Long non-coding RNA LINC00346 regulates proliferation and apoptosis by targeting miR-128-3p/SZRD1 axis in glioma.

OBJECTIVE: Long non-coding RNAs (lncRNAs) participate in multiple processes of malignant tumors, including glioma. In this study, we aimed to explore the effect of LINC00346 on glioma and its underlying mechanism. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the expression patterns and survival risk of LINC00346, miR-128-3p and SUZ RNA binding domain containing 1 (SZRD1) in glioma tissues. The binding sites were predicted by bioinformatic databases, and then, validated by Dual-Luciferase assay and RNA immunoprecipitation (RIP). qRT-PCR and Western blot were performed to evaluate the gene expression levels. CellTiter-Glo® and colony formation assays were used to detect the proliferation of glioma cells. Flow cytometric analysis was used to evaluate the apoptosis of glioma cells. The xenograft models were established to investigate the impact of LINC00346 on tumor growth in vivo. RESULTS: We found that both LINC00346 and SZRD1 expression were negatively related to the poor overall survival rate in glioma patients. However, miR-128-3p showed the opposite effect of survival outcomes. LINC00346 knockdown remarkably restrained cell proliferation both in vitro and in vivo, as well as inducing apoptosis by acting as a molecular sponge of miR-128-3p. Moreover, miR-128-3p bound to SZRD1 3'-UTR in a sequence-specific manner. In addition, LINC00346 knockdown significantly inhibited the expression of SZRD1 and the inhibition could be reversed by miR-128-3p mimics. Furthermore, cell proliferation and apoptosis affected by LINC00346 were partially rescued by modulating miR-128-3p or SZRD1 expression. CONCLUSIONS: LINC00346/miR-128-3p/SZRD1 axis played a crucial role in modulating the malignant progression of glioma, which may serve as a prognostic indicator and a probable therapeutic target for glioma.

[Targeted-knockdown of Yes-associated protein inhibits the Warburg effect and the invasion of laryngeal cancer cells].

Objective: To investigate the migration and invasion behaviors of Hep-2 after the targeted knockdown of yes-associated protein (YAP). Methods: Hep-2 cells were knock-downed for YAP by shRNA as YAP-shRNA group, Hep-2 treated with non-specific shRNA as YAP-NC group, and Hep-2 with no treatment as control. Glucose uptake and lactate production in the cells were examined to assess Warburg effect. The migration and invasion behaviors of cells in three groups were observed. The expressions of vimentin and E-cadherin were detected by RT-PCR and Western Blot. The statistical software GraphPad Prism 7.0 was used to analyze significance of data. Two tailed Student' s t-tests was used to determine significance when only two groups were compared. P values of less than 0.05 was considered statistically significant. Results: Downregulation of YAP led to a obvious decrease in glucose uptake [(18.51±1.72)%] and lactate production [103.40±8.32] in Hep-2 cells compared with control [(41.20±1.11)% and 743.69±19.49, t=19.20 and 52.33, respectively, both P<0.01] and YAP-NC group [(39.60±0.78)% and 705.22±17.20, t=19.34 and 54.56, respectively, both P<0.01]. Compared with the control group (78.32±4.04) and YAP-NC group (77.28±3.11), the scratch healing ability of Hep-2 cells was significantly decreased in YAP-shRNA group (44.71±4.68). The P value was less than 0.01 (t=9.42 and 10.04). The number of cells with YAP-shRNA (33.30±4.19) passing through compartments was remarkable fewer than the control group (133.71±6.72) and YAP-NC group (126.32±4.21). The P value was less than 0.01 (t=21.96 and 27.13). The expression of E-cadherin protein in cells of YAP-shRNA group (6.16±0.11) was up-regulated compared with control (0.97±0.10, t=35.70, P<0.01) and YAP-NC group (1.13±0.09, t=36.28, P<0.01), while the expression of vimentin protein in cells of YAP-shRNA group (1.08±0.09) was down-regulated compared with control (5.67±0.12, t=29.91, P<0.01) and YAP-NC group (5.51±0.12, t=29.04, P<0.01). Conclusions: The down-regulation of YAP in Hep-2 inhibits the migration and invasion of cells via suppressing Warburg and EMT program.

A novel bioprinting method and system for forming hybrid tissue engineering constructs.

