Gregory S Young

The Ohio State University, Columbus, Ohio, United States

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Publications (58)228.02 Total impact

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    ABSTRACT: Objective: As part of the Patient Navigation Research Program, we examined the effect of patient navigation versus usual care on timely diagnostic follow-up, defined as clinical management for women with cervical abnormalities within accepted time frames. Methods: Participants from four Patient Navigation Research Program centers were divided into low- and high-risk abnormality groups and analyzed separately. Low-risk participants (n = 2088) were those who enrolled with an initial Pap test finding of atypical squamous cells of undetermined significance (ASCUS) with a positive high-risk human papillomavirus (HPV) serotype, atypical glandular cells, or low-grade squamous intraepithelial lesion (LGSIL). High-risk participants were those with an initial finding of high-grade squamous intraepithelial lesion (HGSIL) (n = 229). A dichotomous outcome of timely diagnostic follow-up within 180 days was used for the low-risk abnormality group and timely diagnostic follow-up within 60 days for the high-risk group, consistent with treatment guidelines. A logistic mixed-effects regression model was used to evaluate the intervention effect using a random effect for study arm within an institution. A backward selection process was used for multivariable model building, considering the impact of each predictor on the intervention effect. Results: Low-risk women in the patient navigation arm showed an improvement in the odds of timely diagnostic follow-up across all racial groups, but statistically significant effects were only observed in non-English-speaking Hispanics (OR 5.88, 95% CI 2.81-12.29). No effect was observed among high-risk women. Conclusion: These results suggest that patient navigation can improve timely diagnostic follow-up among women with low-risk cervical abnormalities, particularly in non-English-speaking Hispanic women.
    No preview · Article · Dec 2015 · Journal of Women's Health
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    ABSTRACT: The Jak/STAT pathway is activated in human pancreatic ductal adenocarcinoma (PDAC) and cooperates with mutant Kras to drive initiation and progression of PDAC in murine models. We hypothesized that the small-molecule Jak2 inhibitor (BMS-911543) would elicit anti-tumor activity against PDAC and decrease immune suppressive features of the disease. We used an aggressive genetically engineered PDAC model with mutant KrasG12D, tp53R270H, and Brca1 alleles (KPC-Brca1 mice). Mice with confirmed tumor burden were treated orally with vehicle or 30 mg/kg BMS-911543 daily for 14 days. Histologic analysis of pancreata from treated mice revealed fewer foci of adenocarcinoma and significantly decreased Ki67+ cells versus controls. In vivo administration of BMS-911543 significantly reduced pSTAT5 and FoxP3 positive cells within the pancreas, but did not alter STAT3 phosphorylation. Continuous dosing of KPC-Brca1 mice with BMS-911543 resulted in a median survival of 108 days, as compared to a median survival of 87 days in vehicle treated animals, a 23% increase (p = 0.055). In vitro experiments demonstrated that PDAC cell lines were poorly sensitive to BMS-911543, requiring high micromolar concentrations to achieve targeted inhibition of Jak/STAT signaling. Similarly, BMS-911543 had little in vitro effect on the viability of both murine and human PDAC-derived stellate cell lines. However, BMS-911543 potently inhibited phosphorylation of pSTAT3 and pSTAT5 at low micromolar doses in human PBMC and reduced in vitro differentiation of Foxp3+ T regulatory cells. These results indicate that single agent Jak2i deserves further study in preclinical models of PDAC and has distinct inhibitory effects on STAT5 mediated signaling.
    Preview · Article · Nov 2015 · Oncotarget
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    Full-text · Dataset · Nov 2015
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    ABSTRACT: Objective. To test the effectiveness of a colorectal cancer (CRC) screening intervention among adults living in Ohio Appalachia. Methods. We conducted a group-randomized trial of a county-level intervention among adults living in 12 Ohio Appalachian counties who received a media campaign and clinic intervention focused on either CRC screening or fruits and vegetables. Participants’ percentage within CRC screening guidelines was assessed with cross-sectional surveys conducted annually for four years, and validated with medical record review of screening. Results. On average, screening data were obtained on 564 intervention and 559 comparison participants per year. There was no difference in the Wave 4 CRC screening rates of intervention and comparison counties (35.2% versus 31.4%). Multivariate analyses found that high perceived risk of CRC, willingness to have a CRC test if recommended by a doctor, doctor recommendation of a CRC screening test, and patient-physician communication about changes in bowel habits, family history of CRC, and eating fruits and vegetables were significant ( p < 0.05 ) predictors of being within CRC screening guidelines. Conclusions. The intervention was not effective in increasing CRC rates among Ohio Appalachian adults. Future research should determine how media and clinic-based interventions can be modified to improve CRC screening rates among this underserved population.
