Biomarker Research

KMT2A-rearranged acute myeloid leukemia (KMT2Ar-AML) is an aggressive subtype of AML with poor response and prognosis. KMT2Ar-AML has been demonstrated to be sensitive to BCL2 inhibitor venetoclax (VEN), but these patients are unable to benefit from current VEN-based regimen (VEN plus azacitidine or low dose-cytarabine), so a novel and KMT2A rearrangement-specific targeting partner is required, and MENIN inhibitor (MEN1i) is a promising one. Herein, we investigated the effect and mechanism of VEN plus MEN1i in KMT2Ar-AML...

Adoptive cell therapy using T cell receptor-engineered T cells (TCR-T) is a promising approach for cancer therapy with an expectation of no significant side effects. In the human body, mature T cells are armed with an incredible diversity of T cell receptors (TCRs) that theoretically react to the variety of random mutations generated by tumor cells. The outcomes, however, of current clinical trials using TCR-T cell therapies are not very successful especially involving solid tumors. The therapy still faces numerous challenges in the efficient screening of tumor-specific antigens and their cognate TCRs...

Today, adoptive cell therapy has many successes in cancer therapy, and this subject is brilliant in using chimeric antigen receptor T cells. The CAR T cell therapy, with its FDA-approved drugs, could treat several types of hematological malignancies and thus be very attractive for treating solid cancer. Unfortunately, the CAR T cell cannot be very functional in solid cancers due to its unique features. This treatment method has several harmful adverse effects that limit their applications, so novel treatments must use new cells like NK cells, NKT cells, and macrophage cells...

BACKGROUND: Reliable pre-surgical prediction of spreading through air spaces (STAS) in primary lung cancer is essential for precision treatment and surgical decision-making. We aimed to develop and validate a dual-delta deep-learning and radiomics model based on pretreatment computed tomography (CT) image series to predict the STAS in patients with lung cancer. METHOD: Six hundred seventy-four patients with pre-surgery CT follow-up scans (with a minimum interval of two weeks) and primary lung cancer diagnosed by surgery were retrospectively recruited from three Chinese hospitals...

No abstract text is available yet for this article.

Tumor-associated macrophages (TAMs), one of the most abundant immune cell types in the tumor microenvironment (TME), account for approximately 50% of the local hematopoietic cells. TAMs play an important role in tumorigenesis and tumor development through crosstalk between various immune cells and cytokines in the TME. Exosomes are small extracellular vesicles with a diameter of 50-150 nm, that can transfer biological information (e.g., proteins, nucleic acids, and lipids) from secretory cells to recipient cells through the circulatory system, thereby influencing the progression of various human diseases, including cancer...

While the field of precision oncology is rapidly expanding and more targeted options are revolutionizing cancer treatment paradigms, therapeutic resistance particularly to immunotherapy remains a pressing challenge. This can be largely attributed to the dynamic tumor-stroma interactions that continuously alter the microenvironment. While to date most advancements have been made through examining the clinical utility of tissue-based biomarkers, their invasive nature and lack of a holistic representation of the evolving disease in a real-time manner could result in suboptimal treatment decisions...

Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers...

Congenital heart disease (CHD) represents a significant contributor to both morbidity and mortality in neonates and children. There's currently no analogous dried blood spot (DBS) screening for CHD immediately after birth. This study was set to assess the feasibility of using DBS to identify reliable metabolite biomarkers with clinical relevance, with the aim to screen and classify CHD utilizing the DBS. We assembled a cohort of DBS datasets from the California Department of Public Health (CDPH) Biobank, encompassing both normal controls and three pre-defined CHD categories...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Small extracellular vesicles (sEVs) in the blood of cancer patients contain higher amounts of tumor markers than those identified as free-circulating. miRNAs have significant biomedical relevance due to their high stability and feasible detection. However, there is no reliable endogenous control available to measure sEVs-miRNA content, impairing the acquisition of standardized consistent measurements in cancer liquid biopsy. In this study, we identified three miRNAs from a panel of nine potential normalizers that emerged from a comprehensive analysis comparing the sEV-miRNA profile of six lung and ovarian human cancer cell lines in the absence of or under different conditions...

