bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiorespiratory fitness, body mass index and mortality: a systematic review and meta-analysis
Authors: Weeldreyer Nathan R , De Guzman Jeison C , Paterson Craig , Allen Jason D , Gaesser Glenn A , Angadi Siddhartha S
Published: November 2024

Objective

The purpose of this review was to assess the joint relationship of cardiorespiratory fitness (CRF) and Body Mass Index (BMI) on both cardiovascular disease (CVD) and all-cause mortality risk.

Design

A systematic review and meta-analysis was conducted. Pooled HR and 95% CI were calculated using a three-level restricted maximum likelihood estimation random-effects model with robust variance estimation. The reference group was normal weight-fit and was compared with normal weight-unfit, overweight-unfit and fit, and obese-unfit and fit.

Data sources

Electronic databases (PubMed/MEDLINE, Web of Science and SportDiscus) were searched following registration on PROSPERO.

Eligibility criteria

Articles meeting the following criteria were included: (1) published between January 1980 and February 2023, (2) prospective cohort study, (3) CRF assessed using a maximal or VO2peak exercise test, (4) BMI reported and directly measured, (5) joint impact of CRF and BMI on all-cause mortality or CVD mortality were analysed, and (6) the reference group was normal weight, fit individuals.

Results

20 articles were included in the analysis resulting in a total of 398 716 observations. Compared with the reference group, overweight-fit (CVD HR (95% CI): 1.50 (0.82–2.76), all-cause HR: 0.96 (0.61–1.50)) and obese-fit (CVD: 1.62 (0.87–3.01), all-cause: 1.11 (0.88–1.40)) did not have a statistically different risk of mortality. Normal weight-unfit (CVD: 2.04 (1.32–3.14), all-cause: 1.92 (1.43–2.57)), overweight-unfit (CVD: 2.58 (1.48–4.52), all-cause: 1.82 (1.47–2.24)) and obese-unfit (CVD: 3.35 (1.17–9.61), all-cause: 2.04 (1.54–2.71)) demonstrated 2–3-fold greater mortality risks.

Conclusions

CRF is a strong predictor of CVD and all-cause mortality and attenuates risks associated with overweight and obesity. These data have implications for public health and risk mitigation strategies.
Caregiver burden and quality of life in palliative care: cross-sectional study
Authors: Shefeek Suhail K , Joy Teena Mary , Olickal Jeby Jose , Nezrin Malathu Abdulnazer , George Annie , Thankappan Kavumpurathu Raman
Published: November 2024

Background

Literature on caregiver burden is limited in India and Kerala. We examined the prevalence and factors associated with caregiver burden and its impact on their quality of life.

Methods

We conducted a cross-sectional study among 115 informal caregivers (mean age 70 years, 80% female) of palliative care patients in Kerala. Caregivers were interviewed using the Zarit Burden Interview-22 and the WHOQOL-BREF questionnaires. Factors associated with caregiver burden were analysed using binary logistic regression.

Results

The prevalence of moderate to severe burden was 32.1% (95% CI 23.7% to 41.5%), with 6.2% reporting severe burden (95% CI 2.4% to 12.1%). Caregivers of patients aged ≥73 years (adjusted OR (aOR)=7.19, 95% CI 1.87 to 27.71, p=0.004), children acting as caregivers (aOR=11.09, 95% CI 1.21 to 101.03, p=0.033) and those caring for patients with prolonged disease duration (aOR=3.62, 95% CI 1.04 to 12.67, p=0.044) reported significantly higher burden compared with their counterparts. Moderate to severe burden was associated with lower physical (p<0.001), psychological (p<0.001) and social relations (p=0.002) quality of life scores.

Conclusion

Targeted interventions for caregivers of older patients, children acting as caregivers and those taking care of patients with prolonged disease duration are likely to reduce burden and improve their quality of life.
Gallein, G protein βγ subunits inhibitor, suppresses the TGF-α-induced migration of hepatocellular carcinoma cells via inhibition of the c-Jun N-terminal kinase
Authors: Matsushima-Nishiwaki Rie , Honda Yoh , Tokuda Haruhiko , Kozawa Osamu
Published: November 2024

G protein-coupled receptor (GPCR) signaling regulates a wide range of pathophysiological cell functions via G protein α and βγ subunits. Small molecules targeting the subunits of Gα and Gβγ have been developed as cancer therapeutics. We have previously reported that transforming growth factor-α (TGF-α) induces the migration of human hepatocellular carcinoma (HCC) HuH7 cells through the activation of AKT, p38 mitogen-activated protein kinase (MAPK), Rho-kinase and c-Jun N-terminal kinase (JNK). This study aims to determine whether Gβγ subunits regulate the TGF-α-induced migration of HCC HuH7 cells using gallein, a Gβγ subunits inhibitor. The Janus family of tyrosine kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was also involved in the regulation of the migration. Gallein significantly reduced the TGF-α-induced cell migration. In contrast, fluorescein, a gallein-related compound that has no effect on Gβγ subunits, failed to affect the cell migration. Gallein suppressed the TGF-α-stimulated phosphorylation of JNK without affecting the phosphorylation of epidermal growth factor receptor, AKT, p38 MAPK, target protein of Rho-kinase and STAT3. Conversely, fluorescein did not attenuate the phosphorylation of JNK. These results strongly suggest that Gβγ subunits act as positive regulators in TGF-α-induced migration of HCC cells via the JNK signalling pathway.
AcsS inhibits the hemolytic activity and thermostable direct hemolysin (TDH) gene expression in Vibrio parahaemolyticus
Authors: Ni Bin , Tian Zhukang , Chang Jingyang , Zhou Yining , Li Xue , Zhang Miaomiao , Li Wanpeng , Zhang Nan , Luo Xi , Zhang Yiquan , Lu Renfei
Published: November 2024

