Transanal decompression tube is superior to self-expandable metallic colonic stent for malignant colorectal obstruction: a retrospective study.

BACKGROUND: The surgical management of left-sided malignant large bowel obstruction (MLBO) is associated with high morbidity and mortality. Recently, self-expandable metallic colonic stent (SEMS) and transanal decompression tube (TDT) used as a 'bridge to surgery' (BTS) have been widely used. This study aims to compare the clinical outcomes and oncological safety of SEMS and TDT as BTS to transform MLBO into elective surgery. METHODS: Between February 2013 and March 2019, 62 patients with MLBO received SEMS (n = 32) or TDT (n = 30), and elective one-stage surgery later. We evaluated decompression efficiency and oncological safety in selective operation in TDT and SEMS groups, including preoperative preparation time, surgical approach, number of lymphatic dissection and vascular invasion, ulcer formation and histopathological findings of resected specimens. RESULTS: The preoperative preparation time in the SEMS group was shorter than that of the TDT group (P < 0.05). However, there was no significant difference between the groups in postoperative length of hospital stay (P > 0.05). The number of vascular invasions in the TDT group was less than that in the SEMS group (P < 0.05). Furthermore, the risk of wound abscess and ulcer formation in the TDT group was significantly lower than that in the SEMS group (P < 0.05). CONCLUSION: Our findings suggest that SEMS is associated with a relatively poor oncological outcome and the placement of TDT as BTS in MLBO patients may be a better alternation.

Clinical and pathological characteristics and prognosis of 132 cases of rectal neuroendocrine tumors.

BACKGROUND: Neuroendocrine tumors (NETs) frequently occur in the gastrointestinal tract, lung, and pancreas, and the rectum and appendix are the sites with the highest incidence. Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract, including the stomach, intestine, appendix, colon, and rectum. The pathological changes and clinical symptoms of NETs are not specific, and therefore they are frequently misdiagnosed. AIM: To investigate the clinical symptoms, pathological characteristics, treatment, and prognosis of rectal neuroendocrine tumors (RNETs) by analyzing the clinical and pathological data of 132 RNET cases at our hospital. METHODS: All RNETs were graded according to Ki-67 positivity and mitotic events. The tumors were staged as clinical stages I, II, III, and IV according to infiltrative depth and tumor size. COX proportional hazard model was used to assess the main risk factors for survival. RESULTS: These 132 RNETs included 83 cases of G1, 21 cases of G2, and 28 cases of G3 (neuroendocrine carcinoma) disease. Immunohistochemical staining showed that 89.4% of RNETs were positive for synaptophysin and 39.4% positive for chromogranin A. There were 19, 85, 23, and 5 cases of clinical stages I, II, III, and IV, respectively. The median patient age was 52.96 years. The diameter of tumor, depth of invasion, and pathological grade were the main reference factors for the treatment of RNETs. The survival rates at 6, 12, 36, and 60 mo after operation were 98.5%, 94.6%, 90.2%, and 85.6%, respectively. Gender, tumor size, tumor grade, lymph node or distant organ metastasis, and radical resection were the main factors associated with prognosis of RNETs. Multivariate analysis showed that tumor size and grade were independent prognostic factors. CONCLUSION: The clinical symptoms of RNETs are not specific, and they are easy to misdiagnose. Surgery is the main treatment method. The grade and stage of RNETs are the main indices to evaluate prognosis.

Solitary vertebral metastatic glioblastoma in the absence of primary brain tumor relapse: a case report and literature review.

