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)

Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a camptothecin analog, is a novel and specific inhibitor of the nuclear enzyme topoisomerase I. In preclinical studies, topotecan demonstrated significant in vitro activity in a variety of solid tumor explants derived from colorectal, breast, ovarian, renal cell, non-small cell lung cancer, and gastrointestinal sources. Notable activity was also demonstrated in vivo in a wide range of animal tumor models. A large number of phase I studies with topotecan have been conducted since 1992 in both adults and children with a broad range of refractory malignancies and as many as 14 different dosing schedules. Complete, partial, or minor responses were demonstrated in patients with recurrent or refractory neuroblastoma, non-small cell lung cancer, small cell lung cancer, ovarian cancer, breast cancer, colon cancer, esophageal cancer, renal cell carcinoma, and squamous cell carcinoma. The antitumor activity of topotecan in these phase I evaluations was associated more often with frequent or continuous dosing schedules compared with less frequent or short exposure schedules. Maximum tolerated doses were predominantly dependent on the dosing schedule used. Myelosuppression was the major dose-limiting toxicity across all schedules, and nonhematologic toxicities were generally mild. Data from phase I studies have provided valuable information about antitumor responses, maximum tolerated doses, and dose-limiting toxicities associated with different dosing schedules. Based on this information, there was substantial enthusiasm for further evaluating topotecan in a wide range of cancer patients in phase II studies.
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PMID:Review of phase I clinical studies with topotecan. 942 56

We have been investigating the mathematical nature of intercancer linkage that underlies the mutual regulation of cancer risks between any 2 tumors in their variations in time and space. Applications of both sequential regression test and topological manipulation of age-adjusted incidence rate (AAIR) data set enabled us to prepare the oncogene (Onc) activation profile and the tumor suppressor gene (TSG) inactivation profile for each tumor. The purpose of this study was to investigate the relation between the changes of 2 cancer gene profiles and the sex discrimination of cancer risk in 7 human neoplasias. Results obtained are as follows: i) The sex discrimination of cancer risk could better be defined by the use of log-transformed AAIR data rather than of untransformed AAIR data. ii) The sex discrimination of cancer risk, as calculated with the AAIR data of 47 population units of the world, is as follows: a) breast cancer (Br), M:F=1:120.2; b) thyroid cancer (Thy), M:F=1:2. 64; c) colon cancer (Co), M:F=1.18:1; d) liver cancer (Li), M:F=2. 63:1; e) lung cancer (Lu), M:F=3.66:1; f) esophageal cancer (Eso), M:F=3.68:1; g) laryngeal cancer (Lar), M:F=7.26:1. iii) Female-dominant cancers were associated with inversion (Br) or defectiveness (Thy) of male oncogene profile, whereas male-dominant cancers were associated with inversion (Lar) or defectiveness (Li, Lu and Eso) of female Onc profiles. Sex-indifferent cancer, Co, was distinguished from other tumors by the emergence of defectiveness in the TSG profiles of both sexes. TSG defectiveness was also detectable in female (Br, Thy) and bisexual (Lu) tumors. iv) The Onc vs TSG interaction, as assessed in terms of r value of the reciprocal regression analysis, was increasing in its positivity rate from the top of the female-dominant family (Br) through the sex-indifferent tumor (Co) to the bottom of the male-dominant family (Lar). In conclusion, the emergence of sex discrimination of cancer risk was positively correlated to the extent of integrity of oncogene activation in the dominant gender relative to the recessive gender. Findings with 6 sex-discriminant tumors are discussed in their relevancy to tumorigenesis from the point of view of endocrinological epidemiology.
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PMID:Relation between the changes of oncogene versus tumor suppressor gene interaction and the transition of cancer risk from female dominance through no sex discrimination to male dominance, as investigated by the reciprocal regression analysis of 5 human neoplasias. 968 28

In surgery, deep-seated fungal infection is not rare. In our institute, fungal infection was analyzed during postoperative periods. As pathogen, fungus was the second frequent pathogen after the operations for esophageal cancer and gastric cancer, and the third pathogen after hepatobiliopancreatic cancer and colon cancer. Furthermore, fungus was found more frequently pathogen from distant infection than that from local foci. Especially in CV catheter sepsis, fungus was main pathogen (60 %). In order to inhibit CV catheter sepsis, nutrition support team (NST) has been induced in our institute for prevention of external pathway of fungus. After NST, the frequency of CV catheter sepsis decreased from 12 % to 3.6 %, and the isolated frequency of fungus in catheter sepsis patients also decreased from 84 % to 16 %, respectively. It demonstrates that the activity of NST successfully prevents the external pathway of fungus in CV catheter indwelling patients. However, internal pathway (fungal translocation) still remains, and that issue has to be overcome. Molecular biological technique was applied for diagnosis of fungemia. PCR-RFLPs was performed by using specific primer of 18s rRNA in V4 region. Clinical samples were applied for PCR-RFLPs, and antifungal therapy was performed according as the results of PCR-RFLPs. It indicated that molecular biological technique was useful for diagnosis of fungemia.
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PMID:[Deep-seated fungal infection in surgery]. 979 64