Vibrio parahaemolyticus produces a key virulent factor known as thermostable direct hemolysin (TDH). TDH exhibits diverse biological activities, including hemolytic activity. The β-type hemolysis observed on Wagatsuma agar due to TDH is recognized as the Kanagawa phenomenon (KP). The tdh2 gene is primarily responsible for TDH production and the associated KP. AcsS was originally identified as an activator of swimming and swarming motility in V. parahaemolyticus. However, its potential roles in other cellular pathways remain unclear. In this study, we investigated the regulatory effects of AcsS on the hemolytic activity and tdh2 expression in V. parahaemolyticus using phenotypic tests for KP, quantitative real-time polymerase chain reaction, LacZ fusion, and electrophoretic mobility shift assays. The data showed that V. parahaemolyticus hemolytic activity and tdh2 transcription were under the negative control of AcsS. Additionally, in-vitro binding assays revealed that His-AcsS could not bind to the regulatory DNA region of tdh2. However, overexpression of AcsS in an Escherichia coli strain suppressed the expression of tdh2. Collectively, these results suggested that AcsS suppresses the hemolytic activity of V. parahaemolyticus through the downregulation of tdh2 transcription. The data enhanced our understanding of the regulatory networks governing tdh2 expression and the roles of AcsS in this bacterium.
SafeTI: A Hardware Traffic Injector for Complex MPSoC Platform Validation and Characterization
Authors: Fuentes Francisco , Alcaide Sergi , Casanova Raimon , Abella Jaume
Published: November 2024

Functional and timing validation of high performing safety-related platforms requires testing specific traffic patterns in the network-on-chip interconnects. Generally, testing needs to be performed by using software tests whose degree of control on the traffic generated is indirect, and limited to behavior that can be triggered by software, thus often unable to produce traffic generated by peripherals. Therefore, untested traffic scenarios can be abundant and, to a large extent, it is hard to know what traffic scenarios have been effectively tested.

This article presents the
safe traffic injector
, SafeTI, which allows injecting programmable traffic in AMBA AHB interconnects with high flexibility and degree of control, thus easing achieving high coverage in terms of traffic scenarios tested, and mitigating the uncertainty due to the difficulties to relate software tests with actual traffic scenarios tested. We also integrate successfully the SafeTI in the safety open platform SELENE proving the effectiveness of the proposed traffic injector for characterizing the platform memory access capabilities under different patterns of contention on the multi-level cache system.
Tanshinone IIA Protects Ischemia/Reperfusion‐Induced Cardiomyocyte Injury by Inhibiting the HAS2/FGF9 Axis
Authors: Wang Yanzhe , Sun Weixin , Shen Le , Yu Peng , Shen Qiusheng , Zhou Yaozhong , Yao Lu , Chen Xiaohu
Published: November 2024

Purpose. This study aimed to investigate the impacts of tanshinone IIA (Tan IIA) on ischemia/reperfusion (I/R)‐induced cardiomyocyte injury in coronary heart disease (CHD), and to determine whether Tan IIA regulates myocardial cell injury induced by I/R through the Hyaluronan Synthase 2/fibroblast growth factor 9 (HAS2/FGF9) axis. Methods. Weighted gene co‐expression network analysis (WGCNA) of the GSE23561 microarray dataset determined gene modules linked to CHD. The key genes were further explored through differential expression and protein‐protein interaction (PPI) network analyses. Human AC16 cardiomyocytes were treated with Tan IIA, HAS2 knockdown, and FGF9 overexpression and they were exposed to normoxic, hypoxic, and I/R environments. Cell viability, apoptosis, gene/protein expression, and markers of oxidative stress were evaluated in vitro. Results. The turquoise module was significantly correlated with CHD and HAS2 was identified as a hub gene. Under hypoxic conditions, Tan IIA exhibited a dose‐dependent cardioprotective effect. Tan IIA ameliorated I/R‐induced cellular injury, as evidenced by increased cell viability, decreased apoptosis, and regulation of key proteins (PCNA, Bax). After I/R conditions, knockdown of HAS2 increased cell viability and reduced apoptosis, whereas overexpression of FGF9 reversed these effects. Notably, HAS2 knockdown also ameliorated I/R‐induced increases in inflammatory cytokines and oxidative stress, and synergistic protection was provided by combined treatment with FGF9 and Tan IIA. Conclusion. Taken together, our findings confirm that Tan IIA protects cardiomyocytes from I/R‐induced injury by controlling the HAS2/FGF9 axis. These findings reveal the potential therapeutic significance of Tan IIA in alleviating CHD‐related myocardial dysfunction.
Effect of Protease Combined With Heat Treatment on the Stability of Proteins in Liqueur Wine
Authors: Zhao Yuanyuan , Zhang Zhen , Li Wen , Li Wei , Shang Qi , Du Jianming , Wang Li
Published: November 2024

Background: Protein instability has been reported to be an important cause of haze in white wines; to investigate the feasibility of protease as a substitute for bentonite in the protein stability of white grape liqueurs, the effect of protease combined with heat treatment on the composition and protein stability of liqueur wines was investigated by chemical analysis, sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE), and amino acid analysis.

