[Amplifiation of the c-MYC gene in acinar prostate adenocarcinoma. Morphogenic comparisons]. / Amplifikatsiya gena c-MYC pri atsinarnoi adenokartsinome prostaty. Morfogeneticheskie sopostavleniya.

OBJECTIVE: The purpose of this work was to evaluate c-MYC gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the disease, taking into account the morphological characteristics of the tumor. MATERIAL AND METHODS: The number of cases in the study was 82, including the control group - 12 cases. Morphological assessment included: determination of the total Gleason score, grading group, assessment of lymphovascular/perineural invasion, and architectural characteristics of the tumor. Gene amplification was assessed by FISH using the c-MYC (8q24)/SE8 probe. RESULTS: In all cases of the study group, amplification of the c-MYC gene was detected in the tumor, with a significant difference from the control group (p<0.05). When assessing cases with 4-6 fold copies of the gene, significant differences were established between patients with stages II and III of the disease and stage IV (10.0 and 13.5 versus 30.0) (p<0.05). Cluster amplification of the c-MYC gene was detected with equal frequency in groups of patients with stages III and IV of the disease, while in stage II of the disease, the event almost did not occur (p<0.05). A significant increase in the level of c-MYC gene amplification was found in groups with advanced stages of the disease (p<0.02). Non-cluster amplification significantly distinguishes T4M0 and T4M1 stage patients from the rest with a significant increase in the score (p<0.05). In the metastatic stage of the disease, there was an increase c-MYC gene amplification compared to the non-metastatic stage (p<0.02). The copy number of the c-MYC gene was significantly higher in cases with perineural and lymphovascular invasion, as well as in cases of cribriform tumor organization (p<0.05). CONCLUSION: Amplification of the c-MYC gene in prostate tumor cells is associated with advanced stages of the disease (T4M0 and T4M1) with an increase in the copy number of the gene during the metastatic stage of the process. It was found that increased amplification of the c-MYC gene distinguishes groups of patients whose tumors exhibit perineural and lymphovascular invasion, as well as a cribriform pattern of tumor organization.

Impact of coconut kernel extract on carcinogen-induced skin cancer model: Oxidative stress, C-MYC proto-oncogene and tumor formation.

This study aimed at analysing the effects of coconut (Cocos nucifera L.) kernel extract (CKE) on oxidative stress, C-MYC proto-oncogene, and tumour formation in a skin cancer model. Tumorigenesis was induced by dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA). In vitro antioxidant activity of CKE was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), total phenolic and flavonoid content assays. CKE showed a higher antioxidant activity then ascorbic acid (*P < 0.05, ****P < 0.0001). HPLC and NMR study of the CKE revealed the presence of lauric acid (LA). Following the characterization of CKE, mice were randomly assigned to receive DMBA/TPA Induction and CKE treatment at different doses (50, 100, and 200 mg/kg) of body weight. LA 100 mg/kg of body weight used as standard. Significantly, the CKE200 and control groups' mice did not develop tumors; however, the CKE100 and CKE50 treated groups did develop tumors less frequently than the DMBA/TPA-treated mice. Histopathological analysis revealed that the epidermal layer in DMBA-induced mice was thicker and had squamous pearls along with a hyperplasia/dysplasia lesion, indicating skin squamous cell carcinoma (SCC), whereas the epidermal layers in CKE200-treated and control mice were normal. Additionally, the CKE treatment demonstrated a significant stimulatory effect on the activities of reactive oxygen species (ROS), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), as well as an inhibitory effect on lipid peroxidase (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001) and c-MYC protein expression (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). In conclusion, CKE prevents the growth of tumors on mouse skin by reducing oxidative stress and suppressing c-MYC overexpression brought on by DMBA/TPA induction. This makes it an effective dietary antioxidant with anti-tumor properties.

Proteomic characteristics and identification of PM2.5-induced differentially expressed proteins in hepatocytes and c-Myc silenced hepatocytes.

