Relationship of pathological features and a 21 gene expression assay in younger versus older women with node-negative endocrine receptor-positive breast cancer.

PURPOSE: Determining the need for adjuvant chemotherapy in estrogen receptor (ER)+ disease can be influenced by pathological characteristics and gene expression assays [i.e., Oncotype Dx recurrence scores (RSs)]. The primary objective of this study is to investigate the relationship between the RSs and pathological markers in younger (< 50) versus older (≥ 50) women with early-stage node-negative ER+ breast cancer. METHODS: This was a single academic-center retrospective cohort study. Subjects who underwent Oncotype gene expression testing were retrospectively and sequentially identified. 436 Subjects were identified of which 344 were eligible for analysis (133 younger subjects < 50 years of age, and 211 older subjects ≥ 50 years). Pathological data assessed included the progesterone receptor (PR), histological grade (grade), Ki-67, and P53. A multivariable regression analysis was performed using age, PR, and grade as predictor variables for RS. Adjusted R2 was determined. To investigate the primary objective, subjects were stratified based on age, PR, and grade status in that sequence. Within each tumor subtype as determined by PR and grade statuses, the RSs in the younger versus older age group were compared using Student's t-test and the differences in the 95% confidence interval limits in RS means calculated. Age influence on adjuvant chemotherapy recommendation was also assessed by stratifying subjects based on age (< 50 vs. ≥ 50) and then by RS risk group (≤ 10, 11-25, ≥ 26). Subsequently, the proportions of younger versus older subjects within identical RS risk groups who were explicitly advised by their oncologist to proceed with chemotherapy as documented in their electronic health records were compared using χ2 test. RESULTS: Based on the multivariable regression analysis, the adjusted R2 was 0.229232 and RS was found to be independent of age (p = 0.7169). Between younger and older subjects with tumors with similar PR and grade pathological features, the differences in the RS were insignificant (p > 0.05). Chemotherapy was recommended in younger versus older women, in 0% when the RS was ≤ 10, 39% and 40% when the RS was 11-25 (p = 0.82), and 100% and 98% when the RS was ≥ 26 (p = 0.51), respectively. CONCLUSIONS: The relationship between pathological features and RS is consistent irrespective of age; therefore, models predicting RS may be applicable irrespective of age.

Synuclein-γ in uterine serous carcinoma impacts survival: An NRG Oncology/Gynecologic Oncology Group study.

BACKGROUND: Synuclein-γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG-8023). METHODS: High-density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu. Associations of SNCG and other tumor markers with overall and progression-free survival were assessed using log-rank tests and Cox proportional-hazards models, which also were adjusted for age, race, and stage. RESULTS: The overall survival at 5 years was 46% for women with high SNCG expression and 62% for those with low SNCG expression (log-rank P = .021; hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.91-1.9 in adjusted Cox model). The progression-free survival rate at 5 years was worse for women who had high SNCG expression, at 40%, compared with 56% for those who had low SNCG expression (log-rank P = .0081; HR, 1.36; 95% CI, 0.96-1.92 in adjusted Cox model). High levels of both p53 and p16 were significantly associated with worse overall survival (p53: HR, 4.20 [95% CI, 1.54-11.45]; p16: HR, 1.95 [95% CI, 1.01-3.75]) and progression-free survival (p53: HR, 2.16 [95% CI, 1.09-4.27]; p16: HR, 1.53 [95% CI, 0.87-2.69]) compared with low levels. CONCLUSIONS: This largest collection of USCs to date demonstrates that SNCG was associated with poor survival in univariate analyses. SNCG does not predict survival outcome independent of p53 and p16 in models that jointly consider multiple markers. Cancer 2017;123:1144-1155. © 2016 American Cancer Society.

Final Results of a 3-Year Literacy-Informed Intervention to Promote Annual Fecal Occult Blood Test Screening.

