Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

[EX Q]: Bone, as well as the lung and liver, is among the sites of predilection for cancer metastasis. The bone stores large amounts of growth factors such as insulin-like growth factors and transforming growth factor-b, and provides fertile soil for metastatic cancer cells by continuously releasing these bone-stored growth factors, which are a consequence of osteoclastic bone resorption. Metastatic cancer cells in turn produce osteoclast-stimulating cytokines such as parathyroid hormone-related protein( PTH-rP), prostaglandin E2.(PGE2), and various interleukins(ILs). These cancer-produced osteoclast-stimulating cytokines bind to their cognitive receptors and promote the expression of ligands for the receptor activators of nuclear factor kB (RANKL)in osteoblasts. RANKL then binds to its receptor RANK, expressed in pre-osteoclasts, stimulates mature osteoclast formation, and subsequently, osteoclastic bone resorption. This vicious cycle between metastatic cancer cells and osteoclasts is critical to the development and progression of bone metastases. In addition, it is likely that metastatic cancer cells are influenced by bone environments(or niche)and acquire additional capacities such as an epithelial-mesenchymal transition(EMT), allowing them to be resistant to chemotherapy or apoptosis, to survive in a dormant state, or to aggressively spread to distant organs including lung and liver. Thus, the bone can serve as transit port. Disrupting this cycle by inhibiting osteoclastic bone resorption, antagonizing bone-derived growth factors, and neutralizing RANKL or PTH-rP, should be a promising therapeutic intervention for bone metastases. Bisphosphonates(BP)are specific inhibitors of osteoclasts, and have been shown to significantly reduce skeletal-related events(SRE)associated with bone metastasis. Denosumab is a neutralizing monoclonal antibody to RANKL and has recently been found to inhibit SRE more effectively than BP. Further understanding of the crosstalk communication between metastatic cancer cells and bone at the molecular level should lead us to design novel, more effective and specific treatments for cancer patients with bone metastases.
[EX A]: To the ligand of which receptors does Denosumab (Prolia) bind?

[EX Q]: 1st Kings was an electoral district in the Canadian province of Prince Edward Island, which elected two members to the Legislative Assembly of Prince Edward Island from 1873 to 1993.
[EX A]: The year that 1st Kings was created was?

[EX Q]: The origin of brain tumors has attracted much controversy. Recent advances in neural stem cell biology coupled with the new concepts of central nervous system development have raised interesting possibilities regarding the oncogenic properties of neural stem/progenitor cells. To elucidate these putative properties further, the clinical materials from an infant brain tumor were analyzed, focusing on the relation with the neural stem/progenitor cells. The expression of neural stem/progenitor cell markers in the tumor cells and the cellular components of the infant brain tumor were examined using immunohistochemistry. The tumor cell biology was analyzed both in culture and in the grafted brain environment. Three main bodies of evidence were demonstrated indicating that the tumor was of possible subventricular zone postnatal or adult normal neural stem cell origin. First, in the tumor specimen we demonstrated the strong positive expression of the neural stem/progenitor cell markers, nestin and Musashi-1. Second, immunohistochemistry revealed the presence of neuronal, astrocytic, and immature precursor cells in the tumor tissue, similar to the cellular components of the subventricular zone, thereby pointing to the subventricular zone as the possible origin of the tumor. The subventricular zone also is one of the strong candidates for the location of postnatal/adult neural stem cells. This cellular evidence was strengthened further by the clinicoradiological findings that demonstrated the involvement of the subventricular zone of the lateral ventricle by the tumor. Third, in the in vitro and in vivo experiments, a dynamic shift in expression patterns between neural stem cells (nestin, Musashi-1) and differentiated cells (glial fibrillary acidic protein, neuron-specific Class III beta-tubulin) markers was seen, similar to the proposed behavior of postnatal/adult neural stem cells in situ. These findings suggest that this brain tumor originated from neural stem cells located in the subventricular zone, and the further possibility of the general oncogenic potential of neural stem cells.
[EX A]:
Which intermediate filament (IF) protein can be used as a non-specific marker of the neuronal precursor cells of the subventricular zone?