[Analysis of the efficacy and safety of hepatic arterial infusion chemotherapy for unresectable hepatitis B-related intrahepatic cholangiocarcinoma].

Objective: To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC). Methods: This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ2 test or Fisher's exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results: According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant(χ2=4.459,P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant(χ2=4.410,P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95%CI: 5.8 to 13.2 months) and 7.3 months (95%CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95%CI: 12.5 to 33.9 months) and 15.9 months (95%CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion: Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

[Thinking and suggestion on the definition, classification and Chinese nomenclature of carcinoma of the bile ducts].

At present, the classification, nomenclature, and definition of carcinoma of the bile ducts are controversial. Moreover, there is no uniformity between China and aboard, which has brought confusion to clinical practice. It needs to clarify regarding tumor naming principles, anatomical location, tumor origin, pathological classification, biological characteristics, clinical manifestations, treatment methods, etc. Additionally, the WHO tumor classification, UICC staging, ICD disease classification, relevant Chinese regulations, EASL, AJCC staging, and NCCN guidelines were also needed to be referred. After investigating the above-mentioned latest authoritative literature, based on the existing problems, combined with clinical practice in China, the author reevaluated the definition, classification, and nomenclature of cholangiocarcinoma, and proposes updated suggestions. Hoping to standardize and unify clinical practice for classification and nomenclature of cholangiocarcinoma in China.

[Suggestions on the nomenclature of liver cancer].

Currently, the systematized nomenclature of medicine (SNOMED) of liver cancer is confusing, and it is mixed with the SNOMED of cholangiocarcinoma. We hereby presented our own points, hoping to provide a reference for standardizing the nomenclatures and classifications of liver cancer in future clinical studies. The preface of Chinese Guidelines of Primary Liver Cancer Diagnosis and Treatment (2019 Edition) indicated that primary liver cancer mainly includes three different pathological types, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and mixed-type carcinoma of both HCC and ICC. These three types of carcinoma show great differences in terms of pathogenesis, biological behavior, histological morphology, treatment methods, and prognosis, among which, HCC accounts for 85% to 90%. Therefore, this study is a detailed analysis of the above-mentioned related SNOMED and proposes suggestions for corrections.

Correction: Pomalidomide, bortezomib, and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma.

Following the publication of this article, the authors noted that the pomalidomide dose for the additional SC cohort in Fig. 1 was incorrectly listed. The correct dose for pomalidomide in the additional SC cohort should be the maximum tolerated dose of 4 mg/day, not 2 mg/day as listed in the original Fig. 1. The authors apologize for any inconvenience caused.

L-butyl phthalein improves neural function of vascular dementia mice by regulating the PI3K/AKT signaling pathway.

OBJECTIVE: L-3-n-butylphthalide (L-NBP) is a type of anti-ischemic cranial nerve protective drug that may act on vascular dementia (VD). Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway can up-regulate B-cell lymphoma 2 (Bcl-2) expression, reduce reactive oxygen species (ROS) production, and alleviate cell apoptosis. This study aimed at investigating the role of L-NBP on neurological function and cell apoptosis in VD mouse through regulating PI3K/AKT signaling pathway. MATERIALS AND METHODS: The mice were divided into four groups, including Sham, VD, VD + solvent, and VD + L-NBP. HT22 cells were cultured in vitro and treated by ischemia/reperfusion (I/R). HT22 cells were divided into four groups, including I/R, VD + solvent, VD + L-NBP, and VD + L-NBP + LY294002 groups. Phosphorylated AKT (p-AKT) and Bcl-2 expressions were tested. ROS content in hippocampus tissue was detected by flow cytometry. Cell apoptosis was evaluated by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. RESULTS: ROS content and cell apoptosis increased, while p-AKT and Bcl-2 expressions reduced in hippocampus tissue from VD group compared with sham group. L-NBP significantly up-regulated p-AKT and Bcl-2 expressions and decreased ROS content and cell apoptosis in hippocampus tissue. I/R treatment markedly induced HT22 cell apoptosis and ROS production, and reduced p-AKT and Bcl-2 expressions. L-NBP treatment markedly up-regulated p-AKT and Bcl-2 levels, restrained cell apoptosis, and reduced ROS content in TH22 cells intervened by I/R. LY294002 apparently attenuated the protective effect of L-NBP on HT22 cells. CONCLUSIONS: L-NBP protects VD by up-regulating PI3K/AKT signaling pathway, elevating Bcl-2 expression, reducing nerve cell apoptosis, and restraining ROS production.

Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma.

This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m2 days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort. Patients received a median of 2 prior lines of therapy; 97% bortezomib exposed. With no dose-limiting toxicities, MTD was defined as the maximum planned dose: pomalidomide 4 mg, bortezomib 1.3 mg/m2 and LoDEX. All patients discontinued treatment by data cutoff (2 April 2015). The most common grade 3/4 treatment-emergent adverse events were neutropenia (44%) and thrombocytopenia (26%), which occurred more frequently with IV than SC bortezomib. No grade 3/4 peripheral neuropathy or deep vein thrombosis was reported. Overall response rate was 65%. Median duration of response was 7.4 months. Pomalidomide, bortezomib and LoDEX was well tolerated and effective in lenalidomide-refractory and bortezomib-exposed patients with RRMM.

[Multidisciplinary therapeutic strategies for recurrence and metastasis of liver cancer].

With the development of early diagnostic and surgical techniques, the postoperative outcome of patients with liver cancer is gradually improved, but long-term outcome remains unsatisfactory. The therapeutic methods for recurrent tumors include multidisciplinary therapeutic methods such as reoperation, local treatment, and systematic treatment. Multidisciplinary therapies can improve the overall response of recurrent liver cancer, and it can combine various therapies from different disciplines according to the patient's condition and take advantages of each therapy in order to achieve the best therapeutic effect.

Preclinical study on induction of pluripotent stem cells from urine of dilated cardiomyopathy patients.

OBJECTIVE: Dilated cardiomyopathy (DCM) is featured by left or bilateral ventricular dilation combined with systolic dysfunction. Its clinical manifestations include heart enlargement, cardiac failure, arrhythmia and cardiac arrest. Medication and heart transplantation have but only limited treatment effect on DCM. MATERIALS AND METHODS: Induced pluripotent stem cell (iPSC) treatment provides a new solution for DCM treatment. Human renal epithelial cells were extracted from the urine of patients with DCM and transfected with Sendai virus carrying OCT3/4, Sox2, Klf4 and c-Myc gene to generate iPSCs by reprogramming. RESULTS: The morphology and pluripotency of iPSCs obtained from the renal epithelial cells from patients with DCM were confirmed, as well as the growth characteristics, immunohistochemical features and surface markers of embryonic stem cells. Teratoma was formed in vivo. CONCLUSIONS: We demonstrated that it was feasible to obtain iPSCs from the urine of patients with DCM. This technique lays down the cytological foundation for understanding the pathogenesis and for drug screening and gene therapy for DCM.

Detection of acute cerebral hemorrhage in rabbits by magnetic induction

Acute cerebral hemorrhage (ACH) is an important clinical problem that is often monitored and studied with expensive devices such as computed tomography, magnetic resonance imaging, and positron emission tomography. These devices are not readily available in economically underdeveloped regions of the world, emergency departments, and emergency zones. We have developed a less expensive tool for non-contact monitoring of ACH. The system measures the magnetic induction phase shift (MIPS) between the electromagnetic signals on two coils. ACH was induced in 6 experimental rabbits and edema was induced in 4 control rabbits by stereotactic methods, and their intracranial pressure and heart rate were monitored for 1 h. Signals were continuously monitored for up to 1 h at an exciting frequency of 10.7 MHz. Autologous blood was administered to the experimental group, and saline to the control group (1 to 3 mL) by injection of 1-mL every 5 min. The results showed a significant increase in MIPS as a function of the injection volume, but the heart rate was stable. In the experimental (ACH) group, there was a statistically significant positive correlation of the intracranial pressure and MIPS. The change of MIPS was greater in the ACH group than in the control group. This high-sensitivity system could detect a 1-mL change in blood volume. The MIPS was significantly related to the intracranial pressure. This observation suggests that the method could be valuable for detecting early warning signs in emergency medicine and critical care units.

