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1.
Anticancer Res ; 39(11): 6155-6163, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704843

RESUMO

BACKGROUND/AIM: Fluoxetine, an antidepressant, has cytotoxic effects on several cancer cell lines, while paclitaxel is an antineoplastic agent for various cancers. The aim of this study was to evaluate whether fluoxetine enhances the cytotoxic effect of paclitaxel in gastric adenocarcinoma cells and determine the mechanism of cell death. MATERIALS AND METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to examine cell viability and perform cell cycle analysis. Annexin V propidium iodide (PI) staining, 4',6-diamidino-2-phenylindole (DAPI) staining, caspase-3/7 assay, and western blot analysis were performed for determining cell death. RESULTS: Fluoxetine enhanced the anti-proliferative effect of paclitaxel. Fluoxetine-paclitaxel combination caused G2/M arrest and increased events in the sub G0/G1 phase in a time and dose-dependent manner, indicating apoptotic cell death. Combination treatment caused an increase in early apoptotic and late apoptotic cell death compared to single treatment alone. CONCLUSION: Fluoxetine enhanced the antiproliferation effect of paclitaxel in gastric adenocarcinoma AGS cells and the combination caused cell death by triggering apoptosis and necroptosis.


Assuntos
Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Fluoxetina/farmacologia , Necrose , Paclitaxel/farmacologia , Neoplasias Gástricas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Inibidores de Captação de Serotonina/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas
2.
Anticancer Res ; 39(10): 5781-5787, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570482

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) is established in the treatment of ductal pancreatic adenocarcinoma for downsizing borderline-resectable pancreatic cancer (BRPC) and may affect nodal positivity and rates of R0 resection. This study aimed to identify the impact of NAC on postoperative histopathological parameters with a prognostic relevance. PATIENTS AND METHODS: A one-to-three matched-pair analysis, including an overall total of 132 patients (25% treated with NAC and subsequent resection and 75% undergoing upfront surgery) was performed. Influence of NAC on nodal positivity, lymphatic, vascular and perineural invasion, as well as resection stage and grading, was examined. Furthermore, perioperative complications, in-hospital stay, re-admission rates, mortality, as well as preoperative body mass index and American Association of Anesthesiologist classification scores, were evaluated. RESULTS: Patients treated with NAC significantly less frequently had lymphatic tissue invasion (lymph node invasion: 51.5% vs. 72.7%; p=0.032, and lymphatic vessel invasion 9.4% vs. 55.3%; p=0.0004), whereas vascular and perineural invasion, as well as grading and resection state were not significantly different. Carbohydrate antigen 19-9 regression in correlation with nodal positivity also did not differ, and both groups showed comparable perioperative complication rates. Occurrence and severity of postoperative pancreatic fistula (18.2% vs. 24.3%; p=0.034) were significantly lower in patients who had undergone NAC. CONCLUSION: NAC significantly affects postoperative histopathological tumour stage in BRPC and appears to be a safe treatment option without increased perioperative complications, re-admission, in-hospital stay, or mortality. Further studies are mandatory to underline the suitability of NAC for ductal pancreatic adenocarcinoma subgroups in order to guide clinicians in their daily decision-making comprehensively.


Assuntos
Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos
3.
Medicine (Baltimore) ; 98(40): e17443, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577767

RESUMO

RATIONALE: Pancreatic cancer (PC) is considered as one of the deadliest cancers all over the world. Germline and somatic BRCA1/2 mutations have been widely studied in breast and ovarian carcinomas as they have been found to enhance the risk for disease progression. Olaparib, an oral poly(adenosine diphosphate-ribose)polymerase (PARP) inhibitor, has been approved for the treatment strategy of ovarian cancer with any BRCA1/2 mutations. There is a lack of studies which focus on the treatment of other cancer with BRCA-Mutation. PATIENT CONCERNS: This report describes a patient whose presenting complaints were "Physical examination showed that the pancreas was occupied for one month." He initially was diagnosed with stage IV PC based on conventional imaging and pathologic assessment. He had a known germline BRCA 2 mutation, which exhibited a good response to PARP inhibitor therapy. DIAGNOSIS: Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation. INTERVENTIONS: He received gemcitabine and albumin-bound paclitaxel chemotherapy from March 15, 2017 to June 30, 2017, and Nivolumab immunotherapy as the maintenance therapy. After serum CA-199 level increased, Olaparib was orally administered from August 17, 2017 to March. After tumor relapsed, he received multiple lines of chemotherapy, including Trametinib Oxaliplatin, S-1, bevacizumab, and irinotecan liposome injection till July 17, 2018. OUTCOMES: We observed the patient had a good progression-free survival (7.4 months); the lesion of the pancreas was classified as partial disease through Olaparib treatment, which indicated significant shrinkage. But it is difficult to conclude whether such therapy could help prolong the overall survival for such patients. LESSONS: The targeted therapy Olaparib showed early signs of potential in treating PC in patients with mutations of the BRCA genes. With emerging therapeutic modalities and next-generation sequencing development, it is increasingly relevant to consider mutation screenings of patients with PC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Genes BRCA2 , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Idoso , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Neoplasias Pancreáticas/genética
5.
Chirurgia (Bucur) ; 114(4): 443-450, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31511130

