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Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma: common cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall.

AIMS: To characterize the clinicopathological and genetic features of pleomorphic mantle cell lymphoma (PMCL), which morphologically mimics diffuse large B cell lymphoma (DLBCL). METHODS AND RESULTS: We screened systematically 500 B cell lymphomas morphologically compatible with DLBCL using an immunohistochemical algorithm of three markers (CD5, cyclin D1 and SOX11). Ten cases of PMCL were identified for further study and, surprisingly, four (40%) of them were cyclin D1-negative. These 10 patients were mainly elderly males with advanced disease, and their median survival was only 11 months. A

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, sensitizes lung cancer cells to treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major challenge to targeted therapy for non-small cell lung cancer (NSCLC). We investigated whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse EGFR-TKI resistance in human lung cancer cells and explored the underlying mechanisms. We found that PD 0332991 potentiated gefitinib-induced growth inhibition in both EGFR-TKI-sensitive (PC-9) and EGFR-TKI-resistant (PC-9/AB2) cells by down-regulating proliferation and inducing apoptosis and G0/G1 cell cycle arrest. Tumor xenogra

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… Cyclins and the catalytic CDKs form active heterodimers to facilitate phosphorylation of pRb at Ser780 and Ser795 sites. … Antibodies and western blotting Anti-E2F1, anti-CDK4, anti-CDK6, anti-CYCLIN-D antibodies were purchased from Santa Cruz Biotechnology (CA, USA). …

KPT-330, a potent and selective exportin-1 (XPO-1) inhibitor, shows antitumor effects modulating the expression of cyclin D1 and survivin [corrected] in prostate cancer models.

BACKGROUND AND AIMS: Increased expression of Chromosome Region Maintenance (CRM-1)/exportin-1 (XPO-1) has been correlated with poor prognosis in several aggressive tumors, making it an interesting therapeutic target. Selective Inhibitor of Nuclear Export (SINE) compounds bind to XPO-1 and block its ability to export cargo proteins. Here, we investigated the effects of a new class of SINE compounds in models of prostate cancer. MATERIAL AND METHODS: We evaluated the expression of XPO-1 in human prostate cancer tissues and cell lines. Next, six SINE (KPT-127, KPT-185, KPT-205, KPT-225, KPT-251

Expression of Cyclin d1 protein and CCND1 та PNKP genes in peripheral blood mononuclear cells in clean up worker of Chornobyl accident with different state of immune system.

OBJECTIVE: to investigate the Cyclin D1+ cells levels changes, associated CCND1 and PNKP genes in peripheral blood mononuclear cells in clean up workers of Chornobyl accident with different state of immune system in depends on the dose irradiation. MATERIAL AND METHODS: Relative level of Cyclin D1+cells in peripheral blood mononuclears of 39 clean up workers, men, irradiated in dose range (0,01-2,00) Gy have been analyzed. Immunological status of examinee' subjects was determined by CD3/19, CD4/8, CD3/HLA DR, СD3/16/56 testing using flow cytometry method and Ig A,M,G testing by immunoenzymati

Polyploid giant cancer cells with budding and the expression of cyclin E, S-phase kinase-associated protein 2, stathmin associated with the grading and metastasis in serous ovarian tumor.

BACKGROUND: We previously reported that polyploid giant cancer cells (PGCCs) exhibit cancer stem cell properties and express cell cycle-related proteins. HEY PGCCs induced by cobalt chloride generated daughter cells and the daughter cells had a strong migratory and invasive ability. This study is to compare the expression of cyclin E, S-phase kinase-associated protein 2 (SKP2), and stathmin between PGCCs with budding and control HEY cells, and determine the clinicopathological significance of cell cycle-related protein expression in ovarian tumors. METHODS: We used western blot and immunocyto

Pathogenic role of the X-linked cyclin-dependent kinase-like 5 and aristaless-related homeobox genes in epileptic encephalopathy of unknown etiology with onset in the first year of life.

Two genes causally involved in refractory epilepsy with mental retardation, cyclin-dependent kinase-like 5 and aristaless-related homeobox, could account for at least some forms of early onset epileptic encephalopathy that still lack etiological explanation. With the aim of investigating the specific pathogenic involvement of the 2 genes, we have conducted a clinical and molecular study in 80 patients with epileptic encephalopathy of unknown etiology and onset within the first year of life, regardless of the presence of other clinical features or the definition of a precise epileptologic syndr

A proliferation-inducing ligand mediates follicular lymphoma B-cell proliferation and cyclin D1 expression through phosphatidylinositol 3-kinase-regulated mammalian target of rapamycin activation.

