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1.
Nat Prod Res ; : 1-15, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37921074

RESUMO

Formononetin as a Bax agonist exhibits anticancer effects. To identify novel Bax agonist, 18 new structurally modified formononetin derivatives were synthesised and their anticancer activities were evaluated in the A549 and Beas-2b cell lines. The results indicated that 7a elicited the most potent inhibitory effect against the A549 cell line, with an IC50 value of 0.87 µM, and no obvious toxicity to Beas-2b cells. These results indicated that 7a was 40-fold and 6.94-fold more efficacious than Formononetin and Doxorubicin, respectively. Additionally, western blot and immunofluorescence assays demonstrated that 7a downregulated the protein expression of Bcl-2 and upregulated the expressions of Bax to promote A549 apoptosis, the obtained results also suggested that 7a had the potential to be developed into a lead compound that can be applied in the prevention and treatment of lung cancer.

2.
Quant Imaging Med Surg ; 13(6): 3902-3914, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37284072

RESUMO

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(5): 899-905, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36325789

RESUMO

Gastric cancer ranks as the fifth most common malignant tumor worldwide and the fourth leading cause of cancer-related deaths.Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a special type of gastric adenocarcinoma,the prognosis of which can be improved by trastuzumab plus cytotoxic chemotherapy such as cisplatin and fluorouracil.Pembrolizumab on the basis of Tmabplus chemotherapy can further improve the overall response rate,which has become the first-line standardized therapy against HER2-positive gastric cancer.However,there are still some obstacles such as the innate resistance to Tmab in specific populations.The research on HER2-targeted therapy provides clues for clinical decision-making.This review documents the current neoadjuvant and adjuvant therapies against late-stage HER2-positive gastric cancer,as well as the progress in novel HER2 pathway-targeted drugs.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2 , Trastuzumab/uso terapêutico
4.
Nat Prod Res ; : 1-9, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36054816

RESUMO

While a range of pharmacological agents are currently used to alleviate inflammation, the clinical administration of many of these anti-inflammatory drugs is associated with high rates of adverse side effects that make them poorly suited to long-term use. Therefore, there is a critical need for the development of novel anti-inflammatory agents. Natural compounds and derivatives like ethyl ferulate have risen to prominence as a foundation for many drug discovery efforts owing to their structural diversity and wide-ranging biological activities. In the present study, 24 ethyl ferulate derivatives were synthesized. Their anti-inflammatory activity was evaluated in vitro using RAW264.7 cells and CCK-8, ELISA, and Western blotting assays. These analyses revealed that most of the synthesized compounds exhibited moderate to high anti-inflammatory activities. In particular, c10 and c23 exerted more pronounced activity than ethyl ferulate or dexamethasone with respect to the suppression of tumour necrosis factor-α production by RAW264.7 cells through the targeting of the NF-κB and MAPK signalling pathways, suggesting that these compounds warrant further investigation.

5.
Eur Radiol ; 32(12): 8485-8496, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35699767

RESUMO

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Meios de Contraste/farmacologia , Ultrassonografia/métodos , Pâncreas , Neoplasias Pancreáticas/diagnóstico por imagem , Sensibilidade e Especificidade , Diagnóstico Diferencial , Neoplasias Pancreáticas
6.
Cancer Med ; 9(14): 5086-5094, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32459060

RESUMO

The objective of this study was to predict the value of lymphocyte subsets in cancer progression. Peripheral blood was obtained from 327 untreated patients with cancer and 158 healthy volunteers. Levels of lymphocyte subsets were determined by flow cytometry. There were decreased levels of natural killer (NK) cells, CD8+ T cells, and naïve CD4+ /CD4+ T cells in untreated patients with cancer compared to those in healthy controls. Inversely, there were elevated levels of the following T-cell percentages in cancer patients compared to those in healthy controls: memory CD4+ /CD4+ , CD8+ T cells, HLA-DR/CD8+ , CD8+ CD38+ /CD8+ , and CD4+ /CD8+ . In addition, there are a decreasing trend in terms of CD4+ T-cell counts and an increase CD8+ HLA-DR/CD8+ T-cell and CD8+ CD38+ /CD8+ T-cell percentages in the advanced stage. An increasing trend with advanced tumor stage and the percentages of CD8+ HLA-DR/CD8+ T cells and CD8+ CD38+ /CD8+ T cells was shown in this study. There are a negative correlation for CD4+ T-cell counts and positive correlation for percentages of CD8+ HLA-DR/CD8+ T cell and CD8+ CD38+ /CD8+ T cells with the lymph node metastasis. In the presence of distant metastatic spread, we observed higher NK-cell counts, CD8+ HLA-DR/CD8+ T-cell percentages, CD8+ CD38+ /CD8+ T-cell percentages, as well as lower CD4+ T-cell counts than those in the absence of distant metastases spread. Abnormal levels of NK cell, CD8+ T cells, memory CD4+ /CD4+ , naïve CD4+ / CD4+ , CD8+ HLA-DR/CD8+ , CD8+ CD38+ /CD8+ , and CD4+ /CD8+ can be a potential blood biomarkers of cancer development. CD4+ T-cell counts and percentages of CD8+ HLA-DR/ CD8+ and CD8+ CD38+ / CD8+ can predict the cancer progression.


