Sigmoid colonic carcinoma associated with deposited ova of Schistosoma japonicum:A case report

We report a case of sigmoid colonic carcinoma associated with deposited ova of Schistosoma japonicum. A 57-year old woman presented with a 10-mo history of left lower quadrant abdominal pain and a 2-mo history of bloody stools. She had a significant past medical history of asymptomatic schistosomiasis japonica and constipation. A colonoscopy showed an exophytic fragile neoplasm with an ulcerating surface in the sigmoid colon. During the radical operative procedure, we noted the partially encircling tumor was located in the distal sigmoid colon, and extended into the serosa. Succedent pathological analysis demonstrated the diagnosis of sigmoid colonic ulcerative tubular adenocarcinoma, and showed deposited ova of Schistosoma japonicum in both tumor lesions and mesenteric lymph nodes. Three days after surgery the patient returned to the normal bowel function with one defecation per day. These findings reveal that deposited schistosome ova play a possible role in the carcinogenesis of colorectal cancer.

COX MULTIVARIATE REGRESSION ANALYSIS OF RECURRENCE FACTORS FOR COLONIC CARCINOMA

Objective: To determine the independent prognostic factors in the recurrence of colonic carcinoma after curative resection. Methods: Two hundred and one patients undergoing curative resections for colonic carcinoma were investigated by univariate and Cox multivariate regression analyses. Ten factors contributed to the rate were analyzed. Results: Dukes stages, obstruction, postoperative chemotherapy as well as the growth manner of the tumor were significantly associated with the recurrence rate of colonic carcinoma (P<0.05) by univariate analysis, while Dukes stages, obstruction, and postoperative chemotherapy were significant factors by the multivariate analysis. Conclusion: Dukes stages, obstruction, and postoperative chemotherapy are independent prognostic factors in the recurrence of colonic carcinoma.

Colon signet-ring cell carcinoma with chylous ascites caused by immunosuppressants following liver transplantation:A case report

BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.

Laparoscopic radical resection for situs inversus totalis with colonic splenic flexure carcinoma:A case report

BACKGROUND Situs inversus totalis(SIT)is a rare group of congenital developmental malformations in the clinical setting,with all organs in the chest and abdomen existing in a mirror image reversal of their normal positions.Few reports have described laparoscopic surgery for colorectal cancer in patients with SIT,and it is considered difficult even for an experienced surgeon because of the mirror positioning.We present a case report of laparoscopic radical resection of a colonic splenic flexure carcinoma in a patient with SIT.CASE SUMMARY A 72-year-old male was referred to our hospital with colonic splenic flexure carcinoma,and computed tomography showed that all the organs in the chest and abdomen were inverted.Laparoscopic hemicolectomy with complete mesocolic excision was safely performed.The operating surgeon stood on the patient’s left side,which is opposite of the normal location.CONCLUSION Abdominal computed tomography is an effective method for diagnosing SIT preoperatively in patients with colonic splenic flexure carcinomas.Laparoscopic radical resection is difficult,but it is well established and safe.The surgeon should stand in the opposite position and perform backhand operations.

