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Molecules (Basel, Switzerland) Jul 2023The purpose of this study was to evaluate L-cysteine-modified transfersomes as the topical carrier for enhanced epidermal delivery of podophyllotoxin (POD)....
The purpose of this study was to evaluate L-cysteine-modified transfersomes as the topical carrier for enhanced epidermal delivery of podophyllotoxin (POD). L-cysteine-deoxycholic acid (LC-DCA) conjugate was synthesized via an amidation reaction. POD-loaded L-cysteine-modified transfersomes (POD-LCTs) were prepared via a thin membrane dispersion method and characterized for their particle size, zeta potential, morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and in vitro release. Subsequently, in vitro skin permeation and retention, fluorescence distribution in the skin, hematoxylin-eosin staining and in vivo skin irritation were studied. The POD-LCTs formed spherical shapes with a particle size of 172.5 ± 67.2 nm and a zeta potential of -31.3 ± 6.7 mV. Compared with the POD-Ts, the POD-LCTs provided significantly lower drug penetration through the porcine ear skin and significantly increased the skin retention ( < 0.05). Meaningfully, unlike the extensive distribution of the POD-loaded transfersomes (POD-Ts) throughout the skin tissue, the POD-LCTs were mainly located in the epidermis. Moreover, the POD-LCTs did not induce skin irritation. Therefore, the POD-LCTs provided an enhanced epidermal delivery and might be a promising carrier for the topical delivery of POD.
Topics: Animals; Swine; Administration, Cutaneous; Podophyllotoxin; Cysteine; Skin; Epidermis; Particle Size; Drug Carriers; Drug Delivery Systems
PubMed: 37570682
DOI: 10.3390/molecules28155712 -
STAR Protocols Sep 2022Though phospho-receptor-interacting protein 3 (RIP3 or RIPK3) antibodies are used in western blot, immunostaining of murine phospho-RIPK3 is challenging. Here, we verify...
Though phospho-receptor-interacting protein 3 (RIP3 or RIPK3) antibodies are used in western blot, immunostaining of murine phospho-RIPK3 is challenging. Here, we verify and describe a detailed protocol for immunofluorescent detection of phospho-RIPK3 in L929 cells and mouse yolk sacs. We also describe in detail the model construction methods, sample preparation steps, and staining procedures for immunohistochemical labeling of RIPK3 activation in mouse ceca and small intestines by utilizing a specific commercially available antibody. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021) and Wang et al. (2020).
Topics: Animals; Cisplatin; Etoposide; Intestine, Small; Mice; Receptor-Interacting Protein Serine-Threonine Kinases; Staining and Labeling; Yolk Sac
PubMed: 35779260
DOI: 10.1016/j.xpro.2022.101517 -
Molecules (Basel, Switzerland) Jun 2021M. Bieb and L. contain essential oil (EO), while also contains podophyllotoxin, which is used as a precursor for anti-cancer drugs. Two studies were conducted. The...
M. Bieb and L. contain essential oil (EO), while also contains podophyllotoxin, which is used as a precursor for anti-cancer drugs. Two studies were conducted. The first assessed the variability in the EO profile and podophyllotoxin concentration of the two junipers, depending on the location and tree gender. The main EO constituents of were α-cedrol, α-limonene and α-pinene, while the constituents in were sabinene, terpinen-4-ol, myrtenyl acetate and α-cadinol. The podophyllotoxin yield of 18 accessions was 0.07-0.32% (), but this was not found in any of the accessions. The second study assessed the effect of hydrodistillation (Clevenger apparatus) and steam distillation (in a semi-commercial apparatus) on the EO profile and bioactivity. The extraction type did not significantly alter the EO composition. The EO profiles of the two junipers and their accessions were different and may be of interest to the industry utilizing juniper leaf EO. Breeding and selection programs could be developed with the two junipers (protected species) in order to identify chemotypes with (1) a high EO content and desirable composition, and (2) a high concentration of podophyllotoxin in . Such chemotypes could be established as agricultural crops for the commercial production of podophyllotoxin and EO.
Topics: Bulgaria; Distillation; Juniperus; Oils, Volatile; Plant Leaves; Plant Oils; Podophyllotoxin; Slovakia
PubMed: 34203980
DOI: 10.3390/molecules26123659 -
The Journal of Investigative Dermatology Dec 1992The objective of the present study was to assess the utility of Shope rabbit papillomas as an animal model system for studying topical podofilox treatment and to...
