Estrogen receptor a (ERA) is a DNA-binding transcription factor that plays an important role in the regulation of cell growth. Previous studies indicated that the expression of ERa in cell lines and tumors derived from oral squamous cell carcinoma (OSCC). The aim of this study was to examine the activity and function of ERa in OSCC cells and the mechanism underlying ERa activation. Immunochemical analyses in benign (nZ11) and malignant (nZ21) lesions of the oral cavity showed that ERa immunoreactivity was observed in 43% (9/21) of malignant lesions, whereas none of benign lesions showed ERa immunoreactivity. The ERa expression was also found in three OSCC cell lines and its transcriptional activity was correlated with cell growth. Addition of estradiol stimulated cell growth, whereas treatment of tamoxifen or knockdown of ERa expression caused reduced cell growth. Interestingly, the expression and activity of focal adhesion kinase (FAK) were associated with the phosphorylation of ERa at serine 118 in OSCC cells. Elevated expression of FAK in the slow-growing SCC25 cells caused increases in ERa phosphorylation, transcriptional activity, and cell growth rate, whereas knockdown of FAK expression in the rapid-growing OECM-1 cells led to reduced ERa phosphorylation and activity and retarded cell growth. Inhibition of the activity of protein kinase B (AKT), but not ERK, abolished FAK-promoted ERa phosphorylation. These results suggest that OSCC cells expressed functional ERa, whose activity can be enhanced by FAK/AKT signaling, and this was critical for promoting cell growth. Thus, FAK and ERa can serve as the therapeutic targets for the treatment of OSCC. Key Words" oral squamous cell carcinoma " estrogen receptor a " focal adhesion kinase

Androgen receptor (AR) is a steroid hormone receptor that functions as a transcription factor for regulating cell growth and survival. Aberrant AR function becomes a risk factor for promoting the progression of prostate cancer (PCa). In this study, we examined the roles of proline-rich tyrosine kinase 2 (PYK2) and ribosomal S6 kinase 1 (S6K1) in regulating AR expression and activity and growth properties in PCa cells. Compared with normal prostate tissues, PCa tumors exhibited high levels of PYK2 and S6K1 expression. Furthermore, the expression levels of PYK2 and S6K1 were significantly correlated with nuclear AR expression in PCa tissues. We further found the association between PYK2, S6K1, and AR in their protein expression and phosphorylation levels among normal prostate PZ-HPV-7 cells and prostate cancer LNCaP and 22Rv1 cells. Overexpression of the wild-type PYK2 in PZ-HPV-7 and LNCaP cells promoted AR and S6K1 expression and phosphorylation as well as enhanced cell growth. In contrast, expression of the mutated PYK2 or knockdown of PYK2 expression in LNCaP or 22Rv1 cells caused reduced expression or phosphorylation of AR and S6K1 as well as retarded cell growth. Under an androgen-deprived condition, PYK2-promoted AR expression and phosphorylation and PSA production in LNCaP cells can be abolished by knocking down S6K1 expression. In summary, our data suggested that PYK2 via S6K1 activation modulated AR function and growth properties in PCa cells. Thus, PYK2 and S6K1 may potentially serve as therapeutic targets for PCa treatment.

