Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 82 patients, a preoperative diagnosis of primary hyperparathyroidism has been established by means of transfemoral neck vein catheterization and measurement of serum immunoreactive parathyroid hormone (iPTH). Twenty-five of these patients have had cancer in other parts of the body but with no evidence of recurrence or metastasis. One patient had carcinoma of the colon with metastases, and four were members of families with multiple endocrine adenomatosis (MEA, Types I and II). In six other hypercalcemic patients, high levels of iPTH were found also in the effluent blood from cancer sites other than the parathyroid gland, secondary to ectopic hormone production or pseudohyperparathyroidism. In addition, a high serum level of iPTH was found in the superior vena cava of a seventh patient who had carcinoma of the breast but no clinical or radiological signs of recurrence or metastasis with the exception of an enlarged liver. This iPTH finding was interpreted as being, probably, the result of parathyroid adenoma in either the neck or the mediastinum. At the time of operation, a transcervical mediastinal search was made. Four normal cervical parathyroid glands were found; three were removed. Hypercalcemia persisted after operation, and the patient died. At postmortem examination, microscopic study revealed that the disease had metastasized to lungs and hilar lymph nodes. There was massive metastasis in the liver; the liver contained a large amount of iPTH. The results of these investigations suggest that (1) venous catheterization of the neck veins and the effluent blood from extraparathyroid tumors aid in identifying and localizing iPTH production; (2) primary benign hyperparathyroidism is not uncommon in patients with cancer, and its co-existence must be recognized; (3) high serum iPTH level in the superior vena cava may be found in patients with metastatic or primary cancer of the thoracic cavity; and (4) hyperparathyroidism may be the first hint of a familial multiple endocrine syndrome.
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PMID:Hypercalcemia in patients with known malignent disease. 96 5

Hypercalcemia as a complication of carcinoma of the colon is uncommon (1). It usually occurs in the presence of anorectal or rectal carcinoma that metastasizes to the lumbosacral vertebrae (2-4). Hypercalcemia complicating colon carcinoma in the absence of bone metastases--so-called humoral hypercalcemia of malignancy or paraneoplastic hypercalcemia--is rare. Only two such cases associated with adenocarcinoma of the colon (5,6) and two cases associated with adenosquamous carcinoma of the distal colon (rectum and sigmoid) (7) have been reported. We describe the first reported case of an adenosquamous carcinoma of the cecum and ascending colon that was accompanied by severe humoral hypercalcemia. The hypercalcemia was associated with a parathyroid hormone (PTH)-like substance.
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PMID:Humoral hypercalcemia complicating adenosquamous carcinoma of the proximal colon. 291 Jun 74

A rare adenosquamous carcinoma of the colon occurred in a 41-year-old patient. Its presentation with hypercalcemia, in the absence of osseous metastases, has not been described previously. The hypercalcemia in this case was due to the elaboration of a parathyroid hormone-like substance by the tumor. The general characteristics of primary adenosquamous and squamous cell carcinomas of the colon are presented. These tumors present with advanced disease, in younger patients, and follow a highly aggressive course, as compared with adenocarcinomas of the colon. The cause of the malignancies, in the light of current theories regarding their genesis, is discussed.
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PMID:Adenosquamous carcinoma of the colon presenting with hypercalcemia. 330 Sep 49

Parathyroid hormone-related protein (PTHrP) has been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. In addition to its hypercalcemic action, PTHrP has been implicated as an autocrine modulator of growth and differentiation, as well as an early response gene in some tissues. Several different types of tumors have been evaluated for the presence of PTHrP immunoreactivity. In the present study, we evaluated the expression of PTHrP by immunohistochemical staining in tissue samples from normal colorectal mucosa, polyps, and colorectal carcinoma removed from the same patients (n = 10 each). We have used a commercially available monoclonal antibody directed against epitopes between amino acids [53-64] which share no homology to parathyroid hormone (PTH). In normal colon, 94.3 per cent of the tissue samples were negative for PTHrP immunoreactivity. In polyps of the colon, only 22.6 per cent of the cells showed positive immunostaining, whereas 91.5 per cent of the samples from colon cancer stained positive for PTHrP. In the case of polyps, the intensity of staining was 1-3+; however, all of the samples from adenocarcinoma stained with 4+ intensity. In the positive samples, the immunoreactivity was present throughout the cytoplasm of the glandular epithelium. Omission of primary antibody, as well as substitution of the primary antibody by a negative control monoclonal antibody or non-immune rabbit serum, resulted in a negative reaction. All analyses were performed in duplicate, and the data have been presented as mean +/- SEM. Differences in normal polyps, carcinoma of the colon, and PTHrP expression were tested for statistical significance by student's t test. Our results show the expression of PTHrP is enhanced in colon cancer tissue as compared to normal colorectal mucosa and polyps. In addition, the expression appears to be greater in polyp than in normal colon. The role of PTHrP in the pathogenesis of colon cancer deserves further study.
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PMID:Parathyroid hormone-related protein expression in the human colon: immunohistochemical evaluation. 865 48

