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Biomedical subjects

Qiao Zhou

Publications and source records attributed to Qiao Zhou.

At least 19 recordsLinked to original sources

Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder.

The caspase family proteases are key proapoptotic proteins while the inhibitor of apoptosis proteins (IAP) prevent apoptosis by antagonizing the caspases or other key proapoptotic proteins. Limited studies of IAPs suggested their deregulation contributed to urothelial neoplasia. However, the expression status and biologic or prognostic significance of the caspase and IAP family proteins in urothelial neoplasms is not clear. In the present study, we first systematically evaluated the expression profile of the major apoptosis regulators, including caspases (CASP3, 6, 7, 8, 9, 10, and 14), IAPs (survivin/BIRC5, CIAP1, CIAP2, XIAP, and LIVIN), APAF1, SMAC, and BCL2, as well as proliferation markers Ki67 and PHH3, in Ta/T1 human urinary bladder urothelial carcinomas and normal urothelium samples by immunohistochemistry. The analysis showed that survivin/BIRC5 nuclear labeling index (BIRC5-N), but not cytoplasmic staining, was the only apoptotic marker which correlated significantly with tumor grade, stage, and patient outcome. We further analyzed the prognostic value of BIRC5-N in 101 Ta/T1 urinary bladder urothelial carcinomas by univariate analysis, which showed that BIRC5-N as well as the more classical prognosticators (stage, grade, and Ki67 index) were of prognostic significance. However, multivariate analysis by Cox proportional hazard regression demonstrated BIRC5-N was a stronger prognosticator than tumor grade, stage, and Ki67 labeling index. BIRC5-N index of 8% or more predicted unfavorable disease-specific survival (relative risk (RR)=6.6, 95% confidence interval=1.6-26.7, P=0.0080) as well as progression-free survival (RR=4.4, 95% confidence interval=1.3-14.6, P=0.0151). We conclude that BIRC5-N is a superior biologic and prognostic marker for Ta/T1 urothelial carcinomas of urinary bladder.

Aged↗

Microvascular density and vascular endothelial growth factor have little correlation with prognosis of craniopharyngioma.

BACKGROUND: Craniopharyngioma is histologically a benign epithelial tumor located in the supersellar cistern that often presents aggressive growth and repeated recurrence. The authors hypothesized that craniopharyngioma recurrence and invasive growth are angiogenesis dependent and evaluated the significance of vascularization in the prognosis of craniopharyngioma by a prospective cohort study. METHODS: The cohorts consisted of 32 patients with AE and 31 patients with SP tumor. The primary and recurrence removal specimens of the cohort patients were gathered. Microvascular density and VEGF protein in the recurrence group and recurrence-free group were detected by the immunohistochemistry avidin-biotin-peroxidase method and analyzed quantitatively through computer-assisted microscopy to evaluate the correlation of MVD and VEGF with prognosis of craniopharyngiomas. RESULTS: The average follow-up phase was 63.34 months; 14 of 32 patients with AE and 6 of 31 patients with SP had recurrence and underwent operation again. Although MVD and VEGF have significant difference between AE and SP (P=.000, P=.018, respectively), MVD and VEGF have no statistical difference between the recurrence group and recurrence-free group (P>.05). CONCLUSIONS: Microvascular density and VEGF in craniopharyngioma tissue have no correlation with prognosis of the tumor, which may be explained by the minimal blood circulation in the craniopharyngioma. Adamantine epithelioma showed more tendency to recur than SP.

Craniopharyngioma↗

Apoptosis and proliferation markers in diffusely infiltrating astrocytomas: profiling of 17 molecules.

Caspases and inhibitor of apoptosis proteins (IAPs) are antagonizing key apoptosis regulators. Limited studies of a few IAPs indicated their roles in astrocytomas. However, the overall expression status and significance of apoptosis regulators in astrocytomas is not clear. We examined the expression profile of the caspases (CASP3, 6, 7, 8, 9, 10, and 14), APAF1, SMAC, BCL2, the IAPs (BIRC5/survivin, CIAP1, CIAP2, XIAP, and LIVIN), and the proliferation markers Ki67 and PHH3 in 78 diffusely infiltrating astrocytomas and 24 normal brain samples by immunohistochemistry. Western blotting for major caspases and IAPs and reverse transcription-polymerase chain reaction analyses for IAPs were performed on a subset of 27 fresh samples. Our data showed BIRC5 nuclear labeling index (BIRC5-N) was the apoptosis marker most significantly different in World Health Organization grade II to IV astrocytomas and most strongly associated with proliferative activity. Expression level of other apoptosis-related proteins was modest or low in astrocytomas and did not correlate significantly with tumor grade or proliferation. Apoptosis regulators and proliferation markers were not detected in astrocytes of normal brain by immunostaining. This expression profile suggested involvement of apoptosis regulators in astrocytoma tumorigenesis, but tumor progression was more closely associated with proliferative advantages of which BIRC5 nuclear expression appeared to be a manifestation.

