Background: Downregulation of TGF‐β receptors is implicated in colon cancer development. Inactivation of either of the two transmembrane serine/threonine kinases, TGF‐β1 types I/II receptors, is now implicated in carcinogenesis, especially gastrointestinal carcinogenesis. Methods: We generated transgenic mice, called pS2–dnRII or ITF–dnRII, of which the dominant negative mutant of the TGF‐β type II receptor was expressed under the control of tissue‐specific promoters, the pS2 promoter for stomach and ITF for intestine. They were either infected with H.pylori (ATCC 43504 strain, CagA+ and VacA+) or administered with azoxymethane to determine the significance of loss of TGF‐β signalling in gastrointestinal carcinogenesis. Results: Gastric adenocarcinoma developed in pS2–dnRII mice, whereas only chronic active gastritis was noted in wild‐type littermates after 36 weeks of H.pylori infection. Mice lacking in TGF‐β signalling specifically in the stomach showed a significantly higher proliferation cell nuclear antigen‐labelling index when infected with H.pylori than wild‐type littermates (P < 0.01). Development of colonic aberrant crypt foci was provoked in mice by intraperitoneal injections of azoxymethane, and ITF–dnRII mice showed significantly higher incidences of ACF and colon cancers than wild‐type littermates. Conclusions: Maintaining normal TGF‐β signalling in the gastrointestinal tract seems to be important either for preventing abnormal mucosal proliferation, or for suppressing or retarding carcinogenesis.

Constitutively activated Signal Transducer and Activator of Transcription 3 (STAT3) protein has been found to be a key regulator of pancreatic cancer and a target for molecular therapeutic intervention. In this study PG-S3-001, a small molecule derived from the SH-4-54 class of STAT3 inhibitors, was found to inhibit patient-derived pancreatic cancer cell proliferation in vitro and in vivo in the low μM range. PG-S3-001 binds the STAT3 protein potently, Kd = 324 nM by SPR, showed no effect in a kinome screen (> 100 cancer-relevant kinases). In vitro studies demonstrated potent cell killing as well as inhibition of STAT3 activation in pancreatic cancer cells. To better model the tumor and its microenvironment, we utilized 3-Dimensional (3D) cultures of patient-derived pancreatic cancer cells in the absence and presence of cancer-associated fibroblasts (CAFs). In this co-culture model, inhibition of tumor growth is maintained following STAT3 inhibition in the presence of CAFs. Confocal microscopy was used to verify tumor cell death following treatment of 3D co-cultures with PG-S3-001. The 3D model was predictive of in vivo efficacy as significant tumor growth inhibition was observed upon administration of PG-S3-001. These studies showed that the inhibition of STAT3 was able to impact the survival of tumor cells in a relevant 3D model, as well as in a xenograft model using patient-derived cells.

Herpes simplex virus type 2 glycoprotein gG-2 undergoes a cleavage event during its synthesis and processing. The focus of this report is on the detection and fate of the small-molecular-weight component of gG-2, designated the 34K component. In cultures containing the inhibitor monensin, a 31K component accumulated within infected cells. In contrast, the intracellular accumulation of this 31K precursor was not detected in cultures grown in the absence of the inhibitor. However, the 34K component of gG-2 was found in the extraceliular culture fluid. The data suggest that the 31K high-mannose cleavage product of gG-2 is further glycosylated and rapidly secreted from herpes simplex virus type 2-infected cells; however, if glycosylation is perturbed, the 31K high-mannose form remains cell associated.

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Nanomaterial-based biosensors have become one of the major topics in the field of diagnostics. With the growing demand on devices with improved sensitivity and selectivity, rapid response time, and low cost, four categories of nanomaterials have become popular in biosensor research: gold nanoparticles, graphene, carbon nanotubes, and photonic crystals. The ongoing research has brought new designs of biosensors based on nanomaterials, which have greatly improved the potential of field-deployable microfabricated devices. This review describes the recent technologies employing the aforementioned nanomaterials for electrochemical detection of biomolecules, including glucose, DNA, protein, toxins, and so on. We envisage that miniaturized lab-on-a-chip devices employing these nanomaterials will soon be an essential part of our daily life.

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During the synthesis of glycoprotein G-2 (gG-2) of herpes simplex virus type 2, the 104,000-Da gG-2 precursor (104K precursor) is cleaved to generate the 72K and the 31K intermediates. The 72K product is processed to generate the mature gG-2 (molecular mass, 108,000 Da), while the 31K product is additionally processed and secreted into the extracellular medium as the 34K component (H.