Top 100 cited articles in the thromboangiitis obliterans: a bibliometric analysis and visualized study.

OBJECTIVE: Thromboangiitis obliterans (TAO) is one of the most common types of peripheral arterial disease (PAD). This study aimed to explore the characteristics of the top 100 most cited articles in the TAO. METHODS: A bibliometric analysis based on the Web of Science (WOS) database was performed. Literature was retrieved and ranked by the citations. Listed below are the top 100 citations, including original articles, reviews, full-length proceeding papers, and case reports that were included for analysis. The type of literature, research areas, and languages were recorded. The trends of citations including the total citations, an analysis of publication and citation numbers were conducted each year. We analyzed citations from highly cited countries, authors, institutions, and journals. Research hotspots were gathered by a visualized analysis of author keywords. RESULTS: Most of the highly cited literature was original articles. A rising trend was observed in the number of citations per year. The peaks in the number of highly cited articles appeared in the year 1998 and 2006. The majority of the articles focused on the cardiovascular system and surgery. Journal of Vascular Surgery published most of the highly cited articles. The USA and Japan contributed nearly half the number of highly cited articles. Mayo Clinic and Nagoya University were highly cited institutions. Shionoya S and Olin JW were both the author with the largest number of citations and the most highly cited author in the reference. Articles that were highly cited most often addressed the following topics: "vasculitis", "autoimmune disease", and "critical limb ischemia". Keywords that were mostly used in recent years were "stem cell therapy", "progenitor therapy", and "immunoadsorption". The detection of bursts of author keywords showed the following: "permeability", "differentiation", and "critical limb ischemia" are recent keywords that have burst. CONCLUSIONS: In this study, the highly cited contributors in the field of TAO research were identified. Most cited articles in the top 100 focused on the cardiovascular system and surgery. Treatment and pathophysiology including stem cell therapy, progenitor therapy, genetics, autoimmunity, and inflammation are the hotspots of TAO.

Increased expression of macrophage migration inhibitory factor and DJ-1 contribute to cell invasion and metastasis of nasopharyngeal carcinoma.

BACKGROUND AND AIM: Both macrophage migration inhibitory factor (MIF) and DJ-1 protein have been shown to relate with cell invasion and metastasis in tumors. However, the role of DJ-1 in invasion and metastasis of nasopharyngeal carcinoma (NPC) and its relation to MIF expression in NPC are not fully understood. The aim of present study is to determine whether or not MIF and DJ-1 are correlated with tumor invasion and influence a worse outcome in NPC, as well as its related mechanism. METHODS: 125 cases of NPC and 45 normal tissues of nasopharynx were collected. The expression of MIF and DJ-1 in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association of MIF and DJ-1 with cell invasion and migration in NPC cell line were evaluated by small interfering RNA (siRNA) transfection, invasion assay and Western blotting. RESULTS: MIF and DJ-1 staining was diffused and strong in tumor cells, whereas they were generally weaker and less common in normal lining epithelia of nasopharynx. High MIF expression in tumor cells (71.2%, 89/125 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. High expression of DJ-1 (75.2%, 94/125 cases) were closely correlated to lymph node metastasis and MIF high-expression. Only MIF high expression (P = 0.010) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, down-regulated expression of DJ-1 in NPC cell lines by siRNA was observed to reduce cell migration and invasion potential, however, exogenous MIF promoted cells invasion. CONCLUSIONS: The data provided evidence that increased expression of MIF and DJ-1 induced cell invasion and metastasis of NPC, supporting the idea that MIF and DJ-1 may play important roles as regulators in the progression of NPC.

MACC1 down-regulation inhibits proliferation and tumourigenicity of nasopharyngeal carcinoma cells through Akt/ß-catenin signaling pathway.

The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with ß-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and ß-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and ß-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated ß-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), ß-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/ß-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.

Malignant transformation of nasal chondromesenchymal hamartoma in adult: a case report and review of the literature.

