[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.

[Prompt cytogenetic response by venetoclax plus azacitidine regimen in a patient with AML harboring double-minute chromosomes with MYC gene amplification].

Double minute chromosomes (dmin) are small, acentric, and extrachromosomal fragments that frequently mediate oncogene amplification and induce rapid disease progression with poor prognosis, although they are infrequent in myeloid neoplasms. An 81-year-old woman with anemia and thrombocytopenia was admitted to our hospital. Bone marrow examination showed 54.0% of the blasts. She was diagnosed with acute myeloid leukemia (French-American-British classification, M2; World Health Organization classification, acute myeloid leukemia [AML], not otherwise specified, AML with maturation). Chromosomal analysis revealed the presence of 3-45 dmin in the background of 46 and XX in 14 out of 20 metaphases examined. Spectral karyotyping examination demonstrated that the dmins were derived from chromosome 8. Fluorescence in situ hybridization (FISH) targeting the MYC gene demonstrated that dmins contained full-length MYC genes with multiple signals. Finally, she was diagnosed with AML with dmin via MYC amplification and was administered with venetoclax plus azacitidine chemotherapy. After two cycles of the regimen, FISH found no MYC amplification signals, indicating her state being in cytogenetic remission. At present, she has finished four cycles of the regimen and remained in complete remission. Venetoclax plus azacitidine could be an effective regimen for the poor prognosis of AML with dmin through MYC amplification.

The Prognostic Impact of MYC Gene-Related Abnormalities on Multiple Myeloma Outcome through Fluorescence in situ Hybridization Analysis.

INTRODUCTION: Chromosomal abnormalities (CAs) have been identified as important factors in determining the biological features and prognostic value of multiple myeloma (MM). MYC gene-related abnormalities (MYC GAs) are one of the CAs, but their unfavorable impact has not been fully investigated in daily clinical practice. METHODS: This study retrospectively analyzed the prognostic impact of MYC GAs on 81 patients through fluorescence in situ hybridization analysis in our institute. RESULTS: MYC GAs were associated with poor overall survival (hazard ratio [HR], 3.08; 95% confidence interval [CI]: 1.23-7.73; p = 0.017), progression-free survival (PFS) (HR, 2.96; 95% CI: 1.58-5.53; p < 0.001), and time to next treatment (TNT) (HR, 2.11; 95% CI: 1.13-3.93; p = 0.018) in the median follow-up of 34.7 months. Furthermore, MYC GAs with an additional chromosome 8 (MYC-Ch8(+)) were associated with shorter PFS (HR, 3.15; 95% CI: 1.38-7.2; p = 0.0064), whereas MYC GAs without an additional chromosome 8 (MYC-Ch8(-)) were associated with shorter PFS (HR, 3.62; 95% CI: 1.51-8.68; p = 0.004) and shorter TNT (HR, 3.72; 95% CI: 1.41-9.81; p = 0.0078). CONCLUSION: These findings could help identify high-risk patients with MM. Further prospective studies are needed to confirm the significance of MYC GAs for the MM prognostic effect.

HIV-associated DLBCL: Clinicopathological factors including dual-colour chromogenic in situ hybridisation to assess MYC gene copies.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) comprises up to 43% of non-Hodgkin lymphomas in South Africa due to the high seroprevalence of human immunodeficiency virus (HIV) infection in the southern African region. We explored the prognostic influence of an array of clinicopathological factors, including MYC gene copy numbers, within HIV-associated DLBCL. METHODS: The retrospective inclusion of 123 tumours was followed by c-MYC immunohistochemistry and dual-colour MYC and centromere 8 (CEN8) chromogenic in situ hybridisation on formalin-fixed paraffin-embedded sections. Clinicopathological data were collected, interpreted and analysed. RESULTS: HIV seropositive patients comprised 81% (93/115), mean age 42 (SD 10.8) years, with 55% males, HIV negative patients comprised 19% (22/115), mean age 57 (SD 16.7) years (p = 0.001), with 59% males and the HIV status was unknown for 8 patients. The median CD4 count was 162 (IQR 215) cells/mm3, 33% of patients presented with CD4 counts <100 cells/mm3 and the median viral load was 217 (IQR 182 981) copies/mL. There was advanced stage at presentation (i.e., III-IV, 87%), with Ki-67 proliferation indices ≥90% in 85%- and c-MYC expression (i.e., ≥40%) in 58% of tumours. Double expression of c-MYC and BCL2 was associated with a non-germinal center immunophenotype (p < 0.01). Low-level increase of MYC gene copy numbers and MYC rearrangements occurred in 57% and 12%, respectively. C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/increased MYC gene copies were also detected. Inferior median overall survival (OS) occurred when the CD4 counts were <100 cells/mm3 (149 days 95% CI 44-254, p 0,04) and when IPI scores were 3-5 [155 days (95% CI 37-273), p = 0.01]. Concomitant infections negatively impacted the survival outcome, multivariate regression analysis (HR 4.01, 95% CI 1.86-12.20, p = 0.02). CONCLUSION: c-MYC protein expression, low-level increase in MYC gene copy numbers, rearrangement, C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/low-level gains are present in HIV+ DLBCL. CD4 counts < 100 cells/mm3, IPI scores 3-5 and concomitant infections negatively impact the survival outcome.

