白发可能是抗癌反应

日本研究人员发现，毛囊和人类的DNA一样，会受到外在压力的破坏。当压力过大时，毛囊中分化为黑素细胞的干细胞就会死亡，头发就会失去乌黑亮丽的风采。

一种预测个体肿瘤的抗癌药物反应分类计算模型及其应用

目的 不同患者对同一抗癌药物的反应可能不同,了解患者之间对抗癌药物的反应差异对癌症精准医疗具有重大参考价值。方法 高通量测序数据为构建抗癌药物反应分类预测模型提供了强大的数据支撑。针对两大经典数据集癌症细胞百科全书(CCLE)和癌症药物敏感性基因组学数据集(GDSC),本文提出了基于最大相关最小冗余(mRMR)算法和支持向量机(SVM)的计算模型mRMR-SVM。利用基因表达数据,通过方差排序和mRMR算法提取特征基因,借助SVM实现抗癌药物对细胞系的“敏感-抑制”二分类预测。结果 对于CCLE中的22种药物,mRMR-SVM的平均准确率为0.904;对于GDSC中的11种药物,平均准确率为0.851。结论 mRMR-SVM不仅在预测性能方面优于传统的支持向量机、随机森林、深度反应森林、深度神经网络和细胞系-药物复杂网络模型,而且具有良好的泛化能力,对于三类特定组织的抗癌药物反应分类预测也取得了令人满意的结果。此外,mRMR-SVM可以识别与癌症发生发展密切相关的生物标志物。

树突状细胞的肿瘤个体化治疗

肿瘤免疫治疗这一概念是基于机体的免疫系统在对抗肿瘤时的调节与反应。有效的免疫治疗的最主要的优点在于相对较少的副作用,针对肿瘤细胞的靶向特异性,并且能产生对抗肿瘤特异性抗原的长期记忆[1]。

SLC与肺癌免疫治疗

肺癌是发病率和死亡率增长最快,对人类健康和生命威胁最大的恶性肿瘤,近年来人们不断探索新的肿瘤治疗方法。最近发现的一种称为继发淋巴组织趋化因子蛋白(SLC),实验证实能有效治疗动物肺癌。本文就SLC的功能及抗肿瘤机制作一概述。

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: The follow-up study of gastrointestinal cancer patients

AIM: To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic αGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer. METHODS: Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages Ⅰ-Ⅳ without distant metastases were subjected to follow- up. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment. RESULTS: In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and αGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cut- off value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (χ2 = 3.89, all patients; χ2 = 5.34, patients without regional lymph node metastases; P < 0.05). The percentage of patients with a tumor in stage I, whose mean anti-TF IgG level remained above the cut-off value (1.26), was significantly higher than that of patients with the cancer in stages Ⅲ-Ⅳ (χ2 = 4.71, gastric cancer; χ2 = 4.11, gastrointestinal cancer; P < 0.05). The correlation was observed to exist between the level of anti-TF IgG and the count of lymphocytes (r = 0.517, P < 0.01), as well as between the level of anti- Tn IgG and that of serum CA 19-9 (r = 0.481, P < 0.05). No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed. CONCLUSION: The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stage- and morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.

