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ABSTRACT: The expression cold-inducible RNA-binding protein (CIRP) is significantly enhanced in neurons under hypothermia, but its roles remain unclear. This study aims to investigate whether the cerebral protection under hypothermia is mediated by the CIRP-mediated inhibition of neuronal apoptosis.
Primary rat cortical neurons were isolated, cultured, and transduced with lentiviral CIRP-RNAi. Apoptosis of the transduced neurons was induced with 100 μmol/L H₂O₂, the treated cells were divided into two groups, and cultured in 37 °C or 32 °C incubator respectively. Cell viability was detected by MTT colorimetric assay. Neuronal apoptosis was detected by flow cytometry after labeling the cells with Hoechst 33342 and Annexin V-FITC/PI. The protein expressions of CIRP, activated caspase-3, and thioredoxin (TRX) were detected by Western blot.
Under 32 °C, CIRP protein is significantly induced in cortical neurons; the expression of activated caspase-3 decreases, while the TRX expression increases. The rate of neuronal apoptosis is 4.5±0.8%. Under 37 °C, CIRP expression is evidently reduced in cortical neurons; the expression of activated caspase-3 is significantly enhanced with reduced level of TRX expression. The rate of neuronal apoptosis reaches 53.5±1.7% (P < 0.05, compared to that in 32 °C group).
The induction of CIRP protein in rat cortical neurons under hypothermia inhibits H₂O₂-induced neuronal apoptosis and thereby exerts neuroprotective effect, which forms one of the cerebral protective pathways under hypothermia.
Brain research 03/2012; 1441:47-52. · 2.46 Impact Factor
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ABSTRACT: Malignant peripheral nerve sheath tumors (MPNST) represent a group of highly heterogeneous human malignancies often with multiple histological origins, divergent differentiation patterns, and diverse immunohistochemical presentations. The differential diagnosis of MPNST from other spindle cell neoplasms poses great challenges for pathologists. This report provides a mini-review of these unique features associated with MPNST and also presents the first cases of MPNST with six differentiation patterns.
Journal of Cancer. 01/2012; 3:303-9.
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ABSTRACT: Wilms tumor (WT) occurs infrequently in adults. Even rarer is adult WT with extension by direct intravascular spread into the right side of the heart. The present report describes a partially differentiated WT with intracaval and intracardiac extension in a 54-year-old man. The morphologic and immunohistochemical findings confirmed the diagnosis.
Journal of Cancer. 01/2011; 2:132-5.
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ABSTRACT: Solitary fibrous tumor (SFT) is a rare spindle-cell neoplasm, especially in the thyroid. We report a case of primary solitary fibrous tumor of the thyroid gland in a 37 year-old Chinese man. The tumor was characterized by bland-looking spindle cells admixed with thin and thick collagen fibers. On immunohistochemistry study indicated that tumor cells were diffusely positive for CD34, Bcl-2 and CD99, and negative for Desmin, NSE, SMA, S-100, and CD68. The patient remains well 16 months after excision. The morphologic and immunohistochemical features of the thyroid SFTs are similar to their reported counterparts in other anatomic sites.
Journal of Cancer. 01/2011; 2:206-9.
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ABSTRACT: Angiogenesis is a critical factor in tumor growth and metastasis, and microvessel density (MVD) was an important parameter for assessing vessels in tumors. However, radiologic assessment of tumor vascularity is not yet well established. In our study, we aimed at investigating the efficacy of contrast-enhanced ultrasonography (CEUS) in exploring the vascularity of the ovarian tumors or tumor-like lesions to assess the relationship between the parameters of the peak intensity (PI) and area under curve (AUC) on CEUS and MVD in ovarian masses. Compared to the contrast-enhanced ultrasound technique, conventional ultrasound shows limitation in differentiating benign and malignant ovarian tumors. The former is promising in improving the sensitivity of detecting small vessels and blood flow in ovarian tumors. Our results showed clear differences in enhancement patterns between benign and malignant ovary tumors or tumor-like lesions. The PI and AUC in the malignant tumors were significantly higher than those in the benign tumors or tumor-like lesions (p=0.001 and =0.01, respectively). The MVD was 43.1 ± 20.4 in the benign tumors or tumor-like lesions and was 65.3 ± 22.3 in the malignant ones (p= 0.01). In both the benign and malignant groups, the PI and AUC were correlated significantly with the MVD (r=0.595, p = 0.001; r =0.533, p = 0.003, respectively). The PI and AUC in CEUS can reflect the MVD in ovarin tumors. The PI and AUC of the ovarian masses in the contrast transvaginal sonography show significant correlation with the angiogenesis and may help in assessing tumor vascularity in ovarian masses.
