MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

nemoci-sympt/HEMATOLOGIE/lymfom-hodgkinuv/zlepsujici

Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)


Bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine and prednisone (BEACOPP)


CTLA-4 inhibitors


CTLA-4 monoclonal antibodies

  • Ipilimumab
  • Avelumab
  • Durmalumab
  • Consequence is usually about 50% irreversible in immune-related endocrine toxicities. Those toxicities include hypophysitis, adrenal insufficiency, type 1 diabetes mellitus, and thyroid dysfunctions

Celastrol

  • Celastrol (tripterine) is a chemical compound isolated from the root extracts of Tripterygium wilfordii (Thunder god vine) and Tripterygium regelii (Regel's threewingnut).
  • Inhibits proliferation, induces apoptosis and growth arrest of KMH2 via caspase3/7 activation
  • Whereas L428 cells were recalcitrant to this compound
  • Difference in cellular responses of either KMH2 or L428 to the same drug may be related to different subtypes of cHL
  • KMH2 is a cellular model of MC-cHL,
  • L428 of nodular sclerosis cHL.
  • City University of New York (CUNY), CUNY Academic Works, Publications and Research Bronx Community College 2020, CUNY Bronx Community College at.al.
  • Celastrol, an anti-inflammatory compound
  • Recognized HSP90 inhibitor, in Hodgkin and Reed–Sternberg cell lines
  • KM-H2 cells, celastrol inhibited cell proliferation, induced G0/G1 arrest, and triggered apoptosis through the activation of caspase-3/7.
  • L428 cells exhibited resistance to the compound.
  • www.mdpi.com/1422-0067/19/3/836/htm

Curcumin formulated in solid lipid nanoparticles

  • Has enhanced efficacy in Hodgkin's lymphoma in mice
  • When given in combination with bleomycin, doxorubicin and vinblastine, curcumin showed an additive growth inhibitory effect
  • We speculate that curcumin, when appropriately formulated, is a promising adjuvant agent for the treatment of HL and merits further evaluation
  • Curcumin formulated in solid lipid nanoparticles (SLNs) improves its plasma levels.
  • Curcumin formulated in SLN reduces Hodgkin's lymphoma (HL) xenograft growth.
  • Curcumin reduces the levels of inflammatory cytokines in HL cells.
  • Curcumin enhances the growth inhibitory effect of HL chemotherapeutic drugs.

Curcumin (diferuloylmethane)

  • Lipid-soluble yellow compound isolated from the rhizomes of the plant Curcuma longa
  • Induces cell-arrest and apoptosis
    • In association with the inhibition of constitutively active NF-?B and STAT3 pathways in Hodgkin's lymphoma cells
  • curcumin caused cell cycle arrest in G2-M and a significant reduction (80–97%) in H-RS cell viability.
  • curcumin triggered cell death by apoptosis
    • Activation of caspase-3 and caspase-9
    • Changes in nuclear morphology and phosphatidylserine translocation
  • Potential use of curcumin as a therapeutic agent for patients with HL
  • © 2008 Wiley-Liss, Inc.
  • onlinelibrary.wiley.com/doi/10.1002/ijc.23477


Ethacrynic acid (EA) and its derivatives

  • Inhibit the GST alpha, micro, pí subclasses
    • By binding to the substrate-binding site
    • By depleting enzymatic cofactors
-ar.iiarjournals.org/content/36/8/3905

