Rheum khorasanicum. Hydroalcoholic root extract induces cell death in human colorectal adenocarcinoma: An in vitro and in silico study.

Colorectal cancer (CRC) is the second greatest cause of cancer-related death in the world and chemotherapy, as an important part of CRC treatment, has some drawbacks, including systemic toxicity. Therefore, it is crucial to discover new and more effective CRC treatment plans. Rheum khorasanicum (R. khorasanicum) is a medicinal plant with high flavonoids, stilbenes, and anthraquinone contents, so it can be a potential source of antioxidants and can be used for therapeutic purposes and trigger apoptosis in cancer cells. In this study, we investigated the effects of hydroalcoholic root extract of R. khorasanicum treatment on inducing mitochondrial apoptosis of HT-29 and Caco-2 human colorectal adenocarcinoma cells. Firstly, the total phenolic and flavonoid content was determined. Then, the cytotoxic effects of R. khorasanicum on cells of three different types, including HT-29 and Caco-2 colon cancer cells as well as normal 3T3 cells were assessed using the MTT assay. To investigate the characteristics of cellular death, flow cytometry, and western blotting were performed. The results of this study indicated considerable phenolic (356.4±9.4 GAE/gDW) and flavonoid (934.55±17.1 QE/gDW) contents in R. khorasanicum. MTT assay's finding indicated that 100, 60, and 30µg/mL concentrations of R. khorasanicum reduce cell viability in HT-29 and Caco-2 cell lines significantly (P<0.05). It has been also revealed that R. khorasanicum extract induces apoptosis rather than necrosis in these cell lines. Moreover, Bcl-2 expression was significantly reduced in both HT-29 and Caco-2 cell lines, while Bax and cleaved caspase-3 expression soared considerably in the groups under R. khorasanicum treatment (P<0.05). In conclusion, our findings have suggested that high phenol and flavonoid contents of R. khorasanicum root extract possibly play an important role in cell cytotoxicity and apoptosis induction in HT-29 and Caco-2 colon cancer cells.

[Évaluation de la gravité du cancer colorectal dépisté dans le contexte de la crise sanitaire liée au COVID19 en région Ile-de-France]. / Evaluation of the severity of screened colorectal cancer in the context of the health crisis linked to COVID19 in Ile-de-France region.

BACKGROUND: After the announcement in March 2020 of the COVID-19 pandemic, colorectal cancer (CRC) screening programs were suspended in several countries. Compared to the lesions detected during previous campaigns, this study aims to assess the severity of CRC detected during the 2020 screening campaign in Île-de-France, the French region most affected by the 1st wave of the pandemic. METHODS: The descriptive and etiological study included all faecal immunochemical test (FIT) results carried out between January 2017 and December 2020 on people aged 50-74, living in Île-de-France. First, the proportion of colonoscopies performed within one month (One-month-colo) following FIT; the yield of colonoscopy (proportion of colonoscopies with a neoplasm lesion among those performed) and CRC severity (TNM Classification, Level-0: T0/N0/M0, Level-1: T1/T2/N0/M0, Level-2: T3/T4/N0/M0; Level-3: T3/T4/N1/M0; Level-4: M1) were described in 2020 compared to previous campaigns (2017, 2018, and 2019). Subsequently, the link between the level of CRC severity and the predictive factors, including campaign year and time to colonoscopy, was analysed using polytomous multivariate regression. RESULTS: The one-month-colo (2017: 9.1% of 11,529 colonoscopies; 2018: 8.5% of 13,346; 2019: 5.7% of 7,881; 2020: 6.7% of 11,040; p < 0.001), the yield (65.2%, 64.1%, 62.4%, 60.8% respectively, p < 0.001) were significantly different between campaigns. The proportion of CRC level-4 (4.8% in 2017 (653 CRC); 7.6% in 2018 (674 CRC); 4.6% in 2019 (330 CRC) and 4.7% in 2020 (404 CRC); p < 0.29) was not significantly different between campaigns. The probability of having CRC with a high severity level was inversely related to the time to colonoscopy but not to the campaign year. Compared to patients having undergone colonoscopy within 30 days, the odds were significantly reduced by 60% in patients having undergone colonoscopy after 7 months (adjusted Odds-Ratio: 0.4 [0.3; 0.6]; p < 0.0001). CONCLUSIONS: The French indicators were certainly degraded before the first wave of the COVID-19. The delay in access to colonoscopy as well as its extension induced by the COVID-19 crisis had no impact in terms of cancer severity, due to a discriminatory approach prioritizing patients with evident symptoms.

