Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat

Abstract Previous studies have shown that apoptosis is induced by cytotoxic chemotherapy and precedes hypoproliferation of intestinal crypt cells. However, the relationship between the degree of intestinal apoptosis and crypt cell hypoproliferation may not be directly related. The purpose of this study was to investigate the relationship between apoptosis and hypoproliferation with increasing doses of chemotherapy. Eleven groups of breast cancer-bearing DA rats were treated with two doses of methotrexate (MTX) i. m. at varying concentrations (0.5, 1.5, 2.5 and 5.0 mg/kg) or saline (control). Animals were killed at 6 or 24 h following treatment. The small and large intestines were examined for apoptosis, villous area (small intestine), crypt length and mitotic count per crypt. Immunohistochemical expression of p53 and p21^waf1/cip1 (p21) were examined quantitatively. Data were analysed using Peritz F-test. Low dose MTX (0.5 mg/kg) did not change p53 expression at 6 h but induced a 15-fold increase in apoptosis in the crypts of the small intestine. This was associated with only a minor reduction in crypt cell proliferation. Higher doses of MTX increased p53 expression and caused a lower (7-fold) but more prolonged peak of apoptosis that was accompanied by reduced villous area, shortened crypts and a more profound reduction in crypt cell proliferation. Unlike the small intestine, apoptosis in the colon was 10-fold lower, proportional to the dose of MTX and did not induce overt damage. Expression of p21 did not change with any dose at either timepoint. We conclude that apoptosis is not always associated with crypt cell hypoproliferation and that the small intestine can recover after low dose MTX despite a heightened peak of apoptosis of crypt cells.     

康复新液对头颈部肿瘤放疗后重度放射性口腔黏膜炎的治疗作用及对唾液腺的保护作用

目的 探讨康复新液对头颈部肿瘤放疗后重度放射性口腔黏膜炎的治疗作用及对唾液腺的保护作用.方法 选取2016年10月—2019年10月在鄂东医疗集团市中心医院完成根治性放疗且发生重度放射性口腔黏膜炎的116例头颈部肿瘤患者,按随机数字表法将所有患者分为治疗组和对照组,每组各58例.在常规治疗的基础上,治疗组给予康复新液含...     

造血干细胞移植患儿口腔黏膜炎风险预测模型的构建及验证

目的 分析造血干细胞移植患儿口腔黏膜炎的危险因素,构建风险预测模型,并验证其预测效果。方法采用便利抽样法,选取2019年1月—2022年6月于重庆市某三级甲等儿童专科医院行异基因造血干细胞移植的286例患儿作为调查对象,回顾性分析相关资料,通过Logistic回归分析筛选其口腔黏膜炎的危险因素,应用R 3.6.1软件绘制列线图,并进行验证。结果 Logistic回归分析结果显示,BMI<16、口腔pH值≤6.5、口腔清洁度评分为2～3分、预处理方案为减低强度或清髓性预处理、使用甲氨蝶呤、中性粒细胞计数<1.5×109/L是造血干细胞移植患儿口腔黏膜炎的危险因素（P<0.05）。Hosmer-Lemeshow检验结果提示,该风险预测模型具有较好的拟合度（χ2=0.969,P=0.998）。模型验证结果显示,该模型的受试者操作特征曲线下面积为0.881,最佳临界值为0.7,准确度为80.36%,灵敏度为83.59%,特异度为74.88%;预测口腔黏膜炎的一致性指数为0.881,校正一致性指数为0.862。结论 该研究构建的风险预测模型具有良好的区分度与准确度,可为临床护理...     

