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Pathology, Research and Practice Oct 2022Three cases of an unusual association between spindle cell thymoma (WHO type A) and choriocarcinoma are presented. The patients are three men between the ages of 58 and...
Three cases of an unusual association between spindle cell thymoma (WHO type A) and choriocarcinoma are presented. The patients are three men between the ages of 58 and 68 years. Clinically, all the patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Clinical history and physical examination did not reveal the presence of any prior malignancy. Diagnostic imaging showed in the three patients the presence of a large anterior mediastinal mass. A core needle biopsy was obtained in the three patients. In two patients the biopsy showed the classic histology of a spindle cell thymoma while in one patient the biopsy showed the association of two tumors - spindle cell thymoma and choriocarcinoma. Surgical resection via thoracotomy was performed in the three patients. The mediastinal tumors measured between 9 and 17 cm in greatest diameter and were described as solid and lobulated with areas of hemorrhage. Histologically, all the tumors showed similar histological features of spindle cell thymoma (WHO type A) associated with a high-grade neoplasm composed of round and multinucleated giant cells compatible with choriocarcinoma. Immunohistochemical stains showed positive staining for keratin 5/6, and p40 in the spindle cell component, while the choriocarcinomatous component showed positive staining for human chorionic gonadotropin and human placental lactogen. The cases herein presented highlight not only the unusual association of spindle cell thymoma and choriocarcinoma but also raises some issues regarding the histogenesis of germ cell tumors, in this case choriocarcinoma.
PubMed: 36148717
DOI: 10.1016/j.prp.2022.154134 -
IScience May 2020We evaluated the contribution of organic anion transporting polypeptide 2A1 (OATP2A1/SLCO2A1), a high-affinity carrier for prostaglandins (PGs), to the parturition...
We evaluated the contribution of organic anion transporting polypeptide 2A1 (OATP2A1/SLCO2A1), a high-affinity carrier for prostaglandins (PGs), to the parturition process. At gestational day (GD) 15.5, OATP2A1 is co-localized with 15-hydroxy-PG dehydrogenase in the mouse placental junctional zone and facilitates PG degradation by delivering PGs to the cytoplasm. Slco2a1 (+/-) females mated with Slco2a1 (-/-) males frequently showed elevated circulating progesterone at GD18.5 and delayed parturition. Progesterone receptor inhibition by RU486 treatment at GD18.5 blocked the delay of parturition. In the junctional zone, PGE stimulated placental lactogen II (PL-II) production, resulting in higher expression of PL-II in Slco2a1 (-/-) placenta at GD18.5. Indomethacin treatment at GD15.5 suppressed the PL-II overproduction at GD18.5 in Slco2a1 (-/-) embryo-bearing dams, which promoted progesterone withdrawal and corrected the delayed parturition. These results suggest that extracellular PGE reduction by OATP2A1 at mid-pregnancy would be associated with progesterone withdrawal by suppressing PL-II production, triggering parturition onset.
PubMed: 32408168
DOI: 10.1016/j.isci.2020.101098 -
Diabetes Jul 2020Diabetes occurs due to a loss of functional β-cells, resulting from β-cell death and dysfunction. Lactogens protect rodent and human β-cells in vitro and in vivo...
Diabetes occurs due to a loss of functional β-cells, resulting from β-cell death and dysfunction. Lactogens protect rodent and human β-cells in vitro and in vivo against triggers of β-cell cytotoxicity relevant to diabetes, many of which converge onto a common pathway of endoplasmic reticulum (ER) stress. However, whether lactogens modulate the ER stress pathway is unknown. This study examines whether lactogens can protect β-cells against ER stress and mitigate diabetes incidence in Akita (Ak) mice, a rodent model of ER stress-induced diabetes, akin to neonatal diabetes in humans. We show that lactogens protect INS-1 cells, primary rodent and human β-cells in vitro against two distinct ER stressors, tunicamycin and thapsigargin, through activation of the JAK2/STAT5 pathway. Lactogens mitigate expression of proapoptotic molecules in the ER stress pathway that are induced by chronic ER stress in INS-1 cells and rodent islets. Transgenic expression of placental lactogen in β-cells of Ak mice drastically reduces the severe hyperglycemia, diabetes incidence, hypoinsulinemia, β-cell death, and loss of β-cell mass observed in Ak littermates. These are the first studies in any cell type demonstrating that lactogens modulate the ER stress pathway, causing enhanced β-cell survival and reduced diabetes incidence in the face of chronic ER stress.
Topics: Animals; Apoptosis; Cells, Cultured; Diabetes Mellitus; Endoplasmic Reticulum Stress; Female; Glucose; Humans; Insulin; Insulin-Secreting Cells; Janus Kinase 2; Male; Mice; Mice, Inbred C57BL; Placental Lactogen; Prolactin; STAT5 Transcription Factor; Signal Transduction
PubMed: 32332156
DOI: 10.2337/db19-0909 -
PloS One 2020The placenta, a tissue that is metabolically active and rich in mitochondria, forms a critical interface between the mother and developing fetus. Oxidative stress within...
