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ABSTRACT: PURPOSE: To examine changes in cancer-related knowledge, distress, and decisional conflict from pre- to post-genetic counseling (GC) in before (BDS) and after (ADS) definitive surgery breast cancer (BC) patients. METHODS: Sociodemographic and clinical characteristics were collected at baseline; primary outcome data were collected before (T1) and after (T2) pretest GC. Within group changes for cancer-related knowledge, distress, and decisional conflict over genetic testing were compared by Wilcoxon signed-rank tests. RESULTS: Of 103 BC patients, 87 were ADS and 16 were BDS. Analyses revealed that both groups reported significant increases in knowledge between T1 and T2 (median change 4.2, p = 0.004, and 2.7, p < 0.001, for BDS and ADS patients, respectively). Overall cancer-related distress showed a downward trend between T1 and T2 for both groups and was significant for BDS patients (p = 0.041). Reports of BDS patients trended toward overall and subscale-specific increases in decisional conflict, with the exception of the uncertainty which trended downward, but did not reach significance. Overall decisional conflict decreased in ADS patients, approaching marginal significance (p = 0.056), with significant improvements in informed decision making (median change -12.6, p < 0.001; i.e., pretest GC yielded improved knowledge of benefits, risks, and side effects of available options). CONCLUSIONS: These pilot data suggest that pretest GC increases cancer-related knowledge for both BDS and ADS patients, decreases distress in BDS patients, and improves informed decision making in ADS patients. Future studies with larger sample sizes are needed to replicate these results.
Annals of Surgical Oncology 07/2012; · 4.17 Impact Factor
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Susan T Vadaparampil,
Jessica A Kahn,
Daniel Salmon,
Ji-Hyun Lee,
Gwendolyn P Quinn,
Richard Roetzheim,
Karen Bruder,
Teri L Malo,
Tina Proveaux, Xiuhua Zhao,
Neal Halsey,
Anna R Giuliano
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ABSTRACT: The purpose of this study was to determine the prevalence of physician recommendation of human papillomavirus (HPV) vaccination in early (ages 11-12), middle (13-17), and late adolescent/young adult (18-26) female patients by physician specialty, and to identify factors associated with recommendation in early adolescents.
A 38-item survey was conducted April 2009 through August 2009 among a nationally representative random sample of 1538 Family Physicians, Pediatricians, and Obstetricians and Gynecologists obtained from the American Medical Association Physician Masterfile. A multivariable model was used to assess factors associated with frequency of physician recommendation of HPV vaccination ("always"=76-100% of the time vs. other=0-75%) within the past 12 months.
Completed surveys were received from 1013 physicians, including 500 Family Physicians, 287 Pediatricians, and 226 Obstetricians and Gynecologists (response rate=67.8%). Across the specialties, 34.6% of physicians reported they "always" recommend the HPV vaccine to early adolescents, 52.7% to middle adolescents, and 50.2% to late adolescents/young adults. The likelihood of "always" recommending the HPV vaccine was highest among Pediatricians for all age groups (P<0.001). Physician specialty, age, ethnicity, reported barriers, and Vaccines for Children provider status were significantly associated with "always" recommending HPV vaccination for early adolescents.
Findings suggest missed clinical opportunities for HPV vaccination, and perceived barriers to vaccination may drive decisions about recommendation. Results suggest the need for age and specialty targeted practice and policy level interventions to increase HPV vaccination among US females.
Vaccine 09/2011; 29(47):8634-41. · 3.77 Impact Factor
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ABSTRACT: To evaluate satisfaction with (a) the timing and strength of provider recommendation for and (b) information received prior to and during genetic counseling (GC) among breast cancer patients who attended GC before definitive surgery (BDS) or after definitive surgery (ADS). Satisfaction with provider recommendation for and information received about GC was evaluated among breast cancer patients who attended GC as part of their clinical care (n=51). There were no significant differences among breast cancer patients who attended GC BDS or ADS in satisfaction with when the physician referred them for GC, the strength of recommendation for GC, the amount of information provided about the GC, and the information received in GC. From a clinical perspective, the optimal time for attending GC may be BDS. Nevertheless, breast cancer patients appear satisfied with physician recommendation of and information related to GC, regardless of when they attend.
The Breast Journal 01/2011; 17(1):79-82. · 1.64 Impact Factor
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ABSTRACT: Pre-implantation genetic diagnosis (PGD) is an assisted reproductive technology procedure which provides parents with the option of conducting genetic analyses to determine if a mutation is present in an embryo. Though studies have discussed perceptions of PGD from a general population, couples or high-risk women, no studies to date have specifically examined PGD usage among men. This study sought to explore perceptions and attitudes towards PGD among males who either carry a BRCA mutation or have a partner or first degree relative with a BRCA mutation.
A cross-sectional survey was conducted among 228 men visiting the Facing Our Risk of Cancer Empowered or Craigslist website. Eligibility criteria included men who self-reported they had been tested for a BRCA mutation or had a partner or first degree relative tested for a BRCA mutation. A 41-item survey assessed socio-demographic, clinical characteristics, PGD knowledge and attitudinal factors and consideration of the use of PGD. Differences in proportions of subgroups were tested using the Monte Carlo exact test for categorical data. A multiple logistic regression model was then built through a backward elimination procedure.