Three dimensional (3D) bioprinting is a promising approach to form tissue engineering constructs (TECs) via positioning biomaterials, growth factors, and cells with controlled spatial distribution due to its layer-by-layer manufacturing nature. Hybrid TECs composed of relatively rigid porous scaffolds for structural and mechanical integrity and soft hydrogels for cell- and growth factor-loading have a tremendous potential to tissue regeneration under mechanical loading. However, despite excessive progress in the field, the current 3D bioprinting techniques and systems fall short in integration of such soft and rigid multifunctional components. Here we present a novel 3D hybrid bioprinting technology (Hybprinter) and its capability enabling integration of soft and rigid components for TECs. Hybprinter employs digital light processing-based stereolithography (DLP-SLA) and molten material extrusion techniques for soft and rigid materials, respectively. In this study, poly-ethylene glycol diacrylate (PEGDA) and poly-(ε-caprolactone) (PCL) were used as a model material for soft hydrogel and rigid scaffold, respectively. It was shown that geometrical accuracy, swelling ratio and mechanical properties of the hydrogel component can be tailored by DLP-SLA module. We have demonstrated the printability of variety of complex hybrid construct designs using Hybprinter technology and characterized the mechanical properties and functionality of such constructs. The compressive mechanical stiffness of a hybrid construct (90% hydrogel) was significantly higher than hydrogel itself (∼6 MPa versus 100 kPa). In addition, viability of cells incorporated within the bioprinted hybrid constructs was determined approximately 90%. Furthermore, a functionality of a hybrid construct composed of porous scaffold with an embedded hydrogel conduit was characterized for vascularized tissue engineering applications. High material diffusion and high cell viability in about 2.5 mm distance surrounding the conduit indicated that culture media effectively diffused through the conduit and fed the cells. The results suggest that the developed technology is potent to form functional TECs composed of rigid and soft biomaterials.

Transport of equine estrogens: binding of conjugated and unconjugated equine estrogens with human serum proteins.

The binding of ring B unsaturated equine estrogens, equilin sulfate (EqS), equilin (Eq), and 17 beta-dihydroequilin (17 beta-Eq) with human serum proteins was determined and compared with the binding of estrone sulfate (E1S), estrone (E1), estradiol (E2), testosterone (T), and 5 alpha-dihydrotestosterone (5 alpha-DHT). Undiluted serum or 5% human serum albumin (HSA) was incubated with 3H-labeled steroids at 37 C, then subjected to gel filtration at 4 C. Gel filtration of serum from Premarin-treated postmenopausal women or normal women incubated with Eq, E1, E2, or 5 alpha-DHT showed two peaks of radioactivity associated with proteins with average apparent mol wt of 128,000 and 68,000 and average Stokes radii of 48.6 and 34.9 A. These values correspond to those reported for sex hormone-binding globulin (SHBG) and albumin, respectively. Binding to SHBG and albumin was confirmed by removing SHBG or albumin from the serum with Concanavalin-A Sepharose 4B gel or CM-Affi Gel Blue, respectively. In the case of [3H]EqS and [3H]E1S, binding to SHBG was not detectable, and only a peak of radioactivity associated with albumin was found. However, under these conditions, the binding of estrogens to SHBG in serum from normal men was not detectable. Incubation of the above steroids with 5% HSA followed by gel filtration resulted in a single peak of radioactivity associated with the protein peak. Using ultrafiltration dialysis followed by Scatchard analysis, at least two sets of binding sites were found for the interaction of HSA with EqS or E1S. The high and low affinity binding sites had association constants k1 and k2 of approximately 0.9-1.1 (X 10(5) M-1) and 0.5-0.8 (X 10(4) M-1). In contrast with Eq and E1, only the low affinity binding sites were found (apparent Ka congruent to 1 X 10(4) M-1). The binding constants of some estrogens and androgens to SHBG at 37 C determined by competitive Scatchard analysis using DEAE filter assay and [3H]5 alpha-DHT were 0.15, 0.07, 0.22, 0.29, 2.70, and 4.53 (X 10(9) M-1) for Eq, E1, 17 beta-Eq, E2, T, and 5 alpha-DHT, respectively. These results indicate that the equine estrogens bind to SHBG and albumin in a manner similar to that of E1 and E2, and that the low MCR of EqS reported previously may be due to its binding to albumin.

