lncARSR promotes liver cancer stem cells expansion via STAT3 pathway.

Liver cancer stem cells (CSCs) have important functions in tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). lncARSR has been reported to play an important role in the maintenance and self-renewal of renal cancer stem cells, but its role in liver cancer stem cells (CSCs) remains obscure. Herein, we observed high expression of lncARSR in chemoresistant hepatocellular carcinomas (HCCs). A remarkable increase of lncARSR expression in EpCAM or CD133-positive liver CSCs as well as in CSC-enriched hepatoma spheres. Interference lncARSR suppressed liver CSC expansion by inhibiting the dedifferentiation of hepatoma cells and decreasing the self-renewal ability of liver CSCs. Mechanistically, we found STAT3 as the downstream of lncARSR in HCC cells. The special STAT3 inhibitor S3I-201 abolished the discrepancy in liver CSC proportion and the self-renewal capacity between lncARSR knockdown hepatoma cells and control cells, which further confirmed that STAT3 was required in lncARSR promoted liver CSCs expansion. More importantly, interference lncARSR HCC cells were more sensitive to sorafenib or cisplatin treatment. This maybe means that patients with low lncARSR levels benefited from cisplatin or sorafenib treatment, but patients with high lncARSR expression did not. Conclusion: lncARSR was upregulated in liver CSCs and could promote HCC cells dedifferentiation and liver CSCs expansion by targeting STAT3 signaling.

Liver resection is justified for multinodular hepatocellular carcinoma in selected patients with cirrhosis: A multicenter analysis of 1,066 patients.

BACKGROUND: The role of liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) remains unclear, especially among patients with severe underlying liver disease. We sought to evaluate surgical outcomes among patients with cirrhosis and multinodular HCC undergoing liver resection. METHODS: Using a multicenter database, outcomes among cirrhotic patients who underwent curative-intent resection of HCC were examined stratified according to the presence or absence of multinodular disease. Perioperative mortality and morbidity, as well as overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. RESULTS: Among 1066 cirrhotic patients, 906 (85.0%) had single- or double-nodular HCC (the non-multinodular group), while 160 (15.0%) had multinodular HCC (the multinodular group). There were no differences in postoperative 30-day mortality and morbidity among non-multinodular versus multinodular patients (1.8% vs. 1.9%, P = 0.923, and 36.0% vs. 39.4%, P = 0.411, respectively). In contrast, 5-year OS and RFS of multinodular patients were worse compared with non-multinodular patients (34.6% vs. 58.2%, and 24.7% vs. 44.5%, both P < 0.001). On multivariable analyses, tumor numbers ≥5, total tumor diameter ≥8 cm and microvascular invasion were independent risk factors for decreased OS and RFS after resection of multinodular HCC in cirrhotic patients. CONCLUSIONS: Liver resection can be safely performed for multinodular HCC in the setting of cirrhosis with an overall 5-year survival of 34.6%. Tumor number ≥5, total tumor diameter ≥8 cm and microvascular invasion were independently associated with decreased OS and RFS after resection in cirrhotic patients with multinodular HCC.

Effects of adenovirus-mediated PTEN on the proliferation of prostate cancer PC-3 cells and expressions of cyclin D1 and p21 / 中华男科学杂志

<p><b>OBJECTIVE</b>To construct a recombinant adenovirus expression vector containing the anti-oncogene PTEN and to investigate the effects of the PTEN gene on the proliferation of prostate cancer PC-3 cells and the expressions of cyclin D1 and p21 in the PC-3 cells.</p><p><b>METHODS</b>The PTEN gene was amplified from the rat hippocampus by RT-PCR and cloned into the shuttle plasmid pEN-TR2A. The plasmids were constructed and amplified in 293A cells. Prostate cancer PC-3 cells were cultured in vitro and infected with the adenoviral vector carrying the PTEN gene (Ad-PTEN). The up-regulation of the PTEN protein was measured by indirect immuno-fluorescence assay; the expressions of PTEN, cyclin D1 and p21 in the cells infected with Ad-PTEN and Ad-LacZ were determined by</p><p><b>RESULTS</b>The Western blot; and the effect of PTEN on the cell proliferation was detected by MTT assay and plate colony formation. recombinant adenoviral vector Ad-PTEN was successfully constructed. Western blot showed a significantly increased expression of the PTEN protein in the PC-3 cells infected with Ad-PTIEN (0.215 +/-0.065) as compared with that in the control ([0.052 +/-0.009], t = 4. 30, P <0.05) and the Ad-LacZ group ( [0. 056 +/- 0.008 ] , t =4.21, P <0.05). The expression of cyclin D1 was significantly lower in the Ad-PTEN-infected PC-3 cells (0. 256 +/- 0. 072) than in the control ( [0. 502 +/- 0. 087 ], t = 3.77, P < 0.05) and the Ad-LacZ group ([0.498 +/-0.081] , t =3.87, P <0.05), while the expression of p21 remarkably higher in the Ad-PTEN-infected PC-3 cells (0.589 +/-0. 076) than in the control ([0. 146 +/-0.026] , t = 9.55, P<0. 01) and the Ad-LacZ group ([0. 163 +/-0. 024] , t = 9.26, P <0.01). Ad-PTEN significantly inhibited the growth of the PC-3 cells (21.98%) at 48 h (t = 6.80, P <0.01). The colony formation rate of the PC-3 cells was (37.4 +/-4. 18)% in the Ad-PTEN group, significantly lower than (54.9 +/-4.81)% in the control (t =4.76, P<0.01) and (56.5 +/- 5.42)% in the Ad-LacZ group (t=4.83, P<0.01).</p><p><b>CONCLUSION</b>The expression of PTEN induced by Ad-PTEN can significantly inhibit the proliferation of PC-3 cells, down-regulate the expression of cyclin D1, and up-regulate the expression of p21.</p>

