Publications by authors named "Goel Ajay"

Importance: Serial circulating tumor DNA (ctDNA) has emerged as a routine surveillance strategy for patients with resected colorectal cancer, but how serial ctDNA monitoring is associated with potential curative outcomes has not been formally assessed.

Objective: To examine whether there is a benefit of adding serial ctDNA assays to standard-of-care imaging surveillance for potential curative outcomes in patients with resected colorectal cancer.

Design, Setting, And Participants: In this single-center (City of Hope Comprehensive Cancer Center, Duarte, California), retrospective, case cohort study, patients with stage II to IV colorectal cancer underwent curative resection and were monitored with serial ctDNA assay and National Cancer Center Network (NCCN)-guided imaging surveillance from September 20, 2019, to April 3, 2024.

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Article Synopsis
  • The resident microbiota within the tumor immune microenvironment influences tumor development in various cancers, particularly gastric cancer (GC), as shown through analysis of microbiome, transcriptome, and metabolome data.
  • In GC samples, patients with high levels of specific bacteria like Streptococcus or Pseudomonas had poorer survival outcomes, with Streptococcus anginosus identified as a key player in promoting tumor growth and hindering immune response.
  • Antibiotic treatment in mouse models significantly reduced tumor development associated with Streptococcus anginosus, and the bacterium's role in altering the immune microenvironment suggests it could be a useful target for potential diagnostic and therapeutic strategies in gastric cancer.
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Background: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).

Objective: To develop and test a blood-based assay for EAC and BE.

Design: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia () was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE.

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Background: Biomarkers have revolutionized the management of colorectal cancer (CRC), facilitating early detection, prevention, personalized treatment, and minimal residual disease (MRD) monitoring. This review explores current CRC screening strategies and emerging biomarker applications.

Main Body: We summarize the landscape of non-invasive CRC screening and MRD detection strategies, discuss the limitations of the current approaches, and highlight the promising potential of novel biomarker solutions.

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Background: Aronia berry extracts (ABE) have recently been reported to possess significant anti-cancer effects in various malignancies, including colorectal cancer (CRC), due to their high polyphenolic content. However, the molecular mechanism(s) underlying the anti-cancer effects of ABE in CRC remain unclear, which is important to consider when considering their use as complementary medicine approaches in cancer.

Methods: We performed genome-wide transcriptomic profiling and pathway enrichment analysis to identify specific growth signaling pathways associated with ABE treatment in CRC cells.

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Colorectal cancer (CRC) is one of the most prevalent and highly recurrent malignancies worldwide and currently ranks as the second leading cause of cancer-related deaths. The high degree of morbidity and mortality associated with CRC is primarily attributed to the limited effectiveness of current therapeutic approaches and the emergence of chemoresistance to standard treatment modalities. Recent research indicates that several natural products, including Aronia berry extracts (ABE) and oligomeric proanthocyanidins (OPCs), might offer a safe, cost-effective, and multitargeted adjunctive role to cancer treatment.

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, primarily due to the intrinsic development of chemoresistance. The most apparent histopathological feature associated with chemoresistance is the alterations in extracellular matrix (ECM) proteins. Natural dietary botanicals such as berberine (BBR) and emodin (EMO) have been shown to possess chemo-preventive potential by regulating ECM in various cancers.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor survival rates, primarily due to the limited effectiveness of gemcitabine (Gem)-based chemotherapy, as well as the acquisition of chemotherapeutic resistance. Aronia berry extracts (ABEs), abundant in phenolic constituents, have been recently recognized for their anticancer properties as well as their encouraging potential to help overcome chemoresistance in various cancers. In the present study, we explored ABE's potential to overcome Gem resistance in PDAC and identify specific growth regulatory pathways responsible for its anticancer activity.

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Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods.

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Gastrointestinal (GI) cancers, including colorectal, gastric, esophageal, pancreatic, and liver, are associated with high mortality and morbidity rates worldwide. One of the underlying reasons for the poor survival outcomes in patients with these malignancies is late disease detection, typically when the tumor has already advanced and potentially spread to distant organs. Increasing evidence indicates that earlier detection of these cancers is associated with improved survival outcomes and, in some cases, allows curative treatments.

