Therapeutic advances in cardiac targeted drug delivery: from theory to practice.

The most commonly used administration methods in clinics and life are oral administration, intravenous injection, and other systemic administration methods. Targeted administration must be an essential long-term development direction due to the limited availability and a high incidence of systemic side effects. Cardiovascular diseases (CVD) are the leading cause of death all over the world. Targeted drug delivery (TDD) methods with the heart as the target organ have developed rapidly and are diversified. This article reviews the research progress of various TDD methods around the world with a heart as the target organ. It is mainly divided into two parts: the targeting vector represented by nanoparticles and various TDD methods such as intracoronary injection, ventricular wall injection, pericardial injection, and implantable medical device therapy and put forward some suggestions on the development of targeting. Different TDD methods described in this paper have not been widely used in clinical practice, and some have not even completed preclinical studies. Targeted drug delivery still requires long-term efforts by many researchers to realize the true meaning of the heart. HIGHLIGHTS Targeted administration can achieve a better therapeutic effect and effectively reduce the occurrence of adverse reactions. Parenteral administration or medical device implantation can be used for targeted drug delivery. Combined with new dosage forms or new technologies, better-targeted therapy can be achieved. Clinical trials have confirmed the safety and effectiveness of several administration methods.

Clinical evaluation of carcinoembryonic and carbohydrate antigens as cancer biomarkers to monitor palliative chemotherapy in advanced stage gastric cancer.

BACKGROUND: Carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125, CA19-9, and CA72-4 are often found modulated parameters in gastric cancer. OBJECTIVE: Our present study is focused to evaluate the synchronization of these biomarkers in response to palliative chemotherapy. METHOD: A retrospective study was conducted on 216 gastric cancer patients undergoing first-line cisplatin chemotherapy along with antiangiogenic regimen. Blood samples were taken and analyzed biochemically and statistically. RESULTS: Progression occurred in 78 of 216 patients and the median progression-free survival (PFS) was 5 months. For serum CEA, the median PFS was 4 versus 7 months for elevated and normal groups respectively (P = 0.01). The median PFS for normal and elevated CA19-9 and CA72-4 was 6 vs 4 months respectively (P = 0.001). In the multivariate Cox regression model, elevated pretreatment level of CEA, CA19-9, and distant metastases were independent factors associated with increased risk of progression (P = 0.021, P = 0.000, P = 0.006, respectively). CONCLUSIONS: Conclusively, elevated pretreatment level of CEA and CA19-9 is correlated with high risk of progression and worse prognosis. Moreover, an additional antiangiogenic therapy is more effective in decreasing cancer biomarker level after palliative chemotherapy that may be correlated with therapeutic triumph.

Current and future biomarkers in gastric cancer.

Gastric cancer is the fourth most common worldwide cause of cancer-related death. Early gastric cancer has no associated symptoms, for this reason, patients come to the attention of the clinicians only in advanced stages. This paper aims to give a global view on the biomarkers for gastric cancer and the therapy in use. We discuss VEGF family, HER family, E-cadherin, PD-L1, and PD-L2, FGFR, mTOR. Finally, we considered emerging biomarkers as MET, microsatellite instability, and microRNA variations. Furthermore, we have analyzed in depth the chemotherapeutic and adjuvant therapies used in the clinic nowadays, comparing the overall and progression-free survival between them. Identifying and validating diagnostic, prognostic, predictive, and pharmacodynamic biomarkers will be mandatory to the huge impact on patients' outcomes and for improving the efficiency of the drug development process.

The promising future of ventricular restraint therapy for the management of end-stage heart failure.

Complicated pathophysiological syndrome associated with irregular functioning of the heart leading to insufficient blood supply to the organs is linked to congestive heart failure (CHF) which is the leading cause of death in developed countries. Numerous factors can add to heart failure (HF) pathogenesis, including myocardial infarction (MI), genetic factors, coronary artery disease (CAD), ischemia or hypertension. Presently, most of the therapies against CHF cause modest symptom relief but incapable of giving significant recovery for long-term survival outcomes. Unfortunately, there is no effective treatment of HF except cardiac transplantation but genetic variations, tissue mismatch, differences in certain immune response and socioeconomic crisis are some major concern with cardiac transplantation, suggested an alternate bridge to transplant (BTT) or destination therapies (DT). Ventricular restraint therapy (VRT) is a promising, non-transplant surgical treatment wherein the overall goal is to wrap the dilated heart with prosthetic material to mechanically restrain the heart at end-diastole, stop extra remodeling, and thereby ultimately improve patient symptoms, ventricular function and survival. Ventricular restraint devices (VRDs) are developed to treat end-stage HF and BTT, including the CorCap cardiac support device (CSD) (CSD; Acorn Cardiovascular Inc, St Paul, Minn), Paracor HeartNet (Paracor Medical, Sunnyvale, Calif), QVR (Polyzen Inc, Apex, NC) and ASD (ASD, X. Zhou). An overview of 4 restraint devices, with their precise advantages and disadvantages, will be presented. The accessible peer-reviewed literature summarized with an important considerations on the mechanism of restraint therapy and how this acquaintance can be accustomed to optimize and improve its effectiveness.

