Adherence of PARP inhibitor for frontline maintenance therapy in primary epithelial ovarian cancer: a cross-sectional survey.

OBJECTIVE: To identify the adherence rate to poly (ADP-ribose) polymerase (PARP) inhibitors and identify factors contributing to the deterioration of adherence at our institution. METHODS: The adherence rate to PARP inhibitors was calculated using self-reported Adherence to Refills and Medications Scale questionnaires from a cross-sectional survey. Multivariable logistic regression analysis was performed to identify the factors that affected adherence. RESULTS: Of the 131 respondents, 32 (24.4%) showed non-adherence to PARP inhibitors. In the multivariable logistic regression analysis, unemployed or retired status (odds ratio [OR]=4.878; 95% confidence interval [CI]=1.528-15.572; p=0.008), patients receiving niraparib (OR=3.387; 95% CI=1.283-8.940; p=0.014), and a lower score on the quality-of-life assessment (EORTC-QLQ-OV28), which reflects a better quality of life (QOC) with a lower symptom burden (OR=1.056; 95% CI=1.027-1.086; p<0.001) were associated with high adherence to PARP inhibitors. CONCLUSION: Approximately one-fourth of patients with ovarian cancer are non-adherent to PARP inhibitors as maintenance treatment for newly diagnosed advanced ovarian cancer. The occupational status, type of PARP inhibitor, and QOC may affect adherence to PARP inhibitors.

Fixed and random effect selections in generalized linear mixed models.

Generalized linear mixed models are commonly used to describe relationships between correlated responses and covariates in medical research. In this paper, we propose a simple and easily implementable regularized estimation approach to select both fixed and random effects in generalized linear mixed model. Specifically, we propose to construct and optimize the objective functions using the confidence distributions of model parameters, as opposed to using the observed data likelihood functions, to perform effect selections. Two estimation methods are developed. The first one is to use the joint confidence distribution of model parameters to perform simultaneous fixed and random effect selections. The second method is to use the marginal confidence distributions of model parameters to perform the selections of fixed and random effects separately. With a proper choice of regularization parameters in the adaptive LASSO framework, we show the consistency and oracle properties of the proposed regularized estimators. Simulation studies have been conducted to assess the performance of the proposed estimators and demonstrate computational efficiency. Our method has also been applied to two longitudinal cancer studies to identify demographic and clinical factors associated with patient health outcomes after cancer therapies.

Differences in preoperative gastric ultrasound findings in elderly compared to the mid-aged surgical patients: A retrospective observational study.

This study aimed to compare gastric ultrasound assessments between young and elderly patients, to determine whether the cross-section area (CSA) cutoff values for elderly and young patients should be different, and to suggest CSA cutoff values for elderly patients. This study evaluated the data of 120 patients who underwent elective surgery under general anesthesia between July 2019 and August 2020. Demographic and gastric ultrasound assessment data were retrieved. Patients were divided into the elderly group (n = 58, age: ≥65 years) and young group (n = 62, age: <65 years). The CSAs in the supine and right lateral decubitus positions (RLDP), semiquantitative 3-point Perlas grade (grades 0, 1, and 2), and gastric volume (GV) were determined. CSAs according to different Perlas grades were compared between the 2 groups. To compare normally and non-normally distributed continuous data, Student t test and the Mann-Whitney U test were used, respectively. Categorical data were compared using the chi-square test or Fisher exact test, as appropriate. The receiver operating characteristic (ROC) curves were built for the CSAs to predict pulmonary aspiration. The CSA cutoff values for predicting a high risk of pulmonary aspiration in both the groups were determined. Among patients with Perlas grade 0, the CSAsupine (P = .002) and CSARLDP (P = .002) were greater in the elderly group than in the young group. The specificity, positive predictive value, and accuracy of the CSA decreased when the CSA cutoff value for the young group was applied to the elderly group. The CSA cutoff values for the elderly group were: CSAsupine, 6.92 cm2 and CSARLDP, 10.65 cm2. The CSA of the empty stomach was greater in elderly patients than in young patients. We suggest that the following CSA cutoff values should be used for predicting pulmonary aspiration risk in elderly patients: CSAsupine, 6.92 cm2 and CSARLDP, 10.65 cm2.

