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1.
Cancer Sci ; 115(3): 820-835, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151993

RESUMO

Pancreatic cancer (PC) is a highly aggressive and deadly malignancy with limited treatment options and poor prognosis. Identifying new therapeutic targets and developing effective strategies for PC treatment is of utmost importance. Here, we revealed that SHCBP1 is significantly overexpressed in PC and negatively correlated with patient prognosis. Knockout of SHCBP1 inhibits the proliferation and migration of PC cells in vitro, and suppresses the tumor growth in vivo. In addition, we identified AZD5582 as a novel inhibitor of SHCBP1, which efficiently restrains the growth of PC in cell lines, organoids, and patient-derived xenografts. Mechanistically, we found that AZD5582 induced the apoptosis of PC cells by inhibiting the activity of PI3K/AKT signaling and preventing the degradation of TP53. Collectively, our study highlights SHCBP1 as a potential therapeutic target and its inhibitor AZD5582 as a viable agent for PC treatment strategies.


Assuntos
Alcinos , Oligopeptídeos , Neoplasias Pancreáticas , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Transdução de Sinais , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Adaptadoras da Sinalização Shc/metabolismo
2.
Gastroenterology ; 164(7): 1232-1247, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36842710

RESUMO

BACKGROUND & AIMS: Although small patient subsets benefit from current targeted strategies or immunotherapy, gemcitabine remains the first-line drug for pancreatic cancer (PC) treatment. However, gemcitabine resistance is widespread and compromises long-term survival. Here, we identified ubiquitin-conjugating enzyme E2T (UBE2T) as a potential therapeutic target to combat gemcitabine resistance in PC. METHODS: Proteomics and metabolomics were combined to examine the effect of UBE2T on pyrimidine metabolism remodeling. Spontaneous PC mice (LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre; KPC) with Ube2t-conditional knockout, organoids, and large-scale clinical samples were used to determine the effect of UBE2T on gemcitabine efficacy. Organoids, patient-derived xenografts (PDX), and KPC mice were used to examine the efficacy of the combination of a UBE2T inhibitor and gemcitabine. RESULTS: Spontaneous PC mice with Ube2t deletion had a marked survival advantage after gemcitabine treatment, and UBE2T levels were positively correlated with gemcitabine resistance in clinical patients. Mechanistically, UBE2T catalyzes ring finger protein 1 (RING1)-mediated ubiquitination of p53 and relieves the transcriptional repression of ribonucleotide reductase subunits M1 and M2, resulting in unrestrained pyrimidine biosynthesis and alleviation of replication stress. Additionally, high-throughput compound library screening using organoids identified pentagalloylglucose (PGG) as a potent UBE2T inhibitor and gemcitabine sensitizer. The combination of gemcitabine and PGG diminished tumor growth in PDX models and prolonged long-term survival in spontaneous PC mice. CONCLUSIONS: Collectively, UBE2T-mediated p53 degradation confers PC gemcitabine resistance by promoting pyrimidine biosynthesis and alleviating replication stress. This study offers an opportunity to improve PC survival by targeting UBE2T and develop a promising gemcitabine sensitizer in clinical translation setting.


Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Proteína Supressora de Tumor p53/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Modelos Animais de Doenças , Linhagem Celular Tumoral , Neoplasias Pancreáticas
3.
Mol Carcinog ; 63(4): 601-616, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38169303

