Adenocarcinoma Of Large Intestine Research Articles

Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine.

The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.

In silico identification of putative roles of food-derived xeno-mirs on diet-associated cancer

Aim: Dietary miRNAs in foods were recently suggested to be absorbed into the human circulation and engage in human gene regulation. This started a debate on their possible impacts on human diseases which need further investigation. In this study, we aimed to identify the putative functions and possible implications of selected Xeno-miRs in human diseases by using bioinformatic tools. Methods: Seventy-five human absorbable Xeno-miR candidates were selected from literature and narrowed down the list to miRNAs that share sequence homologies with human miRNAs. Sixteen distinct Xeno-miRs of animal species (cow, pig, chicken) were identified to have homologs in human and they were subsequently analyzed with target prediction, functional and pathway analysis tools. Results and Conclusion: Thirteen human genes were common targets of the miRNA sets grouped by species and shown evidence of associations with various cancer categories, specifically in large intestine adenocarcinoma by Ingenuity Pathway Analysis. miRNA functional enrichment analyses also highlighted the putative involvements of the dietary miRNAs in cancer pathways. Our effort provides “in silico” evidence for implications of animal-derived dietary miRNAs in cancer-associated pathways, and this shed on light the necessities of future translational research design to investigate the roles of dietary Xeno-miRs in cancer pathophysiology and nutrition-based interventions towards cancer management.

Adenocarcinoma of the posterior segment of the gastrointestinal tract in dogs - clinical, endoscopic, histopathological and immunohistochemical findings.

Of all the tumours in dogs, three percent are located in the intestines, and 36-60% of those tumours affect the large intestine. Adenocarcinomas of the intestines account for 20-35% of the gastrointestinal tumours and for almost 60% of the large intestine tumours. The aim of the study was to analyze clinical disorders and endoscopic, histopathological and immunohistochemical changes in colorectal adenocarcinomas in dogs with the use of the E-cadherin, β-catenin, cytokeratin 20 (CK20), Ki-67 and minichromosome maintenance 3 (MCM-3). The study comprised 11 dogs of both genders and of different breeds diagnosed with adenocarcinoma of the large intestine. They were from 4 to 11 years old. The large intestine adenocarcinoma was diagnosed in all the patients. 72.7% cases were diagnosed with a rectal adenocarcinoma, and 27.3% were found to have a colonic adenocarcinoma. All the studied proteins were expressed at different levels and, together with the histological findings, indicated different levels of malignancy (G). The statistical analysis revealed no statistically significant differences between the expression of E-cadherin and β-catenin in the studied tissues (p=0.79) and between the expression of Ki-67 andMCM-3 (p=0.39). A strong positive correlation was found between the expression of E-cadherin and β-catenin (r=0.86; p<0.05). The diagnosis of adenocarcinomas of the large intestine may be facilitated by the introduction of immunohistochemical studies using appropriate cell markers. They may also aid in the accurate evaluation of the biological character of the tumours, their origin, the connections between tumour cells and the mitotic index. That, in turn, may help determine the malignancy and the choice of treatment.

Enterohepatic Helicobacter spp. in cats with non-haematopoietic intestinal carcinoma: a survey of 55 cases.

Several enterohepatic Helicobacter spp. (EHS) have been isolated from cats. Despite the reported association between EHS infection and intestinal neoplasia in other species, this association has not been explored in cats. In this study, 55 non-haematopoietic feline intestinal carcinoma cases were histopathologically evaluated. In contrast with prior reports, large intestinal (LI) carcinoma was observed with greater frequency (61 %) relative to small intestinal (SI) carcinoma (35 %). There was a significant association between intestinal location and animal gender. Of males examined, 83 % had LI carcinoma, while no such trend was observed in females. Previously described associations between Siamese breed and intestinal carcinoma could not be definitively confirmed, although the Siamese breed may be predisposed to SI carcinoma location. Of all carcinomas examined in this study, 62 % were classified as adenocarcinoma, although mucinous adenocarcinoma (28 %) and solid carcinoma (11 %) were also identified. Tumours were all moderately or poorly differentiated. When considered by intestinal location and histopathologic classification, LI adenocarcinoma was associated with significantly advanced mean age (13 years) when compared to SI adenocarcinoma and LI mucinous adenocarcinoma (mean, 9 years in both cases), which were also frequently encountered. To determine whether EHS might play a role in feline intestinal neoplasia, Helicobacter genus- and species-specific fluorescence in situ hybridization was performed. Of these carcinoma cases, 56 % were positive for Helicobacter spp. and one or more species-specific assay for Helicobacterbilis, Helicobactercanis or Helicobactermarmotae. The presence of EHS was significantly associated with both LI location (68 %) and mucinous adenocarcinoma (92 %). These findings suggest a role for intestinal bacteria in non-haematopoietic feline intestinal neoplasia.

