[Practical application of the Paris system for reporting urinary cytology].

Objective: To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS). Methods: A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard. Results: Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234). Conclusions: The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.

[Differential expression of LLGL2 in prostate ductal adenocarcinoma and acinar adenocarcinoma and its significance].

Objective: To investigate the expression differences of LLGL2 between prostatic ductal adenocarcinoma (PDA) and prostatic acinar adenocarcinoma, and its potential clinical significance. Methods: Eighteen patients diagnosed of PDA or prostatic acinar adenocarcinoma with PDA component by histopathology during January 2015 and December 2019 in the Beijing Hospital, China were retrospectively studied. The transcriptome analysis was conducted using the tissue of PDA and prostatic acinar adenocarcinoma. Differentially expressed genes and the differences in expression profiles were identified. Further, differentially expressed proteins were verified by immunohistochemistry. Results: The tissue from 8 of the 18 patients were used for transcriptome analysis, the results of which were compared with data from public databases. 129 differentially expressed genes were identified. 45 of them were upregulated while 84 were downregulated. The results of gene enrichment analysis and gene oncology (GO) analysis revealed that the differentially expressed genes were mostly enriched in the hypertrophic cardiomyopathy and interleukin-17 related pathways. GPAT2, LLGL2, MAMDC4, PCSK9 and SMIM6 were differentially expressed between PDA and prostatic acinar adenocarcinoma. Moreover, LLGL2 was more likely expressed in the cytoplasm (P=0.04) than the nucleus (P<0.01) in PDA, compared with prostatic acinar adenocarcinoma. Conclusions: The gene expression profiling indicates that PDA are very similar to prostatic acinar adenocarcinoma. Among the differentially expressed proteins screened and verified in this study, the expression of GPAT2, LLGL2, MAMDC4 and PCSK9 is increased in PDA, while that of SMIM6 is reduced in PDA. The expression of LLGL2 shows significantly different patterns between PDA and prostatic acinar carcinoma, and thus may help differentiate PDA from prostatic acinar adenocarcinoma in clinical practice.

[Diagnostic values of nuclear score combined with cyclin D1 immunocytochemistry in indeterminate thyroid follicular nodules in preoperative fine needle aspiration].

Objective: To assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.

[Clinicopathological significance of 114 cases with positive surgical margin in radical prostatectomy specimens].

Objective: To analyze the clinicopathological features of positive surgical margins (PSM) after radical prostatectomy and to explore its associated factors. Method: A retrospective analysis was conducted on 274 patients who underwent radical prostatectomy in Beijing Hospital from June 2018 to June 2021. The margins of these specimens of radical prostatectomy were directly inked with black ink. According to the margin status (tumor present versus not), the patients were divided into PSM and negative surgical margin (NSM) groups. The clinicopathological characteristics were compared between two groups, including age, preoperative prostate specific antigen (PSA), number of tumors, tumor's location, postoperative pathological Gleason score, tumor burden and postoperative pathological staging. Results: Among the 274 cases, 114 showed PSM, and 160 showed NSM. PSM accounted for 41.6% of the cases. The mean age was 68.3 years, while the PSM group's mean age was 68.0 years, and that of the NSM group was 68.6 years, with no statistical significance between groups (P>0.05). The mean preoperative PSA was 15.8 µg/L in all patients, 21.5 µg/L in the PSM group and 11.3 µg/L in NSM group. PSA in the PSM group was statistically higher than that in the NSM group (P<0.001). The PSA level (10 µg/L, 10-20 µg/L, and >20 µg/L) was associated with the PSM rate (31.1%, 48.7%, and 69.4%). Regarding tumor numbers, 118 cases had a single focus, including 40 cases with PSM (33.9%). In the 156 cases of multiple foci, 74 cases had a PSM (47.4%). There were statistically more PSM cases in the cases with multi-focal disease (P<0.05). Tumors were seen in the transit zone of 44 cases, while 107 cases showed tumors in the peripheral zone, and 123 cases in the whole zone. The PSM rate was 27.3% (12/44), 40.2% (43/107), and 48.0% (59/123) by tumor location, respectively, but the difference among groups was not statistically significant (P>0.05). The postoperative Gleason scores were 3+3=6 in 51 cases, 3+4=7 in 98 cases, 4+3=7 in 81 cases, and ≥8 in 44 cases, with PSM rates of 19.6% (10/51), 38.8% (38/98), 45.7% (37/81) and 65.9% (29/44), respectively (P<0.001 for rate differences). The tumor burden was <30% in 157 cases, 30%-60% in 91 cases, and>60% in 26 cases, with PSM rate of 21.0% (33/157), 65.9% (60/91) and 80.8% (21/26), respectively (P<0.001 for rate differences). Moreover, there were 181 cases of pathological stage T2 (PSM rate, 29.3%) and 93 cases of pathological stage T3 (PSM rate, 65.6%), with statistical difference in PSM rates (P<0.001). The multivariable logistic regression analysis indicated that preoperative PSA >20 µg/L, postoperative Gleason score ≥8, high tumor burden and pathological stags were different between the PSM and NSM groups (P<0.05). Conclusions: The PSM of radical prostatectomy is closely related to the preoperative PSA level, the number of lesions, postoperative Gleason score, tumor burden and pathological stage. Preoperative PSA level >20 µg/L, postoperative Gleason score ≥8, high tumor burden and pathological stage are independent predictors for PSM.

