Clinical and electrocardiographic features in acute total left main coronary artery occlusion without collateral circulation.

BACKGROUNDS: Study concerning the clinical features, electrocardiogram (ECG) findings and outcomes in patients presenting with acute total occlusion of left main coronary artery (LM) without collateral circulation is limited. METHODS: 25 patients with acute total LM occlusion without collateral circulation by emergency coronary angiography, from muti-center registry, were retrospectively studied. The clinical and angiographic characteristics, ECG and in-hospital mortality were reviewed. RESULTS: Nineteen patients (76%) presented with cardiogenic shock. Twelve (60%, 12/20) patients had coronary slow flow or no reflow phenomenon after primary percutaneous coronary intervention (PCI). The in-hospital mortality rate was 88% (n = 22). All the patients presented with ST-segment elevation myocardial ischemia (STEMI) pattern, mostly involving leads I, aVL, V2, V3, V4, V5 and ST-segment depression in leads II, III and aVF. CONCLUSIONS: Acute total LM occlusion without collateral circulation portends high in-hospital mortality. Anterior ST elevation in the precordial leads from V2 to V4 through V6, and ST elevation in leads I and aVL, accompanying with ST depression in the inferior leads is associated with acute total LM occlusion without collateral circulation.

Activation of brown adipocytes by placental growth factor.

Gestational diabetes mellitus (GDM) is a type of diabetes and occurs during pregnancy. Brown adipose tissue (BAT) improves glucose homeostasis and mitigates insulin resistance, however, its activity is reduced in GDM. Placenta growth factor (PlGF) is an angiogenic factor produced by placental trophoblasts. Nevertheless, whether and how PlGF could affect BAT function in GDM are not defined. To investigate this question, 91 non-diabetic pregnant participants and 73 GDM patients were recruited to Gynaecology and Obstetrics Centre in Lu He hospital. Serum levels of PlGF were quantified by ELISA. Skin temperature was measured by far infrared thermography in the supraclavicular region where classical BATs were located. The direct effect of PlGF on BAT function was explored using the established human preadipocyte differentiation system. Thereby, we demonstrated that serum levels of PlGF were lower in GDM patients compared with controls, which was accompanied by decreased skin temperature in the supraclavicular region. By qPCR and western blot, mRNA and protein expression of UCP1 and OXPHOS were elevated in differentiated adipocytes treated with PlGF. PlGF stimulated mitochondrion transcription and increased copy number of mitochondrial. When subjected for respirometry, PlGF-treated differentiated adipocytes showed higher oxygen consumption rates than controls. PlGF induced AMPK phosphorylation and blockade of AMPK phosphorylation blunted UCP1 and OXPHOS expression in differentiated adipocytes. PlGF administration reduced cholesterol and triglyceride content in the liver and improved insulin sensitivity in db mice compared with control. In Conclusion, PlGF could activate BAT function. Downregulation of PlGF might contribute to the reduced BAT activity in GDM.

Anatomical right hemicolectomy: a novel surgical method and its clinical application.

BACKGROUND/AIMS: Presently, the notion of traditional right hemicolectomy has not met the rapidly developed requirements for precise gastrointestinal surgical procedures. In this study, we introduced a novel surgical method, namely "anatomical right hemicolectomy," and evaluated the safety and short-term effects of this method for the treatment of right hemicolon carcinoma. METHODOLOGY: The clinical data of 10 cases with progressive right hemicolon carcinoma underwent anatomical right hemicolectomy from January 2013 to February 2014 were collected and analyzed retrospectively. RESULTS: All the operations were successfully completed. The number of cleared lymph nodes was 18.0±6.7, the mean operative time was 162.7±25.3 mins, the mean blood loss was 95.2±32.5 ml, time to first flatus was 4.2±1.9 days, and the mean size of tumor was 4.96±3.2 cm. In these 10 patients, there was no case of respiratory infections, intestinal obstruction, anastomotic bleeding, anastomotic stricture, anastomotic leakage and other complications. All patients recovered, and subsequently discharged. CONCLUSIONS: In summary, anatomical right hemicolectomy was a safe and feasible method for the treatment of progressive right hemicolon carcinoma; it was worth popularizing widely.

