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| 1 | Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer:The role of inflammation显示文摘Chemotherapy-induced diarrhea(CID)is a common and often severe side effect experienced by colorectal cancer(CRC)patients during their treatment.As chemotherapy regimens evolve to include more efficacious agents,CID is increasingly becoming a major cause of dose limiting toxicity and merits further investigation.Inflammation is a key factor behind gastrointestinal(GI)toxicity of chemotherapy.Different chemotherapeutic agents activate a diverse range of pro-inflammatory pathways culminating in distinct histopathological changes in the small intestine and colonic mucosa.Here we review the current understanding of the mechanisms behind GI toxicity and the mucositis associated with systemic treatment of CRC.Insights into the inflammatory response activated during this process gained from various models of GI toxicity are discussed.The inflammatory processes contributing to the GI toxicity of chemotherapeutic agents are increasingly being recognised as having an important role in the development of anti-tumor immunity,thus conferring added benefit against tumor recurrence and improving patient survival.We review the basic mechanisms involved in the promotion of immunogenic cell death and its relevance in the treatment of colorectal cancer.Finally,the impact of CID on patient outcomes and therapeutic strategies to prevent or minimise the effect of GI toxicity and mucositis are discussed. | Chun Seng Lee Elizabeth J Ryan Glen A Doherty | 2014 | World Journal of Gastroenterology2014，20，14： | 10 |
| 2 | Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer显示文摘Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod(IMQ) in low molecular weight heparin(LMWH)-D-α-tocopheryl succinate(TOS) micelles(LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles(LT-DOX)generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles(LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1(PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer. | Jiaojie Wei Yang Long Rong Guo Xinlei Liu Xian Tang Jingdong Rao Sheng Yin Zhirong Zhang Man Li Qin He | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 8 |
| 3 | Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients显示文摘BACKGROUND Life-long removal of gluten from the diet is currently the only way to manage celiac disease(CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides(GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully established.AIM To assess the performance of enzyme-linked immunosorbent assay(ELISA) and point-of-care tests(PoCTs) for GIP excretion in CeD patients on gluten-free diet(GFD).METHODS We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion(by ELISA in stool and PoCTs(commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study period.RESULTS Forty-four patients were enrolled, of which 19(43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were collected.Eleven out of 44 patients(25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases(Cohen′s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant(concomitantly positive or negative) in 67 out of 74(90.5%) samples. Excretion of GIP was detected in 7(8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary reports.CONCLUSION GIP detects dietary transgressions in patients on long-term GFD, irrespective of the presence of symptoms. PoCT for GIP detection constitutes a simple homebased method for self-assessment of dietary indiscretions. | Ana Florencia Costa Emilia Sugai María de la Paz Temprano Sonia Isabel Niveloni Horacio Vázquez María Laura Moreno M.Remedios Domínguez-Flores Alba Mu?oz-Suano Edgardo Smecuol Juan Pablo Stefanolo Andrea F González Angel Cebolla-Ramirez Eduardo Mauri?o Elena F Verdú Julio César Bai | 2019 | World Journal of Gastroenterology2019，25，11： | 1 |
| 4 | Impact of cell death manipulation on the efficacy of photodynamic therapy-generated cancer vaccines显示文摘The main task of cancer vaccines is to deliver tumorspecific antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic therapy(PDT)-generated vaccines as an example of autologous whole-cell cancer vaccines,the importance is discussed of the expression of death-associated molecules on cancer vaccine cells. This aspect appears critical for the optimal capture of vaccine cells by host's sentinel phagocytes in order that the tumor antigenic material is processed and presented for immune recognition and elimination of targeted malignancy. It is shown that changing death pattern of vaccine cells by agents modulating apoptosis,autophagy or necrosis can significantly alter the therapeutic impact of PDTgenerated vaccines. Improved therapeutic effect was observed with inhibitors of necrosis/necroptosis using IM-54,necrostatin-1 or necrostatin-7,as well as with lethal autophagy inducer STF62247. In contrast,reduced vaccine potency was found in case of treating vaccine cells with apoptosis inhibitors or lethal autophagy inhibitor spautin-1. Therefore,PDT-generated cancer vaccine cells undergoing apoptosis or lethal autophagy are much more likely to produce therapeutic benefit than vaccine cells that are necrotic. These findings warrant further detailed examination of the strategy using cell death modulating agents for the enhancement of the efficacy of cancer vaccines. | Mladen Korbelik | 2015 | World Journal of Immunology2015，5，3： | 0 |
| 5 | Identification of antigenic proteins from salivary glands of female Anopheles maculatus by proteomic analysis显示文摘Objective: To identify antigenic proteins from the salivary glands of female Anopheles maculatus using a proteomic approach to find the biomarker candidate for serological tools.Methods: The identification of antigenic proteins of Anopheles maculatus salivary gland used these techniques: one-dimensional gel electrophoresis(sodium dodecyl sulfate polyacrylamide gel electrophoresis), western blot, and liquid chromatography–mass spectrometry.Results: The proteins that have molecular weight(MW) 43 and 34 k Da were the antigenic protein. Computational bioinformatic analysis by Mascot Server revealed seven novel hypothetical proteins(MW: 43 k Da) and two novel hypothetical proteins(MW:34 k Da). Further analysis(BLASTP, antigenicity, epitope mapping, and specificity analysis) showed that two novel proteins were identified as apolipoprotein D and cathepsin D in Anopheles darlingi.Conclusions: The identified proteins are potential to be developed as a biomarker of mosquito bite's exposure. | Yunita Armiyanti Renam Putra Arifianto Elisa Nurma Riana Kartika Senjarini Widodo Widodo Loeki Enggar Fitri Teguh Wahju Sardjono | 2016 | Asian Pacific Journal of Tropical Biomedicine2016，6，11： | 0 |
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