"Pathways": A hope-enhancing intervention for patients undergoing treatment for advanced lung cancer.

OBJECTIVE: Observational data suggest hope is associated with the quality of life and survival of people with cancer. This trial examined the feasibility, acceptability, and preliminary outcomes of "Pathways," a hope intervention for people in treatment for advanced lung cancer. METHODS: Between 2020 and 2022, we conducted a single-arm trial of Pathways among participants who were 3-12 weeks into systemic treatment. Pathways consisted of two individual sessions delivered during infusions and three phone calls in which participants discussed their values, goals, and goal strategies with a nurse or occupational therapist. Participants completed standardized measures of hope and goal interference pre- and post-intervention. Feasibility was defined as ≥60% of eligible patients enrolling, ≥70% of participants completing three or more sessions, ≥70% of participants completing post-assessments, and mean acceptability ratings ≥7 out of 10 on intervention relevance, helpfulness, and convenience. Linear regression fixed effects models with covariates modeled pre-post changes in complete case analysis and multiple imputation models. RESULTS: Fifty two participants enrolled: female (59.6%), non-Hispanic White (84.6%), rural (75.0%), and with low educational attainment (51.9% high school degree or less). Except for enrollment (54%), feasibility and acceptability markers were surpassed (77% adherence, 77% retention, acceptability ratings ≥8/10). There was moderate improvement in hope and goal interference from pre-to post-intervention (d = 0.51, p < 0.05 for hope; d = -0.70, p < 0.005 for goal interference). CONCLUSIONS: Strong feasibility, acceptability, and patient-reported outcome data suggest Pathways is a promising intervention to increase hope and reduce cancer-related goal interference during advanced lung cancer treatment.

Impact of relative dose intensity on pathologic complete response in human epidermal growth factor receptor 2 positive breast cancer patients receiving neoadjuvant TCHP.

PURPOSE: The standard of care for locally advanced, human epidermal growth factor receptor 2 positive (HER2+) breast cancer includes neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). Many patients do not receive the full course of therapy due to various complications, possibly affecting the potential to achieve a pathologic complete response (pCR). The amount of therapy received is typically measured by relative dose intensity (RDI). This study aimed to evaluate pCR rates in patients receiving optimal and suboptimal RDI TCHP. METHODS: This study was a retrospective chart review of patients treated between 2014 and 2021 at UK HealthCare. Patients included were 18 years of age or older with HER2+ breast cancer and received at least one cycle of neoadjuvant TCHP. The primary objective compared pCR rates in patients receiving ≥ 85% RDI or <85% RDI. Secondary objectives included pCR rates based on clinical stage, age, body mass index, or hormone receptor status; factors leading to discontinuation or delay in treatment; and impact of dose reductions and delays on pCR. RESULTS: A total of 101 patients were included and divided into two cohorts: 54 patients received ≥ 85% RDI and 47 patients received <85% RDI. Patients who received ≥ 85% total RDI had an approximate increase of 17% in pCR rates (59.3% vs 42.6%, p = 0.11). Additionally, 82% of patients experienced a dose delay or adjustment. CONCLUSIONS: Patients who received ≥ 85% RDI had increased pCR rates compared to patients receiving <85% RDI. A larger patient population is needed to formulate definitive conclusions on the impact of RDI and pCR rates.

A Daily Assessment Study of Smoking Cessation After a Head and Neck Cancer Diagnosis.