International journal of biological sciences 01/2011; 7(5):600-6. · 2.70 Impact Factor
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Dengfeng Cao, Aijun Liu,
Fenghua Wang,
Robert W Allan,
Kaiyong Mei,
Yan Peng,
Jun Du,
Shuangping Guo,
Ty W Abel,
Zhaoli Lane,
Joe Ma,
Maria Rodriguez,
Shirin Akhi,
Neha Dehiya,
Jianping Li
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ABSTRACT: LIN28 has been shown to have an important role in primordial germ cell development and malignant transformation of germ cells in mouse. In this study, we examined the immunohistochemical profile of LIN28 in 131 primary human extragonadal germ cell tumors (central nervous system (CNS) 76, mediastinum 17, sacrococcygeal region 30, pelvis 3, vagina 2, liver 1, omentum 1, and retroperitoneum 1), including the following tumors and/or components: 57 seminomas/germinomas, 10 embryonal carcinomas, 74 yolk sac tumors, 6 choriocarcinomas, 15 mature, and 13 immature teratomas. We compared LIN28 with SALL4 to assess its diagnostic value. To determine its specificity, we examined LIN28 in 406 extragonadal-non-germ cell tumors (103 carcinomas, 91 sarcomas, 9 melanomas, 12 mesotheliomas, 83 lymphomas, 9 plasmacytomas, 82 CNS tumors, and 17 thymic epithelial tumors). The staining was semi-quantitatively scored as 0 (no cell stained), 1+ (0-30%), 2+ (31-60%), 3+ (61-90%), and 4+ (>90%). LIN28 staining was seen in all seminomas/germinomas (3+ in 1 and 4+ in 56), embryonal carcinomas (4+ in all 10), and yolk sac tumors (3+ in 3 and 4+ in 71). Variable LIN28 staining was seen in 5 of 6 choriocarcinomas (1+ to 4+), 8 of 13 immature teratomas (1+ to 2+ in immature elements), and in 1 of 15 mature teratomas (1+). Only 11 of 406 non-germ cell tumors showed 1+ LIN28 staining. Therefore, LIN28 is a sensitive (100% sensitivity) marker for primary extragonadal seminomas/germinomas, embryonal carcinomas, and yolk sac tumors with high specificity. Compared with SALL4, LIN28 demonstrated a similar level of diagnostic sensitivity for seminomas/germinomas and embryonal carcinomas. For primary extragonadal yolk sac tumors, although SALL4 stained all tumors (1+ in 1, 2+ in 2, 3+ in 10, and 4+ in 61), LIN28 stained more tumor cells (mean 95 vs 90%, P = 0.03) and was therefore more sensitive. For primary extragonadal yolk sac tumors, combining LIN28 and SALL4 can achieve a higher diagnostic sensitivity than either alone.
