Changes in alcohol consumption and binge drinking during the COVID-19 pandemic among American Indians residing in California and Oklahoma.

Background: This study explored the increased quantity and frequency of alcohol use in the American Indian (AI) population during the COVID-19 pandemic.Objectives: The aims of this study were to explore possible associations between covariables and both binge drinking and alcohol consumption during COVID-19.Methods: This cross-sectional survey study analyzed data from a sample of AI individuals (63% female) residing in California (n = 411) and Oklahoma (n = 657) between October 2020-January 2021. Analysis included summary statistics and multivariable logistic regression, including a variety of socio-economic, COVID-19 concern, and tobacco and marijuana use variables.Results: One or more alcohol binge episodes were reported between October 2020-January 2021 in 19.3% of participants and elevated overall alcohol consumption was reported by 21.6% of participants. Higher odds of elevated alcohol consumption occurred in women and those following more social distancing measures. The odds of binge drinking or elevated alcohol consumption in those using both marijuana and tobacco (aOR/ adjusted odds ratio:18.9, 95% CI = 8.5, 42.2, and aOR:3.9, 95% CI = 1.7, 8.6, respectively) were higher compared to those using neither. Similarly, the odds of binge drinking or elevated alcohol consumption in those using tobacco only (aOR:4.7, 95% CI = 2.9, 7.7 and aOR: 2.0, 95% CI = 1.1, 3.5, respectively) were higher compared to those using neither.Conclusions: This study found high rates of alcohol use and bingeing during the COVID-19 pandemic. Offering collaborative, culturally sensitive, and affordable support services are important components of intervention and preparation for future stressful events on local, as well as global levels.

Iliski, a software for robust calculation of transfer functions.

Understanding the relationships between biological processes is paramount to unravel pathophysiological mechanisms. These relationships can be modeled with Transfer Functions (TFs), with no need of a priori hypotheses as to the shape of the transfer function. Here we present Iliski, a software dedicated to TFs computation between two signals. It includes different pre-treatment routines and TF computation processes: deconvolution, deterministic and non-deterministic optimization algorithms that are adapted to disparate datasets. We apply Iliski to data on neurovascular coupling, an ensemble of cellular mechanisms that link neuronal activity to local changes of blood flow, highlighting the software benefits and caveats in the computation and evaluation of TFs. We also propose a workflow that will help users to choose the best computation according to the dataset. Iliski is available under the open-source license CC BY 4.0 on GitHub (https://github.com/alike-aydin/Iliski) and can be used on the most common operating systems, either within the MATLAB environment, or as a standalone application.

Sociodemographic factors associated with HPV awareness/knowledge and cervical cancer screening behaviors among caregivers in the U.S.

BACKGROUND: Family caregivers may be at a higher risk for several chronic diseases, including cancer. Cervical cancer is one of the most common causes of cancer death among women. Despite family caregivers' vulnerability, the status of their HPV awareness, knowledge, and preventive health behaviors, including cervical cancer screening, has been understudied. Thus, this study aimed to examine the sociodemographic factors associated with HPV awareness and knowledge and adherence to the cervical cancer screening guidelines among caregivers in the U.S. METHODS: Nationally representative cross-sectional survey data were obtained from the Health Information National Trends Survey (HINTS 5, 2017-2020). Female caregivers aged 21-65 were included (N = 1190). Weighted multivariable logistic regression was performed to identify factors associated with HPV awareness (heard of HPV), knowledge (HPV can cause cervical cancer), and adherence to the United States Preventive Service Task Force 2018 cervical cancer screening guidelines by sociodemographic factors (age, race/ethnicity, education, household income, marital status,) and the intensity of caregiving. RESULTS: An estimated 79% of female caregivers were aware of HPV and 84% adhered to the cervical cancer screening guidelines. Caregivers who were older than 50 (OR = 3.62, 1.91-6.85, adherence of aged 21-50 vs. 51-65), Hispanics of race/ethnicity compared with Black/African Americans (OR = 3.14, 1.31-7.52, adherence of Black/African Americans vs. Hispanics), with a high school education or less (OR = 2.34, 1.14-4.82, adherence of Some college or more vs. High school education or less), and with intense caregiving duty (spending 35 h/week or more on caregiving) compared with light-duty (OR = 2.34, 1.10-5.00, adherence of 5-14 h vs. 35 h or more, weekly) had poor adherence to the cervical cancer screening guidelines. Caregivers who were older, racial minorities (Asian, Native Hawaiian/Pacific Islander, American Indian/Alaska Native, Multiple races), and less educated showed lower HPV awareness (Heard of HPV) than their counterparts. CONCLUSIONS: There are caregiving populations whose HPV awareness and cervical cancer screening adherence are low. To improve their awareness and knowledge of HPV and support their cervical cancer screening behaviors, we need to consider interventions that target those specific populations.

