Single-Cell Profiling Reveals the Impact of Genetic Alterations on the Differentiation of Inflammation-Induced Murine Colon Tumors.

Genetic mutations and chronic inflammation of the colon contribute to the development of colorectal cancer (CRC). Using a murine model of inflammation-induced colon tumorigenesis, we determined how genetic mutations alter colon tumor cell differentiation. Inflammation induced by enterotoxigenic Bacteroides fragilis (ETBF) colonization of multiple intestinal neoplasia (MinApcΔ716/+) mice triggers loss of heterozygosity of Apc causing colon tumor formation. Here, we report that the addition of BRAFV600E mutation (BRAFF-V600ELgr5tm1(Cre/ERT2)CleMinApcΔ716/+, BLM) or knocking out Msh2 (Msh2LoxP/LoxPVil1-creMinApcΔ716/+, MSH2KO) in the Min model altered colon tumor differentiation. Using single-cell RNA sequencing, we uncovered the differences between BLM, Min, and MSH2KO tumors at a single-cell resolution. BLM tumors showed an increase in differentiated tumor epithelial cell lineages and a reduction in the tumor stem cell population. Interestingly, the tumor stem cell population of BLM tumors had revival colon stem cell characteristics with low WNT signaling and an increase in RevCSC marker gene expression. In contrast, MSH2KO tumors were characterized by an increased tumor stem cell population that had higher WNT signaling activity compared to Min tumors. Furthermore, overall BLM tumors had higher expression of transcription factors that drive differentiation, such as Cdx2, than Min tumors. Using RNA velocity, we identified additional potential regulators of BLM tumor differentiation such as NDRG1. The role of CDX2 and NDRG1 as putative regulators for BLM tumor cell differentiation was verified using organoids derived from BLM tumors. Our results demonstrate the critical connections between genetic mutations and cell differentiation in inflammation-induced colon tumorigenesis. Understanding such roles will deepen our understanding of inflammation-associated colon cancer.

Parabacteroides distasonis-Derived Outer Membrane Vesicles Enhance Antitumor Immunity Against Colon Tumors by Modulating CXCL10 and CD8+ T Cells.

Purpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer. Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs. Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8+ T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1ß, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety. Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8+ T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.

Engineered Microbial Nanohybrids for Tumor-Mediated NIR II Photothermal Enhanced Ferroptosis/Cuproptosis and Immunotherapy.

The colon tumor microenvironment has a high concentration of H2 S and glutathione, which is highly immunosuppressive and adverse to multiple therapeutic methodologies such as ferroptosis. Here, an engineered microbial nanohybrid based on Escherichia coli (E. coli) and Cu2 O nanoparticles to specific colon tumor therapy and immunosuppression reversion is reported. The as-prepared E. coli@Cu2 O hybrid can accumulate in tumor sites upon intravenous injection, and Cu2 O nanoparticles convert to Cux S by consuming the endogenous H2 S, which exhibits strong photothermal conversion at near-infrared II (NIR II) biological window. Furthermore, E. coli@Cu2 O is able to induce cellular ferroptosis and cuproptosis through inactivation of glutathione peroxidase 4 and aggregation of dihydrolipoamide S-acetyltransferase, respectively. Photothermal-enhanced ferroptosis/cuproptosis achieved by E. coli@Cu2 O reverses the immunosuppression of colon tumors by triggering dendritic cell maturation (about 30%) and T cell activation (about 50% CD8+ T cells). Concerted with immune checkpoint blockade, the engineered microbial nanohybrid can inhibit the growth of abscopal tumors upon NIR illumination. Overall, the designed microbial nanohybrid can achieve tumor-specific photothermal-enhanced ferroptosis/cuproptosis and immunosuppression reversion, showing promise in precise tumor therapy in future clinical translation.

Repurposing Metabolic Inhibitors in the Treatment of Colon Adenocarcinoma Patient-Derived Models.

