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Monica E Lindgren,
Christopher P Fagundes,
Catherine M Alfano,
Stephen P Povoski,
Doreen M Agnese,
Mark W Arnold, William B Farrar,
Lisa D Yee,
William E Carson,
Carl R Schmidt,
Janice K Kiecolt-Glaser
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ABSTRACT: OBJECTIVE: A cancer diagnosis provokes significant levels of emotional distress, with intrusive thoughts being the most common manifestation among breast cancer survivors. Cancer-related intrusive thoughts can take the form of emotional memories, flashbacks, nightmares, and intrusive images. Emotional arousal after a severe life stressor prolongs adrenergic activation, which in turn may increase risk for post-traumatic symptomatology. However, antihypertensive beta-blockers block adrenergic activation and are known to reduce traumatic memories and related psychological distress. Thus, the current study examined the association between beta-blocker use and the severity of cancer-related intrusive thoughts and related symptoms following a cancer diagnosis. METHODS: The 174 breast and 36 female colorectal cancer patients who had recently undergone diagnostic screening or biopsy included 39 beta-blocker users and 171 non-users. Prior to any cancer treatment including surgery, participants completed questionnaires that included the Impact of Events Scale and the Center for Epidemiological Studies Depression Scale. Analyses controlled for age, education, cancer stage, cancer type, days since diagnosis, marital status, depression, and comorbidities. RESULTS: Although the high rates of cancer-related distress in this sample were similar to those of other studies with recently diagnosed patients, beta-blocker users endorsed 32% fewer cancer-related intrusive thoughts than non-users. CONCLUSIONS: Recently diagnosed cancer patients using beta-blockers reported less cancer-related psychological distress. These results suggest that beta-blocker use may benefit cancer patients' psychological adjustment following diagnosis, and provide a promising direction for future investigations on the pharmacological benefits of beta-blockers for cancer-related distress. Copyright © 2012 John Wiley & Sons, Ltd.
Psycho-Oncology 12/2012; · 3.34 Impact Factor
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Robert W Carlson,
D Craig Allred,
Benjamin O Anderson,
Harold J Burstein,
Stephen B Edge, William B Farrar,
Andres Forero,
Sharon Hermes Giordano,
Lori J Goldstein,
William J Gradishar, [......],
Elizabeth C Reed,
Mary Lou Smith,
Hatem Soliman,
George Somlo,
Richard L Theriault,
John H Ward,
Antonio C Wolff,
Richard Zellars,
Rashmi Kumar,
Dorothy A Shead
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ABSTRACT: These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option.
Journal of the National Comprehensive Cancer Network: JNCCN 07/2012; 10(7):821-9. · 4.41 Impact Factor
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Christopher P Fagundes,
Ronald Glaser,
Catherine M Alfano,
Jeanette M Bennett,
Stephen P Povoski,
Adele M Lipari,
Doreen M Agnese,
Lisa D Yee,
William E Carson, William B Farrar,
William B Malarkey,
Janice K Kiecolt-Glaser
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ABSTRACT: Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. The current study sought to determine biomarkers of fatigue that exist before cancer treatment. Relationships between the expression of latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and fatigue were examined in 158 women newly diagnosed with breast cancer or awaiting a positive diagnostic result. Higher CMV antibody titers, but not EBV antibody titers, were associated with a greater likelihood of being fatigued. Associations between fatigue and higher CMV antibody titers remained after controlling for alcohol use, smoking, comorbidities, depressive symptoms, age, BMI, cancer stage, and sleep problems. More sleep problems and higher levels of depressive symptoms were also associated with a greater likelihood of being fatigued. CMV antibody titers, but not EBV antibody titers, were associated with higher levels of C-reactive protein (CRP), but CRP was not associated with fatigue. When the cellular immune system is compromised, reactivation of latent herpesviruses may fuel chronic inflammatory responses. Prior work has suggested that fatigue may be related to inflammation and its associated sickness behaviors; accordingly, our findings may be tapping into this same physiological substrate.
