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Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours.

Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microarray analysis. CYLD mutant tumours were characterised by an absence of copy-number aberrations apart from LOH chromosome 16q, the genomic location of the CYLD gene. Gene expression profiling of CYLD mutant tumours showed dysregulated tropomyosin kinase (TRK) signalling, with overex

Navigating through novelties concerning mCRC treatment-the role of immunotherapy, chemotherapy, and targeted therapy in mCRC.

Over the course of nearly six decades since the inception of initial trials involving 5-FU in the treatment of mCRC (metastatic colorectal cancer), our progressive comprehension of the pathophysiology, genetics, and surgical techniques related to mCRC has paved the way for the introduction of novel therapeutic modalities. These advancements not only have augmented the overall survival but have also positively impacted the quality of life (QoL) for affected individuals. Despite the remarkable progress made in the last two decades in the development of chemotherapy, immunotherapy, and target the

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… However, left-sided CRC patients with mutations in the homologous recombination repair (HRR) pathway displayed notably prolonged OS compared to right-sided CRCs. … Additionally, mutations in the DDR pathway, including those within the homologous recombination repair (HRR) pathway, didn't significantly correlate with improved OS in MSS CRC patients ( 135 ). …

Targeting mast cells tryptase in tumor microenvironment: a potential antiangiogenetic strategy.

Angiogenesis is a complex process finely regulated by the balance between angiogenesis stimulators and inhibitors. As a result of proangiogenic factors overexpression, it plays a crucial role in cancer development. Although initially mast cells (MCs) role has been defined in hypersensitivity reactions and in immunity, it has been discovered that MCs have a crucial interplay on the regulatory function between inflammatory and tumor cells through the release of classical proangiogenic factors (e.g., vascular endothelial growth factor) and nonclassical proangiogenic mediators granule-associated (

Waldenström macroglobulinemia: clinical and immunological aspects, natural history, cell of origin, and emerging mouse models.

Waldenström macroglobulinemia (WM) is a rare and currently incurable neoplasm of IgM-expressing B-lymphocytes that is characterized by the occurrence of a monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of the hematopoietic bone marrow with malignant lymphoplasmacytic cells. The symptoms of patients with WM can be attributed to the extent and tissue sites of tumor cell infiltration and the magnitude and immunological specificity of the paraprotein. WM presents fascinating clues on neoplastic B-cell development, including the recent discovery of a specific gain-of-function

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention.

The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstre

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… BRAC2 interacts with the RAD51 recombinase to stimulate strand invasion which is a critical step in homologous recombination. For RAD51 to bind the DNA double-strand breaks, a complex of BRCA1/partner and localizer of BRCA2 (PALB2)/BRCA2 is required [ 31 ]. …

Genomic innovations in cancer prevention, diagnosis, prognosis and precision therapeutics.

Cancer research has undergone a transformative change with the advent of high-throughput genomic technologies. Advances in next-generation sequencing accelerated the identification of somatic and germline alterations that drive tumorigenesis enabling the transition from traditional histology-based cancer classification to molecularly informed precision oncology. Large-scale sequencing initiatives and clinical genomic profiling facilitated the development of companion diagnostic assays and targeted therapies. Beyond targeted therapies, genomic innovations have also catalyzed the emergence of no

Kinase Inhibitors and Ovarian Cancer.

Ovarian cancer is fifth in the rankings of cancer deaths among women, and accounts for more deaths than any other gynecological malignancy. Despite some improvement in overall-(OS) and progression-free survival (PFS) following surgery and first-line chemotherapy, there is a need for development of novel and more effective therapeutic strategies. In this mini review, we provide a summary of the current landscape of the clinical use of tyrosine kinase inhibitors (TKIs) and mechanistic target of rapamycin (mTOR) inhibitors in ovarian cancer. Emerging data from phase I and II trials reveals that a

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… Emerging evidence suggests that AAs can drive downregulation of genes implicated in homologous recombination (HR) leading to a creation of a HR-deficient state [ 48 , 49 , 50 , 51 ] that can allow a PARP inhibitor to explore further this vulnerability. … Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol. Cell. Biol. 2004;24:8504–8518. doi: 10.1128/MCB.24.19.8504-8518.2004. 50. Chan N., Bristow R.G. …

Feline infectious peritonitis.

