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Programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) are target molecules for immunotherapy in non-small cell lung cancer. PD-L1 is expressed not only in cancer cells, but also on macrophages, and has been suggested to contribute to macrophage-mediated immune suppression. We examined the clinical significance of PD-L1 expression on macrophages in human lung adenocarcinoma. The mechanism of PD-L1 overexpression on macrophages was investigated by means of cell culture studies and animal studies. The results showed that high PD-L1 expression on macrophages was correlated with the presence of EGFR mutation, a lower cancer grade, and a shorter cancer-specific overall survival. In an in vitro study using lung cancer cell lines and human monocyte-derived macrophages, the conditioned medium from cancer cells was found to up-regulate PD-L1 expression on macrophages via STAT3 activation, and a cytokine array revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was a candidate factor that induced PD-L1 expression. Culture studies using recombinant GM-CSF, neutralizing antibody, and inhibitors indicated that PD-L1 overexpression was induced via STAT3 activation by GM-CSF derived from cancer cells. In a murine Lewis lung carcinoma model, anti-GM-CSF therapy inhibited cancer development via the suppression of macrophage infiltration and the promotion of lymphocyte infiltration into cancer tissue; however, the PD-L1 expression on macrophages remained unchanged. PD-L1 overexpression on macrophages via the GM-CSF/STAT3 pathway was suggested to promote cancer progression in lung adenocarcinoma. Cancer cell-derived GM-CSF might be a promising target for anti-lung cancer therapy.

CD163 is one of the scavenger receptors expressed on macrophages. However, several immunohistochemical studies have demonstrated that CD163 is also detected on cancer cells, and is associated with a poor prognosis. In the present study, we detected CD163 staining on cancer cells in lung adenocarcinoma and squamous cell carcinoma (SCC), and investigated the relationship between CD163 on cancer cells and the clinical prognosis. CD163 staining was seen in 128 of 342 adenocarcinoma cases and 35 of 103 SCC cases. Among the lung adenocarcinoma cases, the progression-free survival and overall survival were significantly shorter in the CD163 high group than the CD163 low group. A similar trend was observed among the SCC cases, but the difference was not statistically significant. Additionally, a higher number of macrophages was detected in areas with CD163-positive cancer cells when compared to areas with CD163-negative cancer cells. In summary, we found that CD163-positive cancer cells are a predictor of a worse clinical course in lung adenocarcinoma and SCC.

Macrophages are a representative cell type in the tumor microenvironment. Macrophages that infiltrate the cancer microenvironment are referred to as tumor-associated macrophages (TAMs). TAMs exhibit protumor functions related to invasion, metastasis, and immunosuppression, and an increased density of TAMs is associated with a poor clinical course in many cancers. Phosphoprotein 1 (SPP1), also known as osteopontin, is a multifunctional secreted phosphorylated glycoprotein. Although SPP1 is produced in a variety of organs, at the cellular level, it is expressed on only a few cell types, such as osteoblasts, fibroblasts, macrophages, dendritic cells, lymphoid cells, and mononuclear cells. SPP1 is also expressed by cancer cells, and previous studies have demonstrated correlations between levels of circulating SPP1 and/or increased SPP1 expression on tumor cells and poor prognosis in many types of cancer. We recently revealed that SPP1 expression on TAMs is correlated with poor prognosis and chemoresistance in lung adenocarcinoma. In this review, we summarize the significance of TAMs in lung cancers and discuss the importance of SPP1 as a new marker for the protumor subpopulation of monocyte-derived TAMs in lung adenocarcinoma. Several studies have shown that the SPP1/CD44 axis contribute to cancer chemoresistance in solid cancers, so the SPP1/CD44 axis may represent one of the most critical mechanisms for cell-to-cell communication between cancer cells and TAMs.

Tumor-associated calcium signal transducer 2 (TROP2) is a cell-surface glycoprotein involved in the high malignant potential of several cancers. Antibody-drug conjugates that target TROP2 represent a promising approach for the treatment of TROP2-expressing cancers including lung cancer and breast cancer. TROP2 expression was tested by immunohistochemistry in lung adenocarcinoma (ADC) and squamous cell carcinoma samples, and its correlation with clinicopathological factors, including survival rate and p53 mutation, was statistically analyzed. We found that increased TROP2 expression was significantly associated with a poor clinical course in patients with ADC, but not in patients with squamous cell carcinoma. A more significant association with poor outcome was seen in ADC cases with a high histological grade as well as those without the epidermal growth factor receptor (EGFR) mutation. A significant correlation between TROP2 expression and abnormal p53 nuclear accumulation/expression was also found in ADC. In the present study, we discovered a significant correlation between TROP2 expression and p53 mutation in ADC, and that TROP2 expression was a prognostic factor in ADC cases with a high histological grade as well as those without the EGFR mutation. Signals mediated by mutated p53 might influence TROP2 expression in ADC.

