HPMA-oligolysine copolymers for gene delivery: Optimization of peptide length and polymer molecular weight

Polycations are one of the most frequently used classes of materials for non-viral gene transfer in vivo. Several studies have demonstrated a sensitive relationship between polymer structure and delivery activity. In this work, we used reverse addition-fragmentation chain transfer (RAFT) polymerization to build a panel of N-(2-hydroxypropyl)methacrylamide (HPMA)-oligolysine copolymers with varying peptide length and polymer molecular weight. The panel was screened for optimal DNA-binding, colloidal stability in salt, high transfection efficiency, and low cytotoxicity. Increasing polyplex stability in PBS correlated with increasing polymer molecular weight and decreasing peptide length. Copolymers containing K₅ and K₁₀ oligocations transfected cultured cells with significantly higher efficiencies than copolymers of K₁₅. Four HPMA-oligolysine copolymers were identified that met the desired criteria. Polyplexes formed with these copolymers demonstrated both salt stability and transfection efficiencies on-par with poly(ethylenimine) PEI in cultured cells.     

一氧化氮在神经退行性疾病中的作用:非类固醇性抗炎药的治疗前景(英文)

一氧化氮(nitric oxide, NO)是一类胞内信使。研究表明,神经退行性病人脑组织中催化合成NO的酶的表达水平显著提高,提示NO与神经退行性疾病密切相关。此外,在这些组织中还检测到硝化的蛋白,提示NO在这些组织中具有生物活性。在神经免疫应答中,神经元和胶质细胞(包括小胶质细胞和星形胶质细胞)内都发生了NO水平的改变。很多神经退行性疾病都伴随有神经炎症,抑制神经炎症的信号通路能延迟这些疾病的发展。因此,NO及其释放通路已逐渐成为神经退行性疾病研究领域的热点,对它们的理解能帮助我们找到合适的方案来预防、减缓或者治愈这些疾病。     

EGFR and HER3 mRNA expression levels predict distant metastases in locally advanced rectal cancer

Aberrant activation of the HER signaling pathways plays a critical role in the invasive and metastatic potential of tumors. The aim of this study was to address whether, in rectal cancer, alterations of these pathways could have a value as prognostic factors to be used to identify patients who are at risk of distant metastases. Therefore, the mRNA expression of the four members of the HER family as well as the frequency of PTEN allelic loss and KRAS/BRAF mutations were determined in pretreatment biopsies from a series of 100 locally advanced rectal cancers and then their ability to predict distant metastases was evaluated. Over‐expression of EGFR (p = 0.021), HER2 (p = 0.011) and HER3 (p = 0.020) was significantly associated with worse metastasis‐free survival in univariate analysis. In multivariate analysis, both over‐expression of EGFR (p = 0.028) and HER3 (p = 0.011) remained independent prognostic factors for distant metastasis. In conclusion, quantification of EGFR and HER3 mRNA expression in pretreatment biopsies may be useful to identify patients who are at risk of developing metastases.     

Intrareader variability in mammographic diagnostic and perceptual performance amongst experienced radiologists in Australia

Introduction: The purpose of this study was, for a group of experienced radiologists, to identify the magnitude of and statistical significance of intrareader variability in mammographic diagnostic performance or cancer diagnosis and mammographic perceptual performance or microcalcification detection. Methods: Eight radiologist readers (8–30 years experience in radiology, five current BreastScreen readers) read a set of 100 digital mammograms on two separate reads with random case orders. Twenty‐three of the 100 had proven malignancies, and 52 of the 100 had confirmed microcalcifications. The same mammograms were presented for both reads. The radiologists were requested to clear or call back cases and to indicate if any benign and malignant microcalcifications were present on the mammograms. Reading conditions were standardised. Results: Intrareader variability in accuracy was demonstrated to be between 0% and 6% for the diagnostic task of breast cancer diagnosis and between 0% and 16% for the perceptual task of microcalcification detection. Intrareader agreement in the group of readers was high; between 75% and 93% (κ = 0.36–0.72) for cancer diagnosis and between 77.5% and 93% (κ = 0.17–0.77) for microcalcification detection. There was no correlation between reader's experience in radiology or being a BreastScreen reader and level of intrareader variability in cancer diagnosis and microcalcification detection. Conclusion: There exists intrareader variability in diagnostic and perceptual performance. Despite this variability, intrareader agreement remains high.     