Case 1: The patient was a 29-year-old female with gravida 3, para 2, and abortus1 who had a spontaneous full term vaginal delivery. Her prenatal care was normal and intrapartum course was smooth with no use of pitocin. Spontaneous vaginal delivery with normal neonatal outcome occurred after membrane rupture. She developed profuse vaginal bleeding 1 hour and 10 minutes after delivery. The patient was transferred to our hospital one hour and 22 minutes after the bleeding episode. She presented with massive vaginal bleeding and physical examination revealed a soft uterus and uncoagulated blood in the vagina. Her blood pressure was 80/48 mmHg, with a pulse rate of 120/minute, respiratory rate 20/minute, and body temperature 37.7°C. No respiratory distress was noted. Coagulation studies revealed a fibrinogen of 26.1 mg/ dL, prothrombin time 32.9 seconds (8-12 seconds), Prothrombin International Normalised Ratio (INR) 3.57, partial thromboplastin time 41.7 seconds (23-35 seconds), Fibrinogen Degradation Product (FDP) 829.1 µg/mL (<5.0 µg/mL), D-Dimer 1162 µg/L (<324 µg/L), Hemoglobin (Hb) 7.6 g/dL, Hematocrit (Hct) 24.0%, and platelet count 101× THSD/µL. She was sent to the operative room for uterine curettage due to suspected retained placenta before the coagulation studies, but no abnormalities were found. Therefore, she received total abdominal hysterectomy because of persistent and uncoagulated bleeding. The vital signs and laboratory data became stable after hysterectomy and transfusion of 14 units of packed RBCs, 12 units of fresh frozen plasma, 17 units of cryoprecipitate, and 12 units of platelets.The pathological findings confirmed our diagnosis of AFE and revealed multifocal thrombi with fibrinoid and inflammatory exudates, presence of keratinizing desquamated squamous cells and amorphous materials, and a rare lanugos hair-like structure within the vascular lumen of the cervix and lower uterine segment [Table /Fig-1a1, a2].Case 2: The patient was a 35-year-old female with gravida 3, para 1, and abortus 1. She was at 39 weeks gestation and was otherwise healthy. She had taken no medication and had no known allergy. She was admitted for delivery. The labour course was uneventful without pitocin augumentation. Thin meconium staining was observed. The patient remained haemodynamically stable throughout the labour and delivered a healthy male baby.The obstetrician noted steady and profuse noncoagulated uterine Here, we present an uncommon variant involving isolated disseminated intravascular coagulation that developed without antecedent cardiopulmonary disturbances. Both patients developed symptoms soon after delivery. Blood test was sent at 14 minutes postpartum for the second patient due to suspected amniotic fluid embolism. Fetal components were observed in the uterine veins of the lower uterine segments in both cases. Amniotic fluid embolism with disseminated intravascular coagulopathy typically progresses faster than disseminated intravascular coagulopathy associated with other causes and symptoms. It usuall...

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Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a worldwide distribution. Although intensive studies have been made, the underlying oncogenic mechanism of HNSCC requires further investigation. In this study, we examined the oncogenic role of activated Cdc42‐associated kinase 1 (ACK1), an oncogenic tyrosine kinase, in regulating the proliferation of HNSCC cells and its underlying molecular mechanism. Results from immunohistochemical studies revealed that ACK1 was highly expressed in HNSCC tumors, with 77% (77/100) of tumors showing a high ACK1 immunoreactivity compared to 40% (8/20) of normal mucosa. Knockdown of ACK1 expression in HNSCC cells resulted in elevated p27 expression, reduced cell proliferation, and G1‐phase cell cycle arrest. Rescue of ACK1 expression in the ACK1‐knockdown cells suppressed p27 expression and restored cell proliferation. Compared to ACK1‐knockdown cells, ACK1‐rescued cells exhibited a restored p27 expression after MG132 treatment and showed an elevated level of ubiquitinated p27. Our data further showed that knockdown of ubiquitin ligase Skp2 resulted in elevated p27 expression. Importantly, the expression of p27(WT), p27(Y74F), or p27(Y89F) in ACK1‐overexpressed 293T cells or ACK1‐rescued SAS cells showed higher levels of tyrosyl‐phosphorylated p27 and interaction with ACK1 or Skp2. However, the expression of p27(Y88F) mutant exhibited a relatively low phosphorylation level and barely bound with ACK1 or Skp2, showing a basal interaction as the control cells. These results suggested that ACK1 is highly expressed in HNSCC tumors and functions to promote cell proliferation by the phosphorylation and degradation of p27 in the Skp2‐mediated mechanism.