Adult↗

[A study of correlation between the blood supply types of PHcc on spiral CT and the level of VEGF expression in PHcc].

OBJECTIVE: To study the correlation between the blood supply types of primary hepatocellar carcinoma (PHcc) on Spiral CT and the level of vascular endothelial growth factor (VEGF) expression in PHcc for improvement in treatment strategies and prognostication. METHODS: Forty-five cases of PHcc identified by operation and pathology were investigated. Immunohistochemistry staining in SP was performed. The relationships between blood supply types of PHcc on Spiral CT during dual-phase scanning and the expression levels of VEGF in well-differentiated, moderately differentiated and poorly differentiated PHcc were analyzed. RESULTS: There were four blood supply types of PHcc on Spiral CT. Both the strong positive staining and the positive staining were most frequently seen in the hepatic artery blood supply type, and then were frequently in the double blood supply type, i. e. the hepatic arterial supply combining with the portal blood supply type. The positive staining results were rarely seen in the portal blood supply type and poor blood supply type (P<0.001). And with the escalation of the Edmonson- Steiner histological grades, the VEGF expression levels were shown to increase correspondingly (P < 0.05). CONCLUSION: We can ascertain the blood supply type of PHcc and infer the VEGF expression levels that reflect the PHcc angiogenesis condition and the histological grades by means of Spiral CT during dual- phase scanning. Hence this method is useful for the selection of PHcc treatment plans, including anti-angiogenesis and evaluating the prognosis.

Adult↗

[Detection of API2-MALT1 fusion gene in extranodal B-cell lymphoma and its significance].

OBJECTIVE: To study the expression of API2-MALT1 mRNA in mucosa-associated lymphoid tissue (MALT) lymphoma, extranodal diffuse large B-cell lymphoma (DLBCL) and Hashimoto's thyroiditis, to investigate the expression pattern of API2-MALT1 variants, and to correlate the findings with the clinicopathologic features and prognosis. METHODS: Sixty-two cases of MALT lymphoma (10 from lung, 31 from stomach, 9 from intestine and 12 from thyroid), 32 cases of extranodal DLBCL (16 from stomach, 13 from intestine and 3 from thyroid), 8 cases of Hashimoto's thyroiditis and 5 cases of reactive lymph nodes hyperplasia as negative controls were collected. The expression of API2-MALT1 mRNA was studied in all cases by reverse transcriptase (RT)-polymerase chain reaction (PCR) and nested PCR. The 94 cases of lymphoma were subdivided into API2-MALT1-positive and API2-MALT1-negative groups. Among the patients, 78 were followed up for 6 to 120 months. The differences in clinicopathologic features and prognosis between the two groups were analyzed. RESULTS: API2-MALT1 transcripts were detected in 39 of the 94 lymphoma cases (with 28 cases being MALT lymphoma and 11 cases being extranodal DLBCL). mRNA expression was not detected in all cases of Hashimoto's thyroiditis and the negative controls. Two fusion gene variants, A1446-M1123 and A1446-M814 were found, and A1446-M1123 expression was more common. As for MALT lymphoma cases, the frequency of the fusion gene expression was lower in thyroid, when compared with that in lung, stomach and intestine. API2-MALT1-positive cases had tumors in an earlier stage with milder infiltration of cancer cells, lower relapse rate, and higher five-year survival rate. CONCLUSIONS: The expression of API2-MALT1 mRNA can be detected in both MALT lymphoma and extranodal DLBCL, but not in Hashimoto's thyroiditis. These cases tend to show a more indolent clinical course and better survival. The frequency of t (11; 18) (q21; q21) correlates with the primary sites of MALT lymphoma. The higher incidence of breakpoint at 1123 bp of MALT1 gene in Chinese people may be due to geographical variation.

Caspases↗

[Pathological changes in the testes of the rats with hypospadia induced by dichlorvos].

