Gastric cancer (GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva, stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

Recent advances in gastric cancer early diagnosis.

Extracellular vesicles (EV) are secretory membranous elements used by cells to transport proteins, lipids, mRNAs, and microRNAs (miRNAs). While their existence has been known for many years, only recently has research begun to identify their function in intercellular communication and gene regulation. Importantly, cells have the ability to selectively sort miRNA into EVs for secretion to nearby or distant targets. These mechanisms broadly include RNA-binding proteins such as hnRNPA2B1 and Argonaute-2, but also membranous proteins involved in EV biogenesis such as Caveolin-1 and Neural Sphingomyelinase 2. Moreover, certain disease states have also identified dysregulated EV-miRNA content, shedding light on the potential role of selective sorting in pathogenesis. These pathologies include chronic lung disease, immune response, neuroinflammation, diabetes mellitus, cancer, and heart disease. In this review, we will overview the mechanisms whereby cells selectively sort miRNA into EVs and also outline disease states where EV-miRNAs become dysregulated.

https://www.mdpi.com/2073-4409/9/4/1044/pdf

Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases.

MicroRNAs (miRNAs), small non-coding RNAs (ncRNAs) of about 22 nucleotides in size, play important roles in gene regulation, and their dysregulation is implicated in human diseases including cancer. A variety of miRNAs could take roles in the cancer progression, participate in the process of tumor immune, and function with miRNA sponges. During the last two decades, the connection between miRNAs and various cancers has been widely researched. Based on evidence about miRNA, numerous potential cancer biomarkers for the diagnosis and prognosis have been put forward, providing a new perspective on cancer screening. Besides, there are several miRNA-based therapies among different cancers being conducted, advanced treatments such as the combination of synergistic strategies and the use of complementary miRNAs provide significant clinical benefits to cancer patients potentially. Furthermore, it is demonstrated that many miRNAs are engaged in the resistance of cancer therapies with their complex underlying regulatory mechanisms, whose comprehensive cognition can help clinicians and improve patient prognosis. With the belief that studies about miRNAs in human cancer would have great clinical implications, we attempt to summarize the current situation and potential development prospects in this review.

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miRNA-based biomarkers, therapies, and resistance in Cancer.

Purpose
Cytokine-induced killer (CIK) cells represent an exceptional T cell population uniting a T cell and natural killer cell like phenotype in their terminally differentiated CD3+CD56+ subset, which features non-MHC-restricted tumor-killing activity. CIK cells are expandable from peripheral blood mononuclear cells and mature following the addition of certain cytokines. CIK cells have provided encouraging results in initial clinical studies and revealed synergistic antitumor effects when combined with standard therapeutic procedures.

Cytokine-induced killer (CIK) cells in cancer immunotherapy: report of the international registry on CIK cells (IRCC)

Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3+CD56+ NKT cells which can be easily expanded in vitro from peripheral blood mononuclear cells (PBMC). CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe and effective anti-tumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other anti-tumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, DC cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a CAR (chimeric antigen receptor). Furthermore, we briefly sum up the clinical trials on CIK cells and compare the effect of clinical CIK therapy with other immunotherapies. Finally, further research is needed to clarify the pharmacological mechanism of CIK and provide evidence to formulate uniform culturing criteria for CIK expansion.

/pdf/cytokine-induced-killer-cells-as-pharmacological-tools-for-8cr0uu404l.pdf

Cytokine-Induced Killer Cells As Pharmacological Tools for Cancer Immunotherapy.

A panel of seven-miRNA signature in plasma as potential biomarker for colorectal cancer diagnosis.

The Value of Plasma-Based MicroRNAs as Diagnostic Biomarkers for Ovarian Cancer.

