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Immunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death‐ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR‐TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR‐TKI resistance and lymphocyte infiltration, before and after acquiring EGFR‐TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by in vitro studies, using miRNA PCR arrays. Subsequently, we transfected miRNA‐1 (miR‐1), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR‐1 on EGFR‐TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8‐positive T cells were significantly decreased after development of EGFR‐TKI resistance. In vitro studies revealed that miR‐1 significantly inhibited EGFR‐TKI effect and induction of cytokines, such as C‐C motif chemokine ligand 5 and C‐X‐C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR‐1 might suppress the TIME, following development of EGFR‐TKI resistance. Therefore, miR‐1 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR‐TKI resistance. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of a 12-core prostate biopsy protocol including apical anterior peripheral zone (AAPZ) cores. Methods: Between February 2002 and October 2006, 10-core and 12-core initial transrectal prostate biopsies were performed on 164 and 549 men, respectively. Two AAPZ-directed biopsies were included in the 12-core biopsy. During the same period, 12-core repeat biopsies including six AAPZ sites were performed on 118 men. Results: Cancer was found in 66 cases (40.2%) in the 10-core biopsy group and in 252 (45.9%) in the 12-core biopsy group. In this latter group, 13 (5.2%) of the 252 men with positive biopsy had cancer exclusively in the AAPZ cores. When the cancer detection rate at initial biopsy in AAPZ alone was compared according to the digital rectal examination (DRE) findings, it was significantly higher in men with normal rather than abnormal DRE: 12/250 (3.4%) vs 1/185 (0.5%) ( P < 0.01). In repeat 12-core biopsies, cancer was detected in 25 (21.2%) men and 9 of them (36.0%) had cancer exclusively in the AAPZ cores. The cancer detection rate from AAPZ sites was significantly higher in repeat biopsy than that in initial biopsy ( P < 0.01). Conclusions: Addition of the AAPZ site-directed biopsy had greater utility in men with normal DRE and particularly in patients with a prior negative biopsy. [ABSTRACT FROM AUTHOR]

Tyramide signal amplification–avidin–biotin complex (TSA-ABC) method is a powerful technique used to detect antigens that are not detectable by ordinary immunohistochemistry. It is worth trying in cases where localization of antigens by the conventional method has failed and antibodies are precious. [ABSTRACT FROM AUTHOR]