Browsing by Author "Pradhan, Kamnesh R."

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    Adult BMI change and risk of Breast Cancer: National Health and Nutrition Examination Survey (NHANES) 2005-2010
    (Springer-Verlag, 2015-11) Gathirua-Mwangi, Wambui G.; Zollinger, Terrell W.; Murage, Mwangi J.; Pradhan, Kamnesh R.; Champion, Victoria L.; Department of Epidemiology, Richard M. Fairbanks School of Public Health
    OBJECTIVE: Breast cancer is the second leading cause of cancer mortality among women in the developed world. This study assessed the association between occurrence of breast cancer and body mass index (BMI) change from age 25 to age closest to breast cancer diagnosis while exploring the modifying effects of demographic variables. METHODS: The National Health and Nutrition Examination Survey data were used. Women included were ≥50 years, not pregnant and without a diagnosis of any cancer but breast. The total sample included 2895 women (172 with breast cancer and 2723 controls with no breast cancer diagnosis). Multivariate logistic regression was used to estimate the OR and 95 % CIs and interaction evaluated by including an interaction term in the model. RESULTS: Women whose BMI increased from normal or overweight to obese compared to those who remained at a normal BMI were found to have a 2 times higher odds (OR = 2.1; 95 % CI 1.11-3.79) of developing breast cancer. No significant association was observed for women who increased to overweight. However, a more pronounced association was observed in non-Hispanic black women (OR = 6.6; 95 % CI 1.68-25.86) and a significant association observed when they increased from normal to overweight (OR = 4.2; 95 % CI 1.02-17.75). CONCLUSIONS: Becoming obese after age 25 is associated with increased risk of breast cancer in women over 50 years old, with non-Hispanic black women being at greatest risk.
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    Endocrine and Metabolic Disorders in Survivors of Childhood Cancers and Health-Related Quality of Life and Physical Activity
    (Oxford, 2019-11) Pradhan, Kamnesh R.; Chen, Yan; Moustoufi-Moab, Sogol; Krull, Kevin; Oeffinger, Kevin C.; Sklar, Charles; Armstrong, Gregory T.; Ness, Kirsten K.; Robison, Leslie; Yasui, Yutaka; Nathan, Paul C.; Pediatrics, School of Medicine
    Context Childhood cancer survivors experience chronic health conditions that impact health-related quality of life (HRQOL) and participation in optimal physical activity. Objective The study aimed to determine independent effects of endocrine and metabolic disorders on HRQOL and physical activity. Design, Setting, and Patients Retrospective cohort with longitudinal follow-up of survivors of childhood cancer enrolled in the North American Childhood Cancer Survivor Study. Main Outcome Measures Medical Outcomes Short Form-36 estimated HRQOL, and participation in physical activity was dichotomized as meeting or not meeting recommendations from the Centers for Disease Control and Prevention. Log binomial regression evaluated the association of each endocrine/metabolic disorder with HRQOL scales and physical activity. Results Of 7287 survivors, with a median age of 32 years (range, 18 to 54 years) at their last follow-up survey, 4884 (67%) reported one or more endocrine/metabolic disorders. Survivors with either disorder were significantly more likely to be male, older, have received radiation treatment, and have experienced other chronic health conditions. After controlling for covariates, survivors with any endocrine/metabolic disorder were more likely to report poor physical function risk ratio (RR, 1.25; 95% CI, 1.05 to 1.48), increased bodily pain (RR, 1.27; 95% CI, 1.12 to 1.44), poor general health (RR, 1.49; 95% CI, 1.32 to 1.68), and lower vitality (RR, 1.21; 95% CI, 1.09 to 1.34) compared with survivors without. The likelihood of meeting recommended physical activity was lower among survivors with growth disorders (RR, 0.90; 95% CI, 0.83 to 0.97), osteoporosis (RR, 0.87; 95% CI, 0.76 to 0.99), and overweight/obesity (RR, 0.92; 95% CI, 0.88 to 0.96). Conclusion Endocrine and metabolic disorders are independently associated with poor HRQOL and suboptimal physical activity among childhood cancer survivors.
