[Clinicopathological analysis of 11 cases of hepatic amyloidosis].

Objective: Hepatic amyloidosis is a metabolic disease with a low incidence rate. However, because of its insidious onset, the rate of misdiagnosis is high, and it usually progresses to a late stage when it is diagnosed. This article analyzes the clinical features of hepatic amyloidosis by combining clinical pathology in order to improve the clinical diagnosis rate. Methods: Clinical and pathological data of 11 cases of hepatic amyloidosis diagnosed at the China-Japan Friendship Hospital from 2003 to 2017 were summarized and analyzed retrospectively. Results: The clinical manifestations of 11 cases mainly included abdominal discomfort (4/11), hepatomegaly (7/11), splenomegaly (5/11), fatigue (6/11), etc. Biochemical test results showed that most patients' alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, total bilirubin, direct bilirubin, and total bile acids, accompanied by hypoalbuminemia were elevated, while some patients' 24-h urinary protein, creatinine, and blood urea nitrogen were elevated. Conclusion: All patients had slightly elevated aspartate transaminase levels (within 5 times the upper limit of normal), and 72% had slightly elevated alanine transaminase. Alkaline phosphatase and γ-glutamyl transferase levels were significantly raised in all cases, with the highest result for γ-glutamyl transferase being 51 times the upper limit of normal. Damage to the hepatocytes has an effect on the biliary system as well, leading to symptoms such as portal hypertension and hypoalbuminemia [(0.54~0.63) × upper limit of normal value, 9/11]. Amyloid deposits within the artery wall (54.5% of patients) and portal vein (36.4% of patients) were also indicative of vascular injury. A liver biopsy should be recommended for patients with unexplained elevated transaminases, bile duct enzymes, and portal hypertension in order to establish a definitive diagnosis.

Prognostic role of MUC-2 expression in patients with gastric carcinoma: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to assess the association of MUC-2 expression with clinicopathological parameters in gastric carcinoma (GC) patients. MATERIALS AND METHODS: Clinical databases based on the study aim were searched in detail. The relative risk ratios (RRs) and associated 95% confidence intervals (95% CIs) were computed after eligible trials were included in the study. RESULTS: Nineteen trials involving 2,363 GC patients were included in this meta-analysis. The expression of MUC-2 showed correlation with clinical stage (I/II vs. III/IV) (RR = 1.09, 95% CI: 1.00-1.18, I2 = 24%, p = 0.194), and lymphatic invasion (present vs. absent) (RR = 0.83, 95% CI: 0.72-0.95, I2 = 22.3%, p = 0.252). However, no significant association was identified between the MUC-2 expression and other clinicopathological parameters, including gender (male vs. female), tumor size (>5 vs. ≤5 cm), Lauren's classification (intestinal vs. diffuse), tumor differentiation (poorly vs. well and moderately), lymph node metastasis (present vs. absent), vascular invasion (present vs. absent), and 5-year survival (yes vs. no) of GC patients. CONCLUSIONS: Our meta-analysis findings suggested that MUC-2 positive cases were correlated with lower tumor stage and lower rate of lymphatic invasion. Further clinical studies are warranted to confirm the role of MUC-2 in clinical practice.

[Clinical effects of individualized free anterolateral thigh flap in repairing complex refractory wound].

Objective: To explore the clinical effects of individualized free anterolateral thigh flap in repairing complex refractory wound. Methods: From July 2015 to May 2019, 19 patients with complex refractory wounds were hospitalized in Yulin NO.1 People's Hospital of Guangxi Zhuang Autonomous Region, including 12 males and 7 female, aged 13-67 years. There were 5 patients with multiple tissue defects, 7 patients with large area of wounds, and 7 patients with wounds in special areas. The sizes of wounds after complete debridement were 8 cm×5 cm-23 cm×7 cm. According to the repair demand, the wounds in 5 patients were repaired with anterolateral thigh flaps and flow-through, the wounds in 7 patients were repaired with anterolateral thigh flaps chimed with lateral thigh muscle flaps, with vascular anastomosis in 2 patients, the wounds in 6 patients were repaired with unilateral anterolateral thigh lobulated flaps, and the wound in 1 patient was repaired with bilateral anterolateral thigh flap in series connection. The sizes of flaps were 10 cm×7 cm-25 cm×9 cm. The donor sites were sutured directly or repaired with thin split-thickness skin graft of head. The survival of the flaps, the appearance of the donor sites, and wounds repair after the operation and during follow-up were observed. Results: The lobulated flap in 1 patient had local necrosis after the operation and finally healed by debridement, dressing change, and transplanting medium split-thickness skin graft in groin. The flaps in 18 patients survived with good blood supply, and the lobulated flap tissue was swollen in 1 of 18 patients. The donor sites which were directly sutured in 18 patients only had linear scar, and the donor site which was repaired with thin split-thickness skin graft of head in 1 patient had flaky scar. Follow-up of 1-12 months showed that all the wounds healed well, the flap thinning operations were performed in 5 patients in 3 months post operation because the flaps were slightly bloated. The CT angiography after the operation showed that the anastomosed blood vessels were unobstructed in 7 patients with reconstructed local blood supply. Conclusions: The special forms of anterolateral thigh flap, such as lobulation, series connection, and chimerism can be designed according to the anatomical characteristics of the descending branch of the lateral femoral artery to meet individualized repair demand for complex refractory wounds, and achieve the double purposes of making full use of the donor site tissue and good repair of the recipient site.