Metabolism of [3H]equilin-[35S]sulfate and [3H]equilin sulfate after oral and intravenous administration in normal postmenopausal women and men.

The absorption of equilin sulfate and equilin from the gastrointestinal tract was determined in normal men after the ingestion of [3H]equilin-[35S]sulfate or a mixture of [3H]equilin and equilin-[35S]sulfate, while the metabolism of equilin sulfate was investigated after iv administration of [3H]equilin sulfate to postmenopausal women. After the oral administration of [3H]equilin-[35S]sulfate, equilin sulfate containing both 3H and 35S was isolated from plasma; however, only in the first sample taken at 10 min was the 3H/35S ratio the same as that of the [3H]equilin-[35S]sulfate ingested. The 3H/35S ratio then increased, and by 12 h only traces of equilin-[35S]sulfate were detectable. Similarly, after the ingestion of [3H]equilin and equilin-[35S]sulfate, [3H]equilin-[35S]sulfate was isolated from plasma. The 3H/35S ratio was at all time points greater than the 3H/35S ratio of the ingested mixture. Analysis of urine indicated that over 98% of 35S was not associated with any steroid and was most likely inorganic sulfate. After iv administration of [3H] equilin sulfate to postmenopausal women, equilin, equilenin, 17 beta-dihydroequilin, and 17 beta-dihydroequilenin were isolated from the urine. These results indicate that 1) some of the orally administered equilin sulfate was absorbed from the gut without prior hydrolysis, 2) some equilin sulfate was hydrolyzed in the gut before absorption; 3) equilin was absorbed more efficiently than equilin sulfate; 4) equilin absorbed was readily sulfated and circulated in this form; and 5) equilin sulfate was extensively metabolized, and the metabolites were excreted in the urine mainly conjugated with glucuronic acid.

Colocalization of iron and ceroid in human atherosclerotic lesions.

The presence of ceroid, a complex of protein associated with oxidized lipids, is commonly observed in human atherosclerotic lesions. When the human aortic walls were examined by Perls' staining, it was found that the iron deposits were evident in aortas with atherosclerosis. The extent of iron deposition was associated with the severity of the lesion. Furthermore, the iron deposits appeared to be colocalized with ceroids either extracellularly or intracellularly in foam cell-like macrophages or smooth muscle cells. Electron microscopy and X-ray microanalysis revealed that some of the extracellular iron aggregates were present within the ceroids. Likewise, some of the subcellular iron aggregates were found to be located near the lipid droplets or within the ceroids of foam cells. Collectively, these observations support the theory that the lipid oxidation occurring in lipid-laden cells of aortic lesions is facilitated by iron-overload in these cells.

Influence of 3D-CRT pelvic irradiation on outcome in prostate cancer treated with external beam radiotherapy.

PURPOSE: The role of pelvic irradiation (PRT) in the treatment of prostate cancer remains unclear. We reviewed our institution's experience with three-dimensional conformal external beam radiotherapy (3D-CRT) during the prostate-specific antigen era to determine the influence of PRT on the risk of biochemical recurrence in patients who have a predicted risk of lymph node involvement. METHODS AND MATERIALS: Between March 1985 and January 2001, 1832 patients with clinically localized prostate cancer were treated with definitive 3D-CRT. All treatments involved CT planning to ensure coverage of the intended targets. Treatment consisted of prostate-only treatment, prostate and seminal vesicle treatment, or PRT of lymph nodes at risk followed by a boost. To create relatively homogenous analysis groups, each patient's percentage of risk of lymph node (%rLN) involvement was assigned by matching the patient's T stage, Gleason score, and initial prostate-specific antigen level to the appropriate value as described in the updated Partin tables. Three categories of %rLN involvement were defined: low, 0-5%; intermediate, >5-15%; and high, >15%. Biochemical recurrence was defined as the first occurrence of either the American Society for Therapeutic Radiology and Oncology consensus definition of prostate-specific antigen failure or the initiation of salvage hormonal therapy for any reason. RESULTS: The risk status (%rLN) could be determined for 709 low-risk, 263 intermediate-risk, and 309 high-risk patients. The actuarial freedom from biochemical recurrence (bNED) and the log-rank test for the similarity of the control and treatment survival functions are reported for each risk group. Multivariate analysis demonstrated a statistically significant benefit for the entire population treated with PRT, with a relative risk reduction of 0.72 (95% confidence interval 0.54-0.97). Although the multivariate analysis could not determine the patient population that would most benefit from PRT, the beneficial effect appeared to be most pronounced within the intermediate-risk group. Univariate analysis revealed that the intermediate-risk patients treated with PRT had an improved 2-year bNED rate, 90.1% vs. 80.6% (p = 0.02), and both low-risk and high-risk patients treated with PRT had statistically similar 2-year bNED rates compared with those who did not receive it. CONCLUSION: Pelvic 3D-CRT appears to improve bNED in prostate cancer patients. Additional studies are needed to elucidate the %rLN population for which this treatment should be recommended.

