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1.
Article in English | MEDLINE | ID: mdl-38770399

ABSTRACT

Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.

2.
Article in English | MEDLINE | ID: mdl-38774472

ABSTRACT

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor. Some papers have reported that colonoscopy could be used to treat PEComa with a predominantly pedunculated polyp, whereas surgical intervention is often required for cases with submucosal-type tumors. These findings suggest that the morphology of PEComa changes dramatically with disease progression. Because of the rapid progression of PEComa, endoscopic treatment remains challenging, and early-stage PEComa morphology is not well understood. A 64-year-old man presented to our hospital for a follow-up colonoscopy after undergoing multiple polypectomies. He had a medical history of colorectal adenoma and prostate cancer. A 4-mm pale blue elevated but not pedunculated lesion was observed in the transverse colon, an area where he had not had polyps previously. Since no epithelial change was observed, the presence of a submucosal tumor, such as a gastrointestinal stromal tumor, was suspected. Cold snare polypectomy was performed, and the lesion was completely resected. Histological evaluation using hematoxylin and eosin staining identified that the submucosal tumor included thickened vascular walls and adipose tissue. Although fragmented due to significant degeneration, spindle-shaped cells staining positive for smooth muscle actin were observed within and surrounding the unstructured hyalinized tissue with calcifications. Based on these findings, the lesion was diagnosed as angiomyolipoma, a subtype of PEComa. Complete resection was confirmed by histopathology. To our knowledge, this PEComa is the smallest of any PEComa reported in the literature. Our finding provides valuable insights into the very early stage of colorectal PEComas.

3.
World J Gastrointest Surg ; 16(6): 1953-1955, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983321

ABSTRACT

We recently read the study by Kayano et al on intracorporeal anastomosis (IA) for colon cancer, which assessed bacterial contamination and medium-term oncological outcomes and affirmed that IA is analogous to extracorporeal anastomosis in reducing intraperitoneal bacterial risk and achieving similar oncological results. Our commentary addresses gaps, particularly concerning bowel preparation and surgical site infections (SSIs), and highlights the need for comprehensive details on the bowel preparation methods that are currently employed, including mechanical bowel preparation, oral antibiotics (OA), their combination, and specific OA types. We emphasize the necessity for further analyses that investigate these methods and their correlation with SSI rates, to enhance clinical protocol guidance and optimize surgical outcomes. Such meticulous analyses are essential for refining strategies to effectively mitigate SSI risk in colorectal surgeries.

4.
World J Gastrointest Surg ; 16(6): 1521-1526, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983361

ABSTRACT

In colon cancer surgery, ensuring the complete removal of the primary tumor and draining lymph nodes is crucial. Lymphatic drainage in the colon follows the vascular supply, typically progressing from pericolic to paraaortic lymph nodes. While NCCN guidelines recommend the removal of 10-12 lymph nodes for adequate oncological resection, achieving complete oncological resection involves more than just meeting these numerical targets. Various techniques have been developed and studied over time to attain optimal oncological outcomes. A key technique central to this goal is identifying the ileocolic vessels at their origin from the superior mesenteric vessels. Complete excision of the visceral and parietal mesocolon ensures the intact removal of the specimen, while D3 lymphadenectomy targets all draining regional lymph nodes. Although these principles emphasize different aspects, they ultimately converge to achieve the same goal of complete oncological resection. This article aims to simplify the surgical steps that align with the principle of central vascular ligation and mesocolon mobilization while ensuring adequate D3 dissection.

