Exploring the role of ADAMTSL2 across multiple cancer types: A pan-cancer analysis and validated in colorectal cancer.

BACKGROUND: Recent studies have established a correlation between ADAMTSL2 (ADAMTS-like 2) and the development of various cancers. This study aims to conduct a comprehensive pan-cancer analysis in 37 cancer types and investigate its potential role in colon and rectal adenocarcinoma (COADREAD). METHOD: Pan-cancer and mutation data were sourced from The Cancer Genome Atlas (TCGA) database and analyzed using Sangerbox analysis platform. We explored the expression patterns and prognostic implications of ADAMTSL2, and investigated its relationships with tumor heterogeneity, stemness, immune checkpoint genes, immune cell infiltration, RNA modifications, and mutational profiles across different cancers. Additionally, with Ethics Committee approval, we conducted immunohistochemical (IHC) analysis on 120 COADEAD samples to evaluate ADAMTSL2 expression and its association with clinicopathological parameters. RESULTS: ADAMTSL2 expression was positively correlated with the hazard ratio of OS, DSS, DFI and PFI for ESCA and COADREAD. A negative correlation was observed between ADAMTSL2 expression and NEO levels in COAD. Gene alterations in ADAMTSL2 were observed, with a mutation frequency of 5.0% in COAD. There is a significant correlation between ADAMTSL2 expression and immune cell infiltration in a variety of cancers. The expression level of ADAMTSL2 protein was associated with T stage, N stage, M stage (p < 0.05). Kaplan‒Meier survival curves demonstrated that the high ADAMTSL2 group had a shorter OS time (p = 0.047) and progression free survival time (p = 0.026) than the low ADAMTSL2 group. CONCLUSION: In summary, we conducted a comprehensive pan-cancer analysis of ADAMTSL2 and we demonstrated that ADAMTSL2 may serve as a novel prognostic biomarker and immunotherapy target in COADREAD.

A pan-allelic human SIRPα-blocking antibody, ES004-B5, promotes tumor killing by enhancing macrophage phagocytosis and subsequently inducing an effective T-cell response.

As a major immune cell type in the tumor microenvironment, tumor-associated macrophages secrete suppressive factors that can inhibit antitumor immunity and promote tumor progression. One approach trying to utilize macrophages for immunotherapy has been to block the CD47-SIRPα axis, which mediates inhibitory signaling, to promote phagocytosis of tumor cells. Many CD47-targeted agents, namely, anti-CD47 antibodies and SIRPα fusion proteins, were associated with a diverse spectrum of toxicities that limit their use in clinical settings. Universal expression of CD47 also leads to a severe "antigen sink" effect of CD47-targeted agents. Given that the CD47 receptor, SIRPα, has a more restricted expression profile and may have CD47-independent functions, targeting SIRPα is considered to have distinct advantages in improving clinical efficacy with a better safety profile. We have developed ES004-B5, a potentially best-in-class pan-allelic human SIRPα-blocking antibody using hybridoma technology. ES004-B5 binds to major human SIRPα variants through a unique epitope with high affinity. By blocking CD47-induced inhibitory "don't-eat-me" signaling, ES004-B5 exerts superior antitumor activity in combination with anti-tumor-associated antigen antibodies in vitro and in vivo. Unlike CD47-targeted agents, ES004-B5 exhibits an excellent safety profile in nonhuman primates. ES004-B5 has potential to be an important backbone for SIRPα-based combination therapy and/or bispecific antibodies, which will likely overcome the limitations of CD47-targeted agents encountered in clinical settings.

A neutrophil elastase inhibitor, sivelestat, attenuates sepsis-induced acute kidney injury by inhibiting oxidative stress.