RESUMO

The crucial role of cancer-associated fibroblasts (CAFs) in promoting T-cell exclusion has a significant impact on tumor immune evasion and resistance to immunotherapy. Therefore, enhancing T-cell infiltration into solid tumors has emerged as a pivotal area of research. We achieved a conventional knockout of Shcbp1 (Shcbp1-/- ) through CRISPR/Cas9 gene editing and crossed these mice with spontaneous breast cancer MMTV-PyMT mice, resulting in PyMT Shcbp1-/- mice. The different CAF subtypes were detected by flow cytometry analysis (FCA). We evaluated collagen and CAFs levels using Sirius red staining, immunohistochemistry (IHC), and immunofluorescence (IF). Primary tumor cells and CAFs were isolated from both PyMT Shcbp1+/+ and PyMT Shcbp1-/- mice. We analyzed CAFs' proliferation, invasion, migration, apoptosis, and cell cycle. Transwell coculture experiments were performed with primary tumor cells and CAFs to evaluate the role of CAFs in increasing the sensitivity of tumor cells to Erdafitinib. Tumors from PyMT Shcbp1+/+ and PyMT Shcbp1-/- mice were orthotopically transplanted to assess the therapeutic effect of the Erdafitinib and PD-1 combination. CAFs and T-cell infiltration in these tumors were assessed using FCA and IF. Knockout of Shcbp1 leads to a significant reduction in tumor burden, promotes longer survival, and decreases CAFs in MMTV-PyMT. Moreover, knockout of Shcbp1 enhances the sensitivity of Erdafitinib, leading to effective inhibition of CAFs' proliferation and invasion, as well as the induction of apoptosis. Additionally, it results in cell cycle arrest at the G2/M phase in vitro. Meanwhile, Shcbp1-/- CAFs change the sensitivity of Shcbp1-/- tumor cells to Erdafitinib compared to Shcbp1+/+ CAFs. Importantly, knockout of Shcbp1 boosts the effectiveness of Erdafitinib in combination with immune checkpoint blockade therapy by augmenting T-cell infiltration through CAFs regulation in vivo. Our findings demonstrate that knockout of Shcbp1 holds significant potential in enhancing the therapeutic response of Erdafitinib combined with PD-1 antibody treatment, offering promising prospects for future breast cancer therapies.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias , Animais , Camundongos , Fibroblastos Associados a Câncer/patologia , Receptor de Morte Celular Programada 1/metabolismo , Camundongos Knockout , Neoplasias/metabolismo , Imunoterapia , Fibroblastos/metabolismo , Microambiente Tumoral/genética , Linhagem Celular Tumoral
4.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(2): 261-268, 2024 Apr 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38413234

RESUMO

Recent studies have shown that the formation of the primary cilium is associated with a specific cellular organelle known as the midbody remnant (MBR), which is a point-like organelle formed by shedding of the midbody at the end of mitosis. MBRs move along the cell surface close to the center body and regulate it to form primary cilia at the top of the centriole. Primary cilia can act as an organelle to inhibit tumorigenesis, and it is lost in a variety of tumors. Studies have shown that the accumulation of MBRs in tumor cells affects ciliogenesis; in addition, both MBRs and primary cilia are degraded in tumor cells through the autophagy pathway, and MBRs can also transfer tumor signaling pathway factors to primary cilia affecting tumorigenesis. In this article, the basic structure and the formation process of MBR and primary cilia are reviewed and the mechanism of MBRs regulating ciliogenesis is elaborated. The significance of MBR-mediated ciliogenesis in tumorigenesis and its potential as a target for cancer treatment are discussed.


Assuntos
Cílios , Neoplasias , Cílios/fisiologia , Cílios/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Autofagia/fisiologia , Carcinogênese , Centríolos/metabolismo , Centríolos/fisiologia , Transdução de Sinais , Organelas/metabolismo , Mitose , Animais
5.
Mol Cell Probes ; 72: 101931, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37683830

RESUMO

Although there are several treatments available for gastric cancer (GC), the prognosis of the disease is still poor due to many factors, such as late diagnosis and tumor heterogeneity. To identify potential therapeutic targets, bioinformatics techniques and clinical sample validation were employed and prostate transmembrane protein androgen induced 1 (PMEPA1) was selected for further study. In the present study, we found that elevated PMEPA1 expression correlates with a worse prognosis and weaker anti-tumor immunity in GC patients. Moreover, our study showed that PMEPA1 not only influences cell proliferation, clone formation, invasion, and migration in vitro, but also plays an important role in GC progression in vivo. Mechanically, PMEPA1 exerts its oncogenic effects through activating the Wnt/ß-catenin signaling pathway. Therefore, PMEPA1 is a potential target for treating GC effectively.


