Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Relationship between age and the histopathological features to chemotherapy response in colorectal cancer patients: a prospective observational study

Introduction: Chemotherapy response in early age-onset colorectal cancer patients is still controversial, and the results of chemotherapy response are unknown. Therefore, the purpose of this study is to determine the relationship between the age of colorectal cancer patients and histopathological features and chemotherapy response. Methods: This is a prospective observational study. The subjects in this study were colorectal cancer patients in the Digestive Surgery division at Tertiary Hospital in West Java from September 2021 to September 2022. Results: There were 86 subjects who underwent chemotherapy in accordance with the inclusion and exclusion criteria. Consisting of 39 patients of early age onset and 44 female patients. The most common histopathological feature in early age onset (EAO) and late age onset (LAO) was adenocarcinoma (25% and 46%, respectively). Stage III colorectal cancer affected 38 patients, while stage IV affected 48 patients. There was a significant relationship between early age onset and late age onset with histological features (p < 0.001). The patients with the highest chemotherapy response had stable diseases in EAO (17 patients) and LAO (20 patients). There was no statistically significant relationship between age, histological features, and stage of colorectal cancer and chemotherapy response (p > 0.05). The results of the ordinal logistic regression test showed no systematic relationship between chemotherapy response and age, histopathological features, gender, or cancer stage (p > 0.05). Conclusion: There was no association between age and histopathologic features with chemotherapy response and there is no difference in chemotherapy response between early and late age onset. (AU)

Study of long non-coding RNA Tug 1 expression in Egyptian colorectal adenocarcinoma patients

Purpose: Colorectal cancer (CRC) is one of the most fatal tumors worldwide. In Egypt, most CRC cases occur in individuals > 40 years old. TUG1 has been proved to be disrupted in different malignancies and may have a critical role in tumor progression, invasion, and metastasis. However, its role in CRC has not been adequately studied. Materials / Methods: Quantitative real-time polymerase chain reaction (PCR) was used to evaluate the expression levels of long non-coding RNA (LncRNA) taurine upregulated gene 1 (TUG1), in nonmetastatic and metastatic CRC tissues and adjacent noncancerous tissues as control. Results: LncRNA TUG1 expression was significantly upregulated in both nonmetastatic and metastatic CRC tissues, in comparison with the adjacent noncancerous tissue. It was found that TUG1 could have a possible prognostic role in CRC, by comparing the sensitivity and specificity of TUG1 with those of CEA and CA19-9. Conclusion: The results of the current study suggest that the LncRNA TUG1 participates in the malignant behaviors of CRC cells. (AU)

More attention for high-risk pathological features for stage Ⅱ colorectal cancer required / 中华病理学杂志

Stage Ⅱ (T3-4N0M0) accounts for 25% of colorectal cancer and five-year survival is between 70% and 80%. However, 25% of patients develop distant metastases and have a survival rate similar to that of stage Ⅲ disease. However, whether or not to give adjuvant chemotherapy is still a controversial issue. As a result, there has been a lot of interest in the identification of the pathological factors underlying the poor prognosis associated with this stage, in order to establish a firmer basis for the administration of adjuvant chemotherapy. But not all high-risk factors are equal for stage Ⅱ colorectal cancer, variability still exists in the management and outcomes of high-risk patients. Here be introduced and commented on thinking and understanding about its controversy and evolution for the attention of the working pathologist and gastroenterologist doctors.

Advances on the treatment of Fusobacterium nucleatum-promoted colorectal cancers using nanomaterials / 生物工程学报

Fusobacterium nucleatum (Fn) is an oral anaerobic bacterium that has recently been found to colonize on the surface of colorectal cancer cells in humans, and its degree of enrichment is highly negatively correlated with the prognosis of tumor treatment. Numerous studies have shown that Fn is involved in the occurrence and development of colorectal cancer (CRC), and Fn interacts with multiple components in the tumor microenvironment to increase tumor resistance. In recent years, researchers have begun using nanomedicine to inhibit Fn's proliferation at the tumor site or directly target Fn to treat CRC. This review summarizes the mechanism of Fn in promoting CRC and the latest research progress on Fn-related CRC therapy using different nanomaterials. Finally, the applications perspective of nanomaterials in Fn-promoted CRC therapy was prospected.

Application of preoperative serum CYFRA 21-1 level in the prognosis of colorectal cancer / 中华预防医学杂志

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.