A proliferation-inducing ligand (APRIL), as well as its receptors transmembrane activator and calcium-modulating cyclophilin ligand (CAML) interactor (TACI) and B-cell maturation antigen (BCMA), has been shown to be important in B-cell biology, and overexpression of APRIL in mice results in development of lymphoma. Limited data are available on APRIL-specific signaling responses, but knockout models suggest that signaling through TACI is critical to B-cell homeostasis. To better understand the mechanism by which APRIL exerts its effects and how it may contribute to lymphomagenesis, we sought t

Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67.

Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature "MCL with focal aggressive form (intermediate MCL)". In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27(Kip1), and p21(WAF/Cip1). The median overall survival was 77, 31, and 18 mont

Delayed administration of a potent cyclin dependent kinase and glycogen synthase kinase 3 beta inhibitor produces long-term neuroprotection in a hypoxia-ischemia model of brain injury.

We compared the neuroprotective efficacy of a potent and CNS-penetrant cyclin dependent kinase (CDK) and glycogen synthase kinase 3 beta (GSK3beta) inhibitor (Compound 1) in juvenile (postnatal day 21; P21) and adult C57Bl/6 mice (postnatal day 60; P60) using a model of hypoxic-ischemic brain injury (HI). Neuronal cell counts and density measures from brain sections stained with Cresyl Violet revealed that exposure of P21 mice to 60 min of HI resulted in extensive damage to the ipsilateral cornu ammonis 1 (CA1) region of the hippocampus (40% cell loss) and striatum (30% cell loss) 7 days later

Deregulation of cyclin D2 by juxtaposition with T-cell receptor alpha/delta locus in t(12;14)(p13;q11)-positive childhood T-cell acute lymphoblastic leukemia.

OBJECTIVES: The t(12;14)(p13;q11)--a recurrent translocation in childhood T-cell acute lymphoblastic leukemia (T-ALL)--has very recently been molecularly characterized in one case, which displayed overexpression of the cyclin D2 gene (CCND2). PATIENTS AND METHODS: We have characterized two pediatric t(12;14)-positive T-ALLs using fluorescence in situ hybridization (FISH), cDNA microarray, and real-time polymerase chain reaction (PCR). RESULTS: FISH revealed breakpoints (BPs) in the T-cell receptor alpha/delta locus (14q11) and in the vicinity of the CCND2 gene at 12p13. To investigate the ex

Expression of potential beta-catenin targets, cyclin D1, c-Jun, c-Myc, E-cadherin, and EGFR in chemically induced hepatocellular neoplasms from B6C3F1 mice.

In this study we used liver neoplasms induced by several chemical carcinogens to investigate potential nuclear targets associated with beta-catenin/Wnt signaling and potential membrane-associated beta-catenin binding partners. Strong expression of cyclin D1, in a pattern similar to that observed previously for beta-catenin, was observed by Western analysis for all five hepatoblastomas examined regardless of treatment. Increased expression of cyclin D1 was also detected in 12 of 35 (34%) hepatocellular neoplasms. Ten of 15 tumors (67%) that had mutations in the Catnb gene had upregulation of cy

Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27(kip1).

In normal T-cell development interleukin-7 (IL-7) functions as an antiapoptotic factor by regulating bcl-2 expression in immature thymocytes and mature T cells. Similar to what occurs in normal immature thymocytes, prevention of spontaneous apoptosis by IL-7 in precursor T-cell acute lymphoblastic leukemia (T-ALL) cells correlates with up-regulation of bcl-2. IL-7 is also implicated in leukemogenesis because IL-7 transgenic mice develop lymphoid malignancies, suggesting that IL-7 may regulate the generation and expansion of malignant cells. This study shows that in the presence of IL-7, T-ALL

Clinical outcomes and toxicity in metastatic breast cancer patients treated with first or second-line cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy in Egypt.

INTRODUCTION: cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are widely used to treat hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). This study aimed to assess the real-world efficacy and tolerability of CDK 4/6i in the Egyptian population. METHODS: prospective observational study for HR+/HER2- MBC treated in the clinical oncology department of Ain Shams University Hospitals, Egypt, between July 2022 and September 2024. RESULTS: sixty-two patients were included (mean age, 53.8 years; range, 29-85). Thirty-one (50%) r

An explorative study on the interaction of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1/ANRIL) gene polymorphism with obesity on periodontitis among Norwegian adults.

