Colorectal Cancer Research Articles

The efficacy and safety of neoadjuvant treatment with the PD-1 inhibitor for locally advanced colorectal cancer: a meta-analysis

ObjectiveTo systematically evaluate the efficacy and safety of PD-1 inhibitors in neoadjuvant therapy for locally advanced colorectal cancer (LACRC).MethodRetrieved from PubMed, Embase, and the Cochrane Library, all relevant studies about PD-1 inhibitors for neoadjuvant treatment of LACRC were collected from inception to 31 December 2023. The efficacy was assessed by the rate of pathological complete response (PCR), clinical complete response (CCR), and major pathological response (MPR), and the safety was evaluated by the incidence of all adverse effects (TRAEs). Subgroup analysis was conducted by experimental design, types of PD-1 inhibitors, and disease types.ResultA total of 803 patients were included in 21 studies. The results of the meta-analysis showed that the PCR rate of PD-1 inhibitors in the treatment of LACRC was 54% (95% CI: 43%–65%, P<0.05); the CCR of anti-PD-1 was 40% (95% CI: 26%–54%, P<0.05); the MPR was 66% (95% CI: 56%–76%, P<0.05); and the irAEs was 27% (95% CI: 17%–37%, P<0.05). Subgroup analysis showed that the PCRs in prospective studies and retrospective studies were 49% (95% CI: 32%–66%, P<0.05) and 57% (95% CI: 42%–73%, P<0.05), respectively. Among the 803 patients, 619 (77%) were diagnosed with rectal cancer (RC), and the PCR and MPR were 49% and 65%, respectively; 184 (23%) were diagnosed with colorectal cancer (CRC), and the PCR and MPR were both 67%. In our meta-analysis, types of PD-1 inhibitors, including sintilimab, toripalimab, camrelizumab, avelumab, pembrolizumab, and tislelizumab, and patients who received PD-1 inhibitors alone or in combination achieved good PCR rates.ConclusionNeoadjuvant therapy combined with a PD-1 inhibitor has a favorable PCR and relatively low incidences of irAEs for patients with LACRC, suggesting that this regimen including a PD-1 inhibitor is significantly effective and sufficiently safe.

A Novel Sensitivity Maximization at a Given Specificity Method for Binary Classifications

Abstract In the cancer early detection field, logistic regression is a frequently used approach to establish a combination rule that differentiates cancer from non-cancer. However, the application of logistic regression relies on a maximum likelihood approach, which may not yield optimal combination rules for maximizing sensitivity at a clinically desirable specificity and vice versa. Here, we have developed an improved regression framework, Sensitivity Maximization At a Given Specificity, SMAGS, for binary classification that finds the linear decision rule yielding the maximum sensitivity for a given specificity or the maximum specificity for a given sensitivity. We additionally expand the framework for feature selection that satisfies sensitivity and specificity maximizations. We compare our SMAGS method with normal logistic regression using two synthetic datasets and reported data for colorectal cancer (CRC) from the 2018 CancerSEEK study. In the CRC CancerSEEK dataset, we report 14% improvement in sensitivity at 98.5% specificity (0.31 vs 0.57; p-value:<0.05). The SMAGS method provides an alternative to logistic regression for modeling combination rules for biomarkers and early detection applications.

The Undetermined Significance of Screening for Monoclonal Gammopathy of Undetermined Significance

AbstractThe identification of premalignant lesions in solid tumors such as colorectal and cervical cancer has led to the development of highly effective population-wide screening programs for these malignancies. Although precursor clinical states are not well-established for most hematologic malignancies, multiple myeloma is a notable exception. Virtually all patients with multiple myeloma first develop monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic but easily detectable condition. However, broad screening for MGUS has not been adopted primarily because there is no proven intervention to delay or prevent the progression of MGUS to multiple myeloma. Furthermore, the incidence of MGUS is poorly understood; a better understanding of its epidemiology will be critical in designing appropriate screening guidelines once an effective treatment has been developed. In the current issue of Cancer Epidemiology, Biomarkers & Prevention, Ji and colleagues provide important epidemiologic insights on MGUS, including a critical discussion on how its incidence and preclinical duration vary by age and race, acknowledging that both MGUS and multiple myeloma are more common in Black than White populations.See related article by Ji et al., p. 1690

