Association of sarcopenia with severe chemotherapy toxicities and survival in patients with advanced gastric cancer.

BACKGROUND: Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC. METHODS: Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed. RESULTS: A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001). CONCLUSIONS: Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis.

Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression.

Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.

Development and application of a weighted change score to evaluate interventions for vasomotor symptoms in patients with breast cancer using regression trees: a cohort study.

PURPOSE: Vasomotor symptoms (VMS) are common among individuals with breast cancer (BC) and poorly managed symptoms are associated with reduced quality of life, treatment discontinuation, and poorer breast cancer outcomes. Direct comparisons among therapies are limited, as prior studies evaluating VMS interventions have utilized heterogeneous change measures which may not fully assess the perceived impact of change in VMS severity. METHODS: We performed a prospective study where BC patients chose one of four categories of interventions to manage VMS. Change in VMS severity at 6 weeks was assessed using the validated Hot Flush Rating Scale (HFRS). A novel weighted change score integrating baseline symptom severity and directionality of change was computed to maximize the correlation between the change score and a perceived treatment effectiveness score. Variables influencing change in VMS severity were included in a regression tree to model factors influencing the weighted change score. RESULTS: 100 baseline and follow-up questionnaires assessing VMS were completed by 88 patients. Correlations between treatment effectiveness and VMS outcomes strengthened following adjustment for baseline symptoms. Patients with low VMS severity at baseline did not perceive change in treatment effectiveness. Intervention category was predictive of change in HFRS at 6 weeks. CONCLUSION: Baseline symptom severity and the directionality of change (improvement or deterioration of symptoms) influenced the perception of clinically meaningful change in VMS severity. Future interventional studies utilizing the weighted change score should target moderate-high baseline severity patients.

Impact of early surgical complications on kidney transplant outcomes.

BACKGROUND: Kidney transplantation (KT) improves clinical outcomes of patients with end stage renal disease. Little has been reported on the impact of early post-operative surgical complications (SC) on long-term clinical outcomes following KT. We sought to determine the impact of vascular complications, urological complications, surgical site complications, and peri-graft collections within 30 days of transplantation on patient survival, graft function, and hospital readmissions. METHODS: We conducted a single-centre, observational cohort study examining adult patients (≥ 18 years) who received a kidney transplant from living and deceased donors between January 1st, 2005 and December 31st, 2015 with follow-up until December 31st, 2016 (n = 1,334). Univariable and multivariable analyses were performed with Cox proportional hazards models to analyze the outcomes of SC in the early post-operative period after KT. RESULTS: The cumulative probability of SC within 30 days of transplant was 25%, the most common SC being peri-graft collections (66.8%). Multivariable analyses showed significant relationships between Clavien Grade 1 SC and death with graft function (HR 1.78 [95% CI: 1.11, 2.86]), and between Clavien Grades 3 to 4 and hospital readmissions (HR 1.95 [95% CI: 1.37, 2.77]). CONCLUSIONS: Early SC following KT are common and have a significant influence on long-term patient outcomes.

Cancer care coordination in rural Hawaii: a focus group study.

BACKGROUND: Rural populations consistently experience a disproportionate burden of cancer, including higher incidence and mortality rates, compared to the urban populations. Factors that are thought to contribute to these disparities include limited or lack of access to care and challenges with care coordination (CC). In Hawaii, many patients residing in rural areas experience unique challenges with CC as they require inter-island travel for their cancer treatment. In this focus group study, we explored the specific challenges and positive experiences that impact the CC in rural Hawaii cancer patients. METHODS: We conducted two semi-structured focus group interviews with cancer patients receiving active treatment for any type of cancer (n = 8). The participants were recruited from the rural areas of Hawaii, specifically the Hawaii county and Kauai. Rural was defined using the Rural-Urban Commuting Area Codes (RUCA; rural ≥ 4). The focus group discussions were facilitated using open-ended questions to explore patients' experiences with CC. RESULTS: Content analysis revealed that 47% of the discussions were related to CC-related challenges, including access to care (27.3%), insurance (9.1%), inter-island travel (6.1%), and medical literacy (4.5%). Other major themes from the discussions focused on facilitators of CC (30.3%), including the use of electronic patient portal (12.1%), team-based approach (9.1%), family caregiver support (4.5%), and local clinic staff (4.5%). CONCLUSION: Our findings indicate that there are notable challenges in rural patients' experiences regarding their cancer care coordination. Specific factors such as the lack of oncologist and oncology services, fragmented system, and the lack of local general medical providers contribute to problems with access to care. However, there are also positive factors found through the help of facilitators of CC, notability the use of electronic patient portal, team-based approach, family caregiver support, and local clinic staff. These findings highlight potential targets of interventions to improve cancer care delivery for rural patients. TRIAL REGISTRATION: Not required.

