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1.
J Transl Med ; 20(1): 327, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864528

RESUMO

BACKGROUND: Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. METHOD: FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/ß-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. RESULT: Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P < 0.05). Upregulation of FOXS1 association with poor prognosis of CRC patients. si-FOXS1 induced apoptosis and inhibited proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT), and the Wnt/ß-catenin signaling pathway in vitro; sh-FOXS1 inhibited the volume and weight of subcutaneous xenografts and the number of lung metastases in vivo. LiCl, an activator of Wnt signaling, partially reversed the effect of FOXS1 overexpression on CRC cells. CONCLUSION: FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/ßcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.


Assuntos
Neoplasias Colorretais , Via de Sinalização Wnt , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Interferente Pequeno , Via de Sinalização Wnt/genética , beta Catenina/metabolismo
2.
Medicine (Baltimore) ; 99(3): e18892, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011517

RESUMO

RATIONALE: Small cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before. PATIENT CONCERNS: A 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams including abdomen computed tomography excluded distant metastasis. DIAGNOSES: Primary SCCE (pT1bN1M0, IIB) was established after salvage operation. INTERVENTIONS: The tumor was enlarged after 1 cycle of first-line chemotherapy using irinotecan plus cisplatin, which indicated drug resistance. Second-line oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval) for a month showed efficacy, as shown by decreased serum neuron-specific enolase and stable of the esophageal lesion. Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months. In addition, maintenance therapy using low-dose apatinib (250 mg daily) plus S-1 (40 mg, twice daily for 4 weeks with a 2-week interval) were administered for another 6 months. Then the patient was followed up irregularly at the outpatient clinic. OUTCOMES: The adverse events including hand-foot syndrome, hypertension, vomiting, leukopenia, impaired hepatic function, and fatigue were mainly tolerable. Forty months after the operation, he was readmitted for back pain and disseminated bone metastases appeared in magnetic resonance images. His progression-free survival could not be obtained precisely, and his overall survival was longer than 40 months up to September 2019. LESSONS: S-1 plus apatinib followed by a timely esophagectomy with curative intent might be an alternative option for chemotherapy-refractory SCCE in selected patients. Better evidence is warranted.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Tegafur/uso terapêutico , Carcinoma de Células Pequenas/cirurgia , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Irinotecano/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia de Salvação
3.
Medicine (Baltimore) ; 99(40): e22479, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019440

RESUMO

RATIONALE: Late-onset anastomotic leak (AL) is an uncommon but potentially lethal complication after esophagectomy. PATIENT CONCERNS: A 74-year-old male patient was readmitted due to chest distress and chills about 3 months after initial esophagectomy for cancer. DIAGNOSES: The previous endoscopic biopsy revealed primary esophageal squamous cell carcinoma, and sweet esophagectomy with gastric conduit reconstruction was therefore performed. The patient developed AL 3 months after the surgery. INTERVENTIONS: Naso-leakage extraluminal drainage tube was utilized because the symptoms of the patient were aggravated 1 month after the chest tube drainage since his second admission for AL. OUTCOMES: Twenty-one days after naso-leakage extraluminal drainage, the computed tomography images showed the healing of the leakage. Then the patient was discharged from the hospital. LESSONS: Late-onset AL should be kept in mind when the patient complained of chest distress and fever during the follow up after esophagectomy. In addition, naso-leakage extraluminal drainage could be considered for the treatment of AL. Further trials for better evidence are warranted.


Assuntos
Fístula Anastomótica/etiologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Fístula Anastomótica/patologia , Esofagectomia/métodos , Humanos , Masculino , Complicações Pós-Operatórias/patologia
4.
Medicine (Baltimore) ; 96(47): e8927, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29382032

RESUMO

RATIONALE: The accurate diagnosis and staging of cavitary lung cancer is challenging but essential for the choice of therapy; therefore, the differential diagnosis of cystic pulmonary lesions needs to be elucidated. PATIENT CONCERNS: A patient was admitted with multifocal thin-walled cystic lesions in chest computed tomography. DIAGNOSES: The patient had been diagnosed as heterogeneous bullous emphysema pathologically about 3 years ago. His diagnosis turned out to be metastatic cavitary lung cancer complicated with fungal pneumonia this time. INTERVENTIONS: The patient underwent lung volume reduction surgery during his first hospitalization. Concurrent systemic chemotherapy and whole brain radiotherapy were administered after the diagnosis of cystic lung cancer. OUTCOMES: The patient was lost to follow-up after the chemoradiotherapy. LESSONS: Cavitary lung cancer should always be kept in mind during differential diagnosis of pulmonary cystic lesions. Pathological diagnosis by biopsy and surgery could be considered to avoid delayed treatment of malignancy.


Assuntos
Enfisema/microbiologia , Pneumopatias Fúngicas/complicações , Neoplasias Pulmonares/microbiologia , Pneumonia/microbiologia , Diagnóstico Diferencial , Enfisema/diagnóstico , Humanos , Perda de Seguimento , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico
5.
Ai Zheng ; 26(7): 683-7, 2007 Jul.
Artigo em Zh | MEDLINE | ID: mdl-17626740

RESUMO

BACKGROUND & OBJECTIVE: GRIM-19 (gene associated with retinoid-interferon-induced mortality-19) gene is a specific protein to inhibit signal transducers and activators of transcription 3 (STAT3). STAT3 and its pathway are involved in modulating cell proliferation, apoptosis, differentiation, and mediating malignant transformation of cells. This study was to investigate the expression of GRIM-19 and its target gene STAT3 in human colorectal carcinoma tissues, and explore their roles in the tumorigenesis of colorectal carcinoma. METHODS: The expression of GRIM-19, STAT3 and its activated form p-STAT3 in 40 specimens of colorectal carcinoma, adjacent tissue, and normal tissue was determined by immunohistochemistry and Western blot. The correlations of the expression of GRIM-19, STAT3, and p-STAT3 to various clinicopathologic characteristics of colorectal carcinoma were analyzed statistically. The mRNA expression and gene mutation of GRIM-19 in colon cancer cell line SW480 and 23 specimens of colorectal carcinoma, adjacent tissue, and normal tissue were detected by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. RESULTS: The expression of both STAT3 and p-STAT3 were up-regulated in colorectal carcinoma. The mRNA and protein expression of GRIM-19 was obviously lower in colorectal carcinoma than in normal tissues. The expression of GRIM-19 was correlated to clinical stage and cell differentiation of colorectal cancer (P< 0.05). GRIM-19 expression in colorectal cancer was negatively correlated to STAT3 and p-STAT3 expression (Chi2 = 9.95, P = 0.00; Chi2 = 5.10, P = 0.02). No mutation of GRIM-19 gene was detected in colorectal carcinoma tissues. CONCLUSIONS: The low expression or absence of GRIM-19 may play an important role in the tumorigenesis of colorectal carcinoma. The high expression of STAT3 and the low expression of GRIM-19 co-exist in colorectal carcinoma, and may be related to malignant transformation and abnormal proliferation of cells.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/metabolismo , NADH NADPH Oxirredutases/biossíntese , Fator de Transcrição STAT3/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose/genética , Western Blotting , Diferenciação Celular , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , NADH NADPH Oxirredutases/genética , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais
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