Although 80% of men reported being previously unfamiliar with PGD, after learning the definition of PGD, 34% of the 228 respondents then said they would 'ever consider the use of PGD'. Respondents who thought of PGD only in terms of 'health and safety' were almost three times more likely (OR = 2.82; 95% 1.19-6.71) to 'ever consider the use of PGD' compared with respondents who thought of PGD in terms of both 'health and safety', and 'religion and morality'.
As with other anonymous web-based surveys, we cannot verify clinical characteristics that may impact consideration of PGD use. Our findings indicate high-risk men need more information about PGD and may benefit from educational materials to assist them in reproductive decision-making.
Human Reproduction 10/2010; 25(10):2543-50. · 4.47 Impact Factor
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ABSTRACT: Effective treatments for advanced prostate cancer are much needed. Toward this goal, we show apoptosis and impaired long-term survival of androgen-independent prostate cancer cells (PC3 and PC3 derivatives) co-treated with the cyclin-dependent kinase (CDK) inhibitor roscovitine and an AKT inhibitor (LY294002 or API-2). Apoptosis of PC3 cells by the drug combination required caspase-9 but not caspase-8 activity and thus is mitochondria-dependent. Roscovitine reduced amounts of the caspase inhibitor XIAP, and API-2 increased amounts of the BH3-only protein Bim. PC3 cells apoptosed when co-treated with API-2 and either cdk9 siRNA, dominant-negative cdk9, or the cdk9 inhibitor DRB; they did not apoptose when co-treated with API-2 and XIAP siRNA. Bax accumulated in mitochondria in response to API-2, whereas release of cytochrome c from mitochondria required both API-2 and roscovitine. We suggest that roscovitine elicits events that activate Bax once it translocates to mitochondria and that inactivation of cdk9 signals these events and the down-regulation of XIAP. Collectively, our data show apoptosis of prostate cancer cells by a drug combination and identify Bax activation as a basis of cooperation.
The international journal of biochemistry & cell biology 08/2008; 41(3):595-602. · 4.89 Impact Factor
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ABSTRACT: Toward the goal of developing effective treatments for prostate cancers, we examined the effects of cyclin-dependent kinase inhibitors on the survival of prostate cancer cells. We show that roscovitine, R-roscovitine, and CGP74514A (collectively referred to as CKIs) induce the apoptosis of LNCaP and LNCaP-Rf cells, both of which express wild-type p53. Apoptosis required caspase-9 and caspase-3 activity, and cytochrome c accumulated in the cytosol of CKI-treated cells. Amounts of p53 increased substantially in CKI-treated cells, whereas amounts of the endogenous caspase inhibitor XIAP decreased. CKIs did not appreciably induce the apoptosis of LNCaP cells treated with pifithrin-alpha, which prevents p53 accumulation, or of prostate cancer cells that lack p53 function (PC3 and DU145). Ectopic expression of p53 in PC3 cells for 44 hours did not reduce XIAP abundance or induce apoptosis. However, p53-expressing PC3 cells readily apoptosed when exposed to CKIs or when depleted of XIAP by RNA interference. These findings show that CKIs induce the mitochondria-mediated apoptosis of prostate cancer cells by a dual mechanism: p53 accumulation and XIAP depletion. They suggest that these events in combination may prove useful in the treatment of advanced prostate cancers.
Cancer Research 10/2005; 65(17):7717-23. · 7.86 Impact Factor
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ABSTRACT: p27(Kip1) (p27) is a tumor suppressor whose stability is controlled by proteasome-mediated degradation, a process directed in part by cyclin-dependent kinase 2 (CDK2)-mediated phosphorylation of p27 at Thr(187) and its subsequent interaction with the Skp1-Cullin-F-box protein/Skp2 (Skp2) ubiquitin ligase. The present study shows that 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) arrests ovarian cancer cells in G(1) by stabilizing the p27 protein. 1,25(OH)(2)D(3) initiates a chain of events by decreasing the amounts of cyclin E and cyclin E-associated CDK2 activity. As a result, p27 phosphorylation at Thr(187) and consequently the interaction with Skp2 are decreased. 1,25(OH)(2)D(3) also increases p27 stability by decreasing the abundance of Skp2. It is the combined effect of 1,25(OH)(2)D(3) on both the CDK2-dependent phosphorylation of p27, and thus its affinity for Skp2, and Skp2 expression that dramatically increases the stability of the p27 protein. Similar to its effects in ovarian cancer cells, 1,25(OH)(2)D(3) induces p27 accumulation in wild type mouse embryo fibroblasts and arrests wild type but not p27-null mouse embryo fibroblasts in G(1). Stable expression of Skp2 in OVCAR3 cells diminishes the G(1) arrest and decreases the growth response to 1,25(OH)(2)D(3). Taken together, the results of this study identify p27 as the key mediator of 1,25(OH)(2)D(3)-induced growth suppression in G(1) and show that the hormone achieves this by decreasing the activity of CDK2 and reducing the abundance of Skp2, which act together to degrade p27.
Journal of Biological Chemistry 07/2004; 279(24):25260-7. · 4.77 Impact Factor
