Ginseng polysaccharide promotes the apoptosis of colon cancer cells via activating the NLRP3 inflammasome.

BACKGROUND: Ginseng polysaccharide (GPS) is an ingredient of ginseng with documented anti-tumor properties. However, its effect on colon cancer and the underlying molecular mechanisms have not been investigated clearly. METHODS: Cell viability of HT29 and CT26 cells treated with different concentrations of GPS was assessed using the Cell Counting Kit-8 (CCK-8) assay. Western blot assay was used to detect the expression of apoptotic proteins, while the mRNA levels were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Transwell migration assays were used to examine the migration and invasion of cells. RESULTS: The results revealed that GPS effectively suppressed the proliferation of HT29 and CT26 cells. We demonstrated an upregulation of apoptotic proteins in GPS-treated cells, including Bax, cleaved Caspase-3, and p-p53. GPS treatment also increased the mRNA levels of cytochrome C and Bax. Furthermore, the results showed that GPS treatment concurrently promoted the activation of nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) inflammasome. Transwell migration assays showed that GPS inhibited the migratory and invasive abilities of colon cancer cells. As expected, inhibition of NLRP3 expression using INF39 attenuated the inhibitory effect of GPS on migration and invasion. Upon NLRP3 inhibition, GPS-induced apoptosis was dramatically alleviated, accompanied by a reduction in the expression of apoptotic proteins. CONCLUSION: In conclusion, this research provides compelling evidence that the GPS-induced NLRP3 signaling pathway plays a pivotal role in apoptosis of colon cells, suggesting potential clinical implications for the therapeutic intervention of colon cancer. Thus, GPS might be a promising anti-tumor drug for the treatment of colorectal cancer.

Identification of an Amino Acid Metabolism Reprogramming Signature for Predicting Prognosis, Immunotherapy Efficacy, and Drug Candidates in Colon Cancer.

Colon cancer ranked third among the most frequently diagnosed cancers worldwide. Amino acid metabolic reprogramming was related to the occurrence and development of colon cancer. We looked for the amino acid metabolism genes (AMGs) associated with amino acid metabolism from molecular signatures database as prognostic markers and constructed amino acid metabolism scoring model (AMS). According to AMS, the patients were divided into high AMS and low AMS groups, and the prognostic characteristics, molecular phenotypes, somatic cell mutation characteristics, immune cell infiltration characteristics, and immunotherapy effect of the two groups were systematically analyzed. Finally, the compounds targeting AMGs were also screened. We screen out 6 prognostic AMGs (P < 0.05) and construct an AMS model based on them. K-M curve indicated that OS in low AMS group was significantly higher than that in high group (P < 0.05), which were validated in multiple datasets. And different AMS groups had different molecular phenotypes, somatic cell mutation characteristics and immune cell infiltration characteristics. Low AMS group had a better effect for immunotherapy. In addition, we predicted potential therapeutic compounds that could bind to AMGs target proteins. AMS model can be used as a hierarchical tool to evaluate the prognosis, immune infiltration characteristics and immunotherapy response ability of colon cancer. And the compounds screened based on AMGs may become new anti-tumor drugs.

Safety and efficacy of autologous blood tattooing for preoperative colonic localization: a comparative study with conventional India ink tattooing.

BACKGROUND: India ink has been a popular choice for a tattooing agent in preoperative endoscopic localization but often results in unfavorable effects. Subsequently, autologous blood tattooing has arisen as an alternative option. Due to the limited availability of comparative studies on the matter, we conducted a study to compare the perioperative outcomes associated with India ink tattooing versus autologous blood tattooing. METHODS: A total of 96 patients who underwent minimally invasive surgical procedures for left-sided colonic neoplasm following preoperative endoscopic localization were included in the study. These patients were categorized into two groups: 36 patients who received India ink tattooing and 60 patients who underwent autologous blood tattooing. The perioperative outcomes including procedure-related outcomes and postoperative outcomes were compared between the two groups. RESULTS: There was no significant difference in visibility and spillage of tattooing agent between India ink group and autologous blood group. However, India ink group showed a higher incidence of post-tattooing fever, higher level of postoperative C-reactive protein level, longer time to first flatus, resumption of surgical soft diet, and duration of hospital stay, and a higher occurrence of postoperative complications including ileus and surgical site infection compared with the autologous blood group. In the multivariate analysis, India ink tattooing was significantly associated with the occurrence of postoperative complications. In the subgroup analysis involving patients with intraperitoneal spillage, the autologous blood group demonstrated significantly favorable perioperative outcomes compared with India ink group. CONCLUSIONS: Autologous blood tattooing demonstrated comparable visibility and enhanced safety, establishing it as a potential alternative to India ink for preoperative endoscopic localization.

