Publications by authors named "Hubert Ayala"

Article Synopsis
  • Scientists are looking for better ways to detect pancreatic cancer early so it can be treated more effectively.
  • They studied blood samples from 426 patients to find different markers that could indicate pancreatic cancer compared to other conditions.
  • Results showed that a mix of certain protein markers and DNA changes in the blood can help identify early-stage pancreatic cancer better than just using one marker alone.
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Optimal clinical outcomes in cancer treatments could be achieved through the development of reliable, precise ex vivo tumor models that function as drug screening platforms for patient-targeted therapies. Microfluidic tumor-on-chip technology is emerging as a preferred tool since it enables the complex set-ups and recapitulation of the physiologically relevant physical microenvironment of tumors. In order to overcome the common hindrances encountered while using this technology, a fully 3D-printed device was developed that sustains patient-derived multicellular spheroids long enough to conduct multiple drug screening tests.

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Introduction: 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 to predict patient response to cancer therapy.

Methods: A multicenter, prospective, single-arm observational trial.

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The standard treatment approach for stage II/III rectal cancer is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ-preservation strategies. However, better tools are still needed to personalize therapy for the individual patient.

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Pancreatic ductal adenocarcinoma (PDA) is an aggressive metastatic cancer with a very low survival rate. This tumor is hypovascularized and characterized by severe hypoxic regions, yet these regions are not impeded by the oxidative stress in their microenvironment. PDA's high resilience raises the need to find new effective therapeutic targets.

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Article Synopsis
  • - The study focuses on analyzing cell-free DNA (cfDNA) in plasma to gain insights into various pathological processes, specifically for cancer detection and profiling.
  • - A new assay, called EPINUC, uses single-molecule imaging to evaluate the epigenetics and protein biomarkers associated with nucleosomes from blood samples, enhancing the ability to identify active and repressive histone modifications.
  • - Testing with EPINUC on samples from patients with colorectal and pancreatic cancer, as well as healthy individuals, showed high accuracy in detecting cancer, even in early stages, while also determining the tissue origin of several tumor types.
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Adenocarcinomas of the gastroesophageal junction (GEJ) are tumors whose incidence rates increased significantly in recent years. These tumors have a poor prognosis, and are treated with a palliative approach when diagnosed in an advanced stage. Some tumors overexpress PDL-1 proteins which are partially responsible for the "immune escape" of tumor cells.

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Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death in organs affected by cancer can be detected by tissue-specific methylation patterns of circulating cell-free DNA (cfDNA). We detected elevated levels of hepatocyte-derived cfDNA in the plasma of patients with liver metastases originating from different primary tumors, compared with cancer patients without liver metastases.

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Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples.

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Background: The prognosis of gastric cancer (GC) is poor with a median overall survival (OS) of less than 12 months in advanced-stage disease. The search for distinct genetic subgroups of GC patients and predictive biomarkers is ongoing. While or germline mutations (gBRCAm) have potential therapeutic implications in ovarian, breast and pancreatic cancers, their significance in GC patients has not been established.

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The currently accepted imaging methods have been a central hurdle to imaging the finer details of tumor behavior in three-dimensional (3D) ex vivo multicellular culture models. In our search for an improved way of imaging tumor behavior in its physiological-like niche, we developed a simple, efficient, and straightforward procedure using standard reagents and imaging equipment that significantly enhanced 3D imaging up to a ~200-micron depth. We tested its efficacy on pancreatic spheroids, prototypes of high-density tissues that are difficult to image.

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Mucinous colorectal carcinomas (MC) constitute 10% of colorectal malignancies. Recently, an increased risk of colorectal cancer has been demonstrated in germline mutation carriers. Furthermore, germline mutation carriers have exhibited a higher-than-expected frequency of MC tumors.

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Article Synopsis
  • * A study reported three cases of metastatic PDAC patients with wildtype KRAS, who had rare pathogenic alterations in BRAF or RET and received targeted therapy with varying results.
  • * The authors suggest that these cases highlight the need for more research and clinical trials focused on this small but important population of PDAC patients with uncommon driver mutations.
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Background: Anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left-sided tumors may exhibit superior survival compared with right-sided tumors. The Oncotype Recurrence Score (RS) assay is a clinically validated predictor of recurrence risk in patients with stage II colorectal cancer (CRC). Previous studies had indicated that without adjuvant chemotherapy, CDX2-negative stage II CRC tumors are associated with a lower rate of disease-free survival than CDX2-positive stage II CRC tumors.

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Purpose: Acneiform rash, a common toxicity of epidermal growth factor receptor inhibitors (EGFRIs), can cause patient discomfort, warranting changes in treatment. This study investigated the safety, tolerability, and efficacy of a novel doxycycline foam, FDX104 4%, for managing EGFRI-related skin toxicity.

Methods: This was an exploratory phase 2, randomized, double-blind, placebo-controlled study.

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Tumor genome sequencing is important for increasing our understanding of the development of cancer, which may be affected by different therapies. In the present study, genomic evolution was investigated in a patient with stage IV pancreatic cancer bearing a germline breast cancer 2 () mutation. The patient received cisplatin, a DNA cross-linking agent, which led to a long-lasting complete response.

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Background: Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care.

Objective: To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel.

Patients And Methods: This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy.

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Mutations in the BRCA1/2 genes were recently shown to be associated with an increased risk for colorectal cancer. We characterized the largest cohort available of BRCA1/2 mutation carriers with colorectal cancer. We analyzed 32 patients with lower gastrointestinal cancers and germline BRCA1/2 mutations from two large academic hospital registries; 91% of patients were of Ashkenazi ancestry, 78% were women, and 62.

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Recapitulating the tumor microenvironment is a central challenge in the development of experimental model for cancer. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key features that  exist in the original tumor. Along with this effort, 3-dimentional (3D) cellular models are being extensively studied.

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Molecular portraits of numerous tumors have flooded oncologists with vast amounts of data. In parallel, effective inhibitors of central pathways have shown great clinical benefit. Together, this promises potential clinical benefits to otherwise end-stage cancer patients.

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Background: The prognostic and predictive significance of the high-level microsatellite instability (MSI-H) phenotype in various malignancies is unclear. We describe the characteristics, clinical course, and outcomes of patients with MSI-H malignancies treated in a real-life hospital setting.

Patients And Methods: A retrospective analysis of MSI-H cancer patient files was conducted.

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Background: H19 is a paternally imprinted, oncofetal gene expressed in various embryonic tissues and in 85% of the ovarian tumors. H19-DTA (BC-819) is a DNA plasmid that drives the expression of the diphtheria toxin gene under the regulation of the H19 promoter sequence and therefore is a potential treatment for various tumors that overexpress the H19 gene, among them-ovarian cancer.

Objective: To assess the safety and efficacy of intra-peritoneal (IP) instillations of H19-DTA (BC-819) plasmid in treating ovarian/peritoneal cancer patients with advanced recurrent disease.

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