Biomedical subjects

W L Ho

Publications and source records attributed to W L Ho.

At least 19 recordsLinked to original sources

PubMed2001

Effects of carbon and nitrogen sources, sodium chloride and culture conditions on cytotoxin production by Salmonella choleraesuis.

The effects of carbon and nitrogen sources, incubation temperature, shaking speed, initial pH of culture broth as well as various concentration of NaCl on the production of cytotoxin by Salmonella choleraesuis SC-5 were evaluated in the present study. Results reveal that the optimal temperature, initial medium pH and shaking speed for cytotoxin production was 37 degrees C, pH 6.0-8.0 and 100 rpm, respectively. Tryptone was the best of the eight nitrogen sources tested for toxin production by S. choleraesuis. Among the nine carbon sources tested, S. choleraesuis produced a higher amount of cytotoxin in media containing glucose, fructose, galactose, sorbitol or mannitol as the carbon source. No toxin was detected in broths containing 4.0% or more sodium chloride in Tryptic soy broth (TSB). Cultures of S. choleraesuis in the medium containing 2.0% tryptone, 0.5% NaCl, 0.25% K2HPO4 and 0.25% of the best carbon source under the optimal conditions for 14 h resulted in the highest cytotoxin production. The Vero cell CD50 of S. choleraesuis lysate of cells grown under these optimal conditions was a titer of 589-758 per mg of lysate protein.

Carbon↗

PubMed2001

Liver resection for hepatocellular carcinoma in patients with end-stage renal failure.

BACKGROUND AND OBJECTIVES: Surgical resection remains the main option for curing hepatocellular carcinoma (HCC). However, liver resection in patients with end-stage renal disease (ESRD) is risky. The aim of this study is to clarify the role of liver resection for treating HCC in patients with ESRD. METHODS: A retrospective review was carried out on 468 patients who underwent liver resection for HCC between 1989 and 1999. The clinicopathological characteristics and operative results of 12 patients who had ESRD (ESRD group) were compared with those of the other 456 patients who did not have ESRD (non-ESRD group). In the ESRD group, heparin-free hemodialysis using the periodic saline-rinse method was performed during the perioperative period. RESULTS: The ESRD group had lower hemoglobin and a higher serum creatinine levels. Other patient background and tumor pathological characteristics were comparable between the two groups as well. The operative morbidity and mortality between the two groups were also similar. The 5-year disease-free survival rates for ESRD and non-ESRD groups were 35.0 and 34.2% (P = 0.31), respectively, while the 5-year actuarial survival rates were 67.8 and 53.3% (P = 0.54), respectively. CONCLUSION: With improving techniques and knowledge of dialysis, liver resection for HCC is justified in selected patients with ESRD.

Adult↗

PubMed2001

Histologic study of effects of radiation synovectomy with Rhenium-188 microsphere.

Rhenium-188 microsphere is a relatively new radiation synovectomy agent developed for the treatment of rheumatoid arthritis. It has been shown that the levels of unwanted extra-articular radiation are negligible with this agent. A histologic study was conducted to assess the effect of radiation synovectomy on synovium and articular cartilage after intra-articular injection of various doses of Re-188 microspheres into the knee joints of rabbits. Intra-articular injection of Re-188 microspheres into rabbit knee joints resulted in mild reactive inflammation and thrombotic occlusion of vessels which subsided rapidly. Sclerosis of subsynovium could be seen 12 weeks after injection. No evidence of damage to articular cartilage was noted. There was no significant difference in the articular pattern after injection of 0.3 or 0.6 mCi Re-188 microspheres. This study suggests that a treatment dose of Re-188 microspheres causes transient inflammation of synovium without any detectable damage to the articular cartilage of knee joint.

Animals↗

PubMed2000

An appraisal of liver and portal vein resection for hepatocellular carcinoma with tumor thrombi extending to portal bifurcation.

