Eight human catalytic phosphoinositide 3-kinase (PI3K) isoforms exist which are subdivided into three classes. While class I isoforms have been well-studied in cancer, little is known about the functions of class II PI3Ks.The expression pattern and functions of the class II PI3KC2β isoform were investigated in a panel of tumour samples and cell lines.Overexpression of PI3KC2β was found in subsets of tumours and cell lines from acute myeloid leukemia (AML), glioblastoma multiforme (GBM), medulloblastoma (MB), neuroblastoma (NB), and small cell lung cancer (SCLC). Specific pharmacological inhibitors of PI3KC2β or RNA interference impaired proliferation of a panel of human cancer cell lines and primary cultures. Inhibition of PI3KC2β also induced apoptosis and sensitised the cancer cells to chemotherapeutic agents.Together, these data show that PI3KC2β contributes to proliferation and survival in AML, brain tumours and neuroendocrine tumours, and may represent a novel target in these malignancies.
In the treatment of various retinal pigment epithelium (RPE) related retinal diseases, selective retina therapy (SRT) is highly demanded, as SRT intends to selectively damage the RPE while sparing the neurosensory retina (NSR) and the choroid. A gentle method for removing diseased host RPE cells is still missing regarding RPE stem cell therapy. Cell therapeutics for age-related macular degeneration are often implanted regardless of host RPE status in the target zone, which may result in RPE multilayering. Here, we study a novel laser for selective large-area RPE removal without damaging the surrounding tissue prior to RPE implantation to promote subretinal integration. Therefore, pigmented rabbit eyes were exposed to laser pulses of 8 μs in duration (wavelength, 532 nm; top-hat beam profile, 223 × 223 μm2). Postirradiation retinal changes were assessed with color fundus photography, fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Here we present the histological outcome of four animals after laser treatment. Following euthanization, the eyes of the animals were processed for histology, sectioned in 5 μm paraffin sections and stained with hematoxylin and eosin. Particular emphasis was given to an OCT vs light microscopy comparison. Our results reveal that RPE can be removed selectively using laser pulses of 8 µs duration in the green spectral range without damaging the NSR. Therefore, this regime proves to be applicable in the sense of SRT.
Eight human catalytic phosphoinositide 3-kinase (PI3K) isoforms exist which are subdivided into three classes. While class I isoforms have been well-studied in cancer, little is known about the functions of class II PI3Ks.The expression pattern and functions of the class II PI3KC2β isoform were investigated in a panel of tumour samples and cell lines.Overexpression of PI3KC2β was found in subsets of tumours and cell lines from acute myeloid leukemia (AML), glioblastoma multiforme (GBM), medulloblastoma (MB), neuroblastoma (NB), and small cell lung cancer (SCLC). Specific pharmacological inhibitors of PI3KC2β or RNA interference impaired proliferation of a panel of human cancer cell lines and primary cultures. Inhibition of PI3KC2β also induced apoptosis and sensitised the cancer cells to chemotherapeutic agents.Together, these data show that PI3KC2β contributes to proliferation and survival in AML, brain tumours and neuroendocrine tumours, and may represent a novel target in these malignancies.
