Exosomes from IL-1b-Primed Mesenchymal Stem Cells Inhibited IL-1b- and TNF-a-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells

BACKGROUND@#Exosomes from mesenchymal stem cells (MSCs) show anti-inflammatory effect on osteoarthritis (OA); however, their biological effect and mechanism are not yet clearly understood. This study investigated the anti-inflammatory effect and mechanism of MSC-derived exosomes (MSC-Exo) primed with IL-1β in osteoarthritic SW982 cells. @*METHODS@#SW982 cells were treated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α to induce the OA phenotype. The effect of exosomes without priming (MSC-Exo) or with IL-1β priming (MSC-IL-Exo) was examined on the expression of pro- or anti-inflammatory factors, and the amount of IκBα was examined in SW982 cells. Exosomes were treated with RNase to remove RNA. The role of miR-147b was examined using a mimic and an inhibitor. @*RESULTS@#MSC-IL-Exo showed stronger inhibitory effects on the expression of pro-inflammatory cytokines (IL-1β, IL-6, and monocyte chemoattractant protein-1) than MSC-Exo. The expression of anti-inflammatory factors (SOCS3 and SOCS6) was enhanced by MSCs-IL-Exo. Priming with IL-1β increased RNA content in MSC-IL-Exo, and pretreatment with RNase abolished anti-inflammatory effect in SW982 cells. miR-147b was found in much larger amounts in MSC-IL-Exo than in MSC-Exo. The miR-147b mimic significantly inhibited the expression of inflammatory cytokines, while the miR-147b inhibitor only partially blocked the anti-inflammatory effect of MSC-IL-Exo. MSC-IL-Exo and miR-147b mimic inhibited the reduction of IκBα, an nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, by IL-1β and TNF-α. @*CONCLUSION@#This study showed that MSC exosomes with IL-1β priming exhibit significantly enhanced anti-inflammatory activity in osteoarthritic SW982 cells. The effect of IL-1β-primed MSC exosomes is mediated by miRNAs such as miR-147b and involves inhibition of the NF-κB pathway.

Exosomes from IL-1b-Primed Mesenchymal Stem Cells Inhibited IL-1b- and TNF-a-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells

BACKGROUND@#Exosomes from mesenchymal stem cells (MSCs) show anti-inflammatory effect on osteoarthritis (OA); however, their biological effect and mechanism are not yet clearly understood. This study investigated the anti-inflammatory effect and mechanism of MSC-derived exosomes (MSC-Exo) primed with IL-1β in osteoarthritic SW982 cells. @*METHODS@#SW982 cells were treated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α to induce the OA phenotype. The effect of exosomes without priming (MSC-Exo) or with IL-1β priming (MSC-IL-Exo) was examined on the expression of pro- or anti-inflammatory factors, and the amount of IκBα was examined in SW982 cells. Exosomes were treated with RNase to remove RNA. The role of miR-147b was examined using a mimic and an inhibitor. @*RESULTS@#MSC-IL-Exo showed stronger inhibitory effects on the expression of pro-inflammatory cytokines (IL-1β, IL-6, and monocyte chemoattractant protein-1) than MSC-Exo. The expression of anti-inflammatory factors (SOCS3 and SOCS6) was enhanced by MSCs-IL-Exo. Priming with IL-1β increased RNA content in MSC-IL-Exo, and pretreatment with RNase abolished anti-inflammatory effect in SW982 cells. miR-147b was found in much larger amounts in MSC-IL-Exo than in MSC-Exo. The miR-147b mimic significantly inhibited the expression of inflammatory cytokines, while the miR-147b inhibitor only partially blocked the anti-inflammatory effect of MSC-IL-Exo. MSC-IL-Exo and miR-147b mimic inhibited the reduction of IκBα, an nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, by IL-1β and TNF-α. @*CONCLUSION@#This study showed that MSC exosomes with IL-1β priming exhibit significantly enhanced anti-inflammatory activity in osteoarthritic SW982 cells. The effect of IL-1β-primed MSC exosomes is mediated by miRNAs such as miR-147b and involves inhibition of the NF-κB pathway.

