Clinicopathological and immunophenotypic analysis of 24 cases of transformed mycosis fungoides / 中华皮肤科杂志

Objective:To investigate clinicopathological features and prognosis of transformed mycosis fungoides (TMF) .Methods:A retrospective analysis was performed on clinicopathological data collected from 24 patients with TMF, as well as on flow cytometry results of 16 peripheral blood samples obtained from 11 of the 24 patients, who visited Hospital of Dermatology, Chinese Academy of Medical Sciences between 2014 and 2020.Results:Among the 24 patients, 11 were males and 13 were females. Their average age at diagnosis of TMF was 50.0 years (range: 18 - 77 years), and patients with early-stage TMF (9 cases) and tumor-stage TMF (15 cases) were aged 44.8 and 52.6 years on average, respectively. The average time interval from diagnosis of MF to large cell transformation was 3.7 years, and 8 patients were diagnosed with TMF at the initial visit. Histopathologically, large cells infiltrated in a diffuse pattern in 20 cases, as well as in a multifocal pattern in 4, and the proportion of large cells in 7 cases was greater than 75%. Immunohistochemically, 18 patients showed positive staining for CD30, and the proportion of CD30-positive large cells was greater than 75% in 9; negative staining for CD30 was observed in 6. Flow cytometry of 16 peripheral blood samples showed the presence of cell subsets expressing clonal T cell receptor (TCR) -vβ in 2 of 4 patients with early-stage TMF and 10 of 12 with tumor-stage TMF, and tumor cells with higher forward scatter than normal lymphocytes were detected in 16 samples. During the follow-up, among the patients with early-stage TMF, 3 progressed to tumor-stage TMF 3.3 years on average after large cell transformation, 1 progressed to erythrodermic MF in stage IIIA, and the other 4 still showed an indolent course; among the patients with tumor-stage TMF, 1 progressed to stage-IV TMF, and 5 died 3.3 (1.5 - 6) years after large cell transformation.Conclusion:Large cell transformation may occur in patients with MF in any stage, some patients have poor prognosis, so close follow-up is needed for patients with TMF.

Efficacy and safety of beta carotones in treatment of oral leukoplakia: systematic review and meta-analysis / Eficacia y seguridad de las betacarotonas en el tratamiento de la leucoplasia oral: revisión sistemática y metanálisis

Objectives: A systematic review was conducted to evaluate effectiveness and safety of beta carotenes for the treatment of oral leukoplakia regarding clinical resolution and prevention of malignant transformation. Material and Methods: The systematic search was conducted in three electronic databases and the study's selection was performed according to pre-set eligibility criteria. Four studies evaluating the efficacy of beta carotenes in oral leukoplakia compared to placebo were included in the review; three of which were assigned for quantitative analysis. Data were extracted, tabulated, quality assessed and statistically analyzed. Results: The meta-analysis revealed that when comparing clinical resolution the beta carotene group favored was favored compared to placebo, with statistically significant difference. However, a meta-analysis comparing beta carotene and placebo groups regarding malignant transformation as a primary outcome failed to show any significant benefit. Furthermore, results showed evidence of beta carotene safety. Conclusion: the overall quality of evidence about efficacy of beta carotene in oral leukoplakia treatment was not high. However, given the obvious safety of this agent, data suggests it could have a promising effect in clinical improvement of oral leukoplakia lesions. However, no evidence supporting its benefits in reducing risk of malignant transformation in these lesions was found. Therefore, further long term, well designed randomized clinical trials are highly recommended.

Objetivos: Se realizó una revisión sistemática para evaluar la efectividad y la seguridad de los betacarotenos para el tratamiento de la leucoplasia oral en relación con la resolución clínica y la prevención de la transformación maligna. Material y Métodos: la búsqueda sistemática se realizó en tres bases de datos electrónicas y la selección del estudio se realizó de acuerdo con los criterios de elegibilidad preestablecidos. En la revisión se incluyeron cuatro estudios que evaluaban la eficacia de los betacarotenos en la leucoplasia oral en comparación con el placebo; tres de los cuales fueron asignados para el análisis cuantitativo. Los datos fueron extraídos, tabulados, su calidad evaluada y analizados estadísticamente. Resultados: El metanálisis reveló que al comparar la resolución clínica, el grupo de betacaroteno fue favorecido en comparación con el placebo, con una diferencia estadísticamente significativa. Sin embargo, un metaanálisis que comparó los grupos de betacaroteno y placebo con respecto a la transformación maligna como resultado primario no mostró ningún beneficio significativo. Además, los resultados mostraron evidencia de seguridad de betacaroteno. Conclusión: La calidad general de la evidencia sobre la eficacia del betacaroteno en el tratamiento de la leucoplasia oral no es alta. Sin embargo, dada la obvia seguridad de este agente, los datos sugieren que podría tener un efecto prometedor en la mejora clínica de las lesiones de leucoplasia oral. Sin embargo, no se encontraron pruebas que respalden sus beneficios en la reducción del riesgo de transformación maligna en estas lesiones. Por lo tanto, se recomiendan ensayos clínicos aleatorios bien diseñados a largo plazo.

