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Biomedical subjects

J K Lin

Publications and source records attributed to J K Lin.

At least 91 records · Page 5Linked to original sources
PubMed1997

Suppression of extracellular signals and cell proliferation through EGF receptor binding by (-)-epigallocatechin gallate in human A431 epidermoid carcinoma cells.

Tea polyphenols are known to inhibit a wide variety of enzymatic activities associated with cell proliferation and tumor progression. The molecular mechanisms of antiproliferation are remained to be elucidated. In this study, we investigated the effects of the major tea polyphenol (-)-epigallocatechin gallate (EGCG) on the proliferation of human epidermoid carcinoma cell line, A431. Using a [3H]thymidine incorporation assay, EGCG could significantly inhibit the DNA synthesis of A431 cells. In vitro assay, EGCG strongly inhibited the protein tyrosine kinase (PTK) activities of EGF-R, PDGF-R, and FGF-R, and exhibited an IC50 value of 0.5-1 microgram/ml. But EGCG scarcely inhibited the protein kinase activities of pp60v-src, PKC, and PKA (IC50 > 10 micrograms/ml). In an in vivo assay, EGCG could reduce the autophosphorylation level of EGF-R by EGF. Phosphoamino acid analysis of the EGF-R revealed that EGCG inhibited the EGF-stimulated increase in phosphotyrosine level in A431 cells. In addition, we showed that EGCG blocked EGF binding to its receptor. The results of further studies suggested that the inhibition of proliferation and suppression of the EGF signaling by EGCG might mainly mediate dose-dependent blocking of ligand binding to its receptor, and subsequently through inhibition of EGF-R kinase activity.

Antineoplastic Agents↗
PubMed1997

Induction of glutathione depletion, p53 protein accumulation and cellular transformation by tetrachlorohydroquinone, a toxic metabolite of pentachlorophenol.

Glutathione (GSH) conjugate formation with tetrachlorohydroquione (TCHQ) and the GSH content in vivo were measured by capillary zone electrophoresis. A more than 60% depletion of GSH content was found in liver tissue of mice treated with TCHQ. In addition, p53 protein accumulation and DNA fragmentation was induced by TCHQ. A two-stage model of chemical transformation of mouse embryonic fibroblasts was used to elucidate the transformation activity of TCHQ in vitro, and a 33% foci formation efficiency was found at the concentration of 5 microM. GSH depletion caused by TCHQ could abolish the protective ability of the cell against reactive oxygen species provided by GSH. When DNA was damaged, p53 protein accumulated in the nucleus and, in the case of severe damage, initiated apoptosis. TCHQ's ability to cause GSH depletion and DNA damage may play a role in the cytotoxic and genotoxic properties of its metabolic precursor, PCP.

3T3 Cells↗
PubMed1997

Identification of LDH-ras p21 protein complex and expression of these genes in human ovarian cancer.

Normal ovarian and ovarian cancer tissues from 35 patients were tested for LDH-A-ras protein complex formation, as well as for the expression of ras and LDH-A genes. By immunodetection of the immunoprecipitates, LDH-A-ras protein complexes are present in the homogenates of human ovarian tissues (benign and malignant). Two bands of 21 and 36 kDa were demonstrated in affinity-purified LDH active fractions by Western blot analysis, and these two proteins were proved to be ras p21 and LDH-A by immunodetection. By Northern blot analysis, elevated levels of c-Ki-ras and LDH-A mRNA transcripts were noted in 49% (17/35) and 40% (14/35) of ovarian cancers, respectively. Concurrent high expression of both genes was demonstrated in 11 cases (31%). Tyrosylphosphorylation of LDH-A was demonstrated in normal and malignant ovarian tissues, and the extent of phosphorylation was correlated with the stage of ovarian cancer. The concurrent elevated expression of ras and LDH-A in the same ovarian tissue may imply that the increased synthesis of LDH-A is due to increased or amplified signaling of the ras-cascade pathway. The possible biochemical role of the tyrosylphosphorylated LDH-A complexed with ras p21 in cell transformation and progression of human ovarian cancer is worthy of further investigation.

Female↗
PubMed1997

Large bowel tuberculosis and possible influencing factors for surgical prognosis: 30 years' experience.

