Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 75
Filter
1.
J. coloproctol. (Rio J., Impr.) ; 40(4): 412-420, Oct.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1143169

ABSTRACT

ABSTRACT Introduction: Colorectal cancer is the third most common cancer worldwide, with about 15% of these tumours related with microsatellite instability, which confers distinct characteristics to these tumours, both clinicopathological and in the response to treatments. In fact, the poor response to chemotherapy in these tumours has led to the investigation for new treatments, with immunotherapy being the most successful one to date. The focus of this review is to assess the response of microsatellite unstable colorectal cancer to PD-1 blockade, and the mechanisms behind that response. Methods: A PubMed research was conducted, resulting in the inclusion of 47 articles in this review. Results: Microsatellite instability results in a high neoantigen load, leading to a highly active immune microenvironment of the tumour, mainly due to T-cells. To counteract this, there is an upregulation of PD-1, acting as a "brake" for immune cells, facilitating tumour growth and metastasis. This upregulation makes these tumours great candidates for treatment with PD-1 blockade, as seen in many clinical trials, where the overall responses and progression free survival rates were higher than those observed in microsatellite stable tumours. Conclusion: With the importance of colorectal cancer with microsatellite instability new treatments are necessary. Therefore, PD-1 blockade is a promising treatment for colorectal cancer with microsatellite instability, with improvement in survival rates and a better prognosis for these patients.


RESUMO Introdução: O câncer colorretal é o terceiro mais comum em todo o mundo, com cerca de 15% desses tumores relacionados com instabilidade dos microssatélites, o que confere características distintas a esses tumores, tanto clínico patológicas quanto na resposta aos tratamentos. De fato, a fraca resposta à quimioterapia nesses tumores levou à investigação de novos tratamentos, sendo a imunoterapia a mais bem sucedida até o momento. O foco desta revisão é avaliar a resposta do câncer colorretal com microssatélites instáveis ao bloqueio do PD-1 e os mecanismos por trás dessa resposta. Métodos: Foi realizada uma pesquisa na base de dados PubMed, resultando na inclusão de 47 artigos nesta revisão. Resultados: A instabilidade de microssatélites resulta em uma alta carga de neoantígenos, levando a um microambiente imunológico altamente ativo do tumor, principalmente devido às células T. Para neutralizar isso, há uma maior expressão do PD-1, atuando como um "freio" para as células imunes, facilitando o crescimento do tumor e suas metástases. Essa expressão faz desses tumores grandes candidatos ao tratamento com bloqueio PD-1, como demonstrado em vários ensaios clínicos, onde as respostas globais e as taxas de sobrevivência livres de progressão foram maiores do que as observadas em tumores com microssatélites estáveis. Conclusão: Com a importância do câncer colorretal com instabilidade de microssatélites, novos tratamentos são necessários. Portanto, o bloqueio do PD-1 é um tratamento promissor para o câncer colorretal com instabilidade de microssatélites, com melhora nas taxas de sobrevivência e melhor prognóstico para esses pacientes.


Subject(s)
Humans , Male , Female , Colorectal Neoplasms/pathology , Programmed Cell Death 1 Receptor/therapeutic use , Immunotherapy/methods , Microsatellite Instability
2.
Journal of Experimental Hematology ; (6): 1069-1074, 2020.
Article in Chinese | WPRIM | ID: wpr-827159

ABSTRACT

Abstract  Acute myeloid leukemia (AML) is a malignant clonal proliferative hematological tumor that originates from hematopoietic stem progenitor cells. Traditional chemotherapy can achieve complete remission in most patients, but so far, only allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way to cure AML. Recurrence, drug resistance, and transplant-related deaths remain a key issue for AML treatment. Therefore, finding new treatments to improve the prognosis of patients with AML is urgently needed. In recent years, the emergence of new immunotherapy has revolutionized the concept of cancer treatment in the past few decades. Cellular immunotherapy represented by chimeric-antigen receptor T cell (CAR-T) and immunological detection point inhibitor represented by PD-1 blockade have achieved remarkable effects in hematological malignancies. This article mainly reviews the recent research progress of CAR-T and PD-1 blockade in the clinical treatment of AML.