Brain Behavior and Immunity 03/2012; 26(3):394-400. · 4.72 Impact Factor
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Christopher P Fagundes,
Jeanette M Bennett,
Catherine M Alfano,
Ronald Glaser,
Stephen P Povoski,
Adele M Lipari,
Doreen M Agnese,
Lisa D Yee,
William E Carson, William B Farrar,
William B Malarkey,
Min Chen,
Janice K Kiecolt-Glaser
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ABSTRACT: Both higher socioeconomic status (SES) and supportive personal relationships confer health benefits, including better immune function. This study assessed the joint impact of SES and social support on the expression of a latent herpesvirus, Epstein-Barr virus (EBV), in a group of highly stressed women.
Two-hundred and twenty four women either awaiting further evaluation following an abnormal mammogram or newly diagnosed with breast cancer completed questionnaires and provided blood samples to assess EBV viral capsid antigen (VCA) IgG antibody titers.
More highly educated women with more support from friends had lower EBV VCA antibody titers, reflecting a stronger cellular immune response to the latent virus; however, among less educated women, friend support was not associated with EBV antibody titers. As revealed in an ancillary analysis, more highly educated women with more friend support had lower systolic blood pressure (SBP); however, friend support was not associated with SBP among less educated women. Neither depression nor perceived stress mediated these associations. Neither cancer status nor cancer stage among those diagnosed with cancer was significantly related to these outcomes.
Lower SES women may not reap the same immunological benefits from friend support when experiencing a stressful life event as their higher SES counterparts.
Health Psychology 01/2012; 31(1):11-9. · 3.87 Impact Factor
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Robert W Carlson,
D Craig Allred,
Benjamin O Anderson,
Harold J Burstein,
W Bradford Carter,
Stephen B Edge,
John K Erban, William B Farrar,
Andres Forero,
Sharon Hermes Giordano, [......],
Ingrid A Mayer,
Beryl McCormick,
Lori J Pierce,
Elizabeth C Reed,
Jasgit Sachdev,
Mary Lou Smith,
George Somlo,
John H Ward,
Antonio C Wolff,
Richard Zellars
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ABSTRACT: Overview These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer are the work of the members of the NCCN Breast Cancer Panel. Categories of evidence and consensus were assessed and are noted in the algorithms and text. Although not explicitly stated at every decision point of the NCCN Guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer. The full breast cancer guidelines are not printed in this issue of JNCCN, but can be accessed online at www.NCCN.org. The American Cancer Society estimated that 209,060 new cases of invasive breast cancer were diagnosed and 40,230 people died of breast cancer in the United States in 2010.(1) In addition, approximately 54,010 women were diagnosed with carcinoma in situ of the breast during the same year. Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The incidence of breast cancer has increased steadily in the United States over the past few decades, but breast cancer mortality seems to be declining,(1,2) suggesting a benefit from early detection and more effective treatment. The cause of most breast cancer cases is unknown. However, numerous risk factors for the disease have been established, including female gender, increasing patient age, family history of breast cancer at a young age, early menarche, late menopause, older age at first live birth, prolonged hormone replacement therapy, previous exposure to therapeutic chest...
