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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.
Sci Rep ; 14(1): 16849, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039235

ABSTRACT

The colonic epithelium is comprised of three-dimensional crypts (3D) lined with mucus secreted by a heterogeneous population of goblet cells. In this study, we report the formation of a long-lived, and self-renewing replica of human 3D crypts with a mucus layer patterned in the X-Y-Z dimensions. Primary colon cells were cultured on a shaped scaffold under an air-liquid interface to yield architecturally accurate crypts with a mucus bilayer (605 ± 180 µm thick) possessing an inner (149 ± 50 µm) and outer (435 ± 111 µm) region. Lectins with distinct carbohydrate-binding preferences demonstrated that the mucus in the intercrypt regions was chemically distinct from that above and within the crypts replicating in vivo chemical patterning. Constitutive mucus secretion ejected beads from crypt lumens in 8-10 days, while agonist-stimulated secretion increased mucus thickness by 17-fold in 8 h. The tissue was long-lived, > 50 days, the longest time assessed. In conclusion, the in vitro mucus replicated key physiology of the human mucus, including the bilayer (Z) structure and intercrypt-crypt (X-Y) zones, constitutive mucus flow, spatially complex chemical attributes, and mucus secretion response to stimulation, with the potential to reveal local and global determinants of mucus function and its breakdown in disease.


Subject(s)
Colon , Mucus , Humans , Mucus/metabolism , Colon/metabolism , Intestinal Mucosa/metabolism , Cells, Cultured , Models, Biological , Goblet Cells/metabolism
4.
Acta Chir Belg ; : 1-6, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39058273

ABSTRACT

Background. Intussusception, the invagination of a bowel segment into an adjacent segment, occurs in 5% of adult patients with an obstruction of the bowel. It is often seen as a result of obstructive defecation syndrome or malignancy. However, a sigmoidal malignancy as lead point is rare. Symptoms in adults are less specific than in children, which makes preoperative diagnosis challenging.Reported case. An 85-year-old female presented with bright red anal blood loss. A large palpable mass was found during rectal examination. A computed tomography was performed during workup, which showed a "target-sign" on the location of the laesion. An intussusception of the sigmoid into the rectum was seen over the length of 15 centimetres. This particular type of intussusception is extremely rare.Conclusion. When a neoplasm is suspected to be the lead point, an oncological resection is recommended. We performed a total mesorectal excision, after which the patient had an uneventful recovery.

5.
Biochem Biophys Rep ; 39: 101780, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39044767

ABSTRACT

Background: Colon carcinoma poses a significant health challenge globally, particularly in developed nations where sedentary lifestyles, poor dietary choices, and genetic factors play a crucial role in its prevalence. Chemotherapy, the primary treatment method, carries severe side effects that can jeopardize patients' lives. Herbal extracts such as Ocimum Basillicum extract have shown effectiveness against cancer cells. Additionally, nanoparticles can significantly enhance drug delivery efficacy in these scenarios. Aim: This article aims to investigate the impact of copper nanoparticles coated with Ocimum Bassilicum at chemoradiotherapy of Colon Carcinoma to hopefully create new treatment options with fewer side effects for patients. Methodology: CuO bio-NPs were produced by the addition of 15 mL of extract dropwise to 80 mL of a 5 mM Cu (OAc)2 aqueous solution, which was then refluxed for 2 h at 100 °C. The mixture gradually became darker brown in color as a result of the heating procedure. The production of CuO NPs and the hydrogen-donating activity of antioxidant phenols within the plant are signaled by surface plasmon resonance excitation, which is the cause of this. In the cell culture, LS174t colon cancer cells were treated with OB extract, CuNPs, and OB-coated CuNPs with and without different radiation levels in order to assess cell viability, through the MTT assay, and the pro-apoptotic BAX and anti-apoptotic BCL2 expressions, through qPCR assay. Results: The results demonstrate a decrease in cell viability and the expression of BCL2 and an increase in the expression of BAX especially when treated with OB-coated CuNPs and even furthermore when paired with radiation therapy. Conclusions: After doing the clinical trial studies, the recent nanoparticles can be used for the treatment of Colorectal carcinoma.