The effect of agonists on AMP-activated protein kinase (AMPK), mainly metformin and phenformin, has been appreciated in the treatment of multiple types of tumors. Specifically, the antitumor activity of phenformin has been demonstrated in melanomas containing the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) activating mutation. In this report, we elucidated the synergistic antitumor effects of biguanides with metabolism inhibitors on colon tumors. Phenformin with 2-deoxy-D-glucose (2DG) inhibited tumor cell growth in cancer cell lines, including HT29 cells harboring BRAF- and p53-mutations. Biochemical analyses showed that two chemotherapeutics exerted cooperative effects to reduce tumor growth through cell cycle arrest, apoptosis, and autophagy. The drugs demonstrated activity against phosphorylated ERK and the gain-of-function p53 mutant protein. To demonstrate tumor regressive effects in vivo, we established patient-derived models, including xenograft (PDX) and organoids (PDO). Co-treatment of biguanides with chemotherapeutics efficiently reduced the growth of patient-derived colon models in comparison to treatment with a single agent. These results strongly suggest that significant therapeutic advantages would be achieved by combining AMPK activators such as phenformin and cancer metabolic inhibitors such as 2DG.

Retroperitoneal abscess as a presentation of colon cancer: The largest case set analysis to date, which extracted from our unit and the literature.

Objective: Colon cancer with retroperitoneal abscess is a rare and easily misdiagnosed disease and has only been reported via case. There is an urgent need to conduct a dataset analysis for such patients, which is crucial to improving the survival rate and quality of life of these patients. Methods: Patients with colon cancer associated with retroperitoneal abscess were extracted from our hospital and the PubMed, EMBASE and Web of Science databases. Clinical information, including the patients' basic characteristics, clinical symptoms, laboratory tests, imaging examinations, treatment methods and prognosis was analyzed. Results: Sixty-one patients were analyzed, with an average age of 65 years. The proportions of right and left colon cancers were 63.9% and 36.1%, respectively. A total of 98.0% of the patients had adenocarcinoma. Many patients have insidious symptoms such as fever and weight loss. At the first medical visit, pain was the most common symptom (71%), with pain in the thigh (21.8%), abdomen (21.8%), and waist and back (14.5%) ranking among the top three. The misdiagnosis rate of the patients referred to our department was 75%, while the overall misdiagnosis rate in the literature was 43.9%. Laboratory tests show that these patients often have elevated white blood cells and anemia. CT examination showed that 87.2% of patients had an iliopsoas muscle abscess, and tumors were not simultaneously detected in 37.2%. A total of 33.9% of patients had local abscesses of the iliopsoas muscle, 26.4% had drainage into the subcutaneous tissue of the waist and upper buttocks, and 22.6% had drainage around the adductor muscle group of the thigh. These patients have a variety of treatments, and many patients have undergone multiple and unnecessary treatments. Thirteen patients died after surgery, and 6 died in the hospital, of whom four were patients undergoing direct surgery, and the other 7 died after discharge due to cachexia. Conclusion: Colorectal cancer with retroperitoneal abscess is a relatively rare and easily misdiagnosed subtype of colon cancer. It is more likely to occur in right-sided colon adenocarcinoma. The main clinical symptom is pain caused by the drainage of pus to the corresponding areas of the waist, abdomen, and legs. CT is the preferred diagnostic method. Actively treating the abscess and then transitioning to standard colon cancer treatment can prevent patient death and improve treatment quality.

Reactive Oxygen Species-Sensitive Biodegradable Mesoporous Silica Nanoparticles Harboring TheraVac Elicit Tumor-Specific Immunity for Colon Tumor Treatment.

Immunotherapy has revolutionized the field of cancer treatment through invigorating robust antitumor immune response. Here, we report the development of a therapeutic vaccine [consisting of high mobility group nucleosome-binding protein 1 (HMGN1), resiquimod/R848, and anti-PD-L1 (αPD-L1)]-loaded reactive oxygen species (ROS)-responsive mesoporous silica nanoparticle (MSN@TheraVac) for curative therapy of colon cancer. In MSN@TheraVac, αPD-L1 conjugated onto the surface of MSNs via a diselenide bond, which can be rapidly released under the oxidative condition of the tumor microenvironment to avert immunosuppression and effector T cell exhaustion while coloaded HMGN1 and R848 would cooperatively trigger robust tumor-infiltrating dendritic cell (TiDC) maturation and elicitation of antitumor immune responses. Indeed, MSN@TheraVac induced the maturation and activation of dendritic cells (DCs) by promoting the surface expression of CD80, CD86, and CD103 as well as the production of pro-inflammatory cytokines, including TNFα, IL-12, and IL-1ß. Importantly, treatment with intravenous MSN@TheraVac led to a complete cure of 100% of BALB/c mice bearing large colon tumors and induced the generation of tumor-specific protective memory without apparent toxicity. Thus, MSN@TheraVac provides a timely release of TheraVac for the curative treatment of colon tumors and holds potential for translation into a clinical therapy for patients with immunologically "cold" colorectal cancers. This ROS-responsive MSN platform may also be tailored for the selective delivery of other cancer vaccines for effective immunotherapy.

