Terapia com células CAR-T: reprogramação celular para o combate de neoplasias malignas / CAR-T cell therapy: cell reprogramming to combat malignant neoplasms

As células CAR-T são linfócitos geneticamente modificados para reconhecerem um espectro amplo de antígenos de superfície celulares. Além disso, atacam células tumorais malignas, que expressam esses antígenos, por meio da ativação da coestimulação citoplasmática, secreção de citocinas, citólise de células tumorais e proliferação de células T. O objetivo desse estudo é abordar a imunoterapia com células CAR-T, a fim de explicar seu conceito, processo de fabricação e papel no tratamento de neoplasias hematológicas e tumores sólidos. Foi realizada uma revisão através do portal PubMed, utilizando como descritores: "car-t cell therapy" e "neoplasms", determinados com base nos "Descritores em Ciências da Saúde". Foram obtidos, inicialmente, 10 artigos, os quais foram lidos integralmente para a confecção dessa revisão. Além disso, foram adicionados 3 ensaios clínicos atualizados sobre o tema. Na terapia com células CAR-T, as células T são coletadas do paciente, geneticamente modificadas para incluir receptores de antígeno específicos e, posteriormente, expandidas em laboratórios e transfundidas de volta para o paciente. Assim, esses receptores podem reconhecer células tumorais que expressam um antígeno associado a um tumor. A terapia com células CAR-T é mais conhecida por seu papel no tratamento de malignidades hematológicas de células B, sendo a proteína CD19 o alvo antigênico mais bem estudado até o momento. Entretanto, estudos estão sendo feitos para verificar a eficácia desse tratamento, também, em tumores sólidos. Portanto, apesar de inicialmente ser indicada apenas para um grupo seleto de pessoas, essa terapia tem demonstrado grande potencial para atuar em um espectro maior de pacientes.

The CAR-T cells are lymphocytes genetically modified to recognize a broader spectrum of cell surface antigens. In addition, they attack malignant tumor cells, which express these antigens, by activating cytoplasmic co-stimulation, cytokine secretion, tumor cell cytolysis and T cell proliferation. The aim of this study is to address immunotherapy with CAR-T cells, in order to explain its concept, manufacturing process and role in the treatment of hematological neoplasms and solid tumors. This is a literature review conducted through the PubMed portal, that uses the terms "car-t cell therapy" and "neoplasms" as descriptors, determined based on the DeCS (Descritores em Ciências da Saúde). To prepare this review, initially 10 articles were found and read in full. In addition, 3 updated clinical trials on the subject were added. For CAR-T cell therapy, T cells are collected from the patient, genetically modified to include specific antigen receptors, and later expanded in laboratories and transfused back to the patient. Thus, these receptors can recognize tumor cells that express a tumor-associated antigen. CAR-T cell therapy is best known for its role in the treatment of B cell hematological malignancies, with the CD19 protein being the most studied antigenic target to date. However, studies are being conducted to verify the effectiveness of this treatment, also, in solid tumors. Therefore, despite being formulated only for a selected group of patients, this therapy has great potential to act on a broader spectrum of patients.

TAT and PIC better than D-dimer in monitoring hypercoagulability of cancer patients / 中华检验医学杂志

Objective@#The aim of this study is to investigate the variation tendency of coagulation and fibrinolysis biomarkers in cancer patients and to explore the effect of these biomarkers for the diagnosis of thrombosis in cancer patients.@*Methods@#171 cancer patients admitted to hospital from September 2017 to July 2019 were enrolled in the study, including 40 cancer patients undergoing surgery, 108 cancer patients without surgery in control group and 23 cancer patients with thrombus. New coagulation and fibrinolysis biomarkers, TM (Thrombomodulin), TAT (Thrombin -antithrombin complex), PIC (Plasmin alpha 2-plasmin inhibitor complex) and t-PAI·C (Tissue plasminogen activator-plasminogen activator inhibitor-1 complex), were tested in every patient. In addition, these new biomarkers are compared with D-dimer.@*Results@#A statistically difference was available on the value of TAT, TM, PIC, t-PAIC, between postoperative cancer patients group and control group (P<0.05, respectively). TAT, TM and PIC in thrombosis cancer group were higher than those in non-thrombosis cancer group (P<0.05; respectively). ROC was used to evaluate the performance of D-dimer, TAT and PIC on thrombosis in cancer patients. The results showed that the AUC of PIC and TAT were both higher than D-dimer (0.871 vs. 0.619; 0.788 vs. 0.619). The specificity of PIC alone was higher than that of D-dimer (91.9% vs. 82.4%), and the sensitivity of PIC and TAT alone was higher than that of D-dimer (73.9% vs. 47.8%, 73.9% vs. 47.8%, respectively).@*Conclusions@#The activity of coagulation and fibrinolysis in cancer patients was abnormally enhanced. TAT and PIC were better than D-dimer for the diagnosis of thrombosis in cancer patients.