Three cancers in the renal pelvis,bladder,and colon:A case report

BACKGROUND Multiple primary cancers are rare occurrences that can involve either metachronous or synchronous development.It is particularly rare for an individual to have more than two primary cancers.In this report,we present a case study of an elderly man who was diagnosed with three heterochronous cancers in the renal pelvis,bladder,and colon.CASE SUMMARY On December 30,2014,a 51-year-old Chinese man was admitted to our hospital with complaints of intermittent painless gross hematuria for the preceding week.A computed tomography(CT)scan revealed wall thickening in the left ureter’s upper segment,while a CT urography revealed a left renal pelvis tumor.A successful laparoscopic radical resection of the left renal pelvis tumor was subsequently performed at Shanghai Zhongshan Hospital in January 2015.The pathological findings after the surgery revealed a low-grade papillary urothelial carcinoma of the renal pelvis.The final pathological tumor stage was pT1N0M0.After surgery,this patient received 6 cycles of intravenous chemotherapy with gemcitabine and carboplatin,as well as bladder infusion therapy with gemcitabine.On December 18,2017,the patient was admitted once again to our hospital with a one-day history of painless gross hematuria.A CT scan showed the presence of a space-occupying lesion on the posterior wall of bladder.Cystoscopic examination revealed multiple tumors in the bladder and right cutaneous ureterostomy was performed under general anesthesia on December 29,2017.The postoperative pathological findings disclosed multifocal papillary urothelial carcinoma of the bladder(maximum size 3.7 cm×2.6 cm).The bladder cancer was considered a metastasis of the renal pelvis cancer after surgery.The pathological tumor stage was pT1N0M1.The patient refused chemotherapy after surgery.After another six years,the patient returned on February 28,2023,complaining of periumbilical pain that had lasted six days.This time,a CT scan of the abdomen showed a tumor in the ascending colon,but a subsequent colonoscopy examination indicated a tumor in the descending colon.On March 12,2023,a subtotal colectomy and an ileosigmoidal anastomosis were carried out under general anesthesia.Postoperative pathological findings revealed that all three tumors were adenocarcinomas.The final pathological tumor stage was pT3N0M0.The patient had an uneventful postoperative recovery and was discharged without complications.CONCLUSION The case of this elderly man presents a rare occurrence of metachronous primary cancers in the renal pelvis and colon.Bladder cancer is considered a metastasis of renal pelvis cancer after surgery.Optimal treatment can be implemented by evaluating the patient’s histological features,clinical history,and tumor distribution correctly.

Laparoscopic right radical hemicolectomy: Central vascular ligation and complete mesocolon excision vs D3 lymphadenectomy - How I do it?

In colon cancer surgery,ensuring the complete removal of the primary tumor and draining lymph nodes is crucial.Lymphatic drainage in the colon follows the vascular supply,typically progressing from pericolic to paraaortic lymph nodes.While NCCN guidelines recommend the removal of 10-12 lymph nodes for ade-quate oncological resection,achieving complete oncological resection involves more than just meeting these numerical targets.Various techniques have been developed and studied over time to attain optimal oncological outcomes.A key technique central to this goal is identifying the ileocolic vessels at their origin from the superior mesenteric vessels.Complete excision of the visceral and parietal mesocolon ensures the intact removal of the specimen,while D3 lymphade-nectomy targets all draining regional lymph nodes.Although these principles emphasize different aspects,they ultimately converge to achieve the same goal of complete oncological resection.This article aims to simplify the surgical steps that align with the principle of central vascular ligation and mesocolon mobilization while ensuring adequate D3 dissection.

Mucinous cystadenoma of the appendix associated with adenocarcinoma of the sigmoid colon and hepatocellular carcinoma of the liver:Report of a case

Mucinous cystadenoma of the appendix is a rare condition and represents one of the three entities with the common name mucocele of the appendix. It is characterized by a cystic dilatation of the lumen with stasis of mucus inside it. Histopathologically mucocele is divided into three groups： focal or diffuse mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma. This condition is often associated with other neoplasia, especially adenocarcinoma of the colon and ovaries. We here describe a 57 year old male patient who presented with abdominal discomfort, constipation, fresh blood in stool and frequent urination. He had a big cystadenoma of the appendix associated with adenocarcinoma of the colon and hepatocellular carcinoma of the liver. The patient underwent right haemicolectomy, sigmoid colon resection and segmental resection of the liven Now 3 years later he has no evidence of disease relapse. According to this, we stress the need of accurate preoperative diagnosis and intraoperative exploration of the whole abdomen in these patients.

