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Lipolysis‑stimulated lipoprotein receptor (LSR) is a novel molecule present at tricellular contacts which recruits tricellulin (TRIC), a molecular component of tricellular tight junctions (tTJs). LSR and TRIC are colocalized with the bicellular tight junction (bTJ) protein claudin (CLDN)‑1‑based tight junction strands at tricellular corners. Knockdown of LSR in normal epithelial cells affects tTJ formation and the epithelial barrier function. In cancer cells knockdown of LSR has been demonstrated to increase cell invasion. However, the detailed mechanisms of how the downregulation of LSR enhances cell invasion in cancer remain unclear. In the present study, knockdown of LSR by small interfering RNA (siRNA) in Sawano human endometrial adenocarcinoma cells induced cell invasion. In LSR‑knockdown Sawano cells, upregulation of CLDN‑1 protein, which contributes to the cell invasion via matrix metalloproteinases (MMPs), was observed compared with the control group by western blotting and immunostaining. Knockdown of LSR significantly induced Sp1 transcription factor activity in the CLDN‑1 promoter region. In LSR‑knockdown Sawano cells, DNA microarray analysis demonstrated that MMP‑1, MMP‑2 and MMP‑10 mRNA levels were increased, and the protein levels of membrane‑type 1‑MMP, MMP‑2, MMP‑9 and MMP‑10 were shown to be increased on western blots. Knockdown of CLDN‑1 with siRNA prevented the upregulation of cell invasion induced by the knockdown of LSR in Sawano cells. On the invasive front of human endometrial carcinoma tissue samples, a decrease in LSR and increase in CLDN‑1 protein levels were observed using immunohistochemical methods. In conclusion, the results indicate that the downregulation of LSR promotes cell invasion of human endometrial cancer via CLDN‑1 mediation of MMPs. This mechanism is important for studying the association of tTJs with the cellular invasion of cancer. [ABSTRACT FROM AUTHOR]

Objective: Combined therapy with bevacizumab and paclitaxel (BP regimen) as a first-line treatment has proven highly effective with good tolerance for patients with metastatic breast cancer (MBC). The objective of this study was to examine the efficacy and safety of the BP regimen for Japanese patients with MBC in real-world clinical settings. Methods: From June 2012 through May 2014, we recruited 94 patients at 10 medical institutions. The primary endpoint was time to treatment failure (TTF), and the secondary endpoints were overall survival (OS) and safety. Objective response was assessed according to the Response Evaluation Criteria in Solid Tumors. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0-Japan Clinical Oncology Group. Results: Nighty patients with MBC (mean 58 years, range: 34-80 years) were enrolled, and 60 (66.6%) and 52 (57.7%) had undergone prior chemotherapy as adjuvant treatment and treatment for MBC, respectively. Median TTF was 6.2 months (95% confidence interval [CI], 4.2-8.3 months), and median OS was 15.4 months (95% CI, 12.0-18.9 months). The overall response rate was 67.8% (95% CI: 57.1-77.2%). A total of 28 patients (31.1%) required a dose reduction of paclitaxel. Forty-five, 42, and 3 patients received the initial doses of 90, 80, and 60 mg/m², respectively. Among patients who received the initial doses of 90 mg/m², 13 patients (28.9%) unexpectedly required a dose reduction of ≥20 mg/m². The BP regimen was discontinued for 66 (73.3%) of the 90 patients, 52 (57.7%) of whom experienced "disease progression." Grade 3/4 hematologic AEs developed in 51 patients (56.6%), with leukopenia and neutropenia in 16 patients (17.8%) and 21 patients (23.3%), respectively. Grade 3 nonhematologic AEs developed in 8 patients (8.9%), with the most common nonhematologic AE of peripheral neuropathy in 4 patients (4.4%). No Grade 4 nonhematologic AEs developed. Peripheral neuropathy [56 patients (62.2%)], nail discoloration [53 patients (58.9%)], and fatigue [51 patients (56.7%)] were the most predominant AEs--the known AEs of paclitaxel. Conclusions: The BP regimen was active and well tolerated in the real-world clinical settings. As many as 28.9% of patients who received the initial dose of 90 mg/m² required a dose reduction of paclitaxel by 20 mg/m². Therefore, there is a need to find a therapeutic regimen that is less likely to result in dose reductions for patients with MBC who undergo a BP regimen using the initial paclitaxel dose of 90 mg/m². [ABSTRACT FROM AUTHOR]