The wood of the Cupressaceae conifer family is widely used for many purposes, such as the structural and interior elements of buildings. Several studies have reported the effects of the Cupressaceae wood odor on humans. However, only a few studies have investigated the effects of the volatile compounds on psychophysiological responses in an indoor environment. In this study, the psychophysiological effects following the inhalation of volatile essential oils from the Hinoki cypress (Chamaecyparis obtusa) and Sawara cypress (Chamaecyparis pisifera) woods were evaluated. Levels of salivary stress markers were used to determine the study participants’ endocrinological responses as well as the changes in their autonomic nervous systems during the experimental period. A questionnaire survey was also conducted to assess the perceptions of the odors in the experimental rooms and the participants’ psychological states. It was found that olfactory stimulation with volatile compounds from the essential oil of the Hinoki cypress wood increased salivary dehydroepiandrosterone sulfate levels in the rest period following stressful work. Sympathetic nervous activity levels were lower, and parasympathetic nervous activity levels were higher immediately following stressful work. A similar tendency was observed with exposure to the essential oil of the Sawara cypress wood. These observations suggest that an environment with the Hinoki or Sawara cypress wood odor may be useful in promoting physiological relaxation following stressful work.

In this study, AlGaN-based ultraviolet-B band laser diodes with 150-mW peak output power in pulsed operation were demonstrated at room temperature. The oscillation wavelength, differential quantum efficiency, and slope efficiency of a laser diode were 300 nm, 3.6%, and 0.15 W/A, respectively. These results were obtained by increasing the injection efficiency and decreasing the positive fixed polarization charge formed at the interface between a p-side waveguide layer and an electron blocking layer when polarization doping is formed in a p-AlGaN cladding layer.

Thin films of AlN, AlGaN, and AlGaN-based device structures of approximately 1 cm2 formed on a sapphire substrate were successfully exfoliated from the substrate by immersion in heated (115 °C) and pressurized (170 kPa) water. These thin films were crystalline, grown on periodically formed AlN nanopillars. The water was permeated through intentional voids formed in the AlGaN or AlN crystalline layers by using periodic AlN nanopillars. The exfoliated AlGaN exhibited clear X-ray diffraction peaks from its (0002) plane diffraction. Transmission electron microscopy (TEM) confirmed that exfoliation introduced few additional dislocations and that the device structure was maintained.

Osteopontin, also called secreted phosphoprotein 1 (SPP1), is a multifunctional secreted phosphorylated glycoprotein. SPP1 is also expressed in tumor cells, and many studies demonstrated that a high level of circulating SPP1 is correlated with a poor prognosis in various cancers. SPP1 is expressed not only by tumor cells but also by stromal cells, such as macrophages. However, there have been no studies distinguishing the SPP1 expression of cancer cells and tumor-associated macrophages (TAMs). Thus, in this study, we tried to accurately evaluate the SPP1 expression status on cancer cells and TAMs separately in patients with non-small cell lung cancer by using double immunohistochemistry. We demonstrated that high SPP1 expression on TAMs predicted a poor prognosis in lung adenocarcinoma patients. Additionally, we investigated the expression mechanisms related to SPP1 using human-monocyte-derived macrophages and revealed that the SPP1 expression level increased in macrophage differentiation mediated by granulocyte-macrophage colony-stimulating factor. Furthermore, SPP1 contributed to anti-cancer drug resistance in lung cancer cell lines. In conclusion, SPP1 production on TAMs predicted a poor prognosis in lung adenocarcinoma patients, and TAM-derived SPP1′s involvement in the chemo-resistance of cancer cells was suggested.