Risk factors for residual cancer or lymph node metastasis after endoscopic noncurable resection of early colorectal cancer / 中华肿瘤杂志

Objective: Risk factors related to residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer were analyzed to predict the risk of residual cancer or lymph node metastasis, optimize the indications of radical surgical surgery, and avoid excessive additional surgical operations. Methods: Clinical data of 81 patients who received endoscopic treatment for early colorectal cancer in the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences from 2009 to 2019 and received additional radical surgical surgery after endoscopic resection with pathological indication of non-curative resection were collected to analyze the relationship between various factors and the risk of residual cancer or lymph node metastasis after endoscopic resection. Results: Of the 81 patients, 17 (21.0%) were positive for residual cancer or lymph node metastasis, while 64 (79.0%) were negative. Among 17 patients with residual cancer or positive lymph node metastasis, 3 patients had only residual cancer (2 patients with positive vertical cutting edge). 11 patients had only lymph node metastasis, and 3 patients had both residual cancer and lymph node metastasis. Lesion location, poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion were associated with residual cancer or lymph node metastasis after endoscopic (P<0.05). Logistic multivariate regression analysis showed that poorly differentiated cancer (OR=5.513, 95% CI: 1.423, 21.352, P=0.013) was an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer. Conclusions: For early colorectal cancer after endoscopic non-curable resection, residual cancer or lymph node metastasis is associated with poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion and the lesions are located in the descending colon, transverse colon, ascending colon and cecum with the postoperative mucosal pathology result. For early colorectal cancer, poorly differentiated cancer is an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection, which is suggested that radical surgery should be added after endoscopic treatment.

Poly-G for tumor matched samples chronicles the evolution of human colorectal cancer / 中华肿瘤杂志

Objective: To analyze poly-guanine (poly-G) genotypes and construct the phylogenetic tree of colorectal cancer (CRC) and provide an efficient and convenient method for the study of intra-tumor heterogeneity and tumor metastasis pathway. Methods: The clinicopathological information of patients with primary colorectal cancer resection with regional lymph node metastases were retrospectively collected in the Department of General Surgery, General Hospital of Tianjin Medical University from January 2017 to December 2017. The paraffin sections of the paired tumor samples were performed consecutively, and multi-region microdissection was performed after histogene staining. The phenol-chloroform extraction and ethanol precipitation scheme was used to obtain DNA, and Poly-G multiplex PCR amplification and capillary electrophoresis detection were performed. The correlation between Poly-G mutation frequency and clinicopathological parameters was analyzed. Based on the difference of Poly-G genotypes between paired samples, the distance matrix was calculated, and the phylogenetic tree was constructed to clarify the tumor metastasis pathway. Results: A total of 237 paired samples were collected from 20 patients including 134 primary lesions, 66 lymph node metastases, 37 normal tissues, and Poly-G mutation was detected in 20 patients (100%). The mutation frequency of Poly-G in low and undifferentiated patients was (74.10±23.11)%, higher than that in high and medium differentiated patients [(31.36±12.04)%, P<0.001]. In microsatellite instability patients, the mutation frequency of Poly-G was (68.19±24.80)%, which was higher than that in microsatellite stable patients [(32.40±14.90)%, P=0.003]. The Poly-G mutation frequency was not correlated with age, gender, and pathological staging (all P>0.05). Based on Poly-G genotype difference of the paired samples, the phylogenetic trees of 20 patients were constructed, showing the evolution process of the tumor, especially the subclonal origins of lymph node metastasis. Conclusion: Poly-G mutations accumulate in the occurrence and development of CRC, and can be used as genetic markers to generate reliable maps of intratumor heterogeneity in large numbers of patients with minimal time and cost expenditure.

Advances in three-dimensional tumor models for colorectal cancer / 中华肿瘤杂志

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor / 中华肿瘤杂志

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Methylated SDC2 testing in stool DNA for early screening of colorectal cancer in Shipai Town, Dongguan City / 中华胃肠外科杂志

