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Asian Pacific Journal of Cancer... Jun 2024Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor...
OBJECTIVE
Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities.
METHODS
In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient.
RESULTS
Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF.
CONCLUSION
This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.
Topics: Humans; Photochemotherapy; NF-kappa B; Photosensitizing Agents; Aminolevulinic Acid; Female; Cell Proliferation; Breast Neoplasms; Dimethyl Fumarate; Apoptosis; Reactive Oxygen Species; Tumor Cells, Cultured; Cell Line, Tumor
PubMed: 38918667
DOI: 10.31557/APJCP.2024.25.6.2051 -
Translational Oncology Jun 2024One of the main causes of death on the globe is cancer. Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors, including PPARα, PPARδ and... (Review)
Review
One of the main causes of death on the globe is cancer. Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors, including PPARα, PPARδ and PPARγ, which are important in regulating cancer cell proliferation, survival, apoptosis, and tumor growth. Activation of PPARs by endogenous or synthetic compounds regulates tumor progression in various tissues. Although each PPAR isotype suppresses or promotes tumor development depending on the specific tissues or ligands, the mechanism is still unclear. PPARs are receiving interest as possible therapeutic targets for a number of disorders. Numerous clinical studies are being conducted on PPARs as possible therapeutic targets for cancer. Therefore, this review will focus on the existing and future uses of PPARs agonists and antagonists in treating malignancies. PubMed, Science Direct, and Scopus databases were searched regarding the effect of PPARs on various types of cancers until the end of May 2023. The results of the review articles showed the therapeutic influence of PPARs on a wide range of cancer on in vitro, in vivo and clinical studies. However, further experimental and clinical studies are needed to be conducted on the influence of PPARs on various cancers.
PubMed: 38917593
DOI: 10.1016/j.tranon.2024.102039 -
PloS One 2024This study evaluates the impact of dietary supplementation of the blue-green alga Arthrospira platensis NIOF17/003 nanoparticles (AN) on the growth performance,...
Arthrospira platensis nanoparticles dietary supplementation improves growth performance, steroid hormone balance, and reproductive productivity of Nile tilapia (Oreochromis niloticus) broodstock.
This study evaluates the impact of dietary supplementation of the blue-green alga Arthrospira platensis NIOF17/003 nanoparticles (AN) on the growth performance, whole-body biochemical compositions, blood biochemistry, steroid hormonal, and fry production efficiency of Nile tilapia (Oreochromis niloticus) broodstock, during the spawning season. After a 21-day preparation period to equip the females and ensure that their ovaries were filled with eggs, mating between the mature females and males took place in a 3:1 ratio during a 14-day spawning cycle. A total of 384 tilapia broodstock 288 females and 96 males with an initial body weight of 450.53±0.75, were divided into four groups; AN0: a basal diet as a control group with no supplementation of Arthrospira platensis, and the other three groups (AN2, AN4, and AN6) were diets supplemented with nanoparticles of A. platensis at levels of 2, 4, and 6 g kg─1 diet, respectively. The results found that fish-fed group AN6 showed the highest significant differences in weight gain (WG), final weight (FW), feed conversion ratio (FCR), protein efficiency ratio (PER), and feed efficiency ratio (FER). Females fed the AN6 diet showed the highest significant fat content. Compared to the AN0 group, fish fed on the supplemented diets showed significant improvement (p < 0.05) in triglyceride, glucose, and aspartate aminotransferase (AST). A gradual increase in AN inclusion level resulted in a gradual increase in the concentrations of luteinizing hormone (LH), and follicle-stimulating hormone (FSH), testosterone, progesterone, and prolactin. The rates (%) of increase in fry production for females fed supplemented diets were 10.5, 18.6, and 32.2% for AN2, AN4, and AN6, respectively, compared to the control group. This work concluded that the inclusion levels of 6 g kg─1 of A. platensis nanoparticles in the diet of Nile tilapia broodstock significantly improved the growth performances, steroid hormone concentrations, and increased the fry production efficiency by 32.2%, respectively. These findings revealed that A. platensis nanoparticles resulted in a significantly enhanced female' reproductive productivity of Nile tilapia broodstock.
