Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors

AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively.RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels.CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.

Antidepressant fluoxetine and its potential against colon tumors

Colon cancer is one of the most common tumors worldwide,with increasing incidence in developing countries.Patients treated with fluoxetine(FLX) have a reduced incidence of colon cancer,although there still remains great controversy about the nature of its effects.Here we explore the latest achievements related to FLX treatment and colon cancer.Moreover,we discuss new ideas about the mechanisms of the effects of FLX treatment in colon cancer.This leads to the hypothesis of FLX arresting colon tumor cells at the at G1 cell-cycle phase through a control of the tumor-related energy generation machinery.We believe that the potential of FLX to act against tumor metabolism warrants further investigation.

Fuji Intelligent Chromo Endoscopy and staining technique for the diagnosis of colon tumor

Background Colon cancer is a common malignant tumor in the clinic with an incidence rate that is increasing in recent years. The key point for improving the survival rate is the diagnosis and treatment at an early stage. The purpose of this study was to compare the difference of the Fuji Intelligent Chromo Endoscopy （FICE） and staining technique for the diagnosis of colon tumors and non-tumor lesions. Methods From March to November 2007, 654 patients were examined with ordinary colonoscopy. Among them 223 patients with colon neoplasm or polypoid lesion were included. The patients were examined with a magnifying ordinary colonoscopy, a magnifying FICE technique and magnifying staining technique. The pit pattern and blood capillary form of the lesion were examined, an endoscopic diagnosis was made and it was compared with the pathologic diagnosis.Results Four hundred and fifty-one neoplasms were detected in the 223 patients, among those 91.1% （411/451） were detected with the magnifying ordinary endoscopy while 99.1% （447/451） were detected with the FICE technique; there was a significant difference between the two methods. FICE could clearly show the structure and form of mucosal blood capillaries （P 〈0.01） but there was no significant difference between the two methods for showing the pit pattern. The coincident rate of FICE for the diagnosis of tumor and non-tumor lesions was 91.6% （413/451）, that of the magnifying staining technique was 82.0% （370/451） （P〈0.05）. Conclusions Magnifying FICE could show the mucosal microstructure and blood capillary form and it had a superiority of high coincident rate, high sensitivity and specificity when compared with ordinary magnifying colonoscopy and magnifying staining endoscopy. In addition, it was easy to operate and a biopsy could be taken from the target, so it has a satisfactory clinical practical value.

Smaller tumor size is associated with poor survival in T4b colon cancer

AIM: To hypothesize that in patients with colon cancer showing heavy intestinal wall invasion without distant metastasis(T4b N0-2M0), small tumor size would correlate with more aggressive tumor behaviors and therefore poorer cancer-specific survival(CSS).METHODS: We analyzed T4 b N0-2M0 colon cancer patients in the Surveillance, Epidemiology and End Results(SEER) database. A preliminary analysis of T4 b N0-2M0 colon cancer patients at the Fudan University Shanghai Cancer Center is also presented.RESULTS: A total of 1734 T4 b N0-2M0 colon cancer patients from the SEER database were included. Kaplan-Meier analysis revealed decreasing CSS with decreasing tumor size(P < 0.001). Subgroup analysis showed a significant association between poorer CSS with smaller tumor size in T4 b N0 patients(P = 0.024), and a trend of association in T4 b N1(P = 0.182) and T4 b N2 patients(P = 0.191). Multivariate analysis identified tumor size as an independent prognostic factor for CSS in T4 b N0-2M0 patients(P = 0.024). Preliminary analysis of Fudan University Shanghai Cancer Center samples suggested the 5-year CSS was 50.0%, 72.9% and 77.1% in patients with tumors ≤ 4.0 cm, 4.0-7.0 cm and ≥ 7.0 cm.CONCLUSION: Smaller tumor size is associated with poorer CSS in the T4 b N0-2M0 subset of colon cancer, particularly in the T4 b N0M0 subgroup.

Colon and rectal cancer:An emergent public health problem

Colorectal cancer ranks third globally,with a high mortality rate.In the United States,and different countries in Europe,organized population screenings exist and include people between 50 and 74 years of age.These screenings have allowed an early diagnosis and consequently an improvement in health indicators.Colon and rectal cancer(CRC)is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and mortality.This study is a review of CRC pathology and includes the most recent scientific evidence regarding this pathology,as well as a diagnosis of the epidemiological situation of CRC.Finally,the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.