Laparoscopic versus open right hemicolectomy with curative intent for colon carcinoma

AIM: Laparoscopic surgery, especially laparoscopic rectal surgery, for colorectal cancer has been developed considerably. However, due to relatively complicated anatomy and high requirements for surgery techniques, laparoscopic right colectomy develops relatively slowly. This study was designed to compare the outcomes of laparoscopic right hemicolectomy (LRH) with open right hemicolectomy (ORH) in the treatment of colon carcinoma. METHODS: Between September 2000 and February 2003, 30 patients with colon cancer who underwent LRH were compared with 34 controls treated by ORH in the same period. All patients were evaluated with respect to surgery related complications, postoperative recovery, recurrence and metastasis rate, cost-effectiveness and survival. RESULTS: Among 30 LRH, 2 (6.7%) were converted to open procedure. No significant differences were observed in terms of mean operation time, blood loss, post-operative complications, and hospital cost between LRH and ORH groups. Mean time for bowel movement, hospital stay, and time to resum?early activity in the LRH group were significantly shorter than those in the ORH group (2.24±0.56 vs 3.25±1.29 d, 13.94?.5 vs 18.25±5.96 d, 3.94±1.64 vs 5.45±1.82 d respectively, P<0.05). As to the lymph node yield, the specimen length and total cost for operation and drugs, there was no significant difference between the two groups. Local recurrence rate and metachronous metastasis rate had no marked difference between the two groups. Cumulative survival probability at 40 mo in LRH group (76.50%) was not obviously different compared to the ORH group (74.04%). CONCLUSION: LRH in patients with colon cancer has statistically and clinically significant advantages over ORH. Thus, LRH can be regarded as a safe and effective procedure.

Clinicopathologic significance of BAG1 and TIMP3 expression in colon carcinoma

AIM: To explore the expression of BAG1 and tissue inhibitor of metalloproteinase 3 (TIMP3) in colon carcinoma and their correlation and clinicopathologic significance. METHODS: SABC immunohistochemistry was used to detect the expression of BAG1 and TIMP3 in 80 colon carcinoma tissues and 20 normal colonic mucosa. RESULTS: Positive rate of BAG1 in colon carcinoma tissue (80%) was notably higher compared to normal colonic mucosa (10%) (P < 0.05). However, no significant difference was observed in positive rate of TIMP3 in colon carcinoma tissue (43.75%) as compared with normal colonic mucosa (60%) (P > 0.05). Expression of BAG1 and TIMP3 was strongly associated with colon carcinoma differentiation, Duke's staging, lymph node metastasis and survival rate (P < 0.05), but not associated with gender and age. Moreover, BAG1 expression was not correlated with TIMP3. CONCLUSION: Our results suggest that over-expression of BAG1 or attenuated expression of TIMP3 may play an important role in genesis and development of colon carcinoma. The protein expression levels of BAG1 and TIMP3 are related to the malignant degree, infiltration and metastasis of colon carcinoma. BAG1 and TIMP3 might be new biological parameters in predicting invasion and metastasis of colon carcinoma.

Antitumor activity of anti-type IV collagenase monoclonal antibody and its lidamycin conjugate against colon carcinoma