Subject(s)
Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive , Leukemia, Myeloid, Acute , Programmed Cell Death 1 Receptor , Receptors, Chimeric Antigen
3.
Chinese Journal of Biotechnology ; (12): 969-978, 2020.
Article in Chinese | WPRIM | ID: wpr-826879

ABSTRACT

Drugs targeting immune checkpoint are used for cancer treatment, but resistance to single drug may occur. Combination therapy blocking multiple checkpoints simultaneously can improve clinical outcome. Therefore, we designed a recombinant protein rPC to block multiple targets, which consists of extracellular domains of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). The coding sequence was inserted into expression vector and stably transfected into HEK293 cells. The culture supernatant was collected and rPC was affinity-purified. Real-time quantitative PCR was used to evaluate the expression levels of ligands for PD-1 and CTLA-4 in several human cancer cell lines. The binding of rPC with cancer cells was examined by immunofluorescence cell staining, the influence of rPC on cancer cell growth was assayed by CCK-8. The results showed that rPC could be expressed and secreted by stably transfected HEK293 cells, the purified rPC could bind to lung cancer NCI-H226 cells which have high levels of ligands for PD-1 and CTLA-4, no direct impact on cancer cell growth could be observed by rPC treatment. The recombinant protein rPC can be functionally assayed further for developing novel immunotherapeutic drugs for cancer.


Subject(s)
Animals , CTLA-4 Antigen , Genetics , Cell Proliferation , HEK293 Cells , Humans , Lung Neoplasms , Metabolism , Programmed Cell Death 1 Receptor , Genetics , Protein Binding , Protein Domains , Genetics , Recombinant Fusion Proteins , Genetics , Metabolism
4.
National Journal of Andrology ; (12): 944-948, 2020.
Article in Chinese | WPRIM | ID: wpr-880297

ABSTRACT

Prostate cancer (PCa) has become one of the common malignant diseases in elderly men, and its incidence is increasing year by year. Apart from surgery, radiotherapy and chemotherapy, immunotherapy, as with the programmed death receptor-1 (PD-1) or the programmed death ligand-1 (PD-L1) inhibitor, is a most promising new strategy for the treatment of PCa. PD-1 and PD-L1 inhibitors restore the activity of T cells by blocking the PD-1/PD-L1 signaling pathway in tumor cells, reverse the mechanism of tumor immune escape, recover the immune system and directly kill tumor cells. This review focuses on the current progress in the studies of PD-1 and PD-L1 inhibitors in the treatment of PCa.


Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy , Male , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Prostatic Neoplasms/drug therapy , Signal Transduction
5.
Immune Network ; : 8-2020.
Article in English | WPRIM | ID: wpr-811174

ABSTRACT

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anti-cancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.


Subject(s)
Acceleration , B7-H1 Antigen , Biomarkers , Biopsy , Drug-Related Side Effects and Adverse Reactions , Fatal Outcome , Humans , Prognosis , Programmed Cell Death 1 Receptor
6.
Chinese Journal of Biotechnology ; (12): 1395-1404, 2020.
Article in Chinese | WPRIM | ID: wpr-826837

ABSTRACT

By inserting microRNAs into the intron of EF1α promoter, we constructed a novel lentiviral vector knocking down PD-1 gene via microRNA and applied it to CAR-T cells. Lentiviral transduction efficiency and PD-1-silencing efficiency were detected by flow cytometry. PD-1 expression was detected by Western blotting. Relative expression of microRNA was measured by Q-PCR. Cytotoxicity of CAR-T cells based on this vector was tested by luciferase bioluminescence and flow cytometry. Compared with lentiviral vector with microRNA transcribed by U6 promotor, the transduction efficiency of lentiviral vector with microRNA which was inserted into the intron of EF1α promoter was more significant, and the knockdown rate of PD-1 was more than 90%, which was validated by flow cytometry and Western blotting. And the relative expression level of microRNA in Jurkat cells transduced with this novel lentiviral vector was shown by Q-PCR. Compared with normal CAR-T cells, CAR-T cells based on this vector showed stronger cytotoxicity against PD-L1 positive Raji cells. We successfully constructed a novel lentiviral vector that knocked down PD-1 via microRNA and verified the superiority of its transduction efficiency and knockdown efficiency of PD-1. CAR-T cells based on this vector can exert a more powerful cytotoxicity, thus providing theoretical support for the subsequent treatment of PD-L1 positive tumors.


