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Pharmaceuticals (Basel, Switzerland) May 2024The circulatory system is a closed conduit system throughout the body and consists of two parts as follows: the cardiovascular system and the lymphatic system.... (Review)
Review
The circulatory system is a closed conduit system throughout the body and consists of two parts as follows: the cardiovascular system and the lymphatic system. Hematological malignancies usually grow and multiply in the circulatory system, directly or indirectly affecting its function. These malignancies include multiple myeloma, leukemia, and lymphoma. -linked β-N-acetylglucosamine (-GlcNAc) transferase (OGT) regulates the function and stability of substrate proteins through -GlcNAc modification. Abnormally expressed OGT is strongly associated with tumorigenesis, including hematological malignancies, colorectal cancer, liver cancer, breast cancer, and prostate cancer. In cells, OGT can assemble with a variety of proteins to form complexes to exercise related biological functions, such as OGT/HCF-1, OGT/TET, NSL, and then regulate glucose metabolism, gene transcription, cell proliferation, and other biological processes, thus affecting the development of hematological malignancies. This review summarizes the complexes involved in the assembly of OGT in cells and the role of related OGT complexes in hematological malignancies. Unraveling the complex network regulated by the OGT complex will facilitate a better understanding of hematologic malignancy development and progression.
PubMed: 38931332
DOI: 10.3390/ph17060664 -
Nutrients Jun 2024Cancer therapy, from malignant tumor inhibition to cellular eradication treatment, remains a challenge, especially regarding reduced side effects and low energy...
Cancer therapy, from malignant tumor inhibition to cellular eradication treatment, remains a challenge, especially regarding reduced side effects and low energy consumption during treatment. Hence, phytochemicals as cytotoxic sensitizers or photosensitizers deserve special attention. The dark and photo-response of Yemenite 'Etrog' leaf extracts applied to prostate PC3 cancer cells is reported here. An XTT cell viability assay along with light microscope observations revealed pronounced cytotoxic activity of the extract for long exposure times of 72 h upon concentrations of 175 μg/mL and 87.5 μg/mL, while phototoxic effect was obtained even at low concentration of 10.93 μg/mL and a short introduction period of 1.5 h. For the longest time incubation of 72 h and for the highest extract concentration of 175 μg/mL, relative cell survival decreased by up to 60% (below the IC). In combined phyto-photodynamic therapy, a reduction of 63% compared to unirradiated controls was obtained. The concentration of extract in cells versus the accumulation time was inversely related to fluorescence emission intensity readings. Extracellular ROS production was also shown. Based on an ATR-FTIR analysis of the powdered leaves and their liquid ethanolic extract, biochemical fingerprints of both polar and non-polar phyto-constituents were identified, thereby suggesting their implementation as phyto-medicine and phyto-photomedicine.
Topics: Humans; Male; Plant Extracts; Photochemotherapy; Prostatic Neoplasms; Plant Leaves; Cell Survival; Photosensitizing Agents; PC-3 Cells; Reactive Oxygen Species; Yemen; Cell Line, Tumor; Antineoplastic Agents, Phytogenic
PubMed: 38931175
DOI: 10.3390/nu16121820 -
Plants (Basel, Switzerland) Jun 2024, popularly used in México, possesses bioactive lignans. These compounds are low in the bark, and its extraction endangers the life of the trees. The aim of the present...
, popularly used in México, possesses bioactive lignans. These compounds are low in the bark, and its extraction endangers the life of the trees. The aim of the present investigation was to search for alternative sources of cytotoxic compounds in . prepared as leaves and in vitro callus cultures. The friable callus of was established using a combination of plant growth regulators: 4 mgL of 2,4-dichlorophenoxyacetic acid (2,4-D), 1 mgL Naphthaleneacetic Acid (NAA) and 1 mgL Zeatin. The maximum cell growth was at day 28 with a specific growth rate of μ = 0.059 days and duplication time td = 11.8 days. HPLC quantification of the dichloromethane callus biomass extract showed that Scopoletin, with a concentration of 10.7 µg g dry weight, was the main compound inducible as a phytoalexin by the addition of high concentrations of 2,4-D, as well as by the absence of nutrients in the culture medium. In this same extract, the compounds γ-sitosterol and stigmasterol were also identified by GC-MS analysis. Open column chromatography was used to separate and identify yatein, acetyl podophyllotoxin and 7',8'-dehydropodophyllotoxin in the leaves of the wild plant. Cytotoxic activity on four cancer cell lines was tested, with PC-3 prostate carcinoma (IC of 12.6 ± 4.6 µgmL) being the most sensitive to the wild-type plant extract and HeLa cervical carcinoma (IC of 72 ± 5 µgmL) being the most sensitive to the callus culture extract.
PubMed: 38931054
DOI: 10.3390/plants13121622 -
Molecules (Basel, Switzerland) Jun 2024The crystal structures of two newly synthesized nitrilotriacetate oxidovanadium(IV) salts, namely [QH][VO(nta)(HO)](HO) () and [(acr)H][VO(nta)(HO)](HO) (), were...