A log odds of positive lymph nodes-based predictive model effectively forecasts prognosis and guides postoperative adjuvant chemotherapy duration in stage III colon cancer: a multi-center retrospective cohort study.

BACKGROUND: The log odds of positive lymph nodes (LODDS) was considered a superior staging system to N stage in colon cancer, yet its value in determining the optimal duration of adjuvant chemotherapy for stage III colon cancer patients has not been evaluated. This study aims to assess the prognostic value of a model that combines LODDS with clinicopathological information for stage III colon cancer patients and aims to stratify these patients using the model, identifying individuals who could benefit from varying durations of adjuvant chemotherapy. METHOD: A total of 663 consecutive patients diagnosed with stage III colon cancer, who underwent colon tumor resection between November 2007 and June 2020 at Sun Yat-sen University Cancer Center and Longyan First Affiliated Hospital of Fujian Medical University, were enrolled in this study. Survival outcomes were analyzed using Kaplan-Meier, Cox regression. Nomograms were developed to forecast patient DFS, with the Area Under the Curve (AUC) values of time-dependent Receiver Operating Characteristic (timeROC) and calibration plots utilized to assess the accuracy and reliability of the nomograms. RESULTS: Multivariate analysis revealed that perineural invasion (HR = 1.776, 95% CI: 1.052-3.003, P = 0.032), poor tumor differentiation (HR = 1.638, 95% CI: 1.084-2.475, P = 0.019), and LODDS groupings of 2 and 1 (HR = 1.920, 95% CI: 1.297-2.842, P = 0.001) were independent predictors of disease-free survival (DFS) in the training cohort. Nomograms constructed from LODDS, perineural invasion, and poor tumor differentiation demonstrated robust predictive performance for 3-year and 5-year DFS in both training (3-year AUC = 0.706, 5-year AUC = 0.678) and validation cohorts (3-year AUC = 0.744, 5-year AUC = 0.762). Stratification according to this model showed that patients in the high-risk group derived significant benefit from completing 8 cycles of chemotherapy (training cohort, 82.97% vs 67.17%, P = 0.013; validation cohort, 89.49% vs 63.97%, P = 0.030). CONCLUSION: The prognostic model, integrating LODDS, pathological differentiation, and neural invasion, demonstrates strong predictive accuracy for stage III colon cancer prognosis. Moreover, stratification via this model offers valuable insights into optimal durations of postoperative adjuvant chemotherapy.

Application value of dexmedetomidine in anesthesia for elderly patients undergoing radical colon cancer surgery.

BACKGROUND: Colon cancer presents a substantial risk to the well-being of elderly people worldwide. With advancements in medical technology, surgical treatment has become the primary approach for managing colon cancer patients. However, due to age-related physiological changes, especially a decline in cognitive function, older patients are more susceptible to the effects of surgery and anesthesia, increasing the relative risk of postoperative cognitive dysfunction (POCD). Therefore, in the surgical treatment of elderly patients with colon cancer, it is of paramount importance to select an appropriate anesthetic approach to reduce the occurrence of POCD, protect brain function, and improve surgical success rates. AIM: To explore the value of dexmedetomidine (Dex) in anesthesia for elderly patients undergoing radical colon cancer surgery. METHODS: One hundred and seventeen patients with colon cancer who underwent elective surgery under general anesthesia were selected and divided into two groups: A and B. Group A received Dex before anesthesia induction, and B group received an equivalent amount of normal saline. Changes in the mini-mental state examination, regional cerebral oxygen saturation (rSO2), bispectral index, glucose uptake rate (GluER), lactate production rate (LacPR), serum S100ß and neuron-specific enolase (NSE), POCD, and adverse anesthesia reactions were compared between the two groups. RESULTS: Surgical duration, duration of anesthesia, and intraoperative blood loss were comparable between the two groups (P > 0.05). The overall dosage of anesthetic drugs used in group A, including propofol and remifentanil, was significantly lower than that used in group B (P < 0.05). Group A exhibited higher rSO2 values at the time of endotracheal intubation, 30 min after the start of surgery, and immediately after extubation, higher GluER values and lower LacPR values at the time of endotracheal intubation, 30 min after the start of surgery, immediately after extubation, and 5 min after extubation (P < 0.05). Group A exhibited lower levels of serum S100ß and NSE 24 h postoperatively and a lower incidence of cognitive dysfunction on the 1st and 5th postoperative days (P < 0.05). CONCLUSION: The use of Dex in elderly patients undergoing radical colon cancer surgery helps maintain rSO2 Levels and reduce cerebral metabolic levels and the incidence of anesthesia- and surgery-induced cognitive dysfunction.