T-cell lymphoblastic acute leukemia (T-ALL) is an aggressive blood cancer, characterized by restricted cellular subsets with enriched leukemia initiating cells (LICs). Recently, Ephrin receptors (Eph) were described to be highly expressed in cancer stem cells. Here, using public RNA-Seq datasets of human T-ALL, we reported that EphB6 was the only member within the Eph family overexpressed in over 260 samples. We also found the highest level of EphB6 in a minor cell subpopulation within bulk tumors of patient-derived xenografts, obtained through the injection of primary patient biopsy material into immunocompromised NOD-Scid/IL2Rγc-/- (NSG) mice...

Genomic testing is crucial for the management of ovarian cancer. DNA from biopsies at diagnostic laparoscopies or interval debulking surgery after neoadjuvant chemotherapy, has a high failure rate. At relapse, biopsies may not be feasible. The aim of our study was to evaluate the feasibility and usefulness of measuring genomic instability score (GIS) on cell-free DNA (cfDNA) from ascites.Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples. CfDNA was extracted from 1 to 4 ml of double-centrifuged fresh ascites...

Light chain amyloidosis (AL) is a rare disease caused by the generalized deposition of misfolded free light chains. Patients with immunoglobulin M gammopathy (IgM) and indolent B-cell lymphoma such as marginal zone lymphoma (MZL) may in some instances develop AL amyloidosis. So far, CAR T cells for AL amyloidosis have only been reported utilizing the B cell maturation antigen as target, while CD19 has so far not been used in AL amyloidosis.We report the case of a 71-year-old male, diagnosed with systemic AL kappa amyloidosis and MZL, receiving third-generation CAR T cell therapy targeting CD19...

BACKGROUND: Recent advances in circulating cell-free DNA (cfDNA) analysis from biofluids have opened new avenues for liquid biopsy (LB). However, current cfDNA LB assays are limited by the availability of existing information on established genotypes associated with tumor tissues. Certain cancers present with a limited list of established mutated cfDNA biomarkers, and thus, nonmutated cfDNA characteristics along with alternative biofluids are needed to broaden the available cfDNA targets for cancer detection...

Mitochondria are energy-generated organelles and take an important part in biological metabolism. Mitochondria could be transferred between cells, which serves as a new intercellular communication. Mitochondrial transfer improves mitochondrial defects, restores the biological functions of recipient cells, and maintains the high metabolic requirements of tumor cells as well as drug resistance. In recent years, it has been reported mitochondrial transfer between cells of bone marrow microenvironment and hematological malignant cells play a critical role in the disease progression and resistance during chemotherapy...

Pancreatic cancer is one of the most challenging cancers due to its high mortality rates. Considering the late diagnosis and the limited survival benefit with current treatment options, it becomes imperative to optimize early detection, prognosis and prediction of treatment response. To address these challenges, significant research efforts have been undertaken in recent years to develop liquid-biopsy-based biomarkers for pancreatic cancer. In particular, an increasing number of studies point to cell-free DNA (cfDNA) methylation analysis as a promising non-invasive approach for the discovery and validation of epigenetic biomarkers with diagnostic or prognostic potential...

BACKGROUND AND AIM: The presence of microvascular invasion (MVI) will impair the surgical outcome of hepatocellular carcinoma (HCC). Adipose and muscle tissues have been confirmed to be associated with the prognosis of HCC. We aimed to develop and validate a nomogram based on adipose and muscle related-variables for preoperative prediction of MVI in HCC. METHODS: One hundred fifty-eight HCC patients from institution A (training cohort) and 53 HCC patients from institution B (validation cohort) were included, all of whom underwent preoperative CT scan and curative resection with confirmed pathological diagnoses...

Major histocompatibility complex class I related chain A (MICA) is an important and stress-induced ligand of the natural killer group 2 member D receptor (NKG2D) that is expressed in various tumour cells. Given that the MICA/NKG2D signalling system is critically embedded in the innate and adaptive immune responses, it is particularly involved in the surveillance of cancer and viral infections. Emerging evidence has revealed the important roles of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in different cancer types...