A5019153476- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- Cancer Cells and Metastasis
- BRCA gene mutations in cancer
- Glutathione Transferases and Polymorphisms
- Adipose Tissue and Metabolism
- HER2/EGFR in Cancer Research
- Gene expression and cancer classification
- Single-cell and spatial transcriptomics
- Exercise and Physiological Responses
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Bioinformatics and Genomic Networks
- Muscle Physiology and Disorders
- Neuropeptides and Animal Physiology
- Cancer, Stress, Anesthesia, and Immune Response
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Receptor Mechanisms and Signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Cell Adhesion Molecules Research
- Reproductive System and Pregnancy
- Muscle metabolism and nutrition
Brigham and Women's Hospital
2012-2022
Dana-Farber Cancer Institute
2012-2022
Harvard University
2011-2022
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2006-2018
Universitat de Barcelona
2006-2018
Hospital Clínic de Barcelona
2006-2016
Fundació Clínic per a la Recerca Biomèdica
2012-2016
Memorial Sloan Kettering Cancer Center
2012-2014
Harvard Stem Cell Institute
2014
Johns Hopkins University
2014
Intratumor heterogeneity is a major clinical problem because tumor cell subtypes display variable sensitivity to therapeutics and may play different roles in progression. We previously characterized 2 populations human breast tumors with distinct properties: CD44+CD24- cells that have stem cell-like characteristics, CD44-CD24+ resemble more differentiated cancer cells. Here we identified 15 genes required for growth or proliferation large-scale loss-of-function screen found inhibition of...
The 8q24 gene desert contains risk loci for multiple epithelial cancers, including colon, breast, and prostate. Recent evidence suggests these contain enhancers. In this study, data are presented showing that each locus bears epigenetic marks consistent with enhancer elements forms a long-range chromatin loop the MYC proto-oncogene located several hundred kilobases telomeric interactions tissue-specific. We therefore propose operate through common mechanism—as tissue-specific enhancers of .
Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis cellular heterogeneity for genetic and phenotypic features their spatial distribution in breast pre- post-neoadjuvant chemotherapy. We found intratumor diversity was tumor-subtype specific, it did not with partial or no response. However, lower pretreatment significantly associated pathologic complete In contrast,...
Metastatic disease is the main cause of cancer-related mortality due to almost universal therapeutic resistance. Despite its high clinical relevance, our knowledge how cancer cell populations change during metastatic progression limited. Here, we investigated intratumor genetic and phenotypic heterogeneity breast cancer. We analyzed cellular genotypes phenotypes at single level by performing immunoFISH in intact tissue sections distant tumors from rapid autopsy cases primary matched lymph...
BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations PTEN TP53. Here we describe the analysis BRCA1, PTEN, p53 at single cell level in 55 computational methods to predict relative temporal order events, on basis frequency cells with or combined alterations. Although there is no obligatory found that most common first event associated basal-like subtype, whereas majority luminal tumors, mutation TP53 occurs mutant PIK3CA rarely detected. We also observed...
Targeted therapy for patients with HER 2‐positive ( 2+) breast cancer has improved overall survival, but many still suffer relapse and death from the disease. Intratumor heterogeneity of both estrogen receptor ER ) 2 expression been proposed to play a key role in treatment failure, little work done comprehensively study this at single‐cell level. In study, we explored clinical impact intratumor protein expression, gene copy number alterations. Using combined immunofluorescence situ...
Abstract Inflammatory breast cancer (IBC) is a difficult-to-treat disease with poor clinical outcomes due to high risk of metastasis and resistance treatment. In cancer, CD44+CD24− cells possess stem cell-like features contribute progression, we previously described CD44+CD24−pSTAT3+ cell subpopulation that dependent on JAK2/STAT3 signaling. Here report are the most frequent type in IBC commonly pSTAT3+. Combination inhibition paclitaxel decreased xenograft growth more than either agent...
Abstract In cancer cachexia both cardiac and skeletal muscle suffer an important protein mobilization as a result of increased proteolysis. Administration the β2-agonist formoterol to rats mice bearing highly cachectic tumors resulted in reversal muscle-wasting process. The anti-wasting effects drug were based on activation rate synthesis inhibition Northern blot analysis revealed that treatment decrease mRNA content ubiquitin proteasome subunits gastrocnemius muscles; this, together with...
Abstract ERBB receptor transmodulation by heterologous G-protein–coupled receptors (GPCR) generates functional diversity in signal transduction. Tachykinins are neuropeptides and proinflammatory cytokines that promote cell survival cancer progression activating several GPCRs. In this work, we found the pain-associated tachykinin Substance P (SP) contributes to persistent of receptors, EGFR HER2, breast cancer, acting enhance malignancy therapeutic resistance. SP its high-affinity NK-1R were...
NK1 is a tachykinin receptor highly relevant to tumorigenesis and metastasis development in breast cancer other carcinomas. Despite the substantial efforts done develop potent antagonists, none of these antagonists had shown good antitumor activity clinical trials. Now, we have tested effect inhibition neuropeptide Substance P (SP), ligand, as potential therapeutic approach cancer. We found that SP with antibodies strongly inhibit cell growth induce apoptosis breast, colon, prostate lines....
Administration of interleukin‐15 (IL‐15) to rats bearing the Yoshida AH‐130 ascites hepatoma (a tumour that induces an important cachectic response) resulted in a significant reduction muscle wasting, both measured as weight and protein content different types skeletal muscle. In addition, administration cytokine completely reversed increased DNA fragmentation observed tumour‐bearing animals. Concerning mechanism(s) involved anti‐apoptotic effects IL‐15 on muscle, considerable decrease R1...
The efficacy of oxaliplatin in cancer chemotherapy is limited by the development drug resistance. MMP7 has been related to loss tumor cell response cytotoxic agents although exact mechanism not fully understood. Moreover, an independent prognosis factor for survival patients with colorectal cancer. aim present study was analyze role and its cross-talk Fas/FasL system during acquisition resistance colon cells.For this purpose we have developed three different oxaliplatin-resistant lines...
The frequency and proliferative activity of tissue-specific stem progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast risk mammary epithelial expressing p27, estrogen receptor (ER), Ki67 in normal tissue. We performed a nested case-control study 302 women (69 cases, 233 controls) who had been initially diagnosed benign disease according Nurses' Health Studies. Immunofluorescence for ER, was on tissue microarrays...
Incubation of rat isolated skeletal muscles (extensor digitorum longus) in the presence 100 ng/ml human recombinant interleukin-15 (IL-15) resulted a significant decrease total proteolytic rate, while it had no effect on protein synthesis as measured by incorporation 14C-phenylalanine into muscle protein. In addition, IL-15 either amino acid uptake (as determined tissue labelled [1-14C]MeAIB) or alanine utilization incubated muscles. Similarly, single injection (100 µg/kg) vivo did not...