[Effect of Pterostilbene Regulating Nuclear Factor E2-Related Factor 2 on Apoptosis of Colon Cancer Cells in Vitro].

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2 (Nrf2) in the process of pterostilbene acting on LoVo cells. Methods LoVo cells were treated with different concentrations (5,10,20,40,60,80,100 µmol/L) of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Transwell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochondrial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlorofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic proteins (Bcl2 and Bax) were determined by Western blotting.In addition,cell viability,Nrf2 expression,and apoptosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane. Results Compared with the control group,40,60,80,100 µmol/L pterostilbene reduced the viability of LoVo cells (P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 µmol/L did not show effects on cell viability but inhibited cell migration (P=0.008,P<0.001,P<0.001) and invasion (all P<0.001).Pterostilbene at 40,60,80 µmol/L increased apoptosis (P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization (P=0.026,P<0.001,P<0.001) and reactive oxygen species accumulation (all P<0.001),and down-regulated the expression of phosphorylated Nrf2 (P=0.030,P<0.001,P<0.001),heme oxygenase 1 (P=0.015,P<0.001,P<0.001),and Bcl2 (P=0.039,P<0.001,P<0.001) in LoVo cells.Pterostilbene at 60,80 µmol/L down-regulated Nrf2 expression (P=0.001,P<0.001) and up-regulated Bax expression (both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability (P<0.001),apoptosis (P<0.001),and Nrf2 expression (P=0.022). Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Berberine suppressed the epithelial-mesenchymal transition (EMT) of colon epithelial cells through the TGF-ß1/Smad and NF-κB pathways associated with miRNA-1269a.

Objective: To explore the mechanisms of the TGF-ß1/Smad and NF-κB pathways in the effect of berberine (BBR) on colon cancer epithelial-mesenchymal transition (EMT) and their regulatory relationships with microRNAs (miRNAs). Methods: TGF-ß1 was used to induce EMT in normal colon epithelial HCoEpiC cells and colon cancer HT29 cells in vitro. After BBR intervention, the expression of EMT-related markers and the major molecules involved in the TGF-ß1/Smad and NF-κB pathways were detected via western blotting. Cell migration was detected via wound healing assays. SMAD2 and NF-κB p65 were overexpressed and transfected into cells, and the inhibitors SB431542 and BAY 11-7082 were added to block the TGF-ß1/Smad and NF-κB pathways, respectively. The mRNA expression levels of related microRNA genes were detected by using RT‒PCR. Results: Treatment with 10 ng/ml TGF-ß1 for 72 h significantly induced EMT in HCoEpiC and HT29 cells, which was repressed by BBR. BBR significantly inhibited the TGF-ß1-induced migration of HCoEpiC and HT29 cells and the TGF-ß1-promoted expression of p-Smad2/3, NF-κB p65, and p-IκBα. Compared to those in the group treated with TGF-ß1, the expression of NF-κB p65 and p-Smad2 in the group treated with NF-κB pathway inhibitor BAY 11-7082 was decreased (P < 0.05), and TGF-ß1 signalling inhibitor SB431542 significantly reduced the expression of NF-κB p65 (P < 0.05). Overexpression of NF-κB p65 and SMAD2 in HT29 cells decreased the expression of E-cadherin and caused a relative increase in N-cadherin. BBR mediated the expression profile of microRNAs in TGF-ß1-induced HCoEpiC cells, but this pattern differed from that in HT29 cells. SB431542 and BAY 11-7082 significantly reduced the mRNA level of miR-1269a in HCoEpiC and HT29 cells (P < 0.05). Overexpressed NF-κB p65 and SMAD2 increased the mRNA level of miR-1269a in both cell lines; however, this increase was significantly lower than that in the TGF-ß1 treatment group (P < 0.05). Conclusion: BBR can significantly inhibit TGF-ß1-induced EMT in normal and cancerous colon epithelial cells through the inhibition of the TGF-ß1/Smad and NF-κB p65 pathways. TGF-ß1/Smads can promote the NF-κB p65 pathway, which is a common target of miR-1269a, and can partially regulate the expression of miR-1269a.