[Clinical features and outcome of treatment for novel coronavirus pneumonia: a meta-analysis].

Objective: To investigate the clinical features and outcome of treatment for novel coronavirus pneumonia. Methods: Literature on novel coronavirus pneumonia was retrieved from PubMed and EMBASE databases. The relevant data was extracted and a meta-analysis was performed using StatsDirect statistical software V.2.8.0 to calculate the combined odds ratio. Results: Seven studies were included, consisting of 1594 cases. The meta-analysis result showed that the most common clinical symptoms of the novel coronavirus pneumonia were fever (91.6%) and cough (64.5%), followed by dyspnea (32.8%) and sputum (28.1%). Headache (10.5%), sore throat (11.2%), hemoptysis (3.2%), diarrhea (6.6%) and the other symptoms were relatively rare. Aspartate aminotransferase (29%), alanine transaminase (22.7%), and total bilirubin (11.7%) levels were elevated, except for serum albumin levels (80.4%). The common therapeutic agents used were antibiotics (87.7%), antiviral drugs (75.5%), and glucocorticoids (26.6%), while antifungal agents (7.7%) were used in few. Mechanical ventilation (13.4%), extracorporeal membrane oxygenation (1.9%), and continuous renal replacement therapy (3.8%) were used in severe cases. The rate of mortality in hospital was 7.7%, respectively. Heterogeneity between studies was significant; however, subgroup and sensitivity analysis had failed to identify clear sources of heterogeneity. Conclusion: Fever, cough and liver dysfunction are the main clinical manifestations of this disease and the mortality rate is low.

Association between osteocalcin and glucose metabolism: a meta-analysis.

UNLABELLED: This meta-analysis aimed to investigate the associations between osteocalcin (Ocn) and fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c). It was revealed that both total Ocn and undercarboxylated Ocn (unOcn) were negatively related with FPG and HbA1c, and the association of unOcn with FPG was more pronounced in men. INTRODUCTION: The aim of this study was to investigate the strength of associations between Ocn and FPG and HbA1c using a meta-analysis approach. METHODS: A search was carried out using the databases of PubMed, ISI Web of Science, and the Cochrane library from 2007 to 2014 to identify related studies. A pooled effect size with 95 % confidence intervals (CI) was derived. RESULTS: The meta-analysis included 39 studies involving 23,381 participants. The overall correlation was -0.16 (95 % CI, -0.19 to -0.14) between total Ocn (tOcn) and FPG and -0.15 (95 % CI, -0.20 to -0.11) between undercarboxylated Ocn (unOcn) and FPG. In the analysis of the association between Ocn and HbA1c, the pooled correlation was -0.16 (95 % CI, -0.18 to -0.14) for tOcn and -0.16 (95 % CI, -0.23 to -0.08) for unOcn. The magnitude of the correlation between unOcn and FPG is significantly higher in men than in women (r = -0.18, 95 % CI, -0.21 to -0.14; r = -0.09, 95 % CI, -0. 13 to -0.05, respectively; P for interaction < 0.05). Similar trend was also found between unOcn and HbA1c but without significance (for men, r = -0.19, 95 % CI, -0.24 to -0.14; for women, r = -0.09, 95 % CI, -0.22 to 0.04, respectively; P for interaction > 0.05). No indication of significant publication bias was found in any method. CONCLUSIONS: This meta-analysis demonstrated that both unOcn and tOcn were similarly and negatively correlated with FPG and HbA1c in humans. The negative correlations between unOcn and glucose metabolism appear to be more pronounced in men than in women.