Healthcare Disparities Identified Between Hmong and Other Asian Origin Groups Living with Chronic Hepatitis B Infection in Sacramento County 2014-2017.

Chronic hepatitis B (CHB) disproportionately affects non-US born Asians. The Hmong have been shown to have the highest rates of CHB and mortality from liver cancer compared to other Asian groups. From September 2014 to September 2017, testing for CHB within Sacramento County was conducted through community-based testing events and an electronic health record alert that identified Asian patients by surname. Demographic and laboratory data were collected for analysis and patients were followed through the study period to assess linkage to care and treatment to compare differences between Asian origin groups. Of 4350 patients tested for CHB, 318 (7.3%) were HBsAg positive, including 90 Chinese, 47 Hmong, and 101 Vietnamese. Hmong were more likely to have Medicaid insurance compared to other Asian origin groups (15%, p < 0.001). Hmong had significantly lower rates of hepatitis B DNA testing (p < 0.001), referral to hepatology (p < 0.001), attendance of first (p < 0.001) and second medical visit (p = 0.0003), and lower rates of antiviral treatment compared to other Asian origin groups. Hmong also had the highest proportion of non-English speakers (p < 0.001). Hmong patients in the Sacramento CHB testing and linkage to care program experience socioeconomic disadvantages compared to Vietnamese and Chinese patients. These factors may contribute to decreased linkage of care and decreased anti-viral treatment rates for CHB.

Time, trust, and transparency: Lessons learned from collecting blood biospecimens for cancer research from the Asian American community.

BACKGROUND: Biospecimens from racially diverse groups are needed to advance cancer research. The Asian American Cancer Education Study was developed to increase the number and proportion of blood biospecimen donations from Asian Americans for cancer research. METHODS: The authors' targeted approach included 2 types of community engagement, in-reach (within institution to Asian American patients with cancer) and outreach (external to institution to the general Asian American community). Participants received in-language biospecimen education followed by the opportunity to donate blood biospecimens. Outreach participants donated through our community biospecimen blood drives, and in-reach participants consented to donating an extra tube of blood during their routine blood draws as a patient. Donated blood biospecimens were spun down to serum and plasma to be stored in a biorepository or were sent to the laboratory to test for cancer-related risk factors. RESULTS: Three hundred eighty-eight Asian Americans donated 1127 blood biospecimens for cancer research. Four hundred twenty tubes of plasma and serum are currently being stored at the cancer center's biorepository, 39 tubes have been used for cancer genomic research, and 668 tubes were used to characterize cancer-related risk factors. CONCLUSIONS: Building upon the past decade of the National Cancer Institute-funded Asian American Network for Cancer Awareness, Research, and Training's foundation of trust and service among Asian Americans, researchers were able to leverage relationships not only to introduce the idea of biospecimen contribution to the community but to also exceed expectations with regard to the quantity of blood biospecimens collected from Asian Americans. Cancer 2018;124:1614-21. © 2018 American Cancer Society.

High frequency of the PNPLA3 rs738409 [G] single-nucleotide polymorphism in Hmong individuals as a potential basis for a predisposition to chronic liver disease.