The crystal structures of two newly synthesized nitrilotriacetate oxidovanadium(IV) salts, namely [QH][VO(nta)(HO)](HO) () and [(acr)H][VO(nta)(HO)](HO) (), were determined. Additionally, the cytotoxic effects of four N-heterocyclic nitrilotriacetate oxidovanadium(IV) salts-1,10-phenanthrolinium, [(phen)H][VO(nta)(HO)](HO) (), 2,2'-bipyridinium [(bpy)H][VO(nta)(HO)](HO) (), and two newly synthesized compounds () and ()-were evaluated against prostate cancer (PC3) and breast cancer (MCF-7) cells. All the compounds exhibited strong cytotoxic effects on cancer cells and normal cells (HaCaT human keratinocytes). The structure-activity relationship analysis revealed that the number and arrangement of conjugated aromatic rings in the counterion had an impact on the antitumor effect. The compound (III), the 1,10-phenanthrolinium analogue, exhibited the greatest activity, whereas the acridinium salt (II), with a different arrangement of three conjugated aromatic rings, showed the lowest toxicity. The increased concentrations of the compounds resulted in alterations to the cell cycle distribution with different effects in MCF-7 and PC3 cells. In MCF-7 cells, compounds and were observed to block the G/M phase, while compounds and were found to arrest the cell cycle in the G/G phase. In PC3 cells, all compounds increased the rates of cells in the G/G phase.
Topics: Humans; Antineoplastic Agents; Breast Neoplasms; Male; Female; MCF-7 Cells; Prostatic Neoplasms; Nitrilotriacetic Acid; Structure-Activity Relationship; Cell Line, Tumor; Cell Proliferation; Heterocyclic Compounds; Vanadium; PC-3 Cells; Cell Cycle; Molecular Structure; Salts; Cell Survival; Apoptosis
PubMed: 38930989
DOI: 10.3390/molecules29122924 -
Journal of Personalized Medicine May 2024, , , and are known cancer predisposition genes (CPGs), but tumor risk in patients with simultaneous pathogenic variants (PVs) in CPGs remains largely unknown. In this...
BACKGROUND/OBJECTIVES
, , , and are known cancer predisposition genes (CPGs), but tumor risk in patients with simultaneous pathogenic variants (PVs) in CPGs remains largely unknown. In this study, we describe six patients from five families with multiple cancers who coinherited a combination of PVs in these genes.
METHODS
PVs were identified using NGS DNA sequencing and were confirmed by Sanger.
RESULTS
Families 1, 2, and 3 presented PVs in and , family 4 in and , and family 5 in and . PVs were identified using NGS DNA sequencing and were confirmed by Sanger. The first family included patients with kidney, prostate, and breast cancer, in addition to pancreatic adenocarcinomas. In the second family, a female had breast cancer, while a male from the third family had prostate, gastric, and pancreatic cancer. The fourth family included a male with pancreatic cancer, and the fifth family a female with breast cancer.
CONCLUSIONS
The early age of diagnosis and the development of multiple cancers in the reported patients indicate a very high risk of cancer in double-heterozygous patients associated with PVs in HR-related CPGs. Therefore, in families with patients who differ from other family members in terms of phenotype, age of diagnosis, or type of cancer, the cascade testing needs to include the study of other CPGs.
PubMed: 38929805
DOI: 10.3390/jpm14060584 -
Medicina (Kaunas, Lithuania) May 2024: Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively.... (Review)
Review
: Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively. Primary signet-ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. : In June of 2023, a 54-year-old Caucasian male presented with a complaint of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups, including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma stage IV. Unfortunately, due to the advanced stage of the disease, PE, and third-degree thrombocytopenia, the patient was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. : Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results, which may contribute to its late diagnosis. Inconsistent immunohistochemical findings and an unpredictable response to hormonal treatment together pose both diagnostic and therapeutic challenges that negatively affect the prognosis. : This study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease, which may positively influence the prognosis.
Topics: Humans; Male; Middle Aged; Prostatic Neoplasms; Carcinoma, Signet Ring Cell; Mucins; Adenocarcinoma; Fatal Outcome
PubMed: 38929494
DOI: 10.3390/medicina60060877 -
Antioxidants (Basel, Switzerland) May 2024Prostate cancer remains a significant global health concern, posing a substantial threat to men's well-being. Despite advancements in treatment modalities, the...
Prostate cancer remains a significant global health concern, posing a substantial threat to men's well-being. Despite advancements in treatment modalities, the progression of prostate cancer still presents challenges, warranting further exploration of novel therapeutic strategies. In this study, osthole, a natural coumarin derivative, inhibited cell viability in cancer cells but not in the normal prostate cell line. Moreover, osthole disrupted cell cycle progression. Furthermore, osthole reduces mitochondrial respiration with mitochondrial membrane potential (ΔΨm) depolarization and reactive oxygen species (ROS) generation, indicating mitochondrial dysfunction. In particular, osthole-induced ROS generation was reduced by N-acetyl-L-cysteine (NAC) in prostate cancer. In addition, using calcium inhibitors (2-APB and ruthenium red) and endoplasmic reticulum (ER) stress inhibitor (4-PBA), we confirmed that ER stress-induced calcium overload by osthole causes mitochondrial dysfunction. Moreover, we verified that the osthole-induced upregulation of tiRNA expression is related to mechanisms that induce permeabilization of the mitochondrial membrane and calcium accumulation. Regarding intracellular signaling, osthole inactivated the PI3K and ERK pathways while activating the expression of the P38, JNK, ER stress, and autophagy-related proteins. In conclusion, the results suggest that osthole can be used as a therapeutic or adjuvant treatment for the management of prostate cancer.
