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)

We have prepared the map of regional distribution of cervical cancer in Hungary. Serial HPV genotyping of sexual partners provided evidence for the sexually transmitted infections. Molecular epidemiology studies revealed activating c-kit mutation in bilateral testicular cancers. A cost-effective molecular staging method was introduced to the management of breast cancer patients. Genomic profiling identified the gene signature of Herceptin and taxane sensitivity of breast cancer. In colon cancer patients we have determined the mutational spectrum of hMLH1 and hMSH2 genes in Hungary. The prognostic power of SHMT and MTHFR polymorphism was determined in colorectal cancer patients. In head and neck cancer the gene signature of cisplatin sensitivity and the EGFR polymorphism was determined. We have introduced a cost-effective in vitro assay to determine the drug resistance of pediatric leukemias. The prognostic power of N-myc genotyping was determined in neuroblastoma patients. A phase I trial for gene therapy of brain cancer was started by using a GM-CSF adenoviral vector system. Using global genomic approaches the gene signature of malignant melanoma and its metastatic disease was determined. We have found that Ca-channel blockers and EGFR tyrosine kinase inhibitors are effective in preclinical human melanoma models in breaking the apoptosis resistance of this tumor.
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PMID:[Activity of the National Oncology R&D Consortium in 2004]. 1590 26

ILEX Oncology is developing the dihydrofolate reductase inhibitor, piritrexim (discovered originally by Burroughs Wellcome), for the potential treatment of cancer. It is in phase II clinical trials for malignant fibrous histiocytoma. ILEX conducted phase II clinical trials in the US and Europe with piritrexim in bladder cancer patients; however, development for this indication was discontinued in the third quarter of 1998 due to lack of efficacy. The company also initiated phase III trials in early 1997 for the treatment of AIDS-related Kaposi's sarcoma, but no further development for this indication has been reported since that time. Piritrexim was discovered by Burroughs Wellcome, which conducted phase I and II clinical trials in more than 700 patients. Due to its potentially superior properties to those of methotrexate, it was expected that piritrexim would be active in certain methotrexate-resistant tumors. Tumor responses were noted in patients with advanced bladder cancer, Kaposi's sarcoma, colon cancer, melanoma, head and neck cancer and other cancer types. In published phase II studies, piritrexim demonstrated objective response rates ranging from 23 to 75% in patients with advanced bladder cancer who failed a standard first-line chemotherapy regimen. In March 1995, ILEX acquired an exclusive, worldwide license to patents held by Burroughs Wellcome covering the composition and use of piritrexim for all cancer indications. Under the terms of the agreement, ILEX paid a licensing fee and is obligated to pay Wellcome royalties on net sales of piritrexim. In December 1996, ILEX formed a joint venture with MPI Enterprises for the manufacture and marketing of piritrexim.
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PMID:Piritrexim (ILEX Oncology). 1611 90

The epidermal growth factor receptor (EGFR) promotes the growth of different cell types and has been implicated in tumorigenesis. The EGFR comprises a family of four structurally similar tyrosine kinases with a complex link to downstream signaling molecules that ultimately regulate key cell processes. Anti-EGFR agents have been developed as promising therapeutic anticancer targets, and some have been recently approved for the treatment of non-small-cell lung cancer and colon cancer. The two anti-EGFR therapies with the greatest clinical application are monoclonal antibodies that block the binding of ligands to EGFR and small-molecule tyrosine kinase inhibitors that inhibit the binding of adenosine triphosphate to the internal tyrosine kinase receptor of EGFR. We attempt to give an overview of the EGFR function and biology, focusing on the most important clinical findings and applications of EGFR inhibitors in lung and head and neck cancer.
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PMID:Targeting the epidermal growth factor receptor. Trials in head and neck and lung cancer. 1656 49