Background: Sivelestat, a selective inhibitor of neutrophil elastase (NE), can mitigate sepsis-related acute lung injury. However, the role of sivelestat in inhibiting oxidative stress and attenuating sepsis-related acute kidney injury (AKI) remains unclear. Here, we reported the effects of sivelestat against oxidative stress-induced AKI by suppressing the production of oxidative stress indicators. Materials and methods: A male Sprague-Dawley rat model of sepsis was established by cecal ligation and puncture (CLP). Sivelestat or normal saline was administered into jugular vein with a sustained-release drug delivery system. Indicators of inflammation and AKI, including white blood cells (WBC), neutrophils, lymphocytes, C-reactive proteins (CRP), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA), were assessed at 24 h post-sivelestat treatment. Indicators of liver injury, including direct bilirubin (DBIL), indirect bilirubin (IBIL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were also assessed at 24 h post-sivelestat treatment. Indicators of oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), were assessed at 12 h and 24 h post-sivelestat treatment. At 24 h post-sivelestat treatment, H&E staining of kidney and liver tissue was performed to observe pathological alterations. Results: At 24 h post normal saline or sivelestat (0.2 g/kg body weight) treatment, WBC, neutrophil, CRP, PCT, MDA, BUN, Cr, UA, AST, ALT, DBIL and IBIL were increased, while SOD and GSH-Px were decreased, in septic rats treated with normal saline compared with that in non-septic rats treated with normal saline (all p < 0.05). The changes of these indicators were reversed in septic rats treated with sivelestat compared with that in septic rats treated with normal saline (all p < 0.05). Similar results were found regarding the levels of oxidative stress indicators at 12 h post-sivelestat treatment. The degenerative histopathological changes in both kidney and liver tissues were ameliorated upon sivelestat treatment. Conclusions: Sivelestat plays a protective role in sepsis-related AKI by inhibiting oxidative stress. Our study reveals a possible therapeutic potential of sivelestat for oxidative stress-induced AKI.

Undifferentiated carcinoma of the liver with osteoclast-like giant cells: a case report and literature review.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Osteoclast-like giant cells (OGCs) are relatively more common in pancreatic cancer, but extremely rare in HCC. Currently, there have been only a few reported cases of OGCs in HCC, and their presence indicates an aggressive clinical course. Here, we present a case of primary undifferentiated carcinoma of the liver with OGCs in a 49-year-old male patient, and through a literature review, we summarize 20 similar cases to further understand the diagnosis, treatment, and clinical course of this disease entity.

A retrospective cohort study to observe the efficacy and safety of Endoscopic Submucosal Dissection (ESD) with adjuvant radiotherapy for T1a-MM/T1b-SM Esophageal Squamous Cell Carcinoma (ESCC).

BACKGROUND AND AIM: The clinical outcome of endoscopy submucosal dissection with subsequent radiotherapy for esophageal squamous cell carcinoma remain unclear. In this study we aim to investigate the efficacy and safety of endoscopic submucosal dissection with adjuvant radiotherapy in the treatment of superficial esophageal squamous cell carcinoma involving the muscularis mucosae (T1a-MM) or the submucosa < 200 µm (T1b-SM1). METHODS: We analyzed 20 patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell carcinoma treated by endoscopic submucosal dissection from 2016 to 2020 in Lihuili Hospital, 9 patients received adjuvant radiotherapy (RT group) and 11 patients received did not (non-RT group). RESULTS: All 20 patients underwent en bloc resection, and both the vertical and horizontal margins were negative. There was no recurrence or lymph node metastasis in the RT group, and no serious complications or death were observed. In the non-RT group, 2 patients had local recurrence and 1 had distant metastasis. None of the 20 patients died of esophageal carcinoma. CONCLUSIONS: Adjuvant radiotherapy following endoscopic submucosal dissection may be a safe and effective method for the treatment of T1a-MM/T1b-SM1 superficial esophageal squamous cell carcinoma.

Mucoepidermoid carcinoma of the pancreas: A case report and literature review.