Screening Outcomes of Supplemental Automated Breast US in Asian Women with Dense and Nondense Breasts.

Background Automated breast (AB) US effectively depicts mammographically occult breast cancers in Western women. However, few studies have focused on the outcome of supplemental AB US in Asian women who have denser breasts than Western women. Purpose To evaluate the performance of supplemental AB US on mammography-based breast cancer screening in Asian women with dense breasts and those with nondense breasts. Materials and Methods A retrospective database search identified asymptomatic Korean women who underwent digital mammography (DM) and supplemental AB US screening for breast cancer between January 2018 and December 2019. We excluded women without sufficient follow-up, established final diagnosis, or histopathologic results. Performance measures of DM alone and AB US combined with DM (hereafter AB US plus DM) were compared. The primary outcome was cancer detection rate (CDR), and the secondary outcomes were sensitivity and specificity. Subgroup analyses were performed based on mammography density. Results From 2785 screening examinations in 2301 women (mean age, 52 years ± 9 [SD]), 28 cancers were diagnosed (26 screening-detected cancers, two interval cancers). When compared with DM alone, AB US plus DM resulted in a higher CDR of 9.3 per 1000 examinations (95% CI: 7.7, 10.3) versus 6.5 per 1000 examinations (95% CI: 5.2, 7.2; P < .001) and a higher sensitivity of 90.9% (95% CI: 77.3, 100.0) versus 63.6% (95% CI: 40.9, 81.8; P < .001) but a lower specificity of 86.8% (95% CI: 85.2, 88.2) versus 94.6% (95% CI: 93.6, 95.5; P < .001) in women with dense breasts. In women with nondense breasts, AB US plus DM resulted in a higher CDR of 9.5 per 1000 examinations (95% CI: 7.1, 10.6) versus 6.3 per 1000 examinations (95% CI: 3.5, 7.1; P < .001), whereas specificity was lower at 95.2% (95% CI: 93.4, 96.8) versus 97.1% (95% CI: 95.8, 98.4; P < .001). Conclusion In Asian women, the addition of automated breast US to digital mammography showed higher cancer detection rates but lower specificities in both dense and nondense breasts. © RSNA, 2023 Supplemental material is available for this article.

Impact of 6-month triptorelin formulation on predicted adult height and basal gonadotropin levels in patients with central precocious puberty.

Background: Triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist, is available in 1-, 3-, and 6-month formulations to treat central precocious puberty (CPP). The triptorelin pamoate 22.5-mg 6-month formulation recently approved for CPP offers greater convenience to children by reducing the injection frequency. However, worldwide research on using the 6-month formulation to treat CPP is scarce. This study aimed to determine the impact of the 6-month formulation on predicted adult height (PAH), changes in gonadotropin levels, and related variables. Methods: We included 42 patients (33 girls and nine boys) with idiopathic CPP treated with a 6-month triptorelin (6-mo TP) formulation for over 12 months. Auxological parameters, including chronological age, bone age, height (cm and standard deviation score [SDS]), weight (kg and SDS), target height (TH), and Tanner stage, were evaluated at baseline, and after 6, 12, and 18 months of treatment. Hormonal parameters, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol for girls or testosterone for boys, were analyzed concurrently. Results: The mean age at treatment initiation was 8.6 ± 0.83 (8.3 ± 0.62 for girls, 9.6 ± 0.68 for boys). The peak LH level following intravenous GnRH stimulation at diagnosis was 15.47 ± 9.94 IU/L. No progression of the modified Tanner stage was observed during treatment. Compared to baseline, LH, FSH, estradiol, and testosterone were significantly reduced. In particular, the basal LH levels were well suppressed to less than l.0 IU/L, and the LH/FSH ratio was less than 0.66. The bone age/chronological age ratio remained stable with a decreasing trend (1.15 at the start of treatment, 1.13 at 12 months, 1.11 at 18 months). PAH SDS increased during treatment (0.77 ± 0.79 at baseline, 0.87 ± 0.84 at the start of treatment, 1.01 ± 0.93 at six months, and 0.91 ± 0.79 at 12 months). No adverse effects were observed during treatment. Conclusion: The 6-mo TP suppressed the pituitary-gonadal axis stably and improved the PAH during treatment. Considering its convenience and effectiveness, a significant shift to long-acting formulations can be expected.

