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Prefoldin (PFDN), a hexameric chaperone complex, is crucial for the correct folding of nascent proteins. PFDN5, a subunit of PFDN, also known as MM-1, plays an essential role in regulating cell migration and senescence. Emerging evidences suggest that PFDN-5 deletion or mutation significantly contributes to the initiation and progression of multiple cancers and the prognosis of patients. In this paper, recent researches on the biological underpinnings of PFDN-5 and its anti-cancer prospect are reviewed, aiming to provide a novel potential therapeutic target for the treatment of malignancies.

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Objective:To explore whether baseline PET metabolic parameters combined with B-cell lymphoma-2 (Bcl-2)/cellular-myelocytomatosis viral oncogene (c-Myc) dual expression (DE) can improve the prognostic stratification of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).Methods:From March 2011 to November 2019, 74 patients (33 males, 41 females; age: 20-87 years) pathologically diagnosed with PGI-DLBCL prior to treatment in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and the First Affiliated Hospital of Nanjing Medical University were retrospectively included. Baseline PET/CT scans were calculated automatically using the boundaries of voxels presenting a SUV max≥2.5, and metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were determined. Expressions of Bcl-2 and c-Myc were detected at protein levels by immunohistochemistry (IHC). A predicting model comprised of MTV and DE was constructed and patients were divided into 3 groups, including low-risk group (low MTV and non-DE), mediate-risk group (high MTV or DE) and high-risk group (high MTV and DE). The distributions of progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results:Of 74 patients, 20 relapsed or progressed, 13 died, and 29.7%(22/74) patients were DE positive. Multivariate analysis revealed that MTV (hazard ratio ( HR)=9.110, 95% CI: 1.429-18.615, P=0.012) and DE ( HR=9.837, 95% CI: 1.690-57.260, P=0.011) were independent predictors of PFS, while MTV ( HR=12.470, 95% CI: 3.356-46.336, P<0.001) was the only independent predictor of OS. In the predicting model for PFS, low-risk group ( n=42) and mediate-risk group ( n=20) exhibited significant difference ( χ2=7.84, P=0.005), and mediate-risk group and high-risk group ( n=12) also exhibited significant difference ( χ2=18.72, P<0.001). Conclusions:MTV and DE can independently predict PFS of patients with PGI-DLBCL, and MTV can independently predict OS. The predicting model for PFS combining MTV with DE may further improve the ability of clinicians to stratify patients in terms of differential prognoses.

Asunto(s)

Biomarcadores de Tumor/análisis , Linfoma de Células B Grandes Difuso/química , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-myc/análisis , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Estudios Retrospectivos , Factores de Tiempo , Translocación Genética

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ABSTRACT Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

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RESUMO Racional: CD133 e AXL são descritos na literatura como marcadores de células-tronco tumorais, e c-MYC cumpre papel chave como mecanismo de regulação celular no câncer colorretal (CCR). Objetivo: Avaliar o papel prognóstico dos biomarcadores CD133, AXL e c-MYC e sua associação com características clinicopatológicas de adenocarcinomas e adenomas colorretais. Métodos: Um total de 156 pacientes com adenocarcinomas de estádio UICC I-IV (n=122) e adenomas (n=34) colorretais foram avaliados. Microarranjos teciduais (TMA) dos tumores primários e adenomas foram realizados em busca de expressão de CD133, c-MYC e AXL, com posterior análise de relação significativa com características clinicopatológicas. Resultados: Adenocarcinomas pobremente diferenciados e progressão de doença foram fatores de risco independentes para má sobrevida global. A taxa mediana de sobrevida global foi de 30 meses. Expressão positiva de CD133 (35,9% dos casos), particularmente em cânceres de cólon direito (44,8% dos casos CD133+), correlacionou-se negativamente com óbito na análise univariada, sem significância estatística na análise multivariada. c-MYC (15,4% dos casos) teve predomínio de expressão em pacientes com estádio avançado com metástases distantes (não-pulmonares/não-hepáticas). Expressão de AXL foi pouco encontrada, com predomínio em adenomas, com menor penetrância em displasia de alto grau. Conclusão: Expressão de CD133 não se associou com sobrevida global inferior em CCR. Enquanto AXL demonstrou resultados inconclusivos, expressão de c-MYC em tumores primários se associou-se à metástases à distância.

