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Background: Bexarotene, also recognized as Targretin, is categorized as a retinoid, a type of cancer drug. Nevertheless, the precise mechanisms of bexarotene in relation to colon cancer remain unclear. In colon cancer, SEZ6L2 was suggested as one of the biomarkers and targets. This study presents a comprehensive exploration of the role of SEZ6L2 in colon cancer. Methods: We utilized both TCGA data and a cohort of Chinese patients. In a meticulous analysis of 478 colon cancer cases, SEZ6L2 expression levels were examined in relation to clinical characteristics, staging parameters, and treatment outcomes. Additionally, we investigated the pharmacological impact of bexarotene on SEZ6L2, demonstrating a significant downregulation of SEZ6L2 at both mRNA and protein levels in colon cancer patients following bexarotene treatment. Results: SEZ6L2 consistently overexpresses in colon cancer, serving as a potential universal biomarker with prognostic significance, validated in a diverse Chinese cohort. In vitro, SEZ6L2 promotes cell viability without affecting migration. Bexarotene treatment inhibits SEZ6L2 expression, correlating with reduced viability both in vitro and in vivo. SEZ6L2 overexpression accelerates declining survival rates in an in vivo context. Bexarotene's efficacy is context-dependent, effective in parental cells but not with SEZ6L2 overexpression. Computational predictions suggest a direct SEZ6L2-bexarotene interaction, warranting further experimental exploration. Conclusion: The study provides valuable insights into SEZ6L2 as a prognostic biomarker in colon cancer, revealing its intricate relationship with clinical parameters, treatment outcomes, and bexarotene effects. Context-dependent therapeutic responses emphasize the nuanced understanding required for SEZ6L2's role in colon cancer, paving the way for targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose–dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs.

Treatment with bexarotene, a selective retinoid X receptor (RXR) agonist, significantly improves behavioral dysfunctions in various neurodegenerative animal models. Additionally, it activates neurodevelopmental and plasticity pathways in the brains of adult mice. Our objective was to investigate the impact of RXR activation by bexarotene on adult neural stem cells (aNSC) and their cell lineages. To achieve this, we treated NSCs isolated from the subventricular zone (SVZ) of adult rat brains from the proliferative stage to the differentiated status. The results showed that bexarotene‐treated aNSC exhibited increased BrdU incorporation, SOX2+ dividing cell pairs, and cell migration from neurospheres, revealing that the treatment promotes self‐renewing proliferation and cell motility in SVZ‐aNCS. Furthermore, bexarotene induced a cell fate shift characterized by a significant increase in GFAP+/S100B+ differentiated astrocytes, which uncovers the participation of activated‐RXR in astrogenesis. In the neuronal lineage, the fate shift was counteracted by bexarotene‐induced enhancement of NeuN+ nuclei together with neurite network outgrowth, indicating that the RXR agonist stimulates SVZ‐aNCS neuronal differentiation at later stages. These findings establish new connections between RXR activation, astro‐ and neurogenesis in the adult brain, and contribute to the development of therapeutic strategies targeting nuclear receptors for neural repair. [ABSTRACT FROM AUTHOR]

The Cambridge Centre for Myelin Repair One (CCMR-One) trial showed that 6 months of bexarotene reduces visual evoked potential (VEP) latency in people with relapsing-remitting multiple sclerosis (MS). In a single-centre follow-up study of these participants, we re-examined full-field VEP and clinical assessments. Twenty participants (12 bexarotene and 8 placebo) were seen on average 27 months after their trial involvement. In an analysis of all eyes with recordable signal (24 bexarotene and 14 placebo), the adjusted bexarotene-placebo treatment difference in P100 latency was −7.79 (95% confidence interval (CI) = −14.76, −0.82) ms, p = 0.044. We conclude that there were durable improvements in VEP latency, suggesting long-term benefits from exposure to a remyelinating drug. [ABSTRACT FROM AUTHOR]

Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.