COVID-19 spike polypeptide vaccine reduces the pathogenesis and viral infection in a mouse model of SARS-CoV-2.

The SARS-CoV-2 coronavirus, which causes a respiratory disease called COVID-19, has been declared a pandemic by the World Health Organization (WHO) and is still ongoing. Vaccination is the most important strategy to end the pandemic. Several vaccines have been approved, as evidenced by the ongoing global pandemic, but the pandemic is far from over and no fully effective vaccine is yet available. One of the most critical steps in vaccine development is the selection of appropriate antigens and their proper introduction into the immune system. Therefore, in this study, we developed and evaluated two proposed vaccines composed of single and multiple SARS-CoV-2 polypeptides derived from the spike protein, namely, vaccine A and vaccine B, respectively. The polypeptides were validated by the sera of COVID-19-vaccinated individuals and/or naturally infected COVID-19 patients to shortlist the starting pool of antigens followed by in vivo vaccination to hACE2 transgenic mice. The spike multiple polypeptide vaccine (vaccine B) was more potent to reduce the pathogenesis of organs, resulting in higher protection against the SARS-CoV-2 infection.

Factors associated with clinical trial participation for patients with renal cell carcinoma.

OBJECTIVE: Recruitment of a diverse and representative study population is critical to the external validity of oncology clinical trials. The primary objective of this study was to characterize the factors associated with clinical trial participation for patients with renal cell carcinoma and the secondary objective was to examine differences in survival outcomes. MATERIALS AND METHODS: We used a matched case-control design by querying the National Cancer Database for patients with renal cell carcinoma who were coded as having enrolled in a clinical trial. Trial patients were matched in a 1:5 ratio to the control cohort based on clinical stage and then sociodemographic variables were compared between the 2 groups. Multivariable conditional logistic regression models evaluated factors associated with clinical trial participation. The trial patient cohort was then matched again in a 1:10 ratio based on age, clinical stage, and comorbidities. Log-rank test was used to compare overall survival (OS) between these groups. RESULTS: From 2004 to 2014, 681 patients enrolled in clinical trials were identified. Clinical trial patients were significantly younger and had a lower Charlson-Deyo comorbidity score. On multivariate analysis, male patients and white patients were more likely to participate compared to their Black counterparts. Having Medicaid or Medicare negatively associated with trial participation. Median OS was greater among clinical trial participants. CONCLUSION: Patient sociodemographic factors remain significantly associated with clinical trial participation and trial participants experienced superior OS to their matched counterparts.

The association between cotinine-measured smoking intensity and sleep quality.

INTRODUCTION: Cigarette smoking is suggested to be associated with sleep problems. This study evaluated the quantitative association between urinary cotinine-verified smoking intensity and sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI). METHODS: This was a cross-sectional study of 189970 participants from the Kangbuk Samsung Health Study recruited between 2016 and 2018. Logistic regression analysis adjusted for covariates was performed to estimate the association between urinary cotinine levels assessed by quartiles and poor sleep quality, defined as global PSQI score >5. RESULTS: The odds ratios (OR) and 95% confidence intervals (CI) for poor sleep quality comparing the highest urinary cotinine quartile to non-smokers were: 1.23 (95% CI: 1.16-1.30) for overall, 1.19 (95% CI: 1.12-1.26) for males, and 1.55 (95% CI: 1.29-1.87) for females. Among self-reported never smokers, cotinineverified smokers had higher odds for decreased sleep quality compared to cotinineverified never smokers with OR of 1.26 (95% CI: 1.08-1.46). CONCLUSIONS: Elevated urinary cotinine levels were associated with poor sleep quality in relatively young and middle-aged South Korean adults. Higher odds for poor sleep quality among cotinine-verified smokers who self-reported as never smokers also demonstrate the value of quantitative measurement of urinary cotinine. Prospective studies are warranted to clarify the cause-effect relationship between smoking and sleep quality.