P16(INK4a) protein expression in endocervical, endometrial and metastatic adenocarcinomas of extra-uterine origin: diagnostic and clinical considerations.

Determining the primary site of uterine adenocarcinoma (ADC) may be problematic, especially with small specimens. This is particularly important in light of the increase of endocervical and endometrial adenocarcinoma and the decrease in incidence of squamous cell carcinoma. P16(INK4a) , a member of the INK4 family of cell cycle regulatory proteins, plays a critical role. It functions as a negative regulator of cell cycle progression and differentiation by controlling the activity of the tumor-suppressor protein retinoblastoma (pRb), which regulates the cell cycle. Its expression is variable according to the tumoral histotype and in metastasis. The aim of this study was to investigate P16(INK4a) expression in endocervical, endometrial, and metastatic ADCs of extra-uterine origin. Fifty gynaecological biopsies (cervix or endometrium) comprised the study for P16(INK4a) determination. Cases were classified as (1) diffuse positive (P), in intense nuclear immunostaining and/or cytoplasmic in > 30% of neoplastic cells; (2) focal positive (FP), in intense immunostaining in 10% to 30% in isolated cells or small groups; and (3) negative (N), in absence of immunostaining or weak, sporadic immunostaining in < 10% of neoplastic cells. Included in the study were the following: 6 endocervical ADCs, 11 endometrioid-type endometrial ADCs, 5 endometrial serous papillary ADCs, 7 ovarian ADCs, 4 large intestine ADCs, 1 breast ADC, 12 not-otherwise-specified (NOS) ADCs, and 4 endocervical biopsy without atypia (as control). Diffuse, strong positivity with P16(INK4a) suggests an endocervical rather than an endometrial or metastatic ADC. In fact, a P16(INK4a) positive immunostaining pattern was prevalent in endocervical (83%) and serous papillary ADCs of endometrial or ovarian origin, whereas endometrioid ADCs such as metastatic non-ovarian lesions generally presented only focal or negative immunostaining. 10/12 cases of ADC-NOS were reclassified using P16(INK4a) immunostaining: 2 as endocervical ADCs (2 P), 4 as endometrioid-type endometrial ADCs (2 FP, 2 N), 3 as endometrial serous papillary ADCs (3 FP), and 1 as ovarian serous papillary ADC (1 FP).

Synchronous appearance of gastric gastrointestinal stromal tumors and colorectal adenocarcinoma:a case report.

Gastrointestinal stromal tumors (GIST) represent the most usual mesenchymal tumors of the gastrointestinal tract. In this paper we present a case of a 59-year old patient with an adenocarcinoma of the transversal colon near the lienal flexure without breaking of the intestinal membrane synchronous with an intramural tumor in the antral region of the stomach which was not registered before the operation. Final immunohistochemical findings of the operation specimens: 1. Adenocarcinoma of the large intestine (histological grade I, nuclear grade I, Dukes A, invasion to submucosa) and 2. GIST with low malignant potential. Synchronous appearance of GISTs and colorectal adenocarcinoma, although very rare, has been increasingly observed in the last five years. Because of the small number of cases, a causal connection between these different types of tumors cannot be proven. Through this case report we hope to contribute to the adequate preoperative preparation, operation technique and postoperative monitoring of such patients. Surgical treatment is a dominant way of treating these synchronous tumors, so the surgeon has high responsibility for adequate selection of operative procedure on these patients.

Abstract LB-243: Discovery of single amino acid changes that confer constitutive activation of mTOR in human cancer