Journal of the National Comprehensive Cancer Network: JNCCN 02/2011; 9(2):136-222. · 4.41 Impact Factor
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Robert W Carlson,
D Craig Allred,
Benjamin O Anderson,
Harold J Burstein,
W Bradford Carter,
Stephen B Edge,
John K Erban, William B Farrar,
Andres Forero,
Sharon Hermes Giordano, [......],
Ingrid A Mayer,
Beryl McCormick,
Lori J Pierce,
Elizabeth C Reed,
Mary Lou Smith,
George Somlo,
Neal S Topham,
John H Ward,
Eric P Winer,
Antonio C Wolff
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ABSTRACT: Overview The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer: Noninvasive and Special Situations presented here are the work of the NCCN Breast Cancer panel members. Categories of evidence and consensus were assessed and are noted in the algorithms and text. Although not explicitly stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer. These NCCN Guidelines focus on noninvasive breast cancer and special situations, such as Paget's disease, phyllodes tumor, breast cancer during pregnancy, and axillary breast cancer. Another NCCN guideline addresses invasive breast cancer (see NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Breast Cancer: Invasive and Inflammatory; to view the complete and most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org). The American Cancer Society estimates that 194,280 new cases of invasive breast cancer were diagnosed and 40,610 died of the disease in the United States in 2009.(1) In addition, approximately 62,280 women were diagnosed with carcinoma in situ of the breast during the same year. Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The incidence of breast cancer has increased steadily in the United States over the past few decades, but breast cancer mortality seems to be declining,(1,2) suggesting a benefit from early detection and more effective treatment. The origin of most breast cancer...
Journal of the National Comprehensive Cancer Network: JNCCN 11/2010; 8(10):1182-207. · 4.41 Impact Factor
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R Michael Tuttle,
Douglas W Ball,
David Byrd,
Raza A Dilawari,
Gerard M Doherty,
Quan-Yang Duh,
Hormoz Ehya, William B Farrar,
Robert I Haddad,
Fouad Kandeel, [......],
Judith C McCaffrey,
John A Olson,
Lee Parks,
John A Ridge,
Jatin P Shah,
Steven I Sherman,
Cord Sturgeon,
Steven G Waguespack,
Thomas N Wang,
Lori J Wirth
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ABSTRACT: Overview Epidemiology Thyroid nodules are approximately 4 times more common in women than in men. Palpable nodules increase in frequency throughout life, reaching a prevalence of approximately 5% in the United States population aged 50 years and older.(1-3) Nodules are even more prevalent when the thyroid gland is examined at autopsy or surgery, or when using ultrasonography, and 50% of these have nodules, which are almost always benign.(2,4) New nodules develop at a rate of approximately 0.1% per year beginning in early life, but at a much higher rate (∼2% per year) after exposure to head and neck irradiation.(5,6) By contrast, thyroid carcinoma is uncommon. For the United States population, the lifetime risk of being diagnosed with thyroid carcinoma is less than 1% (0.83% for women and 0.33% for men).(7) Approximately 37,200 new cases of thyroid carcinoma were diagnosed in the United States in 2009.(8) As with thyroid nodules, thyroid carcinoma occurs 2 to 3 times more often in women than in men. With the incidence increasing by 6.2% per year, thyroid carcinoma is currently the sixth most common malignancy diagnosed in women.(8) Among persons age 15 to 24 years, thyroid carcinoma accounts for 7.5% to 10% of all diagnosed malignancies.(9-11) The disease is also diagnosed more often in white North Americans than in African Americans. Although thyroid carcinoma can occur at any age, the peak incidence from 2004 to 2006 was near age 45 to 49 years in women and 65 to 69 years in men.(7) Thyroid carcinoma has...
Journal of the National Comprehensive Cancer Network: JNCCN 11/2010; 8(11):1228-74. · 4.41 Impact Factor
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ABSTRACT: A clinical trial was designed to test the hypothesis that a psychological intervention could reduce the risk of cancer recurrence. Newly diagnosed regional breast cancer patients (n = 227) were randomized to the intervention-with-assessment or the assessment-only arm. The intervention had positive psychological, social, immune, and health benefits, and after a median of 11 years the intervention arm was found to have reduced the risk of recurrence (hazard ratio, 0.55; P = 0.034). In follow-up, we hypothesized that the intervention arm might also show longer survival after recurrence. If observed, we then would examine potential biobehavioral mechanisms.