Assuntos
Neoplasias Gástricas , Masculino , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Proteínas de Membrana/genética , Via de Sinalização Wnt , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
6.
Mol Cell Probes ; 69: 101915, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37121410

RESUMO

Gastric cancer is one of the most common lethal malignancies in the world, especially in China. Due to the ineffective screening of early gastric cancer and drug resistance of the advanced, the prognosis of gastric cancer remains dismal. Based on bioinformatics and tissue microarray analyses, FBXO5 was selected for analysis in this study. Here, we report the function of FBXO5 in gastric cancer, showing for the first time that it contributes to tumor cell proliferation, clone formation, invasion and migration. In these preliminary findings, FBXO5 promoted the transition of the cell cycle from the G0/G1 to the G2/M phase, which likely resulted from FBXO5 interacting with CDK1 and NCAPG proteins. The relevant mechanism needs to be explored. In addition, FBXO5 participated in the tumor microenvironment and was negatively related to immune activation. FBXO5, an oncogene, plays a role in tumor initiation and progression, and is expected to be a potential target for gastric cancer treatment.


Assuntos
Proteínas F-Box , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Ciclo Celular , China , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Proteínas de Ciclo Celular/metabolismo , Proteínas F-Box/metabolismo
7.
Exp Cell Res ; 388(1): 111824, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31926148

RESUMO

Cell migration and invasion play an important role in the development of cancer. Cell migration is associated with several specific actin filament-based structures, including lamellipodia, filopodia, invadopodia and blebs, and with cell-cell adhesion, cell-extracellular matrix adhesion. Migration occurs via different modes, human epithelial cancer cells mainly migrate collectively, while in vivo imaging studies in laboratory animals have found that most cells migrate as single cells. Rho GTPases play an important role in the process of cell migration, and several Rho GTPase-related signaling complexes are also involved. However, the exact mechanism by which these signaling complexes act remains unclear. This paper reviews how Rho GTPases and related signaling complexes interact with other proteins, how their expression is regulated, how tumor microenvironment-related factors play a role in invasion and metastasis, and the mechanism of these complex signaling networks in cell migration and invasion.


Assuntos
Movimento Celular , Neoplasias/metabolismo , Transdução de Sinais , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Humanos , Invasividade Neoplásica , Neoplasias/genética , Neoplasias/patologia , Proteínas rho de Ligação ao GTP/genética
8.
Neoplasma ; 68(5): 899-906, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34263650

RESUMO

As a common lethal disease, cancer is now responsible for the majority of deaths worldwide and has been the single most important barrier to increasing life expectancy in the world. The pathogenesis of cancer has been the key point of cancer therapeutics research. The primary cilium, a solitary microtubule-based organelle, is considered to be an important sensor for receiving mechanical and chemical stimulation from other cells and environments; it plays an important role in a variety of signal transduction and disease processes. More importantly, the primary cilium can also function as an elaborate structure to regulate cell proliferation because ciliogenesis regulates cell division by sequestering the centriole. Recently, many new findings have suggested that the length and incidence of the primary cilium are closely connected to carcinogenesis and responses to cancer therapy. Here, we review relevant evidences proving that the primary cilium plays a key role in the occurrence and treatment of cancer. We also summarize the primary cilium-associated signaling pathways in cancer, including Wnt signaling, Hedgehog signaling, PDGFR signaling, and Notch signaling, and anticipate that targeting proteins localized in the primary cilium may be a potential anti-cancer strategy.