Hypoxia and Serum deprivation protected MiaPaCa-2 cells from KAI1-induced proliferation inhibition through autophagy pathway activation in solid tumors.

PURPOSE: KAI1 closely correlates with pancreatic cancer metastasis. There might be some factors that protect the cells from a proliferation inhibition by KAI1 in the solid tumors' microenvironment. Hypoxia and ischemia are the main characteristics of the microenvironment within solid tumors. Whether they affect the KAI1 inhibitory effects on cell proliferation is still unclear. METHODS: MiaPaCa-2 human pancreatic cancer cells do not express KAI1 protein. However, after being infected with Ad5-KAI1, they expressed KAI1 protein. We cultured them under hypoxic and serum-free conditions to simulate the solid tumor hypoxic-ischemic microenvironment. The cells were divided into the control, hypoxic, serum-free, and hypoxic with serum-free groups. The proliferation and apoptosis were observed by CCK8 and Annexin V-FITC/PI, respectively. The green fluorescent protein-labeled light chain 3 association with autophagosome membranes was detected by confocal microscopy. The ratio of LC3-II-LC3-I expression level was detected by western blot. Pretreatment of 3-MA was used to inhibit the autophagy. We, then observed whether the hypoxic and serum-free conditions could change the effect of KAI1 on cell survival and whether the pretreatment of 3-MA could inhibit the effect of hypoxic and serum-free conditions on KAI1 function. RESULTS: Hypoxia and serum-free media effectively reduced the apoptosis and proliferation inhibition caused by KAI1 and was beneficial to the cell survival. 3-MA pretreatment effectively blocked the protective effect of hypoxia and serum-free media on the cells by autophagy block. CONCLUSIONS: Serum-free media and hypoxia protected the MiaPaCa-2 cells from a KAI1-induced apoptosis and proliferation inhibition via autophagy induction.

The mechanism of COX-2 regulating HERG channel in gastric cancer cells.

OBJECTIVES: To elucidate the signal transduction pathway, by which cyclooxygenase-2 (COX-2) regulates human erg-related gene (HERG) current in gastric cancer cells. METHODS: The HERG mRNA, protein and current in gastric cancer cells transfected with or without COX-2 antisense vector were measured by RT-PCR, Western blot and patch-clamp, respectively. Cyclic adenosine monophosphate (cAMP) concentration in gastric cancer cells transfected with or without COX-2 antisense vector was measured by ELISA. RESULTS: Transfection with COX-2 antisense vector did not alter the expression of HERG mRNA and protein, but it diminished the amplitude of HERG current in gastric cancer cells (p < 0.05). The cAMP concentration in gastric cancer cells transfected with COX-2 antisense vector was lower than that in parental gastric cancer cells (p < 0.05). COX-2 inhibitor and PGE2 had influence on the HERG current in gastric cancer cells. COX-2 inhibitor reduced the amplitude of HERG current in gastric cancer cells and PGE2 enhanced the amplitude. However, in gastric cancer cells transfected with HERG mutant deleting cAMP-binding domain, both COX-2 inhibitor and PGE2 did not show significant effects on HERG current. cAMP agonist enhanced the amplitude of HERG current and cAMP antagonist reduced the amplitude in gastric cancer cells. Both agonist and antagonist of cAMP had no significant effect on HERG current in gastric cancer cells transfected with HERG mutant deleting cAMP binding domain. PKA inhibitor did not influence the HERG current whether in parental gastric cancer cells or in gastric cancer cells transfected with HERG mutant.

Isolation and characterization of eighteen polymorphic microsatellite loci in Schizopygopsis younghusbandi Regan and cross-amplification in three other Schizothoracinae species.

Eighteen polymorphic microsatellite loci were isolated from Schizopygopsis younghusbandi Regan and the characterization of these loci was assessed in 46 individuals collected from the Yarlung Tsangpo River in Tibet, China. The numberof alleles per locus ranged from 2 to 14. The expected heterozygosity and Shannon-Wiener diversity index ranged from 0.022 to 0.879 and from 0.059 to 2.313, respectively. The cross-species amplification and applicability of these loci were tested in three other Schizothoracinae species belonging to Schizothorax and Oxygymnocypris. These loci will be useful for the evaluation of genetic diversity and population genetic structure in S. younghusbandi and other related species.