INTRODUCTION: Primary mucoepidermoid carcinoma (MEC) is a common malignant neoplasm of the salivary glands, but is very rare in the pancreas. To date, only 10 cases have been reported in the literature. Because MEC of the pancreas is very rare, there is little information about its diagnosis, treatment, and metastasis. Herein, we present the eleventh case and review the relevant literature. PATIENT CONCERNS: A 65-year-old woman presented with a mass in the body of the pancreas and multiple masses in the liver on abdominal magnetic resonance imaging. The patient initially underwent EUS-guided fine-needle aspiration and was diagnosed with adenocarcinoma. After adjuvant chemotherapy, resection of the pancreatic body and tail was performed, and the tissues were pathologically, histologically, and immunochemically examined. Specific strains and gene rearrangements were analyzed. DIAGNOSIS: Mucoepidermoid pancreatic cancer. INTERVENTION: After a 4-month course of adjuvant chemotherapy, laparoscopic surgery was performed. OUTCOMES: The patient is alive until the submission of this paper. CONCLUSION: We presented a case of mucoepidermoid pancreatic cancer in a 65-year-old woman. Pathological examination revealed that the tumor parenchyma consisted of 3 cell types. There are mainly epidermoid cells, intermediate cells between the basal and epidermoid cells, and mucus-producing cells in varying proportions. Immunohistochemical staining showed that there were different types of cells with unique morphological characteristics. In summary, primary MECs of the pancreas are rare and have poor prognosis. Few studies have been conducted on the diagnosis, treatment, and metastasis of MECs; therefore, further studies are needed to detect them.

Case Report: Clinicopathological characteristics of patients with gastric cancer with features of a submucosal tumour.

Purpose: To investigate the clinicopathological characteristics, diagnosis and key points in the differential diagnosis of patients with gastric cancer (GC) with features of a submucosal tumour (GCSMT). Methods: The clinical presentation and imaging findings of four GCSMT cases diagnosed at our centre from 2016 to 2021 were observed and their clinicopathological outcomes were analysed. The related literature was reviewed. Based on our collected data and the related literature, a total of 31 cases of GCSMT can be summarized. Results: 22 out of 31 cases did not present obvious symptoms and were accidentally discovered during gastroscopic examination. Only 10 patients experienced symptoms such as gastric discomfort, upper abdominal swelling and pain, haematemesis, or haematochezia. The male to female ratio was 22:9 and the age of onset ranged from 40 to 81 years (median age: 63 years). Tumours were located in the upper and middle third of the stomach (24/31), and in the lower third(7/31). The tumour diameter ranged from 0.6 to 7.3 cm, with an average value of 2.5 cm. Endoscopically, the disease manifested as SMTs, with the gastric mucosal surface appearing normal. Most patients underwent radical gastrectomy for GC (80.6%, 25/31). The pathological diagnoses of the 31 cases of GCSMT included well- and moderately-differentiated adenocarcinoma (6/31), poorly differentiated adenocarcinoma or signet ring cell carcinoma 6/31), mucinous adenocarcinoma (9/31), lymphoepithelioma-like carcinoma (7/31), gastric adenocarcinoma of the fundic gland type (3/31). Stage T1b and T2 tumours accounted for 56.7% (17/30) and 26.7% (8/30) of all cases. Lymph node metastases were found in six cases (20.0%, 6/30), whereas distant metastasis was not observed in any of the cases. For the 16 patients whose follow-up data were available, the follow-up time was 5-66 months, during which recurrence or metastasis was not observed. Conclusion: GCSMT is a rare disease that is often difficult to accurately diagnose through endoscopic biopsy. The importance of gaining an understanding of this disease lies in differentiating it from other SMTs (mostly mesenchymal tumours) to avoid misdiagnosis and missed diagnosis and enable the early diagnosis and treatment of patients.

Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation.

