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Cancers Jun 2024A prospective observational study was conducted in a cohort of older adults ≥65 years ( = 329), admitted to the acute medical unit (AMU) of a tertiary hospital, to...
A prospective observational study was conducted in a cohort of older adults ≥65 years ( = 329), admitted to the acute medical unit (AMU) of a tertiary hospital, to describe and compare characteristics including frailty status and clinical outcomes. Multivariable models compared older adults with and without a history of cancer to determine characteristics associated with frailty and pre-frailty. An adjusted Poisson regression model was used to compare the length of hospital stay (LOS) between the two groups. About one-fifth (22%) of the cohort had a history of cancer. The most common cancer types were prostate ( = 20), breast ( = 13), lung ( = 8) and gastrointestinal ( = 8). There was no difference in the prevalence of pre-frailty/frailty among patients with or without a history of cancer (58% vs. 57%, > 0.05). Pre-frailty/frailty was associated with polypharmacy (OR 8.26, 95% CI: 1.74 to 39.2) and malnutrition (OR 8.91, 95% CI: 2.15 to 36.9) in patients with a history of cancer. Adjusted analysis revealed that the risk of having a longer LOS was 24% higher in older adults with a history of cancer than those without (IRR 1.24, 95% CI 1.10 to 1.41, < 0.001). Clinicians in the AMU should be aware that older adults with a history of cancer have a higher risk of a longer LOS compared to those without.
PubMed: 38927918
DOI: 10.3390/cancers16122212 -
Cancers Jun 2024The therapeutic potential of cold physical gas plasma operated at atmospheric pressure in oncology has been thoroughly demonstrated in numerous preclinical studies. The...
The therapeutic potential of cold physical gas plasma operated at atmospheric pressure in oncology has been thoroughly demonstrated in numerous preclinical studies. The cytotoxic effect on malignant cells has been attributed mainly to biologically active plasma-generated compounds, namely, reactive oxygen and nitrogen species. The intracellular accumulation of reactive oxygen and nitrogen species interferes strongly with the antioxidant defense system of malignant cells, activating multiple signaling cascades and inevitably leading to oxidative stress-induced cell death. This study aims to determine whether plasma-induced cancer cell death operates through a universal molecular mechanism that is independent of the cancer cell type. Using whole transcriptome data, we sought to investigate the activation mechanism of plasma-treated samples in patient-derived prostate cell cultures, melanoma, breast, lymphoma, and lung cancer cells. The results from the standardized single-cohort gene expression analysis and parallel multi-cohort meta-analysis strongly indicate that plasma treatment globally induces cancer cell death through immune-mediated mechanisms, such as interleukin signaling, Toll-like receptor cascades, and MyD88 activation leading to pro-inflammatory cytokine release and tumor antigen presentation.
PubMed: 38927892
DOI: 10.3390/cancers16122186 -
Cancers Jun 2024The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk...
A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.
The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.
PubMed: 38927884
DOI: 10.3390/cancers16122178 -
Cancers Jun 2024G9a, also named EHMT2, is a histone 3 lysine 9 (H3K9) methyltransferase responsible for catalyzing H3K9 mono- and dimethylation (H3K9me1 and H3K9me2). G9a contributes to... (Review)
Review
G9a, also named EHMT2, is a histone 3 lysine 9 (H3K9) methyltransferase responsible for catalyzing H3K9 mono- and dimethylation (H3K9me1 and H3K9me2). G9a contributes to various aspects of embryonic development and tissue differentiation through epigenetic regulation. Furthermore, the aberrant expression of G9a is frequently observed in various tumors, particularly in prostate cancer, where it contributes to cancer pathogenesis and progression. This review highlights the critical role of G9a in multiple cancer-related processes, such as epigenetic dysregulation, tumor suppressor gene silencing, cancer lineage plasticity, hypoxia adaption, and cancer progression. Despite the increased research on G9a in prostate cancer, there are still significant gaps, particularly in understanding its interactions within the tumor microenvironment and its broader epigenetic effects. Furthermore, this review discusses the recent advancements in G9a inhibitors, including the development of dual-target inhibitors that target G9a along with other epigenetic factors such as EZH2 and HDAC. It aims to bring together the existing knowledge, identify gaps in the current research, and suggest future directions for research and treatment strategies.
PubMed: 38927881
DOI: 10.3390/cancers16122175 -
Bioengineering (Basel, Switzerland) Jun 2024Prostate cancer is a significant health concern with high mortality rates and substantial economic impact. Early detection plays a crucial role in improving patient...