Spindle cell and mixed spindle/lymphocytic thymomas: an integrated clinicopathologic and immunohistochemical study of 81 cases.

Forty-three cases of spindle cell thymoma (medullary, WHO type A) and 38 cases of mixed spindle/lymphocytic thymoma (WHO type AB) were studied for their clinicopathologic and immunohistochemical characteristics. Three histologic patterns of spindle cell thymoma were observed: short-spindled (57%), long-spindled (31%), and micronodular (12%). The short-spindled variant was composed of oval to short spindle cells commonly arranged in a hemangiopericytic or microcystic pattern. The long-spindled variant chiefly consisted of fibroblast-like epithelial cells mimicking fibrohistiocytic neoplasms. The micronodular variant was characterized by small nests of short spindle cells dispersed among a lymphoid stroma with frequent germinal centers. All kinds of spindle cell could be admixed with lymphocyte-rich "cortex"-like areas to constitute mixed spindle/lymphocytic thymomas. Immunohistochemically, the epithelial cells in up to 70% of the short-spindled and long-spindled variants of spindle cell thymoma and 90% of mixed spindle/lymphocytic thymomas were positive for CD20, whereas the epithelial cells in all micronodular spindle cell thymomas were negative. All of the spindle cell thymomas and most of the mixed spindle/lymphocytic thymomas in this study were found in stages I and II. Follow up of the patients did not disclose relapse or mortality directly resulting from the tumors. However, the prognosis of stage I and II spindle cell and mixed spindle/lymphocytic thymomas did not significantly differ from those of stage I and II thymomas of other types by a stage-matched survival analysis. Our data showed that spindle cell and mixed spindle/lymphocytic thymomas are distinctive in histologic pattern and immunohistochemical profile. When interpreted within the context of staging, spindle cell and mixed spindle/lymphocytic thymomas presenting in stages I and II most likely behave in an indolent fashion.

Tubulocystic clear cell adenocarcinoma arising within the prostate.

Neoplasms resembling ovarian common epithelial-type tumors, including clear cell adenocarcinomas, rarely occur in the lower urinary tract of men. When they do, they develop in the urethra or urinary bladder. We report a case of such a tumor arising within the prostate of a 47-year-old man. The tumor was a cystic mass in the left posterolateral region of the prostate. Histologically, the tumor was chiefly composed of tubulocystic and papillary glands lined by glycogen-rich, cuboidal or hobnail cells with clear to eosinophilic cytoplasm. The tumor cells were strongly positive for pan-cytokeratin, low molecular weight cytokeratin, and epithelial membrane antigen, and focally positive for high molecular weight keratin. The tumor did not immunohistochemically express prostate-specific antigen (PSA) and prostatic acid phosphatase. Serologically, the patient had increased levels of CA125 instead of PSA. The clinical as well as the pathologic features are consistent with a clear cell adenocarcinoma as seen in the female genital tract rather than a typical prostatic adenocarcinoma.

The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system.