The objective of the present study was to assess the utility of Shope rabbit papillomas as an animal model system for studying topical podofilox treatment and to evaluate dose-response relations and influence of duration of papilloma growth prior to treatment. New Zealand White rabbits received inoculations of cottontail rabbit papillomavirus (CRPV) virions of two dilutions at four sites total on the dorsum. Two papillomas on the left side were treated with podofilox (Oclassen Pharmaceuticals, Inc., San Rafael, CA). The drug was given topically twice each day, 5 d per week, for 21 d. We evaluated the effects of drug dose and the duration of papilloma growth prior to treatment. Results indicated that treatment beginning on day 28 with both 0.5 and 2.5% (w/v) podofilox inhibited papilloma growth, but 5.0% was more effective. In a separate experiment, papillomas were treated at 7, 21, or 60 d after virus inoculation. At 7 d, the untreated lesions were latent (not visible). At 21 d after infection, they were about 2.5 mm in diameter. At 60 d, papillomas were about 25 mm. Treatment with 5.0% podofilox beginning on any of those days strongly inhibited papilloma growth. Neither Southern blots nor PCR detected CRPV DNA in cured sites of previous virus infection. Antibody production to CRPV virion was not affected by drug treatment. 5.0% podofilox irritated normal skin adjacent to papillomas as evidenced by inflammation, induration, and superficial erosion. However, healing was satisfactory and no scarring resulted. We concluded that the Shope papilloma was a good model system for studying podofilox treatment because the lesions responded to drug across a broad range of drug concentrations and papilloma sizes.
Topics: Administration, Topical; Animals; Dose-Response Relationship, Drug; Female; Male; Papilloma; Podophyllotoxin; Rabbits; Skin Neoplasms; Time Factors
PubMed: 1469296
DOI: 10.1111/1523-1747.ep12614781 -
Cancer Jan 2009Secondary acute leukemia is a devastating complication in children and adolescents who have been treated for cancer. Secondary acute lymphoblastic leukemia (s-ALL) was... (Review)
Review
Secondary acute leukemia is a devastating complication in children and adolescents who have been treated for cancer. Secondary acute lymphoblastic leukemia (s-ALL) was rarely reported previously but can be distinguished today from recurrent primary ALL by comparison of immunoglobulin and T-cell receptor rearrangement. Secondary acute myeloid leukemia (s-AML) is much more common, and some cases actually may be second primary cancers. Treatment-related and host-related characteristics and their interactions have been identified as risk factors for s-AML. The most widely recognized treatment-related risk factors are alkylating agents and topoisomerase II inhibitors (epipodophyllotoxins and anthracyclines). The magnitude of the risk associated with these factors depends on several variables, including the administration schedule, concomitant medications, and host factors. A high cumulative dose of alkylating agents is well known to predispose to s-AML. The prevalence of alkylator-associated s-AML has diminished among pediatric oncology patients with the reduction of cumulative alkylator dose and limited use of the more leukemogenic alkylators. The best-documented topoisomerase II inhibitor-associated s-AML is s-AML associated with epipodophyllotoxins. The risk of s-AML in these cases is influenced by the schedule of drug administration and by interaction with other antineoplastic agents but is not consistently found to be related to cumulative dose. The unpredictable risk of s-AML after epipodophyllotoxin therapy may discourage the use of these agents, even in patients at a high risk of disease recurrence, although the benefit of recurrence prevention may outweigh the risk of s-AML. Studies in survivors of adult cancers suggest that, contrary to previous beliefs, the outcome of s-AML is not necessarily worse than that of de novo AML when adjusted for cytogenetic features. More studies are needed to confirm this finding in the pediatric patient population.
Topics: Adolescent; Adult; Child; Humans; Leukemia, Myeloid, Acute; Neoplasms, Second Primary; Podophyllotoxin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors
PubMed: 19072983
DOI: 10.1002/cncr.23988 -
Cancer Treatment and Research... 2020Etoposide phosphate (VP-16) is a topoisomerase 2 (TOP2) inhibitor that demonstrated activity in patients with metastatic castration-resistant prostate cancer (mCRPC). We...
