Effects of transferred NK4 gene on proliferation, migration, invasion and apoptosis of human prostate cancer DU145 cells

We investigated the ability of NK4, an antagonist of human hepatocyte growth factor （HGF）, to inhibit the influence of HGF on proliferation, migration, invasion and apoptosis of human prostate cancer cells. Expression vector pBudCE4.1-EGFP-NK4 containing NK4 cDNA was used to transfect human prostate cancer DU145 cells, and the effects of the autocrine NK4 on tumor cell proliferation, migration, invasion and apoptosis were assessed in vitro. in vivo, we subcutaneously implanted DU145 cells, mock-transfected clone （DU145/empty vector） cells and NK4- transfected clone （DU145/NK4） cells into nude mice, and then evaluated tumor growth, cell proliferation and cell apoptosis in vivo. We found that DU145/NK4 cells expressed NK4 protein. In the in vitro study, autocrine NK4 at- tenuated the HGF-induced tumor cell proliferation, migration and invasion, and stimulated apoptosis. Furthermore, autocrine NK4 effectively inhibited the HGF-induced phosphorylation of c-Met, extracellular signal-regulated kinase-1 （ERK1）. and protein kinase B 1/2 （Aktl/2）. Histological examination revealed that autocrine NK4 inhibited prolifera- tion and accelerated apoptosis of prostate cancer cells. These results show that genetic modification of DU145 cells with NK4 cDNA yields a significant effect on their proliferation, migration, invasion and apoptosis. Molecular targeting of HGF/c-Met by NK4 could be applied as a novel therapeutic approach to prostate cancer.

The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells

Hepatocyte growth factor （HGF） is a glycoprotein that induces prostate cancer cell proliferation, migration and invasion. The activation of transient receptor potential canonical 6 （TRPC6） channels is considered important in promoting prostate cancer cell proliferation. In this study, we assessed the role of endogenous TRPC6 channels in the HGF-induced cell proliferation of prostate cancer. Reverse transcription-PCR and Western blotting were used to investigate TRPC6 expression. Electrophysiological techniques （whole-cell patch clamp configuration） and Ca^2＋ imaging analysis were used to investigate the channel activity in cells. The effects of TRPC6 channels on cell cycle progression, cell apoptosis and cell growth were also examined. TRPC6 and c-MET were expressed in DU145 and PC3 cells. In addition, functional TRPC6 channels were present in DU145 and PC3 cells, and TRPC6 knockdown suppressed TRPC-Iike currents evoked by oleoyl-2-acetyl-sn-glycerol （OAG）. Inhibition of TRPC6 channels in DU145 and PC3 cells abolished OAG- and HGF-induced Ca^2＋ entry. Furthermore, inhibition of TRPC6 channels arrested DU145 and PC3 cells at the G2/M phase and suppressed HGF-induced cell proliferation. Collectively, our results indicate that TRPC6 has an important role in HGF-induced DU145 and PC3 cell proliferation.

The androgen receptor in hormone-refractory prostate cancer

Advanced prostate cancer is responsive to hormone therapy that interferes with androgen receptor （AR） signalling. However, the effect is short-lived, as nearly all tumours progress to a hormone-refractory （HR） state, a lethal stage of the disease. Intuitively, the AR should not be involved because hormone therapy that blocks or reduces AR activity is not effective in treating HR tumours. However, there is still a consensus that AR plays an essential role in HR prostate cancer （HRPC） because AR signalling is still functional in HR tumours. AR signalling can be activated in HR tumours through several mechanisms. First, activation of intracellular signal transduction pathways can sensitize the AR to castrate levels of androgens. Also, mutations in the AR can change AR ligand specificity, thereby allowing it to be activated by non-steroids or anti-androgens. Finally, overexpression of the wild-type AR sensitizes itself to low concentrations of androgens. Therefore, drugs targeting AR signalling could still be effective in treating HRPC.