Tetraspanin-29 activates Notch signaling by interacting with ADAM10 to enhance its activity in colorectal cancer.

ADAM10 acts upstream of Notch signaling and plays oncogenic roles in various cancers. Tetraspanin family proteins regulate ADAM10 trafficking and activity. Here, we aimed to investigate whether and how tetraspanin-29 modulates ADAM10 in colorectal cancer (CRC). We found that ADAM10 expression was upregulated in CRC tissues and this was cross-validated in the TCGA COAD data set. The ADAM10 protein level and its α-secretase activity were enhanced in CRC cell lines compared with control cell lines. Co-immunoprecipitation showed ADAM10 interacted with tetraspanin-29 in the LoVo cell line. Tetraspanin-29 knockdown reduced the cell surface trafficking and α-secretase activity of ADAM10. In addition, tetraspanin-29 knockdown inhibited Notch activity in a luciferase reporter assay and reduced the levels of cleaved Notch1 and Notch target genes such as HES2, c-MYC, and cyclin D3. Consistently, tetraspanin-29 overexpression increased cleaved Notch1 and this effect was blocked by ADAM10 inhibitors. The TCGA COAD data set confirmed the positive correlations of tetraspanin-29 with HES2, c-MYC, and cyclin D3. Thus, the tetraspanin-29/ADAM10/Notch pathway plays an important role in CRC.

Stereotactic body radiation therapy for colorectal liver metastases.

Multidisciplinary case discussion of patients with colorectal liver metastases (CRLM) has led to improved selection of more complex patients with the oligometastatic disease for treatment with surgical resection, locally ablative therapy or a combination of local modalities to improve the therapeutic ratio in patients with CRLM. Stereotactic body radiation therapy (SBRT) is a noninvasive local therapy with a potential role in the management of oligometastatic CRLM and may be considered as an alternate choice to other locally ablative therapies like radiofrequency ablation, radioembolization, chemoembolization or surgery or after the failure of other local treatment or in combination with surgery. Existing evidence reports for highly selected patients with CRLM, one to five fractions SBRT can be delivered safely, with satisfactory long-term local control, overall survival and quality of life. This review article will present the evidence of SBRT in this setting.

Colorectal cancer screening knowledge and uptake in lebanon: a national survey.

OBJECTIVE: The main aim of this national survey was to identify the levels of colorectal cancer screening knowledge and uptake in Lebanon. METHODS: A total of 1200 participants were enrolled in this cross-sectional household survey targeting the Lebanese population aged 50 years and above. The sample was recruited using a two-stage stratified cluster sampling approach. RESULTS: Of the total sample, 38.3% knew about any screening test for colorectal cancer but only 7.5% had ever used any. Thirty-nine percent of the participants rated their risk of getting colorectal cancer as very low or low, and only 53.5% were confident in their ability to undertake a screening test. Almost all participants agreed that medical advice and test reimbursement would encourage them to do a screening test. At the multivariate analysis level, hearing of an awareness campaign in the last two years showed the strongest association with the knowledge of a colorectal cancer screening test with an estimated ORadj = 5.12 (95%CI: 3.67 - 7.15). Other factors that were significantly associated with this knowledge variable included: a family history of colorectal cancer, a personal history of colorectal illness, having a health coverage, and knowledge of colorectal cancer signs and symptoms. DISCUSSION: This national study highlights an alarming lack of uptake and low levels of knowledge of colorectal cancer screening tests even though it is among the most prevalent cancers in Lebanon and its prevalence has been continuously increasing in the past years. The evidence suggests that people who had an experience with colorectal cancer diagnostic tests, either personally or through a family member, and those who have heard of an awareness campaign about colorectal cancer in the last two years are more likely to know its screening tests. CONCLUSION: Colorectal cancer screening knowledge and uptake in Lebanon are limited and justify the need for public health interventions. This study gives evidence that awareness campaigns, coupled with the involvement of medical providers and the reimbursement of screening test fees, would alleviate the burden of colorectal cancer in Lebanon.