All patients were followed; 62 recurred. Survival analyses included all 62. Upon recurrence diagnosis, those available for further biobehavioral study were accrued (n = 41, 23 intervention and 18 assessment). For those 41, psychological, social, adherence, health, and immune (natural killer cell cytotoxicity, T-cell proliferation) data were collected at recurrence diagnosis and 4, 8, and 12 months later.
Intent-to-treat analysis revealed reduced risk of death following recurrence for the intervention arm (hazard ratio, 0.41; P = 0.014). Mixed-effects follow-up analyses with biobehavioral data showed that all patients responded with significant psychological distress at recurrence diagnosis, but thereafter only the intervention arm improved (P values < 0.023). Immune indices were significantly higher for the intervention arm at 12 months (P values < 0.017).
Hazards analyses augment previous findings in showing improved survival for the intervention arm after recurrence. Follow-up analyses showing biobehavioral advantages for the intervention arm contribute to our understanding of how improved survival was achieved.
Clinical Cancer Research 06/2010; 16(12):3270-8. · 7.74 Impact Factor
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R Michael Tuttle,
Douglas W Ball,
David Byrd,
Gilbert H Daniels,
Raza A Dilawari,
Gerard M Doherty,
Quan-Yang Duh,
Hormoz Ehya, William B Farrar,
Robert I Haddad, [......],
Judith McCaffrey,
John A Olson,
Lee Parks,
John A Ridge,
Jatin P Shah,
Steven I Sherman,
Cord Sturgeon,
Steven G Waguespack,
Thomas N Wang,
Lori J Wirth
Journal of the National Comprehensive Cancer Network: JNCCN 05/2010; 8(5):512-30. · 4.41 Impact Factor
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ABSTRACT: The objective of the study was to determine the outcome of surgical resection of metastatic papillary thyroid cancer (PTC) in cervical lymph nodes after failure of initial surgery and I(131) therapy.
This was a retrospective clinical study.
The study was conducted at a university-based tertiary cancer hospital.
A cohort of 95 consecutive patients with recurrent/persistent PTC in the neck underwent initial reoperation during 1999-2005. All had previous thyroidectomy (+/-nodal dissection) and I(131) therapy. Twenty-five patients with antithyroglobulin (Tg) antibodies were subsequently excluded.
Biochemical complete remission (BCR) was stringently defined as undetectable TSH-stimulated serum Tg.
A total of 107 lymphadenectomies were undertaken in these 70 patients through January 2010. BCR was initially achieved in 12 patients (17%). Of the 58 patients with detectable postoperative Tg, 28 had a second reoperation and BCR was achieved in five (18%), seven had a third reoperation, and none achieved BCR. No patient achieving BCR had a subsequent recurrence after a mean follow-up of 60 months (range 4-116 months). In addition, two more patients achieved BCR during long-term follow-up without further intervention. In total, 19 patients (27%) achieved BCR and 32 patients (46%) achieved a TSH-stimulated Tg less than 2.0 ng/ml. Patients who did not achieve BCR had significant reduction in Tg after the first (P < 0.001) and second (P = 0.008) operations. No patient developed detectable distant metastases or died from PTC.
Surgical resection of persistent PTC in cervical lymph nodes achieves BCR, when most stringently defined, in 27% of patients, sometimes requiring several surgeries. No biochemical or clinical recurrences occurred during follow-up. In patients who do not achieve BCR, Tg levels were significantly reduced. The long-term durability and impact of this intervention will require further investigation.