6.
BMC Cancer ; 24(1): 869, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030523

ABSTRACT

CD8+T cells secreting granzyme A (GZMA) can induce pyroptosis in tumor cells by effectively cleaving gasdermin B (GSDMB), which is stimulated by interferon-γ (IFN-γ). However, the interaction between GZMA-expressing CD8+T cells and GSDMB-expressing tumor cells in colon cancer remains poorly understood. Our research employed multi-color immunohistochemistry (mIHC) staining and integrated clinical data to explore the spatial distribution and clinical relevance of GZMA- and IFN-γ-expressing CD8+ tumor-infiltrating lymphocytes (TILs), as well as GSDMB-expressing CK+ cells, within the tumor microenvironment (TME) of human colon cancer samples. Additionally, we utilizing single-cell RNA sequencing (scRNA-seq) data to examine the functional dynamics and interactions among these cell populations. scRNA-seq analysis of colorectal cancer (CRC) tissues revealed that CD8+TILs co-expressed GZMA and IFN-γ, but not other cell types. Our mIHC staining results indicated that a significant reduction in the infiltration of GZMA+IFN-γ+CD8+TILs in colon cancer patients (P < 0.01). Functional analysis results indicated that GZMA+IFN-γ+CD8+TILs demonstrated enhanced activation and effector functions compared to other CD8+TIL subsets. Furthermore, GSDMB-expressing CK+ cells exhibited augmented immunogenicity. Correlation analysis highlighted a positive association between GSDMB+CK+ cells and GZMA+IFN-γ+CD8+TILs (r = 0.221, P = 0.033). Analysis of cell-cell interactions further showed that these interactions were mediated by IFN-γ and transforming growth factor-ß (TGF-ß), the co-stimulatory molecule ICOS, and immune checkpoint molecules TIGIT and TIM-3. These findings suggested that GZMA+IFN-γ+CD8+TILs modulating GSDMB-expressing tumor cells, significantly impacted the immune microenvironment and patients' prognosis in colon cancer. By elucidating these mechanisms, our present study aims to provide novel insights for the advancement of immunotherapeutic strategies in colon cancer.


Subject(s)
CD8-Positive T-Lymphocytes , Colonic Neoplasms , Granzymes , Interferon-gamma , Lymphocytes, Tumor-Infiltrating , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Granzymes/metabolism , Interferon-gamma/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , Colonic Neoplasms/immunology , Colonic Neoplasms/pathology , Colonic Neoplasms/metabolism , Male , Female , Single-Cell Analysis
7.
J Nanobiotechnology ; 22(1): 427, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030546

ABSTRACT

Colorectal cancer, the third most prevalent cancer globally, contributes significantly to mortality rates, with over 1.9 million reported cases and nearly 935,000 fatalities annually. Surgical resection is a primary approach for localized colorectal tumors, with adjunct therapies like chemotherapy, radiotherapy, and targeted/immunotherapy considered depending on the tumor stage. However, despite preferences for targeted and immunotherapy post-surgery, chemotherapy remains commonly chosen due to its lower cost and high cancer-killing efficiency. Yet, chemotherapy faces issues such as tumor resistance and severe side effects. Nanotechnology has emerged in cancer therapy by alleviating the drawbacks of current treatment approaches. In the past few decades, inorganic nanoparticles have shown promise in combating colorectal cancer, offering advantages over conventional chemotherapy. Compared to organic nanoparticles, inorganic nanoparticles exhibit properties like photosensitivity, conductivity, magnetic allure, and thermal proficiency, allowing them to function as both drug carriers and therapeutic agents. Derived primarily from carbon, silica, metals, and metal oxides, they offer superior drug-loading capacity, heightened quantum yield, and participation in advanced photothermal and photodynamic therapies. This review provides a brief overview of the pathophysiology of colorectal cancer and the pivotal role of inorganic nanoparticles in photothermal therapy photodynamic therapy, and drug delivery. Additionally, it discusses numerous inorganic nanoparticles in colorectal cancer therapy based on recent literature.


