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Cancer Biology & Therapy Dec 2024Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we...
Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we evaluated RNA expression of neuroendocrine genes in a panel of five different cancer types: prostate adenocarcinoma, breast cancer, kidney chromophobe, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. Our results show that specific neuroendocrine genes are significantly dysregulated in these tumors, suggesting that they play an active role in cancer progression. Among others, synaptophysin (SYP), a conventional neuroendocrine marker, is upregulated in prostate adenocarcinoma (PRAD) and breast cancer (BRCA). Our analysis shows that SYP is enriched in small extracellular vesicles (sEVs) derived from plasma of PRAD patients, but it is absent in sEVs derived from plasma of healthy donors. Similarly, classical sEV markers are enriched in sEVs derived from plasma of prostate cancer patients, but weakly detectable in sEVs derived from plasma of healthy donors. Overall, our results pave the way to explore new strategies to diagnose these diseases based on the neuroendocrine gene expression in patient tumors or plasma sEVs.
Topics: Humans; Male; Prostatic Neoplasms; Adenocarcinoma; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Synaptophysin; Extracellular Vesicles; Gene Expression Profiling
PubMed: 38926911
DOI: 10.1080/15384047.2024.2364433 -
Scientific Reports Jun 2024Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their...
Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.
Topics: Male; Humans; Prostatic Neoplasms; Prostatic Hyperplasia; Stem Cells; Adipose Tissue; Prostate; Cell Differentiation; Cell Proliferation; Cytokines; Cells, Cultured; Aged; Middle Aged
PubMed: 38926454
DOI: 10.1038/s41598-024-64625-0 -
Scientific Reports Jun 2024Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to...
Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to distinguish patients with lung cancer from healthy individuals. Additionally, we sought to develop a deep learning model incorporating cfDNA methylation and fragment size profiles. To achieve this, we utilized methylation data collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Then we generated methylated DNA immunoprecipitation sequencing and genome-wide Enzymatic Methyl-seq (EM-seq) form lung cancer tissue and plasma. Using these data, we selected 366 methylation markers. A targeted EM-seq panel was designed using the selected markers, and 142 lung cancer and 56 healthy samples were produced with the panel. Additionally, cfDNA samples from healthy individuals and lung cancer patients were diluted to evaluate sensitivity. Its lung cancer detection performance reached an accuracy of 81.5% and an area under the receiver operating characteristic curve of 0.87. In the serial dilution experiment, we achieved tumor fraction detection of 1% at 98% specificity and 0.1% at 80% specificity. In conclusion, we successfully developed and validated a combination of methylation panel and a deep learning model that can distinguish between patients with lung cancer and healthy individuals.
Topics: Humans; Lung Neoplasms; DNA Methylation; Deep Learning; Biomarkers, Tumor; Female; Male; Middle Aged; Aged; Cell-Free Nucleic Acids; ROC Curve
PubMed: 38926407
DOI: 10.1038/s41598-024-63411-2 -
BMJ Case Reports Jun 2024Multiple myeloma is a rare haematological malignancy characterised by the clonal proliferation of plasma cells within the bone marrow. Typical manifestations include...
Multiple myeloma is a rare haematological malignancy characterised by the clonal proliferation of plasma cells within the bone marrow. Typical manifestations include bone pain, fatigue and monoclonal protein elevation in serum and urine. Less than 1% of cases develop myelomatous pleural effusion, a severe complication indicative of advanced disease and a very poor prognosis.Here, we present a case of a woman with a new diagnosis of multiple myeloma complicated by bilateral myelomatous pleural effusions as the initial presentation. This case underscores the diverse clinical spectrum of multiple myeloma, the significance of timely diagnosis and the threatening implications associated with myelomatous pleural effusions.
Topics: Humans; Multiple Myeloma; Female; Pleural Effusion, Malignant; Middle Aged; Aged; Pleural Effusion
PubMed: 38925672
DOI: 10.1136/bcr-2023-258935 -
Homeopathy : the Journal of the Faculty... Jun 2024Multiple myeloma (MM) is the second most common type of cancer among hematological malignancies and is difficult to treat. Although controversial in nature,...
BACKGROUND
Multiple myeloma (MM) is the second most common type of cancer among hematological malignancies and is difficult to treat. Although controversial in nature, homeopathy's effects have been tested on a wide range of cancer cell types , as well as clinically. However, homeopathic medicines have yet to be tested in MM cells. In this preliminary study, we investigated the effects of , , and 200C on a human MM cell line.
METHODS
The RPMI-8226 MM cell line was cultured for up to 96 hours and treated with each of four homeopathic preparations. The spectrophotometric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric Annexin V-PE/7-actinomycin D (7-AAD) and propidium iodide (PI) staining were each used to examine cell viability, apoptosis and cell cycle, respectively.
RESULTS
The MTT assay showed that all four homeopathic preparations reduced cell viability over time when compared to the control group cells, especially at 72 and 96 hours whereby only 50% of cells remained viable. Similarly, after 96 hours of treatment, the proportion of viable cells was significantly decreased and the proportion of early apoptotic (Annexin-V-PE +/7AAD-) cells was significantly increased for all four homeopathic preparations. Based on the PI-staining cell cycle data, cells treated with and showed a statistically significant accumulation in the sub-G0/G1 phase of the cell cycle ( < 0.05).
CONCLUSION
This is the first study to demonstrate that each of four homeopathic medicines causes apoptosis in a MM cell line. Further exploration of the potential of , , and as a complementary therapeutic option in MM is warranted.
PubMed: 38925208
DOI: 10.1055/s-0044-1786035 -
Tierarztliche Praxis. Ausgabe K,... Jun 2024An acute, unilateral othematoma was diagnosed in a 9-year-old mixed-breed dog. There was no clinical or anamnestic evidence for the cause of the othematoma. During...