[Establishment and comparison of three human multiple myeloma cell line transplantation models in mice].

Objective: To establish three types of xenotransplantation models using human myeloma cell lines ARP1, MM.1S, and NCI-H929 and to compare the proliferation, tumor load, and biological characteristics of the three types of cells after transplantation. Methods: Suspensions of human myeloma cell lines ARP1, MM.1S, and NCI-H929 were implanted into NOD/SCID mice by subcutaneous injection or tail vein injection. The survival of the mice was observed weekly, and the tumor load was measured. Flow cytometry was used to detect the proportion of CD138(+) cells in tumor tissue or the mouse bone marrow. CD138(+) cells and light chains were detected by immunofluorescence. Light chains in bone marow and peipheral blood were measured by ELISA, and bone disease was assessed by micro-CT. Results: Mice injected with ARP1, MM.1S, and NCI-H929 cells all formed tumors subcutaneously in about 2 weeks. Immunofluorescence detection supported plasma cell tumors. Kappa light chains were detected in the peripheral blood of ARP1 mice on day 20 after tail vein transplantation (8.2±1.0 ng/ml) . After 6 weeks of tail vein transplantation, mice in the ARP1 group showed signs of weight loss, mental depression, and dragging legs, and human CD138(+)CD38(+) cells were detected in the bone marrow (BM) . Furthermore, bortezomib (BTZ) treatment given once the tumor was established significantly reduced the tumor burden[ (5.7±0.2) % vs (21.3±2.1) %, P<0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. Conclusion: The results of this study suggest that the mouse models constructed by the three cell lines (ARP1, MM.1S, and NCI-H929) can be used as models for the pathogenesis and clinical research of MM.

Anti-pathogen stainless steel combating COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits strong stability on conventional stainless steel (SS) surface, with infectious virus detected even after two days, posing a high risk of virus transmission via surface touching in public areas. In order to mitigate the surface toughing transmission, the present study develops the first SS with excellent anti-pathogen properties against SARS-COV-2. The stabilities of SARS-CoV-2, H1N1 influenza A virus (H1N1), and Escherichia coli (E.coli) on the surfaces of Cu-contained SS, pure Cu, Ag-contained SS, and pure Ag were investigated. It is discovered that pure Ag and Ag-contained SS surfaces do not display apparent inhibitory effects on SARS-CoV-2 and H1N1. In comparison, both pure Cu and Cu-contained SS with a high Cu content exhibit significant antiviral properties. Significantly, the developed anti-pathogen SS with 20 wt% Cu can distinctly reduce 99.75% and 99.99% of viable SARS-CoV-2 on its surface within 3 and 6 h, respectively. In addition, the present anti-pathogen SS also exhibits an excellent inactivation ability for H1N1 influenza A virus (H1N1), and Escherichia coli (E.coli). Interestingly, the Cu ion concentration released from the anti-pathogen SS with 10 wt% and 20 wt% Cu was notably higher than the Ag ion concentration released from Ag and the Ag-contained SS. Lift buttons made of the present anti-pathogen SS are produced using mature powder metallurgy technique, demonstrating its potential applications in public areas and fighting the transmission of SARS-CoV-2 and other pathogens via surface touching.