Asunto(s)

Humanos , Neoplasias Colorrectales , Biomarcadores de Tumor , Péptidos , Pronóstico , Células Madre Neoplásicas , Glicoproteínas , Antígenos CD , Antígeno AC133

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Thyroid cancer cells have a high amino acid demand for proliferation, invasion, and metastasis. Amino acids are taken up by thyroid cancer cells, both thyroid follicular cell and thyroid parafollicular cells (commonly called "C-cells"), via amino acid transporters. Amino acid transporters up-regulate in many cancers, and their expression level associate with clinical aggressiveness and prognosis. This is the review to discuss the therapeutic potential of amino acid transporters and as molecular targets in thyroid cancer.

Asunto(s)

Sistemas de Transporte de Aminoácidos/antagonistas & inhibidores , Antineoplásicos/uso terapéutico , Terapia Molecular Dirigida , Neoplasias de la Tiroides/tratamiento farmacológico , Animales , Humanos , Proto-Oncogenes Mas , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología

RESUMEN

Objective: To investigate the relationship between the protein expression of C-MYC, bcl-2 and bcl-6 and the clinicopathological characteristics in patients with de novo CD5-positive diffuse large B cell lymphoma (CD5(+)DLBCL). Methods: Fifty seven cases of de novo CD5(+)DLBCL were collected at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2013 to September 2018. The hematoxylin-eosin stained slides were reviewed, and immunohistochemical (IHC) staining and FISH were used to analyze the relationship between C-MYC, bcl-2, bcl-6 expression and the clinicopathologic characteristics of patients. Results: Among these 57 cases, 27 were male and 30 were female. The age of onset was 35-99 years old. The IHC expression rates of C-MYC, bcl-2 and bcl-6 were 50.9% (29/57), 84.2% (48/57), and 75.4% (43/57) respectively; and co-expression rate of C-MYC and bcl-2 proteins was 40.4 (23/57). There was no significant correlation between protein expression and patients' genders, clinical stage, the level of serum LDH,ß2 microglobulin, IPI,B symptoms, bone marrow involvement and central nervous system recurrence (P>0.05). Univariate analysis showed that the median OS of C-MYC negative patients was significantly longer than C-MYC positive patients (P<0.05); and the median OS of patients without double expression was significantly longer than that of patients with positive expression (P<0.05), and bcl-6 positive patients had longer median OS than bcl-6 negative patients (P<0.05). There was no significant correlation between prognosis and bcl-2 protein expression (P>0.05) . Cox multivariate analysis showed C-MYC protein expression was an independent predictor of OS in de novo CD5(+)DLBCL (P<0.05). Conclusions: Bcl-2 protein expression has no effect on the prognosis in de novo CD5(+)DLBCL whereas bcl-6 expression is correlated with good prognosis. C-MYC protein expression could be used as an independent and effective index to predict the prognosis of patients with de novo CD5(+)DLBCL.However, the relationship between protein expression and gene rearrangement of C-MYC, bcl-2 and bcl-6 needs to be further explored.