BACKGROUND: Metastatic glioblastoma presenting as a solitary osteolytic cervical vertebral mass without primary brain tumor relapse is extremely rare with only 1 reported case in the literature. Because of its rarity, it can be easily overlooked and misdiagnosed, posing a diagnostic dilemma. CASE PRESENTATION: A 51-year-old man with right temporal glioblastoma was initially treated by tumor resection, radiotherapy and chemotherapy. Eighteen months after surgery, he was readmitted with complaints of neck pain for 2 weeks. Follow-up magnetic resonance imaging (MRI) and fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed a solitary FDG-avid osteolytic lesion in the 4th cervical vertebral body without other abnormal FDG-uptake in the body and in the absence of local recurrence at the resection cavity. Because of the sudden worsening situation and intractable neck pain, the patient underwent tumor resection. Postoperatively, the pain was obviously reduced and the situation was improved. Interestingly, the immunohistochemical findings of glial fibrillary acidic protein (GFAP) indicated the characteristic of metastatic glioblastoma, despite that the histopathological findings of Hematoxylin & Eosin (H&E) staining was suspicious of osteoclastoma. According to the clinical history, imaging findings, pathological and immunohistochemical results, a final diagnosis of solitary vertebral metastasis from glioblastoma without central nervous system (CNS) relapse was confirmed. Then, the patient received radiotherapy on spine and adjuvant chemotherapy with temozolomide. However, he died suddenly 2 months after the tumor resection, nearly 21 months after the initial diagnosis. CONCLUSION: We emphasize that metastatic glioblastoma should be considered in the differential diagnosis of a solitary FDG-avid osteolytic vertebral mass on PET/CT. And the diagnosis of extracranial metastasis (ECM) from glioblastoma can be achieved through clinical history, imaging findings, pathological examination, and immunohistochemical staining with GFAP.

Structure and function of Septin 9 and its role in human malignant tumors.

The treatment and prognosis of malignant tumors are closely related to the time when the tumors are diagnosed; the earlier the diagnosis of the tumor, the better the prognosis. However, most tumors are not detected in the early stages of screening and diagnosis. It is of great clinical significance to study the correlation between multiple pathogeneses of tumors and explore simple, safe, specific, and sensitive molecular indicators for early screening, diagnosis, and prognosis. The Septin 9 (SEPT9) gene has been found to be associated with a variety of human diseases, and it plays a role in the development of tumors. SEPT9 is a member of the conserved family of cytoskeletal GTPase, which consists of a P-loop-based GTP-binding domain flanked by a variable N-terminal region and a C-terminal region. SEPT9 is involved in many biological processes such as cytokinesis, polarization, vesicle trafficking, membrane reconstruction, deoxyribonucleic acid repair, cell migration, and apoptosis. Several studies have shown that SEPT9 may serve as a marker for early screening, diagnosis, and prognosis of some malignant tumors, and have the potential to become a new target for anti-cancer therapy. This article reviews the progress in research on the SEPT9 gene in early screening, diagnosis, and prognosis of tumors.

High-resolution colonic manometry and its clinical application in patients with colonic dysmotility: A review.

The detailed process and mechanism of colonic motility are still unclear, and colonic motility disorders are associated with numerous clinical diseases. Colonic manometry is considered to the most direct means of evaluating colonic peristalsis. Colonic manometry has been studied for more than 30 years; however, the long duration of the examination, high risk of catheterization, huge amount of real-time data, strict catheter sterilization, and high cost of disposable equipment restrict its wide application in clinical practice. Recently, high-resolution colonic manometry (HRCM) has rapidly developed into a major technique for obtaining more effective information involved in the physiology and/or pathophysiology of colonic contractile activity in colonic dysmotility patients. This review focuses on colonic motility, manometry, operation, and motor patterns, and the clinical application of HRCM. Furthermore, the limitations, future directions, and potential usefulness of HRCM in the evaluation of clinical treatment effects are also discussed.

Review of clinical investigation on recurrence of gastric cancer following curative resection.

OBJECTIVE: To discuss the present status and progress of clinical research on recurrence of gastric cancer after surgery, including patterns, clinicopathologic factors, prognosis, detection, diagnosis, prevention, and treatment strategies. DATA SOURCES: The data used in this review were mainly from PubMed articles published in English from 2000 to August 2011. The search terms were "gastric cancer" and "recurrence". STUDY SELECTION: Articles were selected if they involved clinicopathologic factors, detection methods, and treatment strategies of recurrence of gastric cancer. RESULTS: Peritoneal recurrence is the most common pattern in recurrence of gastric cancer. The main risk factors for recurrence of gastric cancer are tumor stage, including depth of tumor invasion and lymph node metastasis, and Borrmann classification. The prognosis of patients with recurrence is very poor, especially patients with peritoneal recurrence. Systemic chemotherapy is still the main treatment method for patients with recurrent cancer. If complete resection can be accomplished, some benefits may be obtained from surgery for recurrence. However, standard treatment for patients with recurrence has not yet been established. CONCLUSIONS: Early detection and diagnosis of recurrence is quite crucial for treatment and prognosis. The optimal therapeutic strategy for recurrence should be based on a multidisciplinary assessment and the patient's individual state and should involve combined therapy.

