Latest developments in precancerous lesions of hepatocellular carcinoma

Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.

Meta-analysis of ADH1B and ALDH2 polymorphisms and esophageal cancer risk in China

AIM: To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population. METHODS: Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the genealcohol and gene-gene interaction with ESCC risk. Potential sources of heterogeneity between studies were explored, and publication bias was also evaluated. RESULTS: Individuals with ADH1B arginine (Arg)/Arg genotype showed 3.95-fold increased ESCC risk in the recessive genetic model [Arg/Arg vs Arg/histidine (His) + His/His: odds ratio (OR) = 3.95, 95% confidence in- terval (CI): 2.76-5.67]. Signif icant association was found in the dominant model for ALDH2 lysine (Lys) allele [glutamate (Glu)/Lys + Lys/Lys vs Glu/Glu: OR = 2.00,95% CI: 1.54-2.61]. Compared with the non-alcoholics, Arg/Arg (OR = 25.20, 95% CI: 10.87-53.44) and Glu/ Lys + Lys/Lys (OR = 21.47, 95% CI: 6.44-71.59) were found to interact with alcohol drinking to increase the ESCC risk. ADH1B Arg+ and ALDH2 Lys+ had a higher risk for ESCC (OR = 7.09, 95% CI: 2.16-23.33). CONCLUSION: The genetic variations of ADH1B His47Arg and ALDH2 Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption. The individuals carrying both risky genotypes have a higher baseline risk of ESCC.

Dynamic functional and ultrastructural changes of gastric parietal cells induced by water immersion-restraint stress in rats

AIM： To investigate the dynamic functional and ultrastructural changes of gastric parietal cells induced by water immersion-restraint stress （WRS） in rats.METHODS： WRS model of Sprague-Dawley （SD） rats was established. Fifty-six male SD rats were randomly divided into control group, stress group and post-stress group. The stress group was divided into 1, 2 and 4 h stress subgroups. The post-stress group was divided into 24, 48 and 72 h subgroups. The pH value of gastric juice, ulcer index （UI） of gastric mucosa and H^＋, K^＋- ATPase activity of gastric parietal cells were measured. Ultrastructural change of parietal cells was observed under transmission electron microscope （TEM）.RESULTS： The pH value of gastric juice decreased time-dependently in stress group and increased in post-stress group. The H^＋, K^＋-ATPase activity of gastric parietal cells and the UI of gastric mucosa increased time-dependently in stress group and decreased in poststress group. Compared to control group, the pH value decreased remarkably （P = 0.0001）, the UI and H^＋, K^＋- ATPase activity increased significantly （P = 0.0001, P = 0.0174） in 4 h stress subgroup. UI was positively related with stress time （r = 0.9876, P 〈 0.01） but negatively with pH value （r = -0.8724, P 〈 0.05）. The parietal cells became active in stress group, especially in 4 h stress subgroup, in which plenty of intracellular canalicular and mitochondria were observed under TEM. In post-stress group, the parietal cells recovered to resting state.CONCOUSION： The acid secretion of parietal cells is consistent with their ultrastructural changes during the development and healing of stress ulcer induced by WRS and the degree of gastric mucosal lesions, suggesting gastric acid play an important role in the development of stress ulcer and is closely related with the recovery of gastric mucosal lesions induced by WRS.

Expression of c-erbB-2 and glutathione S-transferase-pi in hepatocellular carcinoma and its adjacent tissue

AIM： To investigate the possible role of c-erbB-2 and glutathione S-transferase （GST-Pi） in primary hepatocellular carcinogenesis and the relationship between liver hyperplastic nodule （LHN）, liver cirrhosis （LC）, and hepatocellular carcinoma （HCC）.METHODS： The expression of c-erbB-2 and GST-Pi was detected immunohistochemically in 42 tissue specimens of HCC and 77 specimens of its adjacent tissue.RESULTS： The positive expression of c-erbB-2 in LHN （28.6%） was significantly higher than that in LC （0%） （P = 0.032〈0.05）, but no significant difference was seen between HCC and LHN or LC （P〉0.05, X^2 = 0.002, 3.447）.The positive expression of GST-Pi in HCC （89.6%） or LHN （72.2%） was significantly higher than that in LC（22.9%, P〈0.001, ;X^2= 49.91, 16.96）. There was a significant difference between HCC and LHN （P〈0.05,X^2= 6.353）.CONCLUSION： The c-erbB-2 expression is an early event in the pathogenesis of HCC. GST-Pi may be a marker enzyme for immunohistochemical detection of human HCC and its preneoplastic lesions. LHN seems to be a preneoplastic lesion related to hepatocarcinogenesis.