BACKGROUND: Breast cancer is the most common tumor in women worldwide. Diabetes mellitus is a global chronic metabolic disease with increasing incidence. Diabetes mellitus has been reported to positively regulate the development of many tumors. However, the specific mechanism of hyperglycemic environment regulating breast cancer remains unclear. PFKFB3 (6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3) is a key regulatory factor of the glycolysis process in diabetes mellitus, as well as a promoter of breast cancer. So, we want to explore the potential link between PFKFB3 and the poor prognosis of breast cancer patients with hyperglycemia in this study. METHODS: Cell culture was utilized to construct different-glucose breast cancer cell lines. Immunohistochemistry was adopted to analyze the protein level of PFKFB3 in benign breast tissues, invasive ductal carcinoma with diabetes and invasive ductal carcinoma without diabetes. The Kaplan-Meier plotter database and GEO database (GSE61304) was adopted to analyze the survival of breast cancer patients with different PFKFB3 expression. Western blot was adopted to analyze the protein level of PFKFB3, epithelial-mesenchymal transition (EMT)-related protein and extracellular regulated protein kinases (ERK) in breast cancer cells. Gene Set Cancer Analysis (GSCA) was utilized to investigate the potential downstream signaling pathways of PFKFB3. TargetScan and OncomiR were utilized to explore the potential mechanism of PFKFB3 overexpression by hyperglycemia. Transfections (including siRNAs and miRNA transfection premiers) was utilized to restrain or mimic the expression of the corresponding RNA. Cell functional assays (including cell counting, MTT, colony formation, wound-healing, and cell migration assays) were utilized to explore the proliferation and migration of breast cancer cells. RESULTS: In this study, we demonstrated that the expression of PFKFB3 in breast cancer complicated with hyperglycemia was higher than that in breast cancer with euglycemia through cell experiment in vitro and histological experiment. PFKFB3 overexpression decreased the survival period of breast cancer patients and was correlated with a number of clinicopathological parameters of breast cancer complicated with diabetes. PFKFB3 promoted the proliferation and migration of breast cancer in a hyperglycemic environment and might be regulated by miR-26. In addition, PFKFB3 stimulated epithelial-mesenchymal transition of breast cancer in a hyperglycemic environment. In terms of downstream mechanism exploration, we predicted and verified the cancer-promoting effect of PFKFB3 in breast cancer complicated with hyperglycemia through RAS/MAPK pathway. CONCLUSIONS: In conclusion, PFKFB3 could be overexpressed by hyperglycemia and might be a potential therapeutic target for breast cancer complicated with diabetes.

A proposal for grading the risk of lymph node metastasis after endoscopic resection of T1 colorectal cancer.

PURPOSE: At present, for patients with early colorectal cancer as long as having any one risk factor of lymph node metastasis (LNM) after endoscopic resection (ER), additional surgery will be considered, regardless of the degree of LNM risk; however, most patients are free of LNM. This study aimed to further grade these patients according to LNM risk. METHODS: We assessed 271 patients with T1 colorectal cancers treated initially with ER to analyze the correlation between LNM-associated risk factors and LNM rate. Differences in this rate between groups were estimated using the χ2 test or Fisher's exact test. RESULTS: Poorly differentiated adenocarcinoma (Por) (3.4% vs. 40%, p < 0.001) and lymphovascular infiltration (LV) (1.6% vs. 29.0%, p < 0.001) were the only parameters correlated with LNM. When we divided the cases into LV-negative (LV(-)) and LV-positive (LV(+)) groups, we found a significantly higher LNM rate in the LV(+) group (29.0% vs. 1.6%, p < 0.001). Additionally, the rate of LNM in those positive for each parameter did not differ from the control rate in the same group, except in the Por subgroup. When the cases were divided into four groups based on the presence of LV infiltration and Por, the LNM rate in each group was 2/233 cases (0.8%) in the LV(-)Por(-) group, 2/7 cases (28.5%) in the LV(-)Por(+) group, 7/28 cases (25.0%) in the LV(+)Por(-) group, and 2/3 cases (66.6%) in the LV(+)Por(+) group. CONCLUSIONS: Based on LV and histological differentiation, patients were classified into three LNM risk grades: low (LNM, 0.8%), moderate (LNM, 25.0-28.5%), and high (LNM, 66.6%).

Giant desmoplastic small round cell tumor of the abdomen: A case report.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive, mesenchymal malignancy of a separate clinicopathological entity. It has a predilection for young men, with no evidence of any ethnic predilection. The current diagnostic gold standard for DSRCT includes histopathologic, immunohistochemical, and cytogenetic studies in order to confirm the variable phenotypic expression and characteristic chromosomal translocation. Case summary: A 65-year-old man presented with a sensation of an abdominal mass and a presentation of an incomplete bowel obstruction. Initial lab tests were in the normal range except for carbohydrate antigen. Contrast-enhanced CT showed that a large, mass-confounding density was occupied in the omentum majus area of the middle and lower abdominal wall. A 3D reconstruction of the images was performed to clarify the relationship between the tumor and the colon and was confirmed by a colonoscopy. After surgery, immunohistochemistry and fluorescence in situ hybridization (FISH) revealed EWSR1-WT1 gene rearrangement at 22q12, confirming the diagnosis of desmoplastic small round cell tumor. Conclusion: Being different from the predilection of DSRCT for young men, the patient in our case is a 65-year-old man with a huge mass involving the transverse colon and the bladder.

