An engineered biopolymer prevents mucositis induced by 5-fluorouracil in hamsters

Oral mucositis is a common, treatment-limiting, and costly side effect of cancer treatments whose biological underpinnings remain poorly understood. In this study, mucositis induced in hamsters by 5-fluorouracil (5-FU) was observed after cheek-pouch scarifications, with and without administration of RGTA (RG1503), a polymer engineered to mimic the protective effects of heparan sulfate. RG1503 had no effects on 5-FU-induced decreases in body weight, blood cell counts, or cheek-pouch and jejunum epithelium proliferation rates, suggesting absence of interference with the cytotoxic effects of 5-FU. Extensive mucositis occurred in all of the untreated animals, and consisted of severe damage to cheek pouch tissues (epithelium, underlying connective tissue, and muscle bundles). Only half of the RG1503-treated animals had mucositis, over a mean area 70% smaller than in the untreated animals. Basement membranes were almost completely destroyed in the untreated group but was preserved in the RG1503 group. RG1503 blunted or abolished the following 5-FU-induced effects: increases in matrix metalloproteinase (MMP)-2, MMP-9, and plasmin, and decreases in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These data indicate that mucositis lesions are related to massive release of proteolytic enzymes and are improved by RG1503 treatment, this effect being ascribable in part to restoration of the MMP-TIMP balance. RG1503 given with cancer treatment might protect patients from mucositis.     

Morphology of experimental acute pancreatitis during treatment with 5-fluorouracil

In experimental pancreatitis induced by a modified method (Arai, 1965) 5-fluorouracil has a marked therapeutic action, preventing the development of necrosis of the acini and suppurative liquefaction of the gland tissue. The authors attribute the therapeutic effect of 5-fluorouracil to its inhibitory action on RNA synthesis and blockade of the liberation of secretion from the exocrine part of the pancreas.Department of Abdominal Surgery and Department of Surgical Anatomy, A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Kraevskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 366–368, March, 1980.     

美宝加地塞米松预防盖诺所致静脉炎的研究

目的　探讨美宝加地塞米松预防盖诺所致静脉炎的疗效。方法　对 92例使用盖诺的患者随机分为对照组和实验组。对照组在静脉输注盖诺前、后仅输入地塞米松 ;实验组在对照组的基础上 ,在输注盖诺前、后沿静脉走行的皮肤涂抹美宝湿润烧伤膏 ,观察两组病人局部组织反应及静脉炎的发生率。结果　实验组局部组织反应及静脉炎的发生率显著降低 (P <0 .0 1)。结论　美宝湿润烧伤膏联合地塞米松可明显降低盖诺所致静脉炎的发生率 ,且反应时间明显延后 ,程度明显减轻 ,可推广应用     

Prevention of murine EAE by oral hydrolytic enzyme treatment

Clinical trials that test the efficacy of Phlogenzym (consisting of the hydrolytic enzymes bromelain and trypsin and the anti-oxidant rutosid) as a treatment for T cell-mediated autoimmune diseases including multiple sclerosis (MS), type 1 diabetes and rheumatoid arthritis are presently ongoing. We tested the effects of Phlogenzym treatment in the murine model for MS, experimental allergic encephalomyelitis (EAE), a disease induced in SJL mice by immunization with proteolipid protein (PLP) peptide 139-151. Oral administration of Phlogenzym resulted in complete protection from EAE. In Phlogenzym-treated mice, the dose response curve of the PLP:139-151-specific T cell response was shifted to the right, that is, the primed T cells required higher peptide concentrations to become activated. Additionally, the T cell response to this peptide was shifted towards the T helper 2 cytokine profile. Both effects are consistent with an increased T cell activation threshold. In support of this interpretation, we found that the accessory molecules CD4, CD44, and B7-1 (all of which are involved in T cell co-stimulation) were cleaved by Phlogenzym, while CD3 and MHC class II molecules (which are involved in the recognition of antigens by T cells) and LFA-1 were unaffected. These data show the efficacy of oral Phlogenzym treatment in an animal model of T cell-mediated autoimmune disease and suggest that the protective effect might be the result of an increase in the activation threshold of the autoreactive T lymphocytes brought about by the cleavage of accessory molecules involved in the interaction of T cells and antigen presenting cells.     

Combination chemotherapy with 5-fluorouracil and heptaplatin as first-line treatment in patients with advanced gastric cancer

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.     

胃癌干细胞对5-氟尿嘧啶的敏感性

背景：5-氟尿嘧啶是一种常用的胃癌化疗药物,但临床治疗过程中较易出现耐药现象,影响治疗效果。研究表明肿瘤干细胞对化疗药敏感性较低,可能是导致化疗耐药的重要原因。 目的：体外环境下分析胃癌干细胞对5-氟尿嘧啶的敏感性,了解胃癌化疗耐药相关机制。 方法：基于克隆形态的分选策略,从人胃癌AGS细胞系内分离胃癌干细胞克隆,采用免疫细胞化学染色分析不同克隆CD44和胸苷酸合成酶的表达,克隆形成实验评估不同类型克隆的自我更新能力,CCK-8法检测不同浓度5-氟尿嘧啶作用下人胃癌AGS细胞克隆生长抑制率。 结果与结论：人胃癌AGS细胞经低密度接种培养后,可形成32个不同形态的克隆,其中,副克隆、次克隆、全克隆所占比例分别为19%(6/32)、66%(21/32)、16%(5/32)。全克隆高表达CD44和胸苷酸合成酶,接种后可再次形成大量二代克隆;次克隆弱表达CD44和胸苷酸合成酶,接种后形成少量的二代克隆;副克隆不表达或弱表达CD44和胸苷酸合成酶,接种后未形成二代克隆。在不同浓度5-氟尿嘧啶的作用下,次克隆以及人胃癌AGS细胞的生长抑制率均显著高于全克隆(P均 < 0.05)。结果表明,在体外条件下,胃癌干细胞对5-氟尿嘧啶敏感性较低,推测其可能为临床化疗耐药的重要机制。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Effects of benzydamine on radio-polychemotherapeutic mucositis of the oral cavity