BACKGROUND
Etoposide phosphate (VP-16) is a topoisomerase 2 (TOP2) inhibitor that demonstrated activity in patients with metastatic castration-resistant prostate cancer (mCRPC). We investigated the sensitivity of prostate cancer (PCa) cells (LNCaP, 22Rv1, PC3, DU145, PDB and MDB) to VP-16 and the possible relationship between VP-16 activity and TOP2 expression. The activity of VP-16 was compared with that of docetaxel, enzalutamide and olaparib. The prevalence and clinical significance of TOP2 genetic and transcriptomic alterations was also explored in mCRPC.
METHODS
Cell cultures and crystal violet cell proliferation assays were performed. Specific antibodies were used in western blots analyses of cell protein extracts. Datasets were analyzed in cBioportal.
RESULTS
VP-16 was active in all PCa cell lines analyzed and demonstrated increased activity in PC3 and DU145 cells. VP-16 was more cytotoxic compared to the other treatments, except for LNCaP and 22Rv1, which were more sensitive to docetaxel. Maintenance of antiandrogen treatment in MDB and PDB increased sensitivity to VP-16, docetaxel and enzalutamide. TOP2A was found overexpressed in 22Rv1, DU145 and PC3, whereas TOP2B was overexpressed in 22Rv1 and PDB. In the mCRPC datasets analysis, TOP2A mRNA overexpression was associated with worse patients' prognosis, with the molecular features of neuroendocrine prostate cancer (NEPC) and with lower androgen receptor (AR) score. Patients overexpressing TOP2A mRNA were more likely to harbor RB1 loss.
CONCLUSIONS
Specific subpopulations of patients with aggressive variant prostate cancer (AVPC) could benefit from VP-16 treatment. TOP2A overexpression, rather than TOP2B, might be a good biomarker to predict response to VP-16.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Etoposide; Humans; Male; Organophosphorus Compounds; Prostatic Neoplasms, Castration-Resistant; Topoisomerase II Inhibitors
PubMed: 33091733
DOI: 10.1016/j.ctarc.2020.100221 -
Biomedicine & Pharmacotherapy =... Apr 2023Increased activation and proliferation of T lymphocytes plays an essential role in the development of chronic inflammation and autoimmune diseases. Currently used...
Increased activation and proliferation of T lymphocytes plays an essential role in the development of chronic inflammation and autoimmune diseases. Currently used immunosuppressive drugs often do not provide long-lasting relief of symptoms and show a gradual loss of efficacy over time, and are accompanied by various side effects. Therefore, novel immunosuppressive lead substances are needed. For this purpose, an in-house library consisting of 600 extracts of plants from Panama was screened for inhibition of human T lymphocyte proliferation. As one of the hits, an ethyl acetate extract from the aerial parts of Hyptis brachiata (Lamiaceae) exhibited strong inhibitory effects. Subsequent investigation resulted in the isolation of seven aryltetralin lignans, five arylnaphthalene lignans, two flavonoids, three triterpenes, and cinnamyl cinnamate. Aryltetralin lignans inhibited T lymphocyte proliferation in a concentration-dependent manner without induction of apoptosis. No relevant inhibition was observed for the arylnaphthalene lignans, flavonoids, and triterpenes. Additional cell cycle arrest investigations revealed that isolated aryltetralin lignans potently inhibited cell division in G2/M phase similarly to podophyllotoxin. Multifluorescence panel analyses of the extract also showed weak suppressive effects on the production of IL-2 and TNF-α. Therefore, preparations made out of H. brachiata could be further explored as an interesting herbal alternative in the treatment of autoimmune diseases.
Topics: Humans; Lignans; Hyptis; Podophyllotoxin; Lamiaceae; Cell Proliferation
PubMed: 36739759
DOI: 10.1016/j.biopha.2023.114328 -
Clinical and Translational Medicine Apr 2023
Topics: Humans; Graves Ophthalmopathy; Podophyllotoxin; Adipocytes
PubMed: 37012693
DOI: 10.1002/ctm2.1218 -
Molecular Medicine Reports Feb 2021Lung cancer is the most common cancer type worldwide and the leading cause of cancer-related mortality. Diabetes is closely associated with the occurrence, development...