Proteomics and bioinformatics were applied to explore PM2.5-induced differentially expressed proteins (DEPs) in hepatocytes (L02 cells) and c-Myc-silenced hepatocytes. L02 cells and c-Myc-silenced hepatocytes were treated with PM2.5 for 24 h. Fifty-two DEPs were screened in L02 hepatocytes, of which 28 were upregulated and 24 were downregulated. Forty-one DEPs were screened in the c-Myc-silenced hepatocytes, of which 31 were upregulated and 10 were downregulated. GO analysis showed that DEPs in L02 cells were mainly concentrated in the cytosol and were involved in biological processes such as the response to metal ions. DEPs in c-Myc-silenced cells were mainly enriched in the extracellular space and were involved in lipoprotein metabolism. KEGG analysis showed that DEPs in L02 cells were mainly involved in arachidonic acid metabolism and mineral absorption. DEPs in c-Myc-silenced cells were mainly enriched in pathways involving nerve absorption, complement and coagulation cascades, and other pathways. Twenty key proteins, including Metallothionein-2A (MT2A), Metallothionein-1X (MT1X), zinc transporter ZIP10 (SLC39A10) and Serine protease 23 (PRSS23) were screened in two groups through analysis of protein-protein interactions. Based on the identification of the selected DEPs, PRSS23 and SLC39A10 might be the potential biomarker of PM2.5-induced carcinogenesis, which provide the scientific basis for further research into the carcinogenic mechanisms of PM2.5.

Association between the CEBPA and c-MYC genes expression levels and acute myeloid leukemia pathogenesis and development.

CEBPA and c-MYC genes belong to TF and play an essential role in hematologic malignancies development. Furthermore, these genes also co-regulate with RUNX1 and lead to bone marrow differentiation and may contribute to the leukemic transformation. Understanding the function and full characteristics of selected genes in the group of patients with AML can be helpful in assessing prognosis, and their usefulness as prognostic factors can be revealed. The aim of the study was to evaluate CEBPA and c-MYC mRNA expression level and to seek their association with demographical and clinical features of AML patients such as: age, gender, FAB classification, mortality or leukemia cell karyotype. Obtained results were also correlated with the expression level of the RUNX gene family. To assess of relative gene expression level the qPCR method was used. The expression levels of CEBPA and c-MYC gene varied among patients. Neither CEBPA nor c-MYC expression levels differed significantly between women and men (p=0.8325 and p=0.1698, respectively). No statistically significant correlation between age at the time of diagnosis and expression of CEBPA (p=0.4314) or c-MYC (p=0.9524) was stated. There were no significant associations between relative CEBPA (p=0.4247) or c-MYC (p=0.4655) expression level and FAB subtype and mortality among the enrolled patients (p=0.5858 and p=0.8437, respectively). However, it was observed that c-MYC and RUNX1 expression levels were significantly positively correlated (rS=0.328, p=0.0411). Overall, AML pathogenesis involves a complex interaction among CEBPA, c-MYC and RUNX family genes.

Anti-cancer activity of benzoxazinone derivatives via targeting c-Myc G-quadruplex structure.

AIMS: This study aimed to analyze the impact of four synthesized benzoxazinone derivatives as screening drugs on c-Myc-overexpressed cancer cells (H7402, HeLa, SK-RC-42, SGC7901, and A549) and to explore their interaction mechanisms in detail. MATERIALS AND METHODS: Using morphological analysis, real-time cytotoxicity analysis, wound healing assay, reverse transcription PCR, electrophoretic mobility shift assay, and circular dichroism spectroscopy techniques. KEY FINDINGS: Results revealed that these four compounds could inhibit proliferation of SK-RC-42, SGC7901, and A549 cells in five cancer cell lines to varying degrees and significantly hinder migration. More importantly, the RT-PCR assay showed that the compounds could surprisingly downregulate the expression of c-Myc mRNA in a dose-dependent manner in the five cancer cells, which may be one of the causes of cancer cell proliferation in vitro inhibition. Further EMSA assays demonstrated that at the molecular level of DNA, four compounds can induce the formation of G-quadruplexes (G4-DNAs) in the c-Myc gene promoter. In addition, the CD result of compound 1 clearly indicates that it specifically induces a c-Myc GC-rich 36mer double-stranded DNA in the c-Myc promoter to form a G-quadruplex hybrid configuration. In conclusion, the compounds studied could dose-dependently inhibit the growth and migration of the cancer cells being investigated. This is positively associated with the reduction of overexpression of the c-Myc gene, which may be significantly regulated by the association of compounds with the G-quadruplexes produced in the c-Myc gene promoter region. SIGNIFICANCE: We conclude that three compounds merit further study, particularly against non-small-cell lung cancer, as leading compounds of anticancer drugs.