More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment.

The NOTCH1 gene encodes a transmembrane receptor protein with activating mutations observed in many T-cell acute lymphoblastic leukemias (T-ALLs) and lymphomas, as well as in other tumor types, which has led to interest in inhibiting NOTCH1 signaling as a therapeutic target in cancer. Several classes of Notch inhibitors have been developed, including monoclonal antibodies against NOTCH receptors or ligands, decoys, blocking peptides, and γ-secretase inhibitors (GSIs). GSIs block a critical proteolytic step in NOTCH activation and are the most widely studied. Current treatments with GSIs have not successfully passed clinical trials because of side effects that limit the maximum tolerable dose. Multiple γ-secretase-cleavage substrates may be involved in carcinogenesis, indicating that there may be other targets for GSIs. Resistance mechanisms may include PTEN inactivation, mutations involving FBXW7, or constitutive MYC expression conferring independence from NOTCH1 inactivation. Recent studies have suggested that selective targeting γ-secretase may offer an improved efficacy and toxicity profile over the effects caused by broad-spectrum GSIs. Understanding the mechanism of GSI-induced cell death and the ability to accurately identify patients based on the activity of the pathway will improve the response to GSI and support further investigation of such compounds for the rational design of anti-NOTCH1 therapies for the treatment of T-ALL. IMPLICATIONS FOR PRACTICE: γ-secretase has been proposed as a therapeutic target in numerous human conditions, including cancer. A better understanding of the structure and function of the γ-secretase inhibitor (GSI) would help to develop safe and effective γ-secretase-based therapies. The ability to accurately identify patients based on the activity of the pathway could improve the response to GSI therapy for the treatment of cancer. Toward these ends, this study focused on γ-secretase inhibitors as a potential therapeutic target for the design of anti-NOTCH1 therapies for the treatment of T-cell acute lymphoblastic leukemias and lymphomas.

MYC status in HIV-associated plasmablastic lymphoma: dual-colour CISH, FISH and immunohistochemistry.

AIMS: We utilised chromogenic and fluorescence in-situ hybridisation (CISH and FISH) to evaluate MYC gene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBLs). Thereafter, clinicopathological features were explored retrospectively. METHODS AND RESULTS: Sixty-seven (n = 67) patients were included and the HIV seropositive status was confirmed in 98% (63 of 64) with a median viral load of 55 587 (IQR 273 582) copies/ml and median CD4 count of 170 (IQR 249) cells/µl. The mean age was 41 ± 10.1 years and females comprised 54%. PBL was documented predominantly at extra-oronasal topographic regions. Starry-sky (SS) appearance was evident in 33% in association with monomorphic morphology (P-value 0.02). c-MYC protein was expressed in 81% and latent EBV infection was detected in 90%. EBER ISH-positive status and MYC rearrangement occurred in 67% of HIV PBL. MYC aberrations included MYC rearrangement (70%), low-level increase in MYC gene copy numbers (43%), concurrent MYC rearrangement and increased MYC gene copy numbers (49%) as well as low-level chromosome 8 polysomy (6%). MYC aberrations in HIV PBLs were significantly associated with SS appearance (P -0.01), monomorphic morphology (P - 0.03), c-MYC protein expression ≥40% (P - 0.03) and mortality (P - 0.03). There was advanced stage (Ann Arbor III/IV) at presentation (77%) and the median overall survival for HIV PBL was 75 days (95% CI 14-136). CONCLUSION: Majority of the HIV-associated PBL tumours harbour MYC aberrations. Due to the persistently inferior survival outcome of HIV-associated PBL in the era of antiviral treatment, targeted and/or intensified therapy of oncogenic MYC may need to be explored in future.