Serotonin's Role in Inflammatory Signaling Pathway Modulation for Colon Cancer Suppression.

Background Neurons can be effectively regulated by serotonin and dopamine. Their role in anti-inflammatory pathways opens new doors for therapeutic research, particularly in chemotherapeutics. The present study investigated serotonin's role in suppressing inflammation and its potential anticancer effects in KERATIN-forming tumor cell line HeLa cells (KB cells).  Methods - in vitro and in silico analysis The study delved further into the molecular mechanisms by assessing the expression levels of key markers involved in inflammation and cancer progression, such as B-cell leukemia/lymphoma 2 protein (BCl-2), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) using Real-time reverse-transcriptase-polymerase chain reaction at concentrations below the IC50 (50 and 100 µg/ml). The binding capability of serotonin (CID 5202) with glycoform of human interleukin 6 (PDB: 7NXZ) was analyzed with the help of Schrodinger molecular suites. Results The findings showcased serotonin's potent growth inhibition in KB cells, with an IC50 value of 225±3.1µg/ml. Additionally, it demonstrated a multifaceted impact by downregulating the expression of BCl-2, TNF-α, and IL-6, pivotal factors in cancer cell survival and inflammation regulation. The docking score was - 5.65 (kcal/mol) between serotonin and glycoform of Human Interleukin 6. It is bound with ASN 143 by two hydrogen bonds. Thus, molecular docking analysis showed an efficient bounding pattern. The research findings indicate that serotonin successfully blocks NF-κB pathways in KB cells, underscoring its therapeutic promise against colon cancer and offering vital information for additional clinical investigation.  Conclusion According to the study's conclusion, serotonin has a remarkable anticancer potential by effectively blocking NF-κB B pathways in KB cells, revealing its promising potential as a therapeutic agent against colon cancer. These comprehensive findings offer significant insights into serotonin's intricate molecular interactions and its profound impact on cancer-related signaling pathways, paving the way for further exploration and potential clinical applications in cancer treatment strategies.

Current sessile serrated lesion incidence: implications for future clinical practice.

BACKGROUND: Sessile serrated lesions (SSL) account for up to 30% of colorectal carcinoma pathogenesis. With multiple classification changes and improvements in colonoscopy equipment and technique, historical reporting may have underestimated the true incidence of SSLs. This study aimed to determine the incidence of SSLs in patients undergoing colonoscopic investigation in Canterbury, New Zealand over a 1-year period and describe their clinical and pathological characteristics. METHODS: Electronic records were searched to identify all lower endoscopy procedures with polypectomy performed from 1 January 2022 to 1 December 2022 (inclusive). Patients' electronic records were used to collect histological classification, location and size of each polyp removed during their procedure. The primary outcome was the number of procedures that had one or more SSL, adenoma or hyperplastic polyp identified. Secondary outcomes included histological classification, location and size of each polyp removed. RESULTS: There were 4346 procedures completed during the study period. Of these, 64.1% (2786) had a polypectomy and 18.6% (808) had at least one SSL excised. Individual polyp analysis was completed on 9166 polyps and found that 24.0% of polyps removed were SSLs and they were found predominately in the right colon (65.1% right colon, 32.6% left colon, 2.3% rectum). SSLs were typically <10 mm (84.8%). CONCLUSION: This study found a higher incidence of SSLs compared to previous research. These results raise questions regarding whether SLL rates have been historically underestimated, whether SSL detection rate should be included as a key performance indicator and raises further concerns regarding the use of computed tomography colonography as a screening tool.

Morchella conica, Morchella esculenta and Morchella delicosa Induce Apoptosis in Breast and Colon Cancer Cell Lines via Pro-apoptotic and Anti-apoptotic Regulation.