Association between the Red Cell Distribution Width and Vasospastic Angina in Korean Patients

PURPOSE: The association between the red cell distribution width (RDW) and vasospastic angina (VSA) has not been elucidated. We investigated the association of the RDW with the incidence and angiographic subtypes of VSA in Korean patients. MATERIALS AND METHODS: A total of 460 patients who underwent intracoronary ergonovine provocation tests were consecutively enrolled and classified into two groups: the VSA group (n=147, 32.0%) and non-VSA group (n=313, 68.0%). The subjects were classified into 3 subgroups (tertiles) according to the baseline level of RDW assessed before the angiographic provocation test. RESULTS: The VSA group had a higher RDW than the non-VSA group (12.9±0.8% vs. 12.5±0.7%, p=0.013). The high RDW level demonstrated an independent association with the high incidence of VSA [second tertile: hazard ratio (HR) 1.96 (1.13-2.83), third tertile: HR 2.33 (1.22-3.47), all p<0.001]. Moreover, the highest RDW tertile level had a significant association with the prevalence of the mixed-type coronary spasm [HR 1.29 (1.03-1.59), p=0.037]. CONCLUSION: The high level of RDW was significantly associated with the prevalence of VSA and the high-risk angiographic subtype of coronary spasm, suggesting that a proactive clinical investigation for VSA could be valuable in Korean patients with an elevated RDW.

Microalbuminuria is Independently Associated with Arterial Stiffness and Vascular Inflammation but not with Carotid Intima-Media Thickness in Patients with Newly Diagnosed Type 2 Diabetes or Essential Hypertension

The association between microalbuminuria (MAU) and the indices of macrovascular complication in patients with newly diagnosed type 2 diabetes (D) or essential hypertension (H) was evaluated. Total 446 patients were classified into four groups according to the urinary albumin-to-creatinine ratio: MAU-D (n = 104), normoalbuminuria (NAU)-D (n = 114), MAU-H (n = 116), and NAU-H (n = 112). The indices of macrovascular complication including arterial stiffness evaluated by pulse-wave-velocity (PWV), carotid intima-media thickness (IMT), and vascular inflammation marked by high-sensitivity C-reactive protein (hsCRP) were assessed. PWV, IMT, and hsCRP were higher in patients with MAU than in those with NAU in both diabetes and hypertension groups. In both MAU-D and MAU-H groups, PWV and hsCRP levels were positively correlated with MAU level (MAU-D: r = 0.47, 0.41, MAU-H: r = 0.36, 0.62, respectively, P < 0.05). Additionally, PWV and hsCRP were independent factors predicting MAU (diabetes group: OR 1.85, 1.54, hypertension group: OR 1.38, 1.51, respectively, P < 0.001), but not IMT. MAU is independently associated with arterial stiffness and vascular inflammation but not with IMT in patients with newly diagnosed type 2 diabetes or essential hypertension, which emphasizes the importance of proactive clinical investigations for atherosclerotic complications in patients with MAU, even in newly diagnosed diabetes or hypertension.

The Effect of Cilostazol on Stent Thrombosis After Drug-Eluting Stent Implantation

BACKGROUND AND OBJECTIVES: Placement of drug-eluting stents (DES) can be complicated by stent thrombosis; prophylactic antiplatelet therapy has been used to prevent such events. We evaluated the efficacy of cilostazol with regard to stent thrombosis as adjunctive antiplatelet therapy. SUBJECTS AND METHODS: A total of 1,315 patients (846 males, 469 females) were prospectively enrolled and analyzed for the frequency of stent thrombosis. Patients with known risk factors for stent thrombosis, except diabetes and acute coronary syndrome, were excluded from the study. All patients maintained antiplatelet therapy for at least six months. To evaluate the effects of cilostazol as another option for antiplatelet therapy, triple antiplatelet therapy (aspirin+clopidogrel+cilostazol, n=502) was compared to dual antiplatelet therapy (aspirin+clopidogrel, n=813). Six months after stent placement, all patients received only two antiplatelet drugs: treatment either with cilostazol+aspirin (cilostazol group) or clopidogrel+aspirin (clopidogrel group). There were 1,033 patients (396 in cilostazol group and 637 in clopidogrel group) that maintained antiplatelet therapy for at least 12 months and were included in this study. Stent thrombosis was defined and classified according to the definition reported by the Academic Research Consortium (ARC). RESULTS: defined and classified according to the definition reported by the Academic Research Consortium (ARC). RESULTS: During follow-up (561.7+/-251.4 days), 15 patients (1.14%) developed stent thrombosis between day 1 to day 657. Stent thrombosis occurred in seven patients (1.39%) on triple antiplatelet therapy and four patients (0.49%) on dual antiplatelet therapy (p=NS) within the first six months after stenting. Six months and later, after stent implantation, one patient (0.25%) developed stent thrombosis in the cilostazol group, and three (0.47%) in the clopidogrel group (p=NS). CONCLUSION: During the first six months after DES triple antiplatelet therapy may be more effective than dual antiplatelet therapy for the prevention of stent thrombosis. However, after the first six months, dual antiplatelet treatment, with aspirin and cilostazol, may have a better cost benefit ratio for the prevention of stent thrombosis.