The Journal of clinical endocrinology and metabolism 03/2010; 95(5):2187-94. · 6.50 Impact Factor
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Therese B Bevers,
Benjamin O Anderson,
Ermelinda Bonaccio,
Saundra Buys,
Sandra Buys,
Mary B Daly,
Peter J Dempsey, William B Farrar,
Irving Fleming,
Judy E Garber, [......],
Seema A Khan,
Helen Krontiras,
Gary Lyman,
Elizabeth Rafferty,
Sara Shaw,
Mary Lou Smith,
Theodore N Tsangaris,
Cheryl Williams,
Thomas Yankeelov,
Thomas Yaneeklov
Journal of the National Comprehensive Cancer Network: JNCCN 11/2009; 7(10):1060-96. · 4.41 Impact Factor
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Robert W Carlson,
D Craig Allred,
Benjamin O Anderson,
Harold J Burstein,
W Bradford Carter,
Stephen B Edge,
John K Erban, William B Farrar,
Lori J Goldstein,
William J Gradishar, [......],
Lisle M Nabell,
Lori J Pierce,
Elizabeth C Reed,
Mary Lou Smith,
George Somlo,
Richard L Theriault,
Neal S Topham,
John H Ward,
Eric P Winer,
Antonio C Wolff
Journal of the National Comprehensive Cancer Network: JNCCN 03/2009; 7(2):122-92. · 4.41 Impact Factor
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ABSTRACT: BACKGROUND.The question of whether stress poses a risk for cancer progression has been difficult to answer. A randomized clinical trial tested the hypothesis that cancer patients coping with their recent diagnosis but receiving a psychologic intervention would have improved survival compared with patients who were only assessed.METHODS.A total of 227 patients who were surgically treated for regional breast cancer participated. Before beginning adjuvant cancer therapies, patients were assessed with psychologic and behavioral measures and had a health evaluation, and a 60-mL blood sample was drawn. Patients were randomized to Psychologic Intervention plus assessment or Assessment only study arms. The intervention was psychologist led; conducted in small groups; and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care. Earlier articles demonstrated that, compared with the Assessment arm, the Intervention arm improved across all of the latter secondary outcomes. Immunity was also enhanced.RESULTS.After a median of 11 years of follow-up, disease recurrence was reported to occur in 62 of 212 (29%) women and death was reported for 54 of 227 (24%) women. Using Cox proportional hazards analysis, multivariate comparison of survival was conducted. As predicted, patients in the Intervention arm were found to have a reduced risk of breast cancer recurrence (hazards ratio [HR] of 0.55; P = .034) and death from breast cancer (HR of 0.44; P = .016) compared with patients in the Assessment only arm. Follow-up analyses also demonstrated that Intervention patients had a reduced risk of death from all causes (HR of 0.51; P = .028).CONCLUSIONS.Psychologic interventions as delivered and studied here can improve survival. Cancer 2008. © 2008 American Cancer Society.
Cancer 12/2008; 113(12):3450 - 3458. · 4.77 Impact Factor
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ABSTRACT: The question of whether stress poses a risk for cancer progression has been difficult to answer. A randomized clinical trial tested the hypothesis that cancer patients coping with their recent diagnosis but receiving a psychologic intervention would have improved survival compared with patients who were only assessed.
A total of 227 patients who were surgically treated for regional breast cancer participated. Before beginning adjuvant cancer therapies, patients were assessed with psychologic and behavioral measures and had a health evaluation, and a 60-mL blood sample was drawn. Patients were randomized to Psychologic Intervention plus assessment or Assessment only study arms. The intervention was psychologist led; conducted in small groups; and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care. Earlier articles demonstrated that, compared with the Assessment arm, the Intervention arm improved across all of the latter secondary outcomes. Immunity was also enhanced.
After a median of 11 years of follow-up, disease recurrence was reported to occur in 62 of 212 (29%) women and death was reported for 54 of 227 (24%) women. Using Cox proportional hazards analysis, multivariate comparison of survival was conducted. As predicted, patients in the Intervention arm were found to have a reduced risk of breast cancer recurrence (hazards ratio [HR] of 0.55; P = .034) and death from breast cancer (HR of 0.44; P = .016) compared with patients in the Assessment only arm. Follow-up analyses also demonstrated that Intervention patients had a reduced risk of death from all causes (HR of 0.51; P = .028).
Psychologic interventions as delivered and studied here can improve survival.
