Long-term efficacy and safety of anticoagulant for cavernous transformation of the portal vein cirrhotic patient with extrahepatic portal vein obstruction.

BACKGROUND/AIMS: Cavernous transformation of the portal vein (CTPV) in cirrhotic patients with extrahepatic portal vein obstruction (EHPVO) was a relatively rare disease and had no consensus on the treatment. Our study aimed to explore the value of anticoagulation with warfarin treatment for CTPV cirrhotic patients with EHPVO. METHODS: From January 2015 to December 2019, the clinical characteristics of cirrhotic patients who were diagnosed as CTPV with EHPVO were retrospectively analyzed. Eligible patients were distributed into the anticoagulation group (n = 46) and control group (n = 38). The change of portal vein thrombosis, hepatic decompensation, survival and adverse events were evaluated between the two groups. RESULTS: The median follow-up of our patients was 51 months in the anticoagulation group and 44 months in the control group. The progress rate of the portal vein was higher in patients from the control groups (n = 12) than in patients from the anticoagulation group (n = 4, p = 0.008). There was no significant difference between the partial recanalization rate and stable rate between the two groups. Patients in anticoagulation group developed less hepatic decompensation than those in control group (13.0% vs 34.2%, p = 0.021). The Kaplan-Meier curve showed that patients in the anticoagulation group had a better prognosis than patients in the control group (P < 0.022). There were no serious complications due to warfarin treatment. CONCLUSION: For CTPV cirrhotic patients with EHPVO, anticoagulation with warfarin treatment was effective and safe. Anticoagulants could prevent portal vein thrombosis progression, hepatic decompensation and death. In addition, our results showed little benefit of anticoagulants on thrombosis recanalization.

Second near-infrared photothermal-amplified immunotherapy using photoactivatable composite nanostimulators.

BACKGROUND: The construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response. RESULTS: Here, a composite nanostimulator (CNS) was constructed for the release of second near-infrared (NIR-II) photothermal-mediated immune agents, thereby achieving spatiotemporally controllable photothermal-synergized immunotherapy. CNS nanoparticles comprise thermosensitive liposomes as an outer shell and are internally loaded with a NIR-II photothermal agent, copper sulfide (CuS), toll-like receptor-9 (TLR-9) agonist, cytosine-phospho-guanine oligodeoxynucleotides, and programmed death-ligand 1 (PD-L1) inhibitors (JQ1). Following NIR-II photoirradiation, CuS enabled the rapid elevation of localized temperature, achieving tumor ablation and induction of immunogenic cell death (ICD) as well as disruption of the lipid shell, enabling the precise release of two immune-therapeutical drugs in the tumor region. Combining ICD, TLR-9 stimulation, and inhibited expression of PD-L1 allows the subsequent enhancement of dendritic cell maturation and increases infiltration of cytotoxic T lymphocytes, facilitating regional antitumor immune responses. CONCLUSION: CNS nanoparticle-mediated photothermal-synergized immunotherapy efficiently suppressed the growth of primary and distant tumors in two mouse models and prevented pulmonary metastasis. This study thus provides a novel sight into photo-controllably safe and efficient immunotherapy.

MIR210HG regulates glycolysis, cell proliferation, and metastasis of pancreatic cancer cells through miR-125b-5p/HK2/PKM2 axis.

