A5043748556- Retinoids in leukemia and cellular processes
- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- PARP inhibition in cancer therapy
- Endoplasmic Reticulum Stress and Disease
- interferon and immune responses
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Multiple Myeloma Research and Treatments
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Ovarian cancer diagnosis and treatment
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- RNA Research and Splicing
- DNA Repair Mechanisms
- Immunotherapy and Immune Responses
- ATP Synthase and ATPases Research
- MicroRNA in disease regulation
Mario Negri Institute for Pharmacological Research
2016-2025
Università della Svizzera italiana
2020-2025
Institute of Oncology Research
2019-2025
SIB Swiss Institute of Bioinformatics
2020-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2025
University of Perugia
2019
Politecnico di Milano
2016
Ospedale Papa Giovanni XXIII
2016
Weatherford College
2015
Microbes hijack prostate cancer therapy Androgens such as testosterone and dihydrotestosterone are essential for male reproduction sexual function. can also influence the growth of tumor cells, androgen deprivation (ADT) either by surgical means (castration) or pharmacological approaches (hormone suppression), is cornerstone current treatments. Pernigoni et al . found that when body was deprived androgens during ADT, gut microbiome could produce from precursors (see Perspective McCulloch...
Abstract Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe an androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa). RNA whole-exome sequencing the PDX organoids confirmed transcriptomic genomic similarity primary tumor. PNPCa harbors BRCA2 CHD1 somatic mutations, shows SPOP/FOXA1 -like signature microsatellite...
Abstract Cells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype, and promote proliferation metastatic dissemination. Removal of (senolytic therapy) has therefore emerged as promising therapeutic strategy. Here, using single-cell RNA-sequencing, we find that rely on the anti-apoptotic gene Mcl-1 for their survival. is upregulated in cells, including...
Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence thus improve healthspan. Here, we show daily oral administration standardized extract Salvia haenkei (Haenkenium (HK)) extended lifespan healthspan naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis markers across several tissues,...
Abstract Comprehensive genomic studies have delineated key driver mutations linked to disease progression for most cancers. However, corresponding transcriptional changes remain largely elusive because of the bias associated with cross-study analysis. Here, we overcome these hurdles and generate a comprehensive prostate cancer transcriptome atlas that describes roadmap tumor in qualitative quantitative manner. Most cancers follow uniform trajectory characterized by upregulation...
Selenoprotein N (SEPN1) is a protein of the endoplasmic reticulum (ER) whose inherited defects originate SEPN1-related myopathy (SEPN1-RM). Here, we identify an interaction between SEPN1 and ER-stress-induced oxidoreductase ERO1A. ERO1A, both enriched in mitochondria-associated membranes (MAMs), are involved redox regulation proteins. ERO1A depletion knockout cells restores ER redox, re-equilibrates short-range MAMs, rescues mitochondrial bioenergetics. mouse background loss blunts stress...
Forty-two cell lines recapitulating mammary carcinoma heterogeneity were profiled for all-trans retinoic acid (ATRA) sensitivity. Luminal and ER(+) (estrogen-receptor-positive) are generally sensitive to ATRA, while refractoriness/low sensitivity is associated with a Basal phenotype HER2 positivity. Indeed, only 2 (MDA-MB157 HCC-1599) highly the retinoid. Sensitivity of HCC-1599 cells confirmed in xenotransplanted mice. Short-term tissue-slice cultures surgical samples validate cell-line...
Bromodomain and Extra‐Terminal (BET) proteins are historically involved in regulating gene expression BRD4 was recently found to be DNA damage regulation. Aims of our study were assess regulation homologous recombination‐mediated repair explore novel clinical strategies through the combinations pharmacological induction epigenetic BRCAness BRCA1 wild‐type triple negative breast cancer (TNBC) cells by means BET inhibitors compounds already available clinic. Performing a dual approach...
Tau (MAPT) is a microtubule-associated protein causing common neurodegenerative diseases or rare inherited frontotemporal lobar degenerations. Emerging evidence for non-canonical functions of in DNA repair and P53 regulation suggests its involvement cancer. To bring new relevant role cancer, we carried out an in-silico pan-cancer analysis MAPT transcriptomic profile over 10000 clinical samples from 32 cancer types 1300 pre-clinical 28 provided by the TCGA DEPMAP datasets respectively....
Abstract Background Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated potential oncogenic drivers, molecular programs contributing to progression are not fully understood. Methods We analyzed expression clinical samples across different stages and investigated its functional role Pten -deficient mouse model. performed histopathological...
Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential stratification, by utilizing gene co-expression network transcriptomics data in addition laser-microdissected proteomics from human and murine prostate FFPE samples. We show up-regulation oxidative phosphorylation (OXPHOS) PCa on the transcriptomic level TCA cycle/OXPHOS proteomic level, which is inversely correlated STAT3 expression....
Abstract Driver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that prostate cancer driver alterations involving the ERG transcription factor and ubiquitin ligase adaptor SPOP synthetic sick. At molecular level, incompatible pathways driven by opposing functions SPOP. upregulates wild type dampen androgen receptor (AR) signaling sustain activity through degradation of bromodomain histone...
The role of natural killer (NK) cells in the immune response against vaccines is not fully understood. Here, we examine function infiltrated NK initiation inflammatory triggered by inactivated influenza virus vaccine draining lymph node (LN). We observed that, following vaccination, are recruited to interfollicular and medullary areas LN become activated type I interferons (IFNs) produced macrophages. activation leads their early production IFNγ, which turn regulates recruitment IL-6+ CD11b+...
The mechanisms by which prostate cancer shifts from an indolent castration-sensitive phenotype to lethal castration-resistant (CRPC) are poorly understood. Identification of clinically relevant genetic alterations leading CRPC may reveal potential vulnerabilities for therapy. Here we find that CUB domain-containing protein 1 (CDCP1), a transmembrane acts as substrate SRC family kinases (SFKs), is overexpressed in subset CRPC. Notably, CDCP1 cooperates with the loss tumor suppressor gene PTEN...
Abstract Occurrence of resistance to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) approved in ovarian carcinoma, has already been shown clinical settings. Identifying combination treatments sensitize tumor cells and/or overcome olaparib is critical. Polo-like kinase 1 (PLK1), master regulator mitosis, also involved the DNA damage response promoting homologous recombination (HR)-mediated repair and recovery from G2/M checkpoint. We hypothesized that PLK1 inhibition could...
Abstract Cancer cells adapt to harsh environmental conditions by inducing the Unfolded Protein Response (UPR), of which ERO1A is a mediator. aids protein folding acting as disulfide oxidase, and under cancer-related hypoxia conditions, it favors angiogenic VEGFA, leading tumor thrive spread. The upregulation in cancer cells, oppositely dispensability activity healthy renders perfect target for therapy. Here, we report cohort aggressive triple-negative breast (TNBC) patients levels correlate...