Prognostic Impact of Preoperative Assessment of Muscle Mass and Strength in Surgically Resected Lung Cancer.

BACKGROUND/AIM: The association between resected non-small cell lung cancer (NSCLC) and long-term outcomes of muscle mass depletion and muscle weakness has also not been well documented. This study evaluated whether muscle mass depletion assessed by bioelectrical impedance analysis (BIA) and low muscle strength assessed by the peak expiratory flow rate as a percentage of predicted value (%PEFR) were associated with surgical outcomes in patients with resected NSCLC. PATIENTS AND METHODS: This retrospective study included 219 patients with resected NSCLC between 2016 and 2021. The cutoff value for muscle mass depletion was according to guidelines, for low muscle strength, we defined by receiver operating characteristics analysis for recurrence-free survival (RFS). Survival analysis was performed, and postoperative outcomes were compared. RESULTS: A total of 76 patients (34.7%) had muscle mass depletion, and 114 patients (52.1%) had low muscle strength. Muscle mass depletion and low muscle strength were independent poor prognostic factors for overall survival [hazard ratio (HR)=2.631, p=0.003; HR=1.983, p=0.044] and RFS (HR=3.120, p<0.001; HR=1.857, p=0.028) in multivariate analysis. Postoperative complication was associated with low muscle strength (p=0.009). Postoperative recurrence was associated with muscle mass depletion (p=0.03). CONCLUSION: Preoperative muscle mass depletion assessed by BIA and low muscle strength determined by %PEFR are worse prognostic factors after surgical resection for NSCLC. Our results may provide some important information for preoperative management.

Effect of Postoperative Muscle Loss After Resection of Non-small Cell Lung Cancer on Surgical Outcomes.

BACKGROUND/AIM: Preoperative depletion of psoas muscle mass index (PMI) in lung cancer patients is an unfavorable prognostic factor. The relationship between post-surgical changes in PMI and survival is not clear. Therefore, we conducted a retrospective study to clarify the prognostic significance of preoperative and postoperative PMI changes. PATIENTS AND METHODS: We retrospectively reviewed lung cancer patients, who underwent curative surgical resection with lymph node dissection and computed tomography (CT) approximately six months post-surgery between 2010 and 2019. Pre- and postoperative PMI was measured from CT images at the third lumbar vertebra level. A sex-dependent PMI change ratio (postoperative PMI/preoperative PMI) was used to divide patients into two groups: high PMI loss (67 patients, ≤25th lower quartile) and low PMI loss/PMI increase (204 patients, >25th lower quartile), and clinicopathological features were compared. RESULTS: Age ≥70 years, elevated preoperative carcinoembryonic antigen levels, advanced pathological stage, lymphatic permeation, vascular invasion, performance of adjuvant platinum-doublet chemotherapy, low body mass index, and postoperative recurrence were significantly higher in the high PMI loss group. Logistic regression analysis found that Charlson comorbidity index, low body mass index, advanced pathological stage, and postoperative recurrence were associated with high PMI loss. The five-year postoperative overall survival rate was 50% in the high PMI loss group and 79% in the low PMI loss/PMI increase group (p<0.001). High PMI loss was also an unfavorable factor in a multivariable Cox's proportional hazard model (p=0.002). CONCLUSION: Postoperative muscle loss was an independent prognostic factor for poorer overall survival regardless of preoperative sarcopenia, in non-small cell lung cancer.

Evaluation of balloon pulmonary angioplasty using lung perfusion SPECT in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: The aim of this study was to evaluate the effect of balloon pulmonary angioplasty (BPA) using lung perfusion single-photon emission computed tomography (SPECT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: 20 consecutive patients (64 ± 15 years) who were diagnosed with CTEPH and underwent BPA were included in this study. All patients underwent lung perfusion SPECT before and after BPA. The relationship between functional %volume of the lung calculated from the lung perfusion SPECT (FVL-LPSPECT), and other clinical parameters before and after BPA was assessed using the Wilcoxon signed-rank test. The correlation between each parameter and mean pulmonary artery pressure (mPAP) using the Spearman's correlation was performed. To determine predictors of mPAP for evaluating treatment effectiveness, significant parameters were included in multiple regression analysis. After BPA, world health organization functional classification, six-minute walk distance (6MWD), mPAP, and FVL-LPSPECT significantly improved. FVL-LPSPECT (r = - 0.728, P < 0.001) and 6MWD (r = - 0.571, P = 0.009) were significant correlation of mPAP. In the multiple regression analysis, FVL-LPSPECT was the most significant predictor of improvement in mPAP after BPA (P < 0.001). CONCLUSIONS: This study demonstrated that the lung perfusion SPECT could be a potential measurement of the effectiveness of BPA in patients with CTEPH.