Cellular Localization of Selected Porphyrins and Their Effect on the In Vitro Motility of Human Colon Tumors and Normal Cells.

Standard therapies for colorectal cancer cannot eliminate or sufficiently reduce the metastasis process. Photodynamic therapy (PDT) may be an alternative to minimizing this problem. Here, we examined the cellular localization of selected porphyrins and determined whether free-base and manganese (III) metallated porphyrins may limit colon cancer cells' (HT29) or normal colon epithelial cells' (CCD 841 CoTr) motility in vitro. White light irradiation was used to initiate the photodynamic effect. Porphyrin uptake by the cells was determined by porphyrin fluorescence measurements through the use of confocal microscopy. Free-base porphyrin was found in cells, where it initially localized at the edge of the cytoplasm and later in the perinuclear area. The concentrations of porphyrins had no effect on cancer cell migration but had a significant effect on normal cell motility. Due to the low concentrations of porphyrins used, no changes in F-actin filaments of the cellular cytoskeleton were detected. Signal transmission via connexons between neighbouring cells was limited to a maximum of 40 µm for HT29 and 30 µm for CCD 841 CoTr cells. The tested porphyrins differed in their activity against the tumor and normal cells' migration capacity. Depending on the porphyrin used and the type of cells, their migration changed in relation to the control sample. The use of white light may change the activity of the porphyrins relative to the migratory capacity of the cells. The aim of the present study was to analyse the intracellular localization of tested porphyrins and their influence on the mobility of cells after irradiation with harmless white light.

Fluvoxamine prompts the antitumor immune effect via inhibiting the PD-L1 expression on mice-burdened colon tumor.

A colon tumor, one of the digestive tract malignant tumors, is harmful to human health. A potential new treatment still deserves attention. The development of a new drug needs more resources, including time and expense. Therefore, the old drug with new targets has become a current research hotspot. Fluvoxamine, as an antidepressant, could play an effect on inhibiting 5-hydroxytryptamine reuptake. In the present research, the antitumor effects and possible mechanisms of fluvoxamine are validated. The results showed that fluvoxamine significantly suppressed the migration and proliferation of tumor cells, and increased the apoptosis in vitro. Additionally, fluvoxamine significantly delays tumor development, and prompts the apoptosis in tumor tissues of mice-burdened colon tumors in vivo. The tumor suppression might be related with that fluvoxamine inhibits the expression of phosphorylated signal transducer and activator of transcription 3, matrix metalloproteinase 2, and cleaved-caspase 3. Importantly, fluvoxamine significantly reduces the expression level of programmed cell death ligand 1. This could be a possible reason that treatment with fluvoxamine drives the infiltration of T lymphocytes and M1-type macrophages in tumor tissues. Taken together, this research suggests that fluvoxamine might be a promising drug to treat colon cancer by inhibiting the proliferation and migration, inducing apoptosis, and even increasing the immune response of antitumor.

Synergy of Polydopamine Nanovaccine and Endostar Alginate Hydrogel for Improving Antitumor Immune Responses Against Colon Tumor.

Background: Tumor immunotherapy, a novel type of therapeutic treatment, has a wide range of applications with potentially prolonged benefits. However, current immunotherapy has a low overall response rate in treating a variety of tumors. Combination of immunotherapy with other therapies can improve the therapeutic response rates. The purpose of this work was to explore the potential of anti-angiogenic treatment in combination with tumor cell lysate loaded polydopamine nanoparticle vaccine as a therapeutic strategy for colon tumor. Methods: We grafted tumor cell lysate onto polydopamine nanoparticles as nano-vaccine (TCLN) and fabricated alginate hydrogel loaded with Endostar (EH), then detected characteristics of EH and TCLN. We also estimated the cytotoxicity of EH/TCLN in vitro. In the tumor-bearing mouse model, we evaluated the antitumor effect of EH/TCLN treatment, and developed the animal survival study. After performing the EH/TCLN treatment, we also analyzed T cells and DCs using flow cytometry, and determined T cell responses and tumor microenvironmental cytokines. At last, we assessed the effect of the EH/TCLN treatment on anti-angiogenesis further. Results: When applied in combination with TCLN in MC-38 tumor-bearing mice, EH/TCLN significantly suppressed tumor growth with more than half of the mice showing tumor regression. In addition, EH/TCLN treatment resulted in noticeable changes in the tumor microenvironment. As compared with the control group, EH/TCLN treatment led to significantly reduced tumor angiogenesis and expression of tumor microenvironment-related cytokines (TMCs), increased proportion of CD8+ T cells in the spleen, lymph node and tumor, elevated activity of cytotoxic T lymphocytes (CTLs) and tumor cell apoptosis. Conclusion: The present study demonstrated that the EH/TCLN treatment effectively created a favorable immune microenvironment for the induction of antitumor immunity and improved antitumor immune responses.