Biological function and regulatory mechanism of epithelial-mesenchymal transition-related long non-coding RNAs in liver cancer / 临床肝胆病杂志

Liver cancer has a high degree of malignancy, and many oncogenes and tumor suppressor genes play an important regulatory role in the development and progression of liver cancer. Epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells transform into mesenchymal cells, which can increase the migration and invasion abilities of tumor cells. Long non-coding RNAs (lncRNAs) can regulate EMT process in various ways. This article reviews the research advances in the main biological functions and regulatory mechanisms of EMT-related lncRNAs in liver cancer.

Biological function and regulatory mechanism of epithelial-mesenchymal transition-related long non-coding RNAs in liver cancer / 临床肝胆病杂志

Liver cancer has a high degree of malignancy, and many oncogenes and tumor suppressor genes play an important regulatory role in the development and progression of liver cancer. Epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells transform into mesenchymal cells, which can increase the migration and invasion abilities of tumor cells. Long non-coding RNAs (lncRNAs) can regulate EMT process in various ways. This article reviews the research advances in the main biological functions and regulatory mechanisms of EMT-related lncRNAs in liver cancer.

Malignant transformation of abdominal wall endometriosis to clear cell carcinoma: case report

ABSTRACT BACKGROUND: Malignant transformation of endometriosis in the abdominal wall is a rare and still poorly understood event. Less than 30 cases have been reported in the worldwide literature. Most cases of solid tumors are report in a previous abdominal scar with malignant transformation of a focus of endometriosis. Presence of lymph node metastases in nearby chains is frequent and is associated with poor prognosis. CASE REPORT: We report a case of a 42-year-old woman with a history of abdominal surgery (Pfannenstiel) to resect abdominal wall endometriosis. Physical examination revealed a solid mass of approximately 10 cm x 6 cm in the anterior wall of the abdomen. Computed tomography (CT) of the abdomen and pelvis showed a heterogeneous, predominantly hypoattenuating expansive formation measuring 10.6 cm x 4.7 cm x 8.3 cm. The patient underwent exploratory incisional laparotomy, block resection of the abdominal mass and lymphadenectomy of the external and inguinal iliac chains. The abdominal wall was reconstructed using a semi-absorbable tissue-separating screen to reconstitute the defect caused by resection of the tumor. Histological evaluation revealed infiltration by malignant epithelioid neoplasia, thus confirming the immunohistochemical profile of adenocarcinoma with clear cell components. Lymphadenectomy showed metastatic involvement of an external iliac chain lymph node. CONCLUSION: Resection of the mass along with the abdominal wall, with wall margins, is the most effective treatment. Reconstruction is a challenge for surgeons. The patient has been followed up postoperatively for eight months, without any evidence of disease to date.

Clinical characteristics and survival analysis of de novo grade 3 or transformed follicular lymphoma patients / 中华血液学杂志

Objective@#To evaluate the clinical characteristics and survival outcomes of patients with de novo grade 3 or transformed follicular lymphoma (FL).@*Methods@#Fifty-two patients treated at Peking University Cancer Hospital between January 2009 and September 2017 were assessed, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. Baseline characteristics, survival and prognostic factors were analyzed.@*Results@#① Twenty-six male and 26 female patients were enrolled, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. ②The 3-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 56.0% and 80.6%, respectively. Patients with international prognostic index (IPI) score 0-1 demonstrated significantly better 3-year PFS (80.3% vs 20.1%; t=18.902, P<0.001) and OS (95.7% vs 57.0%; t=10.406, P<0.001) than patients with IPI score 2-3. Three-year PFS (94.1% vs 37.2% vs 25.2%; P=0.002) and OS (100.0% vs 76.0% vs 59.8%; P=0.020) were also significantly different among patients with FLIPI 1 score 0-1, 2, ≥3. FLIPI 2 score was also identified as a prognostic factor for 3-year PFS (68.4%, 0, 0; P=0.001) and OS(87.5%, 76.2%, 0; P=0.003). ③Multivariate analysis indicated a significant association of PFS (HR=3.536, P=0.015) and OS (HR=15.713, P=0.015) with IPI. FLIPI 2 was associated with OS (score 0-1, HR=0.078, P=0.007; score 2, HR=0.080, P=0.022).@*Conclusion@#De novo grade 3 or transformed FL might be a group of curable disease with current treatment strategies. IPI is still a prognostic tool in this scenario.