Antibody-mediated blockade for galectin-3 binding protein in tumor secretome abrogates PDAC metastasis.

The major challenges in pancreatic ductal adenocarcinoma (PDAC) management are local or distant metastasis and limited targeted therapeutics to prevent it. To identify a druggable target in tumor secretome and to explore its therapeutic intervention, we performed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis of tumors obtained from a patient-derived xenograft model of PDAC. Galectin-3 binding protein (Gal-3BP) is identified as a highly secreted protein, and its overexpression is further validated in multiple PDAC tumors and primary cells. Knockdown and exogenous treatment of Gal-3BP showed that it is required for PDAC cell proliferation, migration, and invasion. Mechanistically, we revealed that Gal-3BP enhances galectin-3-mediated epidermal growth factor receptor signaling, leading to increased cMyc and epithelial-mesenchymal transition. To explore the clinical impact of these findings, two antibody clones were developed, and they profoundly abrogated the metastasis of PDAC cells in vivo. Altogether, our data demonstrate that Gal-3BP is an important therapeutic target in PDAC, and we propose its blockade by antibody as a therapeutic option for suppressing PDAC metastasis.

Changes in prostate cancer survival among insured patients in relation to USPSTF screening recommendations.

BACKGROUND: To investigate the effects of the U.S. Preventive Services Task Force's (USPSTF) 2012 recommendation against prostate-specific antigen (PSA)-based screening for prostate cancer on survival disparities based on insurance status. Prior to the USPSTF's 2012 screening recommendation, previous studies found that insured patients with prostate cancer had better outcomes than uninsured patients. METHODS: Using the SEER 18 database, we examined prostate cancer-specific survival (PCSS) based on diagnostic time period and insurance status. Patients were designated as belonging to the pre-USPSTF era if diagnosed in 2010-2012 or post-USPSTF era if diagnosed in 2014-2016. PCSS was measured with the Kaplan-Meier method, while disparities were measured with the Cox proportional hazards model. RESULTS: During the pre-USPSTF era, uninsured patients experienced worse PCSS compared to insured patients (adjusted HR 1.256, 95% CI 1.037-1.520, p = 0.020). This survival disparity was no longer observed during the post-USPSTF era as a result of decreased PCSS among insured patients combined with unchanged PCSS among uninsured patients (adjusted HR 0.946, 95% CI 0.642-1.394, p = 0.780). CONCLUSIONS: Although the underlying reasons are not clear, the USPSTF's 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without affecting the survival of uninsured patients.

Genomic analysis and long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy.

Purpose: Approximately 7% of patients with newly diagnosed prostate cancer (PCa) in the US will have have metastatic disease. The dogma that there is no role for surgery in this population has been questioned recently. Here we report long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy. Materials and methods: This is a multicenter phase 1 trial. The major inclusion criterion was biopsy proven N1M0 or NxM1a/b PCa. Primary end point was the Clavien-Dindo-based major complication rate. Secondary outcomes were biochemical progression and overall survival. RNA-seq correlative study was conducted in nine select cases as a pilot study. Results: Final accrual was 32 patients of which 25 and 7 were cNxM1 and cN1M0, respectively. With the median follow-up of 46 months (interquartile range 31.7 - 52.7 months), 25 out of the 32 patients (75%) were alive at the time of last contact. There were three disparate groups based on the oncologic outcome: favorable, intermediate, and poor. In seven men with favorable response, androgen deprivation therapy was switched to intermittent approach and five remain free of any evidence of disease after more than two years off all systemic therapy with the normalization of serum testosterone. Of these five patients, three had M1 disease. Long-term use of one pad or less per day was 80%. RNA-seq analysis revealed an enriched downregulation of tumor necrosis factor (TNF)-α signature in the favorable group. Conclusion: Overall long-term oncologic outcome of cytoreductive radical prostatectomy was significantly higher than historical results. Importantly, the combination of surgery with systemic therapy may result in a long durable response in a minority of men who present with metastatic PCa.

