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Article ; Online: The transformation of HIV therapy: One pill once a day.

Choudhary, Madhu C / Mellors, John W

2022 Volume 27, Issue 2, Page(s) 13596535211062396

Abstract: A co-formulated, one pill once a day antiretroviral regimen (single-tablet regimen), containing efavirenz, emtricitabine, and tenofovir disoproxyl fumarate ( ...

Abstract	A co-formulated, one pill once a day antiretroviral regimen (single-tablet regimen), containing efavirenz, emtricitabine, and tenofovir disoproxyl fumarate (
MeSH term(s)	Adenine/therapeutic use ; Anti-HIV Agents ; Deoxycytidine ; Drug Combinations ; HIV Infections/drug therapy ; Humans ; Organophosphonates/therapeutic use ; Tablets/therapeutic use
Chemical Substances	Anti-HIV Agents ; Drug Combinations ; Organophosphonates ; Tablets ; Deoxycytidine (0W860991D6) ; Adenine (JAC85A2161)
Language	English
Publishing date	2022-05-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1339842-8
ISSN	2040-2058 ; 1359-6535
ISSN (online)	2040-2058
ISSN	1359-6535
DOI	10.1177/13596535211062396
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Zs.A 4877: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 174: Show issues

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Article ; Online: How could HIV-1 drug resistance impact preexposure prophylaxis for HIV prevention?

Parikh, Urvi M / Mellors, John W

Current opinion in HIV and AIDS

2022 Volume 17, Issue 4, Page(s) 213–221

Abstract: Purpose of review: To review current laboratory and clinical data on the frequency and relative risk of drug resistance and range of mutations selected from approved and investigational antiretroviral agents used for preexposure prophylaxis (PrEP) of ... ...

Abstract	Purpose of review: To review current laboratory and clinical data on the frequency and relative risk of drug resistance and range of mutations selected from approved and investigational antiretroviral agents used for preexposure prophylaxis (PrEP) of HIV-1 infection, including tenofovir disproxil fumarate (TDF)-based oral PrEP, dapivirine ring, injectable cabotegravir (CAB), islatravir, lenacapavir and broadly neutralizing antibodies (bNAbs). Recent findings: The greatest risk of HIV-1 resistance from PrEP with oral TDF/emtricitabine (FTC) or injectable CAB is from starting or continuing PrEP after undiagnosed acute HIV infection. By contrast, the dapivirine intravaginal ring does not appear to select nonnucleoside reverse transcriptase inhibitor resistance in clinical trial settings. Investigational inhibitors including islatravir, lenacapavir, and bNAbs are promising for use as PrEP due to their potential for sustained delivery and low risk of cross-resistance to currently used antiretrovirals, but surveillance for emergence of resistance mutations in more HIV-1 gene regions (gag, env) will be important as the same drugs are being developed for HIV therapy. Summary: PrEP is highly effective in preventing HIV infection. Although HIV drug resistance from PrEP use could impact future options in individuals who seroconvert on PrEP, the current risk is low and continued monitoring for the emergence of resistance and cross-resistance during product development, clinical studies, and product roll-out is advised to preserve antiretroviral efficacy for both treatment and prevention.
MeSH term(s)	Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Anti-Retroviral Agents/therapeutic use ; Broadly Neutralizing Antibodies ; Drug Resistance ; Emtricitabine ; HIV Infections/drug therapy ; HIV Infections/prevention & control ; HIV-1/genetics ; Humans ; Pre-Exposure Prophylaxis ; Tenofovir/therapeutic use
Chemical Substances	Anti-HIV Agents ; Anti-Retroviral Agents ; Broadly Neutralizing Antibodies ; Tenofovir (99YXE507IL) ; Emtricitabine (G70B4ETF4S)
Language	English
Publishing date	2022-06-30
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2502511-9
ISSN	1746-6318 ; 1746-630X
ISSN (online)	1746-6318
ISSN	1746-630X
DOI	10.1097/COH.0000000000000746
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Article ; Online: Improving the Outcomes of Immunocompromised Patients With Coronavirus Disease 2019.

Haidar, Ghady / Mellors, John W

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 73, Issue 6, Page(s) e1397–e1401

Abstract: Recent case studies have highlighted the fact that certain immunocompromised individuals are at risk for prolonged SARS-CoV-2 replication, intrahost viral evolution of multiply-mutated variants, and poor clinical outcomes. The immunologic determinants of ...

Abstract	Recent case studies have highlighted the fact that certain immunocompromised individuals are at risk for prolonged SARS-CoV-2 replication, intrahost viral evolution of multiply-mutated variants, and poor clinical outcomes. The immunologic determinants of this risk, the duration of infectiousness, and optimal treatment and prevention strategies in immunocompromised hosts are ill defined. Of additional concern is the widespread use of immunosuppressive medications to treat COVID-19, which may enhance and prolong viral replication in the context of immunodeficiency. We outline the rationale for 4 interrelated approaches to usher in an era of evidence-based medicine for optimal management of immunocompromised patients with COVID-19: multicenter pathogenesis and outcomes studies to relate the risk of severe disease to the type and degree of immunodeficiency, studies to evaluate immunologic responses to SARS-CoV-2 vaccines, studies to evaluate the efficacy of monoclonal antibodies for primary prophylaxis, and clinical trials of novel antiviral agents for the treatment of COVID-19.
MeSH term(s)	Antiviral Agents/therapeutic use ; COVID-19 ; COVID-19 Vaccines ; Humans ; Immunocompromised Host ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; COVID-19 Vaccines
Language	English
Publishing date	2021-05-05
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab397
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Article ; Online: Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer.