[Pathological complete response of a metastatic MisMatch Repair deficient/MicroSatellite Instable colon cancer after immunotherapy: A case report]. / Réponse histologique complète d'un cancer colique métastatique de phénotype MisMatch Repair déficient/MicroSatellite Instable après immunothérapie : à propos d'un cas.

Immunotherapies are part of the therapeutic strategy in many cancers and are indicated for metastatic colorectal adenocarcinoma with loss of expression of MisMatch Repair system proteins or with microsatelite instability (dMMR/MSI) in the United States. The rate of pathological response to immunotherapy remains poorly documented, but several cases of complete or major pathological response have recently been described. We decided to report the case of a complete pathological response to immunotherapy of a dMMR/MSI colorectal adenocarcinoma in a 74-year-old patient, initially inoperable due to duodenal invasion. Three months after the introduction of immunotherapy, the patient developed drug-induced colitis that contraindicated further treatment. Histological examination of the subtotal colectomy specimen revealed no residual tumour cells. The patterns of tumour regression were mainly represented by colloid regression, infarctoid-type necrosis and a resorptive inflammatory reaction. Although the operative indications for patients with metastatic dMMR/MSI colorectal cancer treated by immunotherapy are still very limited, the number of such specimens is expected to increase rapidly. The management of these specimens, as well as the possibility of a complete histological response, must be known by pathologists who play a key role in the pathophysiological knowledge of these lesions.

[Medical oncological treatment of colorectal cancer in the elderly]. / Traitement chirurgical du cancer colorectal chez la personne âgée.

Approximately a quarter of patients undergoing colorectal cancer surgery are over 75 years of age. Their care must therefore be adapted to minimise his functional consequences, which can be more significant in an elderly patient.

[Medical oncological treatment of colorectal cancer in the elderly]. / Traitement oncologique médical du cancer colorectal chez la personne âgée.

Medical treatment with chemotherapy is discussed in several situations in the treatment of colon cancer. In the adjuvant setting, chemotherapy with 5FU±oxaliplatin for six months should be considered in the case of lymph node involvement. In the metastatic setting, several protocols exist. The choice of treatments should be based on the expected objectives in terms of response and survival gain, but also of tolerance and quality of life for the patient. A thorough oncogeriatric assessment helps to better define the therapeutic programme. The continuation of geriatric follow-up throughout the treatment process shows a benefit for the patient in terms of quality of life and tolerance of treatments.

The lncRNA TUG1 promotes cell growth and migration in colorectal cancer via the TUG1-miR-145-5p-TRPC6 pathway.

Colorectal cancer (CRC) is the third-most prevalent malignant tumor. Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), is reportedly involved in the physiological and pathological processes of CRC. However, the role of TUG1 in the progression of CRC and its underlying mechanisms are largely unknown. Here, we measured the expression of TUG1 in clinical samples from CRC patients and found that the expression level of TUG1 was higher in CRC tissues compared with the normal adjacent tissues. We then performed knockdown of TUG1 with siRNAs in two CRC cell lines and found that TUG1 knockdown inhibited the viability, proliferation, and migration of CRC cells, and reduced the ability of CRC cells to form subcutaneous tumors. Furthermore, we discovered that TUG1 affects the cellular processes in CRC cells by sponging miR-145-5p. We further found that miR-145-5p inhibits the expression of the protein-encoding gene Transient Receptor Potential Cation Channel Subfamily C Member 6 (TRPC6), and that overexpression of TRPC6 restored the inhibitory role of miR-145-5p in CRC cells. In conclusion, we have demonstrated that TUG1 exerts its role by modulating the TUG1-miR-145-5p-TRPC6 regulatory axis, thus revealing a novel molecular mechanism for the effects of TUG1 in the progression of CRC. Our data indicate that the TUG1-miR-145-5p-TRPC6 signaling pathway could serve as a target for the diagnosis and treatment of CRC.