AIM： Type IV collagenase including MMP-2 and -9 plays an important role in cancer cell invasion and metastasis and is an attractive target for rnAb-directed therapy. The irnrnunoreactivity of rnAb 3G11, a rnAb directed against type Ⅳ collagenase in human colorectal carcinomas, was studied by irnrnuno-histochernical （IHC） staining, rnAb 3G11 was conjugated to an antiturnor antibiotic lidarnycin （LDM）. The antiturnor activity of 3G11-LDM conjugate against colon carcinoma was investigated in mice. METHODS： ELISA, gelatin zyrnography, and Western blot assay were used for the biological characterization of rnAb 3G11. The irnrnunoreactivity of rnAb 3G11 with human colorectal carcinomas was detected by IHC staining. The cytotoxicity of LDM and 3G11-LDM conjugate to human colon carcinoma HT-29 cells was examined by clonogenic assay and MTT assay. The therapeutic effect of conjugate 3G11-LDM was evaluated with colon carcinoma 26 in mice. RESULTS： As shown in ELISA, mAb 3Gll reacted specifically with type IV collagenase, while 3G11-LDM conjugate also recognized specifically its respective antigen. In IHC assay, mAb 3G11 showed positive irnrnunoreactivity in most cases of colorectal carcinoma, and negative irnrnunoreactivity in the adjacent non-malignant tissues. By gelatin zyrnography, the inhibition effect of rnAb 3G11 on the secretion activity of type IV collagenase was proved. In terms of IC50 values in MTT assay, the cytotoxicity of LDM to human colon carcinoma HT-29 cells was 10 000-fold more potent than that of rnitornycin C （MMC） and adriarnycin （ADM）. 3G11- LDM conjugate also displayed extremely potent cytotoxicity to human colon carcinoma HT-29 cells with an IC50 value of 5.6× 10^-19 mol/L. 3G11-LDM conjugate at the doses of 0.05 and 0.1 mg/kg inhibited the growth of colon carcinoma 26 in mice by 70.3 and 81.2%, respectively. CONCLUSION： mAb 3G11 is immunoreactive with human colorectal carcinoma and its conjugate with LDM is highly effective against colon carcinoma in mice.

Synchronous isolated splenic metastasis from colon carcinoma and concomitant splenic abscess:A case report and review of the literature

This study aimed to describe a case in which an isolated splenic metastasis was synchronous with the colonic primary and a concomitant splenic abscess was associated. A wide review of the literature was also performed. A 54-year-old woman with abdominal pain and fever was admitted to our department. Abdominal CT revealed two low-density areas in the spleen and wall-thickening of the left colonic flexure,which was indistinguishable from the spleen parenchyma. The patient underwent emergency celiotomy,with the presumptive diagnosis of obstructing colon carcinoma of the splenic flexure,and concomitant splenic abscess. Subtotal colectomy and splenectomy were performed. Pathological findings were consistent with mucinous colonic carcinoma,synchronous isolated splenic metastasis and concomitant splenic abscess. This paper is also a review of the existing literature on the association between colorectal cancer and splenic metastasis. Only 41 cases of isolated splenic metastasis from colon carcinoma have been reported in the literature. This report is the third described case of synchronous isolated splenic metastasis from colon carcinoma. Only one case with concomitant splenic abscess has been previously reported. When obstructing left-sided colorectal cancer is suspected,careful CT examination can allow early diagnosis of splenic involvement by the tumor. The literature review suggests that there might be a significant improvement in survival following splenectomy for a metachronous isolated splenic metastasis from colon carcinoma. Prognosis for synchronous splenic metastasis seems to be related to the advanced stage of the disease. Nevertheless,no definitive conclusions can be drawn because of the small number of cases.

Silencing Fas-associated phosphatase 1 expression enhances efficiency of chemotherapy for colon carcinoma with oxaliplatin

AIM:To investigate whether silencing Fas-associated phosphatase 1(FAP-1)expression enhances the efficiency of chemotherapy for colon carcinoma with oxaliplatin.METHODS:Expression of FAP-1 in mRNA and protein was detected by reverse transcription polymerase chain reaction(RT-PCR)and flow cytometry.Small interfering RNA(siRNA)was designed according to the FAP-1 mRNA sequence.Cell proliferation was evaluated by methyl thiazolyl tetrazolium(MTT)assay.Anenxin V-and propidine iodine(PI)were assayed by flow cytometry for the detection of apoptosis. RESULTS:The expression of FAP-1 was increased in SW480 cells after chemotherapy with oxaliplatin. Transfection of FAP-1 siRNA into SW480 cells silenced the expression of FAP-1 and consequently abolished the inhibitory function of Fas/FasL-mediated apoptosis pathway,thus increasing the efficacy of chemotherapy for colon carcinoma with oxaliplatin. CONCLUSION:RNA interference combined with conventional chemotherapy is more effective against colon cancer.