Results: The results showed that the contents of total acid, volatile acid, pH, and glycerol were not significantly different from the blank control; the effect on total protein content and thermal stability were similar to the bentonite treatment; the L∗, b∗, and values of liqueur wines increased by 5.59%, 4.33%, and 4.33% after protease combined with heat treatment (p < 0.05); SDS‐PAGE results confirmed that protease combined with heat treatment had good hydrolysis for thaumatin‐like proteins (TLPs) and chitinases (CHIs) in liqueur wines. Amino acid analysis revealed that the levels of threonine, serine, tyrosine, arginine, and proline had increased, respectively, and isoleucine (1.26 mg/L) and leucine (1.16 mg/L) were newly detected after protease combined with heat treatment. Particle size analysis showed that the protease combined with heat treatment had less effect on the particle size distribution of the wines.

Conclusion: Protease combined with heat treatment had a certain protein stabilizing effect and had no significant negative impact on other nutrients of liqueur wines. Thus, it can be used as an alternative to bentonite for the protein stabilization of liqueur wines.
Abstract A015: Validation of a cancer early-detection assay on liquid biopsies using DNA methylation
Authors: Gracheva Ekaterina
Published: November 2024

There is growing awareness of the benefits of early cancer detection. Early intervention can improve patient outcomes, leading to a reduction in the health care burden associated with cancer, and can also provide critical information for personalized treatments. Liquid biopsies enable quick, easy, non-invasive, and real-time testing that is suitable for screening and increases accessibility, particularly in developing countries. The use of epigenomic techniques, such as DNA methylation profiling, enhances the depth and breadth of screening beyond what standard genetic analysis can offer. Universal Diagnostics (UDx), a respected pioneer in the field of early cancer detection, has partnered with Hologic Diagenode, which brings 20 years of experience in epigenomics, to develop a customized early detection workflow for colorectal cancer (CRC). This analysis relies on DNA methylation biomarkers identified within cell-free DNA (cfDNA) from plasma. The UDx assay provides not only easy screening but also a more comprehensive analysis than that possible with conventional markers. Genome-wide methylation profiles from healthy individuals and cancer patients were used to identify biomarkers. These biomarker candidates were then validated for performance; the results of which are presented in this poster.

Citation Format: Ekaterina Gracheva. Validation of a cancer early-detection assay on liquid biopsies using DNA methylation [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A015.
Abstract A021: Analytical platform to validate microRNA cancer biomarkers
Authors: Kanavarioti Anastassia , Rehman M. Hassaan , Qureshi Salma , Rafiq Aleena , Sultan Madiha
Published: November 2024

We developed and tested a novel assay to quantify and validate microRNA (miRNA) cancer biomarkers in liquid biopsies. The assay is amplification-free, exploits a commercially available nanopore-array device for detection (MinION from Oxford Nanopore Technologies), uses total RNA isolated from biospecimen as the miRNA source, and proprietary osmylated oligonucleotides, complementary to the target miRNA, as probes. The assay exploits a bracketing experimental protocol to quantify miRNA, and yields miRNA copy numbers (copies) per 1microLiter of isolated total RNA, with an unprecedented accuracy of approximately +/- 20% across all concentrations. For development purposes and as a control/reference the combined serum of healthy men (# H6914 from Sigma-Aldrich) was used. During a period of 4 years different lots of H6914 yielded, within experimental error, comparable miRNA copies for let-7b, miR-16, miR-21, miR-15b, miR-375 and miR-141. Serum samples from healthy individuals and cancer patients were also tested. Once data were normalized to the same total RNA content, miRNA copies appeared to belong to one of two groups. The first group included miR-21, miR-375 and miR-141 copies in H6914 and in healthy samples. The second group included miR-21, miR-375 and miR-141 copies in cancer samples exhibiting an approximate 1.8-fold overexpression compared to the first group. miR-15b copies in H6914, healthy and cancer samples were all in the first group. The two groups exhibited zero data overlap which is unprecedented in the miRNA/cancer literature. Zero data overlap was the result of (i) the assay’s bracketing approach with a protocol-defined accuracy of approximately +/-20%, and (ii) the normalization of miRNA copies to the same total RNA content. Notably, these two groups included both serum and urine samples from cancer patients and healthy individuals. All subjects were deselected regarding age, sex, and ethnicity, while patients were selected for breast, prostate or pancreatic cancer, Stage I or II, pretreatment. To the best of our knowledge, this is the first-time agreement between serum and urine miRNA copies is reported and leads to the suggestion that a urine sample may replace a blood draw for the tested miRNAs. Not only clear discrimination between healthy and cancer samples was possible, but this analytical platform may be used to validate tentative cancer/disease biomarkers when miRNA overexpression between cancer/disease and healthy is equal or higher than 1.8-fold. Non-Coding RNA 2024, 10(4), 42; https://doi.org/10.3390/ncrna10040042