Inhibition of HSP90

  • Induces apoptosis in Hodgkin's lymphoma cell lines

Luteolin

  • Induces Cytotoxicity in Mix Cellularity Classical Hodgkin's Lymphoma via Caspase Activated-cell Death
  • Luteolin (3,4,5,7-tetrahydroxy flavone, LUT)
  • Flavonoid found in common foods demonstrated in studies in multiple human malignancies such as lung, breast, glioblastoma, prostate, colon, and pancreatic cancers
  • Trigger apoptosis
  • Inhibit cell growth,
  • Stimulate cell cycle arrest
  • Disrupt metastasis and cell migration
  • Dietary intake of flavonoids was associated with reduced risk of occurrence non-Hodgkin’s lymphoma
  • LUT suppresses the growth of cHL, in vitro
    • Both cell lines, KMH2 and L428, showed dose-dependent cell growth responses to LUT treatment
  • LUT in part, suppresses viability of KMH2 via caspase activation.
  • City University of New York (CUNY), CUNY Academic Works, Publications and Research Bronx Community College 2020, CUNY Bronx Community College at.al.




Melatonin

  • Triggers autophagic cell death by regulating RORC in Hodgkin lymphoma
  • Melatonin exerted anti-tumor activities in Hodgkin lymphoma via inhibiting cell proliferation and promoting cell apoptosis.
  • Melatonin treatment induced autophagy in Hodgkin lymphoma cells.
  • Melatonin induces autophagy by increasing the expression of RORC.
  • Mel treatment increased expression of LC3-II and decreased p62 proteins with the enhanced production of autolysosome
    • Induced activation of autophagy
  • Together with autophagy inhibitors 3-MA or CQ exacerbated the damage effect of Mel in HL cells
    • Autophagy plays a protective role in this process.
  • Mel treatment increased the expression of G protein-coupled receptors MT2 and retinoic acid-related orphan receptors (RORs), eg. RORA, RORB and RORC.
    • While RORC has the highest increase in Mel treated HL cells.
    • RORC overexpression induced autophagy activation.
  • Therefore, Mel showed tumor-suppressive role due to an increased level of RORC induced autophagy in HL.
  • www.sciencedirect.com/science/article/pii/S0753332220300019

Nano-curcumin

PD-L1 inhibitors


PD-L1 inhibitory

  • PD-L1 (or B7-H1) is a protein produced by cancer cells
    • Interacts with PD-1
    • Suppresses activated T-cell from engaging with cancer cells
  • PD-L1 ligand activity may also induce apoptosis of T-cells.
  • PD-L1 overexpression is observed in melanoma, pancreatic, lung, and other types of cancer cells.
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC6949899/

Resveratrol

Extract of Anoectochilus formosanus Hayata

  • Anoectochilus formosanus extract (AFE)
  • Inhibits the constitutive expression of PD-L1 and accumulation of its protein
  • Induces the expression of pro-apoptotic genes but inhibits the expression of proliferative and metastatic genes
  • AFE induces anti-proliferation in cancer cells
  • AFE reduced blood glucose concentrations as well as metformin
  • Producing a hypoglycemic effect, ROS scavenging, and PD-L1 suppression.
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC6949899/

Pembrolizumab and nivolumab

  • Thyroid abnormalities like thyrotoxicosis, hypothyroidism, painless thyroiditis, and even thyroid storms are more commonly related to applying anti-PD-1 antibodies

Curcumin

  • Inhibit CSN5 to diminish PD-L1 expression in cancer cells
  • curcumin inhibits the expression of PD-L1 and p-STAT3Y705 both in vitro and in vivo
  • Treatment can change the immunosuppressive tumor microenvironment.
  • curcumin promoted an antitumor immune response effectively in tongue squamous cell carcinoma
  • Bisdemethoxycurcumin
    • A naturally produced curcumin dimethoxy derivative
    • Reduce PD-L1 expression to provide a promising environment for T-cell responses against bladder cancer
  • Combination of curcumin and apigenin
    • Suppresses cancer cell growth
    • Induces pro-apoptotic effects in melanoma cells

Apigenin

  • Inhibited IFN-gamma-induced PD-L1 up-regulation
    • Via significantly inhibiting STAT1 phosphorylation
  • Combined treatment sensitizes cancer cells to anti-CTLA4 therapy
www.ncbi.nlm.nih.gov/pmc/articles/PMC6949899/