Topics: Animals; Dietary Supplements; Nanoparticles; Female; Reproduction; Spirulina; Cichlids; Male; Animal Feed; Gonadal Steroid Hormones
PubMed: 38917116
DOI: 10.1371/journal.pone.0299480 -
BioRxiv : the Preprint Server For... Jun 2024Many transgender youth seek gender affirming care, such as puberty suppression, to prolong decision-making and to align their physical sex characteristics with their...
UNLABELLED
Many transgender youth seek gender affirming care, such as puberty suppression, to prolong decision-making and to align their physical sex characteristics with their gender identity. During peripubertal growth, connective tissues such as tendon rapidly adapt to applied mechanical loads (e.g., exercise) yet if and how tendon adaptation is influenced by sex and gender affirming hormone therapy during growth remains unknown. The goal of this study was to understand the how pubertal suppression influences the structural and functional properties of the Achilles tendon using an established mouse model of transmasculine gender affirming hormone therapy. C57BL/6N female-born mice were assigned to experimental groups to mimic gender-affirming hormone therapy in human adolescents, and treatment was initiated prior to the onset of puberty (at postnatal day 26, P26). Experimental groups included controls and mice serially treated with gonadotropin release hormone analogue (GnRHa), delayed Testosterone (T), or GnRHa followed by T. We found that puberty suppression using GnRHa, with and without T, improved the overall tendon load capacity in female-born mice. Treatment with T resulted in an increase in the maximum load that tendon can withstand before failure. Additionally, we found that GnRHa, but not T, treatment resulted in a significant increase in cell density at the Achilles enthesis.
NEW & NOTEWORTHY
These findings demonstrate that puberty suppression or testosterone does not negatively influence tendon structural or functional properties in a mouse model of transmasculine gender affirming care. In all treatment groups, the ability of the tendon to withstand load was significantly increased. Puberty suppression with GnRHa significantly increased enthesis cell density, suggesting an extended growth phase. These findings elucidate the effects of gender affirming care on the structural and functional properties of the tendon and enthesis.
PubMed: 38915724
DOI: 10.1101/2024.06.10.598308 -
Frontiers in Microbiology 2024head blight (FHB) is a destructive disease caused by several species of , such as and . FHB affects cereal crops, including wheat, barley, and rice, worldwide....
head blight (FHB) is a destructive disease caused by several species of , such as and . FHB affects cereal crops, including wheat, barley, and rice, worldwide. -infected kernels not only cause reduced yields but also cause quality loss by producing mycotoxins, such as trichothecenes and zearalenone, which are toxic to animals and humans. For decades, chemical fungicides have been used to control FHB because of their convenience and high control efficacy. However, the prolonged use of chemical fungicides has caused adverse effects, including the emergence of drug resistance to pathogens and environmental pollution. Biological control is considered one of the most promising alternatives to chemicals and can be used for integrated management of FHB due to the rare possibility of environment pollution and reduced health risks. In this study, JCK-7158 isolated from rice was selected as an ecofriendly alternative to chemical fungicides for the management of FHB. JCK-7158 produced the extracellular enzymes protease, chitinase, gelatinase, and cellulase; the plant growth hormone indole-3-acetic acid; and the 2,3-butanediol precursor acetoin. Moreover, JCK-7158 exhibited broad antagonistic activity against various phytopathogenic fungi and produced iturin A, surfactin, and volatile substances as active antifungal compounds. It also enhanced the expression of , a known induced resistance marker gene, in transgenic plants expressing β-glucuronidase (GUS) fused with the promoter. Under greenhouse conditions, treatments with the culture broth and suspension concentrate formulation of JCK-7158 at a 1,000-fold dilution inhibited the development of FHB by 50 and 66%, respectively. In a field experiment, treatment with the suspension concentrate formulation of JCK7158 at a 1,000-fold dilution effectively controlled the development of FHB with a control value of 55% and reduced the production of the mycotoxin nivalenol by 40%. Interestingly, treatment with JCK-7158 enhanced the expression of plant defense-related genes in salicylic acid, jasmonic acid, ethylene, and reactive oxygen species (ROS) signaling pathways before and after FHB pathogen inoculation. Taken together, our findings support that JCK-7158 has the potential to serve as a new biocontrol agent for the management of FHB.