An in‐loop 11C‐carbonylation process for the radiosynthesis of 11C‐carboxylic acids and esters from halide precursors has been developed. The reaction proceeds at room temperature under mild conditions and enables 11C‐carbonylation of both electron deficient and electron rich (hetero)aromatic halides to provide 11C‐carboxylic acids and esters in good to excellent radiochemical yields, high radiochemical purity, and excellent molar activity. The process has been fully automated using commercial radiochemistry synthesis modules, and application to clinical production is demonstrated via validated cGMP radiosyntheses of [11C]bexarotene and [11C]acetoacetic acid. [ABSTRACT FROM AUTHOR]

The synthetic retinoid bexarotene (BXT), used in the treatment of cutaneous T-cell lymphoma (CTCL), has been associated with central hypothyroidism due to suppression of thyrotropin (TSH) secretion and upregulation of peripheral thyroxine (T4) and triiodothyronine (T3) metabolism. We present a case of a 41-year-old man with CTCL who developed central hypothyroidism within 1 month of receiving BXT. He required sequential uptitration of levothyroxine (LT4) over 15 months, and free T4 (FT4) and total T3 levels were normalized by a daily regimen of LT4 600 mcg and liothyronine (LT3) 15 mcg. While almost all patients regain normal hypothalamic-pituitary-thyroid axis function after cessation of BXT, there are limited data regarding LT4 and LT3 dosing required to adequately treat central hypothyroidism in patients on BXT. Our patient required an LT4 dose approximately 2.8 times the calculated weight-based dose and LT3 supplementation, demonstrating a large LT4/LT3 combination dose may be required to compensate for BXT-induced central hypothyroidism. [ABSTRACT FROM AUTHOR]

Abstract Adult T‐cell leukaemia‐lymphoma (ATL) is a mature T‐cell malignancy, with more than 50% of cases showing cutaneous involvement. Patients with cutaneous‐type ATL (cATL) in the indolent type (i.e., favourable chronic or smouldering type) can usually be managed by watchful waiting and they are primarily treated with skin‐directed therapies until the disease progresses to acute crisis, with multiple tumours usually considered intractable. ATL tends to present in older patients, and those with multiple cATL tumours face difficulties in obtaining multiagent chemotherapy used for aggressive types. Although bexarotene is a third‐generation novel retinoid X receptor‐selective retinoid treatment that is effective for cutaneous T‐cell lymphoma, few reports have demonstrated its effectiveness for cATL. We describe an 86‐year‐old woman with cATL treated safely and successfully with a combination of oral bexarotene and skin‐directed therapies, despite renal dysfunction and previous hypothyroidism. After 10 months of treatment, we observed neither new tumours nor disease recurrence, with complete response maintained at 24 months until now while continuing bexarotene. Our experience suggests that oral bexarotene is an effective treatment option, even for elderly patients with cATL.