RESUMO

Background: To evaluate the prognostic role of Positron Emission Tomography/Computed Tomography (PET/CT) and Endoscopic Ultrasound (EUS) performed before neoadjuvant chemotherapy (NAC) and surgery for oesophageal adenocarcinoma (OAC) patients, focusing on lymph node (LN) assessment. Methods: OAC patients treated in a single tertiary center during January 2008 until December 2014 were retrospectively studied. All patients had PET/CT and EUS before NAC and oesophagectomy. PET-FDG-avid local LNs and maximum standardized uptake value (SUVmax) of the primary tumour, EUS positive LNs and EUS tumour length were recorded. Univariate, multivariate and survival analyses were performed. Results: Following exclusions 151consecutive patients met the inclusion criteria, (median age 62 years). PET/CT and EUS sensitivity for local LNs metastasis was 39.2% and 88.6%, with specificities of 83.33% and 19.15% respectively. No overall survival (OS) difference was found between patients with PET/CT FDG-avid LNs and those with negative LNs (p=0.347). SUVmax uptake was divided into high and low (median cut-off value: 10) with no significant difference in OS between groups (p=0.141). EUS tumour length was not prognostic (OS, p=0.455). Conclusions: Initial LN staging in OA is inaccurate. Although PET/CT and EUS assessments may be complimentary, none independently predicted survival.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Endossonografia , Neoplasias Esofágicas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Antineoplásicos/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Fluordesoxiglucose F18 , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias/métodos , Cuidados Pré-Operatórios , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Resultado do Tratamento
6.
Life Sci ; 235: 116798, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472149

RESUMO

Lung cancer is the leading cause for cancer death due to refractory nature to current treatment strategies, understanding the regulatory mechanism of therapy resistance of lung cancer is important for lung cancer therapy. Here, we aimed to study the role of SHCBP1 in lung cancer cisplatin resistance, we found SHCBP1 was upregulated in lung cancer tissues and cells, patients with high SHCBP1 had poor prognosis. SHC binding and spindle associated 1 (SHCBP1) overexpression promoted cisplatin induced apoptosis resistance, migration and invasion determined by apoptosis assay and transwell assay with or without Matrigel, while SHCBP1 knockdown inhibited cisplatin induced apoptosis resistance, migration and invasion. Wnt pathway promoted lung cancer progression, we found SHCBP1 activated Wnt pathway, characterized by promoting ß-catenin nuclear translocation. Inhibition of Wnt pathway in SHCBP1 overexpression cells reversed the effect of SHCBP1 overexpression, confirming SHCBP1 promoted lung cancer progression through activating Wnt pathway. We also found SHCBP1 expression was positively corrected with Wnt pathway activity in lung cancer samples. In summary, we found SHCBP1 promoted cisplatin induced apoptosis resistance, migration and invasion through activating Wnt pathway, providing a potential target for lung cancer therapy.


Assuntos
Apoptose , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Movimento Celular , Proliferação de Células , Células Cultivadas , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Invasividade Neoplásica , Prognóstico , Proteínas Adaptadoras da Sinalização Shc/genética , Taxa de Sobrevida , Proteínas Wnt/genética , Via de Sinalização Wnt , beta Catenina/genética
7.
J Cancer Res Clin Oncol ; 145(11): 2855-2862, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31506738