Subject(s)
Colorectal Neoplasms , Nanoparticles , Photochemotherapy , Humans , Colorectal Neoplasms/drug therapy , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Photochemotherapy/methods , Animals , Drug Delivery Systems/methods , Drug Carriers/chemistry , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
8.
Clin Epigenetics ; 16(1): 95, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030645

ABSTRACT

BACKGROUND: Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. RESULTS: We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. CONCLUSIONS: This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.


Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , Colonic Neoplasms , DNA Methylation , Humans , Colonic Neoplasms/genetics , Colonic Neoplasms/diagnosis , Colonic Neoplasms/blood , DNA Methylation/genetics , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Female , Male , Middle Aged , Liquid Biopsy/methods , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Aged , Early Detection of Cancer/methods , Epigenesis, Genetic , Case-Control Studies , Sensitivity and Specificity , Cell-Free Nucleic Acids/genetics , Cell-Free Nucleic Acids/blood , Adult , Prognosis
9.
BMC Cancer ; 24(1): 878, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039514

ABSTRACT

PURPOSE: Oxaliplatin-containing adjuvant chemotherapy yields a significant survival benefit in stage III colon cancer and is the standard of care. Simultaneously, it causes dose-dependent peripheral neuropathy that may increase the risk of fall-related injury (FRI) such as fracture and laceration. Because these events carry significant morbidity and the global burden of colon cancer is on the rise, we examined the association between treatment with a full versus shortened course of adjuvant chemotherapy and post-treatment FRI and fracture. METHODS: In this overlap propensity score weighted, retrospective cohort study, we included patients aged ≥ 18 years with resected stage III colon cancer diagnosed 2007-2019 and treated with oxaliplatin-containing adjuvant chemotherapy (oxaliplatin plus a fluoropyrimidine; capecitabine [CAPOX] or 5-fluorouracil and leucovorin [FOLFOX]). Propensity score methods facilitate the separation of design from analysis and comparison of baseline characteristics across the weighted groups. Treatment groups were defined as 50% (4 cycles CAPOX/6 cycles FOLFOX) and > 85% (7-8 cycles CAPOX/11-12 cycles FOLFOX) of a maximal course of adjuvant chemotherapy to approximate the treatment durations received in the IDEA collaboration. The main outcomes were time to any FRI and time to fracture. We determined the subdistribution hazard ratios (sHR) estimating the association between FRI/fracture and treatment group, accounting for the competing risk of death. RESULTS: We included 3,461 patients; 473 (13.7%) received 50% and 2,988 (86.3%) received > 85% of a maximal course of adjuvant therapy. For post-treatment FRI, median follow-up was 4.6 years and total follow-up was 17,968 person-years. There were 508 FRI, 301 fractures, and 692 deaths. Treatment with > 85% of a maximal course of therapy conferred a sHR of 0.84 (95% CI 0.62-1.13) for post-treatment FRI and a sHR of 0.72 (95% CI 0.49-1.06) for post-treatment fracture. CONCLUSION: For patients with stage III colon cancer undergoing treatment with oxaliplatin-containing adjuvant chemotherapy, any potential neuropathy associated with longer durations of treatment was not found to result in greater rates of FRI and fracture. Within the limits of this retrospective study, our findings suggest concern about FRI, while mechanistically plausible, ought not to determine treatment duration.