Significance of Inflammatory Markers in Diabetic Patients with Stable Coronary Artery Disease

BACKGROUND/AIMS: Patients with diabetes are prone to coronary artery disease (CAD); however, the majority of diabetic patients show normal coronary arteries. We examined differences in the clinical aspects of diabetic patients with insignificant and with significant stenosis of the coronary artery. METHODS: A total of 418 consecutive diabetic patients with stable angina who had undergone coronary angiography from January 2004 to March 2007 were included in this study. Patients were subdivided into control and CAD groups and then clinical characteristics and CAD-associated factors were evaluated. RESULTS: A total of 92 (22%) patients were assigned to the control group and 326 (78%) patients were assigned to the CAD group. Using univariate regression analysis, we found that patients with CAD were significantly older (control vs. CAD; 59+/-21 vs. 64.7+/-33.7, years, p<0.001), had a longer duration of diabetes (8.2+/-21.8 vs. 10.2+/-29.8, years, p=0.027), higher titers of high sensitivity C-reactive protein (hsCRP; 0.3+/-6.79 vs. 0.9+/-12.6, mg/dL, p=0.015), and increased hemoglobin A1c (HbA1c) levels (7.1+/-3.8 vs. 7.5+/-4.8, %, p=0.007) compared to control patients. Multivariate regression analysis showed that only differences in age, hsCRP, and HbA1c were statistically significant. When patients were subdivided into groups based on hsCRP levels (208 patients in the low group [49.8%], 210 patients in the high group [50.2%]), we found that patients with higher hsCRP levels showed more frequent multivessel disease. CONCLUSIONS: In diabetic patients, age, hsCRP, and HbA1c were associated with stable CAD. Among these factors, hsCRP levels were significantly correlated with multivessel involvement in diabetic CAD. Therefore, high hsCRP levels may be a strong predictor for atherosclerotic progression of the coronary arteries in diabetic patients, suggesting that regular screening tests should be performed.

Erratum: The usefulness of ischemia modified albumin as an early ischemic marker to detect coronary artery disease in patients with chest pain presenting to the emergency department / 대한내과학회지

No abstract available.

Utilization Pattern of Drug-Eluting Stents and Prognosis of Patients Who Underwent Drug-Eluting Stenting Compared with Bare Metal Stenting in the Real World

BACKGROUND AND OBJECTIVES: Currently, the drug-eluting stent (DES) has been widely used because of its excellent clinical outcome. We compared the utilization patterns and clinical outcomes between the DES and the bare metal stent (BMS) in the real world. SUBJECTS AND METHODS: We retrospectively reviewed the stent registry at the Catholic Medical Center between January 2002 and October 2004. There were 1120 patients treated with DES (n=1837) who were compared to 910 patients who received BMS implantation (n=1238). RESULTS: Patients with de novo lesions in the DES group more frequently had multivessel disease and received a greater number of stents than those in BMS group (p<0.001). The mean diameter of inserted stents was smaller in the DES group (p<0.001). The follow-up rate for clinical and angiographic evaluations at 6 months after stenting was 91% and 65% (n=592) in the BMS group and 90% and 74% (n=829) in the DES group, respectively. The rate of major adverse cardiac events (death, nonfatal myocardial infarction, or target vessel revascularization) at 6 months was 7.3% in the DES group and 17.5% in the BMS group (p<0.001). The rates of target vessel revascularization in the DES group and in the BMS group were 4.2% and 12.9%, respectively (p<0.001). CONCLUSION: The patients in the DES group had longer length, smaller diameter and higher number of placed stents, compared to the BMS group. The rates of revascularization and major adverse cardiac events in the DES group were lower than those in the BMS group.