Extract of Cycas revoluta Thunb. enhances the inhibitory effect of 5-fluorouracil on gastric cancer cells through the AKT-mTOR pathway

BACKGROUND Gastric cancer is one of the most common and deadly malignancies worldwide.Despite recent medical progress, the 5-year survival rate of gastric cancer is still unsatisfactory. 5-fluorouracil(5-Fu) is one of the first-line antineoplastic treatments for gastric cancer, as it can effectively induce cancer cell apoptosis.However, the effect of 5-Fu is limited due to drug resistance of the malignant tumor. Previous studies have reported that Sotetsuflavone from Cycas revoluta Thunb. can markedly suppress lung cancer cell proliferation by apoptosis,though its effect on gastric cancer remains unknown.AIM To investigate the inhibitory effect of Cycas revoluta Thunb. and to determine whether it can overcome gastric cancer cell drug resistance to 5-Fu.METHODS Cell viability was examined to determine whether the natural extract of Cycas revoluta Thunb. induced gastric cancer cell death. The half-maximal effective concentration and the half-maximal lethal concentration were calculatede.Wound-healing and transwell assays were performed to examine gastric cancer cell motility. Clonogenic assays were performed to investigate the synergistic effects of Cycas revoluta Thunb. with 5-Fu, and apoptotic bodies were detected by Hoechst staining. Western blotting was performed to examine the expression of related proteins and to investigate the molecular mechanism of Cycas revoluta Thunb.-induced cancer cell apoptosis. The expressions of proteins, including mammalian target of rapamycin(mTOR) and p-AKT, were detected in different combinations of treatments for 48 h, then analyzed by ECL detection.RESULTS Gastric cancer cells were more sensitive to the natural extract of Cycas revoluta Thunb. compared to normal gastric epithelial cells, and the extract effectively inhibited gastric cancer cell migration and invasion. The extract improved the anti-cancer effect of 5-Fu by enhancing the chemosensitization of gastric cancer cells. Extract plus 5-Fu further reduced the expression of the drug-resistancerelated proteins p-AKT and mTOR after 48 h compared to 5-Fu alone. Compared to 5-Fu treatment alone, mTOR and p-AKT expression was significantly reduced by about 50% and 75%, respectively. We also found that the natural extract of Cycas revoluta Thunb. further increased 5-Fu-induced gastric cancer cell apoptosis. Expression of apoptosis-related protein X-linked inhibitor of apoptosis protein and apoptosis inducing factor were significantly reduced and increased,respectively, in the 5-Fu-resistant gastric cancer line SGC-7901/R treated with extract plus 5-Fu, while the expression of survivin did not change.CONCLUSION The natural extract of Cycas revoluta Thunb. effectively inhibited gastric cancer cell growth and enhanced the anti-cancer effect of 5-Fu through the AKT-mTOR pathway.

Changes of microcirculation in healthy volunteers and patients with septic shock in Xining

