Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer.

Multidrug resistance (MDR) due to enhanced drug efflux activity of tumor cells can severely impact the efficacy of antitumor therapies. We recently showed that increased activity of the efflux transporter P-glycoprotein (P-gp) associated with activation of Snail transcriptional regulators may be mediated mainly by moesin in lung cancer cells. Here, we aimed to systematically evaluate the relationships among mRNA expression levels of efflux transporters (P-gp, breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2)), scaffold proteins (ezrin (Ezr), radixin (Rdx), and moesin (Msn); ERM proteins), and SNAI family members (Snail, Slug, and Smac) in clinical lung cancer and noncancer samples. We found high correlations between relative (cancer/noncancer) mRNA expression levels of Snail and Msn, Msn and P-gp, Slug and MRP2, and Smuc and BCRP. These findings support our previous conclusion that Snail regulates P-gp activity via Msn and further suggest that Slug and Smuc may contribute to the functional regulation of MRP2 and BCRP, respectively, in lung cancer cells. This trial is registered with UMIN000023923.

Ramucirumab-related Oral Pyogenic Granuloma: A Report of Two Cases.

Pyogenic granuloma (PG) is a granulomatous elevated lesion that occurs on the skin and mucous membranes. We herein report two cases of intra-oral PG that developed during the administration of ramucirumab for gastric cancer. Case 1 involved a 55-year-old man with a 6-mm tumor on the right tongue, and case 2 involved a 67-year-old man with a 5-mm tumor on the upper lip. The imbalance in angiogenesis caused by ramucirumab and the deterioration in the local oral environment were suggested to have caused the PG. Medical and dental collaboration is essential during the administration of ramucirumab.

Metachronous bilateral breast metastases of a lung neuroendocrine tumor: A case report.

Breast metastases of primary lung neuroendocrine tumors are rarely reported. The current report presents the case of a 41-year old female with no history of smoking who initially underwent surgery for a breast fibroadenoma, during which a neuroendocrine tumor of the right lung was detected via chest X-ray. The patient underwent surgery for the tumor and developed right breast nodules after adjuvant chemotherapy. Histological and immunohistochemical examinations of biopsies from these nodules indicated breast metastasis of the primary lung neuroendocrine tumor. The patient underwent mastectomy of the right breast but subsequently developed metastases in the left breast, for which local radiotherapy was administered. The observed metachronous bilateral breast metastases indicated that the contralateral breast should be considered during an investigation of metastasis.

Moesin-Mediated P-Glycoprotein Activation During Snail-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells.

Epithelial-mesenchymal transition (EMT) plays a role in not only cancer metastasis, but also drug resistance, which is associated with increased levels of efflux transporters such as P-glycoprotein (P-gp). Here, we examined whether P-gp activation during Snail-induced EMT of lung cancer cells is mediated by ezrin, radixin, and moesin (ERM), which regulate transporter localization. HCC827 lung cancer cells overexpressing the transcription factor Snail showed increased Rhodamine123 efflux and increased paclitaxel resistance, reflecting increased P-gp activity. Concomitantly, the expression level of moesin, but not ezrin or radixin, was significantly increased. The increase of P-gp activity was suppressed by knockdown of moesin. Thus, the increase of P-gp activity associated with Snail-induced EMT may be mediated mainly by moesin in HCC827 cells. On the other hand, the Snail mRNA expression level was correlated with the expression level of each ERM in 4 non-small-cell lung cancer cell lines (HCC827, A549, H441, H1975) and in tumor tissues, but not normal tissues, of patients with lung cancer. These results suggest that P-gp activation during EMT is at least partially due to increased expression of moesin. Coadministration of moesin inhibitors with anticancer drugs might block P-gp-mediated drug efflux organ-specifically, improving treatment efficacy and minimizing side effects on other organs.

Renal primitive neuroectodermal tumor with elevated plasma adrenocorticotropic hormone levels: A case report.

INTRODUCTION: Primitive neuroectodermal tumors are small round-cell tumors - Ewing sarcoma family, frequently occurring in the extremities, but rarely in the kidney. CASE PRESENTATION: A 58-year-old woman presented with whole-body edema and weakness of lower limb muscles. Computed tomography revealed a left renal tumor, and the plasma adrenocorticotropic hormone level was elevated. The tumor was surgically removed without complications, her plasma adrenocorticotropic hormone reverted to normal levels, and symptoms disappeared after surgery. Histopathological examination revealed a primitive neuroectodermal tumor arising in her kidney. The patient was alive without metastasis 3 years after the surgery. CONCLUSION: We report the first case of renal primitive neuroectodermal tumor accompanying elevated plasma adrenocorticotropic hormone levels which are thought to be produced and secreted in an ectopic fashion.

[USEFULNESS OF VIVID (VISUALIZATION OF VARIOUS INTEGRATION WITH DIFFUSION) ON COGNITIVE FUSION PROSTATE BIOPSY].