Teas and various herbal teas are well-known beverages and are commonly consumed around the world. In this study, we focused on kuromoji tea. Kuromoji is a deciduous shrub of the Lauraceae family, and the plucked leaves and branches have been drunk as a tea in production areas for a long time. However, no studies have investigated the subjective and physiological effects of kuromoji tea. In this study, the effects of kuromoji tea were examined on the basis of the measurements of heart rate variability and cerebral blood flow, core body temperature and subjective assessments. Moreover, the results of this study showed that a pleasant subjective feeling could be obtained by sniffing the aroma of kuromoji teas, especially tea leaves. It was also found that the aroma of kuromoji teas has the potential to stimulate saliva secretion and increase subjective and physiological excitements in the oral cavity. 1,8-Cineole, linalool, terpinen-4-ol, carvone and geraniol were determined in both kuromoji leaves and branches. In this study, the beneficial effects of kuromoji teas when drunk conventionally were investigated.

Essential oils have potential to mitigate stress symptoms and treat symptoms related to mental health. Few studies have investigated the effects of wood-derived aromatics on endocrinological and psychological responses in an actual space. In this study, we evaluated the effects of essential oil derived from Japanese cedar (Cryptomeria japonica) wood on the recovery state of female participants after they performed monotonous work. We determined the levels of salivary stress markers to describe the endocrinological responses. And we also used questionnaires to assess the perception of the odor of experimental rooms and psychological states. We found that olfactory stimulation with the volatile compounds of essential oil derived from Japanese cedar wood modulates mood states, and may transiently decrease sympathetic nervous activity. We suggest that olfactory stimulation with the volatile compounds of essential oil derived from Japanese cedar wood could be useful for maintaining mental health among women.

In recent years, highly antimicrobial properties of cedar heartwood essential oil against the wood-rotting fungi and pathogenic fungi have been reported in several papers. Antimicrobial properties against oral bacteria by hinokitiol contained in Thujopsis have been also extensively studied. The relation of naturally derived components and human immune system has been studied in some previous papers. In the present study, we focused on Japanese cedar, which has the widest artificial afforestation site in the country among various tree species. Extract oil was obtained from mixture of sapwood and heartwood of about 40-year cedar grown in Oguni, Kumamoto, Japan. We examined the influence of extract components from Japanese cedar woods on the expression of heat shock protein 70 (Hsp70) during heating, and on the micronucleus formation induced by the treatment of bleomycin as a DNA damaging agent. Cell lines used in this study were human fetal glial cells (SVGp12) and human glioma cells (MO54). Remarkable suppression of the Hsp70 expression induced by heating at 43°C was detected by the treatment of cedar extract in both SVGp12 and MO54 cells. We also found that cedar extract had an inhibitory tendency to reduce the micronucleus formation induced by bleomycin. From these results, the extract components from Japanese cedar woods would have an inhibitory effect of the stress response as a suppression of the heat-induced Hsp70 expression, and might have a reductive effect on carcinogenicity.

The present study investigated the effect of adjuvant chemotherapy and radiation on survival among patients undergoing chest wall resection for T3N0 non-small cell lung cancer (NSCLC).Patients with T3N0 NSCLC who underwent chest wall resection were identified in the National Cancer Data Base in 2004 to 2012. The cohort was divided into patients who had received adjuvant chemotherapy, radiation therapy, chemoradiation therapy, or no adjuvant treatment. Kaplan-Meier and log-rank tests were used to compare overall survival, and a bootstrapped Cox proportional hazards model was used to determine the significant contributors to survival. A subset analysis was performed with stratification by margin status and tumor size.Of 759 patients identified, 42.0% underwent surgery alone, 23.3% underwent surgery followed by chemotherapy, 22.3% underwent surgery followed by chemoradiation therapy, and 12.3% underwent surgery followed by radiotherapy alone. Tumors 4 cm benefited from adjuvant chemotherapy and radiation therapy in the multivariable analysis, and those ≤ 4 cm benefited only from adjuvant chemotherapy. The subgroup analysis by margin status identified that margin-positive patients with tumors4 cm benefited significantly from either adjuvant chemoradiation therapy or radiation therapy alone.T3N0 NSCLC with chest wall invasion requires unique management compared with other stage IIB tumors. An important determinant of management is tumor size, with tumors ≤ 4 cm benefiting from adjuvant chemotherapy and tumors4 cm benefiting from adjuvant chemotherapy if margin negative and adjuvant chemoradiation therapy or radiotherapy if margin positive.