PubMed: 38915299
DOI: 10.3389/fmicb.2024.1358689 -
Cell Death & Disease Jun 2024Endocrine resistance poses a significant clinical challenge for patients with hormone receptor-positive and human epithelial growth factor receptor 2-negative...
Endocrine resistance poses a significant clinical challenge for patients with hormone receptor-positive and human epithelial growth factor receptor 2-negative (HR + HER2-) breast cancer. Dysregulation of estrogen receptor (ER) and ERBB signaling pathways is implicated in resistance development; however, the integration of these pathways remains unclear. While SMAD4 is known to play diverse roles in tumorigenesis, its involvement in endocrine resistance is poorly understood. Here, we investigate the role of SMAD4 in acquired endocrine resistance in HR + HER2- breast cancer. Genome-wide CRISPR screening identifies SMAD4 as a regulator of 4-hydroxytamoxifen (OHT) sensitivity in T47D cells. Clinical data analysis reveals downregulated SMAD4 expression in breast cancer tissues, correlating with poor prognosis. Following endocrine therapy, SMAD4 expression is further suppressed. Functional studies demonstrate that SMAD4 depletion induces endocrine resistance in vitro and in vivo by enhancing ER and ERBB signaling. Concomitant inhibition of ER and ERBB signaling leads to aberrant autophagy activation. Simultaneous inhibition of ER, ERBB, and autophagy pathways synergistically impacts SMAD4-depleted cells. Our findings unveil a mechanism whereby endocrine therapy-induced SMAD4 downregulation drives acquired resistance by integrating ER and ERBB signaling and suggest a rational treatment strategy for endocrine-resistant HR + HER2- breast cancer patients.
Topics: Humans; Smad4 Protein; Female; Breast Neoplasms; Signal Transduction; Drug Resistance, Neoplasm; Receptor, ErbB-2; Receptors, Estrogen; Cell Line, Tumor; Animals; Tamoxifen; Mice; Antineoplastic Agents, Hormonal; Mice, Nude; Gene Expression Regulation, Neoplastic; Autophagy; ErbB Receptors
PubMed: 38914552
DOI: 10.1038/s41419-024-06838-9 -
Frontiers in Oncology 2024Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative...
BACKGROUND
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer. However, optimal treatment after disease progression is a matter of debate. We aimed to assess predictive and prognostic factors associated with the treatment outcome following CDK4/6i progression.
METHODS
We retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone.
RESULTS
Five hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1-76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6-26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3-94.8%] compared to 21.1% [95% CI 12.2-31.7%] for patients with non-tailored treatment.
CONCLUSIONS
Tailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.
PubMed: 38912058
DOI: 10.3389/fonc.2024.1408664 -
PeerJ 2024The domain of unknown function 668 (DUF668) is a gene family that may play a key role in plant growth and development as well as in responding to adversity coercion...
The domain of unknown function 668 (DUF668) is a gene family that may play a key role in plant growth and development as well as in responding to adversity coercion stresses. However, the DUF668 gene family has not yet been well identified and characterized in tomato. In this study, a total of nine putative genes were identified in tomato, distributed on six chromosomes. Phylogenetic analyses revealed that SlDUF668 proteins were classified into two major groups. Members within the same group largely displayed analogous gene structure and conserved motif compositions. Several -elements were exhibited in the upstream sequences of the genes, including elements implicated in plant growth and development processes, abiotic stress and hormone responses. Further, the study assessed the expression patterns of the SlDUF668 gene family in various tomato tissues, five plant hormones treatments, three abiotic stresses using qRT-PCR. The genes expressed ubiquitously in various tissues, and five genes (, , , and ) showed tissue specificity. And genes responded to abiotic stresses such as salt, drought and cold to varying degrees. Overall, our study provided a base for the tomato DUF668 gene family and laid a foundation for further understanding the functional characteristics of genes in tomato plants.