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Introduction: Individuals with familial adenomatous polyposis (FAP) have an almost 20% lifetime risk of duodenal adenocarcinoma, currently the leading cause of death in FAP. The Spigelman staging system provides guidance on the surveillance intervals and timing of prophylactic surgery. Still, its accuracy in predicting duodenal and papillary cancer development has not been systematically evaluated.

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Background: Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown.

Methods: Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.

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This study investigates methylation patterns in circulating cell-free DNA (ccfDNA) for their potential role in colorectal cancer (CRC) detection and the monitoring of treatment response. Through methylation microarrays and quantitative PCR assays, we analyzed 440 samples from The Cancer Genome Atlas (TCGA) and an additional 949 CRC samples. We detected partial or extensive methylation in over 85% of cases within three biomarkers: EFEMP1, SFRP2, and UNC5C.

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Bisulfite sequencing (BS-seq) to detect 5-methylcytosine (5mC) is limited by lengthy reaction times, severe DNA damage, overestimation of 5mC level and incomplete C-to-U conversion of certain DNA sequences. We present ultrafast BS-seq (UBS-seq), which uses highly concentrated bisulfite reagents and high reaction temperatures to accelerate the bisulfite reaction by ~13-fold, resulting in reduced DNA damage and lower background noise. UBS-seq allows library construction from small amounts of purified genomic DNA, such as from cell-free DNA or directly from 1 to 100 mouse embryonic stem cells, with less overestimation of 5mC level and higher genome coverage than conventional BS-seq.

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We are delighted to share with you our thirteenth Journal Club and highlight some of the most interesting papers published recently [...

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Article Synopsis
  • Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, often diagnosed too late due to vague symptoms and lack of early detection methods; the study aimed to create a noninvasive circular RNA (circRNA)-based biomarker panel for earlier diagnosis.
  • Researchers identified 10 circRNA candidates linked to PDAC through a genome-wide discovery, narrowing it down to 5 for a liquid biopsy assay, which effectively distinguished between early and late disease stages with strong diagnostic accuracy.
  • Combining the circRNA panel with the cancer antigen 19-9 levels significantly improved early detection rates, achieving a high area under the curve (0.94) in validation tests,
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Background: Some genetic polymorphisms (SNPs) have been proposed as predictors for different colorectal cancer (CRC) outcomes. This work aims to assess their performance in our cohort and find new SNPs associated with them.

Methods: A total of 833 CRC cases were analyzed for seven outcomes, including the use of chemotherapy, and stratified by tumor location and stage.

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  • The MAPK/MEK/ERK pathway is commonly activated in colorectal cancer (CRC), but MEK/ERK inhibitors have limited clinical effectiveness.
  • Research indicates that ELK4 plays a crucial role in promoting CRC tumor growth by forming a complex with transcription factors SP1 and SP3, rather than the previously thought SRF.
  • Targeting the ELK4-SP1/SP3 complex using MEK/ERK inhibitors combined with the SP1 inhibitor mithramycin A shows promising anti-tumor effects, and ELK4 serves as a potential prognostic marker for CRC.
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Gasdermin (GSDM) family, the key executioners of pyroptosis, play crucial roles in anti-pathogen and anti-tumor immunities, although little is known about the expression of GSDM in lung diseases at single-cell resolution, especially in lung epithelial cells. We comprehensively investigated the transcriptomic profiles of GSDM members in various lung tissues from healthy subjects or patients with different lung diseases at single cell level, e.g.

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Developing safe and effective therapeutic modalities remains a critical challenge for improving the prognosis of patients with colorectal cancer (CRC). In this regard, targeting epigenetic regulation in cancers has recently emerged as a promising therapeutic approach. Since several natural compounds have recently been shown to be important epigenetic modulators, we hypothesized that Ginseng might exert its anticancer activity by regulating DNA methylation alterations in CRC.

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Background: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico.

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We are delighted to share with you our twelfth Journal Club and highlight some of the most interesting papers published recently [...

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