Abstract Mammalian target of rapamycin (mTOR), a serine/threonine kinase that belongs to the PI3K related kinase family, plays critical roles in a variety of cellular processes including protein synthesis, growth, cell cycle and autophagy in response to growth factor, nutrient and energy conditions. Overactivation of the mTOR signaling is observed in a number of human cancer. Inhibitors of mTOR such as rapamycin and its derivatives are being evaluated in clinical trials. Despite these developments that point to the significance of mTOR in human cancer, no mutations in mTOR have so far been identified in human cancer. Here we report novel mTOR mutations identified in human cancer by mining human cancer genome database. Of 889 cancer samples mined, we identified 14 amino acid changes in mTOR. Characterization of the mTOR signaling after expressing some of these mutants led to the identification of two single amino acid changes (S2215Y and R2505P) that confer constitutive activation of mTOR as detected by the phosphorylation of S6K, 4E-BP1 and S6 under nutrient starvation conditions. The mutation directly affects mTOR complex 1 (mTORC1), as the complex isolated from cells expressing the mutant mTOR after nutrient starvation still retained the activity to phosphorylate 4E-BP1 in vitro. On the other hand, we did not observe significant effects on the activity of mTORC2. The cells expressing the mTOR mutant exhibited resistance to cell size decrease by amino acid starvation and showed increased percentage of S-phase cells. The cells expressing the activated mutant were resistance to 1-butanol treatment and partially resistant to hydrogen peroxide treatment. However, they were sensitive to rapamycin. The mutations are located within the kinase domain at positions that correspond to regions where oncogenic mutations of PI3 kinase were identified. It is interesting to point out that the mTOR S2215Y mutation was identified in large intestine adenocarcinoma together with K-rasG13D mutation, while the mTOR R2505P mutation was identified in renal cell carcinoma together with CDC25A F218I mutation, raising the possibility that the mTOR mutations may cooperate with mutations in other signaling proteins. Since “we are moving into an era in which it will be possible to obtain the complete DNA sequence of large numbers of cancer genomes” (Stratton et al., Nature 458, 719), our study points to the idea that mTOR activating mutations can be identified in a wide range of human cancer yielding valuable information on the significance of mTOR in human cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-243.

Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy. In a variety of cancer cells, overactivation of mTOR has been reported. In addition, mTOR inhibitors, such as rapamycin and its derivatives, are being evaluated in clinical trials as anticancer drugs. However, no active mutants of mTOR have been identified in human cancer. Here, we report that two different point mutations, S2215Y and R2505P, identified in human cancer genome database confer constitutive activation of mTOR signaling even under nutrient starvation conditions. S2215Y was identified in large intestine adenocarcinoma whereas R2505P was identified in renal cell carcinoma. mTOR complex 1 prepared from cells expressing the mutant mTOR after nutrient starvation still retains the activity to phosphorylate 4E-BP1 in vitro. The cells expressing the mTOR mutant show increased percentage of S-phase cells and exhibit resistance to cell size decrease by amino-acid starvation. The activated mutants are still sensitive to rapamycin. However, they show increased resistance to 1-butanol. Our study points to the idea that mTOR activating mutations can be identified in a wide range of human cancer.

Clinical significances of the expression of metallothionein in five types epithelium cell cancer

ObjectiveTo study the expressions of metallothionein and the significances in cervical squamous cell cancer (CSC), bladder transitional cell cancer (BTC), esophageal squamous cell cancer (ESC), gastral tubular adenocarcinoma (GC) and large intestinal tubular adenocarcinoma (LIC).MethodsImmunohistochemical method was used to examine the expression rates of MT in five types of cancer tissue.ResultsThe expression rates of MT were 75.00% (24/32) in ESC, 52.27% (46/88) in GTC, 59.46% (44/74) in LIC, 64.86% (48/74) in BTC and 58.57% (41/70) in CSC respectively. The positive rates of MT expression were higher in low differentiation and deep muscular group than those in medium or high differentiation and superficial muscular invasion group (P<0.05).ConclusionThe expression of MT is related to differentiation degree and invasion degree.

Biologically active sphingolipids in transplantable tumors of different histogenesis

The composition of biologically active sphingolipids in hepatoma 22, breast adenocarcinoma, Lewis lung carcinoma, large intestine adenocarcinoma, cervical carcinoma, and melanomas M3 and B16 was compared to elucidate the similarity and differences in sphingolipids of subcutaneously transplantable murine tumors. The sphingolipid composition of the tumors was found to widely vary. The sphingomyelin, ceramide, glucosyl- and lactosylceramide, and ganglioside GD3 contents in hepatoma 22 are higher than those in normal tissue. No common regularities for tumors of different origin were observed in the ratios of bioeffectors inhibiting proliferation and stimulating apoptosis and bioeffectors stimulating cell growth and survival. However, the Cer/(GlcCer + LacCer) ratios were very low and practically equal in two melanoma strains, which probably indicates the degree of tumor malignancy. The results suggest that the content and composition of sphingolipids in tumors depend on their histogenesis.