Antiangiogenic therapy for human pancreatic carcinoma xenografts in nude mice

AIM: To investigate the anti-tumor effects of antiangiogenic therapy (a combination of TNP-470, an antiangiogenic compound, with gemcitabine, an antimetabolite) on human pancreatic carcinoma xenografts and its mechanism. METHODS: A surgical orthotopic implantation (SOI) model was established by suturing small pieces of SW1990 pancreatic carcinoma into the tail of pancreas in nude male mice. Mice then received either single therapy (n = 24) or combined therapy (n = 32). Mice receiving single therapy were randomly divided into control group, G100 group receiving 100 mg/kg gemcitabine IP on d O, 3, 6 and 9 after transplantation, and T30 group receiving 30 mg/kg TNP-470 s.c on alternate days for 8 wk. Mice receiving combined therapy were randomly divided into control group, T15 group, G50 group and combination group (TNP-470 30 mg/kg and gemcitabine 50 mg/kg). Animals were killed 8 wk after transplantation. Transplanted tumors, liver, lymph node and peritoneum were removed. Weight of transplanted tumors, the T/C rate (the rate of mean treated tumor weight to mean control tumor weight), change of body weight, metastasis rate, and 9-wk survival rate were investigated. Tumor samples were taken from the control group, T30 group, G100 group and combination group. PCNA index (PI) and microvessel density (MVD) were investigated by immunohistochemical staining for PCNA and factor VIII, respectively. RESULTS: There was a significant inhibitory effect on primary tumor growth of pancreatic carcinoma in G100 group, compared to T30 group, whereas tumor metastasis was significantly inhibited in T30 group compared to G100 group. There was no significant improvement in survival rate in these two groups. No significant inhibitory effect on tumor growth and metastasis in T15 group and G50 group. However, significant anti-tumor and anti-metastatic effects were observed in the combination group with a significant improvement in survival rate. The inhibitory effect on tumor growth in combination group enhanced 2 times in comparison with G50 group and 5 times in comparison with T15 group. Moreover, 25% of the animals hearing tumors were cured by the combination therapy. The levels of MVD and PI were 14.50±5.93 and 0.41±0.02,12.38±1.60 and 0.30±0.07, 7.13±2.99 and 0.37±0.03, and 5.21±1.23 and 0.23±0.02 respectively in the control group, G100 group, T30 group and combination group. A significant inhibitory effect on PI level and MVD level was observed in G100 group and T30 group respectively whereas both MVD and PI levels were significantly inhibited in the combination group (P<0.05). CONCLUSION: Antiangiogenic therapy shows significant anti-tumor and anti-metastatic effects, and is helpful to reduce the dosage of cytotoxic drugs and the side effects. These effects are related to the antiangiogenic effect of TNP-470 and cytotoxic effect of gemcitabine.

Relationship between the downregulation of HLA class Ⅰ antigen and clinicopathological significance in gastric cancer

AIM:To discuss the expression of human leukocyte antigen (HLA) class Ⅰ antigens in gastric cancer and correlate these with pathologic type and TNM stage. METHODS: The expression of HLA class Ⅰ antigen was detected by immunohistochemistry in 185 specimens of gastric cancer, 20 gastric cancer specimens with lymphatic metastasis and 22 controls of normal gastric mucosa using four monoclonal antibodies. RESULTS: The expression of HLA class Ⅰ antigen (B/C locus) was significantly downregulated in gastric cancer and in lymphatic metastasis than that in normal gastric mucosa (x2=7.712, P<0.05). The expression of other HLA class Ⅰ antigens was also downregulated, but the change was slight. There was no relationship between the downregulation of HLA class Ⅰ antigen and that of β2m and LMP2. The expression of HLA class Ⅰ (B/C locus) was statistically correlated with pathologic stage in gastric adenocarcinoma (x2=4.164,P<0.05). CONCLUSION: The expression of HLA class Ⅰ antigen (B/C locus) was obviously downregulated in gastric cancer and in lymphatic metastasis. This abnormal expression would provide the tumor cells with a way to avoid immunological recognition.

科学家发现抑制抗肿瘤免疫细胞新细胞

玛嘉烈公主癌症中心的科学家日前发现了肿瘤中一种特殊的细胞群体可以抑制人体的抗癌免疫反应。这项研究成果近日发表在《Nature Medicine》上，研究资深作者Pamela Ohashi认为这让我们更深入地理解了患者为何对免疫治疗有效或者无效。

Radiation Recall Reaction:Two Case Studies Illustrating an Uncommon Phenomenon Secondary to Anti-Cancer Agents

Radiation recall phenomenon is a tissue reaction that develops throughout a previously irradiated area,precipitated by the administration of certain drugs.Radiation recall is uncommon and easily neglected by physicians;hence,this phenomenon is underreported in literature.This manuscript reports two cases of radiation recall.First,a 44-year-old man with nasopharyngeal carcinoma was treated with radiotherapy in 2010 and subsequently developed multi-site bone metastases.A few days after the docetaxel-based chemotherapy,erythema and papules manifested dermatitis,as well as swallowing pain due to pharyngeal mucositis,developed on the head and neck that strictly corresponded to the previously irradiated areas.Second,a 19-year-old man with recurrent nasal NK/T cell lymphoma initially underwent radiotherapy followed by chemotherapy after five weeks.Erythema and edema appeared only at the irradiated skin.Both cases were considered chemotherapeutic agents that incurred radiation recall reactions.Clinicians should be knowledgeable of and pay attention to such rare phenomenon.

