Return to work in young and middle-aged colorectal cancer survivors:Factors influencing self-efficacy,fear,resilience,and financial toxicity

BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.

Colonoscopy plays an important role in detecting colorectal neoplasms in patients with gastric neoplasms

BACKGROUND Gastric cancer(GC)and colorectal cancer(CRC)are the fifth and third most common cancer worldwide,respectively.Nowadays,GC is reported to have a potential predictive value for CRC,especially for advanced CRC.AIM To evaluate the necessity of colonoscopy for gastric neoplasm(GN)patients.METHODS Four databases,including PubMed,EMBASE,the Cochrane Library,and Ovid,were used to perform the search strategy on May 2,2023.The prevalence of colorectal neoplasms(CRN)and baseline characteristics were compared between the neoplasm group and the control group.Continuous variables are expressed as the mean difference and standard deviation.Relationships of categorical variables in the two groups are expressed as odds ratios(OR)and 95%confidence intervals(95%CIs).Subgroup analysis according to different kinds of GNs was conducted for more in-depth analysis.The results of this study are represented by forest plots.Publication bias was evaluated by a funnel plot.All data analyses were performed by STATA SE 16.0 software.RESULTS A total of 3018 patients with GNs and 3905 healthy controls(age and sex matched)were enrolled for analysis.After comparing the prevalence of CRNs between the two groups,CRNs were detected significantly more frequently in GN patients than in controls(OR=1.69,95%CI=1.28 to 2.23,I^(2)=85.12%,P=0.00),especially in patients with GC(OR=1.80,95%CI=1.49 to 2.18,I^(2)=25.55%,P<0.1).Moreover,other risk factors including age(OR=1.08,95%CI=1.00 to 1.17,I^(2)=90.13%,P=0.00)and male sex(OR=2.31,95%CI=1.26 to 4.22,I^(2)=87.35%,P=0.00),were related to the prevalence of CRNs.For patients in the GN group,body mass index(BMI,OR=0.88,95%CI=0.80 to 0.98,I^(2)=0.00%,P=0.92)and smoking(OR=1.03,95%CI=1.01 to 1.05,I^(2)=0.00%,P=0.57)were protective and risk factors for CRNs,respectively.CONCLUSION Patients are recommended to undergo colonoscopy when diagnosed with GNs,especially GC patients with a low BMI and a history of smoking.

Management of obstructed colorectal carcinoma in an emergency setting:An update

Colorectal carcinoma is common,particularly on the left side.In 20%of patients,obstruction and ileus may be the first clinical manifestations of a carcinoma that has advanced(stage II,III or even IV).Diagnosis is based on clinical presentation,plain abdominal radiogram,computed tomography(CT),CT colonography and positron emission tomography/CT.The best management strategy in terms of short-term operative or interventional and long-term oncological outcomes re-mains unknown.For the most common left-sided obstruction,the first choice should be either emergency surgery or endoscopic decompression by self-expen-dable metal stents or tubes.The operative plan should be either one-stage or two-stage resection.One-stage resection with on-table bowel decompression and irrigation can be accompanied or not accompanied by proximal defunctioning stoma(colostomy or ileostomy).Primary anastomosis is more convenient but has increased risks of anastomotic leakage and morbidity.Two-stage resection(Hart-mann’s procedure)is safer and the most widely used despite temporally affecting quality of life.Damage control surgery in high-risk frail patients is less frequently performed since it can be successfully substituted with endoscopic stenting or tubing.For the less common right-sided obstruction,one-stage surgical resection is more beneficial than endoscopic decompression.The role of minimally invasive surgery(laparoscopic or robotic)is a subject of debate.Emergency laparoscopic-assisted management is advantageous to some extent but requires much expertise due to inherent difficulties in dissecting the distended colon and the risk of rup-ture and subsequent septic complications.The decompressing stent as a bridge to elective surgery more substantially decreases the risks of morbidity and mortality than emergency surgery for decompression and has equivalent medium-term overall survival and disease-free survival rates.Its combination with neoadjuvant chemotherapy or radiation may have a positive effect on long-term oncological outcomes.Management plans are crucial and must be individualized to better fit each case.Core Tip:Acute obstruction is common in patients with more advanced colorectal carcinoma and may be the first manifestation mainly of left-sided obstruction and in elderly individuals.Emergency decompression is mandatory.Emergency surgical resection and primary anastomosis accompanied or not accompanied by proximal defunctioning stoma must be the first treatment choice for fit patients under 70 years.Hartmann’s two-stage procedure,although more preferable,must be the second alternative choice.Emergency endoscopic self-expendable metal stents must be preferred in unfit patients as a bridge to surgery and for palliative treatment in all inoperable cases.However,these basic management principles constitute a general direction.Decision-making is important and should be individualized.