The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practice.

Gastric cancer (GC) is one among the major cancer types, causing human deaths and present noticeable heterogeneity. The incidences and mortality rates are higher in males in comparison to females with a male to female ratio of 2.3:1. A lot of studies have revealed out the molecular basis, pathogenesis, invasion and metastasis related findings of gastric stomach cancer. Present review encompasses the salient information on various biomarkers for the early diagnosis, treatment and prognosis of gastric cancer elaborate the clinical importance of serum tumor markers in patients with this cancer as well as checking the growths, together with epigenetic changes and genetic polymorphisms. A deep and rigorous search was carried out in Pub Med/MEDLINE using specific key words; "gastric cancer", with "tumor marker". Our search yielded 4947 important reports about related topic from books and articles that were published before the end of August 2017. Conclusively, Scientists are utilizing high time and resource to salvage this nemesis which is of global importance and cause health burden. Classical and novel biomarkers are important for treatment as well as pre- and post- diagnosis of GC. Major causes for GC are cigarette smoking, infection by Helicobacter pylori, atrophic gastritis, sex/gender, and high salt intake. Early diagnoses of GC is important for the management, treatment, pathological diagnoses by stage prognosis and metastatic setting; although the treatment outcome proved to be not much fruitful following chemotherapy, and oral medication with oxaliplatin, capecitabine, cisplatin and 5- fluorouracil (5-FU). More research studies and exploring the practical usage of gastric cancer biomarkers in diagnosis, prognosis and pre- and post- chemotherapy in clinical practice for countering gastric cancers would alleviate to some extent the ill health sufferings of humans being caused by this important and common cancerous condition.

Influence of Calcineurin Gene Polymorphisms on the Efficacy of Cyclosporine A / 中国药房

OBJECTIVE:To study the influence of calcineurin gene polymorphism on the efficacy of cyclosporine A (CsA). METHODS:The blood samples of patients treated with CsA were collected. The trough blood concentration of CsA was detected by EMIT. The genotype of PPP3CA and PPP3CB was assayed by RFLP-PCR method. The expression of NFAT-regulated gene IL-2, IFN-γand GM-CSF were measured by RT-qPCR,which were used to define the index of indirect efficacy of CsA. The relationship of gene polymorphism with CsA efficacy was study by relationship analysis and multiple factor regression method,etc. RESULTS:A to-tal of 100 blood samples were collected. There was no significant correlation between the expression of CsA efficacy-related NFAT-reg-ulated gene GM-CSF and trough concentration of CsA(rGM-CSF=-0.04,P=0.238);the expression of IL-2 and IFN-γ were negatively correlated with trough concentration of CsA significantly(rIL-2=-0.384 3,P0.05). Stratified analysis showed that among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 genovariation(TC+TT) were better than those with wild-type gene (CC)(P<0.05). After the efficacy was normalized by CsA trough concentration, multivariate analysis showed that normalized efficacy of CsA was negatively correlated with gender,PPP3CB rs3763679,lactate dehy-drogenase and creatinine significantly,but positively correlated with PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate,etc. CONCLUSIONS:PPP3CB rs3763679 gene polymorphism influence the efficacy of CsA;among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 TT+TC is better than that of CC type. At the same time,gender,PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate and other factors all can influence the nor-malized efficacy of CsA to different extent. Multiple factors should be considered when using CsA.

Protective effects of losartan potassium on 5/6 nephrectomy-induced chronic heart failure in rats / 中国药科大学学报

@#The purpose of this research is to investigate the therapeutic effects of losartan potassium on 5/6 nephrectomy rats with chronic heart failure(CHF)and to explore the mechanism. 24 Rats were randomly divided into three groups namely sham group(Sham), pathology group(Nx)and losartan potassium group(Lst), respectively. CHF model in rats were induced by 5/6 nephrectomy. At the 7th week, rats of Lst group were given losartan potassium(50 mg/L)for consecutive 2 weeks. Then all rats were measured for hemodynamic parameters, cardiac index, creatinine, urea nitrogen in serum, and expressions of CD133, VEGFR2, Sox2, cleaved Caspase-3 and Bcl-2 in heart. Compared with Nx group, rats of Lst group improved cardiac and renal functions: decreased LVDP, LVEDP, cardiac index, creatinine, urea nitrogen and increased LVSP. Furthermore, losartan potassium up-regulated gene expression of CD133, VEGFR2, Sox2 and protein level of Bcl-2, and down-regulated cleaved Caspase-3 protein expression. Results suggest that losartan potassium can improve cardiac function of rats with CHF which may be correlated with mobilizing bone marrow stem cells, increasing endothelial progenitor cells(EPCs)level in heart, repairing endothelial function, and inhibiting myocardial apoptosis.