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    Human Proangiogenic Circulating Hematopoietic Stem and Progenitor Cells Promote Tumor Growth in an Orthotopic Melanoma Xenograft Model
    (Springer, 2013) Mund, Julie A.; Shannon, Harlan; Sinn, Anthony L.; Cai, Shanbao; Wang, Haiyan; Pradhan, Kamnesh R.; Pollok, Karen E.; Case, Jamie; Pediatrics, School of Medicine
    We previously identified a distinct population of human circulating hematopoietic stem and progenitor cells (CHSPCs; CD14(-)glyA(-)CD34(+)AC133(+/-)CD45(dim)CD31(+) cells) in the peripheral blood (PB) and bone marrow, and their frequency in the PB can correlate with disease state. The proangiogenic subset (pCHSPC) play a role in regulating tumor progression, for we previously demonstrated a statistically significant increase in C32 melanoma growth in NOD.Cg-Prkdc (scid) (NOD/SCID) injected with human pCHSPCs (p < 0.001). We now provide further evidence that pCHSPCs possess proangiogenic properties. In vitro bio-plex cytokine analyses and tube forming assays indicate that pCHSPCs secrete a proangiogenic profile and promote vessel formation respectively. We also developed a humanized bone marrow-melanoma orthotopic model to explore in vivo the biological significance of the pCHSPC population. Growth of melanoma xenografts increased more rapidly at 3-4 weeks post-tumor implantation in mice previously transplanted with human CD34(+) cells compared to control mice. Increases in pCHSPCs in PB correlated with increases in tumor growth. Additionally, to determine if we could prevent the appearance of pCHSPCs in the PB, mice with humanized bone marrow-melanoma xenografts were administered Interferon α-2b, which is used clinically for treatment of melanoma. The mobilization of the pCHSPCs was decreased in the mice with the humanized bone marrow-melanoma xenografts. Taken together, these data indicate that pCHSPCs play a functional role in tumor growth. The novel in vivo model described here can be utilized to further validate pCHSPCs as a biomarker of tumor progression. The model can also be used to screen and optimize anticancer/anti-angiogenic therapies in a humanized system.
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    Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial
    (Elsevier, 2012-12) Robertson, Kent A.; Nalepa, Grzegorz; Yang, Feng-Chun; Bowers, Daniel C.; Ho, Chang Y.; Hutchins, Gary D.; Croop, James M.; Vik, Terry A.; Denne, Scott C.; Parada, Luis F.; Hingtgen, Cynthia M.; Walsh, Laurence E.; Yu, Menggang; Pradhan, Kamnesh R.; Edwards-Brown, Mary K.; Cohen, Mervyn D.; Fletcher, James W.; Travers, Jeffrey B.; Staser, Karl W.; Lee, Melissa W.; Sherman, Marcie R.; Davis, Cynthia J.; Miller, Lucy C.; Ingram, David A.; Clapp, D. Wade; Pediatrics, School of Medicine
    BACKGROUND: Plexiform neurofibromas are slow-growing chemoradiotherapy-resistant tumours arising in patients with neurofibromatosis type 1 (NF1). Currently, there are no viable therapeutic options for patients with plexiform neurofibromas that cannot be surgically removed because of their proximity to vital body structures. We undertook an open-label phase 2 trial to test whether treatment with imatinib mesylate can decrease the volume burden of clinically significant plexiform neurofibromas in patients with NF1. METHODS: Eligible patients had to be aged 3-65 years, and to have NF1 and a clinically significant plexiform neurofibroma. Patients were treated with daily oral imatinib mesylate at 220 mg/m(2) twice a day for children and 400 mg twice a day for adults for 6 months. The primary endpoint was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data were analysed on an intention-to-treat basis; a secondary analysis was also done for those patients able to take imatinib mesylate for 6 months. This trial is registered with ClinicalTrials.gov, number NCT01673009. FINDINGS: Six of 36 patients (17%, 95% CI 6-33), enrolled on an intention-to-treat basis, had an objective response to imatinib mesylate, with a 20% or more decrease in tumour volume. Of the 23 patients who received imatinib mesylate for at least 6 months, six (26%, 95% CI 10-48) had a 20% or more decrease in volume of one or more plexiform tumours. The most common adverse events were skin rash (five patients) and oedema with weight gain (six). More serious adverse events included reversible grade 3 neutropenia (two), grade 4 hyperglycaemia (one), and grade 4 increases in aminotransferase concentrations (one). INTERPRETATION: Imatinib mesylate could be used to treat plexiform neurofibromas in patients with NF1. A multi-institutional clinical trial is warranted to confirm these results.