Objective: The purpose of this study is to investigate the characteristic of microcirculation in healthy volunteers and patients with septic shock in both Xining(2 260 m) and Nanjing(10 m). Methods: A total of 62 cases, 33 healthy volunteers, 22 cases in Xining,(2 260 m above sea level) and 11 cases in Nanjing(10 m above sea level); and 29 septic shock, 13 cases in Xining and 16 cases in Nanjing were collected. The total vessel density(TVD), perfused vessel density(PVD), proportion of perfused vessel(PPV) and microcirculation flow index(MFI) of both healthy volunteers and septic shock had been investigated by using sidestream dark field(SDF). Analyzed and managed the image data by using AVA3.0 software. Results: In the healthy volunteers in Xining area(22 cases),the volume of TVD(15.59 ± 2.58 mm/mm^2), PVD(15.58 ± 2.58 mm/mm^2) and PPV(96.60% ± 4.63%) were significant higher than the volume of TVD(10.0 ± 2.10 mm/mm^2), PVD(10.81 ± 2.38 mm/mm^2) and PPV(84.24% ± 8.00%) of the volunteers(11 cases) in Nanjing(11 cases). But the MFI(2.17 ± 0.31) of the healthy volunteers in the Xining was significant lower(P<0.05) than the MFI(3.21 ± 0.34) in the healthy volunteers of Nanjing. In the septic shock group(13 cases) in the Xining, the volume of TVD(5.44 ± 1.94 mm/mm^2), PVD(4.18 ± 1.61 mm/mm^2), PPV(42.14%± 5.38%) and MFI(1.05 ± 0.32) compared with the volume of the healthy volunteers in Xining, the TVD(15.59 ± 2.58 mm/mm^2), PVD(5.58 ± 2.58 mm/mm^2), PPV(96.60% ± 4.63%) and MFI(2.17 ± 0.30) were significant lower(P<0.05). In the healthy volunteers compare with septic shock group in Nanjing area, the TVD(6.80±1.72 vs 10.00±2.10, P<0.05), PVD(5.86±1.58 vs10.81±2.38,P<0.05), PPV(45.42±4.86 vs 84.24±4.86, P<0.05), MFI(1.28±0.28 vs 3.21±0.34 P<0.05), there was significant decreased. In the septic shock group in the Xining compared with the septic shock in Nanjing, there was no significant difference. 10 of 13 patients with septic shock were survived in Xining. 13 of 16 patients with septic shock were survived in Nanjing. Conclusion: The changes of physiological and pathophysiological characteristic in microcirculation induced by hypoxia would be useful for clinical treatment of septic shock at high altitude.

Activities of autonomic neurotransmitters in meibomian gland tissues are associated with menopausal dry eye

The secretory activities of meibomian glands are regulated by the autonomic nervous system, The change in density and activity of autonomic nerves in meibomian glands during menopause play an important role in the pathogenesis of dry eye. In view of this, we established a dry eye rat model by removing the bilateral ovaries. We used neuropeptide Y and vasoactive intestinal polypeptide as markers of autonomic neurotransmitters. Our results showed that the concentration of estradiol in serum significantly decreased, the density of neuropeptide Y immunoreactivity in nerve fibers significantly increased, the density of vasoactive intestinal polypeptide immunoreactivity in nerve fibers significantly decreased, and the ratio of vasoactive intestinal polypeptide/neuropeptide Y positive staining significantly decreased. These results suggest that a decrease in ovary activity may lead to autonomic nervous system dysfunction, thereby affecting the secretory activity of the meibomian gland, which participates in sexual hormone imbalance-induced dry eye.

Eradication of Helicobacter pylori increases childhood growth and serum acylated ghrelin levels

AIM: To determine whether Helicobacter pylori (H. pylori)infected children have reduced body weight (BW) and height (BH) growth, and if H. pylori eradication may restore growth while improving serum acylated ghrelin. METHODS: This longitudinal cohort study with oneyear follow-up enrolled 1222 children aged 4 to 12 years old into an observation cohort (18 with and 318 without H. pylori ) and intervention cohort (75 with and 811 without). The 7-d triple therapy was used for eradication in the intervention cohort. The net increases of BW and BH as well serum acylated ghrelin after oneyear follow-up were compared between successful eradicated H. pylori-infected children and controls. RESULTS: In the observation cohort, the H. pylori - infected children had lower z score of BW (-1.11 ± 0.47 vs 0.35 ± 0.69, P = 0.01) and body mass index (BMI) (0.06 ± 0.45 vs 0.44 ± 0.73, P = 0.02) at enrollment and lower net BW gain after one-year follow-up (3.3 ± 2.1 kg vs 4.5 ± 2.4 kg, P = 0.04) than the non-infected controls. In the intervention cohort, the H. pylori - infected children had lower z score of BMI (0.25 ± 1.09 vs 0.68 ± 0.87, P = 0.009) and serum acylated ghrelin levels (41.8 ± 35.6 pg/mL vs 83.6 ± 24.2 pg/mL, P < 0.001) than the non-infected controls. In addition to restoring decreased serum ghrelin levels (87.7 ± 38.0 pg/mL vs 44.2 ± 39.0 pg/mL, P < 0.001), the H. pylori - infected children with successful eradication had higher net gains (P < 0.05) and increase of z scores (P < 0.05) of both BW and BH as compared with non-infected controls after one-year follow-up. CONCLUSION:H. pylori-infected children are associated with low serum acylated ghrelin and growth retardation. Successful eradication of H. pylori restores ghrelin levels and increases growth in children.