Assuntos
Biomarcadores Tumorais/metabolismo , Contagem de Linfócitos/métodos , Linfócitos/metabolismo , Neoplasias/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral , Adulto Jovem
7.
Endocrine ; 68(2): 448-457, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32124259

RESUMO

BACKGROUND: Insulinoma is a subtype of pancreatic neuroendocrine tumors. Many patients with insulinoma are obese due to frequent food intake. Ghrelin is associated with obesity and blood levels of insulin. It is not clear if plasma levels of ghrelin in insulinoma patients correlate with hyperinsulinemia and obesity. Expression of ghrelin and its receptor has not been well demonstrated in insulinoma. OBJECTIVE: To study if plasma levels of ghrelin is associated with obesity and hyperinsulinemia or hyperproinsulinemia in patients with insulinoma, and to detect the expression of ghrelin and its receptor in insulinoma. METHODS: Plasma levels of acylated ghrelin, insulin, and proinsulin were measured in 37 patients with insulinoma and 25 controls by ELISA. Expression of ghrelin and its receptor GHS-R1A was examined in 20 insulinoma and paired pancreatic specimens by immunostaining. P ≤ 0.05 was considered significant. RESULTS: The plasma levels of acylated ghrelin in patients with insulinoma were significantly lower than that in the controls (median 15 pg/ml vs. 19 pg/ml, respectively, P = 0.016). The reduced plasma levels of acylated ghrelin in patients were significantly correlated with obesity, hyperinsulinemia, and hyperproinsulinemia (P = 0.029 and P = 0.028, respectively). Expression of ghrelin and its receptor GHS-R1A was shown in the majority of insulinoma specimens. The expression of GHS-R1A was positively correlated with ghrelin expression in insulinoma (P = 0.014). CONCLUSIONS: Plasma levels of acylated ghrelin decreased in patients with insulinoma, probably due to the hyperinsulinemia and obesity in the patients. Expression of both ghrelin and its receptor is common in insulinoma.


Assuntos
Insulinoma , Neoplasias Pancreáticas , Grelina , Humanos , Insulina , Receptores de Grelina
8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(1): 117-123, 2020 Feb 28.
Artigo em Chinês | MEDLINE | ID: mdl-32131950

RESUMO

Tumors are highly complex systems. Understanding the compositions and functions of the tumor immune microenvironment is a prerequisite for effective tumor immunotherapy. Single-cell RNA sequencing can detect the transcriptome of a cell at the resolution of single-cell level,describe its functional status,and thus deepen the understanding of the composition and function of different cell clusters in tumor immune microenvironment. This article reviews the application of single-cell RNA sequencing in research on tumor immune microenvironment.


Assuntos
Neoplasias/genética , Neoplasias/imunologia , Análise de Sequência de RNA , Análise de Célula Única , Microambiente Tumoral , Humanos , Imunoterapia , Transcriptoma
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(6): 825-830, 2020 Dec 30.
Artigo em Chinês | MEDLINE | ID: mdl-33423733

RESUMO

While immune checkpoint inhibitors(ICIs)are effective and promising treatments for a variety of malignancies,they also have safety concerns,especially the immune-related adverse events(irAEs).Unlike the side effects of traditional chemotherapy and targeted therapy,irAEs are adverse events caused by immune activation after ICIs treatment and thus may involve almost every system of the body.Therefore,biomarkers for predicting irAEs after ICIs treatment are urgently needed.Here we review the currently available predictive biomarkers of irAEs.