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    A Pilot Study of Circulating Endothelial and Hematopoietic Progenitor Cells in Children With Sarcomas
    (Wolters Kluwer, 2015-08) Pradhan, Kamnesh R.; Mund, Julie A.; Claussen, Heather L.; Gosiengfiao, Yasmin C.; Radulescu, Vlad C.; Ballard, Jennifer J.; Liu, Ziyue; Vik, Terry A.; Case, Jamie; Department of Pediatrics, IU School of Medicine
    Utilizing a multiparametric flow cytometry protocol, we assessed various cell types implicated in tumor angiogenesis that were found circulating in the peripheral blood of children with sarcomas (cases) based on their cell surface antigen expression. Circulating endothelial cells (CECs), endothelial colony-forming cells (ECFCs), and the ratio of 2 distinct populations of circulating hematopoietic stem and progenitor cells (CHSPCs), the proangiogenic CHSPCs (pCHSPCs) and nonangiogenic CHSPCs (nCHSPCs) were enumerated. Multiparametric flow cytometry was analyzed in cases at baseline and at 4 additional timepoints until the end of treatment and levels compared with each other and with healthy controls. At all timepoints, cases had significantly lower levels of CECs, but elevated ECFCs and a pCHSPC:nCHSPC ratio compared with controls (all P-values <0.05). There was no significant difference in any of the cell types analyzed based on tumor histology, stage (localized vs. metastatic), or tumor size. After treatment, only the CECs among the complete responders were significantly lower at end of therapy (P<0.01) compared with nonresponders, whereas the ECFCs among all cases significantly increased (P<0.05) compared with baseline. No decline in the pCHSPC:nCHSPC ratio was observed despite tumor response. On the basis of these results, a validation of CECs as prognostic biomarker is now warranted.
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    Psychometric Testing of Attitudes Toward Physical Activity Scale for Adolescent and Young Adult Survivors of Pediatric Cancer
    (Mary Ann Liebert, Inc., 2022-10) Hullmann , Stephanie E.; Biederman, Erika; Monahan, Patrick O.; Champion, Victoria L.; Pradhan, Kamnesh R.; Psychiatry, School of Medicine
    Purpose: Adolescent and young adult (AYA) survivors of pediatric cancer experience chronic health problems following treatment, many of which could be prevented through healthy lifestyle choices. This report describes the development of the AYA Cancer Survivor Attitude (AYA-CSA) Scale, an attitudinal scale that is associated with physical activity in AYA survivors of pediatric cancer. Methods: AYA survivors (n = 100) completed a survey to evaluate their attitudes toward engagement in physical activity. Internal consistency was calculated using Cronbach's alpha. Construct validity was assessed by exploratory factor analysis, correlation with physical activity intention and physical activity behavior, and prediction of physical activity, after adjusting for past physical activity, survivor age, gender, and family income. Results: Data demonstrated a single 6-item scale with excellent internal consistency (α = 0.82). Construct validity was supported by significant correlations with physical activity intention (r = 0.553, p < 0.001) and physical activity behavior (r = 0.489, p < 0.001). After controlling for past physical activity and demographic covariates, survivor age, attitude toward physical activity, and intention were significant predictors of physical activity, and the overall model (F(6, 77) = 7.722, p < 0.001) predicted 39.5% of the variability in physical activity. Conclusion: The AYA-CSA scale demonstrates good reliability and construct validity, most important of which was the ability to predict actual physical activity in AYA survivors of pediatric cancer. This reliable and valid measure is an important tool in the design of behavioral interventions to improve physical activity engagement in AYA survivors.