Clinical characteristics and survival analysis of de novo grade 3 or transformed follicular lymphoma patients / 中华血液学杂志

Objective: To evaluate the clinical characteristics and survival outcomes of patients with de novo grade 3 or transformed follicular lymphoma (FL). Methods: Fifty-two patients treated at Peking University Cancer Hospital between January 2009 and September 2017 were assessed, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. Baseline characteristics, survival and prognostic factors were analyzed. Results: ① Twenty-six male and 26 female patients were enrolled, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. ②The 3-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 56.0% and 80.6%, respectively. Patients with international prognostic index (IPI) score 0-1 demonstrated significantly better 3-year PFS (80.3% vs 20.1%; t=18.902, P<0.001) and OS (95.7% vs 57.0%; t=10.406, P<0.001) than patients with IPI score 2-3. Three-year PFS (94.1% vs 37.2% vs 25.2%; P=0.002) and OS (100.0% vs 76.0% vs 59.8%; P=0.020) were also significantly different among patients with FLIPI 1 score 0-1, 2, ≥3. FLIPI 2 score was also identified as a prognostic factor for 3-year PFS (68.4%, 0, 0; P=0.001) and OS(87.5%, 76.2%, 0; P=0.003). ③Multivariate analysis indicated a significant association of PFS (HR=3.536, P=0.015) and OS (HR=15.713, P=0.015) with IPI. FLIPI 2 was associated with OS (score 0-1, HR=0.078, P=0.007; score 2, HR=0.080, P=0.022). Conclusion: De novo grade 3 or transformed FL might be a group of curable disease with current treatment strategies. IPI is still a prognostic tool in this scenario.

Squamous cell carcinoma arising within a maxillary odontogenic keratocyst: A rare occurrence

Squamous cell carcinoma (SCC) arising within the lining of an odontogenic keratocyst (OKC) is a rare occurrence. Although potentially locally destructive, OKC is a benign odontogenic process that typically presents with clinical and radiographic features characteristic of a benign intraosseous neoplasm. We present the clinical and radiographic features of a maxillary mass that demonstrated SCC arising from the lining of an OKC. Although the initial clinical and radiographic presentation suggested an infection or malignant neoplasm, biopsies revealed an infiltrative well-differentiated SCC contiguous with and arising from the focus of a pre-existing OKC. The patient subsequently underwent a type II hemi-maxillectomy with neoadjuvant chemoradiation. This report discusses the clinical and radiographic features associated with intraosseous malignancies, especially those arising from an otherwise benign odontogenic lesion. While the majority of OKCs are benign, the current report illustrates the potential for carcinomatous transformation within the lining of an OKC.

Expression of interleukin-13 and its receptors in mycosis fungoides / 中华皮肤科杂志

Objective To measure the expression of interleukin-13 (IL-13) and its receptors in mycosis fungoides (MF) lesions,and to investigate their clinical significance.Methods A total of 34 paraffin-embedded specimens of MF,which was confirmed by clinical and histopathological features,immunophenotyping and/or T-cell receptor gene rearrangements,were collected from Hangzhou Third People's Hospital between January 2010 and March 2016.According to the tumor-node-metastasis (TNM) staging system,5 patients were at stage I A,9 at stage Ⅰ B,17 at stage Ⅱ A,and 3 at stage Ⅱ B.Ten normal skin tissue specimens served as controls.Immunohistochemical study was conducted to measure the expression of IL-13,IL-13Rα1 and IL-13Rα2.Results IL-13,IL-13Rα1 and IL-13Rα2 were all expressed in atypical lymphoid cells and epidermotropic lymphoid cells in MF lesions at various stages.IL-13Rα2 was highly expressed in all the MF lesions.None of IL-13 and its receptors were expressed in normal skin tissues and lymphocytes.The expression rates of IL-13 and its receptors in MF lesions increased along with the progression of MF.Additionally,the expression rates of IL-13 (10.00％ ± 3.14％),IL-13Rα1 (21.43％ ± 6.88％) and IL-13Ro2 (31.14％ ± 6.38％) significantly decreased in MF lesions at stage Ⅰ compared with those at stage Ⅱ (27.50％ ± 11.00％,39.45％ ± 9.43％,44.40％ ± 11.15％,respectively,all P ＜ 0.05),but no significant differences were observed between stage Ⅰ A and Ⅰ B,or between stage Ⅱ A and Ⅱ B (P ＞ 0.05).Conclusion IL-13 and its receptors,especially IL-13Rα2,may be expected to serve as biomarkers for early diagnosis of MF and prediction of its biological behaviors.