Prospective, Randomized, Preliminary Clinical Trial with Low-Molecular-Weight Heparin or Unfractionated Heparin as Periprocedural Anticoagulant during Elective Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: LMWH as a periprocedural anticoagulant during PCI has not yet been extensively studied. The aim of this study is to compare the clinical outcomes of enoxaparin to those of unfractionated heparin (UH) during elective PCI. SUBJECTS AND METHODS: The eligible patients were randomized 1:1 into two treatment arms, either a single IV bolus of enoxaparin (75 IU/kg) or UH (100 IU/kg). The patients who had received any anticoagulants at therapeutic doses were excluded in this study. Data on patient characteristics, angiographic complications, laboratory variables and the in-hospital and 1-month clinical outcomes were compared between the two groups. RESULTS: Of the 139 patients enrolled in this study, 68 received enoxaparin and 71 received UH. The patients' demographic and angiographic characteristics (gender, weight, creatinine and the PCI target vessel) were not different except for age between the groups. Multi-vessel angioplasty was performed in 59 (42.4%) patients. At least one stent was implanted in 130 (93.5%) patients. The sheath was removed immediately after PCI, except for one case, and then a collagen plug was applied in all the cases. There were no significant differences in angiographic complications like no reflow, thrombus at the treated lesion site, occlusion of collateral branches, distal embolism, dissection, coronary rupture or abrupt closure. Cardiac markers including CK (6 [8.8%] in the LMWH group vs 8 [11.3%] in the UH group), CK-MB (6 [8.8%] vs 8 [11.3%], respectively), and troponin-I (6 [8.8%] vs 10 [14.1%], respectively) were slightly increased after PCI compared to the last value obtained before the procedure in both groups, but the differences were not statistically significant. One patient in the enoxaparin arm and 2 patients in the UH arm developed NSTEMI during their admission. Four patients from the UH arm and 3 from the enoxaparin arm experienced hematoma at the puncture site. After discharge, no other events were reported at the 1-month follow-up. CONCLUSION: The use of enoxaparin (75 IU/kg) during elective PCI was effective and safe as using UH. Enoxaparin could be used like UH as a periprocedural anticoagulant in the elective PCI setting.

Prospective, Randomized, Preliminary Clinical Trial with Low-Molecular-Weight Heparin or Unfractionated Heparin as Periprocedural Anticoagulant during Elective Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: LMWH as a periprocedural anticoagulant during PCI has not yet been extensively studied. The aim of this study is to compare the clinical outcomes of enoxaparin to those of unfractionated heparin (UH) during elective PCI. SUBJECTS AND METHODS: The eligible patients were randomized 1:1 into two treatment arms, either a single IV bolus of enoxaparin (75 IU/kg) or UH (100 IU/kg). The patients who had received any anticoagulants at therapeutic doses were excluded in this study. Data on patient characteristics, angiographic complications, laboratory variables and the in-hospital and 1-month clinical outcomes were compared between the two groups. RESULTS: Of the 139 patients enrolled in this study, 68 received enoxaparin and 71 received UH. The patients' demographic and angiographic characteristics (gender, weight, creatinine and the PCI target vessel) were not different except for age between the groups. Multi-vessel angioplasty was performed in 59 (42.4%) patients. At least one stent was implanted in 130 (93.5%) patients. The sheath was removed immediately after PCI, except for one case, and then a collagen plug was applied in all the cases. There were no significant differences in angiographic complications like no reflow, thrombus at the treated lesion site, occlusion of collateral branches, distal embolism, dissection, coronary rupture or abrupt closure. Cardiac markers including CK (6 [8.8%] in the LMWH group vs 8 [11.3%] in the UH group), CK-MB (6 [8.8%] vs 8 [11.3%], respectively), and troponin-I (6 [8.8%] vs 10 [14.1%], respectively) were slightly increased after PCI compared to the last value obtained before the procedure in both groups, but the differences were not statistically significant. One patient in the enoxaparin arm and 2 patients in the UH arm developed NSTEMI during their admission. Four patients from the UH arm and 3 from the enoxaparin arm experienced hematoma at the puncture site. After discharge, no other events were reported at the 1-month follow-up. CONCLUSION: The use of enoxaparin (75 IU/kg) during elective PCI was effective and safe as using UH. Enoxaparin could be used like UH as a periprocedural anticoagulant in the elective PCI setting.