Role of 7-chloro-4-(phenylselanyl) quinoline in the treatment of oxaliplatin-induced hepatic toxicity in mice.

There is an increasing incidence of hepatotoxicity induced by oxaliplatin (OXA); therefore, researchers' attention has been drawn to therapeutic alternatives that may decrease OXA-induced hepatotoxicity. Studies indicate that oxidative stress plays a major role in OXA-induced liver injury. As several pharmacological effects of 7-chloro-4-(phenylselanyl) quinole (4-PSQ) involve its antioxidant action, the hypothesis that this organoselenium compound could be promising for the treatment or prevention of hepatotoxicity induced by treatment with OXA was investigated. To test this hypothesis, male Swiss mice received OXA (10 mg·kg-1) on days 0 and 2, followed by oral administration of 4-PSQ (1 mg·kg-1) on days 2 to 14. 4-PSQ reduced the plasma aspartate, and alanine aminotransferase activity increased by exposure to OXA. The histopathological examination of the liver showed that 4-PSQ markedly improved OXA-induced hepatic injury. In addition, treatment with 4-PSQ reduced the oxidation of lipids and proteins (thiobarbituric acid reactive species levels and protein carbonyl content) and attenuated the increase of hepatic catalase and glutathione peroxidase activity caused by OXA. The inhibition of hepatic δ-aminolevulinic dehydratase activity induced by OXA was reverted by 4-PSQ. In conclusion, results indicate that 4-PSQ may be a good therapeutic strategy for attenuating OXA-induced liver damage.

[Colorectal cancer screening program : Test completion rate and follow-up results after selective mailing of the test kit, based on likelihood of participation]. / Dépistage organisé du cancer colorectal : taux de réalisation du test et résultats du suivi après un envoi postal sélectif du kit de test, basé sur la probabilité de participation.

BACKGROUND: Even though theinterest of a Colorectal-Cancer Screening Program has been amply demonstrated, in French departments the participation rate (PR) seldom reaches 45%. In the absence of mass mailing, a strategy (S-1) consisting in mailing a test kit to people having made a request was implemented in 2015. In 2017, another mailing strategy (S-2), which consisted in sending the test kit only to people likely to take the test, was programmed. This study assesses the respective impact of these two strategies as compared to the standard approach (S-0). METHODS: The study included 254,113 (S-0), 4,130 (S-1) and 10,887 (S-2) people aged 50-74, targeted during the 2016-2017 campaign in Seine-Saint-Denis (France). S-0 persons received a 2nd reminder without a test-kit, while S-1 persons received, at their request, a mailed test kit. Without having made a request, S-2 persons the mailed test kit according to probability of participation (Proba) which was estimated a priori by the ratio between the sum total of index values (frequency of previous participation, date of most recent participation, age) and a theoretical maximum. Completion rates (test/colonoscopy) were compared 18 months after the last S-2 kit was sent. RESULTS: PR was highest in S-1 (S-0: 5.8%, S-1: 74.9%, S-2: 31.3%; p < 0.0001). In S-2, PR rose as Proba increased (Proba: ]0-30%], ]30-50%], ]50-75%], ]75-100%]; PR: 21.1%, 23.3%, 36.2%, 52.8% respectively; p < 0.05). Compared to the ≥70 years age-group, the 50-54 years age-group presented a lower PR in S-1 (65.9% vs. 85.1%; p < 0.05) whereas it presented a higher PR in S-0 (4.3% vs. 7.1%; p < 0.05) and in S-2 (23.2% vs. 54.5%; p < 0.05). All in all, colonoscopy completion rates were highest in S-1 (S-0: 62.2%, S-1: 80.0%, S-2: 65.0%; p < 0.001). CONCLUSION: Test-kit mailing without spontaneous request does not lead to an optimal level of participation, thereby highlighting a need to give thought to new and improved mobilization methods. The relatively pronounced participation of younger persons, who are not favored by present-day testing specifications, underscores the interest of a specific approach addressed to active people, who are less inclined than elderly individuals to regularly consult their attending physicians.

