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Toremifene given in different sizes of silastic capsules was used to treat MCF-7 tumors in athymic mice. Toremifene inhibited the estradiol-stimulated growth of MCF-7 tumors in athymic mice. Average serum concentrations of toremifene obtained using a sustained-release preparation of the drug (in 0.5-, 1.0-, and 2.0-cm silastic capsules) increased gradually in a capsule-size-dependent fashion. Much higher levels of toremifene or N-demethyl-toremifene were detected in tumors (target tissues of estrogen) as compared with muscles (non-target tissues of estrogen). The concentration of toremifene in serum (i.e., 10-30 ng ml-1) was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumors at physiological (i.e., 200-400 pg ml-1) serum estradiol concentrations in premenopausal women. No significant difference in estrogen receptor (ER) levels was found between the estradiol-alone group and the toremifene-treated groups. However, the ER levels in the toremifene-alone group and the no-treatment group (no toremifene or estradiol) tended to increase as compared with the estradiol-alone group. Toremifene blocked the estradiol-induced increase in progesterone receptor levels in a dose-dependent fashion. Insulin-like growth factor-1 (IGF-1) levels in the MCF-7 tumors significantly decreased in the toremifene-alone group as compared with the estradiol-alone group. These results show the antiestrogenic action of toremifene on hormone-dependent MCF-7 tumors in athymic mice. [ABSTRACT FROM AUTHOR]

Preimplantation embryonic development is orchestrated by dynamic changes in the proteome and transcriptome, regulated by mechanisms such as maternal-to-zygotic transition. Here, we employed label-free quantitative proteomics to comprehensively analyze proteome dynamics from germinal vesicle oocytes to blastocysts in mouse embryos. We identified 3490 proteins, including 715 consistently detected across all stages, revealing stage-specific changes in proteins associated with translation, protein modification, and mitochondrial metabolism. Comparison with transcriptomic data highlighted a low correlation between mRNA and protein levels, underscoring the significance of non-transcriptional regulatory mechanisms during early development. Additionally, we analyzed WD repeat-containing protein 74 (WDR74)-deficient embryos generated using CRISPR-Cas9 genome editing. WDR74, a pre-60S ribosome maturation factor, was found to be critical for ribosome biogenesis and cell division. Furthermore, WDR74 deficiency led to a significant reduction in ribosomal protein large subunit and impaired progression beyond the morula stage. Key ribosomal proteins such as ribosomal protein L24 (RPL24) and ribosomal protein L26 (RPL26), which influence cell division timing, were notably affected, while small subunit proteins remained largely unchanged. Taken together, our study demonstrates the utility of integrating genome editing with proteomic analysis to elucidate molecular mechanisms underlying early embryogenesis, and provides new insights into protein-level regulation of preimplantation development., (© 2025 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background/aim: Serum-derived macrophage activating factor (serum-MAF) is expected to have adjuvant effects through rapid phagocytic activation, which depends on F-actin accumulation in multi-layered membrane ruffles induced within 5 min after serum-MAF addition. This study aimed to elucidate the importance of annexin A2, which is a multifunctional Ca 2+ -binding protein related to cytoskeletal membrane dynamics, in serum-MAF signalling., Materials and Methods: Annexin A2 and F-actin localizations were analyzed via immunostaining and confocal microscopy. Using EGTA as chelator, the role of Ca 2+ in serum-MAF signalling was examined., Results: Annexin A2 was found to translocate from the cytosol to the cell cortex within 30 s of serum-MAF stimulation. Ca 2+ chelation inhibited the translocation of annexin A2, frill-like structure formation, and phagocytic activation by serum-MAF., Conclusion: Annexin A2 and Ca 2+ were responsible for the rapid phagocytic activation by serum-MAF. This study provides an understanding of phagocytic activation in macrophages, which could be beneficial for cancer immunotherapy., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In multicellular organisms, oocytes and sperm undergo fusion during fertilization and the resulting zygote gives rise to a new individual. The ability of zygotes to produce a fully formed individual from a single cell when placed in a supportive environment is known as totipotency. Given that totipotent cells are the source of all multicellular organisms, a better understanding of totipotency may have a wide-ranging impact on biology. The precise delineation of totipotent cells in mammals has remained elusive, however, although zygotes and single blastomeres of embryos at the two-cell stage have been thought to be the only totipotent cells in mice. We now show that a single blastomere of two- or four-cell mouse embryos can give rise to a fertile adult when placed in a uterus, even though blastomere isolation disturbs the transcriptome of derived embryos. Single blastomeres isolated from embryos at the eight-cell or morula stages and cultured in vitro manifested pronounced defects in the formation of epiblast and primitive endoderm by the inner cell mass and in the development of blastocysts, respectively. Our results thus indicate that totipotency of mouse zygotes extends to single blastomeres of embryos at the four-cell stage.