Citation Format: Anastassia Kanavarioti, M. Hassaan Rehman, Salma Qureshi, Aleena Rafiq, Madiha Sultan. Analytical platform to validate microRNA cancer biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A021.
Abstract A033: Leveraging mass cytometry for phenotyping CTCs in SCLC liquid biopsies: Tracking therapy resistance at a personalized level
Authors: Karacosta Loukia G , Bhattacharyya Sayantan , Stewart Allison , Victorian Ashley , Lujan Ester F , Ehsan Shafqat , Kim Subin , Duarte Alberto , Wang Runsheng , Anchang Benedict , Wang Jing , Byers Lauren
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR005) of the Conference Program/Proceedings.

Citation Format: Loukia G Karacosta, Sayantan Bhattacharyya, Allison Stewart, Ashley Victorian, Ester F Lujan, Shafqat Ehsan, Subin Kim, Alberto Duarte, Runsheng Wang, Benedict Anchang, Jing Wang, Lauren Byers. Leveraging mass cytometry for phenotyping CTCs in SCLC liquid biopsies: Tracking therapy resistance at a personalized level [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A033.
Abstract A047: Detecting Hypoxic Circulating Tumor Cells (H-CTC) with a novel technique
Authors: Zayas Beatriz , Rios Karoline , Cox Osvaldo
Published: November 2024

There is a continues need to develop technologies to detect and characterize circulating tumor cells that can become aggressive, metastatic, and hard to treat. Among these aggressive CTC are cells known as Hypoxic cell populations that learn to adapt and survive to low oxygen levels. Our project aims to test the applicability of a novel technique to detect Hypoxic Circulating Tumor Cells (H-CTC) that can move from tumors to circulating blood invading other tissues and becoming resistant to chemotherapy and radiation. The proposed assay incorporates a set of patented organic compounds as markers of hypoxic circulating tumor cells (H-CTC) with potential clinical applications. To date, our research has generated preliminary in-vitro studies with a novel NBQ-TOM demonstrating its capacity as markers of hypoxic human cancer cells in vitro. Comparison with the control Pimonidazole demonstrated the advantages of novel NBQ- TOM compounds as hypoxic marker. To determine the capacity of NBQ-TOM as hypoxic fluorescent marker, samples of 15 ml human whole blood were spiked with hypoxic or normoxic colon cancer cells (COLO 205). Spiked hypoxic or normoxic cells are then enriched, recovered, and treated with NBQ-TOM (25uM) for 24 hours. After treatment generated fluorescence is measured with an OPTIMA BMG Fluorimeter to demonstrate the significant formation of a fluorescent metabolite on hypoxic tumor cells in contrast to cells treated under normoxic environment. Also, fluorescence microscopy analysis confirmed the stronger fluorescence generation at hypoxic conditions. These preliminary results strongly support the applicability of these molecules for an in-vitro detection assay of hypoxic CTC in circulating blood that can become metastatic. Additional sensitivity and specificity analysis needs to be implemented.

Citation Format: Beatriz Zayas, Karoline Rios, Osvaldo Cox. Detecting Hypoxic Circulating Tumor Cells (H-CTC) with a novel technique [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A047.
Abstract A048: Screening early detection of HPV-associated oropharynx cancers with multi- feature HPV whole genome sequencing liquid biopsy
Authors: Kuhs Krystle , Robbins Hilary , Das Dipon , Bryan Michael , Aye Ling , Al-Inaya Yana , Hirayama Shun , Adalsteinsson Viktor , Lawrence Michael , Waterboer Tim , Faden Daniel L
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR007) of the Conference Program/Proceedings.

Citation Format: Krystle Kuhs, Hilary Robbins, Dipon Das, Michael Bryan, Ling Aye, Yana Al-Inaya, Shun Hirayama, Viktor Adalsteinsson, Michael Lawrence, Tim Waterboer, Daniel L Faden. Screening early detection of HPV-associated oropharynx cancers with multi- feature HPV whole genome sequencing liquid biopsy [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A048.
Abstract A058: Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma
Authors: Lee Hyung Keun , Kim So Young , Chung Soo-Hyun , Jang Sung Ill , Choi Bongkun , Kim Ji-Eun , Yoon Dohee , Yeo Areum , Kang Hyun Goo , Lee Jusung , Choi Yoon Ha , Park Joon Seong , Sung Yoolim , Kim Jong Kyoung , Chang Eun-Ju , Lee Dong Ki
Published: November 2024

