bims-netuvo 2022-06-05 papers

Adv Biol (Weinh). 2022 Jun 03. e2200033

Schwann Cells in Peripheral Cancers: Bystanders or Promoters?

Ümmügülsüm Yurteri, Kaan Çifcibaşı, Helmut Friess, Güralp O Ceyhan, Rouzanna Istvanffy, Ihsan Ekin Demir.

The tumor microenvironment is subject to intense investigation in terms of its influence on tumorigenesis. Despite the fact that Schwann cells are cancer cells' early interaction partners, investigations on tumor progression and the molecular drivers of carcinogenesis do not place enough emphasis on them. Recent studies have shown that malignant cells and nerves interact on several levels during early carcinogenesis. For instance, the emergence of nerves in cancer, known as cancer neo-neurogenesis, is one important mechanism that contributes to cancer progression. Recent studies on Schwann cells brought the investigation of tumor-nerve interactions to a whole new level. Schwann cells make up the majority of glial cells in the peripheral nervous system, are outstandingly plastic cells, and serve a variety of roles in most organs. All these properties make Schwann cells excellent potential targets for tumor cells to exploit and turn them into promoters of carcinogenesis. In the present review, the distinctive features of Schwann cell-tumor cell interactions and the implications of this interaction on the tumor microenvironment are outlined. Further, this study points out the neglected aspects of Schwann cells in the tumor microenvironment and provides a potential new avenue for future research.

Keywords: Schwann cells; cancer; immune cells pancreatic cancer; tissue repair

DOI: https://doi.org/10.1002/adbi.202200033

J Gastrointest Cancer. 2022 Jun 02.

Prognostic Factors in Resected Pancreatic Ductal Adenocarcinoma: Is Neutrophil-Lymphocyte Ratio a Useful Marker?

Ignacio Merlo, Victoria Ardiles, Rodrigo Sanchez-Clariá, Eugenia Fratantoni, Eduardo de Santibañes, Juan Pekolj, Oscar Mazza, Martín de Santibañes.

BACKGROUND: The aim of this study is to analyze the role of neutrophil-lymphocyte ratio (NLR) and its variation pre- and postoperatively (delta NLR) in the overall survival after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) at a single center and to identify factors associated with overall survival.
METHODS: A retrospective study of consecutive patients undergoing pancreatectomy due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between the evaluated factors and overall survival was analyzed using a log-rank test and Cox proportional hazard regression model.
RESULTS: Overall, 242 patients underwent pancreatectomy for PDAC or undifferentiated carcinoma. OS was 22.8 months (95% confidence interval (CI): 19.5-29), and survival rates at 1, 3, and 5 years were 72%, 32.5%, and 20.8%, respectively. NLR and delta NLR were not significantly associated with survival (hazard ratio (HR) = 1.14, 95%CI: 0.77-1.68, p = 0.5). Lymph node ratio was significantly associated (HR = 1.66, 95%CI: 1.21-2.26, p = 0.001) in the bivariate analysis. In multivariable analysis, the only factors that were significantly associated with survival were perineural invasion (HR = 1.94, 95%CI: 1.21-3.14, p = 0.006), surgical margin (HR = 1.83, 95%CI: 1.10-3.02, p = 0.019), tumor size (HR = 1.01, 95%CI: 1.003-1.027, p = 0.16), postoperative CA 19-9 level (HR = 1.001, p < 0.001), and completion of adjuvant treatment (HR = 0.53, 95%CI: 0.35-0.8, p = 0.002).
CONCLUSION: Neutrophil-lymphocyte ratio and delta NLR were not associated with the overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level, and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor.

Keywords: Neutrophil-to-lymphocyte ratio; Pancreatic cancer; Perineural invasion; Survival analysis

DOI: https://doi.org/10.1007/s12029-022-00839-7

World J Surg Oncol. 2022 May 28. 20(1): 170

Minimal extrathyroidal extension is associated with lymph node metastasis in single papillary thyroid microcarcinoma: a retrospective analysis of 814 patients.

Ra-Yeong Song, Hee Sung Kim, Kyung Ho Kang.