Effector molecules of mouse CD4 T cell converted double negative T cell / 国际外科学杂志

Objective To investigate the function characteristics of CD4 T cell converted double negative T cell and provide a basis for further insight into the characteristics of mouse converted double negative T cell.Methods The gene expression profile was analyzed by transcriptome sequencing and protein mass spectrometry.The expression of cell active marker CD44,CD69 and OX40 was investigated by flow cytometry and the cytotoxicity of mouse double negative T cell was verified by CFSE staining.Results Mouse CD4 T cell converted double negative T cell expressed cell phenotype that differed from other mature CI4 T cells.Mouse converted double negative T cell expressed high level of active marker of CD44,CD69 and OX40.Cytotoxicity of PrfO DN T was significantly reduced.Conclusions Mouse CD4 T cell converted double negative T cell has distinguishing cell phenotypes,that are not identical to other mature CD4 T cells.Mouse double negative T cell overexpresses cell activation marker and cytotoxic cytokines.The immune suppressive function of mouse double negative T cell is mainly dependent on perforin pathway.

Malignant transformation of ovarian mature cystic teratoma into squamous cell carcinoma: a Taiwanese Gynecologic Oncology Group (TGOG) study / 부인종양

OBJECTIVE: The malignant transformation (MT) of ovarian mature cystic teratoma (MCT) to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiple medical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, and prognostic factors of this disease and reviewed related literature. METHODS: Pathological reports of 16,001 patients with primary ovarian cancer who were treated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients with MT of MCT to SCC were identified. RESULTS: Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age of patients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40 cm). We analyzed the patients in our study and those in the literature and determined that early identification and complete surgical resection of the tumor are essential for long-term survival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be used to treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTs are suitable indicators predicting the risk of MT of MCT to SCC. CONCLUSION: Similar to general epithelial ovarian cancers, the early detection of MT of MCT to SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should be evaluated to exclude potential MT to SCC.

Effects of rapamycin on proliferation and epithelial-mesenchymal transition of lung cancer A549 cells-derived spheres / 肿瘤

Objective: To study the effect of rapamycin on lung cancer stem cellderived spheres, and explore its related mechanism. Methods: The lung cancer A549 cell-derived spheres were obtained by culture with tumor stem cell conditioned medium. The proportion of CD133+ CD44+ cells in A549 cellderived spheres was detected by flow cytometry. Then the spheres were treated with three concentrations (20, 50 and 100 ng/mL) of rapamycin, respectively. After that, the inhibition effect of rapamycin on the expression of phospho-mammalian target of rapamycin (p-mTOR) was detected by Western blotting, and the optimal inhibition concentration of rapamycin was selected for further research. After A549 cell-derived spheres were treated with 100 ng/mL rapamycin for 24 h, the expression levels of E-cadherin, vimentin, phospho-signal transducer and activator of transcription 3 (p-STAT3), phospho-p70 ribosomal protein S6 kinase (p-p70S6K) and phospho-4E-binding protein 1 (p-4EBP1) were detected by Western blotting, while the mRNA levels of SRY (sex-determining region Y)-box 2 (Sox2), Oct4, CD133 and Nanog were examined by real-time fluorescent quantitative-PCR. The proliferative activities of A549 cells after rapamycin treatment for 1-7 days were detected by MTT method, and the size of the spheres after rapamycin treatment for 14 d was observed by contrast microscopy. Results: The A549 cell-derived spheres were successfully obtained by suspension culture, and proportion of CD1 33+ CD44+ cells in the spheres was (75.0±8.7)%. All three concentrations of rapamycin (20, 50 and 100 ng/mL) inhibited the expression of p-mTOR protein, and 100 ng/mL was the optimal inhibition concentration (P < 0.05). After treatment with 100 ng/mL rapamycin for 24 h, the expression level of E-cadherin protein in A549 cell-derived spheres was obviously increased (P < 0.05), but the expression levels of vimentin, p-STAT3, p-p70S6K and p-4EBP1 proteins were decreased (P < 0.05), and the levels of Sox2, Oct4, CD1 33 and Nanog mRNAs were also decreased (P < 0.05). Rapamycin could significantly inhibit the proliferation of A549 cells during 3-7 days, and the size of the spheres on the 14th day was smaller than that of the spheres without rapamycin treatment. Conclusion: Rapamycin can inhibit the proliferation of A549 cell-derived spheres, the sphereformation ability and epithelial-mesenchymal transition. The mTOR-STAT3 and p-70S6K signaling pathways may play important roles in these processes.