Asunto(s)

Linfoma de Células B Grandes Difuso , Adulto , Anciano , Anciano de 80 o más Años , China , Femenino , Genes myc , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas c-myc

RESUMEN

Objective: To investigate whether C-myc is involved in the modulation of protein kinase B (PKB, also known as AKT) on the expression of phosphate and tension homology deleted on chromsome ten (PTEN) in hepatoma HepG2 cells. Methods: HepG2 cells were treated with different concentrations of AKT inhibitor Capivasertib (5, 10 and 20 nmol/L). The expression levels of AKT, phosphorylated (p)-AKT, Bad, p-Bad, C-myc and p-C-myc proteins were detected by Western blotting. The transcription levels of C-myc downstream genes eukaryotic initiation factor-4E (eIF-4E), branched‐chain amino acid aminotransferase 1 (BCAT1) and WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) were detected by real-time fluorescent quantitative PCR. The expressions of eIF-4E, BCAT1 and WWP1 genes were silenced by siRNA, then the transcription and expression of PTEN were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The effects of Capivasertib treatment or WWP1 gene silence on the expression and localization of PTEN protein in HepG2 cells were detected by cell immunofluorescence technique. Results: In HepG2 cells treated with different concentrations of Capivasertib for 8 h, the expression levels of p-AKT, p-C-myc and p-Bad were significantly downregulated as compared with the control group (all P < 0.01), and the expression levels of eIF-4E, BCAT1 and WWP1 mRNAs were also downregulated (all P < 0.01). Silencing eIF-4E, BCAT1 and WWP1 gene expressions had no significant effect on the transcription of PTEN (all P 0.01) but the silence of WWP1 gene could significantly enhance the expression of PTEN protein (P < 0.01). Both Capivasertib treatment and WWP1 gene silence could increase the expression level of PTEN and induce its aggregation on the cell membrane. Conclusion: AKT is able to affect the transcription of WWP 1 gene by C-myc pathwaty, and ultimately participates in the modulation of PTEN expression in HepG2 cells.

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ABSTRACT Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

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RESUMO Racional: CD133 e AXL são descritos na literatura como marcadores de células-tronco tumorais, e c-MYC cumpre papel chave como mecanismo de regulação celular no câncer colorretal (CCR). Objetivo: Avaliar o papel prognóstico dos biomarcadores CD133, AXL e c-MYC e sua associação com características clinicopatológicas de adenocarcinomas e adenomas colorretais. Métodos: Um total de 156 pacientes com adenocarcinomas de estádio UICC I-IV (n=122) e adenomas (n=34) colorretais foram avaliados. Microarranjos teciduais (TMA) dos tumores primários e adenomas foram realizados em busca de expressão de CD133, c-MYC e AXL, com posterior análise de relação significativa com características clinicopatológicas. Resultados: Adenocarcinomas pobremente diferenciados e progressão de doença foram fatores de risco independentes para má sobrevida global. A taxa mediana de sobrevida global foi de 30 meses. Expressão positiva de CD133 (35,9% dos casos), particularmente em cânceres de cólon direito (44,8% dos casos CD133+), correlacionou-se negativamente com óbito na análise univariada, sem significância estatística na análise multivariada. c-MYC (15,4% dos casos) teve predomínio de expressão em pacientes com estádio avançado com metástases distantes (não-pulmonares/não-hepáticas). Expressão de AXL foi pouco encontrada, com predomínio em adenomas, com menor penetrância em displasia de alto grau. Conclusão: Expressão de CD133 não se associou com sobrevida global inferior em CCR. Enquanto AXL demonstrou resultados inconclusivos, expressão de c-MYC em tumores primários se associou-se à metástases à distância.

Asunto(s)

Humanos , Masculino , Femenino , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Biomarcadores de Tumor/análisis , Antígeno AC133/análisis , Pronóstico , Células Madre Neoplásicas/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Metástasis de la Neoplasia

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Ovarian involvement as the initial manifestation of a Burkitt lymphoma without detectable extra-ovarian disease is rare, which is why it is usually not included in the differential diagnosis when an ovarian tumor is detected. A missed diagnosis will lead to the wrong treatment being given, and this can compromise any future reproductive wishes of the patient. In this article, a patient presents a Burkitt lymphoma with ovarian involvement as an initial manifestation and an unusually rapid systemic progression of the disease. Prompted by this case and its unusual course, we reviewed the existing literature.