Time to Diagnosis and Treatment Initiation During the COVID-19 Pandemic Among Rural Patients With Cancer.

Time to diagnosis (TTD) and treatment initiation (TTI) are important measures of access to and quality of cancer care. This study addressed the knowledge gap on the impact of the COVID-19 pandemic on TTD and TTI for rural cancer patients. Sixty-three cancer patients residing in rural areas of the state of Hawaii were surveyed in 2020 to 2021. Overall, 67.5% of participants reported TTD within one month of reporting symptoms to a health care provider. Mean TTI for the overall sample was 55.3 days, and among breast cancer patients, 57.9 days. Compared with pre-pandemic state registry data, mean TTI for the overall sample and breast cancer patients were significantly longer than the state registry null value of 40 days (P = .02 and P =.05, respectively). During the COVID-19 pandemic, cancer patients in rural Hawaii experienced substantial delays in TTI compared with pre-pandemic years.

Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influence on tacrolimus dose adjusted concentrations in adult heart transplant recipients.

CYP3A5 genetic variants are associated with tacrolimus metabolism. Controversy remains on whether CYP3A4 increased [*1B (rs2740574), *1 G (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This retrospective cohort study aims to address whether tacrolimus dose-adjusted trough concentrations differ between combined CYP3A (CYP3A5 and CYP3A4) phenotype groups. Heart transplanted patients (n = 177, between 2008 and 2020) were included and median age was 54 years old. Significant differences between CYP3A phenotype groups in tacrolimus dose-adjusted trough concentrations were found in the early postoperative period and continued to 6 months post-transplant. In CYP3A5 nonexpressers, carriers of CYP3A4*1B or *1 G variants (Group 3) compared to CYP3A4*1/*1 (Group 2) patients were found to have lower tacrolimus dose-adjusted trough concentrations at 2 months. In addition, significant differences were found among CYP3A phenotype groups in the dose at discharge and time to therapeutic range while time in therapeutic range was not significantly different. A combined CYP3A phenotype interpretation may provide more nuanced genotype-guided TAC dosing in heart transplant recipients.

Patient reports of cancer care coordination in rural Hawaii.

PURPOSE: Rural residents experience disproportionate burdens of cancer, and poorer cancer health outcomes in rural populations are partly attributed to care delivery challenges. Cancer patients in rural areas often experience unique challenges with care coordination. In this study, we explored patient reports of care coordination among rural Hawaii patients with cancer and compared rural and urban patients' perceptions of cancer care coordination. METHODS: 80 patients receiving active treatment for cancer from rural Hawaii participated in a care coordination study in 2020-2021. Participants completed the Care Coordination Instrument, a validated oncology patient questionnaire. FINDINGS: Mean age of rural cancer patients was 63.0 (SD = 12.1), and 57.7% were female. The most common cancer types were breast and GI. Overall, rural and urban patients' perceptions of care coordination were comparable (p > 0.05). There were statistically significant differences between rural and urban patients' perceptions in communication and navigation aspects of care coordination (p = 0.02 and 0.04, respectively). Specific differences included a second opinion consultation, clinical trial considerations, and after-hours care. 43% of rural patients reported traveling by air for part or all of their cancer treatment. CONCLUSIONS: Findings suggest that while overall perceptions of care coordination were similar between rural and urban patients, differential perceptions of specific care coordination areas between rural and urban patients may reflect limited access to care for rural patients. Improving access to cancer care may be a potential strategy to enhance care coordination for rural patients and ultimately address rural-urban cancer health disparities.

