Detection in Molecular Communications with Ligand Receptors under Molecular Interference

Abstract The fertility potential of human sperm populations can be assessed by the presence of head-directed mannose ligand receptors (mannose-specific lectin) and the occurrence of spontaneous acrosome reactions after incubation under capacitating conditions in vitro. We have reported previously on the interaction between anti-hypertensive medications and their effects on these parameters of male fertility potential. In this report we document the effects of cessation of calcium ion channel blocker medication on male fertility. Motile spermatozoa from a 30 year old infertile patient on a calcium ion channel blocker as anti-hypertensive treatment had subnormal expression of mannose-specific lectin and did not exhibit spontaneous acrosome reactions. Three months following discontinuation of the medications, complete recovery of both the expression of head-directed mannose ligand receptors and the acrosome reaction was documented, though sperm motility and morphology remained unchanged. The couple had 2 years of infertility and previously failed to conceive through seven cycles of Pergonal/intra-uterine insemination. Conception occurred on the second Pergonal/intra-uterine insemination cycle after the husband discontinued calcium ion channel blocker medication. Calcium ion channel blockers may adversely affect sperm fertilizing potential. Discontinuation of such medications enhances the chances for conception.

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PARP inhibition and immune modulation: scientific rationale and perspectives for the treatment of gynecologic cancers

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920944116 ◽

2020 ◽

Vol 12 ◽

pp. 175883592094411

Author(s):

Elizabeth K. Lee ◽

Panagiotis A. Konstantinopoulos

Keyword(s):

Immune Modulation ◽

Killer Cell ◽

Adenosine Diphosphate ◽

Parp Inhibitors ◽

Immune Checkpoint Blockade ◽

Parp Inhibition ◽

T Cell Infiltration ◽

Ligand Receptors ◽

Sting Pathway ◽

Oncologic Therapy

Poly[adenosine diphosphate (ADP) ribose]polymerase (PARP) has multifaceted roles in the maintenance of genomic integrity, deoxyribonucleic acid (DNA) repair and replication, and the maintenance of immune-system homeostasis. PARP inhibitors are an attractive oncologic therapy, causing direct cancer cell cytotoxicity by propagating DNA damage and indirectly, by various mechanisms of immunostimulation, including activation of the cGAS/STING pathway, paracrine stimulation of dendritic cells, increased T-cell infiltration, and upregulation of death-ligand receptors to increase susceptibility to natural-killer-cell killing. However, these immunostimulatory effects are counterbalanced by PARPi-mediated upregulation of programmed cell-death-ligand 1 (PD-L1), which leads to immunosuppression. Combining PARP inhibition with immune-checkpoint blockade seeks to exploit the immune stimulatory effects of PARP inhibition while negating the immunosuppressive effects of PD-L1 upregulation.

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