Assuntos
Biomarcadores , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias , Humanos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico
10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 636-645, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699194

RESUMO

Objective To compare the differences in fecal flora among patients with esophageal cancer,gastric cancer,or colorectal cancer and between patients with gastrointestinal tumors and healthy people.Methods The 16S rRNA method was used to analyze the differences in fecal flora among 13 patients with esophageal squamous cell carcinoma,23 patients with gastric cancer,6 patients with colorectal cancer,and 49 healthy persons.Results Bifidobacterium,Faecalibacterium prausnitzii,and Ruminococcus callidus were less abundant in the fecal flora of cancer patients than in those of healthy controls(all P<0.05).Some species of Firmicutes and Actinobacteria were significantly reduced in the feces of patients with esophageal cancer or gastric cancer than in healthy people(P<0.05),whereas others showed consistency with the intestinal cancer group.Anti-tumor treatment,antibiotics,and lactic acid could affect the fecal flora of cancer patients.Conclusion The gut microbiota compositions(mainly Firmicutes and Actinobacteria)and some specific bacteria species in the feces of patients with esophageal cancer and gastric cancer are similar to those in the feces of patients with intestinal cancer,suggesting these bacteria may be involved in the development of upper gastrointestinal tumors.


Assuntos
Bactérias/classificação , Neoplasias Esofágicas/microbiologia , Carcinoma de Células Escamosas do Esôfago/microbiologia , Microbioma Gastrointestinal , Estudos de Casos e Controles , Fezes/microbiologia , Humanos , RNA Ribossômico 16S/genética
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(1): 63-67, 2019 Feb 28.
Artigo em Chinês | MEDLINE | ID: mdl-30837044

RESUMO

Objective To investigate the expression of α-smooth muscle actin(α-SMA)in advanced colorectal cancer tissue and its association with chemotherapy response and prognosis.Methods The expression of α-SMA was detected by immunohistochemistry in tissues from 52 advanced colorectal cancer patients who received oxaliplatin plus 5-fluorouracil regimen as first-line chemotherapy. Its relationship with clinical characteristics,chemotherapy response,and survival were analyzed.Results Of these 52 patients,29(55.8%)were α-SMA overexpression,and the expression of α-SMA protein was not significantly associated with the age(χ 2=0.113,P=0.730),gender(χ 2=0.515,P=0.332),tumor location(χ 2=3.675,P=0.159),and tissue differentiation(χ 2=1.852,P=0.604). The chemotherapy resistance rate was 65.5%(19/29)in patients with high α-SMA expression,which was significantly higher than that (13.0%,3/23)in patients with low α-SMA expression(χ 2=14.470,P=0.000). Patients with high α-SMA expression exhibited a significantly shorter progression-free survival(PFS)compared with those with low α-SMA expression [(6.4±1.0)months vs.(16.0±3.5)months; χlog-rank2=5.985,P=0.018]. Conclusion High α-SMA expression is associated with resistance to first-line chemotherapy and poor prognosis in advanced colorectal cancer patients.


Assuntos
Neoplasias Colorretais , Actinas , Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila , Humanos , Músculo Liso , Compostos Organoplatínicos , Prognóstico
12.
World J Surg Oncol ; 17(1): 3, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606195

RESUMO

BACKGROUND: Although pathological evaluation has been considered an effective evaluation method, some problems still exist in practice. Therefore, we explored whether there are more reasonable and practical pathological evaluation criteria for neoadjuvant chemotherapy in patients with advanced gastric cancer. Here, we aim to determine pathological judgment criteria for neoadjuvant chemotherapy in patients with advanced gastric cancer. METHODS: Eighty-seven patients with cT2-4 or cN+ were enrolled in this study. Pathological factors for overall survival (OS) were investigated using univariate and multivariate analyses, and the pathological criteria for neoadjuvant chemotherapy were then determined. RESULTS: A total of 87 patients underwent 3-4 cycles of neoadjuvant chemotherapy, with 67 (77.0%), 15 (17.2%), and 5 (5.8%) receiving Folfox6, Xelox, and SOX regimens, respectively. All patients showed different levels of graded histological regression (GHR) of the primary tumor, with a ≥ 50% regression rate of 50.6%. The univariate analysis showed that GHR ≥ 50% (p = 0.022), 66.7% (p = 0.013), and 90% (p = 0.028) were significantly correlated with OS. The multivariate analysis demonstrated that ypTNM (II/III) stage was significantly associated with OS compared with ypTNM (0+I) stage [HR = 3.553, 95% CI 1.886-6.617; HR = 3.576, 95% CI 1.908-6.703, respectively] and that the Lauren classification of diffuse type was also an independent risk factor for OS compared with the intestinal type (HR = 3.843, 95% CI 1.443-10.237). CONCLUSIONS: The Lauren classification and ypTNM stage after neoadjuvant chemotherapy are independent prognostic factors in advanced gastric cancer. A GHR ≥ 50%/< 50% can be used as the primary criterion for advanced gastric cancer after neoadjuvant chemotherapy to determine postoperative adjuvant chemotherapy regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/métodos , Seleção de Pacientes , Neoplasias Gástricas/terapia , Estômago/patologia , Feminino , Seguimentos , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Estômago/cirurgia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento
13.
Medicine (Baltimore) ; 97(45): e12750, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30407280

