A5023010386- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Estrogen and related hormone effects
- Ferrocene Chemistry and Applications
- CRISPR and Genetic Engineering
- Breast Cancer Treatment Studies
- Ovarian cancer diagnosis and treatment
- Cancer-related Molecular Pathways
- Computational Drug Discovery Methods
- Cancer Cells and Metastasis
- Reproductive System and Pregnancy
- Gene expression and cancer classification
- Coral and Marine Ecosystems Studies
- Cancer Mechanisms and Therapy
- Marine Sponges and Natural Products
- CAR-T cell therapy research
- Marine Biology and Environmental Chemistry
Sheba Medical Center
2010-2020
Hebrew University of Jerusalem
2008
Tel Aviv University
2006-2007
Emerging mutations in the ESR1 gene that encodes for estrogen receptor (ER) are associated with resistance to endocrine therapy. rarely exist primary tumors (~ 1%) but relatively common (10-50%) metastatic, therapy-resistant cancers and a shorter progression-free survival. Little is known about incidence clinical implication of these early recurrence events, such as local recurrences or newly diagnosed metastatic disease.We collected 130 archival tumor samples from 103 breast cancer patients...
Germline BRCA-associated pancreatic ductal adenocarcinoma (glBRCA PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with glBRCA PDAC were stratified based on the spectrum response platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable followed by acquired resistance (OS <36 months), (iii) long-term responders >36 months). Patient-derived xenografts (PDX) generated from 25 at different time points. Response...
Bioerosion by boring sponges is an important mechanism shaping the structure of coral reefs all around world. To determine excavation rate sponges, we developed a system in which chemical and mechanical rates [calcium carbonate (CaCO(3)) dissolution chip production, respectively] were measured simultaneously experimental tanks containing reefal rock inhabited sponge. Pione cf. vastifica (Hancock 1849) was chosen as model species to study erosion sponges. It abundant Nature Reserve Reef,...
Abstract Aberrant Ras pathway functions contribute to the malignant phenotype of lung cancers. Inhibitors might therefore be considered as potential drugs for cancer therapy. Here, we show that inhibitor farnesylthiosalicylic acid (salirasib) inhibits proliferation human cells harboring a mutated K-ras gene (A549, H23, or HTB54) overexpressing growth factor receptor (H1299 HTB58) and enhances cytotoxic effect chemotherapeutic drug gemcitabine. Salirasib inhibited active K-Ras in A549 cells,...
RSK4 promotes invasiveness and drug resistance in lung bladder cancer inhibition of this kinase shows therapeutic potential.
Abstract Deregulation of Ras pathways results in complex abnormalities multiple signaling cascades that contribute to human malignancies. is therefore considered an appropriate target for cancer therapy. In light the complexity deregulated pathway, it important decipher at molecular level response cells inhibitors would reregulate it. present study, we used gene expression profiling as a robust method global dissection alterations resulted from treatment with inhibitor...
In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of fallopian tube epithelial cells (FTECs) has gained evidence. However, mechanistic pathway for this process not been revealed yet. current study, we propose mutator protein activation-induced cytidine deaminase (AID) as a link between in FTECs and genotoxic damage leading to carcinogenesis. We show AID, previously shown be functional only B lymphocytes, is expressed under physiological...
We present a new approach for the conversion of active sequences proteins and peptides into small molecules. A library macrocyclic disulfide molecules was made, in which pharmacophores parent peptide are preserved while size macromolecular scaffold on arranged is varied. This enables systematic search macromolecules an appropriate conformation biological activity. developed two procedures synthesis such libraries from building blocks that include commercial amino acids functionalized...
Recent studies have suggested that epigenetic modulation with chromatin-modifying agents can induce stemness and dedifferentiation increase developmental plasticity. For instance, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has been shown to promote self-renewal/expansion of hematopoietic stem cells facilitate the generation induced pluripotent (iPSCs). Previously, we observed downregulation embryonic renal stem/progenitor genes in adult kidney was associated, at least part,...
High-grade serous ovarian carcinoma (HGSOC) is the most common type of epithelial cancer. The majority cases are diagnosed at advanced stages, when intraperitoneal (IP) spread has already occurred. Despite significant surgical and chemotherapeutic advances in HGSOC treatment over past decades, survival rates with have only modestly improved. Chimeric antigen receptor (CAR)-T cells enable T to directly bind tumor-associated antigens a major histocompatibility complex-independent manner,...
Epithelial-to-mesenchymal transition (EMT) plays a major role in breast cancer progression and the development of drug resistance. We have previously demonstrated trans-differentiation therapeutic approach targeting invasive dedifferentiated cells. Using combination PPARγ agonists MEK inhibitors, we forced differentiation disseminating cells into post-mitotic adipocytes. Utilizing murine cells, broad class effect inhibitors inducing cell Both Rosiglitazone Pioglitazone effectively induced...
Ex vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform predict patient response therapy.A multicenter, prospective, single-arm observational trial. Samples obtained from patients newly diagnosed bladder who underwent transurethral resection tumor and core needle biopsies metastatic cancer. The tumors cut into 250 μM slices cultured within 24 h, then incubated 96 h vehicle or...
Abstract Emerging mutations in the ESR1 gene that encodes for estrogen receptor (ER) have been recently associated with resistance to endocrine therapy ER positive metastatic breast cancer patients. These promote active conformation of receptor, conferring therapy, and were shorter progression free survival. found rarely exist primary tumors (~1%) but are relatively common metastatic, therapy-resistant lesions, an estimated prevalence ~10-50%. Nevertheless, not much is known about incidence...
Abstract Precision cancer therapy has the potential to revolutionize treatment outcome. While genomic analysis become central personalized medicine, recent studies have not shown that it drastically improves patient survival as compared standard drug selection. Additionally, mutations may suggest several protocols without elucidating which approach will yield best clinical response. Moreover, for many drugs no genetic predictive biomarkers are available. To advance precision diagnostics, we...
Abstract In recent years, the notion that serous ovarian carcinoma results from ovulation-induced inflammation of fallopian tube epithelial cells (FTECs) has gained evidence. However, mechanistic pathway leads to mutagenesis and genomic instability not been revealed yet. The mutator enzyme activation-induced cytidine deaminase (AID), which is known be involved in process immunoglobulin somatic hypermutations, also recently implicated inflammation-induced malignancies. current study, we...
Abstract Tumor heterogeneity frequently develops through the course of disease, therapy and metastasis. This molecular evolution is a major challenge in clinical setting main reason for resistance to therapy. Although metastatic disease cause death breast cancer, most studies involve primary tumors compared normal breast. An alternative approach serial assessments can add an informative value highlight important players that may be otherwise underestimated. We sought explore alterations by...