STAT3 activation mediates epithelial-to-mesenchymal transition in human hepatocellular carcinoma cells.

BACKGROUND/AIMS: Epithelial-to-mesenchymal transition (EMT) is critical for the development of the invasion and metastasis in human cancers. Recently, signal transducer and activator of transcription 3 (STAT3) activation has been linked to EMT program in breast cancer. However, the actual association of STAT3 activation with EMT, and its mediated tumor invasion and metastasis remains elusive in hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between STAT3 activation and EMT, as well as the underlying mechanism involved in HCC progression. METHODOLOGY: We treated SMMC-7721 cells with a known STAT3 activator, epithelial growth factor (EGF); in the absence or presence of JSI-124, a selective STAT3 inhibitor. The EMT-associated morphologic and molecular changes of cells were analyzed. The EMT-mediated HCC cell invasion, migration and adhesion were evaluated. RESULTS: In this study, we found that STAT3 activation induced by EGF was associated significantly with morphologic changes, cytoskeleton rearrangement and molecular changes consistent with EMT in SMMC-7721 cells; STAT3 activation-mediated EMT may be transcriptionally induced by Twist. STAT3 activation-mediated EMT also promoted HCC cell invasion, migration and adhesion significantly. CONCLUSIONS: In summary, our study show for the first time that STAT3 activation may induce invasion and metastasis through the mediation of EMT in HCC cells. Activated STAT3 and EMT markers can serve as molecular targets for HCC treatment.

Aberrant estrogen receptor alpha expression correlates with hepatocellular carcinoma metastasis and its mechanisms.

BACKGROUND/AIMS: Metastasis one of the obstacles before poor prognosis of hepatocellular carcinoma (HCC) is improved. Estrogen receptor alpha (ERalpha) plays an important role in the development and progression of HCC. However, the molecular mechanism of ERalpha in mediating HCC metastasis is still unclear. The aim of the present study was to detect aberrant ERalpha expression in HCC and elucidate its possible mechanisms in HCC metastasis. METHODOLOGY: We detected expression of ERalpha, phospho-estrogen receptor alpha (p-ERalpha), nuclear factor kappa B (NF-kappaB) p65 and Matrix metalloproteinase-9 (MMP-9) between HCC tissues with portal vein tumor thrombus (PVTT) and those without PVTT by immunohistochemical method. Moreover, the expression of above parameters was also determined in HCC cells of different metastatic potential by using immunocytochemical and reverse transcriptase-polymerase chain reaction (RT-PCR) methods. RESULTS: The expression of ERalpha and p-ERalpha was lower in HCC with PVTT than those without PVTT. Meanwhile, the expression pattern of above parameters was also similar in HCC cells of different metastatic potential, whereas, the expression of NF-kappaB p65 and MMP-9 was higher in HCC with PVTT than those without PVTT. The expression of NF-kappaB p65 and MMP-9 in HCC cells was also analogous to the tissues. CONCLUSIONS: These results demonstrated that expression of ERalpha, p-ERalpha, NF-kappaB p65 and MMP-9 correlated with invasion and metastasis in HCC. The mechanism of HCC metastasis may mediate through cross-talk between the NF-KB and ER signaling pathways. Meanwhile, ERa regulated MMP-9 through NF-kappaB indirectly.

Overexpression of HOXA13 as a potential marker for diagnosis and poor prognosis of hepatocellular carcinoma.

