• Home
  • Josep Domingo-Domenech
Josep Domingo-Domenech

Josep Domingo-Domenech
Mayo Clinic · Urology department

M.D., Ph.D.

About

89
Publications
10,522
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,597
Citations
Additional affiliations
July 2012 - present
Icahn School of Medicine at Mount Sinai
Position
  • Icahn School of Medicine at Mount Sinai
September 2007 - July 2012
Columbia University
Education
September 2007 - July 2012
Columbia University
Field of study
  • Pathology and Cell Biology Program
September 2003 - September 2007
University of Barcelona
Field of study
  • Pathology and Cell Biology Program
February 2002 - February 2003
ESADE Business School
Field of study
  • Health Care Management

Publications

Publications (89)
Article
Full-text available
Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer st...
Article
Loss of the retinoblastoma (RB) tumor suppressor protein is a critical step in reprogramming biological networks that drive cancer progression, although mechanistic insight has been largely limited to the impact of RB loss on cell-cycle regulation. Here, isogenic modeling of RB loss identified disease stage–specific rewiring of E2F1 function, provi...
Preprint
Full-text available
Triple negative breast cancer (TNBC) remains clinically challenging as patients have heterogeneous responses to current standard of care therapies. Chemotherapy sensitivity is a strong predictor of long-term outcomes for patients, and incomplete response of early stage disease to chemotherapy treatment is associated with a much higher risk of disea...
Article
Full-text available
The ability of small extracellular vesicles (sEVs) to reprogram cancer cells is well established. However, the specific sEV components able to mediate aberrant effects in cancer cells have not been characterized. Integrins are major players in mediating sEV functions. We have previously reported that the αVβ3 integrin is detected in sEVs of prostat...
Article
Purpose: PSA has limited performance in detecting prostate cancer (PCa). The transcription factor GATA2 is expressed in aggressive PCa. Here we analyzed the predictive value of urine extracellular vesicle (EV) GATA2 mRNA alone and in combination with a multigene panel to improve detection of PCa and high-risk disease. Materials and methods: GATA...
Article
Over the past 5 years, the advent of combination therapeutic strategies has substantially reshaped the clinical management of patients with advanced prostate cancer. However, most of these combination regimens were developed empirically and, despite offering survival benefits, are not enough to halt disease progression. Thus, the development of eff...
Article
Full-text available
Background Prostate specific antigen (PSA) detection in blood is widely used to screen for prostate cancer (PCa). However, PSA has limited utility in discriminating high risk tumors (Gleason score≥7) from indolent-low risk tumors, which leads to unnecessary biopsies and highlights the need to identify better biomarkers for the detection of clinical...
Article
121 Background: It is uncertain whether the same criteria for active surveillance can be applied universally across races. This population-based study was undertaken to quantify racial differences in long-term risk of prostate cancer-specific mortality (PCSM) among patients with low-risk prostate cancer (PCa) receiving conservative management. Meth...
Article
18 Background: Prostate specific antigen (PSA) detection in blood is widely used to screen for prostate cancer (PCa). However, PSA has limited utility in discriminating tumors at high risk of progression from indolent-low risk tumors, which leads to PCa overtreatment and highlights the need to identify better biomarkers for the detection of clinica...
Article
Full-text available
Cancers infiltrated with T-cells are associated with a higher likelihood of response to PD-1/PD-L1 blockade. Counterintuitively, a correlation between epithelial-mesenchymal transition (EMT)-related gene expression and T-cell infiltration has been observed across tumor types. Here we demonstrate, using The Cancer Genome Atlas (TCGA) urothelial canc...
Article
Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer...
Article
Full-text available
Background: Chemotherapy may exert immunomodulatory effects, thereby combining favorably with the immune checkpoint blockade. The pharmacodynamic effects of such combinations, and potential predictive biomarkers, remain unexplored. Objective: To determine the safety, efficacy, and immunomodulatory effects of gemcitabine and cisplatin (GC) plus i...
Article
Full-text available
Microtubule targeting agents (MTAs) are a mainstay in the treatment of a wide range of tumors. However, acquired resistance to chemotherapeutic drugs is a common mechanism of disease progression and a prognostic-determinant feature of malignant tumors. In prostate cancer (PC), resistance to MTAs such as the taxane Docetaxel dictates treatment failu...
