Depleting NFAT1 expression inhibits the ability of invasion and migration of human lung cancer cells.

BACKGROUND: Nuclear factor of activated T-cells (NFAT) is a general name applied to a family of transcription factors shown to be important in immune response. One or more members of the NFAT family are expressed in most cells of the immune system. NFAT1 is considered to involve in the development of cardiac, skeletal muscle, nervous systems, and tumorigenesis. METHODS: In the current study, we analyzed MEKK1 expression in 159 surgically resection non-small cell lung cancer patient's samples by immunohistochemistry and determined its role in SK-EMS-1 cells via RNAi experiment. RESULTS: The abilities of invasion, motility, and adhesion of SK-EMS-1 cells were detected by transwell assay, wound healing assay and adhesion assay, respectively. The result showed NFAT1 was highly expressed in lung tumor tissues instead of adjacent lung tissues (54.1% vs 8.8%, p < 0.05); its overexpression was positively correlated with lymph node metastasis (p < 0.05). Depleting its expression in SK-EMS-1 cells can inhibit its invasion and migration abilities significantly (p < 0.05); and also can reduce proliferation of lung cancer cells (p < 0.05). CONCLUSION: Our study showed NFAT1 plays an important role in origination, invasion and metastasis of non-small lung cancer cells; its underlying action mechanism needs further study.

Expression and unique functions of four nuclear factor of activated T cells isoforms in non-small cell lung cancer.

Nuclear factor of activated T cells (NFAT) is an important family of transcription factors that can be activated by calmodulin and calcineurin in human cells. To investigate the expression and clinical significance of NFAT isoforms and calcineurin in non-small cell lung cancer (NSCLC), we collected tumor and adjacent normal tissues from 159 NSCLC patients and assembled them in a tissue microarray. Protein levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin were determined using immunohistochemistry. Correlations between NFAT and calcineurin expression and clinicopathologic characteristics were analyzed. We found that the positive rates of NFAT1 (52.8%, 84/159), NFAT2 (11.3%, 18/159), NFAT3 (28.3%, 45/159), NFAT4 (47.2%, 75/159), and calcineurin (47.8%, 76/159) expression were significantly higher in tumor tissues than in adjacent normal lung tissues (P<0.001), respectively. The positive rate of NFAT1 expression was significantly higher in patients with adenocarcinoma (63.5%, 47/74) than in those with squamous cell carcinoma (43.5%, 37/85) (χ2=6.340, P=0.012); with lymph node metastasis (61.6%, 53/86) than without lymph node metastasis (42.5%, 31/73) (χ2=5.818, P=0.016); and with stage-II and -III diseases (61.8%, 55/89) than with stage-I disease (41.4%, 29/70) (χ2=6.524, P=0.011). Moreover, the overexpression of NFAT1 was associated with poor survival of NSCLC patients (χ2=5.006, P=0.025). The positive rate of NFAT4 was significantly higher in patients with squamous carcinoma (57.6%, 49/85) than in those with adenocarcinoma (35.1%, 26/74) (χ2=8.045, P=0.005) and with high and moderate differentiation (54.9%, 61/111) than with low differentiation (29.2%, 14/48) (χ2=8.943, P=0.003). Calcineurin overexpression was significantly associated with histologic type (higher in squamous carcinoma than in adenocarcinoma, χ2=8.897, P=0.003), differentiation grade (higher in high-moderation grade than in low grade, χ2=9.566, P=0.002) and gender (higher in male than in female, χ2=5.766, P=0.016). Furthermore, calcineurin expression was significantly correlated with NFAT4 level (r=0.429, P<0.001). These results suggest that NFAT1 expression is associated with lung adenocarcinoma progression, and NFAT4 expression, which was higher in squamous lung cancer, is associated with calcineurin expression and differentiation grade.

[Prognostic factors for survival after lung cancer surgery in elderly patients].

BACKGROUND: With the improvement of the surgical and anesthetic techniques, there are increasing numbers of elderly surgical patients with lung cancer. The purpose of this study is to examine the prognostic factors of surgical resection in patients more than 70 years of age. METHODS: Data were retrospectively analyzed from 192 patients aged ≥70 years who underwent lung cancer surgery. Of these patients, 48.4% were in stage I, 20.8% in stage II, 19.3% in stage III, and 2.1% in stage IV. Patient demographics were the following: 79.2% male and 20.8% female; 21.9% ≥75 years older; and 11.5% had significant co-morbidities. Tumor characteristics: squamous cell carcinoma 49.0%, adenocarcinoma 35.9%, adenosquamous carcinoma 8.3%, small cell lung cancer 4.7%, others 2.1%. OPERATIONS: exploration 2.1%, wedge resection 8.3%, lobectomy 72.4%, more than lobectomy 12.5%, pneumonectomy 4.7%. Of these operations, 91.1% were radical surgery. The significance of prognostic factors was assessed by univariate and multivariate COX regression analyses. RESULTS: The total 5-year survival rate was 33.5% in this series. Age, sex, symptom and co-morbidity had no impact on survival. Multivariable COX analysis demonstrated that incomplete resection (P=0.003), advanced surgical-pathological stage (P < 0.001) and other type of the tumor (P=0.016) were significant, independent, unfavorable prognostic determinants in patients. CONCLUSIONS: Thoracic surgery is a safe and feasible approach in elderly patients with lung cancer. Every effort should be made to detect early stage patients who might benefit from surgical treatment. Lobectomy is still the ideal surgical option for elderly patients who are able to tolerate the procedure. More limited lung surgery may be an adequate alternative in patients with associated co-morbidities.