The usefulness of ischemia modified albumin as an early ischemic marker to detect coronary artery disease in patients with chest pain presenting to the emergency department / 대한내과학회지

BACKGROUND: A diagnosis of coronary artery disease (CAD) in the early phase of acute chest pain is often difficult in an emergency department (ED) due to the lower sensitive ECG and delayed expression of the cardiac necrosis markers. Ischemia modified albumin (IMA) has recently been reported to be an early sensitive biochemical marker of ischemia. The aim of this study was to evaluate the diagnostic value of IMA in patients with suspected CAD and less sensitive ECG/delayed cardiac necrosis markers. METHODS: 100 consecutive patients (mean age: 5413 years, male: 66%) presenting to the ED with suspected CAD and chest pain within 6 hours of chest pain were enrolled in this study. An ECG check and blood sampling for IMA and CK-MB, cardiac troponin-T (TnT) were done within 1 hour at the ED. The diagnosis of CAD was based upon the clinical findings, results of serial ECG/TnT and coronary angiography. The ideal cutoff value of IMA for CAD was calculated by the Receiver Operator Characteristic (ROC) curve analysis. RESULTS: CAD including acute coronary syndrome was diagnosed in 69/100 (69%). The optimum diagnostic cutoff point for the IMA levels in these study populations was found by ROC analysis to be 99.5 U/mL. The ROC curve area for the IMA test was 0.901 (95% confidential interval, 0.840-0.961, p=0.001). The IMA levels >99.5 U/mL demonstrated a sensitivity of 86%, specificity of 81%, positive predictive value of 90% and negative predictive value of 74% for the diagnosis of CAD. The combination of IMA-ECG-CKMB/TnT increased the sensitivity for detecting ischemia to 94%, with a negative predictive value of 85%. IMA is a highly sensitive with a high negative predictive value, and might improve the utility of standard biomarkers for CAD. CONCLUSIONS: IMA might be a useful ischemic marker of coronary artery disease in patients presenting within 6 hours after the onset of chest pain.

Comparison of the Long-Term Prognosis between Coronary Vasospasm and Intermediate Vasoconstriction Induced by the Administration of Acetylcholine

BACKGROUND AND OBJECTIVES: The degree of coronary vasoconstriction induced by acetylcholine administeration can vary. We compared the prognosis between coronary vasospasm and intermediate vasoconstriction, which were both induced by acetylcholine administration. SUBJECTS AND METHODS: The subjects were 156 patients with the coronary vasospasm or intermediate vasoconstriction, as observed on the acetylcholine provocation tests that were performed from January, 2000 to January, 2004. The patients with a spasm showing greater than 90% reduction of vessel diameter along with chest pain or ST changes or both were classified as having 'strong positive vasospasm' (n=113). The patients with 70-90% reduction of diameter were classified as having 'intermediate vasoconstriction' (n=43). The mortality, frequency of chest pain and clinical events were then analyzed. RESULTS: A smoking history (p<0.001) and multivessel involvement (p=0.02) were more frequent in the strong positive group. We compared the mortality and clinical events due to chest pain during the average 26.4+/-14.1 months of follow-up. There were 5 patients (4.4%) who incurred cardiac death in the strong positive group as compared with none in the intermediate group. The total clinical events were more frequent in the strong positive group (p<0.001). Also, the strong positive group showed a significantly higher frequency of chest pain (p<0.001). CONCLUSION: The long-term prognosis of the intermediate vasoconstriction was better than that of strong positive vasospasm. Thus, the intermediate vasoconstriction must be ruled out by strict application of the positive criteria for the acetylcholine provocation test.

