The diagnostic value of contrast-enhanced ultrasound LI-RADS for hepatocellular carcinoma in patients with cirrhosis and chronic hepatitis B.

PURPOSE: To explore the diagnostic value of American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADS) for hepatocellular carcinoma (HCC) in patients with cirrhosis and chronic hepatitis B. METHODS: A total of 205 patients at high risk of HCC with solitary hepatic nodule were enrolled and retrospectively analyzed. All patients were over 18 years old and had a single lesion with a diameter < 50 mm. Lesions were categorized according to size and contrast enhancement patterns in the arterial, portal venous and late phases. Diagnostic efficacy of CEUS LI-RADS for HCC, and the rate of non-HCC malignancies in the LR-M class were compared between patients with cirrhosis and chronic hepatitis B. RESULTS: Of all 205 nodules (median nodule size was 34 mm), 142 (69.3%) were HCC. Of the 127 (61.9%) LR-5 category nodules, 95.8% (92/96) nodules were corresponded to HCC in cirrhosis, while 61.3% (19/31) nodules were corresponded to HCC in chronic hepatitis B (P = 0.000). Positive predictive value (PPV) of LR-5 category for HCC was 95.8% in cirrhosis and 61.3% in chronic hepatitis B (P = 0.000). More category of LR-4 nodules were proved to be HCC in patients with cirrhosis than chronic hepatitis B (80.0% vs 8.3%, P = 0.000). Of 41 LR-M category nodules, more non-HCC malignancies were found in chronic hepatitis B (76.0%) than that in cirrhosis (25.0%, P = 0.001). CONCLUSIONS: The LR-5 category is highly specific for the diagnosis of HCC in patients with cirrhosis. However, LR-5 category nodules require further CT or MRI examination or histological confirmation in patients with chronic hepatitis B for its unsatisfactory PPV for HCC.

Experimental study on soil fire temperature field of harvested site of Larix olgensis plantation.

We established a fire simulation experiment in the harvested site of Larix olgensis plantation and recorded the temperature of each test point at 500, 1000 and 1500 s during the fire by thermocouple temperature measurement. The data were displayed in the form of images to show soil temperature field at each layer during the fire. The results showed that when the wind speed was less than or equal to 2 m·s-1 or greater than or equal to 10 m·s-1, combustibles could not be fully burned. In the case of full combustion of combustibles, soil temperature at each layer was the highe-st when the wind speed was 6 m·s-1, with the affected soil depth being up to 12 cm or more. The maximum temperature at soil layer of 3 cm could reach 300 ℃. Compared with that at the non-cut stump, soil at the stump had a higher maximum temperature during the fire, with the soil temperature being higher near the stump. When the wind speed was 6 m·s-1, the temperature range at soil layer of 3 cm from the farthest and the nearest to the stump was from 198 ℃ to 315 ℃. With the deepening of soil layer, soil temperature sharply decreased. The temperature at the soil layer of 15 cm was almost unchanged during the fire test. The temperature at the soil layer of 12 cm was increased only when the wind speed was 6 m·s-1, and the temperature at the soil layer of 3 cm was the highest. When the wind speed was 6 m·s-1, the influence of fire on the soil temperature was the greatest, and soil at stump had the severest damage.

Perfusion Characteristics of Hepatocellular Carcinoma at Contrast-enhanced Ultrasound: Influence of the Cellular differentiation, the Tumor Size and the Underlying Hepatic Condition.

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p < 0.05). More well differentiated HCCs (63.4%) performed late washout or no washout while compared with moderately (37.8%) or poorly (24.1%) differentiated HCCs (p < 0.05). Poorly differentiated HCCs showed the shortest washout time (83.0 ± 39.8 s), moderately differentiated HCCs showed the moderate washout time (100.4 ± 52.1 s), and well differentiated HCCs showed the longest washout time (132.3 ± 54.2 s) (p < 0.05). Lesions > 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p < 0.05). The dynamic enhancement procedure of HCC was influenced by the cellular differentiation and the tumor size. While, hepatic background showed no influence on the dynamic enhancement of HCC.

TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway.

Osteosarcoma is the most common type of bone cancer, and the second leading cause of cancer-related death in children and young adults. Osteosarcoma stem cells are essential for osteosarcoma initiation, metastasis, chemoresistance and recurrence. In the present study, we report that: 1) higher TSSC3 expression indicates a better prognosis for osteosarcoma patients, and; 2) overexpression of TSSC3 significantly decreases sphere-forming capacity, tumor initiation, stemness-related surface markers and Nanog expression in osteosarcoma cells. We also discovered that higher Nanog expression correlates to a worse prognosis for osteosarcoma patients, and overexpression of Nanog increases the stem-related phenotype in osteosarcoma cells. Knockdown of Nanog suppresses these phenotypes. Inhibition of Nanog expression and self-renewal of osteosarcoma cells by TSSC3 overexpression appears to be mediated through inactivation of the Src/Akt pathway. In the clinical setting, expression of TSSC3, p-Src and Nanog is associated with recurrence, metastasis and surgical intervention. Lower TSSC3 expression, higher Nanog expression or higher p-Src expression indicate a poor prognosis for osteosarcoma patients. Overall, our study demonstrates that TSSC3 inhibits the stem-like phenotype and Nanog expression by inactivation of the Src/Akt pathway; this emphasizes the importance of Nanog in osteosarcoma stem cells.

High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells.

Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Niacin receptor GPR109A inhibits insulin secretion and is down-regulated in type 2 diabetic islet beta-cells.

OBJECTIVES: We previously found niacin receptor GPR109A was expressed in murine islet beta-cells, and signaling through GPR109A inhibited glucose stimulated insulin secretion (GSIS). However, the expression of GPR109A in human islets and its functional relevance is still not known. METHODS: The expression of GPR109A was examined by antibody staining and in situ hybridization on pancreatic paraffin sections. GPR109A was cloned and expressed in INS-1 islet beta-cells. Intracellular cAMP and GSIS were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of GPR109A was confirmed in murine islet beta-cells and further detected in human counterparts by using commercially available polyclonal antibodies. In situ hybridization study detected the transcripts of GPR109A, but not that of closely related GPR109B. Furthermore, GPR109A was significantly reduced in islets from diabetic individuals and animal model of db/db mice as compared to their respective controls. Further, GPR109A levels in insulinoma were also reduced dramatically as compared to islets found in corresponding non-tumor normal tissues. Quantitative RT-PCR analysis demonstrated that GPR109A transcripts were severely down-regulated in rodent insulinoma cell lines as compared to that of freshly isolated islets from mice. Finally, human and murine GPR109A expression cassettes were transfected into INS-1 cells, which resulted in reduced accumulation of cAMP and insulin secretion after incubation with niacin. The effect could be completely abrogated by pretreatment with pertussis toxin. CONCLUSIONS: These results demonstrate that GPR109A is functionally expressed in both human and murine islet beta-cells. However, the role of GPR109A in the prevention of diabetes or insulinoma needs further study.

Dynamic enhancement patterns of intrahepatic cholangiocarcinoma in cirrhosis on contrast-enhanced computed tomography: risk of misdiagnosis as hepatocellular carcinoma.

This study aimed to assess the features of intrahepatic cholangiocarcinoma (ICC) at computerized tomography (CT) and verify the risk of misdiagnosis of ICC as hepatocellular carcinoma (HCC) in cirrhosis. CT appearances of 98 histologically confirmed ICC nodules from 84 cirrhotic patients were retrospectively reviewed, taking into consideration the pattern and dynamic contrast uptake during the arterial, portal venous and delayed phases. During the arterial phase, 53 nodules (54.1%) showed peripheral rim-like enhancement, 35 (35.7%) hyperenhancement, 9 (9.2%) hypoenhancement and 1 (1.0%) isoenhancement. The ICC nodules showed heterogeneous dynamic contrast patterns, being progressive enhancement in 35 nodules (35.7%), stable enhancement in 28 nodules (28.6%), wash-in and wash-out pattern in 15 nodules (15.3%) and all other enhancement patterns in 20 nodules (20.4%). There were no significant differences in the dynamic vascular patterns of ICC according to nodule size (p > 0.05). ICC in cirrhosis has varied enhancement patterns at contrast-enhanced multiphase multidetector CT. Though the majority of ICC did not display typical radiological hallmarks of HCC, if dynamic CT scan was used as the sole modality for the non-invasive diagnosis of nodules in cirrhosis, the risk of misdiagnosis of ICC for HCC is not negligible.