Prostate cancer is a significant health concern with high mortality rates and substantial economic impact. Early detection plays a crucial role in improving patient outcomes. This study introduces a non-invasive computer-aided diagnosis (CAD) system that leverages intravoxel incoherent motion (IVIM) parameters for the detection and diagnosis of prostate cancer (PCa). IVIM imaging enables the differentiation of water molecule diffusion within capillaries and outside vessels, offering valuable insights into tumor characteristics. The proposed approach utilizes a two-step segmentation approach through the use of three U-Net architectures for extracting tumor-containing regions of interest (ROIs) from the segmented images. The performance of the CAD system is thoroughly evaluated, considering the optimal classifier and IVIM parameters for differentiation and comparing the diagnostic value of IVIM parameters with the commonly used apparent diffusion coefficient (ADC). The results demonstrate that the combination of central zone (CZ) and peripheral zone (PZ) features with the Random Forest Classifier (RFC) yields the best performance. The CAD system achieves an accuracy of 84.08% and a balanced accuracy of 82.60%. This combination showcases high sensitivity (93.24%) and reasonable specificity (71.96%), along with good precision (81.48%) and F1 score (86.96%). These findings highlight the effectiveness of the proposed CAD system in accurately segmenting and diagnosing PCa. This study represents a significant advancement in non-invasive methods for early detection and diagnosis of PCa, showcasing the potential of IVIM parameters in combination with machine learning techniques. This developed solution has the potential to revolutionize PCa diagnosis, leading to improved patient outcomes and reduced healthcare costs.
PubMed: 38927865
DOI: 10.3390/bioengineering11060629 -
Bioengineering (Basel, Switzerland) Jun 2024Prostate cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. The...
Prostate cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. The accurate prediction of cancer grade is paramount for timely interventions. This paper introduces an approach to prostate cancer grading, framing it as a classification problem. Leveraging ResNet models on multi-scale patch-level digital pathology and the Diagset dataset, the proposed method demonstrates notable success, achieving an accuracy of 0.999 in identifying clinically significant prostate cancer. The study contributes to the evolving landscape of cancer diagnostics, offering a promising avenue for improved grading accuracy and, consequently, more effective treatment planning. By integrating innovative deep learning techniques with comprehensive datasets, our approach represents a step forward in the pursuit of personalized and targeted cancer care.
PubMed: 38927860
DOI: 10.3390/bioengineering11060624 -
Genes May 2024Molecular radiotherapy (MRT), also known as radioimmunotherapy or targeted radiotherapy, is the delivery of radionuclides to tumours by targeting receptors overexpressed... (Review)
Review
Molecular radiotherapy (MRT), also known as radioimmunotherapy or targeted radiotherapy, is the delivery of radionuclides to tumours by targeting receptors overexpressed on the cancer cell. Currently it is used in the treatment of a few cancer types including lymphoma, neuroendocrine, and prostate cancer. Recently reported outcomes demonstrating improvements in patient survival have led to an upsurge in interest in MRT particularly for the treatment of prostate cancer. Unfortunately, between 30% and 40% of patients do not respond. Further normal tissue exposure, especially kidney and salivary gland due to receptor expression, result in toxicity, including dry mouth. Predictive biomarkers to select patients who will benefit from MRT are crucial. Whilst pre-treatment imaging with imaging versions of the therapeutic agents is useful in demonstrating tumour binding and potentially organ toxicity, they do not necessarily predict patient benefit, which is dependent on tumour radiosensitivity. Transcript-based biomarkers have proven useful in tailoring external beam radiotherapy and adjuvant treatment. However, few studies have attempted to derive signatures for MRT response prediction. Here, transcriptomic studies that have identified genes associated with clinical radionuclide exposure have been reviewed. These studies will provide potential features for seeding multi-component biomarkers of MRT response.
Topics: Humans; Biomarkers, Tumor; Radioimmunotherapy; Male; Gene Expression Regulation, Neoplastic; Neoplasms; Prostatic Neoplasms; Radioisotopes
PubMed: 38927624
DOI: 10.3390/genes15060688 -
Biomedicines Jun 2024The GeneCaRNA human gene database is a member of the GeneCards Suite. It presents ~280,000 human non-coding RNA genes, identified algorithmically from ~690,000...
