Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

Stat3-siRNA inhibits the growth of gastric cancer in vitro and in vivo.

Gastric cancer remains one of the most prevalent and lethal malignancies in the world. Despite new advances in treatment and diagnosis, patients with advanced gastric cancer are still difficult to cure resulting in a high mortality rate and poor prognosis. Signal transducer and activator of transcription 3 (Stat3) is observed aberrant in multiple tumours, including gastric cancer. Stat3 overexpression was confirmed performing a vital role in tumorigenesis. In the present study, we constructed a pSi-Stat3 plasmid to silence Stat3 and investigated the effect of pSi-Stat3 on cell proliferation, apoptosis and cell cycle progression in gastric cancer cell line SGC-7901 and mice xenograft model. Downstream proteins of Stat3, including Cyclin-D1, Survivin and Bcl-2, were detected as well for the underlying mechanism exploration. It showed that pSi-Stat3 can effectively silence the expression of Stat3 and inhibits the growth of gastric tumour both in vitro and in vivo significantly via cell apoptosis and cell cycle shift induction. The findings suggest that Stat3 signal pathway might be a promising therapeutic target for tumour treatment, including gastric cancer.

Synergistic suppression of prostatic cancer cells by coexpression of both murine double minute 2 small interfering RNA and wild-type p53 gene in vitro and in vivo.

Our objective was to evaluate cell growth and death effects by inhibiting Murine Double Minute 2 (MDM2) expression in human prostate cancer cells overexpressing the wild-type (WT) p53 gene. Prostate PC-3 tumor cells were transfected with a plasmid containing either mdm2 small interfering (Si-mdm2) or the WT p53 gene (Pp53) alone, or both (Pmp53), using Lipofectamine in vitro and attenuated Salmonella enterica serovar Typhi vaccine strain Ty21a (Salmonella Typhi Ty21a) in vivo. Cell growth, apoptosis, and the expression of related genes and proteins were examined in vitro and in vivo by flow cytometry and Western blot assays. We demonstrated that human prostate tumors had increased expression of MDM2 and mutant p53 proteins. Transfection of the PC-3 cells with the Pmp53 plasmid in vitro offered significant inhibition of cell growth and an increase in apoptotic cell death compared with that of the Si-mdm2 or Pp53 group. These effects were associated with up-regulation of p21 and down-regulation of hypoxia-inducible factor 1α expression in Pmp53-transfected cells. To validate the in vitro findings, the nude mice implanted with PC-3 cells were treated with attenuated Salmonella Typhi Ty21a carrying the plasmids, which showed that the Pmp53 plasmid significantly inhibited the tumor growth rate in vivo compared with that of the Si-mdm2 or Pp53 plasmid alone. Tumor tissues from mice treated with the Pmp53 plasmid showed increased expression of p21 and decreased expression of hypoxia-inducible factor 1α proteins, with an increased apoptotic effect. These results suggest that knockdown of mdm2 expression by its specific small interfering RNA with overexpression of the WT p53 gene offers synergistic inhibition of prostate cancer cell growth in vitro and in vivo.

[Expressions of survivin and GRIM-19 in prostate cancer].

OBJECTIVE: To investigate the expressions of survivin and GRIM-19 in prostatic cancer tissue and their clinical implications. METHODS: We detected the expressions of survivin and GRIM-19 in the tissues of normal prostate (NP), benign prostate hyperplasia (BPH) and prostate cancer (PCa) using immunohistochemical staining, RT-PCR and Western blot, and processed the data by SPSS12. RESULTS: The positive rates of survivin expression were 6.25% , 18.18% and 90.62% in NP, BPH and PCa (P < 0.01), while those of GRIM-19 were 87.50%, 81.82% and 9.37% , respectively (P < 0.01). Semiquantitative RT-PCR and immunohistochemical staining showed that both survivin mRNA and survivin expressions were highly positive in PCa but negative in NP and BPH. Western blot exhibited that the survivin protein was expressed strongly in PCa but weakly in NP and BPH, while the GRIM-19 protein was expressed just contrariwise (P < 0.01). CONCLUSION: The expressions of survivin and GRIM-19 may be closely correlated with the pathogenesis of prostate cancer.

Differential protein expression in heart in UT-B null mice with cardiac conduction defects.