Primary hepatic neuroendocrine tumors: clinical characteristics and imaging features on contrast-enhanced ultrasound and computed tomography.

OBJECTIVE: Primary hepatic neuroendocrine tumor (PHNET) is an extremely rare liver neoplasm, and its clinical characteristics and imaging features are not well understood. The aim of this study was to analyze the clinical profiles and imaging features of PHNETs on contrast-enhanced ultrasound (CEUS) and computed tomography (CT) METHODS: Patients with PHNET between January 2008 and December 2015 were retrospectively identified, and their demographics, laboratory data, and imaging characteristics on CEUS and CT analyzed. RESULTS: Ten consecutive patients with PHNETs were included (including one G1, seven G2, and two G3 of tumor grades).The median age of patient was 45 years (range: 27-72 years), and 60.0% of patients were male. The most common symptom was abdominal pain (60.0%), and cirrhosis was found in 40.0% of patients. Tumors were confined within the liver in 60.0% of patients, while the remaining patients had extra-hepatic metastasis. The tumors revealed hyperechoic in 60% of patients and mixed echoic in 30% of patients on conventional US, displaying intense arterial enhancement followed by washout in the portal and/or the late phases in 80.0% of patients on CEUS and 60% at CT. CONCLUSIONS: Although PHNET is a very rare liver tumor, it should be considered as a possible differential diagnosis in the management of hepatic tumors. Most PHNETs were hyperechoic or mixed echoic on conventional US, showing similar enhancement patterns to that of hepatocellular carcinoma on CEUS.

Comparison of CT and contrast-enhanced ultrasound findings in hepatic angiomyolipoma with pathological correlations.

OBJECTIVE: To compare imaging findings of CT and contrast-enhanced US (CEUS) in hepatic angiomyolipoma (HAML) and investigate their pathological correlations. METHODS: Imaging findings and preoperative diagnosis of CT and CEUS were retrospectively compared head to head in 46 patients with 54 histologically proven HAMLs. Correlations between imaging features and preoperative diagnosis with pathological types of HAMLs were analyzed. RESULTS: Fat was detected in 100% of lipomatous type, 84.6% of mixed type, and 7.1% of myomatous type (p = 0.000) of HAML at unenhanced CT. Well-defined hyper-echogenicity was displayed in 100% of lipomatous type, 88.5% of mixed type, 50% of myomatous type, and 66.7% of angiomatous type of HAMLs at unenhanced US. More arterial hyper-enhancement was noted on CEUS (100%) than on CT (73.1%) in mixed type (p = 0.015) and in lipomatous type (90.9% vs. 9.1%, p = 0.000) of HAMLs. Washout was present in more HAMLs on CT than on CEUS (42.6% vs. 18.5%, p = 0.007). Correct preoperative diagnosis was suggested in more HAMLs of myomatous type on CEUS than on CT (42.9% vs. 0%, p = 0.016) but showed no difference in other types of HAMLs. CONCLUSION: There are considerable discrepancies between CT and CEUS findings of HAMLs, and the imaging appearance and preoperative diagnosis of HAMLs on CT and CEUS are significantly affected by pathological types of HAMLs.

Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study. METHODS: From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted. RESULTS: In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28-74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19-9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116). Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000). CONCLUSIONS: The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.

Diagnosis of Hepatic Angiomyolipoma by Combination of Baseline and Contrast-Enhanced Ultrasound--A Prospective Study in Non-Cirrhotic Patients.