The GeneCaRNA human gene database is a member of the GeneCards Suite. It presents ~280,000 human non-coding RNA genes, identified algorithmically from ~690,000 RNAcentral transcripts. This expands by ~tenfold the ncRNA gene count relative to other sources. GeneCaRNA thus contains ~120,000 long non-coding RNAs (LncRNAs, >200 bases long), including ~100,000 novel genes. The latter have sparse functional information, a vast terra incognita for future research. LncRNA genes are uniformly represented on all nuclear chromosomes, with 10 genes on mitochondrial DNA. Data obtained from MalaCards, another GeneCards Suite member, finds 1547 genes associated with 1 to 50 diseases. About 15% of the associations portray experimental evidence, with cancers tending to be multigenic. Preliminary text mining within GeneCaRNA discovers interactions of lncRNA transcripts with target gene products, with 25% being ncRNAs and 75% proteins. GeneCaRNA has a biological pathways section, which at present shows 131 pathways for 38 lncRNA genes, a basis for future expansion. Finally, our GeneHancer database provides regulatory elements for ~110,000 lncRNA genes, offering pointers for co-regulated genes and genetic linkages from enhancers to diseases. We anticipate that the broad vista provided by GeneCaRNA will serve as an essential guide for further lncRNA research in disease decipherment.
PubMed: 38927512
DOI: 10.3390/biomedicines12061305 -
Biomedicines Jun 2024The evaluation of in vitro biological activity of several previously reported quinolinequinones () against 60 human cancer cell lines (NCI-60) used by the National...
The evaluation of in vitro biological activity of several previously reported quinolinequinones () against 60 human cancer cell lines (NCI-60) used by the National Cancer Institute's Developmental Therapeutics Program (DTP) contributed to our earlier research on possible anticancer and/or antibacterial agents. Of interest, NCI-60 screening revealed that two quinolinequinones ( and ) significantly reduced the proliferation of several cancer genotypes. Following the administration of a single dose and five additional doses, all quinolinequinones demonstrated a significant inhibitory effect on the growth of leukemia and other cancer cell lines. Hence, a series of subsequent in vitro biological assessments were performed to further understand the mechanistic impact of the compounds. In MTT assays, it was found that and exhibited higher efficacy against DU-145 cells (IC 4.18 µM and 4.17 µM, respectively) compared to MDA-MB-231 (IC 8.27 and 13.33 µM, respectively) and HCT-116 cells (IC 5.83 and 9.18 µM, respectively). Additionally, demonstrated greater activity in this context. Further investigations revealed that inhibited DU-145 cell growth and migration dose-dependently. Remarkably, arrest of the DU-145 cell cycle at G0/G1 phase and ROS elevation were observed. Pharmacokinetic (PK) studies revealed that has better PK parameters than with %F of 9.83 in rat. Considering the data obtained with human liver microsomal stability studies, should have a better PK profile in human subjects. In silico studies (molecular dynamics) with three kinases (CDK2, CDK4, and MAPK) leading to cell cycle arrest at G/G identified MAPK as a probable target for . Taken together, our results showed that could be a potential chemotherapeutic lead molecule for prostate cancer.
PubMed: 38927448
DOI: 10.3390/biomedicines12061241 -
Biomolecules Jun 2024Cytochrome (Cyt) is important for both mitochondrial respiration and apoptosis, both of which are altered in cancer cells that switch to Warburg metabolism and manage...
Cytochrome (Cyt) is important for both mitochondrial respiration and apoptosis, both of which are altered in cancer cells that switch to Warburg metabolism and manage to evade apoptosis. We earlier reported that lysine 53 (K53) of Cyt is acetylated in prostate cancer. K53 is conserved in mammals that is known to be essential for binding to cytochrome oxidase and apoptosis protease activating factor-1 (Apaf-1). Here we report the effects of this acetylation on the main functions of cytochrome by expressing acetylmimetic K53Q in cytochrome double knockout cells. Other cytochrome variants analyzed were wild-type, K53R as a control that maintains the positive charge, and K53I, which is present in some non-mammalian species. Intact cells expressing K53Q cytochrome showed 49% decreased mitochondrial respiration and a concomitant increase in glycolytic activity (Warburg effect). Furthermore, mitochondrial membrane potential was decreased, correlating with notably reduced basal mitochondrial superoxide levels and decreased cell death upon challenge with HO or staurosporine. To test for markers of cancer aggressiveness and invasiveness, cells were grown in 3D spheroid culture. K53Q cytochrome -expressing cells showed profoundly increased protrusions compared to WT, suggesting increased invasiveness. We propose that K53 acetylation of cytochrome is an adaptive response that mediates prostate cancer metabolic reprogramming and evasion of apoptosis, which are two hallmarks of cancer, to better promote tumor survival and metastasis.
Topics: Prostatic Neoplasms; Humans; Cytochromes c; Male; Acetylation; Apoptosis; Lysine; Cell Line, Tumor; Mitochondria; Membrane Potential, Mitochondrial; Metabolic Reprogramming
PubMed: 38927098
DOI: 10.3390/biom14060695