[Tumour deposition (TD), a probably underestimated poor prognostic criterion, to be taken into account in the therapeutic management of patients with stage III colon cancer]. / Les dépôts tumoraux (DT), un critère pronostique péjoratif probablement sous-estimé, à prendre en compte dans la prise en charge thérapeutique des malades atteints de cancer colique de stade III.

The management of colorectal cancer (CRC) relies heavily on TNM staging. In order to improve this staging, it is essential to identify all histological markers bearing a significant prognostic value. Among these, tumor deposits (TDs), defined as tumor foci in the pericolonic or perirectal adipose tissue with no residual lymph node tissue, have been shown to be associated with poor prognosis in cohort studies leading to their individualization in the TNM7 classification as pN1c. However, TDs are only considered in the absence of lymph node metastases. There is no consensus on this particular way of integrating TDs in the TNM classification. Indeed, at the time when the choice of the type of adjuvant treatment and its duration in stage III colon cancers (i.e. with lymph node metastases) is based on pT and pN criteria, taking into account TDs only in the absence of concomitant lymph node metastases is potentially responsible for a misclassification of some patients and wrong therapeutic decisions. In addition, many questions concerning the true definition of TDs, their origin, their prognostic value and the optimization of their consideration remain open. The objective of this review is to provide a synthesis of current knowledge on TDs in CRC, in view of their prognostic importance, their biological complexity and the scientific interest they are currently the subject of.

Down-regulation of NTSR3 inhibits cell growth and metastasis, as well as the PI3K-AKT and MAPK signaling pathways in colorectal cancer.

Colorectal cancer is a common malignancy. NTS receptor 3 (NTSR3) is known to play an important role in several cancers. This study examined the effects of NTSR3 on cell growth and metastasis in colorectal cancer. Western blot analysis, real-time PCR, immunofluorescence staining, MTT, cell cycle assay, cell apoptosis assay, Hoechst staining, caspase-3 and caspase-9 activity assays, cell adhesion assay, wound healing assay, and a Transwell assay were used in this study. We found that NTSR3 was expressed at relatively high levels in the colorectal cancer cell lines SW620 and SW480. NTSR3 knockdown suppressed cell growth and promoted cell apoptosis. Meanwhile, the protein expression levels of cyclinD1, cyclinE1, CDK4, and p-RB were reduced, and the levels of p-P27, P15, P21, cleaved caspase-3, and cleaved caspase-9 protein were increased. Cell invasiveness and cell migration were reduced with knockdown of NTSR3. In addition, our rescue experiments demonstrated that overexpression of the siRNA-resistant alleles of NTSR3 abrogated the NTSR3-siRNA-mediated effects on cell function. Further, down-regulation of NTSR3 inactivated the PI3K-AKT and MAPK signaling pathways. Collectively, these data demonstrate that knockdown of NTSR3 inhibits cell growth and metastasis, as well as the PI3K-AKT and MAPK signaling pathways in colorectal cancer. Thus, our results indicate that NTSR3 is a potential therapeutic target for treating colorectal cancer.

PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2.

The purpose of this study was to characterize the expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a membrane-bound homodimeric enzyme that specifically hydroxylates lysine in the telopeptide of procollagens, and assess the clinical significance of PLOD2 in colorectal cancer (CRC). Our results show that PLOD2 is highly expressed in CRC tumor tissues and cell lines, both at the mRNA and protein levels. Next, we found that PLOD2 was positively correlated with tumor grade (P = 0.001), T stage (P = 0.001), N stage (P < 0.001), and an advanced TNM stage (P < 0.001). Knockdown of PLOD2 attenuated CRC cell proliferation, migration, and invasiveness, in vitro. Our analysis of the mechanism behind the effects of PLOD2 suggests that PLOD2 affected glycolysis by regulating the expression of hexokinase 2 (HK2). HK2 reverses the inhibitory effects of PLOD2 knockdown in CRC. Furthermore, the data suggest that PLOD2 regulates the expression of HK2 via the STAT3 signaling pathway. Survival analysis revealed that high expression levels of PLOD2 (HR = 3.800, P < 0.001) and HK2 expression (HR = 10.222, P < 0.001) correlated with the overall survival rate. After analyzing their expression and correlation, PLOD2 positively correlated with HK2 (r = 0.590, P < 0.001). Our findings have revealed that PLOD2 is a novel regulatory factor in glucose metabolism, exerted via controlling HK2 expression in CRC cells, suggesting PLOD2 as a promising therapeutic target for CRC treatment.