RESUMO

PURPOSE: The treatment of pancreatic carcinoma remains a challenge as prognosis is poor, even if confined to a single anatomical region. A regional treatment of pancreatic cancer with high drug concentrations at the tumor site may increase response behaviour. Intra-arterial administration of drugs generates homogenous drug distribution throughout the entire tumor volume. METHODS: We report on treatment outcome of 454 patients with advanced pancreatic carcinoma (WHO stage III: 174 patients, WHO stage IV: 280 patients). Patients have been separated to two different treatment protocols. The first group (n = 233 patients) has been treated via angiographically placed celiac axis catheters. The second group (n = 221 patients) had upper abdominal perfusion (UAP) with stopflow balloon catheters in aorta and vena cava. Both groups have been treated with a combination of cisplatin, adriamycin and mitomycin. RESULTS: For stage III pancreatic cancer, median survival rates of 8 and 12 months were reached with IA and UAP treatment, respectively. For stage IV pancreatic cancer, median survival rates of 7 and 8.5 months were reached with IA and UAP treatment, respectively. Resolution of ascites has been reached in all cases by UAP treatment. Toxicity was generally mild, WHO grade I or II, toxicity grade III or IV was only noted in patients with severe systemic pretreatment. The techniques, survival data and detailed results are demonstrated. CONCLUSIONS: Responsiveness of pancreatic cancer to regional chemotherapy is drug exposure dependent. The isolated perfusion procedure is superior to intra-arterial infusion in survival times.


Assuntos
Abdome/irrigação sanguínea , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infusões Intra-Arteriais/mortalidade , Neoplasias Pancreáticas/mortalidade , Abdome/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
8.
J Cancer Res Clin Oncol ; 145(11): 2649-2661, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31529191

RESUMO

PURPOSE: The incidence of Urothelial carcinoma of bladder (UBC) is gradually increasing by changing lifestyle and environment. The development of a tumor has been noted to be accompanied by modifications in the extracellular matrix (ECM) consisting of CD44, hyaluronic acid (HA) and its family members. The importance of CD44 splice variants and HA family members has been studied in UBC. METHODS: The cohort of study included 50 UBC patients undergoing radical cystectomy and 50 healthy subjects. The molecular expression of CD44 and HA family members was determined. Effect of CD44 variant-specific silencing on downstream signaling in HT1376 cells was investigated. Combinatorial treatment of 4-MU (4-methylumbelliferone) with cisplatin or doxorubicin on chemosensitivity was also explored. RESULTS: Higher expression of HA, HAS2, and CD44 was observed in Indian UBC patients which also showed the trend with severity of disease. Splice variant assessment of CD44 demonstrated the distinct role of CD44v3 and CD44v6 in bladder cancer progression. shRNA-mediated downregulation of CD44v3 showed an increase effect on cell cycle, apoptosis and multiple downstream signaling cascade including pAkt, pERK and pSTAT3. Furthermore, 4-MU, an HA synthesis inhibitor, observed to complement the effect of Cisplatin or Doxorubicin by enhancing the chemosensitivity of bladder cancer cells. CONCLUSIONS: Our findings exhibit involvement of CD44 splice variants and HA family members in UBC and significance of 4-MU in enhancing chemosensitivity suggesting their novel therapeutic importance in disease therapeutics.


Assuntos
Processamento Alternativo , Receptores de Hialuronatos/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias da Bexiga Urinária/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Apoptose , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Fator de Transcrição STAT3/genética , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
10.
Medicine (Baltimore) ; 98(36): e17009, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490383

RESUMO

Erythrina corallodendron L., a kind of landscape tree, has long been used as a traditional medicine. In this study, the composition of essential oil extracted from the leaves was analysed by GC-MS (gas chromatograph-mass spectrometer), with linalool identified as the main compound. Its cytotoxicity against MDA-MB-231, MCF-7 and HMLE cells was examined by MTT and cloning assays. Transwell and wound-healing assays were used to examine the inhibition of migration and invasion. Western blot, qRT-PCR and immunofluorescence staining were used to measure the mRNA and protein expression of factors related to EMT (snail, slug, E-cadherin, N-cadherin and vimentin). The essential oil of Erythrina corallodendron leaves was found to inhibit the proliferation, migration and invasion of breast cancer cells in a dose-dependent manner. The findings of this study suggest that the essential oil of E. corallodendron leaves may merit further investigation as a potential clinical or adjuvant drug for treating breast cancer migration and invasion.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/análise , Neoplasias da Mama/tratamento farmacológico , Erythrina/química , Óleos Voláteis/uso terapêutico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Células MCF-7 , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Fitoterapia , Folhas de Planta/química
11.
Anticancer Res ; 39(8): 4431-4440, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366541

