Coexisting pathology of ectopic pregnancy and dermoid cyst: An uncommon occurrence

Mature cystic teratomas (dermoid cysts) are common benign ovarian neoplasms. About 10% of dermoid cysts are detected duringpregnancy. Multiple gynecologic pathologies occurring together are uncommon, and both an ectopic pregnancy and dermoid cystare seen concurrently being unknown and poorly documented. Here, we report a case of ectopic pregnancy and dermoid cystoccurring simultaneously in a 30-year-old woman

Penerapan Model Pembelajaran Numbered Heads Together (Nht) Dalam Upaya Untuk Meningkatkan Keaktifan Dan Hasil Belajar Mahasiswa Prodi Pendidikan IPA Ust YOGYAKARTA Tahun Akademik

: This research has been done to know how NHT as a model of study could increase activity and achievement the students of natural science education department on 2013/2014 of academic year. This was a class action research. This research consisted of two cycles. Each cycles was consist of planning, doing, observing and reflecting. The instruments of this research were lecture-observing papers, students-observing papers, evaluating papers and statements papers. The result showed increasing of students\u27 activity. At first discussion on first cycles, there were 52.5% active students, at last discussion on second cycles there were 90.8% active students. The average of students\u27 achievement has increased 15.3 points, i.e. from 63.2 to 78.5

Synergy of water soluble prodrug triptolide (minnelide) with gemcitabine and nab-paclitaxel in pancreatic cancer

259 Background: Gemcitabine with nab-paclitaxel is the standard of care for metastatic Pancreatic Ductal Adenocarcinoma (PDAC). Addition of nab-paclitaxel to gemcitabine improves the survival of patients with metastatic pancreatic cancer by only 6 weeks while increasing toxicity. Meaningful combinations that reduce the doses while improving efficacy are required. Water soluble prodrug of triptolide (Minnelide) is effective against PDAC in preclinical studies and has demonstrated activity in the ongoing phase I trial. We have evaluated the combination of low dose triptolide prodrug with lowered doses of Abraxane and gemcitabine in PDAC. Methods: Pancreatic cancer cell lines S2-013 and S2-VP10 were xenografted both subcutaneously as well as orthotopically in athymic nude mice. Efficacy of a combination of triptolide prodrug (Minnelide: 0.21mg/kg) with reduced dose of gemcitabine 100mg/kg + Abraxane 10mg/kg (~40% of the clinically effective dose) was evaluated and compared with both standard of care gemcitabine 250mg/kg + Abraxane 25mg/kg as well as reduced dose of gemcitabine + Abraxane in animal models. We also used the immunocompetent model where murine PDAC cell line KPC001 implanted subcutaneously in C57/bl6 mice. Results: In subcutaneous syngeneic model, combination of triptolide prodrug and paclitaxel significantly inhibited tumor growth (tumor volumes expressed as % of Control, Mean±SEM: triptolide prodrug: 75.4±25, paclitaxel: 50.0 ±3, triptolide prodrug + paclitaxel: 11.0 ±1). In metastasis model combination therapy markedly improved survival (median survival in days: Vehicle-13, triptolide prodrug -20, standard of care -45, reduced dose standard of care-30, and Minnelide + reduced dose standard of care (all mice alive at 90 days). Combination of triptolide prodrug and low dose gemcitabine + nab-paclitaxel decreased tumor size, increased survival, reduced metastases and malignant ascites in orthotopic model of PDAC. Conclusions: Triptolide prodrug synergizes with reduced dose standard of care (gemcitabine and nab-paclitaxel) and helps in reducing the doses of these toxic drugs all the while achieving same or better efficacy in animal models of PDAC

Modulation of post-translational modifications in β-catenin and LRP6 inhibits Wnt signaling pathway in pancreatic cancer

β-Catenin/Wnt signaling pathway is critically regulated in a normal cell by a number of post-translational modifications. In pancreatic cancer however, aberrant activation of this pathway plays a significant role in tumor progression and metastasis. Though a number of studies have focused on understanding Wnt signaling pathway in pancreatic cancer, there has been no systematic study to evaluate molecules that may be affecting this pathway. In the current study, we used a diterpene triepoxide, triptolide, to inhibit post-translational modifications in Wnt pathway and evaluated how this compound may be affecting the intricate signaling that regulates cell proliferation in pancreatic cancer. Our results showed that triptolide inhibits the activation of WNT1, FZD1, and disheveled (DSH) in pancreatic cancer cell lines MIA PaCa-2 and S2-VP10 by inhibiting the phosphorylation of LRP6 and simultaneously blocked translocation of β-catenin to the nucleus by inhibiting its glycosylation. Additionally, inhibition of post-translational modification of the Wnt-signaling pathway also demonstrated regression of tumor growth in a Syngenic Tumor Implantation Model (STIM). Interestingly, these findings suggest Wnt signaling is a vital molecular pathway in pancreatic cancer and may be amenable to targeted drug therapy

