Publications by authors named "Jianjun Gao"

190 Publications

9p21 loss confers a cold tumor immune microenvironment and primary resistance to immune checkpoint therapy.

Nat Commun 2021 Sep 23;12(1):5606. Epub 2021 Sep 23.

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Immune checkpoint therapy (ICT) provides substantial clinical benefits to cancer patients, but a large proportion of cancers do not respond to ICT. To date, the genomic underpinnings of primary resistance to ICT remain elusive. Here, we performed immunogenomic analysis of data from TCGA and clinical trials of anti-PD-1/PD-L1 therapy, with a particular focus on homozygous deletion of 9p21.3 (9p21 loss), one of the most frequent genomic defects occurring in ~13% of all cancers. We demonstrate that 9p21 loss confers "cold" tumor-immune phenotypes, characterized by reduced abundance of tumor-infiltrating leukocytes (TILs), particularly, T/B/NK cells, altered spatial TILs patterns, diminished immune cell trafficking/activation, decreased rate of PD-L1 positivity, along with activation of immunosuppressive signaling. Notably, patients with 9p21 loss exhibited significantly lower response rates to ICT and worse outcomes, which were corroborated in eight ICT trials of >1,000 patients. Further, 9p21 loss synergizes with PD-L1/TMB for patient stratification. A "response score" was derived by incorporating 9p21 loss, PD-L1 expression and TMB levels in pre-treatment tumors, which outperforms PD-L1, TMB, and their combination in identifying patients with high likelihood of achieving sustained response from otherwise non-responders. Moreover, we describe potential druggable targets in 9p21-loss tumors, which could be exploited to design rational therapeutic interventions.
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http://dx.doi.org/10.1038/s41467-021-25894-9DOI Listing
September 2021

Evaluation of Technology-Enabled Monitoring of Patient-Reported Outcomes to Detect and Treat Toxic Effects Linked to Immune Checkpoint Inhibitors.

JAMA Netw Open 2021 Aug 2;4(8):e2122998. Epub 2021 Aug 2.

Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston.

Importance: Immune checkpoint inhibitors can produce distinct toxic effects that require prompt recognition and timely management.

Objective: To develop a technology-enabled, dynamically adaptive protocol that can provide the accurate information needed to inform specific remedies for immune toxic effects in patients treated with immune checkpoint inhibitors.

Design, Setting, And Participants: An open-label cohort study was conducted at a single tertiary referral center from September 6, 2019, to September 3, 2020. The median follow-up duration was 63 (interquartile range, 35.5-122) days. Fifty patients with genitourinary cancers treated with immune checkpoint inhibitors were enrolled.

Interventions: A fit-for-purpose electronic platform was developed to enable active patient and care team participation. A smartphone application downloaded onto patients' personal mobile devices prompted them to report their symptoms at least 3 times per week. The set of symptoms and associated queries were paired with alert thresholds for symptoms requiring clinical action.

Main Outcomes And Measures: The primary end point of this interim analysis was feasibility, as measured by patient and care team adherence, and lack of increase in care team staffing. Operating characteristics were estimated for each symptom alert and used to dynamically adapt the alert thresholds to ensure sensitivity while reducing unnecessary alerts.

Results: Of the 50 patients enrolled, 47 had at least 1 follow-up visit and were included in the analysis. Median age was 65 years (range, 37-86), 39 patients (83%) were men, and 39 patients (83%) had metastatic cancer, with the most common being urothelial cell carcinoma and renal cell carcinoma (22 [47%] patients each). After initial onboarding, no further care team training or additional care team staffing was required. Patients had a median study adherence rate of 74% (interquartile range, 60%-86%) and 73% of automated alerts were reviewed within 3 days by the clinic team. Symptoms with the highest positive predictive value for adverse events requiring acute intervention included dizziness (21%), nausea/vomiting (26%), and shortness of breath (14%). The symptoms most likely to result in unnecessary alerts were arthralgia and myalgia, fatigue, and cough.

Conclusions And Relevance: The findings of this cohort study suggest an acceptable and fiscally sound method can be developed to create a dynamic learning system to detect and manage immune-related toxic effects.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.22998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406081PMC
August 2021

BK Channel Deficiency in Osteoblasts Reduces Bone Formation via the Wnt/β-Catenin Pathway.

Mol Cells 2021 Aug;44(8):557-568

Department of Pharmacology, School of Pharmacy & Minhang Hospital, Fudan University, Shanghai 201203, China.

Global knockout of the BK channel has been proven to affect bone formation; however, whether it directly affects osteoblast differentiation and the mechanism are elusive. In the current study, we further investigated the role of BK channels in bone development and explored whether BK channels impacted the differentiation and proliferation of osteoblasts via the canonical Wnt signaling pathway. Our findings demonstrated that knockout of Kcnma1 disrupted the osteogenesis of osteoblasts and inhibited the stabilization of β-catenin. Western blot analysis showed that the protein levels of Axin1 and USP7 increased when Kcnma1 was deficient. Together, this study confirmed that BK ablation decreased bone mass via the Wnt/β-catenin signaling pathway. Our findings also showed that USP7 might have the ability to stabilize the activity of Axin1, which would increase the degradation of β-catenin in osteoblasts.
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http://dx.doi.org/10.14348/molcells.2021.0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424144PMC
August 2021

Reply by Authors.

J Urol 2021 Aug 10:101097JU000000000000194302. Epub 2021 Aug 10.

Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1097/JU.0000000000001943.02DOI Listing
August 2021

Validation of Prognostic Scores in Patients With Metastatic Urothelial Cancer Enrolling in Phase I Targeted Therapy or Next Generation Immunotherapy Trials.

