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[Effect of estrogens on the concentration of carcinoembryonal antigen in the serum of rats with intestinal neoplasms and in the presence of non-specific injuries to its mucous membrane].

Carcinoembryonal antigen (CEA) was shown to be present in 70% of rats with tumours of the large intestine induced with 1,2-dimethyl-hydrazine and in rats with posttraumatic mucosa regeneration of the same organ. After treatment with estrogen--diethyl stilbestrol propionate (0.57 microgram/day for 6 days) the incidence of CEA finding in the serum of these rats was increased. In rats with an injured mucosa of the large intestine estrogen treatment prevented the natural decrease of CEA during the decline of regeneration.

Animals↗

Growth factors and intestinal neoplasms.

Signals that control normal and neoplastic epithelial proliferation are not completely understood. We have reviewed the importance of the possible roles of the following control mechanisms: polyamine biosynthesis, intraluminal nutrients, gastrointestinal hormones and growth factors, bowel resection, carcinogens, and oncogenes. The mechanisms by which these agents act and the precise roles they play in normal and abnormal proliferation of intestinal mucosa have not yet been clearly defined. Peptide hormones and growth factors exert their mitogenic effects by first interacting with specific receptors in the cell membrane. Oncogenes induce production of growth factors or replace growth factors and, by themselves, stimulate growth. We believe that no single agent is likely to be responsible; rather, multiple agents are involved in stimulation of growth of normal and neoplastic intestinal epithelial cells. A clear understanding of the factors responsible for regulation of normal and abnormal intestinal cell growth will greatly facilitate the development of therapeutic strategies for the prevention and treatment of gastrointestinal cancers.

Animals↗

Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'.

A method is described enabling the direct measurement of vincristine resistance in intact tissues in vivo by morphological study. Using the metaphase arresting properties of the drug, counts were made of escaping anaphase and telophase mitotic figures at a range of doses. The proportion of post-metaphase mitotic figures is called the post-metaphase index (PMI). In 95 primary intestinal tumours induced by dimethylhydrazine (DMH) in rats, an increase in resistance to vincristine was shown over normal mucosa (P less than 0.001). The data were analysed by computer modelling and a linear relationship is demonstrated between the logit of the post-metaphase index, and log dose of vincristine. To achieve a PMI of 1% the fitted lines show an enhanced vincristine dose requirement over normal mucosa of 6 times in colonic tumours, and 8 times in small intestinal tumours. Non-neoplastic mucosa from the DMH-treated animals requires an enhanced dose of vincristine of 1.5 times, compared with normal mucosa, to achieve a PMI of 1%. Given current interest in the mechanism of vincristine resistance in cell lines this new approach provides a technique for assessing the resistance of solid tumours, both in vivo and in vitro, and for subsequent experimental manipulation.

Animals↗

[Entero-uterine fistual as the first symptom of intestinal neoplasms. Description of a case].

Vaginal elimination of stool due to sigmoid-uterine fistula was the first symptom in a case of neoplasia of the sigma. Few instances of a similar fistula appear in the literature. Bouskela, Chérisié, Yourde and Taieb observed one case starting from the uterus. McGregor & Bacon have described a fistula starting from the colon due to diverticulitis, as have Colceck & Staumann, Smalley et al., and Johnston & Stubbs. No previous example of tumour of the large intestine as the cause of a fistula with the corpus uteri could be found. On examination, the patient presented losss of stool via the vagina and a sigmoid-uterine fistula. Her condition was poor. Blood glucose was high, the protein picture was altered with a los of albumin, and infection was present. Radical management was impossible. Left colostomy reduce the causes of infection and permitted devitalisation of the fistula. Subjective and objective improvement followed, though further enlargement of the tumour engulfing the sigma and uterus led to death some months later due to the onset of renal block.

Adenocarcinoma, Mucinous↗

[Expression of epithelial oncoproteins in large intestine neoplasms].

The high incidence of the colorectal cancer in the industrialized countries has drawn the interest of the scientific community to detect and investigate its morphologic precursors. Growth factors and oncoproteins could be useful to investigate the morphologic and biologic evolution of precancerous lesions of the large bowel. Therefore the Authors report the results obtained from 30 selected patients with hyperplastic and adenomatous polyps, and different histotypes of colorectal cancer, investigated using the EGF-r and p62 protein expression. The results show the potential usefulness of such markers to evaluate the biology of intestinal tumors.

ErbB Receptors↗

Acromegaly and intestinal neoplasms.