This three arm study was designed to make CRC screening with FOBTs more accessible, understandable and actionable for patients cared for in predominantly rural Federally Qualified Health Centers. Patients in an enhanced version of usual care received an annual CRC recommendation and FOBT kit; those in the education arm additionally received brief literacy and culturally appropriate education and those in the nurse arm received the education by a nurse manager who followed up by telephone. Baseline FOBT rates in this population were 3 %. We evaluated if FOBT rates could be sustained over 3 years. A three-arm, quasi-experimental evaluation was conducted among eight clinics in Louisiana. Screening efforts included: (1) enhanced usual care, (2) literacy-informed education of patients, and (3) education plus nurse support. Overall, 961 average-risk patients, ages 50-85, eligible for routine CRC screenings were recruited. The primary outcome was completing three annual FOBT tests. Of 961 patients enrolled, 381 (39.6 %) participants did not complete a single FOBT, 60.4 % completed at least one FOBT of which 318 (33.1 %) completed only one, 162 (16.9 %) completed two and 100 (10.4 %) completed three FOBTs over the 3-year period (the primary study outcome). The primary outcome, return of three FOBT kits over the 3-year period, was achieved by 4.7 % in enhanced care, 11.4 % in education and 13.6 % in the nurse arm (p = 0.005). Overall 3-year FOBT screening rates were not sustained with any of the three interventions, despite reports of promising interim results at years 1 and 2. New strategies for sustaining FOBT screening over several years must be developed.

Comparing the Performance of the S-TOFHLA and NVS Among and Between English and Spanish Speakers.

Given the growing body of evidence demonstrating the significant implications of health literacy on a myriad of outcomes, researchers continue to incorporate health literacy metrics in studies. With this proliferation in measurement of health literacy in research, it has become increasingly important to understand how various health literacy tools perform in specific populations. Our objective was to compare the performance of two widely used tests, the Short Test of Functional Health Literacy in Adults (S-TOFHLA) and the Newest Vital Sign (NVS) among and between a sample of English and Spanish-speaking patients. Adults (N = 402) ages 50-75 years participating in a trial to promote colorectal cancer screening completed in-person interviews which included both measures of health literacy. In the full sample, the tests were moderately correlated (r = 0.69, p < .0001); however, there was a stronger correlation among those completing the test in Spanish (r = 0.83) as compared with English (r = 0.58, p < .0001). English speakers more often were categorized as having adequate literacy by the S-TOFHLA as compared with the NVS, whereas Spanish speakers scored consistently low on both instruments. These findings indicate that the categorization of participants into levels of literacy is likely to vary, depending on whether the NVS or S-TOFHLA is used for assessment, a factor which researchers should be aware of when selecting literacy assessments.

Improving mammography screening among the medically underserved.

BACKGROUND: We evaluated the effectiveness and cost-effectiveness of alternative interventions designed to promote mammography in safety-net settings. METHODS: A three-arm, quasi-experimental evaluation was conducted among eight federally qualified health clinics in predominately rural Louisiana. Mammography screening efforts included: 1) enhanced care, 2) health literacy-informed education of patients, and 3) education plus nurse support. Outcomes included mammography screening completion within 6 months and incremental cost-effectiveness. RESULTS: Overall, 1,181 female patients ages 40 and over who were eligible for routine mammography were recruited. Baseline screening rates were < 10%. Post intervention screening rates were 55.7% with enhanced care, 51.8% with health literacy-informed education and 65.8% with education and nurse support. After adjusting for race, marital status, self-efficacy and literacy, patients receiving health-literacy informed education were not more likely to complete mammographic screening than those receiving enhanced care; those additionally receiving nurse support were 1.37-fold more likely to complete mammographic screening than those receiving the brief education (95% Confidence Interval 1.08-1.74, p = 0.01). The incremental cost per additional women screened was $2,457 for literacy-informed education with nurse support over literacy-informed education alone. CONCLUSIONS: Mammography rates were increased substantially over existing baseline rates in all three arms with the educational initiative, with nurse support and follow-up being the most effective option. However, it is not likely to be cost-effective or affordable in resource-limited clinics.

Venous thromboembolism in advanced ovarian cancer patients undergoing frontline adjuvant chemotherapy.