Subject(s)
Cell Line, Tumor , Gene Knockdown Techniques , Genetic Vectors , Genetics , Humans , Lentivirus , Genetics , MicroRNAs , Metabolism , Programmed Cell Death 1 Receptor , Promoter Regions, Genetic , Genetics
7.
Article in Chinese | WPRIM | ID: wpr-829048

ABSTRACT

OBJECTIVE@#To study the expression of multiple negative costimulatory molecules on peripheral blood T cells in patients with acute myeloid leukemia (AML) and its affection on prognosis.@*METHODS@#The peripheral blood samples from patients with newly diagnosed AML, complete remission (CR), and no-remission (NR) were collected, the expression levels PD-1、VISTA and TIM-3 in CD4 and CD8 T cells were detected by flow cytometry , and the clinical data of patients were analyzed.@*RESULTS@#The expression levels of PD-1、VISTA and TIM-3 of CD4 and CD8 T cells in the newly diagnosed AML patients were significantly higher than those in control group (P<0.05). The expression levels of PD-1、TIM-3 and VISTA of CD4 and CD8 T cells in the CR group were significantly lower than those in newly diagnosed and the NR group (P<0.05). The TIM-3 expression level positively correlated with VISTA expression level of CD4 and CD8 T cells in newly diagnosed AML patients (r=0.85 and 0.73). The VISTA and PD-1 expression level of CD4 T cells in newly diagnosed AML, NR after first induction chemotherapy and high risk patients significantly increased (P<0.05), the TIM-3 expression level of CD8 T cells in high risk group significantly increased (P<0.05), and the VISTA expression level of CD8 T cells in CBFβ-MYH11 mutation-positive group significantly decreased (P<0.05).@*CONCLUSION@#The expression of PD-1、TIM-3 and VISTA in AML peripheral blood T cells may be involved in the immune escape of AML and can be the targets of treatment for acute myeloid leukemia patients.


Subject(s)
B7 Antigens , CD8-Positive T-Lymphocytes , Flow Cytometry , Hepatitis A Virus Cellular Receptor 2 , Humans , Leukemia, Myeloid, Acute , Programmed Cell Death 1 Receptor
8.
Chinese Medical Journal ; (24): 2456-2465, 2020.
Article in English | WPRIM | ID: wpr-877844

ABSTRACT

Immunotherapy has become the mainstay for lung cancer treatment, providing sustained therapeutic responses and improved prognosis compared with those obtained with surgery, chemotherapy, radiotherapy, and targeted therapy. It has the potential for anti-tumor treatment and killing tumor cells by activating human immunity and has moved the targets of anti-cancer therapy from malignant tumor cells to immune cell subsets. Two kinds of immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), are the main targets of current immunotherapy in lung cancer. Despite the successful outcomes achieved by immune checkpoint inhibitors, a small portion of lung cancer patients remain unresponsive to checkpoint immunotherapy or may ultimately become resistant to these agents as a result of the complex immune modulatory network in the tumor microenvironment. Therefore, it is imperative to exploit novel immunotherapy targets to further expand the proportion of patients benefiting from immunotherapy. This review summarizes the molecular features, biological function, and clinical significance of several novel checkpoints that have important roles in lung cancer immune responses beyond the CTLA-4 and PD-1/PD-L1 axes, including the markers of co-inhibitory and co-stimulatory T lymphocyte pathways and inhibitory markers of macrophages and natural killer cells.


Subject(s)
CTLA-4 Antigen , Humans , Immunotherapy , Lung Neoplasms/therapy , Programmed Cell Death 1 Receptor , T-Lymphocytes , Tumor Microenvironment
9.
Rev. Hosp. Ital. B. Aires (2004) ; 39(4): 146-148, dic. 2019. ilus
Article in Spanish | LILACS | ID: biblio-1099838

ABSTRACT

Los anticuerpos monoclonales que inhiben los puntos de control PD-1 y CTLA-4 se usan actualmente en el tratamiento del melanoma y cáncer metastásico de pulmón de células no pequeñas, entre otros. Se refiere el caso de una paciente con cáncer de pulmón en tratamiento con pembrolizumab. La paciente se presentó con edema facial y parálisis facial periférica. En el laboratorio se observó la hormona tirotrofina (TSH) elevada y se llegó al diagnóstico de hipotiroidismo por pembrolizumab. Inició tratamiento con levotiroxina con mejoría clínica. Se presenta este caso por el importante papel del dermatólogo en el manejo multidisciplinario del paciente oncológico. (AU)