A Case of Gastrointestinal Bleeding Caused by Dieulafoy-like Lesions of the Stomach and Rectum in a Patient with Chronic Renal Failure / 대한소화기내시경학회지

Dieulafoy's lesion is a very rare cause of gastrointestinal bleeding that occurs after rupture of an exposed submucosal artery. The majority of lesions are found in the stomach, but rarely it has also been identified in the duodenum, small bowel, colon and rectum. We describe a 78-year-old female with chronic renal failure who presented with melena and was subsequently found to have a Dieufaloy-like lesion in the stomach. The bleeding was successfully managed by endoscopic hemoclipping. During the follow-up, massive gastrointestinal bleeding was developed by a Dieulafoy-like lesion in the rectum. This lesion was managed by endoscopic band ligation, but there was recurrent bleeding from the ulcer site. The ulcer site was locally excised and primary closure was carried out.

A case of acquired hemophilia detected after influenza vaccination / 대한내과학회지

Acquired hemophilia is a rare disorder associated with development of factor VIII inhibitors. Acquired inhibitors against factor VIII in nonhemophilic patients are associated with various conditions, including autoimmune diseases, malignancies, the postpartum state, drug reactions. In this report, we described the case of a 65 year-old female, who developed generalized petechiae and gross hematuria due to the appearance of inhibitors against factor VIII following influenza vaccination. She was treated with steroid and cyclophosphamide but retroperitoneal hemorrhage developed, and she died.

Primary Hyperaldosteronism with Increased Plasma Renin Activity due to Secondary Hypertensive Renal Impairment / 대한내분비학회지

An increased plasma aldosterone concentration, with suppressed plasma renin activity (PRA), is an abnormal finding in primary hyperaldosteronism. A suppressed PRA is caused by aldosterone- dependent sodium retention and extracellular volume expansion. A case of primary hyperaldosteronism, due to adenoma, with increased PRA, was observed. An adrenalectomy and intraoperative renal biopsy was performed. In our patient, histologically proven renal arteriosclerosis was the probable cause of the escape of the PRA from the suppression by an aldosterone-producing adenoma. Normal blood pressure was not attained after the adrenalectomy. However, the blood pressure was then controlled by small doses of antihypertensive drug before resection of the tumor. In this case, the patient was treated with spironolactone, but the blood pressure was not correctly controlled. After the adrenalectomy, the blood pressure was well controlled with smaller dose of calcium channel blockers. So, an early adrenalectomy may be beneficial as soon as the diagnosis of an aldosterone-producing adenoma is confirmed, even in patients with hypertensive nephrosclerosis.

Superior Vena Cava Thrombosis Treated Successfully by Percutaneous Insertion of Metallic Stent in a Patient with Behcet's Disease / 대한류마티스학회지

The venous thrombosis is the most common vascular event in Behcet's disease. Among the thrombotic complications of Behcet's disease, thrombosis in superior vena cava is rare, but once it happens, it may be life-threatening. In this report, we describe a case of 45-year-old female with Behcet's disease complicated by the superior vena cava thrombosis, which was treated successfully with the operation and then endovascular stenting. This case shows that endovascular stent may be one of good strategies for the management of vascular complication in Behcet's disease.

A Case of Type 1 Renal Tubular Acidosis Accompanying Renal Stone and Nephrocalcinosis Caused by Hypocitraturia / 대한신장학회잡지

Renal stone and nephrocalcinosis are common clinical manifestations of type 1 renal tubular acidosis. In normal state, citrate plays the most critical role in suppressing stone formation as it combines with calcium. In type 1 RTA, increased reabsorption of citrate in proximal tubule results in low citrate excretion, which precipitates renal stone formation. We report a case of type 1 RTA accompanying renal stone and nephrocalcinosis caused by hypocitraturia. A 16-year-old male patient who had renal stone and nephrocalcinosis showed hypocitraturia. Incomplete type 1 RTA was proved as the cause of hypocitraturia by bicarbonate and ammonium loading test in the patient.

Immunohistochemieal Study of Expression of nm23 and CD44 Protein in

Gene expression of the nm23 and CD44 has been investigated in number of tumors, in cluding colorectal cancer, breast cancer, and hepatocellular carcinoma. This study was conducted to clarify the association between nm23 and CD44 protein expression and metastatic potential in human colorectal cancer. To elucidate the role of the nm23 and CD44 in human colorectal cancer, sections of formalin-fixed, paraffin-embeded tissue from 59 primary colorectal cancer were stained immunohistochemically against nm23 and CD44 proteins. Expression of the nm23 protein is not significantly correlate with Dukes'stage and recurrence. However, the expression of the CD44 protein is significantly higher in Dukes stage C as comparing with stage B.