Modern Pathology 11/2010; 24(2):288-96. · 4.79 Impact Factor
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ABSTRACT: CIRP (cold-inducible RNA-binding protein) mRNA is highly expressed in hypothermic conditions in mammalian cells, and the relationship between CIRP and neuroprotection for cerebral ischemia under hypothermia has been focused upon. At present, however, the expression characteristics of CIRP under hypothermia and cerebral ischemia in vivo are not clearly elucidated. In this study, CIRP mRNA expression in various regions of rat brain was examined by reverse transcriptase polymerase chain reaction (RT-PCR). CIRP expression levels were found to be similar in the hippocampus and cortex. Real-time quantitative PCR analysis revealed increasing CIRP mRNA expression in the cortex during the 24-h observation period following treatment with hypothermia or cerebral ischemia, with a greater increase in the hypothermia group. When cerebral ischemia was induced following hypothermia, CIRP mRNA expression in the cortex again showed a significant increasing tendency, but ischemia delayed the appearance of this increase. To reveal the relationship between CIRP and energy metabolism in the rat brain, lactate and pyruvate concentrations in the cortex of the rats treated with hypothermia, ischemia and ischemia after hypothermia were determined by spectrophotometric assay, and levels of phosphofructokinas-1 (PFK-1), the major regulatory enzyme of the glycolytic pathway, in the rat cortex in the three groups was also analyzed by Western blot. Using linear correlation, lactate and pyruvate concentrations, and PFK-1 levels, were each analyzed in the three groups in association with CIRP mRNA expression levels. The analysis did not reveal any correlation between the three metabolic parameters and CIRP mRNA expression induced by hypothermia, suggesting that while playing a role in neuroprotection under hypothermia, CIRP does not affect cerebral energy metabolism.
Brain research 08/2010; 1347:104-10. · 2.46 Impact Factor
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ABSTRACT: Primary mediastinal germ cell tumors (GCTs) are rare and sometimes they pose diagnostic difficulty without immunohistochemical studies. Here, we investigated the diagnostic utility of 6 stem cell markers (SCMs) SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in 16 primary mediastinal seminomas, 3 embryonal carcinomas (ECs), 10 yolk sac tumors (YSTs), 7 teratomas (4 mature, 3 immature), and 1 choriocarcinoma. The percentage of tumor cells stained was scored as: 0 (no tumor cell staining), 1+ (< or =30%), 2+ (31% to 60%), 3+ (61% to 90%), and 4+ (>90%). The staining intensity of SCMs was scored as weak, moderate, or strong. We also compared them with currently used GCT markers placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), c-KIT, CD30, and glypican-3. All 16 seminomas showed staining for SALL4 (4+ in 15, 2+ in 1) (15 strong, 1 moderate), OCT4 (4+ in 11, 3+ in 4, 2+ in 1) (13 strong, 3 moderate), and UTF1 (4+ in 13, 3+ in 2, 2+ in 1) (7 strong, 5 moderate, 4 weak). Positive staining was shown by 9/9 seminomas tested for NANOG (4+ in 7, 2+ in 2) (8 strong, 1 weak), TCL1 (4+ strong in all), c-KIT (4+ in all), and PLAP (4+ in 5, 3+ in 1, 2+ in 2, 1+ in 1), but SOX2 staining was negative in all these tumors. All 3 ECs showed 4+ strong staining for SALL4, OCT4, and UTF1 but negative for TCL1. SOX2 staining was seen in 3/3 ECs (4+ strong in 1, 3+ weak to moderate in 2) whereas NANOG staining was seen in 2/3 ECs (2+ weak, 1+ moderate). CD30 staining was seen in 3/3 ECs (1+, 2+, 4+). Strong SALL4 staining was seen in 10/10 YSTs (4+ in 9, 2+ in 1). All 10 YSTs showed AFP (1+ in 7, 2+ in 1, 3+ in 2) and glypican-3 (1+ in 3, 2+ in 1, 3+ in 5, 4+ in 1) staining but only 4/10 YSTs showed PLAP staining (1+ in all 4). The mean percentage of YST cells stained with SALL4 was 92%, whereas it was 23% for AFP, 50% for glypican-3, and 4% for PLAP (P<0.01). Focal (1+) SALL4 (weak) and SOX2 (weak to moderate) staining was seen in 2/7 and 4/7 teratomas, respectively. The choriocarcinoma was negative for all 6 SCMs. Eleven thymomas and 6 thymic carcinomas were negative for 6 SCMs. No staining of NANOG and SOX2 was seen in 20 lymphomas (5 Hodgkin, 5 large B cell, 5 lymphoblastic, 5 anaplastic large cell) (other 4 SCMs in lymphomas earlier studied). Our study indicates that SALL4, OCT4, NANOG, SOX2, UTF1, and TLC1 are novel sensitive diagnostic markers for primary mediastinal GCTs, with high specificity. Of these 6 SCMs, SALL4 is the only 1 expressed in YST. These novel SCMs are more sensitive than the currently used markers for mediastinal GCTs.
