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1.
Zhonghua Yi Xue Za Zhi ; 101(12): 831-835, 2021 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-33789362

RESUMO

Pancreatic ductal adenocarcinoma is one of the common malignant tumors of the digestive tract. It has the characteristics of strong occlusion, aggressiveness, easy metastasis, and resistance to radiotherapy and chemotherapy. Therefore, its five-year survival rate is extremely low, with a rate of less than 8%. Looking for a new treatment is an urgent need to improve the prognosis of pancreatic ductal adenocarcinoma. In recent years, a large number of clinical trials have been carried out, such as immune checkpoint inhibitors, monoclonal antibodies to important antigens, and immune cell therapy. However, it is disappointing that no satisfactory clinical benefits have been achieved. The special microenvironment of pancreatic cancer nests makes immunotherapy not as effective as other malignant tumors. This article introduces the characteristics of the suppressive immune microenvironment of pancreatic cancer and the latest clinical studies of different types of immunotherapy at home and abroad, and analyzes the mechanisms and potentials of combined treatment based on the characteristics of the immune microenvironment.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/terapia , Terapia Combinada , Humanos , Imunoterapia , Neoplasias Pancreáticas/terapia , Microambiente Tumoral
2.
Nat Commun ; 12(1): 1453, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674603

RESUMO

A major roadblock prohibiting effective cellular immunotherapy of pancreatic ductal adenocarcinoma (PDAC) is the lack of suitable tumor-specific antigens. To address this challenge, here we combine flow cytometry screenings, bioinformatic expression analyses and a cyclic immunofluorescence platform. We identify CLA, CD66c, CD318 and TSPAN8 as target candidates among 371 antigens and generate 32 CARs specific for these molecules. CAR T cell activity is evaluated in vitro based on target cell lysis, T cell activation and cytokine release. Promising constructs are evaluated in vivo. CAR T cells specific for CD66c, CD318 and TSPAN8 demonstrate efficacies ranging from stabilized disease to complete tumor eradication with CD318 followed by TSPAN8 being the most promising candidates for clinical translation based on functionality and predicted safety profiles. This study reveals potential target candidates for CAR T cell based immunotherapy of PDAC together with a functional set of CAR constructs specific for these molecules.


Assuntos
Adenocarcinoma/metabolismo , Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Moléculas de Adesão Celular/metabolismo , Imunoterapia/métodos , Neoplasias Pancreáticas/metabolismo , Tetraspaninas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/terapia , Animais , Antígenos de Neoplasias/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Citocinas/metabolismo , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Fatores Imunológicos , Ativação Linfocitária , Camundongos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Linfócitos T/imunologia , Tetraspaninas/genética
3.
BMC Surg ; 21(1): 110, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658016

RESUMO

BACKGROUND: Ductal adenocarcinoma of the pancreas (PDAC) remains one of the most lethal malignancies. To date, no guidelines exists for isolated resectable metachronous disease. It is still unknown, which patients may benefit from relapse surgery. The aim of our study was to compare disease free survival (DFS) and post relapse survival (PRS) in patients with isolated local recurrence, metachronous hepatic or pulmonary metastases. METHODS: Patients with isolated resectable local recurrence, metachronous hepatic or pulmonary metastases were included for survival analyses. PRS of surgically treated patients (local (n = 11), hepatic (n = 6) and pulmonary metastases (n = 9)) was compared to conservatively treated patients (local (n = 17), hepatic (n = 37) and pulmonary metastases (n = 8)). RESULTS: Resected PDAC patients suffering from isolated metachronous hepatic metastases initially had a higher T-stage and venous invasion (V1) compared to the other patients. DFS in the metachronous pulmonary metastases group was longer compared to DFS of the hepatic metastases and local recurrence groups. Surgical resection significantly improved PRS in patients with local recurrence and pulmonary metastases, when compared to patients receiving chemotherapy alone. Very-long term survivors (> 5 years) were detected following secondary resection of local recurrence and 45% of these patients were still alive at the end of our study period. CONCLUSION: Although DFS in PDAC patients suffering from isolated local recurrence was dismal and comparable to that of patients with isolated hepatic metastases, very-long term survivors were present only in this group. These results indicate that a surgical approach for isolated local recurrence, if anatomically possible, should be considered.