We present herein a case of sigmoid colon cancer associated with primary hyperparathyroidism (PHP). PHP is known to be associated with malignancy, and decreased intracolonic calcium (Ca) resulting from increased vitamin D (VD) levels may play a role in colorectal carcinogenesis. PHP was diagnosed in this patient by preoperative screening blood chemistry examination. The blood level of intact parathyroid hormone (PTH) was elevated and a parathyroid gland scintigram demonstrated abnormal uptake near the right lower lobe of the thyroid. There was no evidence of bone metastasis, and a sigmoid colectomy was performed with curative intent. The patient had an uneventful postoperative course without a critical elevation of the serum Ca level. This case report suggests that a relationship exists between PHP and colon cancer, and the possible mechanisms of this association are presented in our discussion.
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PMID:Sigmoid colon cancer associated with primary hyperparathyroidism: report of a case. 1048 59

Hypercalcemia is a well-known manifestation of paraneoplastic syndromes associated with a variety of malignancies. However, colon cancer has only rarely been associated with hypercalcemia of malignancy. We present the case of a patient with recurrent adenosquamous carcinoma of the ascending colon found to have hypercalcemia. The patient is a 76-year-old white woman who initially presented with colon cancer in the cecum and underwent a right hemicolectomy. All lymph nodes and surgical margins were free of tumor. Pathological examination at that time revealed adenosquamous carcinoma of the colon. Eight months later she complained of dizziness, anorexia, and constipation and was found to have a calcium level of 13.6 mg/dL. CT scan revealed a mass measuring 10.5 to 12.7 cm in the right hepatic lobe, and a bone scan was normal. Her intact parathyroid hormone (PTH) level was 6 pg/mL (normal 12-72) and her PTH-related protein (PTHrP) level was 25.7 pmol/L (normal <1.3). She then underwent a hepatic resection. The serum PTH, calcium, and PTHrP levels normalized after resection. Hypercalcemia of malignancy in colon cancer is rare and has an association with adenosquamous histology. The hypercalcemia is attributed to PTHrP, and here we demonstrate this in the serum and tumor specimens. The effects of PTHrP are shown to be short-lived postoperatively. We find only 14 other cases in the literature of hypercalcemia related to a colonic neoplasm, and this is the only patient reported to be surviving. The diagnosis of a paraneoplastic syndrome mediated via PTHrP should be considered when hypercalcemia is encountered in the setting of metastatic colon carcinoma.
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PMID:Paraneoplastic hypercalcemia in a patient with adenosquamous cancer of the colon. 1140 9

Humoral hypercalcemia is rarely associated with colon carcinoma; cutaneous metastases from colon carcinoma are also infrequent. To the authors' knowledge, no cases of colon carcinoma presenting with both hypercalcemia and cutaneous metastases have been reported to date. A case of advanced poorly differentiated colon carcinoma with neuroendocrine features with both humoral hypercalcemia of malignancy (HHM) and cutaneous metastases is presented. A poorly differentiated colon carcinoma with neuroendocrine features occurred in a 42-year-old patient with metastases to the liver, both femurs, left orbit, and scalp. The hypercalcemia was caused by the expression of a parathyroid hormone related peptide by both the primary and cutaneous metastatic tumors. Bisphosphonate treatment helped normalize serum calcium in a few days, but hypercalcemia recurred approximately 3 weeks later. Chemotherapy only mildly reduced the size of the cutaneous metastases. The patient died 8 months after initial diagnosis. To the authors' knowledge, the case presented in the current study is the first to be reported with both HHM and cutaneous metastases. Hypercalcemia and cutaneous metastases are separately associated with a poor prognosis and indicate advanced and widely metastatic disease. Although still unclear, the mechanism by which colon cancer causes cutaneous metastases and hypercalcemia, in light of current theories presented in the literature, is discussed.
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PMID:Poorly differentiated colon carcinoma with neuroendocrine features presenting with hypercalcemia and cutaneous metastases: case report and review of the literature. 1194 94