OBJECTIVE: The aim of this study was to define the incidence and prognostic significance of venous thromboembolism (VTE) in patients with advanced, epithelial ovarian cancer undergoing frontline adjuvant chemotherapy after an extended period (28 days) of postoperative prophylaxis. METHODS: A retrospective analysis of patients with advanced, epithelial ovarian cancer who underwent surgery and chemotherapy at a single institution from January 2008 through December 2011 was performed. Exclusion criteria were history of VTE, VTE during the postoperative period, clear cell histology, use of anticoagulation for a different indication, and lack of compliance with 28 days of postoperative prophylaxis with a low-molecular-weight heparin. Baseline patient demographics and oncologic outcomes were analyzed. Clinically symptomatic VTE was identified and confirmed with imaging studies. Otherwise, VTE was identified on imaging studies done to assess disease status at the conclusion of adjuvant chemotherapy. RESULTS: One hundred twenty-eight patients met criteria for inclusion. Sixteen patients had a reported VTE during the time they were on frontline chemotherapy (12.5%). Nine patients (7%) had a pulmonary embolus, and 8 (6.3%) had a deep vein thrombus. The mean BMI in the group that developed VTE was 28, and in the group without VTE, it was 26.5 (P = 0.23). Three (23%) of the 16 patients who developed VTE had undergone a suboptimal cytoreduction compared with 12 (11%) of the 112 in the group with no VTE (P = 0.4). Six (37%) of the 16 patients who developed VTE during chemotherapy underwent a bowel resection and/or splenectomy during their cytoreductive surgery compared with 18 (16%) of the 112 patients who did not develop VTE (P = 0.079). Eight of the patients in the VTE group had indwelling venous catheters during chemotherapy (50%) compared with 39 (35%) in the group with no VTE (P = 0.27). In the group that developed VTE, there was a trend toward increased preoperative CA-125, higher rates of bowel resection and/or splenectomy during surgery, decreased use of aspirin, and inferior survival. On multivariate analysis, patients who developed VTE had significantly longer postoperative hospital stays (7 vs 5 days [P = 0.009]) and lower rates of complete response (P = 0.01). CONCLUSIONS: A 12.5% risk for VTE merits consideration of prophylaxis during chemotherapy in this cohort. A randomized, controlled trial is needed to clarify whether the benefits of long-term prophylaxis outweigh the risks and costs of such therapy.

Reproductive outcomes after multiagent chemotherapy for high-risk gestational trophoblastic neoplasia.

OBJECTIVE: To analyze the reproductive outcomes of women with high-risk gestational trophoblastic neoplasia (GTN) treated with multiagent EMA-CO chemotherapy. STUDY DESIGN: Of 212 patients treated with chemotherapy for GTN between 1986 and 2012, 65 (31%) could be contacted by telephone or mail and consented to participate in a questionnaire designed to assess their menstrual and reproduction outcomes. RESULTS: Twenty-four high-risk (HR) and 41 low-risk (LR) patients consented to the study. Fifteen (63%) HR and 34 (83%) LR women had not undergone hysterectomy (p = 0.08). Of the 12 HR and 33 LR women who could recall their menstrual history, all 12 (100%) HR and 32 (97%) LR women resumed menses after chemotherapy. Both groups also had a similar age of menopause (HR, 43.8 years; LR, 48.5 years) (p = 0.19). Although fewer women in the HR group desired to become pregnant after chemotherapy (HR 5/15 [33%] vs. LR 25/34 [74%]) (p = 0.01), 8 HR women (53%) and 29 LR women (85%) eventually became pregnant (p = 0.03), with equivalent live birth rates of 74% and 76%, respectively. CONCLUSION: Multiagent EMA-CO chemotherapy did not significantly alter menstrual or reproductive outcomes compared to single-agent methotrexate chemotherapy for GTN.

Improving colon cancer screening in community clinics.

BACKGROUND: The authors evaluated the effectiveness and cost effectiveness of 2 interventions designed to promote colorectal cancer (CRC) screening in safety-net settings. METHODS: A 3-arm, quasi-experimental evaluation was conducted among 8 clinics in Louisiana. Screening efforts included: 1) enhanced usual care, 2) literacy-informed education of patients, and 3) education plus nurse support. Overall, 961 average-risk patients ages 50 to 85 years were eligible for routine CRC screening and were recruited. Outcomes included CRC screening completion and incremental cost effectiveness using literacy-informed education of patients and education plus nurse support versus enhanced usual care. RESULTS: The baseline screening rate was <3%. After the interventions, the screening rate was 38.6% with enhanced usual care, 57.1% with education, and 60.6% with education that included additional nurse support. After adjusting for age, race, sex, and literacy, patients who received education alone were not more likely to complete screening than those who received enhanced usual care; and those who received additional nurse support were 1.60-fold more likely to complete screening than those who received enhanced usual care (95% confidence interval, 1.06-2.42; P = .024). The incremental cost per additional individual screened was $1337 for education plus nurse support over enhanced usual care. CONCLUSIONS: Fecal occult blood test rates were increased beyond enhanced usual care by providing brief education and nurse support but not by providing education alone. More cost-effective alternatives to nurse support need to be investigated.

