Metabolic risk factors of colorectal cancer: Umbrella review.

Background And Aim: The association between metabolic factors and colorectal cancer (CRC) risk is inconclusive. This umbrella review aimed to summarise and describe the association using existing systematic reviews and/or meta-analyses.

Method: Four databases (Medline, Scopus, Web of Science, and Cochrane Library) were searched for systematic reviews and/or meta-analyses of observational studies.

A blood test measuring DNA methylation of BCAT1 and IKZF1 for detection of lung adenocarcinoma.

Background: Colorectal (CRC) and lung adenocarcinoma share many genetic and pathological similarities. A circulating tumor DNA (ctDNA) test for CRC may also be useful for detection of lung adenocarcinoma. This study determined if a methylated BCAT1/IKZF1 ctDNA test for CRC can be used for detection of lung adenocarcinoma.

Faecal immunochemical tests can improve colonoscopy triage in patients with iron deficiency: A systematic review and meta-analysis.

Background: Use of the faecal immunochemical test (FIT) to triage patients with iron deficiency (ID) for colonoscopy due to suspected colorectal cancer (CRC) may improve distribution of colonoscopic resources. We reviewed the diagnostic performance of FIT for detecting advanced colorectal neoplasia, including CRC and advanced pre-cancerous neoplasia (APCN), in patients with ID, with or without anaemia.

Methods: We performed a systematic review of three databases for studies comprising of patients with ID, with or without anaemia, completing a quantitative FIT within six months prior to colonoscopy, where test performance was compared against the reference standard colonoscopy.

Elevation of the tumor marker CA19-9 in a pancreatic cancer survivor with benign prostatic hyperplasia: A clinical case report.

Serum carbohydrate antigen 19-9 (CA19-9) is used for recurrence surveillance in patients with resected pancreatic ductal adenocarcinoma (PDAC). This report describes the association of increasing CA19-9 in a male PDAC survivor with presence of prostatic hyperplasia. Unexplained elevation of CA19-9 in male PDAC survivors might be attributable to benign prostatic conditions.

Accuracy, Acceptability, and Application: Fecal Immunochemical Tests for Early Detection of Advanced Neoplasia in Colonoscopy-Based Surveillance.

Background: The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening, but limited data exist for its application in individuals at above-average risk for CRC who complete surveillance colonoscopies.

Aim: To assess the accuracy, acceptability, and effectiveness of FIT in the interval between surveillance colonoscopies, for predicting advanced neoplasia (advanced adenoma or CRC) at the next colonoscopy.

Methods: Individuals enrolled in an Australian surveillance program were included.

, and : methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas.

Introduction: Methylated circulating tumour DNA (ctDNA) blood tests for (COLVERA) and (Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize and methylation in different gastrointestinal adenocarcinoma and non-gastrointestinal tumours to determine if these validated CRC biomarkers might be useful for pan-gastrointestinal adenocarcinoma detection.

Comparing a fecal immunochemical test and circulating tumor DNA blood test for colorectal cancer screening adherence.

Background And Aim: Colorectal cancer (CRC) screening programs are most effective at reducing disease incidence and mortality through sustained screening participation. A novel blood test modality is being explored for CRC screening, but it is unclear whether it will provide sustained screening participation. This study aimed to investigate whether a circulating tumor DNA (ctDNA) blood test improved CRC screening re-participation when compared with a fecal immunochemical test (FIT) and to define the predictors of sustained CRC screening in an Australian population.

Evaluating the Role of Methylated Circulating Tumor DNA in Combination With Pathological Prognostic Factors for Predicting Recurrence of Colorectal Cancer.

Background: Colorectal cancer (CRC) has a high rate of recurrence, in particular for advanced disease, but prognosis based on staging and pathology at surgery can have limited efficacy. The presence of circulating tumor DNA (ctDNA) at diagnosis could be used to improve the prediction for disease recurrence.

Objectives: To assess the impact of detecting methylated ctDNA at diagnosis in combination with demographic, lifestyle, clinical factors and tumor pathology, to assess predictive value for recurrence.

The Diagnostic Accuracy of a Fecal Immunochemical Test in Detecting Colorectal Cancer and Advanced Precancerous Colorectal Neoplasia in Patients with Iron Deficiency: A Protocol for Systematic Review and Meta-Analysis.

. Iron deficiency (ID) is a common micronutrient deficiency and the leading cause of anemia worldwide. ID can be caused by chronic occult blood loss from colorectal neoplasia including colorectal cancer (CRC) and advanced precancerous colorectal lesions.

Progress in the field of noninvasive diagnostics for colorectal cancer: a systematic review for the accuracy of blood-based biomarkers for detection of advanced pre-cancerous lesions.

Background: Early detection of pre-cancerous adenomas through screening can reduce colorectal cancer (CRC) incidence. Fecal immunochemical tests are commonly used, but have limited sensitivity for pre-cancerous lesions. Blood-based screening may improve test sensitivity.

Selective inhibition of CDK9 in triple negative breast cancer.

Targeted therapy for triple-negative breast cancers (TNBC) remains a clinical challenge due to tumour heterogeneity. Since TNBC have key features of transcriptionally addicted cancers, targeting transcription via regulators such as cyclin-dependent kinase 9 (CDK9) has potential as a therapeutic strategy. Herein, we preclinically tested a new selective CDK9 inhibitor (CDDD11-8) in TNBC using cell line, patient-derived organoid, and patient-derived explant models.

FIT for purpose: study protocol for a randomized controlled trial to personalize surveillance colonoscopy for individuals at elevated risk of colorectal cancer.