Expression and functional significance of Twist1 in hepatocellular carcinoma: its role in vasculogenic mimicry.

UNLABELLED: The up-regulation and nuclear relocation of epithelial-mesenchymal transition (EMT) regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). The term vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. However, the relationship between Twist1 and VM formation is not clear. In this study, we explored HCC as a VM and EMT model in order to investigate the role of Twist1 in VM formation. We first examined the expression of Twist1 in human HCC samples and cell lines and found that Twist1 was frequently overexpressed in the nuclear relocation occurring in VM-positive HCCs (13/18 [72%]). Twist1 nuclear expression was likewise significantly associated with VM formation. Clinicopathological analysis revealed that both VM and Twist1 nuclear expressions present shorter survival durations than those without expression. We consistently demonstrated that an overexpression of Twist1 significantly enhanced cell motility, invasiveness, and VM formation in an HepG2 cell. Conversely, a knockdown of Twist1 by the short hairpin RNA approach remarkably reduced Bel7402 cell migration, invasion, and VM formation. Using chromatin immunoprecipitation, we also showed that Twist1 binds to the vascular endothelial (VE)-cadherin promoter and enhances its activity in a transactivation assay. CONCLUSION: The results of this study indicate that Twist1 induces HCC cell plasticity in VM cells more through the suppression of E-cadherin expression and the induction of VE-cadherin up-regulation than through the VM pattern in vivo and in a three-dimensional in vitro system. Our findings also demonstrate a novel cogitation in cancer stem-like cell differentiation and that related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis.

[The mechanisms of microenvironments influence on vasculogenic mimicry between intraocular and subcutaneous melanoma].

OBJECTIVE: To investigate the influence of different microenvironments on melanoma vasculogenic mimicry, invasiveness and metastasis behavior. METHODS: It was an experimental study. Sixty C57BL/6J mice were randomly divided into two groups with 30 mice per group. Melanoma B16 cells were injected into the subretinal space and groin area of mice synchronously. The number of each type of microcirculation pattern was counted. The invasion and metastasis were observed. EphA2, MMP-2 and MMP-9 expression and their mRNA levels were detected by immunohistochemical staining and real time RT-PCR and compared between two groups. RESULTS: Five invasions and six lung metastases were found in the subretinal group while no invasion and metastasis were found in the groin group. The number of VM channels was significantly higher in subretinal group (t = 4. 188, P = 0.000). However, no significant difference of mosaic vessel and endothelium-dependent vessel was observed between two groups (t = 1.473, 1.805; P = 0.146, 0.076, respectively). EphA2, MMP-2 and MMP-9 expression was significantly higher in the subretinal group (data not shown). The mRNA levels of EphA2, MMP-2 and MMP-9 were rather higher in the subretinal tumor (t = 3.642, 8.109, 9.357; P = 0.002, 0.001 and 0.001, respectively). There was a positive association in melanoma cells of the VM between expression of EphA2 (r = 0.412, P = 0.021) but no statistically significant correlation between VM and MMP-2 (P > 0.05), nor between VM and MMP-9. CONCLUSIONS: Different microenvironments affect invasiveness and blood supply patterns of melanoma. Melanoma cells in intraocular microenvironment increased EphA2 expression which induced the formation of VM channels. Moreover, the expression of MMP-2 and MMP-9 in tumor tissue increased to enhance the invasiveness and metastasis behavior.

[Correlation between expressions of matrix metalloproteinase-2 & 9 and vasculogenic mimicry in gastrointestinal stromal tumors].