Challenges following CRS and HIPEC surgery in cancer patients with peritoneal metastasis: a comprehensive review of clinical outcomes

Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are a pair of relatively modern therapeutic surgical methods in advanced cancerous patients with peritoneal metastasis (PM). The goal of CRS + HIPEC is treatment or to improve survival outcomes, which are linked to high morbidity side effects and complications, even with their possible advantages. Surgical-related, chemotherapy-related, anesthetic-related, gastrointestinal, organs and systemic complications are the categories into which complications are separated according to frequency, risk factors, and effect on patient outcomes. In this narrative review of the literature, the side effects and complications of HIPEC + CRS in cancer patients with PM are examined. The present knowledge on the incidence, frequency, kinds, and risk factors of acute complications following CRS + HIPEC is summarized in this study. This review emphasizes the need for careful patient selection criteria, precise surgical technique, and thorough intraoperative care to reduce or manage these risks. Moreover, it highlights the need for interdisciplinary collaboration in treating these patients. This study aims to know these complications, improve clinical practice, and guide future studies to increase the safety and efficacy of CRS + HIPEC in treating metastatic colorectal cancer.

Design and Analytical Modeling of a Dumbbell-Shaped Balloon Anchoring Actuator for Safe and Efficient Locomotion Inside Gastrointestinal Tract.

Colorectal cancer stands as one of the most prevalent cancers globally, representing 9.8% of total cases and contributing to 9.2% of mortalities annually. Robotic "front-wheel" navigating colonoscopes mitigate aggressive stretching against the long and tortuous colonic wall, alleviating associated discomfort and pain typically experienced by patients inspected by conventional "back-wheel" navigating colonoscopes. The anchoring unit of most "front-wheel" navigating colonoscopes plays a crucial role in ensuring effective locomotion by preventing slipping during elongation/contraction of the central actuation part. The soft balloon anchoring actuator emerges as a promising solution due to its high compliance. This study introduces a dumbbell-shaped balloon anchoring actuator (DBAA) integrating an "inflation and suction" mechanism to address the inherent conflict between achieving sufficient anchoring force and minimizing expansion and potential trauma of the colonic wall, commonly encountered in current balloon anchoring actuators. Analytical modeling of DBAA and soft external lumen, encompassing geometric deformation and anchoring force, were proposed to characterize the actuator and provide guidelines for designing and controlling DBAA in further applications, enabling autonomous anchoring within different diameter lumens and achieving the expected anchoring force. A comprehensive set of validation experiments was conducted, and the outcomes revealed high consistency with analytical predictions, confirming the effectiveness of the proposed analytical modeling approach. Furthermore, the results demonstrated a significant enhancement in anchoring force with the proposed actuator and corresponding mechanism while concurrently maintaining low-lumen expansion. For instance, in a lumen sample with the anchoring force reaches 14.5 N with 50 kPa negative pressure, which is 12.4 times of the force (1.17 N) observed without applying negative pressure.

The use of nutrigenomics and nutritional biomarkers with standard care of long-term recurrent metastatic rectal cancer: a case report

IntroductionDistant metastases following standard treatment for locally advanced rectal cancer (LARC) are typically associated with poor disease-free survival. We report on a 52-year-old Australian male of Dutch ancestry with no family history of colorectal cancer or significant medical history who experienced bleeding per rectum for several months prior to a colonoscopy in July 2010. He was subsequently diagnosed with Stage IIb LARC.Case presentationDespite treatment with curative intent, a distant recurrence to his left lung was detected in May 2012, upstaging him to Stage IV rectal cancer. He had repeated distant metastatic recurrences over the next 8 years, and treatment included multiple surgeries, chemotherapies, radiation treatments, a “watch and wait” period of 20 months, and personalised dietary management. Genetic and nutrigenomic testing identified that the case had KRAS and MTHFR mutations. As part of his dietary management, the case also had his levels of folate, vitamin B12, and vitamin D regularly monitored because of his genetic predisposition and history of deficiency for these key nutrients. Apart from changes in his CEA levels, sudden increases in the patient’s folate levels, inconsistent with dietary exposures preceded detection of each new distant recurrence, with significant decreases in the levels at the next follow-up measurement.ConclusionA multimodal approach to this patient’s management appeared to contribute to his long-term survival of nearly 10 years from the initial diagnosis. Multidisciplinary management, including the use of additional biomarkers, may enhance survival rates in other similar cases with advanced disease resistant to differing therapies, and with potentially poor prognosis.