The expressions and significance of α-,β-catenins and cyclin D1 in breast cancers

Objective： To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis of breast cancer. Methods： High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-, β-catenins and cyclin D1 in the 60 cases of breast cancer tissues. Results： Abnormal immunoreactivities of α- and β-catenins were observed in 37 （61.7%） and 42 （70%） cases of breast cancer tissues, respectively. There were 28 cases （46.7%） who showed cyclin D1 overexpression. The abnormal expression rates of α- and β-catenins in infiltrating Iobular carcinoma （ILC） were significantly higher than those in infiltrating ductal carcinoma （IDC） （P 〈 0.05）, but they had no relations to the extent of differentiation and lymphatic metastasis of breast cancer （P 〉 0.05）. The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer （P 〈 0.05）, but not with histological type and the extent of differentiation （P 〉 0.05）. Cyclin D1 overexpression was observed in 57.1% （24/42） of these cases that showed abnormal staining of β-catenin, but only observed in 22.2% （4/18） of these cases with normal membranous staining of β-catenin. There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1 （r, = 0.321, P 〈 0.05）. Conclusion： The abnormal expression of β-catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer. The abnormal expressions of α- and β-catenins are not a key factor in malignant cell metastasis in breast cancer, but may also involve in the progress.

Role of DJ-1-induced PTEN down-regulation in migration and invasion of human glioma cells

Background and Objective: DJ-1, a suppressor of PTEN, promotes metastasis of different tumors, but its function and mechanisms in glioma metastasis remain unclear. This study aimed to investigate the effect of the DJ-1 protein on the migration and invasion of human glioma cells, and to explore potential mechanisms. Methods: The eukaryotic expression vector pEGFP/DJ-1 and small interfering RNA (siRNA) were constructed and transfected into human glioma SWO-38 cells. The expression of DJ-1 and PTEN in SWO-38 cells were detected by Western blot. Cell migration and invasion were detected by transwell assay. Results: After transfection of pEGFP/DJ-1, the expression of DJ-1 (1.28 ± 0.15 vs. 0.89 ± 0.04, P < 0.05) and focal adhesion kinase (FAK) phosphorylation (0.76 ± 0.12 vs. 0.51 ± 0.04, P < 0.05) were increased, whereas the expression of PTEN (0.74 ± 0.2 vs. 1.04 ± 0.14, P < 0.05) was suppressed. After transfection of DJ-1 siRNA, both DJ-1 (0.33 ± 0.04 vs. 0.88 ± 0.06, P < 0.05) and p-FAK levels (0.33 ± 0.01 vs. 0.44 ± 0.05, P < 0.05) were decreased, but PTEN expression (1.1 ± 0.06 vs. 0.81 ± 0.12, P < 0.05) was increased. Transwell assay data showed that pEGFP/DJ-1 transfection promoted SWO-38 cell migration (57.2 ± 6.50 vs. 40.4 ± 5.0, P < 0.05) and invasion (54.6 ± 4.9 vs. 27 ± 6.7, P < 0.05), whereas DJ-1 siRNA transfection inhibited SWO-38 cells migration (54.4 ± 6.9 vs. 73.4 ± 7.6, P < 0.05) and invasion (44.6 ± 5.8 vs. 69.2 ± 9.2, P < 0.05). Conclusion: Over-expression of DJ-1 promotes SWO-38 cell migration and invasion possibly through the DJ-1 and the PTEN/FAK pathway.