High Receptor-interacting Serine/Threonine-protein Kinase 3 (RIP3) Expression Serves as an Independent Poor Prognostic Factor for Triple-negative Breast Carcinoma.

BACKGROUND/AIM: Receptor-interacting serine/threonine-protein kinase 3 (RIP3) is a key component related to tumor necrosis factor-dependent necroptosis. RIP3 has been known to be a predictive biomarker in many types of carcinomas. We aimed to investigate whether RIP3 expression is correlated with clinicopathological characteristics and the outcomes of patients with breast carcinoma. PATIENTS AND METHODS: We performed immunostaining for RIP3 and analyzed the association of RIP3 expression status with the clinicopathological characteristics and survival of 203 patients with invasive ductal carcinoma of the breast. RESULTS: High RIP3 expression was significantly correlated with lymph node metastasis and human epidermal growth factor receptor 2 positivity. In patients with triple-negative breast carcinoma (TNBC), high RIP3 expression was an independent prognostic factor for disease-free survival (DFS). RIP3-high TNBC showed the lowest DFS rate. CONCLUSION: High RIP3 expression is associated with aggressive clinical behavior of breast carcinoma. Our data suggest that RIP3 serves as an independent prognostic factor in TNBC.

A Paradoxical Effect of Interleukin-32 Isoforms on Cancer.

IL-32 plays a contradictory role such as tumor proliferation or suppressor in cancer development depending on the cancer type. In most cancers, it was found that the high expression of IL-32 was associated with more proliferative and progression of cancer. However, studying the isoforms of IL-32 cytokine has placed its paradoxical role into a wide range of functions based on its dominant isoform and surrounding environment. IL-32ß, for example, was found mostly in different types of cancer and associated with cancer expansion. This observation is legitimate since cancer exhibits some hypoxic environment and IL-32ß was known to be induced under hypoxic conditions. However, IL-32θ interacts directly with protein kinase C-δ reducing NF-κB and STAT3 levels to inhibit epithelial-mesenchymal transition (EMT). This effect could explain the different functions of IL-32 isoforms in cancer. However, pro- or antitumor activity which is dependant on obesity, gender, and age as it relates to IL-32 has yet to be studied. Obesity-related IL-32 regulation indicated the role of IL-32 in cancer metabolism and inflammation. IL-32-specific direction in cancer therapy is difficult to conclude. In this review, we address that the paradoxical effect of IL-32 on cancer is attributed to the dominant isoform, cancer type, tumor microenvironment, and genetic background. IL-32 seems to have a contradictory role in cancer. However, investigating multiple IL-32 isoforms could explain this doubt and bring us closer to using them in therapy.

Comparison of the Seven Interleukin-32 Isoforms' Biological Activities: IL-32θ Possesses the Most Dominant Biological Activity.

Cytokines are significantly associated with the homeostasis of immune responses in health and disease. Interleukin-32 (IL-32) is a cytokine originally discovered in natural killer cell transcript 4. IL-32 with different disorders has been described in terms of pathogenesis and the progression of diseases. Clinical studies have investigated IL-32 under various conditions, such as viral infection, autoimmune diseases, inflammatory diseases, certain types of cancer, vascular disease, and pulmonary diseases. The high expression of IL-32 was identified in different tissues with various diseases and found to have multiple transcripts of up to seven isoforms. However, the purification and biological activities of these isoforms have not been investigated yet. Therefore, in this study, we purified and compared the biological activity of recombinant IL-32 (rIL-32) isoforms. This is the first time for seven rIL-32 isoforms (α, ß, δ, γ, ϵ, ζ, and θ) to be cloned and purified using an Escherichia coli expression system. Next, we evaluate the biological activities of these seven rIL-32 isoforms, which were used to treat different types of cells by assessing the levels of inflammatory cytokine production. The results revealed that rIL-32θ possessed the most dominant biological activity in both immune and non-immune cells.

