Nimbolide induced apoptosis by activating ERK-mediated inhibition of c-IAP1 expression in human hepatocellular carcinoma cells.

Nimbolide is one of the major compounds from the leaves and flowers of the neem tree and exhibits antitumor properties on various cancer cells. However, no report has shown that nimbolide induces apoptosis in vitro and in vivo in human hepatocellular carcinoma cells. Our results indicated that it inhibited cell growth in Huh-7 and PLC/PRF/5 cells. We also found that nimbolide induced cell death through the induction of G2/M phase arrest and mitochondrial dysfunction, accompanied by the increased expression of cleaved caspase-7, caspase-9, caspase-3, caspase-PARP, and Bax and decreased expression of Mcl-1 and Bcl-2. A human apoptosis antibody array analysis demonstrated that inhibition of the apoptosis family proteins (XIAP, c-IAP1, and c-IAP2) was one of the major targets of nimbolide. Additionally, nimbolide sustained activation of ERK expression. Moreover, pretreatment with U0126 (MEK inhibitor) markedly abolished nimbolide-inhibited cell viability, induced cell apoptosis, ERK phosphorylation, cleaved caspase-9, caspase-3, cleaved-PARP activation, and increased c-IAP1 expression in Huh-7 cells. An in vivo study showed that nimbolide significantly reduced Huh-7 tumor growth and weight in a xenograft mouse model. This study indicated the antitumor potential of nimbolide in human hepatocellular carcinoma cells.

ß-mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP-2 and MMP-9 expression and activating the ERK and JNK pathways.

ß-mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of ß-mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that ß-mangostin did not induce cytotoxicity in human HCC cells (SK-Hep-1, Huh-7 and HA22T/VGH cells). ß-mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, ß-mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP-2/-9 and invasion by ß-mangostin treatment in Huh-7 cells. In addition, ß-mangostin effectively restored the protein levels and transcription activity of MMP-2 and MMP-9 in siERK or siJNK-transfected Huh-7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of ß-mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC.

Inhibition of pentraxin 3 in glioma cells impairs proliferation and invasion in vitro and in vivo.

Pentraxin 3 (PTX3) is an inflammatory molecule that is involved in immune responses, inflammation, and cancer. Recent evidence suggests that PTX3 plays a critical role in tumor progression; however, its impact on the biological function of gliomas remains unknown. In the present study, immunohistochemical staining showed that patients with high-grade gliomas exhibited increased expression levels of PTX3 compared to those with low-grade gliomas (P < 0.001). Furthermore, knockdown of PTX3 in GBM8401 cells inhibits proliferation, increases p21 protein levels, and decreases cyclin D1 protein levels, resulting in cell cycle arrest at the G0/G1 phase. In addition, knockdown of PTX3 significantly decreases GBM8401 cell migration and invasion through the downregulation of matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) expression. In a GBM8401 xenograft animal model, PTX3 knockdown decreases tumor growth in vivo. In conclusion, PTX3 plays an important role in glioma cell proliferation and invasion, and may thus serve as a novel potential therapeutic target in the treatment of gliomas.

4-Phenylbutyric Acid (4-PBA) and Lithium Cooperatively Attenuate Cell Death during Oxygen-Glucose Deprivation (OGD) and Reoxygenation.

Hypoxia is an important cause of brain injury in ischemic stroke. It is known that endoplasmic reticulum (ER) stress is an important determinant of cell survival or death during hypoxia. However, the signaling pathways and molecular mechanisms involved remain to be studied in more detail. To investigate whether inhibition of ER stress promotes neuroprotection pathways, we applied an in vitro oxygen-glucose deprivation (OGD) followed by reoxygenation model of human SK-N-MC neuronal cell cultures in this study. Our results showed that neuronal cell death was induced in this model during the OGD reoxygenation by the sustained ER stress, but not during OGD phase. However, treatment of the cultures with lithium with the OGD reoxygenation insult did not result in neuroprotection, whereas concomitant treatment of chemical chaperon 4-phenylbutyric acid (4-PBA) provides protective effects in ER stress-exposed cells. Moreover, 4-PBA rescued ER stress-suppressed Akt protein biosynthesis, which works cooperatively with lithium in the activation of Akt downstream signaling by inhibition of autophagy-induced cell death. Taken together, our finding provides a possible mechanism by which 4-PBA and lithium contribute to mediate neuroprotection cooperatively. This result may potentially be a useful therapeutic strategy for ischemic stroke.

