[Utility of Measurement of Low Attenuated Area(LAA)for the Prediction of Surgical Outcome in Digestive Cancer].

Previous reports have shown that a low attenuated area(LAA)in chest CT reflects the prognosis or therapeutic outcomes for chronic obstructive pulmonary disease(COPD). COPD has been reported as one of the important predictive factors for postoperative pulmonary complications(PPCs). In this retrospective study, we analyzed 100 patients who underwent surgery for gastric or colorectal cancer between January 2020 and August 2022, and investigated the impact of the LAA volume ratio(LAAv%)on short term surgical outcomes. Twenty-two cases developed PPCs, and their Clavien-Dindo grades were Grade Ⅰ-Ⅱ(for 21 patients)and Grade Ⅳa(in 1). We found that high-LAAv% and high-BMI were independent risk factors of PPCs in uni- and multi-variate analyses. In a sub analysis of the limited high-LAAv% group, surgical time qA found to be an independent risk factor of PPCs, and it's cut-off value was calculated as 189 minutes(sensitivity 88.2%, specificity 42.4%). The incidence of PPCs might be avoidable in patients with high-LAAv% through selection of the surgical approach or applying respiratory function training when appropriate.

Intracellular chloride regulates cell proliferation through the activation of stress-activated protein kinases in MKN28 human gastric cancer cells.

Recently, we reported that reduction of intracellular Cl(-) concentration ([Cl(-)](i)) inhibited proliferation of MKN28 gastric cancer cells by diminishing the transition rate from G(1) to S cell-cycle phase through upregulation of p21, cyclin-dependent kinase inhibitor, in a p53-independent manner. However, it is still unknown how intracellular Cl(-) regulates p21 expression level. In this study, we demonstrate that mitogen-activated protein kinases (MAPKs) are involved in the p21 upregulation and cell-cycle arrest induced by reduction of [Cl(-)](i). Culture of MKN28 cells in a low Cl(-) medium significantly induced phosphorylation (activation) of MAPKs (ERK, p38, and JNK) and G(1)/S cell-cycle arrest. To clarify the involvement of MAPKs in p21 upregulation and cell growth inhibition in the low Cl(-) medium, we studied effects of specific MAPKs inhibitors on p21 upregulation and G(1)/S cell-cycle arrest in MKN28 cells. Treatment with an inhibitor of p38 or JNK significantly suppressed p21 upregulation caused by culture in a low Cl(-) medium and rescued MKN28 cells from the low Cl(-)-induced G(1) cell-cycle arrest, whereas treatment with an ERK inhibitor had no significant effect on p21 expression or the growth of MKN28 cells in the low Cl(-) medium. These results strongly suggest that the intracellular Cl(-) affects the cell proliferation via activation of p38 and/or JNK cascades through upregulation of the cyclin-dependent kinase inhibitor (p21) in a p53-independent manner in MKN28 cells.

Chloride ions control the G1/S cell-cycle checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells.

The aim of the present study is to investigate whether the chloride affects cell growth and cell-cycle progression of cancer cells. In human gastric cancer MKN28 cells, the culture in the Cl(-)-replaced medium (replacement of Cl(-) by NO(3)(-)) decreased the intracellular chloride concentration ([Cl(-)](i)) and inhibited cell growth. The inhibition of cell growth was due to cell-cycle arrest at the G(0)/G(1) phase caused by diminution of CDK2 and phosphorylated Rb. The culture of cells in the Cl(-)-replaced medium significantly increased expressions of p21 mRNA and protein without any effects on p53. These observations indicate that chloride ions play important roles in cell-cycle progression by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells, leading to a novel, unique therapeutic strategy for gastric cancer treatment via control of [Cl(-)](i).

Prognostic and clinical evaluation of axillary lymph node metastasis in esophageal cancer.

Axillary lymph node metastasis (ALNM) from esophageal cancer is rare. Its prognosis and effective treatments remain unknown. Between 1997 and 2005, esophagectomy was performed in 361 patients with esophageal cancer in our hospital. ALNM was identified in four patients (1.1%). All patients had left ALNM with ipsilateral left supraclavicular lymph node metastasis. In two patients ALNM developed after radical esophagectomy with regional lymphadenectomy and in the other two patients after chemoradiotherapy of primary lesions. Axillary lymphadenectomy with chemoradiotherapy was given to all patients. Median survival time and disease-free survival (DFS) after initial treatment for primary esophageal cancer were 30.5 months and 11.5 months, respectively. One patient, who had a small number of regional lymph node metastases (two lymph nodes) at esophagectomy and prolonged DFS (22 months) until axillary node recurrence, is still alive, 67 months after axillary lymphadenectomy. The other three patients, who had larger numbers of regional lymph node metastases (average, 8.3) and shorter DFS (average, 9.7 months), died of recurrence an average of 13.3 months after axillary lymphadenectomy. In conclusion, although ALNM is considered a type of distant organ metastasis, if it is a solitary recurrence, good survival may be obtained after appropriate loco-regional therapy. The number of metastatic regional lymph nodes at initial esophagectomy and the duration of DFS until axillary node recurrence can help to guide the decision whether aggressive treatments are warranted.

Synthesis of 4'-substituted cordycepins.

Synthesis of 4'-substituted analogues of cordycepin was carried out. Electrophilic addition of N-iodosuccinimide/benzoic acid to 2',5'-bis-O-(tert-butyldimethyl-silyl)-3',4'-unsaturated adenosine (5) enabled the introduction of a leaving group to the 4'-position. The resulting product 7 was converted to 4'-(benzoyloxy) cordycepin (8) upon removal of the 3'-iodine atom. Compound 8 serves as a common precursor for the synthesis of the title compounds through nucleophilic substitution using organoaluminum and organosilicon reagents.