Factors Associated With Palliative Intervention Utilization for Metastatic Renal Cell Carcinoma.

INTRODUCTION: Several guidelines have adopted early integration of palliative intervention (PI) into oncologic care to improve quality of life among patients with advanced malignancies. However, PI utilization patterns and factors associated with its use in metastatic renal cell carcinoma are poorly understood. PATIENTS AND METHODS: Using the National Cancer Database (NCDB), we abstracted patients diagnosed with Stage IV RCC from 2004 to 2014 and evaluated the utilization of PI within this cohort. Socioeconomic and clinical factors were compared for patients receiving and not receiving PI for metastatic RCC. Multivariable logistic regression (MLR) models identified factors that were associated with receipt of PI within overall cohort and treatment-based cohorts. RESULTS: We identified 42,014 patients with Stage IV RCC, of which 7,912 patients received PI. From 2004 to 2014, the use of PI minimally increased from 17% to 20% for Stage IV RCC. MLR analysis demonstrated that increased comorbidities, insurance status, higher education status, facility location, care at a comprehensive cancer program or integrated network, sarcomatoid histology, and treatment type significantly increased the likelihood of PI use. Various socioeconomic, clinical, and geographical factors that are associated with use of PI-based on the treatment received for Stage IV RCC. CONCLUSIONS: While PI utilization has minimally increased for Stage IV RCC, there are several geographic, socioeconomic, and clinical factors that predict its use among patients with Stage IV RCC in a treatment-specific manner. Taken together, this suggests the need for earlier initiation of PI in a more equitable and systematic fashion among patients with metastatic RCC.

Association of Lymph Node Count and Survival after Primary Retroperitoneal Lymphadenectomy for Nonseminomatous Testicular Cancer.

PURPOSE: Retroperitoneal lymph node dissection (RPLND) for men with clinical stage (CS) I or II testicular nonseminomatous germ cell tumor (NSGCT) has both staging and therapeutic implications. We aimed to investigate the impact of lymph node count (LNC) on outcome after primary RPLND for men with CS I or II NSGCT using a nationally representative data set. MATERIALS AND METHODS: A retrospective analysis of men who received a primary RPLND for CS I or II NSGCT was performed using the National Cancer Database. The Kaplan-Meier method was used to determine overall survival (OS) according to LNC. Logistic regression analyses were used to identify factors associated with LNC >20 and factors predictive of lymph node-positive (pN+) disease after primary RPLND. RESULTS: Of 1,376 men who comprised our analytical cohort, 50.1% and 49.9% had 1-20 lymph nodes (LNs) and >20 LNs removed, respectively. Five-year OS rates were 96.4% and 99.1% for men with 1-20 and >20 LNs resected, respectively (p=0.004). A higher proportion of men with >20 LNs removed were treated at academic centers, had private insurance, presented with higher AJCC (American Joint Committee on Cancer) CS and were more likely to have pN+ disease, compared to those with 1-20 LNs removed. Factors significantly associated with pN+ disease after RPLND include higher AJCC CS and LNC (per 10-count increase). CONCLUSIONS: Higher LNC after primary RPLND significantly increases the likelihood of identifying pN+ disease and is associated with improved OS. Our data support the therapeutic implications of a thoroughly performed RPLND in the primary setting.

Aberrant Transcript Usage Is Associated with Homologous Recombination Deficiency and Predicts Therapeutic Response.