RESUMO

BACKGROUND/AIM: To identify risk factors of early recurrence after neoadjuvant chemoradiation therapy (NACRT) and curative pancreatectomy in patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Sixty-one patients with BR-PDAC who underwent curative resection after NACRT during July 2009-June 2014 were included. Patients were divided into early recurrence (i.e., developed recurrence within 1 year after pancreatectomy; n=30) and late/non-recurrence groups (n=31). The patient characteristics, clinicopathological factors of early recurrence, and survival time were retrospectively compared between groups. RESULTS: In the univariate analysis, the maximum standardized uptake value (SUVmax), microvascular invasion, and lymph node metastasis were associated with early recurrence. In the multivariate analysis, the pre-NACRT SUVmax and microvascular invasion in the early recurrence group were significantly different from that in the late/non-recurrence group. A pre-NACRT SUVmax >4.1 was an independent predictor of poor recurrence-free and overall survival. CONCLUSION: SUVmax and microvascular invasion are independent predictors of poor recurrence-free and overall survival after NACRT for BR-PDAC. Although complete pancreatectomy after NACRT was performed, approximately half of the patients had recurrence within 1 year.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Fatores de Risco
12.
J Surg Oncol ; 120(6): 976-984, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31452208

RESUMO

BACKGROUND AND OBJECTIVES: Conclusive evidence in favor of neoadjuvant therapy for those with non-metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non-metastatic PDAC. METHODS: The study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent-to-treat basis. RESULTS: In the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P < .002), and less lymph node metastasis (45% vs 78%, P < .001). CONCLUSIONS: The strategy of neoadjuvant therapy before surgical resection appears to offer pathologic effect and survival benefit for the patients presenting with non-metastatic PDAC.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Análise de Intenção de Tratamento , Terapia Neoadjuvante/mortalidade , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Pontuação de Propensão , Taxa de Sobrevida , Adulto Jovem
15.
Gene ; 713: 143964, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279707

RESUMO

This study aimed to investigate single-nucleotide polymorphisms (SNPs) associated with lobaplatin-induced thrombocytopenia in patients with advanced lung cancer in China. Thirty-nine patients who received lobaplatin-based chemotherapy in the 307 Hospitals of Chinese People's Liberation Army from April 2017 to March 2018 were enrolled as study subjects. Peripheral blood DNA was extracted, and 79 candidate SNP positions were selected. A Sanger sequencing platform was employed to measure genotypes for locating the SNP positions associated with lobaplatin-induced thrombocytopenia. Of the 79 candidate genes, SNPs rs342275 and rs7694379 were significantly associated with lobaplatin-induced decrease in platelet (PLT) count (P < 0.05). SNPs rs342275, rs342293, rs11789898, and rs17824620 showed significant association with lobaplatin-induced lowest PLT counts (P < 0.05). SNPs rs342275, rs342293, rs11789898, rs17824620, and rs7694379 can be used as predictors of thrombocytopenia induced by lobaplatin-based chemotherapy in patients with advanced lung cancer in China.


Assuntos
Adenocarcinoma/tratamento farmacológico , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Ciclobutanos/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Polimorfismo de Nucleotídeo Único , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Trombocitopenia/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , China , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/genética
16.
Clin Nucl Med ; 44(10): 838-839, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31283614

RESUMO

A 76-year-old man with metastatic adenocarcinoma of the prostate presented with increasing dyspnea. After being treated initially with drainage and afterwards with pleurodesis, he was referred for Ga-prostate-specific membrane antigen 11 PET/CT imaging for restaging purposes. PET/CT demonstrated extensive Ga-prostate-specific membrane antigen 11 uptake in the right pleura. Histopathology confirmed the rare case of malignant pleural effusion from metastatic prostate cancer.