OBJECTIVES: Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal tumor of the liver and its diagnosis has been considered challenging. The aim of this study was to investigate prospectively the diagnostic efficacy of the incorporation of both baseline ultrasound (US) and contrast-enhanced ultrasound (CEUS) features of HAML in patients without cirrhosis. MATERIALS AND METHODS: Consecutive 1748 non-cirrhotic patients with focal liver lesions (FLLs) were prospectively enrolled. Baseline US and CEUS were performed before resection or biopsy. Ultrasound imaging diagnosis of FLLs was compared with the pathological results. RESULTS: Final diagnoses were established in 41 patients with HAML (2.3%) with normal alpha fetal protein (AFP) level and in 1707 patients with FLL other than HAML. Diagnostic criteria for HAML was based on the combination of baseline US and CEUS appearance of the nodule: (1) Well-defined, marked hyper-echoic nodule without surrounding hypo-echoic halo on baseline US; (2) hyper-enhancement in the arterial phase (exclude initial peripheral nodular enhancement and spoke-wheel arteries) and remains hyper-enhancement or iso-enhancement in the late phase. The diagnostic criteria were fulfilled in 31 HAMLs, 1 hepatocellular adenoma and 1 hemangioma. Ten HAMLs were misdiagnosed as other liver tumors because they did not meet the diagnostic criteria mentioned above and consequently yielded a sensitivity, specificity, positive predictive values, negative predictive values and Youden index of 75.61%, 99.88%, 93.94%, 99.42%, and 0.75 respectively. CONCLUSION: The combination of baseline US and CEUS may lead to the correct diagnosis noninvasively in the majority of HAMLs in non-cirrhotic patients with normal AFP level.

Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis.

AIM: To verify if detailed analysis of temporal enhancement patterns on contrast enhanced ultrasound (CEUS) may help differentiate intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in cirrhosis. METHODS: Thirty three ICC and fifty HCC in cirrhosis were enrolled in this study. The contrast kinetics of ICC and HCC was analyzed and compared. RESULTS: Statistical analysis did not reveal significant difference between ICC and HCC in the time of contrast first appearance and arterial peak maximum time. ICC displayed much earlier washout than that of HCC (47.93±26.45 seconds vs 90.86±31.26 seconds) in the portal phase, and most ICC (87.9%) showed washout before 60 seconds than HCC (16.0%). Much more ICC (78.8%) revealed marked washout than HCC (12.0%) while most HCC (88.0%) showed mild washout or no washout in late part of the portal phase (90-120 seconds). Twenty six out of thirty three ICC (78.8%) demonstrated both early washout(<60 seconds) and marked washout in late part of the portal phase, whereas, only six of fifty HCC (12.0%)showed these temporal enhancement features (p = 0.000).When both early washout and marked washout in the portal phase are taken as diagnostic criterion for ICC, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 78.8%,88.0%,81.3%,86.3%,and 84.3% respectively by CEUS. CONCLUSIONS: Analysis of detailed temporal enhancement features on CEUS is helpful differentiate ICC from HCC in cirrhosis.If a nodule in cirrhotic liver displays hyper-enhancement in the arterial phase followed by early and marked washout in the portal phase, the nodule is highly suspicious of ICC rather than HCC.

Endothelial cells promote stem-like phenotype of glioma cells through activating the Hedgehog pathway.

