surgical-trunk-oriented-laparoscopic-right-hemicolectomy-st-lrh-for

Surgical Trunk Oriented Laparoscopic Right Hemicolectomy (ST-LRH) for Right-Sided Colon Cancer

Laparoscopic right hemicolectomy is a commonly utilized surgical procedure for the treatment of right-sided colon cancer. However, the high degree of ...

Southern Medical University

Intestinal injury has long been considered to play a crucial role in the pathophysiology of sepsis and has even been characterized as the "motor" of it. Thus, we explored the effects of connexin43 (Cx43) on sepsis-induced intestinal injury in order to provide potential therapeutic strategies. Rat cecal ligation and puncture (CLP) models  and cell models (IEC-6 cells) pretreated with LPS  were used in the current study. Firstly, different methods, such as Cx43 inhibitors (18--GA and oleamide) or siRNA targeting Cx43 and N-acetyl cysteine (NAC) (a kind of ROS scavenger), were used to observe the effects of Cx43 channels mediating ROS transfer on intestinal injury. Secondly, the influence of ROS content on the activity of the JNK1/Sirt1/FoxO3a signaling pathway was explored through the application of NAC, sp600125 (a JNK1 inhibitor), and nicotinamide (a Sirt1 inhibitor). Finally, luciferase assays and ChIP were used to determine the direct regulation of FoxO3a on proapoptotic proteins, Bim and Puma. The results showed that sepsis-induced intestinal injury presented a dynamic change, coincident with the alternation of Cx43 expression. The inhibition of Cx43 attenuated CLP-induced intestinal injury  and LPS-induced IEC-6 injury . The changes of Cx43 channel function regulated ROS transfer between the neighboring cells, which mediated the activation of the JNK1/Sirt1/FoxO3a signaling pathway. FoxO3a directly affected its downstream target genes, Bim and Puma, which are responsible for cell or tissue apoptosis. In summary, our results suggest that Cx43 inhibition suppresses ROS transfer and inactivates the JNK1/Sirt1/FoxO3a signaling pathway to protect against sepsis-induced intestinal injury.

Cx43 Inhibition Attenuates Sepsis-Induced Intestinal Injury via Downregulating ROS Transfer and the Activation of the JNK1/Sirt1/FoxO3a Signaling Pathway.

BMP3 gene is often found hypermethylated and hence inactivated in several types of cancers including colorectal cancer (CRC), indicating that it has a suppressor role in carcinogenesis. Though BMP3 is a reliable biomarker for screening CRC, the molecular mechanism of BMP3 in carcinogenesis remains largely unknown.

BMP3 suppresses colon tumorigenesis via ActRIIB/SMAD2-dependent and TAK1/JNK signaling pathways.

Colorectal cancer (CRC) is one of the most common primary malignancies worldwide. Numerous studies have demonstrated that long non-coding RNAs (lncRNAs) are considered as crucial regulators of tumor progression. In particular, upregulation of the lncRNA KCNQ1OT1 was reported in various types of malignancy as a promoter of tumor progression. However, the role and underlying mechanism of KCNQ1OT1 in CRC remain unclear. Thus, the present study aimed to investigate the role of KCNQ1OT1 in colorectal cancer through GEPIA, reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses, and cell assays. GEPIA analysis demonstrated that high expression levels of KCNQ1OT1 in CRC tissues predicted a poor prognosis for patients with CRC. KCNQ1OT1 was overexpressed in CRC tissues and cell lines via RT-qPCR analysis. Furthermore, the results from the cell viability assay, colony formation assay, wound healing assay, invasion assay and flow cytometric analysis demonstrated that KCNQ1OT1 knockdown significantly inhibited CRC cell proliferation, migration and invasiveness, and promoted CRC cell apoptosis, leading to cell cycle arrest. Western blot analysis demonstrated that KCNQ1OT1 knockdown inhibited the PI3K/AKT signaling pathway. These results suggest that KCNQ1OT1 may act as an oncogene through the PI3K/AKT signaling pathway in CRC.

lncRNA KCNQ1OT1 knockdown inhibits colorectal cancer cell proliferation, migration and invasiveness via the PI3K/AKT pathway.

 Tumor dormancy is an important way to develop drug resistance. This study aimed to identify the characteristics of colorectal cancer (CRC) cell dormancy.  Based on the CRC cohorts, a total of 1,044 CRC patients were included in this study, and divided into a dormant subgroup and proliferous subgroup. Non-negative matrix factorization (NMF) was used to distinguish the dormant subgroup of CRC  transcriptome data of cancer tissues. Gene Set Enrichment Analysis (GSEA) was used to explore the characteristics of dormant CRC. The characteristics were verified in the cell model, which was used to predict key factors driving CRC dormancy. Potential treatments for CRC dormancy were also examined.  The dormant subgroup had a poor prognosis and was more likely to relapse. GSEA analysis showed two defining characteristics of the dormant subgroup, a difference in energy metabolism and synergistic effects of cancer-associated fibroblasts (CAFs), which were verified in a dormant cell model. Transcriptome and clinical data identified , and  as important factors associated with cell dormancy and verified that erlotinib, and CB-839 were potential treatment options.  Dormant CRC is associated with high glutamine metabolism and synergizes with CAFs in 5-FU resistance, and the key effectors are LMOD1, MAB21L2, and ASPN. Austocystin D, erlotinib, and CB-839 may be useful for dormant CRC.

Transcriptomics and Metabolomics Identify Drug Resistance of Dormant Cell in Colorectal Cancer.