    Full-text · Article · Oct 2015 · BioMed Research International

  • No preview · Article · Oct 2015 · Cancer Prevention Research
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    ABSTRACT: Scope: UVB exposure, a major factor in the development of skin cancer, has differential sex effects. Tomato product consumption reduces the intensity of UVB-induced erythema in humans, but the mechanisms are unknown. Methods and results: Four week old SKH-1 hairless mice (40 females, 40 males) were divided into two feeding groups (control or with 10% tangerine tomatoes naturally rich in UV-absorbing phytoene and phytofluene) and two UV exposure groups (with or without UV). After 10 weeks of feeding, the UV group was exposed to a single UV dose and sacrificed 48 hours later. Blood and dorsal skin samples were taken for carotenoid analysis. Dorsal skin was harvested to assess sex and UV effects on carotenoid deposition, inflammation (skinfold thickness, myeloperoxidase levels) and DNA damage (cyclobutane pyrimidine dimers, p53). Females had significantly higher levels of both skin and blood carotenoids relative to males. UV exposure significantly reduced skin carotenoid levels in females but not males. Tomato consumption attenuated acute UV-induced increases in CPD in both sexes, and reduced myeloperoxidase activity and % p53 positive epidermal cells in males. Conclusion: Tangerine tomatoes mediate acute UV-induced skin damage in SKH-1 mice via reduced DNA damage in both sexes, and through reduced inflammation in males. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Molecular Nutrition & Food Research
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    Full-text · Dataset · Aug 2015
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    ABSTRACT: There is a lack of information about the correlates of completing all three cancer screening tests among women living in Appalachia. Cross-sectional telephone interviews were conducted (April-September 2013) among women (n=637) ages 51-75 from 12 Appalachia Ohio counties. Outcomes of within screening guidelines were verified by medical record. Multivariable logistic regression models identified correlates of being within guidelines for all three cancer screening tests. Screening rates were: mammography (32.1%), Pap test (36.1%), and a colorectal cancer test (30.1%). Only 8.6% of women were within guidelines for all tests. Having had a check-up in the past two years and having received a screening recommendation were significantly related to being within guidelines for all three tests (p<0.01). Participants with higher annual household incomes ($60,000+; OR=3.53, 95% CI: 1.49, 8.33) and conditions requiring regular medical visits (OR=3.16, 95% CI: 1.29, 7.74) were more likely to be within guidelines for all three screening tests. Less than 10% of women had completed screening within guidelines for all three screening tests. Regular contact with the healthcare system and higher incomes were significant predictors of being within guidelines. Within guidelines rates for the three recommended cancer screening tests is low among women in Appalachia Ohio. This finding illustrates the need for innovative interventions to improve rates of multiple cancer screening tests. Copyright © 2015, American Association for Cancer Research.
    No preview · Article · Aug 2015 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: Epidemiological associations suggest populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, cross-over trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy-bread and soy-almond bread. The primary objective was to investigate isoflavone bioavailability and metabolite profile. Secondary objectives include safety, compliance and assessment of biomarkers linked to prostate carcinogenesis. Two distinct soy breads were formulated to deliver ~60 mg aglycone equivalents of isoflavones/day. The isoflavones were present as aglycones (~78% as aglycones,) in the soy-almond bread (SAB) while in the standard soy bread (SB) predominantly as glucosides (18% total isoflavones as aglycones). Compliance to SB (97%±4%) and SAB (92%±18%) was excellent, toxicity was rare and limited to grade I gastrointestinal complaints. Pharmacokinetic studies between SB and SAB showed modest differences. Peak serum concentration time (Tmax) was significantly faster with SAB meal compared with SB in some isoflavonoids and AUC0 to 24 hr of dihydrodaidzein and O-desmethylangolensin was significantly greater after a SB meal. An exploratory cluster analysis was used to identify four isoflavone metabolizing phenotypes. Insulin-like growth factor binding protein increased significantly by 41% (p=0.024) with soy intervention. Findings from this study provide the necessary framework to study isoflavone metabolizing phenotypes as a strategy for identification of individuals that might benefit or show resistance to cancer preventive strategies using dietary soy. A standardized soy bread used for future large-scale randomized clinical trials to impact human prostate carcinogenesis is feasible. Copyright © 2015, American Association for Cancer Research.
