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Test Sensitivity

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166421. Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. (PubMed)

Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. Few family studies have investigated the effects of genetic, environmental, and host factors on melanoma risk, and most have been restricted to high-risk families. We assessed the role of these factors on melanoma risk in two types of families: families ascertained through melanoma probands but unselected by family history and melanoma-prone (...) of the regressive model were used to compute odds ratios associated with each risk factor and age-specific melanoma risk depending on the genotype at the melanoma-predisposing gene and the effects of risk factors. All statistical tests were two-sided.In the families unselected by family history, there was statistically significant evidence (P<.001) for a dominant gene, with melanoma risk reaching 0.49 and 0.67 by age 80 years in male and female gene carriers, respectively. Melanoma risk was statistically

2004 Journal of the National Cancer Institute

166422. Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects. (PubMed)

Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects. In preclinical studies, lysolipid-based temperature-sensitive liposomes (LTSLs) containing chemotherapy drugs administered in combination with local hyperthermia have been found to increase tumor drug concentrations and improve antitumor efficacy of the drugs. We used a novel magnetic resonance imaging (MRI) method to measure the temporal and spatial patterns of drug delivery in a rat (...) resonance changes were used to calculate intratumoral doxorubicin concentrations throughout treatment. Tumors were monitored until they reached five times their volume on the day of treatment or 60 days. Doxorubicin concentrations and times for tumors to reach five times their volume on the day of treatment were analyzed using the Kruskal-Wallis test and the Kaplan-Meier product-limit method, respectively. All statistical tests were two-sided.Administration of Dox/Mn-LTSLs before, during, and both

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2007 Journal of the National Cancer Institute

166423. Urinary mesothelin provides greater sensitivity for early stage ovarian cancer than serum mesothelin, urinary hCG free beta subunit and urinary hCG beta core fragment. (PubMed)

Urinary mesothelin provides greater sensitivity for early stage ovarian cancer than serum mesothelin, urinary hCG free beta subunit and urinary hCG beta core fragment. Early detection of ovarian cancer should improve overall survival. Multiple serum markers have been evaluated as possible tests to detect early stage disease, but few urine markers have been studied. Mesothelin has been detected in serum from patients with ovarian cancer, but has not been previously reported in urine.Mesothelin (...) of serum to urine creatinine; and (3) normalized using the Cockroft-Gault formula for glomerular filtration rate (GFR). Urines were also assayed for human chorionic gonadotropin (hCG) free beta subunit and beta subunit core fragment and similarly normalized.Optimal sensitivity for early stage disease was obtained when urine mesothelin was normalized using GFR. A greater fraction of patients with early stage disease was detected with the mesothelin urine assay (42%) than with the serum assay (12

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2007 Gynecologic Oncology

166424. Inhibition of phosphatidylinositol-3-kinase causes increased sensitivity to radiation through a PKB-dependent mechanism. (PubMed)

Inhibition of phosphatidylinositol-3-kinase causes increased sensitivity to radiation through a PKB-dependent mechanism. To identify whether inhibition of phosphatidylinositol-3-kinase (PI3K) causes increased radiosensitivity through inhibition of protein kinase B (PKB), implicating PKB as an important therapeutic target in prostate cancer.The prostate cancer cell line LNCaP was treated with the PI3K inhibitor LY294002, radiation, and combinations of the two therapies. Apoptosis and survival (...) were measured by cell cycle analysis, Western blot analysis for cleaved poly (ADP-ribose) polymerase, and clonogenic survival. To test the hypothesis that inhibition of PKB is responsible for LY294002-induced radiosensitivity, LNCaP cells expressing a constitutively active form of PKB were used.The combination of PI3K inhibition and radiation caused an increase in apoptosis and a decrease in clonogenic survival when compared to either modality alone. The expression of constitutively activated PKB

2005 Biology and Physics

166425. Development and evaluation of a highly sensitive human papillomavirus genotyping DNA chip. (PubMed)

Development and evaluation of a highly sensitive human papillomavirus genotyping DNA chip. Test of human papillomavirus (HPV) is a useful adjunctive tool of Pap smear to screen cervical cancer. We have developed a novel HPV genotyping DNA chip arrayed by multiple oligonucleotide probes of both L1 and E6/E7 gene sequence of 42 types of anogenital HPV.Consensus PCR products of L1 and E6/E7 gene sequences of HPV are hybridized to arrayed probes on the HPV chip and HPV genotypes are identified (...) to direct DNA sequencing in detection of mixed infection.These results suggest that HPV DNA chip analysis in the present study is highly accurate for detection and genotyping of HPV and may have potential value as a robust, high-throughput screening test of uterine cervix cancer.