Objective ANRIL is a pleiotropic gene with a strong link to periodontitis. ANRIL gene variant rs1537373 is associated with altered CDKN2B gene expression, which is linked to obesity. In this explorative, cross-sectional population-based study, we aimed to investigate the hypothesis that ANRIL (rs1537373) T>G may be associated with periodontitis through interactions, focusing on rs1537373×obesity interaction. Methods Genotyping for ANRIL (rs1537373), and clinical and periodontal examination were performed in 3554 participants (aged 40-93 years, 52% women) from the seventh survey of the Tromsø S

Cancer outcomes in patients eligible for adjuvant cyclin-dependent kinase 4 and 6 inhibitors but spared adjuvant chemotherapy by Oncotype Dx: A multicenter retrospective GBECAM 0520 study.

BackgroundIn pivotal CDK4/6 inhibitor (CDK4/6i) adjuvant trials, most patients received chemotherapy (CT). However, the role of CDK4/6i in patients spared CT by a genomic signature remains unclear. We investigated the proportion of patients without genomic CT indication but eligible for adjuvant abemaciclib or ribociclib, and estimated their potential benefit from CDK4/6i.MethodsThis retrospective, real-world study included patients with T1-T3, N0-N1, HR+/HER2- early breast cancer (eBC) who underwent Oncotype DX (ODX) testing (2005-2024) at nine Brazilian institutions. Genomic CT indication fo

Associations of maternal cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1(CDKAL1) gene variants with adverse pregnancy outcome in Chinese women.

OBJECTIVE: To test associations of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene variants with the risk of adverse pregnancy outcome in Chinese women and whether the association was mediated by occurrence of gestational diabetes mellitus. METHODS: We organized a 1:1 age-matched study nested within a prospective cohort of pregnant women (207 pairs) established in urban Tianjin. Adverse pregnancy outcome was defined as a composite outcome of preterm birth, low birth weight or macrosomia. Logistic regression analyses were used to estimate associations of

Investigating the inhibitory potential of natural bioactive compounds against cyclin-dependent kinase 13: virtual high throughput screening and MD simulation studies to target CDK signaling.

Cyclin-dependent kinase 13 (CDK13) belongs to the cyclin-dependent kinase (CDK) family that is actively involved in transcription regulation and RNA splicing. CDK13 binds with its partner, cyclin K, to regulate several biological processes. CDK13 and cyclin K complex phosphorylates RNA pol II carboxyl-terminal domain (CTD) at several serine residues, creating transcription elongation. The upregulation of the kinase contributes to tumor growth and cell proliferation, and is highly associated with various cancers, including skin, stomach, and ovarian. Thus, it can be considered an efficient ther

Do proton pump inhibitors affect the effectiveness of cyclin-dependent kinase 4/6 inhibitors in advanced HR positive, HER2 negative breast cancer? A meta-analysis.

BACKGROUND: The CDK 4/6 inhibitors, including palbociclib and ribociclib, are the standard first-line treatment for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Proton pump inhibitors are one of the most globally prescribed types of medications as part of the treatment for gastroesophageal reflux and heartburn complaints. Medication interactions have been demonstrated, leading to a decrease in the effectiveness of chemotherapy drugs such as capecitabine and pazopanib. However, their role and interaction with targeted th

A new cyclin-dependent kinase-9 inhibitor A09-003 induces apoptosis in acute myeloid leukemia cells with reduction of myeloid cell leukemia sequence-1 protein.

Acute myeloid leukemia (AML) is the most common type of hematological disease in adults, and has a very poor outcome [1]. Based on its wide range of efficacy in AML models, a small-molecule inhibitor of the anti-apoptotic protein BCL-2, venetoclax (ABT-199/GDC-0199), was developed for clinical trials. However, venetoclax showed limited monotherapy activity [2]. The overexpression of myeloid cell leukemia sequence-1 protein (Mcl-1)-due to mutations in Fms-like tyrosine kinase 3 internal tandem duplication (FLT-3 ITD)-was considered to be the main reason for low efficacy of venetoclax in clinica

A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line.

Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purification of the 95% ethanolic extract of Thymus capitatus. Identification of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non-small cell lung cancer