Equine adenocarcinomas of the large intestine with osseous metaplasia

Large intestinal adenocarcinoma with osseous metaplasia was diagnosed in two horses, a 15-year-old standard bred gelding and a 9-year-old Haflinger mare. Clinically, both animals had displayed weight loss and anaemia. A presumptive diagnosis of abdominal neoplasia was made and the horses were humanely killed. At necropsy, the gelding and the mare were found to have ulcerated tumours growing into the lumen of the caecum and colon, respectively. In the mare, the mass extended through the mesocolon and was evident in the left dorsal and ventral colon. Histopathologically, the tumours consisted of well-differentiated cords of single-layered columnar to cuboidal epithelial cells. Mitotic figures were very uncommon. In both lesions, well-formed bony spicules and osteoid were present in the fibrovascular stroma. The tumours were well-demarcated from surrounding mucosal tissue but had invaded the intestinal wall. Metastases were not observed.

Ornithine decarboxylase activity and polyamine content in adenocarcinomas of human stomach and large intestine

Ornithine decarboxylase (ODC) activity and differential polyamine composition have been studied in macroscopically normal mucosa, adjacent mucosa, and neoplastic tissue of 95 patients with adenocarcinomas of stomach and large intestine. In tumors, we found increased ODC activity and polyamine content as compared with surrounding mucosa. ODC activity in macroscopically normal tissue of patients with tumors of stomach and large intestine increased as the disease progressed. An inverse relationship was observed between ODC activity in adenocarcinomas and differentiation.

Intestinal adenocarcinomas metastatic to the ovaries. A clinicopathologic evaluation of 22 cases.

The most common secondary ovarian neoplasm to mimic an ovarian primary tumor is metastatic large intestinal adenocarcinoma. Even after histologic examination, metastases often are mistaken for primary adenocarcinomas, especially endometrioid carcinoma. We analyzed the clinical and pathologic features of 22 cases of documented large intestinal carcinoma metastatic to the ovary. Patients' ages ranged from 42 to 76 years. None of the intestinal primary tumors were Dukes stage A, 32% were Dukes B, and 68% were Dukes C. In nine patients (41%), the intestinal carcinomas had been resected previously from 4 to 60 months before removal of the ovarian metastases. Both ovaries were involved in 43% of the cases. Histologically, 19 cases were classified as pseudoendometrioid type, two as mucinous type, and one as mixed pseudoendometrioid-mucinous type. The most characteristic microscopic features of the ovarian metastases were garland and cribriform growth patterns, intraluminal "dirty" necrosis, segmental destruction of glands, and absence of squamous metaplasia. Special stains for mucosubstances were variable and not helpful in differential diagnosis. Immunohistochemical staining for carcinoembryonic antigen (CEA) was strongly positive. Recognition of these distinctive histologic features is crucial to proper identification of the intestinal origin of these ovarian tumors. Inappropriate treatment as primary ovarian carcinomas thereby is avoided, and more accurate assessment of prognosis is achieved.

Mucin secreting cancer with mesangial IgA deposits

Subclinical immune complex glomerular deposits occurred in 20% (11 of 55) of cancer cases examined postmortem. Eight of 11 (72.7%) mucin secreting adenocarcinomas of lung, stomach, large intestine and pancreas showed glomerular mesangial deposits of IgA, with associated IgM and C3 in one-half of them. The glomerular morphology showed predominantly minimal or minor changes, and less frequently mesangial cell proliferation. None of the patients exhibited clinical evidence of glomerulonephritis. The nature of the antigen(s) in the paraneoplastic phenomenon was not defined, but there may have been environmental antigen(s) or specific immune response in the local population to explain the IgA deposition.

Ultrastructural markers of colonic adenocarcinoma.

A mixed population of 96 adenocarcinomas was examined by electron microscopy to establish the presence of organ specific features. This resulted in the identification of fine structural characteristics, occurring consistently in colorectal adenocarcinomas but not in other epithelial tumors. The colorectal "ultrastructural profile" consists of microvilli with dense cores of microfilaments extending as long rootlets into a clear zone of apical cytoplasm, apical electron dense bodies, and abundant glycocalyceal bodies. Of these features, the long rootlets constitute the best morphologic marker for large intestinal type adenocarcinoma. Using these characteristics in another series of 58 adenocarcinomas studied in a double-blind manner, it was possible to distinguish colorectal adenocarcinomas from other carcinomas on ultrastructural grounds alone.

Malignant transformation of adenoma in large intestine--especially on villous adenoma.

The incidence of 454 resected adenomas was histologically 87.8% of tubular, 7.7% of tubulovillous and 4.5% of villous adenomas, respectively. Eigtosigmoid region. Male to female ratio was 1 to 1.8, 1.5 to 1 and 1.8 to 1 for the villious, tubulovillous and tubular adenomas, respectively. Adenocarcinomas of large intestine consisted of 684 cases, 709 lesions and male to female ratio was 1 to 1.01. It should be considered that the adenomas in female may grow largely compared with those in male, with subsequent malignant transformation. Although the adenomas were found at the rate of 26.4% in the rectosigmoid region, 74.2% of the adenocarcinomas were found in this region, because the adenomas in this region grow largely compared with the other regions. Mucinous carcinomas were found in 33%, 23% and 9%, respectively, in the adenocarcinomas with remaining adenoma showing villous, tuvulovillous and tubular types.