Pancreatic cancer has the worst prognosis of all common cancers. Pancreatic cancer cells have a metabolic advantage due to their swiftly adaptive responses to hypoxic and low-nutrient medium. This advantage contributes to the aggressivity of pancreatic cancer. In this study, lncRNA MIR210HG was abnormally upregulated within pancreatic cancer. It acted as a key oncogenic regulator of pancreatic cancer aggressiveness and glycolysis. Knockdown of MIR210HG significantly inhibited the aggressive phenotype of pancreatic cancer cells and inhibited the growth of xenograft tumours. More importantly, MIR210HG knockdown inhibited pancreatic cancer cell glycolysis via regulating the glycolysis-related hexokinase 2 (HK2) and Pyruvate kinase muscle isozyme M2 (PKM2) expression. Compared with the MIR210HG knockdown group, miR-125b-5p inhibition promoted the aggressive phenotypes and glycolysis of pancreatic cancer cells. Furthermore, the effects of MIR210HG knockdown on HK2 and PKM2 expression, pancreatic cancer cell aggressive phenotypes, and glycolysis were significantly reversed by miR-125b-5p inhibition. In tissue samples, MIR210HG expression was negatively correlated with miR-125b-5p levels and positively correlated with HK2 and PKM2 expression. miR-125b-5p expression was negatively correlated with HK2 and PKM2 expression. In conclusion, MIR210HG affected the phenotypes of pancreatic cancer cells, including proliferation, invasion, migration, and glycolysis, via modulating the miR-125b-5p/HK2/PKM2 axis.

Expression of CAMK1 and its association with clinicopathologic characteristics in pancreatic cancer.

Calcium/calmodulin-dependent protein kinase (CAMKs) can control a wide range of cancer-related functions in multiple tumour types. Herein, we explore the expressions and clinical significances of calcium/calmodulin-dependent protein kinase 1 (CAMK1) in pancreatic cancer (PC). The expression of CAMK1 in PC was analysed by Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database and the Oncomine database. For further validation, the protein level of CAMK1 in PC tissues was also detected in the Human Protein Atlas (HPA) database and the tissue microarray (TMA)-based immunohistochemistry (IHC). GEPIA 2 and Kaplan-Meier Plotter (KM Plotter) databases were used to explore the prognostic significances of CAMK1 in overall survival (OS) and disease-free survival (DFS) of PC at mRNA level. The relationship between CAMK1 expression and the clinicopathological characteristics of PC was further explored. Additionally, the Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyse protein-protein interactions (PPI). We found CAMK1 was highly expressed in PC both in bioinformatics analyses and TMA-IHC results. The prognostic analyses from the public databases also showed consistent results with follow-up data. The PPI network suggested that CALM1, CALM3, CREB1, CALM2, SYN1, NOS3, ATF1, GAPDH, PPM1F and FBXL12 were important significant genes associated with CAMK1. Our finding revealed CAMK1 has prognostic value in PC patients, suggesting that CAMK1 may has a distinct role in PC patients and can be used as a candidate marker for investigating clinical prognosis of PC.

An iodine-125 seed strand combined with a metal stent versus a metal stent alone for obstructive jaundice caused by pancreatic ductal adenocarcinoma.

PURPOSE: The purpose of this study was to assess the efficacy of an iodine-125 (125I) seed strand combined with a metal stent compared with a metal stent for treatment of obstructive jaundice caused by pancreatic ductal adenocarcinoma (PDAC). METHODS AND MATERIALS: A retrospective analysis was carried out of patients who were referred to Shanghai Zhongshan Hospital of Fudan University with a diagnosis of PDAC between January 1, 2010 and January 31, 2019. A total of 110 consecutive patients with obstructive jaundice caused by PDAC were divided into the iodine-125 seed strand combined with a metal stent group (Group A = 48) and the metal stent group (Group B = 62). The primary outcome was stent obstruction-free survival time, and secondary outcomes were overall survival and complications. RESULTS: The median stent obstruction-free survival time was 133.0 (95% confidence interval (CI): 166.093-149.907) days, and the median overall survival was 212.0 (95% CI: 187.183-236.817) days in all patients. Median stent obstruction-free survival time was 175 days (95% CI 103.165-246.835 days) in Group A versus 120 days (95% CI 87.475-152.525 days) in Group B (p = 0.035). A lower Eastern Cooperative Oncology Group (ECOG) score (p = 0. 000) and iodine-125 seed strand combined with metal stent implantation (p = 0.008) were associated with a longer stent obstruction-free survival time. Obstruction length (p = 0.083), ECOG score (p = 0.000), and iodine-125 seeds (p = 0.037) might have potential impact on stent obstruction-free survival time and were included for multivariable analysis using the Cox proportional hazards model. Stent restenosis was observed in 18.8% (9/48) of patients in Group A and 54.8% (34/62) in Group B, respectively. There was no significant difference in median survival between Group A and Group B (p = 0.409). The median survival in Group A was 209 days (95% CI 150.750-267.250) and 202 days (95% CI 190.624-233.376) in Group B. The median survival of patients with a lower ECOG score was better than that of patients with a higher ECOG score (267 days vs 132 days, p = 0.000). The Grade 3 or 4 complications occurred in 4 (8.3%) of the 48 patients in Group A (one case of hemobilia, one case of liver abscess, two cases of choleperitonitis) and in 5 (8.1%) of the 62 patients in Group B (one case of hemobilia, two cases of liver abscess, two cases of choleperitonitis) (p = 0.972). CONCLUSIONS: Implantation of an iodine-125 seed strand combined with a metal stent provides longer obstruction-free survival time compared with a metal stent in patients with obstructive jaundice caused by PDAC. It seems reasonable to choose an iodine-125 seed strand combined with a metal stent as a treatment for these patients.