Cardiac conduction defects were found in transgenic mice deficient in urea transporter UT-B. To investigate the molecular mechanisms of the conduction defects caused by UT-B deletion, we studied the protein expression profiles of heart tissue (comprising most conduction system) in wild-type versus UT-B null mice at different ages. By two-dimensional electrophoresis-based comparative analysis, we found that more than dozen proteins were modulated (>two-fold) in the myocardium of UT-B null mice. Out of these modulated proteins, troponin T (TNNT2) presented significant changes in UT-B null mice at early stage prior to the development of P-R interval elongation, while the change of atrial natriuretic peptide (ANP) occurred only at late stage in UT-B null mice that had the AV block. These data indicate that UT-B deletion caused the dynamic expression regulation of TNNT2 and ANP, and these proteins may provide new clues to investigate the molecular events involved in cardiac conduction.

Diagnostic strategies and the incidence of prostate cancer: reasons for the low reported incidence of prostate cancer in China.

We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer (IARC), the age-standardized incidence of prostate cancer in China is 1.6/10(5) person years (PY), with a mortality rate of 1.0/10(5) PY and mortality-to-incidence rate ratio (MR/IR) = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia (MR/IR = 0.57) and much higher than that in North America (MR/IR = 0.13). These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen (PSA) screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.

Mass screening-based case-control study of diet and prostate cancer in Changchun, China.

AIM: To investigate possible correlation factors for prostate cancer by a population-based case-control study in China. METHODS: We carried out a mass screening of prostate cancer in Changchun, China, using a prostate-specific antigen assisted by Japan International Cooperation Agency. From June 1998 to December 2000, 3 940 men over 50 years old were screened. Of these, 29 men were diagnosed with prostate cancer. We selected 28 cases and matched them with controls of low prostate-specific antigen value (< 4.1 ng/mL) by 1:10 according to age and place of employment. A case-control study of diet and prostate cancer was then carried out. RESULTS: After adjustment for education, body mass index (BMI), smoking, alcohol consumption, marriage and diet, intake of soybean product was discovered to be inversely related to prostate cancer. Men who consumed soybean product more than twice per week on different days had a multivariate odds ratio (OR) of 0.38 (95% confidence interval [CI], 0.13-1.12). In addition, men who consumed soybean products more than once per day had a multivariate OR of 0.29 (95% CI, 0.11-0.79) compared with men who consumed soybean products less than once per week. The P for trend was 0.02, which showed significant difference. There was no significant difference in P trend for any dairy food. Even when we matched the cases and controls by other criteria, we found that soybean food was the only preventive factor associated with prostate cancer. CONCLUSION: Our study suggests that consumption of soybeans, one of the most popular foods in Asia, would decrease the risk of prostate cancer.

[Influence of expression of six transmembrane epithelial antigen of the prostate-1 on intracellular reactive oxygen species level and cell growth: an in vitro experiment].

OBJECTIVE: To investigate the STEAP1 gene function of the newly discovered gene six transmembrAne epithelial antigen of the prostate-1 (STEAP1). METHODS: Total RNA was obtained from human prostate cancer tissue and underwent PCR amplification. The full length of STEAP1 gene thus obtained was cloned. Mammalian expression vector pcDNA3. 1-STEAP1 was constructed and stably transfected into the human thyroid epithelial cells of the line FRTAP2320. A growth curve of the transfected cells was drawn. The intracellular reactive oxygen species (ROS) level was determined by flow cytometry (FC) with dichlorodihydrofluorescein diacetate (DCFHDA). RESULTS: The growth curve showed that the STEAP1 transfected cells grew faster than the control cells. FC showed that the fluorescence intensity of he intracellular ROS of the STEAP1 transfected cells was 42.13 +/- 1.13, significantly higher than those of the cell transfected with blank plasmid (10.02 +/- 1.42) and un-transfected cells (13.02 +/- 2.42, both P < 0.01). CONCLUSION: STEAP1 promotes the cell growth through inducing the intracellular ROS level.

[3,3-diindolylmethane enhances the inhibitory effect of idarubicin on the growth of human prostate cancer cells].

