Clinical Effects of PET-CT Before Definite Concurrent Chemoradiotherapy in Patients With Unresectable Stage IIIA-IIIB Squamous Cell Carcinoma of the Lungs.

PURPOSE: No large-scale, retrospective cohort study with a long-term follow-up time has yet evaluated the effects of preoperative 18 F-FDG PET-CT on survival in patients with unresectable stages IIIA-IIIB squamous cell lung carcinoma (SqCLC) who received definite concurrent chemoradiotherapy (CCRT). METHODS: We included patients with unresectable stages IIIA-IIIB SqCLC receiving definite CCRT and categorized them into 2 groups. The case group comprised patients who underwent pre-CCRT 18 F-FDG PET-CT, and the comparison group comprised patients who did not receive pre-CCRT 18 F-FDG PET-CT; the groups were matched at a ratio of 1:1. RESULTS: The matching process yielded a final cohort of 4042 eligible patients (2021 and 2021 in the case and comparison groups, respectively). Multivariable Cox regression analyses revealed a positive correlation between patients with unresectable stages IIIA-IIIB SqCLC receiving definite CCRT and all-cause death in the pre-CCRT 18 F-FDG PET-CT (adjusted hazard ratio, 0.85; 95% confidence interval, 0.80-0.91; P < 0.0001). CONCLUSION: Pre-CCRT 18 F-FDG PET-CT was associated with more favorable survival in both patients with unresectable clinical stage IIIA and those with stage IIIB receiving definite CCRT.

Transcriptional ITPR3 as potential targets and biomarkers for human pancreatic cancer.

Inositol 1,4,5-Triphosphate Receptor Family (ITPRs) are necessary intracellular Ca2+-release channel encoders and participate in mammalian cell physiological and pathological processes. Previous studies have suggested that ITPRs participate in tumorigenesis of multiple cancers. Nevertheless, the diverse expression profiles and prognostic significance of three ITPRs in pancreatic cancer have yet to be uncovered. In this work, we examined the expression levels and survival dates of ITPRs in patients with pancreatic cancer. As a result, we identified that ITPR1 and ITPR3 expression levels are significantly elevated in cancerous specimens. Survival data revealed that over-expression of ITPR2 and ITPR3 resulted in unfavourable overall survival and pathological stage. The multivariate Cox logistic regression analysis showed that ITPR3 could be an independent risk factor for PAAD patient survival. Moreover, to investigate how ITPRs work, co-expressed genes, alterations, protein-protein interaction, immune infiltration, methylation, and functional enrichment of ITPRs were also analyzed. Then, we evaluated these findings in clinical samples. Moreover, the gain and loss of function of ITPR3 were also conducted. The electron microscope assay was employed to explore the role of ITPR3 in pancreatic cancer cell lines' endoplasmic reticulum stress. In summary, our findings demonstrated that ITPR3 has the potential to be drug targets and biomarkers for human pancreatic cancer.

The Mechanism and Clinical Significance of Circular RNAs in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. In view of the lack of early obvious clinical symptoms and related early diagnostic biomarkers with high specificity and sensitivity, most HCC patients are already at the advanced stages at the time of diagnosis, and most of them are accompanied by distant metastasis. Furthermore, the unsatisfactory effect of the follow-up palliative care contributes to the poor overall survival of HCC patients. Therefore, it is urgent to identify effective early diagnosis and prognostic biomarkers and to explore novel therapeutic approaches to improve the prognosis of HCC patients. Circular RNA (CircRNA), a class of plentiful, stable, and highly conserved ncRNA subgroup with the covalent closed loop, is dysregulated in HCC. Increasingly, emerging evidence have confirmed that dysregulated circRNAs can regulate gene expression at the transcriptional or post-transcriptional level, mediating various malignant biological behaviors of HCC cells, including proliferation, invasion, metastasis, immune escape, stemness, and drug resistance, etc.; meanwhile, they are regarded as potential biomarkers for early diagnosis and prognostic evaluation of HCC. This article reviews the research progress of circRNAs in HCC, expounding the potential molecular mechanisms of dysregulated circRNAs in the carcinogenesis and development of HCC, and discusses those application prospects in the diagnosis and prognosis of HCC.

Exosomal Noncoding RNAs in Hepatobiliary Cancer: A Rising Star.

Hepatobiliary cancers are a heterogeneous group of malignancies with a dismal prognosis. Despite intensive research efforts focused on these tumors, methods for early diagnosis and effective targeted therapies are still lacking. Exosomes, released by most cells, exist in all kinds of body fluids and play an important role in cell-to-cell communication. They are small membranous vesicles containing biological molecules, such as noncoding RNAs (ncRNA), which are not translated into proteins, but they exert effects on the regulation of gene transcription and translation. There is growing evidence for the essential roles of ncRNAs in exosomes in both physiologic and pathologic conditions of hepatobiliary cancers. They have been identified as sensitive diagnostic biomarkers as well as potential therapeutic targets. The present review discusses recent findings in the cross-talk between hepatobiliary cancers cells and the surrounding cells of the microenvironment and discuss their potential clinical usage.

LncRNA DiGeorge syndrome critical region gene 5: A crucial regulator in malignant tumors.