Percutaneous intraductal radiofrequency ablation combined with biliary stent placement for treatment of malignant biliary obstruction.

PURPOSE: To determine the safety and efficacy of percutaneous intraductal radiofrequency ablation (RFA) combined with biliary metal stent placement for patients with unresectable malignant biliary obstruction. METHODS: From a cohort of 70 patients with unresectable malignant biliary obstruction, 28 patients received percutaneous intraductal RFA combined with biliary stent placement (group A) and the remaining 42 were treated with biliary metal stent placement only (group B). Stent patency, overall survival (OS), alleviation of jaundice, and postoperative complications were assessed. RESULTS: The technical success rate for both groups was 100%. No severe complications (e.g., biliary bleeding, perforation) occurred. In both groups, jaundice was relieved and the decrease of the total and direct bilirubin concentration was significant (p < 0.01). The median time of stent patency in group A and group B were 6.6 ± 0.3 months (95% CI 6.1-7.1 months) and 4.9 ± 0.4 months (95% CI 4.2-5.6 months), respectively (p < 0.01). The median overall survival times in Group A were 7.2 ± 0.3 months (95% CI 6.5-7.9 months) versus 5.6 ± 0.4 months (95% CI 4.8-6.4 months) in group B (p < 0.01). In univariate and multivariate analyses, intraductal RFA, stent patency, and decreased baseline serum direct bilirubin concentration were associated with greater OS (p < 0.05). CONCLUSION: Percutaneous intraductal RFA combined with stent placement is a safe and effective method for patients with malignant biliary obstruction. As compared to stent placement alone, percutaneous intraductal RFA can significantly prolong stent patency and improve the overall survival of patients with malignant biliary obstruction.

The Efficacy and Safety of Transcatheter Arterial Embolization to Treat Renal Hemorrhage after Percutaneous Nephrolithotomy.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of transcatheter arterial embolization (TAE) in patients with renal hemorrhage after percutaneous nephrolithotomy (PCNL) and evaluate the risk factors that may result in severe bleeding requiring TAE. METHODS: We retrospectively reviewed 121 patients with post-PCNL renal hemorrhage. Thirty-two patients receiving endovascular embolization were compared with 89 patients only receiving conservative treatment. The demographic and clinical data were recorded and compared between the two groups. The values of estimated glomerular filtration rate (eGFR) and serum creatinine (SCr) were recorded preoperatively, postoperatively, and at last follow-up and analyzed to evaluate the safety and efficiency of TAE. RESULTS: The successful hemostasis rate of conservative therapy was 73.6% (89/121) and that of TAE was 100% (32/32). SCr and eGFR were not significantly different before PCNL and after the last follow-up of TAE (SCr: 0.95 vs. 0.95 mg/dl, P=0.857; eGFR: 86.77 vs. 86.18 ml/min/1.73m2, P=0.715). The univariate analysis demonstrated that advanced age, urinary tract infection, and diabetes mellitus were significantly associated with severe bleeding during PCNL. Multivariate analysis further identified that diabetes mellitus was an independent risk factor for severe bleeding needing TAE [odds ratio (OR): 3.778, 95% confidence interval (CI):1.276-11.190, and P=0.016]. CONCLUSION: TAE is a safe and effective procedure to treat renal hemorrhage that cannot be resisted by conservative treatment after PCNL. Diabetes mellitus was associated with high risks of severe bleeding needing TAE after PCNL.