Analysis of a mouse germ cell tumor model establishes pluripotency-associated miRNAs as conserved serum biomarkers for germ cell cancer detection.

Malignant testicular germ cells tumors (TGCTs) are the most common solid cancers in young men. Current TGCT diagnostics include conventional serum protein markers, but these lack the sensitivity and specificity to serve as accurate markers across all TGCT subtypes. MicroRNAs (miRNAs) are small non-coding regulatory RNAs and informative biomarkers for several diseases. In humans, miRNAs of the miR-371-373 cluster are detectable in the serum of patients with malignant TGCTs and outperform existing serum protein markers for both initial diagnosis and subsequent disease monitoring. We previously developed a genetically engineered mouse model featuring malignant mixed TGCTs consisting of pluripotent embryonal carcinoma (EC) and differentiated teratoma that, like the corresponding human malignancies, originate in utero and are highly chemosensitive. Here, we report that miRNAs in the mouse miR-290-295 cluster, homologs of the human miR-371-373 cluster, were detectable in serum from mice with malignant TGCTs but not from tumor-free control mice or mice with benign teratomas. miR-291-293 were expressed and secreted specifically by pluripotent EC cells, and expression was lost following differentiation induced by the drug thioridazine. Notably, miR-291-293 levels were significantly higher in the serum of pregnant dams carrying tumor-bearing fetuses compared to that of control dams. These findings reveal that expression of the miR-290-295 and miR-371-373 clusters in mice and humans, respectively, is a conserved feature of malignant TGCTs, further validating the mouse model as representative of the human disease. These data also highlight the potential of serum miR-371-373 assays to improve patient outcomes through early TGCT detection, possibly even prenatally.

Endogenous Rab38 regulates LRRK2's membrane recruitment and substrate Rab phosphorylation in melanocytes.

Point mutations in leucine-rich repeat kinase 2 (LRRK2) cause Parkinson's disease and augment LRRK2's kinase activity. However, cellular pathways that endogenously enhance LRRK2 kinase function have not been identified. While overexpressed Rab29 draws LRRK2 to Golgi membranes to increase LRRK2 kinase activity, there is little evidence that endogenous Rab29 performs this function under physiological conditions. Here, we identify Rab38 as a novel physiologic regulator of LRRK2 in melanocytes. In mouse melanocytes, which express high levels of Rab38, Rab32, and Rab29, knockdown (or CRISPR knockout) of Rab38, but not Rab32 or Rab29, decreases phosphorylation of multiple LRRK2 substrates, including Rab10 and Rab12, by both endogenous LRRK2 and exogenous Parkinson's disease-mutant LRRK2. In B16-F10 mouse melanoma cells, Rab38 drives LRRK2 membrane association and overexpressed kinase-active LRRK2 shows striking pericentriolar recruitment, which is dependent on the presence of endogenous Rab38 but not Rab32 or Rab29. Consistently, knockdown or mutation of BLOC-3, the guanine nucleotide exchange factor for Rab38 and Rab32, inhibits Rab38's regulation of LRRK2. Deletion or mutation of LRRK2's Rab38-binding site in the N-terminal armadillo domain decreases LRRK2 membrane association, pericentriolar recruitment, and ability to phosphorylate Rab10. In sum, our data identify Rab38 as a physiologic regulator of LRRK2 function and lend support to a model in which LRRK2 plays a central role in Rab GTPase coordination of vesicular trafficking.

MiR-410-3p suppresses primary gastric cancer and exosomes regulate endogenous expression of miR-410-3p.

