Skin friction blistering: computer model

BACKGROUND/PURPOSE: Friction blisters, a common injury in sports and military operations, can adversely effect or even halt performance. Given its frequency and hazardous nature, recent research efforts appear limited. Blistering can be treated as a delamination phenomenon; similar issues in materials science have been extensively investigated in theory and experiment. An obstacle in studying blistering is the difficulty of conducting experiment on humans and animals. Computer modeling thus becomes a preferred tool. METHOD: This paper used a dynamic non-linear finite-element model with a blister-characterized structure and contact algorithm for outer materials and blister roof to investigate the effects on deformation and stress of an existing blister by changing the friction coefficient and elastic modulus of the material in contact with the blister. RESULTS: Through the dynamics mode and harmonic frequency approach, we demonstrated that the loading frequency leads to dramatic changes of displacement and stress in spite of otherwise similar loading. Our simulations show that an increased friction coefficient does not necessarily result in an increase in either the stress on the hot spot or blister deformation; local maximum friction stress and Von Mises stress exist for some friction coefficients over the wide range examined here. In addition, the stiffness of contact material on blistering is also investigated, and no significant effects on deformation and Von Mises stress are found, again at the range used. The model and method provided here may be useful for evaluating loading environments and contact materials in reducing blistering incidents. CONCLUSION: The coupling finite-element model can predict the effects of friction coefficient and contacting materials&apos stiffness on blister deformation and hot spot stress.     

甲磺酸伊马替尼诱导的皮肤反应与治疗对策

甲磺酸伊马替尼为酪氨酸激酶Bcr-Abl、c-Kit、血小板生长因子受体的抑制剂,在肿瘤治疗方面起到了积极的作用.近年来随着用药后皮肤不良反应事件的报道,其安全性及毒性受到越来越多的关注,虽然甲磺酸伊马替尼可引起剥脱性皮炎、玫瑰糠疹、重症多形红斑等皮肤反应,但大部分可在停药或加用糖皮质激素后缓解,仍然可以作为慢性粒细胞白血病、急性淋巴细胞白血病、胃肠间质瘤治疗的有效药物.     

Hyalinized collagen in a dermatofibrosarcoma protuberans after treatment with imatinib mesylate

We report a novel histological finding in a dermatofibrosarcoma protuberans (DFSP) after treatment with imatinib mesylate: copious amounts of hyalinized collagen. A 57-year-old female was referred for evaluation and treatment of a 7 x 8 x 10 cm tumor on the right anterior shoulder. Histological evaluation of the incisional biopsy showed a highly cellular dermal neoplasm composed of spindle cells arranged in a storiform pattern with minimal collagen. A CD34 immunohistochemical stain was strongly positive, highlighting atypical spindle cells in the dermis. A diagnosis of DFSP was made and the patient was enrolled in the Southwest Oncology Group trial. She received imatinib mesylate 400 mg per day for 1 year. At the end of therapy, the DFSP decreased in size to 5.5 x 4 x 4 cm. The tumor was excised. Histological evaluation showed a residual dermal neoplasm composed of atypical spindle cells and a copious amount of hyalinized collagen. Areas of necrosis were not seen. A CD34 stain confirmed the presence of residual DFSP, highlighting atypical spindle cells. A procollagen I stain was strongly positive, confirming the presence of abundant collagen in the dermis. A similar finding has been reported in gastrointestinal stromal tumor, which shows deposition of myxohyaline stroma after treatment with imatinib mesylate.     

Treatment of advanced dermatofibrosarcoma protuberans with imatinib mesylate with or without surgical resection

Background Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma of the skin characterized by the presence of specific COL1A1–PDGFB fusion protein, which appears as a consequence of the t(17;22) (q22;q13) translocation. Objective The aim of the study was to perform an analysis of patients with advanced DFSP treated with imatinib, with or without surgery, in clinical practice outside trials. Patients and Methods We analysed the data of 15 patients (6 male, 9 female; median age 56 years) with locally advanced/initially inoperable and/or metastatic DFSP treated with imatinib 400–800 mg daily between 12/2004 and 06/2009. All diagnoses were ascertained cytogenetically (fluorescent in situ hybridization). Median follow‐up time was 16 months (range: 4–81). Results Metastases were present in six cases (two lungs, two soft tissue, two lymph nodes). Fibrosarcomatous transformation (FS‐DFSP) was confirmed in seven patients (47%). A 2‐year progression‐free survival (PFS) rate was 60%, and a 2‐year overall survival (OS) rate was 78% (median time for PFS/OS was not reached). The best overall responses were: 10 partial responses (67%, including 5 FS‐DFSP – 1 progressed during the follow‐up), 2 stable diseases (13%) and 3 progressive diseases (20%). Seven patients (47%) underwent resection of residual disease and remained free of disease. Conclusions We have confirmed the profound anti‐tumour effect of imatinib in DFSP harbouring t(17;22) with long‐term responses. Imatinib therapy may in some cases lead to tumour resectability of lesser disfiguration.     

