A Comparison of Clinicopathologic Outcomes and Patterns of Lymphatic Spread Across Neoadjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy, and Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) is recommended as the treatment standard for locally advanced esophageal squamous cell carcinoma (ESCC). The use of immunotherapy in the neoadjuvant setting has gained attention. Multiple, clinical trials have explored the efficacy and safety of neoadjuvant immunochemotherapy (NICT). We evaluated the differences in clinicopathologic outcomes and the patterns of lymphatic spread among patients receiving neoadjuvant chemotherapy (NCT), NCRT, and NICT before esophagectomy for locally advanced ESCC. METHODS: A total of 702 patients with ESCC who completed transthoracic esophagectomy followed neoadjuvant therapy were included. Pathological characteristics, including pathologic complete response (pCR), tumor regression grade (TRG) score and patterns of lymphatic spread, were evaluated. RESULTS: Compared with the NCT group, the NCRT group and NICT group had an advantage in pathological response (P < 0.05). The pCR rate was 8.1% in the NCT group, 29.9% in the NCRT group, and 23.6% in the NICT group. The TRG score (P < 0.05) and pathologic T stage (P < 0.05) in the NCT group were significantly higher. Compared with NICT, NCRT can significantly reduce the rate of lymph node metastasis rate in station 1R (0 vs. 3.4%, P < 0.05) and 2R (1.1% vs. 6.8%, P < 0.05). Subgroup analysis according to the tumor location distribution showed that NICT group had higher lymph node metastasis rate in station 2R (9.1%) in middle thoracic cases (P < 0.05) and in station 18 (7.5%) (P < 0.05) in lower thoracic cases. CONCLUSIONS: NCRT or NICT followed by surgery may result in a promising pCR rate and show a better performance in therapeutic response of primary lesion. For patients with lymph node metastasis in station 1R and 2R, NCRT should be the optimal preoperative treatment strategy.

Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215).

Background: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC. Methods: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768. Findings: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1-15.1). Median OS was 13.7 months (95% CI 9.3-17.7). Median DoR was 8.1 months (95% CI 1.7-10.6). ORR was 20% (95% CI 5.7-43.7). DCR was 95% (95% CI 75.1-99.9). CBR was 60% (95% CI 36.1-80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3-4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders. Interpretation: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population. Funding: This study was supported by the National Natural Science Foundation of China (82102954 to Wensi Zhao) and the Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).

Efficacy of endoscopic therapy for T1b esophageal cancer and construction of prognosis prediction model: a retrospective cohort study.

BACKGROUND: The efficacy of endoscopic therapy on the long-term survival outcomes of T1b oesophageal cancer (EC) is unclear, this study was designed to clarify the survival outcomes of endoscopic therapy and to construct a model for predicting the prognosis in T1b EC patients. METHODS: This study was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017 of patients with T1bN0M0 EC. Cancer-specific survival (CSS) and overall survival (OS) were compared between endoscopic therapy group, esophagectomy group and chemoradiotherapy group, respectively. Stabilized inverse probability treatment weighting was used as the main analysis method. The propensity score matching method and an independent dataset from our hospital were used as sensitivity analysis. The least absolute shrinkage and selection operator regression (Lasso) was employed to sift variables. A prognostic model was then established and was verified in two external validation cohorts. RESULTS: The unadjusted 5-year CSS was 69.5% (95% CI, 61.5-77.5) for endoscopic therapy, 75.0% (95% CI, 71.5-78.5) for esophagectomy and 42.4% (95% CI, 31.0-53.8) for chemoradiotherapy. After stabilized inverse probability treatment weighting adjustment, CSS and OS were similar in endoscopic therapy and esophagectomy groups ( P =0.32, P =0.83), while the CSS and OS of chemoradiotherapy patients were inferior to endoscopic therapy patients ( P <0.01, P <0.01). Age, histology, grade, tumour size, and treatment were selected to build the prediction model. The area under the curve of receiver operating characteristics of 1, 3, and 5 years in the validation cohort 1 were 0.631, 0.618, 0.638, and 0.733, 0.683, 0.768 in the validation cohort 2. The calibration plots also demonstrated the consistency of predicted and actual values in the two external validation cohorts. CONCLUSION: Endoscopic therapy achieved comparable long-term survival outcomes to esophagectomy for T1b EC patients. The prediction model developed performed well in calculating the OS of patients with T1b EC.

