Roles of the Nanog protein in murine F9 embryonal carcinoma cells and their endoderm-differentiated counterparts

Nanog is a recently discovered homeodomain transcription factor that sustains the pluripotency of embryonic stem （ES） cells and blocks their differentiation into endoderm. The murine F9 embryonal carcinoma cell line is a well-documented model system for endoderm cell lineage differentiation. Here, we examined the function of Nanog in F9 cell endoderm differentiation. Over-expression of Nanog returns the F9 cells to the early status of ES cells and represses the differentiation of primitive endoderm and parietal endoderm in F9 cells, whereas it has no effect on the differentiation of visceral endoderm. In contrast, the expression of C-terminal domain-truncated Nanog spontaneously promotes endoderm differentiation in F9 cells. These data suggest that Nanog is required to sustain the proper undifferentiated status of F9 cells, and the C-terminal domain of Nanog transduces the most effects in repressing primitive endoderm and parietal endoderm differentiation in F9 cells.

Real case of primitive embryonal duodenal carcinoma in a young man

We report here the case of a young man suffering from a rare germ cell tumour. The patient was a 25-year-old man who was referred to our centre for asthenia, stinging epigastric pain, and an iron deficiency anaemia. Gastroscopy revealed a circumferential vegetating lesion on the second portion of the duodenum. The lesion was indurated at the third portion of the duodenum, responsible for a tight stenosis. A computerized tomography-scan of the chest, abdomen and pelvis, and a pancreatic MRI showed a circumferential lesion with a bi-ductal dilatation (i.e., of the common bile duct and Wirsung’s duct) without metastatic localisation. The patient underwent a pancreaticoduodenectomy with lymph node dissection including all cellular adipose tissues of the hepatic pedicle from the hepatic common artery and of the retroportal lamina. Histological findings were suggestive of a duodenal embryonal carcinoma with pancreatic infiltration. This is the second published case highlighting the duodenal primitive localisation of an embryonal carcinoma with pancreatic infiltration.

Wwp2 mediates Oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner

Transcription factor Oct4 plays critical roles in maintaining pluripotency and controlling lineage commitment of embryonic stem cells （ESCs）. Our previous study indicates that Wwp2, a mouse HECT-type E3 ubiquitin ligase, ubiquitinates Oct4 and promotes its degradation in a heterologous system. However, roles of Wwp2 in regulating en- dogenous Oct4 protein levels as well as molecular characteristics of the function of Wwp2 have not been determined. Here, we report that Wwp2 plays an important role in Oct4 ubiquitination and degradation during differentiation of embryonal carcinoma cells （ECCs）, although it does not appear to affect Oct4 protein levels in the undifferentiated ECCs and ESCs. Importantly, inhibition of Wwp2 expression by specific RNA interference elevates the Oct4 protein level, leading to attenuation in retinoid acid-induced activation of differentiation-related marker genes. Mechanisti- cally, Wwp2 catalyzes Oct4 poly-ubiquitination via the lysine 63 linkage in a dosage-dependent manner. Interest- ingly, Wwp2 also regulates its own ligase activity in a similar manner. Moreover, auto-ubiquitination of Wwp2 occurs through an intra-molecular mechanism. Taken together, these results demonstrate a crucial role of Wwp2 in con- trolling endogenous Oct4 protein levels during differentiation processes of ECCs and suggest an interesting dosage- dependent mechanism for regulating the catalytic activity of the E3 ubiquitin ligase, Wwp2.

Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors

Testicular germ cell tumors(TGCTs)are a cancer pharmacology success story with a majority of patients cured even in the highly advanced and metastatic setting.Successful treatment of TGCTs is primarily due to the exquisite responsiveness of this solid tumor to cisplatin-based therapy.However,a significant percentage of patients are,or become,refractory to cisplatin and die from progressive disease.Mechanisms for both clinical hypersensitivity and resistance have largely remained a mystery despite the promise of applying lessons to the majority of solid tumors that are not curable in the metastatic setting.Recently,this promise has been heightened by the realization that distinct(and perhaps pharmacologically replicable)epigenetic states,rather than fixed genetic alterations,may play dominant roles in not only TGCT etiology and progression but also their curability with conventional chemotherapies.In this review,it discusses potential mechanisms of TGCT cisplatin sensitivity and resistance to conventional chemotherapeutics.

A Nano-and Micro-Integrated Protein Chip Based on Quantum Dot Probes and a Microfluidic Network

A novel nano-and micro-integrated protein chip(NMIPC)that can detect proteins with ultrahigh sensitivity has been fabricated.A microfl uidic network(μFN)was used to construct the protein chips,which allowed facile patterning of proteins and subsequent biomolecular recognition.Aqueous phase-synthesized,water-soluble fl uorescent CdTe/CdS core-shell quantum dots(aqQDs),having high quantum yield and high photostability,were used as the signaling probe.Importantly,it was found that aqQDs were compatible with microfluidic format assays,which afforded highly sensitive protein chips for cancer biomarker assays.