A case of minimal change nephrotic syndrome complicated by Kimura disease treated with rituximab.

Kimura disease (eosinophilic granuloma of the soft tissue) is a benign granulomatous disease complicated by nephrotic syndrome. Herein, we report a case of recurrent minimal change nephrotic syndrome (MCNS) complicated by Kimura disease that was successfully treated with rituximab. A 57-year-old man presented to our hospital with relapsed nephrotic syndrome with worsening swelling of the right anterior ear and elevated serum IgE. MCNS was diagnosed on renal biopsy. Treatment with 50 mg of prednisolone rapidly placed the patient in remission. Therefore, RTX 375 mg/m2 was added to the treatment regimen, and steroid therapy was tapered. Early steroid tapering was successful, and the patient is currently in remission. In this case, the nephrotic syndrome flare-up was accompanied by worsening Kimura disease. Rituximab reduced the worsening of symptoms related to Kimura disease, including head and neck lymphadenopathy and elevated IgE levels. Kimura disease and MCNS may share a common IgE-mediated type I allergic condition. Rituximab effectively treats these conditions. In addition, rituximab suppresses Kimura disease activity in patients with MCNS, enables early tapering of steroids, and reduces the total dose of steroids.

Absolute configuration of tetrandrine and isotetrandrine influences their anti-proliferation effects in human T cells via different regulation of NF-κB.

Natural compound tetrandrine was reported to inhibit the proliferation of T cells by inhibiting activation of NF-κB. Chemically, isotetrandrine differs from tetrandrine only in the stereochemistry at the chiral centers. The present study aimed to compare their anti-proliferation effects on human T cells with a focus on NF-κB. The IC50 values of tetrandrine against MOLT-4 cells, MOLT-4/DNR cells, and concanavalin A-activated peripheral blood mononuclear cells of healthy subjects and dialysis patients were 4.43 ± 0.22, 3.62 ± 0.22, 1.91 ± 0.22 and 3.03 ± 0.28 µM, respectively. Whereas, the IC50 values of isotetrandrine against the above immune cells were 2.19 ± 0.27, 2.28 ± 0.33, 1.29 ± 0.14 and 1.55 ± 0.26 µM, respectively. The inhibitory effect of isotetrandrine against the proliferation of T cells was stronger than that of tetrandrine significantly (p < 0.05). Molecular mechanism investigation showed that 10 µM of isotetrandrine largely decreased the expression of p-NF-κB and NF-κB in both MOLT-4 and MOLT-4/DNR T cells (p < 0.05), whereas 10 µM of tetrandrine slightly inhibited the phosphorylation of p-NF-κB with little influence on the expression of NF-κB. Taken together, absolute configurations of tetrandrine and isotetrandrine are suggested to influence on their anti-proliferation effects in human T cells via different regulation of NF-κB.

Cesarean section predominantly affects right ventricular diastolic function during the early transitional period.

BACKGROUND: Although the mode of delivery is well known to affect pulmonary function, the effects of a cesarean delivery on postnatal changes in cardiac mechanics have not been clearly defined. METHODS: To evaluate whether delivery mode influences cardiac function in the early transitional period, 42 infants delivered by cesarean section (CS) and 110 by vaginal delivery (VD) were enrolled, and they underwent serial echocardiography at 0, 1, 2, and 5 days of age. Longitudinal changes in ejection fraction (EF), fractional area change (FAC), mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), Tei index, ratio of peak early diastolic flow velocity (E) to peak early diastolic annular velocity (e') (E/e'), and deceleration time (DcT) were compared between the two groups. RESULTS: FAC and DcT of both ventricles increased during the first week, whereas Tei index of each chamber decreased irrespective of delivery mode. E/e's of both ventricles were significantly higher and MAPSE was significantly lower in the CS than VD group throughout the observation period. After adjustment for the effects of birth weight, gestational age, and oxygen administration by multivariate analysis, right ventricular E/e', which reflects diastolic function of the right ventricle, was most affected by delivery mode. CONCLUSION: CS affected diastolic function of the right ventricle in the 2nd day after giving birth and did not persist. Delayed adaptation of the neonatal myocardium and/or persistence of pulmonary hypertension might explain the hemodynamic changes in neonates born by CS.

