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Peng Qi,1–3 Wan-run Lin,4 Meng Zhang,1–3 Dan Huang,1–3 Shu-juan Ni,1–3 Xiao-li Zhu,1–3 Qian-ming Bai,1–3 Wei-qi Sheng,1–3 Xiang Du,2 Xiao-yan Zhou1–3 1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Institute of Pathology, Fudan University, Shanghai, China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 4Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA Background: Long noncoding RNAs (lncRNAs) have been shown to play important regulatory roles in human cancer. We previously verified that the lncRNA long stress-induced noncoding transcript 5 (LSINCT5) is overexpressed in gastric cancer (GC) cells and closely correlated with cell proliferation and patient prognosis. However, whether aberrant LSINCT5 expression has an important effect on GC progression is unclear, and the potential mechanisms remain unknown. In GC, E2F1 expression is also aberrant, but the biological functions of E2F1 are controversial, and the correlation between E2F1 and lncRNAs remains unknown. Materials and methods: Expression of LSINCT5 was analyzed in metastatic GC tissues compared with nonmetastatic tissues using quantitative real-time PCR (qRT-PCR) assays. Gain and loss of function approaches were used to investigate the biological role of LSINCT5 in GC cell migration and invasion. A computational screen of LSINCT5 promoter was conducted to search for transcription factor-binding sites. LSINCT5 promoter activities were examined by ChIP and luciferase reporter assays. qRT-PCR and western blotting assays were performed to detect the expression of multiple EMT markers in cells in which LSINCT5 was overexpressed or knocked down. Results: An integrated quantitative analysis revealed that LSINCT5 was significantly overexpressed in metastatic GC tissues. Forced LSINCT5 expression promoted cell migration and invasion, whereas loss of LSINCT5 function decreased cell migration and invasion. Mechanistic investigations showed that LSINCT5 is a direct transcriptional target of E2F1. Moreover, LSINCT5 overexpression was found to play an important role in the epithelial-to-mesenchymal transition by regulating the expression of E-cadherin, N-cadherin, vimentin, and matrix metalloproteinase-2. Conclusion: These data suggest that E2F1-mediated activation of LSINCT5, a regulator of cell migration and invasion, constitute the mechanistic link between the E2F1-mediated pathway and lncRNA that regulates cell migration and invasion. Thus, LSINCT5 may be a target for new GC therapies. Keywords: E2F1, LSINCT5, metastasis, gastric cancer

Shujuan Ni,1,2,* Weiwei Weng,1,2,* Midie Xu,1,2 Qifeng Wang,1,2 Cong Tan,1,2 Hui Sun,1,2 Lei Wang,1,2 Dan Huang,1,2 Xiang Du,1,2 Weiqi Sheng1,2 1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China *These authors contributed equally to this work Background: Although miR-106b-5p has been reported to play a pivotal role in various human malignancies, its role in colorectal cancer (CRC) remains unknown. In this study, we comprehensively investigated miR-106b-5p expression and biologic functions in CRC and the molecular mechanism involved. Patients and methods: miR-106b-5p expression was detected in CRC tissues and cell lines by quantitative reverse transcription-polymerase chain reaction. The effects of miR-106b-5p on metastasis were determined in vitro using transwell assays, and in vivo effects were evaluated using a mouse tail vein injection model. Downstream targets of miR-106b-5p were confirmed using bioinformatics programs, luciferase assays, and rescue experiments. Target gene expression and clinicopathologic parameters were also analyzed. Results: miR-106b-5p expression was lower in CRC tissues than in corresponding nontumorous tissues (P=0.009), and miR-106b-5p downregulation was negatively associated with lymph node metastasis (P=0.006). Functional assays demonstrated that miR-106b-5p overexpression suppressed CRC cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, luciferase assays confirmed that miR-106b-5p directly bound to the 3' untranslated region of cathepsin A (CTSA) and that miR-106b-5p suppressed CRC cell migration and invasion by targeting CTSA. Clinicopathologic analysis showed that CTSA was significantly upregulated in CRC, and increased CTSA was negatively associated with lymph node metastasis (P=0.012). Conclusion: Our findings revealed that miR-106b-5p inhibits CRC metastasis by upregulating CTSA expression, which may lead to novel therapeutic strategies for CRC patients. Keywords: colorectal cancer, metastasis, miR-106b-5p, cathepsin A