MiRNA-221 negatively regulated downstream p27Kip1 gene expression involvement in pterygium pathogenesis.

PURPOSE: MiRNAs are small noncoding RNAs that have been implicated in tumor development. They regulate target gene expression either by mRNA degradation or by translation repression. Activation of ß-catenin has been linked to pterygium progression. Here, we hypothesize that ß-catenin-associated miRNA, miRNA-221, and downstream p27Kip1 gene expression are correlated with the pathogenesis of pterygium. METHODS: We collected 120 pterygial and 120 normal conjunctival samples for this study. Immunohistochemistry and real-time reverse transcription (RT)-PCR were performed to determine ß-catenin protein localization, miR-221, and p27Kip1 gene expression. Pterygium cell line (PECs) cell models were used to confirm the effect of ß-catenin, miR-221, and p27Kip1 gene in the proliferation of pterygium cells. RESULTS: Seventy-two (60.0%) pterygial specimens showed high miR-221 expression levels, which was significantly higher than the control groups (13 of 120, 10.8%, p<0.0001). MiR-221 expression was significantly higher in ß-catenin-nuclear/cytoplasmic-positive groups than in ß-catenin membrane-positive and negative groups (p=0.001). We also found that p27Kip1 gene expression in pterygium was negatively correlated with miR-221 expression (p=0.002). In the clinical association, miR-221 expression was significantly higher in the fleshy and intermediate groups than in the atrophic group (p=0.007). The association of miR-221, p27Kip1 and proliferation of pterygium were also confirmed in the PECs model. CONCLUSIONS: Our study demonstrated that activation of ß-catenin in pterygium may interact with miR-221, resulting in p27Kip1 gene downregulation that influences pterygium pathogenesis.

Expression of protein kinase C α and the MZF-1 and Elk-1 transcription factors in human breast cancer cells.

Recently, our research into hepatocellular carcinoma (HCC) has shown that the transcription factors Myeloid Zinc Finger-1 (MZF-1) and Ets-like-protein 1 are related to protein kinase C alpha (PKCα) expression. The purpose of this study was to determine the correlation of the expression of PKCαwith the expressions of Elk-1 and MZF-1 in various differentiated breast cancer cell lines: MDA- MB-231, Hs57BT, SKBR3, MDA-MB-468 and MCF-7. The malignant potential in the five lines of breast cancer cells was examined by using a cell proliferation/migration/invasion assay and the protein and mRNA levels of PKCα, ElK-1 and MZF-1 were examined by Western blot and RT-PCR analysis, re- spectively. The results showed that there were obvious signs of migration and invasion of cells in MDA- MB-231 and Hs57BT cells, little signs of cell migration and invasion in MDA-MB-468 cells, and no sign in SKBR3 and MCF-7 cells. Moreover, the highest expression levels of PKCα, Elk-1 and MZF-1 were also observed in MDA-MB-231 and Hs57BT cells when compared to the other breast cancer cell lines. These findings confirm that elevated expression of PKCαin breast cancer cells may be correlated with the potential of cell migration and invasion, and suggest an association between the expression of PKCα and the expression of the transcription factors Elk-1 and MZF-1.

Serum cellular apoptosis susceptibility protein is a potential prognostic marker for metastatic colorectal cancer.

Colorectal cancer has high rates of recurrence and metastasis. Many patients with similar histopathological features show significantly different clinical outcomes, and these differences are primarily related to metastases undetected by current diagnostic methods. There is no useful serological marker for metastatic disease. We investigated the cellular apoptosis susceptibility (CSE1L/CAS) protein in comparison with carcinoembryonic antigen (CEA) as a marker for metastatic colorectal cancer. Using serum from 103 patients with stage I, II, III, and IV disease, CSE1L was detected in 36.0% (9 of 25), 57.7% (15 of 26), 71.4% (30 of 42), and 88.9% (8 of 9) of patients, respectively; a pathological CEA level was found in 16.0% (4 of 25), 42.3% (11 of 26), 47.6% (20 of 42), and 77.8% (7 of 9) of patients, respectively; a combined CSE1L/CEA assay was detected in 48.0% (12 of 25), 65.4% (17 of 26), 88.1% (37 of 42), and 100% (9 of 9) of patients, respectively. Lymphatic metastasis is an important predictor of poor prognosis and crucial for determination of therapeutic strategy. Serum CSE1L was detected in 74.5% (38 of 51) of patients with lymph node metastasis, whereas a pathological CEA level was found in only 52.9% (27 of 51) of the same patients (P < 0.001); the combined CSE1L/CEA assay increased sensitivity to 90.2% (46 of 51). Animal experiments showed CSE1L reduction in B16-F10 melanoma cells correlated with decreased metastasis to the colorectal tract in C57BL/6 mice. These results indicate that assay of serum CSE1L may facilitate diagnosis of colorectal cancer lymphatic metastases; furthermore, CSE1L is a possible therapeutic target.