Mycosis fungoides (MF) progresses slowly before advancing to skin tumors followed by lymph node and visceral involvement. Among MF progression, stage IIB is an initial time point of tumor formation in MF. Since MF in tumor stage possess abundant blood vessels, it is important to evaluate the pro‐angiogenic factors before and after MF in stage IIB. In this report, we investigated pro‐angiogenic soluble factors in MF patients, as well as its pro‐angiogenetic effects on tumor cells and stroma cells. We first evaluated the serum levels of pro‐angiogenic factors in 9 MF patients without tumor formation and 8 MF patients with tumor formation. Among them, the serum MMP‐9 and plasminogen activator inhibitors 1 (PAI‐1) was significantly increased in MF with tumor formation compared in MF without tumor formation, leading to favorable formation of human dermal microvascular endothelial cells tube networks. Moreover, PAI‐1 stimulation significantly increased the mRNA expression and protein production MMP‐9 on monocytes derived M2 macrophages and HUT‐78. Furthermore, since MMP‐9 production from tumor cells as well as stromal cells is suppressed by bexarotene, we evaluate the baseline serum pro‐angiogenic factors including MMP‐9 in 16 patients with advanced cutaneous T cell lymphoma treated with bexarotene. The serum levels of MMP‐2 and MMP‐9 was significantly increased in bexarotene non‐responded patients compared to responded patients. Our present study suggested the significance of MMP‐9 and PAI‐1 for the progression of MF stage toward to the tumor stage, and could be a therapeutic target in future. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most widespread form of senile dementia worldwide and represents a leading socioeconomic problem in healthcare. Although it is widely debated, the aggregation of the amyloid β peptide (Aβ) is linked to the onset and progression of this neurodegenerative disease. Molecules capable of interfering with specific steps in the fibrillation process remain of pharmacological interest. To identify such compounds, we have set up a small molecule screening process combining multiple experimental methods (UV and florescence spectrometry, ITC, and ATR-FTIR) to identify and characterise potential modulators of Aβ1-42 fibrillation through the description of the biochemical interactions (molecule–membrane Aβ peptide). Three known modulators, namely bexarotene, Chicago sky blue and indomethacin, have been evaluated through this process, and their modulation mechanism in the presence of a biomembrane has been described. Such a well-adapted physico-chemical approach to drug discovery proves to be an undeniable asset for the rapid characterisation of compounds of therapeutic interest for Alzheimer's disease. This strategy could be adapted and transposed to search for modulators of other amyloids such as tau protein. [ABSTRACT FROM AUTHOR]

Abstract is missing (Quiz)

Bexarotene is an effective oral drug for the treatment of cutaneous T‐cell lymphoma, but careful management is required due to its various side effects. In particular, hypertriglyceridemia often requires a reduction or even suspension of bexarotene therapy. The risk factors of bexarotene‐associated severe hypertriglyceridemia are not clear. Here, we conducted a post hoc analysis of the data from our previous clinical trial, which confirmed the efficacy and safety of combined bexarotene and phototherapy, to evaluate the effect of body mass index on bexarotene‐associated hypertriglyceridemia. Twenty‐five subjects were divided into two subgroups: normal and underweight (body mass index [BMI] <25 kg/m2 group) and overweight and obese (BMI ≥25 kg/m2 group) patients. The overall incidence of hypertriglyceridemia was 81.3% (13/16) in the BMI <25 kg/m2 group and 88.9% (8/9) in the BMI ≥25 kg/m2 group. The incidence of grade ≥3 hypertriglyceridemia (≥500 mg/dL) was 7.7% (1/13) in the BMI <25 kg/m2 group and 7/8 (87.5%) in the BMI ≥25 kg/m2 group (P < 0.001). Consequently, dose reduction in the BMI ≥25 kg/m2 group was larger than that in the BMI <25 kg/m2 group. The bexarotene‐induced change in the serum triglyceride concentration was significantly increased in cutaneous T‐cell lymphoma patients with a higher body mass index (ρ = 0.508, P = 0.009). The area under the curve was 0.886 (95% confidence interval 0.748–1.000, P = 0.002). With a body mass index cut‐off of 24.85 kg/m2, the sensitivity and specificity for identifying grade ≥3 hypertriglyceridemia were 0.875 and 0.882, respectively. The present findings suggest that BMI ≥25 kg/m2 is a risk factor for bexarotene‐associated severe hypertriglyceridemia, therefore overweight and obese patients treated with bexarotene should receive lipid‐lowering drugs prophylactically. Further studies for optimizing the initial bexarotene dose in such patients are required. [ABSTRACT FROM AUTHOR]