BACKGROUND: The role of surgical resection for hepatocellular carcinoma with tumor thrombi involving the major portal vein is controversial because of a high operative risk and poor prognosis. Previously, a resection was performed only when the tumor thrombi were limited to the first branch of the portal vein without extension to the portal bifurcation. HYPOTHESIS: Concomitant liver and portal vein resection may be beneficial in patients with hepatocellular carcinoma with tumor thrombi extending to portal bifurcation. DESIGN: Retrospective review. SETTING: University hospital, tertiary referral center. PATIENTS: Among 368 patients with hepatocellular carcinoma who underwent a curative resection, portal vein involvement occurred in 112 patients. Fifteen of the 112 patients underwent a concomitant liver and portal vein resection owing to extension of tumor thrombi to the portal bifurcation (group 1). The remaining 97 patients did not need portal vein resection (group 2). INTERVENTION: Surgical indications, procedures, and results of pathological examination of resected specimens were assessed in patients in group 1. The clinicopathological characteristics, operative morbidity and mortality, and operative results were compared between the 2 groups. MAIN OUTCOME MEASURES: Disease-free and actuarial survival rates. RESULTS: Intramural tumor infiltration was found at the site of thrombi adhesion to the portal vein cuff in 11 of 15 patients in group 1. Owing to patient selection bias, patients in group 1 were significantly younger and had better liver function and greater resected liver weight. The operative time, postoperative hospitalization, operative blood loss, amount of blood transfusion, and operative morbidity and mortality did not differ significantly between the 2 groups. The 5-year disease-free survival rates of groups 1 and 2 were 21.6% and 20.4% (P =.19), respectively, while the actuarial survival rates were 26. 4% and 28.5% (P =.33), respectively. CONCLUSION: Liver resection with partial resection of the portal vein is justified in selected patients with hepatocellular carcinoma with tumor thrombi extending to portal bifurcation.

Carcinoma, Hepatocellular↗

PubMed2000

Selective sentinel lymph node dissection in breast cancer: experiences from Taiwan.

The significance of the sentinel lymph node (SLN) was examined in 58 Chinese breast cancer patients. The method of technetium-99m sulfur colloid injection and the intraoperative gamma probe was found to be very useful for identifying the SLN. The positive predictive value was 64.5%, and the negative predictive value was 93.2%. Findings suggest that lymph node dissection is not necessary in breast cancer patients with a negative SLN.

Adult↗

PubMed2000

Lymph node revealing solution and traditional 10% buffered formaldehyde for detecting lymph nodes in colorectal carcinoma.

BACKGROUND: Cancer stage has been the most important factor in evaluating the prognosis and treatment of colorectal carcinoma, and the presence of lymph node metastasis in the resected specimen plays a key role in serial staging. We evaluated a newly proposed "lymph node revealing solution" (LNRS) that proponents claim is inexpensive, easy, rapid, and innocuous, and that could help to establish the stage of disease more accurately than buffered formaldehyde (formalin). Our study compared traditional 10% formalin and LNRS as second search solutions to determine whether LNRS is a more useful and practical solution than formalin. METHODS: Thirty randomly selected colorectal carcinomas from low anterior resection (LAR) were studied. The specimens were handled routinely on the first day. Then, the entire fat of odd-numbered cases was immersed in three times its volume of LNRS, and the entire fat of even-numbered cases was immersed in 10 times its volume of formalin overnight. The chi-squared test was used to evaluate the results. RESULTS: Of 145 cassettes in the second search by LNRS, seven had no lymph nodes. Of 107 cassettes in the second search by formalin, 18 had no lymph nodes. Totally, 792 lymph nodes were found with an average number of 26.4 per case and 1.53/cm (per centimeter of specimen) in all 30 cases. By the LNRS method, 138 lymph nodes were found in the 15 odd-numbered cases, and by the formalin method, 89 lymph nodes were found in the 15 even-numbered cases. We were able to adjust the stage upward in two cases by LNRS-fixation method. There were no changes in staging in the formalin-fixation method cases. CONCLUSIONS: LNRS showed no statistically significant difference from formalin in the numbers of total lymph nodes, positive lymph nodes, or minute (less than 1 mm) lymph nodes found. Nonetheless, we do believe that LNRS is a potential replacement solution for formalin due to its fast fixation, ease of searching, high identification rate and time-saving procedure.

Colorectal Neoplasms↗

PubMed2000

Hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia was first described by Thurnam in 1848. It is a rare, X-linked, recessive disorder characterized by anhidrosis or hypohidrosis, hypotrichosis, dental hypoplasia and characteristic facial features. Herein, we report a typical case of hypohidrotic ectodermal dysplasia. A 20-year-old male presented with the above symptoms at birth. When a family history was taken, it was discovered that his uncle (mother's brother) had the same characteristic facial features and hypotrichosis.