Researchers have investigated green tea as a potential protectant against cancer. This review focuses on studies of green tea in humans. Green tea contains polyphenols, chemicals that act as powerful antioxidants. Epidemiological and human studies have shown varying results. Thirty-one human studies and four reviews were examined. Among five studies reporting on colon cancer, three found an inverse association and one reported a positive association. For rectal cancer, only one of four studies reported an inverse association; increased risks were seen in two of the studies. An inverse association is suggested for urinary bladder cancer in two of two studies. Of 10 studies examining the association of green tea and stomach cancer, 6 suggest an inverse and 3 a positive association. The most comprehensive of these studies supports an inverse association of green tea and stomach cancer. Pancreatic cancer studies hint at an inverse association in two of three studies. A strong inverse effect was found with green tea and esophageal cancer. Lung cancer studies have shown an inverse effect with Okinawan tea, yet tentatively increased risk was shown in another study. Although human studies have their limitations, the research has warranted a further look into the effects of green tea and cancer.
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PMID:Green tea and cancer in humans: a review of the literature. 979 66

In various types of human malignant tumors, the presence or absence of expression of apoptosis-associated gene products (p53 protein and Bcl-2 protein) and the tumor proliferation activity-related factor (Ki-67) was assessed by immunohistochemical staining and the correlation between this expression and chemosensitivity to anticancer drugs was investigated. Study subjects comprised 55 preoperative patients with untreated malignant tumors (9 with esophageal cancer, 11 with stomach cancer, 11 with colon cancer, 13 with hepatic cancer and 11 with breast cancer). A chemosensitivity test was carried out with the histoculture drug response assay (HDRA) method using 4 drugs, mitomycin C (MMC), 5-fluorouracil (5-FU), doxorubicin hydrochloride (ADM), and cisplatin (CDDP). Immunohistochemical staining was used to assess expression of p53 protein, Bcl-2 protein and Ki-67. The tumor growth inhibition index (I.I.) of the 4 drugs was significantly lower in a group of the patients with p53 protein overexpression-type (mutant p53 protein positive expression-type) tumors than in a group with p53 protein negative expression-type tumors (p<0.05). No significant correlation was found between the expression of the Bcl-2 protein by and the I.I. of any drug studied in any type of cancer. A negative correlation was found between the labeling index (L.I.) for Ki-67 in all cases and I.I. for MMC and ADM and thus, chemosensitivity of the tumors with high growth activity was lower. Furthermore, a positive correlation existed between the L.I. for Ki-67 and that for p53 protein. The patients with p53 protein overexpression-type (mutant p53 protein positive) tumors showed low chemosensitivity. In addition, overexpression of p53 protein is suggested to be one of the factors involved in the lowered chemosensitivity of the tumors with high growth activity. Summarizing these findings, the p53 protein can play an important role in cancer therapy.
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PMID:Usefulness of p53 protein, Bcl-2 protein and Ki-67 as predictors of chemosensitivity of malignant tumors. 1020 14

R. Mayer (USA), summarizing the data presented during the three-day conference, stressed the importance of the development of new cytotoxic drugs and -- particularly -- biological therapies as forms of treatment for patients with gastrointestinal malignancies. He also acknowledged the increasing application of molecular biology to gastrointestinal cancer through the identification of genetically-defined high-risk patients who merit costly screening techniques and the increased use of molecular 'markers' to serve as prognostic indicators and criteria for stratification in future clinical trials. Dr Mayer cautioned against allowing long-term frustration over poor surgical outcomes in patients with T3-4 esophageal cancer and enthusiasm derived from uncontrolled (i.e., phase II) trials to lead to the premature acceptance of preoperative chemoradiation therapy as standard treatment for such patients in the absence of properly controlled, adequately powered randomized studies. Dr Mayer reinforced the progress that has been made in the adjuvant treatment of colon cancer and noted the increasing number of new randomized studies that have been proposed to further enhance the likelihood for cure, particularly in patients with stage III disease. Dr Mayer concluded by presenting a series of hypothetical agenda items for the Fourth International Conference on Biology, Prevention, and Treatment of Gastrointestinal Malignancies to be held in the new millennium which he hoped would demonstrate the incorporation of biological agents into clinical trials, would document more concerted efforts to study the biology and improve the treatment for pancreatic cancer, and would begin to consider the use of 'risk-adapted' management strategies into clinical trials, based on such preclinical biological markers as intratumoral thymidylate synthase levels, apoptotic indices, allelic deletions, and the like.
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PMID:Third International Conference on Biology, Prevention and Treatment of Gastrointestinal Malignancies. Cologne, 23-26 September 1998. 1035 71