PubMed: 38929108
DOI: 10.3390/antiox13060669 -
Ga-PSMA PET/CT in Recurrent Prostate Cancer after Radical Prostatectomy Using PSMA-RADS Version 2.0.Diagnostics (Basel, Switzerland) Jun 2024Ga-PSMA PET/CT is superior to standard-of-care imaging for detecting regional and distant metastatic recurrent prostate cancer. The objective of our study was to...
BACKGROUND
Ga-PSMA PET/CT is superior to standard-of-care imaging for detecting regional and distant metastatic recurrent prostate cancer. The objective of our study was to evaluate the performance of Ga-PSMAPET/CT in our patient population, using the new PSMA-RADS version 2.0.
METHODS
A total of 128 patients scanned with Ga-PSMA PET/CT for detection of recurrence after RP were analyzed with PSMA-RADS version 2.0. For the analysis of the detection rate, categories PSMA-RADS 3 to 5 were considered as "positive for malignancy" and 1-2 as "negative".
RESULTS
According to PSMA-RADS v2.0, we classified patients as follows: 23 patients without PSMA-RADS because they were negative; PSMA-RADS 1: 10 patients; PSMA-RADS 2: 4 patients; PSMA-RADS 3A: 11 patients; PSMA-RADS 3B: 2 patients; PSMA-RADS 3C: 2 patients; PSMA-RADS 3D: 2 patients; PSMA-RADS 4: 13 patients; PSMA-RADS 5: 61 patients.
CONCLUSIONS
The overall detection rate of Ga-PSMA PET/CT was 71%. By dividing the patients into fourgroups according to PSA level before examination, we obtained the following detection rates: PSA < 0.2 ng/mL 38%; 0.2 ≤ PSA < 0.5 ng/mL 57%; 0.5 ≤ PSA ≤ 1 ng/mL 77%; and PSA > 1 ng/mL 95%.
CONCLUSION
Using PSMA-RADS version 2.0, we obtained detection rate values comparable with recent literature both in absolute terms and in relation to different PSA levels.
PubMed: 38928706
DOI: 10.3390/diagnostics14121291 -
Diagnostics (Basel, Switzerland) Jun 2024Oligometastatic patients at [F]F-Fluorocholine (F-choline) PET/CT may be treated with metastasis-directed therapy (MDT). The aim of this study was to combine radiomic...
ML Models Built Using Clinical Parameters and Radiomic Features Extracted from F-Choline PET/CT for the Prediction of Biochemical Recurrence after Metastasis-Directed Therapy in Patients with Oligometastatic Prostate Cancer.
UNLABELLED
Oligometastatic patients at [F]F-Fluorocholine (F-choline) PET/CT may be treated with metastasis-directed therapy (MDT). The aim of this study was to combine radiomic parameters extracted from F-choline PET/CT and clinical data to build machine learning (ML) models able to predict MDT efficacy.
METHODS
Oligorecurrent patients (≤5 lesions) at F-choline PET/CT and treated with MDT were collected. A per-patient and per-lesion analysis was performed, using 2-year biochemical recurrence (BCR) after MDT as the standard of reference. Clinical parameters and radiomic features (RFts) extracted from F-choline PET/CT were used for training five ML Models for both CT and PET images. The performance metrics were calculated (i.e., Area Under the Curve-AUC; Classification Accuracy-CA).
RESULTS
A total of 46 metastases were selected and segmented in 29 patients. BCR after MDT occurred in 20 (69%) patients after 2 years of follow-up. In total, 73 and 33 robust RFTs were selected from CT and PET datasets, respectively. PET ML Models showed better performances than CT Models for discriminating BCR after MDT, with Stochastic Gradient Descent (SGD) being the best model (AUC = 0.95; CA = 0.90).
CONCLUSION
ML Models built using clinical parameters and CT and PET RFts extracted via F-choline PET/CT can accurately predict BCR after MDT in oligorecurrent PCa patients. If validated externally, ML Models could improve the selection of oligorecurrent PCa patients for treatment with MDT.
PubMed: 38928679
DOI: 10.3390/diagnostics14121264 -
International Journal of Molecular... Jun 2024Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including...
Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133/CD44 cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.
Topics: Humans; Gallbladder Neoplasms; MicroRNAs; RNA, Long Noncoding; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Octamer Transcription Factor-3; Female; Epithelial-Mesenchymal Transition; Drug Resistance, Neoplasm; Male; Neoplasm Invasiveness; Cisplatin; Middle Aged; Neoplastic Stem Cells; Fluorouracil; Lymphatic Metastasis
PubMed: 38928444
DOI: 10.3390/ijms25126740