Baicalein inhibits the migration and invasive properties of human hepatoma cells.

Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-ß. In addition, baicalein reduced the phosphorylation levels of PKCα and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo.

Increased cellular apoptosis susceptibility (CSE1L/CAS) protein expression promotes protrusion extension and enhances migration of MCF-7 breast cancer cells.

Microtubules are part of cell structures that play a role in regulating the migration of cancer cells. The cellular apoptosis susceptibility (CSE1L/CAS) protein is a microtubule-associated protein that is highly expressed in cancer. We report here that CSE1L regulates the association of α-tubulin with ß-tubulin and promotes the migration of MCF-7 breast cancer cells. CSE1L was associated with α-tubulin and ß-tubulin in GST (glutathione S-transferase) pull-down and immunoprecipitation assays. CSE1L-GFP (green fluorescence protein) fusion protein experiments showed that the N-terminal of CSE1L interacted with microtubules. Increased CSE1L expression resulted in decreased tyrosine phosphorylation of α-tubulin and ß-tubulin, increased α-tubulin and ß-tubulin association, and enhanced assembly of microtubules. Cell protrusions or pseudopodia are temporary extensions of the plasma membrane and are implicated in cancer cell migration and invasion. Increased CSE1L expression increased the extension of MCF-7 cell protrusions. In vitro migration assay showed that enhanced CSE1L expression increased the migration of MCF-7 cells. Our results indicate that CSE1L plays a role in regulating the extension of cell protrusions and promotes the migration of cancer cells.

An association between BPDE-like DNA adduct levels and CYP1A1 and GSTM1 polymorphisma in pterygium.

PURPOSE: Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), an ultimate metabolite of benzo[a]pyrene, attacks deoxyguanosine to form a BPDE-N2-dG adduct resulting in p53 mutations. Both cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) have been demonstrated to be involved in the metabolism of polycyclic aromatic hydrocarbons. The relationship between BPDE-like DNA adduct levels and CYP1A1 and GSTM1 gene polymorphisms in pterygium is not clear. Therefore, BPDE-like DNA adducts and CYP1A1 and GSTM1 polymorphisms were detected in this study to provide more molecular evidence to understand the cause of BPDE-like DNA adduct formation in pterygium. METHODS: In this study, immunohistochemical staining using a polyclonal antibody on BPDE-like DNA adducts was performed on 103 pterygial specimens. For the analysis of CYP1A1 and GSTM1 polymorphisms, DNA samples were extracted from epithelial cells and then subjected to restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) for the determination of mutation and genotype of CYP1A1 and GSTM1. RESULTS: BPDE-like DNA adducts were detected in 33.0% (34/103) of the pterygium samples. The differences in DNA adduct levels were associated with the genetic polymorphisms of CYP1A1 but not GSTM1. Additionally, the risk of BPDE-like DNA adduct formation for patients with CYP1A1 m1/m2 (C/T) andm2/m2 (T/T) was 9.675 fold higher than that of patients with CYP1A1 m1/m1 (C/C) types (p=0.001, 95% Confidence Interval 2.451-38.185). CONCLUSIONS: Our data provide evidence that the BPDE-like DNA adduct formation in pterygium samples was associated with CYP1A1 polymorphisms.

CyclinD1 protein expressed in pterygia is associated with ß-catenin protein localization.

BACKGROUND: The Wnt (Wg/Wnt) signaling cascade plays an important role in tumorigenesis. Our previous report indicated that aberrant localization of ß-catenin proteins was a feature of pterygia. Therefore, this study aimed to analyze the association of ß-catenin protein and expression of a downstream gene, cyclin D1, in pterygial tissues. METHODS: Using immunohistochemistry, ß-catenin and cyclin D1 protein expression was studied, in 150 pterygial specimens and 30 normal conjunctivas. RESULTS: Seventy-three (48.7%) and 60 (40.0%) pterygial specimens tested positive for ß-catenin and cyclin D1 protein expression, respectively. Cyclin D1protein expression was significantly higher in ß-catenin-nuclear/cytoplasmic positive groups than in ß-catenin membrane positive and negative groups (p < 0.0001). In addition, cyclin D1 expression was significantly higher in the fleshy group than in the atrophic and intermediate groups (p = 0.006). CONCLUSIONS: Our study demonstrated that ß-catenin expressed in nuclei/cytoplasm increases cyclinD1 protein expression, which invokes pterygial cell proliferation.