Avidin-biotin system pretargeting radioimmunoimaging and radioimmunotherapy and its application in mouse model of human colon carcinoma

AIM： To evaluate the multi-step pretargeting radioimmunoimaging （RII） and radioimmunotherapy （RTT） in nude mice bearing human colon carcinoma with avidin-biotin system labeled with 153^Sm. METHODS： Two- and three-step strategies for avidinbiotin system pretargeting techniques were established. In a three-step procedure, human colon carcinoma bearing nude mice were first injected with biotinylated monoclonal antibody （McAb-Bt） followed by cold avidin （Av） 48 h later and then 153^Sm-DB2 24 h thereafter; whereas the twostep procedure consisted of injection of 153^Sm-SA 48 h after pretargeting with biotinylated anti-CEA monoclonal antibody （CEA McAb-Bt）. SPECT imaging and biodistribution were performed at 4, 24, 48, or 72 h after injection of 153^Sm-labeled compounds. Five groups of nude mice subcutaneously grafted with human colon carcinoma were treated 3 d after grafting. One group received the injection with 100 μg CEA McAb-Bt followed by cold avidin （80 μg） after 2 d and 11.1 MBCl I53Sm-DB2 after 1 d. Four control groups were treated respectively with 11.1 MBq 153^Sm- CEA McAb, ii.i MBq 153^Sm-nmIgG, ii.i MBq 153^Sm-DB2, 100 μL normal saline. Toxicity was evaluated by changes of leukocyte count, and the efficacy by variation in tumor volume. Histological analyses of tumors were performed. RESULTS： The three-step procedure allowed faster blood clearance and yielded higher tumor blood ratios （5.76 at 4 h and 12.94 at 24 h） of the 153^Sm-DB2. The tumor was clearly visualized at 4 h in y-imaging after the injection of 153^Sm-DB2, while a significant accumulation of 153^Sm-SA in the tumor was observed only 24 h after the injection and tumor blood ratios at 4 and 24 h were 1.00 and 2.03, respectively, in the two-step procedure. Pretargeting RIT and 153^Sm-CEA McAb had a strong tumor-inhibiting effect.The tumor inhibitory rate was 80.67% and 78.44%, respectively, five weeks after therapy. Histopathological evidence also indicated radioactive damage in tumor tissues as necrosis of tumor cells, while in the other organs such as liver and kidney no radioactive damage was observed. Leukocyte counts showed significant decrease after treatment in groups of 153^Sm-CEA McAb and 153^Sm- nmIgG. CONCLUSION： The two kinds of pretargeting strategies can elevate the target-to-nontarget ratio, decrease the blood background and shorten the imaging time compared to 153^Sm-CEA McAb. Three-step pretargeting RIT is as effident as 153^Sm-CEA McAb, but markedly less toxic. This study provides experimental evidence for the clinical application of pretargeting RII and RIT.

Reduced expression ofβ-catenin inhibitor Chibby in colon carcinoma cell lines

AIM： To analyse the Chibby expression and its function in colon carcinoma cell lines and colorectal carcinoma （CRC）. METHODS： Chibby expression levels were investigated by quantitative RT-PCR in a panel of seven different colon carcinoma cell lines. By sequencing, we analysed mutational status of Chibby. To test whether Chibby exhibited effects on β-catenin signalling in colon carcinoma cells, we transfected SW480 cells with Chibby expression plasmid and, subsequently, analysed activity of β-catenin and tested for alterations in cellular phenotype. In addition, we examined Chibby mRNA levels in samples of colorectal carcinomas and adjacent normal tissues by using quantitative RT-PCR and hybridised gene chips with samples from CRC and normal tissues. RESULTS： Chibby mRNA expression was strongly downregulated in colon carcinoma cell lines in comparison to normal colon epithelial cells and no mutation in any of the examined colon carcinoma cell lines was found. Further, we could show that Chibby inhibited β-catenin activity in TOPflash assays when over-expressed in SW480 cells. Proliferation and invasion assays with Chibby transfected SW480 cells did not reveal profound differences compared to control cells. In contrast to these in vitro data, quantitative RT-PCR analyses of Chibby mRNA levels in CRC tumor samples did not show significant differences to specimens in adjacent non-cancerous tissue. Consistent with these findings, gene chips analysing tissue samples of tumors and corresponding normal tissue did not show altered Chibby expressionCONCLUSION： Altered Chibby expression might be observed in vitro in different colon carcinoma cell lines. However, this finding could not be confirmed in vitro in CRC tumors, indicating that Chibby is not likely to promote CRC tumor development or progression. As Chibby is an important inhibitor of β-catenin signalling, our data implicate that the usability of colon carcinoma cell lines for in vitro studies analysing the Wnt/β-catenin pathway in colorectal carcinoma needs extensive verification.