Clinicopathological features of early stage gastric adenocarcinoma of fundic gland type: Case series.

INTRODUCTION: Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by a well-differentiated neoplasm. More than 100 cases have been reported, but only a few cases have been described in China. Therefore, its clinicopathological characteristics need to be investigated further. Herein, we report five cases and briefly review the relevant literature. PATIENT CONCERNS: Five patients, including three women and two men, were identified in the Ningbo Clinical Pathological Diagnosis Center between March 2017 and July 2020. Patients (case 1, case 2, and case 5) underwent gastroscopy due to epigastric pain. Apart from the lesion, others were occasionally discovered on physical examination. DIAGNOSIS: Gastric adenocarcinoma of the fundic gland type (GA-FG). INTERVENTION: Five patients were treated with endoscopic submucosal dissection. OUTCOMES: Surgical outcomes were good. Esophagogastroduodenoscopy showed a scar with no recurrence, and no postoperative symptoms were observed from 3 to 43 months during the follow-up. CONCLUSION: We present five cases of well-differentiated tubular adenocarcinoma that mimicked the fundic glands. Cell differentiation by MUC2, MUC5AC, MUC6, pepsinogen-I, and H+/K+-ATPase. Immunohistochemical findings in GA-FG suggested differentiation of the fundic glands. In addition, it has a low proliferation. p53 and Her-2 were negative, and ß-catenin was positive in the cytoplasm, indicating that the pathogenesis of this tumor was different from that of traditional intestinal and diffuse gastric carcinomas. In summary, this neoplasm is rare and unusual. To better understand this issue, similar cases should be monitored in the future.

Expression of SET domain bifurcated histone lysine methyltransferase 1 and its clinical prognostic significance in hepatocellular carcinoma.

BACKGROUND: To detect the expression of histone methyltransferase SETDB1 in hepatocellular carcinoma, and to analyze the relationship between SETDB1 expression and tumor size, microvascular invasion, pTNM stage, gender, age, tumor number, tumor differentiation, and other clinicopathological characteristics. METHODS: Immunohistochemical method was used to detect the expression of SETDB1 proteins in liver cancer tissues and adjacent tissues of 100 cases. The qRT-PCR method was used to detect the expression of SETDB1 mRNA in hepatocellular carcinoma and adjacent tissues of 64 cases. RESULTS: The expression of SETDB1 protein and mRNA in hepatocellular carcinoma was higher than that of adjacent normal liver tissue (p < 0.05). High protein expression of SETDB1 was associated with tumor size, MVI presence, and pTNM stage (p < 0.05). Univariate analysis revealed that the tumor size, tumor differentiation, MVI grade, and pTNM stage were correlated with DFS, while tumor size, MVI grade, pTNM stage, and SETDB1 protein expression were correlated with OS. Multivariate analysis showed that the combination of MVI grade and pTNM stage has statistical significance in predicting prognosis, while SETDB1 protein expression was not significant prognosis factor. CONCLUSIONS: SETDB1 has a certain role in HCC progression and may act as a prognostic predictor concerning the survival of HCC patients.

Extended pancreato-duodenectomy coupled with adjuvant chemotherapy for SMARCB1/INI1 deficient pancreatic carcinoma: A case report and literature review.

INTRODUCTION: SMARCB1/INI1 gene deletion appears to be associated with a rare, malignant and aggressive form of pancreatic carcinoma whose diagnosis is challenging. Our objective is to illustrate that the tumor may masquerade as a duodenal papillary carcinoma, be difficulty to identify on diagnostic imaging and that making an accurate diagnosis may be challenging, however surgical resection may be possible. CASE REPORT: We present a case of a 24-year old male patient presenting with jaundice and itchy skin, elevated TBIL, AST, ALP and CA125. A 2.2 × 1.7 cm pancreatic nodule, later diagnosed as a SMARCB1/INI deficient pancreatic carcinoma was detected on Endoscopic Ultrasound - Fine Needle Aspiration (EUS-FNA). The patient was successfully treated with extended pancreato-duodenectomy coupled with adjuvant chemotherapy, a 7 × 5 × 5 cm tumor resected. DISCUSSION: SMARCB1/INI deficient pancreatic carcinoma has been reported in couple of other articles. However, unlike other cases, in our case identification and accurate assessment of the tumor was particularly difficulty both on imaging and during operation. Our patient has thus far had a positive outcome with no recurrence. CONCLUSION: For rare forms of pancreatic carcinoma, identification and assessment of the tumor size may be challenging on imaging and during operation. However, careful assessment should be performed before ruling out surgical resection. Furthermore, adjuvant chemotherapy may be beneficial to the patient.