BACKGROUND: An exploratory study was performed to determine the prevalence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs78409 [G] allele among the Hmong as a risk factor for nonalcoholic fatty liver disease (NAFLD). NAFLD/nonalcoholic steatohepatitis is the world's most common chronic liver disease and is expected to replace viral hepatitis as the leading cause of cirrhosis and potential precursor to hepatocellular carcinoma (HCC). Of all populations in California, the Hmong experience the highest risk of death from HCC and the highest prevalence of metabolic syndrome risk factors among Asians that predispose them to NAFLD. Here a genetic explanation was sought for the high rates of chronic liver disease among the Hmong. The literature pointed to the PNPLA3 rs738409 [G] allele as a potential genetic culprit. METHODS: Cell-free DNA was isolated from 26 serum samples previously collected in community settings. Quantitative polymerase chain reaction-based single-nucleotide polymorphism (SNP) genotyping was performed with a validated TaqMan SNP genotyping assay, and results were analyzed with TaqMan Genotyper software. RESULTS: The PNPLA3 rs738409 [C>G] variant occurred at a frequency of 0.46 (12 of 26; 95% confidence interval, 0.27-0.67). This carrier rate would rank the Hmong as the third highest population in the 1000 Genomes Project. CONCLUSIONS: Although this small sample size limits the generalizability, the high frequency rates of this allele along with the presence of metabolic syndrome risk factors warrant further studies into the etiology of NAFLD among the Hmong. Cancer 2018;124:1583-9. © 2018 American Cancer Society.

Emergence of African species of dermatophytes in tinea capitis: A 17-year experience in a Montreal pediatric hospital.

BACKGROUND/OBJECTIVES: An increase in dermatophyte infections caused by African species is reported in countries receiving African immigrants. Our goal was to determine the epidemiologic and clinical characteristics of tinea capitis in children infected with African species of dermatophytes in Montreal, Canada. METHODS: Demographic and clinical data from medical records of children infected with African species of dermatophytes were retrieved retrospectively (2000-2016) at Sainte-Justine University Hospital Center. RESULTS: In Montreal, the number of tinea capitis cases caused by African species of dermatophytes increased sixfold over 17 years. African immigrant children (84%), men and boys (61%), and preschoolers (2-5 years old) (51%) were the most frequently affected in our 315 cases. Family contamination was frequent (45%). Referring physicians prescribed systemic antifungal treatment in 39% of cases and pediatric dermatologist consultants in 90%. Treatment failure to oral terbinafine occurred in 39% of Microsporum audouinii infections. CONCLUSION: In Montreal, there was a significant increase in tinea capitis caused by African species of dermatophytes. Microsporum audouinii is highly transmissible and often resistant to oral terbinafine. Recognizing tinea capitis trends in a given environment will improve patient care.

Diabetes Prevalence and Risk Factors in Four Asian American Communities.

Our objective was to estimate the prevalence of diabetes and pre-diabetes and the risk associated with BMI above the Asian cut-point of 23 in 4 Asian American communities. In a convenience sample of 981 Chinese, Hmong, Korean, and Vietnamese Americans in Sacramento County, California we measured hemoglobin A1c (HbAlc), height, weight, and waist circumference. Diabetes was defined as self-reported diabetes diagnosis or HbA1c ≥ 6.5 %, and pre-diabetes as HbAlc 5.7-6.4 % with no diabetes diagnosis. We computed age-standardized prevalence of diabetes, pre-diabetes, and BMI and waist circumference above standard and Asian cut-points, and developed multivariable models of the association of diabetes and pre-diabetes with BMI and waist circumference. The 4 ethnic groups differed substantially with respect to diabetes prevalence, BMI, and waist circumference. Hmong had the highest prevalence of diabetes (15.0 %, 95 % confidence interval [CI] 10.7-19.4 %). Diabetes and pre-diabetes were associated with BMI ≥ 25 (diabetes: odds ratio [OR] 3.4, 95 % CI 2.1-5.7; pre-diabetes: OR 4.0, 95 % CI 2.7-5.8) or between 23 and 25 (diabetes: OR 1.8, 95 % CI 1.0-3.1; pre-diabetes: OR 1.6, 95 % CI 1.0-2.4). When waist circumference was added to the model, BMI effects were attenuated, and waist circumference ≥40 inches (men) or ≥35 inches (women) was associated with increased risk of diabetes (OR 3.2, 95 % CI 1.6-6.2) and pre-diabetes (OR 1.7, 95 % CI 1.0-2.9). Our findings support the use of a BMI cut-point of 23 and the importance of central adiposity as a risk factor for diabetes in Asians. Diabetes risk reduction interventions for Asians are essential.

PML mediates glioblastoma resistance to mammalian target of rapamycin (mTOR)-targeted therapies.