Navigating veterans with an abnormal prostate cancer screening test: a quasi-experimental study.

BACKGROUND: Prostate cancer disproportionately affects low-income and minority men. This study evaluates the impact of a patient navigation intervention on timeliness of diagnostic resolution and treatment initiation among veterans with an abnormal prostate cancer screen. METHODS: Participants were enrolled between 2006 and 2010. The intervention involved a social worker and lay health worker navigation team that assisted patients in overcoming barriers to care. For navigated (n = 245) versus control (n = 245) participants, we evaluated rates of diagnostic resolution and treatment and adjusted for race, age, and Gleason score. RESULTS: Of 490 participants, 68% were African American, 47% were ≥ 65 years old, and 35% had cancer. Among those with an abnormal screen, navigation did not have a significant effect on time to diagnostic resolution compared to controls (median days of 97 versus 111; adj. HR 1.17, 95% CI, 0.96-1.43, p = 0.12). On analysis of the period beyond 80 days, navigated men reached resolution faster than controls (median of 151 days versus 190 days; adj. HR 1.41, 95% CI, 1.07-1.86, p = 0.01). Among those with cancer, navigation did not have a significant effect on time to treatment initiation compared to controls (median of 93 days versus 87 days; adj. HR 1.15, 95% CI, 0.82-1.62, p = 0.41). CONCLUSION: Our navigation program did not significantly impact the overall time to resolution or treatment for men with prostate cancer compared to controls. The utility of navigation programs may extend beyond targeted navigation times, however, and future studies focusing on other outcomes measures are therefore needed.

Design of a prostate cancer patient navigation intervention for a Veterans Affairs hospital.

BACKGROUND: Patient navigation programs have been launched nationwide in an attempt to reduce racial/ethnic and socio-demographic disparities in cancer care, but few have evaluated outcomes in the prostate cancer setting. The National Cancer Institute-funded Chicago Patient Navigation Research Program (C-PNRP) aims to implement and evaluate the efficacy of a patient navigation intervention for predominantly low-income minority patients with an abnormal prostate cancer screening test at a Veterans Affairs (VA) hospital in Chicago. METHODS/DESIGN: From 2006 through 2010, C-PNRP implemented a quasi-experimental intervention whereby trained social worker and lay health navigators worked with veterans with an abnormal prostate screen to proactively identify and resolve personal and systems barriers to care. Men were enrolled at a VA urology clinic and were selected to receive navigated versus usual care based on clinic day. Patient navigators performed activities to facilitate timely follow-up such as appointment reminders, transportation coordination, cancer education, scheduling assistance, and social support as needed. Primary outcome measures included time (days) from abnormal screening to diagnosis and time from diagnosis to treatment initiation. Secondary outcomes included psychosocial and demographic predictors of non-compliance and patient satisfaction. Dates of screening, follow-up visits, and treatment were obtained through chart audit, and questionnaires were administered at baseline, after diagnosis, and after treatment initiation. At the VA, 546 patients were enrolled in the study (245 in the navigated arm, 245 in the records-based control arm, and 56 in a subsample of surveyed control subjects). DISCUSSION: Given increasing concerns about balancing better health outcomes with lower costs, careful examination of interventions aimed at reducing healthcare disparities attain critical importance. While analysis of the C-PNRP data is underway, the design of this patient navigation intervention will inform other patient navigation programs addressing strategies to improve prostate cancer outcomes among vulnerable populations.

Literacy barriers to colorectal cancer screening in community clinics.