Radiotherapy plus camrelizumab and irinotecan for oligometastatic esophageal squamous cell carcinoma patients after first-line immunotherapy plus chemotherapy failure: An open-label, single-arm, phase II trial.

BACKGROUND AND PURPOSE: Immunotherapy has revolutionized the treatment of advanced and metastatic esophageal squamous cell carcinoma (ESCC), but most patients eventually developed disease progression. Immuno-resistance is becoming an unavoidable clinical problem. Oligometastasis is a limited-metastatic state, and patients at this stage should be evaluated for the addition of metastasis-directed local intervention, which may be associated with improved prognosis. As an immunomodulator, radiotherapy may exhibit synergistic effect when added to immunotherapy. This study assessed the efficacy and safety of low-dose radiotherapy plus immunotherapy and second-line chemotherapy in oligometastatic ESCC. MATERIALS AND METHODS: In this phase II trial (ChiCTR2000040533), oligometastatic ESCC patients after first-line immunotherapy plus chemotherapy failure were treated with low dose radiotherapy plus camrelizumab and second-line irinotecan chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety. Abscopal response rate (ARR) and abscopal control rate (ACR) were also been explored. RESULTS: Between November 19, 2018 and March 17, 2021, 49 patients were enrolled. With a median follow-up of 12.8 months, median PFS and OS were 6.9 months (95%CI, 4.6-9.3) and 12.8 months (95%CI, 10.1-15.5), respectively. ORR was 40.8% (95%CI, 27.3-55.7). DCR was 75.5% (95%CI, 60.8-86.2). ARR was 34.7% (95%CI, 22.1-49.7). ACR was 69.4% (95%CI, 54.4-81.3). The most common adverse effects of any grade were myelosuppression, weight loss and fatigue. Grade 3 or 4 treatment-related adverse events occurred in 31 (63.3%) patients, with the most common being leukopenia (30.6%). No treatment-related deaths occurred. CONCLUSION: Low dose radiotherapy plus camrelizumab and irinotecan exhibited survival benefit with manageable safety for oligometastatic ESCC patients after first-line immunotherapy plus chemotherapy failure. It deserves to be validated in a larger trial.

USP14 promotes colorectal cancer progression by targeting JNK for stabilization.

MAPK/JNK signaling is pivotal in carcinogenesis. However, ubiquitin-mediated homeostasis of JNK remains to be verified. Here, with results from RNA sequencing (RNA-seq) and luciferase reporter pathway identification, we show that USP14 orchestrates MAPK/JNK signaling and identify USP14 as a deubiquitinase that interacts and stabilizes JNK. USP14 is elevated in colorectal cancer patients and is positively associated with JNK protein and downstream gene expression. USP14 ablation reduces cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by downregulating MAPK/JNK pathway activation. Moreover, USP14 expression is induced by TNF-α, forming a feedback loop with JNK and leading to tumor amplification. Our study suggests that elevated expression of USP14 promotes MAPK/JNK signaling by stabilizing JNK, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased USP14 expression.