Microenvironmental regulation of cancer stem cells (CSCs) strongly influences the onset and spread of cancer. The way in which glioma cells interact with their microenvironment and acquire the phenotypes of CSCs remains elusive. We investigated how communication between vascular endothelial cells and glioma cells promoted the properties of glioma stem cells (GSCs). We observed that CD133(+) GSCs were located closely to Shh(+) endothelial cells in specimens of human glioblastoma multiforme (GBM). In both in vitro and in vivo studies, we found that endothelial cells promoted the appearance of CSC-like glioma cells, as demonstrated by increases in tumourigenicity and expression of stemness genes such as Sox2, Olig2, Bmi1 and CD133 in glioma cells that were co-cultured with endothelial cells. Knockdown of Smo in glioma cells led to a significant reduction of their CSC-like phenotype formation in vitro and in vivo. Endothelial cells with Shh knockdown failed to promote Hedgehog (HH) pathway activation and CSC-like phenotype formation in co-cultured glioma cells. By examination of glioma tissue specimens from 65 patients, we found that the survival of glioma patients was closely correlated with the expression of both Shh by endothelial cells and Gli1 by perivascular glioma cells. Taken together, our study demonstrates that endothelial cells in the tumour microenvironment provide Shh to activate the HH signalling pathway in glioma cells, thereby promoting GSC properties and glioma propagation.

[Effects of Bmi1 gene on endothelial cells promoting glioma stem cell-like phenotype].

OBJECTIVE: To explore the effects of B-cell specific Maloney leukemia virus integration site 1 (Bmi1) gene on endothelial cells promoting glioma stem cell (GSC)-like phenotype. METHODS: Glioblastoma cell line GL261 and brain micro-vessel endothelial cell line b.END3 were used. Transwell co-culture system, limit dilution assay, xenograft, real-time polymerase chain reaction (PCR), Western blot, fluorescence activating cell sorter (FACS) and gene knock-down assay were used to determine the GSC-like phenotype and Bmi1 gene expression in glioma cells. RESULTS: Compared with the control of GL261 cell alone, (1) more and larger tumor spheres formed after co-culturing with endothelial cells (62.5% ± 1.5% vs 25.0% ± 4.6% at 40 cells/well, P = 0.000). Xenografts generated by GL261 cells with b.END3 cells appeared earlier and were larger than that by GL261 cells alone ((0.798 ± 0.297) cm(3) vs (0.362 ± 0.123) cm(3), P = 0.000); (2) CD133 positive glioma cells increased after co-culturing with endothelial cells (8.48% ± 0.78% vs 4.81% ± 0.37%, P = 0.000); (3) the expression of Bmi1 in co-cultured glioma cells was up-regulated at mRNA level (2.72 ± 0.18 vs 1.00 ± 0.15, P = 0.000) and at protein level; (4) the above phenomenon was attenuated when Bmi1 gene expression was inhibited by siRNA in glioma cells, CD133 positive portion of Bmi1-knockdown GL261 cells co-culturing with b.END3 cells decreased than that of wildtype GL261 cells (0.34% ± 0.21% vs 1.70% ± 0.69%, P = 0.025). CONCLUSION: Endothelial cells promote GSC-like phenotype by up-regulating the expression of Bmi1 in glioma cells.

Glioma stem cells enhance endothelial cell migration and proliferation via the Hedgehog pathway.

The aim of the present study was to determine the possible mechanism underlying the enhanced migration and proliferation of endothelial cells caused by glioma stem cells (GSCs). Tumor spheres enriched in GSCs derived from the mouse GL261 glioma cell line, and the brain microvessel endothelial cell line, b.END3, were used in this study. A Transwell co-culture system, RNAi experiments, quantitative polymerase chain reaction, western blotting and enzyme-linked immunosorbent, cell counting kit-8 (CCK-8) proliferation, Transwell migration and wound-healing assays were used in this study to determine the migration and proliferation ability, as well as the Hedgehog (HH) pathway-related gene expression in the b.END3 cells. Based on the results, it was demonstrated that the migration and proliferation of the endothelial cells were enhanced following co-culture with GSCs. The gene expression of the HH pathway-related genes, Sonic Hedgehog (Shh) and Hedgehog-interacting protein (Hhip) was altered in the endothelial cells when co-cultured with GSCs. Overexpression of glioma-associated oncogene homolog 1 indicated activation of the HH pathway. Following knockdown of smoothened (Smo) in the endothelial cells, the migration and proliferation abilities of the cells were inhibited. GSCs have little effect on enhancing these behaviors in endothelial cells following Smo-knockdown. Further investigation revealed that Shh levels in the supernatant of the co-culture system were elevated, indicating the importance of secreted Shh from the endothelial cells. In conclusion, GSCs enhanced the migration and proliferation of the endothelial cells in vitro, which was likely associated with the activation of the HH pathway in the endothelial cells, caused by the increased secretion of Shh.

