Translational crossroads for biomarkers.

A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (d) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute-supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development.     

Cannabis and tobacco smoke are not equally carcinogenic

More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.     

Logistic regression in case-control studies: The effect of using independent as dependent variables

In case-control studies, cases are sampled separately from controls. In such studies the primary analysis concerns the estimation of the effect of covariables on being a case or a control. To explore causal pathways, further secondary analysis could concern the relationships among the covariables. In this paper the validity of such secondary analysis is addressed. In particular, the use of multiple logistic regression in case-control studies where the dependent variable is not the case/control indicator is explored. It is shown that only under very restrictive conditions will sample regression coefficients correctly estimate their true value. In many situations, it may be valid to regress one covariable on others in the control group, but not in the case group or the combined sample. This principle is illustrated by a study of sexually transmitted disease in Kenya.     

Preliminary assessment of fluorine-18 fluorodeoxyglucose positron mission tomography in patients with bladder cancer

The purpose of this study was to assess the feasibility of imaging of bladder cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning. We studied 12 patients with histologically proven bladder cancer who had undergone surgical procedures and/or radiotherapy. Retrograde irrigation of the urinary bladder with 1000–3710 ml saline was performed during nine of the studies. Dynamic and static PET images were obtained, and standardized uptake value images were reconstructed. FDG-PET scanning was true-positive in eight patients (66.7%), but false-negative in four (33.3%). Of 20 organs with tumor mass lesions confirmed pathologically or clinically, 16 (80%) were detected by FDG-PET scanning. FDG-PET scanning detected all of 17 distant metastatic lesions and two of three proven regional lymph node metastases. FDG-PET was also capable of differentiating viable recurrent bladder cancer from radiation-induced alterations in two patients. In conclusion, these preliminary data indicate the feasibility of FDG-PET imaging in patients with bladder cancer, although a major remaining pitfall is intense FDG accumulation in the urine. Present address: Department of Radiology, National Defense Medical College, 3-2 Namiki, Tokorozawa 359, Japan     

Intraocular pressure effects on optic nerve-head oxidative metabolism measured in vivo

The effects of acute intraocular pressure (IOP) on the reduction/oxidation ratio of cytochromea,a ₃ were measured from intact cat optic nerve by microfiber reflection spectrophotometry. This enabled the real-time analysis of optic nerve-head oxidative metabolism following IOP or mean arterial pressure (MAP) changes. Findings included: (1) cytochromea,a ₃ became more reduced and relative blood volume decreased at lower perfusion pressures, even at IOP of <20 mm Hg; (2) metabolic inhibition began at variable perfusion pressures but invariably progressed as perfusion pressure declined; and (3) increased IOP or decreased MAP caused metabolic inhibition. These findings demonstrate that: (1) optic nerve metabolic dysfunction is possible at low IOPs; (2) lowering IOP can reverse metabolic dysfunction; (3) the metabolic response is dependent on IOP and/or MAP changes; and (4) the metabolic inhibition is related to optic nerve ischemia. Presented at the 8th International Congress of Eye Research-Symposium on Retinal Oxygenation, San Francisco, September 1988     

Sexual self views of women with disabilities: The relationship among age-of-onset,nature of disability and sexual self-esteem

The sexual self-esteen of 43 women with mobility impairments was examined on the basis of age-of-onset and nature (fluctuating versus stable health conditions) of disability. Based on past literature, it was hypothesized that women with earlier age-of-onset disabilities would report lower positive levels of sexual self-esteem compared to women with later age-of-onset disabilities. Subjects were acquired through two computer on-line services, two large urban universities, and nationally based disability-related organizations. A hierarchical multiple regression indicated that as age-of-onset of disability increased (i.e. the disability occurred later in life), positive sexual self-esteem decreased significantly. Future research should acquire participants from residential institutions other than rehabilitation facilities and those who remain at home. The necessity of creating psychological scales and tools applicable to this population is discussed.     

Odor-induced EEG changes in PTSD Vietnam veterans

Electroencephalogram (EEG) changes in response to trauma and non-traumarelated odors were examined in five Vietnam veterans with a DSM-III-R diagnosis of Post-traumatic Stress Disorder (PTSD) and in five Vietnam veterans with adjustment-related problems (non-PTSD). Period analysis of the EEG indicated that the odors differentially affected the PTSD group's theta and alpha activity compared to the non-PTSD group. The greatest EEG and self-report odor and PTSD effects were found in response to a trauma odor which simulated burning flesh. These findings have important implications in the detection of veterans who attempt to feign deliberately the psychophysiological response pattern associated with PTSD.