Vitamin K1 and Vitamin K2 immunopharmacological effects on the peripheral lymphocytes of healthy subjects and dialysis patients, as estimated by the lymphocyte immunosuppressant sensitivity test.

WHAT IS KNOWN AND OBJECTIVE: Renal transplant recipients receive immunosuppressive therapy to prevent acute rejection. We evaluated the immunopharmacological efficacy of vitamin K1 (VK1) and vitamin K2 (VK2) on T-cell mitogen-activated-peripheral lymphocytes of dialysis patients and healthy subjects. METHODS: The effects of VK1 and VK2 on the T-cell mitogen-stimulated proliferation of peripheral blood mononuclear cells (PBMCs) obtained from 12 healthy subjects and 12 dialysis patients were estimated. Seven cytokines produced from the activated PBMCs were measured by a BD Cytometric Beads Array kit. Regulatory T cells (Tregs) in PBMCs were analysed as CD4 + CD25 + FoxP3 +  lymphocytes by flow cytometry. RESULTS: VK2 dose-dependently suppressed the concanavalin A-stimulated proliferation of PBMCs from healthy subjects and dialysis patients, whereas VK1 had no significant effect on the PBMC proliferation. VK1 and VK2 did not influence the production of most of the Th1/Th2/Th17 cytokines from the activated PBMCs of these subjects, although VK2 increased the IL-4 production from PBMCs of healthy subjects. The Treg percentages in the PBMCs of dialysis patients were markedly decreased compared to healthy PBMCs after the treatment with relatively low concentrations of VK2. WHAT IS NEW AND CONCLUSION: The present data suggest that VK2 has immunosuppressive efficacy. VK2 may enhance the immunosuppressive efficacies of glucocorticoids while preventing osteoporosis caused by glucocorticoids.

Immunosuppressive efficacy of tetrandrine combined with methylprednisolone against mitogen-activated peripheral blood mononuclear cells of haemodialysis patients.

Immunosuppressive therapy for prevention of acute rejection episode occasionally causes serious adverse effects, and thus it is important to develop new therapeutic approach for renal transplant recipients. This study evaluated the immunosuppressive pharmacodynamics of tetrandrine (TET) and/or methylprednisolone (MP) in haemodialysis patients in vitro by using the peripheral blood mononuclear cells (PBMCs) isolated from whole blood of haemodialysis patients. The median (range) of MP IC50 values against the proliferation of patients PBMCs was 7.04 (2.30-500.00) ng/mL. In contrast, the median (range) of MP IC50 values against the proliferation of healthy PBMCs was 4.44 (3.19-5.08) ng/mL. The median (range) of TET IC50 values against the proliferation of patients PBMCs was 1.61 (1.04-4.79) µmol/L. Lower concentrations of TET (0.3-300 nmol/L) were able to decrease the IC50 values of MP and thus potentiate the MP immunosuppressive effect on patient PBMCs. The median (range) of MP IC50 values in combination with 0.3, 3, 30, and 300 nmol/L TET were 0.92 (0.49-8.39), 2.10 (0.45-20.00), 0.35 (0.092-1.05), and 0.14 (0.05-6.78) ng/mL, respectively. TET potentiates the MP immunosuppressive pharmacodynamics and thus, it was possible to use the combination of MP and TET to attenuate MP side effects. There were significant correlations between the IC50 values of TET and stimulation indices (P=0.04, r=.58), the IC50 values of TET and the haemodialysis periods (P=0.04, r=.57), or the IC50 values of MP combined with 0.3 nmol/L TET and C-reactive protein concentrations (P=0.04, r=.64), respectively.

Evaluation of the Infection Risk in Dialysis and Chronic Kidney Disease Patients Using an ATP Monitoring Assay.

