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Canadian Medical Association Journal Jun 1978
Topics: Coumarins; Ficusin; Humans; Photochemotherapy; Psoriasis; Ultraviolet Therapy
PubMed: 657023
DOI: No ID Found -
British Medical Journal Apr 1977
Topics: Coumarins; Ficusin; Furocoumarins; Humans; Methoxsalen; Psoriasis
PubMed: 851774
DOI: No ID Found -
Nature Genetics Nov 2023Somatic mutations are hypothesized to play a role in many non-neoplastic diseases. We performed whole-exome sequencing of 1,182 microbiopsies dissected from lesional and...
Somatic mutations are hypothesized to play a role in many non-neoplastic diseases. We performed whole-exome sequencing of 1,182 microbiopsies dissected from lesional and nonlesional epidermis from 111 patients with psoriasis to search for evidence that somatic mutations in keratinocytes may influence the disease process. Lesional skin remained highly polyclonal, showing no evidence of large-scale spread of clones carrying potentially pathogenic mutations. The mutation rate of keratinocytes was similarly only modestly affected by the disease. We found evidence of positive selection in previously reported driver genes NOTCH1, NOTCH2, TP53, FAT1 and PPM1D and also identified mutations in four genes (GXYLT1, CHEK2, ZFP36L2 and EEF1A1) that we hypothesize are selected for in squamous epithelium irrespective of disease status. Finally, we describe a mutational signature of psoralens-a class of chemicals previously found in some sunscreens and which are used as part of PUVA (psoralens and ultraviolet-A) photochemotherapy treatment for psoriasis.
Topics: Humans; Ficusin; PUVA Therapy; Psoriasis; Furocoumarins; Mutation
PubMed: 37884686
DOI: 10.1038/s41588-023-01545-1 -
Scientific Reports Mar 2023Anti-neoplastic effect of DNA cross-linking agents such as cisplatin, mitomycin C, and psoralen is attributed to their ability to induce DNA interstrand cross-links...
Anti-neoplastic effect of DNA cross-linking agents such as cisplatin, mitomycin C, and psoralen is attributed to their ability to induce DNA interstrand cross-links (ICLs), which block replication, transcription, and linear repair pathways by preventing DNA strand separation and trigger apoptosis. It is generally agreed that the Fanconi anemia (FA) pathway orchestrates the removal of ICLs by the combined actions of various DNA repair pathways. Recently, attention has been focused on the ability of the NEIL3-initiated base excision repair pathway to resolve psoralen- and abasic site-induced ICLs in an FA-independent manner. Intriguingly, overexpression of NEIL3 is associated with chemo-resistance and poor prognosis in many solid tumors. Here, using loss- and gain-of-function approaches, we demonstrate that NEIL3 confers resistance to cisplatin and participates in the removal of cisplatin-DNA adducts. Proteomic studies reveal that the NEIL3 protein interacts with the 26S proteasome in a cisplatin-dependent manner. NEIL3 mediates proteasomal degradation of WRNIP1, a protein involved in the early step of ICL repair. We propose that NEIL3 participates in the repair of ICL-stalled replication fork by recruitment of the proteasome to ensure a timely transition from lesion recognition to repair via the degradation of early-step vanguard proteins.
Topics: Humans; Cisplatin; Cross-Linking Reagents; DNA; DNA Damage; DNA Repair; DNA Replication; Ficusin; Proteomics
PubMed: 36997601
DOI: 10.1038/s41598-023-32186-3 -
Annals of Clinical and Translational... Oct 2021The voltage-gated potassium channel Kv1.3, which is expressed on activated, disease-associated microglia and memory T cells, constitutes an attractive target for...