The Gleason grading system of prostatic adenocarcinoma does not account for the existence of a tertiary (third most prevalent) pattern, and there are no studies concerning the latter's prognostic influence. The authors analyzed 114 radical prostatectomies with small tertiary components, which mostly occupied less than 5% of whole tumors. These specimens were compared with a prostatectomy database comprised of 2,276 cases without a tertiary component. The pathologic stages of "typical" Gleason score 5 to 6 tumors (Gleason scores 2 + 3 = 5, 3 + 2 = 5, 3 + 3 = 6), which contained tertiary patterns 4 or 5, were significantly higher than those of "typical" Gleason score 5 to 6 tumors without pattern 4 (p = 0.018) but lower than those of "typical" Gleason score 7 tumors (p = 0.021; Gleason scores, 3 + 4 = 7, 4 + 3 = 7). Typical Gleason score 7 tumors with a tertiary pattern 5 showed significantly worse pathologic stages than typical Gleason score 7 tumors (p = 0.008) without pattern 5 and were not different statistically from typical Gleason score 8 (Gleason score, 4 + 4 = 8) tumors. Both typical Gleason score 5 to 6 and 7 tumors with tertiary components revealed significantly higher progression rates than typical Gleason score 5 to 6 tumors (p <0.0001) and Gleason score 7 tumors (p = 0.003) without tertiary components, and progressed like typical Gleason score 7 and 8 tumors respectively. Tertiary high-grade components have an adverse impact on biologic behavior. The authors propose that the Gleason system for radical prostatectomy specimens be modified to take into account small volumes of patterns 4 and 5, which are important prognostically.

Applicability of the product isolation and the radiometric aromatase assays for the measurement of low levels of aromatase: lack of aromatase activity in the human endometrium.

The purpose of this investigation was to assess the applicability of two well established procedures: (i) the product isolation assay and (ii) the radiometric 3H2O assay for the determination of very low levels of aromatase activity. The methods were validated and used to assess the capacity of normal and neoplastic human endometrium to synthesize oestrogens from androgens. Using the product isolation assay, various specimens (n = 27) of normal and neoplastic endometrium were incubated with [1,2,6,7-3H]testosterone either by a standard incubation procedure or by a superfusion technique. Following the incubation, carrier oestrone and oestradiol or [14C]oestrone and [14C]oestradiol were added, and the oestrogens were isolated and purified by paper chromatography and high-performance liquid chromatography. The radiochemical purity of oestrone and oestradiol was checked by the isotope dilution technique. In all samples, the 3H associated with oestrone and oestradiol failed to recrystallize as oestrone and oestradiol. No radioactivity was detectable in the oestrone and oestradiol crystals after acetylation. Similarly, 16 endometrial samples were tested for aromatase activity by the 3H2O release assay using [1 beta-3H]androstenedione as substrate. The results indicate that 3H2O was indeed released during these incubations, but this activity could not be inhibited by the aromatase inhibitor 4-hydroxyandrostenedione, by excess substrate or by heat inactivation of the tissue. Furthermore, the release of 3H2O from [1 beta-3H]androstenedione under the incubation conditions used (Dulbecco's modified Eagle's medium or RPMI-1640 containing fetal bovine serum and NADPH) also occurred in the absence of any tissue. This activity was not inhibited by 4-hydroxyandrostenedione nor by excess substrate. The results demonstrate that the human endometrium does not contain detectable levels of aromatase activity and that the radiometric assay can give rise to false-positive results if used for detection of very low levels of aromatase activity.

Comparative analysis of sampling methods for grossing radical prostatectomy specimens performed for nonpalpable (stage T1c) prostatic adenocarcinoma.

Scant data are available comparing sampling methods of radical prostatectomy specimens performed for clinical stage T1c (nonpalpable) cancer. Seventy-eight stage T1c radical prostatectomies that had 1 or more of the following adverse pathologic findings-Gleason score > or = 7, positive margins, and extraprostatic extension-were compared using 10 different sampling techniques. Of the 78 entirely submitted cases, 52 had Gleason score > or = 7, 14 had positive margins, and 54 had extraprostatic extension (mean 34 slides). Of the partial sampling methods, we favor the following two methods. The first is submitting every posterior section plus 1 midanterior section from right and left sides; if either of these anterior sections show sizeable tumor, all ipsilateral anterior slides are examined. This method detects 98% of tumors with Gleason score > or = 7, 100% of positive margins, and 96% of cases with extraprostatic extension (mean 27 slides). The second method is to use the above method but restrict it to sections ipsilateral to the previous positive needle biopsy. This method detects 92% of tumors with Gleason score > or = 7, 93% of positive margins, and 85% of cases with extraprostatic extension (mean 17 slides). Partial sampling can detect important prognostic parameters. By balancing the extra expense and time involved to process and examine additional sections with the risk of missing important prognostic parameters, pathologists can decide which sampling method to use.

The clinicopathological correlation of epithelial subtyping in thymoma: a study of 112 consecutive cases.