BRCA1/2 mutations account for only a small fraction of homologous recombination (HR) deficiency (HRD) cases. Recently developed genomic HRD (gHRD) tests suffer confounding factors that cause low precision in predicting samples that will respond to PARP inhibitors and DNA damaging agents. Here we present molecular and clinical evidence of transcriptional HRD (tHRD) that is based on aberrant transcript usage (aTU) of minor isoforms. Specifically, increased TU of nonfunctional isoforms of DNA repair genes was prevalent in breast and ovarian cancer with gHRD. Functional assays validated the association of aTU with impaired HR activity. Machine learning-based tHRD detection by the transcript usage (TU) pattern of key genes was superior to directly screening for gHRD or BRCA1/2 mutations in accurately predicting responses of cell lines and patients with cancer to PARP inhibitors and genotoxic drugs. This approach demonstrated the capability of tHRD status to reflect functional HR status, including in a cohort of olaparib-treated ovarian cancer with acquired platinum resistance. Diagnostic tests based on tHRD are expected to broaden the clinical utility of PARP inhibitors. SIGNIFICANCE: A novel but widespread transcriptional mechanism by which homologous recombination deficiency arises independently of BRCA1/2 mutations can be utilized as a companion diagnostic for PARP inhibitors.

Marginal improvement in survival among patients diagnosed with metastatic prostate cancer in the second-line antiandrogen therapy era.

Since 2004, multiple blockbuster drugs have been approved for men with metastatic prostate cancer. Nevertheless, it has been reported that no improvement in survival was observed between 2004 and 2009. Herein, we have analyzed the SEER database to assess the survival outcome of metastatic prostate cancer patients since 2000. The results demonstrated that there was an improvement in both overall and prostate cancer-specific survival for 4 months among men diagnosed with metastatic prostate cancer from 2010 to 2016 when compared to those in the pre-2010 period. Interestingly, this survival benefit was limited to patients with bone and visceral metastasis (M1b and M1c stages). Collectively, our observation suggests that despite the new treatment agents such as second-line antiandrogen therapies introduced in the modern era, the improvement in survival of metastatic prostate cancer patients has been surprisingly small.

Metagenomic analysis of gut microbiome reveals a dynamic change in Alistipes onderdonkii in the preclinical model of pancreatic cancer, suppressing its proliferation.

Pancreatic cancer is a lethal cancer with aggressive and invasive characteristics. By the time it is diagnosed, patients already have tumors extended to other organs and show extremely low survival rates. The gut microbiome is known to be associated with many diseases and its imbalance affects the pathogenesis of pancreatic cancer. In this study, we established an orthotopic, patient-derived xenograft model to identify how the gut microbiome is linked to pancreatic ductal adenocarcinoma (PDAC). Using the 16S rDNA metagenomic sequencing, we revealed that the levels of Alistipes onderdonkii and Roseburia hominis decreased in the gut microbiome of the PDAC model. To explore the crosstalk between the two bacteria and PDAC cells, we collected the supernatant of the bacteria or cancer cell culture medium and treated it in a cross manner. While the cancer cell medium did not affect bacterial growth, we observed that the A. onderdonkii medium suppressed the growth of the pancreatic primary cancer cells. Using the bromodeoxyuridine/7-amino-actinomycin D (BrdU/7-AAD) staining assay, we confirmed that the A. onderdonkii medium inhibited the proliferation of the pancreatic primary cancer cells. Furthermore, RNA-seq analysis revealed that the A. onderdonkii medium induced unique transcriptomic alterations in the PDAC cells, compared to the normal pancreatic cells. Altogether, our data suggest that the reduction in the A. onderdonkii in the gut microbiome provides a proliferation advantage to the pancreatic cancer cells. KEY POINTS: • Metagenome analysis of pancreatic cancer model reveals A. onderdonkii downregulation. • A. onderdonkii culture supernatant suppressed the proliferation of pancreatic cancer cells. • RNA seq data reveals typical gene expression changes induced by A. onderdonkii.