Publications by authors named "Misha Mao"

The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8 T cell activation without exhaustion.

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  • Cushing's syndrome is linked to high levels of glucocorticoids and is associated with increased plasma levels of ACBP/DBI, which stimulates food intake and fat production.
  • Researchers explored multiple methods to inhibit ACBP/DBI in mice, including genetic modifications and antibody injections, to address Cushing's symptoms.
  • The findings suggest that targeting ACBP/DBI could be an effective strategy for treating Cushing's syndrome and its related complications like obesity and diabetes.
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  • Higher plasma levels of ACBP/DBI, linked to age and obesity, are associated with an increased risk of cancer, especially in patients with genetic predispositions like BRCA1/2 or TP53 mutations.
  • In studies, elevated ACBP/DBI levels were predictive of future cancer development, particularly lung cancer, while neutralization of ACBP/DBI slowed tumor growth and enhanced the effects of chemoimmunotherapy in animal models.
  • The research suggests that ACBP/DBI functions as an immune suppressor and indicates that targeting it may improve cancer immunotherapy outcomes.
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Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations.

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  • Successful cancer treatment often requires the activation of adaptive immune responses that specifically target tumor-related antigens through immunogenic cell death (ICD) of cancer cells.
  • ICD turns cancer cells into a sort of vaccine that helps generate a long-lasting immune memory against tumors.
  • ICD activators are categorized into three types: inducers that boost cell immunogenicity, sensitizers that prepare cells for ICD, and enhancers that improve how immune cells recognize ICD signals.
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Accurate pathologic diagnosis and molecular classification of breast mass biopsy tissue is important for determining individualized therapy for (neo)adjuvant systemic therapies for invasive breast cancer. The CassiII rotational core biopsy system is a novel biopsy technique with a guide needle and a "stick-freeze" technology. The comprehensive assessments including the concordance rates of diagnosis and biomarker status between CassiII and core needle biopsy were evaluated in this study.

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Background: Cancer-associated fibroblasts (CAFs) constitute the primary constituents of the tumor microenvironment (TME) and exert significant influences on cancer progression. However, adequate comprehension of CAF profiles in breast cancer, as well as the precise mechanisms underlying their promotion of cancer, remains lacking.

Objectives: To discerns the biological differences between normal fibroblasts (NFs) and CAFs in breast cancer and explore the underlying mechanism.

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  • Scientists created a phenotypic screening platform to explore dendritic cells (DC) and discovered that BCL2 acts as an inhibitor of DC function through a genome-wide CRISPR screen.
  • Knocking out BCL2 led to increased DC activity, improved tumor control, and enhanced effects when combined with PD-1 blockade treatments.
  • Pharmacological inhibitors of BCL2 showed similar results, demonstrating that targeting BCL2 can activate DCs and improve anti-cancer immunity, particularly in combination with existing immunotherapy strategies.
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  • Current immunotherapies are mostly based on complex and costly recombinant proteins and cell-based methods, highlighting the need for new small molecule treatments to simplify manufacturing and logistics.
  • Researchers developed a miniature immune system to screen drug libraries, leading to the discovery of two promising compounds: astemizole, which activates T cells independently of dendritic cells, and ikarugamycin, which enhances dendritic cell function by inhibiting a key enzyme.
  • Both drugs showed improved anticancer effects when combined with the chemotherapy agent oxaliplatin, with astemizole also promoting a beneficial change in T cell ratios within tumors, suggesting potential for enhanced cancer treatment strategies.
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Toll-like receptor 3 (TLR3) agonists such as polyinosinic:polycytidylic acid (poly(I:C)) have immunostimulatory effects that can be taken advantage of to induce anticancer immune responses in preclinical models. In addition, poly(I:C) has been introduced into clinical trials to demonstrate its efficacy as an adjuvant and to enhance the immunogenicity of locally injected tumors, thus reverting resistance to PD-L1 blockade in melanoma patients. Here, we report the pharmacokinetic, pharmacodynamic, mechanistic and toxicological profile of a novel TLR3 agonist, TL-532, a chemically synthesized double-stranded RNA that is composed by blocks of poly(I:C) and poly(A:U) (polyadenylic - polyuridylic acid).