Assuntos
Carcinoma Ductal Pancreático , Recidiva Local de Neoplasia , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/terapia , Terapia Combinada , Humanos , Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/terapia , Análise de Sobrevida , Resultado do Tratamento
4.
J Surg Oncol ; 123(3): 751-759, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33595893

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal cancer with an urgent need for better medical therapies. Efforts have been made to investigate the efficacy of immunotherapy, particularly given the hallmarks of immune suppression and exhaustion in PDAC tumors. Here, we review the molecular components responsible for the immune-privileged state in PDAC and provide an overview of the immunotherapeutic strategies for PDAC including vaccine therapy, checkpoint blockade, myeloid-targeted therapy, and immune agonist therapy.


Assuntos
Carcinoma Ductal Pancreático/terapia , Imunoterapia/métodos , Neoplasias Pancreáticas/terapia , Animais , Vacinas Anticâncer/uso terapêutico , Carcinoma Ductal Pancreático/imunologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Neoplasias Pancreáticas/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Z Gastroenterol ; 59(2): 143-148, 2021 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-33556973

RESUMO

BACKGROUND: Neuroendocrine tumors (NET) diagnosed during pregnancy are extremely rare. This case report describes diagnosis and treatment of a metastasized pancreas NET that became symptomatic in the second trimester. CASE DESCRIPTION: A 33-year-old patient presented to the emergency department in the 19th week of pregnancy (WOP) with persistent diarrhea. Laboratory tests showed a pronounced hypercalcemia (3.53 mmol/l). Imaging revealed a mass in the pancreatic corpus/tail with extensive liver metastasis. Histologically, a NET (G2, SSTR-positive) with paraneoplastic parathormone-related-peptide secretion was found to be the cause of hypercalcemia. Under a treatment with octreotide, calcium values normalized and diarrhea stopped. After delivery of a healthy child (32.WOP via cesarean section) tumor progress was found. The pancreatic mass was resected completely, the liver metastases as far as possible. Postoperatively, in a CT scan, residual suspicious liver lesions could be found, and a palliative therapy with lanreotide was initiated. With this treatment, the patient has been asymptomatic for one year, and serum calcium remained normal. The child developed normally. DISCUSSION: This unusual case shows that even in extensively metastasized symptomatic NETs during pregnancy, there may be sufficient diagnostic and therapeutic options that allow for a continuation of pregnancy in close interdisciplinary cooperation under careful risk-benefit assessment for mother and child.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Diarreia/etiologia , Hipercalcemia/tratamento farmacológico , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/fisiopatologia , Octreotida/uso terapêutico , Neoplasias Pancreáticas/fisiopatologia , Adulto , Cesárea , Feminino , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Hiperparatireoidismo/sangue , Hiperparatireoidismo/complicações , Recém-Nascido , Neoplasias Hepáticas/patologia , Metástase Neoplásica , Tumores Neuroendócrinos/sangue , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/terapia , Proteína Relacionada ao Hormônio Paratireóideo/sangue , Gravidez , Resultado da Gravidez , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Arch Immunol Ther Exp (Warsz) ; 69(1): 2, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33630157

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, treatment-resistant cancer. Five-year survival rate is about 9%, one of the lowest among all solid tumors. Such a poor outcome is partly due to the limited knowledge of tumor biology, and the resulting lack of effective treatment options and robust predictive biomarkers. The leukemia inhibitory factor (LIF) has recently emerged as a potential biomarker and therapeutic target for PDAC. Accumulating evidence has suggested that LIF plays a role in supporting cancer evolution as a regulator of cell differentiation, renewal and survival. Interestingly, it can be detected in the serum of PDAC patients at higher concentrations than healthy individuals, this supporting its potential value as diagnostic biomarker. Furthermore, preliminary data indicate that testing for LIF serum concentration or tissue expression may help with treatment response monitoring and prognostication. Finally, studies in PDAC mouse models have also shown that LIF may be a valuable therapeutic target, and first-in-human clinical trial is currently ongoing. This article aims to review the available data on the role of LIF in PDAC promotion, and to discuss the evidence supporting its potential role as a biomarker and target of effective anti-cancer therapy in this setting.