5.
World J Methodol ; 14(2): 92612, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38983654

ABSTRACT

BACKGROUND: The first wave of coronavirus disease 2019 (COVID-19) pandemic in Spain lasted from middle March to the end of June 2020. Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods. In our centre, we managed patients previously and newly diagnosed with cancer. We established a strategy based on limiting perioperative social contacts, preoperative screening (symptoms and reverse transcription-polymerase chain reaction) and creating separated in-hospital COVID-19-free pathways for non-infected patients. We also adopted some practice modifications (surgery in different facilities, changes in staff and guidelines, using continuously changing personal protective equipment…), that supposed new inconveniences. AIM: To analyse cancer patients with a decision for surgery managed during the first wave, focalizing on outcomes and pandemic-related modifications. METHODS: We prospectively included adults with a confirmed diagnosis of colorectal, oesophago-gastric, liver-pancreatic or breast cancer with a decision for surgery, regardless of whether they ultimately underwent surgery. We analysed short-term outcomes [30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection] and outcomes after 3 years (adjuvant therapies, oncological events, death, SARS-CoV-2 infection and vaccination). We also investigated modifications to usual practice. RESULTS: From 96 included patients, seven didn't receive treatment that period and four never (3 due to COVID-19). Operated patients: 28 colon and 21 rectal cancers; laparoscopy 53.6%/90.0%, mortality 3.57%/0%, major complications 7.04%/25.00%, anastomotic leaks 0%/5.00%, 3-years disease-free survival (DFS) 82.14%/52.4% and overall survival (OS) 78.57%/76.2%. Six liver metastases and six pancreatic cancers: no mortality, one major complication, three grade A/B liver failures, one bile leak; 3-year DFS 0%/33.3% and OS 50.0%/33.3% (liver metastases/pancreatic carcinoma). 5 gastric and 2 oesophageal tumours: mortality 0%/50%, major complications 0%/100%, anastomotic leaks 0%/100%, 3-year DFS and OS 66.67% (gastric carcinoma) and 0% (oesophagus). Twenty breast cancer without deaths/major complications; 3-year OS 100% and DFS 85%. Nobody contracted SARS-CoV-2 postoperatively. COVID-19 pandemic-related changes: 78.2% treated in alternative buildings, 43.8% waited more than 4 weeks, two additional colostomies and fewer laparoscopies. CONCLUSION: Some patients lost curative-intent surgery due to COVID-19 pandemic. Despite practice modifications and 43.8% delays higher than 4 weeks, surgery was resumed with minimal changes without impacting outcomes. Clean pathways are essential to continue surgery safely.

6.
Ann Coloproctol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38988019

ABSTRACT

The purpose of this video is to demonstrate how to achieve adequate length and blood supply of the proximal colon for a perineal pull-through procedure, without splenic flexure mobilization during natural orifice specimen extraction. Key steps of the procedure include lateral mobilization of the colon, D3 lymph node dissection, preservation of the left colic artery, low ligation of the inferior mesenteric vein, ligation and washout of the distal bowel lumen, extra-abdominally proximal resection of sigmoid colon, purse-string sutures on the distal sigmoid colon, and an air leak test. Transluminal specimen extraction with extra-abdominal resection was found to be a cost-effective procedure with good cosmetic effects. Tension-free anastomosis was achieved by preservation of the left colic artery and low ligation of the inferior mesenteric vein. The purse-string sutures were placed on the proximal and distal bowel to avoid crossing the staples line. Transluminal specimen extraction with extra-abdominal resection required minimal manipulation intra-abdominally in comparison with other natural orifice specimen extraction techniques.

7.
Cancer Immunol Immunother ; 73(9): 175, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953994

ABSTRACT

Tumor immunotherapies targeting PD-(L)1 exhibit anti-tumor efficacy in only 10-30% of patients with various cancers. Literature has demonstrated that a "hot tumor" which contains high T lymphocytes in the tumor microenvironment exhibits a better response to immunotherapies than a "cold tumor." This study aimed to investigate whether tumor-intrinsic IFNα and CXCL10 determine the recruitment and activation of CD8+ T cells to become "hot tumor." In this study, we found that CXCL10 overexpressed in a variety of tumors including lung, colon, and liver tumors with a correlation with PD-L1. High PD-L1 and CXCL10 are associated with better survival rates in tumor patients receiving immunotherapies. IFNs-downstream transcriptional factor IRF-1 and STAT1 were correlated with PD-L1 and CXCL10 expression. We demonstrated that IRF-1 and STAT1 were both bound with the promoters of PD-L1 and CXCL10, sharing the same signaling pathway and determining IFNs-mediated PD-L1 and CXCL10 expression. In addition, IFNα significantly increased activation marker IFNγ in PBMCs, promoting M1 type monocyte differentiation, CD4+ T, and CD8+ T cell activation. Particularly, we found that CD8+ T lymphocytes abundantly expressed CXCR3, a receptor of CXCL10, by flow cytometry, indicating that tumor-intrinsic CXCL10 potentially recruited CD8+ T in tumor microenvironment. To demonstrate the hypothesis, immunotherapy-sensitive CT26 and immunotherapy-resistant LL/2 were used and we found that CT26 cells exhibited higher IFNα, IFNγ, CXCL10, and PD-L1 levels compared to LL/2, leading to higher IFNγ expression in mouse splenocytes. Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect. We then confirmed that CT26-derived tumor was sensitive to αPD-L1 immunotherapy and LL/2-tumor was resistant, whereas αPD-L1 significantly increased T lymphocyte activation marker CD107a in CT26-derived BALB/c mice. In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting "hot tumor" characteristic of sensitizing αPD-L1 immunotherapies.