HOXA13 is a member of homeobox genes that encode transcription factors regulating embryonic development and cell fate. Abnormal HOXA13 expression was reported in hepatocellular carcinoma (HCC), but its correlation with tumor angiogenesis and prognosis still remain unclear. This study was aimed to uncover the expression, diagnostic and prognostic significance of HOXA13 in HCC. Immunohistochemistry was performed to detect HOXA13 expression in HCC and corresponding paracarcinomatous tissues from 90 patients. Enzyme-linked immunosorbent assay was used to detect serum HOXA13 in 90 HCC patients and 20 healthy volunteers. Receiver operating characteristics was analyzed to calculate diagnostic accuracy of serum HOXA13, alpha-fetoprotein (AFP) and their combination. Immunoreactivity of HOXA13 was detected in 72.2% of HCC, and 12.2% of adjacent non-cancerous samples. HOXA13 expression was significantly associated with tumor size, microvascular invasion, pathological grade, tumor capsula status, AFP level, tumor-node-metastasis stage and positively correlated with VEGF (p < 0.001) and microvessel density (p < 0.001). The combination of serum HOXA13 and AFP had a markedly higher area under the curve than HOXA13 alone. HOXA13 expression was associated with unfavorable overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001). Multivariate analysis indicated that patients with HOXA13-expressing tumors had a significantly shorter OS (p = 0.030) and DFS (p = 0.005) than those with HOXA13-negative tumors. Thus, HOXA13 expression possibly plays an important role in tumor angiogenesis, progression and prognosis of HCC. Moreover, we demonstrate that serum HOXA13 may serve as a biomarker for early HCC diagnosing and predicting outcome.

Clinical characteristics and treatment compounds of obesity-related kidney injury.

Disorders in energy homeostasis can lead to various metabolic diseases, particularly obesity. The obesity epidemic has led to an increased incidence of obesity-related nephropathy (ORN), a distinct entity characterized by proteinuria, glomerulomegaly, progressive glomerulosclerosis, and renal function decline. Obesity and its associated renal damage are common in clinical practice, and their incidence is increasing and attracting great attention. There is a great need to identify safe and effective therapeutic modalities, and therapeutics using chemical compounds and natural products are receiving increasing attention. However, the summary is lacking about the specific effects and mechanisms of action of compounds in the treatment of ORN. In this review, we summarize the important clinical features and compound treatment strategies for obesity and obesity-induced kidney injury. We also summarize the pathologic and clinical features of ORN as well as its pathogenesis and potential therapeutics targeting renal inflammation, oxidative stress, insulin resistance, fibrosis, kidney lipid accumulation, and dysregulated autophagy. In addition, detailed information on natural and synthetic compounds used for the treatment of obesity-related kidney disease is summarized. The synthesis of detailed information aims to contribute to a deeper understanding of the clinical treatment modalities for obesity-related kidney diseases, fostering the anticipation of novel insights in this domain.

Prognostic significance of osteopontin in hepatocellular carcinoma: a meta-analysis.

Osteopontin (OPN) has been implicated in tumor development and progression for several years. However, the prognostic value of OPN overexpression in patients with hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to assess the relationship between OPN overexpression and clinical outcome of HCC. A meta-analysis of seven studies (1,158 patients) was carried out to evaluate the association between OPN and overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between OPN and tumor vascular invasion or other invasion-related parameters was also assessed. Data were synthesized with random effect model of DerSimonian and Laird, hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that high OPN expression predicted poor OS (HR: 1.37, 95% CI: 1.21-1.55) and DFS (HR: 1.62, 95% CI: 1.24-2.11) of HCC. OPN overexpression tended to be associated with the presence of tumor vascular invasion (OR: 1.93, 95% CI: 0.97-3.84) and advanced tumor grade (OR: 1.74, 95% CI: 0.95-3.18). By this study, we conclude that OPN overexpression indicates a poor prognosis for patients with HCC, it may also have predictive potential for HCC invasion and metastasis.

Activation of STAT3 signal pathway correlates with twist and E-cadherin expression in hepatocellular carcinoma and their clinical significance.