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.

Prognostic analysis of interim 18F-FDG PET/CT in patients with diffuse large B cell lymphoma after one cycle versus two cycles of chemotherapy.

OBJECTIVES: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is routinely used in diffuse large B cell lymphoma (DLBCL) for staging, assessment of remission and recurrence, and estimation of therapeutic efficacy. In this study, we aimed to assess the role of an early interim PET/computed tomography (CT) in the evaluation of response in DLBCL. METHODS: Sixty primary DLBCL patients (31 females) were analyzed. Baseline and follow-up 18F-FDG PET/CT was performed in patients after one cycle (n = 30) and two cycles (n = 30) of chemotherapy. The ΔSUVmax% was calculated. Patients were additionally evaluated using the conventional Deauville five-point scale (D-5PS) system. Fluorescence in situ hybridization (FISH) was employed to characterize the MYC gene status. We determined the optimum cutoff value of ΔSUVmax% using receiver operating characteristic (ROC) analysis. Kaplan-Meier analysis was applied to test for the influence of prognostic values. RESULTS: The optimal cutoff for the prediction of treatment outcome was a ΔSUVmax% of 57% (after one cycle) and 63% (after two cycles); we could not detect a difference in accuracy with respect to a PET scan performed after one cycle and two cycles of chemotherapy (P > 0.05). The ΔSUVmax% and the D-5PS (score 5) showed the highest prognostic value compared to a score of 3 and/or 4 (both after one cycle and two cycles). No significant difference in sensitivity, specificity, accuracy, or the area of under the curve (AUC) of ΔSUVmax% and D-5PS (score 5) was observed between PETs performed after one cycle or two cycles of therapy (P > 0.05). ΔSUVmax%, D-5PS (score 5), and MYC gene rearrangement correlated significantly (P < 0.001). CONCLUSION: Interim 18F-FDG PET/CT after one cycle of chemotherapy is feasible and yields similar predictive results as compared to an interim 18F-FDG PET/CT after two cycles of chemotherapy in patients suffering from DLBCL. The combination of interim 18F-FDG PET/CT with the MYC gene diagnosis might provide increased prognostic value for DLBCL.

The ERH gene regulates migration and invasion in 5637 and T24 bladder cancer cells.

BACKGROUND: This study aimed to determine whether the enhancer of the rudimentary homolog (ERH) gene regulates cell migration and invasion in human bladder urothelial carcinoma (BUC) T24 cells and the underlying mechanism. METHODS: First, we knocked down ERH in BUC T24 and 5637 cells by shRNA and then used wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays to determine the migration and invasion ability after ERH was knocked down. Moreover, we used gene expression profiling chip analysis and further functional experiments to explore the possible mechanism through which ERH knockdown downregulated metastasis ability in T24 cells. RESULTS: Wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays all showed that the metastasis ability was significantly inhibited in human BUC T24 and 5637 cells with ERH knockdown. A gene expression profiling chip analysis in T24 cells showed that the MYC gene may be an important downstream target of the ERH gene, and the functional experiments showed that MYC is a functional target of ERH in BUC T24 cells. CONCLUSION: ERH knockdown could inhibit the metastasis of BUC T24 cells in vitro and in vivo. This study further explored the mechanism of the ERH gene in the metastasis of the T24 human bladder cancer cell line and found that ERH may regulate MYC gene expression. The results of this research provide a basis for the clinical application of ERH as a potential target for BUC treatment.

[Correct use of Kreatech DNA probes to detect MYC gene amplification in medulloblastomas by fluorescence in situ hybridization]. / Korrektnoe ispol'zovanie DNK-zondov Kreatech dlia vyiavleniia amplifikatsii gena MYC v medulloblastomakh metodom fliuorestsentnoi gibridizatsii in situ.

In most cases, oncogene amplification are prognostic and predictive markers for various tumors, therefore DNA probes are unable to reveal changes in the copy numbers should not be used to diagnose malignant tumors. OBJECTIVE: To comparatively analyze DNA probes from different manufacturers to detect MYC gene amplification in routine practice. MATERIAL AND METHODS: The study material was formalin-fixed paraffin-embedded medulloblastoma fragments from 4 patients, with discrepancies in the results in the detection of MYC gene amplification. RESULTS: MYC gene amplification was determined using DNA probes: Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG, and Zytolight SPEC MYC/CEN 8 Dual Color Probe. The use of the probes Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color probe failed to detect MYC gene amplification; this probe showed a balanced profile of chromosome 8. CONCLUSION: In routine practice, fluorescence in situ hybridization with the DNA probes Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG and Zytolight SPEC MYC/CEN 8 Dual Color Probe can be the method of choice for studying the copy number of the MYC gene. However, the authors strongly recommend that the Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color should not be used for this purpose. In addition, probes for fluorescence in situ hybridization must be necessarily tested in large reference laboratories dealing with one or another area of oncopathology.

