Combretastatin A-4 prodrug inhibits growth of human non-small cell lung cancer in a murine xenotransplant model

BACKGROUND: Combretastatin A-4 prodrug (CA-4PD) has been identified as a potent antivascular agent in various rodent tumor models. The aim of this study was to investigate the effect of CA-4PD on human non-small cell lung cancer (NSCLC). METHODS: Cytostatic and cytotoxic effects of CA-4PD on selected NSCLC cells, Colo-699 and KNS-62, were studied in vitro. After subcutaneous xenotransplantation the effect of systemically administrated CA-4PD on tumor growth was investigated in vivo. A newly established orthotopic xenotransplant model was employed to estimate prolongation of survival after intrapulmonary tumor induction with secondary metastatic disease. RESULTS: In vitro, CA-4PD displayed a time and dose dependent antiproliferative effect on human lung cancer cells. In vivo, CA-4PD significantly delayed growth of subcutaneously induced lung cancer. This growth delay was translated into a prolongation of survival in the metastasizing orthotopic xenotransplant model. CONCLUSIONS: In vitro CA-4PD inhibits proliferation of NSCLC cells, most likely by disruption of microtubule assembly. In vivo, systemic treatment inhibits growth of subcutaneously xenotransplanted tumors by an antivascular effect. In the case of metastasizing human lung cancer this translated into a prolongation of survival.     

Protective effects of some antineoplastic agents on ischemia-reperfusion injury in epigastric island skin flaps

Neutrophil depletion has a beneficial effect on ischemic myocardium and skeletal muscle upon reperfusion. Antineoplastic agents reduce blood neutrophils effectively, and lead to neutrophil depletion. The purpose of this study was to investigate the effects of four antineoplastic agents in low doses (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) on ischemia-reperfusion injury, using an epigastric island skin-flap model in rats. Fifty male Sprague-Dawley rats, weighing 250-300 g, were randomly divided into five groups, each consisting of 10 rats: control, cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil groups. Epigastric island skin flaps (measuring 3.5 x 4 cm) were raised and subjected to 10 h of in situ ischemia, followed by 7-day reperfusion and evaluation. Treatment with antineoplastic agents (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) was used to introduce neutropenia. Complete blood counts, cutaneous bleeding time, and skin-flap survival were evaluated. Additionally, levels of malonyldialdehyde (MDA), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured from extracted skin tissue. Numbers of leukocytes and platelets were decreased in all experimental groups. However, neutropenia and thrombocytopenia were not seen. Cutaneous bleeding activity was prolonged in all experimental groups, but not above the normal value. MDA and NO levels were found to be lower in all four antineoplastic agent groups than in the control group, while GSH, GSH-Px, and SOD enzyme activities were significantly higher (P < 0.05). However, MDA and NO levels were significantly decreased in the cyclophosphamide and 5-fluorouracil groups, as compared to the cisplatinum and mitomycin-C groups (P < 0.01). Also, GSH, GSH-Px, and SOD enzyme activities were significantly increased in the cyclophosphamide and 5-fluorouracil groups, compared to the other two antineoplastic agent groups (P < 0.01). We conclude that antineoplastic agents have beneficial effects on ischemia-reperfusion injuries when their doses are carefully adjusted, by decreasing the number of leukocytes and platelets, and altering the activity of free oxygen radicals.     

蛋白类抗肿瘤药物及其应用研究进展

蛋白类抗肿瘤药物高效低毒,且能有效避免放疗化疗的副作用,一直以来都是肿瘤治疗的研究目标,其中靶向性蛋白药物的研究更是近年来抗肿瘤研究的热点.目前,通过基因工程技术构建融合蛋白,靶向治疗肿瘤,已成为蛋白类药物抗肿瘤研究的主要方向.     

A review for clinicians: Prostate cancer and the antineoplastic properties of metformin

Objectives

Metformin has numerous antineoplastic effects including an AMP-activated protein kinase–dependent mechanism, AMP-activated protein kinase–independent mechanisms, alteration of insulin and insulin-like growth factor signaling pathways, and suppression of androgen signaling pathways that trigger prostate cancer growth and proliferation. In contrast to other malignancies that are associated with increased incidence among patients with obesity and type II diabetes mellitus (T2DM), epidemiological studies suggest that obesity and T2DM may impart a protective effect on prostate cancer incidence by creating a set of metabolic conditions that lower androgen levels.