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis, largely due to late diagnosis and limited treatment options. The immunosuppressive tumor microenvironment (TME) further exacerbates the situation, hindering the effectiveness of traditional therapies. This study investigates the potential of IL-10R2/IL-22R1 expressing immune cells as novel biomarkers for early PDAC detection and recurrence monitoring, offering a potential avenue for improved patient outcomes. The research revealed a significant increase in the number of IL-10R2/IL-22R1 expressing immune cells in the peripheral blood of PDAC patients compared to healthy controls. These cells were found to infiltrate PDAC tissue and exhibit immunosuppressive functions, contributing to the TME's suppression of the immune response. Further investigation using a mouse model of PDAC demonstrated that early tumor progression was accompanied by a rise in IL-10R2/IL-22R1 expressing immune cells in the blood, highlighting their potential role in tumor development. In post-pancreatectomy patients, the study observed that elevated levels of IL-10R2+ immune cells were associated with earlier recurrence compared to the currently employed biomarker, CA19-9. This finding suggests that IL-10R2/IL-22R1 expressing immune cells could serve as valuable tools for predicting PDAC recurrence and potentially improving treatment outcomes. This research provides compelling evidence for the potential of IL-10R2/IL-22R1 expressing immune cells as promising biomarkers for early PDAC diagnosis and recurrence monitoring. However, further research is crucial to comprehensively understand their generation, function, and clinical utility. Larger-scale studies are needed to validate these findings and translate them into practical clinical applications for improved patient care.

Citation Format: Hyung Keun Lee, So Young Kim, Soo-Hyun Chung, Sung Ill Jang, Bongkun Choi, Ji-Eun Kim, Dohee Yoon, Areum Yeo, Hyun Goo Kang, Jusung Lee, Yoon Ha Choi, Joon Seong Park, Yoolim Sung, Jong Kyoung Kim, Eun-Ju Chang, Dong Ki Lee. Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A058.
Abstract A065: Estimation of HPV16-induced cervical cancer cells in routine Thin-prep cytology samples of cancer patients
Authors: Raman Srishty , Tanwar Pranay , Bhatla Neerja , Chandra Yadav Subhash
Published: November 2024

Persistent infection with human papillomavirus has been implicated in the etiology of cervical cancer and sustained expression of its E7 oncoprotein has been rendered suggestive of malignant transformation. However, there are limited E7 protein-based detection assays. This might be due to paucity of data on steady-state expression level of E7 protein and the number of HPV-induced cervical cancer cells in routine Thin-prep cytology samples. So, the objective of the present study was to identify and estimate HPV16-induced cervical cancer cells in cytology samples of cancer patients, with the goal to generate a quantitative immunological method in the cytological diagnosis of cervical lesions. We collected 25 Thin-prep cytology samples of cervical cancer patients (PAP test confirmed) from Obstetrics and Gynecology department, AIIMS, New Delhi. Samples were conditioned to enrich cellular components and were then quantified using hemocytometer for total cell count, PAP staining for cancerous cell count and immunofluorescence using HPV16 E7 antibody for HPV16-induced cancerous cell count. The method devised efficiently found an average number of 7 × 103 cells/ ml to be E7 positive, out of total 27 x 104 cells/ ml. Although PAP test detected 71 x 103 cells/ ml to be abnormal or cancerous, only 10% of them were found to be HPV16 transformed, suggesting HPV E7 as the primary marker for detecting transformed cells and thereby, identifying patients at-risk and prompting a better prognosis. This simple and efficient method deduced allows optimizing the number of HPV16-induced cervical cancer cells from cytology samples which directly correlates to the amount of HPV-16 major oncoprotein- E7 expression, and the disease severity.

Citation Format: Srishty Raman, Pranay Tanwar, Neerja Bhatla, Subhash Chandra Yadav. Estimation of HPV16-induced cervical cancer cells in routine Thin-prep cytology samples of cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A065.
Abstract A068: Evaluate the performance of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma
Authors: Siguencia Fernando , Matsuda Michitaka , Pandyarajan Vijay , Tanaka Sunao , Smith Steven M , Seki Ekihiro , Rosser Charles J , Furuya Hideki
Published: November 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), fibrosis, and cirrhosis are risk factors for hepatocellular carcinoma (HCC). Blood-based assays to date have limited accuracy for detecting MASLD and cirrhosis, and thus have not been widely adopted in the clinical setting. The identification and validation of a multiplex molecular signature associated with liver disease may address this unmet need. This prospective single-center US study evaluated the performance of the non-invasive Liver FibraChek Dx serum assay for detecting MASLD. The study algorithm analyzes weighted values of five serum biomarkers (AST, ALT, taurocholic acid, L-tyrosine, and platelet count) plus age to derive a risk score. Samples comprised 14 MASLD cases, 19 HCC cases, and 12 healthy controls. Liver status was confirmed by tissue biopsy. Wilcoxon rank sum tests determined the association between the risk score and confirmed liver histology. Diagnostic performance was assessed using ROC curves. The probability of identifying MASLD and/or HCC by Liver FibraChek Dx, in conjunction with other patient parameters, was demonstrated by an AUROC of 0.890 (95% CI: 0.776-1.000), with 93.9% sensitivity, 75.0% specificity, 91.1% positive predictive value, 81.8% negative predictive value, and 88.9% accuracy. Risk scores associated with the biomarker panel enabled accurate discrimination of liver disease from healthy controls. The non-invasive multiplex Liver FibraChek Dx test can effectively and accurately detect and classify hepatic fibrosis risk in peripheral blood samples and may have utility in diagnosing and monitoring liver pathogenesis.