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La afectación ovárica como debut de un linfoma de Burkitt sin enfermedad extraovárica detectable es anecdótica, por lo que habitualmente no se incluye como hipótesis diagnóstica tras el hallazgo de una tumoración ovárica. Su desconocimiento lleva a realizar un tratamiento equivocado que puede llegar a comprometer el deseo reproductivo de la paciente. Presentamos el caso de una paciente que presenta un linfoma de Burkitt con afectación ovárica como manifestación inicial. La paciente desarrolló una progresión sistemática excepcionalmente rápida. A propósito de este caso y de su inusual evolución, revisamos la literatura existente.

Asunto(s)

Linfoma de Burkitt/diagnóstico , Neoplasias Ováricas/diagnóstico , Adolescente , Linfoma de Burkitt/patología , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Ováricas/patología , Proto-Oncogenes Mas

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Abstract Background: Diffuse large B-cell lymphoma (DLBCL) makes up from 25% to 40% of all non-Hodgkin lymphomas (NHL) and is the most common histological subtype worldwide. In Ecuador, DLBCL makes up 49% of all NHL cases, but there have been no studies on the immunophenotypic classificationof DLBCL in germinal center (GC) and non-germinal center (NGC)subtypes.This study was conducted to ascertain the immunophenotypic profile of DLBCL in an Ecuadorian hospital. Methods: A total of 38 DLBCL cases from 2006 to 2015 were compiled from the Pathology Service at Metropolitan Hospital (HM) in Quito, Ecuador. Eleven of these cases failed to meet the inclusion criteria; thus, the final sample consisted of 27 cases. Manual tissue microarrays were constructed, and three immunohistochemical markers (CD10, BCL6, and MUM1) were applied according to the Hans algorithm; in addition, the expression of the c-myc protein expression was also investigated. Results: The results showed that 77.8% of cases were of the GC subtype, 11.1% were NGC, and 11.1% were unclassifiable according to the Hans algorithm. Conclusions: The most frequent DLBCL subtype was GC, with 21 cases; and 40.7% of these cases overexpressed c-myc.

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Resumen Antecedentes: El linfoma difuso de células grandes B (LDCGB) constituye el 25 al 40% del total de los linfomas no Hodgkin (LNH) y es el subtipo histológico más frecuente en el mundo. En Ecuador el LDCGB corresponde al 49% del total de los casos de LNH, sin embargo no hay estudios de clasificación inmunofenotípica del LDCGB en centro germinal (CG) y no centro germinal (NCG). Este estudio se realizó para conocer el perfil inmunofenotípico del LDCGB en un hospital de Ecuador. Métodos: Se recopiló del Servicio de Patología del Hospital Metropolitano de Quito, Ecuador, un total de 38 casos de LDCGB desde el 2006 al 2015, de los cuales 11 no cumplieron con los criterios de inclusión. La muestra final fue de 27 casos. Se realizaron microarreglos tisulares manuales para la aplicación de tres marcadores de inmunohistoquímica según el algoritmo de Hans (CD10, BCL6 y MUM1) y luego se correlacionó con la sobreexpresión de la proteína c-MYC. Resultados: El 77,8% de casos fue tipo CG, 11,1% fue NCG y 11,1% fueron inclasificables según Hans. Conclusiones: El subtipo de LDCGB más frecuente fue CG con 21 casos y de estos 40,7% sobreexpresaron c-MYC.