T1 Colorectal Cancer: What Are the Barriers to Minimizing Unnecessary Surgical Interventions?

T1 Colorectal Cancer: What Are the Barriers to Minimizing Unnecessary Surgical Interventions?

The Determinants of Long-Term Outcomes After Colorectal Cancer Surgery: A Literature Review

The Determinants of Long-Term Outcomes After Colorectal Cancer Surgery: A Literature Review

CircEIF3I Promotes Colorectal Cancer Metastasis by Regulating the miR‐328‐3p/NCAPH Axis

ABSTRACTColorectal cancer (CRC) is the most common gastrointestinal malignancy, with its recurrence and metastasis significantly affecting patient survival. Circular RNAs (circRNAs), a novel class of noncoding RNAs, have emerged as crucial contributors to CRC pathogenesis. However, the role of circEIF3I in CRC metastasis remains unclear. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was applied to assess circEIF3I, microRNA (miR)‐328‐3p, and NCAPH expression. CRC cell migration and invasion were determined via Transwell assays. Western blot analysis was utilized to define the protein expression of epithelial‐mesenchymal transition (EMT) markers and NCAPH. Xenograft tumor was established for exploration into the function of circEIF3I in CRC metastasis to the liver and lung. The binding between miR‐328‐3p and circEIF3I or NCAPH was predicted through ENCORI or TargetScan platform and ascertained through dual‐luciferase reporter assays. circEIF3I and NCAPH expression were found to be elevated in CRC tissues and cells, while miR‐328‐3p was downregulated. Functionally, circEIF3I knockdown inhibited CRC cell migration, invasion, EMT, and tumor metastasis. Mechanistic analyses revealed that circEIF3I can target miR‐328‐3p, while NCAPH was targeted by miR‐328‐3p. Furthermore, circEIF3I facilitated NCAPH expression in CRC cells by sequestering miR‐328‐3p. Notably, miR‐328‐3p inhibitor or NCAPH overexpression negated the effects of circEIF3I knockdown on preventing CRC progression in vitro. Taken together, circEIF3I elevated NCAPH expression by sponging miR‐328‐3p, thereby promoting CRC metastasis. These findings suggest that the circEIF3I/miR‐328‐3p/NCAPH axis represents a novel therapeutic target for CRC.

Change in Cardiorespiratory Fitness and the Risk of Colorectal and Prostate Cancer Incidence in Men.

The aim of this prospective cohort study was to investigate the associations between changes in cardiorespiratory fitness (CRF) and the risk of colorectal and prostate cancer in men. Data from men who completed a health assessment both in military conscription in youth and an occupational health profile assessment (HPA) later in life were used. CRF was assessed as estimated V̇O2max, using a cycle ergometer fitness test at both time points. We linked the assessment data to national register data on colorectal and prostate cancer incidence, and hazard ratios and confidence intervals were estimated using Cox proportional hazard regression. 139,764 men with a mean age of 18 (SD 0.6) at conscription and 43 (SD 8.9) at HPA were included. The average time between the two assessments was 25.9 (SD 9.0) years and mean follow-up time following HPA test was 10.0 (SD 5.6) years for prostate and colorectal cancer. Annual percentage change in relative and absolute V̇O2max from conscription to HPA was inversely associated with the risk of colorectal cancer incidence, hazard ratio of 0.83 (95% CI [0.72-0.94]) and 0.88 (95% CI [0.79-0.99]), respectively. These associations were driven by data from individuals in the lowest and moderate level fitness tertials at conscription. Change in CRF was not associated with prostate cancer incidence risk. Changes in, not only level of, CRF from youth to adulthood are related to colorectal cancer incidence risk and therefore, improving CRF should be considered as an important colorectal cancer risk reduction strategy.