Improving chemotherapeutic drug penetration in melanoma by imatinib mesylate

BACKGROUND: Imatinib mesylate has specific activity in inhibiting select tyrosine kinase receptors, including platelet-derived growth factor receptors (PDGFRs) and c-kit. In general, melanomas widely express PDGFR and c-kit, and their in vivo resistance to chemotherapy is attributable to high tumor interstitial fluid pressure (IFP). Recent studies have suggested that PDGFR-beta inhibition reduces tumor IFP, and thus increases the uptake of concomitantly administered drugs. OBJECTIVE: The present study was designed to investigate the potential of imatinib mesylate as a therapy for melanoma or as an adjuvant to chemotherapeutics. METHODS: Using in vivo mouse models, the effect of imatinib mesylate on the growth of melanoma with or without dacarbazine was studied. RESULTS: Imatinib mesylate enhanced the antitumor effect of dacarbazine on in vivo growth and lung metastases of melanoma cells, although treatment with only imatinib mesylate had no effect. We could detect perivascular expression of PDGF beta-receptor in melanoma tumors. Interestingly, dacarbazine uptake in melanoma was more than three-times increased by treatment with imatinib mesylate, while its uptake in serum or bone marrow was not affected by imatinib mesylate. CONCLUSIONS: These data suggest interference with PDGF receptors, or their ligands, as a novel strategy to increase drug uptake and therapeutic effectiveness of chemotherapy for melanoma.     

甲磺酸伊马替尼致扁平苔藓样药疹二例

例1 女,58岁。因体检白细胞计数异常行进一步检查后诊断为慢性粒细胞白血病（CML）,给予甲磺酸伊马替尼（格列卫）400 mg/d治疗,服药1月余后于双腿开始出现暗红色皮疹,伴瘙痒,并逐渐扩散至上肢及躯干部……     

Marked response to imatinib mesylate in metastatic acral lentiginous melanoma on the thumb

We report a case of melanoma that had a marked response to treatment with imatinib mesylate (IM). The patient was a 61‐year‐old man who presented with a small red nodule on the thumb and destruction of the nail plate. On histological examination, this lesion was diagnosed as a melanoma, and computed tomography revealed lymph‐node swelling in the left axilla and nodules in both lung fields. Although the patient received intratumoral injections of interferon‐β and systemic administration of dacarbazine, both primary and metastatic lesions increased in size. Immunochemistry detected a KIT mutation, which was confirmed by DNA sequencing analysis, and patient was given IM. Within 2 weeks of starting the IM regimen, the size of the nodule on the nail plate markedly decreased, and the axillary lymph‐node swelling and lung‐nodule formation regressed. This case suggests that IM may be a promising treatment option for KIT mutation‐positive melanoma.     

甲磺酸伊马替尼对人黑素瘤细胞c-KIT表达的影响

目的:探讨甲磺酸伊马替尼对体外培养的人黑素瘤细胞系c-KIT表达及增殖的影响.方法:采用免疫组化和Western 印迹法检测人黑素瘤M14细胞和鼠黑索瘤B16F10细胞中c-KIT的表达,四甲基偶氮唑蓝(MTT)法分析3种浓度(5、10、20μmol/L)甲磺酸伊马替尼对M14细胞和B16F10细胞的生长抑制作用,Western印迹法观察M14细胞c-KIT和p-c-KIT蛋白的表达情况.结果:M14细胞存在c-KIT表达,B16F10细胞未见表达.3种浓度甲磺酸伊马替尼均能抑制M14细胞的增殖,导致其形态改变:10、20μmol/L甲磺酸伊马替尼均能抑制B16F10细胞的增生,5μmol/L甲磺酸伊马替尼对其无影响.不同浓度甲磺酸伊马替尼均能抑制M14细胞p-c-KIT蛋白的表达,但对c-KIT蛋白无影响.结论:甲磺酸伊马替尼能抑制M14细胞的增殖,机制可能与抑制c-KIT的磷酸化有关.