Transradial access chemoembolization for hepatocellular carcinoma in comparation with transfemoral access.

BACKGROUND: This study aimed to compare the safety and efficacy of transradial access (TRA) with transfemoral access (TFA) chemoembolization in treatment of hepatocellular carcinoma (HCC). METHODS: HCC patients who were late for curative treatment on initial diagnosis or HCC patients who had undergone one or several rounds of transarterial chemoembolization (TACE) were enrolled. The clinical and angiographic characteristics, the procedure related details, and the follow-up data from patients who underwent TRA and TFA were analyzed and compared. RESULTS: In total, 112 patients undergoing 160 TRA-TACE and 107 patients undergoing 163 TFA-TACE were included. The technical success rate of TRA was 95.0% and that of TFA was 98.8% (P=0.102). In the TFA-TACE group, 5.5% of cases suffered access site-related complications, including 6 with minor bleeding and 3 with severe bleeding or pseudoaneurysm. In the TRA-TACE group, 1.9% of cases underwent crossover to femoral access for selective cannulation failure. The rate of radial artery occlusion (RAO) was 2.7% (3 of 112 patients), and none of the RAO patients suffered paresthesia, pain at the site of occlusion, hand function loss or distal ischemia. Comparing patients with/without access site-related complications in the TFA-TACE group, there was a statistical difference in patient age and in the percentage of patient with a PT time >15 s (72.6% vs. 57.1%, P<0.001; 44.4% vs. 11.7%, P=0.022). CONCLUSIONS: TRA is a safe and effective method for patients undergoing TACE. Compared with TFA, TRA may reduce the occurrence of access site-related bleeding and vascular complications. TRA-TACE may especially benefit older patients or those with a longer prothrombin time (PT).

A Dual Targeting Dendrimer-Mediated siRNA Delivery System for Effective Gene Silencing in Cancer Therapy.

Small interfering RNA (siRNA) is emerging as a novel therapeutic for treating various diseases, provided a safe and efficient delivery is available. In particular, specific delivery to target cells is critical for achieving high therapeutic efficacy while reducing toxicity. Amphiphilic dendrimers are emerging as novel promising carriers for siRNA delivery by virtue of the combined multivalent cooperativity of dendrimers with the self-assembling property of lipid vectors. Here, we report a ballistic approach for targeted siRNA delivery to cancer cells using an amphiphilic dendrimer equipped with a dual targeting peptide bearing an RGDK warhead. According to the molecular design, the amphiphilic dendrimer was expected to deliver siRNA effectively, while the aim of the targeting peptide was to home in on tumors via interaction of its warhead with integrin and the neuropilin-1 receptor on cancer cells. Coating the positively charged siRNA/dendrimer delivery complex with the negatively charged segment of the targeting peptide via electrostatic interactions led to small and stable nanoparticles which were able to protect siRNA from degradation while maintaining the accessibility of RGDK for targeting cancer cells and preserving the ability of the siRNA to escape from endosomes. The targeted system had enhanced siRNA delivery, stronger gene silencing, and more potent anticancer activity compared to nontargeted or covalent dendrimer-based systems. In addition, neither acute toxicity nor induced inflammation was observed. Consequently, this delivery system constitutes a promising nonviral vector for targeted delivery and can be further developed to provide RNAi-based personalized medicine against cancer. Our study also gives new perspectives on the use of nanotechnology based on self-assembling dendrimers in various biomedical applications.