TAT and PIC better than D-dimer in monitoring hypercoagulability of cancer patients / 中华检验医学杂志

Objective The aim of this study is to investigate the variation tendency of coagulation and fibrinolysis biomarkers in cancer patients and to explore the effect of these biomarkers for the diagnosis of thrombosis in cancer patients. Methods 171 cancer patients admitted to hospital from September 2017 to July 2019 were enrolled in the study, including 40 cancer patients undergoing surgery, 108 cancer patients without surgery in control group and 23 cancer patients with thrombus. New coagulation and fibrinolysis biomarkers, TM (Thrombomodulin), TAT (Thrombin-antithrombin complex), PIC (Plasmin alpha 2-plasmin inhibitor complex) and t-PAI · C (Tissue plasminogen activator-plasminogen activator inhibitor-1 complex), were tested in every patient. In addition, these new biomarkers are compared with D-dimer. Results A statistically difference was available on the value of TAT, TM, PIC, t-PAIC, between postoperative cancer patients group and control group (P<0.05, respectively). TAT, TM and PIC in thrombosis cancer group were higher than those in non-thrombosis cancer group (P<0.05;respectively). ROC was used to evaluate the performance of D-dimer, TAT and PIC on thrombosis in cancer patients. The results showed that the AUC of PIC and TAT were both higher than D-dimer (0.871 vs. 0.619;0.788 vs. 0.619). The specificity of PIC alone was higher than that of D-dimer(91.9％ vs. 82.4％), and the sensitivity of PIC and TAT alone was higher than that of D-dimer(73.9％ vs. 47.8％, 73.9％ vs. 47.8％, respectively). Conclusions The activity of coagulation and fibrinolysis in cancer patients was abnormally enhanced. TAT and PIC were better than D-dimer for the diagnosis of thrombosis in cancer patients.

Relation between macroscopic type and cellular origin of intrahepatic cholangiocarcinoma / 国际外科学杂志

Intrahepatic cholangiocarcinoma,which occurrence and development involved kinds of cells and genes changes,is a vital part of the primary carcinoma of liver.The cellular origin may includes bile duct epithelial cells,hepatic stem cells and hepatic cells.The macroscopic type may includes:nass-forming types,periductal infiltrating types,intraductal growth types.The fact was revealed that different macroscopic type of intrahepatic cholangiocarcinoma has different clinical features,outcomes and prognosis.The author reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma,focusing especially on the macroscopic subtypes and related cell features,to discover the relaticn between macroscopic type and cellular origin of intrahepatic cholangiocarcinoma and better understand the pathogenesis of intrahepatic cholangiocarcinoma.

Coexpression of p53 and Ki 67 and lack of c-erbB2 expression in oral leukoplakias in India

Oral cancer is commonly preceded by premalignant lesions and conditions. The clinician's ability to identify lesions at an increased risk of cancer development is critical for its control. The purpose of this study was to compare the expression of tumor suppressor gene p53, proliferation marker Ki-67, and oncogene c-erbB2 and to evaluate the relevance of their co-expression in the diagnosis of, and prognosis for, oral leukoplakia. In the present study, the expression of biomarkers was studied immunohistochemically in 55 cases of leukoplakia (26 without dysplasia, 29 with dysplasia) and 10 cases of normal epithelia. The Labeling Indices (LI) of p53 and Ki-67 were found to increase significantly with an increase in the grade of dysplasia. A significant correlation was also found between the LI of p53 and that of Ki-67. It was also observed that c-erbB2 expression was only cytoplasmic, indicating incomplete receptor degradation. Hence, it can be concluded from the present study that the increased expression of p53 and Ki-67 with an increase in the grade of dysplasia suggests that their co-expression may be used for the identification of high-risk lesions. Also, c-erbB2 has no pathogenetic role in early carcinogenesis in the studied population, although incomplete receptor degradation, as evidenced by cytoplasmic staining, may indicate an early change.