Feasibility of individualized treatment for hepatitis C patients in the real world.

BACKGROUND AND AIM: Individualized treatment with a combination of peg-interferon and ribavirin for patients with hepatitis C virus (HCV) infection has been validated in randomized controlled clinical trials, but its usefulness in the real world is unknown. The aim of the present study was to assess the feasibility of individualized treatment for HCV patients compared with standard therapy in a real-life clinical setting. METHODS: A total of 253 naïve patients with HCV infection who received peg-interferon and ribavirin combination treatment were analyzed and grouped into one of three clinical settings: (i) infection with genotype non-1 (HCV non-1) and treatment for standard 24 weeks (n = 105; none received an abbreviated therapy); (ii) genotype 1 (HCV-1) and standard therapy for either 24 weeks (n = 71) or 48 weeks (n = 21); and (iii) HCV-1 and individualized treatment (n = 56). The individualized therapy used was an abbreviated 24-week treatment for HCV-1 patients who achieved a rapid virological response, otherwise patients received a 48-week course of treatment. Early termination of treatment at week 16 was recommended for non-responders. RESULTS: A sustained virological response (SVR) was achieved in 83.8% of patients with HCV non-1 infection. Among the HCV-1-infected patients, 53.5% of patients who underwent standard 24-week treatment, 66.7% of patients who underwent standard 48-week treatment, and 64.3% of patients treated by individualized therapy achieved SVR. Patients infected with HCV-1 and treated by individualized therapy had a similar efficacy response compared with the standard 48-week therapy (adjusted odds ratio [OR] 0.765, 95% confidence interval [CI], 0.220-2.659, P = 0.673). Both individualized therapy (adjusted OR 2.855, 95% CI 1.189-6.855, P = 0.019) or standard 48-week treatment (adjusted OR 3.733, 95% CI 1.073-12.986, P = 0.038) had significantly higher odds of SVR compared with HCV-1 patients treated by standard 24-week course. CONCLUSION: Individualized therapy is feasible in the real world, especially for patients with HCV-1 infection.

Presence of secretory cellular apoptosis susceptibility protein in cerebrospinal fluids of patients with intracerebral hemorrhage caused by stroke and neurotrauma.

OBJECTIVE: The blood-brain barrier (BBB) is a specialized structure that separates blood vessels from the central nervous system (CNS) and restricts the entry of biomolecules and cells into the brain. Matrix metalloproteinase-2 (MMP-2) produced by interferon-gamma-activated microglia (brain macrophages) is essential for disrupting the glia limitans of BBB, which is critical for lymphocytes penetration into brain capillaries in various CNS disorders. The cellular apoptosis susceptibility (CSE1L/CAS) protein has been shown to regulate MMP-2 secretion. METHODS: We examined if CSE1L played a role in regulating the progression of intracerebral brain hemorrhage disorders. RESULTS: CSE1L was detected by immunoblotting in cerebrospinal fluids (CSFs) of patients with intracerebral hemorrhage brain disorders, including stroke and neurotrauma. Interferon-gamma treatment induced CSE1L expression and increased the secretions of CSE1L and MMP-2 by U937 macrophages. Moreover, tranfection of U937 macrophages with siRNA that targeted CSE1L inhibited interferon-gamma-induced CSE1L and MMP-2 secretion by U937 macrophages. The numbers of lymphocytes in CSF were correlated with the levels of CSE1L and MMP-2 in patients' CSF. CONCLUSIONS: Our results suggest that CSE1L plays a role in regulating MMP-2-mediated BBB breakdown and it may be a target for control of BBB permeability in intracerebral brain hemorrhage disorders.

Higher prevalence of secretory CSE1L/CAS in sera of patients with metastatic cancer.