MUTATIONAL SCREEN AT THE OEYTS-JEGHERS (LKB1) LOCUS IN SPORDIC COLON AND OVARIAN TUMORS

Objective: To screen LKB1 mutation in sporadic colon and ovarian tumors. Methods: Using PCR-SSCP analysis, 72 colon cancer, 45 ovarian cancer, 14 granulosa cell tumor were screened for LKB1 mutation. Results: no mutation was in sporadic colon and ovarian adenocarcinomas. Two mutations were detected in one of the granulosa cell tumors: a mis-sense mutation affecting the putative start codon (ATG→ACG, MIT); and a silent change in erxon 7 (CTT→CTA, leucine). Conclusion: LKB1 mutations in sporadic colon and ovarian cancers are rare event and LKB1 is not the target gene lost on chromosome 19p13.3 in ovarian cancers.

Rectal Endometriosis Revealed by a Colonic Tumor Obstruction: A Case Report

Endometriosis is defined as the presence of endometrial tissue that is located outside the uterine cavity, associated with fibrosis and inflammatory reaction. The most common atypical locations are the gastrointestinal tract, urinary tract, lung, as well as abdominal surgical scars. Its diagnosis is still very difficult, especially when it manifests itself as an acute large bowel obstruction. We report the rare case of a 41-year-old patient diagnosed with acute colonic obstruction following a rectal tumor. She had undergone colonostomy even though colonoscopy biopsies were nonspecific, and a computed tomography (CT) scan was requested. It showed an adnexal heterogenous mass, therefore the patient had a laparotomy and a subtotal hysterectomy with bilateral salpingo-oophorectomy and a biopsy of the recto-colonic hinge. Histologic examination revealed a diagnosis of rectal endometriosis. The purpose of this work is to report a rare case of colonic endometriosis responsible for an acute large bowel obstruction.

Melanotic Xp11-associated tumor of the sigmoid colon:A case report

BACKGROUND Melanotic Xp11-associated tumors are rare mesenchymal-derived tumors. So far,most primary melanotic Xp11-associated tumors have been reported in the kidney, and reports of this tumor in the gastrointestinal tract are rare.CASE SUMMARY Here we describe the case of a 25-year-old woman who presented with a melanotic Xp11-associated tumor in the sigmoid colon. Colonoscopy revealed a large mucosal bulge in the sigmoid colon, approximately 32 cm inside the anus.The surface was rough with local erosion. The tumor was brittle on biopsy and bled easily. Computed tomography revealed thickening of the rectal wall with edema. Postoperative pathology indicated the likelihood of a perivascular epithelioid cell tumor. Histologically, the tumor comprised plump epithelioid cells with abundant clear to lightly eosinophilic cytoplasm and round nuclei arranged in an alveolar or trabecular pattern. The tumor cells were strongly positive for HMB-45, Melan-A, Cathepsin K, and TFE3 but negative for vimentin,smooth muscle actin, S100 protein, CD10, CK20, and desmin. The tumor cells had a low Ki-67 labeling index(approximately 2%). Fluorescence in situ hybridization revealed TFE3 fracture. Based on these histologic and immunohistochemical features, a diagnosis of melanotic Xp11-associated tumor of the sigmoid colon was made.CONCLUSION In summary, we report the clinicopathological features of a primary tumor that is extremely rare in the sigmoid colon and review the clinicopathological characteristics of melanotic Xp11-associated tumors, compatible with the very rare tumor termed "melanotic Xp11 translocation renal cancer" in all aspects.

Thymoquinone Suppresses Cellular Proliferation, Inhibits VEGF Production and Obstructs Tumor Progression and Invasion in the Rat Model of DMH-Induced Colon Carcinogenesis