Based on accumulating evidence, cholesterol metabolism dysfunction has been suggested to contribute to the pathophysiological process of traumatic brain injury (TBI) and lead to neurological deficits. As a key transporter of cholesterol that efflux from cells, the ATP‐binding cassette (ABC) transporter family exerts many beneficial effects on central nervous system (CNS) diseases. However, there is no study regarding the effects and mechanisms of ABCG1 on TBI. As expected, TBI resulted in the different time‐course changes of cholesterol metabolism‐related molecules in the injured cortex. Considering ABCG1 is expressed in neuron and glia post‐TBI, we generated nestin‐specific Abcg1 knockout (Abcg1‐KO) mice using the Cre/loxP recombination system. These Abcg1‐KO mice showed reduced plasma high‐density lipoprotein cholesterol levels and increased plasma lower‐density lipoprotein cholesterol levels under the base condition. After TBI, these Abcg1‐KO mice were susceptible to cholesterol metabolism turbulence. Moreover, Abcg1‐KO exacerbated TBI‐induced pyroptosis, apoptosis, neuronal cell insult, brain edema, neurological deficits, and brain lesion volume. Importantly, we found that treating with retinoid X receptor (RXR, the upstream molecule of ABCG1) agonist, bexarotene, in Abcg1‐KO mice partly rescued TBI‐induced neuronal damages mentioned above and improved functional deficits versus vehicle‐treated group. These data show that, in addition to regulating brain cholesterol metabolism, Abcg1 improves neurological deficits through inhibiting pyroptosis, apoptosis, neuronal cell insult, and brain edema. Moreover, our findings demonstrate that the cerebroprotection of Abcg1 on TBI partly relies on the activation of the RXRalpha/PPARgamma pathway, which provides a potential therapeutic target for treating TBI. [ABSTRACT FROM AUTHOR]

Background and Aims: The objective of this work was to formulate liposomal gel formulation of bexarotene for Cutaneous T-cell Lymphoma (CTCL). Low solubility and high log P value make the drug a poor candidate for its penetrability and absorption through the transdermal route. When bexarotene is incorporated into liposomal formulation, its solubility and permeability can enhance. Methods: In the present investigation, the liposomes of bexarotene were prepared by thin film-hydration method and optimized for different critical processing parameters such as the amount of lipid and the time of stirring. Checkpoint batches were prepared to validate the mathematical model. Results: The final optimized liposome formulation, which has more than 85% entrapment efficiency and vesicle size of 625 nm, was prepared. The optimized liposomes were loaded (equivalent to 1% w/w bexarotene) into the carbopol gel (1.5% w/w) and, evaluated for physico-chemical parameters. In vitro drug permeation and deposition of promised liposomal gel were performed through rat skin. The skin irritation studies of the liposomal gel were examined on rats, in vivo. MTT assay was performed to determine the cytotoxicity and cell apoptosis on CTCL specified cell line (Hut-78) by bexarotene liposomal gel. The optimized liposomes of bexarotene (FL1) were found to be spherical having a vesicle size of 639 nm with PDI 0.115 and a zeta potential value of -19.3 mV. The promised liposomal gel (LG5) evaluations were found in the limit. The LG5 was shown 31% bexarotene deposition in the skin. The experiment revealed a significant decrease (p<0.005) in the number of viable cells following MTT assay. Conclusion: The liposomal gel formulation of bexarotene improved the treatment and management of CTCL. [ABSTRACT FROM AUTHOR]

Abstract is missing (Quiz)

Objective: To investigate the protective effect of bexarotene in radiation-induced skin injury and elucidate underlying mechanism. Methods: Irradiated cellular and animal models were established using an X-ray linear accelerator. Cell viability and apoptosis were evaluated by CCK8 and flow cytometry. In vivo protective effect of bexarotene was measured in irradiated SD rats. The antioxidant capacity of bexarotene was validated by DCF-DA method. The signaling pathways involved in bexarotene-mediated skin repair were enriched by RNA sequencing. Results: Bexarotene could significantly restore the proliferation and inhibit the apoptosis of WS1 cells with radiation damage (P ​

Bexarotene-tethered RuII(arene) compounds with 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (PTA) were prepared as an analog of RAPTA antitumor complexes in order to evaluate their in vitro antiproliferative activity against human cancer cell lines. [ABSTRACT FROM AUTHOR]