This article examines the relationship between literacy and colorectal cancer (CRC) screening knowledge, beliefs, and experiences, with a focus on fecal occult blood tests (FOBTs). Participants were 975 patients in 8 Louisiana federally qualified health centers. Participants were 50 years of age or older and not up to date with CRC screening; approximately half (52%) had low literacy (less than a 9th-grade level). Participants with low literacy were less likely than were those with adequate literacy to be aware of advertisements promoting CRC screening (58.7% vs. 76.3%, p < .0001) or to believe it was very helpful to find CRC early (74.5% vs. 91.9%, p < .0001). The majority of participants had positive beliefs about the benefits of CRC screening using FOBTs. Participants with low literacy had more perceived barriers to FOBT completion and were more likely to strongly agree or agree that FOBTs would be confusing, embarrassing, or a lot of trouble; however, none of these remained significant in multivariate analyses controlling for relevant covariates. Confidence in being able to obtain an FOBT kit was high among those with low and adequate literacy (89.8% vs. 93.1%, respectively, p = .20); yet multivariate analyses revealed a significant difference in regard to literacy (p = .04) with low-literacy participants indicating less confidence. There was no significant difference by literacy in ever receiving a physician recommendation for CRC screening (38.4% low vs. 39.0% adequate, p = .79); however, multivariate analyses revealed significant differences in FOBT completion by literacy (p = .036). Overall, findings suggest that literacy is a factor in patients' CRC knowledge, beliefs, and confidence in obtaining a FOBT.

Predicted the P2RX7 rs3751143 polymorphism is associated with cancer risk: a meta-analysis and systematic review.

BACKGROUND: Both meta-analyses and systematic reviews were used to assess the relationship between purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) rs3751143 polymorphism and the risk of cancer. MATERIALS AND METHODS: The data used in this research were collected from Google Scholar, Web of Science, CNKI, and Wan Fang Data databases. The final retrieval ended on 22 February 2019. The strength of correlation was assessed using odds ratios and 95% confidence intervals. Based on the heterogeneity test results, fixed-effect (Mantel-Haenszel) or random-effects (DerSimonian-Laird) models were selected to summarise the collective effects. RESULTS: Eight separate studies containing 1462 cancer cases and 3037 controls were enrolled. Overall, there was no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, or recessive models. CONCLUSIONS: Our meta-analysis indicates that there is no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, and recessive models.

miR-525-5p Modulates Proliferation and Epithelial-Mesenchymal Transition of Glioma by Targeting Stat-1.

BACKGROUND: Glioma is the most aggressive human brain tumor. Recent studies revealed that microRNAs play vital roles in glioma. However, the function of microRNA-525-5p (miR-525-5p) in glioma remains unclear. METHODS: qRT-PCR and Western blotting were used to evaluate mRNA and protein levels in glioma tissues and cells. Colony formation, CCK-8, and Edu assays evaluated the growth of glioma cells. Wound-healing, transwell, and 3D invasion assays examined the migration and invasion activities of glioma cells. Luciferase reporter assays assessed the regulatory relationship interaction between miR-525-5p and Stat-1. A mouse xenograft model was used to examine the effect of miR-525-5p on glioma in vivo. RESULTS: miR-525-5p expression was downregulated in glioma tissues and cells. Overexpressing miR-525-5p decreased the growth of glioma cells and reduced the migration, invasion, and epithelial-mesenchymal transition of glioma cells. Bioinformatics analysis identified Stat-1 as a potential target of miR-525-5p, and dual luciferase reporter assays revealed that miR-525-5p negatively regulates Stat-1. Decreased Stat-1 led to the inhibition of FOXM1, affecting NF-κB signaling activity. Overexpressing miR-525-5p reduced tumor development in vivo. CONCLUSION: miR-525-5p negatively regulates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in glioma, and Stat 1 is a target of miR-525-5p. miR-525-5p may be a potential target for glioma treatment.

Upregulation of HOTAIRM1 increases migration and invasion by glioblastoma cells.

Long noncoding RNAs (lncRNAs) promote invasion and migration by glioblastoma (GBM) cells. In this study, quantitative real-time polymerase chain reaction was used to detect expression levels of the lncRNA HOTAIRM1 in GBM tissue samples and cells. The function of HOTAIRM1 was examined using wound healing assays, transwell assays, and in vivo experiments after GBM cells were transfected with either sh-ctrl or sh-HOTAIRM1. Luciferase reporter assays and RIP assays were performed to determine the interactions between HOTAIRM1 and miR-153-5p and between miR-153-5p and SNAI2. We also used luciferase reporter assays and ChIP assays to assess the transcriptional regulation of HOTAIRM1 by SNAI2 and CDH1. HOTAIRM1 was significantly overexpressed in GBM tissues and cells. HOTAIRM1 knockdown significantly weakened the migration and invasion by GBM cells. HOTAIRM1 was found to sponge miR-153-5p, and SNAI2 is a direct target of miR-153-5p. In addition, SNAI2 was shown to force HOTAIRM1 expression through directly promoting transcription and suppressing the negative regulation of CDH1 on transcription. Our results indicate a positive feedback loop between HOTAIRM1 and SNAI2, and suggest that the lncRNA HOTAIRM1 is a potential biomarker and therapeutic target in GBM.

NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression.

BACKGROUND: NUDT21, an RNA binding protein, has been reported to play an important role in the regulation of multiple biological responses. Detection of NUDT21 expression may lead to the identification of a novel marker for breast cancer. PURPOSE: The aim of this study was to investigate the clinical significance and functional role of NUDT21 in breast cancer. METHODS: The protein expression of NUDT21 was examined by immunohistochemistry (IHC) in 100 paraffin-embedded, archived breast cancer samples and 100 benign breast tissues. Then, the correlations between the NUDT21 expression and clinicopathologic characteristics and prognoses of the breast cancer patients were analyzed. In addition, the function of NUDT21 in breast cancer cell lines was detected by the methyl thiazolyl tetrazolium, colony formation and transwell assays. Finally, mass spectrometry analysis and Western blotting were used to identify the proteins that interact directly with NUDT21. RESULTS: IHC analysis revealed that the expression of NUDT21 was significantly lower in breast cancer tissues compared with benign breast disease tissues. The correlation analysis revealed that low expression of NUDT21 was positively correlated with tumor size, lymph node metastasis, and TNM stage. Also, Kaplan-Meier survival curves showed that patients with lower NUDT21 expression had shorter overall survival and relapse-free survival compared with higher NUDT21 expression. In addition, the knockdown of NUDT21 enhanced cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Consistently, the overexpression of NUDT21 inhibited cell proliferation, migration, invasion, and EMT. In addition, NUDT21 directly interacted with CPSF6 and negatively regulated its expression. Moreover, the knockdown of CPSF6 reversed NUDT21 expression-induced cancer cell migration and invasion. CONCLUSION: NUDT21 might play a tumor-suppressive role by inhibiting cell proliferation and invasion via the NUDT21/CPSF6 signaling pathway in breast cancer cells.

HOXC13-AS-miR-122-5p-SATB1-C-Myc feedback loop promotes migration, invasion and EMT process in glioma.

PURPOSE: Differentially expressed long non-coding ribonucleic acids (lncRNAs) have been reported as a key factor of glioma carcinogenesis, but the underlying mechanism involved is still unknown. MATERIALS AND METHODS: In the present study, lncRNA HOXC13 antisense RNA (HOXC13-AS) was identified as a potential oncogene in glioma, and Western blotting, wound healing and Transwell assays were carried out to explore the effects of HOXC13-AS on the epithelial-mesenchymal transition (EMT) process as well as the migration and invasion of glioma cells. RESULTS: A further mechanistic study showed that HOXC13-AS sponged miR-122-5p to indirectly regulate SATB1 expression and affect the EMT process via the Wnt/ß-catenin pathway. Meanwhile, the promoter activity was significantly increased via c-Myc, a key factor of the Wnt/ß-catenin pathway, thus forming a positive HOXC13-AS-miR-122-5p-SATB1-c-Myc feedback loop to drive the malignant behavior in glioma. DISCUSSION: This study evidences the constitutive HOXC13-AS-miR-122-5p-SATB1-c-Myc feedback loop and provides a potential therapeutic target for glioma treatment.

The selected biomarker analysis in 5 types of uterine smooth muscle tumors.

Uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (ULM). The genetic alterations in LMS are complex, with some genetic alterations present in both LMS and other atypical histologic variants of USMT. In this study, we reviewed 119 USMTs with a diagnosis of LMS, smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, and cellular leiomyoma, as well as 46 ULMs and 60 myometrial controls. We selected 17 biomarkers highly relevant to LMS in 4 tumorigenic pathways including steroid hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]), cell cycle/tumor suppressor genes, AKT pathway markers, and associated oncogenes. ER and PR expression was significantly lower in LMS than smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, cellular leiomyoma, and ULM (P < .01). Sixty-five percent of LMSs showed complete loss of ER, and 75% of LMSs showed complete loss of PR. All cell cycle genes were differentially expressed in different types of tumor, but significant overlap was noted. More than 75% of LMSs had Ki-67 index greater than 33%, and only 5% in all other types of USMT. Expression of the selected oncogenes varied widely among different types of USMT. PR positivity and p53 had a borderline association with progression-free survival (P = .055 for PR and P = .0847 for p53). Furthermore, high PR expression was significantly associated with a longer overall survival (P = .0163, hazard ratio 0.198). Cell proliferative indices (Ki-67) and sex steroid hormone receptors were the most valuable markers in differentiating LMS from other USMT variants.