The incidence of tuberculosis is rising in the United States. Similarly, the incidence of pulmonary tuberculosis in Taiwan is increasing, but that of large bowel tuberculosis in this region has not been reported. The purpose of this study was to investigate the changing disease pattern and to determine some possible surgical prognostic factors for large bowel tuberculosis. Seventy cases of large bowel tuberculosis treated at our institute during the period 1965-1995 were reviewed and analyzed. A steady decline in the case number of large bowel tuberculosis were noted from 1975, but there seems to be a slight increase in cases since 1990. The average age of these patients was 65.1 years, and none had human immunodeficiency virus infection. The ileocecum is the most common region of involvement. Of these 70 patients, 59 had not been definitively diagnosed until surgery. Active pulmonary tuberculosis was found in 18 patients (25.7%). The incidence of postoperative pulmonary complications was higher in patients with active pulmonary tuberculosis or disseminating large bowel tuberculosis. Postoperative abdominal complications, including intestinal obstruction, abdominal cutaneous fistula, and wound infection, were seen in 13 patients, none of whom had active pulmonary tuberculosis. Although the incidence of tuberculosis has been reduced for years, it is now rising. Physicians should bear in mind the possibility of large bowel tuberculosis in patients with intestinal obstruction without specific origin. Postoperative respiratory care is important for patients with pulmonary tuberculosis, with either active or disseminating lesions.

Adolescent↗
PubMed1997

Stability of curcumin in buffer solutions and characterization of its degradation products.

The degradation kinetics of curcumin under various pH conditions and the stability of curcumin in physiological matrices were investigated. When curcumin was incubated in 0.1 M phosphate buffer and serum-free medium, pH 7.2 at 37 degrees C, about 90% decomposed within 30 min. A series of pH conditions ranging from 3 to 10 were tested and the result showed that decomposition was pH-dependent and occurred faster at neutral-basic conditions. It is more stable in cell culture medium containing 10% fetal calf serum and in human blood; less than 20% of curcumin decomposed within 1 h, and after incubation for 8 h, about 50% of curcumin is still remained. Trans-6-(4'-hydroxy-3'-methoxyphenyl)-2,4-dioxo-5-hexenal was predicted as major degradation product and vanillin, ferulic acid, feruloyl methane were identified as minor degradation products. The amount of vanillin increased with incubation time.

Antioxidants↗
PubMed1997

PIG-A gene mutations in four Taiwanese patients with paroxysmal nocturnal haemoglobinuria following aplastic anaemia.

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder caused by deficient biosynthesis of the glycosyl phosphatidylinositol (GPI) anchor in haemopoietic stem cells. PIG-A, an X-linked gene that participates in the first step of GPI-anchor synthesis, is responsible for PNH. Various abnormalities of the PIG-A gene have been demonstrated in all patients with PNH so far examined. In this study we characterized the somatic mutations in PIG-A gene in four Taiwanese patients with PNH. We identified five novel mutations in the PIG-A gene, three single nucleotide substitution mutations (-342, C-->G, codon 335, GGT-->AGT and codon 405, GCT-->GTT) and two frameshift mutations (codon 22, GGA-->G-A and codon 356, TGT-->TGTT) in the PIG-A gene. The -342 mutation was judged to be a polymorphism. Furthermore, three patients had previous clinicopathologic evidence which suggested aplastic anaemia (AA), before the development of PNH. One of these was found to have thrombocytopenia during follow-up. We suggest that the somatic PIG-A gene mutations highlight a subgroup of AA having a pathogenetic link with PNH.

Anemia, Aplastic↗
PubMed1997

Inhibitory effects of phytopolyphenols on TPA-induced transformation, PKC activation, and c-jun expression in mouse fibroblast cells.

The effects of 12 phytopolyphenols, including 3 catechin derivatives, 8 flavanols, and curcumin, on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced transformation in mouse fibroblast cells are described. The location of hydroxyl functional groups at 2', 3', or 4' site(s), especially at the 4' site, as in apigenin, fisetin, morin, myricetin, and quercetin, seems essential for anti-TPA-induced transformation, anti-protein kinase C (PKC) activation, and anti-TPA-induced c-jun expression activities. Among the catechin derivatives, those with a cis form structure and with an additional hydroxyl group at the R1 site and galloyl groups at the R2 site, such as epigallocatechin gallate, have stronger inhibitory effects on the above-mentioned biochemical activities. Considering their polarities and chemical structures, these compounds have different oxygen radical absorbance capacity in the in vitro assay. In addition, curcumin also has these inhibitory effects on the above-mentioned biochemical activities and antioxidant activities for peroxyl radical but not hydroxyl radical. In addition to PKC activation, active oxygen species production, and c-jun induction, our data suggest that TPA treatment induces cellular transformation by other unknown routes, because some tested compounds have an inhibitory effect on TPA-induced transformation but have no or a slight inhibitory effect on PKC activation, active oxygen species production, and c-jun induction.

