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The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy.

(1) Background: Small ubiquitin-like modifiers (SUMOs) are pivotal in post-translational modifications, influencing various cellular processes, such as protein localization, stability, and genome integrity. (2) Methods: This review explores the SUMO family, including its isoforms and catalytic cycle, highlighting their significance in regulating key biological functions in thyroid cancer. We discuss the multifaceted roles of SUMOylation in DNA repair mechanisms, protein stability, and the modulation of receptor activities, particularly in the context of thyroid cancer. (3) Results: The aberran

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… Two primary pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are used by cells to repair the most severe form of DNA damage known as double-strand breaks (DSBs). … The deSUMOylase SENP2 coordinates homologous recombination and nonhomologous end joining by independent mechanisms. Genes. Dev. 2019;33:333–347. doi: 10.1101/gad.321125.118. 131. Wang Q., Xia N., Li T., Xu Y., Zou Y., Zuo Y., Fan Q., Bawa-Khalfe T., Yeh E.T., Cheng J. …

Replacement of miR-155 Elicits Tumor Suppressive Activity and Antagonizes Bortezomib Resistance in Multiple Myeloma.

Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given th

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… In MM cells, we previously demonstrated that bortezomib treatment induces a “BRCAness” status which leads to the repression of genes involved in homologous recombination, including BRCA1 [ 49 ]. … Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation Proc. Natl. Acad. Sci. USA 2014 111 4536 4541 10.1073/pnas.1402604111 24616504 PMC3970505 36. Wang J. Yu F. Jia X. Iwanowycz S. Wang Y. Huang S. Ai W. Fan D. …

Риски гематологических обледенений у пациентов, прошедших лечение от твердых опухолей, связанных с использованием пегилизованных гранулоцитов-стимулирующих факторов: 2005.

Широкое применение пегилизованных гранулоцитов (PGCS), в частности pegfilgrastim и липегфилграстим, в целях сокращения числа случаев нейтрализации женских половых органов у пациентов, проходящих химиотерапию. Вместе с тем по-прежнему сохраняется озабоченность по поводу долгосрочной безопасности ПХГФ, в частности по поводу риска вторичных гематологических заболеваний. Цель настоящего исследования заключалась в оценке распространенности вторичных гематологических заболеваний у пациентов, которые лечились от твердых опухолей с помощью PGCSF в одном учреждении 2005 в адрес 2019. Ретроспективный ан

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… PALB2 is a tumour suppressor gene that works as a crucial partner for the BRCA2 protein, helping to localize it and facilitate its essential function in DNA double-strand break repair via homologous recombination ( 32 ). … Leuk Lymphoma 60 1823 1826 2019 10.1080/10428194.2018.1551539 30614742 32 Sy SM Huen MS Chen J PALB2 is an integral component of the BRCA complex required for homologous recombination repair Proc Natl Acad Sci USA 106 7155 7160 2009 10.1073/pnas.0811159106 19369211 PMC2678481 …

Ubiquitin-specific peptidases in lymphoma: a path to novel therapeutics.

BackgroundUbiquitin-specific peptidases (USPs), also known as deubiquitinating enzymes (DUBs), play a crucial role in maintaining cellular homeostasis by selectively removing ubiquitin molecules from targeted proteins. This process affects protein stability, subcellular localization, and activity, thereby influencing processes such as DNA repair, cell cycle regulation, and apoptosis. Abnormal USP activities have been linked to various diseases, including cancer. Emerging evidence in lymphoma studies highlights the significance of USPs in controlling signaling pathways related to cancer initiat

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… . | N/A | Wei et al. (2016) 3.1.1 USPs regulate cell cycle progression by regulating cycle-related factors USP2 stabilizes cyclin D1, which participates in homologous recombination (HR)-mediated DNA repair. In numerous cell types, it promotes cell-cycle progression from G1 to S. … homologous recombination. Ak strain transforming. mouse double minute 2 homolog. human double minute 2. …

Hallmarks of Cancer Affected by the MIF Cytokine Family.

