinoma tissues examined, we observed positive immunohistochemical staining of tie-1 PTK in 69 and positive staining of axl kinase in 71 tissues. Statistical analysis with clinicopathological features indicates that tie-1 kinase expression is inversely correlated with patients' survival, whereas axl fails to show similar clinical significance. Our results illustrate the utility of tyrosine kinase gene family profiling in human gastric cancers and show that tie-1 tyrosine kinase may serve as a novel independent prognostic marker for gastric adenocarcinoma patients.

Adenocarcinoma↗

Pharmacodynamic and pharmacokinetic studies of anthraquinone 2-carboxylic acid on passive cutaneous anaphylaxis in rats.

The objectives of this study are to describe the inhibitory effect of 9,10-anthraquinone 2-carboxylic acid (AQCA) on IgE-mediated passive cutaneous anaphylaxis (PCA) reaction, and the pharmacokinetics of AQCA. Pharmacodynamic assessments were performed at 0.5, 1 and 2 mg/kg (i.v.) and 5, 10 and 20 mg/kg (p.o) dose levels. In separate groups, pharmacokinetics were assessed at 5 mg/kg (i.v.) and 5, 10, and 20 mg/kg (p.o.) dose levels. Intravenous and oral administration of AQCA inhibited the PCA reaction in rats in a dose-dependent manner. The PCA-inhibitory activity of AQCA (20 mg/kg) lasted more than 12 hrs after oral administration. The oral bio-availability decreased with increasing dosage, from 96% (5 mg/kg) to 81% (10 and 20 mg/kg). The absorption after oral administration was prolonged with Tmax values ranging from 1 to 6 h; while t(1/2) (4.8-16 h) values appeared to be comparable. These results suggest that AQCA has a potent and long acting anti-PCA activity. It is likely to be therapeutically useful in the treatment of asthma.

Administration, Oral↗

2-Phenyl-4-quinolone prevents serotonin-induced increases in endothelial permeability to albumin.

To investigate the role of 2-phenyl-4-quinolone in enhancing endothelial monolayer paracellular barrier function and preventing the disturbance of paracellular barrier function by vasoactive agents, the study examined the effect of 2-phenyl-4-quinolone on serotonin-mediated macromolecule transfer and microfilament changes in cultured rat heart endothelial cells. Serotonin-treated endothelial cells induced concentration-dependent increases in the passage of Evans blue dye-bound bovine serum albumin. Incubation of the endothelial monolayers with 2-phenyl-4-quinolone antagonized serotonin- and cytochalasin B-induced macromolecular permeability. 2-Phenyl-4-quinolone also opposed the effect of serotonin or cytochalasin B on the distribution and quantity of actin filaments in the endothelial cytoskeleton. Furthermore, 2-phenyl-4-quinolone alone led to an apparent quantitative increase in F actin fluorescence in endothelial cells. The addition of 10(-7) M 2-phenyl-4-quinolone had an effect on serotonin-induced changes in the myosin and distribution of myosin were comparable to that on serotonin monolayers. In conclusion, 2-phenyl-4-quinolone attenuated the serotonin-induced permeability of rat heart endothelial cells and this was associated with stabilization of F actin microfilaments and changes in the myosin organization. This result suggests that influences on cytoskeletal assembly may be involved in this process.

Actin Cytoskeleton↗

Decreased protein kinase C activation mediates inhibitory effect of norathyriol on serotonin-mediated endothelial permeability.