The placenta, a tissue that is metabolically active and rich in mitochondria, forms a critical interface between the mother and developing fetus. Oxidative stress within this tissue, derived from the dysregulation of reactive oxygen species (ROS), has been linked to a number of adverse fetal outcomes. While such outcomes have been associated with mitochondrial dysfunction, the causal role of mitochondrial dysfunction and mitochondrially generated ROS in altering the process of placentation remains unclear. In this study, mitochondrial complex I activity was attenuated using 10 nM rotenone to induce cellular oxidative stress by increasing mitochondrial ROS production in the BeWo choriocarcinoma cell line. Increased mitochondrial ROS resulted in a significant decrease in the transcripts which encode for proteins associated with fusion (GCM1, ERVW-1, and ERVFRD-1) resulting in a 5-fold decrease in the percentage of BeWo fusion. This outcome was associated with increased indicators of mitochondrial fragmentation, as determined by decreased expression of MFN2 and OPA1 along with an increase in a marker of mitochondrial fission (DRP1). Importantly, increased mitochondrial ROS also resulted in a 5.0-fold reduction of human placental lactogen (PL) and a 4.4-fold reduction of insulin like growth factor 2 (IGF2) transcripts; hormones which play an important role in regulating fetal growth. The pre-treatment of rotenone-exposed cells with 5 mM N-acetyl cysteine (NAC) resulted in the prevention of these ROS mediated changes in BeWo function and supports a central role for mitochondrial ROS signaling in the maintenance and function of the materno-fetal interface.
Topics: Cell Fusion; Cells, Cultured; Female; Humans; Membrane Potential, Mitochondrial; Mitochondria; Oxidative Stress; Placental Hormones; Pregnancy; Reactive Oxygen Species; Rotenone; Signal Transduction; Trophoblasts
PubMed: 32092105
DOI: 10.1371/journal.pone.0229332 -
International Journal of Molecular... Jul 2021Deficiency of the placental hormone chorionic somatomammotropin (CSH) can lead to the development of intrauterine growth restriction (IUGR). To gain insight into the...
Deficiency of the placental hormone chorionic somatomammotropin (CSH) can lead to the development of intrauterine growth restriction (IUGR). To gain insight into the physiological consequences of CSH RNA interference (RNAi), the trophectoderm of hatched blastocysts (nine days of gestational age; dGA) was infected with a lentivirus expressing either a scrambled control or CSH-specific shRNA, prior to transfer into synchronized recipient sheep. At 90 dGA, umbilical hemodynamics and fetal measurements were assessed by Doppler ultrasonography. At 120 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies with the HO transplacental diffusion technique at 130 dGA. Nutrient uptake rates were determined and tissues were subsequently harvested at necropsy. CSH RNAi reduced ( ≤ 0.05) both fetal and uterine weights as well as umbilical blood flow (mL/min). This ultimately resulted in reduced ( ≤ 0.01) umbilical IGF1 concentrations, as well as reduced umbilical nutrient uptakes ( ≤ 0.05) in CSH RNAi pregnancies. CSH RNAi also reduced ( ≤ 0.05) uterine nutrient uptakes as well as uteroplacental glucose utilization. These data suggest that CSH is necessary to facilitate adequate blood flow for the uptake of oxygen, oxidative substrates, and hormones essential to support fetal and uterine growth.
Topics: Animals; Blastocyst; Female; Fetal Blood; Fetal Growth Retardation; Fetus; Gestational Age; Glucose; Hemodynamics; Insulin-Like Growth Factor I; Male; Nutrients; Placenta; Placental Lactogen; Pregnancy; RNA Interference; RNA, Small Interfering; Sheep; Signal Transduction; Ultrasonography, Doppler; Uterus
PubMed: 34360913
DOI: 10.3390/ijms22158150 -
The American Journal of Case Reports Nov 2021BACKGROUND When a woman becomes pregnant, the placenta produces human placental lactogen (hPL). The anti-insulin effect of hPL raises maternal blood glucose levels,...
BACKGROUND When a woman becomes pregnant, the placenta produces human placental lactogen (hPL). The anti-insulin effect of hPL raises maternal blood glucose levels, allowing the fetus to use glucose as a nutrient. Because hPL is produced by the placenta until delivery, insulin requirements in patients with gestational diabetes mellitus (GDM) typically increase, but in some cases, they may decrease. We retrospectively examined data from women with GDM who received insulin and delivered at our hospital. CASE REPORT From April 2019 to March 2020, we targeted patients who were diagnosed with GDM, received insulin, and delivered at our hospital. GDM was diagnosed based on the guidelines from the Japanese Society of Obstetrics and Gynecology. The rate of change in insulin dosage was calculated as: (insulin dosage at delivery - insulin dosage 14 days before delivery) divided by 14. Two patients whose insulin dosage was significantly reduced developed a syndrome of hemolysis, elevated liver enzymes, and low platelet count or acute fatty liver of pregnancy and underwent emergency cesarean section. CONCLUSIONS The present case report suggests that a decrease in insulin requirement in pregnant patients with GDM can predict maternal abnormalities due to placental dysfunction.
Topics: Blood Glucose; Cesarean Section; Diabetes, Gestational; Female; Hemolysis; Humans; Insulin; Liver; Placenta; Platelet Count; Pregnancy; Retrospective Studies
PubMed: 34744160
DOI: 10.12659/AJCR.933460