Case: Stress fractures of the first rib rarely have been reported in association with sports activities. We report a case of a cerebellar infarction that possibly was associated with arterial thoracic outlet syndrome (aTOS) that developed as a result of extensive callus formation in a young baseball player with a stress fracture of the first rib. Conclusion: According to the literature, almost all cases of stress fracture in the first rib have a relatively good prognosis, and there are only a few reports of TOS occurring as a rare late complication. To our knowledge, there have been no prior reports of cerebellar infarction associated with aTOS following a stress fracture of the first rib. [ABSTRACT FROM AUTHOR]

Background: Uterine sarcoma is a rare tumor that is often difficult to classify based on morphological and immunohistochemical analysis alone. Limited access to molecular biological analysis in routine practice would hinder making a definitive diagnosis. Case Presentation: In this report, we describe a case of a mesenchymal tumor arising from the uterine cervix in a 52-year-old woman. From microscopic morphology of the resected specimen, epithelioid leiomyosarcoma, high-grade endometrial stromal sarcoma, or uterine gastrointestinal stromal tumor (GIST) were considered as differential diagnoses. The immunophenotype of the tumor featured smooth muscle differentiation and hormone receptor expression. The cell membrane and cytoplasm were positive for c-kit, although no mutation was found in the c-kit or PDGFRA gene. Fluorescence in situ hybridization (FISH) analysis revealed a relatively low frequency of YWHAE rearrangement, whereas there were few NUTM2A and NUTM2B split signals. Conclusions: In this case, the tumor was not typical of any three of the differential diagnoses mentioned above. However, insufficient frequency of YWHAE, NUTM2A, and NUTM2B gene rearrangement and absence of mutation in both the c-kit and PDGFRA genes suggested that this tumor should be categorized as epithelioid leiomyosarcoma. This is an instructive case showing a potential diagnostic pitfall of uterine sarcoma. Comprehensive approaches including molecular biological techniques are required for definitive diagnosis. [ABSTRACT FROM AUTHOR]

Background. Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined.Methods. Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions.Results. New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected.Conclusion. Ligation and cutting of several supplying arteries by RT induces new areterial vascularization and it does not seem to affect fetal growth and placental function.

Preeclampsia is often accompanied by hypoxia of the placenta and this condition induces apoptosis in trophoblastic cells. The aim of this study was to characterize global changes of apoptosis-related proteins induced by hypoxia in trophoblastic cells so as to clarify the mechanism of hypoxia-induced apoptosis by using the PoweBlot, an antibody-based Western array. Human choriocarcinoma cell line JAR was cultured for 24 hours under aerobic and hypoxic conditions. Hypoxia induced apoptosis accompanied by increased expression of Bcl-x, Caspase-3 and -9, Hsp70, PTEN, and Bag-1. Bad, pan-JNK/SAPK-1, Bcl-2, Bid, and Caspase-8 showed decreased expression. Hypoxia-induced apoptosis was increased with the transfection of a bag-1 antisense oligonucleotide. The bag-1 antisense oligonucleotide affected the expression of Bid, Bad, Bcl-2, JNK, and phosphorylated JNK, although expression of PTEN and Bcl-X did not change. Bag-1 may inhibit apoptosis by suppressing the expression of Bid and Bad. It may also enhance apoptosis by inhibiting the expression of Bcl-2 and by modulating phosphorylation of JNK. Both mitochondrial and stress-activated apoptosis pathways played important roles in the hypoxia induced cell death of trophoblastic cells. These findings will contribute to establish new approach to detect hypoxic stress of the placenta, which leads to preeclampsia and other hypoxia-related obstetrics complications.