Reciprocal expression of TFF-1 (trefoil factor-1) and TTF-1 (thyroid transcription factor-1) in lung adenocarcinomas.
肺腺癌中 TFF-1 (三叶因子-1) 和 TTF-1 (甲状腺转录因子-1) 的相互表达。
- 作者列表："Matsubara D","Yoshimoto T","Soda M","Amano Y","Kihara A","Funaki T","Ito T","Sakuma Y","Shibano T","Endo S","Hagiwara K","Ishikawa S","Fukayama M","Murakami Y","Mano H","Niki T
:Molecular targeted therapies against EGFR and ALK have improved the quality of life of lung adenocarcinoma patients. However, targetable driver mutations are mainly found in TTF-1/NKX2-1-positive terminal respiratory unit (TRU) types and rarely in non-TRU types. To elucidate the molecular characteristics of the major subtypes of non-TRU-type adenocarcinomas, we analyzed 19 lung adenocarcinoma cell lines (11 TRU types and 8 non-TRU types). A characteristic of non-TRU-type cell lines was the strong expression of TFF-1 (trefoil factor-1), a gastric mucosal protective factor. An immunohistochemical analysis of 238 primary lung adenocarcinomas resected at Jichi Medical University Hospital revealed that TFF-1 was positive in 31 cases (13%). TFF-1 expression was frequently detected in invasive mucinous(14/15,93%), enteric(2/2,100%), and colloid(1/1,100%) adenocarcinomas, less frequent in acinar(5/24,21%), papillary(7/120,6%), and solid(2/43,5%) adenocarcinomas, and negative in micropapillary(0/1,0%), lepidic(0/23,0%), and microinvasive adenocarcinomas or adenocarcinoma in situ(0/9,0%). TFF-1 expression correlated with the expression of HNF4alpha and MUC5AC (p<0.0001, p<0.0001, respectively) and inversely correlated with that of TTF-1/NKX2-1 (p<0.0001). These results indicate that TFF-1 is characteristically expressed in non-TRU-type adenocarcinomas with gastrointestinal features. TFF-1-positive cases harbored KRAS mutations at a high frequency, but no EGFR or ALK mutations. TFF-1 expression correlated with tumor spread through air space (STAS), and a poor prognosis in advanced stages. Moreover, the knockdown of TFF-1 inhibited cell proliferation and soft-agar colony formation and induced apoptosis in a TFF-1-high and KRAS-mutated lung adenocarcinoma cell line. These results indicate that TFF-1 is not only a biomarker, but also a potential molecular target for non-TRU-type lung adenocarcinomas.
: 针对 EGFR 和 ALK 的分子靶向治疗改善了肺腺癌患者的生活质量。然而，可靶向驱动突变主要见于 TTF-1/NKX2-1-positive 末端呼吸单位 (TRU) 类型，而非 TRU 类型很少。为了阐明非 TRU 型腺癌主要亚型的分子特征，我们分析了 19 个肺腺癌细胞系 (11 个 TRU 型和 8 个非 TRU 型)。非 TRU 型细胞系的一个特点是强表达胃粘膜保护因子 TFF-1 (三叶因子-1)。对吉奇医科大学医院切除的 238 例原发性肺腺癌进行免疫组织化学分析，发现 31 例 (13%) TFF-1 阳性。TFF-1 在浸润性粘液性腺癌 (14/15，93%) 、肠道腺癌 (2/2，100%) 和胶质腺癌 (1/1，100%) 中频繁检测到，在腺泡状腺癌 (5/24，21%) 中较少见。乳头状 (7/120，6% ), 和实性 (2/43，5%) 腺癌，微乳头状 (0/1，0% ), lepidic(0/23，0% ), 和微浸润腺癌或原位腺癌 (0/9,0%)。TFF-1 与 hnf4 α 和 MUC5AC 的表达呈正相关 (p<0.0001，p<0.0001)，与 TTF-1/NKX2-1 的表达呈负相关 (p<0.0001)。这些结果表明，TFF-1 在具有胃肠道特征的非 TRU 型腺癌中特征性表达。TFF-1-positive 病例存在高频率的 KRAS 突变，但无 EGFR 或 ALK 突变。TFF-1 表达与肿瘤通过空气间隙扩散 (STAS) 相关，晚期预后较差。此外，在 TFF-1 和 KRAS 突变的肺腺癌细胞系中，TFF-1-high 的敲除抑制细胞增殖和软琼脂集落形成并诱导细胞凋亡。这些结果表明，TFF-1 不仅是生物标志物，而且是非 TRU 型肺腺癌的潜在分子靶点。
METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.
METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.
METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.