2006 Gynecologic Oncology

166426. Mutagen sensitivity and neoplastic progression in patients with Barrett's esophagus: a prospective analysis. (PubMed)

measured sensitivity to bleomycin in peripheral blood lymphocytes in a cohort of 220 patients with Barrett's esophagus. We followed these patients for 1,230 person-years (range, 3 months to 10.1 years; median, 6.4 years), using development of cancer and aneuploidy as end points. A subset of these patients was evaluated for inactivation of tumor-suppressor genes CDKN2A/p16 and TP53 [by mutation and loss of heterozygosity (LOH)] in their Barrett's segments at the time of, or before, the bleomycin test (...) Mutagen sensitivity and neoplastic progression in patients with Barrett's esophagus: a prospective analysis. Defects in DNA damage recognition and repair have been associated with a wide variety of cancers. We conducted a prospective study to determine whether mutagen sensitivity, as determined by an in vitro assay, was associated with the future development of cancer in patients with Barrett's esophagus, which is associated with increased risk of progression to esophageal adenocarcinoma.We

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2006 Cancer Epidemiology & Biomarkers and Prevention

166427. Broad spectrum receptor tyrosine kinase inhibitor, SU6668, sensitizes radiation via targeting survival pathway of vascular endothelium. (PubMed)

Broad spectrum receptor tyrosine kinase inhibitor, SU6668, sensitizes radiation via targeting survival pathway of vascular endothelium. Recent studies have demonstrated radiosensitization by inhibiting receptor tyrosine kinases (RTKs). Irradiation activates RTKs and their downstream prosurvival molecule, Akt. In this study, we investigated the mechanism by which SU6668, an inhibitor of RTKs involved in angiogenic pathways, enhances effects of irradiation.Western blots were used to determine Akt (...) phosphorylation. Clonogenic assays were performed to determine endothelial survival after combination of SU6668 and irradiation. This combination therapy was also tested in mouse models with Lewis lung carcinoma or glioblastoma multiforme (GL261) for inhibition of tumor growth and tumor vasculature by examining tumor volume, tumor vascular window, and blood flow.We found that SU6668 inhibited the Akt activation inducible by irradiation. Clonogenic survival of endothelial cells was decreased after the combined

2004 Biology and Physics

166428. Specific telomere dysfunction induced by GRN163L increases radiation sensitivity in breast cancer cells. (PubMed)

that is complementary to the template region of the telomerase ribonucleic acid component (hTR). We hypothesized that exposure to GRN163L, either through immediate inhibition of telomerase activity or through eventual telomere shortening and dysfunction, may enhance radiation sensitivity. Our goal was to test whether the treatment with GRN163L enhances sensitivity to irradiation (IR) in MDA-MB-231 breast cancer cells.The MDA-MB-231 breast cancer cells were treated with or without GRN163L for 2-42 days. Inhibition (...) Specific telomere dysfunction induced by GRN163L increases radiation sensitivity in breast cancer cells. Telomerase is expressed in 80-90% of tumor cells, but is absent in most somatic cells. The absence of telomerase activity results in progressive telomere shortening, leading to cellular senescence or death through deoxyribonucleic acid (DNA) damage signals. In addition, a role for telomerase in DNA damage repair has also been suggested. A specific telomerase inhibitor, GRN163L

2007 Biology and Physics

166429. Antisense-MDM2 sensitizes LNCaP prostate cancer cells to androgen deprivation, radiation, and the combination in vivo. (PubMed)

Antisense-MDM2 sensitizes LNCaP prostate cancer cells to androgen deprivation, radiation, and the combination in vivo. To test the effects of antisense (AS)-MDM2 alone and with androgen deprivation (AD), radiotherapy (RT), and AD + RT on wild-type LNCaP cells in an orthotopic in vivo model.Androgen-sensitive LNCaP cells were grown in the prostates of nude mice. Magnetic resonance imaging-based tumor volume and serum prostate-specific antigen (PSA) measurements were used to assess effects (...) doubling time was from AS-MDM2 + AD + RT, although the effect of AS-MDM2 + AD was substantial. Expression of MDM2 was significantly reduced by AS-MDM2 in the setting of RT.This is the first in vivo investigation of the effects of AS-MDM2 in an orthotopic model and the first to demonstrate incremental sensitization when added to AD and AD + RT. The results with AD underscore the potential to affect micrometastatic disease, which is probably responsible for treatment failure in 30-40% of men with high

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2007 Biology and Physics

166430. American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. (PubMed)

American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. To develop a clinical practice guideline for the management of men with metastatic, recurrent, or progressive carcinoma of the prostate. The focus of this document is on the use, combinations, and timing of various forms of androgen deprivation therapy (ADT) for the palliation of men with androgen-sensitive disease.An expert panel (...) in addition to castrate therapy. Until data from studies using modern medical diagnostic/biochemical tests and standardized follow-up schedules become available, no specific recommendations can be issued regarding the question of early versus deferred ADT. A discussion about the pros and cons of early versus deferred ADT should occur.