Clin Genitourin Cancer 2021 Jul 12. Epub 2021 Jul 12.

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Introduction: Enrolling patients with metastatic urothelial carcinoma (mUC) in phase I trials provides an opportunity to identify biological drug activity. Developing prognostic scores may aid in patient selection for phase 1 trials.

Patients And Methods: We analyzed records of patients with mUC who participated in targeted therapy and immunotherapy phase I clinical trials at MD Anderson Cancer Center (MDACC). The Bellmunt and Bajorin scores were calculated as bladder cancer-specific prognostic scores. The Royal Marsden Hospital (RMH) and MDACC scores were calculated as phase I prognostic scores. Hazard ratios (HR) were calculated using the Cox proportional hazard model. The prognostic value of the Bellmunt, Bajorin, RMH, and MDACC scores were assessed using the Likelihood ratio (LR) χ2 test and the c-index.

Results: Between 2015 and 2019, 43 patients were enrolled in phase I trials and 12 were enrolled in >I trial leading to a total of 57 trial participants (TPs). Ninty-seven percent of TPs received prior platinum therapy and 60% received a prior checkpoint inhibitor. Median overall survival (OS) and progression-free survival (PFS) were significantly shorter with increasing Bajorin, RMH, or MDACC scores, but not with increasing Bellmunt score. The RMH (c-index=0.658, LR χ2=11.8, P=.008) and MDACC scores (c-index =0.66, LR χ2=12.76, P=.01) outperformed the Bajorin score (c-index=0.522, LR χ2=1.22, P=.5) and the Bellmunt score (c-index=0.537, LR χ2=0.36, P=.9) in predicting overall survivalover. The Bajorin, RMH, and MDACC scores, but not the Bellmunt score, were also predictive of progression-free survival (PFS)prog. The RMH and MDACC scores again outperformed the Bajorin scoreand the Bellmunt score for predicting PFS.

Conclusion: The RMH and MDACC phase I prognostic scores accurately predicted survival in patients with mUC and outperformed the bladder cancer-specific scores at time of enrollment on phase 1 clinical trials. The RMH and MDACC scores could optimize selection of patients with mUC for phase I clinical trials.
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http://dx.doi.org/10.1016/j.clgc.2021.07.004DOI Listing
July 2021

Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events.

J Immunother Cancer 2021 Jul;9(7)

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Immune checkpoint therapy (ICT) prolongs survival in subsets of patients with cancer but can also trigger immune-related adverse events (irAEs) requiring treatment discontinuation. Recent studies have investigated safety of ICT rechallenge after irAEs, and evidence suggests that rechallenge may be associated with improved antitumor responses. However, data are limited on response duration after ICT rechallenge, particularly after severe irAEs.

Objective: To evaluate safety and efficacy of ICT rechallenge after moderate-to-severe irAEs in patients with renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer.

Methods: In this retrospective cohort study, medical records from September 25, 2013, to June 1, 2020, for patients with genitourinary (GU) cancers at MD Anderson Cancer Center who were rechallenged with the same or different ICT following irAEs were reviewed. Demographics, ICT exposure, irAEs (grade and treatment), ICT discontinuation or rechallenge, rates of subsequent irAEs (new or recurrent) and antitumor activity (objective response rates and response duration) were reviewed.

Results: Sixty-one patients with RCC, UC, and prostate cancer were rechallenged with ICT after experiencing 105 total irAEs. Objective response rates after rechallenge, that is, upgrade in response, were 14% in RCC (4/28), 21% in UC (3/14), and 0% in prostate cancer. All seven patients who achieved upgrade in response had initial grade 2 or 3 irAEs. Responses were durable among these seven patients, with median radiographic progression-free survival not reached (range: 3.7-66.4 months) as of the March 8, 2021, data cut-off (median follow-up 40.9 months (95% CI 35.3 to 46.5)). All achieved complete response except one patient who was lost to follow-up. The rate of subsequent grade 3 or 4 irAEs after rechallenge was 30%, with no fatal irAEs. The rate of recrudescence of the same irAE was 26% (16/61). 54% of patients received corticosteroids (33/61), and 21% received targeted immunosuppression (13/61) for the initial irAEs.

Conclusions And Relevance: ICT rechallenge after moderate-to-severe irAEs was associated with deep and durable responses in a subset of patients with RCC and UC, with acceptable safety and no fatal events. Strategies to enable ICT resumption after moderate-to-severe irAEs, such targeted immunosuppression, warrant further study.
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http://dx.doi.org/10.1136/jitc-2021-002850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323401PMC
July 2021

Phase 1b study of pegylated arginine deiminase (ADI-PEG 20) plus Pembrolizumab in advanced solid cancers.

Oncoimmunology 2021 12;10(1):1943253. Epub 2021 Jul 12.

Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: Pegylated arginine deiminase (ADI-PEG 20) is a metabolism-based strategy that depletes arginine, resulting in tumoral stress and cytotoxicity. Preclinically, ADI-PEG 20 modulates T-cell activity and enhances the therapeutic efficacy of programmed death-1 (PD-1) inhibition.

Methods: A phase 1b study, including a dose-escalation cohort and an expansion cohort, was undertaken to explore the effects of ADI-PEG 20 in combination with pembrolizumab, an anti-PD-1 antibody, for safety, pharmacodynamics, and response. CD3 levels and programmed death-ligand 1 (PD-L1) expression were assessed in paired biopsies collected prior to and after ADI-PEG 20 treatment but before pembrolizumab.