Value of different anastomoses in laparoscopic radical right hemicolectomy for right-sided colon cancer: retrospective study and literature review.

BACKGROUND: This study aimed to analyze the safety of circular lateral anastomosis and cross-lateral anastomosis in laparoscopic radical resection of right-sided colon cancer. METHODS: From January 2018 to March 2021, 147 patients with right-sided colon cancer were admitted to the Department of General Surgery, Cancer Hospital, Zhengzhou University. The experimental group comprised patients with circular lateral anastomosis, whereas the control group comprised patients with cruciform lateral anastomosis. The general clinical data, intraoperative features, and postoperative results of the two groups were compared and analyzed. RESULTS: Both groups successfully underwent laparoscopic lateral ileocolic anastomosis, with significant differences in anastomotic leakage (χ2=4.520, P < 0.05). By contrast, body mass index (t = 1.568, P = 0.119), histological typing (χ2 = 2.067, P = 0.559), intraoperative bleeding (t = 0.418, P = 0.677), and intestinal obstruction (χ2 = 2.564, P = 0.109) were not significantly different between the groups (P > 0.05). CONCLUSIONS: In laparoscopic-assisted radical hemicolectomy for right-sided colon cancer, the incidence of postoperative anastomotic leakage was lower with circular lateral anastomosis than with cross-lateral anastomosis, and circular lateral anastomosis was superior to cross-lateral anastomosis in terms of reducing the length of hospital stay and improving patients' postoperative quality of life.

Comparison of the diagnostic performance of NBI, Laser-BLI and LED-BLI: a randomized controlled noninferiority trial.

BACKGROUND AND AIMS: New image-enhanced endoscopy (IEE), blue Light Imaging (LED-BLI) is launched in USA and Europe, whereas Blue Laser Imaging (Laser-BLI) is available only Asian and some countries. No studies have directly compared the diagnostic accuracy of narrow band imaging (NBI), Laser-BLI and LED-BLI for colorectal tumors. The present study aimed to compare the diagnostic accuracy of the three methods for colorectal tumor using the NBI international colorectal endoscopic (NICE) classification and the Japanese NBI Expert Team (JNET) classifications. METHODS: This was a multi-center evaluator-blinded, randomized control trial of patients who underwent endoscopic colorectal tumor resection. The patients were randomly assigned to NBI, Laser-BLI or LED-BLI. Cropped images were sent to blinded external evaluators and diagnosed according to NICE and JNET classifications. The diagnostic accuracy of each endoscopy system was compared with non-inferiority test. RESULTS: A total of 619 colonic tumors were resected from 230 patients and evaluated by external four evaluators. The diagnostic accuracy of NBI for NICE 1, NICE 2, NICE 3 was 90.6%, 90.3% and 99.5%, respectively and for JNET 1, JNET 2A, JNET 2B and JNET 3, it was 94.6%, 72.0%, 79.2% and 99.1%, respectively. In non-inferiority test, Laser-BLI and LED-BLI revealed non-inferiority to NBI in all NICE and JNET categories (p<0.001). CONCLUSIONS: Laser-BLI and LED-BLI had high diagnostic accuracy and non-inferiority of NBI, especially for hyperplastic polyp/sessile serrated lesion and low-grade dysplasia. This is first trial to compare the diagnostic accuracy with NBI, Laser-BLI and LED-BLI and useful to understand the position of each IEE. This trial was registered as UMIN000032107.