The pathophysiology of venous hypertensive myelopathy--study of an animal model: laboratory investigation.

OBJECT: The authors undertook this study to establish an animal model to investigate the pathophysiological changes of venous hypertensive myelopathy (VHM). METHODS: This study was a randomized control animal study with blinded evaluation. The VHM model was developed in 24 adult New Zealand white rabbits by means of renal artery and vein anastomosis and trapping of the posterior vena cava; 12 rabbits were subjected to sham surgery. The rabbits were investigated by spinal function evaluation, abdominal aortic angiography, spinal MRI, and pathological examination of the spinal cord at different follow-up stages. RESULTS: Twenty-two (91.67%) of 24 model rabbits survived the surgery and postoperative period. The patency rate of the arteriovenous fistula was 95.45% in these 22 animals. The model rabbits had significantly decreased motor and sensory hindlimb function as well as abnormalities at the corresponding segments of the spinal cord. Pathological examination showed dilation and hyalinization of the small blood vessels, perivascular and intraparenchymal lymphocyte infiltration, proliferation of glial cells, and neuronal degeneration. Electron microscopic examination showed loose lamellar structure of the myelin sheath, increased numbers of mitochondria in the thin myelinated fibers, and pyknotic neurons. CONCLUSIONS: This model of VHM is stable and repeatable. Exploration of the sequential changes in spinal cord and blood vessels has provided improved understanding of this pathology, and the model may have potential for improving therapeutic results.

Extranodal follicular dendritic cell sarcoma of the pharyngeal region: a potential diagnostic pitfall, with literature review.

Extranodal follicular dendritic cell sarcoma (FDCS) of the pharyngeal region is a rare malignant tumor recognized in recent years, with approximately 37 cases so far reported in the literature. It is often not considered at the initial evaluation and may be misdiagnosed in a small biopsy specimen. We report 4 cases of extranodal FDCS, 2 cases in the nasopharynx that were diagnosed as undifferentiated carcinomas because they were characterized by syncytial epithelial cells with sheet or nest-like distribution and 2 cases in the tonsil and soft palate that were characterized by vaguely concentric whorls consisting of spindle to ovoid cells. The latter case was diagnosed as ectopic meningioma. The analysis of all cases from the literature and ours shows that 58% (21/36) of the cases are misdiagnosed initially, often as undifferentiated carcinoma or meningioma, which the differential diagnoses should be mostly focused on. With a median follow-up of 27 months, the recurrence, metastasis, and mortality rates are 23%, 21%, and 3%, respectively, suggesting that extranodal FDCS of the pharyngeal region remains a low-grade sarcoma. Radical surgery is recommended, whereas there is no evidence to support adjuvant therapy.

[Clinical related factors of portal vein tumor thrombosis in patients with hepatocellular carcinoma: a logistic regression analysis].

OBJECTIVE: To investigate the related factors of portal vein tumor thrombosis (PVTT) in patients with HCC. METHODS: A total number of 234 patients with hepatocellular carcinoma (HCC) were included in this retrospective study. Uni-variate and multi-variate logistic regression analysis were employed to analyze the association between PVTT and 18 routine clinical parameters. RESULTS: Among the 234 patients with HCC, 15% of patients (35/235) had PVTT. Univariate logistic regression analysis revealed significant association of age (P = 0.016), gamma glutamyl transferase (GGT, P = 0.003), number of segmental invasion (P = 0.007), microvascular invasion (P < 0.01), segment location of S2 (P = 0.001), S3 (P = 0.000), S4 (P = 0.004) and S6 (P = 0.016). Multivariate analysis shows potential significant predictors of PVTT in HCC were age (RR: 0.373; 95% CI: 0.146-0.954; P = 0.040), the tumor location of S3 (RR: 4.625; 95% CI: 1.916-11. 165;P = 0.001), GGT (RR: 4.091; 95% CI: 1.448-11.553; P = 0.008) and microvascular invasion (RR: 20.912; 95% CI: 4.745-92.172; P < 0.01). CONCLUSIONS: PVTT occurred more commonly in the younger (< 50 years old), and those with high level of GGT, segment location of S3 and microvascular invasion.