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Humanos , Linfoma de Células B , Ecuador , Proteína C , Hospitales

RESUMEN

PURPOSE: Recent studies have shown that long non-coding RNA (lncRNA) play an important role in cancer metabolism and development. The lncRNA small nucleolar RNA host gene 7 (SNHG7) was reported to be upregulated in colorectal cancer and contribute to its progression. In the current study, we investigated the role of lncRNA-SNHG7 in breast cancer and explored the underlying mechanism. METHODS: We monitored the expression of lncRNA-SNHG7 in breast cancer tissues and breast cancer cell lines. We evaluated the effects of lncRNA-SNHG7 on cell proliferation and glycolysis in breast cancer cells by knocking down or overexpressing lncRNA-SNHG7. We searched for the potential microRNA (miRNA) target of lncRNA-SNHG7 and evaluated the effects of the target miRNA on glycolysis. We evaluated the potential regulation of lncRNA-SNHG7 by c-Myc. RESULTS: LncRNA-SNHG7 was up-regulated in both breast cancer tissues and breast cancer cell lines. Knocking down lncRNA-SNHG7 inhibited breast cancer cell proliferation while overexpressing lncRNA-SNHG7 enhanced cell proliferation. Knocking down lncRNA-SNHG7 resulted in decreased expression of lactate dehydrogenase A (LDHA) and decreased glycolysis. LncRNA-SNHG7 targeted miR-34a-5p to regulate LDHA expression and glycolysis. c-Myc bound to promoter of lncRNA-SNHG7 and positively regulated lncRNA-SNHG7 expression. CONCLUSION: We demonstrated that c-Myc regulated glycolysis through the lncRNA-SNHG7/miR-34a-5p/LDHA axis in breast cancer cells.

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Asunto(s)

Neoplasias de la Mama , Mama , Línea Celular , Proliferación Celular , Neoplasias Colorrectales , Glucólisis , L-Lactato Deshidrogenasa , Metabolismo , MicroARNs , Proteínas Proto-Oncogénicas c-myc , ARN Largo no Codificante , ARN Nucleolar Pequeño

RESUMEN

La afectación ovárica como debut de un linfoma de Burkitt sin enfermedad extraovárica detectable es anecdótica, por lo que habitualmente no se incluye como hipótesis diagnóstica tras el hallazgo de una tumoración ovárica. Su desconocimiento lleva a realizar un tratamiento equivocado que puede llegar a comprometer el deseo reproductivo de la paciente. Presentamos el caso de una paciente que presenta un linfoma de Burkitt con afectación ovárica como manifestación inicial. La paciente desarrolló una progresión sistemática excepcionalmente rápida. A propósito de este caso y de su inusual evolución, revisamos la literatura existente.

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Ovarian involvement as the initial manifestation of a Burkitt lymphoma without detectable extra-ovarian disease is rare, which is why it is usually not included in the differential diagnosis when an ovarian tumor is detected. A missed diagnosis will lead to the wrong treatment being given, and this can compromise any future reproductive wishes of the patient. In this article, a patient presents a Burkitt lymphoma with ovarian involvement as an initial manifestation and an unusually rapid systemic progression of the disease. Prompted by this case and its unusual course, we reviewed the existing literature.

Asunto(s)

Humanos , Femenino , Adolescente , Neoplasias Ováricas/diagnóstico , Linfoma de Burkitt/diagnóstico , Neoplasias Ováricas/patología , Linfoma de Burkitt/patología , Progresión de la Enfermedad , Diagnóstico Diferencial

RESUMEN

Objective: To study the correlation between expression of oncogene C-MYC protein and gene abnormality in diffuse large B-cell lymphoma (DLBCL). Methods: The expression of C-MYC protein and gene abnormality were detected by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively, in 42 cases of paraffin-embedded DLBCL. All cases were collected at Department of Pathology, Weifang People's Hospital during January 2015 to October 2016. Results: The positive rate of C-MYC protein expression was 47.6% (20/42) and the rate of abnormal C-MYC gene by FISH was 26.2%(11/42), including translocation (23.8%, 10/42) and gene amplification (2.4%, 1/42). There was a close relationship between the protein expression and gene translocation (χ(2)=11.813; P=0.001) and gene translocation occurred primarily in GCB (χ(2)=4.029; P=0.045). Conclusion: The high expression (≥40%) of C-MYC protein is associated with its gene translocation, suggesting that C-MYC protein detection can be used as a surrogate marker for C-MYC gene translocation in DLBCL.