INTRODUCTION: This intensive longitudinal study describes key events in the process of smoking cessation after a new head and neck cancer (HNC) diagnosis. Prior longitudinal studies show some cancer patients quit, while others continue to smoke, but details about the pattern in which these discrete outcomes arise are scarce. This study is meant to help rectify this gap in the literature. AIMS AND METHODS: Participants were 42 HNC patients who reported current smoking at enrollment. Participants were recruited from an outpatient oncology clinic and completed a baseline questionnaire prior to begin a 30-day daily assessment. RESULTS: Few participants (9.52%) achieved 30-day continuous abstinence from smoking. On average, participants reported 9.64 ± 11.93 total days of abstinence. Nearly, all (94.44%, n = 34) participants made at least one quit attempt, with an average of 16.94 ± 11.30 quit attempt days. Fewer participants were able to achieve a 24-hour quit attempt (52.78%, n = 19), with a corresponding average of 5.50 ± 8.69 24-hour days. The median time to first 24-hour quit attempt was 13 days after enrollment. Based on smoking behavioral patterns, participants were categorized into five groups, the most common being "persistent attempters," which involved unsuccessful quit attempts throughout the study. Only 45% of participants (n = 19) used evidence-based treatment, the most common being cessation medication. CONCLUSIONS: This intensive longitudinal study found that cancer diagnosis can spur a lot of efforts to quit smoking. Unfortunately, this study suggests that many quit attempts are short lived, possibly a result of an absence or insufficient use of evidence-based treatments. IMPLICATIONS: For adults who are current smokers at the time of cancer diagnosis, there is a high likelihood of persistent cigarette smoking and use of other tobacco products in the weeks and months after a cancer diagnosis. Furthermore, this study shows that while a lot of quit attempts may occur, few are successful, which may be partly attributable to the low use of evidence-based tobacco treatment. Future research with cancer patients should aim to identify predictors of quit attempts and abstinence as well as treatment utilization.

Using Implementation Science to Disseminate a Lung Cancer Screening Education Intervention Through Community Health Workers.

National lung cancer screening with low dose computed tomography (LDCT) uptake is suboptimal. One factor contributing to slow uptake is lack of awareness. Trained Community Health Workers (CHWs) may be effective in increasing lung cancer screening awareness among disparate populations, however little is known about the processes necessary to scale an intervention for implementation by CHWs in a new area. We examined implementation processes with the RE-AIM framework and pilot tested a CHW-delivered lung cancer education intervention based on the Health Belief Model. We measured pre-post participant knowledge, attitudes and beliefs regarding cancer screening, lung cancer stigma, and intent to obtain LDCT screening. We used community-engaged strategies to collaborate with a local health system, to identify CHWs. CHWs were trained to recruit participants and deliver the one-session lung cancer education intervention. Seven CHWs and eight community sites participated. Participants (n = 77) were female (53%) primarily low income (62.9%); tobacco use was high (36.9%). Post intervention changes in lung cancer screening knowledge (p = < .0001), attitudes regarding lung cancer screening benefit (p = .034) and lung cancer stigma. (p = .024) We learned important lessons that will be useful in subsequent scaling. Collaborating with a local health system is a promising method to disseminate a lung cancer screening education intervention.

Estimation of exposure distribution adjusting for association between exposure level and detection limit.

In environmental exposure studies, it is common to observe a portion of exposure measurements to fall below experimentally determined detection limits (DLs). The reverse Kaplan-Meier estimator, which mimics the well-known Kaplan-Meier estimator for right-censored survival data with the scale reversed, has been recommended for estimating the exposure distribution for the data subject to DLs because it does not require any distributional assumption. However, the reverse Kaplan-Meier estimator requires the independence assumption between the exposure level and DL and can lead to biased results when this assumption is violated. We propose a kernel-smoothed nonparametric estimator for the exposure distribution without imposing any independence assumption between the exposure level and DL. We show that the proposed estimator is consistent and asymptotically normal. Simulation studies demonstrate that the proposed estimator performs well in practical situations. A colon cancer study is provided for illustration. Copyright © 2017 John Wiley & Sons, Ltd.

Cutting Edge: IFN-γ Produced by Brain-Resident Cells Is Crucial To Control Cerebral Infection with Toxoplasma gondii.

In vitro studies demonstrated that microglia and astrocytes produce IFN-γ in response to various stimulations, including LPS. However, the physiological role of IFN-γ production by brain-resident cells, including glial cells, in resistance against cerebral infections remains unknown. We analyzed the role of IFN-γ production by brain-resident cells in resistance to reactivation of cerebral infection with Toxoplasma gondii using a murine model. Our study using bone marrow chimeric mice revealed that IFN-γ production by brain-resident cells is essential for upregulating IFN-γ-mediated protective innate immune responses to restrict cerebral T. gondii growth. Studies using a transgenic strain that expresses IFN-γ only in CD11b(+) cells suggested that IFN-γ production by microglia, which is the only CD11b(+) cell population among brain-resident cells, is able to suppress the parasite growth. Furthermore, IFN-γ produced by brain-resident cells is pivotal for recruiting T cells into the brain to control the infection. These results indicate that IFN-γ produced by brain-resident cells is crucial for facilitating both the protective innate and T cell-mediated immune responses to control cerebral infection with T. gondii.