A germline sequence alteration at codon 1307 of the APC gene (I1307K) has been reported in 6-7% of the Ashkenazi Jewish population in the United States. This alteration is believed to predispose the APC gene to a secondary mutation at the same locus, resulting in an increased risk of colorectal carcinoma. There is an increased risk of colorectal carcinoma in patients with inflammatory bowel disease (IBD), a relatively large proportion of whom are Ashkenazi Jews. We therefore sought to determine whether the I1307K sequence variant occurred in the germline DNA of IBD patients. To our surprise, we found this sequence in only two of 267 patients with IBD (0.7%), occurring in only 1.5% of Jewish IBD patients. The I1307K sequence variant was not found in 67 patients with esophageal cancer, 53 patients with gastric carcinoma (13 MSI-H and 44 MSI-negative), or ten patients with sporadic MSI-H colon cancer. These findings suggest that the I1307K sequence is relatively rare in the germline of Jewish as well as non-Jewish IBD patients. It does not appear to contribute to the increased colorectal cancer risk present in these patients.
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PMID:Low prevalence of the APC I1307K sequence in Jewish and non-Jewish patients with inflammatory bowel disease. 1044 54

Vascular endothelial growth factor (VEGF) is a most potent angiogenic molecule. In this article, we demonstrated that VEGF is participated in the tumor angiogenesis of hepatocellular carcinoma, esophageal cancer, and pancreatic cancer. Furthermore, we revealed that VEGF is one of the molecules which are responsible for metastasis and prognosis in esophageal cancer and colon cancer. Although the mechanism on the induction of VEGF gene is still unclear in human cancer tissue, we obtained the informative evidence indicating that p53 mutation is involved in VEGF expression of esophageal cancer. Our experimental study with stable transfectant of VEGF gene provided the confirmative results showing that VEGF gene induces neovascularization in and around tumor and that VEGF augment metastastic potential by accelerating proliferative activity after reaching the target organ.
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PMID:Implication of vascular endothelial growth factor in the development and metastasis of human cancers. 1045 2

The occurrence of multiple primary cancers in the aerodigestive tract is a well known phenomenon that has been explained by the concept of 'field carcinogenesis'. Metachronous or synchronous esophageal cancer has usually been identified in patients with head and neck cancer, gastric cancer or colon cancer. The incidence of multiple primary cancers of the esophagus and thyroid gland is very low. We treated four patients with synchronous cancers of the cervical esophagus and the thyroid gland. Histologically, all of the esophageal cancers were squamous cell carcinomas. Thyroid cancers were evaluated as papillary carcinoma or follicular carcinoma. Both the esophageal cancer and the thyroid cancer frequently metastasized to lymph nodes. All patients had multiple lymph nodes metastasis from the esophageal or the thyroid cancer. In one patient, both the esophageal and the thyroid cancers were detected in the same lymph node. Three of four patients died from recurrence of esophageal cancer. The prognosis of these patients was poor. In the treatment of esophageal carcinoma, cancers of other organs including the thyroid gland should be carefully investigated.
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PMID:Multiple primary cancers of the esophagus and thyroid gland. 1047 Jun 60

The role of laparoscopy in the care of patients with cancer is currently evolving. Numerous experimental and clinical studies have attempted to elucidate the nature and cause of port-site metastases--particularly to discern whether they simply are a marker of advanced disease, or if they are a result of the laparoscopic intervention. Laparoscopy has a role in establishing the diagnosis of cancer in some situations by allowing biopsy of intraperitoneal and retroperitoneal masses, lymph nodes, and visceral lesions, as well as examination of abdominal contents under direct vision or with ultrasound probes. Laparoscopy is useful in the staging of established malignancies such as pancreatic cancer, hepatic lesions, lymphoma, and esophageal cancer. Laparoscopy also has a role in the surgical treatment of a variety of malignancies, including gastric carcinoma, pancreatic cancer, splenic malignancies, adrenal cancers, and colon cancer. The safety of laparoscopy for the definitive resection of colon cancer has not yet been proven, and until the results of a randomized prospective trial currently underway are known, should be performed only in the context of a clinical trial. Lastly, laparoscopy can play an important role in the palliative care of the cancer patient in performing procedures such as feeding-tube placement or intestinal stoma creation. It is imperative that using laparoscopy in the care of patients with malignancies be carefully and thoroughly evaluated since this technique can either benefit or adversely affect survival or quality of life.
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PMID:The role of laparoscopy in the treatment of intra-abdominal malignancies. 1080 31


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