RESUMO
Accumulating evidence suggests an association between iron metabolism and lung cancer progression. In biological systems, iron is present in either reduced (Fe2+ ; ferrous) or oxidized (Fe3+ ; ferric) states. However, ferrous and ferric iron exhibit distinct chemical and biological properties, the role of ferrous and ferric iron in lung cancer cell growth has not been clearly distinguished. In this study, we manipulated the balance between cellular ferrous and ferric iron status by inducing gene mutations involving the FBXL5-IRP2 axis, a ubiquitin-dependent regulatory system for cellular iron homeostasis, and determined its effects on lung cancer cell growth. FBXL5 depletion (ferrous iron accumulation) was found to suppress lung cancer cell growth, whereas IRP2 depletion (ferric iron accumulation) did not suppress such growth, suggesting that ferrous iron but not ferric iron plays a suppressive role in cell growth. Mechanistically, the depletion of FBXL5 impaired the degradation of the cyclin-dependent kinase inhibitor, p27, resulting in a delay in the cell cycle at the G1/S phase. FBXL5 depletion in lung cancer cells also improved the survival of tumor-bearing mice. Overall, this study highlights the important function of ferrous iron in cell cycle progression and lung cancer cell growth.
Assuntos
Proteínas F-Box , Neoplasias Pulmonares , Animais , Camundongos , Complexos Ubiquitina-Proteína Ligase/química , Complexos Ubiquitina-Proteína Ligase/genética , Complexos Ubiquitina-Proteína Ligase/metabolismo , Neoplasias Pulmonares/genética , Ferro/metabolismo , Ubiquitina/metabolismo , Compostos Férricos , Proteínas F-Box/genética , Proteínas F-Box/metabolismoRESUMO
A 36-year-old man, who had never been detected abnormalities on an annual chest X-ray check up, presented with a sudden onset of right-sided chest pain and fever. Contrast-enhanced computed tomography showed an anterior mediastinal mass with necrosis or hemorrhage and right pleural effusion. Neither computed tomography-guided biopsy nor video-assisted thoracic surgery (VATS) yielded definitive histological diagnosis due to insufficiency of the sample. For diagnosis and treatment, we performed thymectomy. Histopathologically, the tumor was almost entirely necrotic with few viable tumor cells on periphery. A diagnosis of B2 thymoma was rendered.
Assuntos
Timoma , Neoplasias do Timo , Adulto , Humanos , Masculino , Necrose , Cirurgia Torácica Vídeoassistida , Timectomia , Timoma/cirurgia , Neoplasias do Timo/cirurgiaRESUMO
In non-small cell lung cancer (NSCLC) cases, detecting potential lymph node metastases is essential to determine the indications for sublobar resection or adjuvant therapy. NUF2 is a tumor-specific antigen that is highly expressed in lung cancer tissues. However, the significance of analyzing NUF2 expression in dissected lymph nodes has not yet been studied. Thus, we investigated the association between NUF2 expression in lung cancer tissues and dissected lymph nodes and early recurrence of NSCLC to determine its usefulness as a marker of lymph node micrometastasis. This retrospective study quantified NUF2 expression in the cancer tissues of 88 patients with NSCLC who underwent complete resection using real-time polymerase chain reaction and investigated its relationship with clinicopathological features and prognosis. We also quantified NUF2 RNA expression in mediastinal lymph nodes from 255 patients with pN0 NSCLC who underwent complete resection with lymph node dissection and analyzed its association with prognosis. NUF2 expression in primary tumors was correlated with lymph node metastasis and unfavorable outcomes in terms of poor recurrence-free and cancer-specific survival. In N0 NSCLC cases, high NUF2 expression in mediastinal lymph nodes indicated poor prognosis, especially in lymph node recurrence. NUF2 emerges as a promising marker for predicting lymph node metastatic recurrence, offering potential utility in guiding post-surgical adjuvant therapy for lung cancer or assisting in intraoperative decisions for sublobar resection.
RESUMO
Accumulating evidence suggests that high levels of Fusobacterium nucleatum in colorectal tumor tissues can be associated with poor prognosis in patients with colorectal cancer (CRC); however, data regarding distinct prognostic subgroups in F. nucleatum-positive CRC remain limited. Herein, we demonstrate that high-iron status was associated with a worse prognosis in patients with CRC with F. nucleatum. Patients with CRC presenting elevated serum transferrin saturation exhibited preferential iron deposition in macrophages in the tumor microenvironment. In addition, F. nucleatum induced CCL8 expression in macrophages via the TLR4/NF-κB signaling pathway, which was inhibited by iron deficiency. Mechanistically, iron attenuated the inhibitory phosphorylation of NF-κB p65 by activating serine/threonine phosphatases, augmenting tumor-promoting chemokine production in macrophages. Our observations indicate a key role for iron in modulating the NF-κB signaling pathway and suggest its prognostic potential as a determining factor for interpatient heterogeneity in F. nucleatum-positive CRC.
Assuntos
Neoplasias Colorretais , Infecções por Fusobacterium , Humanos , Fusobacterium nucleatum/metabolismo , Infecções por Fusobacterium/complicações , Infecções por Fusobacterium/microbiologia , NF-kappa B/metabolismo , Ferro , Neoplasias Colorretais/patologia , Macrófagos/metabolismo , Microambiente Tumoral , Quimiocina CCL8RESUMO
Ciliated muconodular papillary tumor (CMPT) is an extremely rare pulmonary tumor and the clinical characteristics are still unknown. We report the preoperative long-term clinical course and changes in computed tomography (CT) findings of CMPT. A 60-year-old man underwent lower bilobectomy for squamous cell carcinoma in the right lower lobe 18 years before the surgery for CMPT. Twelve years before the surgery for CMPT, a 4-mm small ground glass nodule arose in the left lower lobe. The nodule gradually grew and became dense over time. Because it became mostly solid with central cavities, the patient underwent wedge resection and the tumor was diagnosed as CMPT. There were no recurrences 20 months after surgery. The preoperative CT findings of CMPT were similar to progressive preinvasive lesion, whereas it followed the benign clinical course. To the best of our knowledge, this is the first report on long-term preoperative follow-up of CMPT.