鼻咽癌患者放射治疗前局部冰敷减轻口腔黏膜反应的效果

目的探讨鼻咽癌放射治疗前局部冰敷对口腔黏膜反应的影响。方法 将80例首程放射治疗鼻咽癌患者随机分为试验组和对照组,每组40例。试验组在放疗前将冰袋置于照射野皮肤30min,然后立即进行放射治疗。对照组行常规护理,不进行冰敷。口腔出现黏膜溃疡时,首先用无菌棉签擦干口腔溃疡处,再喷涂重组人表皮生长因子(rhEGF),每天2次。放射治疗第7周,对患者口咽部采样进行微生物学监测。结果放射治疗第3周末、第7周末、结束后1周,试验组口腔黏膜炎明显轻于对照组。咽拭子细菌培养阳性率试验组(17.5%)低于对照组(37.5%)。结论放射治疗前局部冰敷可有效预防与减轻鼻咽癌放射治疗所致口腔黏膜反应,减少口腔真菌感染。     

Management of radiation therapy-induced mucositis in head and neck cancer patients. Part II: supportive treatments

Oropharyngeal mucositis is the acute inflammatory and ulcerative reaction of the oral mucosa following radiation therapy to the head and neck region. It is such a common problem that nearly all head and neck cancer patients develop some degree of mucositis. This complication is usually transient in nature but it also represents an important clinical problem as it is a painful, debilitating, dose-dependent side effect for which there is no widely acceptable prophylaxis or effective treatment. As several authoritative groups have recently either undertaken systematic reviews or issued guidelines on the management of mucositis, it is the aim of this review instead, to provide an overview of all the remedies and pharmaceutical agents available, as well as highlighting to researchers the gaps that need to be filled.     

A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma

Purpose: The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma (HNSCC).

Methods and Materials: Between May 1996 and February 1998, 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study. The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks. The patients were randomized to receive or not 150 mg/m², amifostine (Ethyol, U.S. Bioscience) 15–30 min prior to each radiation session.

Results: Of the 13 patients who received amifostine, definitive interruption of amifostine occurred in 5 cases (38%), due to tolerance problems (vomiting, liver enzyme elevation, generalized erythema). The distribution of Grade 4 mucositis (WHO) was 1 case versus 8 cases, with and without amifostine, respectively. The mean duration of “at least Grade 3” mucositis (WHO) was 25.1 days versus 49.2 days with and without amifostine (p = 0.03). In the amifostine group, 11/13 of the patients required a feeding tube (nasogastric tube or medical gastrostomy), because of acute mucositis, whereas in the control group a feeding tube was necessary in all cases. The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively (p < 0.01). Local-regional control was not different between both arms with a median follow-up of 15 months.

Conclusion: Despite the limited number of patients, this pilot randomized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy. However, the tolerance of this twice daily amifostine schedule was relatively poor.     

Measuring mucosal damage induced by cytotoxic therapy

We scored oral mucositis and gut toxicity and measured sugar permeability testing among 56 recipients of a haematopoietic stem cell transplant (HSCT) given myeloablative conditioning with idarubicin, cyclophosphamide and TBI, and a group of 18 patients given cytotoxic chemotherapy for newly diagnosed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Gut integrity was already disturbed in the AML/MDS group as measured by the lactulose/rhamnose ratio (L/R ratio=0.09) before therapy and was severely perturbed (L/R ratio >0.13) for a month after HSCT. Oral mucositis and to a lesser extent gut toxicity was only significantly correlated with disturbed permeability in the transplant group. The data suggest that sugar permeability, oral mucositis and gut toxicity measure different features of mucosal damage after intensive cytotoxic therapy.     

Symptom control

Symptom control has become increasingly recognized as an important goal in patient care. In this article, advances in symptom assessment, and various definitions of symptom improvement are reviewed. Theoretical concepts underlying symptom control and clinically significant change are presented, as well as the role of symptom control as an endpoint in clinical trials. Symptom control is then surveyed in two broad categories for selected symptoms. The first area is therapy related symptoms, secondary to chemotherapy, radiation, hormonal therapy, and surgery. Symptoms reviewed include chemotherapy related mucositis, emesis, fatigue; hot flashes; and radiation related dermatitis, xerostomia, and mucositis. The second area is palliative oncologic approaches to disease-related symptoms. Results in palliative chemotherapy, palliative radiation therapy, cancer pain, and lack of appetite are summarized. Areas requiring further research are noted. Findings are presented in both a clinical and research context to help guide the reader with interpreting symptom control studies.