Assuntos
Cílios , Neoplasias , Carcinogênese , Proteínas Hedgehog , Humanos , Via de Sinalização Wnt
9.
BMC Gastroenterol ; 20(1): 100, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276616

RESUMO

BACKGROUND: In this study, we aimed to investigate the preoperative serum carcinoembryonic antigen (CEA) in the diagnosis of positive lymph node metastasis (LNM), and to evaluated the relationship between CEA and survival in patients with locally advanced gastric cancer (LAGC). METHODS: The significance of the preoperative serum CEA level for the diagnose of LAGC and prediction of LNM was determined using the receiver operating characteristic (ROC) curve. The areas under the ROC of CEA were compared with those of other tumor markers or imaging examination including CT and MRI. Logistic regression was utilized to identify the risk factors predicting positive LNM. Independent prognosis factors were evaluated using univariate and multivariate COX regression analyses. RESULTS: The ROC curves showed that the AUCs of CEA, CA199, and CA125 for diagnosing LAGC were 0.727, 0.594, and 0.566. When used to predict LNM, the AUC of CEA, CA199 and CA125 were 0.696, 0.531, and 0.588. Logistic regression analysis demonstrated that preoperative serum CEA were significantly associated with positive LNM. On combining imaging examination with CEA, the sensitivity and specificity were 85.3 and 79.4%, respectively, with the AUC equal to 0.853. The combination of CEA and imaging examination preformed the highest levels of AUC and sensitivity for diagnosing LNM, which is significantly higher than using either of them alone. Although patients with abnormal CEA have a poor prognosis, two models of multivariate analysis showed that CEA was not the independent prognosis factor for survival. CONCLUSIONS: CEA can be used to diagnose gastric cancer and determine whether it has LNM. Moreover, combined with CEA could improve the diagnostic sensitivity of imaging examination for lymph node involvement.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Antígeno Carcinoembrionário/sangue , Gastrectomia , Metástase Linfática , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Adulto , Idoso , Área Sob a Curva , Feminino , Seguimentos , Humanos , Modelos Logísticos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios/métodos , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
10.
BMC Surg ; 20(1): 170, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32723381

RESUMO

BACKGROUND: Pancreatic fistula is a common complication after pancreaticoduodenectomy, which could be caused by: soft pancreatic tissue, pancreatic duct diameter < 3 mm and body mass index ≥25 kg/m2. Here we report a case of pancreatic fistula due to obstruction of the jejunal loop due to compression of the jejunal loop by the superior mesenteric vessels. CASE PRESENTATION: A 68-year-old man was admitted to our ward due to intermittent epigastric distension and pain. After various examinations and treatments, he was diagnosed with middle bile duct cancer. Pancreaticoduodenectomy was performed, and pancreaticojejunostomy and hepaticojejunostomy were completed by lifting the jejunal loop from behind the superior mesenteric vessels to the upper region of the colon. On postoperative day 9, the patient developed acute diffuse peritonitis, and on postoperative day 10, the patient underwent a second exploratory laparotomy, during which it was confirmed that the pancreatic fistula was caused by obstruction of the jejunal loop due to compression of the jejunal loop by the superior mesenteric vessels, then the patient recovered and was discharged alive after retrograde drainage in the jejunum. CONCLUSIONS: The superior mesenteric vessels after pancreaticoduodenal surgery can compress the jejunal loop and cause obstruction leading to serious complications, and it is recommended that general surgeons should avoid lifting the jejunal loop from the posterior aspect of the superior mesenteric vessels to complete the anastomosis.


Assuntos
Obstrução Intestinal/etiologia , Artéria Mesentérica Superior , Oclusão Vascular Mesentérica/etiologia , Fístula Pancreática , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Idoso , Anastomose Cirúrgica/efeitos adversos , Humanos , Obstrução Intestinal/cirurgia , Doenças do Jejuno/etiologia , Doenças do Jejuno/cirurgia , Masculino , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(12): 1490-1498, 2020 Dec 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-33473008

RESUMO

Changes in nuclear morphology are common in malignant tumors, but the underlying molecular mechanisms remain poorly understood. Lamins is involved in supporting nuclear structure, and the expression of Lamins is the molecular basis for nuclear morphological changes during tumor progression. In recent years, the research on the relationship between Lamins and malignant tumors has made great progress. Lamins is of great value in the diagnosis, treatment, and prognosis of various malignant tumors.