3T3 Cells↗
PubMed1997

Augmentation of protein kinase C activity and liver cell proliferation in lead nitrate-treated rats.

It is shown that lead alters calcium mediated cellular processes in several biological systems. Calcium enhances the activity of protein kinase C (PKC) which takes part in eliciting cell mitosis. In this study, the effects of lead nitrate on the activity of PKC enzyme were investigated in rat liver. The PKC activity was determined at 12, 24, 48, 72, 120, 168 hours after treatment with a single dose of lead nitrate in male Wistar rats. The results showed that the specific PKC activity of the purified particulate fraction was increased and reached a maximum at 24 hour, and lasted for 48 hours. This augmented activity of PKC was parallel with the increase of the lead level in the purified particulate fraction, although the protein levels of PKC alpha, PKC delta and PKC zeta were unchanged. Moreover, the frequency of mitotic cells also exhibited a significant increase, and like PKC activity, reached its maximum at 24 hour with accompany signs of liver enlargement. The results suggest that the PKC activation may be involved in promoting liver cell proliferation in lead nitrate-treated rats.

Animals↗
PubMed1997

Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan.

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.

Adjuvants, Immunologic↗
PubMed1997

Late-onset life-threatening angioedema and upper airway obstruction caused by angiotensin-converting enzyme inhibitor: report of a case.

Angioedema is a rare but potentially lethal adverse effect when associated with upper airway obstruction. Sporadic cases of angioedema secondary to angiotensin converting enzyme inhibitors (ACEI) have been reported in the literature. The overall incidence is around 0.1% to 0.2%, and the time of onset is usually during the first week of ACEI therapy. Late-onset angioedema secondary to treatment with ACEIs is much more frequent than appreciated, and is largely unrecognized because of the absence of temporal correlation between ACEI therapy and the development of angioedema. Since angioedema may progress to upper airway obstruction, otolaryngologists must be aware of this association. Most importantly, late-onset angioedema should alert the clinician to discontinue the ACEI immediately to prevent further morbidity. This report presents an example of late-onset angioedema which was precipitated by taking a double dose of captopril incidentally. The case is discussed, and the literature, pathophysiology and treatment of angioedema are reviewed.

Age of Onset↗
PubMed1997

Suppression of nitric oxide-induced apoptosis by N-acetyl-L-cysteine through modulation of glutathione, bcl-2, and bax protein levels.

It has been demonstrated that nitric oxide (NO) can promote apoptosis in human cancer cells. To test the protective effects of antioxidants (N-acetyl-L-cysteine (LNAC) and free-radical spin traps (5,5-dimethyl-1-pyrroline N-oxide and 2,2,6,6,-tetramethyl-1-piperidinyloxy) against NO-induced apoptosis, a human colon cancer cell line (COLO 205) was treated with NO, and its survival rate was evaluated both with and without antioxidant therapy. LNAC arrested the development of progression of apoptosis in COLO 205 cells in a dose-dependent manner, promoted long-term survival, and prevented the internucleosomal DNA cleavage induced by NO. The intracellular level of glutathione (GSH) was found to be elevated in cells after exposure to LNAC. The bax protein levels were elevated by NO treatment, and this effect was blocked by LNAC. On the other hand, the bcl-2 oncoprotein level in the LNAC-pretreated cells was significantly elevated in a time-dependent manner compared to cells that received NO pretreatment. In summary, our results suggest that the protective effect of LNAC may be linked to its inducement of increases in cellular GSH and bcl-2 protein levels and to its suppression of cellular bax protein in treated cells.

Acetylcysteine↗
PubMed1997

Enterovesical fistula: 10 years experience.

BACKGROUND: Enterovesical fistula is a relatively uncommon complication of pelvic malignancies, diverticulitis of the colon, postoperative irradiation or trauma. Early diagnosis of enterovesical fistula is difficult and its management, complicated. The main purpose of this study is to investigate the most appropriate diagnostic method and to discuss the choice among different surgical managements. METHODS: From 1986 to 1995, 30 patients with enterovesical fistula were diagnosed and treated at Veterans General Hospital-Taipei. The records were reviewed retrospectively with regard to symptoms, primary disease process, diagnostic studies, management, complications, mortality and follow-up. RESULTS: Recurrent urinary tract infection (UTI) accounted for 73% and was the most common presenting symptom. Fecaluria (43%) and urine per rectum (40%) were another two common presenting symptoms. The major cause of these cases was malignancy (36%), followed by postoperative radiotherapy (17%) and iatrogenic injury (17%). Most of these cases were diagnosed by cystography (90%), barium enema (75%) or cystoscopy (69%). The rectum (52%) was the most common site involved, followed by the sigmoid colon (39%). The surgical management was individualized for each patient according to the general condition and the disease process. CONCLUSIONS: By combining the results of cystography, barium enema and cystoscopy, diagnosis of enterovesical fistula can be established in almost all cases. Single-stage operation for enterovesical fistula should be limited to those patients in good nutritional state and without severe inflammation, radiation injury, intestinal obstruction, other major medical problem, advanced malignancy or old age.