Background Wood is a valuable material for interiors, and the psychophysiological relaxation effects of volatile organic compounds (VOCs) from wood chips and essential oils have been reported. However, few studies have identified the odors in full-scale wooden environment, and also, differences in gender have not been clarified. In this study, we aimed to confirm the effects of VOCs emitted from interior wood walls in both human male and female participants. Methods We used Japanese cedar timber and analyzed VOCs in the experimental rooms with and without Japanese cedar timber by gas chromatography-mass spectrometry (GC-MS). The physiological effects were measured using neuroendocrinological and immunological parameters in saliva. A questionnaire was used to evaluate the subjective responses to each odor in the experimental rooms. Results The main compound emitted from Japanese cedar timber was δ-cadinene, and the total volume of VOCs in the wood condition (presence of VOCs emitted from Japanese cedar) was 282.4 (μg/m3). Significant differences between genders in salivary parameters were shown that there were decreases of α-amylase in wood condition and increases of cortisol in the control (absence of VOCs) condition in female participants compared to male participants. The results demonstrated that VOCs in the experimental room with Japanese cedar timber tend to suppress the activation of the sympathetic nervous activity and non-VOCs of Japanese cedar in the control room increase cortisol in female participants. Conclusions These results suggest that an indoor environment with wood interior materials has the potential to be useful for health management, especially women’s health.

Purpose. To identify prognostic factors for metastatic osteosarcoma patients and establish indication for repeat metastasectomy. Methods. Data from 37 patients with pulmonary metastasis from osteosarcoma who underwent metastasectomy in our institute from 1979 to 2013 were retrospectively reviewed. Results. Prognostic factors analyzed were age, sex, maximal diameter of the tumor at first pulmonary metastasectomy, total number of resected pulmonary metastases at first metastasectomy, number of surgeries, and disease free interval. In our analysis, characteristics associated with an increased overall survival were age > 15 years and fewer metastases (≤3). Of the 37 patients, 13 underwent repeat metastasectomy after the first metastasectomy. Of the 7 patients that underwent only two metastasectomies, three remained disease-free. In contrast, all six patients that underwent three or more metastasectomies died of relapse. Patients who had five or less lesions at second metastasectomy showed better survival compared to those who had six or more lesions. Conclusion. Age > 15 years and number of metastases at first metastasectomy were independent prognostic factors. Metastasectomy may provide curative treatment even in cases requiring repeat surgery. The number of metastases at second metastasectomy may be a potential predictor of the need for repeat surgery.

Employee problems arising from mental illnesses have steadily increased and become a serious social problem in recent years. Wood is a widely available plant material, and knowledge of the psychophysiological effects of inhalation of woody volatile compounds has grown considerably. In this study, we established an experimental method to evaluate the effects of Japanese cedar wood essential oil on subjects performing monotonous work. Two experiment conditions, one with and another without diffusion of the essential oil were prepared. Salivary stress markers were determined during and after a calculation task followed by distribution of questionnaires to achieve subjective odor assessment. We found that inhalation of air containing the volatile compounds of Japanese cedar wood essential oil increased the secretion of dehydroepiandrosterone sulfate (DHEA-s). Slight differences in the subjective assessment of the odor of the experiment rooms were observed. The results of the present study indicate that the volatile compounds of Japanese cedar wood essential oil affect the endocrine regulatory mechanism to facilitate stress responses. Thus, we suggest that this essential oil can improve employees’ mental health.

Lung adenocarcinoma has never before been reported to be associated with von Hippel-Lindau (VHL) disease. Here, we report a case of VHL disease in a patient who had metachronous multiple lung adenocarcinomas. The patient is a 64-year-old-woman with VHL disease. She underwent surgical resection of one adenocarcinoma and one atypical adenomatous hyperplasia. A second lung adenocarcinoma developed metachronously. A point mutation in the VHL gene was confirmed in DNA from a blood sample, and loss of heterozygosity at the VHL locus was detected in the lung adenocarcinoma. The VHL dysfunction may have a role in the development of multiple lung adenocarcinomas.

