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TACC3, correlated with immune cell infiltrates, is a novel prognostic biomarker in BRCA.

Transforming acidic coiled-coil-containing protein 3 (TACC3) plays a crucial oncogenic role in various carcinomas and may act as a novel prognostic factor. However, its prognostic significance and underlying mechanisms in breast cancer (BRCA) remain unclear and require further investigation. This research included 181 breast cancer tissues, and the expression levels of TACC3 were analyzed by immunohistochemistry staining and grading. The mRNA expression of TACC3 in pan-cancer was analyzed with The Cancer Genome Atlas data platform. Receiver operating characteristic curve analysis assessed TACC

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… In the biological processes category, the results indicated that DEGs were significantly enriched in pathways related to chromosome segregation, mitotic cell cycle phase transition, DNA recombination, and noncoding RNA processing, all of which showed positive correlations with TACC3. … According to the results from GO and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, the associated proteins play key roles in a series of biological processes, including organelle fission, nuclear division, mitotic sister chromatid segregation, mitotic nuclear division, chromosome segregation …

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma.

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub

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… As shown in Figure 2(a-e ), GO enrichment analysis demonstrated that for biological process, differentially expressed genes were significantly enriched in organelle fission, nuclear division, light stimulus, and chromosome segregation, which are critical for the mitotic cell cycle. … Enhanced genomic instabilities caused by deregulated microtubule dynamics and chromosome segregation: a perspective from genetic studies in mice. Carcinogenesis. 2009;30(9):1469–1474. [71] Hao X, Qu T. Expression of CENPE and its prognostic role in non-small cell lung cancer. …

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

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… Microtubules are formed during interphase and are vital for correct chromosome segregation and cell division undergoing mitosis [ 16 ]. … Spindle assembly Accurate chromosome segregation during mitosis is ensured by feedback control via the spindle assembly checkpoint [ 31 ]. …

Second-Generation Antimitotics in Cancer Clinical Trials.

Mitosis represents a promising target to block cancer cell proliferation. Classical antimitotics, mainly microtubule-targeting agents (MTAs), such as taxanes and vinca alkaloids, are amongst the most successful anticancer drugs. By disrupting microtubules, they activate the spindle assembly checkpoint (SAC), which induces a prolonged delay in mitosis, expected to induce cell death. However, resistance, toxicity, and slippage limit the MTA's effectiveness. With the desire to overcome some of the MTA's limitations, mitotic and SAC components have attracted great interest as promising microtubule

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… A successful mitosis relies on equal chromosome segregation at the transition from metaphase to anaphase. Kinetochore–microtubule attachment defects lead to the missegregation of chromosomes resulting in genome instability, a hallmark of cancer [ 2 , 3 ]. … Fortunately, the fidelity of chromosome segregation is ensured by the spindle assembly checkpoint (SAC) ( Figure 2 ). The SAC consists of a protein network that delays the anaphase in the presence of erroneous kinetochore–microtubule attachments or the absence of attachments [ 4 ]. …

Beyond Darwin: reactive heredity, burst-drift dynamics and eco‑evolutionary control of cancer.

Darwinian clonal evolution provides a necessary framework for understanding tumour progression, yet emerging evidence shows that some cancers depart from a strictly gradualist tempo through episodic "macroevolutionary" leaps. We propose a unifying Burst-Drift-Control (BDC) model in which short-lived genomic reconfigurations ("bursts") that transiently alter heritable genomic states ("reactive heredity") precede longer intervals of constrained expansion, creating time-bounded vulnerabilities that clinicians may strategically steer ("control"). In this usage, the Drift component refers specifica

Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: e-Posters.

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Pediatric Acute Lymphoblastic Leukemia Emerging Therapies-From Pathway to Target.

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75-80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recog

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… Aurora A overexpression causes centrosome overgrowth, multipolar spindle formation, uneven chromosomal segregation, and aneuploidy, being involved in chromosomal instability and transformation of cancer cells from mitotically active cells [ 38 ]. p53 , BRCA1/2 , and RASSF1A (Ras association domain-containing … Chromosome segregation, spindle assembly checkpoint activation, maintaining genome integrity, and consequently normal cell division are all compromised by the Aurora B mutation [ 43 , 47 ]. …

Резюме докладов 53rd Конференция Европейского общества генетики человека: интерактивные электронные постеры.

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HMMR in human cancers: regulatory mechanism and biological function.

Hyaluronan-mediated motility receptor (HMMR), also referred to as RHAMM or CD168, has gained recognition as a multifunctional protein that mediates the transmission of extracellular matrix-derived hyaluronan (HA) signals to intracellular pathways regulating tumor growth, migration, and mitosis. Overexpression of HMMR is observed in various cancers, including head and neck squamous cell carcinoma, breast cancer, lung cancer, and prostate cancer, as well as several hematologic malignancies. This elevated expression correlates with poor prognosis, rendering it a valuable marker for survival predi

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… By attenuating hyperactive HMMR function, the BRCA1/BARD1 complex ensures the proper localization of TPX2 at spindle poles downstream of the Ran-GTP pathway, thereby maintaining spindle integrity and promoting accurate chromosome segregation [ 74 ]. … The nonmotor adaptor HMMR dampens Eg5-mediated forces to preserve the kinetics and integrity of chromosome segregation. Mol Biol Of The Cell. 2018;29:786–96. 10.1091/mbc.E17-08-0531. 49. He Z, Mei L, Connell M, Maxwell CA. …

Резюме докладов 51st Конференция Европейского общества генетики человека: плакаты

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Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain‑containing protein 4) is a chromatin‑associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, mi

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… Likewise, BRD4 controls the levels of Aurora B which is concentrated around the sites of attachment of chromosomes to spindle microtubules such as the centromeres or kinetochores and allows for chromosome segregation to occur appropriately ( 21 ). …

Автосоматический синдром снотворного синдрома спящей апноэ из-за нового варианта c.980_984dup в COL1A2: A Case Report.