Subject(s)
Chemokine CXCL10 , Immunotherapy , Interferon-alpha , Tumor Microenvironment , Chemokine CXCL10/metabolism , Chemokine CXCL10/immunology , Tumor Microenvironment/immunology , Animals , Mice , Humans , Immunotherapy/methods , Neoplasms/immunology , Neoplasms/therapy , Lymphocyte Activation/immunology , Cell Line, Tumor , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Female , STAT1 Transcription Factor/metabolism
8.
Trials ; 25(1): 438, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956698

ABSTRACT

BACKGROUND: Colon cancer is a global health concern, ranking fifth in both new diagnoses and deaths among tumors worldwide. Surgical intervention remains the primary treatment for localized cases, with a historical evolution marked by a focus on short-term outcomes. While Japan pioneered radical tumor removal with a systematic categorization of lymph nodes (D1, D2, D3), the dissemination of Japanese practices to the West was delayed until 90th of last century. Discrepancies between Japanese D3 dissection and the CME with CVL principle persist, with variations in longitudinal margins and recommended procedures. Non-randomized trials indicate the superiority of D3 over D2, but a consensus is lacking. METHODS: This prospective, international, multicenter, randomized controlled trial employs a two-arm, parallel-group, open-label design to rigorously compare the 5-year overall survival outcomes between D2 and D3 lymph node dissection in stage II-III right colon cancer. Building on prior studies, the trial aims to address existing knowledge gaps and provide a comprehensive evaluation of the outcomes associated with D3 dissection. The study population comprises patients with right colon cancer, ensuring a focused investigation into the specific context of this disease. The trial design emphasizes its global scope and collaboration across multiple centers, enhancing the generalizability of the findings. DISCUSSION: This study's primary objective is to elucidate the potential superiority in 5-year overall survival benefits of D3 lymph node dissection compared to the conventional D2 approach in patients with stage II-III right colon cancer. By examining this specific subset of patients, the research aims to contribute valuable insights into optimizing surgical strategies for improved long-term outcomes. The trial's international and multicenter nature enhances its applicability across diverse populations. The outcomes of this study may inform future guidelines and contribute to the ongoing discourse surrounding the standardization of colon cancer surgery, particularly in the context of right colon cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03200834. Registered on June 27, 2017.


Subject(s)
Colonic Neoplasms , Lymph Node Excision , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Humans , Colonic Neoplasms/surgery , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Prospective Studies , Treatment Outcome , Time Factors , Neoplasm Staging , Lymphatic Metastasis , Lymph Nodes/pathology , Lymph Nodes/surgery , Colectomy/adverse effects , Colectomy/methods
9.
Clin Case Rep ; 12(7): e9178, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39005578