A myriad of medicinal effects has been attributed to Thymoquinone (TQ), the major biological-active component of Nigella sativa. TQ has been shown to exhibit potent anti-tumor activities. The present work was undertaken to further explore TQ’s chemopreventive efficacy against 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis in the rat model through a two-phase study (initiation and post-initiation) and to evaluate its potential impact on tumor progression and invasion in vivo. TQ treatment in the initiation phase significantly reduced tumor incidence, multiplicity and mean tumor volume. However, although mean tumor volume and multiplicity were decreased upon TQ treatment in the post-initiation phase, TQ did not reduce incidence significantly. Cellular proliferation, as assessed by expression of colonic PCNA, was shown to be inhibited in consequence to TQ treatment in both phases, with a more pronounced reduction in the initiation phase. In addition, our results demonstrated an appreciable negative impact of TQ on vascular endothelial growth factor (VEGF) production in tumor-bearing rats. Furthermore, we provided evidence that TQ-treatment, in both phases, tended to considerably suppress tumor progression and invasion. Taken together, the present study demonstrated that TQ, at an orally daily dose of 10 mg/kg, has a chemopreventive effect in the initiation phase, and has the potential to attenuate tumor burden, suppress progression of pre-neoplastic lesions and to inhibit tumor growth in the post-initiation phase of DMH-induced colon carcinogenesis, We surmise that such effects of TQ may be due to suppression of cellular proliferation and inhibition of VEGF production. The results could provide an effective chemopreventive approach in the primary prevention of colon cancer in humans in the next future, and illuminate a promising horizon to combat progression of benign colonic pre-neoplastic lesions into malignant metastatic tumors and to manage colon cancer.

A self-guidance biological hybrid drug delivery system driven by anaerobes to inhibit the proliferation and metastasis of colon cancer

Colorectal cancer is often accompanied by multiple organ metastasis.Anaerobic Bifidobacterium Infantis(BI)bacterial can selectively grow in hypoxic colorectal tumor microenvironment(TME),to own the natural advantage of preferentially colorectal tumor targeting.Herein,a self-guidance biological hybrid drug delivery system(BI-ES-Fe Alg/DOX)based on BI was constructed to inhibit the proliferation and metastasis of colon cancer.Results demonstrated that BI-ES-Fe Alg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues.Then DOX was released to kill tumor cells along with the phase transition(solid to liquid)of Fe Alg hydrogel,due to Fe3+was reduced to Fe^(2+)by intracellular GSH.Meanwhile,BI-ES selectively colonized into tumors and expressed endostatin(ES)protein to down-regulate VEGF and b FGF expression,exerting anti-angiogenic effect.Moreover,Fe Alg catalyzed H_(2)O_(2)in the local tumor to generate cytotoxic·OH,further enhancing the antitumor effect.The pharmacodynamic result in AOM/DSS model proved that BI-ES-Fe Alg/DOX had the best therapeutic effect,with the final V/V0of 2.19±0.57,which was significantly lower than the other groups.Meanwhile,on CT-26tumor-bearing model,it also showed an outstanding anti-tumor effect with inhibition rate of 82.12%±3.08%.In addition,lung metastases decreased significantly in tumor metastasis model after BI-ES-Fe Alg/DOX treatment.

^(60)Co照射对Colon 26/IL-21细胞生长及其抗肿瘤效应的影响

目的探讨经高剂量同位素照射后肿瘤细胞(瘤苗)生长变化及其抑瘤效应。方法单次给予60Co50Gy照射转染IL-21的结肠癌细胞株Colon 26/IL-21制备瘤苗,MTT法及RT-PCR法测定细胞代谢活力变化、基因转录水平及凋亡率、细胞周期变化;采用细胞接种方法测定瘤苗成瘤情况,ELISA法测定共培养液中IFN-γ水平和抗肿瘤效应。结果瘤苗处于G1期的细胞在群体中明显增高,其细胞增殖指数明显下降,凋亡率明显增加;瘤苗保持较高的IFN-γ分泌水平,接种2×106/200μl后肿瘤细胞生长明显受抑。结论高剂量同位素照射可制备具有转基因生物学活性的瘤苗,其高剂量接种后具有抗肿瘤效应。

Analysis of risk factors associated with complications of colonic stenting for malignant obstruction

Self expanding metalic stent(SEMS) application can cause serious problems up to one third of the patients and some studies reported negative effect of SEMSs on survival in patients with malignancy. The SEMS type especially the rigid one like Wall-stent rather than more flexible type Ultraflex was also reported to have bad impact on the risk of perforation we believe that stent based management protocol for patients with non-perforating left sided obstructing colorectal cancer is a complex method that needs qualified medical and technical team.