Dysregulated microRNAs (miRNAs) in the plasma of patients with lung squamous cell carcinoma (LSCC) might serve as biomarkers for LSCC diagnosis. The expression of miRNAs was performed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on the basis of Exiqon panels in the initial screening phase including three male LSCC pool samples and one normal control (NC) pool sample (per 10 samples were pooled as one pool sample). After the training (32 LSCC vs. 31 NCs), the testing (55 LSCC vs. 55 NCs), and the external validation (15 LSCC vs. 15 NCs) stages via qRT-PCR, a four-miRNA signature (miR-181a-5p, miR-21-5p, miR-106a-5p, and miR-93-5p) was identified for LSCC detection. Areas under the receiver operating characteristic (ROC) curve (AUC) of the four-miRNA panel for the training, the testing, and the external validation phases were 0.795, 0.827, and 0.914, respectively. Then, the four miRNAs were explored in LSCC tissue samples (23 LSCC vs. 23 NCs), and their expression was significantly up-regulated. However, none of the four miRNAs found significantly up-regulated in plasma exosomes expect miR-93-5p with borderline significance (16 LSCC vs. 16 NCs). In summary, our study established a four-miRNA peripheral plasma signature, which contributed to diagnosing male LSCC patients in China to a certain degree.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.1490

Identification of four plasma microRNAs as potential biomarkers in the diagnosis of male lung squamous cell carcinoma patients in China.

Background Circulating microRNAs (miRNAs) have been implicated as novel biomarkers for various types of cancers. The aim of the study is to identify serum miRNAs with potential in detecting gastric cardia adenocarcinoma (GCA). Methods A three-phase study was designed with 102 GCA patients and 84 cancer-free controls. In the screening phase (3 GCA pools vs. 1 normal control (NC) pool), a total of 35 miRNAs were identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel. Subsequently, these miRNAs were further assessed by qRT-PCR in the training phase (30 GCAs vs. 30 NCs) and testing phase (72 GCAs vs. 54 NCs). Finally, the expression levels of the identified miRNAs were assessed in GCA tissues and exosomes. Results Five up-regulated miRNAs (miR-200a-3p, miR-296-5p, miR-132-3p, miR-485-3p and miR-22-5p) were identified in serum of the GCA patients compared with NCs. The areas under the receiver operating characteristic curve (AUCs) of the five-miRNA panel were 0.766 and 0.724 for the training and testing phases, respectively. In addition, miR-200a-3p, miR-296-5p, miR-485-3p and miR-22-5p were significantly up-regulated in GCA tissues. However, none of the miRNAs in the exosomes showed different expression between GCA patients and NCs. Conclusions We identified a five-miRNA panel in peripheral serum samples as a non-invasive biomarker in detection of GCA.

Five serum-based miRNAs were identified as potential diagnostic biomarkers in gastric cardia adenocarcinoma

Cytokine-induced killer (CIK) cells exert high impact on adoptive immunotherapeutic approaches for malignant tumors. This study aimed to evaluate the effect of adjuvant immunotherapy with CIK cells on the prognosis of solid tumor. Peripheral blood mononuclear cells were collected by a blood cell separator from 40 patients, then expanded by priming them with interferon-gamma followed by monoclonal antibody against CD3 and interleukin-2 the next day. The phenotypic patterns of CIK cells were characterized by flow cytometry on days 0, 7, 10, 14 and 21 of incubation, respectively. Then, 5 ml of venous blood was obtained from 40 patients before and after CIK cells were transfused into patients to assess the influence of CIK cells on the percentages of effector cells. After 14 days of incubation in vitro, the percentages of CD3+, CD8+, CD3+ and CD56+ increased significantly (P < 0.05). The clinical symptoms of 40 patients were improved apparently. The 6-month, 1-year and 3-year overall survival rates were 70.0, 60.0 and 57.5%, respectively. Our results indicated that CIKs immunotherapy can be an effective adjuvant instrument of the routine therapy of malignancy.

Jinying Zhang

Papers

A panel of seven-miRNA signature in plasma as potential biomarker for colorectal cancer diagnosis.

The Value of Plasma-Based MicroRNAs as Diagnostic Biomarkers for Ovarian Cancer.

Identification of four plasma microRNAs as potential biomarkers in the diagnosis of male lung squamous cell carcinoma patients in China.

Five serum-based miRNAs were identified as potential diagnostic biomarkers in gastric cardia adenocarcinoma

The effects of cytokine-induced killer cells for the treatment of patients with solid tumors: a clinical retrospective study