Delay discounting and self-reported impulsivity in adolescent smokers and nonsmokers living in rural Appalachia.

Background and Objectives This study evaluated whether impulsivity (delay discounting and BIS-11-A) is associated with adolescent smoking status in a region with strong environmental risk factors for smoking. Methods Forty-two adolescent smokers and nonsmokers from rural Appalachia completed discounting and self-reported impulsivity assessments. Results The BIS-11-A, but not the measure of discounting, was associated with smoking status; however, neither assessment predicted smoking status once parent/best-friend smoking variables were statistically accounted for. Discussion and Conclusions In regions with strong environmental risk factors for smoking, delay discounting may play a more limited role in risk of initiation. Scientific Significance Helps to better define impulsivity as risk factors for smoking in relation to familial and broader cultural variables.

A rural Appalachian faith-placed smoking cessation intervention.

Although health promotion programming in faith institutions is promising, most faith-based or placed health projects focus on diet, exercise, or cancer screening and many have been located in urban environments. This article addresses the notable absence of faith programming for smoking cessation among underserved rural US residents who experience tobacco-related health inequities. In this article, we describe our faith-oriented smoking cessation program in rural Appalachia, involving 590 smokers in 26 rural churches randomized to early and delayed intervention groups. We present three main themes that account for participants' positive evaluation of the program; the program's ability to leverage social connections; the program's convenience orientation; and the program's financial support for smoking cessation. We also present themes on the roles of faith and church in smoking cessation programming, including some mixed perceptions on smoking stigma and comfort in church settings; challenges in faith-placed smoking cessation recruitment; and the positive perception of such programming by church leaders. We conclude that faith-placed smoking cessation programs offer great potential, although they must be administered with great sensitivity to individual and community norms.

A Social Media-Delivered Melanoma Prevention Program for Young Women Engaged in Frequent UV Tanning: Protocol for a Randomized Controlled Trial.

BACKGROUND: Rates of melanoma have increased dramatically in the United States over the past 25 years, and it has become among the most prevalent cancers for young adult women. Intentional skin tanning leads to a pattern of intense and intermittent UV radiation exposure that is associated with increased risk of melanoma. Frequent tanning is most common among young women and is linked to a variety of sociocultural pressures that negatively impact body image and drive appearance control behaviors. Unfortunately, there are no established interventions designed for frequent tanners. This intervention addresses this gap with unique content informed by body image and acceptance-based interventions. The intervention is delivered using Facebook secret groups, an approach designed to support behavior change and ensure scalability. OBJECTIVE: This study aims to describe the rationale and methodology of a randomized controlled trial of a melanoma prevention program targeting young women engaged in frequent indoor or outdoor UV tanning. METHODS: Participants are women aged 18-25 years who report high-risk tanning (ie, at least 10 indoor tanning sessions in the past 12 months or 10 outdoor sessions in the previous summer). After recruitment and screening, participants completed a baseline survey and were randomly assigned to receive the intervention or an attention-matched control condition. Both conditions were 8-week-long Facebook groups (approximately 25 members each) with daily posting of content. Follow-up surveys are administered at 3, 8, and 18 months after baseline. The primary trial outcome is the combined number of indoor and outdoor tanning sessions reported at the 8-month follow-up. Hypothesized intervention mediators are assessed at the 3-month follow-up. RESULTS: This project was funded by a National Cancer Institute award (R01 CA218068), and the trial procedures were approved by the University of Kentucky Institutional Review Board in February 2020. Trial recruitment and enrollment occurred in 6 waves of data collection, which started in February 2022 and closed in May 2023. The study is closed to enrollment but remains open for follow-ups, and this protocol report was prepared before data analyses. As of February 2024, all participants have completed the 8-month follow-up assessment, and data collection is scheduled to close by the end of 2024 after the collection of the 18-month follow-up. CONCLUSIONS: This trial will contribute unique knowledge to the field of skin cancer prevention, as no fully powered trials have examined the efficacy of an intervention designed for frequent indoor or outdoor tanning. The trial may also contribute evidence of the value in translating principles of body image and acceptance-based interventions into the field of skin cancer prevention and beyond. If successful, the use of the Facebook platform is intended to aid in dissemination as it provides a way to embed the intervention into individuals' everyday routines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03441321; https://clinicaltrials.gov/study/NCT03441321. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56562.