Assuntos
Radioisótopos de Gálio , Glutamato Carboxipeptidase II/metabolismo , Derrame Pleural Maligno/diagnóstico por imagem , Derrame Pleural Maligno/metabolismo , Pleurodese , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Transporte Biológico , Humanos , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
17.
Anticancer Res ; 39(7): 3609-3614, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262886

RESUMO

BACKGROUND/AIM: The novel cytidine analog RX-3117, which is activated by uridine-cytidine kinase 2 (UCK2), shows encouraging activity in pancreatic and bladder cancer Phase IIa studies. In this study we highlight the potential role of UCK2 as a biomarker for selecting patients for RX-3117 treatment. PATIENTS AND METHODS: The online genomics analysis and visualization platform, R2, developed by the Oncogenomics department at the AMC (Amsterdam, The Netherlands) was used for in silico UCK2-mRNA correlation with overall survival of pancreatic cancer patients, while UCK2 protein expression was evaluated by immunohistochemistry on pancreatic tumor formalin-fixed-paraffin-embedded sections from independent pancreatic cancer patients. mRNA expression was also determined for SUIT-2, PANC-1 and PDAC-3. Lastly, the drug sensitivity to RX-3117 was investigated using the Sulforhodamine-B cytotoxicity assay. RESULTS: The in silico data showed that a high UCK2-mRNA expression was correlated with a shorter overall survival in pancreatic cancer patients. Moreover, UCK2 protein expression was high in 21/25 patients, showing a significantly shorter mean. Overall Survival (8.4 versus 34.3 months, p=0.045). Sensitivity to RX-3117 varied between 0.6 and 11 µM. CONCLUSION: Pancreatic cancer cells are sensitive to pharmacologically achievable RX-3117 concentrations and UCK2 might be exploited as a biomarker for patient treatment selection.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Citidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Uridina Quinase/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Citidina/farmacologia , Feminino , Humanos , Masculino , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , RNA Mensageiro/metabolismo , Uridina Quinase/genética
18.
Anticancer Res ; 39(7): 3621-3631, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262888

RESUMO

BACKGROUND/AIM: Cetrimonium bromide (CTAB), a quaternary ammonium surfactant, is an antiseptic agent against bacteria and fungi. However, the mechanisms by which its pharmacological actions affect epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells, such as adenocarcinoma in SK-HEP-1 cells, have not been investigated. We, thereby, investigated whether CTAB inhibits cellular mobility and invasiveness of human hepatic adenocarcinoma in SK-HEP-1 cells. MATERIALS AND METHODS: SK-HEP-1 cells were treated with CTAB, and subsequent migration and invasion were measured by wound healing and transwell assays. Protein expression was detected by immunoblotting analysis. RESULTS: Our data revealed that treatment of SK-HEP-1 cells with CTAB altered their mesenchymal spindle-like morphology. CTAB exerted inhibitory effects on the migration and invasion of SK-HEP-1 cells dose-dependently, and reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, snail, slug, twist, vimentin, fibronectin, N-cadherin, Smad2, Smad3, Smad4, phosphoinositide-3-kinase (PI3K), p-PI3K, Akt, p-Akt, ß-catenin, mammalian target of rapamycin (mTOR), p-mTOR, p-p70S6K, p-extracellular signal-regulated kinases (ERK)1/2, p-p38 mitogen-activated protein kinase (MAPK) and p-c-Jun N-terminal kinase (JNK), but increased protein levels of tissue inhibitor matrix metalloproteinase-1 (TIMP-1), TIMP-2, claudin-1 and p-GSK3ß. Based on these observations, we suggest that CTAB not only inhibits the canonical transforming growth factor-ß (TGF-ß) signaling pathway though reducing SMADs (an acronym from the fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic proteins), but also restrains the non-canonical TGF-ß signaling including MAPK pathways like ERK1/2, p38 MAPK, JNK and PI3K. CONCLUSION: CTAB is involved in the suppression of TGF-ß-mediated mesenchymal phenotype and could be a potent medical agent for use in controlling the migration and invasion of hepatic adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Antineoplásicos/farmacologia , Cetrimônio/farmacologia , Neoplasias Hepáticas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adenocarcinoma/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos
19.
Anticancer Res ; 39(7): 3739-3744, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262900

RESUMO

BACKGROUND/AIM: Cancer incidence and mortalities are growing worldwide, therefore research and development of more effective and less invasive treatments, such as photodynamic therapy, are needed. Herein, we investigated the methylene blue (MB) photoactivation effects in lung epithelial cells (BEAS-2B) and lung adenocarcinoma cells (H-441). MATERIALS AND METHODS: The reactive oxygen species (ROS) produced by the laser photoactivation of MB in aqueous solutions and cell cultures were measured with probes, and the cell viability was evaluated with a colorimetric assay. RESULTS: MB up to 31.26 µM did not induce detectable effects in BEAS-2B cells. However, H-441 cells presented adverse effects below that concentration in the same range of fluencies studied. These results are in concordance with the ROS production in H-441 cells, while in BEAS-2B cells the production of ROS was less significant compared to the control. CONCLUSION: Photoactivation of MB at concentrations below 31.26 µM could be used for the selective treatment of H-441 cells over non-cancer cells.


