Inhibition of DDR1 promotes ferroptosis and overcomes gefitinib resistance in non-small cell lung cancer.

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which serves the critical pillar for the treatment of non-small cell lung cancer (NSCLC). However, the acquired resistance remains a challenge for its clinical application, for which, practical strategies to reverse gefitinib resistance in NSCLC are necessary. Ferroptosis, a programmed cell death driven by ferritin-dependent lipid peroxidation, involves in NSCLC progression and related chemoresistance.

A CTL-Inspired Killing System Using Ultralow-Dose Chemical-Drugs to Induce a Pyroptosis-Mediated Antitumor Immune Function.

A Cytotoxic T lymphocyte-inspired system capable of using ultralow-dose chemical drugs to manipulate cell death is needed to investigate the antitumor immunotherapy. Recent studies reveal pyroptosis promotes antitumor immune function. However, high-dose chemotherapy leads to cytokine release syndrome by pyroptosis.

A cytotoxic T cell inspired oncolytic nanosystem promotes lytic cell death by lipid peroxidation and elicits antitumor immune responses.

Lytic cell death triggers an antitumour immune response. However, cancer cells evade lytic cell death by several mechanisms. Moreover, a prolonged and uncontrolled immune response conversely leads to T-cell exhaustion.

Sparse-to-dense coarse-to-fine depth estimation for colonoscopy.

Colonoscopy, as the golden standard for screening colon cancer and diseases, offers considerable benefits to patients. However, it also imposes challenges on diagnosis and potential surgery due to the narrow observation perspective and limited perception dimension. Dense depth estimation can overcome the above limitations and offer doctors straightforward 3D visual feedback.

Discovery of 4-methoxy-N-(1-naphthyl)benzenesulfonamide derivatives as small molecule dual-target inhibitors of tubulin and signal transducer and activator of transcription 3 (STAT3) based on ABT-751.

Overexpressed tubulin and continuously activated STAT3 play important roles in the development of many cancers and are potential therapeutic targets. A series of 4-methoxy-N -(1-naphthalene) benzenesulfonamide derivatives were designed and optimized based on β-tubulin inhibitor ABT-751 to verify whether STAT3 and tubulin dual target inhibitors have better antitumor effects. Compound DL14 showed strong inhibitory activity against A549, MDA-MB-231 and HCT-116 cells in vitro with IC values of 1.

Mir-4746 inhibits the proliferation of colorectal cancer cells in vitro and in vivo by targeting CCND1.

Colorectal cancer (CRC) is a commonly seen malignant tumor manifesting itself in the digestive tract, but it remains unclear what is the molecular mechanism behind its occurrence and development, which can have a significant impact on the clinical diagnosis and treatment of CRC. According to some studies, microRNA (miRNA) plays an essential role in the occurrence and development of cancer. In spite of this, there are still many miRNAs that play an important role in the progression of CRC but have yet to be reported.

m(6)A demethylase ALKBH5 inhibits cell proliferation and the metastasis of colorectal cancer by regulating the FOXO3/miR-21/SPRY2 axis.

Objective: Colorectal cancer is a common malignancy worldwide. This research aimed to investigate the role of α-ketoglutarate-dependent dioxygenase alkB homologue 5 (ALKBH5), a N-methyladenosine (m(6)A) demethylase, on the cell proliferation and metastasis of colorectal cancer.

Methods: The interaction relationship between FOXO3, miR-21, and SPRY2 were predicted by starBase 2.

Discovery of N-substituted sulfamoylbenzamide derivatives as novel inhibitors of STAT3 signaling pathway based on Niclosamide.

Signal transducer and activator of transcription 3 (STAT3) has been confirmed as an attractive therapeutic target for cancer therapy. Herein, we designed and synthesized a series of N-substituted Sulfamoylbenzamide STAT3 inhibitors based on small-molecule STAT3 inhibitor Niclosamide. Compound B12, the best active compound of this series, was identified as an inhibitor of IL-6/STAT3 signaling with an IC of 0.

MEG3 can affect the proliferation and migration of colorectal cancer cells through regulating miR-376/PRKD1 axis.