OBJECTIVE: To explore the potential apoptotic mechanisms of 3 Morchella extracts (Morchella conica, Morchella esculenta and Morchella delicosa) on breast and colon cancer cell lines using apoptotic biomarkers. METHODS: Human breast cell line (MCF-7) and colon cancer cell line (SW-480) were treated with methanol and ethanol extracts of 3 Morchella species with concentration ranging from 0.0625 to 2 mg/mL. After that their effects on gene expression of apoptosis related markers (pro-apoptotic markers including Bax, caspase-3, caspase-7, and caspase-9, and the antiapoptotic marker including Bcl-2) were determined using reverse transcription polymerase chain reaction. RESULTS: All Morchella extracts reduced breast and colon cancer cells proliferation at half inhibitory concentration (IC50) of 0.02 ±0.01 to 0.68 ±0.30 mg/mL. As expected, all Morchella extracts significantly increased gene expressions of Bax, caspase-3, caspase-7, and caspase-9 and downregulated the gene expression of Bcl-2 in MCF-7 and SW-480 cell lines (P<0.05). CONCLUSIONS: Morchella extracts demonstrated significant anti-proliferative activity against breast and colon cancer cell lines via an apoptosis induction mechanism. Anticancer activity of Morchella extracts and activation of apoptosis in breast and colon cancer cells suggest that it may be used to develop chemotherapeutic agents against cancer in future.

Precision Treatment of Colon Cancer Using Doxorubicin-Loaded Metal-Organic-Framework-Coated Magnetic Nanoparticles.

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe3O4 magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe3O4@ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe3O4@ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe3O4@ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe3O4@ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe3O4@ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

Hospital Service Volume as an Indicator of Treatment Patterns for Colorectal Cancer.

INTRODUCTION: A hospital's approach (volume of cancer treatment services provided) to treating metastatic colorectal cancer influences a patient's treatment as strongly as patient disease status. The implications of hospital-level treatment approaches across disease stages remain understudied. We sought to determine if hospital service volume (SV) for metastatic colorectal cancer could be predictive of nonstandard treatment patterns in stages I-III colon cancer. MATERIALS AND METHODS: Using the National Cancer Database, we examined rates of nonstandard treatment patterns among patients with colon cancer between 2010 and 2017. After adjusting for clinicopathological characteristics using multivariable logistic regression, we evaluated the relationship between hospital-level SV for metastatic colorectal cancer and nonstandard treatment approaches for patients with stages I-III colon cancer. RESULTS: There were significant associations between hospital-level SV for metastatic colorectal cancer and the odds of chemotherapy overtreatment among patients with stage I-III colon cancer, as well as undertreatment among patients with stages II-III disease after adjusting for hospital-, patient-, and tumor-level covariates. Patients at the highest-level SV hospitals for metastatic disease had 1.29 higher odds (95% CI = 1.18-1.41; P < 0.0001) of receiving overtreatment compared to patients from lowest SV hospitals. The odds ratio of undertreatment in highest SV compared to lowest SV was 0.64 (95% CI 0.56-0.72; P< 0.0001). CONCLUSIONS: Hospital-level SV of patients with metastatic colon cancer is a significant indicator of nonstandard treatment patterns among patients with stage I-III colon cancer. Hospitals with the highest volume of cancer treatments have higher odds of providing overtreatment, while low SVs are associated with higher odds of undertreatment.

The role of LPA receptor signaling in modulating cellular responses of colon cancer cells co-cultured with lymphoid endothelial cells under hypoxic stress.

Solid tumors are formed by cancer cells and the surrounding non-cancer stromal cells under hypoxic conditions, collectively referred to as the tumor microenvironment (TME). Lysophosphatidic acid (LPA) receptor (LPA1 to LPA6) signaling is crucial in regulating tumor progression. This study investigated the impact of LPA receptor signaling on the biological behaviors of colon cancer DLD-1 cells co-cultured with lymphatic endothelial SVEC4-10 cells under hypoxic conditions. Expression levels of LPAR1, LPAR2 and LPAR5 genes were significantly higher in DLD-1 cells co-cultured with SVEC4-10 cells compared to those cultured alone. Co-culturing with SVEC4-10 cells increased the motility of DLD-1 cells at 21 % O2. LPA stimulated the motility of DLD-1 cells co-cultured with SVEC4-10 cells but had no effect on DLD-1 cells cultured alone. Furthermore, under 1 % O2 conditions, expression levels of LPAR1, LPAR2, and LPAR5 genes were markedly elevated in DLD-1 cells co-cultured with SVEC4-10 cells compared to 21 % O2. The motility of DLD-1 cells co-cultured with SVEC4-10 cells was enhanced under 1 % O2 conditions. Viability of DLD-1 cells to fluorouracil (5-FU) in SVEC4-10 cell supernatants increased at 21 % O2 and decreased at 1 % O2. Additionally, the LPA2 agonist GRI-977143 increased viability to 5-FU. These findings indicate that LPA receptor signaling plays a critical role in regulating the biological behaviors of DLD-1 cells co-cultured with SVEC4-10 cells under hypoxic conditions.