MicroRNAs play significant roles in cancer initiation and progression. Exosomes are important extracellular vesicles for transporting molecules to distant sites. This study aims to investigate the functional roles of miR-410-3p in primary gastric cancer, as well as the roles of exosomes in regulating expression of miR-410-3p. In this study, forty-seven pairs of human gastric cancer tissue samples were collected. Endogenous expression of miR-410-3p in tissue samples and cell lines, and expression of exosomal miR-410-3p in cell culture medium were evaluated by RT-qPCR. Functional assays including cell proliferation assay by MTT, cell migration and invasion assay by transwell, and cell adhesion assay were performed. Targets of miR-410-3p were screened. Cell culture medium of culturing cell lines established from stomach (AGS and BCG23) was applied for culturing cell lines established from other sites (MKN45 and HEK293T). It was found that miR-410-3p was significantly downregulated in gastric cancer. Overexpression of miR-410-3p inhibited gastric cancer cell proliferation, migration, and invasion. MiR-410-3p mimic enhanced cell adhesion. HMGB1 was a target of miR-410-3p in primary gastric cancer. Expression of exosomal miR-410-3p in cell culture medium was dramatically higher than its endogenous expression. Exosomes from cell culture medium of AGS or BCG23 regulated endogenous expression of miR-410-3p in MKN45. In conclusion, miR-410-3p functioned as a tumor suppressor in primary gastric cancer. MiR-410-3p was higher expressed in exosomes of cell culture medium than its endogenous expression in cells. Endogenous expression of miR-410-3p in a distant site could be regulated by exosomes from the original site.

Can routinely collected administrative data effectively be used to evaluate and validate endpoints used in breast cancer clinical trials? Protocol for a scoping review of the literature.

BACKGROUND: Randomized controlled trials (RCTs) are a critical component of evidence-based medicine and the evolution of patient care. However, the costs of conducting a RCT can be prohibitive. A promising approach toward reduction of costs and lessening of the burden of intensive and lengthy patient follow-up is the use of routinely collected healthcare data (RCHD), commonly called real-world data. We propose a scoping review to identify existing RCHD case definitions of breast cancer progression and survival and their diagnostic performance. METHODS: We will search MEDLINE, EMBASE, and CINAHL to identify primary studies of women with either early-stage or metastatic breast cancer, managed with established therapies, that evaluated the diagnostic accuracy of one or more RCHD-based case definitions or algorithms of disease progression (i.e., recurrence, progression-free survival, disease-free survival, or invasive disease-free survival) or survival (i.e., breast-cancer-free survival or overall survival) compared with a reference standard measure (e.g., chart review or a clinical trial dataset). Study characteristics and descriptions of algorithms will be extracted along with measures of the diagnostic accuracy of each algorithm (e.g., sensitivity, specificity, positive predictive value, negative predictive value), which will be summarized both descriptively and in structured figures/tables. DISCUSSION: Findings from this scoping review will be clinically meaningful for breast cancer researchers globally. Identification of feasible and accurate strategies to measure patient-important outcomes will potentially reduce RCT budgets as well as lessen the burden of intensive trial follow-up on patients. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/6D9RS ).

Analysis of the complete plastomes of Bidens pilosa L. 1753 (Asteraceae, Coreopsideae) from Beijing, China reveals high genetic diversity and possible misidentifications.

Bidens pilosa L. 1753 is a perennial herbaceous flowering plant, traditionally used in foods and medicines. In this study, we sequenced, assembled, and characterized the complete plastome of B. pilosa from Beijing, China. The plastome (MN385242) is circularized with a conservative quadripartite structure. Its length is 150,524 bp, including a large single-copy region (83,535 bp), a small single-copy region (17,627 bp), and a pair of inverted repeat regions (each 24,681 bp). The plastome consists of 128 genes, including 78 unique protein-coding, 28 unique tRNA, and 4 unique rRNA genes. Phylogenetic analyses showed all five B. pilosa plants couldn't form a monophyletic clade and were separated into three clades. The results of K2P distance and molecular markers were all consistent with those of phylogenetic analysis, revealing high genetic diversity and even possible misidentifications of the B. pilosa. Our results highlighted the importance of correct species identification of materials in medicinal products.

Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients.

CYP3A5 genetic variants are associated with tacrolimus metabolism. Controversy remains on whether CYP3A4 increased [* 1B (rs2740574), *1G (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This study aims to address whether tacrolimus dose-adjusted trough concentrations differ between combined CYP3A (CYP3A5 and CYP3A4) phenotype groups. Significant differences between CYP3A phenotype groups in tacrolimus dose-adjusted trough concentrations were found in the early postoperative period and continued to 6 months post-transplant. In CYP3A5 nonexpressers, carriers of CYP3A4*7Bor *7G variants (Group 3) compared to CYP3A4*1/*1 (Group 2) patients were found to have lower tacrolimus dose-adjusted trough concentrations at 2 months. In addition, significant differences were found among CYP3A phenotype groups in the dose at discharge and time to therapeutic range while time in therapeutic range was not significantly different. A combined CYP3A phenotype interpretation may provide more nuanced genotype-guided TAC dosing in heart transplant recipients.

Pediatric considerations for pharmacogenetic selective serotonin reuptake inhibitors clinical decision support.

Pharmacogenetic testing for psychiatry is growing at a rapid pace, with multiple sites utilizing results to help clinical decision-making. Genotype-guided dosing and drug selection have been implemented at several sites, including Vanderbilt University Medical Center, where clinical decision support (CDS) based on pharmacogenetic results went live for selective serotonin reuptake inhibitors in 2020 for both adult and pediatric patients. Effective and appropriate implementation of CYP2D6- and CYP2C19-guided CDS for the pediatric population requires consideration of the evidence for the pharmacogenetic associations, medication indications, and appropriate alternative therapies to be used when a pharmacogenetic contraindication is identified. In this article, we review these pediatric pharmacogenetic considerations for selective serotonin reuptake inhibitor CDS. We include a case study, the current literature supporting clinical recommendations, considerations when designing pediatric CDS, future implications, and examples of sertraline, (es)citalopram, paroxetine, and fluvoxamine alerts.

Tutorial: Using Community Engagement Studios to Enhance Pharmacogenetic Study Design for Maximizing Enrollment of Diverse Children and Pregnant People.

Most pharmacogenetic research is conducted in adult, non-pregnant populations of European ancestry. Study of more diverse and special populations is necessary to validate findings and improve health equity. However, there are significant barriers to recruitment of diverse populations for genetic studies, such as mistrust of researchers due to a history of unethical research and ongoing social inequities. Engaging communities and understanding community members' perspectives may help to overcome these barriers and improve research quality. Here, we highlight one method for engaging communities, the Community Engagement Studio (CES), a consultative session that allows researchers to obtain guidance and feedback based on community members' lived experiences. We also provide an example of its use in pharmacogenetic studies. In designing a survey study of knowledge and attitudes around pharmacogenetic testing among children with chronic conditions and pregnant individuals, we sought input from diverse community stakeholders through CESs at Vanderbilt University Medical Center. We participated in two CESs with community stakeholders representing study target populations. Our goals were to learn specific concerns about pharmacogenetic testing and preferred recruitment strategies for these communities. Concerns were expressed about how genetic information would be used beyond the immediate study. Participants emphasized the importance of clarity and transparency in communication to overcome participation hesitancy and mistrust of the study team. Recruitment strategy recommendations ranged from informal notices posted in healthcare settings to provider referrals. The CES enabled us to modify our recruitment methods and research materials to better communicate with populations currently under-represented in pharmacogenetics research.

Integrating Systematic Reviews into Supportive Care Trial Design: The Rethinking Clinical Trials (REaCT) Program.