The down-regulation of long non-coding RNA (lncRNA) MEG3 has been observed in various cancers; nonetheless, underlying mechanisms are still unclear. The current research work aims at exploring the roles of MEG3 in the pathogenesis of CRC and the associated mechanism. We observed that MEG3 was significantly down-regulated in both CRC tumor tissue and cell lines; also, the transient over-expression of MEG3 in CRC cell line SW480 and LoVo inhibited the proliferation and the migration and clone formation capability of cells; on the other hand, the knockdown of MEG3 has revealed opposite effects.

Design, Synthesis, And Evaluation Of Cyanopyridines As Anti-Colorectal Cancer Agents Via Inhibiting STAT3 Pathway.

Background: Colorectal cancer is one of the common malignant tumors. Cyanopyridine and aminocyanopyridine having a carbon-nitrogen bond have been shown to have significant anticancer effects. STAT3 is a promising therapeutic target in multiple cancers.

Flubendazole demonstrates valid antitumor effects by inhibiting STAT3 and activating autophagy.

Background: Signal transducer and activator of transcription 3 (STAT3) is an oncogene, which upregulates in approximately 70% of human cancers. Autophagy is an evolutionarily conserved process which maintains cellular homeostasis and eliminates damaged cellular components. Moreover, the STAT3 signaling pathway, which may be triggered by cancer cells, has been implicated in the autophagic process.

Collagen facilitates the colorectal cancer stemness and metastasis through an integrin/PI3K/AKT/Snail signaling pathway.

Purpose: Dynamic remodeling of the extracellular matrix (ECM) around tumor cells is crucial for the tumor progressions. However, the mechanism is not well defined. Here, we aimed to reveal the underlying mechanism of ECM induced metastasis and provide innovative strategy to suppress the distant metastasis induced by ECM.

Colonic Lysine Homocysteinylation Induced by High-Fat Diet Suppresses DNA Damage Repair.

Colorectal cancer (CRC) onset is profoundly affected by Western diet. Here, we report that high-fat (HF) diet-induced, organ-specific colonic lysine homocysteinylation (K-Hcy) increase might promote CRC onset by impeding DNA damage repair. HF chow induced elevated methionyl-tRNA synthetase (MARS) expression and K-Hcy levels and DNA damage accumulation in the mouse and rat colon, resulting in a phenotype identical to that of CRC tissues.

Interplay between Trx-1 and S100P promotes colorectal cancer cell epithelial-mesenchymal transition by up-regulating S100A4 through AKT activation.

We previously reported a novel positive feedback loop between thioredoxin-1 (Trx-1) and S100P, which promotes the invasion and metastasis of colorectal cancer (CRC). However, the underlying molecular mechanisms remain poorly understood. In this study, we examined the roles of Trx-1 and S100P in CRC epithelial-to-mesenchymal transition (EMT) and their underlying mechanisms.

MiR-186-5p upregulation inhibits proliferation, metastasis and epithelial-to-mesenchymal transition of colorectal cancer cell by targeting ZEB1.

MicroRNA-186-5p (miR-186-5p) is upregulated and exhibits as a crucial oncogene in various human tumors. However, the functions and underlying mechanisms of this microRNA on colorectal cancer remain largely unknown. Here, we report that miR-186-5p share a lower expression in colorectal cancer cell lines (HT116, H29, SW620 and LoVo) than in normal colonic epithelial cell line NCM460.

Thioredoxin-1 promotes colorectal cancer invasion and metastasis through crosstalk with S100P.

Thioredoxin-1 (Trx-1) is a small redox-regulating protein, which plays an important role in several cellular functions. Despite recent advances in understanding the biology of Trx-1, the role of Trx-1 and its underlying signaling mechanism in colorectal cancer (CRC) metastasis have not been extensively studied. In this study, we observed that Trx-1 expression is increased in CRC tissues compared to the paired non-cancerous tissues and is significantly correlated with clinical staging, lymph node metastasis and poor survival.

miR-600 inhibits cell proliferation, migration and invasion by targeting p53 in mutant p53-expressing human colorectal cancer cell lines.