Осложненный синдром апноэ (OSAS) — сложное расстройство, характеризующееся коллапсом верхних дыхательных путей во время сна. Хотя история семьи часто свидетельствует о наследственной предрасположенности к ОСУС, нет никаких доказательств того, что это на самом деле моногенное расстройство. До настоящего времени не было описано ни одного случая, когда пациент с наследственным OSA из-за патогенной мутации в цепи коллагенов типа I альфа-2 (COL1A2). Пациенткой была 72-летняя женщина, которая страдала бессонницей с 35 лет. С тех пор ОСУС подозревалось, но было подтверждено только в возрасте 67 лет п

Proceedings of the CIMAGO Meeting - Challenges in Oncobiology Coimbra, 31st january 2020.

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… Errors during cell division and chromosome segregation generate genetic variability, with changes in chromosome content and, consequently, changes in the relative gene dosage. They are the primary cause of birth defects and infertility and also have important implications in oncogenesis. …

Prognostic heterogeneity and clonal dynamics within distinct subgroups of myelodysplastic syndrome and acute myeloid leukemia with TP53 disruptions.

TP53 aberrations constitute the highest risk subset of myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The International Consensus Classification questions the blast threshold between MDS and AML. In this study, we assess the distinction between MDS and AML for 76 patients with TP53 aberrations. We observed no significant differences between MDS and AML regarding TP53 genomics. Median overall survival (OS) was 223 days for the entire group, but prognostic discrimination within subgroups showed the most inferior OS (46 days) for AML with multihit allelic state plus TP53 varian

Abstracts of the 12th European Cytogenomics Conference 2019 : Salzburg, Austria. 6-9 July 2019

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Association of coronary artery disease related single nucleotide-polymorphisms with extreme Prakriti types: Insights from a case control study.

BACKGROUND: Coronary artery disease has well-established genetic variants but identification of susceptible ones is needed. Ayurveda stratifies people phenotypically termed as "Prakriti" to assess the risk. OBJECTIVES: The present research was aimed to identify Prakriti stratified genetic risks for CAD. MATERIAL AND METHODS: Initially, literature search was done using bioinformatics and manual-curation, to identify susceptible SNPs. Further, global-screening-array was performed to evaluate association of these polymorphisms in Prakriti stratified 200 CAD patients and 100 healthy controls. Th

Health Equity Among Black Women in the United States.

Black women in the United States have experienced substantial improvements in health during the last century, yet health disparities persist. These health disparities are in large part a reflection of the inequalities experienced by Black women on a host of social and economic measures. In this paper, we examine the structural contributors to social and economic conditions that create the landscape for persistent health inequities among Black women. Demographic measures related to the health status and health (in)equity of Black women are reviewed. Current rates of specific physical and mental

Acute myeloid leukemia synchronous with multiple myeloma successfully treated by azacytidine/lenalidomide and daratumumab without a decrease in myeloid clone size.

Synchronous diagnosis of acute myeloid leukemia (AML) and symptomatic multiple myeloma (MM) is a rare situation that poses serious therapeutic difficulties. We report the case of a 68-year-old male which evolved simultaneously to symptomatic MM and AML. Both diseases first responded to treatment for 40 months after 7+3 induction and maintenance therapy of azacytidine + lenalidomide. MM relapsed first and was treated with azacytidine + daratumumab, which led an additional 15 months of progression-free survival. Little myeloid clonal size reduction over time was seen. This case shows that AML an

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]).

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outc

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… Alterations in the cell cycle due to TTFields result in abnormal chromosomal segregation, micronucleation, alterations in the duration of various mitotic phases, and decrease in cellular proliferation ( Kirson et al., 2007 ; Gera et al., 2015 ; Giladi et al., 2016 ; Kim et al., 2016 , 2019 ; Voloshin … Mitotic spindle disruption by alternating electric fields leads to improper chromosome segregation and mitotic catastrophe in cancer cells. Sci. Rep. 5, 18046. Giladi M., Weinberg U., Schneiderman R.S.et al. (2014b). …

Double jeopardy: how BRCA2, TP53, and DNMT3A redefine the link between infertility and cancer risk.

BackgroundGermline mutations in genes governing DNA repair, cell cycle regulation, and epigenetic modification are now recognized as common etiological factors for both cancer predisposition and reproductive dysfunction. This reveals a profound intersection between reproductive biology and oncogenesis.MethodA systematic narrative review was conducted. The literature search spanned PubMed/MEDLINE, Scopus, and Web of Science using keywords and MeSH terms related to infertility phenotypes, cancer predisposition syndromes, and shared molecular mechanisms (e.g., DNA repair, epigenetics).OutcomesThe

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… This dual pathology arises because CHEK2 phosphorylates both meiotic cohesins (required for chromosome segregation) and somatic tumor suppressors like BRCA1 ( Stolz et al., 2010 ). … Meiotic Crossover: During prophase I of meiosis, MLH1-MLH3 foci mark crossover sites (chiasmata), ensuring proper chromosome segregation. Loss of MLH1 or MSH5 disrupts this process, causing aneuploid gametes. …