Asunto(s)

Genes myc , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Amplificación de Genes , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Proto-Oncogenes Mas , Translocación Genética

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Objective: To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis. Methods: 100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein. The tumors were classified into two subtypes according to Hans classification.The expression of PRDM1 and C-MYC gene in tumor group and control group was detected by reverse transcription PCR (RT-PCR) and the relationship between PRDM1 and C-MYC gene was analyzed.OCI-LY1 (GCB subtype) and OCI-LY3 (non-GCB subtype) cell lines were transfected with small interfering RNA by cationic liposome reagent transfection, and the expression of C-MYC in the transfected cell lines was detected by RT-PCR and Western blot. The Kaplan-Meier method was used to analyze the prognostic significance of PRDM1/Blimp1 and C-MYC at protein and mRNA levels. Results: There were 27 cases of GCB subtype and 73 cases of non-GCB subtype according to Hans classification. The positive expression of Blimp1 in DLBCL group and proliferative lymph nodes in control group was seen in 26(26.0%) and 20 cases(100%), respectively. There were 58 cases with high expression of PRDM1 at mRNA level, including 22 cases of GCB subtype and 36 cases non-GCB subtype, and the difference was statistically significant (P=0.004). There were differences in PRDM1 gene expression between the two immunological subtypes, serum lactate dehydrogenase (serum LDH) level, presence of B symptoms, tumor primary sites and other clinical pathological parameters, while C-MYC expression was different in gender, IPI score, and serum LDH levels. Upon PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene expression were up-regulated in the transfection group, compared with the blank control group and negative control group by reverse transcription PCR and Western blot analyses. Moreover, PRDM1 expression was significantly associated with C-MYC(χ(2)=7.648, P=0.006) at mRNA level. Conclusion: The up-regulation of C-MYC gene expression induced by PRDM1 inactivation in DLBCL may play an important role for the development of DLBCL.PRDM1 protein and mRNA are associated with immunophenotyping and PRDM1 mRNA is a marker of poor prognosis.

Asunto(s)

Silenciador del Gen , Genes myc , Linfoma de Células B Grandes Difuso/genética , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Antígenos CD20/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunofenotipificación , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/patología , Factor de Transcripción PAX5/metabolismo , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Pronóstico , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Mensajero/metabolismo , Proteínas Represoras/metabolismo , Regulación hacia Arriba

RESUMEN

Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis. Conclusions: Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/mortalidad , Reordenamiento Génico , Linfoma de Células B Grandes Difuso/mortalidad , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/terapia , Variaciones en el Número de Copia de ADN , Femenino , Dosificación de Gen , Genes bcl-2 , Genes myc , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Hibridación Fluorescente in Situ , Factores Reguladores del Interferón/metabolismo , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/terapia , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Neprilisina/metabolismo , Pronóstico , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Análisis de Supervivencia , Tasa de Supervivencia , Translocación Genética

RESUMEN

Objective@#To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis.@*Methods@#100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein. The tumors were classified into two subtypes according to Hans classification.The expression of PRDM1 and C-MYC gene in tumor group and control group was detected by reverse transcription PCR (RT-PCR) and the relationship between PRDM1 and C-MYC gene was analyzed.OCI-LY1 (GCB subtype) and OCI-LY3 (non-GCB subtype) cell lines were transfected with small interfering RNA by cationic liposome reagent transfection, and the expression of C-MYC in the transfected cell lines was detected by RT-PCR and Western blot. The Kaplan-Meier method was used to analyze the prognostic significance of PRDM1/Blimp1 and C-MYC at protein and mRNA levels.@*Results@#There were 27 cases of GCB subtype and 73 cases of non-GCB subtype according to Hans classification. The positive expression of Blimp1 in DLBCL group and proliferative lymph nodes in control group was seen in 26(26.0%) and 20 cases(100%), respectively. There were 58 cases with high expression of PRDM1 at mRNA level, including 22 cases of GCB subtype and 36 cases non-GCB subtype, and the difference was statistically significant (P=0.004). There were differences in PRDM1 gene expression between the two immunological subtypes, serum lactate dehydrogenase (serum LDH) level, presence of B symptoms, tumor primary sites and other clinical pathological parameters, while C-MYC expression was different in gender, IPI score, and serum LDH levels. Upon PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene expression were up-regulated in the transfection group, compared with the blank control group and negative control group by reverse transcription PCR and Western blot analyses. Moreover, PRDM1 expression was significantly associated with C-MYC(χ2=7.648, P=0.006) at mRNA level.@*Conclusion@#The up-regulation of C-MYC gene expression induced by PRDM1 inactivation in DLBCL may play an important role for the development of DLBCL.PRDM1 protein and mRNA are associated with immunophenotyping and PRDM1 mRNA is a marker of poor prognosis.