Adult↗

PubMed2000

Histopathologic analysis of sentinel lymph nodes in breast carcinoma.

BACKGROUND: Intraoperative lymphatic mapping and identification of the first draining lymph node (the sentinel lymph node) may allow some patients with breast cancer to avoid the morbidity of formal axillary clearance. The aim of this study was to determine the accuracy of sentinel lymph node (SLN) biopsy in predicting axillary nodal involvement. METHODS: From August, 1998 until July, 1999, 41 patients with clinically node-negative breast cancer underwent SLN biopsy that was immediately followed by axillary lymph node dissection. If the SLN section was found free of metastasis by routine hematoxylin and eosin staining (H&E), then an additional four sections of the SLN were cut and examined for the presence of tumor cells by H&E staining (three sections) and by cytokeratin immunohistochemical staining (IHC) (one section). If the SLN had metastatic cells and the other remaining nonsentinel axillary lymph nodes were free of metastases by routine H&E staining, then an additional three sections of the nonsentinel axillary lymph nodes were cut and examined for the presence of tumor cells by H&E staining. RESULTS: The 41 patients had a mean of 2.2 sentinel (range, 1-7) and 14.6 nonsentinel (range, 5-32) lymph nodes excised per patient. Routine H&E staining identified 13 patients (31.7%) with SLN metastases and 28 patients (68.3%) with tumor-free SLNs. Applying IHC and the additional three sections stained with H&E to these tumor-free SLNs showed one additional patient with sentinel node metastasis. The conversion rate from being a sentinel node-negative patient to a sentinel node-positive patient was 3.6% (1/28). Overall, SLN metastases were detected in 14 (34.1%) of the 41 patients. The SLNs were negative in 27 patients (65.9%), two of whom had at least one positive nonsentinel lymph node each (7.4% "skip" metastasis). Biopsy of SLNs was 92.6% accurate in predicting the absence of nonsentinel nodal metastasis (p=0.001). CONCLUSIONS: Our results suggest that formal axillary lymph node dissection may need only be performed in SLN-positive patients. Nonetheless, further experience and refinement are needed to perfect this technique.

Adult↗

PubMed2000

Benign metastasizing leiomyoma of the lung: a case report.

Benign metastasizing leiomyoma (BML) refers to benign pulmonary neoplasm associated with a previous or coincident history of uterine leiomyomata. We report the case of a 56-year-old postmenopausal woman with a 4-year history of multiple benign leiomyomatous lesions in bilateral lungs and the uterus. The tumor cells from the lungs and uterus were focally immunoreactive for HMB-45 antibody and progesterone receptor. Immunoreactivity to HMB-45 is well known in smooth muscle cells of hamartomatous neoplasms, such as angiomyolipoma and lymphangioleiomyomatosis, but has not been reported in BML previously. These features suggest a multifocal hamartomatous histogenesis rather than metastasis in the present case.

Antigens, Neoplasm↗

PubMed1999

Involvement of cyclin-dependent kinase activities in CD437-induced apoptosis.

A novel synthetic retinoid, 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437), is a selective ligand of the RARgamma nuclear receptor. We examined the in vitro effects of CD437 and found that CD437 induces S phase arrest within 24 to 48 h, followed by cell death, in the p53-negative Hep3B and the p53-positive HepG2 human hepatoma cell lines. Based on observations of cellular and nuclear fragmentation, chromatin condensation, and DNA fragmentation, the CD437-mediated cell-killing effect appears to be due to apoptosis. On morphological examination, a number of CD437-treated cells were found to have increased 5- to 10-fold in size and persisted as single giant cells without cell division, while the remainder underwent nuclear division (multiple nuclei) but were unable to complete cytokinesis, and finally all died by apoptosis. In HepG2 cells that possessed wild-type p53, CD437-induced S phase arrest and apoptosis were accompanied by the up-regulation of cyclin A, cyclin B, p53, p21(CIP1/Waf1), Bad, and Bcl-Xs proteins and by a decrease in Bcl-2 protein levels. In Hep3B cells, CD437-mediated S phase arrest and apoptosis were also associated with a concomitant up-regulation of cyclin A, cyclin B, Bad, and Bcl-Xs. However, Hep3B cells did not express p53 or Bcl-2 messages. Olomoucine and roscovitine, the potent p34(cdc2) and CDK2 inhibitors, effectively blocked CD437-mediated cyclin A- and B-dependent kinase activation and prevented CD437-induced cell death. Furthermore, antisense oligonucleotide complementary to cyclin A and B mRNA significantly rescued CD437-induced apoptosis. These findings suggest that activation of cyclin A- and B-dependent kinases is a critical determinant of apoptotic death mediated by CD437.