The expression of Usp26 gene in mouse testis and brain

Deubiquitinating enzymes （DUBs） play an important role in ubiquitin-dependent processes as negative regulators of protein ubiquitination. Ubiquitin-specific protease 26 （USP26） is a member of this family. The expression of Usp26 in mammalian testis and in other tissues has yet to be fully elucidated. To study the expression of Usp26 mRNA and protein in various murine tissues, reverse transcription （RT）-PCR and immunohistochemistry analyses were carried out. The RT-PCR analysis showed that the Usp26 transcript was expressed in all of the tested tissues. USP26 protein localization was examined by immunohistochemistry, and it was shown that USP26 was not detectable at 20 days postpartum, with the expression restricted to the cytoplasm of condensing spermatids （steps 9-16）, Leydig cells and nerve fibers in the brain. In addition, the USP26 protein was detected at moderate levels in myocardial ceils, the corpus of epidydimis, epithelium of the renal tubules and the seminal gland of postnatal day 35 mice. Its spatial and temporal expression pattern suggests that Usp26 may play an important role in development or function of the testis and brain. Further research into these possibilities is in progress.

Transplantation of olfactory ensheathing cells promotes axonal regeneration in a rat model of spinal cord injury

BACKGROUND：Transplantation of olfactory ensheathing cells （OECs） into the injured spinal cord has been shown to promote axonal regeneration and functional recovery.However,the mechanisms underlying the effects of OEC transplantation remain controversial.OBJECTIVE：To observe fibrotic scar formation and axonal regeneration in the damaged spinal cord following OEC transplantation,and to determine whether OEC transplantation promotes neural regeneration by attenuating fibrotic scar formation.DESIGN,TIME AND SETTING：A randomized,controlled animal experiment was performed at the Department of Developmental Morphology,Tokyo Metropolitan Institute for Neuroscience,Fuchu,Japan and at the Department of Human Anatomy,College of Basic Medical Sciences,China Medical University,China between April 2007 and May 2009.MATERIALS：OECs were obtained from olfactory nerves and olfactory bulbs of male,4-week-old,Sprague Dawley rats.Rabbit anti-serotonin polyclonal antibody,rabbit anti-calcitonin gene-related peptide polyclonal antibody,rabbit anti-glial fibrillary acidic protein polyclonal antibody,rabbit anti-type IV collagen polyclonal antibody,and mouse anti-rat endothelial cell antigen-1 monoclonal antibody were used.METHODS：Male,Sprague Dawley rats aged 8 weeks were randomly divided into three groups：sham-surgery （n = 3）,surgery （n = 9）,and OEC transplantation （n = 11）.Spinal cord transection at the T9-10 level was performed and the rats were transplanted with a 2-μL （1 × 105 cells） cell suspension.MAIN OUTCOME MEASURES：Formation of glial and fibrotic scars was examined using immunohistochemistry for glial fibrillary acidic protein and type IV collagen.Serotonin-positive and calcitonin gene-related peptide-positive axons were visualized by immunohistochemistry,respectively.Double immunofluorescence for type IV collagen and rat endothelial cell antigen-1 was also performed to determine co-localization of type IV collagen deposition and blood vessels.RESULTS：At 1 week after spinal cord injury,numerous glial cells were observed around the lesion site.Formation of fibrotic scar was determined by a large amount of type IV collagen deposition in the lesion center,and descending serotonin- or ascending calcitonin gene-related peptideconiaining axons stopped at the fibrotic scar that was formed in the lesion site.At week after transplantation,the formation of fibrotic scar was significantly inhibited.In addition,the fibrotic structure was partly formed and centralized in the blood vessel,and serotonergic and calcitonin gene-related peptide-containing axons were regenerated across the lesion site.CONCLUSION：OEC transplantation into the injured spinal cord attenuated fibrotic scar formation and promoted axon regeneration.