Adult↗
PubMed1997

(-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappaB.

Nitric oxide (NO) plays an important role in inflammation and multiple stages of carcinogenesis. We investigated the effect of various tea polyphenols and caffeine on the induction of NO synthase (NOS) in thioglycollate-elicited and lipopolysaccharide (LPS)-activated peritoneal macrophages. Gallic acid (GA), (-)-epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG), the major tea catechin, were found to inhibit inducible NOS (iNOS) protein in activated macrophages. EGCG, a potent antitumor agent with anti-inflammatory and antioxidant properties, inhibited NO generation, as measured by the amount of nitrite released into the culture medium. Inhibition of NO production was observed when cells were cotreated with EGCG and LPS. iNOS activity in soluble extracts of lipopolysaccharide-activated macrophages treated with EGCG (5 and 10 microM) for 6-24 hr was significantly lower than that in macrophages without EGCG treatment. Western blot, reverse transcription-polymerase chain reaction, and Northern blot analyses demonstrated that significantly reduced 130-kDa protein and 4.5-kb mRNA levels of iNOS were expressed in lipopolysaccharide-activated macrophages with EGCG compared with those without EGCG. Electrophoretic mobility shift assay indicated that EGCG blocked the activation of nuclear factor-kappaB, a transcription factor necessary for iNOS induction. EGCG also blocked disappearance of inhibitor kappaB from cytosolic fraction. These results suggest that EGCG decreases the activity and protein levels of iNOS by reducing the expression of iNOS mRNA and the reduction could occur through prevention of the binding of nuclear factor-kappaB to the iNOS promoter, thereby inhibiting the induction of iNOS transcription.

Animals↗
PubMed1997

Does anastomotic method affect functional outcome of low anterior resection for rectal carcinoma?

BACKGROUND: Anorectal dysfunction may occur following sphincter-saving resection for rectal carcinoma. The dysfunction may present clinically with increased stool frequency and varying degrees of fecal incontinence. It is postulated that these presentations come about from reduced neorectal capacity, as well as internal anal sphincter injury, during transanal instrumentation or through damage to the nerve supply in the course of rectal dissection. The purpose of this study was to assess the functional results of low anterior resection (LAR), and the relative importance of each mechanism. METHODS: Thirty-one patients were included in this study, eighteen of whom had standard LAR for rectal carcinoma. Bowel continuity was reestablished by handsewn (HS) 2-layer suture in 10 patients and stapled EEA (U.S. Surgical Corporation) anastomosis in the other 8 patients. Thirteen patients who had received abdominal surgery other than LAR were the control group. Anorectal manometry was performed preoperatively and one week, then six months post-operatively. Clinical assessment was done pre-operatively and six months post-operatively. RESULTS: Resting anal pressure was significantly reduced in both HS and EEA groups post-operatively (HS: 69.4 +/- 14.8 mmHg, median: 71.5 mmHg vs. 43.7 +/- 16.2 mmHg, median: 48.5 mmHg, 95% confidence interval of mean difference: 6.4-24.6 mmHg; EEA: 51.3 +/- 14.6 mmHg, median: 48.0 mmHg vs. 38.8 +/- 16.6 mmHg, median: 41.5 mmHg, 95% confidence interval of mean difference: 5.6-49.8 mmHg), partial recovery was noted in the HS group six months later. The squeeze pressure and functional length of the anal canal showed no difference pre- and post-operatively. Rectoanal inhibitory reflex was present in 90% of the patients preoperatively, but in only 70% of the HS, and 38% of the EEA group, six months post-operatively. Clinically, increased bowel frequency and varying degrees of incontinence were experienced postoperatively. There was no difference in bowel frequency between the two groups, but worse continence grade was seen in the EEA group. CONCLUSIONS: LAR for rectal carcinoma resulted in impaired anorectal function. Handsewn anastomosis seemed to have a better functional outcome than EEA stapled anastomosis.

Aged↗
PubMed1997

Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin.