Piloting a Patient Tool to Aid Palliative Care Referrals during Advanced Lung Cancer Treatment.

CONTEXT: Patient misperceptions are a strong barrier to early palliative care discussions and referrals during advanced lung cancer treatment. OBJECTIVES: We developed and tested the acceptability of a web-based patient-facing palliative care education and screening tool intended for use in a planned multilevel intervention (i.e., patient, clinician, system-level targets). METHODS: We elicited feedback from advanced lung cancer patients (n = 6), oncology and palliative care clinicians (n = 4), and a clinic administrator (n = 1) on the perceived relevance of the intervention. We then tested the prototype of a patient-facing tool for patient acceptability and preliminary effects on patient palliative care knowledge and motivation. RESULTS: Partners agreed that the intervention-clinician palliative care education and an electronic health record-integrated patient tool-is relevant and their feedback informed development of the patient prototype. Advanced stage lung cancer patients (n = 20; age 60 ± 9.8; 40% male; 70% with a technical degree or less) reviewed and rated the prototype on a five-point scale for acceptability (4.48 ± 0.55), appropriateness (4.37 ± 0.62), and feasibility (4.43 ± 0.59). After using the prototype, 75% were interested in using palliative care and 80% were more motivated to talk to their oncologist about it. Of patients who had or were at risk of having misperceptions about palliative care (e.g., conflating it with hospice), 100% no longer held the misperceptions after using the prototype. CONCLUSION: The palliative care education and screening tool is acceptable to patients and may address misperceptions and motivate palliative care discussions during treatment.

Human NK cells proliferate and die in vivo more rapidly than T cells in healthy young and elderly adults.

NK cells are essential for health, yet little is known about human NK turnover in vivo. In both young and elderly women, all NK subsets proliferated and died more rapidly than T cells. CD56(bright) NK cells proliferated rapidly but died relatively slowly, suggesting that proliferating CD56(bright) cells differentiate into CD56(dim) NK cells in vivo. The relationship between CD56(dim) and CD56(bright) proliferating cells indicates that proliferating CD56(dim) cells both self-renew and are derived from proliferating CD56(bright) NK cells. Our data suggest that some dying CD56(dim) cells become CD16(+)CD56(-) NK cells and that CD16(-)CD56(low) NK cells respond rapidly to cellular and cytokine stimulation. We propose a model in which all NK cell subsets are in dynamic flux. About half of CD56(dim) NK cells expressed CD57, which was weakly associated with low proliferation. Surprisingly, CD57 expression was associated with higher proliferation rates in both CD8(+) and CD8(-) T cells. Therefore, CD57 is not a reliable marker of senescent, nonproliferative T cells in vivo. NKG2A expression declined with age on both NK cells and T cells. Killer cell Ig-like receptor expression increased with age on T cells but not on NK cells. Although the percentage of CD56(bright) NK cells declined with age and the percentage of CD56(dim) NK cells increased with age, there were no significant age-related proliferation or apoptosis differences for these two populations or for total NK cells. In vivo human NK cell turnover is rapid in both young and elderly adults.

Mobile mammography in underserved populations: analysis of outcomes of 3,923 women.

Mobile health units are increasingly utilized to address barriers to mammography screening. Despite the existence of mobile mammography outreach throughout the US, there is a paucity of data describing the populations served by mobile units and the ability of these programs to reach underserved populations, address disparities, and report on outcomes of screening performance. To evaluate the association of variables associated with outcomes for women undergoing breast cancer screening and clinical evaluation on a mobile unit. Retrospective analysis of women undergoing mammography screening during the period 2008-2010. Logistic regression was fitted using generalized estimating equations to account for potential repeat annual visits to the mobile unit. In total, 4,543 mammograms and/or clinical breast exams were conducted on 3,923 women with a mean age of 54.6, 29 % of whom had either never been screened or had not had a screening in 5 years. Age < 50 years, lack of insurance, Hispanic ethnicity, current smoking, or having a family relative (<50 years of age) with a diagnosis of cancer were associated with increased odds of a suspicious mammogram finding (BIRADS 4,5,6). Thirty-one breast cancers were detected. The mobile outreach initiative successfully engaged many women who had not had a recent mammogram. Lack of insurance and current smoking were modifiable variables associated with abnormal screens requiring follow up.