The ATP monitoring assay is a useful biomarker for risk monitoring to detect infection and rejection episodes in transplant recipients. Hemodialysis patients have a higher rate of infectious mortality. Infections in hemodialysis patients are mainly caused by venous catheters, uremia, malnutrition and inflammation. However, the risk of infection episodes has not been evaluated using a lymphocyte ATP monitoring assay in hemodialysis and chronic kidney disease (CKD) patients. We measured the ATP amounts in the peripheral CD4+ cells of CKD (N = 85) and dialysis patients (N = 17) using an "Immuknow" assay kit. These CKD patients were divided, according to kidney disease stage, into G3a, G3b, G4, and G5 groups. The ATP amounts in CD4+ cells of the dialysis patients and each of the CKD groups were compared with healthy subjects. In both the dialysis and CKD patients, the ATP amounts in CD4+ cells were lower than in healthy subjects. Furthermore, there were significant differences in the ATP amounts between healthy subjects and each of the CKD-G3a, CKD-G3b, and CKD-G4 groups (P < 0.05). Patients with CKD-G3a, CKD-G3b and CKD-G4 were evaluated as being at high risk for infection according to the lymphocyte ATP monitoring assay. However, the ATP amounts in the dialysis and CKD-G5 patients did not differ from those in healthy subjects to a statistically significant extent. These results suggest that the ATP amount in the CD4+ cells of these patients with serve renal failure are influenced by dialysis treatment, uremia and/or oxidative stress.

A randomized, placebo-controlled trial of acupuncture in patients with chronic obstructive pulmonary disease (COPD): the COPD-acupuncture trial (CAT).

BACKGROUND: Dyspnea on exertion (DOE) is a major symptom of chronic obstructive pulmonary disease (COPD) and is difficult to control. This study was performed to determine whether acupuncture is superior to placebo needling in improving DOE in patients with COPD who are receiving standard medication. METHODS: Sixty-eight of 111 patients from the Kansai region of Japan who were diagnosed as having COPD and were receiving standard medication participated in a randomized, parallel-group, placebo-controlled trial (July 1, 2006, through March 31, 2009) in which the patients, evaluators, and statistician were unaware of the random allocation. Participants were randomly assigned to traditional acupuncture (real acupuncture group, n=34) or placebo needling (placebo acupuncture group, n=34). Both groups received real or placebo needling at the same acupoints once a week for 12 weeks. The primary end point was the modified Borg scale score evaluated immediately after the 6-minute walk test. Measurements were obtained at baseline and after 12 weeks of treatment. RESULT: After 12 weeks, the Borg scale score after the 6-minute walk test was significantly better in the real acupuncture group compared with the placebo acupuncture group (mean [SD] difference from baseline by analysis of covariance, -3.6 [1.9] vs 0.4 [1.2]; mean difference between groups by analysis of covariance, -3.58; 95% CI, -4.27 to -2.90). Patients with COPD who received real acupuncture also experienced improvement in the 6-minute walk distance during exercise, indicating better exercise tolerance and reduced DOE. CONCLUSION: This study clearly demonstrates that acupuncture is a useful adjunctive therapy in reducing DOE in patients with COPD. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000001277.

Rho-kinase inhibition ameliorates peritoneal fibrosis and angiogenesis in a rat model of peritoneal sclerosis.

BACKGROUND: Peritoneal fibrosis (PF) and angiogenesis are typical morphological changes, leading to loss of peritoneal functions in patients undergoing peritoneal dialysis. The small G protein, Rho, and its downstream effector Rho-kinase have been shown to be involved in the tissue fibrosis process. This study was undertaken to investigate the role of Rho-kinase in the pathogenesis of these alterations. METHODS: PF was induced by intraperitoneal administration of chlorhexidine (CHX) in male rats (CHX group). These rats were treated with a Rho-kinase inhibitor, fasudil (Fas group). Human pleural mesothelial cells, MeT-5A cells, were stimulated by glucose with or without another Rho-kinase inhibitor, Y-27632. RESULTS: Peritoneal damage including peritoneal thickening, fibrous changes, macrophage migration and angiogenesis were evident in the CHX group and were ameliorated in the Fas group. The expression of markers of tissue fibrosis, such as transforming growth factor (TGF)-ß, fibronectin and α-smooth muscle cell actin, were increased in the CHX group and were downregulated by fasudil. Similar results were also seen with an inducer of angiogenesis, vascular endothelial growth factor (VEGF). Rho-kinase was activated in the peritoneum of the CHX group, which was inhibited by fasudil. In MeT-5A cells, high glucose increased TGF-ß expression and VEGF secretion, which were blocked by Y-27632. CONCLUSIONS: The activation of Rho-kinase is involved in peritoneal damage at multiple stages including tissue fibrosis and angiogenesis. The inhibition of Rho-kinase constitutes a novel strategy for the treatment of PF.