OBJECTIVE: To study the correlation between the expression of matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF) and vasculogenic mimicry (VM) in gastrointestinal stromal tumors (GIST). METHODS: The immunohistochemical staining indices (SI) of MMP-2, MMP-9, VEGF were assessed on specimens of 84 human cases with GIST (21 VM-positive cases). Gelatin zymography analysis of the activity of MMP-2 and MMP-9 activities were performed on another 42 human cases of GIST with fresh tissue (22 VM-positive cases). RESULTS: The staining indices (SI) of MMP-2 and MMP-9 were higher in the VM-positive group (4.10 +/- 2.05 and 3.43 +/- 1.89 respectively) than in the VM-negative group (2.98 +/- 1.97 and 2.38 +/- 1.84 respectively, both P < 0.05); there was no statistic difference in the SI of VEGF between VM-positive and VM-negative group. Gelatin zymography analysis showed that the activity of MMP-2 and MMP-9 were significantly higher in the VM-positive group (3.62 +/- 3.95 and 4.77 +/- 5.29 respectively) than in the VM-negative group (1.26 +/- 1.21 and 2.11 +/- 1.54 respectively, both P < 0.05). CONCLUSION: The expression of MMP-2 and MMP-9 correlates with VM formation in GIST.

[Correlation of vasculogenic mimicry with clinicopathologic features and prognosis of ovarian carcinoma].

OBJECTIVE: To explore the existence of vasculogenic mimicry (VM) in ovarian carcinoma and its correlationship with the clinicopathologic features and prognosis of the tumor. METHODS: A total of 84 ovarian carcinoma cases were collected with complete clinical and prognostic data. CD31 immunohistochemistry and PAS special stain were used to investigate VM in the tumor tissue. Immunohistochemical staining of VEGF, MMP-2, MMP-9, E-cadherin, beta-catenin, and Vimentin were used to explore the pathogenesis of VM. RESULTS: Totally 36 of 84 cases exhibited evidence of VM. FIGO classification, pathologic grades and histological types were significantly different between the VM and non-VM groups. Expression of VEGF, MMP-2, MMP-9, E-cadherin and beta-catenin were higher in the VM group than in the non-VM group. Kaplan-Meier survival curve analysis showed that cases of the VM group had a lower survival rate than that of the non-VM group (P = 0.04). CONCLUSIONS: Vasculogenic mimicry exists in ovarian carcinoma. Ovarian carcinomas with a high grade malignancy have a high incidence of VM formation, a higher incidence of metastases and a lower survival rate. High expression of MMP-2 and MMP-9 may contribute to the formation of VM in the ovarian cancer.

[Diagnostic value of SYT-SSX fusion gene detection by fluorescence in-situ hybridization for synovial sarcoma].

OBJECTIVE: To establish a method of SYT-SSX fusion gene detection by FISH and to explore its diagnostic value for synovial sarcoma. METHODS: The presence of SYT-SSX fusion gene was determined by FISH using a tissue microarray containing 62 known synovial sarcomas, 60 non-synovial sarcomas and 133 equivocal synovial sarcomas. FISH results were compared with those of RT-PCR published previously. RESULTS: Overall, 96.9% (247/255) of the cases were successfully analyzed by FISH. The sensitivity of FISH for known synovial sarcomas was 96.7% (58/60), and the specificity for the non-synovial sarcoma was 100% (59/59). Moreover, SYT-SSX gene fusion was detected in 78.1% (100/128) of the equivocal synovial sarcomas. The concordance rate between FISH and RT-PCR was 83.6% (102/122) in those equivocal synovial sarcomas, and overall 79.7% (106/133) of these cases were confirmed as synovial sarcomas either by RT-PCR or by FISH. CONCLUSIONS: The sensitivity and specificity of FISH detection of SYT-SSX fusion gene are high. FISH and RT-PCR are complementary to each other in the confirmation of synovial sarcomas, particularly those questionable cases.

Functional significance of VEGF-a in human ovarian carcinoma: role in vasculogenic mimicry.