Monoclonal antibodies that inhibit PD-1 and CTLA-4 control points are currently used in the treatment of melanoma and metastatic non-small cell lung cancer, among others. The case of a patient, with lung cancer being treated with Pembrolizumab. The patient was presented with facial edema and peripheral facial paralysis and in the laboratory the elevated hormone Tyrotrophin (TSH) was observed, the diagnosis of pembrolizumab hypothyroidism was reached. She started treatment with levothyroxine with clinical improvement. This case is presented by the important role of the dermatologist in the multidisciplinary management of the cancer patient. (AU)


Subject(s)
Humans , Female , Middle Aged , M Phase Cell Cycle Checkpoints/drug effects , Immunotherapy/adverse effects , Antibodies, Monoclonal/adverse effects , Thyroxine/therapeutic use , Brain Neoplasms/complications , Brain Neoplasms/drug therapy , Thyrotropin/analysis , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Tumor Suppressor Proteins/drug effects , Dermatology , Facial Injuries , Facial Paralysis , CTLA-4 Antigen/drug effects , CTLA-4 Antigen/physiology , Programmed Cell Death 1 Receptor/drug effects , Programmed Cell Death 1 Receptor/physiology , Pemetrexed/administration & dosage , Melanoma/complications , Melanoma/drug therapy , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Neoplasm Metastasis/drug therapy
10.
Article in Chinese | WPRIM | ID: wpr-781648

ABSTRACT

Bladder urothelial carcinoma(BUC)is a common malignant tumor in the urinary system.Pt-based chemotherapy has long been a standard therapeutic method for resectable or metastatic BUC,but with poor outcomes.Immune checkpoint inhibitors specific to programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)and cytotoxic T lymphocyte-associated protein 4(CTLA-4)pathways have shown significant antitumor activities,safety,and enduring reactivity in clinical trials,thus creating a new epoch for the treatment of advanced-stage BUC.This article reviews the relationships of BUC with PD-1/PD-L1 and CTLA-4 pathways,as demonstrated in clinical trials.In particular,the authors elucidate the clinical studies on the application of immune checkpoint inhibitors in different BUC stages and their optimal combining strategies,with an attempt to improve the clinical use of immune inhibitors for BUC treatment.


Subject(s)
Apoptosis , B7-H1 Antigen , CTLA-4 Antigen , Immunotherapy , Programmed Cell Death 1 Receptor , Signal Transduction
11.
Journal of Experimental Hematology ; (6): 2019-2023, 2019.
Article in Chinese | WPRIM | ID: wpr-781501

ABSTRACT

Abstract  Tumor cells avoid immune surveillance by overexpressing ligands of checkpoint receptors on tumor cells or adjacent cells, resulting in inability or exhaustion of T cells. Numerous studies have shown that lymphoma cells highly expressed programmed cell death ligand-1 (PD-L1), suggesting that PD-1 may become an important target for lymphoma treatment. By targeting the PD-1 protein, the cellular activity of T cells will be significantly enhanced, and the tumor growth will be inhibited. Recently, antibodies against PD-1 have shown high efficacy and safety in the clinical studies of lymphoma, which are expected to become the targeted therapeutic drugs for lymphoma. In order to deeply understand the application of PD-1 antibody in treatment of lymphoma, this review briefly summaries the present state of lymphoma studies, the action mechanism and preparation method of PD-1 antibody in clinical treatment of lymphoma.


Subject(s)
Antibodies, Monoclonal , Apoptosis , B7-H1 Antigen , Humans , Lymphoma , Programmed Cell Death 1 Receptor
12.
Chinese Journal of Lung Cancer ; (12): 250-254, 2019.
Article in Chinese | WPRIM | ID: wpr-775635