Wood has been used since ancient times as a building material around the world. One of the characteristics of wood is volatile organic compounds (VOCs), which indicates the relaxant effects on human body. In this study, we attempt to evaluate the psychophysiological responses to VOCs emitted from interior walls containing Japanese cedar ( Cryptomeria japonica ). Japanese cedar is the most commonly planted in forests and the timber has often been used as an interior material in Japan. The evaluation indices of the participants are arithmetic performance, subjective assessments of VOC, salivary stress markers, and temporal changes in heart rate and autonomic nerve activity. We found that the inhalation of air containing VOCs emitted from Japanese cedar interior walls suppresses the increase in salivary α-amylase activity and chromogranin A secretion. And it causes participants to feel that the odor is pleasant. The present study thus indicated that VOCs emitted from Japanese cedar walls affect the autonomic nervous system and emotion. Therefore, we suggested that an interior containing Japanese cedar can help people maintain an optimum living environment.

Volatile constituents from natural plants have sometimes been used for the treatment of mental disorders, but the efficacy of many plants has not been determined. Here, we investigated the effects of the essential oil of the Siberian fir tree, Abies sibirica (Pinaceae), on individuals during and after performance of a sustained task on a visual display terminal (VDT). Participants who breathed air containing the essential oil showed prolonged heartbeat intervals and increased theta activity as measured by electroencephalography in the recovery period after the VDT task, but not during the task. The volatile constituents emitted from the essential oil of A. sibirica through the odorant delivery system for 40 min were a-pinene (80.4 μg), santene (3.1 μg), tricyclene (2.4 μg), camphene (24.2 μg), β-pinene (2.6 μg), myrcene (1.0 μg), 6-3-carene (14.4 μg), limonene (3.8 μg), and bornyl acetate (1.0 μg). These results show that the essential oil of A. sibirica reduced arousal levels after the VDT task, and might be useful for the prevention of VDT-related mental health disturbance.

スギ製材工程で大量に発生する樹皮の有効利用を図るため，スギ樹皮のアンモニア吸着能に着目した鶏ふん堆肥化過程の臭気低減効果について検討した。粉砕処理したスギ樹皮を620ppmに調製したバッグ内のアンモニアガスと5分間接触させたところ99.5％のアンモニアが除去された。鶏ふん堆積物の表面をスギオガクズまたはスギ樹皮で被覆し，堆肥化過程で発生するアンモニアの吸着を試みたところ，スギオガクズは1g当たり11mgのアンモニアを吸着したのに対し，スギ樹皮では33mgに達した。堆肥化後，スギ樹皮中の窒素の形態を調査したところ，水溶性窒素が22％，イオン交換性窒素が23％，有機態窒素47％であり，高い陽イオン交換能に伴うイオン結合だけでなく，共有結合による除去も示唆された。スギ樹皮は，アンモニアガス発生源の表面を被覆するだけで発生量を抑制でき，安価で簡便な臭気対策資材としての活用が期待される。

Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. Recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation, at least in part, by directly interacting with AR. Our observations suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from anandrogen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling.

Androgen signaling plays key roles in the development and progression of prostate cancer, and numerous ongoing studies focus on the regulation of androgen receptor (AR) transactivity to develop novel therapies for the treatment of androgen-independent prostate cancer. FoxH1, a member of the Forkhead-box (FOX) gene family of transcription factors, takes part in mediating transforming growth factor-β/activin signaling through its interaction with the Smad2·Smad4 complex. Using a series of experiments, we found that FoxH1 repressed both ligand-dependent and -independent transactivation of the AR on androgen-induced promoters. This action of FoxH1 was independent of its transactivation capacity and activin A but relieved by Smad2·Smad4. In addition, the repression of the AR by FoxH1 did not require deacetylase activity. A protein-protein interaction was identified between the AR and FoxH1 independently of dihydrotestosterone. Furthermore, a confocal microscopic analysis of LNCaP cells revealed that the interaction between the AR and FoxH1 occurred in the nucleus and that FoxH1 specifically blocked the foci formation of dihydrotestosterone-activated AR, which has been shown to be correlated with the AR transactivation potential. Taken together, our results indicate that FoxH1 functions as a new corepressor of the AR. Our observations not only strengthen the role of FoxH1 in AR-mediated transactivation but also suggest that therapeutic interventions based on AR-coregulator interactions could be designed to block both androgen-dependent and -independent growth of prostate cancer.

