bims-netuvo 2022-01-30 papers

Issue of 2022‒01‒30
four papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

Oncol Rep. 2022 Apr;pii: 64. [Epub ahead of print]47(4):

High‑glucose microenvironment promotes perineural invasion of pancreatic cancer via activation of hypoxia inducible factor 1α.

Lun Zhang, Wunai Zhang, Xin Zhang, Yihe Min, Yang Zhao, Baofeng Wang, Wei Li, Shuai Mao, Weili Min.

Pancreatic cancer (PC) is one of the most lethal diseases, with a 5‑year survival rate of <9%. Perineural invasion (PNI) is a common pathological hallmark of PC and is correlated with a poor prognosis in this disease. Hyperglycemia has been shown to promote the invasion and migration of PC cells; however, the effect of hyperglycemia on the PNI of PC and its underlying mechanism remains unclear. In the present study, Western blotting was utilized to detect the expression of hypoxia inducible factor 1α (HIF1α) and nerve growth factor (NGF). Transwell and wound‑healing assays were performed to detect the influence of hyperglycemia on the invasion and migration ability of PC cells. An in vitro PC‑dorsal root ganglion (DRG) co‑culture system and an in vivo PNI sciatic nerve‑infiltrating tumor model were used to evaluate the severity of PNI in hyperglycemic conditions. In the results, hyperglycemia promoted the invasion/migration ability and elevated the expression of NGF in PC by upregulating HIF1α. Moreover, in vitro short‑term hyperglycemia caused little damage on the DRG axons and accelerated both the PNI of the PC and the outgrowth of the DRGs by increasing the expression of NGF via activation of HIF1α. Indeed, in vivo long‑term hyperglycemia promoted the infiltration and growth of PC, and then disrupted the function of the sciatic nerve in a HIF1α‑dependent manner. In conclusion, a high‑glucose microenvironment promotes PNI of PC via activation of HIF1α.

Keywords: HIF1α; PC; PNI; hyperglycemia

DOI: https://doi.org/10.3892/or.2022.8275

Radiother Oncol. 2022 Jan 20. pii: S0167-8140(22)00019-6. [Epub ahead of print]

Benefit from adjuvant radiotherapy according to the number of risk factors in cutaneous squamous cell carcinoma.

Adeline Pêtre, Pascal Pommier, Tristan Brahmi, Sylvie Chabaud, Sophie King, Jérôme Fayette, Eve-Marie Neidhart, Mona Amini-Adle.

INTRODUCTION: Indications of adjuvant radiotherapy (RT) for high-risk cutaneous squamous cell carcinoma (cSCC) are not clearly defined. We aimed to identify factors predicting relapse in cSCC patients treated with surgery or RT alone and to assess in which clinical setting adjuvant RT was beneficial in term of progression free survival (PFS).METHODS: This retrospective analysis included patients with resectable primary cSCC treated with surgery and/or RT in curative intent, managed at Centre Léon Bérard (Lyon, France) from April 2010 to September 2020.
RESULTS: A total of 303 patients with 529 cSCC were included. 31 (5.9%) cSCC were treated with surgery and adjuvant RT. With a median follow-up of 54 (0.2-126) months, 103 (19.5%) cSCC relapsed. In multivariate analysis, the highest predictive factor of relapse in cSCC was the number of risk factors (HR=15.110 [95% CI: 3.91-58.40] for ≥3 risk factors p<0.001), followed by poor differentiation (HR=4.930 [95% CI: 2.47-9.86], p<0.001) and perineural invasion (HR=2.442 [95% CI: 1.11-5.38], p=0.027). For cSCC with ≥3 risk factors, PFS was significantly higher in cSCC treated with surgery and adjuvant RT compared to those treated with surgery or RT alone (the 36-month PFS was 74% [95% CI: 43-90%] and 31% [95% CI: 10-54%] respectively, p=0.008).
CONCLUSION: An increased number of risk factors was identified as being the highest predictive factor of relapse in cSCC. Adjuvant RT improved PFS for high-risk cSCC with ≥3 risk factors.

Keywords: Adjuvant; Carcinoma; Progression-free survival; Radiotherapy; Risk factors; Skin neoplasms; Squamous cell

DOI: https://doi.org/10.1016/j.radonc.2022.01.015

J Cancer. 2022 ;13(2): 401-412

Chronic stress model simulated by salbutamol promotes tumorigenesis of gastric cancer cells through β2-AR/ERK/EMT pathway.

YanJie Lu, Ying Zhang, HanZheng Zhao, Qingshan Li, Ying Liu, YanZhen Zuo, Qian Xu, Hongyan Zuo, Yang Li, YuHong Li.

Chronic stress induced by long-term anxiety and depression can promote the malignant progression of gastric cancer. β2-adrenergic receptor (β2-AR) is a critical mediator for chronic stress-induced multiple processes of tumor cells. However, the function of chronic stress in gastric cancer and its potential mechanisms in vivo and in vitro, especially at the cellular level, remain unknown. Here, we provide further evidence that chronic stress affected behavior and hypothalamus pituitary adrenal axis related hormone levels in mice. Furthermore, immunofluorescence showed that emotion affected the expression of epithelial-mesenchymal transition (EMT) markers in patients' tissues. To address this, salbutamol, a specific agonist of β2-AR, was utilized for simulating chronic stress and demonstrating the mechanism of stress in tumor progression at the molecular level both in vivo and in vitro. Salbutamol significantly induced EMT, migration and invasion via ERK (Extracellular-signal-regulated kinase) phosphorylation, and the effects were reversed by the β2-AR antagonist ICI-118,551. The promoting effects of salbutamol on EMT, migration and invasion were inhibited by phosphorylation inhibitor of ERK PD98059 in vitro. Analysis of xenograft models revealed that salbutamol significantly promoted tumor growth and adrenal volume, while ICI-118,551 inhibited these effects. In addition, salbutamol increased the expression of mesenchymal marker N-cadherin and decreased epithelial marker E-cadherin in transplanted tumor tissue. In conclusion, salbutamol simulates a chronic stress model, which promotes tumorigenesis of gastric cancer cells through β2-AR/ERK/EMT pathway.

Keywords: ERK; chronic stress; epithelial-mesenchymal transition; gastric cancer; salbutamol; β2-AR

DOI: https://doi.org/10.7150/jca.65403

Biomed J Sci Tech Res. 2021 Jul;37(1): 29134-29138

Stress and Molecular Drivers for Cancer Progression: A Longstanding Hypothesis.

J Wendel, A Verma, V Dhevan, S C Chauhan, M K Tripathi.

Stress management is becoming very important part of cancer patient care. Chronic stressors lead to boost tumorigenesis and promote cancer development, recurrence, and drug resistant leading to poor health outcomes. The Hypothalamic-Pituitary-Adrenal (HPA) axis, which is activated by stress, also regulates Hypothalamic-Pituitary-Thyroid (HPT) axis. Stress related changes in immune function and inflammatory response also leads to reduced immune surveillance resulting in tumorigenesis. This article explores the hormonal axis impacted by stress and how chronic stress can lead to poor outcome of a cancer patient.

Keywords: Cancer Progression; Cancer Recurrence; Drug Resistance; HPA Axis; HPT Axis; Stress

DOI: https://doi.org/10.26717/bjstr.2021.37.005953