UMLS:C0699790 - FACTA Search

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Query: UMLS:C0699790 (colon cancer)
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Vitamin D derivatives can modulate proliferation and differentiation of cancer cells. Our main source of Vitamin D is ultraviolet (UV) radiation-induced synthesis in skin following sun exposure. UV measurements show that the ambient annual UV exposures increase by about 50% from north to south in Norway. As judged from the incidence rates of squamous cell carcinoma, the same is true for the average personal UV exposures. Solar ultraviolet B (UVB) (280-320nm) exhibits a strong seasonal variation with a minimum during the winter months. The present work aims at investigating the impact of season of diagnosis and residential region, both influencing the Vitamin D level, on the risk of death from lung cancer in patients diagnosed in Norway. Data on all incident cases of lung cancer between 1964 and 2000 were collected. Risk estimates were calculated as relative risk (RR), with 95% confidence intervals using Cox regression model. The seasonal variation of 25-hydroxyvitamin D was assessed from routine measurements of 15,616 samples performed at The Hormone Laboratory of Aker University Hospital. Our results indicate that season of diagnosis is of prognostic value for lung cancer patients, with a approximately 15% lower case fatality for young male patients diagnosed during autumn versus winter (RR=0.85; 95% CI, -0.73 to 0.99; p=0.04). Residing in a high UV region resulted in a further lowering of the death risk than residing in a low UV region. We propose, in agreement with earlier findings for prostate-, breast- colon cancer and Hodgkins lymphoma, that a high level of sun-induced 25-hydroxyvitamin D can be a prognostic advantage for certain groups of lung cancer patients, notably for young men. Lung cancer has for several decades been the leading cause of cancer-related mortality in men in Norway and during the last two decades, became the second most common cause of cancer-related death in women . There are two main types of lung cancer: small cell lung cancer for which chemotherapy is the primary treatment and non-small cell lung cancer, which in its early stages is treated primarily with surgery. Gender-related differences have been described in the literature with respect to survival after therapy, male gender being a significant independent negative prognostic factor . In Norway the 5 years relative survival for localized tumours is about 30% for females and 20% for males. Calcitriol, which is the most active form of Vitamin D, is involved in key regulatory processes such as proliferation, differentiation and apoptosis in a wide variety of cells . Mechanisms for these actions have been proposed to be the interaction of active Vitamin D derivatives with a specific nuclear receptor (VDR receptor) and/or with membrane targets . In vitro studies, performed with lung cancer cell lines, have shown an inhibitive effect of Vitamin D derivatives on cell-growth and proliferation . Furthermore, animal studies have demonstrated the capability of these compounds to suppress invasion, metastasis and angiogenesis in vivo , suggesting that administration of Vitamin D derivatives may be used as adjuvant therapy for lung cancer. Humans get optimal Vitamin D levels by exposure to sun or artificial ultraviolet B (UVB, 280-320nm) sources , and possibly also by consumption of food rich in this nutrient (fat fish, eggs, margarine, etc.) or of vitamin supplements . Among these sources, solar radiation appears to be the most important one . Thus, the Vitamin D status (assessed by the serum levels of 25-hydroxyvitamin D, calcidiol) exhibits a strong seasonal variation that parallels the seasonal change in the fluence of solar UVB that reaches the ground. During winter, the UVB fluence rate in the Nordic countries (50-71 degrees N) is below the level required for Vitamin D synthesis in skin . The maximal level of calcidiol is reached between the months July and September, and is 20-120% higher than the corresponding winter level . Recently we hypothesised that the seasonal variation of calcidiol might be of prognostic significance for colon-, breast- prostate cancer as well as for Hodgkins lymphoma in Norway. Patients diagnosed during summer and autumn have a better survival after standard treatment than patients diagnosed during the winter season . This might be a consequence of a higher Vitamin D level. An American study investigated the effect of season of surgery and recent Vitamin D intake on the survival of non-small cell lung cancer patients. The authors reported a significant beneficial joint effect of summer season and high Vitamin D intake compared with winter season and low Vitamin D intake while Vitamin D intake alone did not affect prognosis. Similar results were recently reported from a large study in United Kingdom involving over a million cancer patients including over 190,000 patients diagnosed with lung cancer . Norway (58-71 degrees N) has a significant north-south variation in UV fluence. This makes the country suitable for studies relating cancer epidemiology to UV levels . We investigated whether variations in UV, and, consequently, in Vitamin D level, influence the prognosis of lung cancer, using season of diagnosis and residential regions as variables. Survival data obtained for patients diagnosed over a 40 years period were compared with variations in serum Vitamin D levels obtained from routine measurements performed in The Hormone Laboratory of Aker University Hospital during the period 1996-2001. Seasonal and gender variations in Vitamin D level have been estimated from the analyses.
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PMID:Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role? 1720 91