[Gene expressions of DNA methyltransferase 1 and human leukocyte antigen-DRalpha in hepatocelluar carcinoma and their clinical significance].

OBJECTIVE: To investigate the clinical significance and prognostic value of the expression of DNA methyltransferase 1 (DNMT1) and human leukocyte antigen-DRalpha (HLA-DRalpha) in hepatocelluar carcinoma (HCC). METHODS: Paraffin-embedded tissues of 234 HCC underwent curative liver resection and 18 healthy adult liver samples from January 1991 to June 2002 in our department were used for the tissue microarray. Immunohistochemical technique (EnVision) was applied to detect the expression of DNMT1 and HLA-DRalpha. The relationships between DNMT1, HLA-Ralpha and clinicopathological variables were analyzed statistically. RESULTS: The rates of positive expression of DNMT1 and HLA-DRalpha were 27.4% and 39.3%. The significant correlation was present between DNMT1 and portal vein tumor thrombus, alpha fetoprotein (AFP) level or TNM staging (P < 0.05), but no significant correlation was present between DNMT1 and lymph node invasion. The significant correlation was present between HLA-DRalpha and lymph node invasion or TNM staging (P < 0.05), but no significant correlation was present between HLA-DRalpha and lymph node invasion or AFP level (P > 0.05). The postoperative median survival time was 6.87 months and the 1-, 3-, 5-year cumulative survival rate was (38.89+/-6.63)%, (19.92+/-5.48)%, (17.58+/-5.31)% respectively in HCC with positive DNMT1, while the median survival time was 40.33 months and the 1-, 3-, 5-year cumulative survival rate was (81.01+/-4.41)%, (50.78+/-5.84)%, (38.04+/-6.09)% respectively in patients with negative DNMT1(P < 0.001). The postoperative median survival time was 40.33 months and the 1-, 3-, 5-year cumulative survival rate was (81.01+/-4.41)%, (50.78+/-5.84)%, (38.04+/-6.09)% respectively in HCC with positive HLA-DRalpha, while the median survival time was 12.43 months and the 1-, 3-, 5-year cumulative survival rate was (51.72+/-6.56)%, (26.44+/-5.91)%, (13.71+/-6.83)% (P < 0.01) respectively in patients with negative HLA-DRalpha (P < 0.001). CONCLUSION: DNMT1 and HLA-DRalpha are prognostic factors for HCC, which may be promising molecular prognostic factors for HCC.

Construction of anti-lung tumor gene differentially expressed bank of wild mouse / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To construct the anti-lung tumor gene differentially expressed bank of wild mouse and to explore the mechanisms of the TW wild mouse suppressing the occurring of lung tumor.</p><p><b>METHODS</b>Using suppression subtractive hybridization (SSH) technique, the differentially expressed genes between TAF1 mouse and A/wy mouse were selected out and the subtracted cDNA bank was constructed. 166 clones were performed DNA sequencing and then were assayed by blast programme.</p><p><b>RESULTS</b>Among the blast results of 166 differentially expressed clones, 87 known genes (mRNA or cDNA) were in homology with 134 clones and were divided into 7 classifications according to the biological role.14 DNA fragments were in homology with 32 clones, in which 20 clones were in homology with 9 mouse DNA sequences, 2 clones were in homology with one bacterial gene sequences and 3 clones were clone vector.</p><p><b>CONCLUSION</b>With SSH technique, the anti-lung tumor gene differentially expressed bank of wild mouse are successfully constructed.</p>