Acromegalic subjects show increased frequency of neoplastic lesions in the colon and rectum with respect to the general population. Recent prospective studies using colonoscopy have shown a 3 time higher prevalence of intestinal polyps and up to 4 time increased presence of colorectal cancer in acromegaly, independently of sex, age, duration of disease and clinical status of the patients. The polyps are distributed throughout the extension of the large bowel and are often multiple, showing at least two different histologic types: hyperplastic and adenomatous. Sometimes they are associated with intestinal carcinomas. Pancolonoscopy is the procedure of choice for the diagnosis of large bowel neoplasms, even though it may be difficult to complete in these subjects because of the frequent presence of an enlarged and elongated colon. It shows a higher sensitivity and specificity compared to other tests such as the barium enema, fecal occult blood test and serum levels of carcinoembryonic antigen. Therefore, it is recommended to follow up acromegalic patients using pancolonoscopy to obtain early detection of neoplastic lesions in the large bowel.

Acromegaly↗

Acromegaly and intestinal neoplasms.

Acromegalic subjects show increased frequency of neoplastic lesions in the colon and rectum with respect to the general population. Recent prospective studies using colonoscopy have shown a 3 time higher prevalence of intestinal polyps and up to 4 time increased presence of colorectal cancer in acromegaly, independently of sex, age, duration of disease and clinical status of the patients. The polyps are distributed throughout the extension of the large bowel and are often multiple, showing at least two different histologic types: hyperplastic and adenomatous. Sometimes they are associated with intestinal carcinomas. Pancolonoscopy is the procedure of choice for the diagnosis of large bowel neoplasms, even though it may be difficult to complete in these subjects because of the frequent presence of an enlarged and elongated colon. It shows a higher sensitivity and specificity compared to other tests such as the barium enema, fecal occult blood test and serum levels of carcinoembryonic antigen. Therefore, it is recommended to follow up acromegalic patients using pancolonoscopy to obtain early detection of neoplastic lesions in the large bowel.

Acromegaly↗

Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation.

The transforming growth factor-beta (TGF-beta) signaling pathway is a tumor-suppressor pathway that is commonly inactivated in colon cancer. TGF-beta is a secreted ligand that mediates its effects through a transmembrane heteromeric receptor complex, which consists of type I (TGFBR1) and type II subunits (TGFBR2). Approximately 30% of colon cancers carry TGFBR2 mutations, demonstrating that it is a common target for mutational inactivation in this cancer. To assess the functional role of TGFBR2 inactivation in the multistep progression sequence of colon cancer, we generated a mouse model that recapitulates two common genetic events observed in human colon cancer by mating Apc(1638N/wt) mice with mice that are null for Tgfbr2 in the intestinal epithelium, Villin-Cre;Tgfbr2(E2flx/E2flx) mice. In this model, we observed a dramatic increase in the number of intestinal adenocarcinomas in the Apc(1638N/wt);Villin-Cre;Tgfbr2(E2flx/E2flx) mice (called Apc(1638N/wt);Tgfbr2(IEKO)) compared with those mice with intact Tgfbr2 (Apc(1638N/wt);Tgfbr2(E2flx/E2flx)). Additionally, in vitro analyses of epithelial tumor cells derived from the Apc(1638N/wt);Tgfbr2(IEKO) mice showed enhanced expression and activity of matrix metalloproteinase MMP-2 and MMP-9, as well as increased TGF-beta1 secretion in the conditioned medium. Similarly, primary tumor tissues from the Apc(1638N/wt);Tgfbr2(IEKO) mice also showed elevated amounts of TGF-beta1 as well as higher MMP-2 activity in comparison with Apc(1638N/wt);Tgfbr2(E2flx/E2flx)-derived tumors. Thus, loss of TGFBR2 in intestinal epithelial cells promotes the invasion and malignant transformation of tumors initiated by Apc mutation, providing evidence that Wnt signaling deregulation and TGF-beta signaling inactivation cooperate to drive the initiation and progression, respectively, of intestinal cancers in vivo.

Animals↗

Intestinal neoplasm mimicking a Meckel's diverticulum on scintigraphic imaging.

A 33-year-old man presented with colicky, intermittent, midabdominal pain with nausea and vomiting. A Tc-99m pertechnetate abdominal scan was performed and revealed a focal area of increased uptake in the midabdomen associated with dilated proximal loops of small bowel. Surgery revealed a high-grade partial obstruction of the midportion of the jejunum secondary to an annular adenocarcinoma of the jejunum. This is the first known report of abnormal Tc-99m pertechnetate accumulation in an adenocarcinoma of the small bowel.

Adenocarcinoma↗