Aim : We investigated whether preoperative or postoperative inflammatory markers and psoas muscle index (PMI), and their change after surgery, could predict postoperative recurrence in gastric cancer (GC). Methods : Thirty-five patients who underwent curative gastrectomy for pStage II and III GC were retrospectively reviewed. The relationship between neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), and PMI, as well as postoperative recurrence, was analyzed presurgery and at 6 months after surgery. Results : In the preoperative data, there was a significant association between postoperative recurrence and high NLR, low total protein, low albumin, low PNI, and high GPS. In the data from 6 months after surgery, there was a significant association between postoperative recurrence and high NLR, high C-reactive protein, and high GPS. The reduction in PMI at 6 months after surgery relative to preoperative data was significantly greater in the cases with recurrence than in those without recurrence. No patients whose PMI increased compared with presurgery had recurrence. Conclusions : The postoperative reduction in PMI at 6 months after surgery relative to presurgery could be a predictive marker of recurrence after curative gastrectomy for patients with pStage II and III GC. J. Med. Invest. 68 : 119-124, February, 2021.

Introduction: Persistent Müllerian duct syndrome (PMDS) is a rare disease occurring in men with an otherwise completely normal phenotype, in which female internal sex organs are present, including a uterus, fallopian tubes, cervix, and vagina. We report a case of bilateral recurrent inguinal hernia due to PMDS treated by transabdominal preperitoneal repair (TAPP)., Patient Concerns: A 72-year-old male presented with a complaint of swelling on both sides of the groin. The patient had undergone bilateral inguinal hernia suture repair 50 years ago., Diagnosis: Bilateral recurrent inguinal hernia INTERVENTIONS:: TAPP was performed. There was a fibrous structure linking the left and right hernia orifice and a muscular structure in the hernia sac on the left. We noticed that the muscular structure was a vagina and fibrous structure was the salpinx, and we diagnosed the patient with PMDS. Supravaginal hysterectomy and right salpingectomy were performed. After that a preperitoneal mesh repair was performed for bilateral inguinal hernia., Outcomes: Histologically, the diagnosis was confirmed as PMDS. The patient had an uneventful recovery., Conclusion: This case is the first case of bilateral recurrent inguinal hernia due to PMDS managed by TAPP.

Purpose: We introduced a new concept of ex vivo gene expression analysis (Mitsuhashi, Clin Chem 53:148-149, 2007), where drug action was simulated under physiological conditions. This model system was applied to study various fields of drug development., Materials and Methods: Heparinized human whole blood was incubated with drugs for less than 4h. The changes of specific mRNA were then quantified using the method we developed (Mitsuhashi, Tomozawa, Endo, and Shinagawa, Clin Chem 52:634-642, 2006)., Results: The mRNA quantitation method was used as a model system to study the following areas: (1) identification of respondents and non-respondents, (2) ex vivo compound screening, (3) determination of individually optimized doses, (4) drug-to-drug comparison, (5) assessment of leukocyte toxicity, (6) discovery of molecular targets, (7) assessment of the action of dietary supplements, and (8) characterization of respondents and non-respondents for various dietary supplements., Conclusion: Since ex vivo assays are safe, a large number of healthy donors and disease patients can be recruited to identify individual-to-individual variations, which is not available from current preclinical study models. Although each system should be validated using a large number of samples, the ex vivo analysis will be a new tool for the development of drugs and dietary supplements in future.