Objective: To explore the utility of stool-based DNA test of methylated SDC2 (mSDC2) for colorectal cancer (CRC) screening in residents of Shipai Town, Dongguan City. Methods: This was a cross-sectional study. Using a cluster sampling method, residents of 18 villages in Shipai Town, Dongguan City were screened for CRC from May 2021 to February 2022. In this study, mSDC2 testing was employed as a preliminary screening method. Colonoscopy examination was recommended for individuals identified as high-risk based on the positive mSDC2 tests. The final screening results, including the rate of positive mSDC2 tests, the rate of colonoscopy compliance, the rate of lesions detection, and the cost-effectiveness of screening, were analyzed to explore the benefits of this screening strategy. Results: A total of 10 708 residents were enrolled and completed mSDC2 testing, giving a participation rate of 54.99% (10 708/19 474) and a pass rate of 97.87% (10 708/10 941). These individuals included 4 713 men (44.01%) and 5 995 women (55.99%) with a mean age of (54.52±9.64) years. The participants were allocated to four age groups (40-49, 50-59, 60-69, and 70-74 years), comprising 35.21%(3770/10 708), 36.25% (3882/10 708), 18.84% (2017/10 708), and 9.70% (1039/10 708) of all participants, respectively. mSDC2 testing was positive in 821/10 708 (7.67%) participants, 521 of whom underwent colonoscopy, resulting in a compliance rate of 63.46% (521/821). After eliminating of 8 individuals without pathology results, data from 513 individuals were finally analyzed. Colonoscopy detection rate differed significantly between age groups (χ2=23.155, P<0.001),ranging from a low of 60.74% in the 40-49 year age group to a high of 86.11% in the 70-74 year age group. Colonoscopies resulted in the diagnosis of 25 (4.87%) CRCs, 192 (37.43%) advanced adenomas, 67 (13.06%) early adenomas, 15 (2.92%) serrated polyps, and 86 (16.76%) non- adenomatous polyps. The 25 CRCs were Stage 0 in 14 (56.0%) individuals, stage I in 4 (16.0%), and Stage II in 7(28.0%). Thus, 18 of the detected CRCs were at an early stage. The early detection rate of CRCs and advanced adenomas was 96.77% (210/217). The rate of mSDC2 testing for all intestinal lesions was 75.05% (385/513). In particular, the financial benefit of this screening was 32.64 million yuan, and the benefit-cost ratio was 6.0. Conclusion: Screening for CRCs using stool-based mSDC2 testing combined with colonoscopy has a high lesion detection rate and a high cost-effectiveness ratio. This is a CRC screening strategy that deserves to be promoted in China.

Molecular mechanism and treatment strategy of colorectal cancer peritoneal metastasis / 中华胃肠外科杂志

Peritoneal metastatic colorectal cancer (pmCRC) is common and has been considered as the terminal stage. The theory of "seed and soil" and "oligometastasis" are the acknowledged hypotheses of pathogenesis of pmCRC. In recent years, the molecular mechanism related to pmCRC has been deeply researched. We realize that the formation of peritoneal metastasis, from detachment of cells from primary tumor to mesothelial adhesion and invasion, depends on the interplay of multiple molecules. Various components of tumor microenvironment also work as regulators in this process. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been widely used in clinical practice as an established treatment for pmCRC. Besides systemic chemotherapy, targeted and immunotherapeutic drugs are also increasingly used to improve prognosis. This article reviews the molecular mechanisms and treatment strategies related to pmCRC.

Establishment of treatment center for peritoneal metastasis in colorectal cancer / 中华胃肠外科杂志

The prognosis of patients with peritoneal metastasis from colorectal cancer is poor. At present, the comprehensive treatment system based on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly improved the survival of these patients. However, CRS and HIPEC have strict indications, high procedural difficulty, and high morbidity and mortality. If CRS+HIPEC is performed in an inexperienced center, overall survival and quality of life of patients may bo compromised. The establishment of specialized diagnosis and treatment centers can provide a guarantee for standardized clinical diagnosis and treatment. In this review, we first introduced the necessity of establishing a colorectal cancer peritoneal metastasis treatment center and the construction situation of the diagnosis and treatment center for peritoneal surface malignancies at home and abroad. Then we focused on introducing our construction experience of the colorectal peritoneal metastasis treatment center, and emphasized that the construction of the center must be done well in two aspects: firstly, the clinical optimization should be realized and the specialization of the whole workflow should be strengthened; secondly, we should ensure the quality of patient care and the rights, well-being and health of every patient.

Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axis via downregulating PTEN / 南方医科大学学报

OBJECTIVE@#To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects.@*METHODS@#Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice.@*RESULTS@#Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis.@*CONCLUSION@#Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.

Value of fecal immunochemical test in colorectal cancer screening / 中华肿瘤杂志

Screening and early diagnosis and treatment have been proven effective in reducing the incidence and mortality of colorectal cancer. Colonoscopy combined with pathological examination is the gold standard for colorectal cancer screening. However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits. Additionally, it describes the current situation of colorectal cancer screening in China and summarizes the challenges faced in colorectal cancer screening in order to optimize the FIT-based colorectal cancer screening strategies in the population and provide theoretical reference for effective colorectal cancer screening.