Two susceptible diabetogenic variants near/in MTNR1B are associated with fasting plasma glucose in a Han Chinese cohort.

AIMS: To investigate the two variants (rs1387153 and rs10830963) near/in the melatonin receptor 1B gene (MTNR1B) and to determine their association with Type 2 diabetes, as well as with the regulation of fasting plasma glucose (FPG) in Han Chinese subjects. METHODS: The two variants were genotyped in 1912 unrelated Type 2 diabetic patients and 2041 healthy individuals. Association with Type 2 diabetes was calculated by logistic regression with adjustments for sex, age and body mass index. The possible connection between the risk alleles and FPG was analysed by multiple linear regression. RESULTS: The two polymorphisms were associated with FPG levels in the healthy individuals (P = 0.003 and P = 0.002, respectively), and the G allele of rs10830963 was also associated with an increased risk of Type 2 diabetes in our patient sample (odds ratio, 1.12; 95% confidence interval, 1.02-1.23; P = 0.024). Moreover, the linkage disequilibrium degree of two single nucleotide polymorphisms was high (r(2) = 0.66), which is similar to that of Europeans. CONCLUSIONS: The common variant in MTNR1B confers the risk of Type 2 diabetes and modulates FPG in both the Han Chinese and European populations.

Differential expression of metastasis-associated genes in papilla of vater and pancreatic cancer correlates with disease stage.

PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer. PATIENTS AND METHODS: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins. RESULTS: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages. CONCLUSION: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities.

[The effect of autocrine factors on development of early embryos of mouse].

Two-cell-stage embryos were flushed from the oviducts on Day 2. Zygotes were collected from oviducts on Day 1 (Fertilization In Situ, ISF) or derived from fertilization in vitro (IVF). 2-cell embryos had a high rate of blastocyst development to each embryo concentration from 1 embryo/microliter to 1 embryo/1000 microliters. The zygotes produced by either ISF or IVF were adversely affected by reducing the embryo concentration over this range (P < 0.001), with approximately 82.5% of ISF zygotes developing to blastocysts at highest concentration but only 22.3% at the lowest. For IVF zygotes the corresponding results were 46.3% and 5.2%. The number of cells in each blastocyst from 2-cell embryos was significantly higher than that from ISF and IVF group. The media supplementing Platelet-activating factor (PAF) caused a significant increase in the rate of blastocyst development of IVF zygotes at embryo concentration of 1 embryo/10 microliters (10 ng/ml) and 1 embryo/100 microliters (100 ng/ml). Insulin-like growth factor (IGF) (10 ng/ml) also stimulated development of IVF zygotes when they were cultured at the concentration of 1 embryo/10 microliters. Epidermal growth factor (EGF) was no effect over range of 1-1000 ng/ml to embryo development. The results show that factors necessary for normal embryo development are diluted to suboptimal levels during culture at low embryo concentration. The PAF, IGF-I partially compensate the effects of low embryo concentration during culture and play important roles as autocrine embryotrophic factors.

Expression of estrogen receptor (ER) -alpha and -beta transcripts in the neonatal and adult rat cerebral cortex, cerebellum, and olfactory bulb.

In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximately 3-days-old) and adult (250 to approximately 350 g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERalpha transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERalpha was present in the adult cerebral cortex. No significant difference in ERbeta transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERalpha expression was significantly weaker than ERbeta. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERalpha transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERalpha/ERbeta transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.

Connective tissue growth factor in human liver cirrhosis.

BACKGROUND: Connective tissue growth factor (CTGF) belongs to a family of factors that regulate fibrogenesis and wound healing. While the significance of transforming growth factor beta (TGF-beta) in liver fibrosis is well established, the role of CTGF in fibrosing hepatopathy is still unknown. METHODS: CTGF was analyzed in 10 normal and in 16 cirrhotic liver tissue samples. Northern blot analysis was used to examine the concomitant expression of CTGF and TGF-beta1 mRNAs, and the cellular localization of CTGF mRNA was studied by in situ hybridization. For identification of myofibroblasts and activated hepatic stellate cells, alpha-smooth muscle actin (alpha-SMA) immunohistochemistry was used. RESULTS: Northern blot analysis showed 6.5-fold enhanced expression of CTGF mRNA and 7.8-fold enhanced expression of TGF-beta1 mRNA in liver cirrhosis in comparison with normal controls (p<0.01). By in situ hybridization, CTGF mRNA was detectable in only a few spindle cells in the portal tracts in normal liver samples. In contrast, there was strong expression of CTGF mRNA in fibroblasts and myofibroblast-like cells present in fibrous septa surrounding the cirrhotic nodules, in stellate cells, in endothelial cells and in mesenchymal cells around ductular proliferations, and in ductular epithelial cells. There was a strong correlation between CTGF mRNA and TGF-beta1 mRNA as well as the degree of fibrosis (p<0.01). CONCLUSIONS: Overexpression of CTGF in liver cirrhosis, especially in fibroblasts/myofibroblasts and stellate cells, suggests that this novel factor may play an important role in hepatic fibrosis.

