instruction:
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.
question:
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 -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<0.05), as well as in one of three platinum-sensitive tumors (p=0.04). The combination of GSI and paclitaxel was significantly more effective than GSI alone and paclitaxel alone in all platinum-resistant ovarian tumors (all p<0.05). 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.
answer:
Does inhibition of notch signaling in combination with Paclitaxel reduce platinum-resistant ovarian tumor growth?

question:
The biliary cast syndrome (BCS) is a frequent problem following liver transplantation. The pathogenesis of this complication is not well understood. Previous research has demonstrated that the soluble form of MICA (sMICA) is significantly higher in patients with chronic liver disease and hepatocellular carcinoma (HCC) than in healthy volunteers. The aim of this study is to investigate the possible involvement of sMICA in the formation of BCS after liver transplantation.', 'Serum soluble MICA was retrospectively evaluated in pre- and post-transplant sera from 133 consecutive primary liver transplant patients and in sera from 88 healthy volunteers using sandwich ELISA. Normal distribution of serum sMICA was described by the data obtained from healthy population and sMICA concentration that was greater than the upper bound 95% normal range was considered as high levels of sMICA. Patient records were reviewed to identify patients who developed BCS.', 'The results demonstrated that 37.6% of patients with end-stage liver diseases had significantly higher pre-transplant serum sMICA than in healthy population. 34.4% of recipients with post-transplant high levels of sMICA developed BCS. In contrast, 17.3% of patients with post-transplant normal levels of sMICA developed BCS. The risk of BCS development is significantly associated with the presence of post-transplant high levels of sMICA (P=0.0365). Further analysis disclosed that patients with decreased post-transplant sMICA following liver transplantation had a lower incidence rate of BCS than those with remained high levels of sMICA after transplantation (10.5% vs. 38.7%, P=0.0302). Furthermore, log-rank test showed that BCS occurrence was significantly associated with dynamic changes of sMICA among different groups (P=0.0188).
answer:
Are high levels of soluble Major Histocompatibility Complex class I related chain A ( MICA ) associated with biliary cast syndrome after liver transplantation?

question:
Dopamine and corticotrophin-releasing hormone (CRH; also known as corticotrophin-releasing factor) are key neurotransmitters in the interaction between stress and addiction. Repeated treatment with cocaine potentiates glutamatergic transmission in the rat basolateral amygdala/cortex pathway through a synergistic action of D1 -like dopamine receptors and CRH type-2 receptors (CRF2 receptors). We hypothesized that this observed synergism could be instrumented by heteromers containing the dopamine D1 receptor and CRF2 receptor.', 'D1 /CRF2 receptor heteromerization was demonstrated in HEK293T cells using co-immunoprecipitation, BRET and FRET assays, and by using the heteromer mobilization strategy. The ability of D1 receptors to signal through calcium, when singly expressed or co-expressed with CRF2 receptors, was evaluated by the calcium mobilization assay.', 'D1 /CRF2 receptor heteromers were observed in HEK293T cells. When singly expressed, D1 receptors were mostly located at the cell surface whereas CRF2 receptors accumulated intracellularly. Interestingly, co-expression of both receptors promoted D1 receptor intracellular and CRF2 receptor cell surface targeting. The heteromerization of D1 /CRF2 receptors maintained the signalling through cAMP of both receptors but switched D1 receptor signalling properties, as the heteromeric D1 receptor was able to mobilize intracellular calcium upon stimulation with a D1 receptor agonist.
answer:
Do dopamine D1 and corticotrophin-releasing hormone type-2 receptors assemble into functionally interacting complexes in living cells?