Nasal chondromesenchymal hamartoma (NCMH) is an extremely rare benign tumor arising in the sinonasal tract, predominantly involving infants and children. To date, only 27 cases are reported in the international literature and there have been no reported cases of malignant transformation. We present a 40-year-old female patient with nasal obstruction and bloody rhinorrhea. Computed tomography (CT) of the nose and paranasal sinuses confirmed a heterogeneous polypoid soft-tissue mass filling the nasal cavity and extending into the maxillary and ethmoid sinus. The patient underwent a complete radical resection. Histological and immunohistochemical analyses showed a portion of the mass was consistent with typical NCMH. However, some areas of mass exhibited cytological atypia, marked mitotic activity and foci of necrosis. The atypical mesenchymal spindle cells were immunoreactive for vimentin, CD99 and smooth muscle actin (SMA) diffusely. The cartilaginous cells were immunopositive for S-100 protein. Ki-67 index was high in atypical areas, accounting for 50%. A rapid mass recurrence was observed at the original site only 3 months after surgery. The final diagnosis of NCMH with malignant transformation was made. To our knowledge, this is the first report of malignant transformation occurring in an adult with NCMH. Although NCMH commonly develops in the neonate or young infants and exhibits benign histological appearance and favorable prognosis, there is a possibility of malignant transformation in adult patients. Thoroughly histological inspections are suggested to be necessary to accurately diagnose this tumor when it is encountered in adults.

Unusual primary intracranial dural-based poorly differentiated synovial sarcoma with t(X; 18)(p11; q11).

Synovial sarcoma is a rare aggressive neoplasm occurring at any site of the body, mainly in young adults. It may also arise in the CNS but has seldom been reported. We report a case of unusual intracranial synovial sarcoma in a young male patient. Neuroimaging revealed a large gadolinium-enhancing mass was located at the right anterior cranial fossa and was associated with multiple cyst formation. The mass was dural-based and was observed to invade the right orbital apex and ethmoidal bulla. Histologically, the tumor was composed of uniform oval and round cells with scant cytoplasm and indistinct borders. The tumor cells were observed to form densely cellular sheets, but in some areas, the tumor showed hemangiopericytomatous vascular pattern consisting of tumor cells arranged around dilated, thin-walled blood vessels. By immunohistochemistry, vimentin, CD99 and Bcl-2 were diffusely positive in most cells, and a focally weak reactivity for S-100 protein was also observed. However, the tumor cells were negative for cytokeratin (AE1/AE3), CK7, CK8/18, CK19, epithelial membrane antigen, CD34, synaptophysin, GFAP, desmin, myogenin, and smooth muscle actin. Cytogenetic analysis using fluorescence in situ hybridization (FISH) demonstrated a translocation t(X;18)(p11;q11), an aberration specific for synovial sarcoma. A diagnosis of primary dural-based poorly differentiated synovial sarcoma was made. To our knowledge, this is the first report of a poorly differentiated variant of synovial sarcoma occurring in dura mater and confirmed by cytogenetic analysis. The present case indicates that appropriate immunohistochemical analysis, and in particular molecular analysis, are essential for accurately diagnosing small, round-cell neoplasms in unusual locations.

Astrocyte elevated gene-1 interacts with ß-catenin and increases migration and invasion of colorectal carcinoma.

To investigate the astrocyte elevated gene-1 (AEG-1) expression and its relationship with the clinicopathological features of colorectal carcinoma (CRC) and ß-catenin signaling pathway. Real-time PCR, Western blot, immunohistochemistry, and immunofluorescence staining were performed to detect AEG-1 expression in CRC cell lines, 8 pairs of fresh CRC and adjacent nontumor tissues (ANT), 120 pairs of paraffin-embedded CRC specimens and ANT tissues, and 60 samples of lymph node metastatic CRC tissues. Scratch wound assay and transwell matrix penetration assay were performed to determine migration and invasion of SW480 cell lines with stable AEG-1 overexpression or SW620 cell lines with AEG-1 knockdown. AEG-1 expression was upregulated in CRC cell lines and tissues compared with ANT. Furthermore, AEG-1 expression level significantly correlated with UICC stage, and the N classification. AEG-1 overexpression significantly enhanced migration and invasion of SW480 cell lines. However, AEG-1 knockdown suppressed migration and invasion of SW620 cell lines. Meanwhile, there was a positive correlation between AEG-1 high expression and ß-catenin nuclear expression in CRC. AEG-1 overexpression increased nuclear ß-catenin accumulation in CRC cell lines. AEG-1 knockdown decreased nuclear ß-catenin accumulation in CRC cell lines. Moreover, we firstly found that AEG-1 interacted with ß-catenin in SW480 cell lines. Our results for the first time showed that AEG-1 interacted with ß-catenin in CRC cells and AEG-1 expression was closely associated with progression of CRC. AEG-1 might be a potential therapeutic target in CRC.