The article discusses feline infectious peritonitis (FIP), an important disease frequently seen in veterinary practice. FIP causes many problems to the veterinarian as it can be difficult to definitively diagnose the disease, as there is no effective treatment, and as prophylactic interventions are not very successful. Although intense research has created a lot of new knowledge about this disease in the last years, there are still many unanswered questions. The objective of this article is to review recent knowledge and to increase understanding of the complex pathogenesis of FIP.

Circular RNA SMARCA5 Modulates Epithelial-Mesenchymal Transformation, Proliferation, and Metastasis of Nasopharyngeal Carcinoma Cells via microRNA-582-3p/Phosphatase and Tensin Homolog Axis.

The action mechanism in which circular RNA (circ) SMARCA5 targeted nasopharyngeal carcinoma (NPC) cell proliferation, migration, invasion, and apoptosis via microRNA (miR)-582-3p/phosphatase and tensin homolog (PTEN) axis was explored. The examination was performed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), discovering that circSMARCA5 was elevated while miR-582-3p was silenced in NPC tissues and cells. E-cadherin and N-cadherin were detected. The results illustrated transfection with si-circSMARCA5 or miR-582-3p-mimic was available to repress cancer cell advan

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… PTEN is available to exert a tumor suppressor role via sustaining chromosomal stability and controls DNA repair protein RAD51 to stimulate DNA repair, while silenced PTEN is available to lead to genomic instability and repress homologous recombination [ 42 ]. …

Translational progress on tumor biomarkers.

There is an urgent need to apply basic research achievements to the clinic. In particular, mechanistic studies should be developed by bench researchers, depending upon clinical demands, in order to improve the survival and quality of life of cancer patients. To date, translational medicine has been addressed in cancer biology, particularly in the identification and characterization of novel tumor biomarkers. This review focuses on the recent achievements and clinical application prospects in tumor biomarkers based on translational medicine.

Molecular chess? Hallmarks of anti-cancer drug resistance.

BackgroundThe development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years.ReviewResistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered prolife

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… Liu FW Tewari KS New Targeted Agents in Gynecologic Cancers: Synthetic Lethality, Homologous Recombination Deficiency, and PARP Inhibitors Curr Treat Options Oncol 2016 17 3 12 10.1007/s11864-015-0378-9 26931795 PMC5927601 59. …

XTP8 Promotes Ovarian Cancer Progression by Activating AKT/AMPK/mTOR Pathway to Regulate EMT.

Ovarian cancer (OC) ranks as the fifth leading cause of cancer-related death in women. The main contributors to the poor prognosis of ovarian cancer are the high rates of recurrence and metastasis. Studies have indicated a crucial role for hepatitis B virus X Ag-Transactivated Protein 8 (XTP8), a protein containing the DEP domain, in various cellular processes, including cell growth, movement, and differentiation, across several types of cancers. However, the role of XTP8 in ovarian cancer remains unclear. We observed elevated expression of XTP8 in ovarian cancer. Silencing XTP8 inhibited cell

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… Targeted therapy tailored to the patient’s Homologous Recombination Deficiency (HRD) status may also be administered. Despite these interventions, approximately 80% of patients experience recurrence within 5 years. …

Thrombopoietin Receptor Agonists: Can These Be the Future Answer to the Deadly Thrombocytopenia in Dengue Fever?

Dengue is considered the most prevalent mosquito-borne viral disease worldwide and sometimes turns out to be life-threatening. Thrombocytopenia is frequently observed in mild and severe cases of dengue. Severe thrombocytopenia, with a platelet count much below the normal range and hemorrhagic manifestation, is considered a fatal consequence of dengue that needs proper and timely management. The development of the dengue vaccine is quite challenging due to the existence of four different serotypes of the virus. Currently, neither a specific antiviral therapy nor a vaccine is available, and the

Революция онкологии: роль искусственного интеллекта (AI) в качестве антителного дизайна и средств оптимизации.

Антитела играют решающую роль в защите человеческого тела от болезней, включая такие опасные для жизни заболевания, как рак. Они оказывают посреднические услуги в связи с иммунной реакцией на иностранные антигены и, в некоторых случаях, на самоантигены. С течением времени антителные технологии эволюционировали от моноклонных антител (mAbs) до химерика антигенных рецепторов Т (клеток CAR-T), оказывая значительное влияние на биотехнологию, диагностику и лечение. Хотя эти достижения способствовали активизации терапевтического вмешательства, интеграция искусственного интеллекта (АИ) революционизир

Developments in Point-of-Care Diagnostic Technology for Cancer Detection.

