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Scientific Reports Jun 2024Cancer remains a formidable global health challenge, with metastasis being a key contributor to its lethality. Abundant high molecular mass hyaluronic acid, a major...
Cancer remains a formidable global health challenge, with metastasis being a key contributor to its lethality. Abundant high molecular mass hyaluronic acid, a major non-protein component of extracellular matrix, protects naked mole rats from cancer and reduces cancer incidence in mice. Hyaluronidase plays a critical role in degrading hyaluronic acid and is frequently overexpressed in metastatic cancer. Here we investigated the potential of targeting hyaluronidases to reduce metastasis. A high throughput screen identified delphinidin, a natural plant compound found in fruits and vegetables, as a potent hyaluronidase inhibitor. Delphinidin-mediated inhibition of hyaluronidase activity led to an increase in high molecular weight hyaluronic acid in cell culture and in mouse tissues, and reduced migration and invasion behavior of breast, prostate, and melanoma cancer cells. Moreover, delphinidin treatment suppressed melanoma metastasis in mice. Our study provides a proof of principle that inhibition of hyaluronidase activity suppresses cancer cell migration, invasion and metastasis. Furthermore, we identified a natural compound delphinidin as a potential anticancer therapeutic. Thus, we have identified a path for clinical translation of the cancer resistance mechanism identified in the naked mole rat.
Topics: Animals; Female; Humans; Male; Mice; Anthocyanins; Cell Line, Tumor; Cell Movement; Enzyme Inhibitors; Hyaluronic Acid; Hyaluronoglucosaminidase; Neoplasm Metastasis; Mole Rats
PubMed: 38942920
DOI: 10.1038/s41598-024-64924-6 -
Scientific Reports Jun 2024Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1...
Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.
Topics: Humans; Male; Prostatic Neoplasms; TOR Serine-Threonine Kinases; Gene Expression Regulation, Neoplastic; Disease Progression; Signal Transduction; Cell Line, Tumor; CDC2 Protein Kinase; DNA Methylation; Promoter Regions, Genetic; Cell Proliferation; Down-Regulation; Prognosis; Cell Movement
PubMed: 38942821
DOI: 10.1038/s41598-024-66020-1 -
Scientific Reports Jun 2024Prostate cancer is one of the most common and fatal diseases among men, and its early diagnosis can have a significant impact on the treatment process and prevent...
Prostate cancer is one of the most common and fatal diseases among men, and its early diagnosis can have a significant impact on the treatment process and prevent mortality. Since it does not have apparent clinical symptoms in the early stages, it is difficult to diagnose. In addition, the disagreement of experts in the analysis of magnetic resonance images is also a significant challenge. In recent years, various research has shown that deep learning, especially convolutional neural networks, has appeared successfully in machine vision (especially in medical image analysis). In this research, a deep learning approach was used on multi-parameter magnetic resonance images, and the synergistic effect of clinical and pathological data on the accuracy of the model was investigated. The data were collected from Trita Hospital in Tehran, which included 343 patients (data augmentation and learning transfer methods were used during the process). In the designed model, four different types of images are analyzed with four separate ResNet50 deep convolutional networks, and their extracted features are transferred to a fully connected neural network and combined with clinical and pathological features. In the model without clinical and pathological data, the maximum accuracy reached 88%, but by adding these data, the accuracy increased to 96%, which shows the significant impact of clinical and pathological data on the accuracy of diagnosis.
Topics: Humans; Deep Learning; Prostatic Neoplasms; Male; Middle Aged; Aged; Neural Networks, Computer; Magnetic Resonance Imaging; Multiparametric Magnetic Resonance Imaging; Image Processing, Computer-Assisted; Image Interpretation, Computer-Assisted; Iran
PubMed: 38942817
DOI: 10.1038/s41598-024-65354-0 -
European Journal of Nuclear Medicine... Jun 2024Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal...
Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.
PURPOSE
Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT.
METHODS
A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test.
RESULTS
Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis.
CONCLUSIONS
Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.
PubMed: 38940843
DOI: 10.1007/s00259-024-06802-x -
Cancer Medicine Jul 2024The Cancer Health Awareness through screeNinG and Education (CHANGE) initiative delivers cancer awareness education with an emphasis on modifiable risk factors and...
BACKGROUND
The Cancer Health Awareness through screeNinG and Education (CHANGE) initiative delivers cancer awareness education with an emphasis on modifiable risk factors and navigation to screening for prostate, breast, and colorectal cancers to residents of public housing communities who experience significant negative social determinants of health.
METHODS
Residents of five communities participated. Community advisory board members were recruited and provided feedback to local environmental change projects, recruitment, and community engagement at each site. At each site, four education sessions were provided by trained facilitators on cancer risk factors and etiology, racial disparities, eligibility for cancer screening, and participation in clinical trials. Attendance, knowledge, attitudes and beliefs about cancer, and height, weight, and waist circumference were measured at baseline and 1-week post-CHANGE sessions.
RESULTS
90 residents (60% 65 and older years old, 33% male, 60% High School education, 93% AA) participated in the program. 95% completed post-intervention evaluation. Participants were eligible for breast (n = 12), prostate (n = 15), and colorectal screening (n = 25) based on American Cancer Society guidelines, and 22 for tobacco cessation; 21 participants accepted navigation assistance for these services. At post-test, participants significantly increased in knowledge and behaviors around obesity/overweight risk for cancer, nutrition, and physical activity. Colorectal, prostate, and breast cancer knowledge scores also increased, but were not significant.