Association between coronary artery calcium score on non-contrast chest computed tomography and all-cause mortality among patients with congestive heart failure.

Coronary artery calcium (CAC) score is a robust prognostic tool to predict cardiac events. Although patients with congestive heart failure (CHF) occasionally undergo non-contrast computed tomography (NCCT), the prognostic utility of CAC by NCCT is not widely known. We aimed to determine if CAC measured on NCCT is associated with all-cause mortality (ACM) among patients with CHF. We identified 550 patients admitted due to CHF who underwent NCCT. Patients were categorized into three groups according to CAC scores 0, 1-999, and ≥ 1000. The multivariate Cox proportional hazards model was used to assess if CAC by NCCT was associated with ACM after adjusting for traditional coronary artery disease (CAD) risk factors, brain natriuretic peptide and left ventricular ejection fraction (LVEF). In a subset of 245 patients with invasive coronary angiography (ICA), the associations between CAC scores and ACM were assessed in the multivariate Cox proportional hazards model. Further, we assessed if CAC increased statin use at discharge. During a mean follow-up of 3.3 ± 3.1 years, ACM occurred in 168 patients (30.55%). Compared with patients with CAC 0, those with CAC ≥ 1000 (HR 1.564, 95% CI 0.969-2.524, P = 0.067) were more likely to experience ACM, while those with CAC score 1-999 (HR 0.971, 95% CI 0.673-1.399, P = 0.873) were not. Similarly, a trend toward significance was observed in patients with LVEF < 40% (HR 2.124, 95% CI 0.929-4.856, P = 0.074). In the sub-analysis, patients with CAC ≥ 1000 had increased ACM compared to those with CAC 0, only if ICA ≥ 50% (HR 3.668, 95% CI 1.141-11.797, P = 0.029). Multivariate logistic regression revealed that statin use at discharge was increased with ICA ≥ 50%, but not CAC. The CAC score measured by NCCT tended to be associated with ACM among CHF patients. Statin use was not increased by CAC on NCCT.

Prognostic values of coronary artery calcium score and 123I-BMIPP SPECT in patients with non-ischemic heart failure with preserved ejection fraction.

This study aimed to determine whether coronary artery calcium score (CACS) can be a prognostic indicator for the development of major adverse cardiac events (MACEs) and compare the value of CACS with that of the 123I-betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) defect score (BDS) in patients with non-ischemic heart failure with preserved ejection fraction (NIHFpEF). Among 643 consecutive patients hospitalized due to acute heart failure, 108 (74 ± 13y) were identified to have NIHFpEF on non-contrast regular chest computed tomography and 123I-BMIPP single-photon emission computed tomography (SPECT). We evaluated whether CACS and BDS were associated with MACEs using multivariate Cox models. Thirty-two MACEs developed at a mean follow-up period of 2.4 years. CACS > 0 (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.02-5.54) and higher BDS (HR 16.00, 95% CI 5.88-43.49) were significantly associated with the development of MACEs. The proportion of patients who experienced MACEs was significantly higher in the CACS > 0 and high BDS group than in the CACS = 0 and low BDS group (3% vs. 75%, p < 0.001). CACS, as well as BDS, could serve as potential prognostic indicators in patients with NIHFpEF.

Serum CEA and CYFRA Levels in ALK-rearranged NSCLC Patients: Correlation With Distant Metastasis.

AIM: To clarify the correlation between serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) and metastasis and survival in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: CEA and CYFRA levels in 131 ALK-rearranged NSCLC patients were determined using fluorescence in situ hybridization (FISH), real time-reverse transcription polymerase chain reaction, and immunohistochemistry, using biopsy specimens, cytology specimens, and plasma specimens. Cut-off value of each marker was determined as 10 ng/ml. RESULTS: In logistic regression analysis, higher levels of both markers had a positive relationship with bone metastases, and higher levels of CYFRA was relevant to liver metastases, and multiple-organ metastases. However, these markers were not proven to be poor prognostic factors in Cox's proportional model analysis. CONCLUSION: Elevated serum CEA and CYFRA levels seem to provide useful clinical information about presence of bone and liver metastasis and multiple-organ metastases, although they were not a powerful indicator of prognosis. These two markers may suggest the extension of metastasis and would be helpful in considering treatment options.