Bexarotene, a FDA-approved drug for cutaneous lymphoma, has been shown to exert brain protective effects. In previous study, we demonstrated that Bexarotene protects against cerebral ischemic stroke by suppressing the JNK/Caspase-3 signaling pathway. However, the molecular mechanisms by which Bexarotene-mediated neuroprotective are not fully understood. Based on the isobaric tags for relative and absolute quantification (iTRAQ)-derived proteomics and bioinformatics analysis, 4,454 differentially expressed proteins (DEPs) were identified in upstream of the JNK signaling pathway. Among them, 149 DEPs showed aberrant expression in the vehicle-versus Bexarotene-treated mice. DEPs were primarily enriched in the metabolism, calcium, and MAPK signaling pathways. The largest DEP increase was seen with heat shock protein HSP 70, whereas the largest DEP decrease was seen with JNK scaffold protein JIP3, both of which are involved in the MAPK network. Furthermore, we illustrated the Bexarotene obviously abolished oxygen and glucose deprivation/reperfusion (OGD/R)- induced LDH leakage, cells apoptosis, and the protein expression level of the JIP3,p-ASK1, p-JNK, and Cleaved Caspase3. Together, these results suggest a potential neuroprotective role of Bexarotene via inhibition of the JIP3/ASK1/JNK/Caspase 3 signaling pathway.

Alzheimer’s disease (AD) is the most widespread form of senile dementia worldwide and represents a leading socioeconomic problem in healthcare. Although it is widely debated, the aggregation of the amyloid β peptide (Aβ) is linked to the onset and progression of this neurodegenerative disease. Molecules capable of interfering with specific steps in the fibrillation process remain of pharmacological interest. To identify such compounds, we have set up a small molecule screening process combining multiple experimental methods (UV and florescence spectrometry, ITC, and ATR-FTIR) to identify and characterise potential modulators of Aβ1-42 fibrillation through the description of the biochemical interactions (molecule–membrane Aβ peptide). Three known modulators, namely bexarotene, Chicago sky blue and indomethacin, have been evaluated through this process, and their modulation mechanism in the presence of a biomembrane has been described. Such a well-adapted physico-chemical approach to drug discovery proves to be an undeniable asset for the rapid characterisation of compounds of therapeutic interest for Alzheimer’s disease. This strategy could be adapted and transposed to search for modulators of other amyloids such as tau protein.

Bexarotene is a third-generation retinoid X receptor-selective retinoid that has been approved for use in the treatment of cutaneous T-cell lymphomas (CTCLs). Since the objective response rate of bexarotene is relatively high, with no racial differences, bexarotene can be administered to patients with phototherapy-resistant early CTCL as one of the first-line therapies in real-world clinical practice. Although various adverse events caused by bexarotene have been reported, there have been no reports of drug eruptions caused by bexarotene. One of the possible reasons is that it is difficult to distinguish a drug eruption from recurrence of CTCL, histologically. In this report, drug eruptions in 2 patients with CTCL treated with bexarotene diagnosed by quantitative analysis of immunohistochemical staining by digital microscopy are described.

BACKGROUND: Treatment choices for patients with advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) who have failed first-line systemic therapies can be challenging, as several options are available. However, most evidence is based on observational and early phase studies due to the rarity of the disease. Mogamulizumab has recently been approved for the treatment of adult patients with MF or SS who have received at least one prior systemic therapy; it has a good tolerability profile prompting its use in combination with other agents. This article aims at describing the role of the concomitant use of bexarotene with mogamulizumab in this setting. CASES PRESENTATION: To add information in the field, we describe our experience with four patients with MF/SS who failed first- and second-line treatments and started the combination mogamulizumab in addition to bexarotene. The combination of bexarotene with mogamulizumab in patients with advanced MF/SS after the failure of bexarotene alone obtained a response in all the four patients observed. The response was maintained longer than expected. CONCLUSIONS: The combination is promising and deserves further study. [ABSTRACT FROM AUTHOR]

Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi's sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice. [ABSTRACT FROM AUTHOR]