Antineoplastic Agents↗

PubMed1999

Effects of bis(7)-tacrine, a novel anti-Alzheimer's agent, on rat brain AChE.

The anticholinesterase effects of bis(7)-tacrine were compared with tacrine in vitro and in vivo. Based on IC50 ratios, the dimeric analog bis(7)-tacrine was, in a reversible manner, up to 150-fold more potent and 250-fold more selective than tacrine for acetylcholinesterase (AChE) over butyrylcholinesterase (BChE). Following a single oral administration, both bis(7)-tacrine and tacrine produced dose-dependent inhibitions of AChE in rat brain, but bis(7)-tacrine exhibited higher efficacy and AChE/BChE selectivity than tacrine. The anti-AChE efficacy of bis(7)-tacrine was quite similar following an oral or i.p. administration, but tacrine showed much lower efficacy when administered orally than when given i.p. These findings suggest bis(7)-tacrine, a highly potent and selective inhibitor of AChE, can probably be used as an improved drug in the palliative treatment of AD.

Acetylcholinesterase↗

PubMed1999

Mesohepatectomy for centrally located hepatocellular carcinoma: an appraisal of a rare procedure.

BACKGROUND: For centrally located hepatocellular carcinoma (HCC), extended major hepatectomy is usually recommended, but the risk of postoperative liver failure is high when liver function is not sound. Mesohepatectomy (en bloc resection of Goldsmith and Woodburne's left medial and right anterior segments or Couinaud's segments IV, V, and VIII) is a rare procedure, so its role in treating HCC is unclear. STUDY DESIGN: We retrospectively reviewed 364 patients who underwent a curative resection for HCC. Among them, 15 patients were treated by mesohepatectomy. Their nontumorous liver revealed cirrhosis in 11 and chronic hepatitis in 4. The mean tumor diameter was 12.8 cm. In 10 of the 15 patients, HCC also invaded adjacent organs. The operative results of another 25 patients with different disease extent who underwent extended major hepatectomy were compared. RESULTS: The hepatic inflow occlusion time for mesohepatectomy was longer than for extended hepatectomy (p = 0.01). The mean operative blood loss, amount of blood transfusion, operating time, and postoperative hospital stay in the mesohepatectomy group were 2,450 mL, 1,100 mL, 7.9 hours, and 14.9 days, respectively. In the extended-hepatectomy group, the values were 1,863mL, 768mL, 5.8 hours, and 16.8 days, respectively (all p>0.05 compared with mesohepatectomy). No patient died after mesohepatectomy, but after extended hepatectomy there was one death from liver failure. The Union Internationale contre le cancer (UICC) TNM stages of patients who underwent mesohepatectomy were as follows: stage II in 1, stage III in 4, and stage IVA in 10. All patients who underwent extended hepatectomy presented with stage IVA disease. The 6-year disease-free and actuarial survival rates after mesohepatectomy were 21% and 30%, respectively. The 6-year disease-free survival rate after extended hepatectomy was 9% (p = 0.11 compared with mesohepatectomy). CONCLUSION: Although mesohepatectomy is time-consuming, it is justified for selected patients with centrally located large HCC in a diseased liver.

Adult↗

PubMed1999

Hepatitis viral status in patients undergoing liver resection for hepatocellular carcinoma.

BACKGROUND: Hepatitis B and C viruses are the main causative agents of hepatocellular carcinoma (HCC). The influence of hepatitis viral status on liver resection for HCC remains undetermined. METHODS: Patients who underwent curative resection for HCC were divided into four groups: group 1, seronegative for hepatitis B surface antigen (HBsAg) and antihepatitis C antibody (HCVAb); group 2, seropositive for HBsAg only; group 3, seropositive for HCVAb only; and group 4, seropositive for HBsAg and HCVAb. The clinicopathological characteristics and surgical results of the four groups were compared. Resection of HCC was determined according to liver functional reserve and tumour extent. RESULTS: There were 40, 131, 70 and 20 patients in groups 1, 2, 3 and 4 respectively. Due to patient selection bias, there were significant differences in some background features, resectional extent and pathological characteristics among the four groups. Postoperative morbidity and mortality, as well as the Union Internacional Contra la Cancrum tumour node metastasis stages, did not differ. Patients in group 1 had a higher disease-free survival rate than those in group 2 (P = 0. 02). The actuarial survival rates of patients in groups 2 and 4 were lower than those of groups 1 and 3. CONCLUSION: With careful patient selection, the hepatitis viral status does not influence the surgical risks of hepatectomy for HCC. After liver resection for HCC, the long-term survival rate of patients seronegative for HBsAg is greater than that of patients seropositive for HBsAg.