BACKGROUND: To examine the expression of signal transducer and activator of transcription 3 (STAT3) and its activated form (p-STAT3), Twist, and E-cadherin in hepatocellular carcinoma (HCC), and explore their correlations with HCC progression and prognosis. MATERIALS AND METHODS: The expression profiles of STAT3, p-STAT3, Twist, and E-cadherin were assessed on 100 clinical HCC samples and 10 normal liver tissues by using an immunohistochemical staining method, and their correlations with clinicopathologic parameters and survival of HCC patients were statistically analyzed. RESULTS: The results demonstrated that the positive rate of STAT3, p-STAT3, and Twist in HCC was significantly higher than that in normal liver tissues; furthermore, 52% of HCC lesions showed reduced E-cadherin expression. Correlation analysis indicated that p-STAT3 was positively correlated with Twist expression, whereas Twist was negatively correlated with E-cadherin expression; p-STAT3, Twist, or E-cadherin expression was significantly associated with HCC invasion and metastasis. Survival analysis showed that HCC patients with p-STAT3, Twist positive expression, or reduced E-cadherin expression had a significantly shorter survival duration than those with p-STAT3, Twist negative expression, or those with normal E-cadherin expression. Multivariate analysis identified p-STAT3, Twist, or E-cadherin expression as an independent prognostic factor for overall survival of HCC patients after surgery. CONCLUSIONS: By this study, we suggest that activated STAT3 signal may associate with Twist and E-cadherin expression and mediate HCC invasiveness and metastasis; abnormal p-STAT3/Twist/E-cadherin signal axis may predict poor prognosis of HCC patients.

Efficacy and feasibility of radiofrequency ablation for hepatocellular carcinoma patients.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is a new treatment which is used to treat hepatocellular carcinoma (HCC). We performed this clinical trial to investigate whether it could reduce the damage of residual liver function. METHODOLOGY: We studied 40 hepatitis-related chronic patients who underwent RFA for hepatocellular carcinoma. Indocyanine green (ICG) test was performed pre and postoperatively. RESULTS: There were 32 males and 8 females with an average age of 53.98+12.59 years who underwent RFA for HCC. The mean preoperative ICGR15 value of 40 of the patients was (10.17+9.54) lower than the postoperative ICG retention rate at 15 min (ICGR15) value (14.95+12.71).Differences between the preoperative ICGR15 and the postoperative ICGR15 values were not significantly different (p=0.074). The 1-, 2- and 3-year survival rates were 98.7%, 88.8% and 76.4%, respectively. CONCLUSIONS: The results indicate that RFA is a minimally invasive treatment which provides a possible treatment modality for HCC patients with poor liver function and the efficacy is as well as the surgical treatment for HCC patients within the Milan criteria.

ACE2 pathway regulates thermogenesis and energy metabolism.

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas1 receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. Ace2 knockout mice (Ace2-/y) and Mas1 knockout mice (Mas1-/-) displayed impaired thermogenesis. Mice transplanted with brown adipose tissue from Mas1-/- display metabolic abnormalities consistent with those seen in the Ace2 and Mas1 knockout mice. In contrast, impaired thermogenesis of Leprdb/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of Ace2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids, and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel potential therapeutic targets for the treatment of metabolic disorders.

Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: a meta-analysis of randomized controlled trials.

Available literature on the effects of interferon (IFN) treatment on development and progression of hepatocellular carcinoma (HCC) in patients with chronic virus infection reports controversial results. The primary objective of this meta-analysis was to evaluate the effect of IFN on HCC risk in patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; IFN's efficacy on local tumor progression and survival of advanced HCC patients was also assessed. All randomized controlled trials (RCTs) comparing IFN with no antiviral treatment were selected. Finally, we identified 11 RCTs including 1,772 patients, who met our inclusion criteria to perform this meta-analysis. Our analysis results showed that IFN significantly decreased the overall HCC incidence in HCV-infected patients [relative risk (RR)=0.39; 95% confidence interval (CI)=0.26-0.59; p=0.000], subgroup analysis indicated that IFN decreased HCC incidence in HCV-related cirrhotic patients evidently (RR=0.44; 95% CI=0.28-0.68; p=0.000); but HCC incidence in nonresponders to initial antiviral therapy did not reduce by maintenance IFN therapy (RR=0.96; 95% CI=0.59-1.56; p=0.864). Analysis results also demonstrated that IFN did not significantly affect the overall rate of HCC in HBV-infected patients although there was a trend favoring IFN therapy (RR=0.23; 95% CI=0.05-1.04; p=0.056). Besides, IFN did not improve one-year overall survival of advanced HCC patients significantly (RR=1.61; 95% CI=0.96-2.69; p=0.072); however, a quantitative analysis on local tumor progression could not be performed owing to lack of unified definitions among trials included in our study. By this meta-analysis, we conclude that IFN therapy is effective in reducing overall HCC risk in chronic HCV-infected patients; using it in this subpopulation seems promising, but its administration in other subpopulations still requires further exploration.