The Ron receptor tyrosine kinase activates c-Abl to promote cell proliferation through tyrosine phosphorylation of PCNA in breast cancer.

Multiple growth pathways lead to enhanced proliferation in malignant cells. However, how the core machinery of DNA replication is regulated by growth signaling remains largely unclear. The sliding clamp proliferating cell nuclear antigen (PCNA) is an indispensable component of the DNA machinery responsible for replicating the genome and maintaining genomic integrity. We previously reported that epidermal growth factor receptor (EGFR) triggered tyrosine 211 (Y211) phosphorylation of PCNA, which in turn stabilized PCNA on chromatin to promote cell proliferation. Here we show that the phosphorylation can also be catalyzed by the non-receptor tyrosine kinase c-Abl. We further demonstrate that, in the absence of EGFR, signaling to PCNA can be attained through the activation of the Ron receptor tyrosine kinase and the downstream non-receptor tyrosine kinase c-Abl. We show that Ron and c-Abl form a complex, and that activation of Ron by its ligand, hepatocyte growth factor-like protein (HGFL), stimulates c-Abl kinase activity, which in turn directly phosphorylates PCNA at Y211 and leads to an increased level of chromatin-associated PCNA. Correspondingly, HGFL-induced Ron activation resulted in Y211 phosphorylation of PCNA while silencing of c-Abl blocked this effect. We show that c-Abl and Y211 phosphorylation of PCNA is an important axis downstream of Ron, which is required for cell proliferation. Treatment with a specific peptide that inhibits Y211 phosphorylation of PCNA or with the c-Abl pharmacological inhibitor imatinib suppressed HGFL-induced cell proliferation. Our findings identify the pathway of Ron-c-Abl-PCNA as a mechanism of oncogene-induced cell proliferation, with potentially important implications for development of combination therapy of breast cancer.

Hepatitis B virus reactivation after radiofrequency ablation or hepatic resection for HBV-related small hepatocellular carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: Reactivation of hepatitis B virus (HBV) happens after systemic chemotherapy, transarterial chemoembolization (TACE) or hepatic resection for HBV-related hepatocellular carcinoma (HCC) patients. The incidence and risk factors of HBV reactivation after radiofrequency ablation (RFA) are unclear. PATIENTS AND METHODS: From August 2006 to August 2011, 218 consecutive patients with HBV-related small HCC treated with RFA (n = 125) or hepatic resection (n = 93) were retrospectively studied. The incidence of HBV reactivation and risk factors were analyzed. RESULTS: HBV reactivation developed in 20 (9.2%) patients after treatment. The incidence of HBV reactivation was significantly lower in the RFA group (5.6%, 7/125) than the hepatic resection group (14.0%, 13/93, P = 0.034). On univariate and multivariate analyses, no antiviral therapy (OR 11.7; 95% CI 1.52-90.8, P = 0.018) and treatment with RFA/hepatic resection (OR3.36; 95% CI 1.26-8.97, P = 0.016) were significant risk factors of HBV reactivation. On subgroup analysis, the incidence of HBV reactivation was lower in patients who received antiviral therapy than those who did not receive antiviral therapy in both the hepatic resection group (2.9% vs. 20.7%, P = 0.027) and the RFA group (0% vs. 7.6%, P = 0.188), although the difference was not significant in the latter group. CONCLUSION: The incidence of HBV reactivation after RFA was relatively low when compared with hepatic resection. Prophylactic antiviral therapy is recommended, especially for patients who are going to receive hepatic resection for HBV-related HCC to decrease the incidence of post-treatment HBV reactivation.

Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma.