Circ_0011385 knockdown inhibits cell proliferation, migration and invasion, whereas promotes cell apoptosis by regulating miR-330-3p/MYO6 axis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor. Recent studies have showed circular RNA (circRNA) participates in the development of CRC. The study was designed to reveal the role of circ_0011385 in CRC progression and underneath mechanism. METHODS: The expression circ_0011385, microRNA-330-3p (miR-330-3p) and myosin VI (MYO6) mRNA were determined by quantitative real-time polymerase chain reaction. Protein expression was detected by Western blot assay. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), cell colony formation and flow cytometry assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by wound-healing assay and transwell invasion assay, respectively. The binding sites between miR-330-3p and circ_0011385 or MYO6 were predicted by CircInteractome or starBase online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS: Circ_0011385 and MYO6 expression were dramatically upregulated, while miR-330-3p expression was downregulated in CRC tissues or cells compared with control groups. Circ_0011385 expression was associated with tumor size, tumor-node-metastasis stage (TNM) stage and lymph node metastasis of CRC patients. Circ_0011385 silencing or MYO6 absence repressed cell proliferation, migration and invasion, whereas induced cell apoptosis in CRC. Additionally, miR-330-3p inhibitor or MYO6 overexpression attenuated the repressive impacts of circ_0011385 silencing on CRC process. Circ_0011385 was associated with miR-330-3p, and miR-330-3p targeted MYO6. Circ_0011385 knockdown inactivated MEK1/2/ERK1/2 signaling pathway by miR-330-3p/MYO6 axis. Furthermore, circ_0011385 knockdown suppressed tumor growth in vivo. CONCLUSION: Circ_0011385 regulated CRC process by miR-330-3p/MYO6 axis through MEK1/2/ERK1/2 signaling pathway, providing a novel therapeutic target for CRC.

An exploratory clinical trial of apatinib combined with intensity-modulated radiation therapy for patients with unresectable hepatocellular carcinoma.

PURPOSE: To evaluate the clinical efficacy and safety of apatinib combined with intensity-modulated radiation therapy (IMRT) in patients with unresectable hepatocellular carcinoma (uHCC). MATERIALS AND METHODS: Open-label, single-arm, exploratory clinical trial of apatinib combined with IMRT for uHCC patients. Patients aged 18-75 years with adequate hematological, liver, and renal functions and Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were enrolled in this study from March 2017 to September 2020. Patients were received IMRT (biological effective dose: 46-60 Gy) and continuous apatinib (250-500 mg/day) oral administration until HCC progression or unacceptable toxic effects. The endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and safety. The trial registration number is ChiCTR-OPC-17011890. RESULTS: A total of 33 patients have taken part in the study. The median age was 58 years old (range 32-77), 27 (81.9%) patients were ECOG PS 0-1, and 28 (84.9%) patients were male. In addition, 25 (75.7%) patients suffered from hepatitis B, 32 cases (97.0%) were in Barcelona Clinic Liver Cancer (BCLC) Stages B-C, and eight (24.2%) had portal vein involvement. Moreover, 12 (36.4%) and 21 (63.6%) patients received apatinib as first-line and second or later-line therapy, respectively. The average follow-up was 11.4 months, the median PFS was 7.8 months (95% confidence interval: 3.9-11.7). The OS rates at 6 and 12 months were 96.7% and 66.2%. The ORR and DCR were 15.1% and 81.8%, respectively. Hepatic toxicity was the most common treatment-related adverse events in Grades 3-4 (12.1%). No radiation-induced liver disease and Grade 5 toxicity were recorded. CONCLUSION: Apatinib combined with IMRT is a safe and effective method to improve PFS and DCR and has good anti-tumor activity in patients with uHCC.

Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma.

Importance: The optimal treatment for and potential benefit populations of synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC) remain unclear. Objectives: To evaluate outcomes of concurrent chemoradiotherapy (CCRT) and to construct decision tree models for predicting the risk of progression and mortality in patients with SOESCC. Design, Setting, and Participants: This prognostic study included 532 patients with SOESCC who were treated at 2 cancer centers in China from January 2012 to December 2018 and consisted of a development cohort (n = 381) and a validation cohort (n = 151). Data were analyzed from March 2019 to December 2021. Exposures: All patients received chemotherapy alone or CCRT. Main Outcomes and Measures: The primary end points of the study were progression-free survival (PFS) and overall survival (OS), and the secondary end points were locoregional control and treatment-related toxic effects. Propensity score matching was performed to control potential confounding factors. Cox regression was used to screen important explanatory variables. Decision trees for optimally partitioning patients were established using recursive partitioning analysis and were then subjected to internal and independent external validation. Results: Among the 532 patients (median [range] age, 63 [32-82] years; 367 men [69.0%]), 292 patients received chemotherapy alone and 240 patients underwent CCRT. With a median (IQR) follow-up time of 37.0 (21.6-55.8) months, CCRT was associated with improved objective response rate (139 of 240 [57.9%] vs 123 of 292 [42.1%]; P < .001), median (IQR) PFS (9.7 [8.5-10.9] months vs 7.6 [6.6-8.6] months; P < .001), and median (IQR) OS (18.5 [16.1-20.9] months vs 15.2 [13.6-16.8] months; P < .001) compared with chemotherapy alone. Propensity score matching analysis verified the results. Cox multivariate analysis indicated that treatment modality (CCRT vs chemotherapy alone) was an independent prognostic factor related to PFS (hazard ratio, 0.69; 95% CI, 0.57-0.83; P < .001) and OS (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008). The final decision trees divided patients with SOESCC into low-, intermediate-, and high-risk groups in both the internal and external validations, and the corresponding cumulative risk function curves had significant differences (all P < .001). Time-dependent maximum areas under receiver operating curves of decision trees for progression risk at 3 years and mortality risk at 5 years were 0.820 (95% CI, 0.693-0.948) and 0.894 (95% CI, 0.822-0.966), respectively. Calibration curves also demonstrated that the decision trees had favorable performance of risk stratification. Conclusions and Relevance: In this study, CCRT vs chemotherapy alone as a first-line treatment for patients with SOESCC had superior survival. Patients with low risk had promising long-term survival based on the current treatment modality. The predictive information of the decision tree could provide accurate decision-making for the management of patients with SOESCC.