Weighted mean difference statistics for paired data in the presence of missing values.

Missing data is a common issue in many biomedical studies. Under a paired design, some subjects may have missing values in either one or both of the conditions due to loss of follow-up, insufficient biological samples, etc. Such partially paired data complicate statistical comparison of the distribution of the variable of interest between the two conditions. In this article, we propose a general class of test statistics based on the difference in weighted sample means without imposing any distributional or model assumption. An optimal weight is derived from this class of tests. Simulation studies show that our proposed test with the optimal weight performs well and outperforms existing methods in practical situations. Two cancer biomarker studies are provided for illustration.

Congenic interval of CD45/Ly-5 congenic mice contains multiple genes that may influence hematopoietic stem cell engraftment.

The B6.SJL-Ptprc(d)Pep3(b)/BoyJ (B6.SJL) congenic mouse strain, a valuable and widely used tool in murine bone marrow transplantation studies, has long been considered equivalent to the parental C57B/L6 (B6) strain with the exception of a small congenic interval on chromosome 1 harboring an alternative CD45/Ly-5 alloantigen (Ly-5.1). In this study we compared functional properties of stem and stromal cells between the strains, and delineated the boundary of the B6.SJL congenic interval. We identified a 25% reduction in homing efficiency, 3.8-fold reduction in transplantable long-term hematopoietic stem cells (LT-HSCs), a 5-fold reduction in LT-HSCs capable of 24-hour homing, and a cell-intrinsic engraftment defect of 30% to 50% in B6.SJL-derived bone marrow cells relative to B6-derived cells. These functional differences were independent of stem cell number, cycling, or apoptosis. Genotypic analysis revealed a 42.1-mbp congenic interval in B6.SJL including 306 genes, and at least 124 genetic polymorphisms. Moreover, expression profiling revealed 288 genes differentially expressed between nonhematopoietic stromal cells of the 2 strains. These results indicate that polymorphisms between the B6 and SJL genotype within the B6.SJL congenic interval influence HSC engraftment and result in transcriptional variation within bone marrow stroma.

Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/ß-catenin signaling pathway.

Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of ß-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of ß-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited ß-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggests that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/ß-catenin signaling pathway.

A community-based randomized trial of a faith-placed intervention to reduce cervical cancer burden in Appalachia.

OBJECTIVE: Faith Moves Mountains assessed the effectiveness of a faith-placed lay health advisor (LHA) intervention to increase Papanicolaou (Pap) test use among middle-aged and older women in a region disproportionately affected by cervical cancer and low screening rates (regionally, only 68% screened in prior 3 years). METHOD: This community-based RCT was conducted in four Appalachian Kentucky counties (December 2005-June 2008). Women aged 40-64 and overdue for screening were recruited from churches and individually randomized to treatment (n=176) or wait-list control (n=169). The intervention provided LHA home visits and newsletters addressing barriers to screening. Self-reported Pap test receipt was the primary outcome. RESULTS: Intention-to-treat analyses revealed that treatment group participants (17.6% screened) had over twice the odds of wait-list controls (11.2% screened) of reporting Pap test receipt post-intervention, OR=2.56, 95% CI: 1.03-6.38, p=0.04. Independent of group, recently screened participants (last Pap >1 but <5 years ago) had significantly higher odds of obtaining screening during the study than rarely or never screened participants (last Pap ≥5 years ago), OR=2.50, 95% CI: 1.48-4.25, p=0.001. CONCLUSIONS: The intervention was associated with increased cervical cancer screening. The faith-placed LHA addressing barriers comprises a novel approach to reducing cervical cancer disparities among Appalachian women.

Tobacco Use and Tobacco Treatment Referral Response of Patients With Cancer: Implementation Outcomes at a National Cancer Institute-Designated Cancer Center.