Assessing the In Vitro Activity of Selected Porphyrins in Human Colorectal Cancer Cells.

Standard in vitro analyses determining the activity of different compounds included in the chemotherapy of colon cancer are currently insufficient. New ideas, such as photodynamic therapy (PDT), may bring tangible benefits. The aim of this study was to show that the biological activity of selected free-base and manganese (III) metallated porphyrins differs in the limitation of colon cancer cell growth in vitro. White light irradiation was also hypothesized to initiate a photodynamic effect on tested porphyrins. Manganese porphyrin (>1 µM) significantly decreased the viability of the colon tumor and normal colon epithelial cells, both in light/lack of light conditions, while decreasing a free-base porphyrin after only 3 min of white light irradiation. Both porphyrins interacted with cytostatics in an antagonistic manner. The manganese porphyrin mainly induced apoptosis and necrosis in the tumor, and apoptosis in the normal cells, regardless of light exposure conditions. The free-base porphyrin conducted mainly apoptosis and autophagy. Normal and tumor cells released low levels of IL-1ß and IL-10. Tumor cells released a low level of IL-6. Light conditions and porphyrins were influenced at the cytokine level. Tested manganese (III) metallated and free-base porphyrins differ in their activity against human colon cancer cells. The first showed no photodynamic, but a toxic activity, whereas the second expressed high photodynamic action. White light use may induce a photodynamic effect associated with porphyrins.

A self-guidance biological hybrid drug delivery system driven by anaerobes to inhibit the proliferation and metastasis of colon cancer.

Colorectal cancer is often accompanied by multiple organ metastasis. Anaerobic Bifidobacterium Infantis (BI) bacterial can selectively grow in hypoxic colorectal tumor microenvironment (TME), to own the natural advantage of preferentially colorectal tumor targeting. Herein, a self-guidance biological hybrid drug delivery system (BI-ES-FeAlg/DOX) based on BI was constructed to inhibit the proliferation and metastasis of colon cancer. Results demonstrated that BI-ES-FeAlg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues. Then DOX was released to kill tumor cells along with the phase transition (solid to liquid) of FeAlg hydrogel, due to Fe3+ was reduced to Fe2+by intracellular GSH. Meanwhile, BI-ES selectively colonized into tumors and expressed endostatin (ES) protein to down-regulate VEGF and bFGF expression, exerting anti-angiogenic effect. Moreover, FeAlg catalyzed H2O2 in the local tumor to generate cytotoxic ·OH, further enhancing the antitumor effect. The pharmacodynamic result in AOM/DSS model proved that BI-ES-FeAlg/DOX had the best therapeutic effect, with the final V/V0 of 2.19 ±â€¯0.57, which was significantly lower than the other groups. Meanwhile, on CT-26 tumor-bearing model, it also showed an outstanding anti-tumor effect with inhibition rate of 82.12% ± 3.08%. In addition, lung metastases decreased significantly in tumor metastasis model after BI-ES-FeAlg/DOX treatment.

A new approach: Laparoscopic right hemicolectomy with priority access to small bowel mesentery.

Background: For laparoscopic right hemicolectomy, the intermediate approach is commonly employed. However, this approach possesses several disadvantages. In this study, we compare priority access to the small bowel mesentery and the intermediate approach. Methods: The clinical data of 196 patients admitted to the First Hospital of Chongqing Medical University for laparoscopic right hemicolectomy from January 2019 to January 2022 were retrospectively collected and divided into the small bowel mesenteric priority access and traditional intermediate access groups. The operative time, intraoperative bleeding, number of lymph node dissection, postoperative anal venting time, toleration of solid and liquid intake, and postoperative hospital stay and complications were compared between the two different approaches. Results: In total, 81 cases of small bowel mesenteric priority access and 115 cases of intermediate approach for right hemi-colonic radical resection were compared. The operative time was 191.98 ± 46.05 and 209.48 ± 46.08 min in the small bowel mesenteric priority access and intermediate access groups, respectively; the difference was statistically significant. There were no significant differences in the intraoperative bleeding and lymph node clearance. However, the scatter plot analysis showed that severe intraoperative bleeding was relatively less frequent in the small mesenteric priority access group, compared with that in the intermediate approach group. Additionally, there were no statistically significant differences in the first exhaust and defecation times, hospital stay after operation, toleration of solid and liquid intake, and postoperative complication between the two groups. Conclusion: In laparoscopic right hemicolectomy, the small bowel mesenteric priority approach can significantly shorten the operation time compared with the intermediate approach. It can reduce intraoperative bleeding and the operation is simple and safe to perform, making it suitable for less experienced surgeons. Therefore, the small bowel mesenteric priority approach has the potential to be a suitable alternative and deserves further clinical promotion and application.