ABSTRACT

Key Clinical Message: Primary leiomyosarcoma of the colon is a very rare tumor entity. Because of unspecific findings, diagnostic can be challenging. Most cases are diagnosed in advanced stages with poor overall survival. Unclear histological findings of smooth muscle cell tissue in colon biopsies together with a tumor of the colon wall in computed tomography (CT) imaging should lead to the differential diagnosis of primary colonic leiomyosarcoma and further diagnostic procedures. Abstract: Primary colonic leiomyosarcoma is an extremely rare tumor entity arising from smooth muscle cells in the colon wall. Only 0.1% of all colorectal malignancies are leiomyosarcomas. Most patients are diagnosed in advanced disease stages. The overall survival rates are low, and recurrence rates are high. Only few data regarding the outcome in localized early disease stages are available. We report the case of an early-stage primary leiomyosarcoma of the sigmoid colon treated with surgical resection. We present the case of a 53-year-old male patient who underwent a colonoscopy due to intermittent rectal bleeding. Colonoscopy revealed an intraluminal polypoid growing tumor in the sigmoid colon. A biopsy was performed with inconclusive histological results. A CT scan revealed a process in the sigmoid colon with wall thickening; there was no evidence of metastatic lesions. After laparoscopic oncological resection of the sigmoid colon, histological examination surprisingly revealed a localized high-grade leiomyosarcoma. Primary leiomyosarcoma of the colon is a rare tumor entity and diagnostic can be challenging. Only a few patients with colonic leiomyosarcoma diagnosed in localized early disease stages and treated with complete surgical resection have been reported in the literature. These patients seem to have a better prognosis with longer overall survival. Because of unspecific diagnostic findings and the lack of symptoms in early disease stages, interdisciplinary collaborations between gastroenterologists, radiologists, pathologists, and surgeons are crucial for early diagnosis and treatment.

10.
PeerJ ; 12: e17582, 2024.
Article in English | MEDLINE | ID: mdl-39006025

ABSTRACT

Background: Disruptions in calcium homeostasis are associated with a wide range of diseases, and play a pivotal role in the development of cancer. However, the construction of prognostic models using calcium extrusion-related genes in colon adenocarcinoma (COAD) has not been well studied. We aimed to identify whether calcium extrusion-related genes serve as a potential prognostic biomarker in the COAD progression. Methods: We constructed a prognostic model based on the expression of calcium extrusion-related genes (SLC8A1, SLC8A2, SLC8A3, SLC8B1, SLC24A2, SLC24A3 and SLC24A4) in COAD. Subsequently, we evaluated the associations between the risk score calculated by calcium extrusion-related genes and mutation signature, immune cell infiltration, and immune checkpoint molecules. Then we calculated the immune score, stromal score, tumor purity and estimate score using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. The response to immunotherapy was assessed using tumor immune dysfunction and exclusion (TIDE). Finally, colorectal cancer cells migration, growth and colony formation assays were performed in RKO cells with the overexpression or knockdown SLC8A3, SLC24A2, SLC24A3, or SLC24A4. Results: We found that patients with high risk score of calcium extrusion-related genes tend to have a poorer prognosis than those in the low-risk group. Additionally, patients in high-risk group had higher rates of KRAS mutations and lower MUC16 mutations, implying a strong correlation between KRAS and MUC16 mutations and calcium homeostasis in COAD. Moreover, the high-risk group showed a higher infiltration of regulatory T cells (Tregs) in the tumor microenvironment. Finally, our study identified two previously unreported model genes (SLC8A3 and SLC24A4) that contribute to the growth and migration of colorectal cancer RKO cells. Conclusions: Altogether, we developed a prognostic risk model for predicting the prognosis of COAD patients based on the expression profiles of calcium extrusion-related genes, Furthermore, we validated two previously unreported tumor suppressor genes (SLC8A3 and SLC24A4) involved in colorectal cancer progression.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Humans , Prognosis , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/immunology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Calcium/metabolism , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Male , Female , Mutation
11.
J Agric Food Chem ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38991049

ABSTRACT

Polyunsaturated fatty acids (PUFAs) are essential nutrients for the human body, playing crucial roles in reducing blood lipids, anti-inflammatory responses, and anticancer effect. Quinoa is a nutritionally sound food source, rich in PUFAs. This study investigates the role of quinoa polyunsaturated fatty acids (QPAs) on quelling drug resistance in colorectal cancer. The results reveal that QPA downregulates the expression of drug-resistant proteins P-gp, MRP1, and BCRP, thereby enhancing the sensitivity of colorectal cancer drug-resistant cells to the chemotherapy drug. QPA also inhibits the stemness of drug-resistant colorectal cancer cells by reducing the expression of the stemness marker CD44. Consequently, it suppresses the downstream protein SLC7A11 and leads to ferroptosis. Additionally, QPA makes the expression of ferritin lower and increases the concentration of free iron ions within cells, leading to ferroptosis. Overall, QPA has the dual-function reversing drug resistance in colorectal cancer by simultaneously inhibiting stemness and inducing ferroptosis. This study provides a new option for chemotherapy sensitizers and establishes a theoretical foundation for the development and utilization of quinoa.