    Full-text · Article · Aug 2015 · Cancer Prevention Research
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    ABSTRACT: We hypothesized that soy phytochemicals may have immunomodulatory properties that may impact prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 prostate cancer patients with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to 2 slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on Day 56 versus baseline. Subgroup analysis indicated reduced Th1 (p=0.028) and MDSC-associated cytokines (p=0.035). Th2 and Th17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8+ or CD4+ T cells, but showed increased CD56+ NK cells (p=0.038). The percentage of cells with a T regulatory cell phenotype (CD4+CD25+FoxP3+) were significantly decreased after 56 days of soy bread (p=0.0136). Significantly decreased monocytic (CD33+HLADRnegCD14+) MDSC were observed in patients consuming soy bread (p=0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers relevant to immunomodulation consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required. Copyright © 2015, American Association for Cancer Research.
    Full-text · Article · Aug 2015 · Cancer Prevention Research
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    ABSTRACT: Increased prevalence of overweight and obesity among Appalachian residents may contribute to increased cancer rates in this region. This manuscript describes the design, components, and participant baseline characteristics of a faith-based study to decrease overweight and obesity among Appalachian residents. A group randomized study design was used to assign 13 churches to an intervention to reduce overweight and obesity (Walk by Faith) and 15 churches to a cancer screening intervention (Ribbons of Faith). Church members with a body mass index (BMI) ≥25 were recruited from these churches in Appalachian counties in five states to participate in the study. A standard protocol was used to measure participant characteristics at baseline. The same protocol will be followed to obtain measurements after completion of the active intervention phase (12months) and the sustainability phase (24months). Primary outcome is change in BMI from baseline to 12months. Secondary outcomes include changes in blood pressure, waist-to-hip ratio, and fruit and vegetable consumption, as well as intervention sustainability. Church members (n=664) from 28 churches enrolled in the study. At baseline 64.3% of the participants were obese (BMI≥30), less than half (41.6%) reported regular exercise, and 85.5% reported consuming less than 5 servings of fruits and vegetables per day. Church members recruited to participate in a faith-based study across the Appalachian region reported high rates of unhealthy behaviors. We have demonstrated the feasibility of developing and recruiting participants to a faith-based intervention aimed at improving diet and increasing exercise among underserved populations. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jun 2015 · Contemporary clinical trials
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    ABSTRACT: Background: For women with hormone receptor–positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes.
    No preview · Article · Jun 2015 · JNCI Journal of the National Cancer Institute
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    ABSTRACT: Patient navigation (PN) may improve cancer care by identifying and removing patient-reported barriers to care. In 2012, the American College of Surgeons Commission on Cancer (CoC) announced that health care facilities seeking CoC accreditation must have PN processes in place by January 1, 2015. Given these unfunded mandates, hospitals are looking for cost-effective ways to implement PN. This study examined demographic and psychosocial predictors of barriers to diagnostic resolution among individuals with a cancer screening abnormality enrolled in the Ohio Patient Navigation Research Project. Data were obtained from patients who received care at 1 of 9 Ohio Patient Navigation Research Project intervention clinics. Descriptive statistics and logistic regression models were used. There were 424 participants, and 151 (35.6%) reported a barrier to diagnostic resolution within 90 days of study consent. The most commonly reported barriers were misconceptions about a test or treatment (16.4%), difficulty in communicating with the provider (15.0%), and scheduling problems (11.5%). Univariate analyses indicated that race, education, employment, income, insurance, clinic type, friend support, and physical and psychological functioning were significantly associated with reporting a barrier to diagnostic resolution. Multivariate analyses found that comorbidities (odds ratio, 1.65; 95% confidence interval, 1.04-2.61) and higher intrusive thoughts and feelings (odds ratio, 1.25; 95% confidence interval, 1.10-1.41) were significantly associated with reporting a barrier to diagnostic resolution. The results suggest that demographic and psychosocial factors are associated with barriers to diagnostic resolution. To ensure compliance with the CoC mandate and provide timely care to all patients, CoC-accredited facilities can systematically identify the patients most likely to have barriers to care and assign them to PN. Cancer 2015. © 2015 American Cancer Society. © 2015 American Cancer Society.