Citation Format: Fernando Siguencia, Michitaka Matsuda, Vijay Pandyarajan, Sunao Tanaka, Steven M Smith, Ekihiro Seki, Charles J Rosser, Hideki Furuya. Evaluate the performance of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A068.
Abstract A070: Diagnostic accuracy of Oncuria®-Detect in the detection of upper tract urothelial tumors
Authors: Fujita Kazutoshi , Miyake Makito , Shimizu Takuto , Linehan Jennifer , Gottlieb Joshua , Pagano Ian , Tikhonenkov Sergei , Murakami Kaoru , Lee Riko , Sakatani Toru , Tanaka Sunao , Rosser Charles J , Furuya Hideki
Published: November 2024

Due to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with upper tract urothelial carcinoma. The robust urine-based multiplex assay for diagnosis of upper tract urothelial carcinoma has the potential to address this deficiency and to assist with accurate, non-invasive diagnosis.We previously developedOncuria®-Detect, a multiplex immunoassay capable of detecting bladder cancer using a single voided urine. In this study, its application to upper tract urothelial cancer was evaluated in a multi-institutional cohort of 61 prospectively collected subjects presenting for evaluation of upper tract mass along with 61 prospective collected matched controls. The ability of the test to identify patients harboring upper tract urothelial carcinoma was assessed. Cancer status was confirmed by endoscopy and tissue biopsy or definitive surgery. Oncuria®-Detect provided an AUC of 0.868 (95% CI: 0.802- 0.933) with an overall sensitivity of 96.7%, specificity of 59.0%, NPV 94.7% and PPV 70.2%. Sensitivity values of Oncuria®-Detect for low-grade, high-grade, non-invasive and invasive upper tract urothelial cancer were 100%, 89.7%, 93.3% and 96.2%, respectively. Voided urine cytology showed an overall sensitivity of 54.5%, specificity of 100%, NPV 31.0% and PPV 100%. As a non-invasive test, Oncuria®-Detect outperformed both voided urinary cytology and selective cytology (sensitivities 96.7% vs. 54.5% vs. 81.8%, respectively). Oncuria®-Detect enabled the accurate discrimination of upper tract urothelial carcinoma and controls non-tumor bearing individuals. The Oncuria®-Detect test can achieve the efficient and accurate detection of upper tract urothelial carcinoma in a non-invasive patient setting.

Citation Format: Kazutoshi Fujita, Makito Miyake, Takuto Shimizu, Jennifer Linehan, Joshua Gottlieb, Ian Pagano, Sergei Tikhonenkov, Kaoru Murakami, Riko Lee, Toru Sakatani, Sunao Tanaka, Charles J Rosser, Hideki Furuya. Diagnostic accuracy of Oncuria®-Detect in the detection of upper tract urothelial tumors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A070.
Abstract A071: Performance of the Oncuria®-Detect test for the evaluation of patients presenting with hematuria: Results from a real world clinical setting
Authors: Pagano Ian , Tikhonenkov Sergei , Le Calvez-Kelm Florence , Goodison Steve , Zhang Zhen , Sakatani Toru , Murakami Kaoru , Kim Howard , Lee Riko , Tanaka Sunao , Rosser Charles J , Furuya Hideki
Published: November 2024

Bladder cancer is the 9th most diagnosed cancer worldwide with higher incidences reported in Europe and the United States. Here, we evaluate the performance of a novel, commercially available multiplex immunoassay querying for 10 proteins associated with a bladder cancer diagnostic signature (Oncuria®-Detect, Nonagen Bioscience Corp, Los Angeles, CA, US) for the detection of de novo bladder cancer, in a large prospectively collected real world cohort comprised of 995 patients, across seven centers, presenting with hematuria. The results were compared with the patients’ clinical data and final diagnosis as defined by the results of cystoscopy, with a prevalence of bladder cancer of 15.9%. In the test cohort, Oncuria®-Detect detected bladder tumors in 94/109 cancers, giving overall sensitivity of 86.2% and an overall negative predictive value (NPV) of 96.7% with corresponding specificity of 80.2% with favorable performance characteristics in high grade bladder cancer and muscle-invasive bladder cancer. Patient summary: We conducted a large cross-sectional clinical study for detecting de novo bladder cancer with a novel, simple urine test (Oncuria®-Detect), which measures 10 bladder cancer associated proteins in a single voided urine sample. We analyzed urines from 995 patients and demonstrated that the new urine test can detect bladder cancer with a high degree of accuracy, specifically in patients with high grade or high stage disease. In conclusion, the novel Oncuria®-Detect urine test can be used to help detect new bladder cancers.

Citation Format: Ian Pagano, Sergei Tikhonenkov, Florence Le Calvez-Kelm, Steve Goodison, Zhen Zhang, Toru Sakatani, Kaoru Murakami, Howard Kim, Riko Lee, Sunao Tanaka, Charles J Rosser, Hideki Furuya. Performance of the Oncuria®-Detect test for the evaluation of patients presenting with hematuria: Results from a real world clinical setting [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A071.
Abstract A072: Oncuria®-Monitor, a non-invasive test for the detection of recurrent bladder cancer: Cross sectional performance evaluation from a multicenter study
Authors: Zhang Zhen , Le Calvez-Kelm Florence , Miyake Makito , Pagano Ian , Shimizu Takuto , Tikhonenkov Sergei , Tanaka Sunao , Rosser Charles J , Goodison Steve , Furuya Hideki
Published: November 2024