THE SELECTION OF SURGICAL PROCEDURE IN THE TREATMENT OF OBSTRUCTING CARCINOMA OF THE LEFT COLON

From 1973 to 1989, 90 cases of obstructing carcinoma of the left colon were treated with five different operative procedures, the Incidence of anastomotic leakage was 6.7%, the operative mortality was 7. 8%. Among all the patients, 14 cases were treated by primary resection with anastomosis. Anastomotic leakage occurred in 6 cases, and 5 of them were died. Of 25 cases with the traditional staged management, the tumors were resected only in 20 cases, and not resectable in the other 5 patients. 19 with modified Hartmann's procedure and 26 with extended right hemlcolectomy with ileorectal or low ileosigmoid anastomosis gave satisfactory results. In terms of this series, the five-year survival rate in primary resection group was significantly higher than that in staged resection group (P< 0. 05). It is suggested that extented right hemlcolectomy or modified Hartmann' s procedure in cases of acute cancerous obstruction of the left colon would be favord.

Clinical significance of HOTAIR expression in colon cancer

AIM: To detect the expression of the long noncoding RNA HOTAIR in colon cancer and analyze its relationship with clinicopathological parameters of colon cancer. METHODS: Total RNA was extracted from 80 colon cancer tissues and matched tumor-adjacent normal colon tissues and reverse transcribed. Quantitative polymerase chain reaction was used to detect the expression of HOTAIR. The relationship between the expression of HOTAIR and clinicopathological parameters of colon cancer was analyzed. RESULTS: The expression of HOTAIR was significantly higher in colon cancer tissues than in matched tumoradjacent normal colon tissues(P < 0.05). HOTAIR expression was significantly higher in cases with lymph node metastasis than in those without metastasis; in lowly differentiated and undifferentiated cases than in highly and moderately differentiated cases; and in stages Ⅲ + Ⅳ cases than in stages?Ⅰ?+ Ⅱ cases(P < 0.05).CONCLUSION: HOTAIR expression is upregulated in colon cancer, suggesting that HOTAIR plays an important role in the tumorigenesis, development and metastasis of colon cancer. HOTAIR may act as an oncogene and represents a new molecular target for the treatment of colon cancer.

Gastrointestinal neuroendocrine tumors in 2020

Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological,biological,and clinical characteristics that have increased in incidence and prevalence within the last few decades.They contain chromogranin A,synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor.Ki-67 index and mitotic index correlate with cellular proliferation.Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors.Most of the gastrointestinal neuroendocrine tumors are non-functional.World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm.Gastric neuroendocrine tumors arise from enterochromaffin like cells.They are classified into 4 types.Only type I and type II are gastrin dependent.Small intestinal neuroendocrine tumor is the most common small bowel malignancy.More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve.Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs.Duodenal and jejunoileal neuroendocrine tumors are distinct biologically and clinically.Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver.Appendiceal neuroendocrine tumors are generally detected after appendectomy.Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis.Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000.Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy,endoscopic ultrasound,serology of biomarkers,imaging studies and functional somatostatin scans.Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.

Functional Mechanism of Resveratrol in Inhabiting Growth of Cells ls174t and Its Mechanism in Subcutaneously Transplanted Tumor of Nude Mice

To explore the functional mechanism of Resveratrol against colon cancer cells ls174t and the growth of colon cancer tissue of tumor-bearing mice, MTT method was used to observe the functions of resveratrol for inhibition against cells ls174t in vitro. Transmission electron microscope was used to observe the cell apoptosis. FCM assay was performed to measure the change of the cell apoptosis rate and of cell cycle. RT-PCR method was used to detect the expressions of bcl-2 and bax mRNA. Western blot method was used to detect the expressions of bcl-2 and bax protein. Ceils ls174t were transplanted subcutaneously to nude mice to observe the effect of resveratrol on the growth of subcutaneously transplanted tumor, RT-PCR method was used to detect the expressions of bcl-2 and bax mRNA in the tumor tissue. Western blot method was used to detect the expressions of bcl-2 and bax protein in the tumor tissue. Resveratrol has an effect of inhibiting proliferation of cells ls174t in vitro（P〈0.01）. It is able to induce the apoptosis of cells ls174t, causing the decrease in the expression of bcl-2 and the increase in the expression of bax. Resveratrol could inhibit the growth of subcutaneously transplanted tumor of nude mice（P〈0.05）, causing the decrease in the expression of bcl-2 and the increase in the expression of bax. Resveratrol can inhibit the growth of cells 174t and the growth of subcutaneously transplanted tumor. The mechanism is possibly related to the induction of the cell apoptosis and the regulation of bcl-2/bax expression.