The American journal of surgical pathology 05/2010; 34(5):697-706. · 4.06 Impact Factor
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ABSTRACT: Dr. YG Man's hypothesis that breast tumor invasion is triggered by the aberrant leukocyte infiltration induced by degeneration of myoepithelial cells holds a lot of truth in our clinical practice, and leukocyte infiltration may be regarded as a surrogate marker for diagnosis of invasion.
International journal of biological sciences 01/2010; 6(3):225-7. · 2.70 Impact Factor
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ABSTRACT: Cidofovir (CDV) is an acyclic nucleoside phosphonate analog that shows broad spectrum anti-DNA virus activity. In this study, we have investigated the influence of cidofovir on the tumor xenografts derived from HeLa and SiHa cells on nude mice. The HeLa/SiHa xenografts in nude mice were established by inoculating cells subcutaneously. Administration of cidofovir by intratumoral injection led to significant tumor reduction. Enhanced protein levels of p53 and p-pRb within the tumor samples were observed. Immunohistology analysis of the tumor sections indicated decreased PCNA index and increased apoptosis index. Our study gives more evidence and explanation on in vivo inhibition effect of cidofovir on HPV genome-positive cervical carcinoma cell line xenografts.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 01/2010; 18(11-12):519-27. · 1.30 Impact Factor
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Kaiyong Mei, Aijun Liu,
Robert W Allan,
Peng Wang,
Zhaoli Lane,
Ty W Abel,
Lixin Wei,
Hong Cheng,
Shuangping Guo,
Yan Peng,
Dinesh Rakheja,
Min Wang,
Joe Ma,
Maria M Rodriguez,
Jianping Li,
Dengfeng Cao
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ABSTRACT: Primary germ cell tumors of the central nervous system (CNS) sometimes pose diagnostic difficulty. In this study we analyzed the diagnostic utility of a novel marker, SALL4, in 77 such tumors (59 pure and 18 mixed) consisting of the following tumors/tumor components: 49 germinomas, 7 embryonal carcinomas, 27 yolk sac tumors, 3 choriocarcinomas, and 14 teratomas. We also stained SALL4 in 99 primary non-germ cell tumors to test SALL4 specificity. We compared SALL4 with OCT4 in all germ cell tumors and compared SALL4 with alpha-fetoprotein and glypican-3 in all yolk sac tumors. The staining was semiquantitatively scored as 0 (no staining), 1+ (<or=30%), 2+(31-60%), 3+ (61-90%), and 4+ (>90%). Strong SALL4 staining was observed in all 49 germinomas (4+ in 48, 3+ in 1), 7 embryonal carcinomas (all 4+), and 27 yolk sac tumors (1+ in 1, 2+ in 2, 3+ in 7, 4+ in 17). SALL4 staining, 1+ weak to focally strong, was observed in 2 of 3 choriocarcinomas (in mononucleated trophoblasts) and in 9 of 14 teratomas (in primitive neuroepithelium and teratomatous glands). All germinomas and embryonal carcinomas showed strong OCT4 staining (4+ in all except 1 germinoma with 3+), whereas other germ cell tumors were negative. Out of 27 yolk sac tumors, 26 showed positive alpha-fetoprotein staining (1+ in 9, 2+ in 7, 3+ in 5, and 4+ in 5). All yolk sac tumors showed positive glypican-3 staining (1+ in 6, 2+ in 6, 3+ in 7, and 4+ in 8). The mean percentage of yolk sac tumor cells stained was 84% with SALL4, 45% with alpha-fetoprotein, and 63% with glypican-3 (P<0.01). No non-germ cell tumors showed SALL4 staining. Our results indicate that SALL4 is a novel sensitive diagnostic marker for primary germ cell tumors of the CNS with high specificity. SALL4 is a more sensitive marker than alpha-fetoprotein and glypican-3 for yolk sac tumors.