OBJECTIVE: To study the mechanism of dichlorvos leading to hypospadia of rats. METHODS: From the 12th to the 17th day of conception, 20 pregnant female rats (the experiment group) were given 10 mg/(kg x d) dichlorvos, while another 10 (the control group) administered 1.5 ml 0.9% NaCl/day. Out of 88 male newborns of the 20 experimental mother rats, 22 had hypospadia, while out of the 33 male newborns of the 10 controls, none had the problem. Five hypospadia newborns from the experiment group and another 5 normal ones from the control group were raised to sexual maturity, and then their testes were excised and embedded in paraffin, and the tissue sections were analyzed by regular HE staining and SP immunohistochemical staining with Calretinin. RESULTS: HE staining showed that the number of Leydig cells in the testis tissues of the hypospadia rats decreased significantly compared with the normal ones, but no change was observed either in the number or in the morphology of the seminiferous tubules. Moreover, the Calretinin positive Leydig cells were reduced dramatically in the testes of the hypospadia rats. CONCLUSION: Pregnant female rats, when exposed to dichlorvos, may cause reduction of testis Leydig cells in their male offsprings. Thus the probable mechanism of rat hypospadia induced by dichlorvos may lie in the decrease of the testosterone level caused by damage to Leydig cells from dichlorvos toxicity.

Animals↗

Improved therapeutic effectiveness by combining recombinant CXC chemokine ligand 10 with Cisplatin in solid tumors.

PURPOSE: CXC chemokine ligand 10 (CXCL10) is a potent inhibitor of angiogenesis. We wonder whether the combination of CXCL10 with cisplatin would improve the therapeutic antitumor efficacy. EXPERIMENT DESIGN: We evaluated the antitumor activity of the combination therapy in the immunocompetent C57BL/6 and BALB/c mice bearing LL/2 Lewis lung cancer and CT26 colon adenocarcinoma, respectively. Mice were treated with either CXCL10 s.c. at 25 mug per kg per day once daily for 30 days, cisplatin cycled twice (5 mg/kg i.p. on days 14 and 21 after the initiation of CXCL10), or both agents together. Tumor volume and survival time were observed. Antiangiogenesis of CXCL10 in vivo were determined by alginate capsule models and CD31 immunohistochemistry. Histologic analysis and assessment of apoptotic cells were also conducted in tumor tissues. RESULTS: CXCL10 + cisplatin reduced tumor growth in LL/2 and CT26 tumor model, respectively, more effectively, although cisplatin or CXCL10 individually resulted in suppression of tumor growth and improved survival time of tumor-bearing mice. CXCL10 successfully inhibited angiogenesis as assessed by alginate model and CD31 (P < 0.05). Histologic analysis of tumors exhibited that CXCL10 in combination with cisplatin led to the increased rate of apoptosis, tumor necrosis, and elevated lymphocyte infiltration. CONCLUSIONS: Our data suggest that the combination of CXCL10, a well-tolerated angiogenesis inhibitor, with cisplatin can enhance the antitumor activity. The present findings may be of importance to the further exploration of the potential application of this combined approach in the treatment of lung and colon carcinoma.

Animals↗

Development of a low volume plasma sample precipitation procedure for liquid chromatography/tandem mass spectrometry assays used for drug discovery applications.

The demand for high sensitivity bioanalytical methods has dramatically increased in the drug discovery stage; in addition, there has been a growing trend of reducing the sample volume that is required for these assays. A sensitive high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedure has been developed and tested to meet these needs. The assay requires only a low plasma sample volume (10 microL) and employs a protein precipitation procedure using a 1:6 plasma/acetonitrile ratio. The supernatant is injected directly into the LC/MS/MS system using the selected reaction monitoring (SRM) procedure for detection. A generic HPLC gradient based on a methanol/water mobile phase with a flow rate set to 0.8 mL/min was used. The test method showed very good linearity between 0.1-1000 ng/mL (R2 = 0.9737), precision (%RSD = 6-9), accuracy (%RE = -2) and reproducibility (%RSD = 11). A drug discovery IV/PO study was assayed using both the new low volume method and our standard volume (50 microL) method. The correlation of the two sets of data from the two methods was excellent (R2 = 0.9287). This new assay procedure has been successfully used in our laboratory for over 100 different rat or mouse discovery PK studies.

Animals↗

A study of common discovery dosing formulation components and their potential for causing time-dependent matrix effects in high-performance liquid chromatography tandem mass spectrometry assays.