The role of N-Myc gene amplification in neuroblastoma childhood tumour - single-centre experience.

AIM OF THE STUDY: Neuroblastoma (NBL) is one of the most common extracranial tumours occurring in children with N-Myc gene amplification, acknowledged as a marker of poor prognosis. We assessed the frequency of N-Myc amplification and its impact on NBL markers and on the treatment outcome. MATERIAL AND METHODS: Among 160 children with NBL treated from 1991 to 2015 in one centre 140 patients had known N-Myc gene status, and they were enrolled in the study. The analysed group was divided into two subgroups: with and without N-Myc amplification (25 and 115 children, respectively). Association of N-Myc amplification with stage of the disease, levels of biochemical parameters, overall survival (OS) and failure-free survival (FFS) were analysed. RESULTS: The frequency of N-Myc amplification was 17.9%. Most children with N-Myc amplification (64%) were classified to stage 4 NBL. The levels of biochemical markers of NBL: ferritin, dopamine, NSE, and LDH were significantly higher in the group with N-Myc amplification, whereas the levels of VMA and HVA were lower. OS and FFS were significantly lower in children with N-Myc amplification in comparison to children from the control group (OS 53% vs. 76%, p = 0.03; FFS 50% vs. 72%, p = 0.03). The impact of N-Myc amplification on the treatment outcome was significant in patients with stage 4 NBL and children under one year of age. CONCLUSIONS: N-Myc amplification is a crucial prognostic factor in neuroblastoma, which is associated with almost all features related with poor prognosis and a higher probability of unfavourable outcome.

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.

MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma.

AIMS: We aimed to investigate MYC expression and chromosomal aberration in mantle cell lymphoma (MCL), and the clinical significance of these factors. METHODS AND RESULTS: Sixty-five patients with MCL, including 54 classic, nine blastoid and two pleomorphic variants, were enrolled. Expression of MYC, Ki67 and p53 was assessed by immunohistochemistry. MYC amplification or translocation was examined by fluorescence in-situ hybridization. MYC expression was higher in blastoid/pleomorphic MCL variants (mean, 19.0%) than in classic MCL (mean, 1.9%; P < 0.001). Expression of p53 and Ki67 was also significantly higher in these variants. MYC amplification was found in two of 53 cases tested, both of which were blastoid variants with high MYC expression (29.7% and 20.4%). MYC translocation was found in two of 52 cases tested, both of which were pleomorphic variants with remarkably high MYC expression (68.5% and 71.0%). High MYC or p53 expression was significantly associated with shortened overall survival and progression-free survival in univariable and multivariable analyses (all P < 0.05). CONCLUSIONS: MYC overexpression is a negative predictor of MCL patient outcomes. MYC gene amplification or translocation might be related to the pathogenesis of MCL, particularly in blastoid/pleomorphic variants.

Conventional and molecular cytogenetic characterization of Burkitt lymphoma with bone marrow involvement in Brazilian children and adolescents.

BACKGROUND: Burkitt lymphoma/leukemia (BL/L) is cytogenetically characterized by the t(8;14)(q24;q32) or its variants, t(2;8)(p11;q21), and t(8;22)(q24;q11.2), which juxtapose the MYC oncogene to one of the three immunoglobulin loci. The overall cure rate of BL/L in children is 70-90%, but patients diagnosed with advanced-stage disease have a less favorable prognosis. It is possible that secondary chromosomal abnormalities contribute to this unfavorable prognosis via chemotherapy resistance, but the results of genetic studies have been inconsistent. This study aimed to identify and characterize secondary chromosomal abnormalities associated with the t(8;14) and its variants in children with French-American-British-L3 leukemia or Burkitt lymphoma with bone marrow involvement at the time of diagnosis. PROCEDURE: Chromosome analysis was based on G-banding. Fluorescence in situ hybridization technique was applied using IGH/MYC/CEP8 dual-fusion and MYC break-apart probes. Multicolor chromosome banding was performed according to standard protocol. RESULTS: We describe a group of BL/L with extreme adverse clinical outcome, in which secondary chromosomal abnormalities, particularly those involving the long arms of chromosomes 1 and 13, were found in 71% of cases. The IGH/MYC fusion showed molecular heterogeneity in 14% of cases and two cases exhibited three IGH/MYC fusion signals. CONCLUSIONS: Secondary chromosomal abnormalities were found in a high proportion of patients. We observed an extent of IGH/MYC heterogeneity not previously reported in Burkitt lymphoma, including the novel finding of three fusion signals in two cases.

