KOBV Portal

Hits per page

hits 1 - 10 | 11 hits

Sorting

Online Resource

Table_1.xlsx

Elnaggar, Jacob H. ; Huynh, Victoria O. ; Lin, Daniel ; [et al.]

Frontiers Media SA ; 2023

In: Frontiers in Immunology Vol. 14 ( 2023-3-29)

add to watchlist on the watchlist

Details

In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-29)

Abstract: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. Methods Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer. Results 60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p = 0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295) , Porphyromonas (p=0.034) , and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal. Conclusion Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal Peptoniphilus, Fusobacteria , Porphyromonas , and Prevotella abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.

Type of Medium: Online Resource

ISSN: 1664-3224

URL: Article

DOI: 10.3389/fimmu.2023.1051431

DOI: 10.3389/fimmu.2023.1051431.s001

DOI: 10.3389/fimmu.2023.1051431.s002

DOI: 10.3389/fimmu.2023.1051431.s003

DOI: 10.3389/fimmu.2023.1051431.s004

DOI: 10.3389/fimmu.2023.1051431.s005

DOI: 10.3389/fimmu.2023.1051431.s006

DOI: 10.3389/fimmu.2023.1051431.s007

DOI: 10.3389/fimmu.2023.1051431.s008

DOI: 10.3389/fimmu.2023.1051431.s009

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2023

detail.hit.zdb_id: 2606827-8

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

ATR Inhibitor M6620 (VX-970) Enhances the Effect of Radiation in Non–Small Cell Lung Cancer Brain Metastasis Patient-Derived Xenografts

Baschnagel, Andrew M. ; Elnaggar, Jacob H. ; VanBeek, Haley J. ; [et al.]

American Association for Cancer Research (AACR) ; 2021

In: Molecular Cancer Therapeutics Vol. 20, No. 11 ( 2021-11-01), p. 2129-2139

add to watchlist on the watchlist

Details

In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 20, No. 11 ( 2021-11-01), p. 2129-2139

Abstract: M6620, a selective ATP-competitive inhibitor of the ATM and RAD3-related (ATR) kinase, is currently under investigation with radiation in patients with non–small cell lung cancer (NSCLC) brain metastases. We evaluated the DNA damage response (DDR) pathway profile of NSCLC and assessed the radiosensitizing effects of M6620 in a preclinical NSCLC brain metastasis model. Mutation analysis and transcriptome profiling of DDR genes and pathways was performed on NSCLC patient samples. NSCLC cell lines were assessed with proliferation, clonogenic survival, apoptosis, cell cycle, and DNA damage signaling and repair assays. NSCLC brain metastasis patient-derived xenograft models were used to assess intracranial response and overall survival. In vivo IHC was performed to confirm in vitro results. A significant portion of NSCLC patient tumors demonstrated enrichment of DDR pathways. DDR pathways correlated with lung squamous cell histology; and mutations in ATR, ATM, BRCA1, BRCA2, CHEK1, and CHEK2 correlated with enrichment of DDR pathways in lung adenocarcinomas. M6620 reduced colony formation after radiotherapy and resulted in inhibition of DNA DSB repair, abrogation of the radiation-induced G2 cell checkpoint, and formation of dysfunctional micronuclei, leading to enhanced radiation-induced mitotic death. The combination of M6620 and radiation resulted in improved overall survival in mice compared with radiation alone. In vivo IHC revealed inhibition of pChk1 in the radiation plus M6620 group. M6620 enhances the effect of radiation in our preclinical NSCLC brain metastasis models, supporting the ongoing clinical trial (NCT02589522) evaluating M6620 in combination with whole brain irradiation in patients with NSCLC brain metastases.

Type of Medium: Online Resource

ISSN: 1535-7163 , 1538-8514

URL: Article

DOI: 10.1158/1535-7163.MCT-21-0305

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2021

detail.hit.zdb_id: 2062135-8

SSG: 12

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Microbiome Dynamics During Chemoradiation Therapy for Anal Cancer

Lin, Daniel ; El Alam, Molly B. ; Jaoude, Joseph Abi ; [et al.]