Aged↗

PubMed1999

Discordance between uterine cervical cytology and biopsy: results and etiologies of a one-year audit.

To investigate the etiologies of discrepancies between cervicovaginal smear and corresponding cervical biopsy results, a total of 15,474 cervicovaginal smears were sampled in a one-year period. Among these, 427 patients were diagnosed with atypical squamous cells of undetermined significance (ASCUS), dysplasia, or malignancy. The screen positive rate was 2.8%. All of the positive cases had histologic follow-up. Forty-nine of the 427 patients had a discrepancy of at least two grades (the grades are divided to negative, ASCUS, mild dysplasia, moderate dysplasia, severe dysplasia and invasive carcinoma), between the cytologic and histologic diagnoses. The discrepancy rate was 11.5%. Ten of these discrepant cases had poorly-preserved slides or a not definitely final diagnosis. A total of 39 cases (79.6%) of discrepancy were reviewed in this study. In thirty (77%) of the 39 discrepant cases, the errors were cytologic and in 9 cases (23%) the errors were histologic. Cytologic error was the major cause of cytohistologic discrepancy. The etiologies of cytohistologic discrepancy included: cytologic interpretation error, 17 cases (44%); cytologic sampling error, 10 cases (25%); biopsy sampling error, 6 cases (15%); cytologic screen error, 3 cases (8%); and biopsy interpretation error, 3 cases (8%). The major etiology of cytohistologic discordances was cytologic interpretation error. In this retrospective study, we determined the etiologies of cytohistologic discrepancies. This information can be useful for improving diagnostic accuracy and the quality of patient care.

Biopsy↗

PubMed1999

Liver resection for hepatocellular carcinoma in octogenarians.

BACKGROUND: Liver resection is risky in patients aged > or = 80 years. Because of short life expectancies and improved nonoperative modalities, the role of liver resection in octogenarians with hepatocellular carcinoma (HCC) is unclear. METHODS: A retrospective review of the operative results of 260 patients with HCC between 1991 and 1997 was performed. According to the age at the time of operation, these patients were divided into 2 groups. Group 1 comprised 21 patients aged > or = 80 years, and group 2 comprised the other 239 younger patients. The backgrounds, pathologic features of the tumor, and operative results of the patients were compared. RESULTS: Octogenarians had a higher incidence of associated medical diseases, a higher incidence of negative serum hepatitis B surface antigen, a lower alpha-fetoprotein level, and a higher indocyanine green retention rate. Although octogenarians had a longer postoperative hospital stay, there were no significant differences between the 2 groups regarding operative morbidity and mortality. The 5-year disease-free and actuarial survival rates for octogenarians and younger patients were 50.6% and 35.3% (P = .15) and 40.9% and 59.3% (P = .46), respectively. CONCLUSION: Under meticulous preoperative assessments and postoperative care, liver resection for HCC is justified in selected octogenarians, with short- and long-term results comparable to those of younger patients.

Actuarial Analysis↗

PubMed1999

Long-term outcome of adult patients with minimal urinary abnormalities and normal renal function.