OBJECTIVE: To study the effects of idarubicin (IDA) combined with 3, 3-diindolylmethane (DIM) on the growth inhibition of human prostate cancer cells. METHODS: Human prostate cancer cells of the line PC-3M were cultured and then divided into the following groups: control group with solvent added into the culture fluid; IDA groups, with IDA of the terminal concentrations of 0.5, 1 or 5 mg/L added into the culture fluid; DIM groups, with DIM of the terminal concentrations of 30, 60 or 100 micromol/L added into the culture fluid; and DIM + IDA groups, with 0. 5 mg/L IDA and DIM 30, 60 or 100 micromol/L added into the culture fluid. 48 h later the cell growth inhibition rate was detected by MTT assay. Flow cytometry and acridine orange staining were used to detect the cell cycle and apoptosis. RT-PCR and Western blotting were used to detect the mRNA and protein expression of caspase 9, an apoptosis gene. RESULTS: Both IDA and DIM dose-dependently inhibited the growth of the PC-3M cells. The growth inhibition rate of the 60 micromol/L DIM + 0.5 mg/L IDA group was 69.9%, almost 10 times as that of the 0.5 mg/L IDA group. The apoptosis rate of the 60 micromol/L DIM + 0. 5 mg/L IDA group was 47.0%, significantly higher than that of the 0.5 mg/L IDA group (3.2%, P < 0.05). RT-PCR and Western blotting showed that the combination of DIM and IDA significantly enhanced the mRNA and protein expression of caspase 9. CONCLUSION: DIM enhances the growth inhibition effect of IDA on human prostate cancer cells by the mechanism of induction of apoptosis.

Application of surface-enhanced laser desorption/ionization time-of-flight-based serum proteomic array technique for the early diagnosis of prostate cancer.

AIM: To identify the serum biomarkers of prostate cancer (PCa) by protein chip and bioinformatics. METHODS: Serum samples from 83 PCa patients and 95 healthy men were taken from a mass screening in Changchun, China. Protein profiling was carried out using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The data of spectra were analyzed using two bioinformatics tools. RESULTS: Eighteen serum differential proteins were identified in the PCa group compared with the control group (P < 0.01). There were four proteins at the higher serum level and 14 proteins at the lower serum level in the PCa group. A decision tree classification algorithm that used an eight-protein mass pattern was developed to correctly classify the samples. A sensitivity of 92.0% and a specificity of 96.7% for the study group were obtained by comparing the PCa and control groups. CONCLUSION: We identified new serum biomarkers of PCa. SELDI-TOF MS coupled with a decision tree classification algorithm will provide a highly accurate and innovative approach for the early diagnosis of PCa.

Measurement of serum zinc improves prostate cancer detection efficiency in patients with PSA levels between 4 ng/mL and 10 ng/mL.

AIM: To investigate whether the measurement of serum zinc may improve the detection of prostate cancer (PCa) in men who had total prostate-specific antigen (PSA) levels higher than 4.1 ng/mL. METHODS: A mass screening for PCa of 3940 men over 50 years old was undertaken using total serum PSA. Of the 190 men (4.8%) with elevated PSA, 143 (3.6%) underwent a transrectal ultrasonography (TRUS)-guided biopsy of the prostate, and 42 men (1% of total and 29.3% of men undergoing biopsy) were found to have cancer. The areas under the receiver operating characteristic curves (ROC-AUC) were used to compare the diagnostic power of cancer detection by means of serum zinc, and free PSA/total PSA ratio (f/t). RESULTS: The men with levels of serum zinc that ranged from 40 ng/mL-60 ng/mL, had an age-adjusted odds ratios(OR) of 5.0. A cutoff value of 100 microg/mL for serum zinc concentration provided a sensitivity of 90.5% and a specificity of 32.7% in elevated PSA range, and a sensitivity of 93.3% and specificity of 27.1% in gray zone, respectively. In the gray zone ranges of 4.1 ng/mL-10.0 ng/mL, the ROC-AUC for zinc was 73.0% higher than 62.7% of f/t PSA ratio and 56.7% of total PSA. CONCLUSION: PCa displays a lower serum zinc concentration. The measurement of zinc levels improves PCa detection in the gray zone compared with the f/t PSA ratio and total PSA.

Mass screening of prostate cancer in a Chinese population: the relationship between pathological features of prostate cancer and serum prostate specific antigen.

AIM: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). METHODS: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). RESULTS: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. CONCLUSION: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.

[Proteomic analysis of prostate cancer using surface enhanced laser desorption/ionization mass spectrometry].

OBJECTIVE: To identify the serum biomarkers of prostate cancer by using protein chip and bioinformatics. METHODS: Eighty three prostate cancer (PCA) patients and ninety five healthy people from mass screen in Changchun were detected by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The data of spectra were analyzed by bioinformatics tools-Biomarker Wizard and Biomarker Pattern. RESULTS: Compared with the spectra of healthy people, there were 18 potential markers detected in the spectra of the PCA patients, the protein expression was high in 4 of which and low in the 10 of which. The softwares Biomarkerwizard and Biomarker Pattern automatically, under given conditions, selected 8 biomarker proteins to be used to establish a five layer decision tree differentiate to diagnose PCA and differentiate PCA from healthy people with a specificity of 92.632% and a sensitivity of 96.386%. CONCLUSION: New serum biomarkers of PCA have been identified, and this SELDI mass spectrometry coupled with decision tree classification algorithm will provide a highly accurate and innovative approach for the early diagnosis of PCA.