Contribution of endothelial cell-derived transcriptomes to the colon cancer based on bioinformatics analysis.

Colon tumor endothelial cells (CTECs) plays substantial roles to induce immune invasion, angiogenesis and metastasis. Thus, identification of the CTECs-derived transcriptomes could be helpful for colon cancer diagnosis and potential therapy. METHODS: By analysis of CTECs-derived gene expression profiling dataset, we identified differentially expressed genes (DEGs) between CTECs and colon normal endothelial cells (CNECs). In addition, we identified the significant pathways and protein-protein interaction (PPI) network that was significantly associated with the DEGs. Furthermore, we identified hub genes whose expression was significantly associated with prognosis and immune cell infiltrations in colon cancer. Finally, we identified the significant correlations between the prognostic hub genes and immune-inhibitory markers in colon cancer. RESULTS: We identified 362 DEGs in CTECs relative to the CNECs, including117 up-regulated genes and 245 down-regulated genes in the CTECs. In addition, we identified significantly up-regulated pathways in CTECs that were mainly involved in cancer and immune regulation. Furthermore, we identified hub genes (such as SPARC, COL1A1, COL1A2 and IGFBP3) that are associated with prognosis and immune cells infiltrations in colon cancer. Interestingly, we found that prognosis-associated hub genes (SPARC, COL1A1, COL1A2 and IGFBP3) are positively correlated with immune-inhibitory markers of various immunosuppressive cells, including TAM, M2 macrophage, Tregs and T cell exhaustion. Finally, our findings revealed that prognosis-associated upregulated hub genes are positively correlated with immune checkpoint markers, including PD-L1 and PD-L2 and the immunosuppressive markers including TGFB1 and TGFBR1. CONCLUSIONS: The identification of CTECs-specific transcriptomes may provide crucial insights into the colon tumor microenvironment that mediates the development of colon cancer.

Enabling peristalsis of human colon tumor organoids on microfluidic chips.

Peristalsis in the digestive tract is crucial to maintain physiological functions. It remains challenging to mimic the peristaltic microenvironment in gastrointestinal organoid culture. Here, we present a method to model the peristalsis for human colon tumor organoids on a microfluidic chip. The chip contains hundreds of lateral microwells and a surrounding pressure channel. Human colon tumor organoids growing in the microwell were cyclically contracted by pressure channel, mimicking thein vivomechano-stimulus by intestinal muscles. The chip allows the control of peristalsis amplitude and rhythm and the high throughput culture of organoids simultaneously. By applying 8% amplitude with 8 ∼ 10 times min-1, we observed the enhanced expression of Lgr5 and Ki67. Moreover, ellipticine-loaded polymeric micelles showed reduced uptake in the organoids under peristalsis and resulted in compromised anti-tumor efficacy. The results indicate the importance of mechanical stimuli mimicking the physiological environment when usingin vitromodels to evaluate nanoparticles. This work provides a method for attaining more reliable and representative organoids models in nanomedicine.

A case of iatrogenic intussusception in adults: a rare case report.

BACKGROUND: Intussusception has a low incidence rate in adults. Many cases in adults are caused by tumors. Intussusception results from conditions other than tumors are uncommon. This is the first case report about intussusception that occurred after removing a long intestinal tube (LT). CASE PRESENTATION: A 69-year-old female complained of "recurrent abdominal pain with reduced flatus passage and frequency of bowel movement for 10 days" was admitted to the hospital. Plain abdominal radiography and abdominal CT upon admission showed intestinal obstruction. The patient's abdominal pain was not relieved after symptomatic treatments, which involved fluid and electrolyte replacement, LT placement, spasmolytic agents, and analgesics. Hence, surgical exploration was carried out. The patient had a good recovery postoperatively. No abdominal pain or bloating developed after food intake. The patient passed flatus and had bowel movements later. On postoperative day 9, the LT was removed. On the 10th day, the patient suddenly developed abdominal distension and acute abdominal pain. Emergency abdominal CT showed small bowel intussusception. Surgical exploration was then performed. Severe small bowel dilatation located at 1.5 m from the ligament of Treitz was found during the procedure. Intussusception at the site was observed. No color change of the intestinal wall was detected, suggesting that no necrosis was present. So, a manual reduction was done. The patient was discharged on postoperative day 6. CONCLUSIONS: This case serves as a warning that the simple action of pulling out the LT might also cause serious complications, which should be given more attention.