MicroRNA-518-3p suppresses cell proliferation, invasiveness, and migration in colorectal cancer via targeting TRIP4.

MicroRNA (miR)-518-3p has been shown to function as a tumor suppressor. This study was conducted to investigate the effects of miR-518-3p in colorectal cancer (CRC). The miR-518-3p mimic, mimic negative control (NC), miR-518-3p inhibitor, inhibitor-NC, ShRNA-TRIP4, and ShRNA-NC vectors were transfected into SW480 cells using Lipofectamine 2000. Cell viability was detected using CCK-8. Colony formation, cell invasiveness, and cell migration were assessed by plate colony formation, Transwell assays, and wound healing assays, respectively. Relative mRNA and protein levels were detected using RT-qPCR and Western blot, respectively. The target gene thyroid hormone receptor interactor 4 (TRIP4) of miR-518-3p was identified and further verified using dual-luciferase reporter assay. Compared with normal tissues, levels of miR-518-3p were decreased and TRIP4 was significantly increased in the tissues from patients with CRC. Following transfection with a miR-518-3p mimic or ShRNA-TRIP4, cell viability decreased in a time-dependent manner, and colony formation rate, wound closure rate, and the number of invasive cells were much lower for the transfected cells than in the corresponding NC and control groups. miR-518-3p overexpression or silencing of TRIP4 significantly down-regulated the expression of MMP-2 and MMP-9. Knockdown of miR-518-3p had the opposite effects, and TRIP4 was identified as a target of miR-518-3p. The inhibitory effects of miR-518-3p on the progressions of CRC are associated with TRIP4.

Propofol promotes apoptosis of colorectal cancer cells via alleviating the suppression of lncRNA HOXA11-AS on miRNA let-7i.

To date, surgical resection is the mainstay for the treatment of colorectal cancer (CRC). Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents, has been reported to be involved in modulating the malignancy of a variety of human cancers. However, the underlying mechanisms remain poorly understood. In this study, using a cell counting kit (CCK-8), flow cytometry, and caspase-3 cleavage assays, we found that propofol promoted cell apoptosis and inhibited cell proliferation in both Colo205 and SW620 cells, through the down-regulation of HOXA11-AS and up-regulation of let-7i. Moreover, gain-of-function studies of HOXA11-AS or loss-of-function studies of let-7i also revealed a negative correlation between HOXA11-AS and let-7i in propofol-mediated biological functions of CRC cells. Furthermore, our mechanistic experiments revealed that HOXA11-AS acts as a molecular sponge for let-7i, thereby regulating the expression of ABCC10. We investigate the theory that propofol suppresses colorectal cancer tumorigenesis by modulating the HOXA11-AS-let-7i-ABCC10 regulatory network, indicating the potential for propofol to control CRC development.

The modulatory effects of exercise on the inflammatory and apoptotic markers in rats with 1,2-dimethylhydrazine-induced colorectal cancer.

