Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(16)

Опубликована: Июль 13, 2021

PFKP (phosphofructokinase, platelet), the major isoform of PFK1 expressed in T cell acute lymphoblastic leukemia (T-ALL), is predominantly cytoplasm to carry out its glycolytic function. Our study showed that a nucleocytoplasmic shuttling protein with functional nuclear export and localization sequences (NLSs). Cyclin D3/CDK6 facilitated translocation by dimerization exposing NLS induce interaction between importin 9. Nuclear stimulated expression C-X-C chemokine receptor type 4 (CXCR4), regulating homing/infiltration, promote T-ALL invasion, which depended on activity c-Myc. In vivo experiments promoted homing/infiltration into bone marrow, spleen, liver, could be blocked CXCR4 antagonists. Immunohistochemical staining tissues from clinically well-annotated cohort lymphoma/leukemia patients invasive cancers, but not nonmalignant lymph node or reactive hyperplasia. The presence these specimens correlated poor survival malignancy, suggesting potential utility as diagnostic marker.

Язык: Английский

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The Novel Diagnostic Techniques and Biomarkers of Canine Mammary Tumors

Veterinary Sciences, Год журнала: 2022, Номер 9(10), С. 526 - 526

Опубликована: Сен. 26, 2022

Canine mammary tumors (CMTs) are considered a serious clinical problem in older bitches. Due to the high malignancy rate and poor prognosis, an early diagnosis is essential. This article summary of novel diagnostic techniques as well main biomarkers CMTs. So far, CMTs detected only when changes glands clinically visible surgical removal mass recommended treatment. Proper diagnostics CMT especially important they represent very diverse group therefore different treatment approaches may be required. Recently, new options appeared, like cytological grading system or B-mode ultrasound, Doppler technique, contrast-enhanced real-time elastography, which useful pre-surgical evaluation. However, order detect malignancies before macroscopic visible, evaluation serum tissue should considered. Among them, we distinguish markers cell cycle, proliferation, apoptosis, metastatic potential hormone receptors, inflammatory more recent: metabolomic, gene expression, miRNA, transcriptome sequencing markers. The use couple above-mentioned together seems most for neoplastic diseases evaluate response treatment, presence tumor progression, further prognosis. Molecular aspects seem crucial proper understanding tumorigenesis application individual options.

Язык: Английский

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The Renaissance of CDK Inhibitors in Breast Cancer Therapy: An Update on Clinical Trials and Therapy Resistance

Cancers, Год журнала: 2022, Номер 14(21), С. 5388 - 5388

Опубликована: Ноя. 1, 2022

Cyclin-dependent kinases (CDKs) govern cell-cycle checkpoint transitions necessary for cancer cell proliferation. Recent developments have illustrated nuanced important differences between mono CDK inhibitor (CDKI) treatment and the combination therapies of breast cancers. The CDKIs that are currently FDA-approved therapy oral agents selectively inhibit CDK4 CDK6, include palbociclib (Ibrance), ribociclib (Kisqali), abemaciclib (Verzenio). CDKI is effective in hormone receptor positive (HR+), human epidermal growth factor two negative (HER2-) advanced cancers (ABC) malignancies, but remains susceptible due to estrogen progesterone overexpression. Adding a CDK4/6I endocrine increases efficacy delays disease progression. Given side effects CDKI, identifying potential new treatments enhance effectiveness essential. long-term studies with Palbociclib, including PALLAS PENELOPE B, which failed meet their primary endpoints influencing progression-free survival, suggest deeper mechanistic understanding cyclin/CDK functions required. impact on anti-tumor immune response represents an area great promise. resistance arises provides opportunity specific types clinical trials.

Язык: Английский

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Insights on the Biomarker Potential of Exosomal Non-Coding RNAs in Colorectal Cancer: An In Silico Characterization of Related Exosomal lncRNA/circRNA–miRNA–Target Axis

Cells, Год журнала: 2023, Номер 12(7), С. 1081 - 1081

Опубликована: Апрель 4, 2023

Colorectal cancer (CRC) is one of the most common types, ranking third after lung and breast cancers. As such, it demands special attention for better characterization, which may eventually result in development early detection strategies preventive measures. Currently, components bodily fluids, reflect various disease states, are being increasingly researched their biomarker potential. One these circulating extracellular vesicles, namely, exosomes, demonstrated to carry cargo. Of importance, non-coding RNA cargo especially long RNAs (lncRNAs), circular (circRNAs), micro (miRNAs), potentially serve as significant diagnostic prognostic/predictive biomarkers. In this review, we present existing evidence on value exosomal CRC. addition, taking advantage miRNA sponging functionality lncRNAs circRNAs, demonstrate an experimentally validated CRC RNA-regulated target gene axis benefiting from published studies Hence, a set genes pathways downstream lncRNA/circRNA–miRNA–target along with associated Gene Ontology (GO) terms Kyoto Encyclopedia Genes Genomes (KEGG) pathways, collectively characterize shed light significance diagnosis prognosis/prediction.

