bims-meluca 2020-11-01 papers

Cell Oncol (Dordr). 2020 Oct 30.

Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer.

Ali Fatehi Hassanabad, Kelsey T MacQueen.

BACKGROUND: Metformin, a first-line therapeutic for type 2 diabetes, has been studied for its potential use in cancer treatment following a number of epidemiological studies that have demonstrated reduced cancer incidence and mortality rates among patients treated with the drug. As yet, however, there remains significant uncertainty about the molecular mechanisms by which metformin exerts its anti-cancer effects. Herein, we summarize the evidence surrounding the anti-lung cancer effects of metformin.
CONCLUSIONS: Specifically, we explore protein targets of metformin, including AMPK, PP2A, IRF-1/YAP and HGF and we outline the proposed mechanisms of action for metformin in lung cancer, with particular attention given to apoptosis and autophagy. We also closely examine the synergistic activity of metformin with existing cancer treatment regimens, such as TKI's, platinum-based agents and immune therapeutics. In addition to considering preclinical and clinical studies, we also dissect and contextualize the limitations and inconsistencies of the current literature, especially those of epidemiological studies. Finally, we offer a potential trajectory for future research in this rapidly evolving area of basic and clinical oncology.

Keywords: Clinical outcomes; Lung cancer therapy; Metformin; Molecular targets; Precision medicine; Translational lung cancer research

DOI: https://doi.org/10.1007/s13402-020-00570-0

Diagn Pathol. 2020 Oct 28. 15(1): 133

Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3.

Koudong Zhang, Hang Hu, Juan Xu, Limin Qiu, Haitao Chen, Xingzhi Jiang, Yongqian Jiang.

BACKGROUND: Lung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear.
METHODS: The expression levels of circ_0001421, microRNA-4677-3p (miR-4677-3p) and cell division cycle associated 3 (CDCA3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), Transwell and Tumor formation assays were performed to explore the role of circ_0001421 in LC. Glucose consumption and lactate production were examined by a Glucose assay kit and a Lactic Acid assay kit. Western blot was utilized to examine the protein levels of Hexokinase 2 (HK2) and CDCA3. The interaction between miR-4677-3p and circ_0001421 or CDCA3 was confirmed by dual-luciferase reporter assay.
RESULTS: Circ_0001421 was increased in LC tissues and cells, and knockdown of circ_0001421 repressed cell proliferation, migration, invasion and glycolysis in vitro. Meanwhile, circ_0001421 knockdown inhibited LC tumor growth in vivo. Mechanistically, circ_0001421 could bind to miR-4677-3p, and CDCA3 was a target of miR-4677-3p. Rescue assays manifested that silencing miR-4677-3p or CDCA3 overexpression reversed circ_0001421 knockdown-mediated suppression on cell proliferation, migration, invasion and glycolysis in LC cells.
CONCLUSION: Circ_0001421 promoted cell proliferation, migration, invasion and glycolysis in LC by regulating the miR-4677-3p/CDCA3 axis, which providing a new mechanism for LC tumor progression.

Keywords: CDCA3; Lung cancer; circ_0001421; miR-4677-3p

DOI: https://doi.org/10.1186/s13000-020-01048-1

Support Care Cancer. 2020 Oct 30.

The relationship between nutritional status and prognosis in patients with locally advanced and advanced stage lung cancer.

Busra Gul, Selma Metintas, Guntulu Ak, Senay Yilmaz, Muzaffer Metintas.

PURPOSE: The study aimed to determine the poor nutritional status, related factors, and its effect on the prognosis of patients with locally advanced and advanced stage lung cancer.
METHODS: The study consisted of 539 patients, 412 (76.4%) of whom were non-small cell lung cancer (NSCLC), and 127 (23.6%) were small cell lung cancer (SCLC). The nutritional status of the patients was evaluated by the Controlling Nutritional Status (CONUT) and Prognostic Nutritional Index (PNI). Poor nutritional status was diagnosed with the CONUT score of ≥ 2 and PNI of ≥the median value. The factors related to nutritional status were determined using a multivariate logistic regression model. The effect of poor nutritional status on survival was calculated by Cox regression analysis.
RESULTS: The median age was 64 years (29-87). Poor nutritional status was found in 56.4% (57.8% for NSCLC and 52.0% for SCLC) and 49.2% (51.5% for NSCLC and 41.7% for SCLC) of patients according to CONUT and PNI, respectively. The factors associated with poor nutritional status according to CONUT were age, gender, KPS < 80, and BMI < 18.5 for NSCLC and KPS for SCLC. According to PNI, only KPS < 80 was associated with poor nutritional status by the multivariate logistic regression model. The median overall survival significantly decreased with poor nutritional status according to CONUT and PNI in NSCLC (p < 0.001 and p < 0.001, respectively) and in SCLC (p = 0.05 and p = 0.007, respectively).
CONCLUSION: Poor nutritional status is a common factor associated with poor prognosis in patients with locally advanced and advanced stage lung cancer. Patients should be screened for nutritional status and supported.

Keywords: Advanced staged lung cancer; CONUT; NSCLC; Nutritional status; PNI; SCLC

DOI: https://doi.org/10.1007/s00520-020-05856-5