Chemosensitivity of lung cancer: Differences between the primary lesion and lymph node metastasis

In this study, chemosensitivity tests were performed on both primary lesions (PLs) and lymph node metastases (LMs) from surgically resected non-small cell lung cancer (NSCLC). Differences between the results obtained were evaluated. Operative specimens were obtained from 13 patients with NSCLC [6 with squamous cell carcinoma (SQ) and 7 with adenocarcinoma (AD)] whose lymph nodes were confirmed to be positive for metastasis. Both the PL and LM from the same patient were examined immediately after resection. The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) was used as the chemosensitivity test against six anticancer drugs [5-fluorouracil (5-FU), cisplatin, gemcitabine, docetaxel, vinorelbine and SN-38 (an active metabolite of irinotecan)]. When the growth rate, determined by the T/C ratio (T, signal for viable cells in the treated group and C, signal in the control) was less than 50%, the tumor cells were considered to be sensitive to the drug. Only in 4 cases (2 SQ and 2 AD) was the chemosensitivity of the primary lesion identical to that of LM. In the SQ cases, chemosensitivity of the primary lesions to 5-FU tended to be consistent with that of LMs. In contrast, the primary lesions in 4 of the 7 AD cases were negative for chemosensitivity to 5-FU; however, LMs were sensitive. In many cases, the chemosensitivity of the PLs to each anticancer drug differed from that of the LMs. In conclusion, both primary and metastatic tumors should be examined to ensure maximum clinical efficacy of in vitro drug-sensitivity testing for adjuvant chemotherapy after complete resection of n1 and n2 NSCLC.     

Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD

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Comparison of electromyographic activity of jaw-closing muscles between mixing ability test and masticatory performance test

PurposeThe purpose of this study was to compare the muscle activity of jaw-closing muscles during chewing of a wax cube used for mixing ability test with that of peanuts used for masticatory performance test.MethodsTwenty subjects with complete dentitions (mean age 24.1 years) were directed to perform a mixing ability test and a masticatory performance test. Surface electromyograms (EMGs) were recorded from the masseter and temporalis muscles on right and left sides. Muscle work, maximal voltage and duration were measured on the integrated EMG signal in each muscle. In addition, muscle work was normalized with EMG activity during maximum voluntary clenching at centric occlusion. The mean of the 2nd to 5th cycle in each parameter was employed for statistical analysis.ResultsRepeated measures one-way multiple analysis of variance found a significant effect of chewing test on muscle work, normalized muscle work and maximal voltage (P < 0.002), but no significant effect on duration (P = 0.07). Muscle work, normalized muscle work and maximal voltage for the mixing ability test were significantly less than for the masticatory performance test in all muscles (paired t-test, P < 0.006).ConclusionThe results of this study suggest that muscle activity of jaw-closing muscles in the mixing ability test is less than that in the masticatory performance test using peanuts as test food.     

A case of advanced gastric cancer with abdominal paraaortic lymph node swelling successfully resected following neoadjuvant chemotherapy of TS-1 and low-dose cisplatin

A 63-year-old man who had suffered from anorexia and body weight loss was admitted to the hospital. Upper GI series and an endoscopic examination revealed type 3 cancer in the posterior wall of the cardia. Abdominal CT scan showed enlargement of No. 16 lymph nodes. Preoperative diagnosis was stage IV gastric cancer (T3 (SE) H0 P0 N3), and we considered a curative operation impossible. Therefore, neoadjuvant chemotherapy with TS-1 and low-dose cisplatin (CDDP) was planned. After 4 weeks of administration, the primary lesion was reduced in size and the No. 16 lymph nodes were shrunken remarkably. Therefore, a total gastrectomy with a splenectomy, a distal pancreatectomy, and D3 lymph node dissection was performed. Histological findings demonstrated the degeneration of cancer cells and fibrosis in the primary tumor and metastatic regional lymph nodes. There were no viable cancer cells in the No. 16 lymph nodes. The histological changes against neoadjuvant chemotherapy were judged to be Grade 1b for the main tumor and Grade 3 for the No. 16 lymph nodes. Neoadjuvant chemotherapy with TS-1 and low-dose cisplatin is so effective in a short period that can be adapted to advanced gastric cancer for downstaging.     