Lung cancer is the most common cancer type worldwide and the leading cause of cancer-related mortality. Diabetes is closely associated with the occurrence, development and prognosis of lung cancer. Therefore, the present study aimed to investigate whether SNCG could affect the proliferation of lung cancer cells induced by high glucose. Lung cancer cells induced by high glucose simulated the pathologies of patients with lung cancer with diabetes . The proliferation of HBE cells and lung cancer cells after transfection and treatment of glucose was detected using Cell Counting Kit-8 assay. The mRNA expression levels of synuclein γ (SNCG), insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) in HBE cells and lung cancer cells alone, or cells induced by high glucose were analyzed via reverse transcription-quantitative (RT-q)PCR analysis. Moreover RT-qPCR analysis was used to determine the transfection efficiencies. The clone formation ability, migration and inflammation of lung cancer cells after high glucose induction and transfection were detected using clone formation, wound healing and ELISA assays. The protein expression levels of SNCG, IGF-1, IGF-1R, ERK 1/2, phosphorylated (p)-ERK1/2 and JNK in lung cancer cells after high glucose induction and transfection were determined using western blot analysis. The results suggested that high glucose significantly promoted the proliferation of A549, NCI-H1975 and SK-MES-1 cells at 24 and 48 h, as well as upregulated the expression levels of SNCG, IGF-1 and IGF-1R. Knockdown of SNCG suppressed the proliferation, clone formation ability and migration, but alleviated inflammation in A549 cells induced by high glucose. Knockdown of SNCG suppressed the expression levels of SNCG, IGF-1, IGF-1R, ERK1/2 and p-ERK1/2, while it promoted JNK expression in A549 cells induced by high glucose. The effect of AXL1717 (an IGF-1R inhibitor) treatment on cells was consistent with that of SNCG knockdown. In conclusion, inhibition of SNCG suppresses proliferation of lung cancer cells induced by high glucose.
Topics: Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Knockdown Techniques; Glucose; Humans; Inflammation; Insulin-Like Growth Factor I; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Lung Neoplasms; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neoplasm Proteins; Podophyllotoxin; Receptor, IGF Type 1; Tumor Necrosis Factor-alpha; Tumor Stem Cell Assay; gamma-Synuclein
PubMed: 33313952
DOI: 10.3892/mmr.2020.11777 -
European Journal of Hospital Pharmacy :... Jul 2022According to the manufacturers, the concentration of etoposide solutions should not exceed 0.4 mg/mL due to a risk of precipitation. Stability studies at higher...
OBJECTIVES
According to the manufacturers, the concentration of etoposide solutions should not exceed 0.4 mg/mL due to a risk of precipitation. Stability studies at higher concentrations were conducted and notably demonstrated 28 day stability up to 1.75 mg/mL for etoposide solutions in 5% dextrose (D5W). Nevertheless, colleagues report precipitation even at 0.4 mg/mL in their daily practice. The objective of this work was to reassess the physical stability of highly concentrated etoposide solutions in D5W (1.2 mg/mL), over a large number of preparations and under different manufacturing processes.
METHODS
To study the impact of manufacturing process, etoposide was taken with a spike or a needle and injected in three types of D5W containers (Easyflex, Viaflo and Ecoflac). Forty preparations were made for each container. For half of the preparations, a homogenisation was performed by a syringe rinse. Physical stability was realised by two examiners, with a visual examination searching for the appearance of a precipitate, daily during the first week, then twice a week until day 56.
RESULTS
Hundred and eighteen solutions were clear and colourless. Precipitates were observed for two solutions: one in an Easyflex bag on day 4 and one in an Ecoflac container on day 35.
CONCLUSIONS
The physical stability at 1.2 mg/mL in D5W remains validated. Precipitations are rare and concern less than 2% of preparations. The appearance of a precipitate does not seem to be correlated to the kind of container or manufacturing process. A rinse was performed for these two solutions to assess a mechanical pressure effect more important on the solution, which could lead to a higher risk of precipitations. However, this is not observed in our daily practice, especially at lower concentrated solutions. We only recommend using an administration set with an in-line micro-filter as a precaution in case of precipitations.
Topics: Drug Stability; Etoposide; Glucose; Syringes
PubMed: 33082147
DOI: 10.1136/ejhpharm-2020-002468