Article
Full-text available
Human leukocyte antigen class I (HLA-I) down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs) remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different...
Article
Full-text available
Advanced prostate cancer is a classic example of the intractability and consequent lethality that characterizes metastatic carcinomas. Novel treatments have improved the survival of men with prostate cancer; however, advanced prostate cancer invariably becomes resistant to these therapies and ultimately progresses to a lethal metastatic stage. Cons...
Article
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help reader...
Article
Introduction: There has been a paucity of new therapies developed for the treatment of advanced urothelial cancer due to a convergence of factors including a low prioritization of the disease by industry, therapeutic nihilism, and a limited understanding of the molecular pathogenesis and relevant therapeutic targets. Areas covered: Herein, we revie...
Article
Background: Patients with head and neck squamous cell carcinoma (HNSCC) present different responses to chemotherapy and radiotherapy. One explanation may be the differences in the individual rates of stem cell-like cells. Methods: We included patients with HNSCC and tumor progression or relapse. Tumor samples were obtained before and after prima...
Article
Objective: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterise the role of tumour-initiating cells (T-ICs) and signalling pathways involved in sorafenib resistance. Design: HCC xenograft mice t...
Article
Full-text available
Patient derived xenograft (PDX) models are gaining popularity in cancer research and are used for preclinical drug evaluation, biomarker identification, biologic studies, and personalized medicine strategies. Circulating tumor cells (CTC) play a critical role in tumor metastasis and have been isolated from patients with several tumor types. Recentl...
Article
Elucidating the determinants of aggressiveness in lethal prostate cancer may stimulate therapeutic strategies that improve clinical outcomes. We used experimental models and clinical databases to identify GATA2 as a regulator of chemotherapy resistance and tumorigenicity in this context. Mechanistically, direct upregulation of the growth hormone IG...
Article
The cancer stem cell (CSC) model has been considerably revisited over the last two decades. During this time CSCs have been identified and directly isolated from human tissues and serially propagated in immunodeficient mice, typically through antibody labeling of subpopulations of cells and fractionation by flow cytometry. However, the unique clini...
Article
Full-text available
Acquired resistance has curtailed cancer survival since the dawn of the chemotherapy age more than half a century ago. Although the application of stem cell (SC) concepts to cancer captured the imagination of scientists for many years, only the last decade has yielded substantial evidence that cancer SCs (CSCs) contribute to chemotherapy resistance...
Article
Full-text available
miRNAs are small noncoding RNAs with critical roles in a large variety of biological processes such as development and tumorigenesis. miRNA expression profiling has been reported to be a powerful tool to classify tissue samples, including cancers, based on their developmental lineage. In this study, we have profiled the expression of miRNAs in blad...
Article
Although level I evidence supports the use of neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy for the management of patients with muscle-invasive bladder cancer (MIBC), these treatment modalities are utilized in only a subset of patients. The reasons for lack of implementation of these treatment standards are multiple; patie...
Article
Acquired resistance to Docetaxel precedes fatality in hormone-refractory prostate cancer (HRPC). However, strategies that target Docetaxel resistant cells remain elusive. Using in vitro and in vivo models, we identified a subpopulation of cells that survive Docetaxel exposure. This subpopulation lacks differentiation markers and HLA class I (HLAI)...
Article
Full-text available
Cre-loxp mediated conditional knockout strategy has played critical roles for revealing functions of many genes essential for development, as well as the causal relationships between gene mutations and diseases in the postnatal adult mice. One key factor of this strategy is the availability of mice with tissue- or cell type-specific Cre expression....
Data
qRT-PCR analysis of relative expression levels of Bcl9l, Cxcr5, and Foxr1 in the bladders of Wt (set to 1) and TgUICBAC mice. Mouse Gapdh expression level was used as control. Refer to “Method” for more detail. In a brief summary, Bcl9l showed a 2.2-fold increase in male (p = 0.014) and 1.8-fold increase in female (p = 0.02); Cxcr5 showed a 20.8-fo...
