Publications by authors named "Randall E Brand"

Article Synopsis
  • - Carbohydrate antigen 19-9 (CA19-9) is a clinically established biomarker for pancreatic ductal adenocarcinoma (PDAC) but is not very effective for early detection, prompting the exploration of circulating miRNAs in plasma as potential early biomarkers.
  • - A study analyzed 2083 miRNAs from patients and healthy controls, identifying a three-miRNA signature (let-7i-5p, miR-130a-3p, and miR-221-3p) that effectively distinguished early-stage PDAC from healthy individuals and chronic pancreatitis, showing improved accuracy when combined with CA19-9.
  • - The miRNA signature demonstrated high predictive accuracy in various stages of the disease and
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  • Molecular studies indicate that ALT is a crucial prognostic marker for shorter relapse-free survival (RFS) in pancreatic neuroendocrine tumors (PanNETs) and other neoplasms.
  • The development of a new chromogenic ALT assay (ALT-CISH) was initiated to address clinical limitations of the traditional fluorescence in situ hybridization (FISH) method, showing a 100% agreement with FISH results in validating that ALT is present in 31% of primary PanNETs.
  • The study demonstrated that ALT status is significantly associated with poorer RFS in both PanNET and leiomyosarcoma (LMS) patients, with ALT being an independent prognostic factor
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A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs.

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Multiplexed imaging technologies have made it possible to interrogate complex tissue microenvironments at sub-cellular resolution within their native spatial context. However, proper quantification of this complexity requires the ability to easily and accurately segment cells into their sub-cellular compartments. Within the supervised learning paradigm, deep learning-based segmentation methods demonstrating human level performance have emerged.

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Article Synopsis
  • Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal cancer with most cases being diagnosed at an advanced stage, and there's no recommended population-wide screening despite some benefits from monitoring high-risk individuals.
  • This study aimed to compare survival rates of patients who detected their PDAC through surveillance with a national database, using data from the Cancer of the Pancreas Screening program and matched SEER patients.
  • Results showed that individuals in the screening group were diagnosed at an earlier stage with smaller tumor sizes compared to the control group, but overall survival benefits remain uncertain and require further investigation.
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Tumor-derived extracellular vesicles (EVs) show great potential as biomarkers for several diseases, including pancreatic cancer, due to their roles in cancer development and progression. However, the challenge of utilizing EVs as biomarkers lies in their inherent heterogeneity in terms of size and concentration, making accurate quantification difficult, which is highly dependent on the isolation and quantification methods used. In our study, we compared three EV isolation techniques and two EV quantification methods.

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Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other diseases. Most mutations begin as nucleotide mismatches or damage in one of the two strands of the DNA before becoming double-strand mutations if unrepaired or misrepaired. However, current DNA-sequencing technologies cannot accurately resolve these initial single-strand events.

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A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs.

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Article Synopsis
  • This study looked at people with a specific type of cancer called pancreatic ductal adenocarcinoma (PDAC) and whether their family history affects recommendations for health check-ups.
  • It compared two groups: one that carries certain genetic risks for PDAC and another that does not.
  • The results showed that while many people with genetic risks had no close family history of PDAC, those who did were more likely to have family members with the disease, suggesting family history is important in understanding cancer risk.
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Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium.

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Background: The International Cancer of the Pancreas Screening Consortium recommended annual imaging for individuals at increased risk for developing a pancreatic ductal adenocarcinoma (PDAC) who did not have concerning pancreatic findings or a cyst <3 cm without worrisome features. We aimed to determine if 3-cm cyst size accurately predicted advanced precursor lesions in high-risk individuals undergoing surveillance.

Methods: Imaging for high-risk individuals (HRIs) undergoing PDAC surveillance from 2007 to 2021 was reviewed and pancreatic abnormalities were recorded including dominant cyst size and number of cysts.

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Background: Pancreatic cancer is a leading cause of cancer-related death worldwide. Tryptophan plays a vital role in cell growth and maintenance as a building block of protein and coordination of organismal responses to environmental and dietary cues. Animal model study showed that dietary tryptophan improved treatment response in those who received chemotherapy or immune checkpoint inhibitors.

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Purpose: An effective blood-based test for pancreatic cancer (PC) screening has remained elusive. The IMMray PanCan-d is the first commercially available blood-based test specifically designed for early detection of PC; however, outcomes from its use in clinical practice have not been reported.

Methods: We performed a blinded spike-in study of 100 individuals who had an IMMray PanCan-d test, including 94 high-risk individuals (HRIs) undergoing PC surveillance and six individuals with known PC.