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Purpose: This study aims to evaluate the pain relief function of chemical sphincterotomy in patients undergoing haemorrhoid surgery and compare, through a meta-analysis, the different drugs used to treat this condition.

Methods: We conducted a search in databases including PubMed, EMBASE and Web of Science. The methodological quality was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (ROB2).

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Background: Triple-negative breast cancer is characterized by a poor prognosis and lack of targeted treatments, and thus, new targeting markers and therapeutic strategies are urgently needed. We previously indicated that PLAC8 promotes tumorigenesis and exerts multidrug resistance in breast cancer. Therefore, we aimed to characterize the PLAC8-regulated network in triple-negative breast cancer.

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In the last few decades, YAP has been shown to be critical in regulating tumor progression. YAP activity can be regulated by many kinase cascade pathways and proteins through phosphorylation and promotion of cytoplasmic localization. Other factors can also affect YAP activity by modulating its binding to different transcription factors (TFs).

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Triple-negative breast cancer is still a difficult point in clinical treatment at present, and a deep study of its pathogenesis has great clinical value. Therefore, our research mainly focuses on exploring the progression of triple-negative breast cancer and determines the important role of the HJURP/YAP1/NDRG1 transcriptional regulation axis in triple-negative breast cancer. We observed significantly increased HJURP expression levels in triple-negative breast cancer compared to other subtypes.

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Ferroptosis, which is characterized by intracellular iron accumulation and lipid peroxidation, is a newly described form of regulated cell death that may play a key role in tumour suppression. In the present study, we investigated the expression profiles and biological effects of fascin actin-bundling protein 1 (Fascin, gene name FSCN1) in breast cancer. In addition, bioinformatics analysis of the TCGA cancer database and gain- and loss-of-function studies showed that Fascin enhances sensitivity to erastin-induced ferroptosis.

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Aberrant methylation has been regarded as a hallmark of cancer. 5-hydroxymethylcytosine (5hmC) is recently identified as the ten-eleven translocase (ten-eleven translocase)-mediated oxidized form of 5-methylcytosine, which plays a substantial role in DNA demethylation. Cell-free DNA has been introduced as a promising tool in the liquid biopsy of cancer.

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Autophagy and ferroptosis have been major foci of biomedical research in recent years. Elucidation of their intrinsic molecular relationships is important for cancer prevention and treatment. Metformin can directly inhibit tumorigenesis, although the mechanism responsible for this is not fully understood.

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The role of PLAC8 in tumorigenesis has been gradually elucidated with the development of research. Although there are common molecular mechanisms that enforce cell growth, the impact of PLAC8 is varied and can, in some instances, have opposite effects on tumorigenesis. To systematically understand the role of PLAC8 in tumors, the molecular functions of PLAC8 in cancer will be discussed by focusing on how PLAC8 impacts tumorigenesis when it arises within tumor cells and how these roles can change in different stages of cancer progression with the ultimate goal of suppressing PLAC8-relevant cancer behavior and related pathologies.

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Chemoresistance is a daunting challenge to the prognosis of patients with breast cancer. Signal transducer and activator of transcription (STAT) 5a plays vital roles in the development of various cancers, but its function in breast cancer is controversial, and its role in chemoresistance in breast cancer remains unexplored. Here we identified STAT5a as a chemoresistance inducer that regulates the expression of ABCB1 in breast cancer and can be targeted by pimozide, an FDA-approved psychotropic drug.

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Background: Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment.

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Drug resistance is a daunting challenge in the treatment of breast cancer, making it an urgent problem to solve in studies. Cell lines are important tools in basic and preclinical studies; however, few breast cell lines from drug-resistant patients are available. Herein, we established a novel HER2-positive breast cancer cell line from the pleural effusion of a drug-resistant metastatic breast cancer patient.

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Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM could lead to treatment failure and poor outcome. PLAC8 was reported as a novel highly conserved protein and functioned as an oncogene or tumour suppressor in various tumours.

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Tamoxifen resistance remains the major obstacle to the estrogen receptor positive breast cancer endocrine therapy. Placenta-specific 8 (PLAC8) has been implicated in epithelial-mesenchymal transition and tumorigenesis. However, the molecular mechanisms underlying PLAC8 function in the context of tamoxifen resistance are unclear.

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