Mutations of the tumor protein p53 gene, a tumor suppressor, are one of the most frequent genetic alterations observed in cancer. It has been reported that mutations in p53 result in the loss of wild-type p53 activity, and the gain of novel oncogenic properties that promote tumor growth and progression. Recent studies have demonstrated that a number of microRNAs (miRs) are involved in the post-transcriptional regulation of p53.

Identification of differentially expressed circular RNAs in human colorectal cancer.

Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer.

Prognostic Value of Lymph Node Ratio in Locally Advanced Rectal Cancer Patients After Preoperative Chemoradiotherapy Followed by Total Mesorectal Excision.

Although the absolute number of positive lymph nodes (LNs) has been established as 1 of the most important prognostic factors in rectal cancers, many researchers have proposed that the lymph node ratio (LNR) may have better predicted outcomes. We conducted a retrospective study to compare the predictive ability of LNR and ypN category in rectal cancer. A total of 264 locally advanced rectal cancer (LARC) patients who underwent preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) between 2005 and 2012 were reviewed.

[Expression of long non-coding RNA associated with radiotherapy-resistance in colorectal cancer cell lines with different radiosensitivity].

Objective: To screen long non-coding RNA (lncRNA) associated with radiosensitivity in colorectal carcinoma cell lines.

Methods: Colony formation assay was performed in colorectal cancer cell lines HT29, SW480, RKO, Lovo and HCT116 after irradiation with different radiation doses. Radiation sensitivity of these 5 cell lines was detected through survival fraction at 2 Gy (SF2 value).

[Association of epithermal growth factor receptor expression and its downstream gene mutation status with radiosensitivity of colorectal carcinoma cell lines in vitro].

Objective: To investigate the effect of epithermal growth factor receptor (EGFR) expression and K-ras, B-raf and PIK3CA mutation status on the radiosensitivity of human colorectal carcinoma (CRC) cell lines in vitro.

Methods: Real-time RT-PCR was used to measure EGFR mRNA expression in nine human CRC cell lines, and K-ras, B-raf and PIK3CA mutation status of each CRC cell line was also identified respectively. After treatment with irradiation at graded dose, the cell viability was measured by clonogenic survival assay.

Expression of ZNF148 in different developing stages of colorectal cancer and its prognostic value: a large Chinese study based on tissue microarray.

Background: It has been speculated that zinc finger protein 148 (ZNF148) is a tumor suppressor. However, to the authors' knowledge, little is known about the clinical significance of ZNF148 expression in patients with colorectal cancer (CRC). The objective of the current study was to clarify the association between ZNF148 expression and the postoperative prognosis of patients with CRC.

Identification of miRNA-miRNA synergistic relationships in colorectal cancer.

Purpose: A large list of microRNAs (miRNAs) which may play important roles in the tumorigenesis of colorectal cancer (CRC) were generated recently. The purpose of our study is to analyze the synergistic regulations among miRNAs which were differentially expressed in tumorigenesis of CRC.

Methods: In this study, we downloaded the miRNA microarray and gene expression microarray of CRC from Gene Expression Omnibus (GEO), and identified the differentially expressed miRNAs (DE-miRNAs) and genes (DEGs) in cancer tissues compared with normal controls.

[Impacts of preoperative radiochemotherapy on operation and postoperative complications in patients with mid-low rectal carcinomas].

Objective: To investigate the impact of preoperative radiochemotherapy on postoperative complications in patients with mid-low rectal carcinomas.

Methods: Clinicopathologic data of T3 and T4 patients with mid-low rectal carcinomas in the Department of Colorectal Surgery at the Changhai Hospital of The Second Military Medical University from January 2009 to December 2010 were analyzed retrospectively. This cohort included 81 patients treated with preoperative radiochemotherapy followed by operation(radiochemotherapy group) and 93 cases who underwent surgery alone(control group).

[Laparoscopic total mesorectal excision combined with intersphincteric resection for ultra-low rectal cancer].

Objective: To evaluate clinical outcomes after laparoscopic total mesorectal excision (TME) combined with intersphincteric resection (ISR) for ultra-low rectal tumors.

Methods: Clinical data of 36 patients with ultra-low rectal tumor undergoing laparoscopic TME combined with ISR were analyzed retrospectively.

Results: The median distance from the inferior margin of the tumor to the anal verge was 3.