12.
Rozhl Chir ; 103(6): 232-235, 2024.
Article in English | MEDLINE | ID: mdl-38991788

ABSTRACT

In this article, we present case reports of two patients admitted to the University Hospital in Pilsen for acute abdomen due to a disorder of the passage through the gastrointestinal tract (GIT). Both were indicated for surgery. The patients were diagnosed intraoperatively with rarely occurring cecal volvulus (CV). The findings required an ileocecal resection; nevertheless, both patients fully recovered despite the need the resection.


Subject(s)
Abdomen, Acute , Cecal Diseases , Intestinal Volvulus , Humans , Intestinal Volvulus/surgery , Intestinal Volvulus/diagnostic imaging , Intestinal Volvulus/complications , Abdomen, Acute/etiology , Cecal Diseases/surgery , Cecal Diseases/complications , Cecal Diseases/diagnostic imaging , Cecal Diseases/diagnosis , Male , Ileus/surgery , Ileus/etiology , Ileus/diagnostic imaging , Female , Middle Aged , Aged
13.
Steroids ; : 109469, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992454

ABSTRACT

This is the first report on a unique hybrid molecule made of estradiol and testosterone (TS). This distinctive hybrid molecule (1) was designed to interact with both the estrogen receptor (ER) and the androgen receptor (AR) found in hormone-dependent female and male cancer cells, and was synthesized using ethynylestradiol (17EE) as the estrogenic component and 7α-(4-azido-but-2-enyl)-4-androsten-17ß-ol-3-one as the androgenic counterpart in a seven-step reaction with ∼ 26 % overall yield. We reasoned that the dual receptor binding ability could allow 1 to act as an antihormone. This was tested on hormone-dependent and hormone-independent breast cancer (BCa) and prostate cancer (PCa) cells. The antiproliferative activity was also assessed on colon and skin cancer cells. We found that 1 was active against MCF7 (ER + ) BCa cells (IC50 of 4.9 µM), had lower inhibitory potency on LNCaP (AR + ) PCa cells (IC50 > 5 µM) and no effect on PC3 and DU145 (AR-) PCa cells. This suggests that the estrogenic component of 1 can interact with the ER on MCF7 cells more effectively than the androgenic component with the AR on LNCaP PCa cells, possibly due to a suboptimal spacer or linkage site(s). Nonetheless, the hybrid 1 was active against colon (HT-29) and melanoma (M21) cancer cells (IC50 of 3.5 µM and 2.3 µM, respectively), and had low cross-reactivity with the drug- and androgen-metabolizing cytochrome P450 3A4 (CYP3A4, IC50 ≫ 5 µM). These findings demonstrate the anticancer potential of 1 and warrant further explorations on this new type of hybrids.

14.
Cell Mol Gastroenterol Hepatol ; : 101378, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992465

ABSTRACT

BACKGROUND & AIMS: Addition of sialic acids (sialylation) to glycoconjugates is a common capping step of glycosylation. Our study aims to determine the roles of the overall sialylation in intestinal mucosal homeostasis. METHODS: Mice with constitutive deletion of intestinal epithelial sialylation (IEC Slc35a1-/- mice) and mice with inducible deletion of sialylation in intestinal epithelium (TM-IEC Slc35a1-/- mice) were generated, which were used to determine the roles of overall sialylation in intestinal mucosal homeostasis by ex vivo and muti-omics studies. RESULTS: IEC Slc35a1-/- mice developed mild spontaneous microbiota-dependent colitis. Additionally, 30% of IEC Slc35a1-/- mice had spontaneous tumors in the rectum over the age of 12 months. TM-IEC Slc35a1-/- mice were highly susceptible to acute inflammation induced by 1% DSS vs controls. Loss of total sialylation was associated with reduced mucus thickness on fecal sections and within colon tissues. TM-IEC Slc35a1-/- mice showed altered microbiota with an increase in Clostridia disporicum, which is associated a global reduction in the abundance of at least 20 unique taxa; however, metabolomic analysis did not show any significant differences in short-chain fatty acid levels. Treatment with 5-fluorouracil (5-FU) led to more severe small intestine mucositis in the IEC Slc35a1-/- mice vs. WT littermates, which was associated with reduced Lgr5+ cell representation in small intestinal crypts in IEC Slc35a1-/-;Lgr5-GFP mice. CONCLUSIONS: Loss of overall sialylation impairs mucus stability and the stem cell niche leading to microbiota-dependent spontaneous colitis and tumorigenesis.