OBJECTIVE: To explore the potential of quantitative analysis of contrast-enhanced ultrasonography (CEUS) in differentiating focal nodular hyperplasia (FNH) from hepatocellular carcinoma (HCC). METHODS: 34 cases of FNH and 66 cases of HCC (all lesions <5 cm) were studied using CEUS to evaluate enhancement patterns and using analytic software Sonoliver® (Image-Arena™ v.4.0, TomTec Imaging Systems, Munich, Germany) to obtain quantitative features of CEUS in the region of interest. The quantitative features of maximum of intensity (IMAX), rise slope (RS), rise time (RT) and time to peak (TTP) were compared between the two groups and applied to further characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS. RESULTS: The sensitivity and specificity of CEUS for diagnosis of FNH were 67.6% and 93.9%, respectively. For quantitative analysis, IMAX and RS in FNHs were significantly higher than those in HCCs (p<0.05), while RT and TTP in FNHs were significantly shorter (p<0.05). Both the 11 FNHs and 62 HCCs with hypo-enhancing patterns in the late phase were further characterised with their quantitative features, and the sensitivity and specificity of IMAX for diagnosis of FNH were 90.9% and 43.5%, RS 81.8% and 80.6%, RT 90.9% and 71.0%, and TTP 90.9% and 71.0%, respectively. CONCLUSION: The quantitative features of CEUS in FNH and HCC were significantly different, and they could further differentiate FNH from HCC following conventional CEUS. ADVANCES IN KNOWLEDGE: Our findings suggest that quantitative analysis of CEUS can improve the accuracy of differentiating FNH from HCC.

Hepatocellular carcinoma screening practices and impact on survival among hepatitis B-infected Asian Americans.

Asians Americans have a high burden of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC). HCC screening practices in this population are unknown. We aimed to investigate predictors and patterns of HCC screening and its impact on survival in HBV-infected Asian Americans. Clinical data were obtained from a retrospective cohort of 1870 HBsAg-positive Asians in San Francisco's safety net clinics. In 824 patients at-risk for HCC, screening (≥1 imaging and/or AFP per year) decreased from 67% to 47% to 24% from the 1st to 2nd to 10th year after HBV diagnosis, respectively. AFP, imaging, and imaging plus AFP were used in 37%, 14%, and 49% during the first year after diagnosis, and imaging plus AFP increased to 64% by the 10th year. Among 1431 patients followed in 2007, age 40-64 years, female gender, cirrhosis, hepatologist evaluation, HBV diagnosis after 2003, and testing for HBeAg were associated with HCC screening. Of the 51 patients with HCC, more cirrhotics received screening and were diagnosed with early stage disease. Median survival following HCC diagnosis was higher in screened patients (1624 days vs. 111 days, P = 0.02). MELD score at HCC diagnosis (HR 1.2, 95% CI 1.1-1.3) and receipt of curative therapy (HR 0.3, 95% CI 0.08-0.94) were associated with survival. Screening rates in at-risk Asian Americans, particularly among noncirrhotics, were suboptimal and decreased over time. Among patients with HCC, receipt of prior screening improved survival, and this survival benefit was related to better liver function at HCC diagnosis and receipt of curative therapy.

Radiofrequency ablation as first-line treatment for small solitary hepatocellular carcinoma: long-term results.

AIMS: To evaluate long-term results of patients with small solitary hepatocellular carcinoma (HCC) and well-preserved liver function who received radiofrequency ablation (RFA) as first-line treatment. MATERIALS AND METHODS: Between November 1999 and June 2007, 247 patients with solitary HCC ≤5 cm and liver status scored as Child-Pugh class A were enrolled. RFA was performed in 224 patients as first-line treatment; 23 patients excluded from RFA because of unfavorable tumor location or their unwillingness, and all of these patients converted to surgical resection. RESULTS: In the 224 patients treated with RFA, the overall 5-, 7-, 10-year survival rates were 59.8%, 55.2%, 33.9%, respectively, and the median of overall survival was 76.1 months. Complete ablation was achieved in 216 patients (96.4%). Major complications occurred in two patients (0.9%), with no treatment-related death or needle track seeding. Indocyanine green retention rate in 15 min (ICGR15) (P = 0.014) and prothrombin activity (P = 0.004) were associated with overall survival. A subgroup of patients with ICGR15 ≤ 10% and prothrombin activity >75% had 5-, 7-, 10-year survival rates of 67.1%, 64.2%, 57.1%, respectively, with a median survival of 87.7 months. The 10-year recurrence-free, tumor-free survival rates were 17.5%, 28.2%, respectively. Serum albumin was the only factor that significantly impacted recurrence-free and tumor-free survival (P = 0.008, 0.002, respectively). CONCLUSION: RFA is considered to be the treatment of first choice for patients with solitary HCC ≤5 cm and well-preserved liver function. Surgery can be used as second-line therapy for few patients if RFA is unfeasible.

