Testicular relapse of acute lymphoblastic leukemia (ALL)

Em, Ritzén

doi:10.1016/0165-0378(90)90028-5

Cited by 28 publications

(5 citation statements)

References 8 publications

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“…However, the seminiferous tubule lumen can act as a sanctuary site for some viruses (e.g., Ebola, HIV, Zika) and cancers (e.g., leukemias) because certain xenobiotics cannot effectively cross the tight SC epithelia to achieve pharmacologically relevant concentrations in the adluminal compartment. There are many reports of testicular persistence and/or relapse of viruses and cancers, despite eradication from the blood and other tissues (Byrn and Kiessling, 1998;Deen et al, 2017;Houzet et al, 2014;Kiessling et al, 1998;Ma et al, 2021;Nesbit et al, 1980;Politch et al, 2012;Ritzen, 1990;Robinson et al, 2018). This phenomenon highlights a DMD-MR-2023-001288R1 Hau et al 6 need to identify the mechanisms that permit antiviral or antineoplastic therapies to successfully treat these diseases in the testes.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier

2023

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The blood-testis barrier (BTB) is a selectively permeable membrane barrier formed by adjacent Sertoli cells (SCs) in the seminiferous tubules of the testes that develops intercellular junctional complexes to protect developing germ cells from external pressures. However, due to this inherent defense mechanism, the seminiferous tubule lumen can act as a pharmacological sanctuary site for latent viruses (e.g., Ebola, Zika) and cancers (e.g., leukemia). Therefore, it is critical to identify and evaluate BTB carrier-mediated drug delivery pathways to successfully treat these viruses and cancers. Many drugs are unable to effectively cross cell membranes without assistance from carrier proteins like transporters because they are large, polar, and often carry a charge at physiological pH. SCs express transporters that selectively permit endogenous compounds, such as carnitine or nucleosides, across the BTB to support normal physiological activity, although reproductive toxicants can also use these pathways, thereby circumventing the BTB. Certain xenobiotics, including select cancer therapeutics, antivirals, contraceptives, and environmental toxicants, are known to accumulate within the male genital tract and cause testicular toxicity; however, the transport pathways by which these compounds circumvent the BTB are largely unknown. Consequently, there is a need to identify the clinically relevant BTB transport pathways in in vitro and in vivo BTB models that recapitulate human pharmacokinetics and pharmacodynamics for these xenobiotics. This review summarizes the various in vitro and in vivo models of the BTB reported in the literature and highlights the strengths and weaknesses of certain models for drug disposition studies.

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Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier

2023

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“… 2 However, there are ALL patients who do not respond to chemotherapy or have a cancer recurrence after treatment, with the most common relapses occurring in the bone marrow, central nervous system, or gonads. 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 Acute myeloid leukemia (AML) is a common cancer among adults, with a much lower 5‐year survival rate of 29%. 11 , 12 , 13 Sanctuary sites such as the central nervous system or gonads may provide a location where the cancer can evade first‐line treatments.…”

Section: Introductionmentioning

confidence: 99%

“… 11 , 12 , 13 Sanctuary sites such as the central nervous system or gonads may provide a location where the cancer can evade first‐line treatments. 3 , 4 , 5 , 6 , 7 , 9 Testicular relapse of ALL or AML may require orchiectomy (complete removal of one or both testes) or irradiation, leaving the patient with reduced fertility or irreversible infertility, 8 which can have a devastating quality of life impact. The testis is an immune privileged site, which prevents autoimmunity against germ cells, but impedes the immune system response to cancer present within the testis.…”

Section: Introductionmentioning

confidence: 99%

“…Improved treatment of ALL has increased the 5‐year survival rate to 82% 2 . However, there are ALL patients who do not respond to chemotherapy or have a cancer recurrence after treatment, with the most common relapses occurring in the bone marrow, central nervous system, or gonads 3–10 . Acute myeloid leukemia (AML) is a common cancer among adults, with a much lower 5‐year survival rate of 29% 11–13 .…”

Section: Introductionmentioning

confidence: 99%

“…Acute myeloid leukemia (AML) is a common cancer among adults, with a much lower 5‐year survival rate of 29% 11–13 . Sanctuary sites such as the central nervous system or gonads may provide a location where the cancer can evade first‐line treatments 3–7,9 . Testicular relapse of ALL or AML may require orchiectomy (complete removal of one or both testes) or irradiation, leaving the patient with reduced fertility or irreversible infertility, 8 which can have a devastating quality of life impact.…”

Section: Introductionmentioning

confidence: 99%

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Testicular disposition of clofarabine in rats is dependent on equilibrative nucleoside transporters

Miller

Jilek

McGrath

et al. 2021

Pharmacology Res & Perspec

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Bis(4,7‐dimethyl and 5‐dinitro‐1,10‐phenanthroline) sulfato‐oxovanadium(IV)‐mediated in vivo male germ cell apoptosis

D’Cruz¹,

Uckun²

2001

J of Applied Toxicology

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Oxovanadium(IV) [VO] complexes of 1,10-phenanthroline are a new class of potent apoptosis-inducing cytotoxic agents against human testicular cancer cells in vitro. The present study investigated the in vivo ability of four(bis)-chelated 1,10-phenanthroline [phen] complexes of sulfato-oxovanadium(IV)-VO(phen)(2), VO(Cl-phen)(2), VO(Me(2)-phen)(2) and VO(NO(2)-phen)(2)-with and without substitutions, to induce testicular germ cell apoptosis. Male germ cell loss in mice was measured by determining the epididymal sperm count, testicular weight and histological evaluation of the testes. Repetitive intratesticular injection (7.5 mg kg(-1) testis(-1)) of bis-chelated 1,10-phenanthroline complexes of oxovanadium(IV) with 4,7-dimethyl [VO(Me(2)-phen)(2)] and 5-dinitro [VO(NO(2)-phen)(2)] substitution led to decreased sperm counts and reduced testicular weights. Histopathological examination of testicular sections from VO(Me(2)-phen)(2)- and VO(NO(2)-phen)(2)-treated mice revealed a marked inhibition of spermatogenesis and preferential loss of maturing, as well as elongated spermatids. In situ evaluation of seminiferous tubule cross-sections by terminal deoxynucleotidyl transferase-mediated FITC-deoxyuridine triphosphate nick end-labeling (TUNEL) and laser scanning confocal microscopy showed characteristic apoptotic germ cells delineating the periphery of the seminiferous tubules. The ability of bis-chelated 4,7-dimethyl- and 5-dinitro-substituted 1,10-phenanthroline complexes of oxovanadium(IV) to induce germ cell apoptosis in vivo may have potential utility in the treatment of human testicular germ cell tumors.

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Testicular relapse of acute lymphoblastic leukemia (ALL)

Cited by 28 publications

References 8 publications

In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier

In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier

Testicular disposition of clofarabine in rats is dependent on equilibrative nucleoside transporters

Bis(4,7‐dimethyl and 5‐dinitro‐1,10‐phenanthroline) sulfato‐oxovanadium(IV)‐mediated in vivo male germ cell apoptosis

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