Up to 70% of patients with non-muscle invasive bladder cancer (NMIBC) experience disease recurrence, making it one of the most prevalent cancers in the US. The purpose of this study was to test the performance of Oncuria®-Monitor, a multiplex urinary biomarker assay for the monitoring of voided urine for recurrent bladder cancer. This cross-sectional, multicenter study included a total of 283 subjects with a history of bladder cancer. Voided urine specimens were collected prior to any procedures for multiplex analysis. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values (e.g., sensitivity and specificity) and compared with the patients’ clinical data and final diagnosis as defined by the results of cystoscopy. Oncuria®-Monitor achieved an overall sensitivity of 94.3%, specificity of 83.6% and negative predictive valuer (NPV) of 96.2% for the detection of recurrent bladder cancer. Patient summary: We conducted a large cross-sectional clinical study for detecting recurrent bladder cancer with a novel, simple urine test (Oncuria®- Monitor), which measures 10 bladder cancer associated proteins in a single voided urine and can be used to detect recurrent bladder cancer. We analyzed urines from 283 patients and demonstrated that Oncuria®-Monitor can detect recurrent bladder cancer with a high degree of accuracy, specifically in patients with high grade or high stage disease. In conclusion, the novel Oncuria®-Monitor urine test can be used to surveil patients with a history of bladder cancer.

Citation Format: Zhen Zhang, Florence Le Calvez-Kelm, Makito Miyake, Ian Pagano, Takuto Shimizu, Sergei Tikhonenkov, Sunao Tanaka, Charles J Rosser, Steve Goodison, Hideki Furuya. Oncuria®-Monitor, a non-invasive test for the detection of recurrent bladder cancer: Cross sectional performance evaluation from a multicenter study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A072.
Abstract B013: An mDETECT assay for monitoring treatment response in metastatic breast cancer patients
Authors: Frosst Keira , Wilson Brooke , Cristall Katrina , Crawford-Brown Catherine , Mueller Christopher R
Published: November 2024

Metastatic breast cancer treatment response is currently assessed every 3-6 months and this long delay results in many patients undergoing ineffective and toxic treatments for long periods of time. We have developed the methylation DETEction of Circulating Tumour DNA (mDETECT) assay, a targeted DNA methylation-based Next Generation Sequencing liquid biopsy that detects cancer-specific patterns in all subtypes of breast cancer. The assay targets 60 differentially hypermethylated regions in breast cancer across the genome and assesses over 400 individual CpGs with an average of 8 CpGs per target amplicon. The assay has been assessed on DNA from 73 breast cancer tumour samples which on average had 40 regions hypermethylated per patient with similar rates across all subtypes. We will present results from plasma samples from locally advanced and metastatic breast cancer patients along with plasma from age-matched, healthy female controls. A prospective, multi-centre observational cohort study to monitor metastatic breast cancer patients using the mDETECT liquid biopsy as they undergo treatment is active and recruiting patients. Blood is drawn with every standard-of-care blood draw for up to 3 years. Plasma has been assessed using the mDETECT assay to determine the methylation status of the DNA at each time point. 35 patients have been enrolled to date with ongoing recruitment up to 150 patients. Patients are being monitored with the mDETECT assay for earlier detection of disease progression on a treatment. They will also be monitored through treatment changes to assess a patient’s initial response to a given treatment. Changes in mDETECT levels will be correlated with clinical response to determine if the mDETECT breast cancer assay can detect a response to treatment at an earlier timepoint. This assay could allow for improved monitoring of treatment response allowing clinicians to make informed decisions, improving outcomes and prolonging patient’s lives.

Citation Format: Keira Frosst, Brooke Wilson, Katrina Cristall, Catherine Crawford-Brown, Christopher R Mueller. An mDETECT assay for monitoring treatment response in metastatic breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B013.
Abstract B034: Prevalence and implication of aflatoxin B1 expression in colon cancers diagnosed in Southern Nigeria
Authors: Delu-mozie Chiagoziem Moral , Okoye Jude Ogechukwu
Published: November 2024

Introduction: Mounting evidence shows that there is a high prevalence of late-stage, aggressive, and metastatic adenocarcinoma of the colon (AdCC) in Africa, with high mortality and low survival rate among patients. Literature finger food contaminants such as mycotoxin, especially Aflatoxin, as an attributable factor to the high incidence of abdominal cancers. However, there is a paucity of studies to confirm the hypothesis. Hence, this study determined the prevalence of Aflatoxin B1 in AdCC in Southern Nigeria.

Citation Format: Chiagoziem Moral Delu-mozie, Jude Ogechukwu Okoye. Prevalence and implication of aflatoxin B1 expression in colon cancers diagnosed in Southern Nigeria [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B034.
Abstract B037: Disks large-associated protein 5 (DLGAP5) is a putative prognostic biomarker for intraductal papillary mucinous neoplasm (IPMN) of pancreas
Authors: Janostiak Radoslav , Mačinga Peter , Csergeová Lucia , Fabián Ondřej , Sticová Eva , Zahradník Jiří , Květoň Martin , Hucl Tomáš
Published: November 2024