Zhang, Linan / Cascio, Sandra / Mellors, John W / Buckanovich, Ronald J / Osmanbeyoglu, Hatice Ulku

Communications biology

2024 Volume 7, Issue 1, Page(s) 20

Abstract: High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a highstromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer-associated ... ...

Abstract	High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a highstromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer-associated mesenchymal stem cells, establish a complex network of paracrine signaling pathways with tumor-infiltrating immune cells that drive effector cell tumor immune exclusion and inhibit the antitumor immune response. In this work, we integrate single-cell transcriptomics of the HGSOC TME from public and in-house datasets (n = 20) and stratify tumors based upon high vs. low stromal cell content. Although our cohort size is small, our analyses suggest a distinct transcriptomic landscape for immune and non-immune cells in high-stromal vs. low-stromal tumors. High-stromal tumors have a lower fraction of certain T cells, natural killer (NK) cells, and macrophages, and increased expression of CXCL12 in epithelial cancer cells and cancer-associated mesenchymal stem cells (CA-MSCs). Analysis of cell-cell communication indicate that epithelial cancer cells and CA-MSCs secrete CXCL12 that interacte with the CXCR4 receptor, which is overexpressed on NK and CD8+ T cells. Dual IHC staining show that tumor infiltrating CD8 T cells localize in proximity of CXCL12+ tumor area. Moreover, CXCL12 and/or CXCR4 antibodies confirm the immunosuppressive role of CXCL12-CXCR4 in high-stromal tumors.
MeSH term(s)	Humans ; Female ; Ovarian Neoplasms/genetics ; Single-Cell Analysis ; Signal Transduction ; Antibodies ; Tumor Microenvironment
Chemical Substances	Antibodies
Language	English
Publishing date	2024-01-05
Publishing country	England
Document type	Journal Article
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-05733-x
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Article ; Online: COVID-19: Challenges of Viral Variants.

Jacobs, Jana L / Haidar, Ghady / Mellors, John W

Annual review of medicine

2022 Volume 74, Page(s) 31–53

Abstract: The COVID-19 pandemic has been accompanied by SARS-CoV-2 evolution and emergence of viral variants that have far exceeded initial expectations. Five major variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) have emerged, each having both unique ... ...

Abstract	The COVID-19 pandemic has been accompanied by SARS-CoV-2 evolution and emergence of viral variants that have far exceeded initial expectations. Five major variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) have emerged, each having both unique and overlapping amino acid substitutions that have affected transmissibility, disease severity, and susceptibility to natural or vaccine-induced immune responses and monoclonal antibodies. Several of the more recent variants appear to have evolved properties of immune evasion, particularly in cases of prolonged infection. Tracking of existing variants and surveillance for new variants are critical for an effective pandemic response.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Pandemics ; Antibodies, Monoclonal
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2022-07-18
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	207930-6
ISSN	1545-326X ; 0066-4219
ISSN (online)	1545-326X
ISSN	0066-4219
DOI	10.1146/annurev-med-042921-020956
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Article ; Online: Long-Acting Injectable Cabotegravir for HIV Prevention: What Do We Know and Need to Know about the Risks and Consequences of Cabotegravir Resistance?

Parikh, Urvi M / Koss, Catherine A / Mellors, John W

Current HIV/AIDS reports

2022 Volume 19, Issue 5, Page(s) 384–393

Abstract: Purpose of review: Cabotegravir is a potent integrase strand transfer inhibitor (INSTI) recently approved as a long-acting injectable formulation for HIV prevention (CAB-LA). We summarize what is known about cabotegravir pharmacokinetics, activity, and ... ...

Abstract	Purpose of review: Cabotegravir is a potent integrase strand transfer inhibitor (INSTI) recently approved as a long-acting injectable formulation for HIV prevention (CAB-LA). We summarize what is known about cabotegravir pharmacokinetics, activity, and emergence of resistance from in vitro, macaque and clinical studies, and we evaluate the risk of resistance from CAB-LA with on-time injections and after CAB-LA discontinuation. Recent findings: The accumulation of multiple INSTI mutations is required for high-level cabotegravir resistance, and the same mutation combinations may cause cross-resistance to dolutegravir, which is widely used for first-line antiretroviral therapy in low- and middle-income countries. Though CAB-LA was highly effective in preventing HIV, breakthrough infections did occur in trials of CAB-LA despite on-time injections, resulting in selection of single and combinations of INSTI resistance mutations. As CAB-LA is scaled-up, prompt HIV diagnosis to prevent resistance, and resistance monitoring could help preserve the effectiveness of INSTIs for both HIV treatment and prevention.
MeSH term(s)	Diketopiperazines ; HIV Infections/drug therapy ; HIV Infections/prevention & control ; HIV Integrase Inhibitors/pharmacology ; HIV Integrase Inhibitors/therapeutic use ; HIV-1/genetics ; Humans ; Integrases/pharmacology ; Integrases/therapeutic use ; Pyridones
Chemical Substances	Diketopiperazines ; HIV Integrase Inhibitors ; Pyridones ; Integrases (EC 2.7.7.-) ; cabotegravir (HMH0132Z1Q)
Language	English
Publishing date	2022-09-16
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2151206-1
ISSN	1548-3576 ; 1548-3568
ISSN (online)	1548-3576
ISSN	1548-3568
DOI	10.1007/s11904-022-00616-y
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Zs.A 5920: Show issues