Malignant transformation in a Breast Adenomyoepithelioma Caused by Amplification of c-MYC: A Common pathway to Cancer in a Rare Entity.

Breast adenomyoepitheliomas are composed of a biphasic proliferation of myoepithelial cells around small epithelial-lined spaces. Due to the rarity of adenomyoepitheliomas, the molecular data describing them are limited. Adenomyoepitheliomas are considered to be benign or have low malignant potential, and be prone to local recurrence. Malignant transformation has been associated with homozygous deletion of CDKN2A or somatic mutations in TERT, but remains unexplained in many cases. Here, we describe a case of carcinomatous transformation of both epithelial and myoepithelial cells in an estrogen receptor-negative adenomyoepithelioma caused by amplification of MYC. Break-apart fluorescence in situ hybridization revealed an increase in the MYC gene copy number (3-4 copies/cell in 37%, > 4 copies/cell in 40%). Deregulation of MYC is responsible for uncontrolled proliferation and cellular immortalization in basal-like breast cancers. Our case demonstrates that genomic instability events associated with gene amplification may be involved in the carcinogenesis of malignant adenomyoepitheliomas.

Malignant transformation in a Breast Adenomyoepithelioma Caused by Amplification of c-MYC: A Common pathway to Cancer in a Rare Entity / 한국유방암학회지

Breast adenomyoepitheliomas are composed of a biphasic proliferation of myoepithelial cells around small epithelial-lined spaces. Due to the rarity of adenomyoepitheliomas, the molecular data describing them are limited. Adenomyoepitheliomas are considered to be benign or have low malignant potential, and be prone to local recurrence. Malignant transformation has been associated with homozygous deletion of CDKN2A or somatic mutations in TERT, but remains unexplained in many cases. Here, we describe a case of carcinomatous transformation of both epithelial and myoepithelial cells in an estrogen receptor-negative adenomyoepithelioma caused by amplification of MYC. Break-apart fluorescence in situ hybridization revealed an increase in the MYC gene copy number (3–4 copies/cell in 37%, > 4 copies/cell in 40%). Deregulation of MYC is responsible for uncontrolled proliferation and cellular immortalization in basal-like breast cancers. Our case demonstrates that genomic instability events associated with gene amplification may be involved in the carcinogenesis of malignant adenomyoepitheliomas.

A case of acute promyelocytic leukemia variant with derivative chromosome 3 der(3)t(3;8) associated with 8q partial gain.

BACKGROUND: Acute promyelocytic leukemia (APL) is characterized by fusion of PML/RARα genes as a result of t(15;17)(q24;q21). APL is now one of the curable hematological malignancies thanks to molecularly targeted therapies based on all-trans retinoic acid (ATRA) and arsenic trioxide (ATX). Extramedullary (EM) relapse is a rare event in APL, ear involvement being even more infrequent, with only six cases so far described. About 30-35% of patients with newly diagnosed APL have additional cytogenetics abnormalities, whose prognostic significance is still controversial. The most common additional aberration is trisomy 8 or partial gain 8q. CASE PRESENTATION: We describe here a novel unbalanced translocation der(3)t(3;8)(q29;q23.3-q24.3) associated with 8q partial gain in a 41 year-old man affected by APL in molecular remission after first line treatment, who had a responsive EM relapse in the auditory canal. CONCLUSIONS: EM relapse is a rare event in APL and ear involvement is even more infrequent. To our knowledge, this is the first reported case of APL with a new der(3)t(3;8)(q29;q23.3-q24.3) and 8q partial gain associated with t(15;17)(q24;q21). Despite the recurrence of the disease at EM level, the clinical outcome of this patients was favorable.