An acute, unilateral othematoma was diagnosed in a 9-year-old mixed-breed dog. There was no clinical or anamnestic evidence for the cause of the othematoma. During diagnostic work-up, marked hyperglobulinemia and marked thrombocytopenia were detected. This was a consequence of a multiple myeloma. This is the first case report of a dog with othematoma secondary to coagulopathy associated with multiple myeloma.
Topics: Dogs; Animals; Multiple Myeloma; Dog Diseases; Hematoma; Male; Thrombocytopenia
PubMed: 38925136
DOI: 10.1055/a-2324-0508 -
Neuromuscular Disorders : NMD Jun 2024We present the case of a 79-year-old man with rapidly progressive myopathy as the initial manifestation of light chain amyloidosis associated with multiple myeloma. The...
We present the case of a 79-year-old man with rapidly progressive myopathy as the initial manifestation of light chain amyloidosis associated with multiple myeloma. The patient experienced progressive lower limb weakness resulting in difficulty climbing stairs. Ancillary tests revealed slightly elevated serum creatine kinase levels. The electromyogram revealed a diffuse myogenic pattern while muscle MRI indicated fatty replacement of the quadriceps muscles. Muscle biopsy revealed the presence of amyloid deposits in the vessel walls. An elevated level of lambda (246 mg/L) light chain was detected. The bone marrow aspiration results were consistent with the diagnosis of multiple myeloma. In conclusion, even if amyloid myopathy is a rare condition, routine screening for amyloid deposits in muscle biopsy is crucial and should be performed systematically. In the present case, it enabled a rapid diagnosis and the beginning of treatment.
PubMed: 38925009
DOI: 10.1016/j.nmd.2024.06.002 -
The New England Journal of Medicine Jun 2024
Review
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Immunoglobulin Light Chains; Amyloidosis; Male
PubMed: 38924733
DOI: 10.1056/NEJMra2304088 -
British Journal of Clinical Pharmacology Jun 2024To evaluate relationships between plasma concentrations of belantamab mafodotin, total monoclonal antibody, and its payload and changes in electrocardiogram (ECG)...
AIMS
To evaluate relationships between plasma concentrations of belantamab mafodotin, total monoclonal antibody, and its payload and changes in electrocardiogram (ECG) parameters in patients with relapsed or refractory multiple myeloma from the DREAMM-1 and DREAMM-2 studies.
METHODS
Hysteresis plots and linear regression analyses of pharmacokinetic (PK) analyte (belantamab mafodotin, total monoclonal antibody, and cytotoxic cysteine-maleimidocaproyl monomethyl auristatin F payload) concentrations vs. time-matched ECG parameters (absolute/change from baseline in QT interval corrected for RR interval [QTc/ΔQTc] and QT interval corrected for heart rate by Fridericia's formula [QTcF/ΔQTcF]) were performed. Concentrations of PK analyte required for a 10-ms increase in QTc in DREAMM-2 were calculated via simulation, as was the probability of ΔQTc/ΔQTcF exceeding 10 ms for the expected C of PK analyte concentrations associated with the doses (2.5 and 3.4 mg/kg) administered in DREAMM-2.
RESULTS
Time-matched PK and ECG data from 290 patients (DREAMM-1, n = 73; DREAMM-2, n = 217) were analysed. Hysteresis plots did not clearly indicate any concentration-related prolongation in QTc or QTcF; regression analyses indicated a very small rate of increase in ΔQTc and ΔQTcF with increasing concentrations of PK analytes. Calculated concentrations of PK analyte required for a 10-ms prolongation in QTc were higher than the maximum analyte concentrations observed following treatment with belantamab mafodotin in DREAMM-2; the probability that each dose would prolong ΔQTc and ΔQTcF by >10 ms was 0 and <0.25%, respectively.
CONCLUSION
This study of belantamab mafodotin and its payload did not provide evidence of QT prolongation in patients with relapsed or refractory multiple myeloma at clinically relevant doses.
PubMed: 38924122
DOI: 10.1111/bcp.16133 -
Journal of Cellular and Molecular... Jun 2024Despite remarkable advancements in the treatment of multiple myeloma (MM), relapse remains a challenge. However, the mechanisms underlying this disease remain unclear....
Despite remarkable advancements in the treatment of multiple myeloma (MM), relapse remains a challenge. However, the mechanisms underlying this disease remain unclear. This study aimed to identify potential biomarkers that could open new avenues for MM treatment. Microarray data and clinical characteristics of patients with MM were obtained from the Gene Expression Omnibus database. Differential expression analysis and protein-protein interaction (PPI) network construction were used to identify hub genes associated with MM. Predictive performance was further assessed using receiver operating characteristic curves and nomogram construction. Functional enrichment analysis was conducted to investigate possible mechanisms. Mendelian randomization (MR) was used to evaluate the causal relationship between the crucial gene and MM risk. Topological analysis of the PPI network revealed five hub genes associated with MM, with myeloperoxidase (MPO) being the key gene owing to its highest degree and area under the curve values. MPO showed significant differences between patients with MM and controls across all datasets. Functional enrichment analysis revealed a strong association between MPO and immune-related pathways in MM. MR analysis confirmed a causal relationship between MPO and the risk of MM. By integrating microarray analysis and MR, we successfully identified and validated MPO as a promising biomarker for MM that is potentially implicated in MM pathogenesis and progression through immune-related pathways.
Topics: Multiple Myeloma; Humans; Mendelian Randomization Analysis; Protein Interaction Maps; Biomarkers, Tumor; Peroxidase; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Gene Regulatory Networks; ROC Curve; Microarray Analysis; Nomograms
PubMed: 38923838
DOI: 10.1111/jcmm.18504