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)

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

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

PTH-related peptide (PTHrP) is the major factor responsible for humoral hypercalcemia of malignancy. This paraneoplastic syndrome has been described in association with a number of malignancies, but rarely with carcinoma of the colon. Moreover, little is known about the molecular mechanisms that underlie PTHrP overexpression in tumors. Here we report a patient who presented with hypercalcemia 6 months after resection of a neuroendocrine colonic carcinoma (tumor I). At the time of admission, intact PTH was decreased, circulating PTHrP levels were elevated, and there was tumor recurrence (tumor II). Immunohistochemical staining of paraffin-embedded sections from tumor I did not stain for PTHrP, whereas cells from tumor II stained intensely positive. Southern blot analysis and differential PCR of genomic DNAs from tumor specimens and the patient's leukocytes demonstrated amplification of the PTHrP gene in tumor II. Moreover, staining for p53 protein was evident in tumor II, but not in tumor I, consistent with the presence of a mutant form of p53 and associated loss of tumor suppressor function in the recurrent tumor. PTHrP gene amplification was also detected in one of five other tumors associated with humoral hypercalcemia of malignancy. These findings suggest that a potential mechanism contributing to PTHrP overexpression in malignancies is gene amplification, which could arise from increased genomic instability associated with the progressive stages of neoplasia.
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PMID:Amplification of the parathyroid hormone-related peptide gene in a colonic carcinoma. 876 40

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

The present experiments examined the potential ability of parathyroid hormone-related protein (PTHrP) to influence growth of the human colon cancer cell HT-29 and the ability of the cell to adhere to several extracellular matrix (ECM) proteins found in normal tissues. Addition of PTHrP analogs, PTHrP (1-34), PTHrP (67-86), or PTHrP (107-139), to HT-29 cells in culture did not influence cell growth or the adhesion of the cells to wells coated with fibronectin, laminin, or collagen type I. Likewise, in HT-29 cells induced to overexpress PTHrP by stable transfection with PTHrP cDNA, compared to vector-transfected control HT-29 cells, no effect on cell growth occurred. However, in the transfected cells, the increased production of PTHrP significantly enhanced cell adhesion to type I collagen but not to fibronectin or laminin. The results raise the possibility that PTHrP might play a role in colon tumor invasion and metastasis by influencing cell adhesion to specific extracellular matrix proteins.
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PMID:Parathyroid hormone-related protein overexpression in the human colon cancer cell line HT-29 enhances adhesion of the cells to collagen type I. 1149 75

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

Parathyroid hormone-related protein (PTHrP) has been localized in human colon cancer tissue and cell lines. Tumor cell adhesion to extracellular matrix (ECM) proteins plays a major role in the invasion and metastasis of tumor cells, and is mediated via integrin subunits. The LoVo human colon cancer cell line was used as a model system to study the effects of PTHrP on cell proliferation and adhesion to ECM proteins found in normal liver. Clones of LoVo cells engineered to overexpress PTHrP by stable transfection with a PTHrP cDNA showed enhanced cell proliferation vs. control (empty vector-transfected) cells. PTHrP-overexpressing cells also showed significantly higher adhesion to collagen type I, fibronectin, and laminin, and enhanced expression of the [symbol: see text] integrin subunits. These results indicate that PTHrP may play a role in colon cancer invasion and metastasis by increasing cell proliferation and adhesion to the ECM via upregulation of proinvasive integrin expression.
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PMID:PTH-related protein enhances LoVo colon cancer cell proliferation, adhesion, and integrin expression. 1558 9

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. Here we present the first case of adenosquamous carcinoma of the sigmoid colon in a patient who was found to have hypercalcemia associated with parathyroid hormone-related protein (PTHrP), with no radiological evidence of metastasis to other organs. A 78-year-old woman was admitted to our hospital complaining of lower abdominal pain. Physical examination and computed tomography revealed a tumor, 13 cm in diameter, in the sigmoid colon. Laboratory data showed an elevated serum calcium level (11.2 mg/dl). Primary colostomy was performed. After the primary operation, the patient was found to have hypercalcemia and an elevated PTHrP level. We performed sigmoidectomy, total hysterectomy, and partial urinary bladder resection 1 month after the primary operation, and both PTHrP and calcium levels immediately returned to normal. The histopathologic diagnosis was poorly differentiated adenosquamous carcinoma. The patient died due to tumor recurrence 4 months after the second surgery.
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PMID:Paraneoplastic hypercalcemia with adenosquamous carcinoma of the colon. 1586 2

Parathyroid hormone-related protein (PTHrP) has been localized in human colon cancer tissue and cell lines. We have previously shown that PTHrP increases colon cancer cell proliferation, extracellular matrix adhesion, and cell-surface integrin alpha6beta4 expression. Since cancer cell migration, invasion, and survival are crucial components of metastasis, and colon cancer has a high metastatic potential, in this study we used the human colon cancer cell line LoVo as a model system to study the effects of PTHrP on these parameters. PTHrP expression was modulated by stable transfection with a construct expressing PTHrP (-36 to +139). We report that PTHrP increases cell migration, invasion, and survival. PTHrP altered cell morphology, with PTHrP-overexpressing cells exhibiting increased spreading and several long protrusions. PTHrP also increased the steady-state mRNA levels of the integrin alpha6 and beta4 subunits, indicating a direct and/or indirect effect of PTHrP on the transcriptional and/or post-transcriptional regulation of integrin alpha6 and beta4 expression. Integrin alpha6beta4 activates the phosphoinositol 3-kinase (PI3-K)/Akt pathway, leading to glycogen synthase kinase-3 (GSK-3) deactivation. PTHrP overexpression also led to an increase in active Akt and inactive GSK-3 levels, indicating that the PTHrP-mediated upregulation of integrin alpha6beta4 expression may activate the PI3-K pathway, resulting in increased cell survival, migration and invasion.
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PMID:Increased cell survival, migration, invasion, and Akt expression in PTHrP-overexpressing LoVo colon cancer cell lines. 1727 26

Increasing evidence is emerging highlighting the role of parathyroid hormone-related protein (PTHrP) during metastasis by regulating cell adhesion. The current study demonstrated that modulation of PTHrP expression by PTHrP overexpression and small interfering RNA-induced silencing resulted in changes in cell adhesion and integrin expression. RNA interference of endogenous PTHrP caused a significant reduction in cell adhesion of a breast cancer cell line to collagen type I, fibronectin and laminin (P<0.05) and of a colon cancer cell to collagen type I and fibronectin (P<0.05). Overexpression of PTHrP induced a significant increase in cell adhesion of colon (P<0.0001) and breast (P<0.05) cancer cells to the same extracellular matrix proteins. These PTHrP-mediated effects were attributed to changes in integrin expression as the differences in adhesion profile correlated with the integrin expression profile. In an attempt to elucidate the mechanism whereby PTHrP regulates integrin expression, promoter activity of the integrin alpha5 subunit was analysed and significant increases in transcriptional activity were observed in PTHrP overexpressing cells (P<0.0001), which was dependent on nuclear localisation. These results indicate that modulation of cell adhesion is a normal physiological action of PTHrP, mediated by increasing integrin gene transcription.
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PMID:PTHrP increases transcriptional activity of the integrin subunit alpha5. 1740 57


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