Effect of different expression levels of USP28 on apoptosis and related protein expression in esophageal cancer cell ECA109 after irradiation / 中华放射肿瘤学杂志

Objective To observe the effect of different expression levels of USP28 on the radiosensitivity of ECA109 cells by gene transfection method,aiming to provide theoretical basis for comprehensive treatment of esophageal cancer.Methods The expression levels of USP28 and c-Myc in the esophageal epithelial cells Het-1A,ECA109 and ECA109R were quantitatively measured by qRT-PCR.The specific siRNA sequences were designed according to the USP28 and c-Myc genes.The pcDNA-USP28 and pcDNA-c-Myc plasmids were constructed.The esophageal cancer cell ECA109 was transfected with Lipofectamine 2000 to observe the transfection effect and related protein expression.ECA109 and ECA109R cells were exposed to 6 Gy X-ray radiation.The cell apoptosis in each group was detected by flow cytometry.The radiosensitivity was evaluated by clone formation assay.Results The expression levels of USP28 and c-Myc in ECA109 were significantly higher than those in Het-1A (both P＜0.05),and the expression levels of USP28 and c-Myc in ECA109R were remarkably higher than those in ECA109(both P＜0.05).The pcDNA-USP28 and pcDNA-c-Myc recombinant plasmids were successfully constructed.Compared with the negative control group,the expression of USP28 at the protein and mRNA levels in the si-USP28 group was significantly down-regulated,whereas those in the pcDNA-USP28 group were remarkably up-regulated.Similar results were obtained in terms of c-Myc.Compared with the control group,the expression level of c-Myc protein was significantly up-regulated in the pcDNA-USP28 group,whereas considerably down-regulated in the si-USP28 group.After 6 Gy irradiation,the apoptosis rate and radiosensitivity of ECA109 cells were significantly declined.The apoptosis rate and radiosensitivity of ECA109R cells were increased in the si-USP28 group.Conclusions The expression of USP28 protein is closely correlated with the radiosensitivity of esophageal cancer cells.The underlying mechanism may be related to the regulation of c-Myc expression by USP28.

Effect of different expression levels of USP28 on apoptosis and related protein expression in esophageal cancer cell ECA109 after irradiation / 中华放射肿瘤学杂志

Objective@#To observe the effect of different expression levels of USP28 on the radiosensitivity of ECA109 cells by gene transfection method, aiming to provide theoretical basis for comprehensive treatment of esophageal cancer.@*Methods@#The expression levels of USP28 and c-Myc in the esophageal epithelial cells Het-1A, ECA109 and ECA109R were quantitatively measured by qRT-PCR. The specific siRNA sequences were designed according to the USP28 and c-Myc genes. The pcDNA-USP28 and pcDNA-c-Myc plasmids were constructed. The esophageal cancer cell ECA109 was transfected with Lipofectamine 2000 to observe the transfection effect and related protein expression. ECA109 and ECA109R cells were exposed to 6 Gy X-ray radiation. The cell apoptosis in each group was detected by flow cytometry. The radiosensitivity was evaluated by clone formation assay.@*Results@#The expression levels of USP28 and c-Myc in ECA109 were significantly higher than those in Het-1A (both P<0.05), and the expression levels of USP28 and c-Myc in ECA109R were remarkably higher than those in ECA109(both P<0.05). The pcDNA-USP28 and pcDNA-c-Myc recombinant plasmids were successfully constructed. Compared with the negative control group, the expression of USP28 at the protein and mRNA levels in the si-USP28 group was significantly down-regulated, whereas those in the pcDNA-USP28 group were remarkably up-regulated. Similar results were obtained in terms of c-Myc. Compared with the control group, the expression level of c-Myc protein was significantly up-regulated in the pcDNA-USP28 group, whereas considerably down-regulated in the si-USP28 group. After 6 Gy irradiation, the apoptosis rate and radiosensitivity of ECA109 cells were significantly declined. The apoptosis rate and radiosensitivity of ECA109R cells were increased in the si-USP28 group.@*Conclusions@#The expression of USP28 protein is closely correlated with the radiosensitivity of esophageal cancer cells. The underlying mechanism may be related to the regulation of c-Myc expression by USP28.