OBJECTIVE
The voltage-gated potassium channel Kv1.3, which is expressed on activated, disease-associated microglia and memory T cells, constitutes an attractive target for immunocytoprotection after endovascular thrombectomy (EVT). Using young male mice and rats we previously demonstrated that the Kv1.3 blocker PAP-1 when started 12 h after reperfusion dose-dependently reduces infarction and improves neurological deficit on day 8. However, these proof-of-concept findings are of limited translational value because the majority of strokes occur in patients over 65 and, when considering overall lifetime risk, in females. Here, we therefore tested whether Kv1.3 deletion or delayed pharmacological therapy would be beneficial in females and aged animals.
METHODS
Transient middle cerebral artery occlusion (tMCAO, 60 min) was induced in 16-week-old and 80-week-old male and female wild-type C57BL/6J and Kv1.3 mice. Stroke outcomes were assessed daily with the 14-score tactile and proprioceptive limp placing test and on day 8 before sacrifice by T2-weighted MRI. Young and old female mice were treated twice daily with 40 mg/kg PAP-1 starting 12 h after reperfusion. Microglia/macrophage activation and T-cell infiltration were evaluated in whole slide scans.
RESULTS
Kv1.3 deletion provided no significant benefit in young females but improved outcomes in young males, old males, and old females compared with wild-type controls of the same sex. Delayed PAP-1 treatment improved outcomes in both young and old females. In old females, Kv1.3 deletion and PAP-1 treatment significantly reduced Iba-1 and CD3 staining intensity in the ipsilateral hemisphere.
INTERPRETATION
Our preclinical studies using aged and female mice further validate Kv1.3 inhibitors as potential adjunctive treatments for reperfusion therapy in stroke by providing both genetic and pharmacological verification.
Topics: Age Factors; Animals; Combined Modality Therapy; Disease Models, Animal; Female; Ficusin; Infarction, Middle Cerebral Artery; Kv1.3 Potassium Channel; Male; Mice; Mice, Inbred C57BL; Reperfusion; Stroke
PubMed: 34617690
DOI: 10.1002/acn3.51456 -
Journal of Cancer Research and Clinical... Mar 2024Psoralen is a family of naturally occurring photoactive compounds found in plants that acquire potential cytotoxicity when activated by specific frequencies of... (Review)
Review
Psoralen is a family of naturally occurring photoactive compounds found in plants that acquire potential cytotoxicity when activated by specific frequencies of electromagnetic waves. Psoralens penetrate the phospholipid cellular membranes and insert themselves between the pyrimidines of deoxyribonucleic acid (DNA). Psoralens are initially biologically inert and acquire photoreactivity when exposed to certain classes of electromagnetic radiation, such as ultraviolet light. Once activated, psoralens form mono- and di-adducts with DNA, leading to marked cell apoptosis. This apoptotic effect is more pronounced in tumor cells due to their high rate of cell division. Moreover, photoactivated psoralen can inhibit tyrosine kinase signaling and influence the immunogenic properties of cells. Thus, the cytotoxicity of photoactivated psoralen holds promising clinical applications from its immunogenic properties to potential anti-cancer treatments. This narrative review aims to provide an overview of the current understanding and research on psoralen and to explore its potential future pharmacotherapeutic benefits in specific diseases.
Topics: Humans; Ficusin; Furocoumarins; Ultraviolet Rays; DNA
PubMed: 38489072
DOI: 10.1007/s00432-024-05648-y -
Nature Communications Dec 2020Long noncoding RNAs are thought to regulate gene expression by organizing protein complexes through unclear mechanisms. XIST controls the inactivation of an entire X...
Long noncoding RNAs are thought to regulate gene expression by organizing protein complexes through unclear mechanisms. XIST controls the inactivation of an entire X chromosome in female placental mammals. Here we develop and integrate several orthogonal structure-interaction methods to demonstrate that XIST RNA-protein complex folds into an evolutionarily conserved modular architecture. Chimeric RNAs and clustered protein binding in fRIP and eCLIP experiments align with long-range RNA secondary structure, revealing discrete XIST domains that interact with distinct sets of effector proteins. CRISPR-Cas9-mediated permutation of the Xist A-repeat location shows that A-repeat serves as a nucleation center for multiple Xist-associated proteins and mA modification. Thus modular architecture plays an essential role, in addition to sequence motifs, in determining the specificity of RBP binding and mA modification. Together, this work builds a comprehensive structure-function model for the XIST RNA-protein complex, and suggests a general strategy for mechanistic studies of large ribonucleoprotein assemblies.
