In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

[Q]: Context: Characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, current therapy options are not satisfactory. PKI-587 is a highly potent novel dual inhibitor of PI3K and mTORC1/C2.', 'We assessed the effects of PKI-587 in different GEP-NEN tumor models, including poorly differentiated cell line LCC-18, compared with the established mTORC1 inhibitor everolimus.', 'We treated the cell lines BON, QGP1, KRJ-I and LCC-18 with increasing concentrations of the inhibitor PKI-587, and compared with everolimus and DMSO. We assessed the impact of treatments on viability (WST-1 assay), on apoptotic processes (Caspase 3/7 assay, JC-1) and on cell cycle regulation (flow cytometry). We determined alterations of signaling mediators by phosphor-specific western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology).', 'In all cell lines, PKI-587 dose-dependently inhibited proliferation whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest, induction of apoptosis and successfully suppressed activity of direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT and PI3K pathway genes after treatment. Treatment dependent and cell line characteristic effects on AKT/RB/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this article.\Question: Is inhibition of mTORs Catalytic Site by PKI-587 a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease?
[A]: PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials.


[Q]: Context: In HIV patients, disorders in glucose metabolism seem to be side effects of highly active antiretroviral therapy (HAART) which may be favoured by obesity, abdominal fat accumulation and familial disposition for diabetes mellitus (DM). The aim of our study was to identify patients at high risk for abnormalities in glucose metabolism taking into account HAART, familial disposition for DM and anthropometric parameters.', 'Plasma glucose, insulin, c-peptide and insulin resistance (homeostasis model assessment, HOMA) were determined in 44 HIV patients [16 without HAART, 19 with protease inhibitors (PI), 9 without PI (non-PI)] and in 11 healthy subjects. Glucose tolerance was determined by standard procedures. Body mass index (BMI), triceps skin fold thickness and waist circumference were measured and the waist-to-hip-ratio was calculated. Familial disposition for DM was assessed by questionnaire.', 'Impaired fasting glucose was observed in 28% of HAART-treated patients (21% with PI, 7% non-PI), in 13% of HAART-naive but none in healthy controls. 58% of PI, 44% of non-PI, 38% of HAART-naive and none of healthy controls had a HOMA-index > 2.5 which indicates insulin resistance. HAART-treated patients had significantly higher fasting glucose levels (PI: 97 +/- 11 mg/dL, p = 0.048; non-PI: 109 +/- 58 mg/dL, p = 0.009) compared to healthy controls (72 +/- 8 mg/dL). HOMA-Index was higher in PI treated patients (3.74 +/- 3.08) than in HIV negative controls (0.95 +/- 0.28, p = 0.018). The duration of HAART (p = 0.045), overweight and familial disposition for DM (p = 0.017) significantly affected fasting glucose among PI users. Waist circumference affected c-peptide (p = 0.046) concentration in these patients.\Question: Are overweight HIV patients with abdominal fat distribution treated with protease inhibitors at high risk for abnormalities in glucose metabolism - a reason for glycemic control?
[A]: HIV patients on long-term PI therapy with overweight and familial disposition for DM are at high risk to develop abnormalities of glucose metabolism. Thus, measurements of HOMA-Index, BMI and waist circumference should be routinely done especially in PI medicated patients.


[Q]: Context: Mutation of the Chx10 homeobox gene in mice and humans causes congenital blindness and microphthalmia (small eyes). This study used Chx10-/- (ocular retardation) mice to investigate how lack of Chx10 affects progenitor/stem cell behavior in the retina and ciliary epithelium (CE).', 'The distribution of mitotic retinal progenitor cells (RPCs) during embryonic development was analyzed using phosphohistone 3 (H3)-labeling. DNA flow cytometry was used to measure DNA content. The distribution and phenotype of dividing cells in the postnatal retina and CE was analyzed by incorporation of the thymidine analogue BrdU and immunohistochemistry.', 'The Chx10-/- embryonic retina maintained a constantly sized population of mitotic RPCs during development, causing the mitotic index to increase markedly over time compared with the wild type. Also, the proportion of cells in the G1 phase of the cell cycle was increased compared with the wild type. Of interest, division of RPC-like cells with neurogenic properties persisted in the adult Chx10-/- retina. Colabeling for BrdU and the neural progenitor marker nestin or the neuronal markers beta3-tubulin, syntaxin, and VC1.1 showed that new amacrine-like neurons developed in the adult central retina. By contrast, cells with these characteristics were not observed in the mature wild-type retina. In the mature CE, BrdU-positive cells were observed in both wild-type and Chx10-/- mice. However, neurogenesis from this cell population was not evident.\Question: Does absence of chx10 cause neural progenitors to persist in the adult retina?
[A]:
Without Chx10, proliferative expansion of the embryonic RPC pool is markedly reduced. In the adult retina, lack of Chx10 results in a population of dividing neural progenitor cells that persist and produce new neurons in the central retina.