Success in generating insulin-producing cells (IPCs) from human embryonic stem (hES) cells by genetic manipulation has recently revealed a new therapeutic potential for diabetes. However, clinical application has been hampered by the viral genome integration and the risk of insertion mutagenesis that are entailed. Herein, we report the induction of hEC into IPCs by direct delivery of human Pdx1 proteins per se. Recombinant human Pdx1 proteins (hPdx1), which have an Antennapedia-like protein transduction domain sequence in their structure, can be efficiently translocated into hES cells and function as pancreatic transcription factor. hPdx1 protein activates a group of genes related to pancreatic beta-cell lineage development in hES cells, including NeuroD1, Nkx2.2, Pax4, Pax6, Nkx6.1 and Isl-1. hPdx1-treated hES cells synthesise and release insulin in response to glucose challenge. Therefore, this study constitutes a proof-of-concept demonstration of protein-mediated pancreatic specific differentiation of the hES cells by exploiting specific intrinsic properties of the hPdx1 protein.
Hepatocyte growth factor (HGF) has been shown to be overexpressed in gliomas, and high-grade gliomas (glioblastoma multiforme) express more HGF than lower-grade astrocytoma, and HGF enhances their resistance to radiotherapy. To examine the effect of serum HGF levels on the likelihood of response to radiotherapy and the disease-free survival in patients with glioma, the blood samples of the patients were collected before commencing treatment and serum HGF was measured by quantitative ELISA in 48 patients with glioma grade I-IV, and all patients underwent primary conventionally fractionated radiotherapy. For statistical analysis, SPSS Version 13.0 software was used. Thirty-eight of the 48 patients had a response to treatment, and ten patients had persistent disease at 3 months. Overall, the median serum HGF level was 1,219.5 pg/ml (range 650.4-2,264.7 pg/ml). Eight patients with local failure had HGF levels >1,219.5 pg/ml, and 28 patients with response had serum HGF level of ≤ 1,219.5 pg/ml (P = 0.01). The median time to progression was 6 months in patients with HGF level of >1,219.5 pg/ml compared with 17 months in patients with HGF level of ≤ 1,219.5 pg/ml (log-rank, P = 0.041). In multivariate analysis, serum HGF, the KPS, tumour size and pathological grade, but not the patient's age, gender and oligodendroglial component influenced the progression-free survival. Elevated pre-therapeutic serum HGF levels are associated with poor response and a shorter time to progression in patients with glioma undergoing primary radiotherapy.
Abstract. We herein report a case of recurrent nasal natural killer (NK)/T-cell lymphoma in a 21-year-old male patient. The patient presented with an esophageal mass, fever and difficulty in swallowing. There were no other obvious sites of recurrence apart from the esophageal lesion. Metastatic esophageal lesions are extremely rare. The histological analysis demonstrated a highly aggressive tumor with a characteristic angiodestructive growth pattern and nasal cavity necrosis. The lymphoma cells were immunopositive for leukocyte common antigen, T-cell intracytoplasmic antigen 1 and CD68, negative for CD56 and CD3, and positive for Epstein-Barr virus. A computed tomography scan revealed mild thickening of the wall of the lower esophagus. The barium swallow revealed stiffness of the esophageal wall, with limited expansion and mucosal damage. The final diagnosis was primary nasal NK/T-cell lymphoma, with metastasis to the esophagus. Clinically, it is important to distinguish nasal-type NK/T-cell lymphoma from other types of tumors, as its prognosis and treatment of secondary metastases differ significantly.
We herein report a case of recurrent nasal natural killer (NK)/T-cell lymphoma in a 21-year-old male patient. The patient presented with an esophageal mass, fever and difficulty in swallowing. There were no other obvious sites of recurrence apart from the esophageal lesion. Metastatic esophageal lesions are extremely rare. The histological analysis demonstrated a highly aggressive tumor with a characteristic angiodestructive growth pattern and nasal cavity necrosis. The lymphoma cells were immunopositive for leukocyte common antigen, T-cell intracytoplasmic antigen 1 and CD68, negative for CD56 and CD3, and positive for Epstein-Barr virus. A computed tomography scan revealed mild thickening of the wall of the lower esophagus. The barium swallow revealed stiffness of the esophageal wall, with limited expansion and mucosal damage. The final diagnosis was primary nasal NK/T-cell lymphoma, with metastasis to the esophagus. Clinically, it is important to distinguish nasal-type NK/T-cell lymphoma from other types of tumors, as its prognosis and treatment of secondary metastases differ significantly.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.