We examined the mechanisms of norathyriol on the serotonin-induced increased permeability of rat heart endothelial cell monolayers. The present study showed that the activation of rat heart endothelial cell protein kinase C by phorbol myristate acetate led to the dose-dependent increase in endothelial permeability to albumin, an effect that was inhibited by staurosporine (a protein kinase inhibitor). Staurosporine also attenuated the serotonin-induced increase in permeability. Norathyriol abolished both serotonin- and phorbol myristate acetate-induced permeability. We investigated whether norathyriol, by inhibiting protein kinase C activation, attenuated the serotonin-induced permeability. Immunofluorescence studies demonstrated that norathyriol prevented the redistribution of protein kinase C isozymes following stimulation with serotonin. Western blot analysis showed that norathyriol significantly inhibited the serotonin-induced translocation of the alpha protein kinase C isozyme from the cytosolic to the particulate fraction. In conclusion, norathyriol attenuates the serotonin-induced permeability of rat heart endothelial cells to macromolecules in association with inhibition of protein kinase C activation. This decrease in endothelial cell permeability may be one of the mechanisms for the protective effects of norathyriol against edema formation in response to inflammatory agonists in vivo.

Animals↗

S- and G2-phase cell cycle arrests and apoptosis induced by ganciclovir in murine melanoma cells transduced with herpes simplex virus thymidine kinase.

Mechanism of cell killing by transfer of Herpes simplex virus type-1 thymidine kinase (HSVtk) and subsequent ganciclovir (GCV) treatment was examined in B16F10 murine melanoma model. While parental B16F10 melanoma cells were resistant to GCV at 100 microM or higher, HSVtk-transduced B16F10 melanoma cell clones became susceptible to GCV with IC50 of 0.1 to 0.3 microM. By means of various parameters including characteristic morphological changes, in situ DNA end-labeling, DNA ladder pattern, flow cytometric detection of sub-G1 DNA content, and annexin V binding of inverted cell surface phosphatidylserine, apoptosis was shown to be associated with the cell killing of ganciclovir on HSVtk-transduced melanoma B16F10 cells. Kinetic analysis showed that the signs of apoptosis were observed not until 60 h of continued GCV treatment and preceded first by a rise in p53 protein level in 12 h and then by S-phase/G2-phase cell cycle arrest associated with corresponding increases in the level of cyclin B1 protein but no apparent change in protein level of Bax or Cdc2. These results suggest that apoptosis occurred as a result of ganciclovir-induced cell cycle arrests rather than direct chemical effect on HSVtk-transduced B16F10 melanoma cells.

Animals↗

Molecular analysis of the IL-2 receptor beta chain gene expressed in human tumor cells.

Interleukin-2 (IL-2) is recognized as a T cell growth factor. We have previously reported that human carcinoma cell lines are inhibited in growth by exogenous IL-2, which binds to the IL-2 receptor beta (IL-2Rbeta) chain ubiquitously expressed on the surface of tumor cells. A possibility was considered that IL-2Rbeta on carcinomas responsible for negative signaling was different from that expressed on hematopoietic cells. To investigate this possibility, mRNA for the IL-2Rbeta chain was amplified and compared in carcinoma and lymphoid cells. Using RT-PCR with pairs of sense-antisense oligonucleotide primers specific for the various regions of extracellular, transmembrane and intracellular domains of the IL-2Rbeta chain, we amplified mRNA obtained from three human carcinoma cell lines and human lymphoid cells as controls. The identity of the amplicons was confirmed by Southern analysis with the 32P-labeled cDNA probe coding for the entire span of the IL-2Rbeta chain. In addition, genomic DNA obtained from the tumor cell lines was sequenced to examine the possibility that a mutation is present in the gene coding for the intracellular IL-2Rbeta chain domain. No mutations or deletions were detected. The message for all three domains of the beta chain was identical in tumor cells and in normal lymphoid cells used as controls. Also, by Western blot and northern analyses no differences between IL-2Rbeta chain in tumors vs that expressed in lymphoid cells were demonstrable. The IL-2Rgamma chain, which participates in IL-2/IL-2R signaling pathway, was expressed in tumor cells. Expression of JAK1 transcripts in these cells was comparable to that in lymphocytes. However, RT-PCR analysis identified differences in expression of JAK3 splice variants (B and M) in tumor cells. These differences may be responsible for altered downstream signaling by IL-2. Overall, our data indicate that the same IL-2/IL-2R pathway is operative in human carcinomas and in normal epithelial or lymphoid cells.

Carcinoma, Renal Cell↗