Research Progress on Metastatic Carcinoma of the Spleen

Metastatic carcinoma of the spleen (MCS) is a rare condition which is frequency misdiagnosed. Research progress on the prevalence, clinicopathological features and diagnosis of MCS from the Chinese and English medical literature was reviewed to increase understanding of all aspects related to MCS. It is hoped that a better comprehension of MCS will increase the diagnotic level and the rate of MCS detection.

Detection of Human Papillomaviral Infection on Kazakh Patients with Esophageal Squamous Cell Carcinoma in Xinjiang

OBJECTIVE To investigate the detection rate of humanpapilloma virus (HPV) DNA in the Kazakh esophageal carcinoma(EC) patients of Xinjiang.METHODS We detected the prevalence of a HPV gene in tumortissues from 318 esophageal squamous cell carcinoma (ESCC).Tumor tissues were kept in formalin and embedded in paraffin.One hundred seventeen samples used crude cell suspension, whilethe other 201 used the method of DNA extraction with phenol-Tris/chloroform. We analyzed the relevance to EC of Kazakh's inXinjiang.RESULTS In the ESCC samples of Kazakh's in Xinjiang, totaldetection rate for HPV DNA was 64.5% (205/318). The positiverate of HPV in group of crude cell suspensions was 82.9% (97/117)compared with the rate of 53.7% (108/201) in the group of DNAextraction. The results in the two groups showed significantdiffference (x^2 = 5.711, P < 0.05).CONCLUSION HPV DNA infection may be one of the mostimportant factors related to EC of Kazakh's in Xinjiang.

Clinical significance of heat shock protein 10 in large bowel carcinoma

Objective： To investigate the expression of heat shock protein 10 （HSPIO） during genesis and development of large bowel carcinoma and discuss the clinical significance about its expression. Methods： The expression of HSPIO was observed in specimens from normal colonic mucosa （NC）, colorectal adenomas （CA） and colorectal adenocarcinomas （CAC） by immunohistochemistry EnVisionTM. Its correlations to clinicopathologic features, as well as to postoperative survival time of large bowel carcinoma patients were analyzed. Results： The expression of HSPIO was common in normal colonic mucosa, colorectal adenomas and adenocarcinomas and more intensive in colorectal adenomas and adenocarcinomas than that in normal colonic mucosa （P 〈 0.001）. The positive expression of HSPIO had no correlation to clinicopathologic features, including age, gender, primary tumor, infiltrating of regional lymph node, metastasis, clinical stage and histopathology of large bowel carcinoma patients, as well as to their postoperative survival time. Conclusion： HSPIO was overexpressed in the early stage of colorectal adenocarcinoma suggesting that it could serve as an index for early diagnosis of large bowl carcinoma. The positive expression of HSPIO had no correlation to clinicopathologic features or postoperative survival time of large bowel carcinoma patients.

Research progreess on relevant diseases of RhoA/ROCK signaling pathway

RhoA (Ras homolog gene family member A) belongs to the Rho subfamily of GTPases. ROCK (Rho—associated coiled—coil forming protein kinase) is downstream of the active RhoA and affects the generation and secretion of cellular element, which will result in relevant biologic effects. The RhoA/ROCK signaling pathway consists of these serious reactions. Therefore, the activation and inhibition of this pathway are closely related to the occurrence and development of many diseases. The research on the molecular mechanism of these diseases may be instructive and helpful to the clinical treatmen and prognosis of diseases. Recent studies of these typical diseases related to RhoA/ROCK signaling pathway are viewed in this article.

ULTRASTRUCTURAL STUDY ON THE INVASION OF RETINAL INNER LIMITING MEMBRANE BY THE MALIGNANT TUMOR CELLS

To observe the process of invasion, retina of rat was used as a model to substitute the inner limiting membrane of retina for the basement membrane. Retina invaded by esophageal carcinoma cells and B16 melanoma cells upon the inner limiting membrane was studied by scanning and transmission electron microscopy. The results showed that the inner limiting membrane was destroyed by both kinds of tumor cells. The process of destruction was followed by a series of transformations in the inner limiting membrane, i.e. folding, swelling, thickening, and granular change. The inner limiting membrane was dissolved focally as a result of transformation, and then tumor cells invaded the retina through these dissolved regions. It seems that, as a barrier, the inner limiting membrane plays a similar role as the basement membrane.