Ovarian cancer is a silent killer, and shows early extensive tumor invasion and peritoneal metastasis. The microcirculation of most tumors includes cooperation of pre-existing vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis and vasculogenic mimicry (VM). VM is critical for a tumor blood supply and is asscociated with aggressive features and metastasis. Our studies highlight the plasticity of aggressive human ovarian carcinoma cells and call into question the underlying significance of their ability to form VM in vitro induced by VEGF-a. These studies also show their clinicalpathological features of the cancers with human Paraffin-embedded tumor tissue samples. Results show that the process: VEGF-a-->EphA2-->MMPs-->VM is the main pathway for VM formation and VEGF-a appears to play an important role in the formation of VM based on our in vitro assays and clinical immunohistochemical analyses. VM-targeting strategies for ovarian cancer include anti-VEGF-a treatment, knocking down the EphA2 gene and using antibodies against human MMPs if the tumor is VM positive. This strategy may be of significant value in laying the foundation for a more explicit anti-tumor angiogenesis therapy.

[Effects of endostatin and doxycycline on microcirculation patterns in melanoma and their relevant molecular mechanisms].

OBJECTIVE: To investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms. METHODS: To establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography. RESULTS: Tumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different. CONCLUSION: The combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.

[The influence of different microenvironments on melanoma invasiveness and microcirculation patterns].

OBJECTIVE: To investigate the influence of different microenvironments on tumor microcirculation patterns and invasive capability. METHODS: Melanoma B16 cells were injected into the peritoneal cavity and skeletal muscle of C57 mice synchronously. CK18 expression in melanoma was assessed to distinguish the malignant phenotype of tumors in the peritoneal cavity from that in the skeletal muscle. HIF-1alpha, MMP-2 and MMP-9 protein and mRNA expression were compared in the two microenvironments. Cells positive for each immunohistochemical stain and the vessels representative of each type of microcirculation pattern were evaluated in two microenvironments. RESULTS: CK18 and HIF-1alpha expression in melanoma were significantly higher in the skeletal muscle than in the peritoneal cavity (t = 8.142, t = 3.645, P < 0.05). Compared with the peritoneal cavity, melanoma cells in the skeletal muscle overexpressed MMP-2 and MMP-9 (t = 4.916, t = 7.782, P < 0.05). Real time-PCR results also showed that MMP-2 and MMP-9 mRNA levels in melanoma were higher in the skeletal muscle than in the peritoneal cavity (t = 36.814, t = 26.025, P < 0.05). Vasculogenic mimicry channels and endothelium-dependent vessels were the major microcirculation patterns in the skeletal muscle and in the peritoneal cavity respectively. CONCLUSIONS: Different microenvironments affect invasiveness and blood supply patterns of melanoma. Different microenvironment induced tumor cell secretion of more invasion-related proteins and affect invasiveness and blood supply patterns of melanoma.

[Expression of FasL and apoptosis in pulmonary tissue of rats exposed to silica at different time].

OBJECTIVE: To investigate the change of the expression of the FasL receptor and apoptosis in the pathology of silicosis of the rats exposed to silica and their roles. METHODS: Ninety-six wistar rats were randomizedly divided into the control group and the experimental group. The silicotic animal model was established by the direct tracheal instillation of silica into rat lungs surgically. The control rats underwent directly tracheal instillation of saline into lungs surgically. Eight rats from each group were sacrificed at different days. The expression of FasL receptor in the tissue of the model rats was detected by tissuechip microarray and immunohistochemistry and the cell apoptosis induced by silica was determined by TdT-mediated dUTP nick end-labeling method. The integral optical density of positive cells were quantitatively analyzed using Image-Pro Plus Version 4.5 for windows. RESULTS: The expression of FasL in the lung tissue of the model rats on the 7th, the 14th, the 21st, and the 28th day was significantly higher than that in the control group (P < 0.05), and peaked at the 14th day after exposure to silica. Apoptotic cells in the lung tissue of the model rats on the 1st, the 3rd, the 7th, the 14th, the 21st, and the 28th day were significantly more than those in the control group, and peaked at the 7th and the 14th day after exposure to silica. CONCLUSION: Silica can lead to apoptosis in lung tissues. FasL is expressed in all kinds of cells in the pulmonary tissues of the rats exposed to silica and leads to apoptosis. From the 7th day to 14th day, inflammatory cells dominate in apoptotic cells.