Assuntos
Carcinoma Ductal Pancreático/patologia , Fator Inibidor de Leucemia/fisiologia , Neoplasias Pancreáticas/patologia , Biomarcadores Tumorais/análise , Fibroblastos Associados a Câncer/fisiologia , Carcinoma Ductal Pancreático/etiologia , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/terapia , Resistencia a Medicamentos Antineoplásicos , Humanos , Tolerância Imunológica , Fator Inibidor de Leucemia/análise , Invasividade Neoplásica , Células-Tronco Neoplásicas/fisiologia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/terapia , Microambiente Tumoral
8.
Nat Commun ; 12(1): 647, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510144

RESUMO

Ferroptosis is a type of iron-dependent regulated cell death, representing an emerging disease-modulatory mechanism. Transcription factors play multiple roles in ferroptosis, although the key regulator for ferroptosis in iron metabolism remains elusive. Using NanoString technology, we identify NUPR1, a stress-inducible transcription factor, as a driver of ferroptosis resistance. Mechanistically, NUPR1-mediated LCN2 expression blocks ferroptotic cell death through diminishing iron accumulation and subsequent oxidative damage. Consequently, LCN2 depletion mimics NUPR1 deficiency with respect to ferroptosis induction, whereas transfection-enforced re-expression of LCN2 restores resistance to ferroptosis in NUPR1-deficient cells. Pharmacological or genetic blockade of the NUPR1-LCN2 pathway (using NUPR1 shRNA, LCN2 shRNA, pancreas-specific Lcn2 conditional knockout mice, or the small molecule ZZW-115) increases the activity of the ferroptosis inducer erastin and worsens pancreatitis, in suitable mouse models. These findings suggest a link between NUPR1-regulated iron metabolism and ferroptosis susceptibility.


Assuntos
Proteínas de Ligação a DNA/genética , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Ferro/metabolismo , Lipocalina-2/genética , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Animais , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Humanos , Estimativa de Kaplan-Meier , Lipocalina-2/metabolismo , Camundongos Knockout , Camundongos Nus , Camundongos Transgênicos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Piperazinas/farmacologia , Terapêutica com RNAi/métodos , Transdução de Sinais/genética , Tiazinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
9.
Eur J Cancer ; 144: 200-214, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33370645

RESUMO

Neuroendocrine neoplasms (NENs) are a heterogeneous family of uncommon tumours with challenging diagnosis, clinical management and unique needs that almost always requires a multidisciplinary approach. In the absence of guidance from the scientific literature, along with the rapidly changing data available on the effect of COVID-19, we report how 12 high-volume NEN centres of expertise in 10 countries at different stages of the evolving COVID-19 global pandemic along with members of international neuroendocrine cancer patient societies have suggested to preserve high standards of care for patients with NENs. We review the multidisciplinary management of neuroendocrine neoplasms during the COVID-19 pandemic, and we suggest potential strategies to reduce risk and aid multidisciplinary treatment decision-making. By sharing our joint experiences, we aim to generate recommendations for proceeding to other institutions facing the same challenges.


Assuntos
Tumor Carcinoide/terapia , Neoplasias Gastrointestinais/terapia , Oncologia/normas , Neoplasias Pancreáticas/terapia , Neoplasias Torácicas/terapia , Tumor Carcinoide/diagnóstico , Consenso , Neoplasias Gastrointestinais/diagnóstico , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Torácicas/diagnóstico
10.
J Surg Res ; 257: 605-615, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32947122

RESUMO

BACKGROUND: The clinicopathologic factors associated with the survival of patients with pancreatic ductal adenocarcinoma (PDAC) during the different phases of neoadjuvant treatment (NT)-at diagnosis, restaging, or postoperatively-remain unclear. METHODS: Data of patients with PDAC who underwent pancreatic resection after NT between 2008 and 2018 were retrospectively collected. Clinicopathologic characteristics and outcomes were compared stratified by resection margin status. Three multivariable regression models (at diagnosis, restaging, and postoperatively) were constructed to assess the temporal impact of different prognostic factors on all-cause survival (ACS) and disease-free survival (DFS). RESULTS: All patients were diagnosed with a nonmetastatic PDAC and were appropriate candidates for NT according to the current National Comprehensive Cancer Network guidelines. From a total of 83 patients, 57 (68.7%) had a negative resection margin >1 mm (R0), whereas 26 patients (31.3%) had a positive resection margin (R1). At diagnosis, planned procedure (P = 0.017) and CA19-9 >100 U/mL (P = 0.047) were independent prognostic factors of decreased ACS. At restaging, planned procedure (P = 0.017), FOLFIRINOX (P = 0.026), and tumor size >30 mm (P = 0.030) were independent prognostic factors for increased and decreased ACS, respectively. Postoperatively, R0 was an independent prognostic factor for improved ACS (P = 0.005) and DFS (P = 0.002), whereas adjuvant therapy (P = 0.006) was associated with increased ACS. Lymph node involvement (P = 0.019) was associated with decreased DFS. CONCLUSIONS: At diagnosis, restaging, and postoperatively, different, relevant clinicopathologic factors significantly impact the survival of patients with nonmetastatic PDAC undergoing NT. An R0 resection remains the most important prognostic factor and therefore should be the primary goal of surgical treatment in the neoadjuvant setting.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Idoso , Boston/epidemiologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
11.
Zhonghua Wai Ke Za Zhi ; 59(2): 81-100, 2021 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-33378799