Assuntos
Núcleo Celular , Neoplasias , Humanos , Laminas/genética , Neoplasias/genética , Prognóstico
12.
J Surg Res ; 235: 22-33, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30691798

RESUMO

BACKGROUND: Accumulating evidence indicated that long noncoding RNAs (lncRNAs) have a wide range of biological functions and may play significant roles in tumorigenesis and progression. However, the understanding of its functions and related competitive endogenous RNAs (ceRNAs) networks is much less than that of protein-coding genes, particularly in colon adenocarcinoma. METHODS: We comprehensively analyzed the sequencing data of protein-coding and noncoding RNAs in colon adenocarcinoma patients from The Cancer Genome Atlas (TCGA) database. Next, we constructed colon adenocarcinoma-specific ceRNA network and evaluated the effect of these RNAs on overall survival (OS) for colon adenocarcinoma patients. RESULTS: Totally, 1138 differentially expressed lncRNAs (DElncRNAs), 245 microRNAs (DEmiRNAs), and 2081 mRNAs (DEmRNAs) were identified using a threshold of |log2FoldChange| >2.0 and adjusted P-value < 0.01. Subsequently, a colon adenocarcinoma-specific ceRNA network was successfully established with133 DElncRNAs, 29 DEmiRNAs, and 55 DEmRNAs. Among ceRNA network, seven DElncRNAs (AL590483.1, AP004609.1, ARHGEF26-AS1, HOX transcript antisense RNA (HOTAIR), ITCH-IT1, KCNQ1OT1, and LINC00491), four DEmiRNAs (hsa-mir-143, hsa-mir-183, hsa-mir-216a, and hsa-mir-424), and six DEmRNAs (FJX1, TPM2, ULBP2, PDCD4, PLAU, and SERPINE1) significantly correlated with OS (all P-value < 0.05). Notably, several interactions were highlighted in the ceRNA network, such as "KCNQ1OT1-hsa-mir-183-PDCD4", "KCNQ1OT1-hsa-mir-424-TPM2", "HOTAIR-hsa-mir-143-SERPINE1", and "ARHGEF26-AS1-hsa-mir-143-SERPINE1". CONCLUSIONS: These findings reveal several molecules might be novel important prognostic factors and potential treatment targets for colon adenocarcinoma. In addition, these observations contribute to a more comprehensive understanding of lncRNA-related ceRNA network and provide novel strategies for subsequent functional studies of lncRNAs in colon adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Neoplasias do Colo/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Adenocarcinoma/mortalidade , Biomarcadores Tumorais , Neoplasias do Colo/mortalidade , Redes Reguladoras de Genes , Humanos , Canal de Potássio KCNQ1/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Prognóstico , RNA Mensageiro/genética , Tropomiosina/genética
13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(1): 92-99, 2019 Jan 28.
Artigo em Zh | MEDLINE | ID: mdl-30837409

RESUMO

Gastric neuroendocrine tumors are rarely seen in the gastric tumors, because there are few case reports and the clinical diagnosis rate is low. There is no consensus treatment method in the world. However, with the benefit of esophagogastrodenoscopy and widespread use of proton pump inhibitors, the diagnostic rate of gastric neuroendocrine tumors is on the increase, which gives us an updated understanding for the pathogenesis and pathophysiology of the disease. By studying its pathogenesis, scholars have found that hypergastrinemia caused by various causes is closely related to its occurrence. Gastric neuroendocrine tumors are classified into different types or pathological grades depending on the state of progression of the disease and the unique clinical manifestations. Clinically used diagnostic methods include gastroscopy, medical imageology, nuclear medicine, gastrin, CgA, etc. There are also differences in treatments depending on the clinical classification. If the disease progresses rapidly and the grade is high, surgical resection of the lesion plus postoperative adjuvant chemotherapy should be actively performed. Other better treatments are still being explored.