Topics: Solanum lycopersicum; Plant Proteins; Gene Expression Regulation, Plant; Multigene Family; Phylogeny; Stress, Physiological; Genome, Plant; Gene Expression Profiling; Chromosomes, Plant
PubMed: 38912042
DOI: 10.7717/peerj.17537 -
Frontiers in Immunology 2024Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors.... (Review)
Review
Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors. Fracture healing usually takes several weeks to months, during which patients are frequently immobilized and unable to work. As immobilization is associated with negative health and socioeconomic effects, it would be desirable if fracture healing could be accelerated and the healing time shortened. However, interventions for this purpose are not yet part of current clinical treatment guidelines, and there has never been a comprehensive review specifically on this topic. Therefore, this narrative review provides an overview of the available clinical evidence on methods that accelerate fracture healing, with a focus on clinical applicability in healthy patients without bone disease. The most promising methods identified are the application of axial micromovement, electromagnetic stimulation with electromagnetic fields and direct electric currents, as well as the administration of growth factors and parathyroid hormone. Some interventions have been shown to reduce the healing time by up to 20 to 30%, potentially equivalent to several weeks. As a combination of methods could decrease the healing time even further than one method alone, especially if their mechanisms of action differ, clinical studies in human patients are needed to assess the individual and combined effects on healing progress. Studies are also necessary to determine the ideal settings for the interventions, i.e., optimal frequencies, intensities, and exposure times throughout the separate healing phases. More clinical research is also desirable to create an evidence base for clinical guidelines. To make it easier to conduct these investigations, the development of new methods that allow better quantification of fracture-healing progress and speed in human patients is needed.
Topics: Humans; Fracture Healing; Animals; Fractures, Bone; Bone Regeneration; Magnetic Field Therapy
PubMed: 38911851
DOI: 10.3389/fimmu.2024.1384783 -
Journal of Cancer 2024DNA damage-inducible transcript 3 (DDIT3) is a transcription factor central to apoptosis, differentiation, and stress response. DDIT3 has been extensively studied in...
DNA damage-inducible transcript 3 (DDIT3) is a transcription factor central to apoptosis, differentiation, and stress response. DDIT3 has been extensively studied in cancer biology. However, its precise implications in breast cancer progression and its interaction with the immune microenvironment are unclear. In this study, we utilized a novel multi-omics integration strategy, combining bulk RNA sequencing, single-cell sequencing, spatial transcriptomics and immunohistochemistry, to explore the role of DDIT3 in breast cancer and establish the correlation between DDIT3 and poor prognosis in breast cancer patients. We identified a robust prognostic signature, including six genes (unc-93 homolog B1, TLR signaling regulator, anti-Mullerian hormone, DCTP pyrophosphatase 1, mitochondrial ribosomal protein L36, nuclear factor erythroid 2, and Rho GTPase activating protein 39), associated with DDIT3. This signature stratified the high-risk patient groups, characterized by increased infiltration of the regulatory T cells and M2-like macrophages and fibroblast growth factor (FGF)/FGF receptor signaling activation. Notably, the high-risk patient group demonstrated enhanced sensitivity to immunotherapy, presenting novel therapeutic opportunities. Integrating multi-omics data helped determine the spatial expression pattern of DDIT3 in the tumor microenvironment and its correlation with immune cell infiltration. This multi-dimensional analysis provided a comprehensive understanding of the intricate interplay between DDIT3 and the immune microenvironment in breast cancer. Overall, our study not only facilitates understanding the role of DDIT3 in breast cancer but also offers innovative insights for developing prognostic models and therapeutic strategies. Identifying the DDIT3-related prognostic signature and its association with the immune microenvironment provided a promising avenue for personalized breast cancer treatment.
PubMed: 38911383
DOI: 10.7150/jca.96491