    No preview · Article · Apr 2015 · Cancer
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    ABSTRACT: To test the effectiveness of a colorectal cancer (CRC) screening intervention directed at three levels (clinic, provider, patient) in a primary care setting. We conducted a group randomized trial (Clinical Trials registration no. NCT01568151) among 10 primary care clinics in Columbus, Ohio that were randomized to a study condition (intervention or usual care). We determined the effect of a multi-level, stepped behavioral intervention on receipt of a CRC screening test among average-risk patients from these clinics over the study period. Patients (n=527) who were outside of CRC screening recommendations were recruited. Overall, 35.4% of participants in the intervention clinics had received CRC screening by the end of the study compared to 35.1% of participants who were in the usual care clinics. Time to CRC screening was also similar across arms (HR=0.97, 95% CI=0.65-1.45). The multi-level intervention was not effective in increasing CRC screening among participants who needed a test, perhaps due to low participation of patients in the stepped intervention. Future studies utilizing evidence-based strategies to encourage CRC screening are needed.
    Full-text · Article · Apr 2015
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    ABSTRACT: Patient navigation (PN) may reduce cancer health disparities. Few studies have investigated the effects of PN on patient-reported satisfaction with care or assessed patients’ satisfaction with navigators. The objectives of this study are to test the effects of PN on patient satisfaction with cancer care, assess patients’ satisfaction with navigators, and examine the impact of barriers to care on satisfaction for persons with abnormal cancer-related screening tests or symptoms. Study participants included women and men with abnormal breast, cervical, or colorectal cancer screening tests and/or symptoms receiving care at 18 clinics. Navigated (n = 416) and non-navigated (n = 292) patients completed baseline and end-of-study measures. There was no significant difference between navigated and non-navigated patients in change in patient satisfaction with cancer care from baseline to exit. African-American (p p = 0.03), low income (p p p = 0.04), with full-time employment showing the most improvement. The interaction between satisfaction with navigators and satisfaction with care over time was marginally significant (p = 0.08). Baseline satisfaction was lower for patients who reported a barrier to care (p = 0.02). Patients reporting other-focused barriers (p = 0.03), including transportation (p = 0.02), had significantly lower increases in satisfaction over time. Overall, results suggested that assessing barriers to cancer care and tailoring navigation to barrier type could enhance patients’ experiences with health care. PN may have positive effects for healthcare organizations struggling to enhance quality of care.
    No preview · Article · Dec 2014 · Journal of Cancer Education
  • Paul L Reiter · Mira L Katz · Gregory S Young · Electra D Paskett
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    ABSTRACT: Patient navigation has been effective in improving cancer care, yet little is known about what predicts timely outcomes in navigated patients. To identify predictors of resolution of abnormal cancer screening tests in patients who received navigation. We examined data on patients with abnormal breast (n = 256) or cervical (n = 150) screening tests or symptoms who received navigation as part of the Ohio Patient Navigator Research Program during 2007-2010. We used multivariable Cox proportional hazards regression models to identify predictors of time to resolution (ie, when a patient's clinical abnormality or abnormal screening test was determined to be a benign condition or a cancer diagnosis). The median time to resolution was 183 days for navigated patients with breast abnormalities and 172 days for navigated patients with cervical abnormalities. In patients with breast abnormalities, those who reported at least 1 barrier to care during navigation (HR, 0.66; 95% CI, 0.51-0.86) or higher perceived stress (HR, 0.90; 95% CI, 0.82-0.98) had slower resolution. Among patients with cervical abnormalities, those who reported at least 1 barrier to care during navigation had slower resolution (HR, 0.62; 95% CI, 0.42-0.91). Patients with cervical abnormalities had faster resolution if they had private health insurance, but this effect was present only in younger women (interaction 𝑃 = .003). Unknown generalizability of results because patients were female and from clinics in central Ohio. Several variables predicted whether patient navigation led to faster resolution, and predictors differed somewhat by disease site. Results will be useful in improving current patient navigation programs and designing future programs. ©2014 Frontline Medical Communications.
