TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Development of novel strategies in the treatment of advanced thyroid cancer are needed. Our laboratory has previously identified a role for nuclear factor κB (NF-κB) signaling in human thyroid cancer cell growth, survival, and invasion.', 'Our goal was to establish the role of NF-κB signaling on thyroid cancer growth and metastases in vivo and to begin to dissect mechanisms regulating this effect.', 'We examined tumor formation of five thyroid cancer cell lines in an in vivo model of thyroid cancer and observed tumor establishment in two of the cell lines (8505C and BCPAP).', 'Inhibition of NF-κB signaling by overexpression of a dominant-negative IκBα (mIκBα) significantly inhibited thyroid tumor growth in tumors derived from both cell lines. Further studies in an experimental metastasis model demonstrated that NF-κB inhibition impaired growth of tumor metastasis and prolonged mouse survival. Proliferation (mitotic index) was decreased in 8505C tumors, but not in BCPAP tumors, while in vitro angiogenesis and in vivo tumor vascularity were significantly inhibited by mIkBα only in the BCPAP cells. Cytokine antibody array analysis demonstrated that IL-8 secretion was blocked by mIκBα expression. Interestingly, basal NF-κB activity and IL-8 levels were significantly higher in the two tumorigenic cell lines compared with the nontumorigenic lines. Furthermore, IL-8 transcript levels were elevated in high-risk human tumors, suggesting that NF-κB and IL-8 are associated with more aggressive tumor behavior.

SOLUTION: Is nuclear factor κB-dependent regulation of angiogenesis , and metastasis in an in vivo model of thyroid cancer associated with secreted interleukin-8?

PROBLEM: Ovarian cancer (OvCa) is the most lethal gynecologic malignancy in the United States because of chemoresistant recurrent disease. Our objective was to investigate the efficacy of inhibiting the Notch pathway with a γ-secretase inhibitor (GSI) in an OvCa patient-derived xenograft model as a single agent therapy and in combination with standard chemotherapy.', 'Immunocompromised mice bearing xenografts derived from clinically platinum-sensitive human ovarian serous carcinomas were treated with vehicle, GSI (MRK-003) alone, paclitaxel and carboplatin (P/C) alone, or the combination of GSI and P/C. Mice bearing platinum-resistant xenografts were given GSI with or without paclitaxel. Gene transcript levels of the Notch pathway target Hes1 were analyzed using RT-PCR. Notch1 and Notch3 protein levels were evaluated. The Wilcoxon rank-sum test was used to assess significance between the different treatment groups.', 'Expression of Notch1 and 3 was variable. GSI alone decreased tumor growth in two of three platinum-sensitive ovarian tumors (p\u2009<\u20090.05), as well as in one of three platinum-sensitive tumors (p\u2009=\u20090.04). The combination of GSI and paclitaxel was significantly more effective than GSI alone and paclitaxel alone in all platinum-resistant ovarian tumors (all p\u2009<\u20090.05). The addition of GSI did not alter the effect of P/C in platinum-sensitive tumors. Interestingly, although the response of each tumor to chronic GSI exposure did not correlate with its endogenous level of Notch expression, GSI did negatively affect Notch signaling in an acute setting.

SOLUTION: Does inhibition of notch signaling in combination with Paclitaxel reduce platinum-resistant ovarian tumor growth?

PROBLEM: To establish a cell model by chronically infecting human gastric epithelial cells with H.pylori, and to determine the effect of chronic H.pylori infection on apoptosis of gastric epithelial cells.', 'Human non-tumor gastric epithelial cells GES-1 were cocultured with an H.pylori strain SS1 for 16 weeks, in order to obtain GES-1 "model" cells. Biological characteristics of the model cells including growth, adherence and clone formation were determined. Apoptosis of the "model" cells in response to apoptosis inducers such as H.pylori and other enterobacteria and agents commonly used in the chemotherapy of gastric cancer were measured by flow cytometry.', 'A cell model of human gastric epithelial cells with chronic H.pylori infection (GES-1 model cells) was successfully established. Apoptosis was dramatically decreased in the "model" cells with and without stimulation by H.pylori and other enterobacteria and some chemotherapeutic agents.

SOLUTION:
Does [ Chronic Helicobacter pylori infection induce apoptosis-resistance in gastric epithelial cells ]?