ABSTRACT

BACKGROUND@#Nivolumab is an checkpoint inhibitor combining with programmed death-1 (PD-1) receptor on T cells, which can block the interactions between PD-1 and programmed death ligands (PD-L), including PD-L1 and PD-L2. And then block the immunosuppression mediated by the PD-1 pathway. The aim of the study is to investigate the clinical manifestations, diagnosis, treatment and prognosis of treatment-related skin toxicity caused by PD-1 inhibitor Nivolumab.@*METHODS@#The clinical data of treatment-related skin toxicity caused by PD-1 inhibitor Nivolumab in a patient with advanced lung adenocarcinoma admitted to the Shanghai Chest Hospital was retrospectively analyzed. The diagnosis, treatment and prognosis of the patient were discussed.@*RESULTS@#The patient was a 60-year-old male presented with relapse after surgery and adjuvant postoperative chemotherapy for his lung carcinoma. The patient's condition still progressed after multiple chemotherapy, targeted therapy and local radiotherapy of bone metastasis. Then Nivolumab, a kind of PD-1 inhibitors, was given intravenously every 3 weeks with the average dosage 3 mg/kg. After one cycle of Nivolumab, the patient began to have skin rashes, which aggravated gradually. The patient's skin toxicity was alleviated after enough steroids and was controlled with tapering steroids slowly. Now the patient was still given oral steroids treatment. And the lung disease remained stable.@*CONCLUSIONS@#Immune-related skin toxicity associated with PD-1 inhibitor should be aware of; early detection, early treatment and the prognosis could be better. It is necessary to improve the understanding of Immune-related skin toxicity associated with PD-1 inhibitor, to diagnose and treat it early, and the prognosis could be better.


Subject(s)
Adenocarcinoma of Lung , Drug Therapy , Humans , Male , Middle Aged , Nivolumab , Pharmacology , Therapeutic Uses , Prognosis , Programmed Cell Death 1 Receptor , Skin
13.
Chinese Journal of Lung Cancer ; (12): 369-379, 2019.
Article in Chinese | WPRIM | ID: wpr-775618

ABSTRACT

In recent years, research on immunotherapy has made great progress. Currently, immunotherapy has made significant breakthrough, especially programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors (e.g, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab and Avelumab, etc.) have brought clinical benefits to patients with various pathological types of lung cancer, including squamous cell carcinoma, adenocarcinoma and small cell lung cancer. In this paper, the application value and current status of PD-1/PD-L1 checkpoint inhibitors in lung cancer were comprehensively analyzed by reviewing and interpreting representative clinical studies. Based on the results of various large-scale clinical trials results, the indications of immunotherapy in lung cancer have been continuously broadened, and the details of immunotherapy have also been constantly optimized. However, immunotherapy still faces many challenges, such as the selection of immune combination strategies, the exploration of biomarkers, the management of adverse events, the feasibility of application of driver gene mutation population and so on. In this article, we made a systematic review about the latest progress of PD-1/PD-L1 checkpoint inhibitors in lung cancer, in order to provide cutting-edge reference for the clinical workers.
.


Subject(s)
Animals , Antineoplastic Agents, Immunological , Therapeutic Uses , B7-H1 Antigen , Genetics , Allergy and Immunology , Humans , Immunotherapy , Lung Neoplasms , Drug Therapy , Genetics , Allergy and Immunology , Programmed Cell Death 1 Receptor , Genetics , Metabolism
14.
Article in Korean | WPRIM | ID: wpr-759767

ABSTRACT

Nivolumab is anti-programmed death 1 (PD1) receptor antibody, which can be used in the treatment of metastatic squamous cell cancer. By blocking the PD1 receptors on T cells, it enhances T-cell response against cancer cells. A 69-year-old man, who works as a farmer, presented with erythematous lichenified plaques on sun-exposed areas, such as the face, the chest, and both the forearms. Before the hospital visit, he was receiving lung cancer treatment with paclitaxel and cisplatin, but there was no improvement. Subsequently, the regimen was changed into nivolumab, and PET-CT showed decreased in cancer size. However, skin rashes developed simultaneously. It is consistent with the results of a previous study in which cutaneous side effects developed in 42% of responders compared to 7% of non-responders. Herein, we report a case of nivolumab-induced cutaneous toxicity on sun-exposed areas based on the clinical findings, including the distribution of rashes, which were improved after decreasing the nivolumab dose with literature review.


Subject(s)
Aged , Cisplatin , Exanthema , Farmers , Forearm , Humans , Lung Neoplasms , Neoplasms, Squamous Cell , Paclitaxel , Programmed Cell Death 1 Receptor , T-Lymphocytes , Thorax
15.
Article in Chinese | WPRIM | ID: wpr-687974