    No preview · Article · Dec 2014
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    ABSTRACT: Background: Cervical cancer incidence and mortality rates are disproportionally higher among women living in Ohio Appalachia. Lay health advisor (LHA) interventions among underserved populations have been successful because they typically use trusted community members who serve as a liaison to the health care system and provide information, support, and encouragement. Purpose: To describe the Transtheoretical Model staging before and during a LHA intervention to increase cervical cancer screening rates, and explore the role of reported barriers on stage of change. Methods: Ohio Appalachian women (n=90) who were in need of a Pap test were randomized to a 10-month LHA intervention which consisted of two in-person visits, two phone calls, and four mailed postcards targeted to the participant’s stage of change. Results: Sixty-three percent of participants had forward stage movement after the intervention. The most common reported screening barriers were time constraints, forgetting to make an appointment, and cost. Women reporting the following barriers: doctor not recommending the test, unable to afford the test, and being embarrassed, nervous, or afraid of getting a Pap test were less likely to be in the action stage. Conclusions: Relative to usual care, LHAs accelerate patient movement up the stages of change related to Pap smear testing and help patients to successfully address reported barriers among this underserved population.
    No preview · Conference Paper · Nov 2014
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    ABSTRACT: Background: Research shows that multilevel factors influence healthcare delivery and patient outcomes. The study goal was to examine how clinic type (academic medical center (AMC) or federally-qualified health center (FQHC)) and patient characteristics influence time to resolution (TTR) among individuals with an abnormal cancer screening test enrolled in a patient navigation (PN) intervention. Methods: Data were obtained from the Ohio Patient Navigation Research Project, a group-randomized trial of 862 patients from 18 clinics in Columbus, Ohio. Patient's TTR after an abnormal breast, cervical, or colorectal screening test and the clinics' patient and provider characteristics were obtained. Descriptive statistics and Cox shared frailty proportional hazards regression models of TTR were used. Results: The mean patient age was 44.8 years and 71% of patients were white. In models adjusted for study arm, FQHC patients had a 39% lower rate of resolution than AMC patients (P=0.004). Patient factors of having a college education, private insurance, higher income, and being older were significantly associated with lower TTR. After adjustment for factors that substantially impacted the effect of clinic type (patient insurance status, education level and age), clinic type was not significantly associated with TTR. Conclusions: These results suggest that TTR among individuals participating in PN programs is influenced by multiple socioeconomic patient-level factors rather than clinic type. Consequently, PN interventions should be tailored to address SES factors that influence TTR. Impact: These results provide clues regarding where to target PN interventions and the importance of recognizing predictors of TTR according to clinic type.
    No preview · Article · Oct 2014 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: Background and Purpose Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-Specific Balance Confidence (ABC) Scale in individuals with HD. Methods Participants with HD [n = 20; mean age± SD =50.9 ± 13.7; 7 male] were tested on spatiotemporal gait measures and the TMT, FSST, and ABC Scale before and after a six week period to determine test-retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients. Results Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test-retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and three seconds for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures. Conclusions The high test-retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggests that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD.
    Full-text · Article · Sep 2014 · Gait & Posture
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    ABSTRACT: XPO1/CRM1 is a key nuclear exporter protein that mediates translocation of numerous cellular regulatory proteins. We investigated whether XPO1 is a potential therapeutic target in melanoma using novel selective inhibitors of nuclear export (SINE). In vitro effects of SINE on cell growth and apoptosis were measured by MTS assay and flow cytometry [Annexin V/propidium iodide (PI)], respectively in human metastatic melanoma cell lines. Immunoblot analysis was used to measure nuclear localization of key cellular proteins. The in vivo activity of oral SINE was evaluated in NOD/SCID mice bearing A375 or CHL-1 human melanoma xenografts. SINE compounds induced cytostatic and pro-apoptotic effects in both BRAF wild type and mutant (V600E) cell lines at nanomolar concentrations. The cytostatic and pro-apoptotic effects of XPO1 inhibition were associated with nuclear accumulation of TP53, and CDKN1A induction in the A375 cell line with wild type TP53, while pMAPK accumulated in the nucleus regardless of TP53 status. The orally bioavailable KPT-276 and KPT-330 compounds significantly inhibited growth of A375 (p<0.0001) and CHL-1 (p = 0.0087) human melanoma cell lines in vivo at well tolerated doses. Inhibition of XPO1 using SINE represents a potential therapeutic approach for melanoma across cells with diverse molecular phenotypes by promoting growth inhibition and apoptosis.
    Full-text · Article · Jul 2014 · PLoS ONE