[A study on vasculogenic mimicry in hepatocellular carcinoma].

OBJECTIVE: To explore if vasculogenic mimicry (VM) exists in hepatocellular carcinoma (HCC) and to explain the clinical significance of VM. METHODS: Ninety-nine HCC resection specimens with complete clinical and prognostic data were collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS staining of the histological preparations were conducted to explore if VM exists in those HCC. RESULTS: 12.12% (12 specimens) of the 99 specimens exhibited evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed and the stages of the cancers, using the TNM (tumor, node, metastases) classification criteria, were analyzed. These parameters of the VM and non-VM groups were compared. The mean TNM stage of the VM group was not more advanced than that of the non-VM group. The hematogenous metastases ( lung, bone, peritoneum et al) between the 2 groups were compared, and in the VM group the hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier actuarial survival curves were used to compare the VM group (n = 12) with the non-VM group (n = 87). Median survival time of the VM group was 9 months and that of the non-VM group was 31 months. The VM group had a lower survival rate than the non-VM group (P < 0.01). CONCLUSION: VM exists in HCC, and the higher invasive HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM group had a higher rate of hematogenous metastases, a lower survival rate, and a poorer prognosis.

[Study on the molecular mechanism of endostatin and doxycycline in suppressing melanoma growth].

OBJECTIVE: To investigate the molecular mechanism of endostatin and doxycycline effect on melanoma growth. METHODS: A B16 melanoma mice model was established by intracutaneous injection of B16 cell suspension. The mice were treated with endostatin, doxycycline, endostatin and doxycycline respectively, the control group received no treatment. A time course study of tumor volume was performed to observe the antitumor effect. The expression of matrix metalloproteinase (MMP-9), MMP-2, TIMP-2 were examined by immunohistochemistry staining. RESULTS: Tumors in endostatin treatment group, doxycycline treatment group, endostatin and doxycycline treatment group grew slower than in the control group. The difference of the average tumor volume in the doxycycline group and control group, in the doxycycline with endostatin treatment group and control group were statistically different. The positive expression ratio of MMP-2, MMP-9, TIMP-2 in each treatment group were statistically different from their control groups (F = 12.79, F = 5.56, F = 4.64; P < 0.05). CONCLUSION: Doxycycline and endostatin are able to inhibit the expression of MMPs and promote expression of TIMP, which ultimately inhibits the growth of B16 melonoma.

Sulindac induces apoptosis and protects against colon carcinoma in mice.

AIM: To study the effect of sulindac on colon cancer induction in mice. METHODS: The chemo-preventive action of 80 ppm sulindac fed during initiation and post-initiation and 100 ppm sulindac fed during progressive stages of induction of colon carcinogenesis in mice was investigated using 1,2-dimethylhydrazine (DMH). Using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique and PCNA immunohistochemical staining, we observed the apoptotic and proliferative cell density changes at different carcinogenic stages and the effect of sulindac on these two phenomena. RESULTS: Dietary sulindac significantly inhibited the incidence of colonic neoplasmas in mice. Compared with the control group, feeding sulindac during initiation and post-initiation stages inhibited the incidence by 46.7-50.4%, and feeding sulindac during progressive stages inhibited the incidence by 41.1%. Animals that were fed sulindac showed less serious pathological changes than those that were fed the control diet (P<0.01, H = 33.35). There was no difference in the density of proliferating cells among those groups which were or were not fed sulindac. In the same period, feeding sulindac resulted in a higher density of apoptotic cells than feeding control diet. CONCLUSION: Sulindac has an anti-carcinogenic function in mice. Its effect on preventing colon carcinogenesis is better than its effect on treating established tumors. By inducing apoptosis, sulindac inhibited the development of colon cancer and delayed canceration. Sulindac has no effect on proliferation. The anti-carcinogenic properties of sulindac are most effective in the moderate and severe stages of dysplasia and canceration.