Identification and significance of differential proteins in A549 cells transfected with HLCDG1

HLCDG1, which locates in chromosome 5q33, is a novel gene cloned recently. The HLCDG1 expression was significantly down regulated in the primary lung carcinoma. It was previously studied that HLCDG1 acted like a tumor suppressor gene. In this paper, proteomics studies were performed to analyze the proteomic expression patterns in the HLCDG1-transfected human lung carcinoma cell line (A549-HLCDG1) and in the control vector-transfecred human lung carcinoma cell line (A549-vector). Employing two dimensional gel eleetrophoresis (2DE), the global pattern of protein expressions in A549-HLCDG1 human lung adenocarcinoma cell line expressing stably HL-CDG1 gene were compared with those of control A549-vector cell line to generate a differential protein expression catalog. Forty-two differentially expressed proteins were screened. Thirteen differential proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), which were 6 upregulated (MSH5, MOD, MDH precursor, ETFβ, Prxd Ⅵ and JM23) and 7 downregulated (PLC-δ1, hnRNPA2,hnRNPB1, TIM, TCTP, nm23H-1 and PrxdⅤ) proteins in A549-HLCDG1 cells compared to control A549-vector cells. The above identified proteins were involved in energy metabolism, transcription regulation, antioxidation,cell cycle, metastasis, DNA methylation and mismatch repair. Therefore, these differential expression proteins by HLCDG1 transfection may play some important roles for investigation of the biochemical basis of growth suppression of HLCDG1 gene in lung carcinoma cells A549. Further understanding of this data base may provide valuable resources for the developing novel diagnostic markers and therapeutic targets of lung cancer.

外科医生和病理医生对胸腺恶性肿瘤切除标本的处理方法和程序

胸腺恶性肿瘤发病率低，临床病例分散，需要结合多中心经验才能进行良好的研究，但由于在诸多方面没有统一标准，使得研究与研究之间的可比性差。其中外科医生和病理医生对胸腺恶性肿瘤切除标本的处理是统一标准中至关重要的部分。针对目前胸腺瘤的常用手术方式胸骨劈开根治性R0切除术的标本处理作如下规定，包括切除胸腺瘤及周围的受累结构说明如何处理手术切除标本。活检或细胞学标本的处理另文描述[1]。本文首先由国际胸腺肿瘤协作组织（International hTymic Malignacy Interest Group, ITMIG）中病理医生和外科医生组成的小组回顾相关文献形成初步建议[2,3]，交扩展组审议提炼后分发给ITMIG成员进讨论，再将ITMIG成员回馈的建议和几个大中心试点的情况进行提炼，最终形成的建议经ITMIG批准并被采用。因此，既强调证据又代表ITMIG成员的广泛共识。

Significance and relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma tissues

AIM: To investigate the relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma (HCC) tissues and their clinicopathological features.METHODS: The paraffin-embedded specimens from 70 cases with HCC were stained using EliVision immunohistochemistry with mAbs against CD68, tryptase,and CD34. The counts of tumor-associated macrophage (TAM), mast cell (MC) and tumor microvessel (MV) were performed in the tissue sections.RESULTS: The mean counts of TAM, MC, and MV in HCC tissues were significantly higher than those in pericarcinomatous liver tissues (TAM: 69.31± 11.58 vs 40.23±10.36; MC: 16.74±5.67 vs 7.59±4.18; MV:70.11±12.45 vs 38.52± 11.16, P＜0.01). The MV count in the patients with metastasis was markedly higher than that with non-metastasis (P＜0.01). In addition, the MC count in the patients with poorly differentiated HCC was obviously higher than that with well differentiated HCC (P＜ 0.01). The correlation analysis showed that the TAM count was significantly correlated with the count of MV(r=0.712, P＜0.01), and the MC count was obviously correlated with the MV count (r= 0.336, P＜ 0.05).CONCLUSION: TAM and MC might be closely related to the enhancement of tumor angiogenesis. The MV count might be associated with tumor invasion and metastasis.Moreover, the MC count might be associated with tumor differentiation and prognosis of HCC.