Photodynamic therapy for superficial bladder cancer

In photodynamic therapy, a photosensitizing drug is activated by visible light and in the presence of oxygen, results in local cell death. This evolving modality is now being used to treat and palliate a very wide variety of human solid tumors and carcinoma-in-situ lesions. With regard to bladder cancer, advances in drug development and modern light delivery techniques mean that photodynamic therapy shows promise in the treatment of superficial bladder cancer resistant to conventional treatments.     

FOLFOX方案治疗转移性胃癌临床疗效分析

目的探讨FOLFOX方案治疗转移性胃癌临床疗效和不良反应。方法选择我院2008年至2011年收治的经细胞学或组织学证实的转移性胃癌患者35例,接受FOLFOX方案化疗治疗。3～4周期后评价疗效和不良反应,并对患者的生存状况进行随访。结果 35例患者化疗后总有效率为65.7%,内脏转移患者总有效率为59.1%,显著低于淋巴结转移(P<0.05)。随访率为91.4%,中位TTP为6.4个月,中位OS为11.8个月,3年生存率达43.8%。结论 FOLFOX方案治疗转移性胃癌临床疗效显著,毒副作用较轻,能显著提高患者生存率,对淋巴结转移敏感度更高,值得临床推广。     

Chemoprevention of liver cancer by plant polyphenols

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity.     

Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies. Here we report induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon stimulation of in vivo angiogenesis with vascular endothelial growth factor-A (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis-independent vascular outgrowth in aortic ring cultures is strongly impaired after Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function causes developmental and vascular defects in zebrafish and chick embryos and potent inhibition of tumor angiogenesis in experimental tumor models. Besides blocking tumor cell proliferation, impairing endothelial function is a novel mechanism of action of kinesin inhibitors.     

Sequential Treatment with High-Dose Methotrexate and Fluorouracil in Advanced Colorectal Cancer. Experience of The Southern Italian Oncology Group (GOIM)

Summary

A total of 101 patients with advanced colorectal cancer in two consecutive Southern Italian Oncology Groups (GOIM) studies (8501 and 8801- arm A) were treated with a sequential combination of high dose methotrexate (HDMTX) and fluorouracil (FU). Of the 92 eligible patients, 2 achieved complete response (2%) and 27 partial response (30%), with a median duration of 7 months. When classified according to the time interval between administration of the two drugs, retrospective analysis showed significant improvement (p = 0.04) in overall survival in the shorter time interval group (6 hours). The observed toxicities were generally mild and transient. Our data confirm the efficacy of the synergism between the two chemotherapeutic agents, in particular when administered with a 6-hour interval. Further studies are necessary to establish the possibility of enhancing the efficacy of sequential treatment with the modulation of FU with high-dose folinic acid.     

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS.     

菊花总黄酮对转染RSV的A549细胞RANTES及MCP-1表达的影响

【目的】探讨菊花总黄酮对呼吸道合胞病毒(Respiratory Syncytial Virus,RSV)转染 A549细胞诱导激活正常 T 细胞表达和分泌因子(regulated upon activation ,normal Tcell expressed and secreted ,RANTES)及单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)释放作用影响。【方法】实验分为正常对照组,病毒对照组,菊花总黄酮组和巴韦林组。在人喉癌上皮细胞(Hep-2细胞)和气道上皮细胞(A549)分别加入菊花总黄酮和巴韦林的含药维持液,测定上述两种药物的最大无毒浓度；RSV 转染 Hep-2细胞,观察药物对 RSV 的病毒抑制作用；RSV 转染 A549细胞,ELISA 法测细胞趋化因子 RANTES 及 MCP-1含量。【结果】菊花总黄酮组50%有效率优于巴韦林组,差异有统计学意义(P <0.05)；菊花总黄酮组 RANTES、MCP-1明显降低,但高于正常细胞组,优于巴韦林组,差异有统计学意义(P <0.05)。【结论】菊花总黄酮能够抑制 RSV 活性,明显降低 A549细胞释放 RANTES、MCP-1,缓解患儿的呼吸道症状。     

Overexpression of histone demethylase JMJD5 promotes metastasis and indicates a poor prognosis in breast cancer

In this study, we showed the expression of JMJD5 was increased in breast cancer tissues and breast adenocarcinoma cell lines MCF-7 as well as triple negative breast cancer cell lines MDA-MB-231 compared with paired adjacent normal mammary tissues and normal mammary epithelial cell lines MCF-10A. The higher expression of JMJD5 was significantly corresponded with clinical stage, histological grade and lymph node metastasis. Overexpression of JMJD5 promoted cell invasion and induce EMT, while JMJD5 siRNA inhibits MDA-MB-231 cells invasion in vitro. Moreover, qChIP analysis revealed the Snail family proteins Snai1 was the direct target of JMJD5 in breast cancer cells. Luciferase reporter assays suggested that the overexpression of JMJD5 resulted in the activation of Snail1 promoter-driven luciferase reporter. The changes in the level of RNA and protein implied that the activation of Snail was the important mechanisms by which JMJD5 triggers metastasis. We also detected the higher expression of JMJD5 protein was an independent unfavorable biomarker for worse overall survival in breast cancer patients. Therefore, our results identified an important role for JMJD5 in breast cancer through the regulation of snail1.     

Effects of 5-aminolevulinic acid photodynamic therapy on TLRs in acne lesions and keratinocytes co-cultured with P. acnes

ObjectiveTo investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the expression of Toll like receptors (TLRs) in human keratinocytes and its role in acne treatment.MethodsTLR2 and TLR4 expression in acne lesions before and after ALA-PDT were examined by immunohistochemical assay. Primary keratinocytes were obtained from acne lesions, co-cultured with P. acnes and then treated with ALA-PDT using red or blue LED. Cytokines production were examined by ELISA, TLR2 and TLR4 gene expression by real-time PCR, and TLR2 and TLR4 protein expression by Western-blot assay.ResultsThe overexpression of TLR2 and TLR4 in acne lesion were detected, which became negative or weaker after ALA-PDT. The infection of P. acnes in keratinocytes could significantly increase the levels of early inflammatory cytokines (e.g. IL-1α, TNF-α and IL-8) (P < 0.05). Such responses could be inhibited by ALA-PDT. P. acnes infection could also significantly increase TLR2 and TLR4 expressions in keratinocytes (P < 0.05), which could be down-regulated by ALA-PDT.ConclusionsALA-PDT could inhibit innate immune responses in keratinocytes treated with P. acnes via TLRs pathways.