Cancer 12/2008; 113(12):3450-8. · 4.77 Impact Factor
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ABSTRACT: There are few patient-reported data regarding quality of life after taxane-based adjuvant chemotherapy and none regarding mental health outcomes.
This was a naturalistic, longitudinal study that used a case-control design. Data were derived from a randomized clinical trial in patients who had stage II/III breast cancer (N = 227). Paclitaxel (Taxol) was approved for use midway during the accrual period (1994-1999). Patients who received taxanes as part of their adjuvant chemotherapy (the taxane group; n = 55) were matched with patients receiving regimens without taxanes (the no-taxane group; n = 83) on trial arm, lymph node status, surgery type, menopausal status, and partner status. Mixed-effects models tested for group differences in nurse evaluations of patients' symptoms and Karnofsky performance status and in patient-reported quality of life (the 36-item Medical Outcomes Study Short Form) and emotional distress (Profile of Mood States; Center for Epidemiological Studies Depression scale).
As expected, patients in the taxane group experienced significantly higher rates of selected toxicities, including arthralgia/myalgia (45% vs 26%) and ataxia (20% vs 5%). Patients in the taxane group also had significantly worse emotional distress and mental quality of life throughout adjuvant treatment. Rates of probable clinical depression also were high. In contrast, these outcomes were improving for patients in the no-taxane group (all P < .023). Emotional recovery for patients in the taxane group required 2 years on average versus 6 to 12 months for patients in the no-taxane group. During Years 3 through 5, the groups had similar outcomes.
These data suggested that taxane-based chemotherapies confer risk for significant psychological symptoms. Depression, in particular, should be monitored.
Cancer 08/2008; 113(3):638-47. · 4.77 Impact Factor
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ABSTRACT: Diagnostic (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) is an established method for detecting ovarian cancer. However, there is no established method to detect hypermetabolic tumor intraoperatively to evaluate disease extent and assure complete resection. We describe an innovative approach for intraoperative tumor localization and verification of tumor resection utilizing (18)F-FDG for perioperative PET/CT imaging and intraoperative gamma probe detection in ovarian cancer.
Three patients with recurrent ovarian cancer in the lymph nodes were evaluated. Diagnostic (18)F-FDG PET/CT was performed before surgery to establish the disease location. Preoperatively, (18)F-FDG was injected intravenously. Intraoperatively, tumors were localized with a handheld gamma probe. Postoperatively, resected tumors were scanned with a specimen PET/CT to confirm metabolic activity in those specimens.
All patients had recurrent epithelial ovarian cancer with groin or retroperitoneal lymph node metastasis diagnosed with PET/CT. In two patients, intraoperative gamma probe detection, specimen PET/CT, and postoperative PET/CT verified complete resection of the clinical and hypermetabolic lesions (in one case, the extent of disease was not fully apparent intraoperatively by gross palpation or inspection). The other patient was demonstrated to have extensive, unresectable disease in the porta hepatis and celiac axis, much of which was recognized only with the intraoperative gamma probe and not with the initial intraoperative survey.
Perioperative PET/CT imaging with intraoperative detection using a gamma probe following a single (18)F-FDG injection dose is feasible, establishes the location and extent of disease, and confirms a complete cytoreduction for recurrent ovarian cancer.
Gynecologic Oncology 07/2008; 110(2):152-7. · 3.89 Impact Factor
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ABSTRACT: Anaplastic thyroid cancer is an uncommon, typically lethal malignancy of older adults with no effective systemic therapy. The mean survival time is usually less than 6 months from the time of diagnosis and, unfortunately, this outcome is not fundamentally altered by available treatments. Histologic tissue confirmation is recommended if the diagnosis is not absolutely certain to exclude tumors with better prognosis or that require different treatment. Patency of the airway should be kept in mind throughout the patient's course and individuals with impending airway obstruction, in the absence of imminent death from other sites of disease, should be considered for a tracheostomy to secure the airway. Enrollment in meaningful clinical trials should be given the highest priority at all decision points.
