A5057242325- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Protein Degradation and Inhibitors
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Bladder and Urothelial Cancer Treatments
- 3D Printing in Biomedical Research
- Advanced Breast Cancer Therapies
- Cancer, Stress, Anesthesia, and Immune Response
- Nanoplatforms for cancer theranostics
- Cancer Cells and Metastasis
- Cancer-related molecular mechanisms research
- Neuroendocrine Tumor Research Advances
- Multiple Myeloma Research and Treatments
- Lung Cancer Treatments and Mutations
- Radiomics and Machine Learning in Medical Imaging
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Prostate Cancer Treatment and Research
- Click Chemistry and Applications
- Single-cell and spatial transcriptomics
- Chromatin Remodeling and Cancer
- Computational Drug Discovery Methods
- Genetic factors in colorectal cancer
Bristol-Myers Squibb (United States)
2020-2021
Dana-Farber Cancer Institute
2009-2020
Harvard University
2018
Tufts University
2016
Boston University
2016
Shanghai Jiao Tong University
2012
AstraZeneca (United Kingdom)
2009
National Cancer Center
2009
Antwerp University Hospital
2009
Peking University Cancer Hospital
2009
Immune checkpoint blockade, exemplified by antibodies targeting the PD-1 receptor, can induce durable tumor regressions in some patients. To enhance efficacy of existing immunotherapies, we screened for small molecules capable increasing activity T cells suppressed PD-1. Here, show that short-term exposure to small-molecule inhibitors cyclin-dependent kinases 4 and 6 (CDK4/6) significantly enhances T-cell activation, contributing antitumor effects vivo, due part derepression NFAT family...
Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse hematologic cancers. We hypothesized that checkpoint blockade established by targeting cytotoxic T-lymphocyte–associated protein 4 with ipilimumab could restore reactivity through a graft-versus-tumor effect.
Ex vivo systems that incorporate features of the tumor microenvironment and model dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology development effective combination therapies. Here, we demonstrate ability interrogate ex ICB using murine- patient-derived organotypic spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse human tumors retain autologous lymphoid myeloid cell populations respond short-term three-dimensional microfluidic...
Microfluidic culture has the potential to revolutionize cancer diagnosis and therapy.
While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and in the microenvironment are co-dependent co-evolve. Few human studies date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected non-neoplastic prostate epithelial tissue compared it non-transformed neoplastic low-grade high-grade radical prostatectomies, each with its immediately surrounding Whereas benign prostates without...
KRAS mutation is present in approximately 30% of human lung adenocarcinomas. Although recent advances targeted therapy have shown great promise, effective targeting remains elusive, and concurrent alterations tumor suppressors render KRAS-mutant tumors even more resistant to existing therapies. Contributing the refractoriness are immunosuppressive mechanisms, such as increased presence suppressive regulatory T cells (Treg) elevated expression inhibitory receptor PD-1 on tumor-infiltrating...
Objectives The immune environment and the potential for neuroendocrine tumors (NETs) to respond checkpoint inhibitors remain largely unexplored. We assessed marker expression, lymphocytic infiltrate, associated mutational profiles in a cohort of small intestine pancreatic NETs. Methods expression PDCD1 (PD-1), CD274 (PD-L1), PDCD1LG2 (PD-L2) archival tissue from 64 (SINETs) 31 NETs (pNET). additionally T-cell infiltrates, categorizing subsets based on markers CD3, CD8, CD45RO (PTPRC), or...
Intra-tumoral genetic heterogeneity has been characterized across cancers by genome sequencing of bulk tumors, including chronic lymphocytic leukemia (CLL). In order to more accurately identify subclones, define phylogenetic relationships, and probe genotype–phenotype we developed methods for targeted mutation detection in DNA RNA isolated from thousands single cells five CLL samples. By clearly resolving phylogenic uncovered mutated LCP1 WNK1 as novel drivers, supported functional evidence...
CRA8003 The full, final text of this abstract will be available in Part II the 2009 ASCO Annual Meeting Proceedings, distributed onsite at on May 30, 2009, and as a supplement to June 20, issue Journal Clinical Oncology. [Table: see text]
Current diagnostic and prognostic blood-based biomarkers for neuroendocrine tumors are limited. MiRNAs have tumor-specific expression patterns, relatively stable, can be measured in patient blood specimens. We performed a multi-stage study to identify validate characteristic circulating miRNAs patients with metastatic small intestine tumors, assess associations between miRNA levels survival.Using 742-miRNA panel, we identified candidate similarly expressed 19 matched plasma samples. refined...
