ABSTRACT
Intraoral stents aim to reduce the oral complications associated with head and neck cancers radiotherapy. The aim of this study is to determine the benefits associated with these devices. A systematic review was conducted in PubMed, Web of Science, and Scopus databases selecting full articles published in English, Portuguese, or Spanish until June 6, 2020 (PROSPERO registration: CRD42020185065). The studies were evaluated by Hadorn and Somerfield criteria and guidelines were established. Nineteen studies were identified suggesting the use of intraoral stent for radiotherapy for patients with cancer on/near the mandible to reduce oral mucositis, trismus, xerostomia (LoE III), and dose in healthy structures (LoE IV) and for cancer on/near the maxilla to reduce oral mucositis and dose in healthy structures (LoE IV). Despite the limited scientific evidence, several benefits associated with the use of intraoral stent for radiotherapy of the head and neck neoplasia have been reported.
Subject(s)
Head and Neck Neoplasms , Stomatitis , Xerostomia , Head and Neck Neoplasms/radiotherapy , Humans , Radiotherapy , Stents , TrismusABSTRACT
Resistance to tyrosine-kinase inhibitors is a serious problem in the treatment of chronic myeloid leukemia (CML). Using Western blot, real-time qRT-PCR and flow cytometry, we investigated the expression of survivin, Smac/DIABLO and P-glycoprotein (Pgp) in patients with CML. Survivin overexpression has been associated with cancer progression, multidrug resistance, poor prognosis and short survival in several types of neoplasms including hematological malignancies. In this work, survivin expression was significantly elevated in late, in contrast to early, chronic phase CML (p=0.044). Patients with high or intermediate prognostic Sokal score presented higher survivin levels (p=0.012), as well as Smac/DIABLO levels (p=0.009) compared to low Sokal score. The strong correlation between survivin and Pgp expression in late (p=0.018), but not in early (p=0.5) chronic phase of CML, suggests that this association may play a biological role in late CML phase and may offer an important target for the development of new therapies.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , Inhibitor of Apoptosis Proteins/biosynthesis , Leukemia, Myeloid, Chronic-Phase/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Adult , Apoptosis Regulatory Proteins , Blotting, Western , Humans , Inhibitor of Apoptosis Proteins/genetics , Intracellular Signaling Peptides and Proteins/genetics , K562 Cells , Leukemia, Myeloid, Chronic-Phase/genetics , Leukemia, Myeloid, Chronic-Phase/pathology , Male , Middle Aged , Mitochondrial Proteins/biosynthesis , Mitochondrial Proteins/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Survivin , Young AdultABSTRACT
Despite the relevant therapeutic progresses obtained with imatinib, clinical resistance to this drug has emerged and reemerged after cytogenetic remission in a group of patients with chronic myeloid leukemia (CML). Therefore, novel treatment strategies are needed. In this study, we evaluated the anti-CML activity and mechanisms of action of LQB-118, a pterocarpanquinone structurally related to lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone]. LQB-118 treatment resulted in an important reduction of cell viability in cell lines derived from CML, both the vincristine-sensitive K562 cell line, and the resistant K562-Lucena (a cell line overexpressing P-glycoprotein). In agreement with these results, the induction of caspase-3 activation by this compound indicated that a significant rate of apoptosis was taking place. In these cell lines, apoptosis induced by LQB-118 was accompanied by a reduction of P-glycoprotein, survivin, and XIAP expression. Moreover, this effect was not restricted to cell lines as LQB-118 produced significant apoptosis rate in cells from CML patients exhibiting multifactorial drug resistance phenotype such as P-glycoprotein, MRP1 and p53 overexpression. The data suggest that LQB-118 has a potent anti-CML activity that can overcome multifactorial drug resistance mechanisms, making this compound a promising new anti-CML agent.