Small benzothiazole molecule induces apoptosis and prevents metastasis through DNA interaction and c-MYC gene supression in diffuse-type gastric adenocarcinoma cell line.

Chemo-resistance has been reported as a relevant barrier for the efficiency of gastric cancer treatment. Therefore, the development of effective and safe drugs for cancer chemotherapy is still a challenge. The purpose of this study was to evaluate the anticancer potential of (E)-2-(((2-(benzo[d]thiazo-2-yl)hydrazono)methyl)-4-nitrophenol) (AFN01) against gastric cancer cell lines. Our results showed promising anticancer activity against gastric cancer cells ACP-02 (IC50 = 1.0 µM) and mild activity against other cell lines including non-malignant gastric cell MNP-01 (IC50 = 3.4 µM). This compound significantly induced S phase cell cycle arrest, prevented cell migration and triggered apoptosis in a concentration-dependent manner. Moreover, AFN01 was significantly more genotoxic against tumoral cell ACP-02, when compared to non-malignant cells, such as MNP-01 and healthy peripheral mononuclear blood cells. AFN01 also synergistically interacts with doxorubicin suppressing cell proliferation and c-MYC gene expression in gastric cancer cell line model, with remarkable c-MYC overexpression. Although further pre-clinical and clinical studies are required to explore its safety and efficiency, AFN01 may represent a promising lead anticancer agent for the treatment of gastric cancer.

A B-cell lymphoma case that is unclassifiable, and intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma of lacrimal gland.

A 60-year-old woman presented with acute eyelid swelling and a subcutaneous hemorrhage in the right eye. Magnetic resonance imaging showed a spherical tumor of the lacrimal gland. The tumor was removed by the Kroenlein method. We diagnosed as a B-cell lymphoma that is unclassifiable, and intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (intermediate DLBCL/BL) based on its immunohistopathological examination and c-MYC/IgH rearrangement. We administered six cycles of dose-adjusted-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride, and rituximab) therapy, and remission of the lymphoma was obtained. This is the first case of an intermediate DLBCL/BL of a lacrimal gland.

Effect of antisense locked nucleic acid blocking translation initiation region of c-myc exon 2 on apoptosis of hepatocellular carcinoma cells / 中国病理生理杂志

AIM:To observe the effect of antisense locked nucleic acid (anti-LNA) blocking the translation initiation region of c-myc exon 2 on the viability and apoptosis of hepatocellular carcinoma cells.METHODS:The antiLNA that was complementary to the translation initiation region of c-myc exon 2 was designed,synthesized,and introduced into the HepG2 cells by cationic liposome-mediated transfection.The mRNA and protein levels of c-Myc in the cells were determined by RT-PCR and Western blot.The change of cell apoptosis was analyzed by flow cytometry,and the toxicity of anti-LNA to the cells was detected by MTT assay.RESULTS:Five days after transfection,the mRNA level of c-Myc in anti-LNA group was 0.335 ±0.016,and the protein level was 0.448 ± 0.037,significantly lower than those in control group (both P ＜ 0.05).The ratio of apoptotic cells in anti-LNA group was 32％ ±-6％,which was higher than that in control group (P ＜ 0.05).CONCLUSION:Antisense locked nucleic acid targeting at the translation initiation region of cmyc exon 2 shows strong inhibitory effects on the apoptosis of hepatocellular carcinoma cells.