Different lymph node staging systems for predicting the prognosis of colorectal neuroendocrine neoplasms

BACKGROUND Colorectal neuroendocrine neoplasms(NENs)are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum.Previous studies have pointed out that the status of lymph node may be used to predict the prognosis.AIM To investigate the predictive values of lymph node ratio(LNR),positive lymph node(PLN),and log odds of PLNs(LODDS)staging systems on the prognosis of colorectal NENs treated surgically,and compare their predictive values.METHODS This cohort study included 895 patients with colorectal NENs treated surgically from the Surveillance,Epidemiology,and End Results database.The endpoint was mortality of patients with colorectal NENs treated surgically.X-tile software was utilized to identify most suitable thresholds for categorizing the LNR,PLN,and LODDS.Participants were selected in a random manner to form training and testing sets.The prognosis of surgically treating colorectal NENs was examined using multivariate cox analysis to assess the associations of LNR,PLN,and LODDS with the prognosis of colorectal NENs.C-index was used for assessing the predictive effectiveness.We conducted a subgroup analysis to explore the different lymph node staging systems’predictive values.RESULTS After adjusting all confounding factors,PLN,LNR and LODDS staging systems were linked with mortality in patients with colorectal NENs treated surgically(P<0.05).We found that LODDS staging had a higher prognostic value for patients with colorectal NENs treated surgically than PLN and LNR staging systems.Similar results were obtained in the different G staging subgroup analyses.Furthermore,the area under the receiver operating characteristic curve values for LODDS staging system remained consistently higher than those of PLN or LNR,even at the 1-,2-,3-,4-,5-and 6-year follow-up periods.CONCLUSION LNR,PLN,and LODDS were found to significantly predict the prognosis of patients with colorectal NENs treated surgically.

GLI1 and PTTG1 expression in colorectal carcinoma patients undergoing radical surgery and their correlation with lymph node metastasis

BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more relevant studies and analyses need to be conducted.AIM To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.METHODS This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023.Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1.The correlation of the two genes with patients’clinicopathological data(e.g.,LNM)was explored,and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC.RESULTS Significantly higher positive rates and expression levels of GLI1 and PTTG1 wereobserved in CRC tissue samples compared with adjacent tissues.GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC,with higher GLI1 and PTTG1 levels found in patients with LNM than in those without.The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811,respectively.CONCLUSION GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients.Moreover,high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery.The expression of both genes has certain diagnostic and therapeutic significance.

Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma

BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perioperative indicators,postoperative recovery,and serum inflammation indexes in patients with CRC.METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023,52 of whom underwent conventional five-port laparoscopic surgery(control group)and 63 of whom underwent RPLS(research group).Comparative analyses were performed on the following dimensions:Perioperative indicators[operation time(OT),incision length,intraoperative blood loss(IBL),and rate of conversion to laparotomy],postoperative recovery(first postoperative exhaust,bowel movement and oral food intake,and bowel sound recovery time),serum inflammation indexes[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)],postoperative complications(anastomotic leakage,incisional infection,bleeding,ileus),and therapeutic efficacy.RESULTS The two groups had comparable OTs and IBL volumes.However,the research group had a smaller incision length;lower rates of conversion to laparotomy and postoperative total complication;and shorter time of first postoperative exhaust,bowel movement,oral food intake,and bowel sound recovery;all of which were significant.Furthermore,hs-CRP,IL-6,and TNF-αlevels in the research group were significantly lower than the baseline and those of the control group,and the total effective rate was higher.CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC,resulting in a shorter incision length and a lower conversion rate to laparotomy,while also promoting postoperative recovery,effectively inhibiting the inflammatory response,and reducing the risk of postoperative complications.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Non-participation of asymptomatic candidates in screening protocols reduces early diagnosis and worsens prognosis of colorectal cancer