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study / 中华肿瘤杂志

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Participation rate and detection of colorectal neoplasms based on multi-round fecal immunochemical testing for colorectal cancer screening in the Chinese population / 中华肿瘤杂志

Objective: To evaluate the participation rate and detection of colorectal neoplasms based on annual fecal immunochemical testing (FIT) for three consecutive years in a population-based colorectal cancer screening program in China. Methods: Based on a population-based colorectal cancer screening program conducted from May 2018 to May 2021 in 6 centers in China, 7 793 eligible participants aged 50-74 were included and offered free FIT and colonoscopy (for those who were FIT-positive on initial screening). At baseline, all participants were invited to receive FIT. In subsequent screening rounds, only FIT-positive participants who did not undergo colonoscopy or FIT-negative participants were invited to have repeated FIT screening. FIT-positive participants were recommended to undertake colonoscopy and pathological examination (if abnormalities were found during colonoscopy). An overall of three rounds of annual FIT screening were conducted. The primary outcomes of the study were the participation rate of FIT screening, the compliance rate of colonoscopy for FIT-positive participants, and the detection rate of colorectal neoplasms. Results: Among the 7 793 participants included in this study, 3 310 (42.5%) were male, with age of (60.50±6.49) years. The overall participation rates for the first, second and third round of FIT screening were 94.0%(7 327/7 793), 86.8% (6 048/6 968) and 91.3% (6 113/6 693), respectively. Overall, 7 742 out of 7 793 participants (99.3%) attended at least one round of screening, and 5 163 out of 7 793 participants (66.3%) attended all three rounds of screening. The positivity rate was significantly higher in the first (14.6%, 1 071/7 327) round compared with the second (5.6%, 3 41/6 048) and third (5.5%, 3 39/6 113) screening rounds (P<0.001). The overall compliance rates of colonoscopy examination among FIT-positive subjects were over 70% in three rounds, which were 76.3% (817/1 071), 75.7% (258/341) and 71.7% (243/339), respectively. In a multivariate logistic regression model considering factors including sex, education background, smoking, alcohol drinking, previous colonoscopy examination, colonic polyp history and family history of colorectal cancer among first-degree relatives, gender and smoking status were related factors affecting the participation rate of FIT screening, with higher rate in males and non-smokers. In addition, logistic regression analysis also found that age was negatively correlated with the compliance rate of colonoscopy in FIT positive patients. The detection rate of advanced tumors (colorectal cancer + advanced adenoma) declined from the first round to subsequent rounds [1st round: 1.15% (90/7 793); 2nd round: 0.57% (40/6 968); and 3rd round: 0.58% (39/6 693)], however, the positive predictive value for advanced neoplasms increased round by round, and was 11.02% in the first screening round, 15.50% in the second screening round, and 16.05 % in the third screening round. In each screening round, the detection rate for advanced neoplasms was higher in men than that in women, and increased with age. Conclusions: Annual repeated FIT screening has high acceptance and satisfying detection rates in the Chinese population. To optimize and improve the effectiveness of colorectal cancer screening, multi-round repeated FIT screening should be implemented while ensuring high participation rates.

Colonic stenting in acute malignant large bowel obstruction: audit of efficacy and safety in a Singapore tertiary referral centre

INTRODUCTION@#Acute malignant large bowel obstruction (MBO) occurs in 8%-15% of colorectal cancer patients. Self-expandable metal stents (SEMS) have progressed from a palliative modality to use as bridge to surgery (BTS). We aimed to assess the safety and efficacy of SEMS for MBO in our institution.@*METHODS@#The data of patients undergoing SEMS insertion for MBO were reviewed. Technical success was defined as successful SEMS deployment across tumour without complications. Clinical success was defined as colonic decompression without requiring further surgical intervention. Rates of complications, median time to surgery, types of surgery and rates of recurrence were studied.@*RESULTS@#Seventy-nine patients underwent emergent SEMS placement from September 2013 to February 2020. Their mean age was 68.8 ± 13.8 years and 43 (54%) patients were male. Mean tumour length was 4.2 cm ± 2.2 cm; 89.9% of malignant strictures were located distal to the splenic flexure. Technical and clinical success was 94.9% and 98.7%, respectively. Perforation occurred in 5.1% of patients, with none having stent migration or bleeding. Fifty (63.3%) patients underwent SEMS insertion as BTS. Median time to surgery was 20 (range 6-57) days. Most (82%) patients underwent minimally invasive surgery. Primary anastomosis rate was 98%. Thirty-nine patients had follow-up beyond 1-year posttreatment (median 34 months). Local recurrence and distant metastasis were observed in 4 (10.3%) and 5 (12.8%) patients, respectively.@*CONCLUSION@#Insertion of SEMS for acute MBO has high success rates and a good safety profile. Most patients in this audit underwent minimally invasive surgery and primary anastomosis after successful BTS.

Effect of intra-operative chemotherapy with 5-fluorouracil and leucovorin on the survival of patients with colorectal cancer after radical surgery: a retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection.@*METHODS@#1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC.@*RESULTS@#Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]).@*CONCLUSIONS@#IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery.@*TRIAL REGISTRATION@#chictr.org.cn, ChiCTR 2100043775.