Objective: The purpose of this study was to investigate the clinical and histopathological characteristics of GLUT1 in human tongue squamous cell carcinoma (TSCC) and the role of plumbagin (PLB)‐mediating GLUT1 in the growth of TSCC. Subjects and methods: Forty‐five cases of TSCC samples were collected and the expression and location of GLUT1 was analyzed. The role and mechanism of PLB meditating GLUT1 in the inhibitory growth of human TSCC cell line CAL27 were investigated in vitro and vivo. Results: The expression of GLUT1 was observed in all samples of human TSCC by immunohistochemical staining. GLUT1 expression was significantly correlated with lymph node metastasis and clinical stage in TSCC. PLB treatment decreased cell viability and colony formation, and increased cell apoptosis in association with the downregulation of GLUT1 via inhibiting PI3K/Akt pathway in vitro and PLB suppressed tumor growth in correlation with downregulation of GLUT1, compared with control group in vivo. Conclusions: The findings demonstrated a novel anti‐cancer mechanism of PLB, inhibitory TSCC growth via suppressing PI3K/Akt/GLUT1 pathway, which will supply a theoretical basis for PLB to treat TSCC. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to assess the effect of apical lymph node ( APN) metastasis in predicting prognosis in curatively treated node-positive rectal cancer. We also investigated the relationship between APN metastasis and the total number of metastatic lymph nodes. Method A retrospective study was performed of 510 curatively treated patients with node-positive rectal cancer. Clinicopathological variables, including APN status, were assessed in univariate and multivariate analyses. The prognostic significance of APN status in predicting patient outcomes and the relationship between APN status and American Joint Committee on Cancer ( AJCC) N stage were analysed. Results At a median follow up of 47 months, the 5-year local recurrence ( LR) rate, the disease-free survival ( DFS) rate and the overall survival ( OS) rate were 18.3%, 55.5% and 58.8%, respectively. The 5-year OS rate was 69.6% for patients with no metastasis in APNs ( APN(−)) and 40.8% for patients with metastasis in APNs ( APN(+)). DFS and OS for patients with undetermined APN status were between those for APN(−) and APN(+). Subgroup analysis gave a 5-year OS rate of 48.7% in Stage N1 patients with APN(+) and 58.8% for Stage N2 patients with APN(−) ( P = 0.0004). Conclusion APN metastasis is an important prognostic factor in node-positive rectal cancer, which provides additional survival-related prognostic classification irrespective of N stage. As the APN is usually outside the radiation field, in the era of multidisciplinary treatment its assessment should be incorporated into prognostic evaluation of rectal cancer. [ABSTRACT FROM AUTHOR]

The article reports on the study that evaluates the frequency of metastases in urologic organs found at autopsy of ovarian carcinoma patients. It observes 21.2% of patient with hydronephrosis and 55.6% had ureteral involvement. It suggests that hydronephrosis in late stages of ovarian carcinoma usually attributed to extrinsic compression of the ureter by an abdominal tumor.

Aim: To retrospectively analyse the clinical and MRI data of primary squamous cell carcinoma (SCC), particularly pure squamous cell carcinoma (PSCC) and mixed squamous cell carcinoma (MSCC).Materials and Methods: The MRI data and clinicopathological characteristics of 20 patients with histopathologically confirmed SCC of the breast, including eight PSCC patients and 12 MSCC patients, from multiple centres between January 2013 and December 2020 were analysed retrospectively.Results: Nine of 12 patients in the MSCC group showed hyperintensity on T1-weighted imaging (WI), while this feature was not observed in the PSCC group (p=0.001). Most of the PSCC group showed rim enhancement, whereas most of the MSCC group showed heterogeneous enhancement (p=0.007). In addition, there was no significant difference in the thickness of the rim enhancement and the percentage of necrotic components in the tumours between the two types of SCCs of the breast (p=0.545 and p=0.662, respectively). Four patients (4/12) in the MSCC group had sentinel lymph node metastasis, while only one patient (1/8) in the PSCC group showed lymph node metastasis (p=0.603). Metastatic disease occurred in 25% of patients with PSCC and in approximately 41.7% of patients with MSCC.Conclusion: The signal on T1WI and internal enhancement characteristics were the key features for differentiating PSCC and MSCC. Therefore, MRI phenotypes may provide additional information for the pathological classification of breast SCC. [ABSTRACT FROM AUTHOR]

We evaluated the impact of staging procedures to detect asymptomatic distant metastases (DM) in the management of women with operable invasive breast cancer (BC, entire cohort: n = 866). Out of 472 patients with lymph node (LN)-negative disease (pN0), DM were found in four cases (detection rate: 0.8%). All four patients presented with established risk factors: hormone receptor (HR)-negative status, HER2-positive status, n = 3; ‘triple-negative’ disease, n = 1. Considering the subgroup of LN-negative patients whose tumors showed the risk factor ‘negative HR status’ (n = 66), the detection rate of DM was 6%. The detection rates of DM in higher pN categories were as follows: pN1:1.7%; pN2:9.5%; pN3:13.5%. We generally support the international guidelines, including those published by the European Society for Medical Oncology (ESMO) which emphasize that patients with early-stage BC do not profit from radiological staging for the detection of DM and recommend refraining from this. However, we would expand these guidelines and propose that screening should be carried out in node-negative patients whose tumors show established tumor-related risk factors (e.g. HR-negative and HER2-positive status), since in this particular subcohort, the detection rate of DM is with 6% similarly high as that of patients with four to nine positive LNs. [ABSTRACT FROM PUBLISHER]

Background: Nasopharyngeal carcinoma (NPC) has a highly metastatic character in the clinic, but the underlying mechanism of action is unclear. N,N'-dinitrosopiperazine (DNP), a carcinogen with organ specificity for the nasopharyngeal epithelium, is involved in metastasis of NPC. Findings: Anterior gradient 2 (AGR2) was overexpressed in human NPC tissues, especially in cervical lymph node metastatic NPC (LMNPC). High AGR2 expression was associated with NPC metastasis. DNP induced AGR2 expression and increased cell motility and invasion in the NPC cell line 6-10B. However, DNP-mediated cell motility and invasion was substantially decreased when transfected with siRNA-AGR2. Furthermore, AGR2 directly regulated cathepsin B and D by binding them in vitro. Interpretation: These results indicate that DNP induces AGR2 expression, regulates cathepsin B and D, increases cell motility and invasion, and promotes NPC tumour metastasis. Therefore, DNP-mediated AGR2 expression may be an important factor in prolific NPC metastasis. [ABSTRACT FROM AUTHOR]