Bilateral cerebellar epithelioid hemangioblastoma with possible ependymal differentiation in a patient with von Hippel-Lindau disease.

There are controversies regarding the histogenesis of stromal cells of hemangioblastoma, and no hypothesis has conclusively been proven. We report a case of unusual hemangioblastoma in a middle-aged man with von Hippel-Lindau disease. Neuroimaging revealed multifocal gadolinium-enhancing masses were located within both sides of the cerebellar hemisphere. Histologically, only small areas showing the typical morphology of hemangioblastoma were recognized in masses. Most areas of masses were composed of cohesive epithelioid tumor cells with abundant cytoplasm and distinct boundaries. Epithelioid tumor cells were arranged around blood vessels, exhibiting perivascular anuclear zone structures like ependymoma. The epithelioid tumor cells were diffusely positive for vimentin, CD99, neuron-specific enolase, GFAP and focally positive for epithelial membrane antigen (EMA) and D2-40 in a dot-like pattern. Variable-sized lipid droplets and glycogen particles were noted in the cytoplasm of epithelioid tumor cells under an electron microscope. A diagnosis of epithelioid cellular hemangioblastoma with possible ependymal differentiation (WHO grade I) was made. To our knowledge, only a few cases of hemangioblastoma show epithelioid appearance or EMA immunoreactivity. The present case indicates that the stromal cells of hemangioblastoma might originate from primitive neuroectodermal cells, and they have the capacity to show a distinctive sign of glial or ependymal differentiation.

[Clinicopathological analysis of clear cell meningioma].

We present two cases of clear cell meningioma (CCM) in the intracranial and intraspinal region with anaplastic features. On histological examination, both the tumors exhibited unusual anaplastic appearances with nuclear pleomorphism, a high mitotic activity and necrosis, which were different from classical CCMs. The tumor cells were immunoreactive to epithelial membrane antigen (EMA) and vimentin with a high MIB-1 index of 40%. Total excision of the tumors was performed in both cases. The male patient was found to have local recurrence and lateral ventricle metastasis 3 months after the total excision. We reviewed the clinicopathological features, disagnosis and prognosis of the disease. We recommend that postoperative adjuvant radiotherapy or chemotherapy be performed after total tumor excision, and MRI scan every 3-6 months is mandatory during the initial follow-up period.

Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature.

Only a few cases of extranodal Epstein-Barr virus (EBV)-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL) have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL) developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone), but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas.

The association of genomic variation of Epstein-Barr virus BamHI F fragment with the proliferation of nasopharyngeal carcinoma.

To investigate the f variant of Epstein-Barr virus (EBV) in nasopharyngeal carcinogenesis, we detected the f variant in primary nasopharyngeal carcinoma (NPC), metastatic carcinoma of the lymph node (LN), and chronic inflammation of the nasopharynx from the Guangdong region. Meanwhile, we analyzed the relationship between the f variant of EBV and LMP1, Fascin, pStat3, p53, Bcl-2, and Ki-67 expression in NPC. The results showed that the f variant of EBV was found in 11 cases of primary NPCs with LN metastasis, 12 LN metastases, and 18 primary NPCs without LN metastasis. However, only one demonstrated the F/f variant in 50 cases of chronic inflammation of the nasopharynx. The expression rate of LMP1, Fascin, pStat3, p53, Bcl-2, and Ki-67 in NPC with the f or F/f variant was higher than that with the F prototype. Furthermore, there was a significantly positive correlation between the f variant of EBV and Ki-67 expression (p < 0.05). Our study suggests that the f variant of EBV may be closely related to nasopharyngeal carcinogenesis.