RESUMO

The aim of the present study was to assess the effect of Endostar and temozolomide or dacarbazine plus 5-fluorouracil (5-FU) in patients with advanced pancreatic neuroendocrine tumors (pNETs).Phase II study of 14 patients with locally advanced or metastatic well-differentiated pNETs treated between April 2013 and September 2016. Patients received temozolomide or dacarbazine plus 5-FU, and Endostar. The primary outcome was the radiographic response rate.All 14 patients had nonfunctional pNETs. Six patients received temozolomide and 8 received dacarbazine + 5-FU, combined with Endostar. Thirteen patients were assessable for treatment response: 1(7%) with complete response, 5 (39%) with partial response, 5 (39%) with stable disease, and 2 (15%) with progression. The median progression-free survival was 12 months. The most common grade 1/2 toxicities were neutropenia (43%) and leucopenia (21%).Endostar combined with temozolomide or dacarbazine + 5-FU was effective in the treatment of advanced pNETs. The combinations were well tolerated.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Endostatinas/administração & dosagem , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Recombinantes/administração & dosagem , Adulto , Idoso , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Temozolomida , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(5): 660-666, 2018 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-30404699

RESUMO

Objective To explore the efficacy and prognostic factors of cetuximab therapy for KRAS or all RAS wild-type(WT)metastatic colorectal cancer(mCRC).Methods We screened mCRC patients receiving at least two cycles of cetuximb and chemotherapy from those with KRAS WT(before November 2013)or all-RAS-WT(after November 2013)in the Department of Medical Oncology,Peking Union Medical College Hospital from November 2007 to December 2016. The relationship between the clinicopathological characteristics and the efficacy was retrospectively analyzed.Results A total of 60 patients were included. For the 34 patients receiving cetuximab as first-line treatment,the objective response rate(ORR)was 55.9%,and the progression-free survival and overall survival(OS)was 10 and 24 months,respectively. All-RAS-WT mCRC had significantly lower risk of progression than those with KRAS-only-WT(P=0.012),and left-sided colorectal cancer had higher ORR than right-sided colon cancer(62.1% vs. 0,P=0.033)during the first-line treatment. The median OS of the eight patients continuing cetuximab beyond first-line progression was 35.0(95%CI:23.6-46.4)months.Conclusions The efficacy of cetuximab for left-sided colorectal cancer was better than for right-sided colon cancer,and patients with all-RAS-WT have lower risk of progression than those with KRAS-only-WT. Patients benefiting from first-line cetuximab and continuing cetuximab beyond progression survive longer.


Assuntos
Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Humanos , Mutação , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(2): 211-218, 2018 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-29724311

RESUMO

Objective To investigate the clinicopathological features,treatment,and prognosis of patients with malignant peritoneal mesothelioma(MPM). Methods Clinical data of 25 MPM patients admitted to Peking Union Medical College Hospital from 1993 to 2017 were retrospectively analyzed.Results The mean age of these 25 patients with pathologically confirmed MPM(epithelioid subtype) was 50 years.The tumors were diffuse in 24 patients(96%) and localized in 1 patient(4%).Cytoreductive surgery was performed in 6 patients(24%),intraperitoneal chemotherapy in 12 patients(48%),and systemic chemotherapy in 24 patients(96%).The median overall survival was 26 months,with 1-year survival rate of 74.2% and 5-year survival rate of 16.7%.Cytoreductive surgery or intraperitoneal chemotherapy combined with systemic chemotherapy showed a significant survival advantage over intraperitoneal or intravenous chemotherapy alone(P=0.046,P=0.005).Cytoreductive surgery(P=0.018) showed statistical significance by multivariate analysis as a predictive factor in survival(hazard rate=6.889;95%CI=1.386-34.247).Conclusions MPM has its diverse clinical manifestations.Patients after cytoreductive surgery have longer survival time.Chemotherapy drugs(except for pemetrexed) and targeted therapy may be promising treatments.Cytoreductive surgery is an independent prognostic factor.


