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Discover Oncology Jun 2024Placenta-specific protein 1 (PLAC-1) is a gene primarily expressed in the placenta and the testis. Interestingly, it is also found to be expressed in many solid tumors,...
Placenta-specific protein 1 (PLAC-1) is a gene primarily expressed in the placenta and the testis. Interestingly, it is also found to be expressed in many solid tumors, and it is involved in malignant cell features. However, no evidence has been reported regarding the relationship between PLAC-1 and cancer stem cells (CSCs). In the current research, we explored the expression of the PLAC-1 molecule in prostate cancer stem cells (PCSCs) derived from the human PC-3 cell line. The enrichment of PCSCs was achieved using a three-dimensional cell culture technique known as the sphere-formation assay. To confirm the identity of PCSCs, we examined the expression of genes associated with stemness and pluripotency, such as SOX2, OCT4, Nanog, C-Myc, and KLF-4, as well as stem cell differentiation molecules like CD44 and CD133. These evaluations were conducted in both the PCSCs and the original tumor cells (parental cells) using real-time PCR and flow cytometry. Subsequently, we assessed the expression of the PLAC-1 molecule in both enriched cells and parental tumor cells at the gene and protein levels using the same techniques. The tumor cells from the PC-3 cell line formed spheroids with CSC characteristics in a non-adherent medium. The expression of SOX2, OCT4, Nanog, and C-Myc genes (p < 0.01), and the molecules CD44 and CD133 (p < 0.05) were significantly elevated in PCSCs compared to the parental cells. The expression of the PLAC-1 molecule in PCSCs showed a significant increase compared to the parental cells at both gene (p < 0.01) and protein (p < 0.001) levels. In conclusion, it was indicated for the first time that PLAC-1 is up-regulated in PCSCs derived from human PC-3 cell line. This study may propose PLAC-1 as a potential target in targeted therapies, which should be confirmed through further studies.
PubMed: 38943028
DOI: 10.1007/s12672-024-01121-x -
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: Hyaluronoglucosaminidase; Animals; Mice; Humans; Anthocyanins; Cell Movement; Cell Line, Tumor; Neoplasm Metastasis; Female; Hyaluronic Acid; Male; Enzyme Inhibitors
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 -
Practical Radiation Oncology 2024
Erratum to: Baty M, Pasquier D, Gnep K, et al. Achievable Dosimetric Constraints in Stereotactic Reirradiation for Recurrent Prostate Cancer. Pract Radiat Oncol. 2023;13:e515-e529.
PubMed: 38942574
DOI: 10.1016/j.prro.2024.03.003 -
Planta Medica Jun 2024Hyaluronic acid is composed of repeating sugar units, glucuronic acid and N-acetylglucosamine, which are often associated with increased tumor progression. agglutinin...
Hyaluronic acid is composed of repeating sugar units, glucuronic acid and N-acetylglucosamine, which are often associated with increased tumor progression. agglutinin is a potential component that exhibits a high affinity for binding to N-acetylglucosamine. This study aimed to investigate Agglutinin's potential to inhibit the proliferation and migration of prostate cancer cells with high expression of hyaluronic acid through molecular docking and studies. The expression of hyaluronan synthase genes in prostate tissue and cell lines was checked by an study, and the interaction between hyaluronic acid with both CD44 transmembrane glycoprotein and agglutinin was analyzed through molecular docking. Agglutinin's effect on cell viability (neutral red uptake assay), migration (scratch wound healing assays), and both and expression (quantitative real-time polymerase chain reaction) were assessed . The results showed that in prostate cancer cell lines, the PC3 cell line has the highest expression of hyaluronan synthase genes. agglutinin exhibits an interaction of six specific residues on CD44 compared to hyaluronic acid's singular residue. While agglutinin alone effectively reduced cell viability and wound closer (≥ 150 µg/mL), combining it with hyaluronic acid significantly shifted the effective concentration to a higher dose (≥ 350 µg/mL). These results, together with low and high gene expression, suggest that agglutinin may impair the CD44-HA pathway in PC3 cells. This possibility is supported by Agglutinin's ability to compete with hyaluronic acid for binding to CD44. Based on this, agglutinin as a plant lectin shows promise in inhibiting cancer proliferation and migration by targeting its dependence on hyaluronic acid.
PubMed: 38942031
DOI: 10.1055/a-2324-2250 -
Cancer Epidemiology Jun 2024Data on social inequalities in cancer mortality are sparse, especially in low- and middle-income countries. We aimed to analyze the socioeconomic inequalities in cancer...