RESUMO

The incidence of pancreatic cancer has increased in recent years, and the mortality has ranked the third among malignant tumors. Advances have been made in the diagnosis and treatment of pancreatic cancer in the past decade, however, the current situation is still severe due to the uneven medical level in different regions of China. In 2018, Pancreatic Cancer Committee of Chinese Anti-cancer Association formulated the "Chinese comprehensive guidelines for the diagnosis and treatment of pancreatic cancer (2018 version)", with the view for standardizing and improving the level of diagnosis and treatment of pancreatic cancer in China. In 2020, the committee worked out the latest version of "Chinese comprehensive guidelines for the diagnosis and treatment of pancreatic cancer (2020 version)", based on the development in the past two years. These updates were mainly reflected in the following aspects: breakthroughs in targeted therapy and immunotherapy, and genetic screening and genetic sequencing has been firstly applied in the comprehensive diagnosis and treatment of pancreatic cancer. The practicability and accuracy of the 8th edition of AJCC-TNM staging system for pancreatic cancer has been validated in multi-center of China and has been used in clinical practice. Preoperative neoadjuvant therapy has become the standard treatment for borderline resectable and locally advanced pancreatic cancer, and it is gradually applied to the resectable pancreatic cancer. The surgical exploration after neoadjuvant therapy is particularly important. Chemotherapy-based systemic treatment modality, including targeted therapy and immunotherapy, has been carried out in clinical trial setting, and the benefits of maintenance therapy have been confirmed in advanced pancreatic cancer. The multi-disciplinary and multi-regional collaborative diagnosis and treatment pattern is widely popularized in China and runs through the entire diagnosis and treatment process. The development of domestic clinical trials and multi-center, cross-regional cooperation provides high-level evidence of evidence-based medicine for the new drug development and regimen optimization of pancreatic cancer. By incorporating the above latest advances into the new guideline, we aim to provide further guidance for the comprehensive diagnosis and treatment of pancreatic cancer in China.


Assuntos
Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica , China , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia
13.
Nat Commun ; 11(1): 5332, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087697

RESUMO

Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regressions by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from 35 PDAC patient tumors. This identified a shared HLA-A*0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1) as a putative TAA demonstrating overexpression in multiple tumor types and low or absent expression in essential normal tissues. Here we show that VGLL1-specific CTLs expanded from the blood of a PDAC patient could recognize and kill in an antigen-specific manner a majority of HLA-A*0101 allogeneic tumor cell lines derived not only from PDAC, but also bladder, ovarian, gastric, lung, and basal-like breast cancers. Gene expression profiling reveals VGLL1 as a member of a unique group of cancer-placenta antigens (CPA) that may constitute immunotherapeutic targets for patients with multiple cancer types.


Assuntos
Antígenos de Neoplasias/imunologia , Neoplasias da Mama/imunologia , Proteínas de Ligação a DNA/imunologia , Neoplasias Pancreáticas/imunologia , Fatores de Transcrição/imunologia , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/terapia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Proteínas de Ligação a DNA/genética , Feminino , Perfilação da Expressão Gênica , Antígeno HLA-A1/imunologia , Humanos , Imunoterapia Adotiva , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Placenta/imunologia , Gravidez , Prognóstico , Linfócitos T Citotóxicos/imunologia , Fatores de Transcrição/genética
14.
Zhonghua Wai Ke Za Zhi ; 58(10): 745-748, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-32993259