Hydroxyproyl-beta-cyclodextran (HPBCD), methyl cellulose (MC), Tween 80 and PEG400 are commonly used in dosing formulations in pharmacokinetic (PK) studies during the early drug discovery stage. A series of studies was designed to evaluate the potential matrix effects of these dosing vehicles when the samples are assayed by high-performance liquid chromatography combined with tandem mass spectrometry (HPLC/MS/MS). These dosing vehicles were dosed into the rats via either an intravenous (IV) or an oral route (PO) and plasma samples were collected for a 24-h post-dose period. Five test compounds with CLog P values ranging from 0.9 to 5.4 were spiked into the collected rat plasma. After protein precipitation, these samples were analyzed using a generic fast-gradient HPLC/MS/MS method. Three popular mass spectrometers (Thermo-Finnigan Quantum with ESI and APCI, AB-Sciex API 3000 with ESI and APCI, and Waters-Micromass Quattro Ultima with ESI) were used to test these plasma samples. Results indicated that there was no observed matrix effect for all five compounds when 20% HPBCD or 0.4% MC was used as the vehicle in either the IV or the PO route, respectively. In addition, 0.1% Tween 80 dosed either IV or PO caused significant ion suppression (50-80%, compared to results obtained from plasma samples free from vehicles) for compounds that eluted at the beginning of the chromatogram. Also, PEG400 when used in an oral formulation caused significant ion suppression (30-50%) for early eluting compounds. These matrix effects were not only ionization mode (ESI or APCI) dependent, but also source design (Thermo-Finnigan, AB-Sciex or Waters-Micromass) dependent. Overall, the APCI mode proved to be less vulnerable to matrix effects than the ESI mode. Some possible mechanisms of these matrix effects are proposed and simple strategies to avoid these matrix effects are discussed.

Animals↗

Enhanced antitumor effect of the combination of tumstatin gene therapy and gemcitabine in murine models.

Targeting tumor endothelium is an important strategy for cancer therapy. We evaluated the effectiveness of gene therapy, that is, intramuscular delivery of plasmid DNA encoding tumstatin (pSecTag2B-tum), combined with gemcitabine administration in vitro and in vivo, using colon carcinoma (CT26) and Lewis lung carcinoma (LLC) murine models. The in vitro growth-inhibitory and proapoptotic effects of gemcitabine and/or tumstatin on human umbilical vein endothelial cells (HUVECs) and mouse endothelial cells (SVEC4-10), respectively, were assessed. in vitro, conditioned medium from pSecTag2B-tum-transfected COS cells inhibited the growth of endothelial cells but not of CT26 or LLC cells, whereas gemcitabine inhibited the growth of both endothelial cells and CT26 and LLC cells. Mice bearing subcutaneously established CT26 or LLC tumors received pSecTag2B-tum alone or in combination with gemcitabine to assess tumor growth inhibition. in vivo, combined treatment with pSecTag2B-tum and gemcitabine significantly decreased tumor growth through increased inhibition of tumor angiogenesis and increased tumor cell apoptosis compared with either agent alone. Enhanced antiproliferative and proapoptotic activity of the combination therapy on tumor-associated endothelial cells was calculated to be significant. This study suggests that combined treatment by the intramuscular delivery of plasmid DNA encoding tumstatin and gemcitabine augments tumor growth inhibition by suppressing angiogenesis and enhancing apoptosis in murine models. A combination of these agents could be used in future studies and translated into the clinical setting.

Angiogenesis Inhibitors↗

Primary adenosquamous carcinoma of the jejunum.

Adenosquamous carcinomas of the small intestine are extremely rare, with only three documented jejunal and three ileal cases being reported in the English-language medical literature. Presented herein is a case of primary jejunal adenosquamous carcinoma in an 80-year-old woman. The jejunal carcinoma consisted predominantly of a squamous component throughout the tumor but peritoneal nodules carrying metastases from the adenocarcinoma element were noted, making it the first case of jejunal adenosquamous carcinoma with metastases from the adenocarcinoma component. The finding that metastases could arise from the minor component of a jejunal adenosquamous carcinoma indicates that an accurate diagnosis must be based upon thorough examination of both the primary and the metastases, not just mesenteric nodule biopsy alone. Histological foci of closely intermingled squamous and glandular components with apparent morphological transition were noted, indicating the pathogenetic possibility that the squamous component might arise by transformation from the glandular element. The squamous component was strongly positive with immunostaining for p63 (nuclear staining) and for cytokeratin 10/13 (cytoplasmic staining), while the adenocarcinoma element was negative. The immunohistochemical results suggest that p63 and cytokeratin 10/13 might be useful in identifying squamous differentiation in jejunal carcinoma.