Results: Twenty-five patients, nine in the dose-escalation cohort and sixteen in the expansion cohort, were recruited. Treatment was feasible with adverse events consistent with those known for each agent, except for Grade 3/4 neutropenia which was higher than expected, occurring in 10/25 (40%) patients. Mean arginine levels were suppressed for 1-3 weeks, but increased gradually. CD3 T cells increased in 10/12 (83.3%) subjects following ADI-PEG 20 treatment, including in three partial responders ( = .02). PD-L1 expression was low and increased in 3/10 (30%) of subjects. Partial responses occurred in 6/25 (24%) heavily pretreated patients, in both argininosuccinate synthetase 1 proficient and deficient subjects.

Conclusions: The immunometabolic combination was safe with the caveat that the incidence of neutropenia might be increased compared with either agent alone. ADI-PEG 20 treatment increased T cell infiltration in the low PD-L1 tumor microenvironment. The recommended phase 2 doses are 36 mg/m weekly for ADI-PEG 20 and 200 mg every 3 weeks for pembrolizumab.
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http://dx.doi.org/10.1080/2162402X.2021.1943253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276661PMC
August 2021

Progression of Disease after Bacillus Calmette-Guérin Therapy: Refining Patient Selection for Neoadjuvant Chemotherapy before Radical Cystectomy.

J Urol 2021 Jun 29:101097JU0000000000001943. Epub 2021 Jun 29.

Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: Data from the pre-neoadjuvant chemotherapy (NAC) era suggests patients who progress on bacillus Calmette-Guérin (BCG) to muscle-invasive bladder cancer (P-MIBC) exhibit worse outcomes compared to MIBC (D-MIBC). Herein, we investigate whether P-MIBC is an independent poor risk factor in the setting of contemporary NAC use.

Materials And Methods: A review of patients who underwent radical cystectomy (RC) for cT2-3 MIBC from 2005 to 2018 was performed. Patients were stratified into high risk (lymphovascular invasion, variant histology, hydronephrosis, cT3b) vs low risk (no risk factors) and P-MIBC (≤pT1 treated with at least induction BCG who progressed to ≥cT2) vs D-MIBC.

Results: Among 801 patients who underwent RC 20.3% had P-MIBC and 79.7% had D-MIBC. In low-risk patients treated without NAC, P-MIBC was associated with pathological upstaging (64.9% vs 42.7%, p=0.004) and worse overall (OS, p=0.006) and cancer-specific survival (CSS, p=0.001) compared to D-MIBC. P-MIBC status conferred uniformly poor survival outcomes to patients who did not receive NAC compared to D-MIBC without NAC (median OS 51.5 months [95% CI 40.0-81.0] vs 85.1 months [95% CI 62.8-96.0], p=0.040; median CSS not reached, p=0.014). However, P-MIBC status did not remain a negative prognostic factor in the setting of NAC (median OS 90.5 months [95% CI 34.0-not estimable] vs 87.8 months [95% CI 68.7-not estimable], p=0.606; median CSS not reached, p=0.448).

Conclusions: P-MIBC confers a poor prognosis when managed with RC alone. Treatment with NAC results in equivalent pathological response and survival outcomes compared to D-MIBC. P-MIBC should be included in risk-stratified approaches to NAC selection.
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http://dx.doi.org/10.1097/JU.0000000000001943DOI Listing
June 2021

The evolving treatment landscape of advanced urothelial carcinoma.

Curr Opin Oncol 2021 05;33(3):221-230

Division of Cancer Medicine, MD Anderson Cancer Center, Houston, Texas.

Purpose Of Review: Bladder cancer is the 10th most common cancer in the world and the 6th most common cancer among men. In the past few years, several new agents have been approved for the treatment of urothelial tumors. In this paper, we review the evolving treatment landscape of advanced urothelial carcinoma (UC).

Recent Findings: Since 2016, the Food and Drug Administration (FDA) has approved five immunotherapies targeting programmed cell death 1/programmed cell death 1 legend, an antinectin-4 antibody drug conjugate (ADC), and a fibroblast growth factor receptor (FGFR) inhibitor for the treatment of patients with advanced UC. Moreover, there are multiple targeted agents, immune checkpoint inhibitors (ICI), ADCs, and their combinations currently being tested in clinical studies with the goal of obtaining FDA approval.

Summary: Precision oncology efforts continue to advance our understanding of the UC biology and transform the existing treatment paradigms. An enlarging arsenal of treatment options promises further personalization of UC therapy.
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http://dx.doi.org/10.1097/CCO.0000000000000722DOI Listing
May 2021

The Next Decade of Immune Checkpoint Therapy.

Cancer Discov 2021 Apr;11(4):838-857

Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Immune checkpoint therapy (ICT) can provide durable clinical responses and improve overall survival. However, only subsets of patients with specific tumor types respond to ICT. Thus, significant challenges remain, including understanding pathways of resistance, optimizing patient selection, improving management of immune-related adverse events, and identifying rational therapeutic combinations. These challenges will need a focused approach encompassing both clinical and basic research, with the integration of reverse translational studies. This integrated approach will lead to identification of potential targets for subsequent clinical trials, which will guide decisions as we develop novel combination strategies to maximize efficacy and minimize toxicities for patients. SIGNIFICANCE: ICTs induce durable antitumor responses for subsets of patients with cancer. Recent evidence suggests that rational combinatorial strategies can improve response by overcoming primary and adaptive resistance mechanisms, although these may carry an increased risk of immune-mediated toxicities. This review surveys the current understanding of mechanisms of response and resistance to ICTs and active areas of investigation, and proposes a path forward to improving efficacy and minimizing toxicities through better patient selection and rational combinations.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1680DOI Listing
April 2021

A systematic review for the efficacy of coenzyme Q10 in patients with chronic kidney disease.

