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)

The CHK2 gene encodes a protein kinase that is important for the regulation of cell cycle arrest after DNA damage. CHK2 acts downstream of ataxia teleangiecstasia mutated (ATM), modulates the function of p53 and may help mediate cell cycle arrest at G2/M by phosphorylation of Cdc25C. Recently, the human homolog of the checkpoint kinase Cds1 (CHK2) has been suggested to be a tumor suppressor gene. Heterozygous germline mutations have been reported in Li-Fraumeni syndrome (LFS), a highly penetrant familial cancer phenotype, and in sporadic colon cancer. LFS is associated with the development of lymphoid malignancies, especially childhood ALL. Therefore, we analyzed the DNA from 143 lymphoid malignancies to determine whether they had mutations of the CHK2 gene. The 14 exons of CHK2 were studied by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing of aberrantly migrating bands. One missense mutation changing serine to phenylalanine (codon 428) in an evolutionarily highly conserved domain was found in a non-Hodgkin's aggressive lymphoma. Another point mutation in the non-coding region was identified in one of adult T-cell leukemias (ATL) samples. This result suggests that mutation of the CHK2 gene may rarely be involved in the development of selected lymphomas.
Leuk Lymphoma 2001 Jul
PMID:Analysis of the CHK2 gene in lymphoid malignancies. 1169 18

Mutations in TP53 occur in more than 50% of the lung cancer patients and are associated with an increased resistance to chemotherapy and radiotherapy. The human lung adenocarcinoma cell lines A549 and LXSN contain a wild-type TP53 and were growth arrested at both the G(1)- and G(2)-phase checkpoints after irradiation. However, a TP53-disrupted cell line, E6, was arrested only at the G(2)-phase checkpoint. UCN-01 (7-hydroxystaurosporine), a CHEK1 inhibitor that abrogates the G(2) block, has been reported to enhance radiation toxicity in human lymphoma and colon cancer cell lines. In this study, UCN-01 preferentially enhanced the radiosensitivity of the TP53-disrupted E6 cells compared to the TP53 wild-type cells. This effect was more pronounced in cells synchronized in early G(1) phase, where the E6 cells showed a higher resistance to radiation in the absence of drug. These results indicate that the combination of UCN-01 and radiation can more specifically target resistant TP53 mutated cancer cells and spare TP53 wild-type normal cells.
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PMID:7-Hydroxystaurosporine (UCN-01) preferentially sensitizes cells with a disrupted TP53 to gamma radiation in lung cancer cell lines. 1207 7

Positron emission tomography (PET) with [18F]-fluorodeoxyglucose (FDG) is a tool for the imaging and evaluation of glucose metabolism. This technique has recently become available in more than thirty hospitals and has been approved under Japan's national health insurance program. FDG uptake correlates with glucose utilization in tissue and is widely used for evaluating malignant tumors as well as brain function and myocardial viability. FDG-PET is useful for the diagnosis of lung cancer, colon cancer, esophageal cancer, malignant lymphoma, malignant melanoma, head and neck cancer, myocardial viability, and epileptic focus. A brief summary of the application and utility of FDG-PET for esophageal carcinoma is described in this article. Because of its limited spatial resolution, FDG-PET is not able to evaluate the invasiveness of primary tumors and small lesions. However, the uptake of FDG correlates with the aggressiveness of the tumor and the prognosis of patients with esophageal carcinoma. The sensitivity, specificity, and accuracy of lymph node staging is higher than that with CT. FDG-PET has the advantage of being able to detect distant metastases on a single occasion. Evaluation of the response to therapy and of recurrence is also possible by means of FDG-PET. There is some normal uptake and physiological distribution of FDG in many organs. Physiological status has an effect on the uptake of FDG in normal organs, and, consequently, on lesion uptake. Understanding of these characteristics makes this procedure a useful diagnostic modality for the management of patients with esophageal carcinoma.
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PMID:[Current status of nuclear medicine. Clinical application of FDG-PET for cancer diagnosis. Esophageal cancer]. 1207 32