RESUMEN

Objective@#To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL).@*Methods@#Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis.@*Results@#The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis.@*Conclusions@#Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.

RESUMEN

Objective To observe the effect of Rhy-SLN on the proliferation of rat vascular smooth muscle cells (VSMC) induced by TGF-β1, and explore the mechanism. Methods The primary culture of rat thoracic aortic vascular smooth muscle cells was studied by tissue block culture method. The cells were divided into the control group, TGF-β1 group, TGF-β1+ the high, medium and low dosage groups of Rhy-SLN. In addition to the control group, the cells of the other groups were involved in the intervention of TGF-β1 of 20 g/L, and the high, medium and low dosage groups of Rhy-SLN cells were involved in the intervention of 25, 50, 100 mg/L of the hook teng solid lipid nanoparticles. After 24 hours of culture, MTT assay was used to detect cell proliferation inhibition rate in each group, and the cell cycle was detected by flow cytometry. The expression of c-myc and c-Fos protein in each group was detected by Western blot method. Results Compared with the TGF-β1 group, the absorbance value (0.457 ± 0.046 vs. 0.975 ± 0.049) of TGF-β1+ rhy-sln high dose group significantly decreased (P<0.01); the number of S phase cells (15.87% ± 2.47%, 15.23% ± 1.69%, 17.02% ± 2.87% vs.38.58% ± 2.68%)of TGF-β1+rhy-sln in each dose group significantly decreased(P<0.01);The c-myc(48.65 ±3.65,50.69 ± 4.16,55.29 ± 3.67 vs.68.21 ± 3.25)and c-Fos(38.78 ± 4.25,43.56 ± 3.69,46.58 ± 3.57 vs.66.54 ± 4.09) of the TGF-β1+ rhy-sln each dose group significantly decreased (P<0.01). Conclusions The Rhy-SLN can inhibit the proliferation of VSMC in rats induced by TGF-β1.Its mechanism is related to the conversion of G0/G1 phase to the S phase and the expression of the reduction of c-myc and c-fos protein.

RESUMEN

Objective@#To study the correlation between expression of oncogene C-MYC protein and gene abnormality in diffuse large B-cell lymphoma (DLBCL).@*Methods@#The expression of C-MYC protein and gene abnormality were detected by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively, in 42 cases of paraffin-embedded DLBCL. All cases were collected at Department of Pathology, Weifang People′s Hospital during January 2015 to October 2016.@*Results@#The positive rate of C-MYC protein expression was 47.6% (20/42) and the rate of abnormal C-MYC gene by FISH was 26.2%(11/42), including translocation (23.8%, 10/42) and gene amplification (2.4%, 1/42). There was a close relationship between the protein expression and gene translocation (χ2=11.813; P=0.001) and gene translocation occurred primarily in GCB (χ2=4.029; P=0.045).@*Conclusion@#The high expression (≥40%) of C-MYC protein is associated with its gene translocation, suggesting that C-MYC protein detection can be used as a surrogate marker for C-MYC gene translocation in DLBCL.