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋ （P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

Inhibition of telomerase with human telomerase reverse transcriptase antisense increases the sensitivity of tumor necrosis factor-α-induced apoptosis in prostate cancer cells

Aim： To investigate the effect of inhibition of telomerase with human telomerase reverse transcriptase （hTERT） antisense on tumor necrosis factor-α （TNF-α-induced apoptosis in prostate cancer cells （PC3）. Methods： Antisense phosphorothioate oligodeoxynucleotide （AS PS-ODN） was synthesized and purified. Telomerase activity was measured using the telomeric repeat amplification protocol （TRAP） and polymerase chain reaction enzyme-linked immunoassay （PCR-ELISA）. hTERT mRNA was measured by reverse transcription PCR （RT-PCR） assay and gel-image system, hTERT protein was detected by immunochemistry and flow cytometry. Cell viability was detected by 3-（4, 5-dimethylthiazol-2-yl）-2,5-Diphenyltetrazolium （MTT） assay. Cell apoptosis was observed by morphological method and determined by flow cytometry. Results： The telomerase activity decreased with time after hTERT AS PS-ODN treatment. The levels of hTERT mRNA decreased with time after hTERT AS PS-ODN treatment, which appeared before the decline of the telomerase activity. The percentage of positive cells of hTERT protein declined with time after hTERT AS PS-ODN treatment, which appeared after the decline of hTERT mRNA. There was no difference in telomerase activity, hTERT mRNA and protein levels between hTERT sense phosphorothioate oligodeoxynucleotide （S PS-ODN） and the control group. The cell viability decreased with time after hTERT AS PS-ODN combined with TNF-α treatment. The percentage of apoptosis increased with time after hTERT AS PS-ODN combined with TNF-α treatment. There was no difference in cell viability and the percentage of apoptosis between hTERT S PS-ODN and the control group. Conclusion： hTERT AS PS-ODN can significantly inhibit telomerase activity by downregulating the hTERT mRNA and protein expression, and inhibition of telomerase with hTERT antisense can enhance TNF-α- induced apoptosis of PC3 cells.

Loss of the vitamin D receptor in human breast and prostate cancers strongly induces cell apoptosis through downregulation of Wnt/β-catenin signaling

Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25（OH）2D] are mediated through binding to the vitamin D receptor （VDR）. Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad （MDA-MB-231）, subcutaneously （PC3） or intra-tibially （both cell lines） in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls. These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/0-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1, interleukin-6 （IL-6）, and IL-8. Stabilization of 0-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer.

Inhibitory effect of a new gossypol derivative apogossypolone (ApoG2) on xenograft of human prostate cancer cell line PC-3

Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were established via subcutaneous injection of PC-3 cells and the tumor-transplanted mice were divided into 4 groups: control group and three ApoG2 treatment groups, with 10 mice in each group. Volumes of the tumor were estimated every 2 d and the morphology of tumor tissues was observed. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and caspase-8 in tumor tissues. Results: ApoG2 (2.5 mg/kg-10 mg/kg) given intraperitoneally once a day can obviously inhibit the growth of subcutaneous prostatic carcinoma implant. The tumor volume decreased obviously when the treatment dosage was bigger than 5.0 mg/kg (P<0.01). Meanwhile, ApoG2 decreased the expression of PCNA and CD31, and enhanced the expression of caspases-3, caspase-8 in tumor tissues. Conclusion: ApoG2 exert an inhibitory effect on prostatic carcinoma possibly by inducing apoptosis and inhibiting tumor angiogenesis.