Mediator structure and conformation change.

Mediator is a universal adaptor for transcription control. It serves as an interface between gene-specific activator or repressor proteins and the general RNA polymerase II (pol II) transcription machinery. Previous structural studies revealed a relatively small part of Mediator and none of the gene activator-binding regions. We have determined the cryo-EM structure of the Mediator at near-atomic resolution. The structure reveals almost all amino acid residues in ordered regions, including the major targets of activator proteins, the Tail module, and the Med1 subunit of the Middle module. Comparison of Mediator structures with and without pol II reveals conformational changes that propagate across the entire Mediator, from Head to Tail, coupling activator- and pol II-interacting regions.

A Novel AKR1C3 Specific Prodrug TH3424 With Potent Antitumor Activity in Liver Cancer.

Overexpression of AKR1C3, an aldo-keto reductase, was recently discovered in liver cancers. In this study, an inverse correlation between AKR1C3 expression and survival of patients with liver cancer was observed. AKR1C3 inhibitors, however, failed to suppress liver cancer cell growth. The prodrug TH3424, which releases a DNA alkylating reagent upon reduction by AKR1C3, was developed to target tumors with overexpression of AKR1C3. TH3424 showed specific killing of liver cancer cells with AKR1C3 overexpression both in vitro and in vivo. In patient-derived mouse xenograft models, TH3424 at doses as low as 1.5 mg/kg eliminated liver tumors with no apparent toxicity. Therefore, TH3424 is a promising drug candidate for liver cancer and other types of cancers overexpressing AKR1C3.

Underwater versus conventional endoscopic mucosal resection for small size non-pedunculated colorectal polyps: a randomized controlled trial : (UEMR vs. CEMR for small size non-pedunculated colorectal polyps).

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) is a recently developed technique and can be performed during water-aided or ordinary colonoscopy for the treatment of colorectal polyps. The objective of this clinical trial was to evaluate the efficacy and safety of UEMR in comparison with conventional endoscopic mucosal resection (CEMR) of small non-pedunculated colorectal polyps. METHODS: Patients with small size, non-pedunculated colorectal polyps (4-9 mm in size) who underwent colonoscopic polypectomy were enrolled in this multicenter randomized controlled clinical trial. The patients were randomly allocated to two groups, an UEMR group and a CEMR group. Efficacy and safety were compared between groups. RESULTS: In the intention-to-treat (ITT) analysis, the complete resection rate was 83.1% (59/71) in the UEMR group and 87.3% (62/71) in the CEMR group. The en-bloc resection rate was 94.4% (67/71) in the UEMR group and 91.5% (65/71) in the CEMR group (difference 2.9%; 90% CI - 4.2 to 9.9%), showed noninferiority (noninferiority margin - 5.7% < - 4.2%). No significant difference in procedure time (81 s vs. 72 s, P = 0.183) was observed. Early bleeding was observed in 1.4% of patients in the CEMR group (1/71) and 1.4% of patients in the UEMR group (1/71). None of the patients in the UEMR group complained of postprocedural bloody stool, whereas two patients in the CEMR group (2/64) reported this adverse event. CONCLUSION: Our results indicate that UEMR is safer and just as effective as CEMR in En-bloc resection for the treatment of small colorectal polyps as such, UEMR is recommended as an alternative approach to excising small and non-pedunculated colorectal adenomatous polyps. TRIAL REGISTRATION: Clinical Trials.gov, NCT03833492 . Retrospectively registered on February 7, 2019.

Circular RNA UBAP2 contributes to tumor growth and metastasis of cervical cancer via modulating miR-361-3p/SOX4 axis.