Effect of antisense locked nucleic acid blocking translation initiation region of c-myc exon 2 on apoptosis of hepatocellular carcinoma cells / 中国病理生理杂志

AIM:To observe the effect of antisense locked nucleic acid (anti-LNA) blocking the translation initiation region of c-myc exon 2 on the viability and apoptosis of hepatocellular carcinoma cells.METHODS:The antiLNA that was complementary to the translation initiation region of c-myc exon 2 was designed,synthesized,and introduced into the HepG2 cells by cationic liposome-mediated transfection.The mRNA and protein levels of c-Myc in the cells were determined by RT-PCR and Western blot.The change of cell apoptosis was analyzed by flow cytometry,and the toxicity of anti-LNA to the cells was detected by MTT assay.RESULTS:Five days after transfection,the mRNA level of c-Myc in anti-LNA group was 0.335 ±0.016,and the protein level was 0.448 ± 0.037,significantly lower than those in control group (both P ＜ 0.05).The ratio of apoptotic cells in anti-LNA group was 32％ ±-6％,which was higher than that in control group (P ＜ 0.05).CONCLUSION:Antisense locked nucleic acid targeting at the translation initiation region of cmyc exon 2 shows strong inhibitory effects on the apoptosis of hepatocellular carcinoma cells.

Physiological Expression and Accumulation of the Products of Two Upstream Open Reading Frames mrtl and MycHex1 Along With p64 and p67 Myc From the Human c-myc Locus.

In addition to the canonical c-Myc p64 and p67 proteins, the human c-myc locus encodes two distinct proteins, mrtl (myc-related translation/localization regulatory factor) and MycHex1 (Myc Human Exon 1), from the upstream open reading frames within the 5'-untranslated region of the c-myc P0 mRNA. The aim of this study is to examine simultaneously, for the first time, mrtl, MycHex1, c-Myc p64, and p67 in human tumor cell lines and pediatric brain tumor tissues. Western blot analysis demonstrated endogenous mrtl, MycHex1, c-Myc p64, and p67 simultaneously. The relative abundance of mrtl and MycHex1 were consistent among a variety of human tumor cell lines, and the relative intensities of mrtl and MycHex1 correlated positively. Confocal imaging revealed mrtl predominantly localized to the nuclear envelope, along with prominent reticular pattern in the cytoplasm. MycHex1 was observed as a series of bright foci located within the nucleus, a subset of which colocalized with fibrillarin. mrtl and MycHex1 co-immunoprecipitated with RACK1, c-Myc, fibrillarin, coilin, and with each other. These findings suggest that mrtl and MycHex1 have multiple interaction partners in both the nucleus and cytoplasm. Sequence analyses confirmed a known polymorphism of mrtl at base 1965 (G>T) and new mutations at bases 1900 (C>G) and 1798 (C>G). Evidence is presented for expression and stable accumulation of all four proteins encoded by three distinct non-overlapping open reading frames within the human c-myc locus. Additional work is warranted to further elucidate the functional or regulatory roles of these molecules in regulation of c-Myc and in oncogenesis.

Difference of Bcl-6 and c-myc gene translocation between Xinjiang Uygur and Han diffused large B-cell lymphoma subtypes / 中国肿瘤临床

Objective:To investigate the clinical significance of Bcl-6, c-myc gene abnormalities in Xinjiang Uygur and Han dif-fused large B-cell lymphoma (DLBCL) subtypes. Methods:Bcl-6, c-myc gene was detected by fluorescence in situ hybridization in 233 patients with DLBCL . A relationship was observed among Bcl-6, c-myc gene translocation, and clinical data in DLBCL patients. In addition, a difference was observed among Bcl-6, c-myc gene translocation, and different ethnic groups in different subtypes of DLB-CL. Results:Among the 233 patients, 51 cases (21.89%) had rearranged Bcl 6 gene, and 39 cases (16.74%) had rearranged c-myc gene. Bcl-6 gene translocation and expression was related with age, gender, disease location, clinical stage, and LDH levels (P>0.05), but was not related with nationality , international prognostic index score, extranodal involvement, B symptoms, DLBCL subtypes, and recent efficacy (P0.05), but was not related with nationality, IPI score, extranodal involvement, B symptoms, and recent effica-cy (P0.05). By con-trast, in the Uygur and Han non-GCB groups, Bcl-6, c-myc gene translocation showed significant difference (P>0.05). Conclusion:Bcl-6, C-myc gene translocation was related with age, gender, disease location, clinical stage, and LDH levels. Bcl-6 gene translocation was also correlated with different subtypes of DLBCL.