Signal Transduction Pathways Mediated by Secreted and Non-Secreted Forms of Intact Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) and Its 1-97 N-Terminal Fragment in PC-3 Human Prostate Cancer Cells

Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induce apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and independent manner. This study was undertaken to delineate possible down-stream signaling pathways that are involved in this process. Intact IGFBP-3 and its N-terminal 1-97 fragments with or without a signal propeptide were fused to YFP and expressed in PC-3 human prostate cancer cells. In some cases, the putative IGF-binding site was presented in full length IGFBP-3 and its N-terminal fragment was also mutated. Extent of apoptosis was quantified using FACS. Up-regulation of total Stat-1 and activation of phospho-Stat-1 were shown by western blot. TGF-β signal was measured by luciferase reporter assay. Results from inhibitor studies indicated that both the Caspase 8 and caspase 9 pathways are involved in IGFBP-3 (non-secreted form) which induced apoptosis in PC-3 cells. Exogenous addition of IGFBP-3 to PC-3 cells increased Stat-1 protein expression/tyrosine phosphorylation. Interestingly, results also showed that knockdown of Stat-1 by siRNA potentiated the IGFBP-3 induced apoptosis in PC-3 cells. In addition, both full-length IGFBP-3 and its 1-97 Nterminal fragments inhibited TGF-β signaling in these cells. This is the first report that compares the signal transduction pathways involved in apoptotic pathways mediated by IGFBP-3 in PC-3 human prostate cancer cells. Non-secreted form of full length IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9. Although, only non-secreted form of IGFBP-3 is involved in inducing apoptosis in PC-3 cells via caspase 8 and caspase 9 activation pathways but both secreted and non-secreted forms of IGFBP-3 are involved in modulating Stat-1 and TGF-β pathways to induce apoptotic actions in PC-3 cells. Non-secreted intact IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9 pathways. Modulation in STAT-1 and TGF-β pathways may also be important for IGFBP-3 induced apoptosis in PC-3 cells in general. These studies clearly demonstrate that secreted and non-secreted FL and 1-97 N-terminal fragments induce apoptosis in PC-3 cells by regulating different mechanistic pathways.

<i>N-myc</i>Downstream Regulated Gene 1 Increases Differentiation Factors Level in Human Prostate Cancer Cells without Affecting Cell Proliferation and Cell Cycle Profiles

N-myc downstream regulated gene 1 (NDRG1), also known as differentiation related gene 1, was previously identified as an up-regulated gene upon cellular differentiation. Even though its sequence along with its expressional pattern in cancer cell lines are evident, the functional aspects concerning cell proliferation, viability, differentiation and cell cycle regulation of NDRG1 remains vague. The aim of the present study was to elucidate the functional role of NDRG1 in human prostate cancer. Our results showed basal levels of NDRG1 expression in PC-3 (poorly differentiated, null p53), DU-145 (moderately differentiated, mutant p53) and LNCaP (well-differentiated, wiled type p53). Nevertheless, NDRG1 sequencing assay disclosed no mutations in the gene. Furthermore, human cDNA of NDRG1 from normal placenta was cloned into a eukaryotic expression vector and transfected into the three cancer cell lines. This resulted in over-expression of NDRG1, which in turn markedly up regulated two differentiation markers of the prostate tissue, p21 and cytokeratin 8/18. Unpredictably, cell cycle progression, cell proliferation and DNA synthesis were unaffected following NDRG1 expression. These results revealed that NDRG1 is functional in prostate cancer cells and able to induce expression of differentiation factors through p53 independent pathway. However, the pathway downstream NDRG1, involving p21 and c8/18, regulating cell cycle progression and DNA synthesis is unfunctional. Loss of sensitivity to p21 cell cycle control may be associated with prostatic cancer behavior. Further studies are required to clarify the intra cellular molecular pathways affecting NDRG1 function in human prostate cancer.

Androgen receptors expressed by prostatic stromal cells obtained from younger versus older males exhibit opposite roles in prostate cancer progression

Aging is a major risk factor for prostate cancer （PCa）, and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors （ARs） by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA （shRNA）, matrix metalloproteinase （MMP） expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.

