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排序方式: 共有1517条查询结果,搜索用时 46 毫秒
1.
Yu-Hung Lee Ching-Fang Yu Ying-Chieh Yang Ji-Hong Hong Chi-Shiun Chiang 《International journal of molecular sciences》2021,22(4)
The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade. 相似文献
2.
Abidur Rahman Makoto Kobayashi Kotaro Sugimoto Yuta Endo Manabu Kojima Shigenori Furukawa Takafumi Watanabe Shu Soeda Yuko Hashimoto Keiya Fujimori Hideki Chiba 《International journal of molecular sciences》2021,22(7)
Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases. 相似文献
3.
Agnieszka Rybarczyk-Kasiuchnicz Rodryg Ramlau Katarzyna Stencel 《International journal of molecular sciences》2021,22(2)
Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases. 相似文献
4.
《Planning》2015,(1)
目的 探讨气管上段腺样囊性癌的临床病理特征及诊断和鉴别诊断要点。方法 收集2000年1月至2014年2月在北京协和医院确诊的4例气管上段腺样囊性癌病例,通过光镜、免疫组织化学及组织化学染色分析其临床病理特征、免疫组织化学特点、诊断及鉴别诊断要点。结果 4例气管上段腺样囊性癌患者中,男1例,女3例,平均年龄47岁(38~57岁);既往均无腺样囊性癌病史,1例患者既往有结节性甲状腺肿手术史。镜下检查4例均为筛状/管状型腺样囊性癌,3例累及甲状腺组织,3例累及神经组织,未见淋巴结受累。免疫组织化学染色示4例P16、CD117、BCL2、P63、SMA均阳性,Ki67指数平均8%,TTF1和P53均阴性;4例中基底膜样物胶原Ⅳ阳性;组织化学染色示AB/PAS阳性。术后均接受总剂量为48~56 Gy的放疗,随访6~120个月,平均72.5个月,1例术后96个月复发,3例随访期间无复发及转移。结论 气管上段腺样囊性癌是罕见的原发于气管的低度恶性肿瘤,肿瘤生长缓慢,就诊时多数已侵及甲状腺组织,需要与原发于甲状腺的恶性肿瘤相鉴别,特别是在甲状腺穿刺及术中冰冻检查时。结合电子喉气管镜下表现、典型的形态学及免疫组织化学和组织化学染色有助于准确诊断。手术难以切除干净,术后放疗对延缓疾病复发有一定帮助。 相似文献
5.
图像纹理增强过程中容易丢失平滑区域纹理细节,而分数阶微分增强虽然能够非线性保留平滑区域纹理细节,但对频率分辨率敏感。针对这个问题,提出一种基于小波变换的分数阶微分纹理增强算法,应用于平扫计算机断层扫描(CT)图像的肝脏肿瘤区域的纹理增强。首先,通过小波变换将图像感兴趣区分解成多个子带分量;其次,基于分数阶微分定义构造一个带补偿参数的分数阶微分掩膜;最后,使用该掩膜与每个高频子带分量进行卷积并利用小波逆变换重组图像感兴趣区。实验结果表明,该方法在使用较大分数阶次显著增强肿瘤区域的高频轮廓信息的同时,有效地保留了低频平滑的纹理细节:增强后的肝细胞癌区域与原区域相比,信息熵平均增加36.56%,平均梯度平均增加321.56%,平均绝对差值平均为9.287;增强后的肝血管瘤区域与原区域相比,信息熵平均增加48.77%,平均梯度平均增加511.26%,平均绝对差值平均为14.097。 相似文献
6.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
7.
8.
The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes. 相似文献
9.
CO2激光治疗皮肤基底细胞癌14例临床观察 总被引:4,自引:0,他引:4
目的 :探求一种简单 ,安全 ,效果好的基底细胞癌的治疗方法。方法 :对 1 4例基底细胞癌患者在局麻下用CO2 激光行基底细胞癌切除术或切除 +气化术。结果 :患者术中、术后出血少 ,伤口恢复快 ,愈合良好 ,疤痕表浅 ,随访未见复发。结论 :CO2 激光用于治疗基底细胞癌效果良好 ,无明显副作用 ,操作简单值得推广。 相似文献
10.
在第一部分综合讨论的基础上对甘三酯立体专一分析方法作了初步探讨。以液体油(菜油)及固体脂(猪脂)为基质,系统地研究了这一分析方法,取得了经验并补充了一些具体验证方法。分析液体油的结果与文献数据相一致,分析猪脂的结果欠佳,还存在一些问题需待进一步研究。 相似文献