Overexpression of Necl‐5 correlates with unfavorable prognosis in patients with lung adenocarcinoma

Nectin‐like molecule‐5 (Necl‐5) is an immunoglobulin (Ig)‐like molecule that is up‐regulated in many types of cancer cells. It was shown experimentally that Necl‐5 enhances cell migration, proliferation, and metastasis, but its clinical significance has not been documented. The aim of this study was to observe the expression of Necl‐5 in surgically resected primary lung adenocarcinomas and to investigate its clinical significance. A total of 63 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Necl‐5. The relationship between expression of Necl‐5 and clinicopathological features was analyzed, and the influence of Necl‐5 expression on outcomes in these patients was assessed. A strong expression of Necl‐5 by cancer cells was observed in 43 of the 63 tumors. The overexpression of Necl‐5 by cancer cells was significantly associated with lymph node metastasis (P = 0.0398), TNM staging (P = 0.0367), and the bronchioloalveolar carcinoma ratio of tumors (P = 0.0423). Furthermore, the disease‐free survival rate in patients with positive Necl‐5 overexpression was significantly lower than that in patients with negative Necl‐5 overexpression (P = 0.0004). Multivariate survival analysis revealed Necl‐5 expression to be an independent risk factor for an unfavorable outcome (P = 0.0294). Additionally, an analysis including only the stage I cases revealed that the disease‐free survival rate of the Necl‐5‐positive group was significantly lower than that of the Necl‐5‐negative group (P = 0.0192). These results indicate that Necl‐5 plays a role in mediating tumor cell invasion and that the overexpression of Necl‐5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma. (Cancer Sci 2010; 101: 1326–1330)     

Studies on the role of glycosylation for human corticosteroid-binding globulin: comparison with that for thyroxine-binding globulin

The role of glycosylation on the secretion and the stability of human corticosteroid binding globulin (CBG) was studied. Cells of the human hepatoma line were labeled by [35S]methionine in presence of or absence of tunicamycin (TM). Media or cells were harvested at 0, 3, 6, and 20 h after the addition of excess unlabeled methionine. Media and cell lysates were incubated with anti-CBG serum and immune complexes were precipitated with Staphylococcus aureus protein A (Pansorbin). Immunoprecipitates were analyzed by fluorography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoprecipitation of T4-binding globulin (TBG) was also carried out with anti-TBG serum. Fluorographic analysis revealed three forms of CBG: CBG1, a glycosylated, mature, and secretory form with apparent mol wt of 70 K; CBG2, a glycosylated precursor which due to incomplete carbohydrate processing has an apparent mol wt of 54 K; and CBG3, a nonglycosylated form consisting of the 40 K core protein. In absence of TM, CBG1 was observed in media and CBG2 was detected in cell lysates. The proportion of CBG1 increased during the chase, whereas that of CBG2 decreased, indicating that CBG was secreted after processing of the oligosaccharides on CBG2. In presence of TM, CBG3 was found both in media and cell lysates. The sum of CBG3 in the medium and the cell lysate decreased during the chase, whereas that of CBG1 and CBG2 remained unchanged. Similar to CBG, TBG1 (mature form, 60 K) and TBG2 (partially processed glycosylated form, 54 K) were observed in media and cell lysates, respectively, in absence of TM. However, TBG3 (nonglycosylated, 44 K) was not detected in medium. These results indicate that glycosylation is not a key factor for the secretion of CBG but is important for its stability. On the other hand the glycosylation is indispensable for the secretion of TBG.     

Time interval determination from left atrial appendage ejection flow in patients with mitral stenosis

The feasibility of determining the time interval from left atrial appendage (LAA) flow was examined using transesophageal Doppler echocardiography. Time intervals were compared between LAA flow and mitral flow patterns during late diastole in 8 patients with mitral stenosis and in 12 controls. The start of ejection flow from the LAA was later than the initiation of mitral flow, but the termination was same in both flows, indicating the contribution of LAA ejection to the latter half of the left atrial booster pump function. The pre-ejection time and the time interval from P-wave to end-ejection correlated significantly with left atrial dimensions (r = 0.55, and r = 0.70, respectively). The pre-ejection time, duration of the ejection flow from the LAA, and duration of mitral flow in the atrial contraction phase were significantly longer in patients with mitral stenosis (126 ± 14 msec, 131 ± 36 msec, and 167 ± 28 msec, respectively) than in the controls (109 ± 13 msec, 108 ± 15 msec, and 141 ± 17 msec, respectively). These results indicate that electrical conduction time from the right atrium to LAA can be estimated from the LAA ejection flow, and the time is related to the left atrial size. In patients with mitral stenosis, LAA contraction may contribute to left ventricular filling in the latter half of the atrial contraction phase. © 1997 John Wiley & Sons, Inc. J Clin Ultrasound 25 : 97–102, 1997.     

Left atrial tachycardia after right atrial separation for chronic atrial fibrillation with atrial septal defects

A right atrial separation procedure was performed for the ablation of chronic atrial fibrillation in four cases, concomitant with the repair of the atrial septal defect. After the operation, chronic atrial fibrillation disappeared in three of them and left atrial tachycardia occurred in the other one. Left atrial tachycardia is an arrhythmia encountered after a right atrial separation procedure.