[Application of cell transfer technique in the diagnosis of fine needle aspiration cytology].

Objective: To study the application of cell transfer technology to solve the problem of the limited number of fine needle aspiration cytology (FNAC) smears for various immunocytochemistry (ICC) staining and other auxiliary tests, and to enhance accurate cytological diagnosis. Methods: Thirty-four cases of FNAC smears from January 2020 to April 2020 in the Department of Pathology of Beijing Hospital were collected for investigation of the cell transfer technique. The materials in the most cell smear were divided and transferred to several glass slides. After de-staining, the recipient slides were stained with EnVision ICC. The technique was validated by comparing the consistency of the ICC of transferred cell smears and the corresponding immunohistochemical (IHC) staining on biopsies. Results: There were a total of 180 cell transfer slides from 34 cases, of which 174 had the same cell morphology, size and structure as the original smears, with the success rate of cell transfer of 96.7% (174/180). Totally 174 ICC stains were performed on the successfully transferred cell smears, of which 153 smears had available corresponding IHC staining of histologic specimens. Of these, 148 showed concordance between ICC staining and the IHC staining. Cells were successfully transferred in 96.7 % (148/153) of the cell sheets, keeping the same morphology and structure as compared to their original smears. The diagnosis of all 34 FNAC cases was the same to that of their corresponding pathology on biopsies with 100 % concordance. Conclusions: The cell transfer technique is a simple and effective way to make full use of diagnostic cells on a cell smear, and is valuable for accurate cytological diagnosis.

[Cdc37 Contributes to bortezomib resistance in multiple myeloma via autophagy].

Objective: To explore the role of cell division cycle protein 37 (Cdc37) mediating bortezomib (BTZ) resistance in multiple myeloma (MM) via the regulation of autophagy activity to provide a novel strategy for MM therapy. Methods: The expressions of Cdc37 and LC3b were investigated in BTZ-resistant MM cell line ANBL-6.BR using quantitative real-time PCR (qRT-PCR) and western blot (WB) analysis. Cdc37 was upregulated in ANBL-6.BR cells owing to lentivirus transfection. The LC3b expression was detected with WB, and BTZ-induced apoptosis was explored using flow cytometry. Cdc37 was then down-regulated by shRNA in the MM cell line NCI-H929. Sensitivity of BTZ was evaluated using CCK-8 analysis. WB analysis was performed to check the expression of the AKT/mTOR pathway and autophagy-associated proteins. The sensitivity of NCI-H929 cells to BTZ in the presence of autophagy inhibitor chloroquine (CQ) was analyzed using flow cytometry. Results: Cdc37 was down-regulated, while autophagy-associated gene LC3b was upregulated in BTZ-resistant cell line ANBL-6.BR. Up-regulated Cdc37 in ANBL-6.BR cells could inhibit LC3b expression and increase the sensitivity of MM to BTZ. Suppressing Cdc37 expression in MM cell line NCI-H929 induced BTZ resistance and autophagy activation, while CQ could rescue BTZ resistance caused by Cdc37 inhibition. Conclusion: Cdc37 may participate in BTZ resistance in MM via the regulation of autophagy activity.

[The co-relation of BRAF V600E mutation and factors affecting occurrence and prognosis of papillary thyroid carcinoma].