Assuntos
Adenocarcinoma/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Luz , Neoplasias Pulmonares/tratamento farmacológico , Azul de Metileno/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Adenocarcinoma/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(7): 648-655, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31302963

RESUMO

Objective: To investigate the value of colonoscopic assessment in "watch and wait" strategy for mid-lower rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: A single-center retrospective case series study was performed. Database of mid-lower rectal cancer patients at Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute from March 2011 to June 2017 was retrieved. Inclusion criteria: (1) nCRT was completed (50.6 Gy/22 f, plus oral capecitabine); (2) radical surgery was performed within 12 weeks after nCRT treatment; (3) clinical response to nCRT was determined as clinical complete response (cCR) or near-cCR. Patients who did not undergo colonoscopy and MRI in our center during initial assessment and follow-up, or whose colonoscopy data were unable to re-evaluated, were excluded. Initial evaluation of nCRT response was carried out between 6 and 16 weeks after nCRT. The results of endoscopy (eCR, near-eCR and non-eCR) and MRI (mCR, near-mCR and non-mCR) were compared to local lesion relapse during follow-up. The consistency of the results of colonoscopy and MRI was evaluated by Kappa test (Kappa value of 0.21 to 0.40 indicates general consistency, 0.41 to 0.60 moderate consistency, and 0.61 to 0.80 high consistency). The non-regrowth disease-free survival (NR-DFS) curves of the eCR group and the near-eCR group were plotted by Kaplan-Meier method and compared by log-rank test. Clinical significance of colonoscopy examination in the following "watch and wait" strategy during follow-up period was analyzed. Results: A total of 32 patients were enrolled in the study, including 21 (65.6%) males and 11 (34.4%) females with a median age of 57 years old. The differentiated type of rectal cancer included 1 (3.1%) case of well-differentiated, 26 (81.2%) of moderately differentiated and 5 (15.6%) of poorly differentiated. Clinical stage of the patients included 9 (28.1%) cases of T2-3N0 and 23 (71.9%) of T2-3N+. Median follow-up period was 48 (18 to 80) months. The local regrowth rate was 34.4% (11/32) and median interval of local regrowth was 10.0 (4 to 37) months. Initial colonoscopy evaluation was carried out at a median time of 9 (5 to 19) weeks after nCRT was completed. According to endoscopic findings, patients were divided into 3 groups, including 15 cases in eCR group, 15 cases in near-eCR group and 2 cases in non-eCR group. According to the appearance of MRI, patients were divided into 3 groups, including 8 cases in mCR group, 21 cases in near-mCR group and 3 cases in non-mCR group. The regrowth rate of eCR group was lower than that of mCR group (1/15 vs. 1/8) without significant difference (P=1.000). The regrowth rate of near-eCR group was higher than that of near-mCR group [9/15 vs. 42.9% (9/21)] without significant difference as well (P=0.500). The consistency between colonoscopy and MRI in response evaluation of cCR or near-cCR after nCRT was unsatisfactory (Kappa=0.341, P=0.011). After initial evaluation, 31 patients underwent watch and wait strategy, and 1 underwent local resection. The 1- and 3-year NR-DFS in the eCR group was both 100%, which was higher than that in the near-eCR group (53.3% and 38.9%, respectively), and the difference was statistically significant (P=0.001). During watch and wait period, 11 cases developed local regrowth by colonoscopy examination and the biopsy result included 4 case of high-grade intraepithelial neoplasia (HIN), 6 cases of adenocarcinoma and 1 case of chronic mucosal inflammation. Meanwhile lateral developmental tumor of ascending colon in 1 case and of sigmoid in a case was found by colonoscopy and confirmed as HIN by postoperative pathology. Besides, 4 cases developed colonic multiple adenoma and all underwent endoscopic resection. Conclusion: Colonoscopy examination plays an important role in both initial assessment and regrowth monitoring during watch and wait strategy after nCRT treatment.


Assuntos
Adenocarcinoma/diagnóstico , Quimiorradioterapia/métodos , Colonoscopia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Retais/diagnóstico , Conduta Expectante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Estudos Retrospectivos
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