NDRG1 suppresses TGF-β-induced epithelial-mesenchymal transition in lung cancer A549 cells / 中国医师杂志

Objective To explore the effect and molecular mechanism of N-myc downstream regulated gene 1 (NDRG1) on transforming growth factor-beta (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung cancer cells.Methods Lung cancer A549 cells were transfected with NDRG1 overexpressed vector,and then treated with 5 μg/L TGF-β1.The abilities of invasion were detected by Transwell assay.The expressions of NDRG1 mRNA and protein were analyzed by teal-time reverse transcription polymerase chain reaction (RT-PCR) were examined with Western blot.The expressions of EMT-associated markers E-cadherin and Vimentin,and EMT-associated signaling molecules Snail,AKT and Smad were detected with Western blot.Results We found that TGF-β1 treatment could induce morphological alteration of A549 cells from epithelial morphology to mesenchymal morphology.TGF-β1 significantly increased the migration of A549 cells,and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin.More importantly,overexpression of NDRG1 significandy reversed the effects of TGF-β1 on A549 cells.Moreover,NDRG1 significandy decreased the levels of phospho-AKT,and suppressed the expression of EMT-related transcription factor Snail.Conclusions NDRG1 could reverse the effects of TGF-β1 on EMT in A549 cells,by which mechanism is related to reduction of the expressions of phospho-AKT and Snail.

Effect of over-expressed macrophage migration Inhibitory factor on epithelial-mesenchymal transition in human cervical carcinoma SiHa cells / 中国医师杂志

Objective To investigate the effect of over-expressed macrophage migration inhibitory factor (MIF) on epithelial-mesenchymal transition (EMT) in human cervical carcinoma SiHa cells.Methods Recombinant eukaryotic expression plasmid liposome enhanced transfection of green fluorescent protein gene (pEGFP-N1)-MIF was constructed and then transfected into human cervical cancer SiHa cells.Experimental cells were classified into three groups (SiHa-pEGFP-N1-MIF,SiHa-pEGFP-N1,and SiHa).Western blot was used to detect the expression of MIF protein,and the expressions of EMT-related markers such as E-cadherin and vimentin in SiHa cells were determined before and after transfection.Results The eukaryotic expression vector pEGFP-N1-MIF significantly increased the expression of MIF protein in SiHa cells (P ＜ 0.05),and after overexpression of MIF gene in SiHa cells,the expression of E-cadherin protein in SiHa-pEGFP-N1-MIF group was significantly lower than that in control groups (P ＜0.05),while the expression of vimentin in SiHa-pEGFP-N1-MIF group was significantly higher than that in control groups (P ＜ 0.05).Conclusions Overexpression of MIF in cervical cancer SiHa cells can promote the EMT occurrence.

STAT3 of breast cancer cells regulates matrix metallproteinases and tissue inhibitor of metalloproteinase-1 expression and its relationship with epithelial-mesenchymal transition / 中华老年医学杂志