ABSTRACT

<p><b>OBJECTIVE</b>To assess the association of programmed cell death 1 (PDCD1) gene polymorphisms with the susceptibility and/or progression of colorectal cancer.</p><p><b>METHODS</b>A hospital-based case-control study was carried out, which recruited 426 colorectal cancer patients and 500 healthy individuals. Five single nucleotide polymorphisms, namely rs36084323, rs11568821, rs2227981, rs2227982 and rs10204525, were selected for the study and genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.</p><p><b>RESULTS</b>The G allele of rs36084323 under a dominant model was associated with increased risk of advanced TNM staging of colorectal cancer progression (OR=1.59, 95%CI=1.02-2.48). Haplotypes G-G-C-T-A and A-G-C-C-G of the rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525 were negatively associated with the occurrence of colorectal cancer.</p><p><b>CONCLUSION</b>The G allele of rs36084323 is associated with increased risk of advanced TNM staging of colorectal cancer. Conversely, the incidence of colorectal cancer is negatively associated with the haplotypes G-G-C-T-A and A-G-C-C-G of rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525.</p>


Subject(s)
Asian Continental Ancestry Group , Genetics , Case-Control Studies , China , Ethnology , Colorectal Neoplasms , Genetics , Pathology , Genetic Predisposition to Disease , Haplotypes , Humans , Neoplasm Staging , Polymorphism, Single Nucleotide , Programmed Cell Death 1 Receptor , Genetics
16.
Article in Korean | WPRIM | ID: wpr-738940

ABSTRACT

Anti-programmed cell death-1 (PD-1) humanized monoclonal antibody inhibits PD-1 activity by binding to the PD-1 receptor on T-cells and blocking PD-1 ligands and induces immune tolerance of cancer cells. It has been widely used for various kinds of cancer treatment. However, many immune-related adverse events (irAEs) have been reported because it modulates our immune system. In this case study, we reported a case of 42-year-old woman with Hashimoto's thyroiditis who showed rapid aggravation of thyroid goiter and acute hyperventilation syndrome after treatment with PD-1 inhibitor as a neoadjuvant chemotherapy for breast cancer.


Subject(s)
Adult , Breast Neoplasms , Breast , Drug Therapy , Female , Goiter , Humans , Hyperventilation , Immune System , Immune Tolerance , Ligands , Programmed Cell Death 1 Receptor , T-Lymphocytes , Thyroid Gland , Thyroiditis
17.
Campinas; s.n; 2018. 162 p. ilus, tab.
Thesis in Portuguese | LILACS, Inca | ID: biblio-912068

ABSTRACT

Resumo: Introdução: endometriose é uma doença benigna, capaz de progredir extensamente e gerar clones atípicos. Considerada precursora dos carcinomas de células claras (CCOC) e endometrióide (EOC) de ovário, atualmente chamados carcinomas de ovário associados à endometriose (EAOC). Objetivos: comparar o perfil epidemiológico, a associação com endometriose e a expressão de marcadores imuno-histoquímicos para ARID1A, VEGF, PD-L1 e PARP-1 em mulheres com CCOC e EOC, e sua correlação com a sobrevida livre de progressão (SLP) e sobrevida global (SG). Métodos: estudo de coorte reconstituída, com 50 casos incluídos de CCOC e EOC tratados no CAISM-UNICAMP entre 1995 até 2016, acompanhados até 02/2017. Microarranjos de tecido com amostras de CCOC, EOC e endometriose foram corados com anticorpos monoclonais contra ARID1A, e para os biomarcadores proteicos VEGF, PD-L1, PARP-1 através de imuno-histoquímica. A expressão de ARID1A foi classificada (0 a 100) conforme a porcentagem de células não coradas. A expressão de VEGF, PD-L1 e PARP-1 foi classificada (0 a 300) conforme a multiplicação da porcentagem de células coradas por um fator da intensidade de expressão (ausente=0; fraco=1; moderado=2; forte=3). Idade ao diagnóstico; menopausa; índice de massa corpórea (IMC); CA-125; diagnóstico de endometriose; datas do diagnóstico, da progressão, do óbito e da última consulta foram recuperados dos prontuários. Comparação entre grupos foi realizada através de testes T e de ?2. A SLP (diferença de tempo entre o diagnóstico e a data de progressão) e a SG (diferença de tempo entre o diagnóstico e o óbito ou data da última data de consulta) foi avaliada através de curvas de Kaplan-Meyer e teste de Log-Rank ou regressão de COX. Resultados: 23 mulheres com CCOC (46%), e 27 com EOC (54%) foram incluídas; 80% tinham endometriose associada, 42% eram nulíparas, 42% eram pré-menopausa e CA125 foi elevado em todos estádios (FIGO I-II= média 614.7Ui/mL; FIGO III-IV= media 2361.2Ui/mL). A média de idade ao diagnóstico foi 7 anos menor em mulheres com EOC do que naquelas com CCOC. O CCOC foi mais diagnosticado em estágios iniciais quando associado à endometriose (p=0,03). O prognóstico dos EOC e CCOC em estádios iniciais foi semelhante (p=0,96). Os CCOC não associado à endometriose tiveram menor SG (p=0,04). A expressão de todos os biomarcadores esteve presente nos EAOC e na endometriose. O aumento da expressão de VEGF entre endometriose e câncer foi significativo (p=0,0002). A hiperexpressão de PARP-1 correlacionou-se negativamente com a SLP (p=0,03) e SG (p=0,01) em estádios iniciais. Conclusão: Os CCOC e EOC são comumente diagnosticados em estádios iniciais (FIGO I-II= 68%) e estão frequentemente associados à endometriose (80% dos casos). Quando associados à endometriose, os CCOC foram mais diagnosticados em estádios iniciais e tiveram SG maior. Houve elevada porcentagem de células com ARID1A mutado nos EAOC (>40%). VEGF se expressou mais intensamente nos CCOC e EOC que na endometriose, já a expressão de PD-L1 e de PARP-1 foi similar. Apenas a hiperexpressão de PARP-1 reduziu significativamente a SLP e a SG nos CCOC e EOC nos estádios iniciais(AU)