Rho and Rho-kinase activity in adipocytes contributes to a vicious cycle in obesity that may involve mechanical stretch.

The development of obesity involves multiple mechanisms. Here, we identify adipocyte signaling through the guanosine triphosphatase Rho and its effector Rho-kinase as one such mechanism. Mice fed a high-fat diet (HFD) showed increased Rho-kinase activity in adipose tissue compared to mice fed a low-fat diet. Treatment with the Rho-kinase inhibitor fasudil attenuated weight gain and insulin resistance in mice on a HFD. Transgenic mice overexpressing an adipocyte-specific, dominant-negative form of RhoA (DN-RhoA TG mice) showed decreased Rho-kinase activity in adipocytes, decreased HFD-induced weight gain, and improved glucose metabolism compared to wild-type littermates. Furthermore, compared to HFD-fed wild-type littermates, DN-RhoA TG mice on a HFD showed decreased adipocyte hypertrophy, reduced macrophage recruitment to adipose tissue, and lower expression of mRNAs encoding various adipocytokines. Lipid accumulation in cultured adipocytes was associated with increased Rho-kinase activity and increased abundance of adipocytokine transcripts, which was reversed by a Rho-kinase inhibitor. Direct application of mechanical stretch to mature adipocytes increased Rho-kinase activity and stress fiber formation. Stress fiber formation, which was also observed in adipocytes from HFD-fed mice, was prevented by Rho-kinase inhibition and in DN-RhoA TG mice. Our findings indicate that lipid accumulation in adipocytes activates Rho to Rho-kinase (Rho-Rho-kinase) signaling at least in part through mechanical stretch and implicate Rho-Rho-kinase signaling in inflammatory changes in adipose tissue in obesity. Thus, inhibition of Rho-Rho-kinase signaling may provide a therapeutic strategy for disrupting a vicious cycle of adipocyte stretch, Rho-Rho-kinase signaling, and inflammation of adipose tissue that contributes to and aggravates obesity.

Kidney-specific overexpression of Sirt1 protects against acute kidney injury by retaining peroxisome function.

Sirt1, a NAD-dependent protein deacetylase, is reported to regulate intracellular metabolism and attenuate reactive oxidative species (ROS)-induced apoptosis leading to longevity and acute stress resistance. We created transgenic (TG) mice with kidney-specific overexpression of Sirt1 using the promoter sodium-phosphate cotransporter IIa (Npt2) driven specifically in proximal tubules and investigated the kidney-specific role of Sirt1 in the protection against acute kidney injury (AKI). We also elucidated the role of number or function of peroxisome and mitochondria in mediating the mechanisms for renal protective effects of Sirt1 in AKI. Cisplatin-induced AKI decreased the number and function of peroxisomes as well as mitochondria and led to increased local levels of ROS production and renal tubular apoptotic cells. TG mice treated with cisplatin mitigated AKI, local ROS, and renal tubular apoptotic tubular cells. Consistent with these results, TG mice treated with cisplatin also exhibited recovery of peroxisome number and function, as well as rescued mitochondrial function; however, mitochondrial number was not recovered. Immunoelectron microscopic findings consistently demonstrated that the decrease in peroxisome number by cisplatin in wild type mice was restored in transgenic mice. In HK-2 cells, a cultured proximal tubule cell line, overexpression of Sirt1 rescued the cisplatin-induced cell apoptosis through the restoration of peroxisome number, although the mitochondria number was not restored. These results indicate that Sirt1 overexpression in proximal tubules rescues cisplatin-induced AKI by maintaining peroxisomes number and function, concomitant up-regulation of catalase, and elimination of renal ROS levels. Renal Sirt1 can be a potential therapeutic target for the treatment of AKI.

[Successful treatment of small cell lung cancer with secondary immune thrombocytopenic purpura].