Regional Lymph Node Metastasis and Axillary Surgery of Microinvasive Breast Cancer: A Population-Based Study.

Microinvasive breast cancer (MBC for short) is a rare entity with the decision of axillary surgery under debate in clinical practice. We aimed to unravel the lymph node metastasis (LNM) rate, axillary surgery, and prognosis of MBC based on 11,692 patients derived from the Surveillance Epidemiology and End Results (SEER) database between 2003 and 2015. In this retrospective study, 19.5% (2276/11,692) of patients received axillary lymph node dissection (ALND), 80.5% (9416/11,692) received non-ALND. In the total cohort, 10-year breast cancer-specific survival (BCSS) was 96.3%, and the LNM rate was 6.4% (754/11,692). Multivariate analyses showed that LNM had the strongest predictive weight (N3, HR 14.200, 95% CI 7.933−25.417; N2, HR 12.945, 95% CI 7.725−21.694; N1, HR 3.05, 95% CI 2.246−4.140, all p < 0.001). Kaplan−Meier analyses showed that ALND did not confer a survival benefit on 10-year BCS in patients with N0 (94.7% vs. 97.1%, p < 0.001) and in patients with 1−2 positive nodes (92.1% vs. 89.5%, p = 0.355), respectively, when compared to non-ALND. Our study demonstrated that the vast majority of MBC have a low LNM rate and excellent prognosis; patients with LNM showed poor prognosis. Assessment of lymph node status is necessary, and non-ALND surgery is required and sufficient for MBC with 0−2 positive nodes.

Preoperative Chemotherapy for Limited-stage Small Cell Carcinoma of the Esophagus.

BACKGROUND: The optimal treatment approach for limited-stage small cell carcinoma of the esophagus remains uncertain. This study aimed to evaluate the efficacy and safety of preoperative chemotherapy in combination with surgery vs upfront surgery in those patients. METHODS: From June 2001 to June 2015, a total of 280 patients with limited-stage small cell carcinoma of the esophagus were screened from 60 131 patients with esophageal cancer. Outcome analysis of those patients who underwent preoperative chemotherapy in combination with surgery or upfront surgery was conducted. The primary end point was overall survival, and secondary end points included progression-free survival and safety. RESULTS: Of the 280 patients, 200 were men (71.4%), the median age was 64 years (range, 42-75 years), 171 patients (61.1%) patients had preoperative chemotherapy in combination with surgery, and 109 patients (38.9%) underwent upfront surgery. A pathologic complete response rate of 8.8% was noted in patients who received preoperative chemotherapy. Compared with the upfront surgery group, the preoperative chemotherapy group had a better median overall survival (26.0 months vs 19.5 months, respectively; hazard ratio, 0.69; 95% CI, 0.51 to 0.92; P = .011) and a prolonged progression-free survival (16.0 months vs 13.0 months, respectively; hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P = .039). Postoperative complications and peritreatment mortality were comparable between both groups. CONCLUSIONS: Compared with upfront surgery, preoperative chemotherapy in combination with surgery improves overall survival in patients with limited-stage small cell carcinoma of the esophagus.