Bis-[(p-methoxybenzyl)cyclopentadienyl] titanium dichloride, better known as Titanocene Y, is a newly synthesized titanium-based anticancer drug. We studied the antitumor activity of Titanocene Y with concentrations of 2.1, 21 and 210 micromol/l against a range of freshly explanted human tumors, using an in-vitro soft agar cloning system. The sensitivity against Titanocene Y was highly remarkable in the case of renal cell, ovarian, nonsmall cell lung and colon cancer. In particular the surprisingly good response of nonsmall cell lung cancer and colon cancer against Titanocene Y at its lowest concentration of 2.1 micromol/l was well comparable or better with respect to cisplatin, given at a concentration of 1.0 micromol/l. Further clinical development of Titanocene Y appears to be warranted because of the broad cytotoxic activity shown and the specific activity of Titanocene Y against renal cell cancer.
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PMID:Antiproliferative activity of Titanocene Y against tumor colony-forming units. 1726 65

A series of trans-2-alkyl-4-halopiperidines and 2-alkyl-4-halo-1,2,5,6-tetrahydropyridines were prepared by means of an iron(III) catalyzed process. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780 (ovarian cancer), SW1573 (non-small cell lung cancer), and WiDr (colon cancer). The results on the biological activity revealed that, in general, the 2-alkyl-4-halo-1,2,5,6-tetrahydropyridine analogs are more potent than the trans-2-alkyl-4-halopiperidine derivatives. A remarkable selectivity of the aza compound 5f for the resistant cell line WiDr was observed. Cell cycle studies revealed a G(2)/M phase arrest for 5f.
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PMID:Antiproliferative activity of 2-alkyl-4-halopiperidines and 2-alkyl-4-halo-1,2,5,6-tetrahydropyridines in solid tumor cell lines. 1737 81

The Prins reaction was the basis to synthesize functionalized alkyl chlorodihydropyran derivatives. The inexpensive, stable, and environmentally friendly FeCl(3) promotes the cyclization. The method represents an efficient and regioselective manner to obtain in a single step chlorovinyl-TMS oxacycles. The in vitro antiproliferative activities of the compounds were examined in the human solid tumor cell lines A2780 (ovarian cancer), SW1573 (non-small cell lung cancer), and WiDr (colon cancer). Overall, the results show an enhancement in the cytotoxicity exhibited by the new analogs when compared to their parental compounds.
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PMID:Antiproliferative activity of 4-chloro-5,6-dihydro-2H-pyrans. Part 2: Enhancement of drug cytotoxicity. 1739 91