Endocrinology & Metabolism Clinics of North America 07/2008; 37(2):525-38, xi. · 3.41 Impact Factor
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ABSTRACT: A number of hereditary syndromes have been found to be associated with pheochromocytoma development, but there is a paucity of data regarding secondary molecular events, such as downregulation of the p16INK4A/Cdkn2a gene (hereafter p16), contributing to pheochromocytoma tumorigenesis. Using tissue microarray and immunohistochemistry, we evaluated the expression of p16 in 31 pheochromocytoma tumor specimens. Our results showed that the p16 gene was expressed at low level or even not expressed in all but one specimens [30/31 (96.8%)], indicative of the prevalence of p16 downregulation in pheochromocytomas. In contrast, high expression of pl6 was observed in the majority of control "normal" specimens [5/7 (71.6%)]. To further investigate the molecular mechanisms underlying pl6 downregulation in pheochromocytomas, we used quantitative real-time PCR, methylation-specific PCR, and direct DNA sequencing to analyze these specimens for potential genetic alterations of the p16 gene. Deletions and aberrant CpG methylation of pl6 were identified in 9 (29.0%) and 11 (35.5%) specimens, respectively, while one specimen harbored a point mutation, Ala --> Pro at residue 20 of P16, and this mutation led to an eightfold decrease in the CDK4-inhibitory activity of P16. The overall frequency of pl6 genetic alterations is 67.7%. Taken together, our results demonstrate that reduced expression of pl6 is a common event in human pheochromocytomas, and the primary cause for such downregulation is inactivating genetic abnormalities in the p16 gene.
Gene Expression 01/2008; 14(4):207-16. · 1.31 Impact Factor
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ABSTRACT: Psychological interventions are efficacious in reducing emotional distress for cancer patients. However, it is not clear whether psychological improvements are, in turn, related to improved health. A clinical trial tests whether a psychological intervention for cancer patients can do so, and also tests two routes to achieve better health: (a) reducing patients' Emotional Distress, and/or (b) enhancing their functional immunity.
Post-surgery, 227 breast cancer patients were randomized to intervention or assessment only Study Arms. Conducted in small groups, intervention sessions were offered weekly for 4 months and followed by monthly sessions for 8 months. Measures included psychological (distress), biological (immune), and health outcomes (performance status and evaluations of patient's symptomatology, including toxicity from cancer treatment, lab values) collected at baseline, 4 months, and 12 months.
A path model revealed that intervention participation directly improved health (p<.05) at 12 months. These effects remained when statistically controlling for baseline levels of distress, immunity, and health as well as sociodemographic, disease, and cancer treatment variables. Regarding the mechanisms for achieving better health, support was found for an indirect effect of distress reduction. That is, by specifically lowering intervention patients' distress at 4 months, their health was improved at 12 months (p<.05). Although the intervention simultaneously improved patients' T-cell blastogenesis in response to phytohemagglutinin (PHA), the latter increases were unrelated to improved health.
A convergence of biobehavioral effects and health improvements were observed. Behavioral change, rather than immunity change, was influential in achieving lower levels of symptomatology and higher functional status. Distress reduction is highlighted as an important mechanism by which health can be improved.
Brain Behavior and Immunity 10/2007; 21(7):953-61. · 4.72 Impact Factor
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Steven I Sherman,
Peter Angelos,
Douglas W Ball,
David Byrd,
Orlo H Clark,
Gilbert H Daniels,
Raza A Dilawari,
Hormoz Ehya, William B Farrar,
Robert F Gagel, [......],
Dominick M Lamonica,
Thom R Loree,
William M Lydiatt,
Judith McCaffrey,
John A Olson,
John A Ridge,
Jatin P Shah,
James C Sisson,
R Michael Tuttle,
Marshall M Urist
Journal of the National Comprehensive Cancer Network: JNCCN 08/2007; 5(6):568-621. · 4.41 Impact Factor