C. Heidelberger et al left great gifts to us. Approximately 50 years have elapsed since their discovery of 5-FU in 1957 before eventually elucidating the mechanisms by which the drug exerts its pharmacological actions and provokes its adverse reactions. Namely, 5-FU is a typical antimetabolite with strong time dependency, and continuous venous infusion(CVI) is considered to be its optimal regimen. The following facts may be mentioned to explain why such a long period of time has been spent to reach this level of research: 1) 5-FU, when administered to the living individual, is mostly inactivated by hepatic catabolic enzymes without delay and is then excreted in the urine, thus making it difficult to precisely analyze the relationship of blood 5-FU concentrations with concentration persistence, anticancer activity, and adverse reactions; and 2) unlike other anticancer agents, an antimetabolite 5-FU separately generates metabolites which show anticancer activity and adverse reactions, as well as metabolites which show adverse reactions only. For the last 30 years, we paid attention especially to 5-FU among chemotherapeutic agents for cancer and have sought for a long-lasting therapeutic modality which maintains quality of life of the patient and patient compliance by considering the balancing between its effects and adverse reactions. Consequently, we concretized an innovative therapeutic drug, TS-1 (S-1). We have a long history of research before developing S-1, which is represented by a series of investigations consisting in the developments of Futrafur (FT)--an oral anticancer agent of a 5-FU derivative (prodrug)-in 1970 subsequent to the above discovery of 5-FU, of UFT(FT: Ura=1 : 4) in 1976, and of S-1 in 1999. To date, we took the initiative in the world to devise S-1, the first self-rescuing concept(SRC)-based anticancer agent with dual actions, i.e., enhancement of pharmacological actions of 5-FU and reduction of its adverse reactions, by making use of the biochemical and enzymological properties of 5-FU and by combining FT, which is gradually converted to 5-FU in the body, with a 5-FU's effect-enhancing substance and a 5-FU's adverse reaction-reducing substance. S-1 is an oral anticancer agent in capsule, in which the following 2 modulators for 5-FU are combined to FT: one is CDHP(5-chloro-2,4-dihydroxypyridine) which increases blood concentrations and enhances pharmacological actions of 5-FU by potently inhibiting the degradation of 5-FU; and another is Oxo(potassium oxonate) which is localized in the mucosa of the gastrointestinal (GI) tract after oral administration and reduces GI toxicities provoked by 5-FU. S-1 is an oral anticancer agent in which these 3 components, FT, CDHP, and Oxo, are combined at a molar ratio of 1 : 0.4 : 1. Our conception to develop an SRC-based therapeutic drug and the preclinical concepts validated by numerous basic studies were demonstrated also in the clinical trials. In January 1999, S-1 was approved for the treatment of advanced and recurrent gastric cancers through the priority review system. From 2001 to 2005, S-1 was approved for the treatment of head and neck cancer, colon cancer, non-small cell lung cancer, and breast cancer. S-1 has been applied to acquire its expanded indications for the treatment of pancreatic cancer and biliary tract cancer. We are confident that the combined regimen of S-1 with other anticancer agents and with other therapeutic modalities will contribute to the routine medical practice of cancer treatment in the future.
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PMID:[Timeline from discovery of 5-FU to development of an oral anticancer agent S-1 and its drug concept]. 1689 67

Human papilloma viruses (HPVs) are the main tumor viruses in humans and have been identified in gynecological malignancies, especially carcinomas of the uterine cervix and their precursor lesions. In addition, they are frequently observed in other anogenital tumors such as vulva/vagina, anal and penis carcinoma. Furthermore, the potential association with head and neck cancer, in particular tonsillar carcinoma, is now well documented. However, there are controversial reports on the detection of HPV in various other tumors; these are summarized in the present report. Data revealed that apart from the heart and the kidney, the virus has been found in all other organs that have been analyzed so far, i.e., prostate, urinary bladder, oral cavity, larynx, esophagus, stomach, colon, liver, vagina/vulva, endometrium, ovary, breast, penis, anus, skin, and lung. Some of the detection rates are remarkable, e.g., colon cancer up to 97%, lung cancer 80%, and breast cancer 74%. They point to geographical differences in the incidence of HPV in different populations, but also highlight the need for validation of the results. HPV is nevertheless an important biomarker in molecular tumor diagnostics. Firstly, it is useful for the differentiation of a secondary squamous cell carcinoma from a metastasis. Secondly, HPV-positive carcinomas not only have a distinct etiology but also a particular morphological phenotype. Overall, they are characterized by different tumor biology, such as, for example, increased sensitivity to radiotherapy.
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PMID:[HPV in non-gynecological tumors]. 1903 15

Tyrosine kinase inhibitors (TKI) or monoclonal antibodies targeting EGFR, HER2 or VEGFR receptors have demonstrated substantial clinical benefit in patients with advanced breast cancer, colon cancer, head and neck cancer, non-small cell lung cancer, and renal cell carcinoma. Nevertheless, these drugs have some target related adverse effects, particularly cardiovascular toxicities. We report here the case of a patient included in a phase I trial of a new compound, a tyrosine kinase inhibitor targeting HER1, HER2, HER4 and VEGFR2. The patient developed during this treatment an acute and transient left ventricular systolic dysfunction. Careful management of this adverse effect allowed the patient to continue therapy and to achieve a major partial response.
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PMID:Acute left ventricular dysfunction induced by a panHER and VEGFR tyrosine kinase inhibitor in a phase I trial. 1939