4-Anilinoquinazolines (e.g. Iressa and Glivec) are a class of epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors widely used to treat non-small cell lung cancer and other tumors. However, low clinical response rate, resistance, and host toxicity of currently available EGFR-TK inhibitors prompt the development of second generation of TK inhibitors with improved efficacy, selectivity, and less resistance. CH330331 is a recently synthesized novel 4-anilinoquinazoline analog with confirmed anticancer activity in vitro and in vivo. To predict its oral pharmacokinetic behavior and transport nature in the intestine before entering clinical trials, we have developed and validated a high performance liquid chromatographic (HPLC) method for the determination of CH330331 in Caco-2 (a human colon cancer cell line) monolayers. The developed HPLC method was sensitive and reliable, with acceptable accuracy (90-110% of nominal values) and precision (intra- and inter-assay R.S.D.<10%). The total running time was within 10 min, with acceptable separation of the target analytes. The lower limit of quantitation (LLOQ) value for CH330331 was 200 ng/ml when an aliquot of 100 microl sample was injected onto the HPLC. The validated HPLC method was applied to characterize the epithelial transport of CH330331 in Caco-2 monolayers. The transport of CH330331 across the Caco-2 monolayers from the apical to basolateral side was 8- to 10-fold higher than that from the basolateral to apical side. Co-incubation of sodium azide or MK-571, but not verapamil, significantly inhibited the apical to basolateral transport of CH330331. These findings provide initial evidence that the intestinal absorption of CH330331 is mediated by an active mechanism. Further studies are required to explore the interaction of CH330331 with ATP-binding cassette transporters and the possible influence on its pharmacokinetics and pharmacodynamics.
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PMID:Determination of CH330331, a novel 4-anilinoquinazoline inhibitor of epidermal growth factor receptor tyrosine kinase, in human Caco-2 monolayers by high performance liquid chromatography with ultraviolet detection: application to a trans-epithelial transport study. 1746 48

The use of positron emission tomography (PET) is increasing rapidly in the United States, with the most common use of PET scanning related to oncology. It is especially useful in the staging and management of lymphoma, lung cancer, and colorectal cancer, according to a panel of expert radiologists, surgeons, radiation oncologists, nuclear medicine physicians, medical oncologists, and general internists convened in November 2006 by the National Comprehensive Cancer Network. The Task Force was charged with reviewing existing data and developing clinical recommendations for the use of PET scans in the evaluation and management of breast cancer, colon cancer, non-small cell lung cancer, and lymphoma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, possible future developments, and the role of PET in oncology.
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PMID:NCCN task force report: positron emission tomography (PET)/computed tomography (CT) scanning in cancer. 1750 59

Evidence is scarce about the influence of comorbidity on outcome of surgery, whereas this information is highly relevant for estimating the surgical risk of cancer patients, and for optimising pre-, peri- and postoperative care. In this paper, the prognostic role of increasing age and comorbid conditions in patients diagnosed with stage I-III colorectal, stage I-II NSCLC or stage I-III breast cancer between 1995 and 2004 in the southern part of the Netherlands is summarised. Almost all patients with stage I-III colon cancer or rectal cancer underwent surgery regardless of age or comorbidity. In contrast, the resection rate among elderly patients with stage I-II NSCLC was clearly lower than among younger patients and was significantly lower when COPD, cardiovascular diseases or diabetes were present. Among patients with stage I-III breast cancer, those aged 80 or older underwent less surgery, and the resection rate appeared to be lower when cardiovascular diseases or diabetes were present. Among patients with resected colorectal cancer, postoperative morbidity and mortality were higher among those undergoing emergency surgery, and also among those with reduced pulmonary function, cardiovascular disease or neurological comorbidity. Among those with resected NSCLC, postoperative morbidity and mortality were related to reduced pulmonary function or cardiovascular disease. Since surgery for breast cancer is low risk, elective surgery, morbidity and mortality were not higher for elderly or those with comorbidity. Among patients with colorectal or breast cancer, comorbidity in general, cardiovascular diseases, COPD, diabetes (only colon and breast cancer) and venous thromboembolism had a negative effect on overall survival, whereas the effect of comorbidity on survival of stage I-II NSCLC was less clear. Elderly and those with comorbidity (especially cardiovascular diseases and COPD) among colorectal cancer and NSCLC patients had more postoperative morbidity and mortality. Prospective randomised studies are needed for refining selection criteria for surgery in elderly cancer patients and for anticipation and prevention of complications.
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PMID:Comorbidity in older surgical cancer patients: influence on patient care and outcome. 1768 80