Nuclear morphology in false negative and negative rectal biopsies (author's transl)

An typical nuclear structure consisting of a cribriform and condensed chromatin pattern with hyperchromasia, a small nucleolus and a moderately increased nuclear-cytoplasmic ratio was observed in the epithelial cells of the crypts and in the stromal and muscular cells of 51 out of 70 oncologically negative biopsies of the rectal mucosa. The subsequent retrieval of all clinical and histologia data revealed that the 51 cases included 39 of adenocarcinoma of the large intestine either present (15 cases) at a variable distance from the false negative biopsy or removed previously (24 cases), 7 of extra-intestinal malignant tumor (parotid gland, urinary bladder, endometrium, breast, stomach, metastatic, anus) and 5 with benign conditions of the large intestine. Of the remaining 19 cases whose biopsies did not reveal the atypical nuclear structure 16 had benign lesions of the large intestine and nowhere evidence of malignancy, two had an adenocarcinoma of the large bowel (one present and one removed previously) and one a carcinoma of the anus. In the rectal biopsies examined the atypical nuclear structure was detected in 93.9% of the cases with a malignant tumor either present or removed previously and in 19% of the cases with benign conditions. The morphologic evidence indicated that the atypical nuclear structure was compatible with a possible distrubance of the mitotic cycle since the findings were restricted to the generative compartment of rectal epithelium. The results are discussed in connection with their possible practical use as a diagnostic aid in the evaluation and interpretation of false negative and negative rectal biopsies as well as with their possible significance in the biology of tumor-bearing hosts.

Transplantable adenocarcinomas from color-rectal tumors induced by infusion of N-methyl-N'-nitro-N-nitrosoguanidine in ACI/N rats.

Two transplantable strains of adenocarcinoma were established from the carcinomas of the colon and rectum induced by infusion of N-methyl-N'-nitro-N-nitrosoguanidine in inbred ACI/N rats, The tumors are solid type, not converted to ascite form yet, either papillary or tubulo-papillary adenocarcinomas, and particularly grow slowly, showing 2 to 4 months of survival in animals transplanted subcutaneously. Besides histological resemblance of the tumors to human adenocarcinoma of the large intestine, marked mucin production in tumor was noted in one of these strains.

An investigation into the enzyme histochemistry of adenocarcinomas of human large intestine and of the transitional epithelium immediately adjacent to them.

Histochemical enzymatic studies were performed on 30 freshly resected large bowel carcinomas, 30 samples of normal colonic epithelium, and six samples of the histologically normal epithelium (so-called transitional epithelium) immediately adjacent to a carcinoma. Five enzymes were studied: nicotine adenine dinucleotide tetrazolium reductase (NADH-TR), glucose-6-phosphate dehydrogenase, succinate dehydrogenase, monoamine oxidase, and acid phosphatase. QUANTITATIVE AND QUALITATIVE DIFFERENCES IN ENZYME ACTIVITY WERE OBSERVED BETWEEN NORMAL, TRANSITIONAL, AND CARCINOMATOUS MUCOSA AS FOLLOWS: monoamine oxidase activity was moderate in normal mucosa, high in transitional mucosa, and low in carcinoma. Succinate dehydrogenase activity was high in transitional mucosa and low or moderate in normal and carcinomatous mucosa. Glucose-6-phosphate dehydrogenase activity showed a gradation from low in normal mucosa to high in carcinoma while acid phosphatase showed the reverse of this pattern. The tetrazolium reductase activity was low or moderate in normal and transitional mucosa and high in carcinoma. These differences in enzyme activity and their possible clinical and metabolic significance are discussed.

Relationship of schistosomiasis to polyposis and adenocarcinoma of large intestine.

In Egypt the incidence of polypoid lesions of the rectum and sigmoid colon is high in persons with schistosomiasis. The incidence, 17 to 20 per cent of cases which we studied and reported, is higher than that given in surveys of other countries. During the histologic study of polyps of the rectosigmoid colon we were impressed by the degree of alteration in the epithelial structures, which has been labeled adenomatoid hyperplasia. Kazama' termed the changes of the epithelium caused by the eggs of Schistosoma japonicum as heterotrophic glandular alterations. Faust and Meleney described a similar change in dogs experimentally infected with S. japonicum.