AIM: To define the long-term outcome of patients with minimal urinary abnormalities (defined by the presence of microscopic hematuria with no or less than 1 gm/day proteinuria), and normal renal function (defined by a serum creatinine < 1.3 mg/dl), we retrospectively studied patients who fulfilled the above criteria and had a kidney biopsy done before the year of 1992 (i.e. at least followed up for 5 years), with a definite pathological diagnosis. METHODS: A total of 41 cases among 719 cases of primary glomerulonephritis (5.7%) were enrolled into the study. There were 19 males and 22 females with a mean age of 35.4+/-14.7 years at biopsy. The duration of renal disease was 116.0+/-60.5 months and the duration of follow-up post biopsy was 100.2+/-38.1 months. The pathological diagnosis was: IgA nephropathy (21 cases), focal glomerulosclerosis (9 cases), mesangial proliferative glomerulonephritis (8 cases), membranous glomerulonephritis (2 cases) and acute glomerulonephritis (1 case). RESULTS: At the end of follow-up, 8 cases (19.5%) had a certain degree of renal insufficiency including 2 (4.9%) in end-stage renal disease. The other cases were either in complete remission (6 cases) or stable condition (27 cases) with persistent microscopic hematuria and normal renal function. The long-term outcome was not correlated with any of the following parameters: age, sex, disease duration, serum creatinine at presentation, daily protein loss at presentation, degree of glomerular change and degree of interstitial inflammatory cell infiltration. However, a poor long-term outcome was correlated with tubular atrophy (p < 0.05) and interstitial fibrosis (p < 0.05). CONCLUSION: We conclude that a minimal urinary abnormality with normal renal function at presentation does not necessarily imply a favorable long-term outcome in certain patients. Tubular atrophy and interstitial fibrosis but not glomerular change correlates with a worse prognosis. This further emphasizes the importance of renal biopsy in such cases.

Adult↗

PubMed1999

Attenuation of scopolamine-induced deficits in navigational memory performance in rats by bis(7)-tacrine, a novel dimeric AChE inhibitor.

AIM: To study the effects of 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine [bis(7)-tacrine], a novel dimeric acetylcholine-sterase inhibitor (AChEI) derived from 9-amino-1,2,3,4-tetrahydroaminoacridine (tacrine), on scopolamine-induced spatial memory impairment. METHODS: The effects of bis(7)-tacrine were investigated on the 5-d performance of young adult rats in the Morris water maze. The latency to find the platform in the water maze was measured to evaluate performance. Tacrine was used as a reference drug. RESULTS: Scopolamine (0.3 mg.kg-1, i.p.) resulted in an increase in latency period (> 100% increase) as compared with saline treated controls. Both bis(7)-tacrine and tacrine lessened the increased latency induced by scopolamine to the level of saline control group. The relative potency of bis(7)-tacrine (0.35 mumol.kg-1, i.g. or i.p.) to shorten the escape latency was 24 or 12 times of tacrine (8.52 mumol.kg-1 i.g., 4.26 mumol.kg-1 i.p.) following i.g. or i.p. administration, respectively. There appeared to be an inverse bell-shape dose-dependent effect for both compounds tested. CONCLUSION: Bis(7)-tacrine is a more potent and orally active AChEI than tacrine, and has potential for the palliative treatment of Alzheimer disease.

Animals↗

PubMed1999

Induction of apoptosis by S-nitrosoglutathione and Cu2+ or Ni2+ ion through modulation of bax, bad, and bcl-2 proteins in human colon adenocarcinoma cells.

In this study, the amount of S-nitrosoglutathione (GSNO) was measured spectrophotometrically at 334 nm. A spontaneous decrease in absorbency at 334 nm was detected when GSNO was exposed to 37 degrees C and a high pH (pH 8.0). We investigated the catalytic roles of various metal ions on the decomposition of GSNO. The degradation of GSNO (0.5 mM) was enhanced by the presence of Cu(2+) and Ni(2+) ions. The amount of nitric oxide (NO) released from GSNO degradation was estimated by the Griess reaction based on nitrite accumulation. The results indicated that nitrite production was elevated at least twofold in the presence of Cu(2+). Our study further indicated that Cu(2+) enhanced GSNO-induced apoptosis in human colon adenocarcinoma HT 29 cells. We also found that copper ions modulated the expression of bad, bax, and bcl-2 in GSNO-treated HT 29 cells. The levels of bax and bad proteins in treated cells were significantly elevated about fourfold to sixfold when compared with mock-treated cells 24 h after combined treatment with GSNO plus Cu(2+) or Ni(2+). On the other hand, significant inhibition of bcl-2 occurred in HT 29 cells with simultaneous treatment of GSNO with Cu(2+) (or Ni(2+)). It seemed that Cu(2+) and Ni(2+) can enhance the decomposition of GSNO, which liberates NO to activate the pathways. Our results demonstrated that the apoptotic effects induced by GSNO were promoted by Ni(2+) and Cu(2+) through two different mechanisms: depletion of intracellular glutathione and triggering of NO release from GSNO, which then promotes NO-induced apoptosis in human cells.

Adenocarcinoma↗