Despite their nearly universal activation of mammalian target of rapamycin (mTOR) signaling, glioblastomas (GBMs) are strikingly resistant to mTOR-targeted therapy. We analyzed GBM cell lines, patient-derived tumor cell cultures, and clinical samples from patients in phase 1 clinical trials, and find that the promyelocytic leukemia (PML) gene mediates resistance to mTOR-targeted therapies. Direct mTOR inhibitors and EGF receptor (EGFR) inhibitors that block downstream mTOR signaling promote nuclear PML expression in GBMs, and genetic overexpression and knockdown approaches demonstrate that PML prevents mTOR and EGFR inhibitor-dependent cell death. Low doses of the PML inhibitor, arsenic trioxide, abrogate PML expression and reverse mTOR kinase inhibitor resistance in vivo, thus markedly inhibiting tumor growth and promoting tumor cell death in mice. These results identify a unique role for PML in mTOR and EGFR inhibitor resistance and provide a strong rationale for a combination therapeutic strategy to overcome it.

Resistance to EGF receptor inhibitors in glioblastoma mediated by phosphorylation of the PTEN tumor suppressor at tyrosine 240.

Glioblastoma multiforme (GBM) is the most aggressive of the astrocytic malignancies and the most common intracranial tumor in adults. Although the epidermal growth factor receptor (EGFR) is overexpressed and/or mutated in at least 50% of GBM cases and is required for tumor maintenance in animal models, EGFR inhibitors have thus far failed to deliver significant responses in GBM patients. One inherent resistance mechanism in GBM is the coactivation of multiple receptor tyrosine kinases, which generates redundancy in activation of phosphoinositide-3'-kinase (PI3K) signaling. Here we demonstrate that the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor is frequently phosphorylated at a conserved tyrosine residue, Y240, in GBM clinical samples. Phosphorylation of Y240 is associated with shortened overall survival and resistance to EGFR inhibitor therapy in GBM patients and plays an active role in mediating resistance to EGFR inhibition in vitro. Y240 phosphorylation can be mediated by both fibroblast growth factor receptors and SRC family kinases (SFKs) but does not affect the ability of PTEN to antagonize PI3K signaling. These findings show that, in addition to genetic loss and mutation of PTEN, its modulation by tyrosine phosphorylation has important implications for the development and treatment of GBM.

Twenty years post-NIH Revitalization Act: enhancing minority participation in clinical trials (EMPaCT): laying the groundwork for improving minority clinical trial accrual: renewing the case for enhancing minority participation in cancer clinical trials.

BACKGROUND: The National Institutes of Health (NIH) Revitalization Act of 1993 mandated the appropriate inclusion of minorities in all NIH-funded research. Twenty years after this act, the proportion of minority patients enrolled in cancer clinical trials remains persistently low. Clinical trials are vehicles for the development and evaluation of therapeutic and preventive agents under scientifically rigorous conditions. Without representation in trials, it is projected that disparities in the cancer burden for minorities will increase. METHODS: For this review article, the authors counted the frequency with which minorities were the primary focus of National Cancer Institute-sponsored clinical trials, examined citations from the PubMed database focusing on the search terms "NIH Revitalization Act of 1993" and "enhancing minority accrual to cancer clinical trials," and supplemented the review with their expertise in NIH-funded research related to minority accrual in cancer clinical trials. RESULTS: The reporting and analyses of data based on minorities in clinical trials remain inadequate. Less than 2% of the National Cancer Institute's clinical trials focus on any racial/minority population as their primary emphasis. The current review of the literature indicated that the percentage of authors who reported their study sample by race/ethnicity ranged from 1.5% to 58%, and only 20% of the randomized controlled studies published in a high-impact oncology journal reported analyzing results by race/ethnicity. Proportionately greater population increases in minorities, accompanied by their persistent and disproportionate cancer burden, reinforce the need for their greater representation in clinical trials. CONCLUSIONS: Renewing the emphasis for minority participation in clinical trials is warranted. Policy changes are recommended.

Association Between COVID-19 and Planned and Postponed Cancer Screenings Among American Indian Adults Residing in California and Oklahoma, March-December 2020.