PEComa of the colon resistant to sirolimus but responsive to doxorubicin/ifosfamide

A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular epithelioid cell tumor(PEComa).An magnetic resonance imaging scan showed,in addition to the primary tumor,two large mesenteric lymph node metastases and four metastatic lesions in the liver.The patient underwent right hemicolectomy and left hemihepatectomy combined with wedge resections of metastases in the right lobe of the liver,the resection status was R0.Subsequently,the patient was treated with sirolimus.After 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two new liver metastases and a local pelvic recurrence.The visible tumor formations were again excised surgically,this time the resection status was R2 with regard to the pelvic recurrence.The patient was treated with 12 cycles of doxorubicin and ifosfamide under which the disease was stable for 9 mo.The clinical course was then determined by rapid tumor growth in the pelvic cavity.Second line chemotherapy with gemcitabine and docetaxel was ineffective,and the patient died 23 mo after the onset of disease.This case report adds evidence that,in malignant PEComa,the mainstay of treatment is curative surgery.If not achievable,the effects of adjuvant or palliative chemotherapy are unpredictable.

Expression of calreticulin is associated with infiltration of T-cells in stage ⅢB colon cancer

AIM: To investigate the correlation between expression of calreticulin and infiltration of lymphocytes in stage ⅢB colon cancer. METHODS: Sixty-eight pathologically-confirmed speci-mens were obtained from stage ⅢB (T3N1M0) colon cancer patients who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University, Guangzhou, China. Immuno-histochemical analysis was performed to show infiltration of lymphocytes and expression of calreticulin in colon cancer. Association between calreticulin expression, infiltration of lymphocytes, and 5-year survival rate of patients was assessed. RESULTS: The expression level of calreticulin was lower in cancer nest than in its adjacent normal epithelium since 61.8% (42/68) of the samples were stained with calreticulin in colon cancer. The expression of calreticulin in colon cancer was associated with the infi ltration of CD45RO+ cells rather than with that of CD3+ cells. In addition, the stronger expression of calreticulin and the higher infiltration of CD3+ and CD45RO+ cells in colon cancer were associated with the higher 5-year survival rate of patients. CONCLUSION: Expression of calreticulin is associated with infiltration of T-cells, which implies that a low expression level of molecular marker may represent a new mechanism underlying immune escape in colon cancer.

Perivascular epithelioid cell neoplasm of the colon

A 17-year-old female presented with rectal bleeding from an ulcerated sigmoid mass in 1994.Initial pathological evaluation revealed a rare clear cell neoplasm of the colon,possibly originating from kidneys,adrenals,lung or a gynecologic source as a metastatic lesion.Extensive imaging studies were negative,and over the next 15 years,she remained well with no recurrence.The original resected neoplasm was reviewed and reclassified as a perivascular epithelioid cell neoplasm (PEComa).Although the long-term natural history of PEComas requires definition,increased clinical and pathological awareness should lead to increased recognition of an apparently rare type of colonic neoplasm that likely occurs more often than is currently appreciated.

Effect of Recql5 deficiency on the intestinal tumor susceptibility of Apc^(min) mice

AIM:To investigate whether Recql5,a DNA helicase that plays an important role in the maintenance of genome integrity,is a tumor suppressor in the gastrointestinal tract in mice.METHODS:We generated cohorts of both Recql5-proficient and Recql5-deficient Apcmin/+mice and compared the tumor susceptibility in their gastrointestinal tracts.RESULTS:Recql5 deficiency in Apcmin/+mice resulted in a significant increase in the tumor incidence in both the colon(P=0.0162)and the small intestine(P<0.01).These findings have provided the first genetic evidence for a tumor suppression role of Recql5 in the gastrointestinal tract of mice.Importantly,since mouse Recql5 and human RECQL5 are highly conserved,these findings also suggest that RECQL5 may be a tu-mor suppressor for human colon cancer.CONCLUSION:Recql5 has a tumor suppression role in the mouse gastrointestinal tract.