2004 Journal of Clinical Oncology

166431. American Society of Clinical Oncology Technology Assessment: chemotherapy sensitivity and resistance assays. (PubMed)

American Society of Clinical Oncology Technology Assessment: chemotherapy sensitivity and resistance assays. To develop a technology assessment of chemotherapy sensitivity and resistance assays in order to define the role of these tests in routine oncology practice.The American Society of Clinical Oncology (ASCO) established a Working Group to develop the technology assessment. The Working Group collaborated with the Blue Cross and Blue Shield Association (BCBSA) Technology Evaluation Center (...) in this technology assessment, eight were identified by the original BCBSA systematic review, one was provided by industry, and three were identified by the ASCO updated literature review.Review of the literature does not identify any CSRAs for which the evidence base is sufficient to support use in oncology practice.The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make

2004 Journal of Clinical Oncology

166432. Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. (PubMed)

different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant.A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients). (...) Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases.One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression

2006 Journal of Clinical Oncology

166433. [18F]fluorodeoxyglucose positron emission tomography is more sensitive than skeletal scintigraphy for detecting bone metastasis in endemic nasopharyngeal carcinoma at initial staging. (PubMed)

[18F]fluorodeoxyglucose positron emission tomography is more sensitive than skeletal scintigraphy for detecting bone metastasis in endemic nasopharyngeal carcinoma at initial staging. Bone metastasis occurs frequently in patients with endemic nasopharyngeal carcinoma (NPC). The main objective of this study is to evaluate positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose ([18F]FDG) and conventional skeletal scintigraphy (SS) for detecting bone metastasis at initial (...) staging. Auxiliary objectives are to identify risk factors for bone metastasis and features associated with poor survival in patients with bone metastasis.Patients with endemic NPC before initiation of treatment were enrolled. PET and SS were performed at initial staging and compared using McNemar's paired-sample test. Bone metastasis was considered to be present if there was any reliable evidence identified within 1 year after primary diagnosis. Multiple logistic regression and Cox's proportional

2006 Journal of Clinical Oncology

166434. Cannabis improves night vision: a case study of dark adaptometry and scotopic sensitivity in kif smokers of the Rif mountains of northern Morocco. (PubMed)

-testing of night vision has become possible with a portable device, the LKC Technologies Scotopic Sensitivity Tester-1 (SST-1). This study examines the results of double-blinded graduated THC administration 0-20 mg (as Marinol) versus placebo in one subject on measures of dark adaptometry and scotopic sensitivity. Analogous field studies were performed in Morocco with the SST-1 in three subjects before and after smoking kif. In both test situations, improvements in night vision measures were noted (...) Cannabis improves night vision: a case study of dark adaptometry and scotopic sensitivity in kif smokers of the Rif mountains of northern Morocco. Previous reports have documented an improvement in night vision among Jamaican fishermen after ingestion of a crude tincture of herbal cannabis, while two members of this group noted that Moroccan fishermen and mountain dwellers observe an analogous improvement after smoking kif, sifted Cannabis sativa mixed with tobacco (Nicotiana rustica). Field

2004 Journal of Ethnopharmacology

166435. Cardiovascular responsiveness to brief cognitive challenges and pain sensitivity in women. (PubMed)

Cardiovascular responsiveness to brief cognitive challenges and pain sensitivity in women. The primary purpose of the study was to determine the relationship between cardiovascular (CV) responsiveness to brief cognitive tasks and pain sensitivity in normotensive individuals. Fifty-eight healthy women without a history of chronic pain were exposed to three laboratory tasks (reading aloud, speech task, and tracking task) and repeated pain testing (electrocutaneous and pressure pain stimulation (...) ) while mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Generally, subjects with higher HR responsiveness to the cognitive tasks displayed a reduced pain sensitivity, particularly to electrocutaneous pain stimulation. Moreover, the two types of pain stimulation seemed to trigger somewhat different CV response patterns. Inclusion of pain-related CV changes as control variables affected the relationship between HR responsiveness and pain sensitivity, although differently

2004 European Journal of Pain

166436. Reflex pupillary dilatation in response to skin incision and alfentanil in children anaesthetized with sevoflurane: a more sensitive measure of noxious stimulation than the commonly used variables. (PubMed)