Improved Anti-tumor Efficiency against Prostate Cancer by Docetaxel-loaded PEG-PCL Micelles

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory prostate cancer（HRPC）. By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel（DTX）-loaded mPEG-PCL micelles（DTX-PMs）, with the purpose of eliminating side effects of the commercial formulation（Tween 80） and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of（8.72±1.05）%, and an encapsulation efficiency of（98.1±8.4）%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei, the DTX-PMs dramatically reduced the prostate specific antigen（PSA） level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

Effects of bortezomib in sensitizing human prostate ：ancer cell lines to NK-mediated cytotoxicity

The proteasome inhibitor, bortezomib, has been demonstrated to sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand （TRAIL）-mediated apoptosis. Natural killer （NK） cells represent potent antitumor effector cells. They also express TRAIL. Therefore, we investigated whether bortezomib could sensitize tumor cells to NK cell-mediated killing, and have the same effect in human prostate cancer cell lines （LNCaP and DU145）. We found that bortezomib strongly inhibits proliferation in both cell lines. Furthermore, compared with LNCaP cells, DU145 cells are more sensitive to bortezomib-induced apoptosis. However, bortezomib is unable to sensitize these two cell lines to NK cell-mediated killing in short-term assays. In long-term assays, we found that killing mediated by activated NK cells following bortezomib treatment leads to greater antitumor effects than either treatment alone. In addition, treatment with bortezomib causes these cells to upregulate apoptosis-related mRNA as well as death receptors and downregulate the major histocompatibility class （MHC）-I molecule on the cell surface of DU145 cells. In contrast, LNCaP cells are not sensitized by this treatment. Death receptors and the MHC-I molecule did not change in this cell line. These data suggest that bortezomib can be used to sensitize prostate cancer cells to NK cell-mediated killing and improve current cancer therapies. This theral）eutic stratelzv may be more effective in I）atients with androeen-insensitive orostate cancer.

Somatostatin receptor subtypes in hormone-refractory （castration-resistant） prostatic carcinoma

The aim of this study was to examine the tissue expression and Iocalisation of the somatostatin receptors （SSTRs） in hormone-refractory （HR） prostate cancer （PCa）. Five SSTRs were evaluated immunohistochemically in 20 radical prostatectomies （RPs） with Gleason score （GS） 3＋3=6 PCa, in 20 RPs with GS 4＋4=8 and 4＋5=9 PCa, and 20 transurethral resection of the prostate specimens with HR PCa. The mean values in the cytoplasm （all five SSTRs were expressed）, membrane （only SSTR3 and SSTR4 were expressed） and nuclei （only SSTR4 and SSTR5 were expressed） of the glands in HR PCa were 20-70% lower than in the other two groups, the differences being statistically significant. All five SSTRs were expressed in the smooth muscle and endothelial cells of HR PCa, the mean values being lower than in the other two groups. In conclusion, this study expands our knowledge on the expression and Iocalisation of five SSTRs in the various tissue components in the HR PCa compared with hormone-sensitive PCa.

Inhibitory effects of apogossypolone on subcutaneous implants of human LNCaP prostatic carcinoma cells

Objective:The aim of this study was to investigate the inhibitory effect of apogossypolone (ApoG2) on subcutaneous implants of human LNCaP prostatic carcinoma cells, and explore its mechanism. Methods:To establish human LNCaP prostatic carcinoma cell line subcutaneous xenograft models and observe the inhibitory effect of ApoG2 on the tumor model. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and-8 in tumor tissues. The microvessel density was calculated. Results:ApoG2 could obviously inhibit the growth of subcutaneous prostatic carcinoma implant. ApoG2 decreased the expression of PCNA and CD31, and increased the expression of caspases-3,-8 in tumor tissues. Conclusion:ApoG2 has an inhibitory effect on prostatic carcinoma implants.