RESUMO

The incidence of pancreatic neuroendocrine tumor is increasing gradually in recent years.There are still lots of debated issues in surgical management of this kind of tumor.Whether all small non-functional pancreatic neuroendocrine tumor need to be resected, whether primary and metastatic lesion need to be resected in metastatic disease, whether adjuvant therapy is necessary for resected tumor, whether enucleation is optimal for small pancreatic neuroendocrine tumor.Some data from real world study has provide primary answer to these questions.More high-quality study in the future will provide satisfactory answer.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Terapia Combinada , Humanos , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/terapia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/terapia
15.
Zhonghua Wai Ke Za Zhi ; 58(10): 754-757, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-32993261

RESUMO

Neoadjuvant therapy has been one of the standard therapies for borderline resectable pancreatic cancer and locally advanced pancreatic cancer, but it may deteriorate these patients' nutritional status while controlling the progress of cancer, which inevitably influences these patients' postoperative outcomes and prognosis.In this article, we tried to answer this problem by reviewing other studies.And we found that neoadjuvant therapy would influence patients' postoperative outcomes and prognosis by deteriorating their nutritional status.But effective nutritional support can prevent it.It indicates that there is a need for these patients to receive nutritional support as soon as possible.However, in consideration of the limited number of relevant studies and their limitations, there is a need for more studies with strict design to answer this problem.And it can provide evidence for early nutritional support in pancreatic cancer patients who is going to undergo neoadjuvant therapy.


Assuntos
Terapia Neoadjuvante , Estado Nutricional , Apoio Nutricional , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Período Pós-Operatório , Cuidados Pré-Operatórios , Prognóstico
16.
J Cancer Res Ther ; 16(4): 909-916, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930139

RESUMO

Background: The predictive value of different prognostic biomarkers has been studied in various cancer types. Aims and Objectives: The purpose of this study was to examine the degree of risk and prognostic significance of pretreatment neutrophil-to-lymphocyte ratio (NLR) and carbohydrate antigen (CA) 19-9 levels in patients with metastatic pancreatic cancer (PC) and reveal its relevance with survival. Materials and Methods: Clinical and laboratory data of 118 patients with metastatic PC at the time of diagnosis were retrospectively analyzed. The overall survival (OS) was estimated according to the Kaplan-Meier method. To determine the prognostic factors affecting PC, the Cox regression analysis was performed. Results: The average age of the patients was 67 ± 9.57 years. The patients were analyzed during the follow-up period, and their average OS was 12 months (95% confidence interval [CI] = 9.73-14.26). The cutoff value was 3.54 (area under the curve [AUC] = 0.653, 95% CI = 0.56-0.73, P = 0.006) for NLR and 437 (AUC = 0.670, 95% CI = 0.57-0.75, P = 0.002) for CA19-9. Statistically significant difference was found between CA19-9 (P < 000.1) and NLR (P < 000.1) and OS. Analysis of multivariate Cox regression showed that NLR (hazard ratio [HR] = 2.17, 95% CI = 1.17-4.03, P = 0.013) and CA19-9 (HR = 1.81, 95% CI = 1.08-3.03, P = 0.022) were important prognostic factors in OS analysis. Conclusion: Pretreatment NLR and CA19-9 levels were found to be reliable estimative markers for poor prognosis in patients with metastatic PC. Our findings revealed that NLR and CA19-9 levels can be used to estimate the survival of patients with PC. We believe that our findings will shed light on the management of treatment protocols for patients diagnosed with metastatic PC.


Assuntos
Antígeno CA-19-9/sangue , Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
Zhonghua Wai Ke Za Zhi ; 58(9): 657-667, 2020 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-32878410

RESUMO

In order to improve the overall treatment level of pancreatic cancer in China, Study Group of Pancreatic Surgery in China Society of Surgery of Chinese Medical Association and Pancreatic Disease Committee of China Research Hospital Association have formulated the guideline for neoadjuvant therapy of pancreatic cancer in China (2020 edition). Based on the GRADE system, the guideline has conducted a discussion on the indication, regimen selection, therapeutic effect evaluation, pathological diagnosis and surgery strategy, etc. This guideline has quantified the evidence level of the current clinical researches and provided recommendations for the clinical practice in the neoadjuvant therapy of pancreatic cancer. The guideline has highlighted the role of multiple disciplinary team and represented the conversion of treatment concept in pancreatic cancer. Neoadjuvant therapy has prolonged the survival of the part of pancreatic cancer patients. However, more high-quality clinical researches are in urgent need to improve the level of evidence, optimize the clinical practice and improve the survival of patients.


Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas/terapia , China , Humanos
18.
Medicine (Baltimore) ; 99(33): e21682, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872039

RESUMO

To investigate the clinicopathological characteristics and relevant prognostic factors of gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN), to improve our understanding of GEP-NEN.This was a retrospective analysis of 155 patients (average age 53.7 ±â€Š13.6 years) pathologically diagnosed with GEP-NEN. We analyzed the clinicopathological characteristics, treatment, and prognostic factors of GEP-NEN.The most common primary site was the pancreas (41.9%), followed by the rectum, stomach and duodenum. Most cases were nonfunctional GEP-NENs (149/155) with nonspecific symptoms. TNM stage and histological grade were determined by the latest criteria. Surgical resection was the mainstay of treatment in 150 patients, and 22 patients received chemotherapy under different circumstances. A total of 130 patients were followed up for a median of 44 months, and 1-year and 3-year survival rates were 82.3% and 72.3%, respectively. According to univariate and multivariate analysis, incidental diagnosis, maximum tumor diameter, tumor stage, lymph node and distant metastasis, TNM stage, and histological grade were significantly correlated with overall survival, but histological grade was the only factor confirmed as an independent prognostic factor for long-term survival of GEP-NEN.GEP-NEN, with an increasing trend in incidence, occurred most frequently in the pancreas. Nonfunctional tumors with nonspecific symptoms comprised the majority of cases. The main treatment was surgical resection. Histological grade was confirmed as the only independent prognostic factor.


Assuntos
Neoplasias Intestinais/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Feminino , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/terapia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
19.
Autophagy ; 16(10): 1923-1924, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32809888

RESUMO

The melanoma-associated antigen family A (MAGEA) antigens are expressed in a wide variety of malignant tumors but not in adult somatic cells, rendering them attractive targets for cancer immunotherapy. Recent studies uncovered a role for MAGEA6 in suppression of macroautophagy/autophagy implicating MAGEA6 in tumorigenesis. The impact of cancer-associated MAGEA6 mutations on tumor pathophysiology are less well explored. In pancreatic cancer cell models, MAGEA6 inhibits autophagy, facilitating pancreatic cancer initiation. However, autophagy places a brake on cancer progression and is released upon MAGEA6 degradation, which can be induced by nutrient deficiency or by acquisition of cancer-associated mutations that reinstitute autophagy. Further cancer-associated mutations of the broader MAGEA genes frequently result in degradation of the corresponding protein products by proteasome-dependent machinery, potentially jeopardizing the utility of MAGEA genes as immunotherapeutic targets. Altogether, our findings provide mechanistic insight into the divergent roles of MAGEA6 during pancreatic cancer initiation and progression, and could inform cancer immunotherapeutic strategies for targeting MAGEA antigens.


Assuntos
Autofagia , Neoplasias Pancreáticas , Adulto , Antígenos de Neoplasias/genética , Humanos , Imunoterapia , Proteínas de Neoplasias/genética , Pâncreas , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia
20.
Cancer Radiother ; 24(6-7): 493-500, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32814670

RESUMO

For many years, adjuvant chemoradiotherapy remained essential in the therapeutic management of gastric and pancreatic adenocarcinomas. For these tumours, surgical excision, the only hope of offering the patient prolonged survival, is only possible in 20% of cases. The median survival of operated patients is only 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. For stomach cancers, adjuvant chemoradiotherapy is justified by the results of the phase III trial Intergroup 0116 published by MacDonald et al. The gain in survival was at the cost of significant toxicity. This treatment was supplanted in the early 2000s by perioperative chemotherapy. Currently, neoadjuvant chemoradiotherapy clinical studies are ongoing with the aim of improving treatments observance and tolerance. For pancreatic cancers, the role of adjuvant chemoradiotherapy has long been discussed because of trials with contradictory results. Neoadjuvant radiotherapy has many advantages in terms of efficacy and tolerance. It increases the chances of subsequent complete tumour resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Neoplasias Pancreáticas/terapia , Neoplasias Gástricas/terapia , Humanos
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