Growth factors and cytokines in pancreatic carcinogenesis.

Pancreatic cancer is a deadly disease challenging basic and clinical researchers alike in characterizing its pathobiology and finding better treatment options. A number of molecular alterations including gene mutations such as k-ras, p53, and Smad4 and aberrant expression of a variety of genes have been identified in recent years. This review focuses on two families of growth factors and growth factor receptors which are representative for the molecular alterations observed in pancreatic cancer: the transforming growth factor-beta superfamily of serine-threonine kinase receptors and their ligands, which usually act as negative growth regulators, and the epidermal growth factor receptor family and their ligands, which have the potential to act as growth promoters in pancreatic cancer. In addition, we will discuss the role of the cytokines TNF-alpha, IFN-gamma, and IL-6 and its effects on pancreatic cancer cell proliferation in vitro and in vivo. Pancreatic cancer cell biology consists of complex interactions of various factors, and a better understanding of the molecular pathogenesis of this disorder might lead to better treatment strategies in the near future.

KAI1, a new metastasis suppressor gene, is reduced in metastatic hepatocellular carcinoma.

Down-regulation of KAI1 expression has been shown to be associated with formation of metastases or disease progression in prostate and pancreatic cancer. In the present study we analyzed the expression pattern of KAI1 in metastatic and nonmetastatic hepatocellular carcinomas (HCCs) in comparison with normal livers to evaluate whether alteration of KAI1 also facilitates the metastatic ability in this malignancy. Thirty-nine primary HCCs and 10 normal liver tissue samples were studied for KAI1 messenger RNA (mRNA) expression with use of Northern blot analysis and in situ hybridization. By Northern blot analysis, moderate to strong KAI1 mRNA expression was present in normal liver samples. In contrast, KAI1 mRNA expression in tissue samples of primary HCCs was markedly decreased compared with normal controls. The normal/tumor ratio of KAI1 mRNA expression was 2.6:1 (P <.01). Primary HCCs that gave rise to metastasis showed significantly lower KAI1 mRNA levels than nonmetastasized HCCs (P <. 05). As seen by in situ hybridization, moderate to strong cytoplasmic KAI1 mRNA staining was present in almost all normal hepatocytes. Bile ducts, blood vessels, and connective tissue showed no or only faint KAI1 mRNA expression in the normal liver samples. In nonmetastatic HCCs, the cancer cells exhibited in situ hybridization signals that were similar to the normal controls. In contrast, most of the primary HCC cells in samples with metastases showed only faint or moderate KAI1 mRNA expression predominantly in the perinuclear regions. When KAI1 mRNA expression of primary hepatocellular cancer cells was compared with metastasized cancer cells in lymph nodes, with intrahepatic satellite metastasis, or with peritoneal metastasis in the same patients, significantly lower (P <.01) KAI1 mRNA levels were present in the metastasized HCC cells. Reduced KAI1 mRNA in HCC cells seems to influence their metastatic ability and thereby enhances the malignant potential of HCC.

Computer morphometry for quantitative measurement of liver fibrosis: comparison with Knodell's score, colorimetry and conventional description reports.