Interleukin (IL)-18 plays an important role in enhancing cellular immunity against cancer and bacteria. We constructed retroviral and adenoviral vectors that show improved secretion of bioactive murine IL-18 that could further enhance antitumor immunity in a murine model. Secretion of bioactive IL-18 was facilitated by fusing the leader sequences of prepro-parathyroid hormone (PTH) or IL-1 receptor antagonist (IL-1ra) to the 5; end of the mature murine IL-18 cDNA. Transfectants established by the retroviral vector carrying IL-1ra/IL-18 hybrid showed about 100-fold more IL-18 production and interferon (IFN)-gamma induction from splenocytes when compared with those carrying PTH/IL-18 hybrid. Repeated intraperitoneal injection of an adenoviral vector with IL-1ra/IL-18 hybrid ligated to IL-18 (Ad.IL-1ra.IL-18) successfully prevented establishment of human colon cancer cells in the abdominal cavity of mice. Treatment with Ad.IL-1ra.IL-18 was associated with significantly elevated levels of serum IL-18 and IFN- gamma. IL-18 administration also enhanced the cytostatic activity of peritoneal exudate cells against cancer cells. These improved viral vectors, which efficiently produce bioactive IL-18, could be used as a useful tool for cancer gene therapy.
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PMID:Construction and analysis of new vector systems with improved interleukin-18 secretion in a xenogeneic human tumor model. 1204 49

The parathyroid hormone (PTH) and some of its fragments and analogs stimulate bone growth in various animal models and humans and one of them (hPTH-(1-34)) has been approved by the USFDA for treating osteoporosis. However, there are reports that PTH can stimulate the PI-3 kinase/mitogen-activated protein kinases-mediated proliferation of rat enterocytes and that primary hyperparathyroidism in humans is associated with an increased incidence of colon cancer. Here we have investigated the ability of two PTH fragments, hPTH-(1-34)NH(2) and [Leu(27)]cyclo(Glu(22)-Lys(26))hPTH-(1-31)NH(2) to initiate colon carcinogenesis or increase the initiatory activity of the widely used colon carcinogen azoxymethane (AOM). The initiation of colon carcinogenesis by AOM was indicated by the very early appearance of aberrant crypt foci. While both PTH peptides strongly stimulated femoral bone formation, they did not cause the appearance of ACFs or affect the number or the distribution along the colon of AOM-induced ACFs. Nor did AOM affect the PTHs' ability to stimulate bone formation. Thus, a relatively short PTH treatment that is long enough to strongly stimulate bone formation does not initiate colon carcinogenesis in rats.
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PMID:The effects of parathyroid hormone fragments on bone formation and their lack of effects on the initiation of colon carcinogenesis in rats as indicated by preneoplastic aberrant crypt formation. 1456 63

Although exposure to ultraviolet light is often viewed as pathogenic owing to its role in the genesis of skin cancer and skin aging, there is growing epidemiological evidence that such exposure may decrease risk for a number of more serious cancers, may have a favorable impact on blood pressure and vascular health, and may help to prevent certain autoimmune disorders - in addition to its well-known influence on bone density. Most likely, these health benefits are reflective of improved vitamin D status. Increased synthesis or intake of vitamin D can be expected to down-regulate parathyroid hormone (PTH), and to increase autocrine synthesis of its active metabolite calcitriol in certain tissues; these effects, in turn, may impact cancer risk, vascular health, immune regulation, and bone density through a variety of mechanisms. Presumably, a truly adequate supplemental intake of vitamin D - manyfold higher than the grossly inadequate current RDA - could replicate the benefits of optimal UV exposure, without however damaging the skin. Diets moderately low in bioavailable phosphate - like many vegan diets - might be expected to have a complementary impact on disease risks, inasmuch as serum phosphate suppresses renal calcitriol synthesis while up-regulating that of PTH. A proviso is that the impact of dietary phosphorus on bone health is more equivocal than that of vitamin D. Increased intakes of calcium, on the other hand, down-regulate the production of both PTH and calcitriol - the latter effect may explain why the impact of dietary calcium on cancer risk (excepting colon cancer), hypertension, and autoimmunity is not clearly positive. An overview suggests that a vegan diet supplemented with high-dose vitamin D should increase both systemic and autocrine calcitriol production while suppressing PTH secretion, and thus should represent a highly effective way to achieve the wide-ranging health protection conferred by optimal UV exposure.
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PMID:A moderately low phosphate intake may provide health benefits analogous to those conferred by UV light - a further advantage of vegan diets. 1459 85


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