[Correlation of Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) to fascin and phosphorylated Stat3 in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Latent membrane protein 1 (LMP1) of Epstein-Barr (EB) virus is an important oncogene. Fascin is an actin cross-linking protein involved in cell migration and adhesion. Phosphorylated signal transducer and activator of transcription 3 (pStat3) is a member of STATs family, which is closely related to tumorigenesis. This study was to investigate expressions of LMP1, Fascin and pStat3 in nasopharyngeal carcinoma (NPC) tissues and lymph node metastases of NPC, thus to explore their correlations to the initiation and progression of NPC. METHODS: Expressions of EBV-encoded small RNA (EBER), LMP1, Fascin, pStat3, p53, Ki-67 and Bcl-2 were detected in 43 NPC tissues (21 with and 22 without lymph node metastases) and 21 corresponding lymph node metastases using in situ hybridization or immunohistochemistry (IHC). Data were statistically analyzed. Expressions of pStat3 and Fascin were measured in the NPC cell line CNE1 transfected with LMP1-expressing plasmid using Western blot. RESULTS: Positive EBER expression was detected in all 43 NPC tissues and 21 lymph node metastases in NPC. The expression rates of LMP1, Fascin, pStat3, p53, Ki-67, and Bcl-2 were 69.8% (30/43), 93.0% (40/43), 72.1% (31/43), 90.7% (39/43), 88.4% (38/43) and 88.4% (38/43)in 43 NPC tissues, respectively. LMP1 expression was positively correlated with the expression level of Fascin, pStat3, p53, Ki-67 and Bcl-2 in 43 NPC cases(P < 0.05). LMP1 was found in 10 out of 21 (46.7%) lymph node metastases in NPC. In addition, LMP1 expression dramatically increased pStat3 and Fascin in CNE1 cells. CONCLUSIONS: LMP1 is expressed in lymph node metastatases in NPC. The expression of LMP1 is positively correlated with Fascin, pStat3 and the proliferation index of tumor cells. Moreover, LMP1 up-regulates pStat3 and Fascin in NPC cells.

[Analysis of Epstein-Barr virus BamH I "f" variant in nodal metastasis of nasopharyngeal carcinoma].

OBJECTIVE: To investigate the Epstein-Barr virus (EBV) BamH I "f" variant in primary nasopharyngeal carcinoma (NPC) and its metastases in lymph nodes (LN). METHODS: In situ hybridization was used to detect EBV-encoded small RNA (EBER) expression in 21 paired paraffin-embedded tissue from primary NPC and their lymph node metastases and 22 primary NPC without lymph node metastasis. PCR and restriction fragment length polymorphism (RFLP) assay were used to detect EBV BamH I "f" variant in all cases of NPCs, lymph node metastases and 50 cases of chronic inflammation of nasopharynx from Canton. RESULTS: All cases of NPCs and their lymph node metastases showed EBER expression, indicating a high EBV-positive rate in Cantonese NPC patients. EBV BamH I "f" variant was found in 11 cases (52.4%, 11/21) of primary NPCs with LN metastasis, 12 cases (57.1%, 12/21) of the LN metastases, and 18 cases (81.8%, 18/22) of primary NPCs without LN metastasis. However, of the 50 cases of chronic inflammation of nasopharynx, only one case (2.1%, 1/47) demonstrated BamH I "f" variant. The frequency of BamH I "f" variant in NPC was therefore dramatically higher than that in chronic inflammation of nasopharynx. It is of note that atypical hyperplasia was observed in a few epithelial cells from the case of chronic inflammation of nasopharynx expressing BamH I "f" variant. CONCLUSIONS: The frequency of EBV BamH I "f" variant in NPC is significantly higher than that in chronic inflammation of nasopharynx. It is the first demonstration that the BamH I "f" variant is also present in the LN metastases of NPC. The frequency of BamH I "f" variant in metastatic NPC of the lymph node is almost equal to that of primary NPCs.

[Expressions of h-TERT, c-myc, PCNA and cell apoptosis in liver carcinogenesis].

OBJECTIVE: To investigate the expressions of human telomerase reverse transcriptase (h-TERT), c-myc, and proliferating cell nuclear antigen (PCNA) in chronic viral hepatitis (CVH), liver cirrhosis and primary hepatocellular carcinoma (HCC) and understand their possible role in liver carcinogenesis. METHODS: Totally 157 liver disease specimens were collected, including 56 CVH, 52 liver cirrhosis and 49 primary HCC specimens. In situ hybridization was performed on these specimens to examine the expressions of h-TRET and c-myc mRNA, and immunohistochemistry carried out for PCNA detection, with the cell apoptosis detected with in situ ending labeling. RESULTS: In the CVH, liver cirrhosis and primary HCC specimens, h-TERT expression was detected at the frequencies of 11/56 (19.6%), 43/52 (82.7%) and 44/47 (93.6%), c-myc expression at 7/56 (12.5%), 21/52 (40.4%) and 26/47 (55.3%), with apoptotic index of (27.3-/+4.7)%, (16.5-/+2.6)% and (8.7-/+1.3)% and PCNA expression rate of (17.1-/+2.9)%, (49.3-/+7.8)% and (62.5-/+9.1)%, respectively. Correlations among h-TERT, c-myc, and PCNA expressions and the apoptotic index were not found in the examined tissues (P>0.05). CONCLUSION: Liver carcinogenesis may involve increased h-TERT, c-myc, and PCNA expressions and suppressed cell apoptosis.