Anticancer Activity of Triazolo-Thiadiazole Derivatives and Inhibition of AKT1 and AKT2 Activation.

The fusion of 1,2,4-triazole and 1,3,4-thiadiazole rings results in a class of heterocycles compounds with an extensive range of pharmacological properties. A series of 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles was synthesized and tested for its enzyme inhibition potential and anticancer activity. The results show that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles display potent anticancer properties in vitro against a panel of cancer cells and in vivo efficacy in HT-29 human colon tumor xenograft in CB17 severe combined immunodeficient (SCID) mice. Preliminary mechanistic studies revealed that KA25 and KA39 exhibit time- and concentration-dependent inhibition of Akt Ser-473 phosphorylation. Molecular modeling experiments indicated that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles bind well to the ATP binding site in Akt1 and Akt2. The low acute toxicity combined with in vitro and in vivo anticancer activity render triazolo[3,4-b]thiadiazoles KA25, KA26, and KA39 promising cancer therapeutic agents.

Retrospective Study of Natural Orifice Specimen Extraction Surgery in Resection of Sigmoid and Rectal Tumors.

Background: With the development of surgical technology, surgeons are paying more and more attention to minimally invasive procedures such as injury reduction, pain reduction, and beautiful incisions to ensure the effectiveness of surgical treatment. This article discusses the safety, feasibility, and clinical outcomes of laparoscopic resection of sigmoid colon and rectal tumors via natural orifice specimen extraction surgery (NOSES). Materials and Methods: The clinical data of 39 patients who underwent complete laparoscopic resection of sigmoid colon tumor or rectal tumor at Chengde Medical College Hospital between 2018 and 2020, including general patient data (gender, age, body mass index [BMI], etc.), surgery-related data, general postoperative conditions, and postoperative pathological data, were retrospectively analyzed to explore the feasibility and safety of NOSES. Results: The specimens were all removed through the anorectal resection drag out type. The average age of 39 patients was 61.3 ± 10.2 years, the average BMI was 24.0 ± 3.1 kg/m2, the average postoperative hospital stay was 11.2 ± 4.4 days, 12 patients with sigmoid colon tumors, including 11 malignant tumors and 1 schwannoma, 27 rectal tumors, including 1 rectal villous tubular adenoma, among the 37 patients with malignant tumors, ulcer type 32 cases of adenocarcinoma and 5 cases of mass adenocarcinoma, mean number of lymph nodes detected intraoperatively (11.9 ± 3.9), mean operative time (162.9 ± 43.0 minutes), mean operative bleeding (36.9 ± 13.0 mL), mean time of initial exhaust (4.3 ± 3.0) days, mean time of laparoscopic drainage tube removal (9.8 ± 1.4) days, mean time of postoperative feeding (4.4 ± 3.0) days, the average maximum tumor diameter (3.7 ± 1.4 cm), and the average distance of the tumor from the anal margin (14.1 ± 6.1 cm); after surgery, there were two cases of anastomotic fistula. Conclusion: Laparoscopic resection of sigmoid colon and rectal tumors via natural orifice specimen extraction has the advantages of less pain, reduced incisional complications, good safety, and accurate efficacy in clinical applications.

Synchronous Colon and Pancreatic Rosai-Dorfman Disease.

Rosai-Dorfman disease (RDD) is primarily a disease of massive lymphadenopathy and sinus histiocytosis. It has been documented across extranodal organ systems, but it rarely has been described in the gastrointestinal tract only. Here is the unique case of 2 primary extra-nodal masses found simultaneously in the pancreas and right colon of a patient without the classical concomitant lymphadenopathy. We also reviewed the literature and found 11 additional cases of pancreatic RDD. This is the first male case and 1 of only 2 cases of RDD presenting synchronously in 2 distinct locations within the gastrointestinal system. Furthermore, we discuss the potential use of fine needle aspiration (FNA) and core sample biopsies in confirming a diagnosis of RDD.