A Two-Stage Transferred Cold Atmospheric Plasma as a Unique Therapeutic Strategy for Targeting Colon Cancer Stem Cells.

The study examines the induction of apoptosis in colon cancer stem cells (CCSCs) within a 3D culture setting, employing an innovative cold atmospheric plasma (CAP) transmission method known as two-stage transferred cold atmospheric plasma (TS-TCAP). TS-TCAP is a partially or fully ionized non-thermal gaseous mixture that comprises photons, charged and neutral particles, and free radicals, which has gained traction in biomedical applications such as cancer therapy. TS-TCAP impacts CCSCs via a continuous, two-step transport process, facilitating the efficient delivery of reactive oxygen and nitrogen species (RONS). The key cellular factors of CCSCs impacted by TS-TCAP treatment, encompassing the secretion and expression levels of IL-6 and IL-8, apoptotic cell count, and expression of BAX, BCL-2, and KI-67 proteins, were evaluated using qrt-ELISA, Annexin V, and qrt-PCR procedures, respectively. The outcomes of CCSCs treatment with TS-TCAP reveal a notable rise in the number of apoptotic cells (P<0.0001), diminished secretion, and gene expression of IL-6 and IL-8 (P<0.0001), accompanied by favorable alterations in BCL-2 and BAX gene expression (P<0.0001). Additionally, a notable decrease in KI-67 expression was observed, correlating with a reduction in CCSCs proliferation (P<0.0001). As well, this study underscores the anti-cancer potential of TS-TCAP, showcasing its efficacy in reducing CCSCs survival rates. However, further pre-clinical and clinical trials are necessary to evaluate CAP's efficacy, safety, and potential synergistic effects with other therapies thoroughly. Overall, TS-TCAP presents a promising alternative for CCSCs treatment, pending further investigation and refinement.

Predicting Postoperative Length of Stay in Patients Undergoing Laparoscopic Right Hemicolectomy for Colon Cancer: A Machine Learning Approach Using SICE (Società Italiana di Chirurgia Endoscopica) CoDIG Data.

The evolution of laparoscopic right hemicolectomy, particularly with complete mesocolic excision (CME) and central vascular ligation (CVL), represents a significant advancement in colon cancer surgery. The CoDIG 1 and CoDIG 2 studies highlighted Italy's progressive approach, providing useful findings for optimizing patient outcomes and procedural efficiency. Within this context, accurately predicting postoperative length of stay (LoS) is crucial for improving resource allocation and patient care, yet its determination through machine learning techniques (MLTs) remains underexplored. This study aimed to harness MLTs to forecast the LoS for patients undergoing right hemicolectomy for colon cancer, using data from the CoDIG 1 (1224 patients) and CoDIG 2 (788 patients) studies. Multiple MLT algorithms, including random forest (RF) and support vector machine (SVM), were trained to predict LoS, with CoDIG 1 data used for internal validation and CoDIG 2 data for external validation. The RF algorithm showed a strong internal validation performance, achieving the best performances and a 0.92 ROC in predicting long-term stays (more than 5 days). External validation using the SVM model demonstrated 75% ROC values. Factors such as fast-track protocols, anastomosis, and drainage emerged as key predictors of LoS. Integrating MLTs into predicting postoperative LOS in colon cancer surgery offers a promising avenue for personalized patient care and improved surgical management. Using intraoperative features in the algorithm enables the profiling of a patient's stay based on the planned intervention. This issue is important for tailoring postoperative care to individual patients and for hospitals to effectively plan and manage long-term stays for more critical procedures.

Unique miRNA Expression Profile in MSI- and EMAST-Unstable Sporadic Colon Cancer.

MicroRNAs (miRNAs) are critical post-transcriptional gene regulators and their involvement in sporadic colon cancer (CRC) tumorigenesis has been confirmed. In this study we investigated differences in miRNA expression in microsatellite stable (MSS/EMAST-S), microsatellite unstable marked by high elevated microsatellite alterations at selected tetranucleotide repeats (MSS/EMAST-H), and high microsatellite unstable (MSI-H/EMAST-H) tumor subgroups as well as in tumors with different clinicopathologic characteristics. An RT-qPCR analysis of miRNA expression was carried out on 45 colon cancer and adjacent normal tissue samples (15 of each group). Overall, we found three differentially expressed miRNAs between the subgroups. miR-92a-3p and miR-224-5p were significantly downregulated in MSI-H/EMAST-H tumors in comparison to other subgroups. miR-518c-3p was significantly upregulated in MSS/EMAST-H tumors in comparison to stable and highly unstable tumors. Furthermore, we showed that miR-143-3p and miR-145-5p were downregulated in tumors in comparison to normal tissues in all subgroups. In addition, we showed overexpression of miR-125b-5p in well-differentiated tumors and miR-451a in less advanced tumors. This is the first report on differences in miRNA expression profiles between MSS/EMAST-S, MSS/EMAST-H, and MSI-H/EMAST-H colorectal cancers. Our findings indicate that the miRNA expression signatures differ in CRC subgroups based on their instability status.

Exploring the Therapeutic Potential of 5-Fluorouracil-Loaded Calcium Carbonate Nanoparticles Combined with Natural Compound Thymoquinone for Colon Cancer Treatment.

Given the need for novel and effective therapies for colon cancer, this study aimed to investigate the effects of 5-fluorouracil-loaded calcium carbonate nanoparticles (5FU-CaCO3np) combined with thymoquinone (TQ) against colon cancer. A shaking incubator and a high-speed homogenizer were used to prepare the optimal 5FU-CaCO3np, with characterizations of physicochemical properties, in vitro drug release profile, and biocompatibility. In vitro experiments and molecular docking were employed to evaluate the therapeutic potential of the combination for colon cancer treatment. Study results revealed that 5FU-CaCO3np with a size of approximately 130 nm was synthesized using the high-speed homogenizer. Its favorable biocompatibility, pH sensitivity, and sustained release properties facilitated reduced toxic side effects of 5-FU on NIH3T3 normal cells and enhanced inhibitory effects on CT26 colon cancer cells. The combination of 5FU-CaCO3np (1.875 µM) and TQ (30 µM) showed significantly superior anti-colon cancer effects to 5FU-CaCO3np alone in terms of cell proliferation and migration inhibition, cell apoptosis induction, and spheroid growth suppression in CT26 cells (p < 0.05), with strong interactions between the drugs and targets (E-cadherin, Bcl-2, PCNA, and MMP-2). These results provide evidence for 5FU-CaCO3np as a novel regimen against colon cancer. Combining 5FU-CaCO3np and TQ may offer a new perspective for colon cancer therapy.

Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients.

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single-cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil (5FU)-based chemotherapy. Images underwent segmentation for tumour, stroma, and immune cells, and cancer cell 'state' protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell-T-cell interactions at single-cell level. In our discovery cohort (Memorial Sloan Kettering samples), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU-treated stage III patients. The validation cohort (Huntsville Clearview Cancer Center samples) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between the percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (discovery cohort: p = 0.07; validation cohort: p = 0.19). We next utilised our region-based nearest neighbour approach to determine the spatial relationships between cytotoxic T cells, helper T cells, and cancer cell clusters. In both cohorts, we found that shorter distance between cytotoxic T cells, T helper cells, and cancer cells was significantly associated with increased disease-free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low-risk and high-risk groups (discovery cohort: p = 0.01; validation cohort: p = 0.003). © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

[Corrigendum] The role of IGFBP­5 in mediating the anti­proliferation effect of tetrandrine in human colon cancer cells.

Following the publication of the above article, a concerned reader drew to the authors' attention that, among Figs. 1D, 2A and 4B, certain of the control western blots had been re­used in different blots. The authors have retrieved and re­examined their original data, and were able to identify the correct control western blots where the data had been inadvertently duplicated in the affected original figures. The revised versions of Figs. 2 and 4, now featuring the correct control western blots, are shown in the subsequent two pages. The authors regret that the data in question featured in the original article had been re­used, and thank the Editor of International Journal of Oncology for granting them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 46: 1205­1213, 2015; DOI: 10.3892/ijo.2014.2800].