Bexarotene (BEX) was approved by the FDA in 1999 for the treatment of cutaneous T-cell lymphoma (CTCL). The poor aqueous solubility causes the low bioavailability of the drug and thereby limits the clinical application. In this study, we developed a GCN-based deep learning model (CocrystalGCN) for in-silico screening of the cocrystals of BEX. The results show that our model obtained high performance relative to baseline models. The top 30 of 109 coformer candidates were scored by CocrystalGCN and then validated experimentally. Finally, cocrystals of BEX-pyrazine, BEX-2,5-dimethylpyrazine, BEX-methyl isonicotinate, and BEX-ethyl isonicotinate were successfully obtained. The crystal structures were determined by single-crystal X-ray diffraction. Powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis were utilized to characterize these multi-component forms. All cocrystals present superior solubility and dissolution over the parent drug. The pharmacokinetic studies show that the plasma exposures (AUC0−8h) of BEX-pyrazine and BEX-2,5-dimethylpyrazine are 1.7 and 1.8 times that of the commercially available BEX powder, respectively. This work sets a good example for integrating virtual prediction and experimental screening to discover the new cocrystals of water-insoluble drugs. [ABSTRACT FROM AUTHOR]

Therapeutic targets in cancer cells defective for the tumor suppressor ARID1A are fundamentals of synthetic lethal strategies. However, whether modulating ARID1A function in premalignant breast epithelial cells could be exploited to reduce carcinogenic potential remains to be elucidated. In search of chromatin-modulating mechanisms activated by anti-proliferative agents in normal breast epithelial (HME-hTert) cells, we identified a distinct pattern of genome-wide H3K27 histone acetylation marks characteristic for the combined treatment by the cancer preventive rexinoid bexarotene (Bex) and carvedilol (Carv). Among these marks, several enhancers functionally linked to TGF-β signaling were enriched for ARID1A and Brg1, subunits within the SWI/SNF chromatin-remodeling complex. The recruitment of ARID1A and Brg1 was associated with the suppression of TGFBR2, KLF4, and FoxQ1, and the induction of BMP6, while the inverse pattern ensued upon the knock-down of ARID1A. Bex+Carv treatment resulted in fewer cells expressing N-cadherin and dictated a more epithelial phenotype. However, the silencing of ARID1A expression reversed the ability of Bex and Carv to limit epithelial–mesenchymal transition. The nuclear levels of SMAD4, a canonical mediator of TGF-β action, were more effectively suppressed by the combination than by TGF-β. In contrast, TGF-β treatment exceeded the ability of Bex+Carv to lower nuclear FoxQ1 levels and induced markedly higher E-cadherin positivity, indicating a target-selective antagonism of Bex+Carv to TGF-β action. In summary, the chromatin-wide redistribution of ARID1A by Bex and Carv treatment is instrumental in the suppression of genes mediating TGF-β signaling, and, thus, the morphologic reprogramming of normal breast epithelial cells. The concerted engagement of functionally linked targets using low toxicity clinical agents represents an attractive new approach for cancer interception. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the single and combined antidiabetic activity and side effects of the retinoid X receptor agonist bexarotene and the thioredoxin-interacting protein inhibitor and peroxisome proliferator-activated receptor γ and AMP-activated protein kinase activator icariin., Methods: The rats were grouped as healthy (control), diabetes, diabetes + bexarotene (20 mg/kg), diabetes + icariin (60 mg/kg), diabetes + bexarotene (10 mg/kg) + icariin (30 mg/kg) low-dose combination and diabetes + bexarotene (20 mg/kg) + icariin (60 mg/kg) high-dose combination groups., Key Findings: Icariin treatment led to a significant reduction in glucose levels compared with the diabetes control group, a remarkable outcome observed 45 days after the initial application. HbA1c levels of the icariin and low-dose combination treatment groups were significantly lower than in the diabetes group. Notably, icariin treatment also significantly elevated HOMA-β levels, which is indicative of improved β-cell function. Icariin significantly decreased glucose levels at 30 and 120 min in the oral glucose tolerance test. Moreover, it ameliorated hepatocyte degeneration, hepatic cord dissociation, congestion, mononuclear cell infiltration in the liver, and degeneration in the pancreas., Conclusions: Icariin treatment exhibited robust antidiabetic effects with fewer side effects than other treatment options in this study. In future studies, long-term and varying doses of icariin will contribute to the development of novel antidiabetic drugs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Biologically active derivatives of vitamin A, known as retinoids, can be used to treat cutaneous T-cell lymphomas. Retinoids and their analogs can modulate cell proliferation, differentiation, and apoptosis, and alter the immune response. This study systematically evaluated the safety, efficacy, and tolerability of retinoids for the treatment of cutaneous T-cell lymphomas and considered its limitations, dosing-side effects, and technique with the intent to provide valuable insights for clinicians and patients regarding the treatment of cutaneous T-cell lymphomas with the retinoids. The literature search is conducted using Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) criteria yielding 16 relevant articles. This study explored the different facets of the role of retinoids in the treatment of cutaneous T-cell lymphomas. In conclusion, the available studies and research have shown that retinoids play an important role in the mild and early stages of cutaneous T-cell lymphoma. However, further investigation is required to explain the mechanism of action of retinoids and the impact of their side effects in patients with cutaneous T-cell lymphoma., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ayuthu et al.)