New diagnostic methods and treatments have significantly decreased the mortality rates of cancer patients, but further improvements are warranted based on the identification of novel tumor-promoting molecules that can serve as therapeutic targets. The macrophage migration inhibitory factor (MIF) family of cytokines, comprising MIF and DDT (also known as MIF2), are overexpressed in almost all cancer types, and their high expressions are related to a worse prognosis for the patients. MIF is involved in 9 of the 10 hallmarks of cancer, and its inhibition by antibodies, nanobodies, or small synthe

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

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… Early cytogenetic studies of inversions suggested that non-allelic homologous recombination (NAHR) between inverted repeats at both breakpoints could be the underlying mechanism of formation and the prevalence of NAHR-mediated inversions has been estimated to 67%. …

Design and Preclinical Validation of an Anti-B7-H3-Specific Radiotracer: A Non-Invasive Imaging Tool to Guide B7-H3-Targeted Therapies.

Background: B7-H3, an immunoregulatory protein of the B7 family, has been associated with both anti-cancer immunity and tumor promotion, with its expression commonly correlated with poor prognosis. Although it is frequently expressed across cancers, its heterogeneity may limit the effectiveness of B7-H3-targeted therapies. Consequently, a sensitive and non-invasive method is needed to assess B7-H3 expression for patient selection and stratification. Single-domain antibody fragments (sdAbs) offer a promising platform for developing such a diagnostic tool. Methods: To generate B7-H3 sdAbs, two I

An Analysis Regarding the Association Between Proteasome (PSM) and Hepatocellular Carcinoma (HCC).

BackgroundThe Proteasome (PSM) is a large multi-catalytic protease complex consisting of a 20S core particle and a 19S regulatory particle whose main function is to accept and degrade ubiquitinated substrates, are now considered as one of the potential regulators of tumor proliferation, and stemness maintenance. However, to date, studies on the relationship between PSM and hepatocellular carcinoma (HCC) are limited.MethodsThis study used a bioinformatics approach combining validation experiments to investigate the biological mechanisms that may be related with PSM. A series of experiments in v

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… PSM Correlated with Cancer DNA Repair and Stemness The stability of the cancer genome is largely dependent on the repair of DNA through different mechanisms, including DNA Mismatch Repair (MMR) and Homologous Recombination Repair (HRR), which also contribute to the maintenance of stemness in cancer … Figure 6 PSM correlated with cancer DNA repair and stemness. ( A – C ) Dot plots demonstrate the expression distribution of homologous recombination repair (HRR) signature ( A ), mismatch repair (MMR) ( B ) signature and PSM molecules ( C ) in GSE166635 . ( D – F ) Violin plots demonstrate the expression …

Genome Instability in Multiple Myeloma: Facts and Factors.

Multiple myeloma (MM) is a malignant neoplasm of terminally differentiated immunoglobulin-producing B lymphocytes called plasma cells. MM is the second most common hematologic malignancy, and it poses a heavy economic and social burden because it remains incurable and confers a profound disability to patients. Despite current progress in MM treatment, the disease invariably recurs, even after the transplantation of autologous hematopoietic stem cells (ASCT). Biological processes leading to a pathological myeloma clone and the mechanisms of further evolution of the disease are far from complete

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… The DNA double-strand breaks (DSBs) interrupt the continuity of the DNA molecule and are repaired via two major repair routes: homologous recombination repair (HRR) and nonhomologous end-joining (NHEJ) [ 155 ]. …

Chronic Liver Disease Associated Cholangiocarcinoma: Genomic Insights and Precision Therapeutic Strategies.

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy arising from the biliary epithelium, with an increasing incidence and poor prognosis worldwide. Recent advances in next-generation sequencing have revealed a variety of genomic alterations-such as FGFR2 fusions, IDH1 mutations, and ERBB2 amplification-that may serve as therapeutic targets. However, the influence of underlying etiologic factors, including chronic liver and biliary diseases, on the molecular landscape of CCA remains unclear. Objective: This review aimed to synthesize the current knowledge on the genomic an

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… As key components of the homologous recombination repair pathway, they promote error-free repair of DNA double-strand breaks, thereby maintaining genomic stability [ 107 ]. … Loss-of-function mutations in BRCA1/2 result in homologous recombination deficiency, leading to genomic instability and a significantly increased risk of developing cancers, particularly breast, ovarian, pancreatic, and prostate cancers. …

Checking NEKs: Overcoming a Bottleneck in Human Diseases.

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as th

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… Another study highlighted the role of NEK8 in genomic stability through replication fork protection and homologous recombination (HR) [ 184 ]. … NEK8 has been shown to perform these protective functions by regulating RAD51, an essential factor for homologous recombination and replication fork protection. …

Vaccines against human carcinomas: strategies to improve antitumor immune responses.

Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultim

Многоступенчатые ассоциации патогенеза и болезней Mycobacterium avium подраздел паратуберкулез.

Mycobacterium avium subsp. паратуберкулез (MAP) является основным агентом причинно-следственной связи болезни Джона (JD) в румынках и имеет потенциальные последствия для здоровья населения. Совокупные эпидемиологические и молекулярные данные предполагают, что MAP может способствовать болезни Крона (CD), в то время как его связь с множественным склерозом (MS), тип 1 Болелезный диабет (T1DM) и амиотропический боковой склероз (ALS) остаются ассоциативными без подтвержденной причинно-следственной связи. В настоящем описательном обзоре синтезируются данные о распределении по окружающей среде, генот

Реальное воздействие NVX-CoV2373 COVID-19 вакцина для иммунокомпромиссных людей в Южной Корее.

BackgroundNVX-CoV2373 - наночастица, белковая COVID-19 вакцина. Лица, страдающие от иммунокомпрометированных заболеваний, подвергаются высокому риску инфицирования и серьезных заболеваний; однако в реальном мире NVX-CoV2373 Цель настоящего исследования состояла в том, чтобы оценить, являются ли данные о воздействии в МКС ограниченными. NVX-CoV2373 снижение риска SARS-CoV-2 :: инфекция и серьезные заболевания в ИМС по сравнению с лицами, не имеющими иммунокомпромиссных свойств (не связанными с ИС). Южнокорейский МКС в возрасте ≥12 лет, которые получили первичную серию, третью дозу или четвертую

The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resi

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… DNA damage is mainly repaired by five pathways: homologous recombination (HR), nucleotide excision repair (NER), non-homologous end joining (NHEJ), base excision repair (BER) and mismatch repair (MMR) [ 86 ]. … NEAT1 promotes chemotherapeutic resistance in cancer mainly by enhancing the homologous recombination ability of cancer cells. …

IL-6/IL-12 суперсемейство цитокинов и регламентируемых лимфоцитов играет важнейшую роль в этиологии и борьбе с аутоиммунными заболеваниями CNS.

Цитокины влияют на решения наивных лимфоцитов о клеточной порче и определяют исход иммунной реакции путем подачи сигналов, регулирующих инициирование, интенсивность и продолжительность иммунной реакции. Вместе с тем аномальное регулирование физиологических уровней цитокина способствует развитию аутоиммунных и других подстрекательских заболеваний. Сверхсемейство цитокинов Interleukin 6 (IL-6)/IL-12 оказывает глубокое влияние на все аспекты иммунитета хостинга, и в ходе этого обзора мы уделяем особое внимание сигнальным путям, которые способствуют выполнению их функций, с уделением особого внима

Recent advances in precision oncology research.

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… These inhibitors are especially effective against cancer cells exhibiting gene mutations that are critical in the process of homologous recombination, a process that is crucial for repairing double-stranded DNA breaks. … Niraparib is used as a maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer who are in response to platinum-based chemotherapy, regardless of BRCA or tumor homologous recombination status. …

Cancer immunotherapies: A hope for the uncurable?

The use of cancer immunotherapies is not novel but has been used over the decades in the clinic. Only recently have we found the true potential of stimulating an anti-tumor response after the breakthrough of checkpoint inhibitors. Cancer immunotherapies have become the first line treatment for many malignancies at various stages. Nevertheless, the clinical results in terms of overall survival and progression free survival were not as anticipated. Majority of cancer patients do not respond to immunotherapies and the reasons differ. Hence, further improvements for cancer immunotherapies are cruc

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… This shuttle plasmid is then transfected into HEK293 cells with an adenovirus vector for homologous recombination to occur and create an adenovirus genome incorporating the GOI. … A separate cloning method is the use of shuttle vector containing a 5′-ITR, a packaging signal and sequence of homologous recombination flanking a kanamycin resistance gene. …

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

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… Cells have evolved two major pathways to repair DSBs, non-homologous-end joining (NHEJ), and homologous recombination. … Conservative homologous recombination preferentially repairs DNA double-strand breaks in the S phase of the cell cycle in human cells. Nucleic Acids Res (2004) 32(12):3683–8. 10.1093/nar/gkh703 42. Khanna KK, Lavin MF, Jackson SP, Mulhern TD. …

HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders.

Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient's quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloi