Deliang Fu

Hydrophilic multi-walled carbon nanotubes decorated with magnetite nanoparticles as lymphatic targeted drug delivery vehicles

Hydrophilic multi-walled carbon nanotubes decorated with magnetite nanoparticles were readily taken up into lymph vessels and delivered gemcitabine to lymph nodes with high efficiency under the guidance of a magnetic field.

Magnetic functionalised carbon nanotubes as drug vehicles for cancer lymph node metastasis treatment

Strategies using carbon-based nanomaterials as carriers for delivering chemotherapeutic drugs to cancers have been described well. Here a novel magnetic lymphatic-targeting drug-delivery system, based on functionalised carbon nanotubes (fCNTs), is presented with the aim of improving the outcome of cancer with lymph node involvement. The potential therapeutic effect of gemcitabine (GEM) loading magnetic multiwalled carbon nanotubes (mMWNTs) was compared with that of GEM loading magnetic-activated carbon particles (mACs) in vitro and in vivo. mMWNTs-GEM and mACs-GEM both had high anti-tumour activity in vitro similar to free drug. Subcutaneous administration of GEM loading magnetic nanoparticles resulted in successful regression and inhibition of lymph node metastasis under the magnetic field, with mMWNTs-GEM superior to mACs-GEM, and more effectively in the high-dose versus low-dose groups. The successful application of intra-lymphatic delivery of chemotherapeutics using mMWNTs highlights the clinical potential of fCNTs for future cancer metastasis treatment with high efficacy and minimum side-effects.

LyP-1-conjugated nanoparticles for targeting drug delivery to lymphatic metastatic tumors

Active tumor targeting by biodegradable nanoparticles has been widely studied for cancer diagnosis and therapy. However, target-specific nanoparticles for drug delivery to lymphatic metastases have not been reported yet due to the lack of specific markers in the tumor lymphatics. Recently, peptide LyP-1 has been recognized for its specific home to tumors and their lymphatics. In this study, we tested the possibility of LyP-1 serving as a target-specific peptide of PEG-PLGA nanoparticles to tumor lymph metastases. LyP-1 was synthesized by using Boc-protected amino acids. The copolymers of maleimide-PEG-PLGA were formed by the conjugation of maleimide-PEG-NH(2) to PLGA-COOH, which were applied to prepare pegylated nanoparticles with mPEG-PLGA by means of double emulsion/solvent evaporation technique. LyP-1 with sulfhydryl group was conjugated to the maleimide function located at the distal end of PEG surrounding the nanoparticle surface. LyP-1-conjugated PEG-PLGA nanoparticle (LyP-1-NPs) had a round and regular shape with a diameter around 90 nm. In vitro, cellular uptake of LyP-1-NPs was about four times of that of PEG-PLGA nanoparticles without LyP-1 (NPs). In vivo, the uptake of LyP-1-NPs in metastasis lymph nodes was about eight times of that of NPs. This study indicates that LyP-1-NP is a promising carrier for target-specific drug delivery to lymphatic metastatic tumors.

Liposome based delivery systems in pancreatic cancer treatment: from bench to bedside.

Despite rapid advances in cancer diagnosis and treatment, pancreatic cancer remains one of the most difficult human malignancies to be treated, with a mortality rate nearly equal to its incidence. Although gemcitabine has been established as the standard first-line treatment for advanced pancreatic cancer, gemcitabine-based combination chemotherapy showed either marginal or no improvement in survival. Developments in liposomal delivery systems have facilitated the targeting of specific agents for cancer treatment. Such systems could be developed as platforms for future multi-functional theranostic nanodevices tailor-made for the combined detection of early cancer and functional drug delivery. We systemically review liposome based drug-delivery systems, which can provide improved pharmacokinetics, reduced side effects and potentially increased tumor uptake, for pancreatic cancer therapy. Novel liposomal formulations allowing for higher tumor targeting efficiencies and used in current clinical trials to treat this challenging disease are emphasized.

Emerging inorganic nanomaterials for pancreatic cancer diagnosis and treatment.

Pancreatic cancer is a devastating disease with incidence increasing at an alarming rate and survival not improved substantially during the past three decades. Although enormous efforts have been made in early detection and comprehensive treatment for this disease, little or no survival improvement was obtained, which necessitates the development of novel strategies. Emerging inorganic nanomaterials, such as carbon nanotubes, quantum dots, mesoporous silica/gold/supermagnetic nanoparticles, have been widely used in biomedical research with great optimism for cancer diagnosis and therapy. Such nanoparticles possess unique optical, electrical, magnetic and/or electrochemical properties. With such properties along with their impressive nano-size, these particles can be targeted to cancer cells, tissues, and ligands efficiently and monitored with extreme precision in real-time. In additional to liposome, dendrimer, and polymeric nanoparticles, they are considered the most promising nanomaterials with the capability of both cancer detection and multimodality treatment. Emerging approaches to harness nanotechnology to optimize the existing diagnostic and therapeutic tools for pancreatic cancer have been extensively explored during the recent years. Future options for early detection, individual therapy and monitoring responses of pancreatic cancer are focused on multifunctional nanomedicine. In this review, we present the recent development of clinically applicable inorganic nanoparticles, with focus on the diagnosis and treatment of pancreatic cancer. Furthermore, their advantages in theranostic nanomedicine, and challenges of translation to clinical practice, are discussed.