Relapse of kala-azar after use of multiple drugs: a case report and brief review of literature

We present a case of kala-azar infection that recurred in a patient after completion of the standard treatment course of miltefosine, amphotericin B-deoxycholate (short course), and amphotericin B lipid formulations. The patient was cured after continuous amphotericin B-deoxycholate administration for 4 weeks. This is a unique case of relapse following the use of three important drugs. Although amphotericin B-deoxycholate is a second line drug in Nepal, it has shown a satisfactory clinical response with continuous treatment for 4 weeks. Therefore, an extended course of amphotericin B-deoxycholate may be beneficial in patients with resistance to the standard short course and other anti-leishmania drugs.     

Docetaxel-induced nail toxicity: a case of severe onycholysis and topic review

Docetaxel is a commonly-used anti-cancer chemotherapeutic agent given its efficacy in a large variety of solid tumors. It is associated with various adverse effects one of which is nail toxicity. We report a case of severe onycholysis as a result of treatment with docetaxel in a patient who suffered from metastatic nasopharyngeal carcinoma. The case report will be followed by a discussion on the possible mechanism and preventive strategies for taxane-induced nail toxicity. 

     

Risk Factors for Nonsynchronous Second Primary Malignancy and Related Death in Patients with Differentiated Thyroid Carcinoma

Background  

Differentiated thyroid cancer (DTC) survivors are at increased risk of developing nonsynchronous second primary malignancy (NSPM). This study aims to examine possible risk factors leading to occurrence of NSPM as well as risk factors leading to NSPM-related death in patients with DTC.     

Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network

Purpose

We aimed to validate the Multinational Association for Supportive Care in Cancer (MASCC) risk index, and compare it with the Talcott model and artificial neural network (ANN) in predicting the outcome of febrile neutropenia in a Chinese population.

Methods

We prospectively enrolled adult cancer patients who developed febrile neutropenia after chemotherapy and risk classified them according to MASCC score and Talcott model. ANN models were constructed and temporally validated in prospectively collected cohorts.

Results

From October 2005 to February 2008, 227 consecutive patients were enrolled. Serious medical complications occurred in 22% of patients and 4% died. The positive predictive value of low risk prediction was 86% (95% CI?=?81?C90%) for MASCC score????21, 84% (79?C89%) for Talcott model, and 85% (78?C93%) for the best ANN model. The sensitivity, specificity, negative predictive value, and misclassification rate were 81%, 60%, 52%, and 24%, respectively, for MASCC score????21; and 50%, 72%, 33%, and 44%, respectively, for Talcott model; and 84%, 60%, 58%, and 22%, respectively, for ANN model. The area under the receiver-operating characteristic curve was 0.808 (95% CI?=?0.717?C0.899) for MASCC, 0.573 (0.455?C0.691) for Talcott, and 0.737 (0.633?C0.841) for ANN model. In the low risk group identified by MASCC score????21 (70% of all patients), 12.5% developed complications and 1.9% died, compared with 43.3%, and 9.0%, respectively, in the high risk group (p?<?0.0001).

Conclusions

The MASCC risk index is prospectively validated in a Chinese population. It demonstrates a better overall performance than the Talcott model and is equivalent to ANN model.     

Rotavirus infections with multiple emerging genotypes in Sri Lanka

Rotavirus diarrhea is an important cause of child mortality in developing countries, but studies on this diarrhea are scarce in Sri Lanka. A prospective study conducted in Sri Lanka on rotavirus infection among children in a hospital setting (n = 611) versus children residing in tsunami camps (n = 52) showed that prevalence of rotavirus infection was comparable, 21.9 and 20%, respectively. The hospital and camps were located in different districts. Analysis of the genotypes of 122 rotaviruses from the hospital and 12 from the camps indicated that G9P[8] was associated with 35 and 33%; G12P[8/nt] with 14.7 and 33%; G3P[8/4/nt] with 17 and 8% and G1P[8/4] with 6.5 and 16.7%. Rotaviruses with G2P[8/4/6] and G4P[8/4] were hospital-associated only, and some rotaviruses (9 and 8% from the hospital and the camps, respectively) were G- and P-nontypable. We conclude from the present study that multiple emerging genotypes were prevalent in Sri Lanka, and children in camps were at risk of developing diarrhea due to rotaviruses.