Elsevier BV ; 2022

In: International Journal of Radiation Oncology*Biology*Physics Vol. 113, No. 5 ( 2022-08), p. 974-984

add to watchlist on the watchlist

Details

In: International Journal of Radiation Oncology*Biology*Physics, Elsevier BV, Vol. 113, No. 5 ( 2022-08), p. 974-984

Type of Medium: Online Resource

ISSN: 0360-3016

URL: Article

DOI: 10.1016/j.ijrobp.2022.04.037

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 1500486-7

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Precision Combination Therapies Based on Recurrent Oncogenic Coalterations

Li, Xubin ; Dowling, Elisabeth K. ; Yan, Gonghong ; [et al.]

American Association for Cancer Research (AACR) ; 2022

In: Cancer Discovery Vol. 12, No. 6 ( 2022-06-02), p. 1542-1559

add to watchlist on the watchlist

Details

In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 12, No. 6 ( 2022-06-02), p. 1542-1559

Abstract: Cancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Here, we provide a comprehensive resource of precision combination therapies tailored to oncogenic coalterations that are recurrent across patient cohorts. To generate the resource, we developed Recurrent Features Leveraged for Combination Therapy (REFLECT), which integrates machine learning and cancer informatics algorithms. Using multiomic data, the method maps recurrent coalteration signatures in patient cohorts to combination therapies. We validated the REFLECT pipeline using data from patient-derived xenografts, in vitro drug screens, and a combination therapy clinical trial. These validations demonstrate that REFLECT-selected combination therapies have significantly improved efficacy, synergy, and survival outcomes. In patient cohorts with immunotherapy response markers, DNA repair aberrations, and HER2 activation, we have identified therapeutically actionable and recurrent coalteration signatures. REFLECT provides a resource and framework to design combination therapies tailored to tumor cohorts in data-driven clinical trials and preclinical studies. Significance: We developed the predictive bioinformatics platform REFLECT and a multiomics- based precision combination therapy resource. The REFLECT-selected therapies lead to significant improvements in efficacy and patient survival in preclinical and clinical settings. Use of REFLECT can optimize therapeutic benefit through selection of drug combinations tailored to molecular signatures of tumors. See related commentary by Pugh and Haibe-Kains, p. 1416. This article is highlighted in the In This Issue feature, p. 1397

Type of Medium: Online Resource

ISSN: 2159-8274 , 2159-8290

URL: Article

DOI: 10.1158/2159-8290.CD-21-0832

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2022

detail.hit.zdb_id: 2607892-2

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Characterization of Vaginal Microbial Community Dynamics in the Pathogenesis of Incident Bacterial Vaginosis, a Pilot Study

Elnaggar, Jacob H. ; Lammons, John W. ; Taylor, Christopher M. ; [et al.]

Ovid Technologies (Wolters Kluwer Health) ; 2023

In: Sexually Transmitted Diseases Vol. 50, No. 8 ( 2023-8), p. 523-530

add to watchlist on the watchlist

Details

In: Sexually Transmitted Diseases, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 8 ( 2023-8), p. 523-530

Abstract: Despite more than 60 years of research, the etiology of bacterial vaginosis (BV) remains controversial. In this pilot study, we used shotgun metagenomic sequencing to characterize vaginal microbial community changes before the development of incident BV (iBV). Methods A cohort of African American women with a baseline healthy vaginal microbiome (no Amsel criteria, Nugent score 0–3 with no Gardnerella vaginalis morphotypes) were followed for 90 days with daily self-collected vaginal specimens for iBV (≥2 consecutive days of a Nugent score of 7–10). Shotgun metagenomic sequencing was performed on select vaginal specimens from 4 women, every other day for 12 days before iBV diagnosis. Sequencing data were analyzed through Kraken2 and bioBakery 3 workflows, and specimens were classified into community state types. Quantitative polymerase chain reaction was performed to compare the correlation of read counts with bacterial abundance. Results Common BV-associated bacteria such as G. vaginalis , Prevotella bivia , and Fannyhessea vaginae were increasingly identified in the participants before iBV. Linear modeling indicated significant increases in G. vaginalis and F . vaginae relative abundance before iBV, whereas the relative abundance of Lactobacillus species declined over time. The Lactobacillus species decline correlated with the presence of Lactobacillus phages. We observed enrichment in bacterial adhesion factor genes on days before iBV. There were also significant correlations between bacterial read counts and abundances measured by quantitative polymerase chain reaction. Conclusions This pilot study characterizes vaginal community dynamics before iBV and identifies key bacterial taxa and mechanisms potentially involved in the pathogenesis of iBV.