Actin cytoskeleton is connected with the processes of cell proliferation and migration in colorectal cancer (CRC). However, it is unknown how to accomplish these adjustments in CRC by actin cytoskeleton genes (ACGs) and here we investigated the role of hub prognosis-related ACGs-Diaphanous-related formin 3 (DIAPH3) in CRC, as a potential, novel target.

DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation.

Gap junctions can transmit signals between cells, including miRNAs, leading to the amplification of adjacent cell damage. No previous study has addressed gap junctions and miRNAs in sepsis because the internal mechanism of sepsis-induced intestinal injury is complex. Therefore, we studied the relationship between connexin43 (Cx43) and miR-181b and provided a research direction for further study of sepsis.

Cx43-Delivered miR-181b Negatively Regulates Sirt1/FOXO3a Signalling Pathway-Mediated Apoptosis on Intestinal Injury in Sepsis.

Recent studies have demonstrated the crucial regulatory roles of circular RNAs (circRNAs) in cancer initiation and progression. The sponge mechanism of circRNAs has been shown to be widely active in various types of tumors. However, many circRNAs still have not been verified to function through this mechanism. This study aimed to investigate the regulatory mechanism of hsa_circ_0079557 in colorectal cancer (CRC) and its role in CRC progression.

Hsa_circ_0079557 Promotes the Proliferation of Colorectal Cancer Cells Through the hsa_circ_0079557/miR-502-5p/CCND1 Axis.

Accumulating evidence has indicated the presence of mature microRNAs (miR) in the nucleus, but their effects on steatohepatitis remain elusive. We have previously demonstrated that the intranuclear miR-204-3p in macrophages protects against atherosclerosis, which shares multiple risk factors with metabolic dysfunction-associated steatotic liver disease (MASLD). Herein, we aimed to explore the functional significance of miR-204-3p in steatohepatitis.

Nuclear miR-204-3p mitigates metabolic dysfunction-associated steatotic liver disease in mice.

Laparoscopic complete right hemicolectomy: Surgical trunk-oriented adjuvant radical surgery for right hemicolonic carcinoma-A video vignette.

Colorectal cancer remains a significant threat to human life and health, with Laparoscopic technology represents a pivotal advancement in its treatment. Laparoscopic right hemicolectomy has emerged as the preferred surgical modality for managing right-sided colon cancer, offering minimally invasive benefits and expedited recovery. However, the right colon anatomy, characterized by complex vascular branching patterns and frequent variations, presents significant surgical challenges. Various surgical access methods have been proposed to address these challenges, each with distinct advantages and limitations. To optimize surgical outcomes, our research team has meticulously analyzed these approaches and developed a modified combined approach for laparoscopic right hemicolectomy in the treatment of right-sided colon cancer. This innovative approach integrates the strengths of different methods to enhance surgical efficacy while minimizing intraoperative bleeding, facilitating rapid recovery, and ensuring favorable prognosis. We report a case of a 76-year-old male with hypertension who presented with rectal bleeding. Preoperative evaluation revealed moderately differentiated adenocarcinoma in the ascending colon (clinical stage T3N1bM0). The patient underwent the modified combined approach of laparoscopic right hemicolectomy. The surgery was successful, with few intraoperative complications. Postoperatively, the patient had an uneventful recovery, was discharged after 8 days, and showed no signs of recurrence at 6-month follow-up. We anticipate that this novel surgical approach will provide more precise and efficient treatment options, ultimately improving the overall quality of life for patients with right-sided colon cancer.

A modified combined approach in laparoscopic right hemicolectomy for right-sided colon based on surgical trunk orientation: a case of a new surgical technique.

Article	Year
Cx43 Inhibition Attenuates Sepsis-Induced Intestinal Injury via Downregulating ROS Transfer and the Activation of the JNK1/Sirt1/FoxO3a Signaling Pathway. Mediators of inflammation\| PubMed ID: 30948926	2019
BMP3 suppresses colon tumorigenesis via ActRIIB/SMAD2-dependent and TAK1/JNK signaling pathways. Journal of experimental & clinical cancer research : CR\| PubMed ID: 31665064	2019
lncRNA KCNQ1OT1 knockdown inhibits colorectal cancer cell proliferation, migration and invasiveness via the PI3K/AKT pathway. Oncology letters\| PubMed ID: 32565985	2020
Transcriptomics and Metabolomics Identify Drug Resistance of Dormant Cell in Colorectal Cancer. Frontiers in pharmacology\| PubMed ID: 35462906	2022
DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation. Cancer medicine\| PubMed ID: 35538918	2022
Cx43-Delivered miR-181b Negatively Regulates Sirt1/FOXO3a Signalling Pathway-Mediated Apoptosis on Intestinal Injury in Sepsis. Digestion\| PubMed ID: 37231890	2023
Hsa_circ_0079557 Promotes the Proliferation of Colorectal Cancer Cells Through the hsa_circ_0079557/miR-502-5p/CCND1 Axis. Cancer genomics & proteomics\| PubMed ID: 37889059	2023
Nuclear miR-204-3p mitigates metabolic dysfunction-associated steatotic liver disease in mice. Journal of hepatology\| PubMed ID: 38331323	2024
Laparoscopic complete right hemicolectomy: Surgical trunk-oriented adjuvant radical surgery for right hemicolonic carcinoma-A video vignette. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland\| PubMed ID: 38644650	2024
A modified combined approach in laparoscopic right hemicolectomy for right-sided colon based on surgical trunk orientation: a case of a new surgical technique. Journal of gastrointestinal oncology\| PubMed ID: 40672092	2025

Renli Huang

Biography

JoVE Journal Publications

Other Publications