Subject(s)
Accidental Falls , Antineoplastic Combined Chemotherapy Protocols , Colonic Neoplasms , Fluorouracil , Leucovorin , Neoplasm Staging , Oxaliplatin , Humans , Retrospective Studies , Female , Male , Chemotherapy, Adjuvant/methods , Chemotherapy, Adjuvant/adverse effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Oxaliplatin/administration & dosage , Oxaliplatin/adverse effects , Oxaliplatin/therapeutic use , Aged , Accidental Falls/statistics & numerical data , Leucovorin/therapeutic use , Leucovorin/adverse effects , Leucovorin/administration & dosage , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Fractures, Bone/etiology , Fractures, Bone/epidemiology , Capecitabine/administration & dosage , Propensity Score , Adult , Organoplatinum Compounds
10.
World J Surg Oncol ; 22(1): 187, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039538

ABSTRACT

BACKGROUND: The cranial-caudal-medial approach (CCMA) has been proposed for laparoscopic right hemicolectomy nowadays. This study aimed to investigate the safety and oncological efficacy of CCMA in the treatment of right-sided colon cancer compared to the medial-lateral approach (MLA). METHODS: Patients diagnosed with right-sided colon cancer were included from February 2015 to June 2018, retrospectively, dividing into the CCMA group and the MLA group. We compared the basic characteristics and the short-term and long-term outcomes in two groups. RESULTS: Two hundred and ninety-six patients were included in this study. The baseline characteristics were similar in two groups. Compared with MLA group, CCMA group exhibited shorter operation time (136.3 ± 25.3 min vs. 151.6 ± 21.5 min, P < 0.001), lower estimated blood loss (44.1 ± 15.2 ml vs. 51.4 ± 26.9 min, P = 0.010), and more harvested lymph nodes (18.5 ± 7.1 vs. 16.5 ± 5.7, P = 0.021). The 5-year overall survival (OS) rate for the CCMA group was 76.5%, and the 5-year disease-free survival (DFS) rate was 72.3%, both of which were not inferior to the MLA group. No significant difference was found between two groups in terms of other clinical parameters. CONCLUSION: The CCMA in laparoscopic right hemicolectomy is safe and feasible, making the anatomical plane clearer. This approach can shorten the operation time, reduce intraoperative blood loss, harvest more lymph nodes, and yield satisfactory oncological outcomes.


Subject(s)
Colectomy , Colonic Neoplasms , Laparoscopy , Propensity Score , Humans , Colectomy/methods , Female , Male , Laparoscopy/methods , Retrospective Studies , Colonic Neoplasms/surgery , Colonic Neoplasms/pathology , Middle Aged , Survival Rate , Follow-Up Studies , Aged , Operative Time , Prognosis
11.
Steroids ; 209: 109469, 2024 Sep.
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 âˆ¼ 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.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Estradiol , Testosterone , Humans , Testosterone/pharmacology , Testosterone/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Estradiol/pharmacology , Estradiol/chemistry , Estradiol/chemical synthesis , Drug Screening Assays, Antitumor , Cell Line, Tumor , Structure-Activity Relationship , Receptors, Estrogen/metabolism , Receptors, Androgen/metabolism , Molecular Structure , Male
12.
Life Sci ; 352: 122905, 2024 Sep 01.
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.


Subject(s)
Cell Proliferation , Colonic Neoplasms , Epithelial-Mesenchymal Transition , Hedgehog Proteins , Signal Transduction , Humans , Epithelial-Mesenchymal Transition/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Hedgehog Proteins/metabolism , Hedgehog Proteins/genetics , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Neoplasm Metastasis , Cell Movement , SOXB2 Transcription Factors/metabolism , SOXB2 Transcription Factors/genetics , Octamer Transcription Factor-3/metabolism , Octamer Transcription Factor-3/genetics
13.
Anticancer Res ; 44(8): 3553-3556, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39060046