15.
Life Sci ; : 122905, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992573

ABSTRACT

AIMS: Colon cancer poses a major threat to human health and a heavy burden on the national economy. As a member of the SOX transcription factor family, SRY-box transcription factor 21 (SOX21) is associated with various cancers, but its mechanism of action in colon cancer remains unclear. This study focused on the molecular mechanisms of transcription factor SOX21 in proliferation and metastasis of colon cancer cells. MAIN METHODS: We analyzed SOX21 expression level and its impact on survival in colon cancer patients by bioinformatics analysis. We used public databases for gene correlation, GSEA enrichment analysis. Cell function experiments (colony formation assay, wound healing assay, Transwell migration and invasion assay) were utilized to determine the impact of SOX21 silencing and over-expression on cell proliferation and metastasis. The luciferase reporter assay, CUT&RUN-qPCR assay and Methylation Specific PCR were used to explore SOX21-POU class 4 homeobox 2 (POU4F2) molecular interactions. The molecular mechanisms were verified by Quantitative real-time PCR and Western blot analysis. KEY FINDINGS: SOX21 is highly expressed and affects the overall survival of colon cancer patients. SOX21 can attenuates POU4F2 methylation state by binding with it. In addition, this interaction facilitate its transcriptional activation of Hedgehog pathway, mediates epithelial-mesenchymal transition (EMT), consequently promoting the proliferation and metastasis of colon cancer cells. SIGNIFICANCE: Our study reveals that SOX21 is an oncogenic molecule and suggests its regulatory role in colon carcinogenesis and progression, providing new insights into the treatment of this disease.

16.
BMC Gastroenterol ; 24(1): 222, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992586

ABSTRACT

BACKGROUND: CFAP65 (cilia and flagella associated protein 65) is a fundamental protein in the development and formation of ciliated flagella, but few studies have focused on its role in cancer. This study aimed to investigate the prognostic significance of CFAP65 in colon cancer. METHODS: The functionally enriched genes related to CFAP65 were analyzed through the Gene Ontology (GO) database. Subsequently, CFAP65 expression levels in colon cancer were evaluated by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) and immunoblotting in 20 pairs of frozen samples, including tumors and their matched paratumor tissue. Furthermore, protein expression of CFAP65 in 189 colon cancer patients were assessed via immunohistochemical staining. The correlations between CFAP65 expression and clinical features as well as long-term survival were statistically analyzed. RESULTS: CFAP65-related genes are significantly enriched on cellular processes of cell motility, ion channels, and GTPase-associated signaling. The expression of CFAP65 was significantly higher in colon cancer tissue compared to paratumor tissue. The proportion of high expression and low expression of CFAP65 in the clinical samples of colon cancer were 61.9% and 38.1%, respectively, and its expression level was not associated with the clinical parameters including gender, age, tumor location, histological differentiation, tumor stage, vascular invasion and mismatch repair deficiency. The five-year disease-free survival rate of the patients with CFAP65 low expression tumors was significantly lower than that those with high expression tumors (56.9% vs. 72.6%, P = 0.03), but the overall survival rate has no significant difference (69% vs. 78.6%, P = 0.171). The cox hazard regression analysis model showed that CFAP65 expression, tumor stage and tumor location were independent prognostic factors. CONCLUSIONS: In conclusion, we demonstrate CFAP65 is a potential predictive marker for tumor progression in colon cancer.