Anemia is common in patients with cancer and is a frequent complication of myelosuppressive chemotherapy. In this study, we investigated the incidence and severity of chemotherapy-induced anemia caused by the most common chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults. Five hundred fifty-two patients with histologically proven carcinoma originating from breast (n = 165), lung (n = 128), colon (n = 75), ovary (n = 84), and malignant lymphoma (n = 100) were included in this study. Hemoglobin levels for each patient were measured with an automatic counter during both pretreatment and before each chemotherapy cycle during therapy. To document the incidence of anemia, the National Cancer Institute grading system was used. Before chemotherapy, 44% of patients with breast carcinoma had anemia. There was a 16% increase in the incidence of anemia after chemotherapy. Severe anemia was observed in less than 1% of patients. No difference was found in the incidence of anemia between the fluorouracil, doxorubicin, cyclophosphamide (FAC) and cyclophosphamide, methotrexate, fluorouracil (CMF) regimens used in the adjuvant setting. However, single-agent chemotherapy with newer generation caused more anemia when compared with the FAC regimen (p < 0.005). Chemotherapy resulted in a significant decrease in hemoglobin levels when compared with pretreatment values in patients with lung cancer (p < 0.001). During treatment, the increase in the incidence of grade II anemia was associated with a parallel decrease in the incidence of grade I anemia. The incidence of severe anemia did not exceed 15%. The incidence of anemia was equivalent in both patients with small-cell lung cancer and those with non-small-cell lung cancer treated with the etoposide and cisplatin (EP) combination. Seventy-one percent of patients with colon cancer had anemia before initiation of chemotherapy. No difference was observed in posttreatment hemoglobin values compared with pretreatment values. Patients treated with irinotecan and fluorouracil and leucovorin (FUFA) combination showed similar rates of anemia. Incidence of anemia in patients with ovarian cancer at admission was 68%. Chemotherapy resulted in a prominent increase in incidence of anemia, which increased to 91.5%. There was an increase in grade II anemia, which corresponded to the decrease in grade I anemia. Less than 10% of patients developed severe anemia. No difference in the incidence of anemia was observed in patients with ovarian cancer treated with either cisplatin and cyclophosphamide or cisplatin combination. Showing a high incidence of anemia (82%) at presentation, hemoglobin levels in patients with malignant lymphoma were unaltered with chemotherapy. Severe anemia occurred in less than 3% of patients. There was a higher incidence of anemia in patients with non-Hodgkin's lymphoma receiving the cyclophosphamide, epirubicin, vincristine, prednisone (CEOP) regimen in contrast to patients with Hodgkin's lymphoma treated with the doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) combination. There was a prominent decline in the hemoglobin levels with cisplatin-based combinations in contrast to combinations including noncisplatin agents (p < 0.001). In this study, we have observed equivalent rates of treatment-related anemia when compared with previous data in patients with specific tumor types. The incidence of pretreatment anemia was high in various malignancies. The mechanisms underlying the propensity for a higher risk of pretreatment anemia in patients with malignant disorders and its influence on the outcome has to be elucidated by further population-based and molecular studies.
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PMID:Anemia in oncology practice: relation to diseases and their therapies. 1215 68

Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant disorder featuring familial clustering of colorectal and/or endometrial cancer, and other malignancies. Except for a rare case report, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) have not been considered part of HNPCC. Recent murine models for HNPCC have shown an increased incidence of B- and T-cell lymphoma, as well as tumors of the gastrointestinal tract and other organ systems, involving defects in genes resulting in faulty mismatch repair (MMR) of DNA. These MMR genes include MLH1, MSH2, MSH3, MSH6, PMS1 and PMS2. We sought to analyze the occurrence of NHL and HD in families with clusters of colorectal cancers (CRC). Probands from 21 kindreds were classified as HNPCC (3), HNPCC-like (5), and HNPCC-variant (13); seen and followed by Clinical Genetics at Memorial Hospital the kindreds were assessed for the occurrence of NHL or HD. Of the 21 pedigrees, a total of 37 patients were identified who were diagnosed with leukemia, lymphoma, or HD. Fourteen of the 37 patients with a diagnosis of NHL or HD were further classified and showed varying histologies ranging from chronic lymphocytic leukemia/small lymphocytic lymphoma (2), mycosis fungoides (1), follicular lymphoma (1), extranodal marginal zone lymphoma of MALT type (2), diffuse large B-cell lymphoma (4), nodular sclerosis HD (3), and mixed cellularity HD (1). Microsatellite instability studies were performed on 6 cases but none showed evidence of replication error repair defects. Immunohistochemical stains performed on paraffin sections from these 6 representative cases showed differential protein expression of MLH1, MSH2, MSH6, and PMS2 when compared to normal reactive tissues from the same patient but showed no significant differences when compared to controls of non-familial, sporadic lymphomas. These results suggest that lymphomas arising in the setting of familial CRC do not bear the molecular hallmarks of HNPCC. Further studies are needed to explain the differential patterns of expression of RER-associated proteins in lymphomas, as well as the association of lymphomas and possibly renal cell cancers in a subset of kindreds in which CRC clustering is evident.
Leuk Lymphoma 2002 Aug
PMID:Analysis of mismatch repair defects in the familial occurrence of lymphoma and colorectal cancer. 1240 Jun 5

A variety of malignant complications occur in Crohn's disease, and previous studies have recorded an increased intestinal cancer risk. The present investigation tabulated myeloid and lymphoid malignancies compared with intestinal cancers in 1000 consecutively evaluated patients with Crohn's disease who were followed over an extended period by a single clinician. Myeloid and lymphoid neoplasms were present in 0.5% of patients, while cancer in the intestinal tract was detected in 1%. Most of these patients with a malignancy had Crohn's disease for a prolonged period of more than 20 years and had negative outcomes, including death or presentations with advanced disease. In this cohort, lymphoma was not detected in a single patient after definition of Crohn's disease, possibly reflecting the limited use of immunosuppressives or infused biological agents in this clinical practice. Bypassed rectal 'stumps' were associated with subsequent colorectal cancer in half of all males with colon cancer in this series, suggesting an important risk factor following colectomy in Crohn's disease. Epithelial dysplasia was detected in only a single male patient before colorectal cancer, implying that this histopathological marker may be a poor predictor of subsequent colon cancer development in Crohn's disease, an inflammatory bowel disease process that is typically patchy or focal in distribution in the intestinal tract.
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PMID:Tabulation of myeloid, lymphoid and intestinal malignancies in Crohn's disease. 1246 71

Between 1990 and 2001, altogether 28 new anticancer drugs were approved for use in Israel. The new agents include cytotoxic drugs, biologic compounds, and hormone therapies. Among the cytotoxic agents introduced, the taxanes, vinorelbine, gemcitabine, irinotecan, topotecan and temozolomide, represent important new drugs active in a range of solid malignancies including lung, breast, ovarian, bladder, pancreatic, and colon cancer as well as brain tumors. Epirubicin, idarubicin, and liposomal doxorubicin offer less toxic and in some instances more effective alternatives to older anthracylines for leukemia, breast cancer, ovarian cancer and other diseases. New oral agents are offering a chance for disease palliation without the need for burdensome intravenous access. Rituximab and trastuzumab have introduced monoclonal antibody therapy to the clinic, substantially improving the treatment of patients with lymphoma and breast cancer, respectively. The first tyrosine kinase inhibitor, a molecularly targeted therapy, imatinib, was approved for use in chronic myeloid leukemia and has also shown remarkable activity in gastrointestinal stromal tumors. A variety of aromatase inhibitors have provided less toxic and more effective hormone therapy for the treatment of breast cancer. The challenge for clinicians is to optimize the use of the new available agents for their patients' benefit, and the challenge for health policy-makers in Israel is to integrate the new anticancer pharmaceuticals into the basic health benefits package mandated for all citizens.
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PMID:New drugs for the treatment of cancer, 1990-2001. 1251 6