Risk of recurrence in early-onset versus late-onset non-metastatic colorectal cancer, 2004–2019: a nationwide cohort study

The incidence of colorectal cancer (CRC) in individuals younger than 50 years of age (early-onset CRC) is increasing. Early-onset CRC often present at advanced stage, suggesting a more aggressive cancer course compared to late-onset CRC (age 50-79). This nationwide cohort study estimates the incidence of recurrence following early-onset CRC and late-onset CRC. The study included all Danish patients <80 years old operated for first-time Union for International Cancer Control (UICC) stage I-III CRC between January 2004 and December 2019. Recurrence status was determined by applying a validated algorithm to individual-level data from nationwide health registries. The 5-year cumulative incidence functions (CIF) of recurrence were reported for early-onset versus late-onset CRC. The difference in time to recurrence was estimated as a time ratio (TR) using an accelerated failure time model. Among 25,729 CRC patients, 1441 (5.6%) had early-onset CRC. Compared to late-onset CRC, early-onset was associated with advanced disease stages and higher treatment intensity. The 5-year CIF of recurrence was 29% (95% CI: 26%-31%) in early-onset versus 21% (95% CI: 21%-22%) in late-onset CRC. The higher CIF of recurrence for early-onset patients persisted in stage-stratified analysis. Time to recurrence was shorter in early-onset versus late-onset patients with TR=0.76 (95% CI: 0.67-0.85). The 5-year CIF of recurrence decreased from 2004 to 2019 for both early- and late-onset patients-most prominent for early-onset patients. Early-onset CRC was associated with higher incidence of recurrence at all disease stages. Indicating that the increased risk is not explained by delayed diagnosis. The excess risk diminished from 2004 to 2019, suggesting that early-onset CRC may achieve a similar recurrence risk as late-onset CRC in a contemporary setting. Aarhus University, Novo Nordisk Foundation, Innovation Fund Denmark, and the Danish Cancer Society.

Temporal trends in age and stage-specific incidence of colorectal cancer in Saudi Arabia: A registry-based cohort study between 1997 and 2017

BackgroundIn Saudi Arabia, colorectal cancer (CRC) is the most common cancer in men and the third in women, posing a significant health burden. A comprehensive report of CRC incidence rates and trends in Saudi Arabia is lacking. This study aims to examine trends in CRC incidence among the Saudi population. MethodsWe used data from the Saudi Cancer Registry to examine CRC age-specific incidence rates (ASIR) and age-standardized incidence rates (ASR) between 1997 and 2017. Joinpoint regression analysis was used to determine the magnitude and direction of observed trends stratified by age, sex, and CRC stage at diagnosis. Trends were measured using the annual percentage change (APC) and the average annual percentage change (AAPC) in CRC incidence rates. ResultsIn total, 19,463 new CRC cases were identified during the study period. Since 1997, ASR for CRC has steadily increased in men and women overall, irrespective of disease stages. The ASIR increased across all age groups and was more pronounced in older patients. Women aged 40–49 had a higher increase in incidence than men (AAPC= 5.3 % vs.4.7 %). Males aged 70–79 had an AAPC of 10.2 %, twice that of females (AAPC= 4.9 %). A consistent rise in ASIR was observed across all CRC stages and age groups in males and females. In recent years, males under 50 had a higher APC for distant CRC than females, while females aged 50–74 experienced a steeper increase in distant CRC than males. ConclusionWe report a marked increase in the incidence of CRC over time in Saudi Arabia, affecting men and women across all age groups and disease stages at diagnosis. Our findings underscore the need to identify underlying risk factors and to develop and implement effective prevention policies and strategies, including screening programs to facilitate early detection and treatment.

Systematic Review and Meta-Analysis: Taurine and Its Association With Colorectal Carcinoma.