Objective: To investigate the prevalence of BRAF V600E mutation in thyroid nodules and to analyze the relationship between BRAF V600E mutation and various clinicopathological features. Methods: BRAF V600E mutant gene test was done in 463 cases of thyroid nodules collected from April 2015 to July 2018 in Beijing Hospital. Pathologic sections of 444 cases of papillary thyroid carcinoma were reviewed and clinical information was collected.Statistical analysis of the relationship between BRAF V600E gene mutation and various clinicopathological features was performed with SPSS 21.0 statistical software. Results: There were 109 males and 354 females in the cohort, with a male to female ratio of 1.0∶3.2. The patient ranged in age from 16 to 82 years, with an average age of 46.1 years. The BRAF V600E mutation rates in papillary thyroid carcinoma, benign thyroid nodules and other thyroid carcinoma were 86.5%(384/444),0/15 and 1/4,respectively.There was significant correlation between BRAF V600E mutation and histological diagnosis of papillary thyroid carcinoma (P<0.05). There was no correlation with age, gender, multifocality, bilaterality, coexisting lymphocytic thyroiditis, nodular goiter, maximum diameter, capsule invasion, extrathyroidal extension and clinical stage (P>0.05). Conclusions: BRAF V600E gene mutation is closely related to the occurrence of papillary thyroid carcinoma. BRAF V600E has significant value in the diagnosis of papillary thyroid carcinoma. While BRAF V600E mutation is related to the histological diagnosis, it shows no correlation with other clinicopathologic features. BRAF V600E mutation is not an independent prognostic factor in papillary thyroid carcinoma patients.

The impact of plasma Epstein-Barr virus DNA and fibrinogen on nasopharyngeal carcinoma prognosis: an observational study.

BACKGROUND: The impact of combining plasma fibrinogen levels with Epstein-Barr Virus DNA (EBV DNA) levels on the prognosis for patients with nasopharyngeal carcinoma (NPC) was evaluated. METHODS: In this observational study, 2563 patients with non-metastatic NPC were evaluated for the effects of circulating plasma fibrinogen and EBV DNA levels on disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: Compared with the bottom biomarker tertiles, TNM stage-adjusted hazard ratios (HR, 95% confidence intervals (CIs)) for predicting DFS in fibrinogen tertiles 2 to 3 were 1.26 (1.00 to 1.60) and 1.81 (1.45 to 2.26), respectively; HR for EBV DNA tertiles 2 to 3 were 1.49 (1.12 to 1.98) and 4.24 (3.27 to 5.49), respectively. After additional adjustment for established risk factors, both biomarkers were still associated (P for trend <0.001) with reduced DFS (HR: 1.79, 95% CI, 1.43 to 2.25 for top fibrinogen tertiles; HR: 4.04, 95% CI: 3.10 to 5.27 for top EBV DNA tertiles compared with the bottom tertiles). For patients with advanced-stage disease, those with high fibrinogen levels (3.34 g l(-1)) presented with worse DFS, regardless of EBV DNA 4000 or <4000 copies ml(-1) subgroup. Similar findings were observed for DMFS and OS. CONCLUSIONS: Circulating fibrinogen and EBV DNA significantly correlate with NPC patients survival. Combined fibrinogen and EBV DNA data lead to improved prognostic prediction in advanced-stage disease.

Various clinical presentations of tuberculosis in heart transplant recipients.

The purpose of this study was to clarify the various clinical presentations, incidence, and complications associated with tuberculosis (TB), as well as patient survival in heart transplantation (HTx) recipients. A retrospective review of 177 case records of HTx recipients from May 1989 to April 2003 were evaluated for their clinical course, diagnostic procedures, treatment, and survival. TB was diagnosed by culture. TB was proven in five (2.8%) patients. There were three pulmonary lesions and two extrapulmonary lesions. TB was diagnosed at 3.5 to 85 months after HTx. Pulmonary lesions were detected by cultures of sputum, bronchoalveolar lavage, or pleural effusion. For extrapulmonay lesions, one subject had neck lymphadenopathy shown by biopsy and culture to be TB; another suffered from swelling of the finger joints which upon culture of the aspirate proved to be TB. Treatment consisted of isoniazid (INH), rifampin (RIF), ethambutol, pyrazinamide, streptomycin (STR), ciprofloxacin (Ciproxin), and levofloxacin (Cravit). During the use of RIF, the daily dosage of cyclosporine (CsA) or tacrolimus was increased to maintain appropriate levels. Because of severe hepatotoxicity and interference with CsA, RIF was withdrawn and STR given in the last three patients. In addition, ciprofloxacin was given in the patient with miliary TB. Levofloxacin was given to the other two patients. All patients survived the TB infection under treatment with at least three drugs. There were five clinical presentations of TB in our HTx recipients. Because of the high incidence of hepatitis and severe drug interaction with CsA or tacrolimus on RIF treatment, avoiding the use of RIF but treatment with at least three drugs is recommended.

Antileukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and Houttuynia cordata Thunb.

To evaluate the anti-leukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and Houttuynia cordata Thunb., cytotoxicity tests with an XTT-based colorimetric assay were used. Five leukemic cell lines, namely L1210, U937, K562, Raji and P3HR1, were cultured with hot water extracts of B. pilosa var. minor or H. cordata. Hot water extracts of B. pilosa var. minor inhibited these five leukemic cells with IC50s between 145 microg/ml and 586 microg/ml. The effect was greatest on four cell lines, namely L1210, P3MR1, Raji and K562, with IC50s below 200 microg/ml and a selective index of more than 5. Hot water extract of H. cordata inhibited these five leukemic cells with IC50s between 478 microg/ml and 662 microg/ml. The selective index was between 1.5 and 2.1. B. pilosa var. minor was more effective than H. cordata in inhibiting most of the leukemic cells in our study. We suggest that B. pilosa L. var. minor (Blume) Sherff may prove to be a useful medicinal plant for treating leukemia.

Telomerase activity in human bladder tumors and bladder washing specimens.

Telomerase appears to be an important factor for the control of cellular proliferation and tumorigenesis. Enzyme activity dramatically increases in almost all human tumors. The purpose of our study was to evaluate the role of telomerase activity as a marker for bladder cancer diagnosis and follow-up. By using the PCR-ELISA based on the TRAP (telomerase repeat amplification protocol) method, telomerase activity of bladder tumors (n = 77), normal-appearing adjacent tissues (n = 21) and bladder washings (n = 37) were analyzed. Telomerase activity was detected in 87% (67/77) of cancer tissues and in 38% (8/21) of normal-appearing adjacent tissues. However, the levels of enzyme activity were significantly higher in cancer tissues than in normal-appearing adjacent tissues (p < 0.05). Telomerase activity in bladder cancer tissues was not correlated to the tumor stage or grade. During a 26 months follow-up period, disease progression occurred in 66.7% of patients with invasive tumors where telomerase activity of the normal-appearing adjacent tissue was detectable, as compared to only 14.3% for patients who showed undetectable telomerase activity in adjacent, normal-appearing tissues (p = 0.094). When telomerase activity of bladder washing fluid was compared with its corresponding tumors, sensitivity of detection was 81% and specificity was 75%. In contrast, urine cytology only yielded a sensitivity of 31% in the detection of cancer. The detection ability between telomerase activity measurement in washing fluid and cytological examination had a trend toward the telomerase measurement identifying more cancer cases than the cytologic examination (p = 0.07). In conclusion, telomerase activity is present in early-stage bladder cancer and is a potential molecular marker for bladder tumors diagnosis. The expression of telomerase activity in normal-appearing mucosa adjacent to bladder tumor is probably an indicator of disease progression. Using the telomerase activity to detect exfoliated cells in bladder washing fluids could be a useful method in adjunct to urine cytology and cystoscopy in establishing the diagnosis and follow-up of bladder cancer.

Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin.

Xanthine oxidase inhibitors are known to be therapeutically useful for the treatment of hepatitis and brain tumor. Baicalein, baicalin and wogonin, isolated from Scutellaria rivularis, have been reported to exhibit a strong activity on xanthine oxidase inhibition. In this study, their antioxidant activity was evaluated by modified xanthine oxidase inhibition and cytochrome c reduced methods. The results showed that the order of activity on xanthine oxidase inhibition was baicalein > wogonin > baicalin, IC50 = 3.12, 157.38 and 215.19 microM, respectively, whereas the activity on cytochrome c reduction was baicalin > wogonin > baicalein (IC50 = 224.12, 300.10 and 370.33 microM, respectively). In another study, an electron spin resonance (ESR) technique was used to further confirm the direct free radical scavenging activity. Both baicalein and baicalin demonstrated a strong activity on eliminating the superoxide radical (.O2-) (baicalein: 7.31 x 10(4) u/g; baicalin: 1.19 x 10(5) u/g). The IC50 of baicalein was 2.8 fold higher than that of baicalin. However they had no significant effect on scavenging hydroxyl radical (.OH). The present results demonstrated that baicalein and baicalin posed a different pathological pathway. The antioxidant function of baicalin was mainly based on scavenging superoxide radical whilst baicalein was a good xanthine oxidase inhibitor.

The clinical implications of telomerase activity in upper tract urothelial cancer and washings.

OBJECTIVE: To measure telomerase activity in upper tract urothelial carcinomas (as renal pelvic tumours comprise nearly half of all kidney tumours in Taiwan, a much higher percentage than in other countries) and to determine whether telomerase activity could be used as an additional diagnostic marker in exfoliated cancer cells present in upper tract urothelial washing fluids, thus providing earlier diagnosis and treatment. Materials and methods Telomerase activity was assessed using the telomeric repeat amplification protocol assay in tissue samples from 31 upper tract urothelial carcinomas (from 29 patients). The feasibility of identifying cancer using telomerase activity in exfoliated cancer cells in 17 upper tract urothelial washing samples was also investigated. RESULTS: Telomerase activity was found in 30 (97%) of the 31 upper tract urothelial cancer tissue samples; telomerase activity was detectable in 95% of superficial cancers and in all 11 invasive tumours. The sensitivity of measuring telomerase activity was 100% for grade 1, 93% for grade 2 and 100% for grade 3 tumours. In contrast, telomerase activity was detected in only two (8%) of 26 normal adjacent tissue samples. When the telomerase activity of urothelial washing fluid was compared with that in the corresponding tumours, there was compatible telomerase activity in 15 of the 17 samples. Telomerase activity was more sensitive than voided urine cytology (15%) and washing fluid cytology (53%). In addition, the telomerase activity was high in metastatic lesions. CONCLUSION: Telomerase activity is present in most upper tract urothelial cancer tissues and may be present at an early stage of carcinogenesis. Telomerase activity can be detected in exfoliated cells in urothelial washing fluids in a high proportion of patients with upper tract urothelial cancer. These results suggest that measuring telomerase activity in the exfoliated cancer cells obtained from urothelial washing could be a potentially useful addition to the conventional diagnostic tools used to identify patients with upper tract urothelial carcinoma.

Cyclic hydroxamic acid inhibitors of prostate cancer cell growth: selectivity and structure activity relationships.

BACKGROUND: Clinical symptoms of prostatitis, prostatodynia, and benign prostatic hyperplasia are relieved by the pollen extract cernilton, and the water-soluble fraction of this extract selectively inhibits growth of some prostate cancer cells. A cyclic hydroxamic acid, DIBOA, has been isolated from this extract and mimics its cell growth-inhibitory properties, but the specificity of DIBOA for inhibition of prostate cell growth has not been reported. METHODS: The in vitro growth inhibitory effects of DIBOA and nine structurally related compounds on DU-145 prostate cancer cells, MCF-7 breast cancer cells, and COS-7 monkey kidney cells were determined by treatment of the cells with various concentrations of the compounds for 2-6 days. RESULTS: The compounds exhibited a wide range of potencies, but none of them exhibited selective inhibition of DU-145 cell growth. MCF-7 cells were more sensitive to DIBOA than either DU-145 cells or COS-7 cells. 3,4-dihydroquinoline-2(1H)-one, compound (4), and 1-hydroxy-6-chloro-3,4-dihydroquinolin-2(1H)-one, compound (7), selectively inhibited MCF-7 cell growth at a concentration of 10 micrograms/ml. 1-hydroxy-3,4-dihydroquinolin-2(1H)-one, compound (3), and compound 7 were the most potent inhibitors of DU-145 cell growth. Treatment of DU-145 cells with 3 (100 micrograms/ml) substantially decreased the number of viable cells within 2 days, and no viable cells remained in the culture by day 4. CONCLUSIONS: It is unlikely that DIBOA, compound (1), is responsible for the selective growth inhibition of prostate cancer cells by the water-soluble fraction of the pollen extract cernilton. Cell morphology results indicate that the growth-inhibitory effects of DIBOA and structurally related agents on DU-145 cells are due to their ability to cause cell death.