Reflex pupillary dilatation in response to skin incision and alfentanil in children anaesthetized with sevoflurane: a more sensitive measure of noxious stimulation than the commonly used variables. Estimation of analgesia in anaesthetized children is often imprecise, and consequently, anaesthesiologists commonly evaluate children's response to surgical stimulation by movement or haemodynamic changes. In adults reflex pupillary dilatation has been demonstrated to be a very sensitive measure (...) of noxious stimulation, correlated with opioid concentrations. The autonomic nervous control changes with age, raising the hypothesis that mechanisms involved in pupillary autonomic functions regarding both sympathetic and parasympathetic components may also differ between adults and children. In this pilot study, we tested the hypothesis that the pupillary reflex dilatation might allow assessment of noxious stimulation and analgesic effect of alfentanil in children under sevoflurane anaesthesia

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2006 British Journal of Anaesthesia

166437. Prevention of latex sensitization in guinea pigs by a bacterial and viral filter used in anaesthesia. (PubMed)

Prevention of latex sensitization in guinea pigs by a bacterial and viral filter used in anaesthesia. Preventing anaphylactic reactions as a result of natural rubber latex (NRL) proteins is an important concern in anaesthesia. The clinical relevance of a bacterial/viral filter (Pall BB25) in preventing sensitization to NRL by inhalation was tested in guinea pigs.Guinea pigs (n=8-10 in each group) were exposed to aerosolized NRL-contaminated cornstarch powder or to NRL in saline for 1 h every (...) efficiently protected the guinea pigs from sensitization to NRL. This filter can be used as a complementary measure for avoidance of NRL contact during surgical procedures particularly if the mechanical ventilator apparatus contain NRL devices.

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2005 British Journal of Anaesthesia

166438. Propofol inhibits volume-sensitive chloride channels in human coronary artery smooth muscle cells. (PubMed)

Propofol inhibits volume-sensitive chloride channels in human coronary artery smooth muscle cells. Volume-sensitive chloride channels (VSCC) play an important role in regulation of cell volume and electrical activity. Activation of vascular smooth muscle VSCC causes smooth muscle depolarization and contraction. We investigated the effects of propofol on VSCC in cultured human coronary artery smooth muscle cells by using the chloride-sensitive dye 6-methoxy-N-ethylquinolinium (MEQ). To activate (...) VSCC, cells were superfused for 2 min with hypotonic gluconate solutions and then potassium thiocyanate solution. The percentage reduction in MEQ fluorescence during 60 s in the presence of potassium thiocyanate was measured and used as an index of VSCC activity. 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), a well characterized chloride channel blocker, and propofol were dissolved in hypotonic gluconate solution to test their effect on VSCC activity. The reduction in fluorescence

2003 Anesthesia and Analgesia

166439. High sensitivity 1H-NMR spectroscopy of homeopathic remedies made in water. (PubMed)

High sensitivity 1H-NMR spectroscopy of homeopathic remedies made in water. The efficacy of homeopathy is controversial. Homeopathic remedies are made via iterated shaking and dilution, in ethanol or in water, from a starting substance. Remedies of potency 12 C or higher are ultra-dilute (UD), i.e. contain zero molecules of the starting material. Various hypotheses have been advanced to explain how a UD remedy might be different from unprepared solvent. One such hypothesis posits that a remedy (...) contains stable clusters, i.e. localized regions where one or more hydrogen bonds remain fixed on a long time scale. High sensitivity proton nuclear magnetic resonance spectroscopy has not previously been used to look for evidence of differences between UD remedies and controls.Homeopathic remedies made in water were studied via high sensitivity proton nuclear magnetic resonance spectroscopy. A total of 57 remedy samples representing six starting materials and spanning a variety of potencies from 6 C

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2004 BMC Complementary and Alternative Medicine

166440. Self-reported pain sensitivity: lack of correlation with pain threshold and tolerance. (PubMed)

Self-reported pain sensitivity: lack of correlation with pain threshold and tolerance. Many recent studies and several reviews have highlighted the potential clinical applications of experimental pain testing (e.g., for predicting post-surgical pain, treatment responsiveness, etc.). However, the implementation of quantitative sensory testing of pain sensitivity on a broad scale is limited by requirements of time, equipment, and expertise, and their associated costs. One reasonable question (...) is whether one can obtain, via self-report, a valid index of an individual's pain sensitivity and pain tolerance. We analyzed data from a large number of subjects (n=505) who had undergone standardized thermal pain testing, and found that while higher self-reported pain sensitivity was associated with higher scores on a measure of anxiety, no relationship was observed between subjects' self-report of pain sensitivity and subjects' actual pain threshold or tolerance. These findings suggest

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2007 European Journal of Pain

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