Colorectal cancer (CRC) is one of the most common cancers. Various options are available for treatment, but prognosis is still poor in the more advanced stages. Current screening methods are not as accurate for distinguishing between benign and malignant growths, resulting in unnecessary invasive procedures. Recently a focus has been placed on identifying metabolites. Of these, taurine has frequently been detected, and this particular compound has a multifactorial role in human physiology. We conducted a systematic review of studies up till November 2023. Searches were done in three databases- MEDLINE, CINAHL-Ebsco, and PubMed. Three independent reviewers filter titles, abstracts, and full-texts according to selection criteria. Ten studies (samples = 1714) were identified showing a differential level of taurine in CRC patient samples. Quality assessment accounted for the risk of bias of each study using the 'robvis' tool. Where meaningful comparisons could be made, meta-analyses were carried out using the 'R' program for precalculated effect sizes with 'metagen' in R. The 'meta' package was utilised for creation of forest plots. Taurine was shown to significantly increase odds of CRC. It was also significantly associated with being a discriminator for CRC as a diagnostic metabolite. This was maintained at various stages of CRC. Taurine had increased expression in CRC patients, especially when the matrix utilised was blood. Nevertheless, there was significant heterogeneity for some outcomes. In conclusion, these findings highlight the potential of using taurine as well as other bile acid metabolites (lithocholic and ursodeoxycholic acid) to diagnose CRC and illustrate the link with microbiome interactions. Overall increased taurine concentration are associated with significantly increased odds for CRC. There was mostly an increase in relative expression of taurine in CRC samples, excluding results from Wang etal.

Identification and Validation of Serum Biomarkers to Improve Colorectal Cancer Diagnosis.

The pressing need for reliable biomarkers in colorectal cancer (CRC) diagnosis and prognosis is a major global health concern. Current diagnostic methods rely heavily on invasive procedures like colonoscopy, and existing biomarkers such as Carbohydrate Antigen 19-9 (CA19-9) and Carcinoembryonic Antigen (CEA) exhibit limitations in accuracy and specificity. This study aims to identify and validate novel biomarkers that can enhance the early detection and diagnostic precision of CRC while overcoming the shortcomings of conventional biomarkers. Leveraging advancements in genomic and proteomic technologies, gene expression datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified differentially expressed genes (DEGs) and conducted further analyses, including Gene Ontology (GO) enrichment and Protein-Protein Interaction (PPI) network construction. Five promising biomarkers-INHBA, MMP7, PSAT1, SLC7A5, and TGFBI-were selected based on their robust performance in Receiver Operating Characteristic (ROC) curve analysis. Serum concentrations of these biomarkers were measured in 200 CRC patients and 100 healthy controls. The study revealed significantly elevated expression levels of the selected biomarkers in CRC tissues compared to normal tissues. Additionally, serum concentrations of INHBA, MMP7, PSAT1, SLC7A5, and TGFBI were notably higher in CRC patients than in healthy individuals, with Area Under the Curve (AUC) values ranging from 0.8361 to 0.9869 indicating high diagnostic accuracy. Optimal cutoff values for diagnosis ranged from 38.9 pg/mL to 280.7 pg/mL, yielding sensitivity and specificity values between 74.5% and 92.9%. The findings underscore the potential of INHBA, MMP7, PSAT1, SLC7A5, and TGFBI as effective non-invasive biomarkers for CRC detection. Their elevated serum concentrations and robust discriminatory abilities highlight their promise in improving diagnostic accuracy and patient outcomes compared to traditional biomarkers. The identification and validation of these novel biomarkers represent a significant advancement in CRC diagnosis and management. Further studies are required to validate their clinical applicability in larger cohorts and to elucidate their functional roles in CRC pathogenesis, ultimately enhancing diagnostic strategies and personalized treatment approaches.

Pre-diagnostic plasma advanced glycation end-products and soluble receptor for advanced glycation end-products and mortality in colorectal cancer patients.

Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, Nε-[carboxy-methyl]lysine (CML), Nε-[carboxy-ethyl]lysine (CEL) and Nδ-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (Pinteraction = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HRQ5vs.Q1 = 1.67, 95% CI: 1.21-2.30, Ptrend = .02) or any cause (HRQ5vs.Q1 = 1.38, 95% CI: 1.05-1.83, Ptrend = .09). These associations tended to be stronger among cases with diabetes (Pinteraction = .03) and pre-diabetes (Pinteraction <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.