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells. Hyperglycemia is an on-target side effect of many inhibitors of PI3K/Akt signaling including the specific PI3K inhibitor PX-866. The peroxisome proliferator-activated receptor gamma agonist pioglitazone, used to treat type 2 diabetes, prevents a decrease in glucose tolerance caused by acute administration of PX-866. Our studies have shown that pioglitazone does not inhibit the antitumor activity of PX-866 in A-549 non-small cell lung cancer and HT-29 colon cancer xenografts. In vitro studies also showed that pioglitazone increases 2-[1-(14)C]deoxy-D-glucose uptake in L-6 muscle cells and prevents inhibition of 2-deoxyglucose uptake by PX-866. Neither pioglitazone nor PX-866 had an effect on 2-deoxyglucose uptake in A-549 lung cancer cells. In vivo imaging studies using [18F]2-deoxyglucose (FDG) positron emission tomography showed that pioglitazone increases FDG accumulation by normal tissue but does not significantly alter FDG uptake by A-549 xenografts. Thus, peroxisome proliferator-activated receptor gamma agonists may be useful in overcoming the increase in blood glucose caused by inhibitors of PI3K signaling by preventing the inhibition of normal tissue insulin-mediated glucose uptake without affecting antitumor activity.
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PMID:Peroxisome proliferator-activated receptor gamma agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity. 1913 17

Several trials show a relationship between skin toxicity, response rate, and overall survival in cetuximab-treated patients. We analyzed our database to evaluate the importance of skin rash as a surrogate marker of favorable outcome in cancer patients referred to our institution in the last three years. We retrospectively analyzed 90 cetuximab-treated patients: 57 colon cancer patients, 10 NSCLC patients, 14 locally advanced esophageal cancer patients, and 9 miscellaneous. A significant correlation was observed between skin rash and response to therapy. Skin rash was experienced by 93% of PR and 100% of CR patients. The mean TTP was 184 days in patients showing skin rash and 94 days in patients without skin rash, respectively. On multivariate analysis, skin rash was demonstrated to be the only independent prognostic variable with regard to TTP. Patients who did not develop skin rash had a 2-fold greater likelihood to manifest tumor progression significantly earlier than patients who developed skin rash. In our series, a statistically significant correlation between rash, response rate, and TTP was demonstrated in 90 cetuximab-treated patients. Skin toxicity was confirmed as the only clinical variable able to predict the response to cetuximab.
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PMID:Correlation between efficacy and skin rash occurrence following treatment with the epidermal growth factor receptor inhibitor cetuximab: a single institution retrospective analysis. 1928 4

Synthesis and biological evaluation of novel pyrazoles and pyrazolo[3,4-d]pyrimidines are reported. Fourteen compounds were selected by the NCI and tested for their preliminary in-vitro anticancer activity, whereas all the synthesized compounds were evaluated for their in-vitro antimicrobial activity. Compound 12a was proven to possess the highest anticancer activity with a broad spectrum profile. It showed particular effectiveness towards leukemia HL-60 (TB), K-562, non-small cell lung cancer NCI-H23, and colon cancer HT 29, KM 12 cell lines (GI(50) = 6.59, 4.44, 1.37, 3.33, and 9.63 muM, respectively). Out of the synthesized compounds, thirteen derivatives were found to display pronounced antimicrobial activity especially against P. aeruginosa. Compounds 2c, 5b, 10, 11b, 17b, 18b, and 19 were proven to be the most active with a broad spectrum of activity. Compound 19 was found to be equipotent to ampicillin against B. subtilis, whereas compounds 11b and 19 were four times superior to ampicillin against P. aeruginosa, while compounds 5b and 18b were equipotent to ampicillin against the same organism. Moreover, compounds 2c, 10, and 11b were nearly equipotent to ampicillin against E. coli. On the other hand, compounds 2c, 5b, 10, 11a, 17b, and 18b exerted nearly half the activity of clotrimazole against C. albicans.
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PMID:Synthesis and biological evaluation of novel pyrazoles and pyrazolo[3,4-d]pyrimidines incorporating a benzenesulfonamide moiety. 1934 Aug 37

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