Effect of blocking p38MAPK signal pathway on activity of rat hepatic stellate cells and c-myc protein expression / 重庆医学

Objective To study the effect of p38MAPK on the activity and c-myc protein expression in rat acetaldehyde-induced hepatic stellate cell(HSC),and to investigate the alcoholic liver fibrosis related mechanism.Methods The different concentrations of SB203580 as the p38 specific blocker was adopted to conduct the intervention on rat acetaldehyde-induced HSC.The cellular mor-phological change was observed by the microscope.The cell proliferation was detected by MTT,the cell cycle was analyzed by flow cytometry(FCM),and the expression of c-myc protein was examined by the SABC method.Results (1)after acetaldehyde stimula-tion,HSC was increased in size and proliferated rapidly,but with the added SB203580 concentration increase,the cellular prolifera-tion was slowed down,the cells size was diminished and the deformed cells were increased.(2)The proliferation of acetaldehyde-in-duced HSC was inhibited by different doses of SB203580,and the higher concentration has the more significant inhibiting effect.(3) With the SB203580 concentration increase,the cells at the phase G0 and G1 were increased,while the cells at the phase S were de-creased,at the same time the expression positive rate of c-myc protein was decreased.Conclusion Blocking p38MAPK pathway ac-tivity could inhibit the proliferation of acetaldehyde-induced HSC,which may be related to the down-regulation of C-myc protein ex-pression and blocking the DNA synthesis in cells entering from G0/G1 phase to S phase.

"Transformation of follicular lymphoma to""double-hit""or""triple-hit""lymphoma with c-MYC gene rearrangement:A report of three cases" / 中国肿瘤临床

Objective: To analyze the diagnosis and therapy for double-hit lymphoma (DHL) and triple-hit lymphoma (THL). Methods:This study involves three patients with follicular lymphoma (FL) that transformed into DHL or THL. These patients were ad-mitted to our hospital between January 2011 and December 2012. All patients were diagnosed by immunohistochemistry and fluores-cence in situ hybridization (FISH). Results:One FL patient transformed into THL and died after 3 months. The other two FL patients who transformed into DHL and who received R-CHOP and R-ESHAP regimens still failed to achieve complete remission. Conclusion:DHL is a rare type of lymphoma that usually involves the bone marrow and central nervous system. This condition is highly resistant to intensive chemotherapy. Part of the DHL cases result from FL. FISH is important for diagnosis. However, a standard treatment for this type of lymphoma remains lacking.

Instabilidade genômica em neoplasias malignas da mama em função da concentração de alumínio intracelular / Genomic instability association with intracellular aluminum concentration in breast tumors

Introdução: A hipótese de que os efeitos do alumínio em células humanas podem ter implicações clínicas tem sido levantada há algum tempo, especialmente no que concerne ao câncer de mama. As evidências laboratoriais mostrando altos níveis de alumínio nos tecidos da mama e os efeitos biológicos conhecidos sobre esse metal não são suficientes para estabelecer uma relação causal entre a exposição ao alumínio e o risco aumentando para o desenvolvimento do câncer de mama. O objetivo deste estudo foi estabelecer a concentração de alumínio nas áreas centrais e periféricas de tumores de mama, assim como na área glandular normal da mama e correlacionar esses achados com a instabilidade dos genes ERBB2, C-MYC e CCND1 e a aneuploidia dos cromossomos que contêm estes genes. Métodos: Para este estudo foram incluídas 176 mulheres com diagnóstico de carcinoma invasor de mama, com tumores maiores de 1cm3, sem quimioterapia neoadjuvante, operadas enter 2008 e 2010 no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM) - UNICAMP. Para a análise da concentração de alumínio intracelular, amostras de 150 pacientes foram consideradas viáveis; para a análise da instabilidade genômica em função da concentração de alumínio, 118 amostras foram consideradas viáveis, definindo o espaço amostral de cada um dos artigos apresentados. As amostras das áreas centrais e periféricas dos tumores de mama e das áreas glandulares normais da mama foram obtidas. A quantificação do alumínio contido nos tecidos da mama foi feita através da técnica de Espectrometria de Absorção Atômica em Forno de Grafite (GFAAS). Uma lâmina de Tissue Microarray (TMA), contendo as amostras de tumor e tecido normal foi utilizado para a realização da técnica de FISH para acessar o status dos genes ERBB2, C-MYC e CCND1 e dos centrômeros dos seus respectivos cromossomos 17, 8 e 11. Os dados clínico-patológicos foram obtidos dos prontuários de pacientes...