Panobinostat

Resveratrol

  • Mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation
  • Resveratrol (RSV), a plant-derived stilbene
  • Induces cell death in Hodgkin lymphoma (HL)-derived L-428 cells in a dose-dependent manner
    • (IC50 = 27 µM, trypan blue exclusion assay)
  • At a lower range (25 µM)
    • RSV treatment for 48 hr causes arrest in the S-phase of the cell cycle
  • At a higher concentration range (50 µM)
    • Apoptosis can be detected, with activation of caspase-3.
  • The histone/protein deacetylase SIRT1 has been described as a putative target of RSV action in other model systems, even though its role in cancer cells is still controversial.
  • pubmed.ncbi.nlm.nih.gov/22833338/

Retinoids

  • Modulate cell growth and differentiation in a variety of human tumors.
  • Particularly effective in T-cell and Hodgkin lymphoma cell lines
  • Inhibit cell growth by arresting cells in the G1-phase or inducing apoptosis
  • Reduce the expression of antiapoptotic bcl-2 protein
  • Upregulate proapoptotic bax-proteins
  • Involved in the retinoic acid-induced pathway in T-cell lymphoma were identified
    • Transcription factors
    • Chaperones
    • Ion channels
    • Genes that code for cytoskeletal proteins
  • Retinoic acid (RA)-induced apoptosis may be mediated by way of a cascade of genes that is related to the various cellular functions

Bexarotene

  • RXR-selective retinoid
    • Induces in vitro apoptosis in CTCL cell lines
      • Without inhibiting DNA or inducing differentiation that is associated more with RAR agonists
  • Induced apoptosis of CTCL cells,
  • Suppressed the expression of RXR and RAR alpha proteins and mRNA,
  • Decreased the levels of proapoptotic proteins survivin,
  • Activated caspace-3
  • But did not effect expression of Fas/Fas ligand and bcl-2 proteins
  • www.sciencedirect.com/science/article/abs/pii/S0889858803001072

Roscovitine

  • Cyclin-dependent kinase inhibitor
  • Might be also a potential anticancer agent for treatment of HL.
  • Induces cell-cycle arrest and sensitizes HL cells to apoptosis
  • Agents which increase cytotoxic drug sensitivity of HL
    • Might be a treatment option for patients with chemoresistant HL.
  • ar.iiarjournals.org/content/36/8/3905

Synthetic HDL nanoparticles

  • Killed B-cell lymphoma, the most common form of the disease, in cultured human cells
  • And inhibited human B-cell lymphoma tumor growth in mice.
  • B-cell lymphoma is dependent on the uptake of natural HDL -- short for high-density lipoprotein -- from which it derives fat content, such as cholesterol.
  • Five nanometer gold particle at its core
  • When the nanoparticle is incubated with human B-cell lymphoma cells or used to treat a mouse with the human tumor
    • Socks lymphoma with a double whammy
  • Gold particle’s spongy surface sucks out its cholesterol while the gold core prevents the cell from absorbing more cholesterol typically carried in the core of natural HDL particles.
  • Heavily focused on developing nanoparticles that could remove cholesterol from cells, especially those involved in heart disease
    • To by mohly být třeba cyklodextriny !!!
  • Nanoparticle without drugs was just as effective at killing the B-cell lymphoma cells.
  • Lymphoma cells in patients had an overproduction of these HDL receptors compared to normal lymphocytes.

Vorinostat

  • Expression of histone deacetylase 6 (HDAC6) is also particularly high in HL.
  • HDAC inhibitor inhibits cell proliferation and induces changes in the gene expression pattern of HL cells.
  • Vorinostat increased sensitivity of HL cell lines to chemotherapy, i.e. cisplatin
  • ar.iiarjournals.org/content/36/8/3905

methyl-ß-cyclodextrin

O úroveň výše

Poslední aktualizace: 30. 9. 2024 0:00:36