Topics: Adenine; Animals; Base Sequence; CRISPR-Cas Systems; Cell Line; Conserved Sequence; Cross-Linking Reagents; Female; Ficusin; Formaldehyde; Gene Knock-In Techniques; Humans; K562 Cells; Male; Mice; Mouse Embryonic Stem Cells; Nucleic Acid Conformation; Pregnancy; RNA, Long Noncoding; Ribonucleoproteins; Sequence Analysis, RNA
PubMed: 33268787
DOI: 10.1038/s41467-020-20040-3 -
International Journal of Radiation... Mar 2018This work investigates a new approach to enhance radiotherapy through a photo therapeutic agent activated by Cherenkov light produced from the megavoltage photon beam....
PURPOSE
This work investigates a new approach to enhance radiotherapy through a photo therapeutic agent activated by Cherenkov light produced from the megavoltage photon beam. The process is termed Radiotherapy Enhanced with Cherenkov photo-Activation (RECA). RECA is compatible with various photo-therapeutics, but here we focus on use with psoralen, an ultraviolet activated therapeutic with extensive history of application in superficial and extracorporeal settings. RECA has potential to extend the scope of psoralen treatments beyond superficial to deep seated lesions.
METHODS AND MATERIALS
In vitro studies in B16 melanoma and 4T1 murine breast cancer cells were performed to investigate the potential of RT plus RECA versus RT alone for increasing cytotoxicity (local control) and increasing surface expression of major histocompatibility complex I (MHC I). The latter represents potential for immune response amplification (increased antigen presentation), which has been observed in other psoralen therapies. Cytotoxicity assays included luminescence and clonogenics. The MHC I assays were performed using flow cytometry. In addition, Cherenkov light intensity measurements were performed to investigate the possibility of increasing the Cherenkov light intensity per unit dose from clinical megavoltage beams, to maximize psoralen activation.
RESULTS
Luminescence assays showed that RECA treatment (2 Gy at 6 MV) increased cytotoxicity by up to 20% and 9.5% for 4T1 and B16 cells, respectively, compared with radiation and psoralen alone (ie, Cherenkov light was blocked). Similarly, flow cytometry revealed median MHC I expression was significantly higher in RECA-treated cells, compared with those receiving radiation and psoralen alone (approximately 450% and 250% at 3 Gy and 6 Gy, respectively, P << .0001). Clonogenic assays of B16 cells at doses of 6 Gy and 12 Gy showed decreases in tumor cell viability of 7% (P = .017) and 36% (P = .006), respectively, when Cherenkov was present.
CONCLUSION
This work demonstrates for the first time the potential for photo-activation of psoralen directly in situ, from Cherenkov light generated by a clinical megavoltage treatment beam.
Topics: Animals; Cell Survival; Feasibility Studies; Female; Ficusin; Luminescent Measurements; Major Histocompatibility Complex; Mammary Neoplasms, Animal; Melanoma, Experimental; Mice; Photosensitizing Agents; Phototherapy; Radiotherapy
PubMed: 29413289
DOI: 10.1016/j.ijrobp.2017.11.013 -
Skin Therapy Letter Jun 2007Extracorporeal photopheresis (ECP) and psoralen plus ultraviolet A therapy (PUVA) are widely accepted types of photochemotherapy used for the treatment of cutaneous... (Review)
Review
Extracorporeal photopheresis (ECP) and psoralen plus ultraviolet A therapy (PUVA) are widely accepted types of photochemotherapy used for the treatment of cutaneous T-cell lymphomas (CTCL). PUVA and ECP utilize a photosensitizing agent, that can be taken orally (PUVA) or added to the concentrated sample of white blood cells extracorporeally (ECP) prior to UVA exposure. Both therapies have been shown to be safe and effective for the treatment of CTCL. As a monotherapy, PUVA is preferentially used for treatment of patients at earlier stages with skin involvement alone (T1 and T2). ECP is usually used for patients with erythrodermic skin involvement (T4) in advanced stages (Stage III and IVA) with peripheral blood involvement as in Sézary syndrome (SzS). Use of ECP in earlier stages is controversial and is currently under investigation. Both PUVA and ECP are rarely used as monotherapy, though long-term remissions after PUVA monotherapy for early disease have been reported. CTCL is a rare disease and randomized prospective clinical trials are difficult. The best efficacy data derived from prospective case studies and meta-analysis are reviewed here.