Carboxylesterase 2-based fluorescent probe with large Stokes shift for differentiating colitis from bowel cancer

Colitis is considered a significant risk factor for the development and progression of colorectal cancer due to excessive inflammation formed as a result of inflammatory bowel disease (IBD), which is linked to colorectal cancer development. Colorectal cancer often lacks overt symptoms in its early stages, leading to late-stage diagnosis in most patients. Therefore, timely diagnosis and differentiation of colitis and colorectal cancer are crucial. This study introduces a novel activatable carboxylesterase 2 (CES2) fluorescent probe, DBF-CES2, consisting of a cationic indolium fluorophore and a CES2-specific benzyl ester recognition group. The probe operates via the intramolecular charge transfer (ICT) mechanism. Upon binding and hydrolysis by CES2, a potent electron-donating hydroxyl group is released, enhancing the ICT effect and increasing fluorescence intensity, emitting red fluorescence light (λem = 680nm). The probe had a large Stokes shift of 167nm and a detection limit as low as 0.70ng/mL. It also had high selectivity, sensitivity, and biocompatibility. Cellular imaging experiments demonstrated that CES2 expression levels in colorectal cancer cells were higher than those in normal cells. The DBF-CES2 probe specifically recognized endogenous CES2 in colorectal cancer cells, promptly distinguishing them from normal cells. In vivo imaging in mice confirmed that the probe could differentiate between colitis and colorectal cancer, allowing for the assessment of the therapeutic effects of two drugs. The synthesized CES2-targeting organic small molecule fluorescent probe DBF-CES2 is a new molecular tool for the early diagnosis of colitis and colorectal cancer-related diseases, holding significant potential in clinical diagnostics.

Long non-coding RNA AC105118.1 affects glycolysis to facilitate oxaliplatin resistance in colorectal cancer cells by modulating the miR-378a-3p/KIF26B axis

BackgroundOxaliplatin is a first-line chemotherapy drug for colorectal cancer (CRC), but many patients eventually lose treatment efficacy due to acquired resistance. AC105118.1 is a long non-coding RNA with unknown biological function. This research attempts to probe into the molecular regulatory mechanism of AC105118.1 in CRC oxaliplatin resistance. MethodsThe expression level of AC105118.1 in CRC tissues and cells was measured based on The Cancer Genome Atlas (TCGA) data and quantitative reverse transcription polymerase chain reaction (qRT-PCR). We utilized dual-luciferase assay and RNA immunoprecipitation to analyze the interaction between AC105118.1, miR-378a-3p, and their downstream target KIF26B. CCK-8, colony formation assay, and flow cytometry were employed to assess the half inhibitory concentration (IC50), cell proliferation, and apoptosis rate of HCT116/L-OHP cells treated with oxaliplatin. The glycolysis evaluation was completed by measuring the extracellular acidification rate (ECAR), glucose consumption, lactate production, and glycolysis-related proteins (HK2, GLUT1, and LDHA). TUNEL staining was used to detect the level of apoptosis. ResultsAC105118.1 was specifically upregulated in CRC tissues and cells. AC105118.1 indirectly facilitated the expression of miRNA target gene KIF26B by sequestering miR-378a-3p. In HCT116/L-OHP cells, transfection with si-AC105118.1 resulted in a decrease in glycolysis level, a lower maximum IC50 required for oxaliplatin-treated cells, inhibited cell proliferation, and an increase in apoptosis rate. All of these effects were alleviated when simultaneously transfecting miR-378a-3p inhibitor or oe-KIF26B. Knockdown of AC105118.1 significantly inhibited oxaliplatin resistance to CRC in mice. ConclusionAC105118.1 facilitates glycolysis and increases CRC cells’ resistance to oxaliplatin by targeting the miR-378a-3p/KIF26B axis. The present work shed new insights into the function and mechanism of AC105118.1 in molecular function and suggested that the AC105118.1/miR-378a-3p/KIF26B axis is a promising target for intervening CRC oxaliplatin resistance.

