Abstract Trophoblast are extra-embryonic cells that are essential to maintain pregnancy. Human trophoblasts arise from the morula as trophectoderm (TE), which, after implantation, differentiates into cytotrophoblast (CT), syncytiotrophoblast (ST), and extravillous trophoblast (EVT) composing the placenta. Here we show that naïve, but not primed, human pluripotent stem cells (PSCs) recapitulate trophoblast development. Naïve PSC-derived TE and CT (nCT) recreated the human and monkey TE-to-CT transition. nCT self-renewed as CT stem cells and had the characteristics of proliferating villous CT and CT in the cell column of the first trimester. Notably, although primed PSCs differentiated into trophoblast-like cells (pBAP), pBAP were distinct from nCT and human placenta-derived CT stem cells, exhibiting properties consistent of the amnion. Our findings establish an authentic paradigm for human trophoblast development, demonstrating the invaluable properties of naïve human PSCs. Our system will provide a platform to study the molecular mechanisms underlying trophoblast development and related diseases.
It has been demonstrated that L-3hydroxy-6-oxo-N-cyclopropylmethylmorphinan methansulfonate (20681-S) and L-3,14-dihydroxy-6-oxo-N-cyclopropylmethylmorphinan methansulfonate (20682-S), have antinociceptive and narcotic antagonistic properties. In the rodent antinociceptive test, the action of 20681-S was more potent and of longer duration than that of morphine and of cyclazocine after subcutaneous or oral administration. The antinociceptive effect of 20682-S ranked between that of morphine and that of pentazocine in the mouse acetic acid-writhing test. Both compounds possessed potent narcotic antagonistic activities, 20682-S being more active than naloxone and oxilorphan and 20681-S being equipotent with cyclazocine. The latent side effects (respiratory depression and fall in blood pressure) and the acute toxicity of 20681-S and 20682-S, were less than those of reference narcotic antagonists or of narcotic antagonist analgesics.
HER3 (ErbB-3) is a member of the epidermal growth factor receptor family. HER3 overexpression is associated with worse prognosis in ovarian cancer and squamous cell carcinoma of the cervix. Here, the purpose of the current study is to evaluate the expression and risk factors for postoperative recurrence of HER3 in adenocarcinoma and adenosquamous carcinoma of the cervix.
Methodology
This retrospective study included 100 patients diagnosed with primary cervical cancer who underwent primary surgery between 1997 and 2017 was stained immunohistochemically for HER3 expression. Evaluation of HER3 expression was performed by an experienced pathologist in accordance with the HER2 testing guideline for gastroesophageal cancer from CAP, ASCP, and ASCO. A possible influence of HER3 expression on survival was studied by multivariate Cox regression adjusting for established risk factors for postoperative recurrence.
Results
A positive HER3 expression was found in 68.9% (42/61) of squamous cell carcinoma, 85.1% (23/27) of adenocarcinoma, and 58.3% (7/12) of adenosquamous carcinoma. With a median follow-up period for survivors of 63.1 months, the 3-year disease-free survival rates (DFS) in patients with adenocarcinoma and adenosquamous carcinoma of the cervix were 55.9% in HER3-high and 88.9% in HER3-low/negative (p=0.20). In multivariate analysis, HER3 [HR, 6.62; 95% CI, 1.8–37.1; P=0.03], pelvic lymph nodes [HR, 6.72; 95% CI, 2.0–23.5; P<0.01], vascular invasion [HR, 3.64; 95% CI, 1.1–12.2; P=0.04] were independent predictive factors of DFS.
Conclusion
HER3 overexpression was independent risk factors for postoperative recurrence in patients with adenocarcinoma and adenosquamous carcinoma of the cervix.
AbstractChanges in gastric mucus glycoprotein (mucin) isolated from pirenzepine-treated rats with or without ethanol (50%)-induced gastric damage were studied. The prior administration of pirenzepine inhibited significantly and dose-dependently the occurrence of macroscopically observable hemorrhagic lesions induced by treatment with ethanol. The gastric mucosa was separated into the surface mucosa, including the mucus gel layer, and the deeper mucosa by mechanical scraping, and the mucin in each was isolated. In cthanol-treated animals the mucin content of the deep corpus mucosa was significantly reduced to 68% the control value. This reduction was inhibited by pretreatment with pirenzepine. In the surface mucosa mucin content was also reduced to 48% of control value by ethanol treatment, but pirenzepine pretreatment increased mucin content to 235% the control value. Total mucin content in the entire stomach essentially resumed the control level by pretreatment with 100 mg/kg of pirenzepine. A single oral administration of pirenzepine (100 mg/kg) caused no change in total mucin content, but mucin in the deep corpus mucosa selectively and significantly increased to 124% the control. These and the results of carbohydrate analysis of purified mucin indicate that pirenzepine administration possibly accelerates the secretion of accumulated deep corpus mucus, retains this deep mucus on surface mucosal mucus, and protects the gastric mucosa in ethanol-induced gastric damage. This may be related to the antiulcerogenic effects of pirenzepine.Key Words: Ethanol-induced gastric damagemucus glycoproteinpirenzepine
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)