ABSTRACT

BACKGROUND/AIM: Caudal-type homeobox transcription factor 2 (CDX2) is a master regulator of intestinal development and maintenance of the intestinal epithelium. We previously revealed that CDX2Low colorectal cancers (CRCs) were associated with poor survival and differential response to adjuvant chemotherapy. MicroRNAs (miRNAs), a class of non-coding RNAs typically composed of fewer than 25 nucleotides, are known to regulate gene expression and signaling pathways. This study aimed to identify oncogenic miRNAs induced by CDX2 in CRC. MATERIALS AND METHODS: HCT116 cells were cultured and transfected with CDX2 siRNA. The expression levels of four oncogenic miRNAs (miR-9, miR-25, miR-106b and miR-221) were quantified by RT-qPCR. To understand whether CDX2 represented a key regulator of miR-221 expression in vivo, we analyzed the relationship between CDX2 and miR-221expression levels in the TCGA COAD database (n=454). RESULTS: The expression level of miR-221 was significantly up-regulated in CDX2 knockdown cells (n=2, p<0.05). In the TCGA database, we observed an inverse correlation between CDX2 and miR-221 expression levels, consistent with our in vitro data (r=-0.114, p=0.0149). Furthermore, the expression level of miR-221 was significantly elevated in patients with CDX2Low CRC (p<0.05). CONCLUSION: Knockdown of CDX2 induces microRNA-221 up-regulation in human CRC. Further research is warranted to elucidate the molecular mechanisms underlying miR-221 up-regulation in CDX2Low CRCs.


Subject(s)
CDX2 Transcription Factor , Colonic Neoplasms , Gene Expression Regulation, Neoplastic , MicroRNAs , Up-Regulation , Humans , MicroRNAs/genetics , CDX2 Transcription Factor/genetics , CDX2 Transcription Factor/metabolism , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/metabolism , HCT116 Cells , Gene Knockdown Techniques
14.
J Pharm Biomed Anal ; 249: 116347, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-39029355

ABSTRACT

Gnetum montanum Markgr. (Gnetaceae) is a commonly used traditional herbal medicine among the Yao ethnic group, with potential effects in preventing and treating tumors. However, the substance basis of its anti-tumor properties remains unclear. This study utilized ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to identify the chemical components of G. montanum extract (GME) and its absorbed prototypes in cynomolgus monkey plasma after oral administration. A total of 57 compounds were detected in the GME, with 14 compounds in positive ion mode and 43 compounds in negative ion mode. In the cynomolgus monkey plasma, 17 compounds were identified, with 3 compounds in positive ion mode and 14 compounds in negative ion mode. Subsequently, we utilized high content screening technology to investigate the anti-tumor effects of GME on colon cancer, lung cancer, breast cancer, gastric cancer, liver cancer, and esophageal cancer. We found that the GME exhibited significant proliferation inhibition on colon cancer cells SW480, with an IC50 value of 50.77 µg/mL. Further research using component separation and pharmacological tracking revealed that the F2 component of the GME demonstrated notable anti-tumor effects. Through UPLC-MS identification, the chemical components in the F2 fraction were identified as pinoresinol diglucoside, (+)-pinoresinol-4-O-beta-D-glucopyranoside, ursolic acid, and gnetol. In conclusion, this study contributes to elucidating the anti-tumor pharmacological basis of GME and provides robust support for future drug design and development.

15.
Cells ; 13(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39056778

ABSTRACT

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Current studies have demonstrated that tumor-derived extracellular vesicles (EVs) from different cancer cell types modulate the fibroblast microenvironment to contribute to cancer development and progression. Here, we isolated and characterized circulating large EVs (LEVs), small EVs (SEVs) and non-EV entities released in the plasma from wild-type (WT) mice and the APCMin/+ CRC mice model. Our results showed that human colon fibroblasts exposed from APC-EVs, but not from WT-EVs, exhibited the phenotypes of cancer-associated fibroblasts (CAFs) through EV-mediated NF-κB pathway activation. Cytokine array analysis on secreted proteins revealed elevated levels of inflammatory cytokine implicated in cancer growth and metastasis. Finally, non-activated cells co-cultured with supernatant from fibroblasts treated with APC-EVs showed increased mRNA expressions of CAFs markers, the ECM, inflammatory cytokines, as well as the expression of genes controlled by NF-κB. Altogether, our work suggests that EVs and non-EV components from APCMin/+ mice are endowed with pro-tumorigenic activities and promoted inflammation and a CAF-like state by triggering NF-κB signaling in fibroblasts to support CRC growth and progression. These findings provide insight into the interaction between plasma-derived EVs and human cells and can be used to design new CRC diagnosis and prognosis tools.


