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Garcinia indica (Kokum) and Ilex aquifolium (European Holly)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Dicson Sheeja Malar, Mani Iyer Prasanth, Tewin Tencomnao, James Michael Brimson, Anchalee Prasansuklab
Bioinformatics analysis has predicted the role of STAT3, STAT5 in glioblastoma conditions, which has been substantiated with experimental studies, where several fold-increase in their expression has been reported. Whereas, garcinol treatment showed attenuation of stem cell-like phenotypes with increase in hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratios (Liu et al., 2019). Overexpression of miR-181d has been reported to be associated with inhibition of cancer cell proliferation and migration by targeting K-ras and Bcl-2 (Wang et al., 2012b). Even though garcinol has potential anticancer activity, use of garcinol is still in its pre-clinical stage and this is mainly attributed to the limitations of conclusive evaluation of pharmacological parameters. This necessitates evaluation of garcinol pharmacokinetics to precisely identify an appropriate dose and route of administration, tolerability, and potency under physiological conditions along with characterization of a therapeutic index (Aggarwal et al., 2020).
Nanomaterials for Theranostics: Recent Advances and Future Challenges *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
Recently, signal transducers and activators of transcription (STAT) proteins such as STAT3 and STAT5 have emerged as promising molecular targets for cancer therapy [395], because they are also activated by growth factor receptors that have intrinsic tyrosine-kinase activity. Whereas activation of STAT proteins is tightly regulated in normal cells by the presence or absence of the polypeptide ligands bound to their receptors, increased tyrosine-kinase activity of growth factor receptors can be observed in cancer cells as a result of mutations [403–411].
Non-Melanoma Skin Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Irene De Francesco, Sean Whittaker, Stephen L. Morris
In CTCL, no disease-specific balanced translocations have yet been identified, but molecular cytogenetic studies do indicate that MF and SS have a closely related pattern of chromosomal abnormalities, suggesting that the two conditions share a similar pathogenesis.196,197 Numerical rather than structural abnormalities predominate, with losses of 1p, 10q, 13q, and 17p and gains of 4, 17q, and 18 being common.198–200 Recent genomic studies using high throughput sequencing platforms in MF and particularly SS have shown a wide range of gene mutations specifically targeting TCR signaling, chromatin remodeling, and DNA damage response. Many of these gene variants have been shown to have functional relevance, including causing constitutive transcriptional activation of NFAT, NFkB, and AP1 as well as signal-transducers and activators of transcription, namely STAT3 and STAT5. While this complex mutational landscape has a wide variety of potential consequences, a unifying hypothesis would be that there is dysregulation of T-cell activation in MF/SS, which prevents activation-induced T-cell death.201
Dual inhibition of STAT3 and STAT5 may overcome imatinib resistance in chronic myeloid leukemia
Published in Hematology, 2023
Lingling Yin, Jiawen Xu, Wenjian Wu, Mingshan Niu, Zhenyu Li, Feng Zhu, Kailin Xu
STAT3 and STAT5 are important effectors of cellular transformation. They also contribute to drug resistance in hematopoietic cancers and are now well recognized as common targets in cancer treatment. Previous studies have documented elevated levels of STAT5 in IM-resistant CML patients and K562R cells [22]. The activation of STAT5 contributes to BCR::ABL1-triggered CML via four key mechanisms which are to stimulate cells proliferation, to enhance cell viability by upregulation of anti-apoptotic genes, to counteract TKI-induced cell death and to increase the possibility of acquiring BCR::ABL1 mutations [23,24]. The importance of STAT5 in CML is further emphasized by findings that STAT5 is upregulated during disease progression. Furthermore, STAT5 activity is associated with poor prognosis.
The role of the prolactin receptor pathway in the pathogenesis of glioblastoma: what do we know so far?
Published in Expert Opinion on Therapeutic Targets, 2020
Antonela S Asad, Alejandro J Nicola Candia, Nazareno Gonzalez, Camila F Zuccato, Adriana Seilicovich, Marianela Candolfi
However, PRLR/STAT5 pathway may have opposite effects in breast cancer, depending on the tumor stage [22]. It has been postulated that while this pathway is necessary for breast tumor initiation, it does not seem to be required for its progression [67]. STAT5 is required for the differentiation of the mammary gland under normal conditions, thus PRL may benefit cell differentiation in the established tumor [68]. It has been described that JAK2/STAT5 pathway may inhibit invasion and epithelial-mesenchymal transition (EMT) in breast cancer cell lines [69]. Moreover, there are epidemiologic studies that show loss of STAT5 activation during breast cancer progression [70]. Considering that PRLR isoforms act through different signaling pathways, the relative expression of these isoforms may explain, at least partly, the versatility of PRL actions in normal and tumor tissues [22,39].
Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas
Published in Expert Opinion on Therapeutic Targets, 2018
Anna Orlova, Bettina Wingelhofer, Heidi A. Neubauer, Barbara Maurer, Angelika Berger-Becvar, György Miklós Keserű, Patrick T. Gunning, Peter Valent, Richard Moriggl
The vast majority of medicinal chemistry efforts to target STAT proteins have been conducted to develop specific inhibitors against STAT3 [130–132,136–148], with fewer reports of inhibitory modulators of STAT5A/B. The FDA-approved neuroleptic agent Pimozide was identified in a high-throughput screen as an inhibitor of STAT5 phosphorylation and an inducer of apoptosis in CML cell lines [149]. The underlying mechanism of action is unknown but was suggested to be upstream of STAT5. Furthermore, a non-peptidic chromone-based nicotinyl hydrazine, discovered through a screen of chemical libraries, was shown to weakly inhibit STAT5 activity [150]. This agent selectively inhibited the phosphorylation of STAT5 in lymphoma cell lines by unknown mechanisms. Inhibition of STAT5 activity was also reported for Indirubin derivatives, including E804, which blocked STAT5 phosphorylation and STAT5 DNA-binding activity in CML cells [151], associated with downregulation of MCL-1 and BCL2L1 expression. Based on the structure of the compound, the mechanism of inhibition of STAT5 here is most likely suppression of TK activities.