Sarcopenia in Resected NSCLC: Effect on Postoperative Outcomes.

INTRODUCTION: Skeletal muscle depletion, referred to as sarcopenia, has recently been identified as a risk factor for poor outcomes in various malignancies. However, the prognostic significance of sarcopenia in patients with NSCLC after surgery has not been adequately determined. This study investigated the impact of sarcopenia in patients undergoing pulmonary resection for lung cancer. METHODS: This retrospective study consisted of 328 patients with pathologically confirmed NSCLC who underwent curative resection between January 2005 and April 2017. Preoperative computed tomography imaging at the third lumbar vertebrae level was assessed to measure the psoas muscle mass index (PMI, cm2/m2). Sarcopenia was defined as a cutoff value of PMI less than 6.36 cm2/m2 for males and 3.92 cm2/m2 for females, based on PMI values from "healthy" subjects. RESULTS: The median patient age was 71 years and 59% were male. Sarcopenia was present in 183 (55.8%) and was significantly related with increasing age (p < 0.001), being male (p < 0.001), smoking habit (p < 0.001), lower body mass index (p < 0.001), and postoperative major complication (Clavien-Dindo grade ≥3, p = 0.036). The prevalence of sarcopenia was higher in men than in women, and the prevalence increased with age in men, whereas the prevalence did not increase in females older than 70 years. The 5-year survival rate was 61% in patients with sarcopenia and 91% in those without. Multivariate analysis revealed that sarcopenia was an independent unfavorable prognostic factor (p = 0.019). CONCLUSIONS: Sarcopenia as determined using preoperative computed tomography could be used to predict postoperative major complication and prognosis in patients with resected NSCLC. Our results may provide some important information for preoperative management.

Transcription Elongation Factor P-TEFb Is Involved in IL-17F Signaling in Airway Smooth Muscle Cells.

BACKGROUND: IL-17F is involved in the pathogenesis of several inflammatory diseases, including asthma and COPD. However, the effects of steroids on the function of IL-17F signaling mechanisms are largely unknown. One of the transcription elongation factors, positive transcription elongation factor b (P-TEFb) composed of cyclin T1 and cyclin-dependent kinase 9 (CDK9), is known as a novel checkpoint regulator of gene expression via bromodomain-containing protein 4 (Brd4). METHODS: Human airway smooth muscle cells were stimulated with IL-17F and the expression of IL-8 was evaluated by real-time PCR and ELISA. Next, the phosphorylation of CDK9 was determined by Western blotting. The CDK9 inhibitor and short interfering RNAs (siRNAs) targeting Brd4, cyclin T1, and CDK9 were used to identify the effect on IL-17F-induced IL-8 expression. Finally, the effect of steroids and its signaling were evaluated. RESULTS: IL-17F markedly induced the transcription of the IL-8 gene and the expression of the protein. Pretreatment of CDK9 inhibitor and transfection of siRNAs targeting CDK9 markedly abrogated IL-17F-induced IL-8 production. Transfection of siRNAs targeting Brd4 and cyclin T1 diminished IL-17F-induced phosphorylation of CDK9 and IL-8 production. Moreover, budesonide decreased CDK9 phosphorylation and markedly inhibited IL-17F-induced IL-8 production. CONCLUSIONS: This is the first report that P-TEFb is involved in IL-17F-induced IL-8 expression and that steroids diminish it via the inhibition of CDK9 phosphorylation. IL-17F and P-TEFb might be novel therapeutic targets for airway inflammatory diseases.

Seasonal Influenza Vaccine-induced Pneumonitis Presenting with Multiple Pulmonary Nodules.

A 39-year-old woman received a seasonal influenza vaccine in November 2015 and subsequently experienced malaise, low-grade fever, and chest discomfort. A chest X-ray performed 2 weeks after vaccination showed multiple nodular shadows in both lungs and ground-glass shadows in both lower lung fields. Her bronchoalveolar lavage fluid contained an unusually high number of lymphocytes, and a drug-induced lymphocyte stimulation test for seasonal influenza vaccine was positive. Transbronchial lung biopsy revealed the presence of granulomatous inflammation. Thereafter her abnormal chest shadow spontaneously improved. Based on these findings, the patient was diagnosed with drug-induced pneumonitis due to an influenza vaccine.