Subject(s)
Biomarkers, Tumor , Colonic Neoplasms , Humans , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/metabolism , Colonic Neoplasms/mortality , Male , Female , Middle Aged , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Aged , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Clinical Relevance , Membrane Proteins , Neoplasm Proteins
17.
Animal Model Exp Med ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992956

ABSTRACT

BACKGROUND: A multitude of mouse models are utilized to emulate and study intestinal inflammation. T-cell receptor alpha chain (TCRα)-deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative colitis. However, colitis is triggered late in the life of the mouse (age: 4-5 months), and inflammation does not develop at the same time in different mice. A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα-deficient mice at the age of 6-8 weeks. However, a detailed characterization of ensuing inflammation was not provided. METHODS: We conducted an in-depth examination of piroxicam-triggered colitis in TCRα-deficient mice, with emphasis on spatial histopathologic changes and analysis of expression of inflammatory markers. Furthermore, we tested amelioration of colitis with dexamethasone. RESULTS: We confirmed that piroxicam induced a time-prescribed colitis and did so in the proximal colon as well as the cecum of TCRα-deficient mice. Piroxicam administration was observed to induce epithelial hyperplasia, goblet cell loss, and leukocyte infiltration with occasional ulceration. A Swiss roll technique was used to examine the colon and cecum in its entirety. Importantly, we observed that inflammation was multifocal segmental, with areas of tissue damage in between healthy tissue. In addition, we observed variability in the severity of inflammation among replicate animals and treatments, and that the administration of dexamethasone only partially ameliorated inflammation in the proximal colon. CONCLUSIONS: Piroxicam consistently induced multifocal segmental colitis in the proximal colon and cecum, although the degree of inflammation was reduced in the latter. Importantly, spatial variability in inflammation in the large intestine and the inter-replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis.

18.
J Med Cases ; 15(7): 126-129, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38993809

ABSTRACT

Renal cell carcinoma (RCC) is notorious for spreading to various organs, however, its occurrence in the gastrointestinal (GI) tract is uncommon and poses diagnostic challenges due to vague symptoms. Here, we present the case of a 64-year-old man experiencing recurrent RCC metastasis in the GI tract. He presented with multiple episodes of hematochezia and was found to have masses in the colon, liver, and peritoneum, with histopathology confirming RCC. The patient underwent systemic chemotherapy and palliative radiation therapy, leading to symptom relief. This case emphasizes the rarity of RCC metastasizing to the GI tract and the importance of timely recognition and frequent surveillance during the remission phase to detect recurrence.

19.
J Surg Case Rep ; 2024(7): rjae454, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38993816

ABSTRACT

A 66-year-old man presented to our institution with a positive fecal occult blood test and lower abdominal pain. Although a tumor was found in the sigmoid colon, biopsy and imaging studies failed to enable the diagnosis of the cancer, and the patient underwent surgery for treatment and diagnosis. The tumor had two distinct areas with differing features shown both histopathologically and on imaging; it was thus diagnosed as a leiomyosarcoma of the sigmoid colon with a pleomorphic component. Here, we describe a rare case of leiomyosarcoma of the sigmoid colon with a pleomorphic component. There are no reports of leiomyosarcoma with pleomorphic components arising in the colon in the literature; thus, the recurrence and metastatic characteristics are unknown. Therefore, accumulating cases in the literature may provide valuable insights into diagnosing and treating these rare tumors.

20.
World J Gastrointest Oncol ; 16(6): 2264-2270, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994141

ABSTRACT

In this editorial, I commented on the paper by Lin et al, published in this issue of the World Journal of Gastrointestinal Oncology. The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer (CRC). The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer (GC) stage rather than the CRC stage. Although surveillance was recommended in the conclusion, the authors did not explore this area in their study and did not include tests used for such surveillance. This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs. These include hereditary diffuse GC, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, Lynch syndrome, and three major hamartomatous polyposis syndromes associated with CRC and GC, namely Peutz-Jeghers syndrome, juvenile polyposis syndrome, and PTEN hamartoma syndrome. Careful assessment of these syndromes/conditions, including inheritance, risk of gastric and colorectal or other cancer development, genetic mutations and recommended genetic investigations, is crucial for optimum management of these patients.

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