Assuntos
Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Terapia Combinada , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 39(5): 593-601, 2017 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-29125099

RESUMO

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.


Assuntos
Quinases Lim/genética , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Polimorfismo de Nucleotídeo Único , Povo Asiático , China , Genótipo , Humanos , Doenças do Sistema Nervoso Periférico/genética
17.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 39(4): 562-567, 2017 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-28877836

RESUMO

Objective To explore the efficacy and toxicities of gemcitabine combined with S-1 in treating locally advanced and metastatic pancreatic ductal adenocarcinoma and prognostic factors. Methods We retrospectively analyzed the clinical data of patients with locally advanced and metastatic pancreatic cancer receiving gemcitabine and S-1 as first-line therapy in the Department of Medical Oncology,Peking Union Medical College Hospital from January 2014 to January 2017.Gemcitabine was administered at a dose of 1000 mg/m2 over 30 min-utes on days 1 and 8,and oral S-1 at a dose of 40-60 mg twice daily from days 1 to 14,repeated every 3 weeks.All patients received at least two cycles of chemotherapy. Results A total of 60 patients were included,13(22%) achieved partial remission,37(61%) had stable disease,and 10(17%) experienced progressive disease.The median progression-free survival was 7 months(95% CI=6-10 months) and the median overall survival was 12 months(95% CI=9-20 months).Both univariate and multivariate analyses of prognostic factors showed primary resection was significant in predicting shorter progression-free survival and lung metastasis was significant for shorter overall survival.The most common grade 3-4 toxicities were neutropenia(27%) and leukopenia(18%). Conclusion Gemcitabine combined with S-1 is an effective regimen with manageable toxicities in the treatment of advanced pancreatic cancer and can be used as first-line therapy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/análogos & derivados , Ácido Oxônico/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Tegafur/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Humanos , Ácido Oxônico/administração & dosagem , Estudos Retrospectivos , Tegafur/administração & dosagem , Resultado do Tratamento , Gencitabina
18.
Sci Rep ; 7(1): 2205, 2017 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-28526880

RESUMO

Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10-4 and p = 3.75 × 10-5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.


Assuntos
Biomarcadores Tumorais , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/mortalidade , Proteínas de Filamentos Intermediários/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Ubiquitina Tiolesterase/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/genética , Metilação de DNA , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Incidência , Proteínas de Filamentos Intermediários/genética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Prognóstico , Regiões Promotoras Genéticas , Proteoma , Proteômica/métodos , Análise de Sobrevida , Ubiquitina Tiolesterase/genética , Adulto Jovem
20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 38(3): 300-4, 2016 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-27469915

RESUMO

Objective To explore the efficiency of sunitinib in Chinese pancreatic neuroendocrine tumors (pNET) patients. Methods Advanced pNET patients who had accepted sunitinib treatment in the oncology department of PUMC Hospital from January 2009 to June 2015 after disease progression were enrolled in this study. Data collection included clinicopathological characteristics,medical therapies and outcomes. Results Eighteen pNET patients were collected. The overall response rate (ORR) was 27.7% and the disease control rate (DCR) was 83.3%. Nine patients received sunitinib as the first-line therapy and 9 as the second/post-second line. The median progression-free survival (mPFs)(12 month vs. 12 month;HR:0.92,95%CI:0.31-2.75,P=0.88),ORR (22.2% vs.33.3%;Χ(2)=0.055,P=0.98),and DCR (88.9% vs.77.8%;Χ(2)=0.4,P=0.98)showed no significant difference between first-line therapy and post-second line therapy. The mPFS of Ki-67≥10% and Ki-67<10% group patients was not significantly different (8 months vs. 13 months;HR:1.13,95% CI:0.34-3.77,P=0.845). The commonly reported adverse events included bone marrow suppression,diarrhea,roteinuria,hypertension,and rash. Conclusions First-line or second/post-second line sunitinib treatment has certain antitumor activity in Chinese patients with advanced pNET. The efficiency and commonly reported adverse events of Sunitinib are consistent with the known Western data.


Assuntos
Antineoplásicos/uso terapêutico , Indóis/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Pirróis/uso terapêutico , Intervalo Livre de Doença , Humanos , Sunitinibe
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