The clinicopathological features of 112 thymomas collected from the surgical pathological files of Taipei Veterans General Hospital from 1961 to 1991 were investigated to determinate the clinical efficacy of epithelial subtyping. All thymomas were categorized based on the Müller-Hermelink system into three subtypes: cortical thymoma, mixed thymoma, and medullary thymoma. The former was further subclassified into organoid thymoma, conventional cortical thymoma, and well differentiated thymic carcinoma (WDTC) according to the systems of Pescarmona and Kirchner. The association of each subtype with sex, age at diagnosis, clinical stage, presence of myasthenia gravis, and length of survival was studied. As classified by the Müller-Hermelink system, the cortical thymomas as a whole tended to occur in younger patients and were more frequently associated with myasthenia gravis than the medullary thymomas. The cortical thymomas also showed a propensity to be invasive in nature, whereas the medullary thymomas generally behaved as benign tumors. Further subclassification of cortical thymomas into organoid thymoma, conventional thymoma, and WDTC did not provide more information about clinical behavior. By Kaplan-Meier's actuarial survival analyses none of the epithelial subtypes displayed a statistically significant influence on prognosis. It is concluded that staging remains the most important factor affecting the patient's outcome. Because of the existence of many intermediate forms and the deficiency of clinical relevance, the subclassification of cortical thymomas should be interpreted as a morphological continuum rather than as distinct histological variants.

Argyrophilic nucleolar organizer regions in cells of thymoma and thymic carcinoma: correlation with DNA ploidy and clinicopathologic characteristics.

STUDY OBJECTIVES: To evaluate the usefulness of argyrophilic nucleolar organizer region (AgNOR) counting and flow cytometric DNA analysis in the differential diagnosis of thymoma and thymic carcinoma, as well as in the differences among various stages and histologic subtypes of these tumors. DESIGN AND INTERVENTIONS: Paraffin-embedded blocks of 64 thymic epithelial tumors (20 noninvasive thymomas, 34 invasive thymomas, and 10 thymic carcinomas) were studied by AgNOR counting and flow cytometric DNA analysis. The thymomas were histologically classified as medullary, cortical, or mixed subtype. MEASUREMENTS AND RESULTS: Invasive thymomas had more AgNORs (-/+ SD) than noninvasive thymomas (7.93+/-2.90 vs 5.97+/-1.77; p < 0.01). The number of AgNORs of thymoma increased progressively with advances in stage (p < 0.01). Cortical thymomas had the highest number of AgNORs among the three subtypes (p < 0.05). Patients with thymoma who presented with myasthenia gravis also had a higher number of AgNORs (8.30+/-3.12 vs 6.50+/-2.03; p < 0.01). The AgNOR number did not correlate with the DNA ploidy of all specimens. CONCLUSIONS: AgNOR counting is useful in differentiating between invasive and noninvasive thymomas, and in predicting the stage of thymomas. A greater number of AgNORs was observed in patients with cortical thymoma and in those who presented with myasthenia gravis.

Evaluation and validation of ureteric jet index by glomerular filtration rate.

RATIONALE AND OBJECTIVES: Ureteric jet index (UJI), a newly developed technique derived from color Doppler ultrasonography, may hold promise in evaluating renal function because of its ability to evaluate individual renal function and the use of nonionizing radiation. To assess the usefulness of UJI, the authors in this study analyzed the relation between UJI and the glomerular filtration rate (GFR). METHODS: Fifteen adult patients with a wide range of renal function were included in this study. Subjects were well hydrated before color Doppler ultrasonography examinations. The UJI formula was: Vmean (average jet velocity) x D (jet duration) x F (jet frequency). GFR was calculated by the radionuclide method. Correlations between UJI, serum creatinine, and GFR were analyzed. RESULTS: Ureteric jet index had only a fair correlation with GFR. The coefficient of correlation value was 0.61, and the standard error of estimate of GFR was 17.9 mL/min. CONCLUSIONS: With the measurement of UJI, color Doppler ultrasound can provide both structural images and individual renal function information. It could substitute for a renal scan in determining individual renal function when a radionuclide examination is unavailable. Even if a renal scan were available, UJI can play a valuable role in the ultrasound examination of patients with suspected impaired renal function, providing further assessment of individual renal function.