Article
Alveolar rhabdomyosarcomas (ARMS) are characterised by a PAX3/7-FKHR translocation, which is presumed to promote a differentiation arrest in the myogenic lineage, in which setting secondary genetic events occur, resulting in sarcomagenesis. The aim of this study was to identify the mechanism by which PAX3/7-FKHR expression results in a myogenic dif...
Article
After encouraging results from 2 clinical trials performed at our institution to test intravesical taxane based chemotherapy for bacillus Calmette-Guérin refractory, nonmuscle invasive bladder cancer we designed a study to identify molecular markers linked to the optimal response to such treatment modality. Included in the institutional review boar...
Article
Surgery is the mainstay of treatment for localized melanoma. Postoperative radiation therapy after lymphadenectomy has shown to provide an excellent locoregional control in patients with melanoma node metastases with high risk for loco-regional relapse (lymph nodes ≥ 3 cm, ≥ 3 lymph nodes involved, extracapsular extension and/or recurrent disease)....
Article
The TP63 gene, a member of the TP53 tumor suppressor gene family, can be expressed as at least six isoforms due to alternative promoter use and alternative splicing. The lack of p63 isoform-specific antibodies has limited the analysis of the biological significance of p63. We report a novel set of well-defined antibodies to examine p63 isoforms in...
Article
Full-text available
To present fundamental anatomical aspects and technical skills necessary to urethra and urinary bladder catheterization in female mice and rats. Urethral and bladder catheterization has been widely utilized for carcinogenesis and cancer research and still remains very useful in several applications: from toxicological purposes as well as inflammato...
Article
Surgery is the mainstay of treatment for localized melanoma. Postoperative radiation therapy after lymphadenectomy has shown to provide an excellent locoregional control in patients with melanoma node metastases with high risk for loco-regional relapse (lymph nodes ≥ 3 cm, ≥ 3 lymph nodes involved, extracapsular extension and/or recurrent disease)....
Article
Bladder cancer is the fifth most common human malignancy and the second most frequently diagnosed genitourinary tumor after prostate cancer. The majority of malignant tumors arising in the urinary bladder are urothelial carcinomas. Clinically, superficial bladder tumors (stages Ta and Tis) account for 75% to 85% of neoplasms, while the remaining 15...
Article
Full-text available
The role of adjuvant radiation therapy (RT) following nodal surgery in malignant melanoma remains controversial. There are no published randomised trials comparing surgery alone to surgery with postoperative RT. The purpose of the present retrospective study was to review the results of loco-regional control after postoperative RT in patients with...
Article
Full-text available
Histone deacetylase inhibitors (HDACi) are a new class of anticancer agents that cause growth arrest, differentiation and/or apoptosis in many tumor cells. As acetylation regulates the activity of the anti-apoptotic transcription factor NF-kappaB, we investigated whether the proteasome inhibitor MG-132 would inhibit NF-kappaB activation and as a co...
Article
Single nucleotide polymorphisms of dihydropyrimidine dehydrogenases gene (DPYD) induces dihydropyrimidine dehydrogenase enzyme (DPD) deficiency resulting in increased activity of 5-fluorouracil derivatives. Cytidine-deaminase gene (CDA) polymorphisms have been involved in prognosis in experimental tumours. Analysis of 50 consecutive resected gastri...
Article
22112 Background: Overexpression of the members of HER family has been correlated with high tumor grade, higher metastatic ability and poor prognosis in several epithelial tumors. HER2 amplification has been described in the 25–30% of breast cancer patients and has been associated with chemo and radiotherapy (RT) resistance. Radiosensitivity of a t...
Article
To evaluate serum vascular endothelial growth factor (VEGF) as a prognostic factor in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with metronomic (weekly) paclitaxel. Before-and-after trial. A total of 33 consecutive patients were enrolled. Patients with recurrent and/or metastatic cancer of the he...
Article
Surgically resected stage III melanoma patients commonly receive adjuvant therapy with interferon (IFN) alpha2b. For those patients with high-risk features of draining node recurrence, radiation therapy can also be considered as a treatment option. The purpose of this retrospective study was to assess the efficacy and radiation-related toxicity of...
Article
It was the aim of this study to analyze the clinical value of the determination of serum S-100beta protein in high-risk melanoma patients. Patients were tested for serum S-100beta protein by luminoimmunometric assay after melanoma surgical excision, before starting interferon-alpha2b and every 3 months thereafter, until treatment was completed. Nin...