[Expression of angiogenesis-related factors in invasive breast cancer and its clinical significance].

OBJECTIVE: To investigate the relation between expression of angiogenesis-related factors, namely vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGFbeta(1)), and microvessel count (MVC) in invasive breast cancer and analyze its clinical implications. METHODS: VEGF, TGFbeta (1) and CD34 expressions in 62 surgical specimens of invasive breast cancer and 12 normal breast specimens were examined by immunohistochemistry and HE staining. MVC was calculated according to the quantification of positive CD34 expression. Clinicopathological characteristics of the patients including age, tumor size, histological type and auxiliary lymph node metastasis were recorded and compared with the results of MVC VEGF and TGFbeta1 expression and detection. RESULTS: MVC and of VEGF and expressions TGFbeta (1) in invasive breast cancer group (55.62-/+11.07, 51.61%, 56.45%, respectively) were greater than those in the normal control group (12.65-/+5.73, 16.67%, 16.67%, respectively, P<0.05). MVC and the positivity rates of VEGF and TGFbeta (1) expressions were 65.53-/+20.36, 68.75% and 78.13%, respectively, in invasive breast cancer patients with axillary lymph node metastasis, significantly higher than those without metastasis (P<0.05). MVC was correlated with VEGF and TGFbeta (1) expressions in that MVC was significantly higher in patients positive for VEGF and TGFbeta (1) (62.82-/+16.31 and 59.35-/+12.76) than in those negative for their expressions (51.16-/+12.53 and 50.80-/+15.62, P<0.05). Significant correlation was also found between VEGF and TGFbeta (1) expressions (P<0.05). CONCLUSION: The interaction between VEGF and TGFbeta (1) mediates angiogenesis, and MVC and VEGF and TGFbeta (1) expressions are correlated to lymph node metastasis, which may provide reference for prognostic evaluation of invasive breast cancer.

[Relationship between liver mass and soluble intercellular adhesion molecule-1 in patients with liver cirrhosis].

OBJECTIVE: To investigate the relation of liver mass to, liver hymodynamics and soluble intercellular adhesion molecule-1 in patients with liver cirrhosis. METHODS: The liver mass was measured by liver biopsy, hepatic hemodynamics by ultrasonography, and the contents of hyalurionic acid (HA), human procollagen III (HPC III) and collagen type IV (C IV) by radioimmunoassay in 100 patients with liver cirrhosis in compensation stage and 30 normal control subjects. RESULTS: Greater liver mass was accompanied by more severe liver fibrosis and reduced liver blood flow. The contents of HA, HPC III and C IV were obvious higher in the patients than in the normal controls (P<0.05) and increased with the liver mass. The liver mass was positively related to serum liver fibrosis indices (r=0.5612, P<0.05). CONCLUSION: Liver mass in patients with liver cirrhosis is related to hepatic hemodynamics, indices for liver fibrosis and liver pathology.

[Detection of cytokeratin 19 and thyroperoxidase expressions in the diagnosis of thyroid diseases].

OBJECTIVE: To investigate the value of detecting cytokeratin 19(CK19) and thyroperoxidase (TPO) expression in the diagnosis of thyroid diseases including thyroid carcinoma, multinodular goiter, adenoma and Hashimoto thyroiditis. METHODS: SP immunohistochemistry was used to detect the expressions of CK19 and TPO in paraffin-embedded thyroid tissue specimens obtained from 62 patients with thyroid carcinoma (30 with papillary carcinomas, 22 with follicular variant of papillary carcinomas, and 10 with follicular carcinomas) and 44 with benign thyroid diseases (including 22 with multinodular goiters, 14 with adenoma, and 8 with Hashimoto thyroiditis). RESULTS: CK19 expression was detected in 96.8% of the thyroid carcinomas and in 4.5% of benign thyroid diseases, demonstrating a significant difference in CK19 expression between the two thyroid diseases (P<0.01). TPO expression was found in 100% of benign thyroid disease and in 3.2% of thyroid carcinoma, showing also a significant difference between them (P<0.01). CONCLUSION: CK19 and TPO can be important molecular markers for diagnosing thyroid carcinoma.