The Agatsuma et al’s study shows that despite the evidence of the benefits of an early colorectal cancer(CRC)diagnosis,through screening in asymptomatic subjects,up to 50%of candidates reject this option and many of those affected are diagnosed later,in advanced stages.The efficacy of screening programs has been well-established for several years,which reduces the risk of CRC morbidity and mortality,without taking into account the test used for screening,or other tools.Nevertheless,a significant proportion of patients remain unscreened,so understanding the factors involved,as well as the barriers of the population to adherence is the first step to possibly modify the participation rate.These barriers could include a full range of social and political aspects,especially the type of financial provision of each health service.In Japan,health services are universal,and this advantageous situation makes it easier for citizens to access to these services,contributing to the detection of various diseases,including CRC.Interestingly,the symptomatic CRC group had a lower early-stage diagnosis rate than the patients detected during follow-up for other comorbidities,and symptomatic and cancer screening groups showed similar early-stage diagnosis.

KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients

AIM:To investigate gene mutations and DNA mismatch repair(MMR) protein abnormality in Chinese colorectalcarcinoma(CRC) patients and their correlations with clinicopathologic features.METHODS:Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded.Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used.Expression of MMR proteins including MHL1,MSH2,MSH6 and PMS2 was evaluated by immunohistochemistry.Correlations of KRAS and BRAF mutation status and the expression status of MMR proteins with age,gender,cancer stage,location,and histology were analyzed.Correlations between KRAS or BRAF mutations and MMR protein expression were also explored.RESULTS:The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%,respectively.KRAS mutations were more common in patients ≥ 50 years old(39.8% vs 22% in patients < 50 years old,P < 0.05).The frequencies of BRAF mutants were higher in tumors from females(6.6% vs males 2.8%,P < 0.05),located in the right colon(9.6% vs 2.1% in the left colon,1.8% in the rectum,P < 0.01),with mucinous differentiation(9.8% vs 2.8% without mucinous differentiation,P < 0.01),or being poorly differentiated(9.5% vs 3.4% well/moderately differentiated,P < 0.05).MMR deficiency was strongly associated with proximal location(20.5% in the right colon vs 9.2% in the left colon and 5.1% in the rectum,P < 0.001),early cancer stage(15.0% in stages Ⅰ-Ⅱ vs 7.7% in stages Ⅲ-Ⅳ,P < 0.05),and mucinous differentiation(20.2% vs 9.2% without mucin,P < 0.01).A higher frequency of MLH1/PMS2 loss was found in females(9.2% vs 4.4% in males,P < 0.05),and MSH2/MSH6 loss tended to be seen in younger(<50 years old) patients(12.0% vs 4.0% ≥ 50 years old,P < 0.05).MMR deficient tumors were less likely to have KRAS mutations(18.8% vs 41.7% in MMR proficient tumors,P < 0.05) and tumorswith abnormal MLH1/PMS2 tended to harbor BRAF mutations(15.4% vs 4.2% in MMR proficient tumors,P < 0.05).CONCLUSION:The frequency of sporadic CRCs having BRAF mutation,MLH1 deficiency and MSI in Chinese population may be lower than that in the Western population.

Risk factors for bleeding after endoscopic submucosal dissection of colorectal neoplasms

AIM: To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) treatment for colorectal neoplasms.