INTRODUCTION
Data on social inequalities in cancer mortality are sparse, especially in low- and middle-income countries. We aimed to analyze the socioeconomic inequalities in cancer mortality in Costa Rica between 2010 and 2018.
METHODS
We linked 9-years of data from the National Electoral Rolls, National Birth Index and National Death Index to classify deaths due to cancer and socioeconomic characteristics of the district of residence, as measured by levels of urbanicity and wealth. We analyzed the fifteen most frequent cancer sites in Costa Rica among the 2.7 million inhabitants aged 20 years and older. We used a parametric survival model based on a Gompertz distribution.
RESULTS
Compared to urban areas, mixed and rural area residents had lower mortality from pancreas, lung, breast, prostate, kidney, and bladder cancers, and higher mortality from stomach cancer. Mortality from stomach, lung and cervical cancer was higher, and mortality from colorectal cancer, non-Hodgkin lymphoma and leukemia was lower in the most disadvantaged districts, compared to the wealthiest ones.
CONCLUSION
We observed marked disparities in cancer mortality in Costa Rica in particular from infection- and lifestyle- related cancers. There are important opportunities to reduce disparities in cancer mortality by targeting cancer prevention, early detection and opportune treatment, mainly in urban and disadvantaged districts.
PubMed: 38941875
DOI: 10.1016/j.canep.2024.102604 -
Abdominal Radiology (New York) Jun 2024Prostate magnetic resonance imaging (MRI) stands as the cornerstone in diagnosing prostate cancer (PCa), offering superior detection capabilities while minimizing... (Review)
Review
Prostate magnetic resonance imaging (MRI) stands as the cornerstone in diagnosing prostate cancer (PCa), offering superior detection capabilities while minimizing unnecessary biopsies. Despite its critical role, global disparities in MRI diagnostic performance persist, stemming from variations in image quality and radiologist expertise. This manuscript reviews the challenges and strategies for enhancing image quality in prostate MRI, spanning patient preparation, MRI unit optimization, and radiology team engagement. Quality assurance (QA) and quality control (QC) processes are pivotal, emphasizing standardized protocols, meticulous patient evaluation, MRI unit workflow, and radiology team performance. Additionally, artificial intelligence (AI) advancements offer promising avenues for improving image quality and reducing acquisition times. The Prostate-Imaging Quality (PI-QUAL) scoring system emerges as a valuable tool for assessing MRI image quality. A comprehensive approach addressing technical, procedural, and interpretative aspects is essential to ensure consistent and reliable prostate MRI outcomes.
PubMed: 38940911
DOI: 10.1007/s00261-024-04396-4 -
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 -
European Journal of Nuclear Medicine... Jun 2024Tumour perfusion is a nutrient-agnostic biomarker for cancer metabolic rate. Use of tumour perfusion for cancer growth assessment has been limited by complicated image...
PURPOSE
Tumour perfusion is a nutrient-agnostic biomarker for cancer metabolic rate. Use of tumour perfusion for cancer growth assessment has been limited by complicated image acquisition, image analysis and limited field-of-view scanners. Long axial field-of-view (LAFOV) PET scan using [O]HO, allows quantitative assessment of whole-body tumour perfusion. We created a tool for automated creation of quantitative parametric whole-body tumour perfusion images in metastatic cancer.
METHODS
Ten metastatic prostate cancer patients underwent dynamic LAFOV [O]HO PET (Siemens, Quadra) followed by [F]PSMA-1007 PET. Perfusion was measured as [O]HO K (mL/min/mL) with a single-tissue compartment model and an automatically captured cardiac image-derived input function. Parametric perfusion images were automatically calculated using the basis-function method with initial voxel-wise delay estimation and a leading-edge approach. Subsequently, perfusion of volumes-of-interest (VOI) can be directly extracted from the parametric images. We used a [F]PSMA-1007 SUV 4 fixed threshold for tumour delineation and transferred these VOIs to the perfusion map.
RESULTS
For 8 primary tumours, 64 lymph node metastases, and 85 bone metastases, median tumour perfusion were 0.19 (0.15-0.27) mL/min/mL, 0.16 (0.13-0.27) mL/min/mL, and 0.26 (0.21-0.39), respectively. The correlation between calculated perfusion from time-activity-curves and parametric images was excellent (r = 0.99, p < 0.0001).
CONCLUSION
LAFOV PET imaging using [O]HO enables truly quantitative parametric images of whole-body tumour perfusion, a potential biomarker for guiding personalized treatment and monitoring treatment response.
PubMed: 38940842
DOI: 10.1007/s00259-024-06799-3