[Knockdown of STAT3 expression using siRNA inhibits the growth of prostate cancer cell lines].

OBJECTIVE: To study the effects of pSilencer 1.0-U6-siRNA-STAT3 on the growth of PC3 and LNCaP cells. METHODS: Three pairs of DNA template coding siRNA were synthesized against STAT3 to reconstruct pSilencer 1.0-U6-STAT3-siRNA, which was transfected into PC3 and LNCaP cells. The STAT3 expression in PC3 cells and LNCaP were transfected with pSilencer 1.0-U6-siRNA-STAT3, and it was detected by Western blot and Northern blot. MTT and FCM were used to observe the growth-inhibiting ratio and apoptosis in PC3 cells. RESULTS: Western blot and Northern blot analyses demonstrated that pSilencer 1.0-U6-siRNA-STAT3 could significantly inhibit the expression of STAT3 in PC3 and LNCaP cells; MIT and FCM results showed that it could suppress the growth of PC3 cells and LNCaP and induce apoptosis of PC3 cells in vitro. CONCLUSION: PSilencer 1.0-U6-siRNA-STAT3 could significantly inhibit STAT3 expression, suppress the growth of PC3 and LNCaP cells and induce the apoptosis of PC3 cells.

Mass screening of 12,027 elderly men for prostate carcinoma by measuring serum prostate specific antigen.

BACKGROUND: The incidence of prostate carcinoma (Pca) has been increasing in China. We detected Pca in elderly men in Changchun, north China and the significance of prostate specific antigen (PSA) in mass screening and clinical staging of Pca. METHODS: Serum PSA from 12,027 men over 50 years old from Changchun was analyzed. In case of serum PSA greater than 4.0 ng/ml, the patient was suspected of potentially suffering from Pca, and transrectal six-point puncture prostate biopsies were performed under ultrasound guidance. Pathological examinations were performed on the biopsy tissue, and ABCD and TNM clinical stagings were used in accordance with international standards. Correlations between serum PSA level and clinical stage were analyzed. RESULTS: PSA was greater than 4.0 ng/ml in 813 patients (6.8% of the 12,027 men). Transrectal six-point prostate puncture biopsies guided by ultrasound were performed in 273 patients (33.6% of the 813 patients who were tested positive in the initial mass screening). Of these 273 patients, 69 cases of Pca (25.3% of 273) were confirmed by biopsy in the second screening, with an overall detection rate for Pca of 0.57% (69/12,027). The total number of patients in stages A, B, T1, or T2 was 57.9%, and over 20% of them suffered from late stage Pca with lymph node and bone metastasis. An obvious positive correlation was observed between ABCD staging, TNM staging, and serum PSA level. CONCLUSIONS: Serum PSA level is not only the golden standard for mass screening of Pca, but also the predictor for clinical stage of Pca. PSA testing revealed asymptomatic Pca cases in early, middle, and later stages in the elderly, suggesting that mass screening is of paramount importance.

[Pathological features of prostate cancer in Chinese cohort detected through mass screening and their relationships with serum prostate specific antigen].

OBJECTIVE: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in Chinese cohort and their relationships with serum prostate specific antigen (PSA). METHODS: ELISA was used to measured the serum PSA in 12 027 Chinese men aged 50 and over in Changchun, Jilin Province. Transrectal ultrasound guided six-sextant biopsy was performed on 137 cases with the serum PSA value > 4.0 micro g/L and 21 cases with the serum PSA < 4.0 micro g/L but with urethral obstructive symptoms. Pathological analysis was done with the aid of statistic software SPSS 10.0. RESULTS: Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9%, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34% respectively. In these 41 cases of prostate cancer, a significant linear positive correlation between the serum PSA and the Gleason score (r = 0.329, P < 0.05) and a significant linear positive correlation between the serum PSA and the positive counts of carcinoma in six-sextant biopsy (r = 0.425, P = 0.006) were found. CONCLUSION: The moderately differentiated carcinoma is the most common type of prostate cancer. The approach of mass screening opens a new avenue for the early detection of prostate cancer. Serum PSA value is not only associated with the pathological grading but also with the extension of tumor.

[Mass screening for prostate cancer is the best approach to early diagnosis and treatment of prostate cancer].