PURPOSE: Smoking after a cancer diagnosis is linked to cancer-specific and all-cause mortality, among other adverse outcomes. Yet, 10%-20% of US cancer survivors are current smokers. Implementation of evidence-based tobacco treatment in cancer care facilities is widely recommended, yet rarely accomplished. This study focuses on the early outcomes of a population-based tobacco treatment program integrated within an National Cancer Institute-designated cancer center. METHODS AND MATERIALS: The sample consists of 26,365 patients seen at the cancer center during the first 18 months of program implementation. The study is a retrospective chart review of patients' tobacco use and, among current users, patients' treatment referral response. RESULTS: More than 99% of patients were screened for tobacco use. Current (past month) use was observed in 21.05% of patients; cigarettes were the most popular product. Only 17.22% of current users accepted a referral for tobacco treatment; among current users who declined, the majority were not ready to quit (65.84%) or wanted to quit on their own (27.01%). Multiple demographic variables were associated with tobacco use and treatment referral response outcomes. CONCLUSION: Despite cancer diagnosis presenting a teachable moment for tobacco cessation, patients with cancer may not be ready to quit or engage with treatment. Clinically proven strategies to increase motivation, prompt quit attempts, and encourage treatment use should be key components of tobacco treatment delivery to patients with cancer.

Recombination phenotypes of the NCI-60 collection of human cancer cells.

BACKGROUND: The NCI-60 is a collection of tumor cell lines derived from a variety of human adult cancer tissue types and is commonly used for genetic analysis and screening of potential chemotherapeutic agents. We wanted to understand the contributions of specific mechanisms of genomic instability to the etiology of cancers represented by the NCI-60. RESULTS: We screened the NCI-60 for dysregulated homologous recombination by using the gene cluster instability (GCI) assay we pioneered, and for defects in base excision repair by sensitivity to 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). We identified subsets of the NCI-60 lines that either displayed the characteristic molecular signature of GCI or were sensitive to hmdUrd. With the exception of the NCI-H23 lung cancer line, these phenotypes were not found to overlap. None of the lines examined in either subset exhibited significant changes in the frequency of sister chromatid exchanges (SCE), neither did any of the lines in either subset exhibit microsatellite instability (MSI) indicative of defects in DNA mismatch repair. CONCLUSIONS: Gene cluster instability, sensitivity to hmdUrd and sister chromatid exchange are mechanistically distinct phenomena. Genomic instability in the NCI-60 appears to involve only one mechanism of instability for each individual cell line.

Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/ß-catenin pathway in human colorectal adenocarcinoma DLD1 cells.

Long term exposure to arsenic can increase incidence of human cancers, such as skin, lung, and colon rectum. The mechanism of arsenic induced carcinogenesis is still unclear. It is generally believed that reactive oxygen species (ROS) may play an important role in this process. In the present study, we investigate the possible linkage between ROS, ß-catenin and arsenic induced transformation and tumorigenesis in human colorectal adenocarcinoma cell line, DLD1 cells. Our results show that arsenic was able to activate p47(phox) and p67(phox), two key proteins for activation of NADPH oxidase. Arsenic was also able to generate ROS in DLD1 cells. Arsenic increased ß-catenin expression level and its promoter activity. ROS played a major role in arsenic-induced ß-catenin activation. Treatment of DLD1 cells by arsenic enhanced both transformation and tumorigenesis of these cells. The tumor volumes of arsenic treated group were much larger than those without arsenic treatment. Addition of either superoxide dismutase (SOD) or catalase reduced arsenic induced cell transformation and tumor formation. The results indicate that ROS are involved in arsenic induced cell transformation and tumor formation possible through Wnt/ß-catenin pathway in human colorectal adenocarcinoma cell line DLD1 cells.

Testosterone levels in men with chronic migraine.

Chronic migraine is a frequent and debilitating condition affecting 14% of the general population. This prospective observational pilot study investigated whether men with chronic migraine have lower than expected total serum testosterone levels. We identified 14 men ages 26-51 at our Institution who fulfilled the ICHD-3b criteria for chronic migraine and obtained serum total testosterone levels. The mean total testosterone level in our 14 patients was 322 ng/dL (range: 120-542 ng/dL) which is in the lower 5% of the reference range for our laboratory (300-1080 ng/dL). Men with chronic migraine had lower total testosterone levels compared to published agematched normative median values by a median difference of 62 ng/dL (P=0.0494). This finding suggests that hypothalamic regulation is altered in patients with chronic migraine. Further studies are warranted to determine whether testosterone supplementation in men with chronic migraine reduces the number of headaches or the associated symptoms of hypogonadism.