Prognostic significance of survivin expression in renal cell cancer and its correlation with radioresistance.

Survivin, an important inhibitor of apoptosis, has been found to play an important role in the initiation, progression, and chemoradioresistance of human malignancies. Previously, we have reported that upregulation of survivin in oral squamous cell carcinoma correlates with poor prognosis and chemoresistance. The aim of this study was to assess prognostic significance of survivin protein expression in RCC and analyze its correlation with radiosensitivity of RCC cells. RT-PCR and Western blot assays were performed to detect survivin mRNA and protein expression in normal human kidney epithelial cell line (HKEC) or RCC cell lines. The expression of survivin mRNA in RCC and corresponding nontumor kidney tissues was also detected by RT-PCR. Immunohistochemistry was performed to determine survivin protein expression in 75 cases of RCC tissue samples. Moreover, the association of survivin protein expression with clinicopathogical factors and prognosis of RCC patients was statistically analyzed. Small interfering RNA was used to knockdown the endogenous survivin expression in RCC cell line (ACHN) and evaluate the effects of survivin knockdown on proliferation, apoptosis, and radiosensitivity of RCC cell line. RCC cells showed sufficient expression of survivin mRNA and protein, but the expression of survivin gene was not detected in normal HKEC. Moreover, the expression level of survivin mRNA in RCC tissues was significantly higher than that in corresponding nontumor kidney tissues. The immunostaining of survivin protein was mainly located in cytoplasm of RCC tumor cells. Tumor pathological stage (P = 0.028), grade (P = 0.004), and lymph node metastasis (P = 0.017) of RCC patients were significantly correlated with survivin protein expression. In addition, patients with high survivin levels had a significantly shorter overall survival than those with low levels (P < 0.001), and the expression of survivin protein was an independent prognostic factor for RCC patients (P = 0.008). The expression of survivin gene could be reduced in RCC cell line and survivin knockdown could inhibit growth and enhance in vivo radiosensitivity of RCC cell line by inducing apoptosis enhancement. Taken together, the status of survivin protein expression may be an independent factor for predicting the prognosis of RCC patients and tumor-specific survivin knockdown combined with radiotherapy will be a potential strategy for RCC therapy.

Comparison of biologic activity of two anti-PSA/anti-CD3 bispecific single-chain antibodies / 中华男科学杂志

<p><b>OBJECTIVE</b>To study and compare the biologic activity of two anti-PSA/anti-CD3 bispecific single-chain antibodies.</p><p><b>METHODS</b>Flow cytometry (FCM) was used to detect the binding activity of two antibodies to CD3-positive cell line Jurkat and prostate carcinoma cell line LNCaP. The effect of the two antibodies in mediating tumor cell lysis in vitro was determined by using the 51Cr-release test. For in vivo evaluation of the two antibodies activity, a nude mouse model was used. The mice were inoculated with LNCaP prostate cancer cells.</p><p><b>RESULTS</b>FCM showed that both the antibodies could bind Jurkat and LNCaP cells with high specificity. The percentages of the cells bond by the bispecific single-chain antibodies were 56.3% and 55.4%, and those by the multivalent antibodies were 74.0% and 83.0% respectively. Both the antibodies mediated a specific lysis of LNCaP cells in vitro, with activated CTLs as effector cells, and significantly reduced tumor growth of nude mice in vivo as compared with the untreated controls and the group treated with CTLs only (P <0.05). The experiment also showed that the multivalent antibody had a better activity than the bispecific antibody in binding antigens, mediating lysis of LNCaP cells and reducing tumor growth (P < 0.05).</p><p><b>CONCLUSION</b>Both the anti-PSA/anti-CD3 bispecific single-chain antibody and multivalent antibody have good biologic activity, and the formation of the tetramerization of single-chain antibody can improve its biologic activity.</p>