Abstract: Introduction: Endometriosis is a benign disease, able to progress widely and generate atypical clones. It is a precursor of clear cell ovarian carcinomas (CCOC) and endometrioid ovarian carcinomas (EOCs), now called endometriosis-associated ovarian carcinomas (EAOC). Objectives: To compare the epidemiological profile, association with endometriosis and the expression of immunohistochemical markers for ARID1A, VEGF, PD-L1 and PARP-1 in women with CCOC and EOC, and its correlation with progression-free survival (PFS) and overall survival (OS). Methods: A reconstituted cohort study with 50 cases of CCOC and EOC included. Cases were treated at CAISM-UNICAMP between 1995 and 2016, followed up until 02/2017. Tissue microarrays with CCOC, EOC and endometriosis samples were stained with monoclonal antibodies against ARID1A, and for VEGF, PD-L1, PARP-1 biomarkers by immunohistochemistry. The expression of ARID1A was classified (0 to 100) according to the percentage of unstained cells. The expression of VEGF, PD-L1 and PARP-1 was classified (0 to 300) multiplying the percentage of stained cells by an intensity of expression factor (absent=0, weak=1, moderate=2, strong=3). Age at diagnosis; menopause; BMI (body mass index); CA-125 levels; diagnosis of endometriosis; date of diagnosis, date of progression, date of death and date of last consultation were retrieved from the medical records. Comparison between groups was performed through T and ?2 tests. The PFS (difference in time between diagnosis and progression date) and OS (difference in time between diagnosis and death or the last date of consultation) was assessed using Kaplan-Meyer curves and Log-Rank test or COX multivariate models. Results: twenty-three women with CCOC (46%), and 27 with EOC (54%) were included; 80% had associated endometriosis, 42% were nulliparous, 42% were premenopausal, and CA125 was elevated at all stages (FIGO I-II = mean 614.7Ui / mL; FIGO III-IV = mean 2361.2Ui / mL). The mean age at diagnosis was 7 years lower in women with EOC than in those with CCOC. CCOC when associated with endometriosis were more diagnosed at early stages (p=0.03). The prognosis of EOC and CCOC at early stages was similar (p=0.96). CCOCs not associated with endometriosis had shorter OS (p=0.04). Expression of all biomarkers was present in the EAOC and endometriosis. The increase in VEGF expression between endometriosis and cancer was significant (p=0.0002). The overexpression of PARP-1 correlated negatively with PFS (p=0.03) and OS (p=0.01) at FIGO I-II stages. Conclusion: The diagnosis of women with EOC was made earlier than in those with CCOC. CCOC and EOC are commonly diagnosed in early stages (FIGO I-II - 68%) and were associated with endometriosis (80% of cases). When associated with endometriosis, clear cell carcinomas are more likely diagnosed at early stages, and the association of endometriosis with CCOC improves OS. There was a high percentage of cells with mutated ARID1A gene in EAOC (> 40%). VEGF was expressed more intensely in CCOC and EOC than in endometriosis, whereas expression of PD-L1 and PARP-1 was similar. Only the overexpression of PARP-1 significantly reduced PFS and OS in CCOC and EOC at early stages(AU)