Subject(s)
Extracellular Vesicles , Fibroblasts , NF-kappa B , Signal Transduction , Animals , Extracellular Vesicles/metabolism , NF-kappa B/metabolism , Humans , Mice , Fibroblasts/metabolism , Colon/pathology , Colon/metabolism , Adenomatous Polyposis Coli Protein/metabolism , Adenomatous Polyposis Coli Protein/genetics , Carcinogenesis/pathology , Carcinogenesis/genetics , Carcinogenesis/metabolism , Mice, Inbred C57BL , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/genetics , Tumor Microenvironment , Cytokines/metabolism , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology
16.
Cells ; 13(14)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39056792

ABSTRACT

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix and in mice fed with EAA-rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable antiproliferative properties.


Subject(s)
Apoptosis , Cell Proliferation , Colonic Neoplasms , Animals , Colonic Neoplasms/pathology , Colonic Neoplasms/metabolism , Mice , Cell Proliferation/drug effects , Cell Line, Tumor , Apoptosis/drug effects , Amino Acids/pharmacology , Mice, Inbred BALB C , Amino Acids, Essential/pharmacology
17.
Cell Rep Med ; : 101661, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39059386

ABSTRACT

Identifying patients with stage II and III colon cancer who will benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy is crucial for the advancement of personalized cancer therapy. We employ a semi-supervised machine learning approach to analyze a large dataset with 933 stage II and III colon cancer samples. Our analysis leverages gene regulatory networks to discover an 18-gene prognostic signature and to explore a 10-gene signature that potentially predicts chemotherapy benefits. The 10-gene signature demonstrates strong prognostic power and shows promising potential to predict chemotherapy benefits. We establish a robust clinical assay on the NanoString nCounter platform, validated in a retrospective formalin-fixed paraffin-embedded (FFPE) cohort, which represents an important step toward clinical application. Our study lays the groundwork for improving adjuvant chemotherapy and potentially expanding into immunotherapy decision-making in colon cancer. Future prospective studies are needed to validate and establish the clinical utility of the 10-gene signature in clinical settings.

18.
Sci Rep ; 14(1): 17145, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060367

ABSTRACT

The aim of this study is to compare the diagnostic performance of magnetic resonance imaging (MRI) against computed tomography (CT) in various aspects of local staging in colon cancer patients. This study was a prospective single arm diagnostic accuracy study. All consecutive adult patients with confirmed colon cancer that met the current criteria for surgical resection were considered as eligible. Diagnostic performance assessment included T (T1/T2 vs T3/T4 and < T3ab vs > T3cd) and N (N positive) staging, serosa and retroperitoneal surgical margin (RSM) involvement and extramural vascular invasion (EMVI). Imaging was based on a 3 Tesla MRI system and the evaluation of all sequences (T1, T2 and diffusion-weighted imaging-DWI series) by two independent readers. CT scan was performed in a 128 row multidetector (MD) CT scanner (slice thickness: 1 mm) with intravenous contrast. Pathology report was considered as the gold standard for local staging. Sensitivity (SE), specificity (SP), and area under the curve (AUC) were calculated for both observers. MRI displayed a higher diagnostic performance over CT in terms of T1/T2 vs T3/T4 (SE: 100% vs 83.9%, SP: 96.6% vs 81%, AUC: 0.825 vs 0.983, p < 0.001), N positive (p < 0.001) and EMVI (p = 0.023) assessment. An excellent performance of MRI was noted in the T3ab vs T3cd (CT AUCReader1: 0.636, AUCReader2: 0.55 vs MRI AUCReader1: 0.829 AUCReader2 0.846, p = 0.01) and RSM invasion diagnosis. In contrast to these, MRI did not perform well in the identification of serosa invasion. MRI had a higher diagnostic yield than CT in several local staging parameters.