Genetics of pancreatic cyst-cancer progression: standing on the shoulders of giants

Pancreatic cancer, despite years of study and some progress, presents with a grim prognosis in almost all cases. In the current review, we have discussed recent studies that have attempted to decipher the genetic makeup of pancreatic ductal adenocarcinoma and preneoplastic pancreatic cystic neoplasms. With the advent of high throughput sequencing, the genetic code of pancreatic cancer is beginning to unravel and this new-found information heralds an era of precision cancer care where treatment will be guided by the genetic code of the neoplasm. Results from these studies have pointed towards the complexity and heterogeneity of the pancreatic cancer genome, provided avenues to "tailor therapy" based as well as shed light on progression of preneoplastic pancreatic neoplasms into full blown invasive pancreatic ductal adenocarcinoma. While this progress has made us closer to the model of precision medicine, significant obstacles need to be overcome to use this new-found information to change the way we manage patients with pancreatic cancer

Abstract 5119: Evaluation of Minnelide as potential targeted therapy for triple negative breast cancer

Abstract Recent advances in diagnostics and better understanding of molecular mechanism underlying breast cancer has let to the better therapeutic options and disease outcome for majority of breast cancer patients. However, ~10 - 20% of all breast cancers often referred to as “triple negative” as they lack expression of the estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors convey a poor prognosis due in part to a lack of targeted therapies. The aim of the current study is to evaluate whether triptolide and its water soluble analog Minnelide is effective against triple negative breast cancer cells. We have previously shown that triptolide/Minnelide not only reduces tumor growth in various cancer models but it also regulates epithelial -mesenchymal transition (EMT), an important mechanism underlying metastasis. In our preliminary findings using three triple negative breast cancer (TNBC) cell lines, MDA-MB-231, MDA-MB-468, and MDA-MB-157, we demonstrate that triptolide not only inhibits the proliferation of TNBC cells but also regulates the protein levels of EMT markers including β-Catenin and Vimentin. In order to elucidate the mechanism underlying triptolide mediated inhibition of cellular proliferation and regulation of EMT markers in TNBC cells, we identified Src kinase and Aurora kinase A as two new targets for triptolide action in TNBC cells. By targeting Src and Aurora kinase, triptolide disrupts the integrity of focal adhesion structures and reduces cell spreading via regulating FAK activity. Our preliminary findings regarding potential use of triptolide/Minnelide in TNBC based on in vitro experiments are promising. However, considering the complex pathophysiology of breast cancer and other biological factors playing role in a disease setting, in-vivo experiments to test the efficacy of Minnelide in relevant mouse models for mammary cancers are currently underway. Citation Format: Mahendra K. Singh, Soham Shah, Nikita Satish Sharma, Bhuwan Giri, Sulagna Banerjee, Ashok Saluja. Evaluation of Minnelide as potential targeted therapy for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5119. doi:10.1158/1538-7445.AM2017-5119</jats:p

Inhibition of NF-kappa B pathway leads to deregulation of epithelial-mesenchymal transition and neural invasion in pancreatic cancer

NF-κB has an essential role in the initiation and progression of pancreatic cancer and specifically mediates the induction of epithelial-mesenchymal transition and invasiveness. In this study, we demonstrate the importance of activated NF-κB signaling in EMT induction, lymphovascular metastasis, and neural invasion. Modulation of NF-κB activity was accomplished through the specific NF-κB inhibitor (BAY 11-7085), triptolide, and Minnelide treatment, as well as overexpression of IKBα repressor and IKK activator plasmids. In the classical lymphovascular metastatic cascade, inhibition of NF-κB decreased the expression of several EMT transcription factors (SNAI1, SNAI2, and ZEB1) and mesenchymal markers (VIM and CDH2) and decreased in vitro invasion, which was rescued by IKK activation. This was further demonstrated in vivo via BAY 11-7085 treatment in a orthotopic model of pancreatic cancer. In vivo NF-κB inhibition decreased tumor volume; decreased tumor EMT gene expression, while restoring cell-cell junctions; and decreasing overall metastasis. Furthermore, we demonstrate the importance of active NF-κB signaling in neural invasion. Triptolide treatment inhibits Nerve Growth Factor (NGF) mediated, neural-tumor co-culture in vitro invasion, and dorsal root ganglia (DRG) neural outgrowth through a disruption in tumor-neural cross talk. In vivo, Minnelide treatment decreased neurotrophin expression, nerve density, and sciatic nerve invasion. Taken together, this study demonstrates the importance of NF-κB signaling in the progression of pancreatic cancer through the modulation of EMT induction, lymphovascular invasion, and neural invasion