Colorectal cancer is the second most frequent cause of death among malignant diseases. The mortality of head and neck cancer in Hungary increased by 265 percent in the last thirty years. Both malignancies belong to the most current public health problems in Hungary. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. In case of head and neck cancer the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 gene were analyzed. Intraoperative removed tissue samples were processed and cancer free human samples were used as matched controls. The formalin fixed samples were deparaffinized and digested with proteinase K. Genotyping was performed by PCR amplification, and in case of head and neck cancer a PCR-RFLP method was applied. No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant difference in survival was found between the GSTM1 and p53 gene variants in Dukes'B stage colorectal patients. The survival difference among the XRCC1 194 alleles by head and neck patients in clinical stage III proved to be also significant. The complex analysis of this type of genetic variants may be the future way of the personal risk assessment and the real chance for personal therapy.
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PMID:[Genetic polymorphism in patients with colorectal and with head and neck cancer]. 1964 19

It is not uncommon to find two or more tumors in the same patient, usually based on similar etiologic factors or the use of radiotherapy and/or chemotherapy. This occurs quite often in the case of lung cancer. In this sense, the positron emission tomography with (18)F-FDG (FDG-PET) is widely used for the diagnosis and treatment of cancer patients. It is also especially useful in patients with solitary pulmonary nodule, bronchogenic carcinoma, head and neck cancer, colon cancer, tumors of unknown origin, lymphomas, etc. Its capacity to detect previously unsuspected second or third primary tumors has also been demonstrated. We report a clinical case showing how two synchronous cancers were incidentally detected in a 73-year old patient diagnosed with lung cancer and referred for (FDG-PET) study.
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PMID:[A colon adenocarcinoma and a pharyngeal carcinoma incidentally detected by means of (18)F-FDG PET in a patient diagnosed of lung cancer]. 1996 92

Head and neck cancers are known to synthesize arachidonic acid metabolites. Interfering with arachidonic acid metabolism may inhibit growth and invasiveness of cancer cells. In this study we investigate effects of sulindac (the non-selective COX inhibitor), aspirin (the irreversible, preferential COX-1 inhibitor), NS-398 (the selective COX-2 inhibitor), NDGA (nordihydroguaiaretic acid, the selective LOX inhibitor) and ETYA (5,8,11,14-eicosatetraynoic acid, the COX and LOX inhibitor) on cell viability, MMP-2 and MMP-9 activities, and in vitro invasion of cancer cells derived from primary and metastatic head and neck, and colon cancers. The inhibitors of COX and/or LOX could inhibit cell proliferation, MMP activity and invasion in head and neck and colon cancer cells. However, the inhibitory effect was obviously observed in colon cancer cells. Inhibition of arachidonic acid metabolism caused a decrease in cancer cell motility, which partially explained by the inhibition of MMPs. Therefore, COX and LOX pathways play important roles in head and neck cancer cell growth.
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PMID:Inhibition of arachidonic acid metabolism decreases tumor cell invasion and matrix metalloproteinase expression. 2065 27

Single-nucleotide polymorphisms in genes involved in DNA-damage-induced responses are reported frequently to be a risk factor in various cancer types. Here we analysed polymorphisms in 5 genes involved in DNA repair (XPD Asp312Asn and Lys751Gln, XRCC1 Arg399Gln, APE1 Asp148Glu, NBS1 Glu185Gln, and XPA G-4A) and in a gene involved in regulation of the cell-cycle (CCND1 A870G). We compared their frequencies in groups of colon, head and neck, and breast cancer patients, and 2 healthy control groups: (1) matched healthy Polish individuals and (2) a NCBI database control group. Highly significant differences in the distribution of genotypes of the APE1, XRCC1 and CCND1 genes were found between colon cancer patients and healthy individuals. The 148Asp APE1 allele and the 399Gln XRCC1 allele apparently increased the risk of colon cancer (OR = 1.9-2.3 and OR = 1.5-2.1, respectively). Additionally, frequencies of XPD genotypes differed between healthy controls and patients with colon or head and neck cancer. Importantly, no differences in the distribution of these polymorphisms were found between healthy controls and breast cancer patients. The data clearly indicate that the risk of colon cancer is associated with single-nucleotide polymorphism in genes involved in base-excision repair and DNA-damage-induced responses.
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PMID:Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population. 2072 Mar 10


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