CRA8003 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. Addition vandetanib to docetaxel (doc) prolonged progression-free survival (PFS) in randomized phase II study patients (pts) with previously treated NSCLC (Heymach et al, JCO, 2007). Methods: The primary objective was determine whether 100 mg/day + doc 75 mg/m 2 every 21 days (max 6 cycles) PFS vs placebo doc. Secondary endpoints included overall survival, response rate (ORR), time deterioration...
e18045 Background: Customizing chemotherapy on the basis of biomarkers may improve outcome in advanced non-small cell lung cancer (NSCLC) patients. The purpose this study was to investigate whether expressions DNA repair genes ERCC1 (excision cross complementing 1), RRM1 (ribonucleotide reductase subunit M1) and BRCA1 (breast 1) affected clinical NSCLC Methods: Patients with stage IIIb/IV were given platinum-based chemotherapy. Messenger RNA expression levels ERCC1, determined by real-time...
Quantitative metrics to objectively assess the fidelity of cancer models, such as cell lines, organoids, or patient-derived xenografts (PDXs), remain elusive, with histological criteria presence specific mutations often used driving principles. We show that molecular criteria, based on regulatory proteins responsible for maintaining transcriptional state and its network, are effective in identifying models can recapitulate drug mechanism action sensitivity, independent consideration.
Abstract No consensus currently exist on the optimal treatment of patients with high-risk nonmuscle invasive (HGT1) micropapillary variant bladder cancer (MPBC). Transcripsome analysis may allow stratification MPBC-HGT1 enabling prediction recurrence and guide therapeutic management for individual patients. Whole transcriptome RNA-Sequencing tumors from 23 64 conventional urothelial carcinomas (cUC) (reference set) was performed. Differentially expressed genes between cUC-HGT1 were explored....
Tumour expression of selected microRNAs (miRs) correlates with cisplatin efficacy in multiple cancers. We investigated the role miRs patients receiving cisplatin-based therapy for advanced urothelial carcinoma (UC). RNA was extracted from formalin-fixed paraffin-embedded tumour 83 UC who received cisplatin. A miR panel based on relevance platinum sensitivity and studied by quantitative reverse transcription PCR (RT–qPCR). Association progression-free survival (PFS) analysed using cox...
DNA self-assembly is a nanotechnology that folds into desired shapes. Self-assembled nanostructures, also known as origami, are increasingly valuable in nanomaterial and biosensing applications. Two ways to use nanostructures medicine form nanoarrays, work vehicles drug delivery. The perform well biomaterial these areas because they have spatially addressable size controllable properties. However, manually designing complementary sequences for technically demanding time consuming task, which...
e15518 Background: Docetaxel (DT) is used frequently as second line therapy in metastatic UC, despite low response rates. However, selected patients may derive significant benefit. Circulating miRNAs have been shown to predict DT castration-resistant prostate cancer (Lin et al, BJC 2014). We aimed determine if the same circulating UC. Methods: obtained pre and post plasma samples from included arm of a phase II clinical trial (n = 20). Total RNA was extracted RT-PCR performed on panel known...
364 Background: Docetaxel is frequently used as second-line therapy in advanced bladder cancer. The response rate 10-15% with a median PFS of 2.5 months and without data showing improvement QoL, however, some selected patients derive significant benefit. Understanding the mechanisms underlying sensitivity docetaxel cancer will help to customize treatment second line. Circulating miRNAs have been shown be predict outcome GU malignancies (for example, prostate cancer). Using circulating miRNA...
Abstract Intratumoral genetic heterogeneity has been characterized across cancers, including chronic lymphocytic leukemia (CLL), and presents challenges to therapy as presence of phenotypically diverse cell populations commonly fuels relapse resistance treatment. While insights have previously gained from bulk analysis, further characterization on the single-cell level is needed more accurately dissect pathway regulatory features associated with distinct subclones. In order identify...
Detection of single nucleotide polymorphisms (SNPs) is critical for early stage diagnosis. However, available clinical methods detecting SNPs require strict assay conditions or complicated enzyme reactions. DNA hybridization by Au nanoparticles a new microscopic method detection, which offers many advantages over traditional ones. But currently, this limitedly used because low yield hybridization. Here we report novel strategies use toehold-mediated strand displacement on origami Chip...
4530 Background: Cisplatin based chemotherapy is the gold standard for first line metastatic/locally advanced urothelial carcinoma (aUC). Variant expression of selected miRNAs and transcription factors (TF) are shown to correlate with predict cisplatin efficacy in many types cancers. In this study we aimed confirm role TFs patients receiving combination therapy aUC Methods: 82 clinically annotated (including N1 resected patients), available tumor tissue, were identified, total RNA was...