Chest CT on admission of a 58-year-old woman with bloody sputum showed a mass shadow at the hilum of the right lung suggesting invasion to the mediastinum, and contralateral mediastinal lymph node (#6) metastasis. Bronchial brush cytology yielded a diagnosis of small cell lung cancer (SCLC). The clinical stage was T4N3M0, stage IIIB, limited disease (LD). On admission, her platelet count was only 40 x 10(3)/microl. Blood biochemistry and bone marrow puncture revealed immune thrombocytopenic purpura (ITP). We speculated that she had secondary ITP (ITP-like syndrome) associated with cancer. Only 11 cases of lung cancer with secondary ITP have ever been reported, 4 cases of which attained complete response of cancer and complete remission of ITP by anti-cancer therapy. Therapeutic procedures employed were surgery in 3 cases of adenocarcinoma and a high dose chemotherapy (HDC) with autologous peripheral blood stem cell transplantation (APBSCT) in 1 case of SCLC. In the present case, concurrent chemoradiotherapy (four cycles of cisplatin/etoposide (PE) combined with 45Gy of thoracic radiotherapy) was performed, which resulted in a complete response of SCLC and a complete remission of the secondary ITP. This is apparently the first report of successful treatment of SCLC with secondary ITP by standard chemoradiotherapy. In a SCLC patient with ITP-like symptoms, treatment for SCLC may simultaneously resolve the ITP-like symptoms.

[A case of malignant pleural mesothelioma with gastrointestinal metastases which were diagnosed by endoscopic biopsy].

A 63-year-old man who had general malaise and dyspnea on effort, was admitted to our hospital. Chest X-ray film on admission showed left pleural effusion. Chest and abdominal CT after left chest drainage revealed left pleural thickening, mediastinal lymph node swelling, multiple lung nodules, osteolytic change of the left 4th rib, and multiple liver tumors. Right pleural effusion and ascites was also recognized. Cytology of the left pleural effusion suggested malignant mesothelioma. He had a skin tumor on his anterior chest. Biopsy revealed metastasis of malignant epithelioid mesothelioma. Upper gastrointestinal endoscopy showed a duodenal tumor and colonoscopy showed a cecal erosion. Endoscopic biopsy revealed metastases of malignant mesothelioma identical to the skin tumor. Because of the left pleural thickening, the primary site was considered to be in the left pleura. Here we report a case of malignant pleural mesothelioma (MPM) with multiple distant metastases to the duodenum, cecum, skin, lung, liver, and rib. Gastrointestinal metastases of MPM detected by endoscopic biopsy are very rare. Only one case of cecal metastasis has ever been reported.

ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected].

Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2) that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.

Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression.

NAD(+)-dependent protein deacetylase Sirt1 regulates cellular apoptosis. We examined the role of Sirt1 in renal tubular cell apoptosis by using HK-2 cells, proximal tubular cell lines with or without reactive oxygen species (ROS), H(2)O(2). Without any ROS, Sirt1 inhibitors enhanced apoptosis and the expression of ROS scavenger, catalase, and Sirt1 overexpression downregulated catalase. When apoptosis was induced with H(2)O(2), Sirt1 was upregulated with the concomitant increase in catalase expression. Sirt1 overexpression rescued H(2)O(2)-induced apoptosis through the upregulation of catalase. H(2)O(2) induced the nuclear accumulation of forkhead transcription factor, FoxO3a and the gene silencing of FoxO3a enhanced H(2)O(2)-induced apoptosis. In conclusion, endogenous Sirt1 maintains cell survival by regulating catalase expression and by preventing the depletion of ROS required for cell survival. In contrast, excess ROS upregulates Sirt1, which activates FoxO3a and catalase leading to rescuing apoptosis. Thus, Sirt1 constitutes a determinant of renal tubular cell apoptosis by regulating cellular ROS levels.

Hepatic de novo lipogenesis is present in liver-specific ACC1-deficient mice.