Subject(s)
Colonic Neoplasms , Magnetic Resonance Imaging , Neoplasm Staging , Tomography, X-Ray Computed , Humans , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Male , Female , Middle Aged , Aged , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Prospective Studies , Adult , Aged, 80 and over
19.
Surg Endosc ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060624

ABSTRACT

OBJECTIVE: Splenic flexure mobilization (SFM) is a major challenge in laparoscopic left hemicolectomy. This study aims to assess the safety and effectiveness of the pancreas-guided SFM technique during laparoscopic left hemicolectomy. METHODS: From January 2018 to December 2023, 352 patients with left-sided colon cancer underwent laparoscopic left hemicolectomy. Based on the SFM method used, the patients were divided into the pancreas-guided group (167 cases) or the "Three Approaches Roundabout"/classic group (185 cases). Clinicopathologic characteristics and intraoperative and postoperative variables were compared between the two groups. RESULTS: The two groups had no significant differences in baseline indicators (P > 0.05). All surgeries were successful without needing to convert to laparotomy, and there were no combined organ resections involving the spleen or pancreas in either group. The mean duration of surgery was significantly lower in the pancreas-guided group than in the classic group (P < 0.01). The median volume of intraoperative blood loss in the pancreas-guided group was lower than that in the classic group (P < 0.01). Through video playback, it was found that the retro-pancreatic space had been entered during operation in 8 cases (4.3%) in the classic group, while there were no such occurrences in the pancreas-guided group. This difference was statistically significant (P < 0.05). The difference in the number of lymph nodes cleared, postoperative hospital stays, and incidence of complications were not statistically significant (all P > 0.05) between the groups. CONCLUSION: The pancreas-guided SFM technique is a safe and feasible option for laparoscopic left hemicolectomy. Our study's findings suggest that this approach facilitates accurate access to the correct anatomic plane, potentially improving surgical efficiency.

20.
Cancers (Basel) ; 16(14)2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39061145

ABSTRACT

Liquid biopsy is rapidly becoming an indispensable tool in the oncologist's arsenal; however, this technique remains elusive in a publicly funded healthcare system, and real-world evidence is needed to demonstrate utility and feasibility. Here, we describe the first experience of an in-house point of care liquid biopsy program at a Canadian community hospital. A retrospective review of consecutive cases that underwent plasma-based next-generation sequencing (NGS) was conducted. Liquid biopsy was initiated at the discretion of clinicians. Sequencing followed a point of care workflow using the Genexus™ integrated sequencer and the Oncomine precision assay, performed by histotechnologists. Results were reported by the attending pathologist. Eligible charts were reviewed for outcomes of interest, including the intent of the liquid biopsy, results of the liquid biopsy, and turnaround time from blood draw to results available. A total of 124 cases, with confirmed or suspected cancer, underwent liquid biopsy between January 2021 and November 2023. The median turnaround time for liquid biopsy results was 3 business days (range 1-12 days). The sensitivity of liquid biopsies was 71%, compared to tissue testing in cases with matched tissue results available for comparison. Common mutations included EGFR (29%), in 86 lung cancer patients, and PIK3CA (22%), identified in 13 breast cancer patients. Healthcare providers ordered liquid biopsies to inform diagnostic investigations and treatment decisions, and to determine progression or resistance mechanisms, as these reasons often overlapped. This study demonstrates that rapid in-house liquid biopsy using point of care methodology is feasible. The technique facilitates precision treatment and offers many additional advantages for cancer care.

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