Assuntos
Tumores Neuroendócrinos , Neoplasias Gástricas , Gastrinas , Gastroscopia , Humanos , Inibidores da Bomba de Prótons
14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(2): 216-221, 2018 Feb 28.
Artigo em Zh | MEDLINE | ID: mdl-29559609

RESUMO

Gastric cancer is one of the most common malignant gastrointestinal tumors. Docetaxel alone or combination with other drugs can attenuate the progress of disease, prolong the overall response rate and the median overall survival rate in advanced gastric cancer. However, the incidence of toxicities is high. Moreover, there is no uniform standard for dosage and course for docetaxel treatment. Currently, its efficacy is not definite.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Taxoides/uso terapêutico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Docetaxel , Humanos , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Taxoides/efeitos adversos , Resultado do Tratamento
15.
Cell Physiol Biochem ; 42(6): 2242-2254, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28817816

RESUMO

BACKGROUND/AIMS: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. METHODS: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63) and gastric cancer (SGC7901) cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. RESULTS: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. CONCLUSION: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.


Assuntos
Exossomos/metabolismo , Proteínas Hedgehog/metabolismo , Western Blotting , Células da Medula Óssea/citologia , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Exossomos/transplante , Proteínas Hedgehog/antagonistas & inibidores , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Piridinas/farmacologia , Pirimidinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Receptor Smoothened/genética , Receptor Smoothened/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Microambiente Tumoral/efeitos dos fármacos , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo
16.
Chemotherapy ; 62(5): 290-294, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28490007

RESUMO

Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary tract which has a low incidence rate and nonspecific symptoms. It is difficult to diagnose early, and the misdiagnosis rate is high. CT, MRI, upper gastrointestinal endoscopy, and other advanced imaging modalities should be combined to make a comprehensive evaluation. The diagnostic confirmation of this tumor type mainly depends on the pathological examination. The combination of surgery with other treatment modalities is effective. A review of reports on duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990. However, there are few reports on neoadjuvant chemotherapy for the disease. In this report, preoperative S-1 in combination with oxaliplatin neoadjuvant chemotherapy achieved a complete pathological response in the treatment of duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to be further verified.


Assuntos
Adenocarcinoma/terapia , Neoplasias Duodenais/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Neoplasias Duodenais/tratamento farmacológico , Neoplasias Duodenais/patologia , Duodeno/patologia , Endoscopia Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Tomografia Computadorizada por Raios X
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(6): 713-719, 2017 Jun 28.
Artigo em Zh | MEDLINE | ID: mdl-28690231

RESUMO

Pancreatic cancer is a highly lethal disease in gastrointestinal malignant tumors. The mortality of pancreatic cancer closely parallels its incidence. Most patients with pancreatic cancer remain asymptomatic until the disease reaches an advanced stage. There is no program for screening patients at high risk of pancreatic cancer. Although CT, MRI, positron emission tomography, endoscopic ultrasonography, and endoscopic ultrasonography-guided fine-needle aspiration offer high diagnostic ability for pancreatic cancer, it cannot be found at the early stage easily. Surgical resection is regarded as the only potentially curative treatment and adjuvant chemotherapy is given after surgery. This article reviews epidemiology, risk factors, diagnosis and treatment for pancreatic cancer by summarizing relevant literature.


Assuntos
Neoplasias Pancreáticas , Quimioterapia Adjuvante , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Ultrassonografia
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 41(2): 151-7, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-26932212