Type of Medium: Online Resource

ISSN: 1537-4521 , 0148-5717

URL: Article

DOI: 10.1097/OLQ.0000000000001821

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2023

detail.hit.zdb_id: 2055170-8

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

State of the Art for Diagnosis of Bacterial Vaginosis

Muzny, Christina A. ; Cerca, Nuno ; Elnaggar, Jacob H. ; [et al.]

American Society for Microbiology ; 2023

In: Journal of Clinical Microbiology

add to watchlist on the watchlist

Details

In: Journal of Clinical Microbiology, American Society for Microbiology

Abstract: Bacterial vaginosis (BV) is the most common cause of vaginal discharge among reproductive-age women. It is associated with multiple adverse health outcomes, including increased risk of acquisition of HIV and other sexually transmitted infections (STIs), in addition to adverse birth outcomes. While it is known that BV is a vaginal dysbiosis characterized by a shift in the vaginal microbiota from protective Lactobacillus species to an increase in facultative and strict anaerobic bacteria, its exact etiology remains unknown. The purpose of this minireview is to provide an updated overview of the range of tests currently used for the diagnosis of BV in both clinical and research settings. This article is divided into two primary sections: traditional BV diagnostics and molecular diagnostics. Molecular diagnostic assays, particularly 16S rRNA gene sequencing, shotgun metagenomic sequencing, and fluorescence in situ hybridization (FISH), are specifically highlighted, in addition to multiplex nucleic acid amplification tests (NAATs), given their increasing use in clinical practice (NAATs) and research studies (16S rRNA gene sequencing, shotgun metagenomic sequencing, and FISH) regarding the vaginal microbiota and BV pathogenesis. We also provide a discussion of the strengths and weaknesses of current BV diagnostic tests and discuss future challenges in this field of research.

Type of Medium: Online Resource

ISSN: 0095-1137 , 1098-660X

URL: Article

DOI: 10.1128/jcm.00837-22

RVK:

XA 10000

Language: English

Publisher: American Society for Microbiology

Publication Date: 2023

detail.hit.zdb_id: 1498353-9

SSG: 12

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Table_1.xlsx

Elnaggar, Jacob H. ; Ardizzone, Caleb M. ; Cerca, Nuno ; [et al.]

Frontiers Media SA ; 2023

In: Frontiers in Cellular and Infection Microbiology Vol. 13 ( 2023-6-19)

add to watchlist on the watchlist

Details

In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 13 ( 2023-6-19)

Abstract: Bacterial vaginosis (BV) is the most common vaginal dysbiosis. In this condition, a polymicrobial biofilm develops on vaginal epithelial cells. Accurately quantifying the bacterial burden of the BV biofilm is necessary to further our understanding of BV pathogenesis. Historically, the standard for calculating total bacterial burden of the BV biofilm has been based on quantifying Escherichia coli 16S rRNA gene copy number. However, E. coli is improper for measuring the bacterial burden of this unique micro-environment. Here, we propose a novel qPCR standard to quantify bacterial burden in vaginal microbial communities, from an optimal state to a mature BV biofilm. These standards consist of different combinations of vaginal bacteria including three common BV-associated bacteria (BVAB) Gardnerella spp. (G), Prevotella spp. (P), and Fannyhessea spp. (F) and commensal Lactobacillus spp. (L) using the 16S rRNA gene (G:P:F:L, G:P:F, G:P:L and 1G:9L). We compared these standards to the traditional E. coli (E) reference standard using known quantities of mock vaginal communities and 16 vaginal samples from women. The E standard significantly underestimated the copy numbers of the mock communities, and this underestimation was significantly greater at lower copy numbers of these communities. The G:P:L standard was the most accurate across all mock communities and when compared to other mixed vaginal standards. Mixed vaginal standards were further validated with vaginal samples. This new G:P:L standard can be used in BV pathogenesis research to enhance reproducibility and reliability in quantitative measurements of BVAB, spanning from the optimal to non-optimal (including BV) vaginal microbiota.

Type of Medium: Online Resource

ISSN: 2235-2988

URL: Article

DOI: 10.3389/fcimb.2023.1198113

DOI: 10.3389/fcimb.2023.1198113.s001

DOI: 10.3389/fcimb.2023.1198113.s002

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2023

detail.hit.zdb_id: 2619676-1

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Mycoplasma decontamination in Chlamydia trachomatis culture: a curative approach

Greer, Madison ; Elnaggar, Jacob H ; Taylor, Christopher M ; [et al.]