Acetyl coenzyme A (acetyl-CoA) carboxylase (ACC) catalyzes carboxylation of acetyl-CoA to form malonyl-CoA. In mammals, two isozymes exist with distinct physiological roles: cytosolic ACC1 participates in de novo lipogenesis (DNL), and mitochondrial ACC2 is involved in negative regulation of mitochondrial beta-oxidation. Since systemic ACC1 null mice were embryonic lethal, to clarify the physiological role of ACC1 in hepatic DNL, we generated the liver-specific ACC1 null mouse by crossbreeding of an Acc1(lox(ex46)) mouse, in which exon 46 of Acc1 was flanked by two loxP sequences and the liver-specific Cre transgenic mouse. In liver-specific ACC1 null mice, neither hepatic Acc1 mRNA nor protein was detected. However, to compensate for ACC1 function, hepatic ACC2 protein and activity were induced 1.4 and 2.2 times, respectively. Surprisingly, hepatic DNL and malonyl-CoA were maintained at the same physiological levels as in wild-type mice. Furthermore, hepatic DNL was completely inhibited by an ACC1/2 dual inhibitor, 5-tetradecyloxyl-2-furancarboxylic acid. These results strongly demonstrate that malonyl-CoA from ACC2 can access fatty acid synthase and become the substrate for the DNL pathway under the unphysiological circumstances that result with ACC1 disruption. Therefore, there does not appear to be strict compartmentalization of malonyl-CoA from either of the ACC isozymes in the liver.

Pulmonary infection of Mycobacterium avium-intracellulare complex with simultaneous organizing pneumonia.

A 67-year-old woman presented high-grade fever and dyspnea. Sputum culture confirmed Mycobacterium avium-intracellulare complex (MAC). Transbronchial lung biopsies revealed organizing pneumonia (OP) that was rapidly improved with corticosteroid. Five months after onset, a nodule emerged in the right lung. Although MAC was confirmed, the lesion was deemed too small to merit anti-mycobacterial chemotherapy. Four months later, diffuse infiltrates developed on chest X-ray. Bronchoalveolar lavage study identified MAC and exhibited OP patterns. We commenced antimycobacterial chemotherapy. The infiltrates almost completely improved within a month without corticosteroid.

ABCG2 confers resistance to indolocarbazole compounds by ATP-dependent transport.

The ABC half-transporter, ABCG2, is known to confer resistance to chemotherapeutic agents including indolocarbazole derivatives. MCF7 cells were introduced by either wild type ABCG2 (ABCG2-482R) or mutant ABCG2 (-482T), whose amino acid at position 482 is substituted to threonine from arginine, and their cross-resistance pattern was analyzed. Although this amino acid substitution seems to affect cross-resistance patterns, both 482T- and 482R-transfectants showed strong resistance to indolocarbazoles, confirming that ABCG2 confers resistance to them. For further characterization of ABCG2-mediated transport, we investigated indolocarbazole compound A (Fig. 1) excretion in cell-free system. Compound A was actively transported in membrane vesicles prepared from one of the 482T- transfectants and its uptake was supported by hydrolysis of various nucleoside triphosphates. This transport was inhibited completely by the other indolocarbazole compound, but not by mitoxantrone, implying that the binding site of mitoxantrone or the transport mechanisms for mitoxantrone is different from those of indolocarbazoles. These results showed that ABCG2 confers resistance to indolocarbazoles by transporting them in an energy-dependent manner.

Cystatin-like metastasis-associated protein mRNA expression in human colorectal cancer is associated with both liver metastasis and patient survival.

PURPOSE AND EXPERIMENTAL DESIGN: We previously reported that an increased expression of cystatin-like metastasis-associated protein (CMAP) mRNA is involved in liver-specific metastasis in a mouse model. We also identified its human homologue and showed that the expression of CMAP in various human cancer cell lines correlated with the description of malignancy in these cell lines. However, there is still no information available on the clinical significance of CMAP expression in human cancer specimens. Thus, we studied the CMAP expression levels using a real-time quantitative reverse transcription-PCR for 79 patients with colorectal cancer, including 17 cases with liver metastasis. RESULTS: The mean expression level of CMAP in tumor tissue specimens was significantly higher than in the corresponding normal tissue specimens (P < 0.05). A higher expression of CMAP was significantly correlated with liver metastasis (P < 0.01) as well as with a less differentiated histological type (P < 0.05) of colorectal cancer. An increased expression of CMAP was also identified as the strongest independent factor for liver metastasis based on a multivariate analysis (P < 0.001). Furthermore, the prognosis of the patients with a higher expression of CMAP was significantly worse than those with a lower expression (5-year survival rate; 49.7% and 75.0%, respectively, P = 0.038). CONCLUSIONS: These findings imply that the expression level of CMAP in human cancer may be a new biomarker for both liver metastasis and the patient's outcome.