Bexarotene-tethered RuII(arene) compounds with 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (PTA) were prepared as an analog of RAPTA antitumor complexes in order to evaluate their in vitro antiproliferative activity against human cancer cell lines.

Abstract is missing (Short communication)

Bexarotene, a FDA-approved drug for cutaneous lymphoma, has been shown to exert brain protective effects. In previous study, we demonstrated that Bexarotene protects against cerebral ischemic stroke by suppressing the JNK/Caspase-3 signaling pathway. However, the molecular mechanisms by which Bexarotene-mediated neuroprotective are not fully understood. Based on the isobaric tags for relative and absolute quantification (iTRAQ)-derived proteomics and bioinformatics analysis, 4,454 differentially expressed proteins (DEPs) were identified in upstream of the JNK signaling pathway. Among them, 149 DEPs showed aberrant expression in the vehicle-versus Bexarotene-treated mice. DEPs were primarily enriched in the metabolism, calcium, and MAPK signaling pathways. The largest DEP increase was seen with heat shock protein HSP 70, whereas the largest DEP decrease was seen with JNK scaffold protein JIP3, both of which are involved in the MAPK network. Furthermore, we illustrated the Bexarotene obviously abolished oxygen and glucose deprivation/reperfusion (OGD/R)- induced LDH leakage, cells apoptosis, and the protein expression level of the JIP3,p-ASK1, p-JNK, and Cleaved Caspase3. Together, these results suggest a potential neuroprotective role of Bexarotene via inhibition of the JIP3/ASK1/JNK/Caspase 3 signaling pathway. [ABSTRACT FROM AUTHOR]

Hypothyroidism is a common adverse event of various anticancer treatment modalities, constituting a notable paradigm of the integration of the endocrine perspective into precision oncology. The present narrative review provides a comprehensive and updated overview of anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors. A study search was conducted on the following electronic databases: PubMed, Google Scholar, Scopus.com, ClinicalTrials.gov, and European Union Clinical Trials Register from 2011 until August 2021. In patients with solid non-thyroid tumors, hypothyroidism is a common adverse event of radiotherapy, high-dose interleukin 2 (HD IL-2), interferon alpha (IFN-α), bexarotene, immune checkpoint inhibitors (ICPi), and tyrosine kinase inhibitors (TKIs), while chemotherapy may induce hypothyroidism more often than initially considered. The path forward for the management of anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors is an integrated approach grounded on five pillars: prevention, vigilance, diagnosis, treatment, and monitoring. Current challenges concerning anticancer treatment-induced hypothyroidism await counteraction, namely awareness of the growing list of related anticancer treatments, identification of predictive factors, counteraction of diagnostic pitfalls, tuning of thyroid hormone replacement, and elucidation of its prognostic significance. Close collaboration of oncologists with endocrinologists will provide optimal patient care. [ABSTRACT FROM AUTHOR]