Structural and functional aspects of the liver and liver sinusoidal cells in relation to colon carcinoma metastasis

Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an “overview” of how these cells function in health and in diseases such as

Clear cell adenocarcinoma of the colon is a unique morphological variant of intestinal carcinoma:Case report with molecular analysis

Here we report a new case of clear cell adenocarcinoma (CCA) of the colon in a 54-year-old Caucasian man. Despite of the previous reported cases, the lesion was located in the right colon and was not associated with the conventional adenoma. We performed immunohistochemical and molecular analyses in order to explore whether the CCA had the molecular features generally associated with conventional colorectal carcinoma. The immunohistochemical and molecular analyses showed that the different morphology of CCA does not reflect a distinct biological entity but only an unusual morphological variant of intestinal carcinoma.

Loss of heterozygosity of Kras2 gene on 12p12-13 in Chinese colon carcinoma patients

AIM： To study the loss of heterozygosity （LOH） on 12p12-13 in Chinese colon carcinoma patients.METHODS： DNA was extracted from 10 specimens of cancer tissue, 10 specimens of adjacent tissue and 10 specimens of normal tissue, respectively. LOH of Kras2 gene was analyzed by polymerase chain reaction （PCR） and denaturing polyacrylamide gel electrophoresis using 11 microsatellite markers on 12p-12-13.RESULTS： LOH of Kras gene was detected at least on one marker of 12p-12-13 in 30% （3/10） of adjacent tissue specimens. The highest frequency of LOH was identified on D12S1034 in 28.57% （2]7） of adjacent tissue specimens. LOH was detected at least on one marker of 12p12-13 in 60% （6/10） of carcinoma tissue specimens, the most frequent LOH was found on D12S1034 and D12S1591 in 42.86% （3/7） of carcinoma tissue specimens. LOH was detected in 30% （3/10） of carcinoma tissue specimens, 30% （3/10） of adjacent tissue specimens, and no signal in 1% （1/0） carcinoma tissue specimen. The occurrence of LOH did not correlate with sex, age, tumor size and lymph node metastasis.CONCLUSION： Genomic instability may occur on 12p-12-13 of Kras2 gene in the development and progression of colon carcinoma. The high LOH of Kras2 gene may directly influence the transcription and translation of wild type Kras2 gene.

Effect of bone marrow-derived monocytes transfected with RNA of mouse colon carcinoma on specific antitumor immunity

AIM: To investigate the effect of bone marrow-derived monocytes transfected with RNA of CT-26 (a cell line of mouse colon carcinoma) on antitumor immunity. METHODS: Mouse bone marrow-derived monocytes were incubated with mouse granulocyte macrophage colony stimulating factor (mGM-CSF) in vitro, and the purity of monocytes was detected by flow cytometry. Total RNA of CT-26 was obtained by TRIzol's process, and monocytes were transfected by TransMessenger in vitro. The activity of cytotoxic T lymphocytes (CTL) in vivo was estimated by the modified lactate dehydrogenase (LDH) release assay. Changes of tumor size in mice and animal's survival time were observed in different groups. RESULTS: Monocytes from mouse bone marrow were successfully incubated, and the positive rate of CDllb was over 95%. Vaccination of the monocytes transfected with total RNA induced a high level of specific CTL activity in vivo, and made mice resistant to the subsequent challenge of parental tumor cells. In vivo effects induced by monocytes transfected with total RNA were stronger than those induced by monocytes pulsed with tumor cell lysates. CONCLUSION: Antigen presenting cells transfected with total RNA of CT-26 can present endogenous? tumor antigens, activate CTL, and effectively induce specific antitumor immunity.