IL-17F induces IL-6 via TAK1-NFκB pathway in airway smooth muscle cells.

INTRODUCTION: Interleukin (IL)-17F plays a critical role in the pathophysiology of asthma. However, the precise role of IL-17F in airway smooth muscle cells (ASMCs) and its regulatory mechanisms remain to be defined. Therefore, we sought to investigate the expression of IL-6 by IL-17F and the involvement of transforming growth factor ß-activated kinase 1 (TAK1) and nuclear factor (NF)-κB by in ASMCs. METHODS: ASMCs were cultured in the presence or absence of IL-17F. The expression of IL-6 gene and protein was analyzed using real-time PCR and ELISA, and the activation of TAK1 and NF-κB was detected by Western blotting. The effect of TAK1 inhibitor 5Z-7-oxozeaenol and NF-κB inhibitor BAY 11-7082 on the expression of IL-6 was investigated. Finally, the short interfering RNAs (siRNAs) targeting TAK1 and a subunit of NF-κB, p65 were transfected into ASMCs. RESULTS: The expression of IL-6 gene and protein was significantly induced by IL-17F. IL-17F activated TAK1 and NF-κB in ASMCs. Transfection of siRNAs targeting TAK1 abolished IL-17F-induced phosphorylation of p65. Both 5Z-7-oxozeaenol and BAY 11-7082 significantly inhibited IL-17F-induced IL-6 production in a dose-dependent manner. Similarly, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL-6. CONCLUSIONS: Collectively, these results provided evidence supporting the potential importance of the Th17-ASMCs crosstalk via the IL-17F-IL-6 axis in airway inflammation and as a candidate pharmacological target for airway inflammatory diseases such as asthma.

Synthetic double-stranded RNA induces interleukin-32 in bronchial epithelial cells.

OBJECTIVE: Interleukin (IL)-32 is a novel cytokine and is involved in the pathogenesis of various inflammatory diseases, including asthma and COPD. However, the regulatory mechanisms of IL-32 expression and its precise pathogenic role remain to be defined. Given that viral infections are known to potentially cause and exacerbate airway inflammation, in this study, we investigated the expression of IL-32 induced by synthetic double-stranded (ds) RNA, and its signaling mechanisms involved. METHODS: Bronchial epithelial cells were stimulated with synthetic dsRNA poly I:C. The levels of IL-32 expression were analyzed using real-time PCR and ELISA. The involvement of transforming growth factor ß-activated kinase 1 (TAK1) and a subunit of nuclear factor-κB (NF-κB), p65 was determined by western blot analyses. TAK1 inhibitor, 5Z-7-Oxozeaenol and NF-κB inhibitor, BAY 11-7082 were added to the culture to identify key signaling events leading to the expression of IL-32. Finally, the effect of short interfering RNAs (siRNAs) targeting TAK1 and p65 was investigated. RESULTS: dsRNA significantly induced IL-32 gene and protein expression, concomitant with activation of TAK1 and p65. Pretreatment of 5Z-7-Oxozeaenol diminished dsRNA-induced phosphorylation of NF-κB. Both 5Z-7-Oxozeaenol and BAY 11-7082 significantly abrogated dsRNA-induced IL-32 production. Moreover, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL-32. CONCLUSIONS: The expression of IL-32 is induced by dsRNA via the TAK1-NF-κB signaling pathway in bronchial epithelial cells. IL-32 is involved in the pathogenesis of airway inflammation, and may be a novel therapeutic target for airway inflammatory diseases.

Potential involvement of IL-17F in asthma.

The expression of IL-17F is seen in the airway of asthmatics and its level is correlated with disease severity. Several studies have demonstrated that IL-17F plays a pivotal role in allergic airway inflammation and induces several asthma-related molecules such as CCL20. IL-17F-induced CCL20 may attract Th17 cells into the airway resulting in the recruitment of additional Th17 cells to enhance allergic airway inflammation. We have recently identified, for the first time, that bronchial epithelial cells are its novel cell source in response to IL-33 via ST2-ERK1/2-MSK1 signaling pathway. The receptor for IL-17F is the heterodimeric complex of IL-17RA and IL-17RC, and IL-17F activates many signaling pathways. In a case-control study of 867 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL-17F gene was associated with asthma. In atopic patients with asthma, prebronchodilator baseline FEV1/FVC values showed a significant association with the H161R variant. Moreover, this variant is a natural antagonist for the wild-type IL-17F. Moreover, IL-17F is involved in airway remodeling and steroid resistance. Hence, IL-17F may play an orchestrating role in the pathogenesis of asthma and may provide a valuable therapeutic target for development of novel strategies.