Introduction: It has long been hypothesized if the effects of aluminum on human cells may have clinical implications, especially regarding to breast cancer. The current laboratorial evidence showing higher levels of aluminum in breast tissues and the known biological effects of this metal, are not sufficient to establish a causal relationship between aluminum exposure and increased risk of developing breast cancer. The objective of this study was to establish the aluminum concentration in the central and peripheral areas of breast tumors as well as in normal glandular area of the breast and to correlate these findings with the instability of ERBB2, C-MYC and CCND1, and aneuploidy of chromosomes harboring these genes. Methods: This study included 176 women diagnosed with invasive breast carcinoma with tumors larger than 1cm3 without neoadjuvant chemotherapy, operated between 2008 and 2010 at the Women's Hospital Professor. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM) - UNICAMP. To analyze the intracellular concentration of aluminum, samples from 150 patients were considered viable; for the analysis of genomic instability as a function of the concentration of aluminum, 118 samples were considered viable. These figures define the sample of each of the two articles that this PhD thesis comprises. Evaluation of tissue aluminum content was carried out using Graphite Furnace Atomic Absorption Spectrometry (GFAAS). A TMA slide containing the tumor and normal samples was used in FISH assays to assess ERBB2, C-MYC and CCND1 and the respective chromosomes 17, 8 and 11 centromeres status. Clinicopathological data were obtained from patients' records. Results: The average aluminum content found in breast was 1.88 mg/kg in the central tumor areas, 2.10 mg/ kg in the peripheral tumor areas and 1.68 mg/ kg in the normal tissue areas...

Clinical significance of bcl-6, p53, c-myc aberrations in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective To investigate aberrations of bcl-6,p53,c-myc genes in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods Interphase fluorescence in situ hybridization (I-FISH) was detected in 59 DLBCL patients in vivo tissue bcl-6,p53 protein,c-myc gene status.The patients were treated with CHOP or R-CHOP chemotheralpy,and the survival rates and treatment efficiency were compared.Results The p53 deletion was detected in 18 of the 59 cases (30.5 ％),bcl-6 rearrangement in 11 cases (18.6 ％),5 cases with c-myc rearrangement (8.5 ％).In the aspects of remission rate,p53 deletion positive group contained less advantage than negative ones (33.3 ％ vs 75.6 ％,x2 =9.560,P =0.002).The prognosis of bcl-6 gene rearrangement positive group different from negative group,but the difference was not statistically significant (OS,P =0.107; PFS,P =0.094),p53 deletion positive patients was in significantly worse prognosis than the negative group (OS,P =0.031; PFS,P =0.028),c-myc rearrangement positive group difference in gene rearrangement negative group,but the difference was not statistically significant (OS,P =0.163; PFS,P =0.167).In the CHOP group,prognosis of p53 deletion,c-myc rearrangement positive group were significantly worse than the negative group,the difference was statistically significant (P ＜ 0.05).In R-CHOP group,the prognostic significance of bcl-6 gene rearrangement positive group were worse (OS,P =0.003; PFS,P =0.007).Conclusion DLBCL patients with bcl-6,p53,c-myc genes aberrations are related with poor prognosis,and they can be used as prognostic factors for predicting DLBCL and guiding therapy.