Int Urol Nephrol 2021 Mar 29. Epub 2021 Mar 29.

Out-Patient Department, Chinese PLA Strategic Support Force Characteristic Medical Center (The 306th Hospital of Chinese PLA), 9 AnXiangBeiLi Road, Beijing, 100101, China.

Background: The effects of coenzyme Q10 (CoQ10) supplementation in chronic kidney disease (CKD) patients remain controversial.

Objective: A systematic review of current evidence was performed to systematically and comprehensively summarize the effects of CoQ10 on cardiovascular outcomes, oxidative stress, inflammation, lipid profiles, and glucose metabolism.

Methods: MEDLINE, EMBASE, and the Cochrane Library database (Cochrane Central Register of Controlled Trials) were searched to identify eligible studies investigating the effects of CoQ10 supplementation on patients with CKD.

Results: Twelve independent studies (including seventeen publications) were included in this systematic review. For CKD patients, six studies reported variable cardiovascular outcomes, which yielded inconsistent results. Regarding oxidative stress and inflammation, pooled analysis showed that CoQ10 supplementation significantly reduced malonaldehyde (WMD: - 1.15 95% CI - 1.48 to - 0.81) and high-sensitivity C reactive protein levels (WMD: - 1.18 95% CI - 2.21 to - 0.15). Regarding glucose metabolism, we found that CoQ10 supplementation resulted in significant improvements in HbA1c (WMD: - 0.80; 95% CI: - 1.35 to - 0.24) and QUICKI (WMD: 0.02; 95% CI: 0.01 to 0.03). The pooled results indicated that CoQ10 supplementation had no effects on total cholesterol, or LDL-cholesterol, or on HDL-cholesterol, and triglycerides.

Conclusions: Our systematic review demonstrated that CoQ10 supplementation might have promising effects on oxidative stress. This work provided some clues that CoQ10 supplementation might have the potential to improve inflammation levels, glucose metabolism, cardiac structure, and cardiac biomarkers. However, the effects of CoQ10 supplementation should be confirmed in larger high-quality studies.
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http://dx.doi.org/10.1007/s11255-021-02838-2DOI Listing
March 2021

Case Report: Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Case Series on the Clinical and Histopathologic Spectrum of Adverse Cutaneous Reactions From Fatal Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis to Dermal Hypersensitivity Reaction.

Front Oncol 2021 4;11:621591. Epub 2021 Mar 4.

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Enfortumab vedotin is a Nectin-4 directed antibody-drug conjugate approved in metastatic urothelial carcinoma following progression on a platinum-containing chemotherapy and immune checkpoint blockade. On-target dermatologic toxicity may occur from Nectin-4 expression in the skin. We highlight a case of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis following enfortumab infusions that was ultimately fatal. The second case describes an erythema multiforme-like rash with interface dermatitis related to enfortumab. Dermatologic findings, immunohistochemistry studies, and immune profiling are detailed. These cases demonstrate the potentially catastrophic outcomes in some patients treated with enfortumab. Patients must be monitored for cutaneous toxicities with early involvement of dermatology and dermatopathology.
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http://dx.doi.org/10.3389/fonc.2021.621591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970171PMC
March 2021

Outcomes of patients with intermediate-risk or poor-risk metastatic renal cell carcinoma who received their first cycle of nivolumab and ipilimumab in the hospital because of symptomatic disease: The MD Anderson Cancer Center experience.

Int J Cancer 2021 07 24;149(2):387-393. Epub 2021 Mar 24.

Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Nivolumab plus ipilimumab (nivo/ipi) is an approved therapy for patients with intermediate-risk or poor-risk metastatic renal cell carcinoma (mRCC). Clinical factors that guide the selection of this regimen for patients with mRCC are urgently needed. We retrospectively analyzed medical records of patients with mRCC who were hospitalized at MD Anderson Cancer Center because of cancer-related symptoms and received their first cycle of nivo/ipi in the inpatient setting. Clinical parameters, including demographics, histology, clinical history, response, and survival, were collected. The 4-month survival probability, progression-free survival (PFS), and overall survival (OS) were calculated using Kaplan-Meier methods. Between November 2017 and 21 June 2020 patients were identified that fit the search: 19 patients (91%) had poor-risk disease based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score; 17 patients (81%) had ≥4 risk factors; and 9 patients (43%) had sarcomatoid features on histology. Shortness of breath (28%) and abdominal pain (19%) were the two most common reasons for hospitalization. Partial response was achieved in 14% (3/21) of patients. Median PFS for all patients was 1.7 months (95% CI 0-3.9); median OS for all patients was 1.7 months (95% CI 0-4.2); and the 4-month survival probability was 36% (95% CI 25%-47%). In this retrospective study, patients with intermediate-risk or poor-risk mRCC who are hospitalized at a large tertiary referral center for cancer-related symptoms derive limited clinical benefit from nivo/ipi when started in the inpatient setting. Alternative, more effective systemic therapies should be considered for these patients.
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http://dx.doi.org/10.1002/ijc.33560DOI Listing
July 2021

Novel anticancer drugs approved in 2020.

Drug Discov Ther 2021 ;15(1):44-47

Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao, Shandong, China.