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Article ; Online: Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in Blood of Patients With Coronavirus Disease 2019 (COVID-19): What Does It Mean?

Jacobs, Jana L / Mellors, John W

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2020 Volume 73, Issue 9, Page(s) e2898–e2900

MeSH term(s)	COVID-19 ; Diagnostic Tests, Routine ; Humans ; RNA ; SARS-CoV-2
Chemical Substances	RNA (63231-63-0)
Keywords	covid19
Language	English
Publishing date	2020-09-22
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciaa1316
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Article: Human antibody V

Chu, Xiaojie / Li, Wei / Hines, Margaret G / Lyakhov, Ilya / Mellors, John W / Dimitrov, Dimiter S

Frontiers in oncology

2023 Volume 13, Page(s) 1194972

Abstract: The high expression of uPAR has been linked to tumor progression, invasion, and metastasis in several types of cancer. Such overexpression of uPAR makes it a potential target for immunotherapies across common cancers such as breast, colorectal, lung, ... ...

Abstract	The high expression of uPAR has been linked to tumor progression, invasion, and metastasis in several types of cancer. Such overexpression of uPAR makes it a potential target for immunotherapies across common cancers such as breast, colorectal, lung, ovarian cancer, and melanoma. In our study, two high-affinity and specific human V
Language	English
Publishing date	2023-10-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1194972
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Article ; Online: Human Antibody V

Chu, Xiaojie / Li, Wei / Hines, Margaret G / Lyakhov, Ilya / Mellors, John W / Dimitrov, Dimiter S

Molecular pharmaceutics

2023 Volume 20, Issue 5, Page(s) 2754–2760

Abstract: The elevated expression of GPNMB and VCAM-1 has been observed in many cancers including breast cancer, melanoma, and prostate cancers. Such overexpression of GPNMB and VCAM-1 has been associated with poor prognosis and increased cancer metastasis. Thus, ... ...

Abstract	The elevated expression of GPNMB and VCAM-1 has been observed in many cancers including breast cancer, melanoma, and prostate cancers. Such overexpression of GPNMB and VCAM-1 has been associated with poor prognosis and increased cancer metastasis. Thus, GPNMB and VCAM-1 are potential targets for immunotherapies across multiple cancers. In this study, two high-affinity specific human V
MeSH term(s)	Humans ; Female ; Vascular Cell Adhesion Molecule-1 ; Antibodies ; Melanoma ; Breast Neoplasms/drug therapy ; Immunoglobulin Variable Region ; Transcription Factors ; Membrane Glycoproteins
Chemical Substances	Vascular Cell Adhesion Molecule-1 ; Antibodies ; Immunoglobulin Variable Region ; Transcription Factors ; GPNMB protein, human ; Membrane Glycoproteins
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.3c00173
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Zs.A 6250: Show issues

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Article ; Online: Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer

Linan Zhang / Sandra Cascio / John W. Mellors / Ronald J. Buckanovich / Hatice Ulku Osmanbeyoglu

Communications Biology, Vol 7, Iss 1, Pp 1-

2024 Volume 14

Abstract: Abstract High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a highstromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer- ... ...

Abstract	Abstract High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a highstromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer-associated mesenchymal stem cells, establish a complex network of paracrine signaling pathways with tumor-infiltrating immune cells that drive effector cell tumor immune exclusion and inhibit the antitumor immune response. In this work, we integrate single-cell transcriptomics of the HGSOC TME from public and in-house datasets (n = 20) and stratify tumors based upon high vs. low stromal cell content. Although our cohort size is small, our analyses suggest a distinct transcriptomic landscape for immune and non-immune cells in high-stromal vs. low-stromal tumors. High-stromal tumors have a lower fraction of certain T cells, natural killer (NK) cells, and macrophages, and increased expression of CXCL12 in epithelial cancer cells and cancer-associated mesenchymal stem cells (CA-MSCs). Analysis of cell-cell communication indicate that epithelial cancer cells and CA-MSCs secrete CXCL12 that interacte with the CXCR4 receptor, which is overexpressed on NK and CD8+ T cells. Dual IHC staining show that tumor infiltrating CD8 T cells localize in proximity of CXCL12+ tumor area. Moreover, CXCL12 and/or CXCR4 antibodies confirm the immunosuppressive role of CXCL12-CXCR4 in high-stromal tumors.
Keywords	Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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