Bivalent ß-Carbolines Inhibit Colorectal Cancer Growth through Inducing Autophagy.

In this study, a series of alkyl diamine linked bivalent ß-carbolines was synthesized and evaluated as antitumor agent. The results demonstrated that most compounds displayed good antiproliferative activities with IC50 value lower than 10 µM against a panel of human tumor cell lines, and compound 8 was found to be the most potent antiproliferative agent with IC50 value of 1.39, 1.96, 1.42, 1.49, 1.32, 1.96 and 1.63 µM against human breast cancer cell line (MCF-7), human adenocarcinoma cell line (769-P), human malighant melanoma cell line (A375), human ovarian cancer cell line (SK-OV-3), human colon carcinoma cell line (HCT-116), human gastric cancer cell line (BGC-823) and human esophageal squamous carcinoma cell line (Eca-109), respectively. Further investigations on mechanism of action of this class of compound demonstrated that the representative compound 8 inhibited colorectal cancer growth through inducing autophagy.

Survival impact of concurrent chemoradiotherapy for elderly patients with synchronous oligometastatic esophageal squamous cell carcinoma: A propensity score matching and landmark analyses.

PURPOSE: To evaluate the potential benefits of concurrent chemoradiotherapy (CCRT), and to establish a nomogram for predicting survival outcomes of elderly patients with synchronous oligometastatic esophageal squamous cell carcinoma (SOEC). MATERIALS AND METHODS: This study eventually enrolled 314 elderly patients who initially diagnosed with SOEC from two centers. Treatment responses and outcomes of 151 patients receiving CCRT and 163 patients undergoing chemotherapy alone (CT) were compared. Propensity score matching and landmark analyses were performed to control potential confounding factors. A nomogram was established on the basis of the Cox regression model. RESULTS: After a median follow-up of 42.3 months, CCRT was superior to CT alone in objective response rate (ORR, 59.6% vs. 39.9%, P < 0.001), median progression-free survival (PFS, 10.0 vs. 7.2 months, P < 0.001), and median overall survival (OS, 18.5 vs. 15.6 months, P < 0.001). The propensity score matching (PSM) and landmark analyses redemonstrated the same trend (P < 0.01). On hierarchical analysis, patients with 1-3 metastatic lesions involving one organ displayed longer median PFS (9.0 vs. 7.8 months, P = 0.008) and OS (17.8 vs. 15.2 months, P < 0.001) than those with 4-5 metastatic lesions involving 2-3 organs. The major toxicities of grade III or higher for CCRT included leukocytopenia (23.2%), radiation esophagitis (7.3%), and radiation pneumonitis (8.6%). Cox multivariate analysis showed that the number of metastatic lesions (P = 0.012) and tumor response (P < 0.001) were independent prognostic factors associated with OS. A nomogram was established by incorporating the number of metastatic lesions and tumor response, with a concordance index of 0.743 after internal cross-validation. Calibration curves and decision curve analysis confirmed that nomogram had a favorable predictive value for individualized survival. CONCLUSIONS: Compared with CT alone, CCRT exhibited superior efficacy and acceptable toxicity in the first-line treatment for elderly patients with SOEC. The current study supports the oligometastatic definition of ≤3 metastatic lesions involving one organ for esophageal cancer patients. The constructed nomogram can effectively predict the individualized survival.

Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation.