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.

Burkitt Lymphoma Presenting as Obstructive Jaundice: A Case Report and Literature Review.

Burkitt lymphoma (BL) is an aggressive, high-grade B-cell lymphoma common in children and young adults. Despite being frequently discovered in extranodal sites, BL rarely occurs in the pancreas. We present a case of a patient with BL presenting as obstructive jaundice.

Expression analysis of MYC genes from Tamarix hispida in response to different abiotic stresses.

The MYC genes are a group of transcription factors containing both bHLH and ZIP motifs that play important roles in the regulation of abscisic acid (ABA)-responsive genes. In the present study, to investigate the roles of MYC genes under NaCl, osmotic and ABA stress conditions, nine MYC genes were cloned from Tamarix hispida. Real-time reverse-transcriptase (RT)-PCR showed that all nine MYC genes were expressed in root, stem and leaf tissues, but that the levels of the transcripts of these genes in the various tissues differed notably. The MYC genes were highly induced in the roots in response to ABA, NaCl and osmotic stresses after 3 h; however, in the stem and leaf tissues, MYC genes were highly induced only when exposed to these stresses for 6 h. In addition, most of these MYC genes were highly expressed in roots in comparison with stems and leaves. Furthermore, the MYC genes were more highly induced in roots than in stem and leaf tissues, indicating that these genes may play roles in stress responses mainly in the roots rather than the stems and leaves. The results of this present study suggest that MYCs are involved in salt and osmotic stress tolerances and are controlled by the ABA signal transduction pathway.

Genome-wide identification and expression analysis of the MYC transcription factor family and its response to sulfur stress in cabbage (Brassica oleracea L.).

MYC transcriptional factors are members of the bHLH (basic helix-loop-helix) superfamily, and play important roles in plant growth, biological and abiotic stress. Recent studies have revealed that some MYCs are involved in the synthesis of sulfur-containing secondary metabolites. Cabbage, as a typical sulfur-loving crop and rich in sulfur-containing secondary metabolites, the regulatory relationship between sulfur stress and MYC gene family, related reports are relatively rare. In this study, we conducted the first genome-wide analysis of the MYC transcription factor family of cabbage and identified 17 BoMYC genes. Homology of the 17 BoMYC genes, 12 Arabidopsis, 12 Chinese cabbage, 8 wheat and 21 maize MYC were analyzed using the phylogenetic analysis. Meanwhile, chromosome locations, physical and chemical characteristics, gene structures, conserved motif, cis-element, specific expression in different tissues were studied. Finally, we analyzed the expression of the BoMYC gene under sulfur stress and its GO annotation and KEGG enrichment analysis, determined the expression of the BoMYC gene under hormone treatment and the growth index, photosynthetic capacity and hormone content in the leaves. This study is of great significance for functional identification and revealed the effect of S on BoMYC transcription factors.

Plasmablastic lymphomas show restricted EBV latency profile and MYC gene aberrations.

The pathogenesis of plasmablastic lymphoma (PBL) involves the Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), and MYC gene aberrations. We aimed to determine the EBV latent infection pattern and frequency of MYC gene aberrations in PBLs. Immunohistochemistry was performed using antibodies for EBNA1, EBNA2, and LMP1 while fluorescence in situ hybridization was performed using a MYC probe. The patient cohort comprised 49 adult cases (44 were HIV-positive and three were HIV-negative). Forty-one cases were EBV-positive with 11 EBNA1-positive cases, all cases EBNA2-negative, and four LMP1-positive cases. Latency 0 was determined in 29 cases, latency I in eight cases, and latency II in four cases. The MYC gene was rearranged in eight cases, showed copy number alterations in 11 cases and, no rearrangement in 11 cases. This is the largest cohort of PBLs from South Africa to show a predominantly restricted EBV latency pattern with MYC gene aberrations as a common finding.