BACKGROUND: Extrathyroidal extension (ETE) is considered a major prognostic factor in papillary thyroid carcinoma (PTC). Patients with gross ETE are at increased risk of recurrence and mortality. The importance of minimal ETE still remains controversial, especially in patients with papillary thyroid microcarcinoma (PTMC). The purpose of this study was to evaluate the association between ETE and lymph node (LN) metastasis in single PTMC.
METHODS: A retrospective analysis was performed of 1994 patients underwent thyroidectomy for PTC between 2012 and 2016 in a single institution. Patients with combined thyroid carcinoma of other types and those who underwent completion thyroidectomy were excluded. After further exclusion of PTC larger than 1 cm and multifocal tumors, 814 patients with single PTMC were included in the study.
RESULTS: 72.9% patients had no ETE, 25.1% minimal ETE, and 2.1% gross ETE. ETE was associated with lymphatic invasion, perineural invasion, and vascular invasion. Patients with minimal and gross ETE were also more likely to have LN metastasis, including lateral neck metastasis, compared to those without ETE. In univariate analysis, LN metastasis was associated with male gender, conventional PTC, lymphatic invasion, perineural invasion, and ETE. In multivariate analysis, male gender (OR = 1.987; 95% CI 1.369-2.884), lymphatic invasion (OR = 4.389; 95% CI 1.522-12.658), perineural invasion (OR = 6.545; 95% CI 1.262-33.948), and minimal ETE (OR = 1.852; 95% CI 1.298-2.643) were found to be independent risk factors of LN metastasis.
CONCLUSIONS: Minimal ETE is associated with LN metastasis in single PTMC, compared to no ETE. Minimal ETE should be considered in the management of patients with single PTMC, whether surgical or during active surveillance.

Keywords: Extrathyroidal extension; LN metastasis; Papillary thyroid Microcarcinoma

DOI: https://doi.org/10.1186/s12957-022-02629-8

Adv Biol (Weinh). 2022 Jun 02. e2200031

Circadian Rhythm Disruption Increases Tumor Growth Rate and Accumulation of Myeloid-Derived Suppressor Cells.

Nathan T Roberts, Cameron R MacDonald, Hemn Mohammadpour, Marina P Antoch, Elizabeth A Repasky.

Circadian rhythm disruption is implicated in the initiation and progression of many diseases, including cancer. External stimuli, such as sunlight, serve to synchronize physiological processes and cellular functions to a 24-h cycle. The immune system is controlled by circadian rhythms, and perturbation of these rhythms can potentially alter the immune response to infections and tumors. The effect of circadian rhythm disruption on the immune response to tumors remains unclear. Specifically, the effects of circadian disruption (CD) on immunosuppressive cell types within the tumor, such as myeloid-derived suppressor cells (MDSCs), are unknown. In this study, a shifting lighting schedule is used to disrupt the circadian rhythm of mice. After acclimation to lighting schedules, mice are inoculated with 4T1 or B16-F10 tumors. Tumor growth is increased in mice housed under circadian disrupting lighting conditions compared to standard lighting conditions. Analysis of immune populations within the spleen and tumor shows an increased accumulation of MDSCs within these tissues, suggesting that MDSC mediated immunosuppression plays a role in the enhanced tumor growth caused by circadian disruption. This paves the way for future studies of the effects of CD on immunosuppression in cancer.

Keywords: cancer; circadian rhythm; immunology; immunosuppression; myeloid-derived suppressor cells; tumor immunology

DOI: https://doi.org/10.1002/adbi.202200031

Curr Oncol Rep. 2022 Jun 01.

Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

Amparo Belltall, Guido Mazzinari, Oscar Diaz-Cambronero, Pilar Eroles, María Pilar Argente Navarro.

PURPOSE OF REVIEW: Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action.
RECENT FINDINGS: We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects.

Keywords: Cancer; Cancer growth; Low-dose naltrexone; Methylnaltrexone; Mu-opioid receptor (MOR); Naltrexone; Opioid growth factor (OGF); Opioid growth factor receptor (OGFr); PAMORAs; Peripheral antagonists of mu-opioid receptor; Tumor progression

DOI: https://doi.org/10.1007/s11912-022-01295-z