OBJECTIVE: Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorly estimated. Thus, this study aimed to investigate the expressions of key regulators of apoptosis and autophagy in matched paired samples of primary and recurrent ESCC. METHODS: The medical records of patients with locally advanced ESCC who developed local recurrence after dCRT were reviewed, and the expression profiling of apoptosis-related genes, cell apoptosis, autophagy and autophagy-related proteins were detected in normal esophageal squamous epithelium and paired samples of primary and recurrent ESCC. RESULTS: A total of 126 patients were enrolled, and 52.4% of them had stage III disease. The 1-, 3- and 5-year local recurrence-free survival (LRFS) rates were 54.8, 19.8 and 14.3%, respectively, with a median LRFS of 13.0 months. Patients with T2 tumor or stage II disease showed a significantly prolonged LRFS compared with that of patients with T3-4 tumor or stage III disease. The Apoptotic Machinery key genes expression profiling identified 5 upregulated and 7 downregulated apoptosis-related genes in recurrent tumors compared with their expression levels in the matched primary ESCC tumors. High expression of CD40, TRAF4 and BCL2A1, and low expression of CARD6 and TNFRSF21 were associated with increased risk of early local recurrence after dCRT. No differences in apoptotic index between primary and recurrent samples were detected. However, typical morphological features of autophagosomes and elevated LC3-II protein expression were detected in recurrent tumor samples, and positive LC3-II expression was correlated with increased risk of early local recurrence. CONCLUSION: Our findings indicated that apoptosis and autophagy dysfunction correlated with early local recurrence in patients with locally advanced ESCC receiving dCRT. Further studies are necessary to understand the biology of tumor recurrence in esophageal cancer.

Clinical considerations for the management of cancer patients in the mitigation stage of the COVID-19 pandemic.

The ongoing outbreak of the coronavirus disease 2019 (COVID-19) has become an unprecedented threat to public health around the world. The crisis has also brought great challenges to the routine diagnosis and treatment of cancer patients, especially given the urgency and continuity of cancer care. Cancer patients need to be more prudently and individually managed to combat COVID-19. At present, the COVID-19 epidemic in some countries has moved from the outbreak phase to the remission phase. How to preserve high-quality anti-tumor therapy for cancer patients while maintaining strict prevention and control of COVID-19 is a matter of concern. Here, we summarized essential data about COVID-19 and cancer and provided the clinical recommendations for the management of cancer patients during the COVID-19 pandemic based on our practical experience and relevant literatures.

ALG3 contributes to the malignancy of non-small cell lung cancer and is negatively regulated by MiR-98-5p.

OBJECTIVE: Alpha-1,3-mannosyltransferase (ALG3) is an oncoprotein associated with multiple malignancies. We aimed to investigate the role and potential mechanisms of ALG3 in non-small cell lung cancer (NSCLC). METHODS: We detected the expressions of ALG3 in NSCLC tissues and adjacent tissues by RT-PCR, western blot and immunohistochemistry, respectively. Chi-square test was used to analyze the correlation between ALG3 expression and pathological paremeters. Then we used shRNA to construct a low expression model of ALG3 in NCI-H292 and NCI-H460. CCK-8 assay and transwell assay were then performed to monitor the proliferation, migration and invasion of NSCLC cells. Western blot was to detect the expression of EMT-related indicators. Further, the interaction of miR-98-5p with ALG3 was verified by luciferase reporter assay. RESULTS: The expression of ALG3 in NSCLC tissues was higher than that in normal tissues, and the increase in ALG3 expression was significantly associated with higher T stage, lymph node metastasis, and poor tissue differentiation. Patients with high ALG3 expression had a worse prognosis. ALG3 knockdown inhibited the proliferation, migration and invasion of NSCLC cells. In addition, the knockdown of ALG3 resulted in increased expression of EMT-related protein E-cadherin, while N-cadherin and Vimentin expression was decreased. Dual luciferase assay confirmed that miR-98-5p can specifically bind to the 3'UTR of ALG3 and reduces its expression and activity. CONCLUSION: ALG3 can promote the progression of NSCLC and is negatively regulated by miR-98-5p.

Knockdown of circRNA circ_0087378 Represses the Tumorigenesis and Progression of Esophageal Squamous Cell Carcinoma Through Modulating the miR-140-3p/E2F3 Axis.