Synchronous primary carcinosarcoma and adenosquamous carcinoma of the esophagus.

Reports of adenosquamous carcinoma and carcinosarcoma found at the same esophagus are rare in the literature. We report a case of synchronous adenocarcinoma and carcinosarcoma of the esophagus. The sarcomatous components were immunoreactive for vimentin. Carcinoma, sarcoma, and adenocarcinoma cells distinctively metastasized to different lymph nodes. Further investigations are required to reveal the biological behavior of the tumor.

A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis.

PURPOSE: Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients. EXPERIMENTAL DESIGN: MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I-III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined. RESULTS: We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan-Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan-Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2. CONCLUSIONS: Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31.

[Expression and significance of COX-2 and its transcription factors NFAT3 and c-Jun in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Cyclooxygenases (COX), the key enzymes in the conversion of arachidonic acid (AA) to prostaglandins (PGs), are involved in initiation and progression of cancer. The aim of this study is to explore the relationship between the expressions of COX-2 and several transcription factors in non-small cell lung cancer. METHODS: Immunohistochemistry was performed to assay the expression levels of COX-2, c-Fos, c-Jun and nuclear factor of activated T cells 3 (NFAT3) in tissue microarray containing 159 tumor tissues of non-small cell lung cancer. RESULTS: The positive rate of COX-2 expression was 42.8%, and the expression of COX-2 was significantly higher in squamous cell carcinoma than that in adenocarcinoma (52.9% vs 31.3%, χ²=7.723, P=0.005). The expression of COX-2 was significantly associated with differentiation grade, with the lower level in the poorer differentiation grade group (χ²=7.600, P=0.022). In this panel of samples, the expression of COX-2 was significantly correlated with c-Fos expression (r=0.456, P<0.001) and NFAT3 level (r=0.294, P<0.001). The correlation between the expressions of NFAT3 and c-Fos were also observed (r=0.231, P=0.003). CONCLUSION: The expression of COX-2 was significantly associated with the expressions of transcription factors NFAT3 and c-Fos in nonsmall cell lung cancer.

A retrospective study of unicentric and multicentric Castleman's disease: a report of 52 patients.

Castleman's disease (CD) is a rare disorder characterized by non-cancerous tumor growth that may develop in the lymph node tissue at a single site or throughout the body (Castleman et al. in Cancer 9:822-830, 1956). It involves hyperproliferation of specific B cells that produce the cytokine IL-6. This disorder is often undiagnosed or misdiagnosed. For this reason, only very few patients have been reported, and little information is available in the literature. In hopes of providing a better understanding of this rare disease, this report examines 52 patients with Unicentric Castleman's disease (UCD) and Multicentric Castleman's disease (MCD) treated from 1999-2008 at a single institution. Fifty-two patients with CD, along with their histological diagnoses, were collected. Patients were divided into two groups--the more common UCD and the less common MCD. Relevant clinical, pathological, and laboratory data were examined in order to evaluate treatment responses, with symptom onsets and survival period serving as the endpoints of the assessment. Each of the 48 patients with UCD exhibited benign symptoms and underwent a curative surgical resection with excellent prognosis. All of the four patients with MCD received surgical resection. Three of the four patients relapsed and received radiotherapy and/or chemotherapy. Only one of the three post-treatment patients survived. UCD is manifested in the form of benign, painless, slow lymph node enlargement that is generally asymptomatic. Complete surgical removal is recommended as a course of curative treatment. The multicentric form of CD exhibits a progressive clinical course with potential for malignancy. There is currently no standard therapy for MCD.

Multiple organ metastases of Pulmonary Epithelioid Haemangioendothelioma and a review of the literature.

This report describes a case of pulmonary epithelioid haemangioendothelioma presented as multi-organ metastases including lung, liver and bone in a 56-year-old woman with an initial diagnosis made with thoracoscopic wedge biopsy. The diagnosis is confirmed through immunohistochemistry. This is a rare disease, with approximately 90 cases described in the English literature and approximately 10 cases reported in China. The case of PEH presented as multiple pulmonary nodules and metastasing to liver and bone is rare in the English literature. The rarity of this condition, the lack of clear standards for treatment, and the partial-to-complete spontaneous regression of EHE seen in some patients up to 15 years from initial detection makes it difficult to decide on the most appropriate treatment. This report may contribute to the data on clinical findings and natural history of this rare tumor.

[The role of surgical resection in treating small cell lung cancer].

Compares with non-small cell lung cancer, small cell lung cancer (SCLC) generally has a more rapid doubling time, a higher growth fraction, and earlier development of widespread metastases. Surgical operation has little impact on long-term survival of SCLC patients. Chemotherapy with combined radiotherapy has been recommended as the main treatment of SCLC. Patients with SCLC in excess of stage T2N0 do not benefit from surgical operation. But some data suggest the potential benefit of surgcial resection in the few patients with very limited disease, especially peripheral T1-2N0 lesions. Surgical resection can also prevent the recurrence of local disease. The role of surgical resection in the management of SCLC remains to be defined.