A case-control study comparing percutaneous radiofrequency ablation alone or combined with transcatheter arterial chemoembolization for hepatocellular carcinoma.

AIMS: To assess whether combining percutaneous radiofrequency ablation (PRFA) with transcatheter arterial chemoembolization (TACE) was better than PRFA alone for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundered twenty patients (with a solitary HCC5.0 cm (p=.031) and for multiple tumors (p=.032), but not for tumors 5 cm or multiple tumors.

Effects of intravitreal gas with or without tissue plasminogen activator on submacular haemorrhage in age-related macular degeneration.

PURPOSE: To compare the anatomic and functional outcomes of treating thick submacular haemorrhage with intravitreal gas injection with and without tissue plasminogen activator (t-PA) in patients with age-related macular degeneration. METHODS: A review of age-related macular degeneration patients with submacular haemorrhage who underwent intravitreal gas injection with and without t-PA at a tertiary referral centre was conducted. Main outcome measures were best and final postoperative visual acuity. RESULTS: A total of 53 eyes of 53 patients were included, 28 eyes received intravitreal t-PA and gas injection (t-PA and gas group) and 25 eyes received intravitreal gas injection alone (gas-alone group). Incidence of best visual acuity improvement was significantly higher in the t-PA and gas group than in the gas-alone group (60.7 vs 32.0%; P=0.037). However, subgroup analysis demonstrated that the difference was significant only in eyes with haemorrhage duration of more than 14 days (46.2 vs 8.3%; P=0.035). Incidence of final visual acuity improvement was not significantly different between the two groups (42.9 vs 28.0%; P=0.39). The complications of vitreous haemorrhage and endophthalmitis were similar between the two groups. Multiple logistic regression analysis demonstrated that shorter haemorrhage duration (<14 days) was the main factor predictive of best visual acuity improvement (OR=9.02, P=0.015). Whether t-PA was used was of borderline significance (OR=4.96, P=0.046). CONCLUSIONS: Intravitreal t-PA was valuable for submacular haemorrhage only in eyes with relatively old haemorrhage. For eyes with recent onset of emorrhage, t-PA is suggested only if initial gas injection failed to displace submacular haemorrhage.

Pars plana vitrectomy for diabetic fibrovascular proliferation with and without internal limiting membrane peeling.

OBJECTIVE: To evaluate the anatomical and functional results of internal limiting membrane (ILM) peeling during pars plana vitrectomy for fibrovascular proliferation (FVP) in diabetic retinopathy. METHODS: The study was a prospective comparative case series in design. Patients undergoing pars plana vitrectomy for mild to moderate diabetic FVP were divided into either Group 1: vitrectomy only, or Group 2: further ILM peeling in the macular area. Best-corrected visual acuity, fundus examination, and optical coherence tomography (OCT) were conducted at 3 and 6 months postoperatively. RESULTS: There were 26 eyes of 25 patients in Group 1 (non-ILM peeling) and 23 eyes of 22 patients in Group 2 (ILM peeling). At 6 months postoperatively, OCT-identifiable epiretinal membrane (ERM) was found in 10 of 26 eyes (38.5%) in Group 1and 0 of 23 eyes in Group 2 (P=0.001) and six eyes (23.1%) in Group 1 developed biomicroscopic ERM, whereas no patients in Group 2 had ERM (P=0.02) at 6 months. OCT identifiable ERM correlated significantly with central macular thickness (r=-0.58, P<0.001), the presence of intraretinal cystic space (r=0.60, P<0.001), and fovea depression reappearance (r=0.36, P=0.008). Factors associated with poor visual outcome were macular detachment (P<0.001) and non-ILM peeling (P=0.004). CONCLUSIONS: This pilot study suggests that ILM peeling during vitrectomy for diabetic fibrovascular proliferative membranes may minimize postoperative ERM formation and improve visual prognosis.