Topics: Ficusin; Humans; Lymphoma, T-Cell, Cutaneous; Photopheresis; Photosensitizing Agents; Skin Neoplasms; Treatment Outcome; Ultraviolet Therapy
PubMed: 17609808
DOI: No ID Found -
African Health Sciences Sep 2014Modern studies have shown that psoralen has a significant inhibitory effect on tumor growth in a variety of animals and humans.
BACKGROUND
Modern studies have shown that psoralen has a significant inhibitory effect on tumor growth in a variety of animals and humans.
OBJECTIVE
To obtain coumarin compounds - psoralen and isopsoralen - from traditional Chinese medicine Psoralea corylifolia L. using chromatographic techniques and isolation and purification methods, and to observe the transplanted tumor growth inhibitory effects and adverse reactions of psoralen and isopsoralen in nude rats with osteosarcoma.
METHODS
Dried ripe fruits of Psoralea corylifolia L. were taken as the raw material to prepare crude extract of Psoralea corylifolia L. by ethanol reflux method. Column chromatography was used to isolate the crude extract; compounds were structurally identified based on (1)H-NMR, (13)C-NMR spectra, the two compounds were identified as psoralen andisopsoralen, and their contents were 99.7% and 99.6, respectively. Nude rat model of osteosarcoma was established; the rats were randomized into: normal saline group, psoralen low- and high-dose groups, isopsoralen low- and high-dose groups, and cisplatin group. Osteosarcoma volume and weight inhibition rates in nude rats in each group were observed; radioimmunoassay was used to determine the serum alkaline phosphatase activity; peripheral blood cell and bone marrow nucleated cell counts were determined; light microscopy was used to observe heart, liver, spleen, lung, kidney, and tumor histopathology; and electron microscopy was used to observe the fine structure of tumor cells.
RESULTS
Tumor volume inhibition rates were 43.75% and 40.18%, respectively, in the psoralen and isopsoralen low-dose groups, and tumor weight inhibition rates were 38.83% and 37.77%. Tumor volume inhibition rates were 67.86% and 66.96%, respectively, in the psoralen and isopsoralen high-dose groups, and tumor weight inhibition rates were 49.47% and 47.87%. Psoralen and ispsoralen markedly lowered serum AKP level. Psoralen and isopsoralen induced apoptosis or necrosis of osteosarcoma. After administration of high doses of psoralen and isopsoralen, toxic reactions such as writhing, lassitude, and hypoactivity were seen. Kidney histopathology showed tubulointerstitial dilatation and congestion, and inflammatory cell aggregation in the renal intercellular space. Psoralen and isopsoralen did not cause any significant toxic side effects to the bone marrow, or other organs such as heart, lung, liver, and spleen.
CONCLUSION
Psoralen and isopsoralen have growth inhibitory effects on transplanted tumor in nude rats with osteosarcoma, and can induce tumor cell apoptosis or necrosis, without significant toxic effects.
Topics: Animals; Antineoplastic Agents, Phytogenic; Body Weight; Bone Neoplasms; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Ficusin; Fruit; Furocoumarins; Male; Osteosarcoma; Phytotherapy; Psoralea; Rats; Rats, Nude
PubMed: 25352883
DOI: 10.4314/ahs.v14i3.20