Язык: Английский

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Immunomodulatory effects of CDK4/6 inhibitors

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2023, Номер 1878(4), С. 188912 - 188912

Опубликована: Май 12, 2023

Язык: Английский

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A comprehensive review on Ellagic acid in breast cancer treatment: From cellular effects to molecular mechanisms of action

Food Science & Nutrition, Год журнала: 2023, Номер 11(12), С. 7458 - 7468

Опубликована: Сен. 18, 2023

Abstract Globally, breast cancer (BC) is the leading cause of cancer‐related deaths in women. Hence, developing a therapeutic plan to overcome disease crucial. Numerous factors such as endogenous hormones and environmental may play role pathophysiology BC. Regarding multi‐modality treatment BC, natural compounds like ellagic acid (EA) received has increased interest antitumor efficacy with lower adverse effects. Based on results this comprehensive review, EA multiple effects BC cells including (1) suppresses growth by arresting cell cycle G0/G1 phase, (2) migration, invasion, metastatic, (3) stimulates apoptosis MCF‐7 via TGF‐β/Smad3 signaling axis, (4) inhibits CDK6 that important regulation, (5) binds ACTN4 induces its degradation ubiquitin‐proteasome pathway, inducing decreased motility invasion cells, (6) PI3K/AKT (7) angiogenesis‐associated activities proliferation (reduces VEGFR‐2 tyrosine kinase activity). In conclusion, exhibits anticancer activity through various molecular mechanisms influence key cellular processes apoptosis, cycle, angiogenesis, metastasis However, further researches are essential fully elucidate targets implications for clinical applications.

Язык: Английский

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Prognostic Potential of Cyclin D1 Expression in Colorectal Cancer

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(2), С. 572 - 572

Опубликована: Янв. 10, 2023

Cyclin D1 is mainly known as an oncogenic driver in cancers, and the dysregulated cyclin D1/cyclin-dependent kinase (CDK) 4/6 axis considered attractive target for cancer therapy. Recent studies have reported that tumors respond to therapeutic interventions targeting altered expression via application of CDK4/6 inhibitor. However, prognostic contributions colorectal (CRC) remain controversial. Herein, we assessed associations between clinicopathological factors, including patients' overall survival (OS) recurrence-free (RFS), 495 surgically resected primary CRCs. We also examined previous High expressions (cyclin D1High) was observed 389 CRC cases (78.6%). D1High consistently predicted better patient OS RFS Based on multivariate analysis, young age patients remained independent prognosticators higher rate, whereas D1High, females, chemotherapy, absence nodal metastasis, lower T-category RFS. commonly overexpressed CRCs, its can be used a favorable indicator with CRCs; this may important predicting responses subsequent inhibitors.

Язык: Английский

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Application of codon usage and context analysis in genes up- or down-regulated in neurodegeneration and cancer to combat comorbidities

Frontiers in Molecular Neuroscience, Год журнала: 2023, Номер 16

Опубликована: Июнь 13, 2023

Neurodegeneration and cancer present in comorbidities with inverse effects due to the expression of genes pathways acting opposition. Identifying studying simultaneously up or downregulated during morbidities helps curb both ailments together.This study examines four genes. Three these (Amyloid Beta Precursor Protein (APP), Cyclin D1 (CCND1), E2 (CCNE2) are upregulated, one protein phosphatase 2 activator (PTPA) is disorders. We investigated molecular patterns, codon usage, usage bias, nucleotide bias third position, preferred codons, pairs, rare context.Parity analysis revealed that T over A, G C suggesting composition plays no role upregulated gene sets mutational forces stronger than ones. Transcript length influenced overall %A AGG exerted strongest influence on sets. Codons ending G/C were for 16 amino acids, glutamic acid-, aspartic leucine-, valine-, phenylalanine-initiated pairs all CTA (Leu), GTA (Val), CAA (Gln), CGT (Arg) underrepresented examined genes.Using advanced editing tools such as CRISPR/Cas any other augmentation technique, recoded may be introduced into human body optimize levels augment neurodegeneration therapeutic regimens simultaneously.

Язык: Английский

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Mellitin peptide quantification in seasonally collected crude bee venom and its anticancer effects on myelogenous K562 human leukaemia cell line

BMC Complementary Medicine and Therapies, Год журнала: 2023, Номер 23(1)

Опубликована: Апрель 25, 2023

Abstract Background Apitherapy is an emerging field in cancer research, particularly developing communities. The potency of Melittin (MEL), a major constituent bee venom accounted for the cytotoxic capacity against cells. It postulated that genotype bees and time collection influences its specific activity certain types cancer. Method Hereby, Jordanian crude (JCBV) was collected during different seasons year, specifically spring, summer autumn investigated vitro antitumour effects. Venom springtime comprised highest quantity MEL comparison to some other time. Springtime-collected JCBV extract were tested on immortal myelogenous leukaemia cell line, namely K562 leukemic Treated cells examined modality via flow cytometry analysis death mediating gene expressions. Results showed IC 50 3.7 ± 0.37 μg/ml 1.84 0.75 μg/ml, respectively. In positive control, MEL-treated exhibited late apoptotic with moderate cellular arrest at G0/G1 increase number G2/M phase. Expression NF-κB/MAPK14 axis inhibited JCBV-treated cells, as well expression c-MYC CDK4. Moreover, marked upregulation ABL1, JUN TNF observed. conclusion, springtime-collected content while both pure apoptotic, necrotic, cycle efficiency Conclusion Integration chemotherapy needs more investigation should be carefully translated into clinical use. During such translation, correlation genotype, concentration CBV profiled.

Язык: Английский

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D-Type Cyclins in Development and Disease

Genes, Год журнала: 2023, Номер 14(7), С. 1445 - 1445

Опубликована: Июль 14, 2023

D-type cyclins encode G1/S cell cycle checkpoint proteins, which play a crucial role in defining exit and progression. Precise control of is vital during embryonic development, with defects the pathways regulating intracellular resulting abnormal initiation stem differentiation variety different organ systems. Furthermore, stabilisation observed wide range disorders characterized by cellular over-proliferation, including cancers overgrowth disorders. In this review, we will summarize compare roles played each cyclin development provide examples how their dysregulation can be an underlying cause disease.

Язык: Английский

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