Gene therapy for human colorectal carcinoma using human CEA promoter controlled bacterial ADP-ribosylating toxin genes:PEA and DTA gene transfer

AIM To establish a tissue-specific gene therapy for colorectal carcinoma using bacterial ADP-ribosylating toxin genes.METHODS Pseudomonas exotoxin A domain Ⅱ+Ⅲ (PEA) was cloned from genomic DNA of Pseudomonas aeruginosa. PEA and diphtheria toxin A chain gene (DTA) were modified to express eukaryotically. After sequencing, the toxin genes under the control of human carcinoembryonic antigen (CEA) promoter were cloned into retroviral vectors to construct CEAPEA and CEADTA respectively. In vitro cotransfection of the constructs with luciferase vectors and in vivo gene transfer in nude mice were subsequently carried out.RESULTS Both CEAPEA and CEADTA specifically inhibited the reporter gene expression in the CEA positive human colorectal carcinoma (CRC) cells in vitro. Direct injection of CEAPEA and CEADTA constructs into the established human tumors in BALB/c nude mice led to significant and selective reductions in CRC tumor size as compared with that in control groups.CONCLUSION The toxin genes, working as therapeutic genes, are suitable for the tissue-specific gene therapy for colorectal carcinoma.

Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma

Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma.The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm.Immunohistochemical stains that may be useful in the differential diagnosis of metastatic colorectal tumors to the ovary and primary ovarian tumors are detailed.

Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma

AIM:To investigate semaphorin 4D(Sema4D)and hypoxia-inducible factor-1α(HIF-1α)expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance.METHODS:Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery,and none of them received preoperative radiochemotherapy.Normal proximal adjacent bowel tissue,which served as an internal control,was obtained from 52 randomly selected patients.Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesisrelated protein HIF-1αin normal colorectal tissues and colorectal carcinoma tissues.The relationships between the expression and clinical characters and prognosis were analyzed.RESULTS:HIF-1αand Sema4D were positively expressed in 58%and 60%of colorectal carcinoma tissues,respectively.Significantly lower expression levels were observed in normal mucosa(8%and 12%,respectively).HIF-1αand Sema4D expression was closely correlated with histological tumor type,tumornode-metastasis(TNM)stage,and lymphatic metastasis(P<0.05),but not with age or tumor size(P>0.05).HIF-1αand Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma,as determined by Spearman rank correlation analysis(r=0.567;P<0.01).Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis(P<0.05).CONCLUSION:These findings suggest that HIF-1αand Sema4D expression correlates with histological tumor type,TNM stage,and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.

Differential mucin phenotypes and their significance in a variation of colorectal carcinoma