This study aimed to investigate the underlying mechanisms in anti-tumorigenesis effects of exercise through evaluation of inflammation and apoptosis. Twenty-four Wistar rats were divided into control, exercise, 1,2-dimethylhydrazine (DMH), and DMH + exercise. After a week, rats in the DMH group were given DMH twice a week for 2 weeks. Animals in the exercise groups performed exercise on a treadmill 5 days/week for 8 weeks. After 8 weeks of training, levels of COX-2, PCNA, Bax, Bcl-2, and procaspase-3/cleaved caspase-3 were assessed. Histological changes, number of aberrant crypt foci (ACF), and serum levels of TNF-α and IL-6 were also analyzed. ACF number was significantly decreased following the exercise program. Protein levels of COX-2 and PCNA and serum levels of IL-6 and TNF-α were significantly elevated in the rats receiving DMH and downregulated after performing the exercise program (P < 0.05). Exercise upregulated apoptosis, which was evident from the increased Bax/Bcl2 ratio, and enhanced the expression levels of activated caspase-3 as compared to the DMH group. The colonic architecture was improved in DMH + exercise. Exercise can effectively attenuate DMH-induced increase of inflammatory markers. Exercise induces apoptosis at the downstream of the inflammatory response. Therefore, exercise may play a role as a moderator of inflammation to exert protective effects against colon cancer.

[Estimated impact of the current colorectal screening program in France]. / Estimation de l'impact du programme actuel de dépistage organisé du cancer colorectal.

BACKGROUND: Colorectal cancer is the third most common cancer and the second most deadly in France. A Cochrane meta-analysis has confirmed the benefits of colorectal cancer screening. A nationwide colorectal screening program was set up in France in 2009 for medium-risk, asymptomatic people aged 50 to 74 years. It has been based, since 2015, on the Fecal Immunochemical Test. The participation rate for 2016-2017 was 34%, which is lower than the European objectives. The objective of this study was to evaluate the impact of the program at the current participation rate and at rates of 45% and 65%. METHODS: The epidemiological impact of the program was estimated from the results of an individual simulation model adapted from the Microsimulation Screening Analysis Colon model, calibrated and transposed to the French context. An initial analysis was conducted to estimate the individual impact of screening and a second for the entire eligible population, at various participation rates. RESULTS: The test is associated with a lifetime reduction in the risk of colorectal cancer of 24% for men and 21% for women, and a reduction in the risk of death from colorectal cancer of 51% and 43% respectively. At the current level of participation, the program reduces incidence by 5% and mortality by 14% compared to no organized screening. The impact would be reduced by an additional 3% and 8% for participation rates of 45% and 65% respectively. Similarly, mortality would decrease by an additional 8% and 22%. CONCLUSION: These results confirm that in a population at medium risk for colorectal cancer, the organised programme is an effective strategy for reducing its incidence. They also confirm that the achievement of European objectives remains a key issue for improving the effectiveness of organized screening. An evolution of immunological test delivery modalities could help to achieve these participation objectives.

International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis.

OBJECTIVE: In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis. DESIGN: International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research. RESULTS: Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis. CONCLUSION: Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.

SAV1, regulated by microRNA-21, suppresses tumor growth in colorectal cancer.

This study investigated the role and action of the Salvador 1 protein (SAV1, also called WW45) in colorectal cancer (CRC). For this, CRC SW480 and HCT116 cells were infected with lentiviruses of SAV1 overexpression vector (lenti-SAV1) and SAV1 short hairpin RNA (sh-SAV1) to overexpress and silence SAV1 respectively, or transfected with microRNA-21 (miR-21) mimic to overexpress miR-21. Relative mRNA levels of SAV1 and relative miR-21 levels in CRC tissues or cells were detected. The effects of SAV1 and miR-21 on cell proliferation and apoptosis were evaluated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and annexin V - fluorescein isothiocyanate (FITC) - propidium iodide (PI) flow cytometry, respectively. Our results revealed that SAV1 was downregulated in CRC tissues compared with the adjacent noncancerous tissues. Furthermore, SAV1 overexpression inhibited proliferation and promoted apoptosis in SW480 and HCT116 cells, whereas knockdown of SAV1 exerted the opposite effect. Additionally, the tumorigenesis of SW480 cells in xenografted mice was significantly inhibited by SAV1 overexpression but promoted by SAV1 knockdown. MiR-21 levels significantly and negatively correlated with SAV1 expression in CRC tissues. More importantly, miR-21 overexpression significantly abolished the SAV1-mediated inhibition of proliferation and stimulation of apoptosis of SW480. In conclusion, SAV1 suppresses tumor growth in CRC and is regulated by miR-21.