Objective To investigate the relationship of STAT3 with expressions of MMP-2,MMP-9 and TIMP-1 and with epithelial-mesenchymal transition (EMT) in breast cancer cells,and to explore the clinical significances.Methods The mRNA of STAT3 and the protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 of breast cancer cells in 84 patients with breast cancer were determined by real-time RT-PCR technique and immunohistochemical method in paraffin-embedded specimensm respectively.Normal breast tissues adjacent to breast cancer were taken as controls.Results mRNA expression of STAT3 was significantly higher in breast cancer tissues than in controls (t=4.513,P＜ 0.001).Protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 were higher in breast cancer tissues than in controls (all P＜ 0.05).There were positive correlations between pSTAT3 expression and the expressions of MMP-2,MMP-9 and TIMP-1 in breast cancer tissues (all P＜0.05).The higher levels of pSTAT3 and MMP-2 were associated with poorer differentiation and more lymph node metastasis of breast cancer (both P＜0.05).The positive expression of MMP-9 was correlated with lymph node metastasis (P＜0.05),but not with histological grading (P＞0.05).The positive expression of TIMP-1 had no associations with histological grading and lymph node metastasis (both P＞0.05).There were no significant differences in the protein expressions level of pSTAT3,MMP-2,MMP-9 and TIMP-1 between different ages and different breast tumor sizes (all P＞0.05).Conclusions The increased expression of STAT3 in breast cancer cells is closely correlated with the increased expressions of MMP-2,MMP-9 and STAT3 inhibitor TIMP-1.The activation of STAT3 gene can mediate EMT by inducing the protein expressions of MMP-2,MMP-9,which promotes the invasion and metastasis of breast cancer.

Molecular mechanisms of epithelial-mesenchymal transition in hepatocellular carcinoma / 国际肿瘤学杂志

The poor prognosis of hepatocellular carcinoma (HCC) is strongly associated with invasion and metastasis.Recently,the epithelial-mesenchymal transition (EMT) has been confirmed to be the cytological foundation of invasion and metastasis.Yet,the molecular mechanism of inducing and maintaining EMT has not been expounded completely.However,it has been demonstrated that transforming growth factor-β (TGF-β),phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT),nuclear factor-κB (NF-κB),Wnt/β-catenin signaling pathways play pivotal roles in the initiation and development of EMT.These signaling pathways can affect the prognosis of HCC by regulating EMT.From a drug development perspective,these signal pathways are potential and attractive targets for HCC treatment.

Y-box-binding protein 1 and epithelial-mesenchymal transition / 国际肿瘤学杂志

In the process of epithelial-mesenchymal transition (EMT),cell-cell adherence is disrupted,apico-basal polarity is lost,the ability of anti-apoptosis,migration and invasion is acquired.Y-box-binding protein 1 (YB-1) is a member of the cold-shock protein superfamily,containing a structurally and functionally conserved cold shock domain.Studies indicate that YB-1 can promote the occurrence and development of tumors by regulating EMT.In the process of EMT mediated by YB-1,various transcription factors and signal pathways play important roles.

EMT mediated cancer stemness and tumor / 国际肿瘤学杂志

Epithelial-mesenchymal transition (EMT) is a major mechanism in tumor metastasis.As the key regulatory factor,Twist gene plays an important role in EMT,and it can be induced by radiotherapy,chemotherapy and a variety of cytokines.Researches show that tumor cells can get stem cell-like properties via EMT,which can lead to chemo-radiotherapy resistance,tumor angiogenesis and distant metastasis.EMT has a great influence on the prognosis of tumor,and it is expected to become an important target for tumor treatment.

Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor / 결핵및호흡기질환

BACKGROUND: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. METHODS: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. RESULTS: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. CONCLUSION: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

Preditores moleculares de evolução da mola hidatiforme no tecido trofoblástico / Molecular prognostic predictors in trophoblastic tissue of hydatidiform mole

A mola hidatiforme (MH) é a forma mais comum de doença trofoblástica gestacional e representa uma condição benigna que em alguns casos pode sofrer malignização. Todas as pacientes diagnosticadas com doenças molares são acompanhadas por pelo menos seis meses para detecção precoce da neoplasia trofoblástica gestacional. No momento, existem poucas ferramentas para avaliação prognóstica da mola hidatiforme. Foi descrita a expressão diferencial de diversos fatores em tecido molar em comparação ao trofoblasto não neoplásico. Essas moléculas podem estar relacionadas com o comportamento agressivo da MH e consequentemente poderiam servir para melhor entendimento do processo de malignização e como preditoras da evolução da doença trofoblástica gestacional.

The hydatidiform mole (HM) is the most common form of gestational trophoblastic disease and a benign condition that in some cases may undergo malignant transformation. All patients diagnosed with molar diseases are monitored for at least six months for early detection of gestational trophoblastic neoplasia. Currently, there are few prognostic tools for the prediction of hydatidiform mole evolution. Differential expression on molar tissue of different molecular factors have been described when compared to non-neoplastic trophoblast. These markers may be associated with aggressive behavior of HM and therefore could serve as predictors of the development of gestational trophoblastic disease and to better understand molar malignant transformation. This review article will summarize and evaluate prognostic molecular markers of HM.