Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：診断と治療社  

DOI： 10.34433/pp.0000000865

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blood  

Occupational exposure to medical agents and ionizing radiation has been suggested as a possible risk factor for childhood cancer. However, the relationship between such exposure and pediatric malignant neoplasms has not yet been comprehensively studied. This cohort study aimed to investigate the association between parental occupational exposure to hazardous medical agents or ionizing radiation and the risk of childhood cancer in offspring. Data from a large birth cohort in Japan, which included 104 062 fetuses, were analyzed. The primary outcome was the development of leukemia or brain tumors diagnosed by community physicians during the first 3 years after birth. Exposure factors were medical agents, including anticancer agents, ionizing radiation, and anesthetics, handled by mothers during pregnancy or by fathers for 3 months before conception. The incidence of leukemia, but not of brain tumors, was higher in mothers exposed to anticancer drugs. Multivariable regression analysis showed that maternal exposure to anticancer drugs was associated with an increased risk of leukemia in offspring older than 1 year (adjusted relative risk, 7.99 [95% confidence interval, 1.98-32.3]). Detailed information obtained from medical certificates of patients with identified leukemia revealed no infant leukemia but acute lymphoblastic leukemias in the exposed group. Our findings suggest that maternal occupational exposure to anticancer drugs may be a potential risk factor for acute lymphoblastic leukemia in offspring older than 1 year. Effective prevention methods may be necessary to prevent maternal exposure to anticancer drugs and to reduce the risk of childhood malignant neoplasms.

DOI： 10.1182/blood.2023021008

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Nuclear Medicine  

Immuno-PET is a powerful tool to noninvasively characterize the in vivo biodistribution of engineered antibodies. Methods: L1 cell adhesion molecule–targeting humanized (HuE71) IgG1 and IgG4 antibodies bearing identical variable heavy- and light-chain sequences but different fragment crystallizable (Fc) portions were radiolabeled with 89Zr, and the in vivo biodistribution was studied in SKOV3 ovarian cancer xenografted nude mice. Results: In addition to showing uptake in L1 cell adhesion molecule–expressing SKOV3 tumors, as does its parental counterpart HuE71 IgG1, the afucosylated variant having enhanced Fc-receptor affinity showed high nonspecific uptake in lymph nodes. On the other hand, aglycosylated HuE71 IgG1 with abrogated Fc-receptor binding did not show lymphoid uptake. The use of the IgG4 subclass showed high nonspecific uptake in the kidneys, which was prevented by mutating serine at position 228 to proline in the hinge region of the IgG4 antibody to mitigate in vivo fragment antigen-binding arm exchange. Conclusion: Our findings highlight the influence of Fc modifications and the choice of IgG subclass on the in vivo biodistribution of antibodies and the potential outcomes thereof.

DOI： 10.2967/jnumed.121.262383

Web of Science

Scopus

PubMed

Authorship：Lead author   Language：Japanese  

Authorship：Lead author   Language：Japanese  

Language：English  

Language：Japanese   Presentation type：Oral presentation (general)  

Language：Japanese   Presentation type：Oral presentation (general)  

Language：Japanese   Presentation type：Oral presentation (general)