Long non-coding RNA (lncRNA), a subgroup of ncRNA with a length of more than 200 nt without protein coding function, has been recognized by the academia for its mediating effects of dysregulated expression on the tumorigenesis and development of a variety of tumors. LncRNA DiGeorge syndrome critical region gene 5 (DGCR5), originally found to induce DiGeorge syndrome, has been confirmed to be extremely dysregulated in multiple tumors, which mediates the malignant phenotypes of hepatocellular carcinoma, pancreatic cancer, lung cancer, etc. through the regulation of Wnt/ß-catenin, MEK/ERK1/2 and other cancerous signaling pathways as a molecular sponge. Researches on the cancerous derivation-related pathways involved in DGCR5 can provide potential molecular intervention targets for tumor precision treatment. Moreover, liquid biopsy based on the detection of DGCR5 in body fluids is also expected to provide a non-invasive evaluation method for the early diagnosis and prognostic evaluation of malignant tumors.

Exosomal Non-Coding RNAs: Regulatory and Therapeutic Target of Hepatocellular Carcinoma.

Exosomes are small extracellular vesicles secreted by most somatic cells, which can carry a variety of biologically active substances to participate in intercellular communication and regulate the pathophysiological process of recipient cells. Recent studies have confirmed that non-coding RNAs (ncRNAs) carried by tumor cell/non-tumor cell-derived exosomes have the function of regulating the cancerous derivation of target cells and remodeling the tumor microenvironment (TME). In addition, due to the unique low immunogenicity and high stability, exosomes can be used as natural vehicles for the delivery of therapeutic ncRNAs in vivo. This article aims to review the potential regulatory mechanism and the therapeutic value of exosomal ncRNAs in hepatocellular carcinoma (HCC), in order to provide promising targets for early diagnosis and precise therapy of HCC.

Circular RNA circ_ABCB10 in cancer.

Circular RNA (circRNA), a newly discovered type of endogenous noncoding RNA, has become a focus and hotspot in biological research in recent years. It exists widely and possesses a stable structure, is highly conserved and has cell-specific expression. circRNA is associated with disease occurence in general and cancer specifically due to its role in cell differentiation, proliferation, invasion and metastasis. Recently, circ_ABCB10, an increasingly studied member of the annular RNA family, has attracted considerable attention due to the fact that its expression is upregulated in various tumors, ie, esophageal cancer, breast cancer, lung cancer, and glioma, and may be of prognostic value. Molecular regulation and mechanism of circ_ABCB10 action in cancer are reviewed and its potential as a molecular marker and novel target for diagnosis and treatment are explored..

Effect of six-stitch pancreaticojejunostomy on pancreatic fistula: A propensity score-matched comparative cohort study.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common and severe complication after pancreaticoduodenectomy (PD). Despite the development of numerous anastomotic surgical techniques to minimize CR-POPF, more than 30% of patients who undergo PD develop CR-POPF. Herein, we propose a novel pancreaticojejunostomy (PJ) technique and evaluate its efficacy and safety compared to traditional PJ. METHODS: This retrospective study enrolled 164 consecutive patients who underwent PJ after PD between January 2012 and June 2017. Of them, 78 (47.6%) underwent traditional PJ and 86 (52.4%) underwent six-stitch PJ. The primary outcome was CR-POPF at 1-month follow-up defined according to the revised 2016 International Study Group on Pancreatic Fistula definition. To adjust for baseline differences and selection bias, patients were matched by propensity scores, which left 63 patients with traditional PJ and 63 with six-stitch PJ. RESULTS: Compared to patients who underwent traditional PJ (mean age 56.2 ± 9.4 years), patients who underwent six-stitch PJ (mean age 57.4 ± 11.4 years) had a lower CR-POPF rate. The risk of CR-POPF among patients who underwent six-stitch PJ was decreased by 81.7% after adjustment for age, sex, body mass index, and disease severity compared to patients who underwent traditional PJ. Additionally, the surgery time was reduced from 29 min for traditional PJ to 15 min for six-stitch PJ (P <0.001). Adverse effects such as abdominal fluid collection, abdominal bleeding, and wound infection were similar between two groups. CONCLUSION: Six-stitch PJ may be an effective and efficient PJ technique for patients who undergo PD surgery.

An anti-CD103 antibody-drug conjugate prolongs the survival of pancreatic islet allografts in mice.

CD103 mediates T-cell infiltration and organ allograft rejection, and depletion of CD103-expressing cells is a promising therapeutic strategy for allograft intolerance. Recently, we verified that M290-MC-MMAF, an anti-CD103 antibody-drug conjugate, potently eliminates CD103-positive cells in vivo, with high specificity and minimal toxicity. However, the contribution of M290-MC-MMAF to blocking the CD103/E-cadherin pathway involved in transplant rejection remains unclear. Herein, we examined the impact of systemic administration of M290-MC-MMAF on allografts in an islet transplantation model. M290-MC-MMAF treatment maintained the long-term survival of islet allografts (>60 days) compared to mock injection or unconjugated M290 antibody treatment (<18 days). The change was associated with a decrease in CD103+CD8+ effector T cells and an increase in CD4+CD25+ regulatory T cells. CD103+CD8+ effector T-cell transfer or CD4+CD25+ regulatory T-cell depletion resulted in a rapid loss of allografts in long-surviving islet hosts. Moreover, M290-MC-MMAF treatment reduced IL-4, IL-6, and TNF-α expression levels and increased IL-10 expression in the grafts, which presented an immunosuppressive cytokine profile. In conclusion, targeting CD103 with M290-MC-MMAF induced immunosuppression and prolonged the survival of pancreatic islet allografts in mice, indicating the potential clinical value of M290-MC-MMAF in therapeutic interventions for allograft rejection.