CONCLUSIONS
CHANGE participants demonstrated improved health knowledge and intentions to improve their modifiable health behaviors. Participants reported being motivated and confident in seeking preventive care and satisfaction with community engagement efforts. Replication of this project in similar communities may improve knowledge and health equity among underserved populations.
Topics: Humans; Male; Female; Early Detection of Cancer; Aged; Health Knowledge, Attitudes, Practice; Middle Aged; Health Equity; Prostatic Neoplasms; Health Education; Neoplasms; Breast Neoplasms; Colorectal Neoplasms; Adult; Risk Factors
PubMed: 38940418
DOI: 10.1002/cam4.7357 -
Journal of Integrative Neuroscience Jun 2024Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency...
Differentially Expressed Proteins in the Serum of Elderly Patients Who Experienced Perioperative Neurocognitive Disorders Following Transurethral Resection of the Prostate.
OBJECTIVE
Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND.
METHODS
A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression.
RESULTS
Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase.
CONCLUSION
The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND.
CLINICAL TRIAL REGISTRATION
Registered (ChiCTR2000028836). Date (20190306).
Topics: Humans; Male; Aged; Transurethral Resection of Prostate; Proteomics; Prostatic Hyperplasia; Neurocognitive Disorders; Postoperative Cognitive Complications; Perioperative Period; Aged, 80 and over; Blood Proteins; Computational Biology
PubMed: 38940081
DOI: 10.31083/j.jin2306123 -
Frontiers in Bioscience (Landmark... Jun 2024Transcription factors (TFs) are essential proteins regulating gene expression by binding to specific nucleotide sequences upstream of genes. Among TF families, the... (Review)
Review
Transcription factors (TFs) are essential proteins regulating gene expression by binding to specific nucleotide sequences upstream of genes. Among TF families, the forkhead box (FOX) proteins, characterized by a conserved DNA-binding domain, play vital roles in various cellular processes, including cancer. The FOXA subfamily, encompassing FOXA1, FOXA2, and FOXA3, stands out for its pivotal role in mammalian development. FOXA1, initially identified in the liver, exhibits diverse expression across multiple organ tissues and plays a critical role in cell proliferation, differentiation, and tumor development. Its structural composition includes transactivation domains and a DNA-binding domain, facilitating its function as a pioneer factor, which is crucial for chromatin interaction and the recruitment of other transcriptional regulators. The involvement of FOXA1 in sex hormone-related tumors underscores its significance in cancer biology. This review provides an overview of multifaceted roles of FOXA1 in normal development and its implications in the pathogenesis of hormone-related cancers, particularly breast cancer and prostate cancer.
Topics: Humans; Hepatocyte Nuclear Factor 3-alpha; Male; Female; Breast Neoplasms; Prostatic Neoplasms; Gonadal Steroid Hormones; Neoplasms; Animals; Gene Expression Regulation, Neoplastic
PubMed: 38940052
DOI: 10.31083/j.fbl2906225 -
Frontiers in Pharmacology 2024Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play... (Review)
Review
Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play crucial roles in various cancers, including urologic malignancies. This article provides a summary of the latest research findings, suggesting that lncRNA-mediated autophagy could either suppress or promote tumors in prostate, kidney, and bladder cancers. The intricate network involving different lncRNAs, target genes, and mediated signaling pathways plays a crucial role in urological malignancies by modulating the autophagic process. Dysregulated expression of lncRNAs can disrupt autophagy, leading to tumorigenesis, progression, and enhanced resistance to therapy. Consequently, targeting particular lncRNAs that control autophagy could serve as a dependable diagnostic tool and a promising prognostic biomarker in urologic oncology, while also holding potential as an effective therapeutic approach.
PubMed: 38939836
DOI: 10.3389/fphar.2024.1405199 -
Molecular Therapy. Oncology Jun 2024Advancing chimeric antigen receptor (CAR)-engineered T cells for the treatment of solid tumors is a major focus in the field of cellular immunotherapy. Several hurdles...
Advancing chimeric antigen receptor (CAR)-engineered T cells for the treatment of solid tumors is a major focus in the field of cellular immunotherapy. Several hurdles have hindered similar CAR T cell clinical responses in solid tumors as seen in hematological malignancies. These challenges include on-target off-tumor toxicities, which have inspired efforts to optimize CARs for improved tumor antigen selectivity and overall safety. We recently developed a CAR T cell therapy targeting prostate stem cell antigen (PSCA) for prostate and pancreatic cancers, showing improved preclinical antitumor activity and T cell persistence by optimizing the intracellular co-stimulatory domain. Similar studies were undertaken to optimize HER2-directed CAR T cells with modifications to the intracellular co-stimulatory domain for selective targeting of breast cancer brain metastasis. In the present study, we evaluate various nonsignaling extracellular spacers in these CARs to further improve tumor antigen selectivity. Our findings suggest that length and structure of the extracellular spacer can dictate the ability of CARs to selectively target tumor cells with high antigen density, while sparing cells with low antigen density. This study contributes to CAR construct design considerations and expands our knowledge of tuning solid tumor CAR T cell therapies for improved safety and efficacy.
PubMed: 38939825
DOI: 10.1016/j.omton.2024.200789 -
Frontiers in Oncology 2024[This corrects the article DOI: 10.3389/fonc.2024.1368926.].
[This corrects the article DOI: 10.3389/fonc.2024.1368926.].
PubMed: 38939340
DOI: 10.3389/fonc.2024.1427226