Breast Hormone Concentrations in Random Fine-Needle Aspirates of Healthy Women Associate with Cytological Atypia and Gene Methylation.

Sex steroid hormones contribute to breast cancer development, but data on concentrations of these within breast tissue are limited. We performed simultaneous multiparameter measurement of breast sex steroids, breast epithelial cytology, and DNA methylation in 119 healthy women (54 pre- and 65 postmenopausal) without a history of breast cancer. Random fine-needle aspiration (rFNA) of the breast was performed simultaneously with blood collection. Breast samples were analyzed by LC/MS-MS for estrone, estradiol, progesterone, androstenedione, and testosterone. Blood samples were assayed for estradiol and progesterone by immunoassay. Cytomorphology was classified using the Masood Score, and DNA methylation of eight genes was analyzed using quantitative multiplexed methylation-specific PCR, and expressed as the cumulative methylation index (CMI). Serum and breast concentrations of estradiol and progesterone showed significant correlation (Spearman r = 0.34, Padj = 0.001 and r = 0.69, Padj < 0.0006, respectively). Progesterone concentration was significantly higher in the premenopausal breast (Padj < 0.0008), and showed a luteal surge. Breast estrone and estradiol concentrations did not differ significantly by menopause, but androstenedione concentration was higher in the breasts of postmenopausal women (P = 0.026 and Padj = 0.208). Breast androgens were significantly correlated with breast density (Spearman r = 0.27, Padj = 0.02 for testosterone) and CMI (Spearman r = 0.3, Padj = 0.038 for androstenedione). Our data indicate that future larger studies of breast steroid hormones along with other parameters are feasible. Significant associations of breast androgen concentrations with breast density and gene methylation warrant future study. Cancer Prev Res; 11(9); 557-68. ©2018 AACR.

Impact and management of skin toxicity associated with anti-epidermal growth factor receptor therapy: survey results.

Biologic agents targeting the epidermal growth factor receptor (EGFR) have emerged as a robust treatment option for various solid tumors. Despite lower systemic side effects than conventional chemotherapy, the majority of patients treated with these agents experience cutaneous toxicities, including papulopustular rashes, hair and nail changes, xerosis and pruritus, which have a significant impact on health and quality of life. Currently no consensus or management guidelines exist for these untoward events. Therefore, a retrospective survey was carried out across 110 oncology practioners in the US that were administering EGFR inhibitors. Providers were queried on the impact and management of these untoward events in their practices. Responses suggest that combination therapies (topical and oral) were more effective than either therapy alone, and also lead to a more rapid resolution of the papulopustular rash. Providers also reported that patients frequently complained of physical symptoms associated with the rash (itching and pain), and that they had a positive perception when being treated for their cutaneous side effects. The survey results support that attentive cutaneous care is important in patients treated with EGFR inhibitors, and that proactive/combined interventions may enhance quality of life and optimize consistent drug administration.

Process evaluation in an intervention designed to improve rates of colorectal cancer screening in a VA medical center.

Colorectal cancer (CRC) is the third most common cancer in the United States. Although CRC screening is recommended for individuals 50 years and older, screening completion rates are low. This can be attributed to provider and patient barriers. We developed an intervention to improve provider recommendation and patient screening among noncompliant male veterans in a 2-year randomized controlled trial and examined the relationship between participation and study outcomes among patients and providers. Overall, providers who attended intervention sessions recommended CRC screening during 64% of patient visits and providers who did not attend any intervention sessions recommended screening during 54% of visits (p < .01). Patients of providers who attended intervention sessions also were more likely to be screened (42% versus 29%, p < .05). The patient intervention did not have the desired impact. The subgroup of patients in the patient intervention was not more likely to complete CRC screening.