Liver fibrosis is currently described quite subjectively or, at best, semiquantitatively by scoring systems. In order to measure the severity of liver fibrosis quantitatively and to compare this with established methods, such as Knodell's scoring system, the colorimetric method and conventional description reports, we undertook the present study. A personal computer with an image grabber card and a microscope equipped with a computer-controlled slide-driver was used for computer morphometry. The principle behind morphometry is based on the different colours of hepatocytes and fibres following staining with Masson's trichrome stain. There were 31 patients (25 male, six female) recruited into the present study with a mean +/- SD age of 41.6 +/- 15 years (range 24-66 years). Of these patients, 16 had chronic hepatitis B, 12 had chronic hepatitis C and three were alcoholics. Colorimetric methods and Knodell's fibrosis score were performed according to established protocols. Conventional description reports were obtained from reviews of patient charts. The results from computer morphometry were highly correlated with results from the colorimetric method, with a correlation coefficiency gamma = 0.85 (P<0.0001). The results from computer morphometry also correlated with both Knodell's scoring system (gamma = 0.69; P<0.001) and conventional description reports (gamma = 0.46; P<0.01). Results from Knodell's scoring system were significantly correlated with computer morphometry, as follows: score 0, 2.7 +/- 1.4; score 1, 5.7 +/- 1.2; score 2, 7.7 +/- 2.3; score 3, 10.7 +/- 3.2; score 4, 21.8 +/- 14.1. The trend was statistically significant by the Wilcoxon rank sum test. In conclusion, our computerized morphometry system is a reliable tool for the evaluation of the severity of liver fibrosis and can be used as a tool for the objective quantification of liver fibrosis.

Reduced KAI1 expression in pancreatic cancer is associated with lymph node and distant metastases.

KAI1 belongs to a structurally distinct family of membrane glycoproteins, which function via cell-cell and cell-extracellular matrix interactions, thereby potentially influencing the ability of cancer cells to invade tissues and to metastasize into lymph nodes and distant organs. In the present study, we examined KAI1 expression in lymph node and liver metastases in comparison with primary pancreatic cancer to evaluate its influence on metastasis. KAI1 mRNA analysis was performed by Northern blot analysis and in situ hybridization. In addition, the respective protein was studied by immunostaining. Fourteen primary pancreatic cancer samples in which no lymph node metastases were present and 25 primary pancreatic cancer samples in which lymph node metastases were present at the time of tumor resection were included. In 20 of these cases, primary pancreatic cancer tissues and corresponding lymph node metastases from the same patient were studied. Furthermore, 11 liver metastases were available for KAI1 analysis. Increased steady-state levels of KAI1 mRNA were found in 33/39 (85%) primary pancreatic cancers in comparison with normal controls. Statistical analysis of KAI1 mRNA levels and clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher in non-metastasized tumors compared with tumors in which lymph node or distant metastases were present. In lymph node metastases KAI1 mRNA expression was lower than in the corresponding primary tumors: In 14 of 20 lymph node metastases no KAI1 mRNA expression and in 6 of 20 lymph node metastases only weak KAI1 mRNA levels were present in some cancer cells. Cancer cells of distant metastases were devoid of or exhibited low KAI1 mRNA levels compared with those of primary pancreatic cancers. A similar pattern was observed by immunostaining. These data support the hypothesis that KAI1 gene expression might influence the metastatic ability of pancreatic cancer cells in vivo. Reduction of KAI1 appears to promote cancer cell spread in lymph nodes and distant organs.

KAI1 is unchanged in metastatic and nonmetastatic esophageal and gastric cancers.

Down-regulation of KAI1 mRNA expression has been shown to be associated with the formation of metastases or disease progression in pancreatic cancer. Whether KAI1 possesses similar characteristics in other malignancies of the gastrointestinal tract is not known. Here, we compared the patterns of KAI1 mRNA expression in 41 esophageal cancers and 35 stomach cancers to assess whether KAI1 might also be of biological relevance in the metastatic ability of these tumors. By Northern blot analysis, KAI1 mRNA levels ranged widely in both normal and cancerous esophageal and gastric tissue samples, with no statistical differences. No association between KAI1 mRNA expression and tumor stage or tumor differentiation was seen in these tumors. In addition, KAI1 mRNA expression was similar in primary esophageal and gastric cancer samples with or without metastases. By in situ hybridization, KAI1 mRNA expression was evident in the cytoplasm of most squamous epithelial cells in the normal esophagus and in nonmucosal epithelial cells of the normal stomach. The staining intensity in the esophageal and gastric cancer cells was similar to that in the normal controls. This differential pattern of KAI1 mRNA expression in esophageal and gastric cancers in comparison to pancreatic cancer indicates that KAI1 seems to influence the potential of gastrointestinal cancer cells to metastasize differently. In esophageal and gastric cancers, the formation of metastases is not dependent on the reduction of KAI1 in the cancer cells.