Expression of Tumor Metastasis Associated Gene Ezrin in Nasopharyngeal Carcinoma / 天津医药

Objective: To investigate the expression and clinical significance of Ezrin, a tumor metastasis related gene, in tissues of nasopharyngeal carcinoma (NPC). Methods: The expression of Ezrin was detected with two-step immunohistochemistry technique in tissues of 38 NPC patients and 20 nasopharyngitis patients. All of the Ezrin expression and clinical data (gender, age, clinical stage, recurrence, and ]ymphonode metastasis) were compared and analyzed between two groups. Resuits: The Ezrin expressions were significantly different between NPC tissue (and peri-NPC tissue) and naeopharyngitis tissue (P＜0.05). No significant difference was found in the Ezrin expressions between the NPC tissue and the peri-NPC tissue (P＞0.05). It was found by Spearman analysis method that the Ezrin expression increased with patients' age (P＜0.05), but no significam relationship with gender, clinical stage, recurrence, and lymphonode metastasis (P＞0.05). The Ezrin expression influenced the survival time of NPC patients significantly (P＜0.01). Conclusion: The Ezrin expression can be an useful prognostic factor for NPC patients.

Expressions of CD28/CTLA-4:B7 co-stimulatory molecules in patients with gastric cancer and its clinical significance / 国际检验医学杂志

Objective To investigate.the co-stimulatory pathway of gastric cancer patients by examining the expression of co-stimulatory molecules CD28,CTLA.4(CDl 52)and B7 molecules on peripheral blood lymphocytes(PBLC)in patients with gastric cancer,and to discuss the role of costimulatory pathway in the pathogenesis of gastric cancer.Methods The expression of CD28,CD152,CD3,CD4,CD8 and B7 molecules on peripheral blood lymphocytes and T cell subpopulation were measured by flow cytometry in 56 patients with gastric cancer,and the data was compared and analyzed with that in gastric benign tumor group and healthy control group.Results The expression levels of CD3+,CD4+,CD3+ CD28+,B7-1(CD80),B7-2(CD86)and CD41/CD8+on PBLC in patients with gastric cancer was significantly lower than that of benign stomach tumor group and healthy control group.The expression levels of CD3+ CDl52+ and CD8+ on PBLC in patients with gastric cancer were significantly higher than those of gastric benign tumor group and healthy control group.Conclusion Peripheral lymphocytcs in gastric cancer patients express low level of CD28 and B7 molecules and high level of CDI 52 molecules,which results in dysfunction of B7:CD28/CTLA-4 co-stimulation pathway and in turn affects the capacity of T cell to eliminate tumor cells,which makes tumor cells evading the immune surveillance and metastasizing.

Treatment of Tumor in Nasopharynx and the Base of Nasal Cavity by Hard Palate Approach Through Endoscopic Surgery / 医学研究杂志

Objective To evaluate the practical value tumor from nasopharynxl and the base of nasal cavity . Methods 12 patients , among these 5 cases suffered from the tumor of the base of nasal cavity and 7 from nasopharynx , were treated from January 2001 to January 2005 . After general anesthesia the tumors were incised by hard palate approach , and the preoperative selective intraarterial embolization were used in three nasopharyngeal tumors, and The controlled hypotension were used during surgery ifnecessary.Results Two malignant tumors were changed the type of surgery after the operation quick freeze pathologic examination. The mucosal flaps of other 10 cases survived and the function of phonation、swallowing、respiration and mastication were normal. The patients remained free of disease after follow-up period of over 1 year. Conclusions The endoscopic managent of resection tumor of nasopharynxl and the base of nasal cavity by hard palate approach have great advantage to traditional hard palate approach.