Purpose: There is increasing demand for colorectal cancer (CRC) surveillance, but healthcare capacity is limited. The burden on colonoscopy resources could be reduced by personalizing surveillance frequency using the fecal immunochemical test (FIT). This study will determine the safety, cost-effectiveness, and patient acceptance of using FIT to extend surveillance colonoscopy intervals for individuals at elevated risk of CRC.

Age-Specific Differences in the Risk of Colorectal Precursor Lesions Among Patients with Type 2 Diabetes Undergoing Surveillance Colonoscopy.

Background: The incidence rate of colorectal cancer (CRC) in young adults is rising in parallel with type 2 diabetes (T2D). The majority of CRC develop through two main subtypes of precursor lesions; adenomas and serrated lesions. The associations between age and T2D on development of precursor lesions remain uncertain.

Hot Mail: Temperature Exposure during Mail Return of an Immunochemical Fecal Occult Blood Test.

Background: Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening; however, high ambient temperatures were found to reduce test accuracy. More recently, proprietary globin stabilizers were added to FIT sample buffers to prevent temperature-associated hemoglobin (Hb) degradation, but their effectiveness remains uncertain. We aimed to determine the impact of high temperature (>30°C) on OC-Sensor FIT Hb concentration with current FITs, characterize FIT temperatures during mail transit, and determine impact of ambient temperature on FIT Hb concentration using data from a CRC screening program.

Potent Stimulation of the Androgen Receptor Instigates a Viral Mimicry Response in Prostate Cancer.

Unlabelled: Inhibiting the androgen receptor (AR), a ligand-activated transcription factor, with androgen deprivation therapy is a standard-of-care treatment for metastatic prostate cancer. Paradoxically, activation of AR can also inhibit the growth of prostate cancer in some patients and experimental systems, but the mechanisms underlying this phenomenon are poorly understood. This study exploited a potent synthetic androgen, methyltestosterone (MeT), to investigate AR agonist-induced growth inhibition.

Multiple Negative Fecal Immunochemical Tests Reduce Risk of Advanced Neoplasia in a Colonoscopy Surveillance Program.

Background & Aims: In above-average-risk individuals undergoing colonoscopy-based surveillance for colorectal cancer (CRC), screening with fecal immunochemical tests (FIT) between colonoscopies might facilitate personalization of surveillance intervals. Because a negative FIT is associated with a reduced risk for CRC, we examined the relationship between number of rounds of negative FIT and risk for advanced neoplasia in individuals undergoing surveillance colonoscopy.

Methods: We conducted a retrospective cohort study on 4021 surveillance intervals in 3369 individuals (50-74 years), who had completed a 2-sample FIT between colonoscopies, from 1 to 4 rounds at 1-2 yearly intervals, each with a negative result (<20 μg hemoglobin/g feces).

Accuracy of blood-based biomarkers for screening precancerous colorectal lesions: a protocol for systematic review and meta-analysis.

Introduction: Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer mortality worldwide. Most CRCs develop through either the adenoma-to-carcinoma or the serrated pathways, and, therefore, detection and removal of these precursor lesions can prevent the development of cancer. Current screening programmes can aid in the detection of CRC and adenomas; however, participation rates are suboptimal.

Faecal immunochemical test mitigates risk of delayed colonoscopy in people with elevated risk of colorectal neoplasia.

Background And Aim: Surveillance colonoscopies may be delayed because of pressure on resources, such as the COVID-19 pandemic. This study aimed to determine whether delayed surveillance colonoscopy increases the risk for advanced neoplasia and whether interval screening with faecal immunochemical tests (FITs) and other known risk factors can mitigate this risk.

Methods: A retrospective cohort study of individuals undergoing surveillance colonoscopy for personal or family history of colorectal neoplasia was being provided with FIT between colonoscopies.

Detection of hypermethylated BCAT1 and IKZF1 DNA in blood and tissues of colorectal, breast and prostate cancer patients.

Background: Detection of circulating cell-free DNA (ccfDNA) methylated in BCAT1 and IKZF1 is sensitive for detection of colorectal cancer (CRC), but it is not known if these biomarkers are present in other common adenocarcinomas.

Objective: Compare methylation levels of BCAT1 and IKZF1 in tissue and plasma from breast, prostate, and colorectal cancer patients.

Methods: Blood was collected from 290 CRC, 32 breast and 101 prostate cancer patients, and 606 cancer-free controls.

High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids.

New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids.

Post-transcriptional Gene Regulation by MicroRNA-194 Promotes Neuroendocrine Transdifferentiation in Prostate Cancer.

Potent therapeutic inhibition of the androgen receptor (AR) in prostate adenocarcinoma can lead to the emergence of neuroendocrine prostate cancer (NEPC), a phenomenon associated with enhanced cell plasticity. Here, we show that microRNA-194 (miR-194) is a regulator of epithelial-neuroendocrine transdifferentiation. In clinical prostate cancer samples, miR-194 expression and activity were elevated in NEPC and inversely correlated with AR signaling.

Prostate cancer susceptibility gene is a modulator of androgen receptor signaling and epithelial to mesenchymal transition.

In 2018, approximately 165,000 new prostate cancer (PC) cases will be diagnosed, and over 29,000 men will succumb to PC in the U.S. alone.

Modifier locus mapping of a transgenic F2 mouse population identifies CCDC115 as a novel aggressive prostate cancer modifier gene in humans.

Background: It is well known that development of prostate cancer (PC) can be attributed to somatic mutations of the genome, acquired within proto-oncogenes or tumor-suppressor genes. What is less well understood is how germline variation contributes to disease aggressiveness in PC patients. To map germline modifiers of aggressive neuroendocrine PC, we generated a genetically diverse F2 intercross population using the transgenic TRAMP mouse model and the wild-derived WSB/EiJ (WSB) strain.