PURPOSE: To review the successes and challenges of integrating systematic reviews (SRs) into the Rethinking Clinical Trials (REaCT) Program. METHODS: All REaCT program SRs were evaluated and descriptive summaries presented. RESULTS: Twenty-two SRs have been performed evaluating standard of care interventions for the management of: breast cancer (n = 15), all tumour sites (n = 4), breast and prostate cancers (n = 2), and prostate cancer (n = 1). The majority of SRs were related to supportive care (n = 14) and survivorship (n = 5) interventions and most (19/22, 86%) confirmed the existence of uncertainty relating to the clinical question addressed in the SR. Most SRs (15/22, 68%) provided specific recommendations for future studies and results were incorporated into peer-reviewed grant applications (n = 6) and clinical trial design (n = 12). In 12/22 of the SRs, the first author was a trainee. All SRs followed PRISMA guidelines. CONCLUSION: SRs are important for identifying and confirming clinical equipoise and designing trials. SRs provide an excellent opportunity for trainees to participate in research.

Inhibition of EP2 receptor suppresses tumor growth and chemoresistance of gastric cancer.

Gastric cancer is one of the leading causes of cancer death in the world. Early diagnosis and effective chemotherapy are vital to reduce the overall mortality. Prostaglandin E2 (PGE2) has been implicated as an important factor in gastric cancer carcinogenesis. ECF based regimen (epirubicin, cisplatin, 5-fluorouracil) is the first-line chemotherapy for advanced gastric cancer. However, patients develop resistance after chemotherapy. The aim of this study is sought to investigate the role of EP2 receptor, a PGE2 receptor, and the antagonism of EP2 receptor in response to ECF treatment. Expression of EP2 receptor was evaluated in gastric cancer tissue samples and cell lines. Cell proliferation and cell apoptosis assays were performed in vitro and in vivo, upon knockdown of EP2 receptor, antagonist of EP2 receptor and/or ECF treatment. Western Blot was applied for evaluation of proteins relating to cell cycle, apoptosis and drug transporter. Next generation sequencing and ingenuity pathway analysis were applied for screening for downstream targets of EP2 receptor. Expressions of the targets of EP2 receptor were further evaluated in gastric cancer cells and tissues. In this study, we found that expression of EP2 receptor was significantly upregulated in gastric cancer. Inhibition of EP2 receptor reduced gastric cancer cell proliferation, induced cell cycle arrest proteins, and enhanced cell apoptosis. Moreover, knockdown of EP2 receptor by siRNA or antagonist sensitized gastric cancer cells to ECF. Silence of EP2 receptor also significantly abrogated gastric cancer growth in a mice model. Analysis revealed that CAV1 was a downstream target of EP2 receptor in gastric cancer. Our findings illustrated that blocking EP2 receptor reduced tumor growth and induced apoptosis in gastric cancer. This novel study unraveled CAV1 was a downstream target of EP2 receptor. Antagonizing EP2 receptor could be a potential therapeutic target in gastric cancer, in particular those with high EP2 receptor expression.

The impact of COVID-19 on lung cancer detection, diagnosis and treatment for Maori in Aotearoa New Zealand.

AIM: The purpose of this article is to examine disparities in the impact of the COVID-19 pandemic on access to lung cancer diagnosis and access to clinical services between Maori and non-Maori. METHODS: Using national-level data, we examined age-standardised lung cancer registrations, diagnostic procedures (bronchoscopy) and lung surgeries separately by ethnic group for the years 2018-2020, as well as patterns of stage of diagnosis. RESULTS: We found a trend toward a reduction in rates of lung cancer registration in Maori (but not non-Maori/non-Pacific) New Zealanders in 2020 compared to 2018 and 2019, but no apparent shift in the distribution of stage at diagnosis. We found a trend toward a reduction in rates of bronchoscopy for both Maori and non-Maori/non-Pacific patients, with the largest reduction observed for Maori. Rates of lung cancer surgery appeared to have reduced for Maori patients, although this was based on a small number of procedures. CONCLUSIONS: We observed disparities between Maori and non-Maori/non-Pacific patients in lung cancer registration and bronchoscopy as a result of the COVID-19 pandemic.