Lactic dehydrogenase to albumin ratio in prediction of unresectable pancreatic cancer with intervention chemotherapy.

AIM: To validate the prognostic value of lactic dehydrogenase to albumin ratio (LAR) in patients with unresectable pancreatic cancer treated by intervention chemotherapy. MATERIALS & METHODS: There were 139 patients retrospectively analyzed in this study. The survival was depicted with Kaplan-Meier curves and calculated by log-rank test. We used Cox proportional hazards regression model with univariate and multivariate analyses, and integrated all independent risk factors to establish the nomogram. RESULTS: Patient with higher LAR group had poorer overall survival (OS). The Tumor, Node, Metastasis stage, carcinoembryonic antigen and LAR have been shown to be independent prognostic indicators for OS. The nomogram indicated superior predictive accuracy for OS. CONCLUSION: The preoperative LAR can be a prognostic indicator for unresectable pancreatic cancer patients with interventional therapy.

Detection of CTCs in portal vein was associated with intrahepatic metastases and prognosis in patients with advanced pancreatic cancer.

Pancreatic cancer is amongst the most lethal malignancies with increasing incidence and mortality worldwide. Distant metastases, especially intrahepatic metastases, is the leading cause of death for pancreatic cancer. Circulating tumor cells (CTCs) are neoplastic cells released from the primary tumor into circulation, and play critical roles in metastases of various types of cancers. Though clinical studies showed that detection of CTCs in peripheral circulation was associated with worse prognosis in patients with breast cancer and hepatocellular carcinoma, detection CTCs in peripheral blood of pancreatic cancer was still challenging due to hepatic filtration and technical limitations. Previous studies have demonstrated that CTCs could be detected in portal vein circulation in patients with pancreaticobiliary carcinoma. In the present study, taking advantage of ultrasonography-guided transhepatic puncture, we analysis CTCs in portal vein blood obtained from patients with advanced pancreatic cancer. CTCs were detected in all 29-portal vein blood of samples, and absolute numbers of circulating pancreatic cancer cells in portal vein was significantly higher than that in peripheral circulation. Furthermore, we found that CTC counts in portal vein was highly associated with intrahepatic metastases and indicated poorer prognosis in patients with advanced pancreatic cancer. Short-term expansion and in vitro drug sensitivity assay showed that CTCs derived from portal vein blood were highly resistant to several chemotherapy regimens. In summary, detection of CTCs in portal vein could be a powerful tool to stratify the risk of intrahepatic metastases of pancreatic cancer, and provided new insight into the biological feature of pancreatic cancer metastases and drug resistance.

Endovascular brachytherapy combined with portal vein stenting and transarterial chemoembolization improves overall survival of hepatocellular carcinoma patients with main portal vein tumor thrombus.

Hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus have a median survival time of only about 4 months. We therefore compared the safety and efficacy of endovascular brachytherapy (EVBT) and sequential three-dimensional conformal radiotherapy (3-DCRT). From a cohort of 176 patients, we treated 123 with EVBT using iodine-125 seed strands (group A) and the remaining 53 with sequential 3-DCRT (group B). Overall survival, progression free survival and stent patency characteristics were compared between the two groups. Our analysis demonstrated a median survival of 11.7 ± 1.2 months in group A versus 9.5 ± 1.8 months in group B (p = 0.002). The median progression free survival was 5.3 ± 0.7 months in groupA versus 4.4 ± 0.4 months in group B (p = 0.010). The median stent patency period was 10.3 ± 1.1 months in group A versus 8.7 ± 0.7 months in group B (p = 0.003). Therefore, as compared to sequential 3-DCRT, EVBT combined with portal vein stenting and TACE improved overall survival of HCC patients with main portal vein tumor thrombus.

A pilot study of intraluminal brachytherapy using 125I seed strand for locally advanced pancreatic ductal adenocarcinoma with obstructive jaundice.

