Prostate cancer clinical trials of the Southwest Oncology Group

The changing clinical dynamics of prostate cancer have resulted in a broadening of the research focus of the Genitourinary (GU) Cancer Committee of the Southwest Oncology Group (SWOG). Beginning with an emphasis on hormone-refractory disease in its early years, SWOG prostate cancer trials now cover the entire spectrum of the disease: localized, locally advanced, metastatic and hormone-refractory disease. As the world's largest GU cancer research group, the GU committee of SWOG has pioneered studies in combined androgen therapy for metastatic disease, quality-of-life (QOL) assessments for patients with localized and advanced disease, adjuvant therapy models, and prostate cancer chemoprevention. The committee has also formed the GU Global Group, whose purpose is to convene the chairs of the GU committees of all the major national and international oncology cooperative groups. Meeting semiannually, this group discusses activities within their respective organizations, plans collaborative strategies and protocols, and establishes global strategy in prostate cancer clinical research. The future directions of national and international prostate cancer trials will build on this broad foundation of well-conceived, logically sequenced studies.     

Chromosome 9p deletions in invasive and noninvasive nonfunctional pituitary adenomas: the deleted region involves markers outside of the MTS1 and MTS2 genes

We have screened 57 cases of primary, nonfunctional, pituitary adenomas for loss of heterozygosity of markers on chromosome 9p. Using a panel of 11 microsatellite markers, we found hemizygous deletion with at least one of the markers in 18 tumors (31.5%). The frequency of loss was similar in both noninvasive (8 of 26; 31%) and invasive tumors (10 of 31; 32%), suggesting that loss on this chromosome might be an early event in pituitary tumorigenesis. Two discrete areas of loss were punctuated by a region of retention of heterozygosity between the markers D9S171 and IFNA, indicative of homozygous deletion. However, multiplex PCR analysis (MTS1 and MTS2) and the presence of a 3' untranslated region polymorphism in MTS1 suggested that neither of these tumor suppressor genes was homozygously deleted. In 6 of the 18 tumors showing LOH, sufficient DNA was also available for Southern blot analysis and, in all cases, showed retention of MTS1. Cell mixing experiments of tumor cell DNA homozygously deleted for MTS1 with DNA in which neither copy of the gene was deleted only gave rise to a signal at contamination levels greater than 30% and could discriminate homozygous and hemizygous loss. These studies support the recent findings that mechanisms other than hemi- and homozygous deletion are most likely responsible for the loss of MTS1 gene product in pituitary tumors (M. Woloschak et al., Cancer Res., 56: 2493-2486, 1996.). These data show that losses on either side of 9p21-22, both or either of which may be deleted, are involved in pituitary tumorigenesis and provide evidence for distinct suppressor gene loci, in addition to MTS1, on chromosome 9p.     

Cognitive categorization and quality of performance ratings.

The effects of cognitive categorization of raters on accuracy, leniency, and halo of performance evaluations were investigated in a field setting. One hundered seventy-four subordinates evaluated the performance of their managers on three performance dimensions. Managers were categorized as congruent or incongruent based on subordinates' perceptions of the extent to which the manager's behavior met the subordinates' expectations. The results indicated that the quality of ratings assigned by subordinates was related to the cognitive categories used. As hypothesized, ratings of managers who were categorized as congruent were found to be more accurate and also to contain more leniency and halo tendency than the ratings of managers who were categorized as incongruent. Implications of these findings for performance-appraisal research are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A System for Three-Dimensional Interactive Simulation of Hand Biomechanics

A real-time interactive graphics simulation of the mechanics of the human thumb has been developed. The simulation utilizes a realistic data structure for the bones of the thumb which may be expanded to include the hand and forearm. This is coupled to a model of the kinematics of the joints in a concurrent processing arrangement in which the dynamic graphical transformations for scaling, translation, rotation, perspective, and clipping are all performed on a special-purpose display processor. The model and the control functions are distributed between this processor and a separate general-purpose superminicomputer. The resulting system presents the user with a realistic simulation of the movements of the thumb in normal and impaired states. The user may choose from a menu of options, including an interactive tendon transfer simulation for the current hand being simulated. He may control (interactively and in real time) the view, observation position, skeletal motion, and parameters for use in the model of joint mechanics. This type of computer modeling, utilizing a realistic three-dimensional data structure, models of musculoskeletal kinematics, and interactive programming, shows great potential for bringing mathematical modeling into useful clinical, research, and educational applications.     

Contingent suppression of tolerance to the "anorexigenic" effect of haloperidol.

Whether tolerance develops to the "anorexia" induced by haloperidol (HAL) was determined. Rats were given HAL (2.5 or 5 mg/kg) either before or after access to milk for 53 days. Controls were given injections of saline. On Day 54, when all groups received pretest injections of the drug, only rats previously given posttest injections of HAL were tolerant. The absence of tolerance in rats previously given pretest injections suggests that tolerance is suppressed when rats are given access to food in the drugged state. It is concluded that tolerance develops to HAL as a result of pharmacological exposure but is suppressed by the "anhedonic" effect of the drug. The relevance of these findings to the role of reinforcement in behavioral tolerance is briefly discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peritraumatic dissociation and posttraumatic stress in male Vietnam theater veterans

OBJECTIVE: The aim of this study was to determine the reliability and validity of a proposed measure of peritraumatic dissociation and, as part of that effort, to determine the relationship between dissociative experiences during disturbing combat trauma and the subsequent development of posttraumatic stress disorder (PTSD). METHOD: A total of 251 male Vietnam theater veterans from the Clinical Examination Component of the National Vietnam Veterans Readjustment Study were examined to determine the relationship of war zone stress exposure, retrospective reports of dissociation during the most disturbing combat trauma events, and general dissociative tendencies with PTSD case determination. RESULTS: The total score on the Peritraumatic Dissociation Experiences Questionnaire--Rater Version was strongly associated with level of posttraumatic stress symptoms, level of stress exposure, and general dissociative tendencies and weakly associated with general psychopathology scales from the MMPI-2. Logistic regression analyses supported the incremental value of dissociation during trauma, over and above the contributions of level of war zone stress exposure and general dissociative tendencies, in accounting for PTSD case determination. CONCLUSIONS: These results provide support for the reliability and validity of the Peritraumatic Dissociation Experiences Questionnaire--Rater Version and for a trauma-dissociation linkage hypothesis: the greater the dissociation during traumatic stress exposure, the greater the likelihood of meeting criteria for current PTSD.     

Overexpression of HER2 modulates bcl-2, bcl-XL, and tamoxifen-induced apoptosis in human MCF-7 breast cancer cells

Overexpression of HER2 in estrogen receptor (ER)-positive human breast tumors has been associated with resistance to endocrine therapy. Here we investigated the effects of HER2 on expression of apoptotic pathways and modulation of tamoxifen-induced apoptosis in ER-positive MCF-7 breast cancer cells. We report that HER2 overexpression in MCF-7 cells is accompanied by up-regulation of antiapoptotic Bcl-2 and Bcl-XL proteins and suppression of tamoxifen-induced apoptosis. In addition, human tumor cell lines that are both ER positive and overexpress HER2 also express enhanced levels of Bcl-2 compared to cells that are either ER positive or overexpress HER2 alone. Our findings suggest that possible deregulation of antiapoptotic Bcl-2 and Bcl-XL may be associated with the enhanced survival of HER2-overexpressing and ER-positive breast cancer cells treated with antiestrogens.