Deciphering the Role of Exosomal Non-Coding RNA (ncRNA) in Drug Resistance of Gastrointestinal Tumors; an Updated Review.

One of the most prevalent types of cancer worldwide today is gastric intestinal (GI) tumors. To guarantee their lives, people with a developed GI require palliative care. This covers the application of targeted medicines in addition to chemotherapy treatments including cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed. Because of the evidence of drug resistance emerging in poor patient outcomes and prognoses, determining the exact process of medication resistance is motivated. Besides, it is noteworthy that exosomes and noncoding RNAs, like microRNAs and long non-coding RNAs (lncRNAs), produced from tumor cells are implicated in both GI medication resistance and the carcinogenesis and development of GI disease. Biochemical events related to the cell cycle, differentiation of cells, growth, and pluripotency, in addition to gene transcription, splicing, and epigenetics, are all regulated by noncoding RNAs (ncRNAs). Therefore, it should come as a wonder that several ncRNAs have been connected in recent years to drug susceptibility and resistance as well as tumorigenesis. Additionally, through communicating directly with medications, altering the transcriptome of tumor cells, and affecting the immune system, exosomes may govern treatment resistance. Because of this, exosomal lncRNAs often act as a competitive endogenous RNA (ceRNA) of miRNAs to carry out its role in modifying drug resistance. In light of this, we provide an overview of the roles and processes of ncRNA-enriched exosomes in GI medication resistance.

CRISPR-Cas9 Targeted Enrichment and Next-Generation Sequencing for Mutation Detection.

Despite the rapid application of next-generation sequencing (NGS) technologies, target sequencing in regions of the genome is often required to diagnose many genetic diseases. Target enrichment can be an effective factor in reducing the cost of sequencing and the duration of sequencing. Recently, several clustered system regularly interspaced short palindromic repeats (CRISPR)-based methods (amplification-free sequencing) have been developed to target enrichment in combination with one of the NGS platforms. CRISPR-based target enrichment strategies act as an auxiliary tool to improve NGS analytical performance, thereby indirectly facilitating nucleic acid detection. The direct DNA cleavage approach by CRISPR-CRISPR-associated (Cas) at genome-specific sites enhances the possibility of separating native large fragments from disease-related genomic regions. The CRISPR-Cas can isolate the target region without any amplification; subsequently, long-read sequencing technologies were also implemented. These methods, as promising tools, have the ability to assess genetic and epigenetic composition for clinical application and treatment responses in cancer precision medicine. By modifying CRISPR-based enrichment protocols, it is possible to identify different types of mutations, including structural variants, short tandem repeats, fusion genes, and mobile elements. The Cas9 can specifically eliminate wild-type sequences, and it also enables the enrichment and detection of small amounts of tumor DNA fragments among the highly heterogeneous fragments of wild-type DNA.

Evaluation of the sonographic features of metastatic cervical lymph nodes in patients with head and neck malignancy.

OBJECTIVES: The aim of the study was to evaluate the sonographic findings of metastatic cervical lymph nodes and of differentiating them from benign ones in patients with head and neck malignancy. METHODS: In this study, the cervical lymph nodes of 14 patients (12 female and 2 male patients; mean age, 52.8 years (with head and neck region malignancy were evaluated ultrasonographically. The gray-scale sonographic parameters, which included short- and long-axis lengths, shape index, presence or absence of hilar echoes and cystic necrosis, parenchymal echogenicity and echo texture, margin, and the color Doppler parameter including vascular pattern were evaluated. Finally, sonographic findings were compared with pathologic results. The following statistical analyses were included: χ(2) test, Fisher exact test, and independent-samples t-test. RESULTS: Overall, 88 cervical lymph nodes were evaluated ultrasonographically. According to the histopathologic results, 77% of them were benign, and 23% were malignant. The study's results showed that the metastatic lymph nodes are accompanied with significantly larger size, rounded shape, absence of hilus, and presence of cystic necrosis and mixed and peripheral vascular pattern. The parameters related to minimal and maximal axis diameter had the highest sensitivity (85%), whereas 2 parameters of vascularity pattern and cystic necrosis had 100% specificity in detecting metastatic cervical lymph nodes. CONCLUSIONS: The results of our study revealed that there was a considerable difference in the diagnostic value of the sonographic parameters, in differentiating metastatic lymph nodes from benign ones, between 4 specific neck regions.

Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: In this study, we investigate the effect of hydroxychloroquine on the prevention of Novel Coronavirus Disease (COVID-19) in cancer patients being treated. TRIAL DESIGN: This is a multi-centre, two-arm, parallel-group, triple-blind, phase 2-3 randomised controlled trial. PARTICIPANTS: All patients over the age of 15 from 5 types of cancer are included in the study. Patients with acute lymphoid and myeloid leukemias in the first line treated with curative intent, patients with high-grade non-Hodgkin's lymphoma treated with leukemia protocols and patients with non-metastatic breast and colon cancer in the first line of treatment will enter the study. The exclusion criteria will include known sensitivity to Hydroxychloroquine, weight below 35 kilograms, history of retinopathy, history of any cardiac disease, acute respiratory tract infection in the last 2 months, having COVID-19 in the first two weeks of entering the trial, having Diabetes Mellitus, having an immuno-suppressive disease other than cancer, having chronic pulmonary disease and taking immuno-suppressant drug other than chemotherapeutic agents for current cancer. This study is performed in five academic centres affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. INTERVENTION AND COMPARATOR: Patients are randomly assigned to two groups; one being given hydroxychloroquine and the other is given placebo. During two months of treatment, the two groups are treated with either hydroxychloroquine (Amin® Pharmaceutical Company, Isfahan, Iran) or placebo (identical in terms of shape, colour, smell) as a single 200 mg tablet every other day. Patients will be monitored for COVID-19 symptoms during the follow-up period. If signs or symptoms occur (fever, cough, shortness of breath), they will be examined and investigated with a high-resolution computed tomography (CT) scan of the lungs, COVID-19 specific IgM, IgG antibody assay and a nucleic acid amplification test (NAT) for the SARS-CoV-2 virus. MAIN OUTCOMES: The primary end point of this study is to investigate the incidence of COVID-19 in patients being treated for their cancer over a 2-month period. RANDOMISATION: Randomisation will be performed using randomly permuted blocks. By using an online website (www.randomization.com) the randomization sequence will be produced by quadruple blocks. The allocation ratio in intervention and control groups is 1:1. BLINDING (MASKING): Participants and caregivers do not know whether the patient is in the intervention or the control group. The outcome assessor and the data analyst are also blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 60 patients, with 30 patients in each group. TRIAL STATUS: The trial began on April 14, 2020 and recruitment is ongoing. Recruitment is anticipated to be completed by June 14, 2020 There has been no change in study protocol since approval, protocol version 1 was approved April 12, 2020. TRIAL REGISTRATION: This trial has been registered by the title of "Effect of Hydroxychloroquine on Novel Coronavirus Disease (COVID-19) prevention in cancer patients under treatment" in Iranian Registry of Clinical Trials (IRCT) with code "IRCT20200405046958N1", https://www.irct.ir/trial/46946. Registration date is April 14, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.