In Vitro and in Vivo Study of the Antitumor Effects of a THANK Modified Hepatoma Cell Line

Objective THANK, known as a member of TNF superfamily, is a potent costimulator of both B and T lymphocytes and can promote astrong immune response. To investigate its role in liver immunotherapy, the anti-tumor effects of the THANK-transduced hepatoma cellline SMMU-7721 in vitro and in vivo were studied.Methods THANK full-length cDNA was transfected into SMMU-7721 cell line. The transfectant with stable expression of THANK wasobtained by clone selection and THANK s effects on hepatoma cells were analyzed, further the tumorigenicity of THANK-transduced7721 cells was examined in nude mice.Results THANK's expression in 7721 cells inhibited the growth of hepatoma cells and induced a strong CTL response in vitro. The cellcycle analysis showed that THANK transfected 7721 cells were arrested in the S phase. The expression of THANK in SMMU-7721 cellline not only inhibited the tumorigenicity of 7721 cells, but also induced a systemic immune response against re-challenge of parental7721 tumors.Conclusion THANK transduction in SMMU-7721 cells can induce an effective immune response in nude mice and may be useful for theimmunotherapy of hepatomas.

Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array

AIM： To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer （mCRC） with the aim of identifying prognostic markers.METHODS： The expression of 44 angiogenesis- secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vas- cular endothelial growth factor （VEGF） and its soluble vascular endothelial growth factor receptor （sVEGFR）-I protein levels by enzyme immunoassay （EIA） in a panel of 16 CRC cell lines, mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction （Q-RT-PCR） and vascular en- dothelial growth factor receptor （VEGFR）-2 expressionwas analyzed by flow cytometry.

抗肿瘤，不妨模拟病毒

科技日报2015年8月28日报道，加拿大研究人员以结肠癌干细胞为靶标，发现了一种可模拟病毒并触发抗癌免疫反应的机制。27日在线发表在《细胞》期刊上的此项研究成果，为理解抗肿瘤机制的重大转变指明了方向，同时也确定了对抗结肠癌干细胞的成药目标。 多伦多大学医学院生物物理系助理教授丹尼尔·卡瓦略称，模拟病毒可诱导免疫系统将肿瘤细胞视为需要被摧毁的感染源。研究表明，病毒模拟是一种可行的抗肿瘤策略。目前，结肠癌的复发率约为50％，名列癌症相关致死病因的前三位。

Synthesis of cleavable multi-functional mikto-arm star polymer by RAFT polymerization: example of an anti-cancer drug 7-ethyl-10-hydroxycamptothecin(SN-38) as functional moiety

Multi-functional mikto-arm star polymers containing three different arms [hydrophilic, SN-38-P（OEGMAs_9）11, cationizable, SN-38-P（DMAEMA）3s and hydrophobic, SN-38-P（BMA）26] were prepared by RAFT polymerization via an arm-first approach using a cleavable cross-linker. The star polymers were cleaved to the linear arms with tributylphosphine as a reducing agent. The decrease in molecular weight observed is consistent with the initial stars having approximately five arms, Blue fluorescence was observed when a solution of mikto-arm star was irradiated under a 365 nm light proving the retention of the SN-38 moiety during star formation by RAFT polymerization. Thus these polymer-drug conjugates can be considered as potential delivery vehicles for cancer therapy. The P（DMAEMA） arms can be quaternized using iodomethane, allowing star polymers to bind negatively charged small interfering RNA （siRNA） and potentially be used as a carrier for that material.