PURPOSE: To investigate the safety and feasibility of intraluminal brachytherapy using 125I seed strand for locally advanced pancreatic ductal adenocarcinoma with obstructive jaundice. METHODS AND MATERIALS: From January 2010 to February 2015, 18 consecutive patients diagnosed with locally advanced, nonmetastatic, inoperable pancreatic ductal adenocarcinoma with obstructive jaundice were enrolled and underwent intraluminal brachytherapy using 125I seed strand. Dose calculation was performed using a software. The procedure-related and radiation complications were assessed. Obstruction-free survival and overall survival were calculated using the Kaplan-Meier method. RESULTS: The technique successful rate of 125I seed strand implantation was 100%. Successful bile drainage was achieved in all patients. The estimated mean accumulating dose (R = 5 mm, z = 0, 240 days) was 167.2 Gy, from 164.19 to 170.05 Gy. Two patients had adverse event of Grade 3, one of Grade 4. Stent dysfunction occurred in 1/18 (5.6%) patients. The mean and median obstruction-free survival time were 10.61 months (95% confidence interval [CI]: 7.04, 14.18) and 7.26 months (95% CI: 2.14, 12.38). The mean and median overall survival time were 11.91 months (95% CI: 7.39, 16.43) and 7.26 months (95% CI: 2.14, 12.38). CONCLUSIONS: Intraluminal brachytherapy using 125I seed strand may be consider as a safe treatment option for the therapy of locally advanced pancreatic duct adenocarcinoma complicated by obstructive jaundice with acceptable complication rates.

Mastering Dendrimer Self-Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing.

Self-assembly is a fundamental concept and a powerful approach in molecular science. However, creating functional materials with the desired properties through self-assembly remains challenging. In this work, through a combination of experimental and computational approaches, the self-assembly of small amphiphilic dendrons into nanosized supramolecular dendrimer micelles with a degree of structural definition similar to traditional covalent high-generation dendrimers is reported. It is demonstrated that, with the optimal balance of hydrophobicity and hydrophilicity, one of the self-assembled nanomicellar systems, totally devoid of toxic side effects, is able to deliver small interfering RNA and achieve effective gene silencing both in cells - including the highly refractory human hematopoietic CD34(+) stem cells - and in vivo, thus paving the way for future biomedical implementation. This work presents a case study of the concept of generating functional supramolecular dendrimers via self-assembly. The ability of carefully designed and gauged building blocks to assemble into supramolecular structures opens new perspectives on the design of self-assembling nanosystems for complex and functional applications.

Adaptive amphiphilic dendrimer-based nanoassemblies as robust and versatile siRNA delivery systems.

siRNA delivery remains a major challenge in RNAi-based therapy. Here, we report for the first time that an amphiphilic dendrimer is able to self-assemble into adaptive supramolecular assemblies upon interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the currently available nonviral vectors. In addition, this amphiphilic dendrimer is able to harness the advantageous features of both polymer and lipid vectors and hence promotes effective siRNA delivery. Our study demonstrates for the first time that dendrimer-based adaptive supramolecular assemblies represent novel and versatile means for functional siRNA delivery, heralding a new age of dendrimer-based self-assembled drug delivery in biomedical applications.

Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation.

BACKGROUND: Irritable bowel syndrome (IBS) is characterized by chronic visceral hyperalgesia (CVH) that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H2S) producing enzyme cystathionine beta-synthetase (CBS) and p65 nuclear factor-kappa B subunits in CVH. RESULTS: CVH was induced by neonatal maternal deprivation (NMD) in male rats on postnatal days 2-15 and behavioral experiments were conducted at the age of 7-15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7th to 12th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD), an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD. CONCLUSION: The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS.

An amphiphilic dendrimer for effective delivery of small interfering RNA and gene silencing in vitro and in vivo.

An amphiphilic dendrimer bearing a hydrophobic alkyl chain and hydrophilic poly(amidoamine) dendrons is able to combine the advantageous features of lipid and dendrimer vectors to deliver a heat shock protein 27 siRNA and produce potent gene silencing and anticancer activity in vitro and in vivo in a prostate cancer model. This dendrimer can be used alternatively for treating various diseases.