Vitiligo: An immune disease and its emerging mesenchymal stem cell therapy paradigm

Melanocyte damage, innate immune response, adaptive immune response, and immune inflammatory microenvironment disorders are involved in the development of the immunological pathogenic mechanism of vitiligo. Mesenchymal stem cells are considered an ideal type of cells for the treatment of vitiligo owing to their low immunogenicity, lower rates of transplant rejection, and ability to secrete numerous growth factors, exosomes, and cytokines in vivo. The regulation of signaling pathways related to oxidative stress and immune imbalance in the immunological pathogenesis of vitiligo can improve the immune microenvironment of tissue injury sites. In addition, co-transplantation with melanocytes can reverse the progression of vitiligo. Therefore, continuous in-depth research on the immunopathogenic mechanism involved in this disease and mesenchymal stem cell-based therapy is warranted for the treatment of vitiligo in the future.     

MKK4腺病毒载体的构建及其对胰腺癌细胞增生和浸润能力的影响

目的 观察MKK4对胰腺癌细胞增生和浸润能力的影响.方法 采用Western blot检测常见胰腺癌细胞株中MKK4的表达;构建MKK4的腺病毒载体,感染不表达MKK4的胰腺癌细胞株,采用胸腺嘧啶标记法观察外源性MKK4表达对细胞增生能力的影响,采用体外细胞浸润实验观察外源性MKK4表达对细胞浸润能力的影响.结果 在胰腺癌细胞株AsPC1、BxPC3、Hs766T、MiapaCa2、Pancl中,MKK4在AsPC1和BxPC3细胞中表达缺失.成功构建MKK4的腺病毒载体.以腺病毒LacZ感染作对照,通过胸腺嘧啶标记法观察到AsPC1、BxPC3细胞感染MKK4腺病毒后,细胞增生能力增加53%、61%(P＜0.05);通过体外细胞浸润实验观察到细胞浸润能力增强(8.2±2.7)倍、(15.7±1.6)倍(P＜0.01).结论 MKK4在胰腺癌细胞中表达可增加其增生和浸润能力,具有潜在癌基因作用.     

A review of current and emerging approaches to address failure-to-rescue

Failure-to-Rescue, defined as hospital deaths after adverse events, is an established measure of patient safety and hospital quality. Until recently, approaches used to address failure-to-rescue have been focused primarily on improvement of response to a recognized patient crisis, with limited success in terms of patient outcomes. Less attention has been paid to improving the detection of the crisis. A wealth of retrospective data exist to support the observation that adverse events in general ward patients are preceded by a significant period (on the order of hours) of physiologic deterioration. Thus, the lack of early recognition of physiologic decline plays a major role in the failure-to-rescue problem.     

KIF4A在肝细胞癌中的表达及预后价值分析

背景与目的:肝细胞癌(HCC)是原发性肝癌最常见的病理类型,其起病隐匿,预后较差,位居癌症相关死亡原因第3位.KIF4A在多种恶性肿瘤中呈高表达且与不良预后密切相关,然而其在HCC中的作用及机制尚不清楚.因此,本研究分析KIF4A基因在HCC中的表达情况及预后价值,并探讨相关的分子机制.方法:从癌症基因组图谱(TCGA...     

Sepsis: its causes and effects

Sepsis contracted after malignancy, surgery or trauma is caused by a variety of micro-organisms ranging from viruses and fungi to bacteria. If untreated, it can lead to permanent damage to organs and tissues, or even to the patient's death.     

Glucocorticoid receptors in glioblastoma multiforme: A new approach to antineoplastic glucocorticoid therapy

Summary Glucocorticoid receptors were measured in tissue samples from 12 patients with glioblastoma multiforme. The receptor was found in all patients. The concentration of glucocorticoid receptor was found to be high in the periphery of the tumour, low in the surrounding brain tissue and low in the central part of the tumour in 6 of the patients. The possible role of the glucocorticoid receptor distribution in relation to growth regulation is discussed. A decreasing receptor concentration found at reoperation in two patients indicates a possible antineoplastic effect of high dose methylprednisolone pulse therapy on glucocorticoid receptor positive glioblastomas.     

A behaviorally oriented stress reduction program and its effects upon self-reported gastric complaints

The response of common but disturbing gastric complaints to psychological intervention has not been studied despite evidence that clinical levels of gastrointestinal disorders respond to treatment. The present study examines the effect of a behaviorally oriented stress reduction program on such self-reported gastrointestinal complaints among a group of 179 subjects. Pre-and post-treatment measures were obtained on the frequency of indigestion, nausea, ulcer attacks, colitis, diarrhea, and constipation complaints. Significant decreases were found from pre to post indigestion, nausea, colitis, diarrhea, and constipation and significant decreases were maintained at follow-up for indigestion, nausea and constipation complaints. These results suggest that relief from common gastric complaints may be obtained from a behaviorally oriented treatment program, and that such a program may also affect the potential development of maladaptive learned gastric response habits.