Complementary analysis of microsatellite tumor profile and mismatch repair defects in colorectal carcinomas

Microsatellite instability (MSI) is a prognostic factor and a marker of defi cient mismatch repair (MMR) in colorectal adenocarcinomas (CRC). However, a proper application of this marker requires understanding the following: (1) The MSI concept: The PCR approach must amplify the correct locus and accurately identify the microsatellite pattern in the patient’s normal tissue. MSI is demonstrat- ed when the length of DNA sequences in a tumor differs from that of nontumor tissue. Any anomalous expansion or reduction of tandem repeats results in extra-bands normally located in the expected size range (100 bp, above or below the expected product), differ from the germline pattern by some multiple of the repeating unit, and must show appropriate stutter. (2) MSI mechanisms: MMR gene inactivation (by either mutation or protein down-regulation as frequently present in deep CRC com- partments) leads to mutation accumulation in a cell with every cellular division, resulting in malignant transforma- tion. These mechanisms can express tumor progression and result in a decreased prevalence of aneuploid cells and loss of the physiologic cell kinetic correlations in the deep CRC compartments. MSI molecular mechanisms are not necessarily independent from chromosomal in- stability and may coexist in a given CRC. (3) Because of intratumoural heterogeneity, at least two samples from each CRC should be screened, preferably from the su- perfi cial (tumor cells above the muscularis propria) and deep (tumor cells infi ltrating the muscularis propria) CRC compartments to cover the topographic tumor hetero- geneity. (4) Pathologists play a critical role in identify- ing microsatellite-unstable CRC, such as occur in young patients with synchronous or metachronous tumors or with tumors showing classic histologic features. In these cases, MSI testing and/or MMR immunohistochemistry are advisable, along with gene sequencing and genetic counseling if appropriate. MSI is an excellent functional and prognostically useful marker, whereas MMR immuno- histochemistry can guide gene sequencing.

Effects of Meloxicam on Vascular Endothelial Growth Factor and Angiopoietin-2 Expression in Colon Carcinoma Cell Line HT-29

To investigate the effect of meloxicam, a selected NSAIDs, on cell growth, expression of VEGF and angiopointin-2 （Ang-2） protein in HT-29 cell line, cultured HT-29 cells were treated with meloxicam of various concentrations for various lengths of time. The proliferation of HT-29 was detected by cell counting kit-8 （CCK-8）, the cell cycle was determined by flow cytometer and the levels of VEGF and Ang-2 protein in supernatants were examined by enzyme linked immunosorbent assay （ELISA）. The mRNA expressions of VEGF and Ang-2 in cultured HT-29 were determined by real-time quantitative reverse-transcription polymerase chain reaction. Our results showed that treatment of meloxicam of different concentrations and for various lengths of time had a cytotoxicic effect on the cell proliferation of HT-29 cells in a concentration-dependant and time-dependant manner. Cell cycle analysis showed that the cells were mainly blocked in G0/G1 phase. The VEGF and Ang-2 protein levels in supernatants of the culture medium were decreased gradually in a concentration-dependent or time-dependent fashion. The mRNA expression of cox-2, VEGF and Ang-2 showed a gradual and concentration-dependent reduction. It is concluded that meloxicam can reduce the expression of VEGF and Ang-2 at the protein and mRNA level in colon carcinoma cell line.