Treatment techniques of harvesting injury of donor renal blood vessels / 中华外科杂志

<p><b>OBJECTIVE</b>To study the treatment technique for harvesting injury of donor blood vessels for the clinic application.</p><p><b>METHODS</b>The data of 32 renal transplantation patients with injury of graft blood vessels were retrospectively reviewed. 60 renal transplantation patients with non-injury during the same term were selected as the control group. The treatment techniques for harvesting injury of graft blood vessels mainly includes end-to-end anastomosis of graft artery, side-to-side anastomosis of branch artery, end-to-side anastomosis of branch artery to the main renal artery, reconstruction of multiple segmental arteries by using iliac arterial grafts from cadaveric donors or recipients on the workbench, repairs of injuries for the smaller segmental/polar arteries by using inferior epigastric artery, end-to-end anastomosis of the lower thick segmental/polar arteries with the iliac internal arterial by placing kidney upside down.</p><p><b>RESULTS</b>Those injured included 28 arterial and 4 venous. Average bench surgery time was 42 minutes. Mean warm ischemic time was 31 minutes. No death occurred at an average follow-up of 3.5 years (1 - 5 years). There was no statistical difference in the 1-year graft survival, postoperative 1-year acute rejection, delayed graft function (DGF) and the incidence of constriction of vascular anastomosis rate (96.9%, 12.5%, 21.9%, 3.1%, respectively) compared with non-reconstructed kidneys during the same term (98.3%, 11.7%, 18.3%, 1.7%, P > 0.05, respectively).</p><p><b>CONCLUSION</b>The flexible and appropriate application of different vascular reconstruction means and satisfactory surgery techniques play an important role in assuring quality of kidney with harvesting blood vessels injury and donor kidney availability.</p>

Diagnosis and treatment of seminal vesicle cyst / 中华外科杂志

<p><b>OBJECTIVES</b>To deepen the understanding of patients with seminal vesicle cyst for correct diagnosis and treatment.</p><p><b>METHODS</b>Sixteen patients with seminal vesicle cysts were treated in the period of January 1980-May 2002. Their symptoms, diagnostic results, treatment and outcomes were analyzed retrospectively. The mean age of these patients at diagnosis was 31 years (range 19 - 43). Two patients were associated with ipsilateral renal agenesis. Symptoms included hematospermia in 12 (75%) patients, urinary frequency in 8 (50%), hematuria after ejaculation in 6 (27.5%), perineal malaise in 6 (27.5%), infertility in 3 (13.7%), pain after ejaculation in 3 (13.7%), scrotal pain in 2 (12.5%) and dysuria in 1 (6.3%). Cyst was palpable in 81.3% patients on digital rectal examination. All patients underwent intravenous urography and cystoscopy. Others received ultrasonography, CT scanning, MRI, and vasovesiculography. The size of masses ranged from 3.8 cm x 3.0 cm x 2.6 cm to 9.6 cm x 5.2 cm x 5.0 cm. Final open surgery consisted of vesiculectomy (4 patients) and partial vesiculectomy (12).</p><p><b>RESULTS</b>Postoperative course was uneventful except in 1 patient with epididymitis. All patients were free of symptoms after open surgery.</p><p><b>CONCLUSIONS</b>Seminal vesicle cysts are rare but should be considered in men with hematospermia and otherwise inexplicable bladder irritation symptoms, perineal discomfort or other genitourinary complaints of unknown etiology. Diagnosis consists of digital rectal examination, transrectal and abdominal ultrasonography, CT scan or MRI. Vesiculectomy and partial vesiculectomy give excellent results.</p>

Effects of microwave on the contents of MDA and SOD in renal cortex and testis of mice / 军事医学科学院院刊

Objective: To observe the effects of microwave on the activity of SOD and the contents of MDA in renal cortex and testis of mice. Methods: Microwave generator(2 450 MHz, 10 mW/cm2) was used to expose mice; NBT,DTNB and TBA were used to mearure the activity of SOD and the contents of MDA in renal cortex and testis of the mice after microwave exposure.Results: The content of MDA in renal cortex and testis of the mice increased progressively on days 1,6,12 and reached the highest level on day 24 after the microwave exposure (P<0.01). The activity of SOD in renal cortex and testis of the mice decreased progressively on days 1, 6, 12 and reached the lowest level on day 24 after the microwave exposure (P<0.01). Conclusions: Microwave exposure can produce reactive oxygen free radicals and lead to depress SOD activity.