Ultrasonography (US) is often the first imaging study performed in patients with abdominal pain or vague symptoms related to the gastrointestinal tract. An awareness of the US appearances of diseases of the intestine is essential to achieve the proper diagnosis and to enable appropriate triage of cases. Pathologic processes that affect the intestine generally result in decreased peristalsis and bowel wall thickening, both of which tend to decrease the luminal gas content. These changes permit evaluation of the intestine and surrounding structures with transabdominal and transvaginal US. US is useful in diagnosis of infectious and inflammatory conditions, such as appendicitis, Crohn disease, diverticulitis, epiploic appendagitis, pseudomembranous colitis, small bowel obstruction, small bowel vasculitis, and celiac disease. US is also helpful in diagnosis of tumors, such as gastric cancer, bowel lymphoma, and colon cancer. Familiarity with the US appearances of diseases that affect the intestine may allow specific diagnosis based on the degree and distribution of bowel wall thickening and associated changes of the perienteric tissues.
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PMID:US of gastrointestinal tract abnormalities with CT correlation. 1253 41

Murine tumor models are potent tools for cancer studies, most of which make use of a limited number of murine tumor cell lines that are exchanged by many research groups around the world. Although cross-contamination and in vitro karyotypic progression are well-known risks with respect to the identity of tumor cell lines, these parameters are rarely evaluated. Notably, routine karyotyping of murine cell lines is laborious and technically demanding because mouse chromosomes are morphologically similar. We therefore used a 21-color fluorescence in situ hybridization (FISH) approach (COBRA) for screening two groups of frequently used murine tumor cell lines, each of which shares known immunologic determinants. Multicolor analysis revealed that the sharing of immunologic determinants among three murine lymphoma cell lines (EL-4, MBL-2, and RBL-5) is directly related to their common origin. In several of the cell lines, the chromosomal derivatives had rearranged further, suggesting that the cross-contamination events were not recent. In contrast, karyotypic analysis of three murine colon cancer cell lines (C26, CC36, and C51) showed that these constituted independent tumor clones despite the sharing of immunologic determinants. Our data point out that cross-contamination and in vitro evolution of murine tumor cell lines are a common phenomenon, and that multicolor FISH analysis is an efficient tool for verifying the origin and tracking the evolution of murine cell lines.
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PMID:Application of multicolor fluorescence in situ hybridization analysis for detection of cross-contamination and in vitro progression in commonly used murine tumor cell lines. 1255 Jul 72

Computed tomography (CT) remains the optimal imaging modality for diagnosing tumors in the mesentery. Although primary neoplasms arising from the mesenchymal tissues of the mesentery are rare, the small bowel mesentery is a major avenue for the dissemination of tumor within the peritoneal cavity. Tumors spread to the mesentery by four major routes: (a) direct extension, commonly seen with carcinoid tumor of the small intestine as well as intraabdominal cancers such as pancreatic and colon cancer; (b) lymphatic dissemination of lymphoma and some epithelial malignancies; (c) hematogenic spread resulting in embolic metastases to the small intestinal wall, usually seen in melanoma and breast cancer; and (d) seeding through the peritoneum from ovarian and gastrointestinal malignancies as well as some lymphomas. Although percutaneous imaging-guided or surgical biopsy is often necessary to guide management, analysis of CT features along with the clinical history may be useful in differentiating mesenteric tumors from infectious, inflammatory, or vascular processes affecting the mesentery. The article presents the characteristic appearances of primary and secondary mesenteric neoplasms at CT and offers a rational approach to the differential diagnosis of mesenteric masses depicted at CT.
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PMID:Mesenteric neoplasms: CT appearances of primary and secondary tumors and differential diagnosis. 1264 Jan 60


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