Apigenin, a less-toxic and non-mutagenic flavonoid, suppressed 12-0-tetradecanoyl-phorbol-13-acetate-(TPA)-mediated tumor promotion of mouse skin. TPA had the ability to activate protein kinase C (PKC) and induced nuclear proto-oncogene expression. Our study indicates that apigenin inhibited PKC by competing with adenosine triphosphate (ATP). Apigenin also reduced the level of TPA-stimulated phosphorylation of cellular proteins and inhibited TPA-induced c-jun and c-fos expression. Curcumin, a dietary pigment phytopolyphenol, is also a potent inhibitor of tumor promotion induced by TPA in mouse skin. When mouse fibroblast cells were treated with TPA alone, PKC translocated from the cytosolic fraction to the particulate fraction. Treatment with 15 or 20 microM curcumin for 15 min inhibited TPA-induced PKC activity in the particulate fraction by 26-60%. Curcumin also inhibited PKC activity in vitro by competing with phosphatidylserine. Curcumin (10 microM) suppressed the expression of c-jun in TPA-treated cells. Fifteen flavonoids were examined for their effects on morphological changes in soft agar and cellular growth in v-H-ras transformed NIH3T3 cells. The results demonstrated that only apigenin, kaempferol, and genistein exhibited the reverting effect on the transformed morphology of these cells. Based on these findings, it is suggested that the suppression of PKC activity and nuclear oncogene expression might contribute to the molecular mechanisms of inhibition of TPA-induced tumor promotion by apigenin and curcumin.

Animals↗
PubMed1996

Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells.

Curcumin, widely used as a spice and coloring agent in food, possesses potent antioxidant, anti-inflammatory and anti-tumor promoting activities. In the present study, curcumin was found to induce apoptotic cell death in promyelocytic leukemia HL-60 cells at concentrations as low as 3.5 micrograms/ml. The apoptosis-inducing activity of curcumin appeared in a dose- and time-dependent manner. Flow cytometric analysis showed that the hypodiploid DNA peak of propidium iodide-stained nuclei appeared at 4 h after 7 micrograms/ml curcumin treatment. The apoptosis-inducing activity of curcumin was not affected by cycloheximide, actinomycin D, EGTA, W7 (calmodulin inhibitor), sodium orthovanadate, or genistein. By contrast, an endonuclease inhibitor ZnSO4 and proteinase inhibitor N-tosyl-L-lysine chloro-methyl ketone (TLCK) could markedly abrogate apoptosis induced by curcumin, whereas 12-O-tetradecanoylphorbol-13-acetate (TPA) had a partial effect. The antioxidants, N-acetyl-L-cysteine (NAC), L-ascorbic acid, alpha-tocopherol, catalase and superoxide dismutase, all effectively prevented curcumin-induced apoptosis. This result suggested that curcumin-induced cell death was mediated by reactive oxygen species. Immunoblot analysis showed that the level of the antiapoptotic protein Bcl-2 was decreased to 30% after 6 h treatment with curcumin, and was subsequently reduced to 20% by a further 6 h treatment. Furthermore, overexpression of bcl-2 in HL-60 cells resulted in a delay of curcumin-treated cells entering into apoptosis, suggesting that bcl-2 plays a crucial role in the early stage of curcumin-triggered apoptotic cell death.

Antineoplastic Agents↗
PubMed1996

Inhibition of HIV-1 Tat-mediated transactivation by quinacrine and chloroquine.

The replication of human immunodeficiency virus type 1 (HIV-1) requires cellular components to interact with regulatory elements located in the long terminal repeat (LTR) as well as viral proteins Tat and Rev. Several well known signaling transduction inhibitors were tested to determine their effects on the Tat-mediated transactivation using a transfection assay with the bacterial chloramphenicol acetyltransferase gene under the control of the HIV-1 LTR. The protein kinase C inhibitors curcumin and staurosporine, but not a tyrosine kinase inhibitor herbimycine A, inhibited Tat-mediated LTR-driven transactivation. Two antimalarial drugs quinacrine and chloroquine, that are also arachidonic acid metabolism inhibitors, were found to inhibit the Tat-mediated LTR-driven gene expression. Another inhibitor of arachidonic acid metabolism 4-bromophenacyl bromide was also found to inhibit Tat-mediated gene expression driven by HIV-1 LTR. However, the antimalarial drug quinine elicited no effects on Tat-mediated transactivation. These results suggest that the anti-arachidonic acid metabolism properties of quinacrine and chloroquine may be responsible for their ability to inhibit Tat-mediated LTR-regulated gene expression.

Acetophenones↗