Pilot study of targeting magnetic carbon nanotubes to lymph nodes

AIM The lymphatic distribution of magnetic carbon nanotubes was studied in vivo and compared with magnetic-activated carbon particles, which were selectively taken up in the lymphatic channels and delivered to the regional lymph nodes. MATERIAL & METHODS Magnetic multiwalled carbon nanotubes functionalized with poly(acrylic acid) (mMWNTs) and magnetic-activated carbon particles were subcutaneously injected in mice. The draining lymph nodes were harvested at different times postadministration to examine the lymphatic distribution of these particles. The short-term accumulation and toxicity of mMWNTs in the major organs were studied. RESULTS mMWNTs had the same properties of lymph node mapping as magnetic-activated carbon particles in mice independent of lymph node metastasis. The degree of black staining of lymph nodes and concentration of mMWNTs had a dose-response relationship. Aggregation of magnetic particles was found around the metastatic foci within the lymph nodes. Footpad injection of mMWNTs did not cause any obvious local or systemic toxicities, and no particle agglomerates were found in the major organs. CONCLUSION The feasibility of targeting magnetic carbon nanotubes to lymph nodes was demonstrated and the results support further studies for their potential use in diagnosing and treating cancer.

Benefit from synchronous portal-superior mesenteric vein resection during pancreaticoduodenectomy for cancer: A meta-analysis

BACKGROUND Pancreaticoduodenectomy combined with portal-superior mesenteric vein synchronous resection for cancer remains a hot debate topic. The present study used meta-analytical technique to provide update information and an evidence-based evaluation on both the perioperative benefit and long-term survival. METHODS A meta-analysis was performed to evaluate studies comparing venous resection (VR) versus without venous resection (WVR) groups. 22 retrospective studies including 2890 patients were eligible for an analysis of perioperative morbidity, mortality, and long-term survival. Furthermore, subgroup analysis was made according to histopathology and resection margin status respectively for the purpose of survival assessment. RESULTS There was no difference in perioperative morbidity, mortality and 1-year, 3-year survival between two groups, but showed differences in median tumor size (P < 0.001), R0 resection rate (P < 0.001), lymph node metastasis (P = 0.03), pancreatic fistula (P = 0.01), and 5-year survival (P = 0.03). In subgroup analysis, patients in venous resection group received R0 resection had a significantly better survival comparing with who received R1 resection both at 2-year (P < 0.001) and 5-year (P = 0.00002). In histopathology subgroup, patients in venous resection groups who had true tumor infiltration had a significantly bad survival comparing with whom only with inflammation pathology. CONCLUSION Pancreaticoduodenectomy combined with venous resection can achieve equal perioperative morbidity and mortality as standard resection. However, in order to obtain an optimal survival outcome, surgeons should make an R0 resection as far as possible, especially in cases need synchronous venous resection.

Current status and progress of pancreatic cancer in China

Cancer is currently one of the most important public health problems in the world. Pancreatic cancer is a fatal disease with poor prognosis. As in most other countries, the health burden of pancreatic cancer in China is increasing, with annual mortality rates almost equal to incidence rates. The increasing trend of pancreatic cancer incidence is more significant in the rural areas than in the urban areas. Annual diagnoses and deaths of pancreatic cancer in China are now beyond the number of cases in the United States. GLOBOCAN 2012 estimates that cases in China account for 19.45% (65727/337872) of all newly diagnosed pancreatic cancer and 19.27% (63662/330391) of all deaths from pancreatic cancer worldwide. The populations growing socioeconomic status contributes to the rapid increase of Chinas proportional contribution to global rates. Here, we present an overview of control programs for pancreatic cancer in China focusing on prevention, early diagnosis and treatment. In addition, we describe key epidemiological, demographic, and socioeconomic differences between China and developed countries. Facts including no nationwide screening program for pancreatic cancer, delay in early detection resulting in a late stage at presentation, lack of awareness of pancreatic cancer in the Chinese population, and low investment compared with other cancer types by government have led to backwardness in Chinas pancreatic cancer diagnosis and treatment. Finally, we suggest measures to improve health outcomes of pancreatic cancer patients in China.

A preoperative serum signature of CEA+/CA125+/CA19-9 ≥ 1000 U/mL indicates poor outcome to pancreatectomy for pancreatic cancer

Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high‐volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19‐9 independently indicated surgical response in pancreatic cancer. Patients with CA19‐9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19‐9 levels decreased postoperatively. CEA and CA125 in the presence of CA19‐9 ≥1000 U/mL could independently predict the non‐decrease of CA19‐9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p < 0.001) for the training cohort and 7.0 months vs. 18.2 months (p < 0.001) for the validation cohort and also suggested a higher prevalence of early distant metastasis after surgery. Resected patients with this proposed signature showed no survival advantage over patients in the locally advanced group who did not receive pancreatectomy. Therefore, a preoperative serum signature of CEA+/CA125+/CA19‐9 ≥1000 U/mL is associated with poor surgical outcome and can be used to select appropriate patients with pancreatic cancer for pancreatectomy.

Lanreotide in metastatic enteropancreatic neuroendocrine tumors.

Martyn E. Caplin, D.M., Marianne Pavel, M.D., Jarosław B. Ć wikła, M.D., Ph.D., Alexandria T. Phan, M.D., Markus Raderer, M.D., Eva Sedláčková, M.D., Guillaume Cadiot, M.D., Ph.D., Edward M. Wolin, M.D., Jaume Capdevila, M.D., Lucy Wall, M.D., Guido Rindi, M.D., Ph.D., Alison Langley, M.Sc., Séverine Martinez, B.Sc., Joëlle Blumberg, M.D., and Philippe Ruszniewski, M.D., Ph.D., for the CLARINET Investigators*