NRG1、HER3在前列腺癌组织中的表达及其与临床病理特征和预后的关系

目的研究前列腺癌(PC)组织中神经调节蛋白1(NRG1)、人表皮生长因子受体3(HER3)表达与临床病理特征及预后的关系。方法选取2015年2月—2020年2月吉林省人民医院泌尿外科诊治PC患者96例,免疫组织化学检测组织中NRG1、HER3表达;Kaplan-Meier曲线(Log-Rank检验)比较不同NRG1、HER3表达对PC患者预后的影响;COX回归分析PC患者预后的影响因素。结果PC癌组织中NRG1、HER3阳性率分别为78.13%(75/96)、75.00%(72/96),高于癌旁组织6.25%(6/96)、8.33%(8/96)(χ^(2)/P=101.670/<0.001,87.771/<0.001)。TNM分期Ⅲ期、Gleason评分>7分及术前PSA水平≥20μg/L患者癌组织中NRG1、HER3阳性率大于TNM分期Ⅰ~Ⅱ期、Gleason评分≤7分及术前PSA水平<20μg/L(χ^(2)/P=6.181/0.013,8.533/0.003;7.731/0.005,6.769/0.009;6.508/0.011,7.376/0.007)。NRG1阳性组、HER3阳性组3年累积无进展生存率分别低于NRG1阴性组、HER3阴性组(χ^(2)/P=4.267/0.039,5.499/0.019)。TNM分期Ⅲ期、Gleason评分>7分、术前PSA≥20μg/L、NRG1阳性,HER3阳性是影响PC患者预后的独立危险因素[OR(95%CI)=1.448(1.118~1.875),1.401(1.138~1.724),1.353(1.059~1.728),1.338(1.057~1.692),1.293(1.014~1.649)]。结论PC癌组织中NRG1、HER3表达升高,与PC不良临床病理特征相关,是新的评估PC预后的肿瘤标志物。

钼靶和超声多普勒结合血清肿瘤标志物诊断早期乳腺癌研究

目的:探讨钼靶、超声多普勒和血清肿瘤标志物中血清前列腺特异抗原(PSA)、血清糖类抗原15-3(CA153)、黏蛋白1(MUC1)、人类生长分化因子3(GDF3)单独及联合检测在早期乳腺癌诊断中的价值。方法:选取2018年1月至2021年12月在唐山市人民医院经病理检查确诊的96例乳腺癌患者(乳腺癌组)和同期在本院接受诊治的70例乳腺良性疾病患者(良性病灶组)以及同时选取在本院体检健康的50名体检者(健康对照组),以术后病理检查为“金标准”,比较钼靶、超声多普勒检查以及血清PSA、CA153、MUC1、GDF3单独及6者联合应用对乳腺癌的诊断价值。结果:乳腺癌组96例乳腺癌患者中有78例乳腺超声诊断为恶性,阳性检出率为81.3%;80例钼靶X射线检查诊断为恶性,阳性检出率为83.1%;乳腺癌组的血清PSA、CA153、MUC1及GDF3的水平明显高于良性病灶组和健康对照组,差异均有统计学意义(t_(良性病灶组)=8.783、10.361、11.258、18.965;t_(健康对照组)=9.564、12.658、12.688、20.163,P<0.05);以乳腺癌作为因变量,血清PSA、CA153、MUC1及GDF3为自变量,进行Logistic回归分析,血清PSA、CA153、MUC1及GDF3是乳腺癌的重要危险因素(OR=1.165、1.168、1.472、1.248,P<0.05);受试者工作特征(ROC)曲线分析各指标单独应用时:乳腺超声、钼靶,血清PSA、CA153、MUC1及GDF3的ROC曲线下面积(AUC)(95%CI)、灵敏度和特异度分别为0.723(0.595~0.851)、82.56%和67.32%,0.761(0.636~0.886)、85.79%和65.36%,0.833(0.726~0.941)、81.48%和85.73%,0.837(0.738~0.926)、61.25%和70.17%,0.768(0.648~0.889)、71.49%和80.87%,0.613(0.469~0.758)、52.94%和50.57%;而6项联合应用时AUC(95%CI)、灵敏度和特异度分别为0.958(0.905~0.999)、96.37%和84.83%,其诊断效能更高。结论:钼靶、超声多普勒和血清PSA、CA153、MUC1、GDF3联合检测效能高于单独检测,有助于早期鉴别和诊断乳腺癌。

Co-infection of Epstein-Barr virus and human papillomavirus in human tumorigenesis

Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associated with38%of all virus-associated cancers.The probability of one patient infected with these two distinct types of viruses is increasing.Here,we summarize the co-infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis.