Modern Pathology 10/2009; 22(12):1628-36. · 4.79 Impact Factor
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Fenghua Wang, Aijun Liu,
Yan Peng,
Dinesh Rakheja,
Lixin Wei,
Debin Xue,
Debing Xue,
Robert W Allan,
Kyle H Molberg,
Jianping Li,
Dengfeng Cao
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ABSTRACT: Extragonadal yolk sac tumors (YSTs; primary and metastatic) are rare but are malignant germ cell tumors. Pathologic diagnosis of extragonadal YSTs can be challenging without immunohistochemical markers but markers used for diagnosing these tumors such as placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), and glypican-3 lack adequate sensitivity and/or specificity. In earlier studies with gonadal germ cell tumors, SALL4 has been identified as a novel diagnostic marker for YSTs and other types of primitive germ cell tumors. Here, we investigated the diagnostic utility of SALL4 in 59 extragonadal YSTs (27 primary sacrococcygeal, 15 primary nonsacrococcygeal, and 17 metastatic) by immunohistochemical staining. We also compared SALL4 with PLAP, AFP, and glypican-3. In addition, we performed immunostains for pancytokeratin, epithelial membrane antigen, and OCT4 in these tumors. Our results showed that all 59 YSTs showed strong pancytokeratin staining (70% tumor cells in 1 case, >90% tumor cells in 58) and 10 (17%) of them also showed focal epithelial membrane antigen staining (<3% tumor cells). All 59 YSTs were negative for OCT4. Strong SALL4 staining was seen in all 59 YSTs (in more than 90% tumor cells in 54 and 70% to 85% tumor cells in 5 YSTs). Only 39 of 59 (66%) YSTs showed positive PLAP staining and the staining was often focal (in less than 30% tumor cells) (28 of 39 cases). Positive AFP staining was seen in the vast majority of YSTs (56 of 59 or 95%); however, 32 (54%) YSTs showed staining in less than 30% tumor cells. Although all 59 YSTs showed positive glypican-3 staining, 18 (30%) showed staining in less than 30% tumor cells, and additional 10 (17%) showed staining in between 30% and 60% tumor cells. In these 59 YSTs, the mean percentage of tumor cells stained with PLAP was 14% (range: 0% to 90%), with AFP 35% (range 0% to 95%), and with glypican-3 57% (range: 1% to 100%), whereas the mean percentage of tumor cells stained for SALL4 was 94% (range: 70% to 100%) (P<0.001). Our results indicate that SALL4 is a novel sensitive (100% sensitivity) diagnostic marker for extragonadal YSTs. SALL4 is a more sensitive marker than PLAP, AFP, or glypican-3 for extragonadal YSTs.
The American journal of surgical pathology 08/2009; 33(10):1529-39. · 4.06 Impact Factor
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ABSTRACT: Our recent studies revealed that focal basal cell layer disruption (FBCLD) induced auto-immunoreactions represented a contributing factor for human prostate tumor progression and invasion. As the basement membrane surrounds and attaches to the basal cell layer, our current study assessed whether FBCLD would impact the physical integrity of the associated basement membrane. Paraffin sections from 25-human prostate tumors were subjected to double immunohistochemistry to simultaneously elucidate the basal cell layer and the basement membrane with corresponding biomarkers. The physical integrity of the basement membrane overlying FBCLD was examined to determine the extent of correlated alterations. Of a total of 89 FBCLD encountered, 76 (85 %) showed correlated alterations in the overlying basement membrane, which included distinct focal disruptions or fragmentations. In the remaining 13 (15%) FBCLD, the overlying basement membrane showed significant attenuation or reduction of the immunostaining intensity. The basement membrane in all or nearly all ducts or acini with p63 positive basal cells was substantially thicker and more uniform than that in ducts or acini without p63 positive basal cells, and also, a vast majority of the focal disruptions occurred near basal cells that lack p63 expression. These findings suggest that focal disruptions in the basal cell layer and alterations in the basement membrane are correlated events and that the physical and functional status of the basal cells could significantly impact the physical integrity of the overlying basement membrane. As the degradation of both the basal cell layer and the basement membrane is a pre-requisite for prostate tumor invasion or progression, ducts or acini with focally disrupted basal cell layer and basement membrane are likely at greater risk to develop invasive lesions. Thus, further elucidation of the specific molecules and mechanism associated with these events may lead to the development of a more effective alternative for repeat biopsy to monitor tumor progression and invasion.
