Intrahepatic cholangiocarcinoma (IHCC) is a rare primary hepatic tumor. Outcomes after resection and the use of lymph node dissection have not been well described. From a prospective database, we identified 53 patients with IHCC who underwent exploration between April 1983 and March 2004. Hepatic resection was performed in 44 patients, 30 of whom underwent lymph node dissection. Clinicopathological features and outcomes were analyzed. The actuarial 1-year survival was 66.2% in resected patients, compared to 0% in unresectable patients (p < 0.0001), with a 50% overall survival of 21.5 months and 3.1 months, respectively. The actuarial 3-year and 5-year overall survival rates in resected patients were 38.3% and 26.3%, respectively. Univariate analysis revealed that factors associated with poor overall survival included multiple tumors, extrahepatic bile duct involvement, noncurative resection, and involvement of lymph nodes. Multivariate analysis in resected patients revealed that multiple tumors (p < 0.0074) and non-curative resection (p = 0.0068) were significant risk factors for poor overall survival. The survival rate in patients with three or more positive nodes was significantly lower than in those with fewer than three (p < 0.0001). Three patients with solitary tumors and one or two involved lymph nodes have survived beyond 4 years after extended lobectomy with systemic lymphadenectomy. Curative resection, single tumor, and fewer than two lymph node metastases were prognostic factors for good outcome. Curative resection with lymph node dissection improved survival in patients with no more than two positive lymph nodes.

/VGluT3ϩ terminals, which should include those from GAD67 ϩ /VGluT3 ϩ BST neurons, formed symmetrical synapses. When single axons from VGluT3 ϩ BST neurons were examined, almost all terminals were labeled for VIAAT, whereas VGluT3 was often absent from terminals with high VIAAT loads. VGluT2 ϩ terminals in the VTA exclusively formed asymmetrical synapses, which expressed AMPA receptors on postsynaptic membrane. Therefore, the major mode of the BST-VTA projection is GABAergic, and its activation is predicted to disinhibit VTA DAergic neurons. VGluT2 ϩ and VGluT3 ϩ BST neurons further supply additional projections, which may principally convey excitatory or inhibitory inputs, respectively, to the VTA.

Background: Correlations of disease phenotypes with glycosylation changes have been analysed intensively in the tumor biology field. Glycoforms potentially associated with carcinogenesis, tumor progression and cancer metastasis have been identified. In cancer therapy, drug resistance is a severe problem, reducing therapeutic effect of drugs and adding to patient suffering. Although multiple mechanisms likely underlie resistance of cancer cells to anticancer drugs, including overexpression of transporters, the relationship of glycans to drug resistance is not well understood.

Activation of mu-opioid receptor (MOR) disinhibits dopaminergic neurons in the ventral tegmental area (VTA) through inhibition of γ-aminobutyric acid (GABA)ergic neurons. This mechanism is thought to play a pivotal role in mediating reward behaviors. Here, we characterised VTA-projecting enkephalinergic neurons in the anterior division of the bed nucleus of the stria terminalis (BST) and investigated their targets by examining MOR expression in the VTA. In the BST, neurons expressing preproenkephalin mRNA were exclusively GABAergic, and constituted 37.2% of the total GABAergic neurons. Using retrograde tracer injected into the VTA, 21.6% of VTA-projecting BST neurons were shown to express preproenkephalin mRNA. Enkephalinergic projections from the BST exclusively formed symmetrical synapses onto the dendrites of VTA neurons. In the VTA, 74.1% of MOR mRNA-expressing neurons were GABAergic, with the rest being glutamatergic neurons expressing type-2 vesicular glutamate transporter mRNA. However, MOR mRNA was below the detection threshold in dopaminergic neurons. By immunohistochemistry, MOR was highly expressed on the extrasynaptic membranes of dendrites in GABAergic VTA neurons, including dendrites innervated by BST-VTA projection terminals. MOR was also expressed weakly on GABAergic and glutamatergic terminals in the VTA. Given that GABAA α1 is expressed at GABAergic BST-VTA synapses on dendrites of GABAergic neurons [T. Kudo et al. (2012) J. Neurosci., 32, 18035-18046], our results collectively indicate that the BST sends dual inhibitory outputs targeting GABAergic VTA neurons; GABAergic inhibition via 'wired' transmission, and enkephalinergic inhibition via 'volume' transmission. This dual inhibitory system provides the neural substrate underlying the potent disinhibitory control over dopaminergic VTA neurons exerted by the BST.

Background: Drug resistance is a major problem in cancer chemotherapy. Acquisition of chemoresistance not only reduces the effectiveness of drugs, but also promotes side effects and markedly reduces the patient's quality of life. However, a number of resistance mechanisms have been reported and are thought to be the reason for the difficulties in solving drug-resistance problems.