A double-blind versus placebo study with benzydamine mouthwash, to demonstrate the histoprotective and antiinflammatory effects on the oral mucosa during intra-arterial chemotherapy of the head and neck, confirmed on a preliminary basis that benzydamine had a beneficial effect.     

缺氧诱导因子-1α在大鼠放射性口腔黏膜炎中的表达及意义

目的: 检测缺氧诱导因子-1α(HIF-1α)mRNA及蛋白在大鼠放射性口腔黏膜炎组织中的表达水平，并探讨其在ROM中的作用机制。方法: 建立放射性口腔黏膜炎SD大鼠模型，左侧颊黏膜为试验侧，右侧颊黏膜为自身对照侧，切取左、右侧颊黏膜，用半定量RT-PCR检测各标本HIF-1α的mRNA相对表达值，采用免疫组化SABC法检测HIF-1α蛋白在黏膜炎组织中的表达部位及表达强度。结果: 成功地建立了SD大鼠放射性口腔黏膜炎动物模型；RT-PCR结果显示ROM黏膜组织能够表达HIF-1α mRNA，而右侧自身对照组基本不表达HIF-1α mRNA；免疫组化结果显示：HIF-1α蛋白在ROM黏膜组织中能广泛表达。 结论: 放射性口腔黏膜炎组织有HIF-1α mRNA及蛋白的表达，其表达与放射性口腔黏膜炎的严重程度有关。     

Acute oral poisoning due to chloracetanilide herbicides

Chloracetanilide herbicides (alachlor, butachlor, metachlor) are used widely. Although there are much data about chronic low dose exposure to chloracetanilide in humans and animals, there are few data about acute chloracetanilide poisoning in humans. This study investigated the clinical feature of patients following acute oral exposure to chloracetanilide. We retrospectively reviewed the data on the patients who were admitted to two university hospitals from January 2006 to December 2010. Thirty-five patients were enrolled. Among them, 28, 5, and 2 cases of acute alachlor, metachlor, butachlor poisoning were included. The mean age was 49.8 ± 15.4 yr. The poison severity score (PSS) was 17 (48.6%), 10 (28.6%), 5 (14.3%), 2 (5.7%), and 1 (2.9%) patients with a PSS of 0, 1, 2, 3, and 4, respectively. The age was higher for the symptomatic patients (1-4 PSS) than that for the asymptomatic patients (0 PSS) (43.6 ± 15.2 vs 55.7 ± 13.5). The arterial blood HCO₃ ¯ was lower in the symptomatic patients (1-4 PSS) than that in the asymptomatic patients (0 PSS). Three patients were a comatous. One patient died 24 hr after the exposure. In conclusion, although chloracetanilide poisoning is usually of low toxicity, elder patients with central nervous system symptoms should be closely monitored and cared after oral exposure.     

Anti-inflammatory latex proteins of the medicinal plant Calotropis procera: a promising alternative for oral mucositis treatment

Inflammation Research - Oral mucositis (OM) is an intense inflammatory reaction progressing to tissue damage and ulceration. The medicinal uses of Calotropis procera are supported by...     

Effects of bolus injection of 5-fluorouracil on steady-state plasma concentrations of 5-fluorouracil in Japanese patients with advanced colorectal cancer

Objectives: The irinotecan (CPT-11) + 5-fluorouracil (5-FU)/leucovorin (LV) + UFT/LV chemotherapy, in which repetitive oral administration of UFT/LV replaces the infusion of 5-FU/LV in the FOLFIRI regimen, has been proposed previously. In this study, five of 10 patients were injected with a bolus of 5-FU and the other were not injected with it in order to examine the effect of omitting it in terms of pharmacokinetics of 5-FU.Methods: The treatment consisted of the intravenous infusions of CPT-11 at 100 mg/m² and l-LV at 15 mg/m², and the injection of a bolus of 5-FU at 500 mg/m² on day 1, and the repetitive oral administration of UFT/LV (300 mg/m²/day as tegafur + 75 mg/day of LV) on days 1-5. A total of 13 measurements of the plasma concentrations of uracil, 5-FU and tegafur were made per patient within 48 hr after the start of chemotherapy and the value of area under the concentration-time curve (AUC_0-48) was evaluated. The plasma concentration was also determined at 2 weeks to assess long-term exposure to 5-FU.Results: The plasma concentrations of 5-FU at 24 hr after the start of treatment were 27.4 ng/mL and 9.4 ng/mL in the patients with and without the bolus injection, respectively. At 48 hr, they were 31.3 ng/mL and 10.4 ng/mL with the AUC_0-48 values of 22.16 mg*h/L and 0.65 mg*h/L, respectively. The 5-FU was detected in the plasma at 226 hr after the last administration of UFT/LV for the patients with the bolus injection, but not for those without.Conclusion: A bolus of 5-FU on day 1 provided long-term exposure to 5-FU.     

The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies

The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p <0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p <0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.