Cancer is the cause of death for one in seven individuals worldwide. It is widely acknowledged that screening and early diagnosis are of vital importance for improving the likelihood of recovery. However, given the costly, time-consuming, and invasive nature of the many methods currently in use, patients often do not take advantage of the services available to them. Consequently, many researchers are exploring the possibility of developing fast, reliable, and non-invasive diagnostic tools that can be used directly or by local physicians at the point-of-care. Herein, we look at the use of estab

Протеиновый ингибитор смягчает белку в мышах Lmx1b с дисфункциональной доменой LIM.

Мутации в коэффициенте транскрипции LMX1B были определены в качестве причины синдрома автосомали-доминантного заболевания гвозди-пареллы. Он проявляется в небольших или отсутствующих пателле и диспластике или в отсутствии пальцев и ногтей, но прогноз пациентов определяется появлением почечных симптомов из-за дисфункциональных подоцитов. Патогенетические механизмы, ведущие к повреждению подоцита, и их связь с конкретными мутациями в гене LMX1B не понимаются, что препятствует разработке конкретных терапевтических стратегий. Здесь мы идентифицируем патогенетический механизм, затрагивающий многих

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… b Shown are the respective portions of the murine Lmx1b gene after homologous recombination of the targeting construct employed for the generation of the knock-in mice. NeoR , neomycin resistance cassette flanked by FRT sites. …

A PRoliferation-Inducing Ligand (APRIL) in the Pathogenesis of Immunoglobulin A Nephropathy: A Review of the Evidence.

A PRoliferation-Inducing Ligand (APRIL), the thirteenth member of the tumor necrosis factor superfamily, plays a key role in the regulation of activated B cells, the survival of long-lived plasma cells, and immunoglobulin (Ig) isotype class switching. Several lines of evidence have implicated APRIL in the pathogenesis of IgA nephropathy (IgAN). Globally, IgAN is the most common primary glomerulonephritis, and it can progress to end-stage kidney disease; yet, disease-modifying treatments for this condition have historically been lacking. The preliminary data in ongoing clinical trials indicate

Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises.

Different approaches have been utilized or proposed for the treatment of lysosomal storage disorders (LSDs) including enzyme replacement and hematopoietic stem cell transplant therapies, both aiming to compensate for the enzymatic loss of the underlying mutated lysosomal enzymes. However, these approaches have their own limitations and therefore the vast majority of LSDs are either still untreatable or their treatments are inadequate. Missense mutations affecting enzyme stability, folding and cellular trafficking are common in LSDs resulting often in low protein half-life, premature degradatio

Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer.

Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian cancer remains challenging. Diverse tumour biology and extensive heterogeneity in ovarian cancer can limit the translatability of genetic profiling and contribute to a lack of biomarkers of treatment response. This review addresses the barriers in precision medicine for ovarian cancer, including obtaining adequate and representative tissue samples for analysis, developing functional and standardised screening methods, and navigating data infrastructure and management. Ethical concerns relat

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… An exception to this is mutations in the critical homologous recombination (HR) pathway genes BRCA1/2, which are present in only 10–18% of hereditary ovarian cancer cases [ 7 , 8 ]. … PARP inhibitors (PARPi) are approved for treating recurrent, advanced BRCA1/2-mutant high-grade serous ovarian cancer and have shown improved overall survival mainly in patients with germline and somatic BRCA1/2 pathogenic mutations or homologous recombination deficiency (HRD) [ 9 ], highlighting the …

Advances of HDAC inhibitors in tumor therapy: potential applications through immune modulation.

Histone deacetylase inhibitors (HDAC inhibitors, HDACi) have garnered considerable attention due to their potential in treating various types of malignant tumors. Histone deacetylases (HDACs) not only influence chromatin structure and gene transcription by regulating histone acetylation status but also acetylate various non-histone proteins. They are widely involved in several key biological processes, such as cell cycle regulation, apoptosis induction, and immune responses. HDACi exert their effects by inhibiting HDAC activity; however, these effects are highly concentration-dependent and non