OBJECTIVE: Little is known about how the COVID-19 pandemic affected cancer screenings among American Indian people residing in California and Oklahoma, 2 states with the largest American Indian populations. We assessed rates and factors associated with cancer screenings among American Indian adults during the pandemic. METHODS: From October 2020 through January 2021, we surveyed 767 American Indian adults residing in California and Oklahoma. We asked participants whether they had planned to obtain screenings for breast cancer, cervical cancer, and colorectal cancer (CRC) from March through December 2020 and whether screening was postponed because of COVID-19. We calculated adjusted odds ratios (AORs) for factors associated with reasons for planned and postponed cancer screening. RESULTS: Among 395 participants eligible for breast cancer screening, 234 (59.2%) planned to obtain the screening, 127 (54.3%) of whom postponed it. Among 517 participants eligible for cervical cancer screening, 357 (69.1%) planned to obtain the screening, 115 (32.2%) of whom postponed it. Among 454 participants eligible for CRC screening, 282 (62.1%) planned to obtain CRC screening, 80 of whom (28.4%) postponed it. In multivariate analyses, women who lived with a child (vs did not) had lower odds of planning to obtain a breast cancer screening (AOR = 0.6; 95% CI, 0.3-1.0). Adherence to social distancing recommendations was associated with planning to have and postponement of cervical cancer screening (AOR = 7.3; 95% CI, 0.9-58.9). Participants who received (vs did not receive) social or financial support had higher odds of planning to have CRC screening (AOR = 2.0; 95% CI, 1.1-3.9). CONCLUSION: The COVID-19 pandemic impeded completion of cancer screenings among American Indian adults. Interventions are needed to increase the intent to receive evidence-based cancer screenings among eligible American Indian adults.

"You Don't Know If It's the Truth or a Lie": Exploring Human Papillomavirus (HPV) Vaccine Hesitancy among Communities with Low HPV Vaccine Uptake in Northern California.

BACKGROUND: Vaccine hesitancy, delaying or refusing to vaccinate despite the availability of vaccines, impedes the progress of achieving optimal HPV vaccine coverage. Little is known about the sources of human papillomavirus (HPV) vaccine hesitancy among racially/ethnically and geographically diverse communities. The purpose of this paper is to explore HPV vaccine hesitancy among rural, Slavic, and Latino communities that reside in counties with low HPV vaccine uptake rates. METHODS: Key informant interviews and focus groups were conducted with rural, Slavic, and Latino communities that reside within counties in California that have low HPV vaccine up to date rates (16-25%). Qualitative data were transcribed verbatim and analyzed using inductive and deductive thematic analysis. RESULTS: A total of seven focus groups and 14 key informant interviews were conducted with 39 individuals from seven California counties. Salient themes that contributed to HPV vaccine hesitancy included the following: social media and the anti-vaccination movement; a strong belief in acquiring immunity naturally; prior vaccine experiences; and vaccine timing concerns. Participants suggested the provision of culturally appropriate, in-language, in-person easy to understand HPV vaccine education to mitigate HPV vaccine hesitancy. CONCLUSIONS: Our findings can inform future interventions to increase HPV vaccine uptake among hesitant communities.

Electronic messages increase hepatitis B screening in at-risk Asian American patients: a randomized, controlled trial.

BACKGROUND: Hepatitis B (HBV) induced hepatocellular carcinoma is the greatest cancer health disparity affecting Asian Americans, but the prevalence of screening to detect HBV is suboptimal. AIMS: Our aims were to determine the effectiveness of electronic health record (EHR) prompts to increase ordering of HBV tests among primary care providers (PCPs) within an academic health system. METHODS: We conducted a randomized, controlled trial between April and June 2011 among 76 PCPs caring for 175 outpatient adults with Chinese or Vietnamese surnames, with appointments with providers and no history of HBV testing. Providers were randomized to either receive an EHR prompt for HBV testing prior to patients' appointments or usual care. Primary outcomes were the proportion of patients (1) whose physician ordered a HBsAg test and (2) who completed testing. Secondary outcomes were (A) test results and (B) whether the physicians followed-up on the results. RESULTS: HBsAg tests were ordered for 36/88 (40.9 %) of the intervention patients and 1/87 (1.1 %) of the control patients [χ (2) (df = 1) = 41.48, p < 0.001]. Thirty intervention patients (34.1 %) and no control patients completed the HBsAg test [χ (2) (df = 1) = 35.80, p < 0.001]. Four (13.3 %) of the completed tests were HBsAg-positive, 14 (46.7 %) were immune, and 12 (40 %) were unprotected from HBV. Two HBsAg-positive patients were referred to specialists, and 3 unprotected patients were vaccinated for HBV. CONCLUSIONS: EHR-based provider prompts significantly increased HBV testing in Chinese and Vietnamese patients when compared to "usual care." EHR prompts are a promising intervention that could significantly increase screening for HBV.