To achieve the goal of early detection, diagnosis and treatment of prostate cancer in China, mass screening for prostate cancer using serum prostate specific antigen (PSA) has been performed in men over 50 years. We compared this result with the clinical cases. It proved that only through the mass screening can we really find the early stage prostate cancer and be given the chance of curing the cancer. We also investigated the current treatment situation and problems and figured out the further direction on the prostate cancer research.

Plasmid-based Stat3-specific siRNA and GRIM-19 inhibit the growth of thyroid cancer cells in vitro and in vivo.

It has been shown that overexpression of signal transducer and activator of transcription 3 (Stat3) contribute to the progression and metastasis of various solid tumors and that silencing Stat3 inhibits tumor growth in several types of cancer. Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), a Stat3-inhibitory protein, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis by targeting the transcription factor Stat3 for inhibition. However, little is known about Stat3 and GRIM-19 roles in the tumor growth of thyroid carcinoma cells. In the present study, we developed a dual expression plasmid that co-expressed Stat3-specific siRNA and GRIM-19 (pSi-Stat3-GRIM-19) and transfected it into SW579 cells (thyroid carcinoma cell line) to evaluate its effects on cell proliferation, cell apoptosis, cell migration and cell invasion in vitro and tumor growth in vivo. Simultaneous expression of pSi-Stat3-GRIM-19 in SW579 cancer cells was found to significantly suppress the proliferation, migration and invasion in vitro and tumor growth in vivo, when compared to the controls either Stat3-specific siRNA or GRIM-19 alone. In conclusion, our data demonstrated that a combined strategy of co-expressed Stat3-specific siRNA and GRIM19 synergistically and more effectively suppressed thyroid tumor growth, and have therapeutic potential for the treatment of thyroid cancer.

Prostate-specific antigen screening for prostate cancer: benefits for patients with highly aggressive prostate cancer.

The PSA screening for 25 years in America is the biggest cohort study in a field of public health.27 We should realize not only the significance of the early diagnosis and treatment of PCa, but also the dramatic decrease in PCaMR from 2002 to 2008. The data from the IARC were especially noteworthy.Moreover, the patients with highly aggressive PCa, who account for more than 30% of all PCa patients, could only be diagnosed earlier by PSA screening. The patients would thus gain the opportunity for earlier treatment and would have a prolonged, higher quality life-span. However, the complications of interventional treatments, including biopsy,radical prostatectomy and/or radiation therapy,will become more avoidable in the near future.According to the supporting evidence for the decrease in PCa mortality in PSA screening, we strongly hope that the USPSTF changes the 'D' recommendation for PSA screening.

Small interfering RNA survivin and GRIM-19 co-expression salmonella plasmid inhibited the growth of laryngeal cancer cells in vitro and in vivo.

OBJECTIVE: To investigate the inhibitory effect of plasmid-based survivin-specific short hairpin RNA and GRIM-19 on the growth of Hep-2 laryngeal cancer cells. METHODS: The plasmid expressing survivin-specific short hairpin RNA (shRNA) and GRIM-19 (p-siRNA survivin/GRIM-19) was prepared and transfected into Hep-2 cells with Lipofectamine 2000. The mRNA and protein expression of surviving and GRIM-19 were measured with RT-PCR and western blot assay, respectively. MTT assay was employed to detect the proliferation of Hep-2 cells, and flow cytometry and AO/EB assay were done to determine the apoptosis of Hep-2 cells. RESULTS: In the p-siRNA survivin/GRIM-19, the mRNA and protein expression of survivin was markedly reduced by 54.4% and 42.2%, and the reduction in protein expression of surviving was more obvious than that in the p-siRNA survivin group (37%) (P<0.05). The protein expression of GRIM-19 was markedly enhanced when compared with the control group (P<0.01). MTT assay revealed the proliferation of Hep-2 cells undergoing transfection with p-siRNA survivin/GRIM-19 was markedly inhibited, and the inhibition rate was as high as 79%, which was higher than that in the psi-survivin group (45%) and p-GRIM-19 group (35%). AO/EB assay and flow cytometry indicated that the apoptotic cells in the p-siRNA survivin/GRIM-19 group were dramatically increased as compared to the psi-survivin group and p-GRIM-19 group. CONCLUSION: The p-siRNA survivin/GRIM-19 has marked decrease in survivin expression and dramatic increase in GRIM-19 expression. Moreover, silencing of survivin and over-expression of GRIM-19 can significantly inhibit the growth and induce the apoptosis of Hep-2 in vitro and in vivo.