[Satisfactory outcome with erlotinib after failure with gefitinib in a patient with meningeal carcinomatosis secondary to non-small cell lung cancer].

A 60-year-old man was admitted to our hospital because of the radiologic findings of meningeal carcinomatosis after long-term disease control of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer, with cisplatin-based chemotherapy followed by gefitinib. Brain magnetic resonance imaging (MRI) revealed diffuse and linear enhancement on the surface of the midbrain and along the cerebellar folia. In addition, analysis of his cerebrospinal fluid (CSF) showed an increased WBC count and an elevated level of CEA. He presented no symptoms at the time of diagnosis of meningeal carcinomatosis; however, within 2 weeks, neurological symptoms such as disorientation, dysarthria, and ataxic gait became apparent. Since his symptoms seemed to worsen even under further treatment with different cisplatin-based chemotherapy or retreatment with gefitinib, we decided to initiate erlotinib treatment. His symptoms rapidly improved within a week of beginning treatment with erlotinib, and MRI and CSF examinations also showed remarkable improvement of the meningeal carcinomatosis. This case suggests that erlotinib may be effective in some patients with meningeal carcinomatosis previously treated with gefitinib. However, further studies are required to understand the differential efficacy of these drugs.

[An autopsy case of pulmonary tumor thrombotic microangiopathy complicated with interstitial pneumonia and lipoid pneumonia].

A 67-year-old woman was admitted to our hospital because of progressive dyspnea, cough, bloody sputum, and backache. Chest radiography and CT scans showed bilateral diffuse interstitial shadows, bilateral pleural effusion and dilatation of the pulmonary artery. Echocardiography indicated pulmonary hypertension, and the serum tumor marker levels were elevated. We performed right cardiac catheterization, and withdrew some blood from a pulmonary artery catheter in the wedge position. We confirmed moderate pulmonary hypertension, and adenocarcinoma-like malignant cells were seen in the aspirated blood. The patient died of progressive respiratory failure despite supportive care. In addition to PTTM and lymphangiosis carcinomatosa, autopsy of the right lung revealed interstitial pneumonia and lipoid pneumonia, both of which were not reported before to be associated with PTTM.

Endobronchial metastasis from adrenocortical carcinoma.

Lung parenchymal metastases are common manifestations; however, endobronchial metastasis is rare. We present herein a case of endobronchial metastasis from adrenocortical carcinoma. In the English language literature, this is the first case with such rare metastasis from adrenocortical carcinoma diagnosed antemortem. Although very rare, physicians should keep in mind the possibility of endobronchial metastasis in patients with a history of extrapulmonary malignancy including adrenocortical carcinoma.

Central alveolar hypoventilation syndrome due to surgical resection for bulbar hemangioblastoma.

A 29-year-old man with a history of resected bulbar hemangioblastoma was admitted to hospital with nighttime breathing disturbance, but with apparently normal breathing while awake. After diagnostic work-up, including polysomnographic testing, he was diagnosed as having central alveolar hypoventilation syndrome due to surgical resection for bulbar hemangioblastoma. Non-invasive positive pressure ventilation (NIPPV) via oronasal facemask was given for nocturnal ventilatory support. Two months after leaving our hospital, he was readmitted because of aspiration pneumonia. The pneumonia was successfully treated with antibiotics, but the desaturation during sleep worsened despite non-invasive ventilatory support. Higher bi-level positive pressure using a full facemask successfully alleviated sleep hypoventilation and apnea. To the best of our knowledge, this is the first case report of central alveolar hypoventilation syndrome due to surgical resection for bulbar hemangioblastoma.

[A case of paragonimiasis miyazakii suspected after pathologic examination and subsequently confirmed].

A 58-year-old man presented with right backache and bloody sputum. Chest X-ray revealed a nodular opacity in the right lung. Since could not obtain a diagnosis by bronchoscopy, we performed a lower lobectomy. Histopathologically, there were irregularly shaped necrotizing granulomas and an area of acute hemorrhagic, eosinophilic abscess. We suspected paragonimiasis. The diagnosis of paragonimiasis miyazakii was confirmed by ELISA. This is a valuable case of suspected paragonimiasis confirmed pathologically.