Pancreatic cancer is one of the deadliest malignant diseases, accounting for nearly 500,000 deaths worldwide each year. One of the pancreatic cancer precursors are mucinous pancreatic cystic lesions (PCL). Although only a minority of these PCLs undergo malignant transformation, the clinical significance is considerable, particularly given the prevalence of up to 45% in individuals over the age of 65. The most prevalent type of neoplastic PCL is intraductal papillary mucinous neoplasm (IPMN) and the management of different IPMN grades varies, with high- grade dysplasia and invasive carcinoma being indicated for surgery. However, the current guidelines for patient stratification are limited and often lead to either overtreatment or undertreatment, both of which are associated with high mortality and morbidity. Therefore, there is a pressing need to identify biomarkers associated with progression of IPMN from low to high grade that can be used for more accurate lesion assessment. Here we identified a novel biomarker highly correlated with IPMN progression – DLGAP5. Both mRNA as well as protein expression of DLGAP5 is positively associated with increased grade of IPMNs as determined by analysis of patient derived tumor samples. Additionally, in vitro experiments confirmed that knock down of DLGAP5 in pancreatic cancer cells leads to reduction of cell proliferation, and conversely, overexpression of DLGAP5 in IPMN precursor cells resulted in increased proliferation. Since one of the functions of DLGAP5 is microtubule stabilization, we hypothesized that the secretome of IPMN precursor cells will be altered by the expression of DLGAP5. Indeed, our mass spectrometry-based analysis of secreted proteins identified several hits (e.g. DKK1) that were correlated with DLGAP5 expression and were previously confirmed to be present in IPMN cyst fluid in patients. Subsequently, we aim to validate the correlation of the putative biomarkers in IPMN cyst fluid and serum with IPMN grade and patients’ clinical outcome in a prospective manner. To sum up, we validated DLGAP5 as an IPMN-progression biomarker and identified several secreted proteins that could serve as DLGAP5-surrogate biomarkers for stratification of the patients with IPMN and subsequent treatment optimalization.

Citation Format: Radoslav Janostiak, Peter Mačinga, Lucia Csergeová, Ondřej Fabián, Eva Sticová, Jiří Zahradník, Martin Květoň, Tomáš Hucl. Disks large-associated protein 5 (DLGAP5) is a putative prognostic biomarker for intraductal papillary mucinous neoplasm (IPMN) of pancreas [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B037.
Abstract B051: A T-cell signature in circulating cell-free DNA at time of diagnosis predicts response to checkpoint inhibition
Authors: Xie Phil , Etzioni Zohar , Song Chun-Xiao , Owen Richard P , Middleton Mark R , Lu Xin , Schuster-Boeckler Benjamin
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR017) of the Conference Program/Proceedings.

Citation Format: Phil Xie, Zohar Etzioni, Chun-Xiao Song, Richard P Owen, Mark R Middleton, Xin Lu, Benjamin Schuster-Boeckler. A T-cell signature in circulating cell-free DNA at time of diagnosis predicts response to checkpoint inhibition [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B051.
Abstract B061: Assessing saliva for cancer biomarker discovery: A liquid biopsy approach
Authors: Koduru Srinivas V , Kidd Mark , Halim Abdel B
Published: November 2024

Introduction: Liquid biopsy has been gaining traction as a replacement for invasive tumor biopsies in oncology. Several blood-based in vitro diagnostics have been approved by the FDA and other regulatory agencies, and efforts are being made to validate urine, saliva, and buccal swabs as alternative matrices. The primary aim of this study was to investigate the relative mRNA expression in paired blood and saliva samples from cancer patients and healthy individuals. Methods: We collected matched saliva and blood samples from 35 subjects, comprising 26 patients with prostate, breast, colon, lung, melanoma, and pancreatic cancers, and 9 healthy individuals. Samples were collected using Wren's proprietary stabilization buffer kit, and total RNA extracted by TRIzol-based Qiagen reagents. RNA sequencing (RNA-Seq) was performed on a Novaseq 6000 platform, and data was analyzed using high-performance computing (HPC) with PartekFlow software, employing the BWA aligner (hg38). We focused on comparing gene expression in cancers (as a group) compared to controls. Results: The total number of genes detected in saliva was 3,985, compared to 14,459 genes detected in blood samples. A substantial overlap was observed, with more than 92.8% of saliva-detected genes also found in blood. We also examined housekeeping gene detection in both matrices. In this set of 1,003 housekeeping genes, 30% (n=305) were expressed in both saliva and blood. When we narrowed the scope to only include the 1,154 cancer-related genes as listed by the OncoKB database, 88.3% were detected in saliva and/or blood, with 37.1% of these genes (n=429) were expressed in both saliva and blood. Lastly, we examined a set of 241 cancer-associated biomarkers utilized in RT-PCR-based diagnostic blood assays clinically validated by our laboratory. This subset analysis revealed that 23.2% of these biomarkers were expressed in both saliva and blood. Conclusion: Our data indicate that the majority of mRNA detected in saliva was also detected in blood, with differential expression observed in cancer patients compared to normal controls. Given the relatively high limit of detection (low sensitivity) using RNA-Seq technology compared to PCR and the relatively small number of subjects, the data may suggest that saliva could function as a surrogate biomarker matrix for blood.

Citation Format: Srinivas V Koduru, Mark Kidd, Abdel B Halim. Assessing saliva for cancer biomarker discovery: A liquid biopsy approach [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B061.