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Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients undergoing CRC surveillance will not develop CRC. Therefore, biomarkers that can correctly and consistently predict CRC risk in LS patients are needed to both optimize LS patient surveillance and help identify better prevention strategies that reduce risk of CRC development in the subset of high-risk LS patients.

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Immune checkpoint inhibitors (ICI) have transformed the management of cancer, producing durable responses in a subset of treated patients across multiple malignancies. Immune-mediated diarrhea and colitis (imDC) occurs in up to 20% of ICI-treated patients. The risk of ICI imDC is dependent upon the agent and is commoner with anti-CTLA-4 compared to anti-PD-1 ICIs.

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Article Synopsis
  • * Researchers analyzed DNA from invasive pancreatic adenocarcinomas and precursor lesions of patients with and without ATM genetic variants to assess how these alterations contribute to cancer development.
  • * Findings revealed that somatic ATM alterations were present in a significant majority of invasive cancers (75%) but were much less common in precursor lesions (7.1%), suggesting that alterations may occur later in the progression of pancreatic cancer.*
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Unlabelled: Since its inception two years ago, the international, multicenter Pancreatic Cancer Early Detection (PRECEDE) Consortium has enrolled high-risk individuals (HRI) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Herein we aim to evaluate enrollment disparities in PRECEDE. Data on HRIs enrolled between May 2020 and March 2022 were collected, with HRIs defined as participants enrolled in PRECEDE meeting guideline-based criteria for PDAC surveillance.

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Endometrial carcinoma is the most common extraintestinal cancer in Lynch syndrome (LS). Recent studies have demonstrated mismatch repair (MMR) deficiency can be detected in benign endometrial glands in LS. We performed MMR immunohistochemistry in benign endometrium from endometrial biopsies and curettings (EMCs) from a study group of 34 confirmed LS patients and a control group of 38 patients without LS who subsequently developed sporadic MLH1-deficient or MMR-proficient endometrial carcinoma.

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Article Synopsis
  • The study developed a new DNA/RNA next-generation sequencing platform called PancreaSeq Genomic Classifier to enhance the evaluation of pancreatic cysts, particularly in identifying cystic precursor neoplasms and advanced neoplasia.
  • This platform features a 74-gene targeted NGS panel that assesses various genomic alterations, and it was validated in separate cohorts, demonstrating high sensitivity and specificity for diagnosing pancreatic conditions.
  • The results show that PancreaSeq significantly increased the sensitivity of traditional pancreatic cyst guidelines by over 10% while maintaining high specificity, indicating its potential to improve clinical decision-making.
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Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients undergoing CRC surveillance will not develop CRC. Therefore, biomarkers that can correctly and consistently predict CRC risk in LS patients are needed to both optimize LS patient surveillance and help identify better prevention strategies that reduce risk of CRC development in the subset of high-risk LS patients.

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Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other genetic diseases. Almost all of these mosaic mutations begin as nucleotide mismatches or damage in only one of the two strands of the DNA prior to becoming double-strand mutations if unrepaired or misrepaired. However, current DNA sequencing technologies cannot resolve these initial single-strand events.

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Article Synopsis
  • Pancreatic cancer often has a poor prognosis due to late-stage diagnosis and limited treatment options.
  • Early detection of precancerous conditions and finding molecular targets for therapy could improve survival rates.
  • Current research suggests that high-risk individuals may benefit from pancreatic surveillance, which, alongside new biomarkers, could lead to better risk assessment and prevention strategies for pancreatic cancer.
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Immunoassay based bioanalytical measurements are widely used in a variety of biomedical research and clinical settings. In these settings they are assumed to faithfully represent the experimental conditions being tested and the sample groups being compared. Although significant technical advances have been made in improving sensitivity and quality of the measurements, currently no metrics exist that objectively quantify the fidelity of the measured analytes with respect to noise associated with the specific assay.

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Article Synopsis
  • A multidisciplinary group of 69 experts created the first evidence-based consensus recommendations for managing early-onset colorectal cancer (eoCRC) since existing guidelines are not age-specific.
  • They utilized a Delphi methodology, achieving an 80% consensus on 31 important statements covering diagnosis, genetics, therapy, and more, emphasizing the need for risk stratification and genetic testing for patients under 50.
  • The recommendations highlight that treatments for eoCRC should generally align with those for later-onset cases, but also point out knowledge gaps that require further research, including optimal screening age and post-treatment care.
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