Expression of cyclooxygenase-2 in prostate adenocarcinoma and benign prostatic hyperplasia.

Elevated expression of cyclo-oxygenase (COX)-2 has been found in several human cancers, including prostate adenocarcinoma. To evaluate the potential prognostic role of COX-2 in prostate cancer, we assessed the expression of COX-2 in benign prostatic hyperplasia (BPH) and prostate cancer samples employing immunohistochemistry. COX-2 was over-expressed in 15 out of 18 (83%) prostate cancer samples whereas it was detected in only 22% (4 of 18) paired benign tissues. The intensity of immunostaining correlated with the tumor grading. In addition, COX-2 was expressed in 7 of the 22 (32%) BPH samples examined. The significance a COX-2 expression in the BPH samples is not known at present. This data suggest that COX-2 is over-expressed in prostate cancer and COX-2 inhibitors may be useful in combination chemotherapy or chemoprevention for prostate cancer.

Contribution of immunocytochemistry in routine diagnostic cytology.

The authors report the experience of applying immunocytochemistry in routine cytological examination and its contribution for diagnosis during a period of 3 yr in Veterans General Hospital-Taipei, Taiwan. From August 1991 to July 1994, the cytology laboratory received 5,762 non-gynecologic specimens with urine excluded. Immunocytochemistry was performed selectively in problematic cases. A total of 215 stainings including 124 epithelial markers, 50 lymphoma/leukemia markers, 22 neuroglial and choroid plexus markers, seven mesenchymal markers, six melanoma markers, and six others was performed on 145 specimens consisting of 89 effusions, 28 fine-needle aspirations, 11 cerebrospinal fluids, and 17 other specimens. Effusions were by far the most frequent specimens for immunocytochemistry and the epithelial markers were the most frequently used antibodies. The immunocytochemical results were essential in 41 specimens (28%), confirmatory in 37 (26%), and non-contributory in 67 (46%). Essential and confirmatory results occurred in 49% of effusions (44/89), 71% of fine-needle aspirations (20/28), 55% of cerebrospinal fluids (6/11), and 47% of other specimens (8/17). It is concluded that immunocytochemistry is proved to be a good aid for the final diagnosis of daily cytologic practices in which the fine-needle aspiration specimens are benefitted best.

Congenital nephrotic syndrome. Gallium-67 imaging.

Congenital nephrotic syndrome is a rare disorder. Heavy proteinuria, hypoalbuminemia, and edema occur during the first 3 months of life. Initial cases were reported from Finland and sporadic cases have occurred elsewhere. Finnish cases demonstrated an autosomal recessive inheritance pattern; currently, Finnish and non-Finnish types are recognized. The clinical course consists of failure to thrive, frequent infections, declining renal function, and early death by age 4 years from sepsis or uremia. Recently renal transplantation has improved the prognosis of patients with this disease. An abnormal Ga-67 scan in a case of congenital nephrotic syndrome is presented.

Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-ß signaling.

Endoglin is a transforming growth factor ß (TGF-ß) coreceptor that serves as a prognostic, diagnostic and therapeutic vascular target in human cancer. A number of endoglin ectodomain-targeting antibodies (Abs) can effectively suppress both normal and tumor-associated angiogenesis, but their molecular actions remain poorly characterized. Here we define a key mechanism for TRACON105 (TRC105), a humanized monoclonal Ab in clinical trials for treatment of advanced or metastatic tumors. TRC105, along with several other endoglin Abs tested, enhance endoglin shedding through direct coupling of endoglin and the membrane-type 1 matrix metalloproteinase (MMP)-14 at the cell surface to release the antiangiogenic factor, soluble endoglin (sEng). In addition to this coupling process, endoglin shedding is further amplified by increased MMP-14 expression that requires TRC105 concentration-dependent c-Jun N-terminal kinase (JNK) activation. There were also notable counterbalancing effects on canonical Smad signaling in which TRC105 abrogated both the steady-state and TGF-ß-induced Smad1/5/8 activation while augmenting Smad2/3 activation. Interestingly, TRC105-induced sEng and aberrant Smad signaling resulted in an excessive migratory response through enhanced stress fiber formation and disruption of endothelial cell-cell junctions. Collectively, our study defines endoglin shedding and deregulated TGF-ß signaling during migration as major mechanisms by which TRC105 inhibits angiogenesis.