Protective effects of physiological doses of estrogen during hepatocarcinogenesis induced by diethylnitrosamine and N-nitrosomorpholine.

BACKGROUND/AIMS: Concern that much controversy exists with respect to the role of estrogen in hepatocarcinogenesis prompted us to examine the effect of estrogen, at physiological concentrations, on our established HCC rat model induced by diethylnitrosamine and N-nitrosomorpholine. METHODOLOGY: Female Sprague-Dawley rats were randomly divided into four groups (Group 1: Control, Group 2: Sham-operated, Group 3: Ovariectomy, Group 4: ovariectomy+estrogen) with treatment of a single i.p. injection of diethylnitrosamine (100mg/ kg body weight) followed by N-nitrosomorpholine (100ppm) in drinking water for 20 weeks for the established rat HCC model. Physiological estrogen was administered by 17α-Ethynylestradiol at a dose of 30µg/ kg body weight while rats in the sham-operated group were treated with saline after initiation of liver carcinogenesis. RESULTS: Treatment of ovariectomized animals with 17α-Ethynylestradiol (30µg/kg body weight/ day) resulted in a significant decrease in the initiation, development and metastasis of HCC and an increase in the survival time of animals dead before the termination of experiment as compared with rats treated with ovariectomy only (p<0.05); whereas this difference disappeared when compared with the other three groups. CONCLUSIONS: These findings show for the first time that estrogen, at physiological concentrations may reveal a protective role in hepatocarcinogenesis.

Octreotide therapy for hepatocellular carcinoma: a systematic review of the evidence from randomized controlled trials.

Currently no standard treatment for patients with advanced hepatocellular carcinoma (HCC), and available literature assessing octreotide's treatment effect on HCC reports discordant results. The primary purpose of this study was to evaluate the effect of octreotide therapy on patient survival. The secondary endpoints were to assess tumor response, quality of life and adverse effects. PUBMED, MEDLINE, OVID and SPRINGER databases were searched through January 2009. Randomized controlled trials that compared octreotide treatment with placebo or no treatment were selected. Finally, four randomized controlled trials (three of which were high quality trials) published in 1998 or later with a total of 373 patients were included in this review. Because a significant clinical heterogeneity existed between the included trials, making meta-analysis inappropriate; only a narrative systematic review was performed. Of the three high-quality trials, only one(126 patients) reported octreotide could improve survival and quality of life of HCC patients, whereas the other two(189 patients) suggested octreotide did not have survival benefit in HCC; moreover, none of the three trials indicated that octreotide has significant beneficial effect on tumor regression or decrease of tumor mass. Nonetheless, serious adverse effects were not reported in these included trials. In this review, results from included randomized controlled trials demonstrated no clear benefit of octreotide therapy in advanced HCC patients. In order to detect a realistic treatment advantage, further larger well-designed multicenter randomized trials will have to be conducted.

Can hepatocellular carcinoma be treated by Yondelis through targeting both tumor cells and tumor-associated macrophages?

BACKGROUND/AIMS: The initiation, progression, invasion and metastasis of hepatocellular carcinoma are closely associated with chronic inflammation caused by hepatitis virus infection, while tumor-associated macrophages are a major component of inflammatory infiltrates in intratumoral or peritumoral tissue of hepatocellular carcinoma. METHODOLOGY: Search MEDLINE, PUBMED databases, identify related articles and analyze related data. RESULTS: Evidence indicated that tumor-associated macrophages play an important role in disease progression, recurrence and survival of hepatocellular carcinoma patients. However, recent study showed that Yondelis (ecteinascidin-743) can suppress tumor growth through attacking tumor cells, macrophages and tumor-associated macrophages. CONCLUSIONS: Owing to the importance of tumor cells and tumor-associated macrophages in inflammatory microenvironment of hepatocellular carcinoma, treating hepatocellular carcinoma by Yondelis seems to be a promising therapeutic strategy but requires further study.