The phosphatase and tensin homolog regulates epidermal growth factor receptor (EGFR) inhibitor response by targeting EGFR for degradation.

The phosphatase and tensin homolog (PTEN) is a tumor suppressor that is inactivated in many human cancers. PTEN loss has been associated with resistance to inhibitors of the epidermal growth factor receptor (EGFR), but the molecular basis of this resistance is unclear. It is believed that unopposed phosphatidylinositol-3-kinase (PI3K) activation through multiple receptor tyrosine kinases (RTKs) can relieve PTEN-deficient cancers from their "dependence" on EGFR or any other single RTK for survival. Here we report a distinct resistance mechanism whereby PTEN inactivation specifically raises EGFR activity by impairing the ligand-induced ubiquitylation and degradation of the activated receptor through destabilization of newly formed ubiquitin ligase Cbl complexes. PTEN-associated resistance to EGFR kinase inhibitors is phenocopied by expression of dominant negative Cbl and can be overcome by more complete EGFR kinase inhibition. PTEN inactivation does not confer resistance to inhibitors of the MET or PDGFRA kinase. Our study identifies a critical role for PTEN in EGFR signal termination and suggests that more potent EGFR inhibition should overcome resistance caused by PI3K pathway activation.

Implementation and evaluation of a multilevel intervention to increase uptake of the human papillomavirus vaccine among rural adolescents.

PURPOSE: Geographic disparities exist in uptake of the human papillomavirus vaccine (HPV). In 2020, the National Immunization Survey-Teen reported that adolescents living in nonmetropolitan statistical areas (MSAs) had lower HPV vaccination coverage (≥ 1 dose) compared to adolescents living in MSA principal cities. This paper describes the implementation and evaluation of a multilevel pilot intervention study to increase uptake of the HPV vaccine among adolescent patients ages 11-17 of a rural health clinic. METHODS: This parent, primary care team, and clinic multilevel pilot intervention was guided by evidence-based approaches to increase HPV vaccinations, formative research, and input from the community. HPV vaccination initiation and completion rates were analyzed at baseline and 23 months follow-up. FINDINGS: The proportion of adolescent patients ages 11-17 who had initiated the HPV vaccine series was significantly greater at follow-up compared to baseline, (82.7% compared to 52.4%), χ2 (1, n = 498) = 49.2, P < .0001. The proportion of adolescent patients ages 11-17 who had completed the HPV vaccine series was also significantly greater at follow-up compared to baseline, (58.0% compared to 27.0%), χ2 (1, n = 498) = 50.8, P < .0001. CONCLUSIONS: The multilevel intervention significantly increased HPV initiation and completion rates among adolescent patients ages 11-17 at this rural health clinic. This study demonstrates the feasibility of utilizing a multilevel intervention to address low HPV vaccination rates among rural adolescents and the potential of employing this strategy for a large-scale randomizing-controlled trial.

Avoidance of medical care among American Indians with a history of cancer during the coronavirus pandemic.

Objectives: Assess the percentage of cancer-related appointment delays, cancelations, and the unavailability of medications experienced by American Indian participants during the COVID-19 pandemic. Methods: This cross-sectional survey study was completed between October 2020 and July 2021 by 360 individuals with cancer who lived in California and Oklahoma. Binary and multivariate logistic regression analysis was completed in SAS 9.4. Results: During the initial Covid-19 pandemic, almost one-third (30%) of respondents delayed cancer-related appointments, 42% canceled cancer-related appointments, and one-quarter (24%) were unable to access prescription medications or over-the-counter medications (27%) due to COVID-19. People who underwent testing for COVID-19 were five times more likely to delay a medical appointment [adjusted odds ratio (aOR) = 5.3, 95% CI:2.4, 11.7] and people who followed three or more social distancing measures were more than six times more likely to cancel medical appointments (aOR:6.3, 95% CI:2.9, 13.9). Conclusion: This study identifies delays, cancelations, and medication inaccessibility people identifying as American Indian faced during the coronavirus pandemic. Disparities in healthcare delivery could contribute to increased morbidity and mortality rates of cancer.

Tobacco and marijuana use during the COVID-19 pandemic lockdown among American Indians residing in California and Oklahoma.