Article
5075 Background: We have recently reported that NF-κB/IL-6 was linked to D response in human prostate cancer cells. In this study we investigated the clinical significance of IL-6 serum levels in HIPC pts treated with D and the correlation between serum IL-6 levels and p65/NF-κB tissue expression. Methods: Pts with HIPC treated with D were prospect...
Article
8543 Background: S-100β serum levels have been shown to be useful to monitor response to therapy in metastatic melanoma patients. We have recently reported that S-100β levels could also be useful in the adjuvant context. In this study we analyze the clinical relevance of S-100β serum levels in an homogeneuos stage IIB-III group of patients treated...
Article
11510 Background: Immunohistochemistry (IHC) assay for HER2 in breast cancer (BC) identify patients (pts) who are at benefit from Trastuzumab (T) therapy. The percentage (%) of positive cells is not known to have prognostic significance. Methods: We analyze pts that received T as a treatment for metastatic BC in our center, in monotherapy or in com...
Article
2540 Background: Gene SNPs correlate with survival in cancer patients (pts) treated with chemotherapy (CHM). CYP2C8 and GSTT1, GTSP1 genes are involved in phase 1 and 2 drug cellular metabolisms respectively; MDR1(A) and MDR1(B) are involved in drug membrane transport and ERCC1 in DNA repair Methods: We evaluated the presence of SNPs of these 6 gen...
Article
Intramedullary spinal cord metastases (ISCM) are uncommon and present with rapidly progressing neurological deficits. The objective of this study was to determine the rate, duration of neurological response and survival after radiation therapy. We have retrospectively reviewed the clinical outcome of six cases with a diagnosis of ISCM from primary...
Article
Surgical therapy plays an important role in the management of selected patients with metastatic melanoma. A retrospective review of 13 patients who underwent surgical resection of lung metastases from melanoma from 1996 to 2003 was performed. The aim of the study was to analyze the clinical outcome and survival time. Mean age was 45 years old (rang...
Article
Full-text available
To investigate whether nuclear factor kappaB (NF-kappaB)/interleukin 6 (IL-6) was linked to docetaxel response in human prostate cancer cell lines, and whether inhibition of NF-kappaB sensitized tumor cells to docetaxel. We also aimed to correlate IL-6 (as a surrogate marker of NF-kappaB) and docetaxel response in hormone-independent prostate cance...
Article
Full-text available
We investigated the change of prognosis in resected gastric cancer (RGC) patients and the role of radical surgery and adjuvant chemotherapy. We retrospectively analyze the outcome of 426 consecutive patients from 1975 to 2002, divided into 2 time-periods (TP) cohort: Before 1990 (TP1, n = 207) and 1990 or after (TP2; n= 219). Partial gastrectomy an...
Article
20042 Background: Mechanisms responsible for acquired resistance in colorectal cancer (CRC) tumors are not well understood. Anticancer drugs have been shown to enhance FASL expression by NF-kB induction. Additionally Metalloproteinase (MMP)-7 is over-expressed in CRC and has been shown to inhibit apoptosis by cleavage of FASL. We have previously sh...
Article
4052 Background: Single nucleotide polymorphisms (SNPs) of DPYD gene induces DPD deficiency resulting in decreased activity of 5-fluorouracil derivatives in treatment of colorectal cancer patients (pts). In GCP has not been previously analysed. Methods: We analysed paraffin-embedded biopsies from 50 consecutive resected GCP who received adjuvant ch...
Article
4632 Background: The overexpression of c-erbB-2 has been described as a common event associated to the hormone-independent progression in prostate cancer. The clinical implications of c-erbB-2 expression in HIPC pts are not fully established. In this study we investigated the clinical significance of c-erbB-2 serum levels in HIPC pts treated with D...
Article
Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in surv...
Conference Paper
Full-text available
4694 Objective: Histone deacetylase inhibitors (HDACi) are a new class of anticancer agents which have shown to cause growth arrest, differentiation and/or apoptosis of many tumor cells. Previous studies have implicated acetylases and deacetylases in the regulation of the antiapoptotic transcription factor NF-κB. We hypothesize that proteasome inhi...