International journal of biological sciences 02/2009; 5(3):276-85. · 2.70 Impact Factor
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Lihua Ding,
Zhaoyun Wang,
Jinghua Yan,
Xiao Yang, Aijun Liu,
Weiyi Qiu,
Jianhua Zhu,
Juqiang Han,
Hao Zhang,
Jing Lin, [......],
Xi Qin,
Chang Niu,
Bin Yuan,
Xiaohui Wang,
Cui Zhu,
Yan Zhou,
Jiezhi Li,
Haifeng Song,
Cuifen Huang,
Qinong Ye
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ABSTRACT: The four-and-a-half LIM (FHL) proteins belong to a family of LIM-only proteins that regulate cell proliferation, differentiation, and apoptosis. The exact functions of each FHL protein in cancer development and progression remain unknown. Here we report that FHL1, FHL2, and FHL3 physically and functionally interact with Smad2, Smad3, and Smad4, important regulators of cancer development and progression, in a TGF-beta-independent manner. Casein kinase 1delta, but not the TGF-beta receptor, was required for the FHL-mediated TGF-beta-like responses, including increased phosphorylation of Smad2/3, interaction of Smad2/3 and Smad4, nuclear accumulation of Smad proteins, activation of the tumor suppressor gene p21, and repression of the oncogene c-myc. FHL1-3 inhibited anchorage-dependent and -independent growth of a human hepatoma cell line in vitro and tumor formation in nude mice. Further analysis of clinical samples revealed that FHL proteins are often downregulated in hepatocellular carcinomas and that this correlates with decreased TGF-beta-like responses. By establishing a link between FHL proteins and Smad proteins, this study identifies what we believe to be a novel TGF-beta-like signaling pathway and indicates that FHL proteins may be useful molecular targets for cancer therapy.
Journal of Clinical Investigation 02/2009; 119(2):349-61. · 15.39 Impact Factor
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Hao Zhang,
JiePing Li,
XiaoHui Wang,
Yan Sun,
Bin Yuan,
ZhiHong Yang,
YanChao Jiang,
Min Zeng,
LiHua Ding,
Kang Ning,
JianHua Zhu,
JieZhi Li,
CuiFen Huang, AiJun Liu,
QiNong Ye
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ABSTRACT: To explore the biological roles of human Pescadillo and investigate its potential effect on tumorigenesis, the cDNA of Pescadillo was fused with that of GST. After purification and elution, the purified GST-Pescadillo fusion protein was obtained, and the antibody against the fusion protein was generated. Endogenous Pescadillo protein was observed to be remarkably induced by estrogen. It was mainly distributed in the tissues such as breast, ovary and intestine, all of which contain proliferating cells, and was also detected in many cell lines of human cancer: renal carcinoma, hepatoma, ovarian cancer, colon carcinoma, and breast cancer. The expression level of Pescadillo was increased significantly in breast cancer tissues compared with their paired margin tissues. Taken together, these data suggest that Pescadillo may play important roles in the initiation and development of cancer and may be a potential target in cancer diagnosis and therapy.
Science in China Series C Life Sciences 07/2007; 50(3):298-304. · 1.61 Impact Factor