Cancer is still a major factor threatening human life around the world, and anticancer drugs remain a huge unmet clinical need. Here, we reviewed novel drugs including new molecular entities and new therapeutic biologics approved in the US, EU, Japan, and China that represent the main advances in anticancer drug research and development in 2020. Small molecule inhibitors targeting oncogenes, antibodies, and antibody drug conjugates (ADCs) are the main anticancer drugs that were approved in 2020. More novel anticancer drugs that possess target activity and that overcome drug resistance are anticipated in the future.
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http://dx.doi.org/10.5582/ddt.2021.01013DOI Listing
September 2021

Combination antiangiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes.

Cancer Med 2021 04 1;10(7):2341-2349. Epub 2021 Mar 1.

Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Introduction: Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA-approved as front-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off-protocol and post-front-line experience with combination TKI-IO approaches.

Methods: We conducted a retrospective analysis of mRCC patients who received combination TKI-IO post-first-line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1.

Results: We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI-IO combinations included nivolumab-cabozantinib (N +C; 24 patients), nivolumab-pazopanib (N+P; 13), nivolumab-axitinib (6), nivolumab-lenvatinib (2), and nivolumab-ipilimumab-cabozantinib (3). The median progression-free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event.

Conclusion: To our knowledge, this is the first case series reporting off-label use of combination TKI-IO for mRCC. TKI-IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO.
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http://dx.doi.org/10.1002/cam4.3812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982609PMC
April 2021

CBP/P300 Inhibitors Mitigate Radiation-Induced GI Syndrome by Promoting Intestinal Stem Cell-Mediated Crypt Regeneration.

Int J Radiat Oncol Biol Phys 2021 07 3;110(4):1210-1221. Epub 2021 Feb 3.

Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, China; Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China. Electronic address:

Purpose: Radiation-induced gastrointestinal syndrome (RIGS) is currently the main cause of death for people exposed to a high dose of irradiation during nuclear incidents, and there is currently no approved effective therapy. Here, we found that CBP/P300 inhibitors, with high efficacy and low toxicity, might be promising radiation mitigators that can cure RIGS.

Methods And Materials: Ex vivo 3D organoid cultures derived from mouse jejunum and human ileum and colon were used to examine the radio-mitigative effects of CBP/P300 inhibitors. The radio-mitigative effect was evaluated by quantifying the survival rate and size of organoids after radiation. SGC-CBP30 (50 mg/kg body weight), an inhibitor of CBP/P300, was intraperitoneally injected into C57B/6J mice 24 hours after subtotal-body irradiation or whole-body irradiation. The regenerated crypts and animal survival were determined by microcolony assay and the Kaplan-Meier method, respectively. Lgr5-lacZ mice were used to evaluate the survival of intestinal stem cells after treatments.

Results: We found that CBP/P300 inhibitors were effective mitigators that could be used to treat RIGS. CBP/P300 inhibition promoted the regeneration of intestinal organoids in vitro and of crypts in vivo. Remarkably, the administration of CBP/P300 inhibitors to mice 24 hours after lethal irradiation promoted Lgr5 intestinal stem cell and crypt recovery, resulting in improved mouse survival. Moreover, our data show that CBP/P300 inhibitors rescued irradiated mice from RIGS by delaying intestinal epithelial cell cycle progression after radiation.

Conclusions: These data demonstrate that CBP/P300 inhibitors are effective medical countermeasures to mitigate gastrointestinal toxicity from radiation.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.046DOI Listing
July 2021

Bach2 Deficiency Promotes Intestinal Epithelial Regeneration by Accelerating DNA Repair in Intestinal Stem Cells.

Stem Cell Reports 2021 01 30;16(1):120-133. Epub 2020 Dec 30.

Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai 200032, China; Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China. Electronic address:

Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury, although the repair mechanisms are unclear. Here, we found that Bach2 deficiency promotes intestinal epithelial cell proliferation during homeostasis. Moreover, genetic inactivation of Bach2 in mouse intestinal epithelium facilitated crypt regeneration after irradiation, resulting in a reduction in mortality. RNA-sequencing analysis of isolated crypts revealed that Bach2 deficiency altered the expression of numerous genes, including those regulating double-strand break repair. Mechanistic characterizations indicated that Bach2 deletion facilitated DNA repair in intestinal crypt cells, as evidenced by faster resolution of γ-H2AX and 53BP1 foci in Bach2 crypt cells, compared with Bach2 control. Together, our studies highlight that Bach2 deficiency promotes intestinal regeneration by accelerating DNA repair in intestinal stem cells after radiation damage.
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http://dx.doi.org/10.1016/j.stemcr.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897581PMC
January 2021

SIRT1 inhibitors mitigate radiation-induced GI syndrome by enhancing intestinal-stem-cell survival.

Cancer Lett 2021 03 24;501:20-30. Epub 2020 Dec 24.

Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China. Electronic address:

High-dose radiation exposure induces gastrointestinal (GI) stem cell death, resulting in denudation of the intestinal mucosa and lethality from GI syndrome, for which there is currently no effective therapy. Studying an intestinal organoid-based functional model, we found that Sirtuin1(SIRT1) inhibition through genetic knockout or pharmacologic inhibition significantly improved mouse and human intestinal organoid survival after irradiation. Remarkably, mice administered with two doseages of SIRT1 inhibitors at 24 and 96 h after lethal irradiation promoted Lgr5+ intestinal stem cell and crypt recovery, with improved mouse survival (88.89% of mice in the treated group vs. 0% of mice in the control group). Moreover, our data revealed that SIRT1 inhibition increased p53 acetylation, resulting in the stabilization of p53 and likely contributing to the survival of intestinal epithelial cells post-radiation. These results demonstrate that SIRT1 inhibitors are effective clinical countermeasures to mitigate GI toxicity from potentially lethal radiation exposure.
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http://dx.doi.org/10.1016/j.canlet.2020.12.034DOI Listing
March 2021

TAM kinase inhibition and immune checkpoint blockade- a winning combination in cancer treatment?

Expert Opin Ther Targets 2021 Feb 31;25(2):141-151. Epub 2020 Dec 31.

Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

: Immune checkpoint inhibitors (ICI) have shown great promise in a wide spectrum of malignancies. However, responses are not always durable, and this mode of treatment is only effective in a subset of patients. As such, there exists an unmet need for novel approaches to bolster ICI efficacy.: We review the role of the Tyro3, Axl, and Mer (TAM) receptor tyrosine kinases in promoting tumor-induced immune suppression and discuss the benefits that may be derived from combining ICI with TAM kinase-targeted tyrosine kinase inhibitors. We searched the MEDLINE Public Library of Medicine (PubMed) and EMBASE databases and referred to ClinicalTrials.gov for relevant ongoing studies.: Targeting of TAM kinases may improve the efficacy of immune checkpoint blockade. However, it remains to be determined whether this effect will be better achieved by the selective targeting of each TAM receptor, depending on the context, or by multi-receptor TAM inhibitors. Triple inhibition of all TAM receptors is more likely to be associated with an increased risk for adverse events. Clinical trial designs should use high-resolution clinical endpoints and proper control arms to determine the synergistic effects of combining TAM inhibition with immune checkpoint blockade.
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http://dx.doi.org/10.1080/14728222.2021.1869212DOI Listing
February 2021

Molecular Profiling of Metastatic Bladder Cancer Early-Phase Clinical Trial Participants Predicts Patient Outcomes.

Mol Cancer Res 2021 03 15;19(3):395-402. Epub 2020 Dec 15.

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Prognosis for patients with metastatic bladder carcinoma (mBC) remains limited and in need of novel therapies. We retrospectively analyzed medical records of 43 patients with platinum-refractory metastatic bladder cancer (mBC) who participated in one or more phase I trials of various investigational therapies. Patients' tumors or circulating tumor DNA were analyzed by next-generation sequencing. The median progression-free survival was 4.2 months, the median overall survival was 9.6 months, and the overall response rate was 17.5%. , and alterations were detected in 66%, 29%, 27%, 24%, and 22% of all patients, respectively. Alterations in were almost mutually exclusive of . More than half (64%) of patients with an alt received an FGFR inhibitor, 67% of which achieved disease control. Among patients with urothelial carcinoma histology, those harboring a alteration had a shorter median progression-free survival (PFS) compared with those whose tumors carry wild-type . The reverse relationship was observed in patients harboring an alteration. IMPLICATIONS: Patients with platinum-refractory mBC derive clinical benefit from participating in early-phase clinical trials and their survival outcomes correlate with the genetic profile of the tumor. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/3/395/F1.large.jpg.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0751DOI Listing
March 2021

The obesity paradox: defining the impact of body mass index and diabetes mellitus for patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin.

BJU Int 2021 Jul 5;128(1):65-71. Epub 2020 Dec 5.

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objectives: To evaluate if the obesity paradox, wherein obesity portends worse overall prognosis for a disease but improved outcomes for patients receiving immunotherapy, exists for patients receiving bacillus Calmette-Guérin (BCG) in a contemporary cohort.

Patients And Methods: We performed an Institutional Review Board-approved database review to identify patients with non-muscle-invasive bladder cancer (NMIBC) completing at least an induction course of BCG. Clinicopathological variables collected included: body mass index (BMI), medications, and diabetes mellitus (DM). Outcomes of interest included: recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Univariate and multivariate modelling were used to evaluate the association between outcomes and clinical factors.

Results: A total of 579 patients (median follow-up 4.6 years) received BCG induction for NMIBC; 90% had high-grade disease (47.2% clinical stage T1). In all, 75.7% of patients were overweight or obese and 18% had DM. Aspirin, statins, metformin and β-blockers were used in 34%, 42%, 11%, and 29% of patients, respectively. Overweight and obese patients had improved PFS, CSS and OS. DM was associated with worse RFS. Medications of interest had no association with outcomes.

Conclusion: Elevated BMI is associated with improved outcomes in patients with NMIBC treated with BCG immunotherapy. Patients with DM are at increased risk of recurrence. These findings support a potential obesity paradox in bladder cancer. Evaluation of the underlying mechanism and the role of global patient assessment, counselling, and risk factor modification are warranted.
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http://dx.doi.org/10.1111/bju.15296DOI Listing
July 2021

Outcomes of patients with metastatic renal cell carcinoma with sarcomatoid dedifferentiation to immune checkpoint inhibitors.

Urol Oncol 2021 02 10;39(2):134.e9-134.e16. Epub 2020 Nov 10.

The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Introduction: Metastatic renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is associated with poor survival outcomes. We aimed to analyze the efficacy and safety of immune checkpoint inhibitors (ICI) in patients with sRCC comparing clear-cell (sccRCC) to non-clear cell epithelial histology (snccRCC).

Methods: We performed retrospective analysis of sRCC patients who received ICI at MD Anderson Cancer Center (n = 48, 41 with ccRCC and 7 with nccRCC) to determine the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, we performed a prespecified multivariable Cox regression comparing survival outcomes between sccRCC and snccRCC.

Results: The ORR for the entire cohort was 35.4% (95% confidence interval [CI]: 23.4%, 49.6%), including 8 (16.7%) patients (95% CI: 8.7%, 29.6%) who achieved a complete remission. The disease control rate was 52% (95% CI: 38.3%, 65.5%). In patients with sccRCC, the ORR was 39% (95% CI: 25.7%, 54.3%) and disease control rate 58.5% (43.4%, 72.2%). Among 7 snccRCC patients, only one (14.3%) achieved an objective partial response. At a median follow-up of 51.1 months, the median PFS was 4.9 months (95% CI: 2.7, 16.3) and the median OS was 28.4 months (95% CI: 15.8, NA) for the entire cohort. For patients with sccRCC, the median PFS was 8.9 months, with median OS of 30.1 months, compared with median PFS of 2.3 months (HR 0.25 [95% CI: 0.08, 0.78]; P= 0.0145) and median OS of 6.7 months (HR 0.13 [95% CI 0.04, 0.44]; P=0.0009) for patients with snccRCC.

Conclusion: ICIs appear to be effective in sccRCC while the treatment of snccRCC remains challenging.
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http://dx.doi.org/10.1016/j.urolonc.2020.10.019DOI Listing
February 2021

miR-19a promotes the metastasis and EMT through CUL5 in prostate cancer cell line PC3.

J BUON 2020 Jul-Aug;25(4):2028-2035

Reproductive Endocrinology Department, The Second People's Hospital of Liaocheng, Liaocheng Second Hospital Affiliated to Shandong First Medical University, Linqing 252600, Shandong Province, China.

Purpose: Prostate cancer is an epithelial malignancy that occurs in the prostate and metastasis is a challenge of the treatment of prostate cancer. MicroRNA (miR)-19a was usually upregulated in several cancers at the roles of miR-19a in the metastasis in prostate cancer are still unclear.

Methods: A normal prostate epithelial cell line P69 and two prostate cancer cell lines PC3 and DU145 were used in this study. The mRNA levels of miR-19a and CUL5 were measured using qRT-PCR assay. Transwell and Western blot assays were conducted to calculate cell metastasis and epithelial-mesenchymal transition (EMT) properties in PC3 cells. Luciferase reporter assay was applied to validate that miR-19a targeted to CUL5.

Results: The expression of miR-19a was high in prostate cancer and its overexpression predicted poor outcome of prostate cancer patients. miR-19a regulated the expression of CUL5 by directly targeting its mRNA 3'-UTR in PC3 cells. The expression of CUL5 was lower in prostate cancer tissues and cell lines than in non-tumor tissues and normal cells. Downregulation of CUL5 predicted worse outcome of prostate cancer patients. miR-19a promoted cell migration, invasion and EMT in prostate cancer by directly binding to CUL5 mRNA 3'-UTR. CUL5 partially reversed the roles of miR-19a on the metastasis in prostate cancer.

Conclusion: miR-19a promoted migratory, invasive and EMT abilities by binding to CUL5 in prostate cancer. The newly identified miR-19a/CUL5 axis provides novel insight into the pathogenesis of prostate cancer.
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July 2021

Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma.

Nat Med 2020 12 12;26(12):1845-1851. Epub 2020 Oct 12.

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Immune checkpoint therapy is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma, with one study reporting data in cisplatin-ineligible patients who received anti-PD-L1 monotherapy. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathological complete response rate of 17%. Here we report on the first pilot combination neoadjuvant trial ( NCT02812420 ) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high-risk features (n = 28). High-risk features were defined by bulky tumors, variant histology, lymphovascular invasion, hydronephrosis and/or high-grade upper tract disease. The primary endpoint was safety and we observed 6 of 28 patients (21%) with grade ≥3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (n = 4), hepatitis and colitis (n = 2). We also observed pathological complete response of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (n = 24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized urothelial carcinoma, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment.
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http://dx.doi.org/10.1038/s41591-020-1086-yDOI Listing
December 2020

The Immunotherapy Revolution in Kidney Cancer Treatment: Scientific Rationale and First-Generation Results.

Cancer J 2020 Sep/Oct;26(5):419-431

From the Division of Cancer Medicine, Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.

The recent discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, including the treatment for renal cell carcinoma (RCC). Following the eras of cytokines and molecularly targeted therapies including vascular endothelial growth factor-directed agents and mammalian target of rapamycin (mTOR) inhibitors, ICIs have become the latest addition to the RCC armamentarium. To understand the scientific rationale behind this revolution in RCC treatment, we have reviewed the fundamental discoveries underlying the transition from old (cytokines) to new (ICIs) immunotherapies. We summarize the pivotal trials (CheckMate 025, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, IMmotion151) of checkpoint inhibitors for clear cell RCC in various treatment settings. With the availability of many different combination therapies and many more currently under investigation, clear cell RCC treatment is becoming more complex. Patient preferences, disease volumes, and adverse event profiles are essential in determining which option is the best for an individual patient. In the future, biomarkers currently under development could guide these treatment decisions.
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http://dx.doi.org/10.1097/PPO.0000000000000471DOI Listing
September 2020

Levelling the Evidence: A Comparison of Neoadjuvant and Adjuvant Treatment for Upper Tract Urothelial Carcinoma.

Eur Urol 2021 05 10;79(5):655-656. Epub 2020 Sep 10.

Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2020.08.033DOI Listing
May 2021

Effects of coenzyme Q10 on endothelial and cardiac function in patients undergoing haemodialysis: study protocol for a pilot randomised controlled trial.

BMJ Open 2020 09 1;10(9):e036732. Epub 2020 Sep 1.

Department of Nephrology, Chinese PLA Strategic Support Force Characteristic Medical Center (The 306th Hospital of Chinese PLA), Beijing, China

Introduction: Endothelial and cardiac dysfunction are highly prevalent and are associated with cardiovascular morbidity and mortality among patients undergoing dialysis. For patients undergoing dialysis, no study has explored the effect of supplementation of coenzyme Q10 (CoQ10) on endothelial function. To our best of knowledge, only two small sample studies focused on the efficacy of supplementation of CoQ10 on cardiac function. However, the effect of CoQ10 supplementation on cardiac function remains uncertain in patients who undergo haemodialysis. The aim of this study is to explore whether CoQ10 supplementation can improve endothelial and cardiac function in patients undergoing haemodialysis.

Methods And Analysis: This is a pilot randomised controlled study. Eligible patients undergoing haemodialysis in our haemodialysis centre will be randomly allocated to the CoQ10 and control groups. The follow-up time is 12 months. The primary outcome is to assess the change of brachial artery endothelial-dependent flow-mediated dilation, left ventricular systolic function, diastolic function and Myocardial Performance Index at 12 months from baseline. Secondary outcomes are death or hospitalisation due to cardiovascular events, all-cause mortality, change of CoQ10 concentration, the ratio of ubiquinol to ubiquinone, the change of oxidative stress markers (including malondialdehyde and 8-hydroxy-deoxyguanosine) and Left Ventricular Mass Index.

Ethics And Dissemination: Risks associated with CoQ10 are minor, even at doses as high as 1800 mg according to previous studies. The trial has received ethics approval from the Medical Ethics Committee for Clinical Trials of Drugs, the 306th Hospital of Chinese PLA. The results of the study are expected to be published in a peer-reviewed journal and presented at academic conferences.

Trial Registration Number: ChiCTR1900022258.
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http://dx.doi.org/10.1136/bmjopen-2019-036732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467521PMC
September 2020

Genome-Wide Association Study in 3,173 Outbred Rats Identifies Multiple Loci for Body Weight, Adiposity, and Fasting Glucose.

Obesity (Silver Spring) 2020 10 29;28(10):1964-1973. Epub 2020 Aug 29.

Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Objective: Obesity is influenced by genetic and environmental factors. Despite the success of human genome-wide association studies, the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify the genetic loci underlying obesity and related morphometric and metabolic traits.

Methods: This study measured obesity-relevant traits, including body weight, body length, BMI, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat genome-wide association study to date. Genetic loci were identified using a linear mixed model to account for the complex family relationships of the HS and using covariates to account for differences among the three phenotyping centers.

Results: This study identified 32 independent loci, several of which contained only a single gene (e.g., Epha5, Nrg1, Klhl14) or obvious candidate genes (e.g., Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity-related traits, and there was extensive pleiotropy at individual loci.

Conclusions: This study demonstrates the utility of HS rats for investigating the genetics of obesity-related traits across institutions and identify several candidate genes for future functional testing.
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http://dx.doi.org/10.1002/oby.22927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511439PMC
October 2020

Morphologies, Young's Modulus and Resistivity of High Aspect Ratio Tungsten Nanowires.

Materials (Basel) 2020 Aug 25;13(17). Epub 2020 Aug 25.

State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, Xi'an 710072, China.

High aspect ratio tungsten nanowires have been prepared by selective dissolution of Nickel-aluminum-tungsten (NiAl-W) alloys which were directionally solidified at growth rates varying from 2 to 25 μm/s with a temperature gradient of 300 K·cm. Young's modulus and electrical resistivity of tungsten nanowires were measured by metallic mask template method. The results show that the tungsten nanowires with uniform diameter and high aspect ratio are well aligned. The length of tungsten nanowires increases with prolongation of etching time, and their length reaches 300 μm at 14 h. Young's modulus of tungsten nanowires is estimated by Hertz and Sneddon models. The Sneddon model is proper for estimating the Young's modulus, and the value of calculating Young's modulus are 260-460 GPa which approach the value of bulk tungsten. The resistivity of tungsten nanowires is measured and fitted with Fuchs-Sondheimer (FS) + Mayadas-Shatzkes (MS) model. The fitting results show that the specific resistivity of W nanowires is a litter bigger than the bulk W, and its value decreases with decreasing diameter.
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http://dx.doi.org/10.3390/ma13173749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503276PMC
August 2020

Full control of dual-band vortex beams using a high-efficiency single-layer bi-spectral 2-bit coding metasurface.

Opt Express 2020 Jun;28(12):17374-17383

Vortex beams (VBs) carrying orbital angular moment (OAM) modes have been proven to be promising resources for increasing communication capacity. Although considerable attention has been paid on metasurface-based VB generators due to the unprecedented advantages of metasurface, most applications are usually limited at a single band with a fixed OAM mode. In this work, an emerging dual-band reflection-type coding metasurface is proposed to mitigate these issues by newly engineered meta-atoms, which could achieve independent 2-bit phase modulations at two frequency bands. The proposed coding metasurface could efficiently realize and fully control dual-band VBs carrying frequency selective OAM modes under the linearly polarized incidence. As the first illustrative example, a dual-band VB generator with normal beam direction is fabricated and characterized at two widely used communication bands (Ku and Ka bands). Moreover, by encoding proper coding sequences, versatile beams carrying frequency selective OAM modes can be achieved. Therefore, by adding a gradient phase sequence to the first VB generator, the second one is designed to steer the generated beams to a preset direction, which could enable diverse scenarios. The measurement results of both VB generators agree very well with the numerical ones, validating the full control capability of the proposed approach.
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http://dx.doi.org/10.1364/OE.394571DOI Listing
June 2020
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