Chlorhexidine Dihydrochloride Shows Anti-tumor Effects in Desmoid Tumors and Colorectal Cancer.

Desmoid tumors (DTs), or aggressive fibromatosis, are rare neoplasms arising from connective tissue, frequently exhibiting local invasiveness. The limited treatment options and high recurrence rates of DTs highlight the need for novel therapeutic strategies. This study investigated the efficacy of chlorhexidine dihydrochloride (CD) in inhibiting the growth of DTs and colorectal cancer (CRC). A mouse model with Apc mutations, specifically Apc1638N/+, was generated to study DTs. DT cells (Apc1638N+) (DTA) were collected from the mice for in vitro experiments. DTA were treated with CD, along with a CRC cell line (HCT-116), and tumor organoids derived from Apc1638N/+ mice. The effects of CD were assessed through cell viability assay (WST assay), colony formation assay, and cell migration assay. We tested the induction of cell apoptosis through caspase 3/7 activity assays and immunoblot analysis of cleaved-caspase 3 and cleaved-PARP1. Additionally, CD was tested for its anti-tumor efficacy using an in vivo CRC xenograft model with the HCT-116 cell line. CD significantly inhibited the viability, migration, and colony formation of DTA and CRC cells. It remarkably decreased the tumor growth in organoids derived from intestinal tumor cells in the Apc1638N/+ mouse model. Furthermore, CD showed anti-tumor effects in an in vivo CRC xenograft model using the HCT-116 cell line. CD represents a promising therapeutic strategy for treating both DTs and CRC.

H3K27ac-activated LncRNA NUTM2A-AS1 Facilitated the Progression of Colorectal Cancer Cells via MicroRNA-126-5p/FAM3C Axis.

Long non-coding RNAs (lncRNAs) are of great importance in the process of colorectal cancer (CRC) tumorigenesis and progression. However, the functions and underlying molecular mechanisms of the majority of lncRNAs in CRC still lack clarity. A Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect lncRNA NUTM2A-AS1 expression in CRC cell lines. Cell counting kit 8 (CCK-8) assay and flow cytometry were used to examine the biological functions of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of CRC cells. RT-qPCR and western blot were implemented for the detection of cell proliferation-, apoptosis-related proteins, and FAM3C. Bioinformatics analysis and dual- luciferase reporter assays were utilized to identify the mutual regulatory mechanism of ceRNAs. lncRNA NUTM2A-AS1 notably elevated in CRC cell lines and the silenced of NUTM2A- AS1 declined proliferation and facilitated apoptosis. Mechanistically, NUTM2A-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) enriched at its promoter region, and NUTM2A-AS1 acted as a sponge for miR-126-5p, leading to the upregulation of FAM3C expression in CRC cell lines. Our research proposed NUTM2A-AS1 as an oncogenic lncRNA that facilitates CRC malignancy by upregulating FAM3C expression, which might provide new insight and a promising therapeutic target for the diagnosis and treatment of CRC.

ADAM17 promotes colorectal cancer migration and invasion by regulating the TGF-β/Smad signaling pathway

ObjectiveInvestigate ADAM17 expression in colorectal cancer (CRC) at molecular and cellular levels and its potential mechanism in promoting tumorigenesis by regulating CRC cell migration and invasion. Materials and methodsThe study measured ADAM17 mRNA and protein levels in colorectal cancer cells and tissues using qPCR and immunohistochemical staining, and assessed the cells' proliferation, migration, and invasion abilities. ResultsADAM17 expression was significantly higher in CRC tissues than in non-cancerous tissues and was linked to metastasis and poor prognosis in CRC patients. Silencing ADAM17 reduced cell migration and invasion. Mechanistically, knocking down ADAM17 decreased the expression of TGF-β/Smad pathway-related proteins, which inhibited proteins associated with migration and invasion, thus impairing these cellular processes. ConclusionADAM17 likely promotes the migration and invasion of CRC cells by regulating the TGF-β/Smad signaling pathway. This study aids in understanding the molecular mechanisms of CRC metastasis and development, and supports the development of new therapeutic targets.