RESUMO

OBJECTIVE: To explore the prognosis and surgical method for diffuse-type advanced gastric cancer (AGC).
 METHODS: The clinicopathological data of patient, who underwent curative gastrectomy in the Second Hospital Affiliated to Lanzhou University from 2005 to 2010, were analyzed retrospectively. The prognostic factors of diffuse-type AGC were analyzed by Cox regression models. The patients were divided into a total gastrectomy group (n=120) and a subtotal gastrectomy group (n=167) according to the surgical approach. Survival rates were established by the Kaplan-Meier method and compared by the Log-rank test between the total gastrectomy group and the subtotal gastrectomy group.
 RESULTS: A total of 287 patients with diffuse-type AGC were enrolled in this study, including 120 patients in the total gastrectomy group and 167 patients in the subtotal gastrectomy group. Univariate analysis showed that the prognosis of diffuse-type AGC was associated with body mass index, number of retrieved lymph nodes, Borrmann type, tumor size, T stage, N stage, tumor-node-metastasis (TNM) stage, extent of resection, surgical margin, postoperative complication, perineural and vascular invasion (all P<0.01). Multivariate analysis showed that normal body mass index, tumor size, T stage, N stage, total gastrectomy, surgical margin, postoperative complication were the independent predictors for diffuse-type AGC (all P<0.05). The 5-year overall survival rate and progression-free survival rate for diffuse-type AGC after curative gastrectomy were 17.8% and 13.6%, respectively. The median survival time and progression-free survival of them were 22 and 18 months, respectively. The overall survival rate and progression-free survival rate in the total gastrectomy group was significantly higher than that in the subtotal gastrectomy (P<0.01); the extended extent of lymph node dissection, the lower rate of positive surgical margin and postoperative complications were present in the total gastrectomy group (all P<0.05 or P<0.01).
 CONCLUSION: The patients with diffuse-type AGC have a poor prognosis. The great tumor diameter, advanced T stage, advanced N stage, subtotal gastrectomy, high rate of positive surgical margin and postoperative complication are independent risky factors for the diffuse-type AGC. However, the total gastrectomy may be beneficial to patients.


Assuntos
Gastrectomia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Intervalo Livre de Doença , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Análise Multivariada , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
19.
Zhonghua Wai Ke Za Zhi ; 53(10): 747-51, 2015 Oct 01.
Artigo em Zh | MEDLINE | ID: mdl-26654306

RESUMO

OBJECTIVE: To analyze the clinical features of patients with gallbladder cancer from 17 hospitals in 5 Northwestern provinces (autonomous region) of China from 2009 to 2013. METHODS: A total of 2 379 cases with gallbladder cancer in 17 tertiary hospitals from 5 Northwestern provinces of China from January 2009 to December 2013 were reviewed retrospectively. The clinical data was collected by standardized "Questionnaire for Clinical Survey of Gallbladder Cancer in Northwestern Area of China". χ² test was used to analyze the data. RESULTS: (1) Gallbladder cancer from 17 hospitals accounted for 1.6%-6.8% of all bile tract diseases from 2009 to 2013 in Northwestern China, average was 2.7%. Gallbladder cancer accounted for 0.4%-0.9% of abdominal surgery, average was 0.7%. (2) The incidence of gallbladder cancer was higher in the aged females, the ration of female to male was 1.0 to 2.1. The average age of gallbladder cancer was (64 ± 11) years. The occupation of patients was mainly farmers (χ² = 147.10, P < 0.01). (3) 57.2% of the gallbladder cancers were associated with gallstones. (4) The main pathological patterns of gallbladder cancer were moderate and poor differentiated adenocarcinoma, showing an aggressive malignancy. TNM stage IV accounted for 55.1% of all cases, which was associated with the poor prognosis. (5) The curative resection rate was 30.4%. CONCLUSIONS: Gallbladder cancer is common in the aged females and mainly at advanced stage. The screening and follow-up of high-risk groups with ultrasound and other methods regularly could increase the early diagnosis rate of gallbladder cancer, aggressive surgical resection combined with other comprehensive treatment could improve the prognosis of patients.


Assuntos
Neoplasias da Vesícula Biliar/epidemiologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , China/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/patologia , Cálculos Biliares/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(8): 934-40, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26333505

RESUMO

Gastric cancer (GC) is one of the most common malignant tumors with high heterogeneity. According to Lauren classification, GC is divided into intestinal type and diffuse type. With rapid progress in technologies and ideas in the clinical diagnosis for GC, the normalized and individualized comprehensive treatment has become the main trend. However, the clinicopathological characteristics, remedy and prognosis for GC may be different because of the different classifications and stages.


Assuntos
Neoplasias Gástricas/classificação , Humanos , Prognóstico
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