Project description:Interventions: robot-assisted colorectal cancer surgery using the da Vinci Si Surgical System
Primary outcome(s): The conversion rate to open surgery
Study Design: Single arm Non-randomized
Project description:Interventions: Laparoscopic rectal surgery using da Vinci surgical system
Primary outcome(s): Adverse event rate
Study Design: Single arm Non-randomized
Project description:MicroRNA has a great potential in predicting survival of cancer patient. We used a genome-wide microRNA expression profiling to identify a miRNA signature for the prediction of clinical outcome of primary GBM patients.
Project description:Interventions: A group: We perform radical resection for colorectal cancer by using the da Vinci surgical system. We performe 3 months follow-up for the patients after the operation.
Primary outcome(s): Adverse event rate
Study Design: Single arm Non-randomized
Project description:MicroRNA has a great potential in predicting survival of cancer patient. We used a genome-wide microRNA expression profiling to identify a miRNA signature for the prediction of clinical outcome of primary GBM patients. Total RNA obtained from 82 surgical specimens of primary glioblastoma multiform and 5 normal brain tissues from areas surrounding arteriovenous malformations (AVM) as control.
Project description:Direct reprogramming of human fibroblasts to a pluripotent state has been achieved through ectopic expression of the transcription factors OCT4, SOX2, and either cMYC and KLF4 or NANOG and LIN28. Little is known, however, about the mechanisms by which reprogramming occurs, which is in part limited by the low efficiency of conversion. To this end, we sought to create a doxycycline-inducible lentiviral system to convert primary human fibroblasts and keratinocytes into human induced pluripotent stem (hiPS) cells. hiPS cells generated with this system were molecularly and functionally similar to human embryonic stem (hES) cells, demonstrated by gene expression profiles, DNA methylation status, and differentiation potential. While expression of the viral transgenes was required for several weeks in fibroblasts, we found that 10 days was sufficient for the reprogramming of keratinocytes, suggesting that the kinetics of reprogramming are cell-type dependent. Using our inducible system, we developed a strategy to induce hiPS cell formation at high frequency by generating differentiated cells that contain the viral transgenes in a pattern that enables successful induction of pluripotency. Upon addition of doxycycline to differentiated hiPS-derived cells, we obtained “secondary” hiPS cells at a frequency at least 100-fold greater than the initial conversion. The ability to reprogram cells with high efficiency provides a unique platform to dissect the underlying molecular and biochemical processes that accompany nuclear reprogramming.
Project description:Direct conversion of reactive glial cells to neurons is promising avenue for the replacement therapies after brain injury or neurodegeneration. The overexpression of developmental neurogenic fate determinants in glial cells converts them to neurons. For the repair purposes the conversion is confined to the pathology-induced neuroinflammatory environment. However, very little is known about the influence of injury-induced neuroinflammatory environment on the direct conversion process. We established the new in vitro culture system of postnatal astrocytes that reflects the direct conversion rate in the injured, neuroinflammatory environment in vivo. We could show that the growth factor combination corresponding to the injured environment defines the capacity of the glia to be directly converted to neurons. Using this culture, we showed that the chromatin structural protein high mobility group b2 (Hmgb2) regulates the direct conversion rate downstream of the growth factor combination. We could further show that Hmgb2 cooperates with neurogenic fate determinants such as Neurog2 to open the chromatin containing neuronal maturation and synapse formation genes, leading to early chromatin re-arrangements during the direct fate conversion that are necessary for the full fate conversion. Our data demonstrate the novel, environmental cues controlled level of gene regulation during direct fate conversion necessary for the proper maturation of induced neurons that could be targeted to improve the repair process.
Project description:Direct conversion of reactive glial cells to neurons is promising avenue for the replacement therapies after brain injury or neurodegeneration. The overexpression of developmental neurogenic fate determinants in glial cells converts them to neurons. For the repair purposes the conversion is confined to the pathology-induced neuroinflammatory environment. However, very little is known about the influence of injury-induced neuroinflammatory environment on the direct conversion process. We established the new in vitro culture system of postnatal astrocytes that reflects the direct conversion rate in the injured, neuroinflammatory environment in vivo. We could show that the growth factor combination corresponding to the injured environment defines the capacity of the glia to be directly converted to neurons. Using this culture, we showed that the chromatin structural protein high mobility group b2 (Hmgb2) regulates the direct conversion rate downstream of the growth factor combination. We could further show that Hmgb2 cooperates with neurogenic fate determinants such as Neurog2 to open the chromatin containing neuronal maturation and synapse formation genes, leading to early chromatin re-arrangements during the direct fate conversion that are necessary for the full fate conversion. Our data demonstrate the novel, environmental cues controlled level of gene regulation during direct fate conversion necessary for the proper maturation of induced neurons that could be targeted to improve the repair process.