Vaccines and Antibodies for Therapeutic Use in Cancers

This review describes briefly the beneficial use of two vaccines developed by us for treatment of cancers. The vaccine against Luteinizing Hormone Releasing Hormone (LHRH) is effective in carcinoma of prostate as well as in breast cancers dependent on androgens and estrogens respectively. LHRH being identical in both males and females, the same vaccine is usable in both Prostate and Breast steroid hormones-dependent-cancers. Monoclonal antibodies are finding therapeutic utility in several cancers, and many have received Drugs Regulatory approval. The monoclonals developed by us against hCG and against epitopes present on androgen-independent castration resistant prostate cancers are briefly recapitulated. Anti-hCG antibodies kill several cancers expressing hCG. An example is given of A549 lung carcinoma. MoAb730 and MoAb7B2G10 kill DU-145 and PC-3 androgen-independent castration resistant prostate cancer cells. Some cancers such as MOLT-4, a T-lymphoblastic leukemia, though expressing hCG are not killed by PiPP, the high affinity anti-hCG antibody. Linking the antibody to curcumin however works like a “Magic Bullet”. All MOLT-4 cells are killed by this conjugate, the antibody homes selectively to cancer cells expressing hCG to deliver curcumin which exercises the killing effect. A recombinant vaccine, hCGβ-LTB (human chorionic gonadotropin subunit β linked to B subunit of heat-labile enterotoxin of E. coli) has been made, which induces high titre bioeffective antibodies not only in BalbC, but also in other genetic strains of mice. The vaccine employs autoclaved Mycobacterium indicus pranii (MiP) as adjuvant. MiP invigorates both humoral and cell mediated immune responses against Human chorionic gonadotropin (hCG). Besides being a potent adjuvant, MiP used alone heals anogenital warts in humans and has the property of preventing and curing SP2/O Myelomas in mice.

基于AEP/PI3K/AKT信号通路探讨温肾散结方对人前列腺癌细胞的调控作用和分子机制

目的:基于天冬酰胺内肽酶(AEP)/磷酸酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB/AKT),探讨温肾散结方(WSSJ方)对人前列腺癌细胞增殖和迁移能力的影响,并进一步探讨其潜在的分子机制。方法:制备WSSJ方冻干粉;体外培养人前列腺癌PC3、DU145和22RV1细胞,CCK-8法检测WSSJ方对前列腺癌细胞相对活力的影响并测定最佳给药浓度;集落形成实验检测WSSJ方对单细胞增殖能力的影响;划痕实验检测WSSJ方对前列腺癌细胞迁移能力的影响;RT-qPCR检测细胞内AEP mRNA、PI3K mRNA及AKT mRNA表达;Western blotting检测细胞内AEP、PI3K及AKT蛋白表达。结果:WSSJ方组前列腺癌细胞增殖活力随给药浓度升高逐渐降低;WSSJ方组细胞计数与细胞融合情况均低于对照组;WSSJ方低、中、高剂量组细胞集落形成数量均少于对照组;WSSJ方组细胞迁移率显著低于对照组(P<0.01);WSSJ方组PC3细胞AKT蛋白相对表达量低于对照组,DU145细胞、22RV1细胞AEP、PI3K蛋白相对表达量均低于对照组,差异均有统计学意义(P<0.05或P<0.01);WSSJ方组PC3细胞、DU145细胞、22RV1细胞AEP mRNA、PI3K mRNA及AKT mRNA表达均显著低于对照组(P<0.05或P<0.01)。结论:WSSJ方能有效抑制人前列腺癌细胞的增殖和迁移能力,并且其对肿瘤细胞的抑制呈现剂量依赖性,作用机制可能与下调AEP抑制PI3K/AKT信号通路有关。