Subject(s)
Humans , Female , Prognosis , Carcinoma, Endometrioid , Endometriosis , Survival Rate , Adenocarcinoma, Clear Cell , Vascular Endothelial Growth Factors , Endometriosis/epidemiology , Programmed Cell Death 1 Receptor , Poly (ADP-Ribose) Polymerase-1
18.
Chinese Journal of Lung Cancer ; (12): 697-702, 2018.
Article in Chinese | WPRIM | ID: wpr-772377

ABSTRACT

Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint blockades have dramatically changed the treatment of non-small cell lung cancer (NSCLC). But we still have no definite biomarkers that may predict the efficacy of treatment by PD-1/PD-L1 inhibitors. In the 18th World Conference on Lung Cancer, the biomarkers that may predict the efficacy of treatment by PD-1/PD-L1 inhibitors in patients with lung cancer has been a popular topic, and it has huge potential in the future. In order to enable more patients to get more benefits from treatment, researchers are looking forward to finding the optimum biomarkers. By organizing and summarizing the information about the biomarkers predicting PD-1/PD-L1 in patients with lung cancer, this review mainly focused on the following six aspects to introduce: expression of PD-L1; tumor mutational burden and the ability of mutation repair, malignant tumor driver mutation, biomarker of immunological effect, blood cell account, comprehensive analysis model. We are hoping to help doctors to find the best biomarker, then much more lung cancer patients could obtain antitumor effects in PD-1/PD-L1 inhibitors treatment.
.


Subject(s)
Antineoplastic Agents , Pharmacology , Therapeutic Uses , B7-H1 Antigen , Biomarkers, Tumor , Metabolism , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Genetics , Metabolism , Humans , Lung Neoplasms , Drug Therapy , Genetics , Metabolism , Programmed Cell Death 1 Receptor
19.
Chinese Journal of Lung Cancer ; (12): 918-923, 2018.
Article in Chinese | WPRIM | ID: wpr-772342

ABSTRACT

Small cell lung cancer (SCLC), which accounts for about 15% of lung cancer cases, is an aggressive disease characterized by rapid growth and early widespread metastasis. Despite sensitive to chemotherapy and radiotherapy, SCLC is vulnerable to get resistant and has high recurrence rates. In recent years, immunotherapy has shown good antitumor activity, especially programmed death receptor-1/ligand-L1 (PD-1/L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) Checkpoint inhibitors have changed the pattern of tumor treatment, and SCLC has high immunogenicity, high mutation load and other favorable immune factors, so immuno-checkpoint inhibitors may become an important breakthrough in SCLC treatment. This article will briefly review the clinical research of immunotherapy for small cell lung cancer.
.


Subject(s)
Humans , Immunologic Factors , Genetics , Allergy and Immunology , Immunotherapy , Methods , Lung Neoplasms , Genetics , Allergy and Immunology , Therapeutics , Programmed Cell Death 1 Receptor , Genetics , Allergy and Immunology , Small Cell Lung Carcinoma , Genetics , Allergy and Immunology , Therapeutics
20.
Article in Chinese | WPRIM | ID: wpr-689552

ABSTRACT

In tumor patients, programmed cell death-1 (PD-1) can inhibit T-cell activation and proliferation by binding to its ligand, thereby promote tumor immune escape. A large number of experiments showed that PD-L1 molecule highly expressed on lymphoma cells, while PD-1 expression was up-regulated in tumor-infiltrating lymphocytes, suggesting its role in the development of lymphoma, which may be an important therapeutic target for lymphoma. PD-1 and PD-L1 monoclonal antibodies can block the PD-1 / PD-Ls signaling pathway, restore T cell function, thus inhibit the tumor growth. At present, a number of early clinical trials have demonstrated the significant efficacy and less side effects in various subtypes of recurrent lymphoma, which will be promising therapeutic agents. In this review, the mechanism of PD-1/PD-L1 signal pathway, the expression of PD-1 / PD-L1 in lymphoma and the anti-tumor effect of its antibody in lymphoma are summarized.


Subject(s)
B7-H1 Antigen , Humans , Lymphocytes, Tumor-Infiltrating , Lymphoma , Programmed Cell Death 1 Receptor , Signal Transduction , T-Lymphocytes
SELECTION OF CITATIONS
SEARCH DETAIL