BACKGROUND: Increasing researches have reported that circular RNA UBAP2 (circUBAP2) may be a potential prognosis biomarker and participate in the development of several cancers; however, the role of circUBAP2 in cervical cancer (CC) remains largely unclear. METHODS: We applied qRT-PCR and Western blot to examine expression levels of circUBAP2, miR-361-3p, SOX4, Bax, Bcl-2, Cleaved caspase 3, N-cadherin, Vimentin and E-cadherin. Cell proliferation, apoptosis, invasion and migration were analyzed by MTT assay, Flow cytometry, and Transwell assay, respectively. The interaction between miR-361-3p and circUBAP2 or SOX4 was confirmed by luciferase reporter assay and pull-down assay. Murine xenograft model was established by injecting SiHa cells which stably transfected sh-circUBAP2. RESULTS: CircUBAP2 was up-regulated in CC tissues and cell lines and high circUBAP2 expression predicated poor outcome. Knockdown of circUBAP2 suppressed cell proliferation, migration, invasion and EMT, while induced apoptosis in CC in vitro, and inhibited tumor growth and metastasis in vivo. MiR-361-3p directly bound to circUBAP2 or SOX4, and circUBAP2 could regulate SOX4 expression by sponging miR-361-3p in CC cells. Furthermore, rescue assay results demonstrated that the inhibitory effects of circUBAP2 knockdown on cell growth and metastasis were partially reversed by miR-361-3p down-regulation or SOX4 up-regulation in CC. CONCLUSION: CircUBAP2 represents a prognostic marker and contributes to tumor growth and metastasis via modulating miR-361-3p/SOX4 axis in CC, which indicates a potential therapeutic target for CC treatment.

An AKR1C3-specific prodrug with potent anti-tumor activities against T-ALL.

AKR1C3 overexpression has been reported in various types of cancers, including T-ALL. AST-006 (TH-3424), an AKR1C3-specific prodrug, was reported recently to have potent cytotoxicity against liver cancer cells overexpressing AKR1C3 and T-ALL. In this study, AST-006 demonstrated potent anti-tumor activity against different T-ALL cell lines in vitro and in vivo, including patient-derived xenograft (PDX) model. AST-006 also exhibited minimal cytotoxicity against primary human T-cells in vitro and lymphocytes in cynomolgus monkeys in vivo, indicating that AST-006 is a promising therapeutic for T-ALL.

Circular RNA expression profile in peripheral whole blood of lung adenocarcinoma by high: Throughput sequencing.

BACKGROUND: Lung adenocarcinoma (LA) is a most common form of non-small cell lung cancer (NSCLC). To date, there are still no effective early diagnosis methods for patients to be cured in time. Noncoding RNA plays an important role in oncogenesis and tumor development. The expression profile of circular RNA (circRNA) in peripheral whole blood (PWB) of LA has not been systematically investigated. In this study, we identified the differentially expressed (DE) circRNAs in PWB of LA by high-throughput sequencing. METHODS: Five paired LA and normal participants PWB samples were chosen to investigate the expression profile of circRNAs by high-throughput sequencing. Twenty LA and 10 normal controls PWB samples were subjected to reverse-transcription polymerase chain reaction (RT-PCR) for validation of circRNAs expression profile. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA-miRNA network analysis was also performed to predict the function of circRNAs in PWB. RESULTS: A total of 10566 circRNAs were identified and annotated, most of the circRNAs were exonic (78.14%). Statistical analysis revealed 4390 DE circRNAs, in which were 3009 upregulated circRNAs and1381downregulated circRNAs in LA. RT-PCR results showed that circRNA expression in LA was higher than that in controls. GO functional analysis, KEGG pathway analysis, and circRNA-miRNA network analysis all showed that circRNAs correlated with tumor development and progression to a certain degree. The current study is the first to systematically characterize and annotate circRNA expression in PWB of LA. Some host genes of the DE circRNAs were involved in tumor signaling pathway and had complicated correlations with tumor related miRNAs, indicating that circRNAs might involve in development and progression of LA. CONCLUSIONS: Our study revealed that circRNAs were abnormally expressed in PWB of LA, which might offer potential targets for the early diagnosis of the disease and new genetic insights into LA.