Image-enhanced surgical navigation for endoscopic sinus surgery: evaluating calibration, registration and tracking.

BACKGROUND: Endoscopic sinus surgery (ESS) is generally applied to treat sinusitis when medication is not effective in eliminating the symptoms. Images captured by the endoscope are viewed on a monitor placed near the surgeon. Due to the separation of the handling of the endoscope from the viewing of the image, ESS requires surgeons to have well-trained hand-eye coordination. Unlike the use of the stereo surgical microscope in ENT, the endoscope does not provide the stereo cue for depth perception, hence a surgeon can only perceive depth through motion and shading, which may affect the accuracy of tool placement. Whilst the skill and experience of the surgeon are important factors to the success of ESS, the assistance of image-enhanced surgical navigation (IESN) can further reassure the surgeon's judgement and enhance surgical performance. METHODS: We developed and validated an IESN system (ARView) for a rigid zero-degree endoscope, typically used for ESS. We present the interface, and calibration and registration (pre-operative and intra-operative) methods of the system. We then quantitatively assess the performance of each of the steps needed to generate the overlay of a real endoscope image with its 'virtual' counterpart, obtained from computed tomography (CT) image data of a real skull. These steps include calibration, registration, motion tracking and final overlay. RESULTS: Calibration results using a planar calibration object displayed optimized object space errors of 0.025 +/- 0.013 mm, whilst a non-planar calibration object displayed errors of 0.12 +/- 0.08 mm. Target registration errors (TREs) near the region of interest (ROI), using our pre-operative registration method with the calibration object located near the mouth of the patient (skull), were 2.3 +/- 0.4 mm. The proposed photo-consistency method for intra-operative registration has not yet yielded satisfactory results for ESS-based IESN. (RMS) values for tracking accuracy were found to be around 1.2 mm in a typical workspace of 400 x 400 mm. Object space overlay errors in a small measurement volume of 10 x 10 x 10 mm were found to be around 0.4 +/- 0.02 mm. CONCLUSIONS: We conclude that, in agreement with individual experiments, the current overall overlay accuracy is of the order of 2-3 mm in the x-y plane, which is in line with current conventional SN systems. The method which is most in need of improvement is registration, hence we wish to investigate the application of the proposed photo-consistency method further.

Tea polyphenols, their biological effects and potential molecular targets.

Tea is the most popular beverage in the world, second only to water. Tea contains an infusion of the leaves from the Camellia sinensis plant rich in polyphenolic compounds known as catechins, the most abundant of which is (-)-EGCG. Although tea has been consumed for centuries, it has only recently been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. The results of several investigations indicate that green tea consumption may be of modest benefit in reducing the plasma concentration of cholesterol and preventing atherosclerosis. Additionally, the cancer-preventive effects of green tea are widely supported by results from epidemiological, cell culture, animal and clinical studies. In vitro cell culture studies show that tea polyphenols potently induce apoptotic cell death and cell cycle arrest in tumor cells but not in their normal cell counterparts. Green tea polyphenols were shown to affect several biological pathways, including growth factor-mediated pathway, the mitogen-activated protein (MAP) kinase-dependent pathway, and ubiquitin/proteasome degradation pathways. Various animal studies have revealed that treatment with green tea inhibits tumor incidence and multiplicity in different organ sites such as skin, lung, liver, stomach, mammary gland and colon. Recently, phase I and II clinical trials have been conducted to explore the anticancer effects of green tea in humans. A major challenge of cancer prevention is to integrate new molecular findings into clinical practice. Therefore, identification of more molecular targets and biomarkers for tea polyphenols is essential for improving the design of green tea trials and will greatly assist in a better understanding of the mechanisms underlying its anti-cancer activity.