INTRODUCTION: American Indian (AI) people experience a disproportionate tobacco and marijuana burden which may have been exacerbated by the COVID-19 pandemic. Little is known about the tobacco and marijuana habits of American Indian individuals during the COVID-19 pandemic. The objective of this study is to examine tobacco and marijuana use as well as change in use during the COVID-19 pandemic among the American Indian community. METHODS: This cross-sectional study analyzes survey data from a convenience sample of American Indian individuals residing in California and Oklahoma and included adults with and without cancer that resided in both rural and urban areas (n=1068). RESULTS: During October 2020 - January 2021, 36.0% of participants reported current use of tobacco products, 9.9% reported current use of marijuana products, and 23.7% reported increased use of tobacco and/or marijuana in the past 30 days, with no difference between those with cancer and those without cancer. Tobacco use was associated with marital status, age, employment status, COVID-19 exposure, COVID-19 beliefs, and alcohol consumption. Marijuana use was associated with COVID-19 beliefs, alcohol consumption, and income level. Increased tobacco and/or marijuana use was associated with baseline use of those products. Nearly a quarter of participants reported increased use of tobacco and/or marijuana products during the COVID-19 pandemic. CONCLUSIONS: We observed high rates of tobacco use during the COVID-19 pandemic, consistent with other studies. Research is needed to examine whether tobacco and marijuana use will decrease to pre-pandemic levels post-pandemic or if these behaviors will persist post-pandemic. Given these findings, there is a pressing need to increase access to evidence-based tobacco and marijuana treatment services in the AI population post COVID-19 pandemic.

The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis.

The EGFR/PI3K/Akt/mTOR signaling pathway is activated in many cancers including glioblastoma, yet mTOR inhibitors have largely failed to show efficacy in the clinic. Rapamycin promotes feedback activation of Akt in some patients, potentially underlying clinical resistance and raising the need for alternative approaches to block mTOR signaling. AMPK is a metabolic checkpoint that integrates growth factor signaling with cellular metabolism, in part by negatively regulating mTOR. We used pharmacological and genetic approaches to determine whether AMPK activation could block glioblastoma growth and cellular metabolism, and we examined the contribution of EGFR signaling in determining response in vitro and in vivo. The AMPK-agonist AICAR, and activated AMPK adenovirus, inhibited mTOR signaling and blocked the growth of glioblastoma cells expressing the activated EGFR mutant, EGFRvIII. Across a spectrum of EGFR-activated cancer cell lines, AICAR was more effective than rapamycin at blocking tumor cell proliferation, despite less efficient inhibition of mTORC1 signaling. Unexpectedly, addition of the metabolic products of cholesterol and fatty acid synthesis rescued the growth inhibitory effect of AICAR, whereas inhibition of these lipogenic enzymes mimicked AMPK activation, thus demonstrating that AMPK blocked tumor cell proliferation primarily through inhibition of cholesterol and fatty acid synthesis. Most importantly, AICAR treatment in mice significantly inhibited the growth and glycolysis (as measured by (18)fluoro-2-deoxyglucose microPET) of glioblastoma xenografts engineered to express EGFRvIII, but not their parental counterparts. These results suggest a mechanism by which AICAR inhibits the proliferation of EGFRvIII expressing glioblastomas and point toward a potential therapeutic strategy for targeting EGFR-activated cancers.

PTEN dosage is essential for neurofibroma development and malignant transformation.

Patients with neurofibromatosis type 1 (NF1) carry approximately a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). Although the molecular mechanisms underlying NF1 to MPNST malignant transformation remain unclear, alterations of both the RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways have been implicated. In a series of genetically engineered murine models, we perturbed RAS/RAF/MAPK or/and PTEN/PI3K/AKT pathway, individually or simultaneously, via conditional activation of K-ras oncogene or deletion of Nf1 or Pten tumor suppressor genes. Only K-Ras activation in combination with a single Pten allele deletion led to 100% penetrable development of NF lesions and subsequent progression to MPNST. Importantly, loss or decrease in PTEN expression was found in all murine MPNSTs and a majority of human NF1-associated MPNST lesions, suggesting that PTEN dosage and its controlled signaling pathways are critical for transformation of NFs to MPNST. Using noninvasive in vivo PET-CT imaging, we demonstrated that FDG can be used to identify the malignant transformation in both murine and human MPNSTs. Our data suggest that combined inhibition of RAS/RAF/MAPK and PTEN/PI3K/AKT pathways may be beneficial for patients with MPNST.