[Expression of estrogen receptor α in hepatitis B-related hepatocellular carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression and its clinical significance of estrogen receptor (ERα) and phosphorylated estrogen receptor (p-ERα) in patients with hepatocellular carcinoma. The associations between ERα, p-ERα and IL-6 were also analyzed. METHODS: Immunohistochemistry was used to detect the expression of ERα, p-ERα and IL-6 in tumor tissues from 77 cases with hepatocellular carcinoma. The relations between ERα and the clinical pathological parameters and prognosis were also analyzed. RESULTS: The positive rates of ERα, p-ERα and IL-6 in hepatocellular carcinoma were 39.0% (30/77), 45.4% (35/77) and 72.7% (56/77), respectively. The expression of ERα and p-ERα were negatively correlated with the expression of IL-6 (r=-0.468, P<0.01; r=-0.370, P<0.01, respectively). The positive rate of ERα in patients with tumor size≤5 cm, serum level of alpha-fetoprotein<400 µg/L, with complete encapsulation and non-microvascular invasion was significantly higher than those with tumor size>5 cm, serum level of alpha-fetoprotein≥400 µg/L, non-complete encapsulation and with microvascular invasion (all P<0.05). The overall survival rates of ERα-positive and ERα-negative patients were 66.7% and 23.4% (P<0.05). And the disease-free survival rates of ERα-positive and ERα-negative patients were 83.3% and 57.4% (P<0.05). CONCLUSIONS: The tumor biological features of ERα-positive patients are better than that of ERα-negative patients. The role of ERα in hepatocellular carcinoma may be related to IL-6 level.

Effects of interferon alpha treatment on recurrence and survival after complete resection or ablation of hepatocellular carcinoma: a meta-analysis of randomized controlled trials.

Available literature on the benefit of interferon alpha (IFN-alpha) as adjuvant postsurgical or ablative treatment of hepatocellular carcinoma reports discordant results. By meta-analysis of the available data, we evaluated the effects of IFN-alpha on recurrence and survival after complete resection or ablation of hepatocellular carcinoma. All randomized controlled trials comparing IFN-alpha with placebo or no treatment after tumor resection or ablation were selected. Finally, 6 studies published in 2001 or later with a total of 600 patients were included in this meta-analysis. Data on postsurgical or ablative early recurrence and 1 year survival of hepatocellular carcinoma in IFN-alpha treated and untreated patients were extracted from each study. Proportions were combined, and the odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Analysis results show that IFN-alpha significantly decreased postsurgical or ablative overall early recurrence (OR = 0.62; 95% CI = 0.42-0.93; p = 0.02) and improved overall 1 year survival (OR = 3.14; 95% CI = 1.79-5.52; p < 0.0001). Subgroup analyses show that IFN-alpha decreased postsurgical early recurrence (OR = 0.58; 95% CI = 0.37-0.91; p = 0.02) and improved 1 year survival (OR = 3.19; 95% CI = 1.80-5.67; p < 0.0001) evidently. Subgroup analyses also show that IFN-alpha reduced early recurrence after resection without pre-resection ablation therapy (OR = 0.58; 95% CI = 0.37-0.91; p = 0.02) and improved 1 year survival (OR = 3.83; 95% CI = 2.01-7.27; p < 0.0001). These results suggest that IFN-alpha treatment could significantly decrease early recurrence and improve 1 year survival of patients with hepatocellular carcinoma after complete resection or ablation. The use of IFN-alpha as adjuvant postsurgical or ablative treatment seems promising but requires further study. (c) 2009 UICC.

Four new cytotoxic oligosaccharidic derivatives of 12-oleanene from Lysimachia heterogenea Klatt.

Cytotoxicity-guided phytochemical analysis on the extract of Lysimachia heterogenea Klatt led to the isolation of 3beta,16beta-12-oleanene-3,16,23,28-tetrol (1) and its four new oligosaccharidic derivatives heterogenosides A, B, C, and D (2-5). Their structural elucidation was mainly based on NMR and mass spectral data. The time course experimental results indicated that unlike the likely lysis activity of heterogenosides B-D, heterogenoside A showed a significantly time-dependent cytotoxicity.