The perennial grass Vetiveria zizanioides (vetiver) is mainly cultivated for its fragrant essential oil. Although the components of the oil and their biological activities have been studied extensively, the effect of the volatiles emitted from the roots of V. zizanioides on humans has so far remained unexplored. We investigated the effects of volatile compounds emitted from the cut roots of V. zizanioides (1.0 g, low-dose conditions; 30 g, high-dose conditions) on individuals during a visual display terminal task. Participants who breathed the volatile compounds emitted under low-dose conditions showed faster reaction times and stimulation of sympathetic nerve activity as measured by electrocardiography. These effects were not observed under high-dose conditions. The total amounnt of volatiles emitted during the experiment was 0.25 μg under low-dose conditions and 1.35 μg under high-dose conditions. These findings indicate that volatile compounds emitted from the roots of V. zizanioides under low-dose conditions may have helped subjects to maintain performance in visual discrimination tasks while maintaining high sympathetic nerve system activity.

(-)-Bornyl acetate is the main volatile constituent in numerous conifer oils and has a camphoraceous, pine-needle-like odor. It is frequently used as the conifer needle composition in soap, bath products, room sprays, and pharmaceutical products. However, the psychophysiological effects of (-)-bornyl acetate remained unclear. We investigated the effects of breathing air mixed with (-)-bornyl acetate at different doses (low-dose and high-dose conditions) on the individuals during and after VDT (visual display terminal) work using a visual discrimination task. The amounts of (-)-bornyl acetate through our odorant delivery system for 40 min were 279.4 µg in the low-dose and 716.3 µg in the high-dose (-)-bornyl acetate condition. (-)-Bornyl acetate induced changes of autonomic nervous system for relaxation and reduced arousal level after VDT work without any influences of task performance in low-dose condition, but not in high-dose condition.

The leaves of Laurus noblis L. (laurel) are mainly used as a spice in cooking, and the essential oil obtained by steam distillation of the leaves is used as an additive in foods, drugs and cosmetics. We investigated the effect of the volatiles emitted from the leaves of L. noblis at different doses (low-dose and high-dose groups) on vigilance performance in a visual discrimination task. By inhaling volatiles of the leaves of L. noblis, the decrease of the rate of true hits found in the control group was prevented in the low-dose group. The high-dose group showed higher scores than the low-dose group for subjective effects related to negative emotion. Meanwhile, both groups showed physiological effects suggesting stimulation of circulation. These findings suggest that the volatiles emitted from the leaves of L. noblis at low concentration could be utilized to maintain a high level of vigilance performance, such as the rate of true hits by improving physiological arousal without incurring the detrimental performance effects of negative emotion.

In the course to find a new whitening agent, we evaluated the methanol extract from bud of clove (Syzygium aromaticum) on melanin formation in B16 melanoma cells. Eugenol and eugenol acetate were isolated as the active compounds and showed melanin inhibition of 60% and 40% in B16 melanoma cell with less cytotoxicity at the concentration of 100 and 200 μg/mL, respectively. Furthermore, an essential oil prepared from the bud of clove, which contain eugenol and eugenol acetate as dominant components, showed melanin inhibition of 50% and 80% in B16 melanoma cells at the concentration of 100 and 200 μg/mL, respectively.

Androgen signaling plays key roles in the development and progression of prostate cancer, and numerous ongoing studies focus on the regulation of androgen receptor (AR) transactivity to develop novel therapies for the treatment of androgen-independent prostate cancer. FoxH1, a member of the Forkhead-box (FOX) gene family of transcription factors, takes part in mediating transforming growth factor-beta/activin signaling through its interaction with the Smad2.Smad4 complex. Using a series of experiments, we found that FoxH1 repressed both ligand-dependent and -independent transactivation of the AR on androgen-induced promoters. This action of FoxH1 was independent of its transactivation capacity and activin A but relieved by Smad2.Smad4. In addition, the repression of the AR by FoxH1 did not require deacetylase activity. A protein-protein interaction was identified between the AR and FoxH1 independently of dihydrotestosterone. Furthermore, a confocal microscopic analysis of LNCaP cells revealed that the interaction between the AR and FoxH1 occurred in the nucleus and that FoxH1 specifically blocked the foci formation of dihydrotestosterone-activated AR, which has been shown to be correlated with the AR transactivation potential. Taken together, our results indicate that FoxH1 functions as a new corepressor of the AR. Our observations not only strengthen the role of FoxH1 in AR-mediated transactivation but also suggest that therapeutic interventions based on AR-coregulator interactions could be designed to block both androgen-dependent and -independent growth of prostate cancer.