Metastatic markers are highly useful diagnostic and prognostic indicators of cancer metastasis. Herein, we report that secretory CSE1L/CAS, a cellular apoptosis susceptibility protein, is a new marker for metastatic cancer. CAS was colocalized with matrix metalloproteinase-2 in vesicles surrounding the outside of MCF-7 cell membranes, and the COOH-terminal domain of CAS was associated with matrix metalloproteinase-2-containing vesicles. Immunohistochemical staining for CAS was positive in the stroma and gland lumens of human metastatic cancer tissues. CAS was also detected in conditioned medium from B16-F10 melanoma cells and more frequently in the sera of patients with metastatic cancer than in sera from patients with primary cancer. Specifically, the prevalence of serum CAS in serum samples from 146 patients was 58.2% (32 of 55), 32.0% (8 of 25), and 12.1% (8 of 66) for patients with metastatic, invasive, and primary cancers, respectively. Our results suggest that CAS is a secretory protein associated with cancer metastasis, which may have clinical utility in metastatic cancer screening and diagnosis.

Function of CSE1L/CAS in the secretion of HT-29 human colorectal cells and its expression in human colon.

The secretion of colorectal epithelium is important for maintaining the physiological function of colorectal organ. Herein, we report that cellular apoptosis susceptibility (CAS) (or CSE1L) protein regulates the secretion of HT-29 human colorectal cells. Polarity is essential for directed secretion of substances produced by epithelial cells to the external (luminal) compartment; CAS overexpression induced polarization of HT-29 cells. CAS was punctate stained in the cytoplasm of HT-29 cells, and CAS overexpression increased the translocation of CAS-stained vesicles to the cytoplasm near cell membrane and cell protrusions. CAS overexpression increased the secretion of carcinoembryonic antigen (CEA) and cathepsin D. Immunohistochemistry showed CAS was positively stained in the goblet cells of colon mucosa and cells in the crypts of Lieberkühn of human colon as well as the glands in metastatic colorectal cancer tissue. Our results suggest that CAS regulates the secretion of colorectal cells and may regulate the metastasis of colorectal cancer.

Myasthenia gravis with thymoma and coexistent central hypothyroidism.

Myasthenia gravis (MG) is a well-known acquired autoimmune neuromuscular disorder. Patients with MG have a higher incidence of autoimmune disease than the normal population. MG is frequently associated with autoimmune thyroid disease, the most common of which is thyrotoxicosis. Associated hypothyroidism is not common, and the central (pituitary) origin, to our knowledge, has not yet been reported. We report an MG patient with thymoma that coexisted with central hypothyroidism, the correction of which is mandatory and significant to achieve remission.

Major complications of ultrasound-guided percutaneous radiofrequency ablations for liver malignancies: single center experience.

BACKGROUND AND AIM: Despite radiofrequency ablation (RFA) for malignant liver nodular lesions having promising therapeutic effects, the trade-off between the risks and benefits must be acceptable. This study analyzed the major complications of ultrasound (US)-guided percutaneous RFA procedures encountered at a single center, by a single physician. METHODS: A total of 104 patients (total 183 tumors) underwent 172 US-guided percutaneous RFA sessions between May 2003 and March 2006. The definition of major complications was according to the standardized Society of Interventional Radiology grading system (classification C-E). RESULTS: Eighty-six patients had hepatocellular carcinoma (HCC) and 18 patients had hepatic metastatic tumors. Nine major complications occurred from 172 RFA sessions (9/172, incidence of 5.2% per session); namely, two cases of transient liver function impairment, two cases of infection (liver abscess and septicemia), two cases of tumor seeding along the ablated track, one case of colon perforation, one case of acalculous cholecystitis and, lastly, a case of hemocholecyst. We further analyzed the possible risk factors precipitating these complications, and found that only tumor size (Pearson's correlation coefficient, 0.324; P < 0.05) and baseline liver function reserve (compensated 0%, 0/148 vs decompensated 8.3%, 2/24; P = 0.019) were significant factors for the complication of transient liver function impairment. CONCLUSION: Radiofrequency ablation for liver malignancy is a safe procedure with acceptable incidence of complications. Decompensated baseline liver function reserve and large tumor size are precipitating factors for transient liver function impairment after RFA and warrant a close follow up.

Management and patient survival in hepatocellular carcinoma: does the physician's level of experience matter?