BACKGROUND: We aimed to investigate the function and underlying mechanisms of circ_0087378 in esophageal squamous cell carcinoma (ESCC). METHODS: We verified higher circ_0087378 expression in ESCC tissues by performing qRT-PCR assays. We further confirmed the oncogenic roles of circ_0087378 in ESCC cells through a series of biological function assays. Then, we used an RNA pull-down assay and luciferase reporter assay to identify miR-140-3p that directly interacts with circ_0087378. Subsequent studies were performed to demonstrate that the circ_0087378/miR-140-3p/E2F3 axis promotes ESCC development. RESULTS: We demonstrated that upregulated circ_0087378 expression was positively associated with tumor size, histological grade, tumor stage, the presence of metastasis, and worse survival in patients with ESCC. Our results further revealed that knockdown of circ_0087378 suppressed the proliferation, migration, and invasion of ESCC cells and reduced tumor growth in vivo. Mechanistically, we showed that circ_0087378 could directly bind to miR-miR-140-3p and relieve the suppression for target E2F3, which accelerated cell proliferation, migration, and invasion. Correlation analysis in ESCC specimens supported the involvement of the circ_0087378/miR-140-3p/E2F3 axis in ESCC progression. CONCLUSIONS: This study demonstrated that circ_0087378 might act as a competing endogenous RNA for miR-140-3p, which could inhibit the tumorigenesis and progression of ESCC through upregulating E2F3 expression.

Long-Non Coding RNA SNHG16 Supports Colon Cancer Cell Growth by Modulating miR-302a-3p/AKT Axis.

Small nucleolar RNA host gene 16 (SNHG16) is reported to be involved in the tumorigenesis of various kinds of tumors. SNHG16 expression was reported to be upregulated in colon cancer, however, the underlying mechanism of how SNHG16 affects the colon cancer development remains poorly elucidated. In our study, with the aim to identify the role of SNHG16 on colon cell proliferation, SNHG16 was overexpressed or knocked down in vitro, respectively. SNHG16 overexpression accelerated colon cancer cell growth, while cell growth ability was impaired in SNHG16 silencing cells. Furthermore, the starBase database predicted that miR-302a-3p was the target gene of SNHG16, which was supported by dual luciferase assay. The effect of promoting cell proliferation ability induced by SNHG16 overexpression could be partly reversed by co-transfection of miR-302a-3p mimic. Application of the miRanda database indicated that AKT may be modulated by SNHG16, further evidenced by western blot and quantitative PCR assays. AKT overexpression could partly reverse the attenuated colon cancer cell growth caused by miR-302a-3p mimic transfection. Meanwhile, the combination of miR-302a-3p inhibitor and shAKT achieved the parallel result. In conclusion, our study revealed the SNHG16/miR-302a-3p/AKT axis might play a crucial role in colon cancer cell proliferation, thus participating in the process of colon cancer development.

Neoadjuvant nimotuzumab plus chemoradiotherapy compared to neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma.

Neoadjuvant therapy improves long-term locoregional control and overall survival after surgical resection for esophageal cancer, and neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) are commonly used in clinical practice. Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR), the efficacy of nimotuzumab added to nCRT for esophageal cancer is uncertain. We conducted this retrospective study in which combining neoadjuvant treatment of nimotuzumab with chemoradiotherapy (Nimo-nCRT) is compared with nCRT and nCT for patients with potentially resectable locally advanced esophageal squamous cell carcinoma. One hundred ninety-five patients received neoadjuvant therapy and 172 (88.2%) underwent esophagectomy. Surgical resection was performed in 94.4% after Nimo-nCRT, versus 92.5% after nCRT and 83.5% after nCT (P = 0.026). The R0 resection rate was 100% after Nimo-nCRT, 95.9% after nCRT and 92.6% after nCT (P = 0.030). Pathological complete response (pCR) was achieved in 41.2% after Nimo-nCRT, versus 32.4% after nCRT and 14.8% after nCT (P = 0.0001). Lymph-node metastases were observed in 29.4% in the Nimo-nCRT group, versus 21.6% in the nCRT group and 35.8% in the nCT group (P = 0.093). More patients in the Nimo-nCRT and nCRT group developed grade 3 esophagitis compared to those in the nCT group, P = 0.008. There was no difference in surgical complications between the treatment groups. nCRT results in improved R0 resection, higher pCR rate, and a lower frequency of lymph node metastases compared to nCT, adding nimotuzumab to nCRT is safe and appears to facilitate complete resection and increase the pCR rate.