AIM: To investigate mucin expression profiles in colorectal carcinoma (CRC) histological subtypes with regard to clinicopathologic variables and prognosis. METHODS: Mucin (MUC)2 and MUC5AC expressions were assessed by immunohistochemistry for a total of 250 CRC cases that underwent surgical resection. CRCs included 63 well-to-moderately differentiated adenocar-cinomas (WMDAs), 91 poorly differentiated adenocarcinomas (PDAs), 81 mucinous adenocarcinoma (MUAs), and 15 signet-ring cell carcinomas (SRCCs). MUC2 and MUC5AC were scored as positive when ≥ 25% and ≥ 1% of cancer cells were stained positive, respectively. The human mutL homolog 1 and human mutS homolog 2 expressions were assessed by immunohistochemistry in PDAs to investigate mismatch-repair (MMR) status.Tumors that did not express either of these two were considered MMR-deficient. Results were analyzed for associations with clinicopathologic variables and the prognosis in individual histological CRC subtypes. RESULTS: MUC2-positive and MUC5AC-positive WMDA percentages were 49.2% and 30.2%, respectively. In contrast, MUC2-positive and MUC5AC-positive PDA percentages were 9.5% and 51.6%, respectively. MUC2 levels tended to decrease and MUC5AC levels tended to increase from WMDA to PDA. In 21 tumors comprising both adenoma and adenocarcinoma components in a single tumor (4 WMDAs, 7 PDAs, and 10 MUAs), MUC2 was significantly downregulated in PDA and MUC5AC was downregulated in PDA and MUA in the adenoma-carcinoma sequence. These results suggested that MUC2 levels might be associated with malignant potential and that MUC5AC expression was an early event in tumorigenesis. Despite worse prognoses than WMDA, high MUC2 expression levels were maintained in MUA (95.1%) and SRCC (71.5%), which suggested a pathogenesis for these subtypes distinct from that of WMDA. No significant associations were found between MUC2 expression and any clinicopathologic variables in any histological subtype. MUC5AC expression in PDA was closely associated with right-sided location (P = 0.017), absence of nodal metastasis (P = 0.010), low tumor node metastasis stage (P = 0.010), and MMR deficiency (P = 0.003). MUC2 expression in WMDA was a marginal prognostic factor for recurrence/metastasis-free survival (RFS) by univariate Cox analysis (P = 0.077) but not by multivariate Cox analysis (P = 0.161). MUC5AC expression in PDA was a significant prognostic factor for RFS by univariate Cox analysis (P = 0.007) but not by multivariate Cox analysis (P = 0.104). Kaplan-Meier curves and log-rank tests revealed that MUC2 expression was marginally associated with a better WMDA prognosis [P = 0.064 for RFS and P = 0.172 for overall survival (OS)] but not for PDA. In contrast, MUC5AC expression was significantly and marginally associated with a better PDA prognosis in terms of RFS and OS, respectively(P = 0.004 for RFS and P = 0.100 for OS), but not for WMDA and MUA. CONCLUSION: Mucin core protein expression profiles and clinical significance differ according to histological CRC subtypes. This may reflect different pathogeneses for these tumors.

Regulatory effect and mechanism of gastrin and its antagonists on colorectal carcinoma

AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body.The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis,IP(3) content was determined by radioimmunoassay, Ca(2+) concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain.RESULTS:The volume,weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G(2)M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25mg/L, the amount of viable cells, IP(3) content and Ca(2+) concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32mg/L, they dropped to the lowest level in PG (25mg/L)+PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly differentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocar-cinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin negative group.CONCLUSION:Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly differentiated adenocarcinoma express the highest level gastrin.Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, somatostatin of patients with colorectal carcinoma.

miRNA-338-3p suppresses cell growth of human colorectal carcinoma by targeting smoothened

AIM:To investigate the regulative effect of miRNA-3383p(miR-338-3p) on cell growth in colorectal carcinoma(CRC).METHODS:The lentiviral vector pLV-THM-miR-338-3p and pLV-THM-miR-338-3p-inhibitor were constructed.The recombinant viral vector encoding the pre-miR338-3p or miR-338-3p-inhibitor and the two packaging plasmids psPAX2 and pMD2.G were cotransfected into human embryonic kidney 293T cells to package lentivirus.The supernatant containing the lentivirus particles was harvested to determine the viral titer,and this supernatant was then used to transduce CRCderived cell line,SW-620.Flow cytometry was utilized for sorting the green fluorescent protein(GFP) + cells to establish the SW-620 cell line stably expressing premiR-338-3p or miR-338-3p-inhibitor.Moreover,the expression of miR-338-3p was determined by real-time reverse transcriptase polymerase chain reaction,andWestern blotting was used to detect the expression of the smoothened(SMO,the possible target of miR-3383p) protein in SW-620 cells.Furthermore,the status of CRC cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry,respectively.RESULTS:Restriction enzyme digestion and DNA sequencing demonstrated that the lentiviral vector pLVTHM-miR-338-3p and pLV-THM-miR-338-3p-inhibitor were constructed successfully.GFP was expressed after the SW-620 cells were transduced by the lentivirus.Expression of miR-338-3p in SW-620 cells transduced with the lentivirus pLV-THM-miR-338-3p was significantly increased(relative expression 3.91 ± 0.51 vs 2.36 ± 0.44,P < 0.01).Furthermore,overexpression of miR-338-3p inhibited the expression of SMO protein in SW-620 cells,which showed obviously suppressed proliferation ability [cellular proliferation inhibition rate(CPIR) 61.9% ± 5.2% vs 41.6% ± 4.8%,P < 0.01].Expression of miR-338-3p in SW-620 cells transduced with the lentivirus pLV-THM-miR-338-3p-inhibitor was significantly decreased(relative expression 0.92 ± 0.29 vs 2.36 ± 0.44,P < 0.01).Moreover,the downregulated expression of miR-338-3p caused upregulated expression of the SMO protein in SW-620 cells,which showed significantly enhanced proliferation ability(CPIR 19.2% ± 3.8% vs 41.6% ± 4.8%,P < 0.01).However,anti-SMO-siRNA largely,but not completely,reversed the effects induced by blockage of miR-338-3p,suggesting that the regulative effect of miR-338-3p on CRC cell growth was indeed mediated by SMO.CONCLUSION:miR-338-3p could suppress CRC growth by inhibiting SMO protein expression.

Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma

AIM: To explore the expression of leukemia related protein 16 (LRP16) in colorectal carcinoma, and analyze its correlation with clinicopathologic features and prognosis. METHODS: Immunohistochemistry for LRP16 was performed in 201 cases of colorectal carcinoma and 60 cases of distal normal mucosa. Medical records were reviewed and clinicopathological analysis was performed. RESULTS: LRP16 expression was detected in 117 of 201 cases of the colorectal carcinoma and in 21 cases of 60 distal normal mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa (χ 2 = 9.999, P = 0.002). LRP16 protein expression was found in 43.3% (52/120) of carcinoma at stage Ⅰ and Ⅱ , and 80.2% (65/81) of carcinoma at stage Ⅲ and Ⅳ (χ 2 =27.088, P = 0.001). Correlation between LRP16 expression and clinicopathological factors was significant in differentiation (P = 0.010), tumor size (P = 0.001), infiltrative depth (P = 0.000) and distant metastasis (P = 0.027). The difference of median survival time between cancer patients with LRP16 expression (38.0 mo) and those without was statistically significant (105.0 mo, Log rank = 41.455, P = 0.001). The multivariate survival analysis revealed that LRP16 expression was correlated significantly (Cox’s regression: P = 0.001, relative risk = 2.082) with shortened survival in the patients with colorectal cancer. CONCLUSION: The expression of LRP16 is related to the degree of differentiation, invasiveness, metastasis and prognosis of colorectal carcinoma.

Liver metastasis models of human colorectal carcinoma established in nude mice by orthotopic transplantation and their biologic characteristics

AIM To establish a liver metastasis model of human colorectal carcinoma in nude mice.METHODS Orthotopic transplantation of histologically intact colorectal tissues from patients into colorectal mucosa of nude mice. Tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, electron microscopy and immunohistochemistry.RESULTS Liver metastasis models of human colon carcinoma (HCA-HMN-1) and human rectal carcinoma (HRA-HMN-2) were established after screening from 34 colorectal carcinomas. They had been passaged in vivo for 18 and 21 generations respectively. There were lymphatic, hemotogenous and implanting metastasesis. CEA secretion was maintained after transplantation. The primary and liver metastatic tumors were similar to the original human carcinoma in histopathological and ultrastructural features, DNA content and chromosomal karyotype.CONCLUSION The liver metastasis models provide useful tools for the study of mechanism of metastasis and its treatment of human colorectal cancer.INTRUDUCTIONSome models of nude mice that fresh human colorectal carcinoma tissue or cells were successfully transplanted subcuteneously have been reported at home and abroad[1,2]. But until now there has been no report on a liver metastasis model of human colorectal carcinoma established by orthotopic transplantation in nude mice in China. Based on our previous models of human liver and pancreas carcinoma by orthotopic transplantation[3,4], we established liver metastasis models of colon and rectum carcinoma with a spontaneous metastasis rate of 100%.

Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .