PubMed

(tuberculosis[Title/Abstract]) OR (lung cancer[Title/Abstract])

Filters applied: from 2023/11/1 - 2023/11/30.

1. Cell. 2023 Nov 9;186(23):5135-5150.e28. doi: 10.1016/j.cell.2023.09.016. Epub 2023 Oct 20.

Mechanopathology of biofilm-like Mycobacterium tuberculosis cords.

Mishra R(1), Hannebelle M(2), Patil VP(3), Dubois A(4), Garcia-Mouton C(5),

Kirsch GM(1), Jan M(6), Sharma K(1), Guex N(6), Sordet-Dessimoz J(7), Perez-Gil

J(5), Prakash M(3), Knott GW(4), Dhar N(1), McKinney JD(1), Thacker VV(8).

Author information:

(1)Global Health Institute, École Polytechnique Fédérale de Lausanne, 1015

Lausanne, Switzerland.

(2)Global Health Institute, École Polytechnique Fédérale de Lausanne, 1015

Lausanne, Switzerland; Department of Bioengineering, Stanford University,

Stanford, CA 94305, USA.

(3)Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

(4)BioElectron Microscopy Facility, École Polytechnique Fédérale de Lausanne,

1015 Lausanne, Switzerland.

(5)Department of Biochemistry, University Complutense Madrid, 28040 Madrid,

Spain.

(6)Bioinformatics Competence Centre, University of Lausanne, 1015 Lausanne,

Switzerland; Bioinformatics Competence Centre, École Polytechnique Fédérale de

Lausanne, 1015 Lausanne, Switzerland.

(7)Histology Core Facility, École Polytechnique Fédérale de Lausanne, 1015

Lausanne, Switzerland.

(8)Global Health Institute, École Polytechnique Fédérale de Lausanne, 1015

Lausanne, Switzerland. Electronic address: vivek.thacker@uni-heidelberg.de.

Comment in Cell. 2023 Nov 9;186(23):4994-4995.

Mycobacterium tuberculosis (Mtb) cultured axenically without detergent forms

biofilm-like cords, a clinical identifier of virulence. In lung-on-chip (LoC)

and mouse models, cords in alveolar cells contribute to suppression of innate

immune signaling via nuclear compression. Thereafter, extracellular cords cause

contact-dependent phagocyte death but grow intercellularly between epithelial

cells. The absence of these mechanopathological mechanisms explains the greater

proportion of alveolar lesions with increased immune infiltration and

dissemination defects in cording-deficient Mtb infections. Compression of Mtb

lipid monolayers induces a phase transition that enables mechanical energy

storage. Agent-based simulations demonstrate that the increased energy storage

capacity is sufficient for the formation of cords that maintain structural

integrity despite mechanical perturbation. Bacteria in cords remain

translationally active despite antibiotic exposure and regrow rapidly upon

cessation of treatment. This study provides a conceptual framework for the

biophysics and function in tuberculosis infection and therapy of cord

architectures independent of mechanisms ascribed to single bacteria.

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.cell.2023.09.016

PMCID: PMC10642369

PMID: 37865090 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of interests The authors declare no

competing interests.

2. JAMA Oncol. 2023 Nov 30. doi: 10.1001/jamaoncol.2023.4897. Online ahead of print.

Structural Racism and Lung Cancer Risk: A Scoping Review.

Bonner SN(1)(2), Curley R(3), Love K(4), Akande T(3), Akhtar A(3), Erhunmwunsee

L(3)(5).

Author information:

(1)Department of Surgery, University of Michigan, Ann Arbor.

(2)National Clinician Scholars Program, University of Michigan, Ann Arbor.

(3)Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte,

California.

(4)Library Services, City of Hope, Duarte, California.

(5)Department of Populations Sciences, City of Hope National Medical Center,

Duarte, California.

IMPORTANCE: Structural racism is associated with persistent inequities in health

and health outcomes in the US for racial and ethnic minority groups. This review

summarizes how structural racism contributes to differential population-level

exposure to lung cancer risk factors and thus disparate lung cancer risk across

different racial and ethnic groups.

OBSERVATIONS: A scoping review was conducted focusing on structural racism and

lung cancer risk for racial and ethnic minority groups. The domains of

structural racism evaluated included housing and built environment, occupation

and employment, health care, economic and educational opportunity, private

industry, perceived stress and discrimination, and criminal justice involvement.

The PubMed, Embase, and MedNar databases were searched for English-language

studies in the US from January 1, 2010, through June 30, 2022. The review

demonstrated that racial and ethnic minority groups are more likely to have

environmental exposures to air pollution and known carcinogens due to

segregation of neighborhoods and poor housing quality. In addition, racial and

ethnic minority groups were more likely to have exposures to pesticides, silica,

and asbestos secondary to higher employment in manual labor occupations.

Furthermore, targeted marketing and advertisement of tobacco products by private

industry were more likely to occur in neighborhoods with more racial and ethnic

minority groups. In addition, poor access to primary care services and

inequities in insurance status were associated with elevated lung cancer risk

among racial and ethnic minority groups. Lastly, inequities in tobacco use and

cessation services among individuals with criminal justice involvement had

important implications for tobacco use among Black and Hispanic populations.

CONCLUSIONS AND RELEVANCE: The findings suggest that structural racism must be

considered as a fundamental contributor to the unequal distribution of lung

cancer risk factors and thus disparate lung cancer risk across different racial

and ethnic groups. Additional research is needed to better identify mechanisms

contributing to inequitable lung cancer risk and tailor preventive

interventions.

DOI: 10.1001/jamaoncol.2023.4897

PMID: 38032677

3. Adv Mater. 2023 Nov 15:e2308977. doi: 10.1002/adma.202308977. Online ahead of print.

Nanomedicine Combats Drug Resistance in Lung Cancer.

Zheng X(1), Song X(2), Zhu G(1), Pan D(1), Li H(1), Hu J(2), Xiao K(1), Gong

Q(1)(3)(4), Gu Z(1), Luo K(1)(3), Li W(1)(3).

Author information:

(1)Department of Radiology, Department of Respiratory, Huaxi MR Research Center

(HMRRC) and Critical Care Medicine, Institute of Respiratory Health, Precision

Medicine Center, Frontiers Science Center for Disease-Related Molecular Network,

State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No.

37 Guoxue Alley, Chengdu, 610041, China.

(2)Department of General Surgery, Gastric Cancer Center and Laboratory of

Gastric Cancer, West China Hospital, Sichuan University, No. 37 Guoxue Alley,

Chengdu, 610041, China.

(3)Precision Medicine Key Laboratory of Sichuan Province, Functional and

Molecular Imaging Key Laboratory of Sichuan Province, and Research Unit of

Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China.

(4)Department of Radiology, West China Xiamen Hospital of Sichuan University,

Xiamen, Fujian, 361000, China.

Lung cancer is the second most prevalent cancer and the leading cause of

cancer-related death worldwide. Surgery, chemotherapy, molecular targeted

therapy, immunotherapy, and radiotherapy are currently available as treatment

methods. However, drug resistance is a significant factor in the failure of lung

cancer treatments. Novel therapeutics have been exploited to address complicated

resistance mechanisms of lung cancer and the advancement of nanomedicine is

extremely promising in terms of overcoming drug resistance. Nanomedicine

equipped with multifunctional and tunable physiochemical properties in alignment

with tumor genetic profiles can achieve precise, safe, and effective treatment

while minimizing or eradicating drug resistance in cancer. Here, this work

reviews the discovered resistance mechanisms for lung cancer chemotherapy,

molecular targeted therapy, immunotherapy, and radiotherapy, and outlines novel

strategies for the development of nanomedicine against drug resistance. This

work focuses on engineering design, customized delivery, current challenges, and

clinical translation of nanomedicine in the application of resistant lung

cancer.

© 2023 Wiley-VCH GmbH.

DOI: 10.1002/adma.202308977

PMID: 37968865

4. CA Cancer J Clin. 2023 Nov 1. doi: 10.3322/caac.21811. Online ahead of print.

Screening for lung cancer: 2023 guideline update from the American Cancer

Society.

Wolf AMD(1), Oeffinger KC(2), Shih TY(3), Walter LC(4), Church TR(5), Fontham

ETH(6), Elkin EB(7), Etzioni RD(8), Guerra CE(9), Perkins RB(10), Kondo KK(11),

Kratzer TB(12), Manassaram-Baptiste D(11), Dahut WL(13), Smith RA(11).

Author information:

(1)University of Virginia School of Medicine, Charlottesville, Virginia, USA.

(2)Department of Medicine, Duke University School of Medicine and Duke Cancer

Institute Center for Onco-Primary Care, Durham, North Carolina, USA.

(3)David Geffen School of Medicine and Jonsson Comprehensive Cancer Center,

University of California Los Angeles, Los Angeles, California, USA.

(4)Department of Medicine, University of California San Francisco and San

Francisco Veterans Affairs Medical Center, San Francisco, California, USA.

(5)Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.

(6)Health Sciences Center, School of Public Health, Louisiana State University,

New Orleans, Louisiana, USA.

(7)Department of Health Policy and Management, Columbia University Mailman

School of Public Health, New York, New York, USA.

(8)Fred Hutchinson Cancer Research Center, University of Washington, Seattle,

Washington, USA.

(9)Perelman School of Medicine, University of Pennsylvania, Philadelphia,

Pennsylvania, USA.

(10)Obstetrics and Gynecology, Boston University Chobanian and Avedisian School

of Medicine, Boston, Massachusetts, USA.

(11)Early Cancer Detection Science, American Cancer Society, Atlanta, Georgia,

USA.

(12)Cancer Surveillance and Health Equity Science, American Cancer Society,

Atlanta, Georgia, USA.

(13)American Cancer Society, Atlanta, Georgia, USA.

Lung cancer is the leading cause of mortality and person-years of life lost from

cancer among US men and women. Early detection has been shown to be associated

with reduced lung cancer mortality. Our objective was to update the American

Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at

high risk for lung cancer. The guideline is intended to provide guidance for

screening to health care providers and their patients who are at high risk for

lung cancer due to a history of smoking. The ACS Guideline Development Group

(GDG) utilized a systematic review of the LCS literature commissioned for the US

Preventive Services Task Force 2021 LCS recommendation update; a second

systematic review of lung cancer risk associated with years since quitting

smoking (YSQ); literature published since 2021; two Cancer Intervention and

Surveillance Modeling Network-validated lung cancer models to assess the

benefits and harms of screening; an epidemiologic and modeling analysis

examining the effect of YSQ and aging on lung cancer risk; and an updated

analysis of benefit-to-radiation-risk ratios from LCS and follow-up

examinations. The GDG also examined disease burden data from the National Cancer

Institute's Surveillance, Epidemiology, and End Results program. Formulation of

recommendations was based on the quality of the evidence and judgment

(incorporating values and preferences) about the balance of benefits and harms.

The GDG judged that the overall evidence was moderate and sufficient to support

a strong recommendation for screening individuals who meet the eligibility

criteria. LCS in men and women aged 50-80 years is associated with a reduction

in lung cancer deaths across a range of study designs, and inferential evidence

supports LCS for men and women older than 80 years who are in good health. The

ACS recommends annual LCS with low-dose computed tomography for asymptomatic

individuals aged 50-80 years who currently smoke or formerly smoked and have a

≥20 pack-year smoking history (strong recommendation, moderate quality of

evidence). Before the decision is made to initiate LCS, individuals should

engage in a shared decision-making discussion with a qualified health

professional. For individuals who formerly smoked, the number of YSQ is not an

eligibility criterion to begin or to stop screening. Individuals who currently

smoke should receive counseling to quit and be connected to cessation resources.

Individuals with comorbid conditions that substantially limit life expectancy

should not be screened. These recommendations should be considered by health

care providers and adults at high risk for lung cancer in discussions about LCS.

If fully implemented, these recommendations have a high likelihood of

significantly reducing death and suffering from lung cancer in the United

States.

© 2023 The Authors. CA: A Cancer Journal for Clinicians published by Wiley

Periodicals LLC on behalf of American Cancer Society.

DOI: 10.3322/caac.21811

PMID: 37909877

5. CA Cancer J Clin. 2023 Nov 1. doi: 10.3322/caac.21808. Online ahead of print.

Lung cancer diagnosis and mortality beyond 15 years since quit in individuals

with a 20+ pack-year history: A systematic review.

Kondo KK(1)(2), Rahman B(1), Ayers CK(3), Relevo R(1), Griffin JC(1), Halpern

MT(4).

Author information:

(1)Early Cancer Detection Science, American Cancer Society, Kennesaw, Georgia,

USA.

(2)Research Integrity, Oregon Health & Science University, Portland, Oregon,

USA.

(3)Center to Improve Veteran Involvement in Care, Portland Veterans Affairs

Health Care System, Portland, Oregon, USA.

(4)Division of Cancer Control & Population Sciences, National Cancer Institute,

Bethesda, Maryland, USA.

Current US lung cancer screening recommendations limit eligibility to adults

with a pack-year (PY) history of ≥20 years and the first 15 years since quit

(YSQ). The authors conducted a systematic review to better understand lung

cancer incidence, risk and mortality among otherwise eligible individuals in

this population beyond 15 YSQ. The PubMed and Scopus databases were searched

through February 14, 2023, and relevant articles were searched by hand. Included

studies examined the relationship between adults with both a ≥20-PY history and

≥15 YSQ and lung cancer diagnosis, mortality, and screening ineligibility. One

investigator abstracted data and a second confirmed. Two investigators

independently assessed study quality and certainty of evidence (COE) and

resolved discordance through consensus. From 2636 titles, 22 studies in 26

articles were included. Three studies provided low COE of elevated lung cancer

incidence beyond 15 YSQ, as compared with people who never smoked, and six

studies provided moderate COE that the risk of a lung cancer diagnosis after 15

YSQ declines gradually, but with no clinically significant difference just

before and after 15 YSQ. Studies examining lung cancer-related disparities

suggest that outcomes after 15 YSQ were similar between African American/Black

and White participants; increasing YSQ would expand eligibility for African

American/Black individuals, but for a significantly larger proportion of White

individuals. The authors observed that the risk of lung cancer not only persists

beyond 15 YSQ but that, compared with individuals who never smoked, the risk may

remain significantly elevated for 2 or 3 decades. Future research of nationally

representative samples with consistent reporting across studies is needed, as

are better data from which to examine the effects on health disparities across

different populations.

© 2023 The Authors. CA: A Cancer Journal for Clinicians published by Wiley

Periodicals LLC on behalf of American Cancer Society.

DOI: 10.3322/caac.21808

PMID: 37909870

6. J Infect. 2023 Nov;87(5):373-384. doi: 10.1016/j.jinf.2023.09.004. Epub 2023 Sep 9.

Single-cell RNA-sequencing reveals heterogeneity and intercellular crosstalk in

human tuberculosis lung.

Wang L(1), Ma H(2), Wen Z(2), Niu L(2), Chen X(3), Liu H(4), Zhang S(2), Xu

J(2), Zhu Y(1), Li H(1), Chen H(1), Shi L(1), Wan L(1), Li L(1), Li M(5), Wong

KW(6), Song Y(7).

Author information:

(1)Department of Thoracic Surgery, Shanghai Public Health Clinical Center,

Shanghai, China.

(2)Department of Scientific Research, Shanghai Public Health Clinical Center,

Shanghai, China.

(3)Guangdong Provincial Key Laboratory of Regional Immunity and Diseases,

Department of Pathogen Biology, Shenzhen University School of Medicine,

Shenzhen, China.

(4)NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen

Biology, and Center for Tuberculosis Research, Chinese Academy of Medical

Sciences and Peking Union Medical College, Beijing, China.

(5)Fudan Zhangjiang Institute, Fudan University, Shanghai, China. Electronic

address: limeiyi@sibs.ac.cn.

(6)Department of Scientific Research, Shanghai Public Health Clinical Center,

Shanghai, China. Electronic address: kwwong@gmail.com.

(7)Department of Thoracic Surgery, Shanghai Public Health Clinical Center,

Shanghai, China. Electronic address: yanzhengsong@163.com.

Lung inflammation indicated by 18F-labeled fluorodeoxyglucose (FDG) in patients

with tuberculosis is associated with disease severity and relapse risk upon

treatment completion. We revealed the heterogeneity and intercellular crosstalk

in lung tissues with 18F-FDG avidity and adjacent uninvolved tissues from 6

tuberculosis patients by single-cell RNA-sequencing. Tuberculous lungs had an

influx of regulatory T cells (Treg), exhausted CD8 T cells, immunosuppressive

myeloid cells, conventional DC, plasmacytoid DC, and neutrophils. Immune cells

in inflamed lungs showed general up-regulation of ATP synthesis and

interferon-mediated signaling. Immunosuppressive myeloid and Treg cells strongly

displayed transcriptions of genes related to tuberculosis disease progression.

Intensive crosstalk between IL4I1-expressing myeloid cells and Treg cells

involving chemokines, costimulatory molecules, and immune checkpoints, some of

which are specific in 18F-FDG-avid lungs, were found. Our analysis provides

insights into the transcriptomic heterogeneity and cellular crosstalk in

pulmonary tuberculosis and guides unveiling cellular and molecular targets for

tuberculosis therapy.

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/j.jinf.2023.09.004

PMID: 37690670

Conflict of interest statement: Declaration of Competing Interest The authors

declare that they have no known competing financial interests or personal

relationships that could have appeared to influence the work reported in this

paper.

7. Mil Med Res. 2023 Nov 28;10(1):58. doi: 10.1186/s40779-023-00490-8.

From immunology to artificial intelligence: revolutionizing latent tuberculosis

infection diagnosis with machine learning.

Li LS(1)(2)(3), Yang L(2), Zhuang L(2), Ye ZY(2), Zhao WG(4), Gong WP(5).

Author information:

(1)Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and

Treatment, Senior Department of Tuberculosis, the Eighth Medical Center of PLA

General Hospital, Beijing, 100091, China.

(2)Hebei North University, Zhangjiakou, 075000, Hebei, China.

(3)Senior Department of Respiratory and Critical Care Medicine, the Eighth

Medical Center of PLA General Hospital, Beijing, 100091, China.

(4)Senior Department of Respiratory and Critical Care Medicine, the Eighth

Medical Center of PLA General Hospital, Beijing, 100091, China.

rujiong@ldy.edu.rs.

(5)Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and

Treatment, Senior Department of Tuberculosis, the Eighth Medical Center of PLA

General Hospital, Beijing, 100091, China. gwp891015@whu.edu.cn.

Latent tuberculosis infection (LTBI) has become a major source of active

tuberculosis (ATB). Although the tuberculin skin test and interferon-gamma

release assay can be used to diagnose LTBI, these methods can only differentiate

infected individuals from healthy ones but cannot discriminate between LTBI and

ATB. Thus, the diagnosis of LTBI faces many challenges, such as the lack of

effective biomarkers from Mycobacterium tuberculosis (MTB) for distinguishing

LTBI, the low diagnostic efficacy of biomarkers derived from the human host, and

the absence of a gold standard to differentiate between LTBI and ATB. Sputum

culture, as the gold standard for diagnosing tuberculosis, is time-consuming and

cannot distinguish between ATB and LTBI. In this article, we review the

pathogenesis of MTB and the immune mechanisms of the host in LTBI, including the

innate and adaptive immune responses, multiple immune evasion mechanisms of MTB,

and epigenetic regulation. Based on this knowledge, we summarize the current

status and challenges in diagnosing LTBI and present the application of machine

learning (ML) in LTBI diagnosis, as well as the advantages and limitations of ML

in this context. Finally, we discuss the future development directions of ML

applied to LTBI diagnosis.

© 2023. The Author(s).

DOI: 10.1186/s40779-023-00490-8

PMCID: PMC10685516

PMID: 38017571 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that they have no competing

interests.

8. J Thorac Oncol. 2023 Nov 7:S1556-0864(23)02352-3. doi: 10.1016/j.jtho.2023.11.002. Online ahead of print.

Lung Cancer Risk Prediction Models for Asian Ever-Smokers.

Yang JJ(1), Wen W(2), Zahed H(3), Zheng W(2), Lan Q(4), Abe SK(5), Rahman MS(6),

Islam MR(7), Saito E(8), Gupta PC(9), Tamakoshi A(10), Koh WP(11), Gao YT(12),

Sakata R(13), Tsuji I(14), Malekzadeh R(15), Sugawara Y(14), Kim J(16), Ito

H(17), Nagata C(18), You SL(19), Park SK(20), Yuan JM(21), Shin MH(22), Kweon

SS(23), Yi SW(24), Pednekar MS(9), Kimura T(10), Cai H(2), Lu Y(14), Etemadi

A(25), Kanemura S(14), Wada K(18), Chen CJ(26), Shin A(27), Wang R(28), Ahn

YO(20), Shin MH(23), Ohrr H(29), Sheikh M(3), Blechter B(4), Ahsan H(30),

Boffetta P(31), Chia KS(32), Matsuo K(33), Qiao YL(34), Rothman N(4), Inoue

M(5), Kang D(27), Robbins HA(3), Shu XO(35).

Author information:

(1)Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology

Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center,

Nashville, Tennessee, USA; Department of Surgery, University of Florida College

of Medicine, Gainesville, Florida, USA; University of Florida Health Cancer

Center, Gainesville, Florida, USA.

(2)Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology

Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center,

Nashville, Tennessee, USA.

(3)International Agency for Research on Cancer, Lyon, France.

(4)Division of Cancer Epidemiology and Genetics, Occupational and Environmental

Epidemiology Branch, National Cancer Institute, National Institutes of Health,

Rockville, Maryland, USA.

(5)Division of Prevention, National Cancer Center Institute for Cancer Control,

Tokyo, Japan.

(6)Division of Prevention, National Cancer Center Institute for Cancer Control,

Tokyo, Japan; Research Center for Child Mental Development, Hamamatsu University

School of Medicine, Hamamatsu, Japan.

(7)Division of Prevention, National Cancer Center Institute for Cancer Control,

Tokyo, Japan; Hitotsubashi Institute for Advanced Study, Hitotsubashi

University, Tokyo, Japan.

(8)Institute for Global Health Policy Research, National Center for Global

Health and Medicine, Tokyo, Japan.

(9)Healis - Sekhsaria Institute for Public Health Mahaleb, Navi Mumbai.

(10)Department of Public Health, Hokkaido University Faculty of Medicine,

Sapporo, Japan.

(11)Healthy Longevity Translational Research Program, Yong Loo Lin School of

Medicine, National University of Singapore, Singapore, Singapore; Singapore

Institute for Clinical Sciences, Agency for Science Technology and Research

(A*STAR), Singapore, Singapore.

(12)Department of Epidemiology, Shanghai Cancer Institute Renji Hospital,

Shanghai Jiaotong University School of Medicine, Shanghai, China.

(13)Radiation Effects Research Foundation, Hiroshima, Japan.

(14)Tohoku University Graduate School of Medicine, Miyagi Prefecture, Japan.

(15)Digestive Oncology Research Center, Digestive Diseases Research Institute,

Tehran University of Medical Sciences, Tehran, Iran.

(16)Graduate School of Cancer Science and Policy, National Cancer Center,

Goyang, Republic of Korea.

(17)Division of Cancer Information and Control, Department of Preventive

Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan; Division of

Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine,

Nagoya, Japan.

(18)Department of Epidemiology and Preventive Medicine, Gifu University Graduate

School of Medicine, Gifu, Japan.

(19)School of Medicine & Big Data Research Center, Fu Jen Catholic University,

New Taipei City, Taiwan.

(20)Department of Preventive Medicine, Seoul National University College of

Medicine, Seoul, Republic of Korea.

(21)Division of Cancer Control and Population Sciences, UPMC Hillman Cancer

Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of

Epidemiology, Graduate School of Public Health, University of Pittsburgh,

Pittsburgh, Pennsylvania, USA.

(22)Department of Social and Preventive Medicine, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea.

(23)Department of Preventive Medicine, Chonnam National University Medical

School, Gwangju, Republic of Korea.

(24)Department of Preventive Medicine and Public Health, Catholic Kwandong

University College of Medicine, Gangneung, Republic of Korea.

(25)Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics,

National Cancer Institute, National Institutes of Healsh, Bethesda, Maryland,

USA.

(26)Genomics Research Center, Academia Sinica, Taipei City, Taiwan.

(27)Department of Preventive Medicine, Seoul National University College of

Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National

University, Seoul, Republic of Korea.

(28)Division of Cancer Control and Population Sciences, UPMC Hillman Cancer

Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

(29)Department of Preventive Medicine, Yonsei University College of Medicine,

Seoul, Republic of Korea.

(30)Department of Public Health Sciences, University of Chicago, Illinois, USA.

(31)Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York,

USA; Department of Medical and Surgical Sciences, University of Bologna,

Bologna, Italy.

(32)Saw Swee Hock School of Public Health, National University of Singapore,

Singapore, Singapore.

(33)Division Cancer Epidemiology and Prevention, Aichi Cancer Center Research

Institute, Nagoya, Japan; Department of Cancer Epidemiology, Nagoya University

Graduate School of Medicine, Nagoya, Japan.

(34)School of Population Medicine and Public Health, Chinese Academy of Medical

Sciences and Peking Union Medical College, Beijing, China.

(35)Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology

Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center,

Nashville, Tennessee, USA. Electronic address: xiao-ou.shu@vanderbilt.edu.

OBJECTIVES: Although lung cancer prediction models are widely used to support

risk-based screening, their performance outside Western populations remains

uncertain. This study aims to evaluate the performance of 11 existing risk

prediction models in multiple Asian populations and to re-fit prediction models

for Asians.

METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective

cohorts, we assessed calibration (expected to observed ratios, E/O) and

discrimination (area under the receiver operating characteristic curves, AUCs)

for each model. In addition, we developed the 'Shanghai models' to better refine

risk models for Asians based on two well-characterized population-based

prospective cohorts and externally validated them in other Asian cohorts.

RESULTS: Among 11 models, the Lung Cancer Death Risk Assessment Tool yielded the

highest AUC (AUC [95% CI]=0.71 [0.67-0.74] for lung cancer death and 0.69

[0.67-0.72] for lung cancer incidence), and the Prostate, Lung, Colorectal, and

Ovarian Cancer Screening Trial Model showed good calibration overall (E/O [95%

CI]=1.06 [0.90-1.25]). However, these models substantially underestimated lung

cancer risk among Asians who reported less than 10 smoking pack-years or stopped

smoking ≥20 years ago. The Shanghai models showed marginal improvement overall

in discrimination (AUC [95% CI]=0.72 [0.69-0.74] for lung cancer death and 0.70

[0.67-0.72] for lung cancer incidence) but consistently outperformed the

selected Western models among low-intensity smokers and long-term quitters.

CONCLUSIONS: The Shanghai models had comparable performance overall to the best

existing models, but they improved much in predicting the lung cancer risk of

low-intensity smokers and long-term quitters in Asia.

Copyright © 2023. Published by Elsevier Inc.

DOI: 10.1016/j.jtho.2023.11.002

PMID: 37944700

9. J Thorac Oncol. 2023 Nov 19:S1556-0864(23)02371-7. doi: 10.1016/j.jtho.2023.11.015. Online ahead of print.

Incidentally Detected Lung Cancer in Persons Too Young or Too Old for Lung

Cancer Screening in a Mississippi Delta Cohort.

Liao W(1), Fehnel C(1), Goss J(1), Shepherd CJ(1), Qureshi T(1), Matthews AT(1),

Ray MA(2), Faris NR(1), Pinsky PF(3), Smeltzer MP(2), Osarogiagbon RU(4).

Author information:

(1)Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, Tennessee.

(2)School of Public Health, University of Memphis, Memphis, Tennessee.

(3)Division of Cancer Prevention, National Cancer Institute, National Institutes

of Health, Bethesda, Maryland.

(4)Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, Tennessee.

Electronic address: rosarogi@bmhcc.org.

INTRODUCTION: Lung cancer risk in screening age-ineligible persons with

incidentally detected lung nodules is poorly characterized. We evaluated lung

cancer risk in two age-ineligible Lung Nodule Program (LNP) cohorts.

METHODS: Prospective observational study comparing 2-year cumulative lung cancer

diagnosis risk, lung cancer characteristics, and overall survival between

low-dose computed tomography (LDCT) screening participants aged 50 to 80 years

and LNP participants aged 35 to younger than 50 years (young) and older than 80

years (elderly).

RESULTS: From 2015 to 2022, lung cancer was diagnosed in 329 (3.43%), 39

(1.07%), and 172 (6.87%) LDCT, young, and elderly LNP patients, respectively.

The 2-year cumulative incidence was 3.0% (95% confidence intervals [CI]:

2.6%-3.4%) versus 0.79% (CI: 0.54%-1.1%) versus 6.5% (CI: 5.5%-7.6%),

respectively, but lung cancer diagnosis risk was similar between young LNP and

Lung CT Screening Reporting and Data System (Lung-RADS) 1 (adjusted hazard ratio

[aHR] = 0.88 [CI: 0.50-1.56]) and Lung-RADS 2 (aHR = 1.0 [0.58-1.72]). Elderly

LNP risk was greater than Lung-RADS 3 (aHR = 2.34 [CI: 1.50-3.65]), but less

than 4 (aHR = 0.28 [CI: 0.22-0.35]). Lung cancer was stage I or II in 62.92% of

LDCT versus 33.33% of young (p = 0.0003) and 48.26% of elderly (p = 0.0004) LNP

cohorts; 16.72%, 41.03%, and 29.65%, respectively, were diagnosed at stage IV.

The aggregate 5-year overall survival rates were 57% (CI: 48-67), 55% (CI:

39-79), and 24% (CI: 15-40) (log-rank p < 0.0001). Results were similar after

excluding persons with any history of cancer.

CONCLUSIONS: LNP modestly benefited persons too young or old for screening.

Differences in clinical characteristics and outcomes suggest differences in

biological characteristics of lung cancer in these three patient cohorts.

Copyright © 2023. Published by Elsevier Inc.

DOI: 10.1016/j.jtho.2023.11.015

PMID: 37984678

10. Eur Respir J. 2023 Nov 2;62(5):2301535. doi: 10.1183/13993003.01535-2023. Print 2023 Nov.

Reply: Tuberculosis screening in migrants to the EU/EEA and UK.

Zenner D(1)(2)(3)(4), Cobelens F(3)(4), Abubakar I(5).

Author information:

(1)Faculty of Population Health Sciences, University College London, London, UK

d.zenner@qmul.ac.uk.

(2)Wolfson Institute of Population Health, Queen Mary University of London,

London, UK.

(3)Amsterdam University Medical Centers, location University of Amsterdam,

Department of Global Health, Amsterdam, The Netherlands.

(4)Amsterdam Public Health, Global Health, Amsterdam, The Netherlands.

(5)Faculty of Population Health Sciences, University College London, London, UK.

Comment on Eur Respir J. 2023 Oct 12;62(4):

Tuberculosis incidence estimates from countries of origin alone are often

insufficient to predict TB prevalence among migrants https://bit.ly/3PDc35g

We would like to thank N. Köhler and co-workers for their correspondence

regarding our recent paper [1], comparing and contrasting it with their large

pan-European study. Their study collected aggregate country-specific

tuberculosis (TB) incidence rates as measured by infectious disease surveillance

systems in the country of arrival (CoA) [2] and compared these to World Health

Organization (WHO) TB incidence estimates from their respective country of

origin (CoO). The authors found considerable differences between these incidence

rates and conclude that there are many factors, other than incidence in the CoO,

which determine TB risk. The authors therefore call for more granular screening

policies which consider a wider range of factors including country-specific

incidence as measured in CoAs.

DOI: 10.1183/13993003.01535-2023

PMCID: PMC10620474

PMID: 37918880 [Indexed for MEDLINE]

Conflict of interest statement: Conflicts of interest: D. Zenner reports grants

from Barts Charity, La Caixa Foundation and the European Commission (709624). F.

Cobelens and I. Abubakar have no potential conflicts of interest to disclose.

11. Mol Cancer. 2023 Nov 6;22(1):179. doi: 10.1186/s12943-023-01888-7.

CircHERC1 promotes non-small cell lung cancer cell progression by sequestering

FOXO1 in the cytoplasm and regulating the miR-142-3p-HMGB1 axis.

Cui Y(#)(1), Wu X(#)(1), Jin J(1), Man W(1), Li J(2), Li X(1), Li Y(1), Yao

H(1), Zhong R(1), Chen S(1), Wu J(1), Zhu T(1), Lin Y(3), Xu J(4), Wang Y(5).

Author information:

(1)Beijing Institute of Biotechnology, Beijing, 100071, China.

(2)Department of Thoracic Surgery, The First Medical Center of Chinese PLA

General Hospital, Beijing, 100850, China.

(3)Beijing Institute of Biotechnology, Beijing, 100071, China.

linyl1089@163.com.

(4)Beijing Institute of Biotechnology, Beijing, 100071, China.

xujunjie@sina.com.

(5)Beijing Institute of Biotechnology, Beijing, 100071, China.

wang_you_liang@aliyun.com.

(#)Contributed equally

BACKGROUND: Noncoding RNAs such as circular RNAs (circRNAs) are abundant in the

human body and influence the occurrence and development of various diseases.

Non-small cell lung cancer (NSCLC) is one of the most common malignant cancers.

Information on the functions and mechanism of circRNAs in lung cancer is

limited; thus, the topic needs more exploration. The purpose of this study was

to identify aberrantly expressed circRNAs in lung cancer, unravel their roles in

NSCLC progression, and provide new targets for lung cancer diagnosis and

therapy.

METHODS: High-throughput sequencing was used to analyze differential circRNA

expression in patients with lung cancer. qRT‒PCR was used to determine the level

of circHERC1 in lung cancer tissues and plasma samples. Gain- and

loss-of-function experiments were implemented to observe the impacts of

circHERC1 on the growth, invasion, and metastasis of lung cancer cells in vitro

and in vivo. Mechanistically, dual luciferase reporter assays, fluorescence in

situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down

experiments were performed to confirm the underlying mechanisms of circHERC1.

Nucleocytoplasmic localization of FOXO1 was determined by nucleocytoplasmic

isolation and immunofluorescence. The interaction of circHERC1 with FOXO1 was

verified by RNA pull-down, RNA immunoprecipitation (RIP) and western blot

assays. The proliferation and migration of circHERC1 in vivo were verified by

subcutaneous and tail vein injection in nude mice.

RESULTS: CircHERC1 was significantly upregulated in lung cancer tissues and

cells, ectopic expression of circHERC1 strikingly facilitated the proliferation,

invasion and metastasis, and inhibited the apoptosis of lung cancer cells in

vitro and in vivo. However, knockdown of circHERC1 exerted the opposite effects.

CircHERC1 was mainly distributed in the cytoplasm. Further mechanistic research

indicated that circHERC1 acted as a competing endogenous RNA of miR-142-3p to

relieve the repressive effect of miR-142-3p on its target HMGB1, activating the

MAPK/ERK and NF-κB pathways and promoting cell migration and invasion. More

importantly, we found that circHERC1 could bind FOXO1 and sequester it in the

cytoplasm, adjusting the feedback AKT pathway. The accumulation of FOXO1 in the

cytosol and nuclear exclusion promoted cell proliferation and inhibited

apoptosis. CircHERC1 is a new circRNA that promotes tumor function in NSCLC and

may serve as a potential prognostic biomarker and therapeutic target for NSCLC.

CONCLUSIONS: CircHERC1 is a new circRNA that promotes tumor function in NSCLC

and may serve as a potential diagnosis biomarker and therapeutic target for

NSCLC. Our findings indicate that circHERC1 facilitates the invasion and

metastasis of NSCLC cells by regulating the miR-142-3p/HMGB1 axis and activating

the MAPK/ERK and NF-κB pathways. In addition, circHERC1 can promote cell

proliferation and inhibit apoptosis by sequestering FOXO1 in the cytoplasm to

regulate AKT activity and BIM transcription.

© 2023. The Author(s).

DOI: 10.1186/s12943-023-01888-7

PMCID: PMC10626661

PMID: 37932766 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.

12. Lancet Oncol. 2023 Nov;24(11):1206-1218. doi: 10.1016/S1470-2045(23)00444-8. Epub 2023 Oct 11.

Global variations in lung cancer incidence by histological subtype in 2020: a

population-based study.

Zhang Y(1), Vaccarella S(2), Morgan E(2), Li M(3), Etxeberria J(4), Chokunonga

E(5), Manraj SS(6), Kamate B(7), Omonisi A(8), Bray F(9).

Author information:

(1)Department of Epidemiology and Health Statistics, School of Public Health,

Guangdong Medical University, Dongguan, China.

(2)Cancer Surveillance Branch, International Agency for Research on Cancer,

Lyon, France.

(3)Department of Cancer Prevention, State Key Laboratory of Oncology in South

China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen

University Cancer Center, Guangzhou, China.

(4)Department of Statistics, Computer Science and Mathematics, Institute for

Advanced Materials and Mathematics (INAMAT2), Public University of Navarre,

Pamplona, Spain.

(5)Zimbabwe National Cancer Registry, Harare, Zimbabwe.

(6)Mauritius National Cancer Registry, Mauritius Institute of Health, Port

Louis, Mauritius.

(7)Bamako Cancer Registry, L'Hôpital National du Point G, Bamako, Mali.

(8)Ekiti Cancer Registry, Ekiti State University Teaching Hospital, Ado Ekiti

State, Nigeria.

(9)Cancer Surveillance Branch, International Agency for Research on Cancer,

Lyon, France. Electronic address: brayf@iarc.who.int.

BACKGROUND: Lung cancer is the second most common cancer worldwide, yet the

distribution by histological subtype remains unknown. We aimed to quantify the

global, regional, and national burden of lung cancer incidence for the four main

subtypes in 185 countries and territories.

METHODS: In this population-based study, we used data from Cancer Incidence in

Five Continents Volume XI and the African Cancer Registry Network to assess the

proportions of adenocarcinoma, squamous cell carcinoma, small-cell carcinoma,

and large-cell carcinoma among all lung cancers by country, sex, and age group

and subsequently applied these data to corresponding national (GLOBOCAN)

estimates of lung cancer incidence in 2020. Unspecified morphologies were

reallocated to specified subtypes. Age-standardised incidence rates were

calculated using the world standard population to compare subtype risks

worldwide, adjusted for differences in age composition between populations by

country.

FINDINGS: In 2020, there were an estimated 2 206 771 new cases of lung cancer,

with 1 435 943 in males and 770 828 in females worldwide. In males, 560 108

(39%) of all lung cancer cases were adenocarcinoma, 351 807 (25%) were squamous

cell carcinoma, 163 862 (11%) were small-cell carcinoma, and 115 322 (8%) were

large-cell carcinoma cases. In females, 440 510 (57%) of all lung cancer cases

were adenocarcinoma, 91 070 (12%) were squamous cell carcinoma, 68 224 (9%) were

small-cell carcinoma, and 49 246 (6%) were large-cell carcinoma cases.

Age-standardised incidence rates for adenocarcinoma, squamous cell carcinoma,

small-cell carcinoma, and large-cell carcinoma, respectively, were estimated to

be 12·4, 7·7, 3·6, and 2·6 per 100 000 person-years in males and 8·3, 1·6, 1·3,

and 0·9 per 100 000 person-years in females worldwide. The incidence rates of

adenocarcinoma exceeded those of squamous cell carcinoma in 150 of 185 countries

in males and in all 185 countries in females. The highest age-standardised

incidence rates per 100 000 person-years for adenocarcinoma, squamous cell

carcinoma, small-cell carcinoma, and large-cell carcinoma, respectively, for

males occurred in eastern Asia (23·5), central and eastern Europe (17·5),

western Asia (7·2), and south-eastern Asia (11·0); and for females occurred in

eastern Asia (16·0), northern America (5·4), northern America (4·7), and

south-eastern Asia (3·4). The incidence of each subtype showed a clear gradient

according to the Human Development Index for male and female individuals, with

increased rates in high and very high Human Development Index countries.

INTERPRETATION: Adenocarcinoma has become the most common subtype of lung cancer

globally in 2020, with incidence rates in males exceeding those of squamous cell

carcinoma in most countries, and in females in all countries. Our findings

provide new insights into the nature of the global lung cancer burden and

facilitates tailored national preventive actions within each world region.

FUNDING: None.

Copyright © 2023 World Health Organization. Published by Elsevier Ltd. All

rights reserved. Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/S1470-2045(23)00444-8

PMID: 37837979 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of interests We declare no competing

interests.

13. Cell. 2023 Dec 7;186(25):5536-5553.e22. doi: 10.1016/j.cell.2023.11.002. Epub 2023 Nov 28.

Early cellular mechanisms of type I interferon-driven susceptibility to

tuberculosis.

Kotov DI(1), Lee OV(2), Fattinger SA(2), Langner CA(2), Guillen JV(2), Peters

JM(3), Moon A(4), Burd EM(4), Witt KC(2), Stetson DB(5), Jaye DL(4), Bryson

BD(3), Vance RE(6).

Author information:

(1)Division of Immunology and Molecular Medicine, University of California,

Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University

of California, Berkeley, Berkeley, CA 94720, USA. Electronic address:

dkotov@berkeley.edu.

(2)Division of Immunology and Molecular Medicine, University of California,

Berkeley, Berkeley, CA 94720, USA.

(3)Department of Biological Engineering, Massachusetts Institute of Technology,

Cambridge, MA 02139, USA; Ragon Institute of Mass General, MIT, and Harvard,

Cambridge, MA 02139, USA.

(4)Department of Pathology and Laboratory Medicine, Emory University, Atlanta,

GA 30322, USA.

(5)Department of Immunology, University of Washington, Seattle, WA 98195, USA.

(6)Division of Immunology and Molecular Medicine, University of California,

Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University

of California, Berkeley, Berkeley, CA 94720, USA. Electronic address:

rvance@berkeley.edu.

Mycobacterium tuberculosis (Mtb) causes 1.6 million deaths annually. Active

tuberculosis correlates with a neutrophil-driven type I interferon (IFN)

signature, but the cellular mechanisms underlying tuberculosis pathogenesis

remain poorly understood. We found that interstitial macrophages (IMs) and

plasmacytoid dendritic cells (pDCs) are dominant producers of type I IFN during

Mtb infection in mice and non-human primates, and pDCs localize near human Mtb

granulomas. Depletion of pDCs reduces Mtb burdens, implicating pDCs in

tuberculosis pathogenesis. During IFN-driven disease, we observe abundant

DNA-containing neutrophil extracellular traps (NETs) described to activate pDCs.

Cell-type-specific disruption of the type I IFN receptor suggests that IFNs act

on IMs to inhibit Mtb control. Single-cell RNA sequencing (scRNA-seq) indicates

that type I IFN-responsive cells are defective in their response to IFNγ, a

cytokine critical for Mtb control. We propose that pDC-derived type I IFNs act

on IMs to permit bacterial replication, driving further neutrophil recruitment

and active tuberculosis disease.

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.cell.2023.11.002

PMID: 38029747 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of interests R.E.V. consults for

Ventus Therapeutics, Tempest Therapeutics, and X-biotix Therapeutics.

14. Lancet Respir Med. 2023 Nov 29:S2213-2600(23)00338-7. doi: 10.1016/S2213-2600(23)00338-7. Online ahead of print.

Low-dose CT screening among never-smokers with or without a family history of

lung cancer in Taiwan: a prospective cohort study.

Chang GC(1), Chiu CH(2), Yu CJ(3), Chang YC(4), Chang YH(5), Hsu KH(6), Wu

YC(7), Chen CY(8), Hsu HH(9), Wu MT(10), Yang CT(11), Chong IW(12), Lin YC(13),

Hsia TC(14), Lin MC(15), Su WC(16), Lin CB(17), Lee KY(18), Wei YF(19), Lan

GY(20), Chan WP(21), Wang KL(22), Wu MH(23), Tsai HH(24), Chian CF(25), Lai

RS(26), Shih JY(27), Wang CL(28), Hsu JS(29), Chen KC(30), Chen CK(31), Hsia

JY(32), Peng CK(33), Tang EK(34), Hsu CL(27), Chou TY(35), Shen WC(36), Tsai

YH(37), Tsai CM(38), Chen YM(39), Lee YC(40), Chen HY(41), Yu SL(42), Chen

CJ(43), Wan YL(44), Hsiung CA(45), Yang PC(46); TALENT Investigators.

Collaborators: Chan CC, Chan SW, Chang IS, Chang JH, Chao KS, Chen CJ, Chen HW,

Chiang CJ, Chiou HY, Chou MC, Chung CL, Chung TJ, Guo YL, Hsiao CF, Huang CS, Ko

SF, Lee MH, Li YJ, Liao YS, Lu YH, Ou HY, Wu PA, Yang HI, Yang SY, Yang SC.

Author information:

(1)Department of Internal Medicine, Division of Pulmonary Medicine, Chung Shan

Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan

Medical University, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical

University, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung

Hsing University, Taichung, Taiwan; School of Medicine, National Yang Ming Chiao

Tung University, Taipei, Taiwan; Department of Internal Medicine, Division of

Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

(2)School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan;

Taipei Cancer Center, Taipei Medical University Hospital, Taipei Medical

University, Taipei, Taiwan; Department of Chest Medicine, Taipei Veterans

General Hospital, Taipei, Taiwan.

(3)Department of Internal Medicine, College of Medicine, National Taiwan

University, Taipei, Taiwan; National Taiwan University Hospital, Hsinchu,

Taiwan.

(4)Department of Radiology, College of Medicine, National Taiwan University,

Taipei, Taiwan; Department of Medical Imaging, National Taiwan University

Hospital, Taipei, Taiwan.

(5)Institute of Statistical Science, Academia Sinica, Taipei, Taiwan; Institute

of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli,

Taiwan.

(6)Division of Critical Care and Respiratory Therapy, Taichung Veterans General

Hospital, Taichung, Taiwan.

(7)Department of Surgery, Division of Thoracic Surgery, Taipei Medical

University Hospital, Taipei Medical University, Taipei, Taiwan; Department of

Surgery, Division of Thoracic Surgery, School of Medicine, College of Medicine,

Taipei Medical University, Taipei, Taiwan.

(8)Department of Surgery, Division of Thoracic Surgery, Chung Shan Medical

University Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical

University, Taichung, Taiwan.

(9)Department of Radiology, Tri-Service General Hospital, National Defense

Medical Center, Taipei, Taiwan.

(10)School of Medicine, National Yang Ming Chiao Tung University, Taipei,

Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung

University, Taipei, Taiwan; Department of Radiology, Kaohsiung Veterans General

Hospital, Kaohsiung, Taiwan.

(11)Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital,

Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.

(12)Department of Biological Science and Technology, National Yang Ming Chiao

Tung University, Taipei, Taiwan; Division of Pulmonary and Critical Care

Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; College of

Medicine, Graduate Institute of Medicine, Kaohsiung Medical University,

Kaohsiung, Taiwan.

(13)School of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of

Respiratory and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi,

Taiwan; Department of Respiratory Care, Chang Gung University of Science and

Technology, Taoyuan, Taiwan.

(14)Department of Respiratory Therapy, China Medical University, Taichung,

Taiwan; Department of Internal Medicine, China Medical University Hospital,

Taichung, Taiwan.

(15)Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung

Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan; Chang Gung

Respirology Center of Excellence, Kaohsiung, Taiwan.

(16)Department of Oncology, National Cheng Kung University Hospital, Tainan,

Taiwan; College of Medicine, National Cheng Kung University, Tainan, Taiwan.

(17)Department of Internal Medicine, Division of Chest Medicine, Hualien Tzu Chi

Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; School of

Medicine, Tzu Chi University, Hualien, Taiwan.

(18)Department of Pulmonary Medicine, School of Medicine, College of Medicine,

Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine,

Division of Thoracic Medicine, Shuang Ho Hospital, Taipei Medical University,

Taipei, Taiwan.

(19)Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan;

School of Medicine for International Students, College of Medicine, I-Shou

University, Kaohsiung, Taiwan.

(20)Department of Medical Imaging, Taipei Medical University Hospital, Taipei

Medical University, Taipei, Taiwan.

(21)Department of Radiology, School of Medicine, College of Medicine, Taipei

Medical University, Taipei, Taiwan; Department of Radiology, Wan Fang Hospital,

Taipei Medical University, Taipei, Taiwan.

(22)Department of Radiology, Taichung Veterans General Hospital, Taichung,

Taiwan.

(23)School of Medicine, National Yang Ming Chiao Tung University, Taipei,

Taiwan; Department of Radiology, Taipei Veterans General Hospital, Taipei,

Taiwan; Department of Medical Imaging, Cheng Hsin General Hospital, Taipei,

Taiwan.

(24)Department of Medical Imaging, Chung Shan Medical University Hospital,

Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung,

Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

(25)Department of Internal Medicine, Division of Pulmonary and Critical Care

Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei,

Taiwan.

(26)Department of Internal Medicine, Kaohsiung Veterans General Hospital,

Kaohsiung, Taiwan.

(27)Department of Internal Medicine, College of Medicine, National Taiwan

University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan

University Hospital, Taipei, Taiwan.

(28)Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital,

Taoyuan, Taiwan; Department of Respiratory Therapy, Chang Gung University,

Taoyuan, Taiwan.

(29)Department of Medical Imaging, Kaohsiung Medical University Hospital,

Kaohsiung, Taiwan; Department of Radiology, School of Medicine, Kaohsiung

Medical University, Kaohsiung, Taiwan.

(30)Department of Internal Medicine, Division of Pulmonary Medicine, Chung Shan

Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan

Medical University, Taichung, Taiwan; Department of Internal Medicine, Division

of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan;

Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan.

(31)School of Medicine, National Yang Ming Chiao Tung University, Taipei,

Taiwan; Department of Radiology, Taipei Veterans General Hospital, Taipei,

Taiwan; Division of Cardiopulmonary Radiology, Taipei Veterans General Hospital,

Taipei, Taiwan.

(32)Department of Surgery, Division of Thoracic Surgery, Chung Shan Medical

University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical

University, Taichung, Taiwan.

(33)Department of Internal Medicine, Division of Pulmonary and Critical Care

Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei,

Taiwan; Department of Medical Planning, Medical Affairs Bureau Ministry of

National Defense, Taipei, Taiwan.

(34)Department of Surgery, Division of Thoracic Surgery, Kaohsiung Veterans

General Hospital, Kaohsiung, Taiwan; Shu-Zen Junior College of Medicine and

Management, Kaohsiung, Taiwan.

(35)Institute of Clinical Medicine, National Yang Ming Chiao Tung University,

Taipei, Taiwan; Department of Pathology, Taipei Medical University Hospital,

Taipei Medical University, Taipei, Taiwan.

(36)Artificial Intelligence Center, Chung Shan Medical University Hospital,

Taichung, Taiwan; Department of Medical Informatics, Chung Shan Medical

University, Taichung, Taiwan.

(37)Department of Respiratory Therapy, Chang Gung University, Taoyuan, Taiwan;

Department of Pulmonary and Critical Care, Xiamen Chang Gung Hospital, Xiamen,

China.

(38)Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan;

Cathay General Hospital, Taipei, Taiwan.

(39)School of Medicine, National Yang Ming Chiao Tung University, Taipei,

Taiwan; Department of Chest Medicine, Taipei Veterans General Hospital, Taipei,

Taiwan.

(40)Department of Chest Medicine, Taipei Veterans General Hospital, Taipei,

Taiwan; Department of Pulmonary Medicine, West Garden Hospital, Taipei, Taiwan.

(41)Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.

(42)Department of Clinical Laboratory Sciences and Medical Biotechnology,

College of Medicine, National Taiwan University, Taipei, Taiwan.

(43)Genomics Research Center, Academia Sinica, Taipei, Taiwan.

(44)Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial

Hospital, Taoyuan, Taiwan; Department of Medical Imaging and Radiological

Sciences, Chang Gung University, Taoyuan, Taiwan.

(45)Institute of Population Health Sciences, National Health Research

Institutes, Miaoli, Taiwan.

(46)Department of Internal Medicine, College of Medicine, National Taiwan

University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan

University Hospital, Taipei, Taiwan; Institute of Biomedical Sciences, Academia

Sinica, Taipei, Taiwan. Electronic address: pcyang@ntu.edu.tw.

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of

whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the

efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk

factors for lung cancer.

METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a

nationwide, multicentre, prospective cohort study done at 17 tertiary medical

centres in Taiwan. Eligible individuals had negative chest radiography, were

aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and

stopped smoking for more than 15 years (self-report), and had one of the

following risk factors: a family history of lung cancer; passive smoke exposure;

a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders;

a cooking index of 110 or higher; or cooking without using ventilation. Eligible

participants underwent LDCT at baseline, then annually for 2 years, and then

every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT

scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or

part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass

nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through

invasive procedures, such as image-guided aspiration or biopsy or surgery. Here,

we report the results of 1-year follow-up after LDCT screening at baseline. The

primary outcome was lung cancer detection rate. The p value for detection rates

was estimated by the χ2 test. Univariate and multivariable logistic regression

analyses were used to assess the association between lung cancer incidence and

each risk factor. The sensitivity, specificity, positive predictive value (PPV),

and negative predictive value (NPV) of LDCT screening were also assessed. This

study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing.

FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868

females) were enrolled, of whom 6009 had a family history of lung cancer. Among

12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was

diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had

invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318

participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The

prevalence of invasive lung cancer was higher among participants with a family

history of lung cancer (161 [2·7%] of 6009 participants) than in those without

(96 [1·6%] of 6002 participants). In participants with a family history of lung

cancer, the detection rate of invasive lung cancer increased significantly with

age, whereas the detection rate of adenocarcinoma in situ remained stable. In

multivariable analysis, female sex, a family history of lung cancer, and age

older than 60 years were associated with an increased risk of lung cancer and

invasive lung cancer; passive smoke exposure, cumulative exposure to cooking,

cooking without ventilation, and a previous history of chronic lung diseases

were not associated with lung cancer, even after stratification by family

history of lung cancer. In participants with a family history of lung cancer,

the higher the number of first-degree relatives affected, the higher the risk of

lung cancer; participants whose mother or sibling had lung cancer were also at

an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6%

specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis.

INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year

after baseline LDCT scan. Overdiagnosis could have occurred, especially in

participants diagnosed with adenocarcinoma in situ. In individuals who do not

smoke, our findings suggest that a family history of lung cancer among

first-degree relatives significantly increases the risk of lung cancer as well

as the rate of invasive lung cancer with increasing age. Further research on

risk factors for lung cancer in this population is needed, particularly for

those without a family history of lung cancer.

FUNDING: Ministry of Health and Welfare of Taiwan.

Copyright © 2023 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S2213-2600(23)00338-7

PMID: 38042167

Conflict of interest statement: Declaration of interests We declare no competing

interests.

15. Nat Microbiol. 2023 Nov;8(11):2080-2092. doi: 10.1038/s41564-023-01503-x. Epub 2023 Oct 9.

Intravenous Bacille Calmette-Guérin vaccination protects simian immunodeficiency

virus-infected macaques from tuberculosis.

Larson EC(1)(2), Ellis-Connell AL(3), Rodgers MA(4), Gubernat AK(4), Gleim

JL(4), Moriarty RV(3), Balgeman AJ(3), Ameel CL(4), Jauro S(4), Tomko JA(4),

Kracinovsky KB(4), Maiello P(4), Borish HJ(4), White AG(4), Klein E(5), Bucsan

AN(6), Darrah PA(6), Seder RA(6), Roederer M(6), Lin PL(7), Flynn JL(4)(8),

O'Connor SL(3)(9), Scanga CA(4)(8).

Author information:

(1)Department of Microbiology and Molecular Genetics, School of Medicine,

University of Pittsburgh, Pittsburgh, PA, USA. erl72@pitt.edu.

(2)Center for Vaccine Research, School of Medicine, University of Pittsburgh,

Pittsburgh, PA, USA. erl72@pitt.edu.

(3)Department of Pathology and Laboratory Medicine, University of Wisconsin,

Madison, WI, USA.

(4)Department of Microbiology and Molecular Genetics, School of Medicine,

University of Pittsburgh, Pittsburgh, PA, USA.

(5)Division of Laboratory Animal Resources, School of Medicine, University of

Pittsburgh, Pittsburgh, PA, USA.

(6)Vaccine Research Center, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, MD, USA.

(7)Department of Pediatrics, Children's Hospital of Pittsburgh, School of

Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

(8)Center for Vaccine Research, School of Medicine, University of Pittsburgh,

Pittsburgh, PA, USA.

(9)Wisconsin National Primate Research Center, University of Wisconsin, Madison,

WI, USA.

Update of Res Sq. 2023 Apr 17;:

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the most common

cause of death in people living with human immunodeficiency virus (HIV).

Intra-dermal Bacille Calmette-Guérin (BCG) delivery is the only licensed vaccine

against tuberculosis; however, it offers little protection from pulmonary

tuberculosis in adults and is contraindicated in people living with HIV.

Intravenous BCG confers protection against Mtb infection in rhesus macaques; we

hypothesized that it might prevent tuberculosis in simian immunodeficiency virus

(SIV)-infected macaques, a model for HIV infection. Here intravenous

BCG-elicited robust airway T cell influx and elevated plasma and airway antibody

titres in both SIV-infected and naive animals. Following Mtb challenge, all 7

vaccinated SIV-naive and 9 out of 12 vaccinated SIV-infected animals were

protected, without any culturable bacteria detected from tissues. Peripheral

blood mononuclear cell responses post-challenge indicated early clearance of Mtb

in vaccinated animals, regardless of SIV infection. These data support that

intravenous BCG is immunogenic and efficacious in SIV-infected animals.

© 2023. The Author(s).

DOI: 10.1038/s41564-023-01503-x

PMCID: PMC10627825

PMID: 37814073 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.

16. Radiology. 2023 Nov;309(2):e231988. doi: 10.1148/radiol.231988.

A 20-year Follow-up of the International Early Lung Cancer Action Program

(I-ELCAP).

Henschke CI(#)(1), Yip R(#)(1), Shaham D(1), Markowitz S(1), Cervera Deval J(1),

Zulueta JJ(1), Seijo LM(1), Aylesworth C(1), Klingler K(1), Andaz S(1), Chin

C(1), Smith JP(1), Taioli E(1), Altorki N(1), Flores RM(1), Yankelevitz DF(1);

International Early Lung Cancer Action Program Investigators(1).

Collaborators: Henschke CI, Yankelevitz DF, Yip R, Jirapatnakul A, Flores R,

Kaufman A, Wolf A, Nicastri D, Harkin T, Zulueta JJ, Taioli E, Reeves AP,

Altorki NK, Smith JP, Libby DM, Pasmantier M, Markowitz S, Miller A, Cervera

Deval J, Shaham D, Seijo L, Bastarika G, Montuenga LM, Aylesworth C, Klingler K,

Schöb O, Andaz S, Straznicka M, Chin C, Weiser T, Sone S, Hanaoka T, Roberts H,

Patsios D, Scopetuolo M, Brown A, Bauer T, Canitano S, Giunta S, Wu N, Cole E,

Meyers P, Yeh D, Luedke D, Liu X, Herzog G, Aye R, Rifkin M, Veronesi G, Infante

M, Vafai D, Kopel S, Taylor J, Thurer R, Villamizar N, Austin JHM, Pearson GDN,

Klippenstein D, Litwin A, Loud PA, Kohman LJ, Scalzetti EM, Khan A, Shah R,

Mayfield W, Frumiento C, Smith MV, Thorsen MK, Hansen R, Naidich D, McGuinness

G, Widmann M, Korst R, Lowry J, Salvatore M, Walsh J, Bertsch D, Scheinberg P,

Sheppard B, Cecchi G, Ginsberg MS, Slater D, Welch L, Grannis F, Rotter A,

Connery C, Matalon TAS, Cheung EH, Glassberg R, Olsen D, Mullen D, Odzer SL,

Wiernik PH, Ray D, DeCunzo L, Cohen S, Pass H, Endress C, Vacca A, Kondapaneni

M, Lim M, Kalafer M, Green J, Yoder M, Shah P, Camacho E, O'Brien J, Willey JC,

Rifkin M, Gordon D, Koch A.

Author information:

(1)From the Department of Diagnostic, Molecular, and Interventional Radiology

(C.I.H., R.Y., D.F.Y.), Institute of Translational Epidemiology (E.T.), and

Department of Thoracic Surgery (R.M.F.), Icahn School of Medicine at Mount

Sinai, One Gustave L. Levy Pl, New York, NY 10029; Department of Radiology,

Phoenix Veterans Affairs Health Care System, Phoenix, Ariz (C.I.H.); Department

of Radiology, Hadassah Medical Center, Jerusalem, Israel (D.S.); Faculty of

Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (D.S.); Barry

Commoner Center for Health and the Environment, Queens College City University

of New York, Queens, NY (S.M.); Department of Radiology, Fundación Instituto

Valenciano de Oncología, Valencia, Spain (J.C.D.); Department of Pulmonary,

Critical Care and Sleep Medicine, Mount Sinai West, New York, NY (J.J.Z.);

Department of Pulmonology, Clínica Universidad de Navarra, Pamplona, Spain

(J.J.Z., L.M.S.); Department of Hematology and Oncology, Holy Cross Hospital

Cancer Institute, Silver Spring, Md (C.A.); Department of Pulmonology and Sleep

Medicine Clinic Hirslanden, LungenZentrum Hirslanden, Zurich, Switzerland

(K.K.); Department of Thoracic Surgery, Mount Sinai South Nassau, Oceanside, NY

(S.A.); Department of Thoracic Surgery, Montefiore St Luke's Cornwall, Cornwall,

NY (C.C.); Departments of Pulmonology (J.P.S.) and Surgery (N.A.), Weill Cornell

Medical College, New York, NY; and Department of Thoracic Surgery, Tisch Cancer

Center, New York, NY (E.T.).

(#)Contributed equally

Comment in

    Radiology. 2023 Nov;309(2):e232698.

    Radiology. 2023 Nov;309(2):e232850.

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer

Action Program (ELCAP) participants in 1999 led to the International ELCAP

(I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose

CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the

10-year lung cancer-specific survival of 80% for 484 participants diagnosed with

a first primary lung cancer through annual screening, with a high frequency of

clinical stage I lung cancer (85%). Purpose To update the cure rate by

determining the 20-year lung cancer-specific survival of participants diagnosed

with first primary lung cancer through annual low-dose CT screening in the

expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the

HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed

until December 30, 2022, Kaplan-Meier survival analysis was used to determine

the 10- and 20-year lung cancer-specific survival of participants diagnosed with

first primary lung cancer through annual low-dose CT screening. Eligible

participants were aged at least 40 years and had current or former cigarette use

or had never smoked but had been exposed to secondhand tobacco smoke. Results

Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first

primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72),

with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median

follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage

I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific

survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung

cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91,

98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The

10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP

participants enrolled in annual low-dose CT screening and diagnosed with a first

primary lung cancer has persisted, as shown by the updated 20-year lung

cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also

the editorials by Grenier and by Sequist and Olazagasti in this issue.

DOI: 10.1148/radiol.231988

PMCID: PMC10698500

PMID: 37934099 [Indexed for MEDLINE]

Conflict of interest statement: Disclosures of conflicts of interest: C.I.H. On

the advisory board of LungLife AI; named inventor on patents and patent

applications owned by Cornell Research Foundation; president and serves on the

board of the Early Diagnosis and Treatment Research Foundation. R.Y. No relevant

relationships. D.S. Payment from AstraZeneca made through the institution for

lecturing and organizing an educational event. S.M. No relevant relationships.

J.C.D. No relevant relationships. J.J.Z. Consulting fees from American Heart

Technologies and Median Technologies for service on the medical advisory board;

small amount of equity from American Heart Technologies. L.M.S. Grants from

Serum Median Technologies, SEPAR (Spanish Thoracic Society), and SOLACE

(Strengthening the Screening of Lung Cancer in Europe) Consortium (Funded by

EU4Health); consulting fees from Sabartech, Serum Median Technologies, and Lung

Ambition Alliance; honoraria from AstraZeneca, Merck Sharp & Dohme, Roche, Grupo

Español de Cáncer de Pulmón, Menarini, GlaxoSmithKline, and Chiesi Fundación

Respira; support for attending meetings from AstraZeneca; participation on the

Serum Median Technologies and Lung Ambition Alliance DataSafety Monitoring Board

or advisory board; leadership or fiduciary role in SEPAR (Spanish Thoracic

Society). C.A. No relevant relationships. K.K. No relevant relationships. S.A.

No relevant relationships. C.C. No relevant relationships. J.P.S. No relevant

relationships. E.T. No relevant relationships. N.A. Grants NCI/UH3CA244697,

NIH/NCILC200388, AstraZeneca: Investigator-Initiated Clinical Trial, New York

Genome Center LC200388, NIH/R01 CA271545-01A1, and NIH/U54 CA272688-01;

honoraria from Peer View, AstraZeneca, Roche, and Regeneron. R.M.F. No relevant

relationships. D.F.Y. Royalties from HeartLung and General Electric; consulting

fees from Genentech, AstraZeneca, and Pfizer; named inventor on patents and

patent applications owned by General Electric; on the advisory board of

HeartLung, on the medical advisory boards of Median Technology and Carestream;

consultant and co-owner of Accumetra; owns equity in HeartLung.

17. J Am Chem Soc. 2023 Nov 8;145(44):24153-24165. doi: 10.1021/jacs.3c08032. Epub 2023 Oct 28.

Nebulized Therapy of Early Orthotopic Lung Cancer by Iron-Based Nanoparticles:

Macrophage-Regulated Ferroptosis of Cancer Stem Cells.

Feng Q(1), Fang W(2), Guo Y(1), Hu P(1)(2), Shi J(2).

Author information:

(1)Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of

Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai 200331,

P. R. China.

(2)Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of

Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy

of Medical Sciences (2021RU012), Shanghai 200050, P. R. China.

Cancer stem cells (CSCs) within protumorigenic microlesions are a critical

driver in the initiation and progression of early stage lung cancer, where

immune cells provide an immunosuppressive niche to strengthen the CSC stemness.

As the mutual interactions between CSCs and immune cells are increasingly

recognized, regulating the immune cells to identify and effectively eliminate

CSCs has recently become one of the most attractive therapeutic options,

especially for abundant tumor-associated macrophages (TAMs). Herein, we

developed a nebulized nanocatalytic medicine strategy in which iron-based

nanoparticle-regulated TAMs effectively target CSC niches and trigger CSC

ferroptosis in the early stage of lung cancer. Briefly, the iron-based

nanoparticles can effectively accumulate in lung cancer microlesions (minimum

122 μm in diameter) through dextran-mediated TAM targeting by nebulization

administration, and as a result, nanoparticle-internalized TAMs can play a

predominant role of the iron factory in elevating the iron level surrounding CSC

niches and destroying redox equilibrium through downregulating

glucose-6-phosphate metabolite following their lysosomal degradation and iron

metabolism. The altered microenvironment results in the enhanced sensitivity of

CSCs to ferroptosis due to their high expression of the CD44 receptor mediating

iron endocytosis. In an orthotopic mouse model of lung cancer, the initiation

and progression of early lung cancer are significantly suppressed through

ferroptosis-induced stemness reduction of CSCs by nebulization administration.

This work presents a nebulized therapeutic strategy for early lung cancer

through modulation of communications between TAMs and CSCs, which is expected to

be a general approach for regulating primary microlesions and micrometastatic

niches of lung cancer.

DOI: 10.1021/jacs.3c08032

PMID: 37897426 [Indexed for MEDLINE]

18. JAMA Netw Open. 2023 Nov 1;6(11):e2342681. doi: 10.1001/jamanetworkopen.2023.42681.

Patient Preferences for Lung Cancer Interception Therapy.

Janssen EM(1), Smith IP(1)(2), Liu X(3), Pierce A(3), Huang Q(2), Kalsekar I(2),

Vachani A(4), Mansfield C(3).

Author information:

(1)Global Epidemiology, Janssen Research and Development, Titusville, New

Jersey.

(2)Interventional Oncology, Johnson & Johnson External Innovation, New

Brunswick, New Jersey.

(3)RTI Health Solutions, Research Triangle Park, North Carolina.

(4)University of Pennsylvania Perelman School of Medicine, Philadelphia.

IMPORTANCE: Interception therapy requires individuals to undergo treatment to

prevent a future medical event, but little is known about preferences of

individuals at high risk for lung cancer and whether they would be interested in

this type of treatment.

OBJECTIVE: To explore preferences of individuals at high risk for lung cancer

for potential interception therapies to reduce this risk.

DESIGN, SETTING, AND PARTICIPANTS: This survey study used a discrete-choice

experiment and included hypothetical lung cancer interception treatments with 4

attributes: reduction in lung cancer risk over 3 years, injection site reaction

severity, nonfatal serious infection, and death from serious infection.

Respondents were assigned to a baseline lung cancer risk of 6%, 10%, or 16% over

3 years. The discrete-choice experiment was administered online (July 13 to

September 6, 2022) to US respondents eligible for lung cancer screening

according to US Preventive Services Task Force guidelines. Participants included

adults aged 50 to 80 years with at least a 20 pack-year smoking history.

Statistical analysis was performed from September to December 2022.

MAIN OUTCOMES AND MEASURES: Attribute-level preference weights were estimated,

and conditional relative attribute importance, maximum acceptable risks, and

minimum acceptable benefits were calculated. Characteristics of respondents who

always selected no treatment were also explored.

RESULTS: Of the 803 survey respondents, 495 (61.6%) were female, 138 (17.2%)

were African American or Black, 55 (6.8%) were Alaska Native, American Indian,

or Native American, 44 (5.5%) were Asian or Native Hawaiian or Other Pacific

Islander, 104 (13.0%) were Hispanic, Latin American, or Latinx, and 462 (57.5%)

were White, Middle Eastern or North African, or a race or ethnicity not listed;

and mean (SD) age was 63.0 (7.5) years. Most respondents were willing to accept

interception therapy and viewed reduction in lung cancer risk as the most

important attribute. Respondents would accept a greater than or equal to a 12.0

percentage point increase in risk of nonfatal serious infection if lung cancer

risk was reduced by at least 20.0 percentage points; and a greater than or equal

to 1.2 percentage point increase in risk of fatal serious infection if lung

cancer risk was reduced by at least 30.0 percentage points. Respondents would

require at least a 15.4 (95% CI, 10.6-20.2) percentage point decrease in lung

cancer risk to accept a 12.0 percentage point increase in risk of nonfatal

serious infection; and at least a 23.1 (95% CI, 16.4-29.8) percentage point

decrease in lung cancer risk to accept a 1.2 percentage point increase in risk

of death from serious infection. Respondents who were unwilling to accept

interception therapy in any question (129 [16.1%]) were more likely to be older

and to currently smoke with no prior cessation attempt, and less likely to have

been vaccinated against COVID-19 or examined for skin cancer.

CONCLUSIONS AND RELEVANCE: In this survey study of individuals at high risk of

lung cancer, most respondents were willing to consider interception therapy.

These results suggest the importance of benefit-risk assessments for future lung

cancer interception treatments.

DOI: 10.1001/jamanetworkopen.2023.42681

PMCID: PMC10638649

PMID: 37948077 [Indexed for MEDLINE]

Conflict of interest statement: Conflict of Interest Disclosures: Dr Janssen

reported being a Johnson & Johnson employee during the conduct of the study; and

being a Johnson & Johnson stockholder and employee outside the submitted work.

Dr Smith reported personal fees from Janssen Pharmaceutical outside the

submitted work. Dr Liu reported being a full-time employee of RTI Health

Solutions and compensation was unconnected to the projects on which Dr Liu

worked during the conduct of the study. Dr Pierce reported being a full-time

employee of RTI Health Solutions and compensation was unconnected to the

projects on which Dr Pierce worked during the conduct of the study. Dr Huang

reported receiving salary and stocks from Johnson & Johnson outside the

submitted work. Dr Kalsekar reported being a Johnson & Johnson employee during

the conduct of the study. Dr Vachani reported personal fees from Johnson &

Johnson during the conduct of the study; and grants from Precyte Inc, grants

from Optellum Ltd, grants from Median Technologies, personal fees from Intuitive

Surgical, and grants from National Comprehensive Cancer Network/Astra Zeneca

outside the submitted work. Dr Mansfield reported being a full-time employee of

RTI Health Solutions and compensation was unconnected to the projects on which

Dr Mansfield worked during the conduct of the study. No other disclosures were

reported.

19. Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):189025. doi: 10.1016/j.bbcan.2023.189025. Epub 2023 Nov 20.

Untangling the web of intratumor microbiota in lung cancer.

Liu W(1), Xu J(2), Pi Z(1), Chen Y(3), Jiang G(4), Wan Y(5), Mao W(6).

Author information:

(1)Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of

Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing

Medical University, Wuxi 214023, Jiangsu, China.

(2)Department of Oncology, The First Affiliated Hospital of Nanjing Medical

University, Nanjing 210029, Jiangsu, China.

(3)The Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering,

Binghamton University, Binghamton 13850, USA.

(4)Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of

Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing

Medical University, Wuxi 214023, Jiangsu, China. Electronic address:

jianggy2021@stu.njmu.edu.cn.

(5)The Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering,

Binghamton University, Binghamton 13850, USA. Electronic address:

ywan@binghamton.edu.

(6)Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of

Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing

Medical University, Wuxi 214023, Jiangsu, China. Electronic address:

maowenjun1@njmu.edu.cn.

Microbes are pivotal in contemporary cancer research, influencing various

biological behaviors in cancer. The previous notion that the lung was sterile

has been destabilized by the discovery of microbiota in the lower airway and

lung, even within tumor tissues. Advances of biotechnology enable the

association between intratumor microbiota and lung cancer to be revealed.

Nonetheless, the origin and tumorigenicity of intratumor microbiota in lung

cancer still remain implicit. Additionally, accumulating evidence indicates that

intratumor microbiota might serve as an emerging biomarker for cancer diagnosis,

prognosis, and even a therapeutic target across multiple cancer types, including

lung cancer. However, research on intratumor microbiota's role in lung cancer is

still nascent and warrants more profound exploration. Herein, this paper

provides an extensive review of recent advancements in the following fields,

including 1) established and emerging biotechnologies utilized to study

intratumor microbiota in lung cancer, 2) causation between intratumor microbiota

and lung cancer from the perspectives of translocation, cancerogenesis and

metastasis, 3) potential application of intratumor microbiota as a novel

biomarker for lung cancer diagnosis and prognosis, and 4) promising lung cancer

therapies via regulating intratumor microbiota. Moreover, this review addresses

the limitations, challenges, and future prospects of studies focused on

intratumor microbiota in lung cancer.

Copyright © 2023. Published by Elsevier B.V.

DOI: 10.1016/j.bbcan.2023.189025

PMID: 37980944 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest The authors

declare that they have no competing interests.

20. JAMA Netw Open. 2023 Nov 1;6(11):e2343278. doi: 10.1001/jamanetworkopen.2023.43278.

Second Primary Lung Cancer Among Lung Cancer Survivors Who Never Smoked.

Choi E(1), Su CC(1)(2), Wu JT(3), Aredo JV(4), Neal JW(3)(5), Leung AN(6),

Backhus LM(7), Lui NS(7), Le Marchand L(8), Stram DO(9), Liang SY(10), Cheng

I(11), Wakelee HA(3)(5), Han SS(1)(2)(5)(12).

Author information:

(1)Quantitative Sciences Unit, Stanford University School of Medicine, Stanford,

California.

(2)Department of Epidemiology and Population Health, Stanford University School

of Medicine, Stanford, California.

(3)Department of Medicine, Stanford University School of Medicine, Stanford,

California.

(4)Department of Medicine, University of California, San Francisco.

(5)Stanford Cancer Institute, Stanford, California.

(6)Department of Radiology, Stanford University School of Medicine, Stanford,

California.

(7)Department of Cardiothoracic Surgery, Stanford University School of Medicine,

Stanford, California.

(8)Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu.

(9)Department of Preventive Medicine, Keck School of Medicine, University of

Southern California, Los Angeles.

(10)Sutter Health, Palo Alto Medical Foundation Research Institute, Palo Alto,

California.

(11)Department of Epidemiology and Biostatistics, University of California, San

Francisco.

(12)Department of Neurosurgery, Stanford University School of Medicine,

Stanford, California.

IMPORTANCE: Lung cancer among never-smokers accounts for 25% of all lung cancers

in the US; recent therapeutic advances have improved survival among patients

with initial primary lung cancer (IPLC), who are now at high risk of developing

second primary lung cancer (SPLC). As smoking rates continue to decline in the

US, it is critical to examine more closely the epidemiology of lung cancer among

patients who never smoked, including their risk for SPLC.

OBJECTIVE: To estimate and compare the cumulative SPLC incidence among lung

cancer survivors who have never smoked vs those who have ever smoked.

DESIGN, SETTING, AND PARTICIPANTS: This population-based prospective cohort

study used data from the Multiethnic Cohort Study (MEC), which enrolled

participants between April 18, 1993, and December 31, 1996, with follow-up

through July 1, 2017. Eligible individuals for this study were aged 45 to 75

years and had complete smoking data at baseline. These participants were

followed up for IPLC and further SPLC development through the Surveillance,

Epidemiology, and End Results registry. The data were analyzed from July 1,

2022, to January 31, 2023.

EXPOSURES: Never-smoking vs ever-smoking exposure at MEC enrollment.

MAIN OUTCOMES AND MEASURES: The study had 2 primary outcomes: (1) 10-year

cumulative incidence of IPLC in the entire study cohort and 10-year cumulative

incidence of SPLC among patients with IPLC and (2) standardized incidence ratio

(SIR) (calculated as the SPLC incidence divided by the IPLC incidence) by

smoking history.

RESULTS: Among 211 414 MEC participants, 7161 (3.96%) developed IPLC over

4 038 007 person-years, and 163 (2.28%) developed SPLC over 16 470 person-years.

Of the participants with IPLC, the mean (SD) age at cohort enrollment was 63.6

(7.7) years, 4031 (56.3%) were male, and 3131 (43.7%) were female. The 10-year

cumulative IPLC incidence was 2.40% (95% CI, 2.31%-2.49%) among ever-smokers,

which was 7 times higher than never-smokers (0.34%; 95% CI, 0.30%-0.37%).

However, the 10-year cumulative SPLC incidence following IPLC was as high among

never-smokers (2.84%; 95% CI, 1.50%-4.18%) as ever-smokers (2.72%; 95% CI,

2.24%-3.20%), which led to a substantially higher SIR for never-smokers (14.50;

95% CI, 8.73-22.65) vs ever-smokers (3.50; 95% CI, 2.95-4.12).

CONCLUSIONS AND RELEVANCE: The findings indicate that SPLC risk among lung

cancer survivors who never smoked is as high as among those with IPLC who

ever-smoked, highlighting the need to identify risk factors for SPLC among

patients who never smoked and to develop a targeted surveillance strategy.

DOI: 10.1001/jamanetworkopen.2023.43278

PMCID: PMC10652150

PMID: 37966839 [Indexed for MEDLINE]

Conflict of interest statement: Conflict of Interest Disclosures: Ms Su reported

a summer internship from ZS Associates, Inc outside the submitted work. Dr Neal

reported receiving personal fees and grants from the American Society of

Clinical Oncology outside the submitted work. Dr Backhus reported serving on

advisory boards for AstraZeneca and Genentech outside the submitted work. Dr Lui

reported receiving personal fees from Intuitive Surgical and grants from

Intuitive Foundation, Centese, and Auspex outside the submitted work. Dr Wakelee

reported receiving grants paid to her institution from Arrys, Bayer,

AstraZeneca, Bristol Myers Squibb, Clovis, Genentech/Roche, Merck, Novartis,

SeaGen, Xcovery, and Helsinn and personal fees for data safety and monitoring

committee service from Mirati outside the submitted work. No other disclosures

were reported.