Aged↗

Constructing tissue microarrays without prefabricating recipient blocks: a novel approach.

Tissue microarray (TMA) is a powerful research tool and is applied in such diverse areas as tumor marker validation and laboratory quality control. Existing TMA construction techniques require an essential step of prefabricating recipient paraffin blocks on which holes are punched so that tissue cores can be inserted. This procedure has several disadvantages, such as accidental block breakage during hole punching and difficulty ensuring that the cores are flush with the block surface. We developed a novel TMA construction technique without prefabricating recipient blocks. We used double-sided adhesive tape attached to x-ray film as an adhesive platform on which the tissue cores were placed securely. The array of tissue cores then was embedded in an embedding mold. We have been making high-quality TMAs with up to 220 cores within 2 to 3 hours using this highly dependable, efficient, versatile, and cost-effective technique, which can be adopted by pathology laboratories and researchers with minimal investment.

Histological Techniques↗

[The frequency of API2-MALT1 fusion gene variants in MALT lymphoma and its correlation with apoptosis of MALT lymphoma].

OBJECTIVE: To investigate the frequency of different variant of API2-MALT1 fusion gene in extranodal marginal zone B-cell lymphoma of mucosa-associated tissue(MALT1) lymphoma and the correlation between API2-MALT1 transcript and apoptosis of MALT lymphoma. METHODS: The API2-MALT1 fusion transcripts were detected in 62 cases of MALT lymphoma by reverse transcription-polymeras chain reaction(RT-PCR) and Nested PCR. Five cases with reactive proliferation of lymph node were in use for negative control, and beta-actin was regarded as internal control; the apoptosis index, mRNA and protein of API2 were assayed in all samples by means of TUNEL, RT-PCR and immunohistochemistry respectively. RESULTS: API2-MALT1 transcript was detected in 28 of 62 cases with MALT lymphoma (45.16%). Two kinds of API2-MALT1 variants (A1446-M1123 and A1446-M814) were detected. Variant A1446-M1123 was detected more frequently as compared with A1446-M814. The frequency of API2-MALT1 transcript was lower in thyroid MALT lymphoma(1/12) but similar in pulmonary and gastrointestinal MALT lymphoma. In the group of API2-MALT1(+), the apoptosis index was higher and the API2 mRNA and protein were lower when compared against those in the group of API2MALT1(-). But no significant differences in the levels of apoptosis and API2 were observed between the group of A1446-M1123(+) and A1446-M814(+). CONCLUSION: API2-MALT1 transcript displayed variable frequency in MALT lymphomas of different sites. A1446-M1123 was noted to be probably the main type of API2-MALT1 variant in MALT lymphoma of Chinese. API2-MALT1 transcript was confirmed to be associated with the levels of apoptosis and API2 of MALT lymphoma.

Apoptosis↗

[Detecting the API2-MALT1 fusion gene and its significance in Hashimoto's thyroiditis and thyroid lymphomas].

OBJECTIVE: To investigate the expression of API2-MALT1 fusion gene mRNA in Hashimoto's thyroiditis, thyroid MALT lymphoma and DLBCL, as well as the correlation between the expression and the pathogenesis and prognosis of two types of thyroid lymphoma. METHODS: Eight cases of Hashimoto's thyroiditis, 12 cases of MALT lymphoma and 3 cases of DLBCL in thyroid were selected and retrieved. API2-MALT1 transcripts were investigated in all cases by reverse transcript touchdown-PCR and nested PCR. The effect of API2-MALT1 fusion gene on the prognosis of thyroid lymphomas was assessed by analyzing the clinicopathological features and the follow-up findings. RESULTS: The variant 1446/1123 transcript was detected in 2 of thyroid lymphomas (1 MALT lymphoma, 1 DLBCL) but not in 8 cases of Hashimoto's thyroiditis and 5 cases of chronic lymphadenitis. Both of API2-MALT1-positive cases were accompanied with Hashimoto's thyroiditis, showing stage I E and no involvement of lymph node. CONCLUSION: The incidence of API2-MALT1 transcript in thyroid lymphomas was low; however, the correlation between API2-MALT1 fusion gene and the progression from Hashimoto's thyroiditis to lymphoma could not be excluded; the thyroid lymphoma with API2-MALT1 transcript seemed to develop on a more indolent clinical course.

Adult↗