Expression of organic cation transporter SLC22A16 in human epithelial ovarian cancer: a possible role of the adriamycin importer.

The SLC22A16 is one of the newly isolated organic cation transporters, which is responsible for uptake and transport of adriamycin into cells. Adriamycin is considered to be an active agent for ovarian cancer. Recently, the benefit of adding adriamycin to the current standard regimen, paclitaxel and platinum, is evaluated to improve the outcome of patients with ovarian cancer. Therefore, we examined the expression of SLC22A16 in ovarian cancers. Twelve ovarian carcinoma cell lines were used for immunoblotting and reverse transcription-polymerase chain reaction to confirm the expression of SLC22A16 mRNA and protein. Five normal ovaries, 12 ovarian adenomas, and 94 ovarian cancer cases were obtained from patients after surgical therapy. The specimens were used for immunohistochemistry. The median value of relative SLC22A16 gene expression in cell lines derived from clear-cell adenocarcinoma was significantly higher than that in cell lines from other histologies (P < 0.001). Expression of SLC22A16 protein was also detected in cell lines derived from clear-cell adenocarcinoma. The SLC22A16 immunoreactivity was detected in 15 (16%) of 94 epithelial ovarian cancer, 1 (8.3%) of 12 benign adenomas, but 0 (0%) of 5 normal ovary cases. In ovarian cancer tissues, SLC22A16 immunoreactivity was detected in 2 (5%) of 38 serous adenocarcinoma, 1 (6.7%) of 15 endometrioid adenocarcinoma, 0 (0%) of 14 mucinous adenocarcinoma, and 12 (46.2%) of 26 clear-cell adenocarcinoma (P < 0.0001, clear-cell vs other histologies). In conclusion, SLC22A16 was abundantly expressed in clear-cell adenocarcinoma. Our results suggest that adriamycin-related chemicals that are taken up via SLC22A16 may have the potential to be effective against clear-cell adenocarcinoma.

Peroxisome proliferator-activated receptor gamma and growth inhibition by its ligands in uterine endometrial carcinoma.

PURPOSE: In this study, we evaluated the correlation between endometrial carcinoma and peroxisome proliferator-activated receptor gamma (PPARgamma) expression and assessed whether PPARgamma ligands influence carcinoma growth. EXPERIMENTAL DESIGN: We examined the presence and cellular distribution of PPARgamma protein in 42 normal endometria, 32 endometria with hyperplasia, and 103 endometria with endometrial carcinoma by immunohistochemistry. We then compared PPARgamma mRNA expression in endometrial carcinoma with that in normal endometria using real-time reverse transcription-PCR. We subsequently confirmed expression of PPARgamma mRNA by real-time reverse transcription-PCR and PPARgamma protein by immunoblotting in endometrial carcinoma cell lines (Ishikawa, Sawano, and RL95-2 cells). We further examined the effects of PPARgamma agonist 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a naturally occurring PPARgamma ligand, to these endometrial carcinoma cell lines. We also examined the status of apoptosis and p21 mRNA expression of these endometrial carcinoma cell lines following addition of 15d-PGJ2. RESULTS: PPARgamma immunoreactivity was detected in 11 of 23 (48%) of proliferative-phase endometrium, 14 of 19 (74%) of secretory-phase endometrium, 27 of 32 (84%) of endometrial hyperplasia, and 67 of 103 (65%) of carcinoma cases. PPARgamma immunoreactivity was significantly lower in endometrial carcinoma than in secretory-phase endometrium (P = 0.012) and endometrial hyperplasia (P = 0.006). There was a significant positive association between the status of PPARgamma and p21 expression in endometrial carcinoma (P < 0.0001). There was a significant negative association between the body mass index and PPARgamma labeling index of carcinoma tissue in the patients with endometrial carcinoma (P < 0.0001). PPARgamma mRNA was expressed abundantly in normal endometria but not in endometrial carcinoma. We showed that PPARgamma agonist 15d-PGJ2 inhibited cell proliferation and induced p21 mRNA of endometrial carcinoma cell lines. CONCLUSION: We showed the expression of PPARgamma in human endometrial carcinoma and the effects of PPARgamma ligand in endometrial carcinoma cells. These findings suggest that a PPARgamma ligand, 15d-PGJ2, has antiproliferative activity against endometrial carcinoma.