INTRODUCTION: The prognostic determinants of hepatocellular carcinoma (HCC) depend on tumor stage, liver function reserve, and treatments offered. The clinical impact of the physician's experience on HCC management and the survival outcome is unknown. METHODS: A total of 103 patients were managed by one high-volume physician and 249 patients by seven low-volume physicians. The experience of high-volume physician in HCC management was five times more than that of low-volume physicians. Patient survival was the single end point for this study. RESULTS: Compared to the low-volume physician group, more of the patients allocated to the high-volume physician had early stage HCC on the date of diagnosis (66/103, 64.1%; vs 119/249, 47.8%; P = 0.008), and they received curative therapies including radiofrequency ablation or liver resection (66/103, 64.1% vs 54/249, 21.7%, P < 0.001), and had significantly better survival outcome (median survival of 34 months, 95% confidence interval [CI], 17.6-50.4; vs 6 months, 95% CI, 4.3-7.7; P < 0.001) with a multivariable-adjusted hazard ratio (HR) for survival of 1.94 (95%, CI, 1.31-2.87, P < 0.001). A multivariate analysis of the pretreatment prognostic factors for these two groups identified alpha-fetoprotein (AFP) level (HR, 1.42; 95% CI, 1.01-1.99; P = 0.042), ascites (HR, 1.68; 95% CI, 1.15-2.46; P = 0.007), maximum tumor diameter (HR, 1.78; 95% CI, 1.16-2.74; P = 0.009), and portal vein thrombosis (PVT) (HR, 2.17; 95% CI, 1.49-3.17; P < 0.001) as independent factors for the low-volume physician group. However, only maximum tumor diameter (HR, 4.54; 95% CI, 1.77-11.67; P < 0.001) and PVT (HR, 5.73; 95% CI, 2.30-14.22; P = 0.002) were independent factors for the high-volume physician group. CONCLUSION: The survival of HCC patients was dependent on the level of experience of the physicians who oversaw these patients.

Distinct differences in the induction of stimulus-mediated superoxide generation by polymorphonuclear neutrophils isolated from patients with different types of leukemia.

BACKGROUND/PURPOSE: Accumulating literature has documented that there exists a distinct difference in nitro blue tetrazolium reduction capacity by the polymorphonuclear neutrophils (PMNs) from patients with different types of leukemia. The underlying mechanism associated with this observed phenomenon remains to be clarified. METHODS: The production of O2-, monitored by a validated probe (lucigenin)-based ultraweak chemiluminescence, in resting and/or phorbol-1,2-myristate-1,3-acetate (PMA)- and zymosan-stimulated systems of various leukemic PMNs was measured. In parallel with these studies, we also quantified superoxide dismutase isozymes (Cu, Zn-SOD, Mn-SOD) from these isolated PMNs by established methods. RESULTS: A marked increase was observed in O2- generation by the PMNs from patients with acute myeloid leukemia (AML), and chronic myeloid leukemia (CML), but not from patients with acute lymphocytic leukemia (ALL) when compared with controls either in the resting condition or after being stimulated by either PMA or zymosan. In parallel, we also quantified SOD isozyme activities and found that the total and CuZn-SOD of PMNs from AML were indeed significantly lower than either controls or ALL, implying that higher levels of O2- generation might result from a deficiency in this O2- metabolizing enzyme. CONCLUSION: Our data suggest that a distinct difference in the capability of O2- generation under stimulated conditions between PMNs from ALL and AML (or CML) may be of potential taxonomic or even therapeutic usefulness.

Experience of endoscopic ultrasound-guided fine needle aspiration in a regional teaching hospital.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was first reported in 1991 and 1992 for gastric submucosal tumor and pancreas cancer. Subsequently, the indications have expanded to mediastinal lesions, liver, spleen, adrenal gland, ascites, pleural effusion, intra-abdominal lymph nodes. We report our experience of EUS-FNA and the number of cases required during the learning curve. From May 2005 to December 2007, we did a retrospective analysis of 45 cases (median age: 68 [range] [37-87] years; 34 men and 11 women) of EUS-FNA punctures on solid masses. EUS-FNA was performed with linear echoendoscope (Olympus GF-UCT2000, EUC2000 unit) using 22 gauge needles (Olympus power-shot needle and Wilson Cook echo-tip needle). The procedure was done by a single endoscopist. Patients were divided into 2 groups, the first 30 patients (group A) and the last 15 patients (group B). The median size of tumor was 2.6 cm (range: 1-14 cm) in group A and 2 cm (range: 0.7-3.5 cm) in group B (p=0.023). The median number of punctures was the same in both groups, i.e. 2 (range: 1-4). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy in groups A and B were 55.1% vs. 85.7%, 100% vs. 100% 100% vs. 100%, 7.1% vs. 33.3%, 56.6% vs. 86.6% respectively. Group B patients had smaller tumor size, but with higher sensitivity and accuracy rates. Only one patient in group A needed 4 units of blood transfusion. EUS-FNA is a safe intervention; the sensitivity and accuracy rate can be improved after a learning curve of 30 cases.