Oxford University Press (OUP) ; 2022

In: Pathogens and Disease Vol. 79, No. 9 ( 2022-01-12)

add to watchlist on the watchlist

Details

In: Pathogens and Disease, Oxford University Press (OUP), Vol. 79, No. 9 ( 2022-01-12)

Abstract: Mycoplasma contamination of cell culture represents a serious problem in research and decontamination from cell-propagated obligate intracellular bacteria has proven challenging. Here, we presented an optimized protocol to remove Mycoplasma from contaminated Chlamydia trachomatis culture. A stepwise procedure of Mycoplasma removal entails (i) incubation in nonionic detergent-containing solution and (ii) separation of viable chlamydial organisms by fluorescence-activated cell sorting (FACS), followed by subcloning using a focus-forming assay. We also adapted a polymerase chain reaction (PCR) assay using paired universal and Mycoplasma-specific primers, which are distinguishable from the C. trachomatis counterparts, in combination with Sanger sequencing to determine the presence of mycoplasmas’ 16S rRNA genes. These integrated approaches allow for full removal of Mycoplasma, as verified by the improved PCR assay, without compromising the capacity of viable C. trachomatis to adapt to new infection in epithelial cells. Some pitfalls during the Mycoplasma decontamination process are discussed.

Type of Medium: Online Resource

ISSN: 2049-632X

URL: Article

DOI: 10.1093/femspd/ftab056

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2693712-8

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Impact of testosterone use on the vaginal microbiota of transgender men, including susceptibility to bacterial vaginosis: study protocol for a prospective, observational study

Muzny, Christina A ; Van Gerwen, Olivia T ; Schroeder, Julia A ; [et al.]

BMJ ; 2023

In: BMJ Open Vol. 13, No. 3 ( 2023-03), p. e073068-

add to watchlist on the watchlist

Details

In: BMJ Open, BMJ, Vol. 13, No. 3 ( 2023-03), p. e073068-

Abstract: The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus -dominated and more likely to be enriched with 〉 30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will identify changes in the vaginal microbiota preceding incident BV (iBV) in this cohort while investigating behavioural factors, along with hormonal shifts, which may be associated with iBV. Methods and analysis T-naïve TGM who have not undergone gender-affirming genital surgery with normal baseline vaginal microbiota (ie, no Amsel criteria, normal Nugent Score with no Gardnerella vaginalis morphotypes) will self-collect daily vaginal specimens for 7 days prior to initiating T and for 90 days thereafter. These specimens will be used for vaginal Gram stain, 16S rRNA gene sequencing and shotgun metagenomic sequencing to characterise shifts in the vaginal microbiota over time, including development of iBV. Participants will complete daily diaries on douching, menses and behavioural factors including sexual activity during the study. Ethics and dissemination This protocol is approved through the single Institutional Review Board mechanism by the University of Alabama at Birmingham. External relying sites are the Louisiana State University Health Sciences Center, New Orleans Human Research Protection Program and the Indiana University Human Research Protection Program. Study findings will be presented at scientific conferences and peer-reviewed journals as well as shared with community advisory boards at participating gender health clinics and community-based organisations servicing transgender people. Registration details Protocol # IRB-300008073.

Type of Medium: Online Resource

ISSN: 2044-6055 , 2044-6055

URL: Article

DOI: 10.1136/bmjopen-2023-073068

DOI: 10.1136/bmjopen-2023-073068.supp1

Language: English

Publisher: BMJ

Publication Date: 2023

detail.hit.zdb_id: 2599832-8

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Sunday, 26 August 2012

Kobayashi, J. ; Yoshida, M. ; Tarui, S. ; [et al.]

Oxford University Press (OUP) ; 2012

In: European Heart Journal Vol. 33, No. suppl 1 ( 2012-08-02), p. 19-338

add to watchlist on the watchlist

Details

In: European Heart Journal, Oxford University Press (OUP), Vol. 33, No. suppl 1 ( 2012-08-02), p. 19-338

Type of Medium: Online Resource

ISSN: 0195-668X , 1522-9645

URL: Article

DOI: 10.1093/eurheartj/ehs281

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2012

detail.hit.zdb_id: 2001908-7

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

hits 1 - 10 | 11 hits

Nothing or not found what you are looking for? Please check your search query or use the Interlibrary Loan Search.

Kooperativer Bibliotheksverbund

Berlin Brandenburg