(Purpose) We created an image reconstructing multiparametric MRI system called VIVID (Visualization of Various Integration with Diffusion) and examined the efficacy of VIVID in detecting prostate cancer. (Methods and materials) The subjects were 80 patients who underwent one target biopsy with reference to MRI images in addition to 8-20 biopsies. (Results) The significant cancer detection rate was 61%, the significant cancer detection rate of PI-RADS 4 or 5 was 55%, and the significant cancer detection rate of VIVID score 4 or 5 was 55%. Three cases with PI-RADS 4 at TZ lesion with positive T2WI only were evaluated as having VIVID scores 1 or 2. Cancer was not detected with target biopsy from the site. (Conclusion) Our finding suggest that VIVID correctly excludes TZ lesions with only T2WI positively in multiparametric MRI.

Decreasing expression of glucose-regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma.

BACKGROUND: The immunoglobulin heavy chain binding protein (BiP)/glucose-regulated protein 78 (GRP78) is important in the endoplasmic reticulum stress, and is highly expressed in various human cancers. The clinical and pathological features of GRP78/BiP are unclear in patients with advanced laryngeal squamous cell carcinoma (SCC). The purpose of this study was to investigate the clinicopathological significance of GRP78/BiP as a prognostic marker for laryngeal SCC. METHODS: A total of 59 patients with advanced laryngeal SCC (stage III/IV) were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP and Ki-67. Microvessel density was determined by immunohistochemical staining for CD34 and p53. RESULTS: Expression of GRP78/BiP was confirmed in 87% of cases. Decreased expression of GRP78/BiP was highly associated with positive expression of p53. Decreased GRP78/BiP expression was identified on multivariate analysis as an independent factor of decreased progression-free survival (PFS). CONCLUSION: GRP78/BiP was found to be commonly expressed in laryngeal SCC, whereas its downregulation was found to serve a significant prognostic role for predicting poor survival in patients with laryngeal SCC with advanced disease. GRP78/BiP may be a potentially attractive target for the treatment of various human neoplasms. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1544, 2016.

Tumor-infiltrating CD45RO(+) memory cells are associated with a favorable prognosis breast cancer.

BACKGROUND: CD45RO is a marker for memory lymphocytes. Whether CD45RO(+) tumor-infiltrating lymphocytes (TILs) prevent breast cancer recurrence is unclear. METHODS: In the present study, we evaluated CD45RO expression in TILs as a predictor of prognosis in 98 patients with breast cancer who underwent radical surgery without neoadjuvant chemotherapy. Patients were classified as CD45RO(+)/TILs(High) or CD45RO(+)/TILs(Low) based on median immunohistochemistry levels. RESULTS: CD45RO(+)/TILs(High) were associated with smaller tumor size. The CD45RO(+)/TILs(High) group also had significantly fewer metastatic lymph nodes (P = 0.0082) and fewer peritumoral lymphatic invasions (P = 0.0284). The CD45RO(+)/TILs(High) group enjoyed longer recurrence-free survival (P = 0.0453) but not cancer-specific survival (P = 0.0640) in univariate analysis. CONCLUSIONS: These results suggested that CD45RO(+) effector cells may both help eradicate local tumors and prevent metastases to the lymphatic systems in breast cancer patients. High ratio of CD45RO expressing TILs was associated with recurrence-free survival improvement and a trend toward cancer-specific survival improvement in breast cancer patients.

Expression of Amino Acid Transporters (LAT1 and ASCT2) in Patients with Stage III/IV Laryngeal Squamous Cell Carcinoma.

The aim of this study is to evaluate the clinicopathological significance of L-type amino acid transporter 1 (LAT1) expression in patients with advanced laryngeal squamous cell carcinoma (LSCC). A total of 73 patients with advanced LSCC were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, 4F2hc, system ASC amino acid transporter-2 (ASCT2), cell proliferation by Ki-67, microvessel density (MVD) determined by CD34 and p53. A positive LAT1, 4F2hc and ASCT2 expression (staining more than a quarter) in the primary sites were recognized in 85, 80 and 45 %, respectively, and a high LAT1, 4F2hc and ASCT2 expression (staining more than a half) yielded 48, 31 and 18 %, respectively. High expression of LAT1 was significantly associated with lymph node metastasis, 4F2hc, ASCT2, Ki-67 and p53. The expression of LAT1 was significantly correlated with ASCT2, 4F2hc, cell proliferation, and MVD. By univariate analysis, there was no statistically significant relationship between LAT1 expression and prognosis in advanced LSCC. LAT1, 4F2hc and ASCT2 were highly expressed in patients with advanced laryngeal cancer. Our study suggests that the expression of LAT1 plays a crucial role in the metastasis and tumor progression in advanced LSCC.