bims-netuvo 2023-04-02 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–04–02
fourteen papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

The tumor-nerve circuit in breast cancer.
Genomic Interplay between Neoneurogenesis and Neoangiogenesis in Carcinogenesis: Therapeutic Interventions.
Vagus innervation in the gastrointestinal tumor: Current understanding and challenges.
Melanoma-associated repair-like Schwann cells suppress anti-tumor T-cells via 12/15-LOX/COX2-associated eicosanoid production.
Prognostic Factors and the Role of Adjuvant Chemotherapy in Pathological Node-Negative T3 Gastric Cancer.
Incidence and Predicting Factors of Histopathological Features at Robot-Assisted Radical Prostatectomy in the mpMRI Era: Results of a Single Tertiary Referral Center.
In Vitro Effects of Photon Beam and Carbon Ion Radiotherapy on the Perineural Invasion of Two Cell Lines of Neurotropic Tumours.
Predictive Factors for Gleason Score Upgrading in Patients with Prostate Cancer after Radical Prostatectomy: A Systematic Review and Meta-Analysis.
[Concordance between three integrated scores based on prostate biopsy and grade-grouping of radical prostatectomy specimen].
Generation of human iPSC-derived neurofibromaspheres for in vitro and in vivo uses.
Development and validation of prognostic model based on extra-gastric lymph nodes metastasis and lymph node ratio in node-positive gastric cancer: a retrospective cohort study based on a multicenter database.
Sympathetic β2-adrenergic receptor blockade overcomes docetaxel resistance in prostate cancer.
Anaesthesia and cancer recurrence: the influence of perioperative anaesthetic technique on cancer recurrence after surgery.
Anesthesia and Cancer: Something More than Avoid Stress Response.

Cancer Metastasis Rev. 2023 Mar 31.

The tumor-nerve circuit in breast cancer.

Qiuxia Cui, Dewei Jiang, Yuanqi Zhang, Ceshi Chen.

  It is well established that innervation is one of the updated hallmarks of cancer and that psychological stress promotes the initiation and progression of cancer. The breast tumor environment includes not only fibroblasts, adipocytes, endothelial cells, and lymphocytes but also neurons, which is increasingly discovered important in breast cancer progression. Peripheral nerves, especially sympathetic, parasympathetic, and sensory nerves, have been reported to play important but different roles in breast cancer. However, their roles in the breast cancer progression and treatment are still controversial. In addition, the brain is one of the favorite sites of breast cancer metastasis. In this review, we first summarize the innervation of breast cancer and its mechanism in regulating cancer growth and metastasis. Next, we summarize the neural-related molecular markers in breast cancer diagnosis and treatment. In addition, we review drugs and emerging technologies used to block the interactions between nerves and breast cancer. Finally, we discuss future research directions in this field. In conclusion, the further research in breast cancer and its interactions with innervated neurons or neurotransmitters is promising in the clinical management of breast cancer.

Keywords:  Breast cancer; Innervation; Neurotransmitter; Psychological stress; β-blockers

DOI:  https://doi.org/10.1007/s10555-023-10095-1
Cancers (Basel). 2023 Mar 16. pii: 1805. [Epub ahead of print]15(6):

Genomic Interplay between Neoneurogenesis and Neoangiogenesis in Carcinogenesis: Therapeutic Interventions.

Zodwa Dlamini, Richard Khanyile, Thulo Molefi, Botle Precious Damane, David Owen Bates, Rodney Hull.

  Angiogenesis, the generation of new blood vessels, is one of the hallmarks of cancer. The growing tumor requires nutrients and oxygen. Recent evidence has shown that tumors release signals to attract new nerve fibers and stimulate the growth of new nerve fibers. Neurogenesis, neural extension, and axonogenesis assist in the migration of cancer cells. Cancer cells can use both blood vessels and nerve fibers as routes for cells to move along. In this way, neurogenesis and angiogenesis both contribute to cancer metastasis. As a result, tumor-induced neurogenesis joins angiogenesis and immunosuppression as aberrant processes that are exacerbated within the tumor microenvironment. The relationship between these processes contributes to cancer development and progression. The interplay between these systems is brought about by cytokines, neurotransmitters, and neuromodulators, which activate signaling pathways that are common to angiogenesis and the nervous tissue. These include the AKT signaling pathways, the MAPK pathway, and the Ras signaling pathway. These processes also both require the remodeling of tissues. The interplay of these processes in cancer provides the opportunity to develop novel therapies that can be used to target these processes.

Keywords:  angiogenesis; axonogenesis; growth factor; metastasis; neural stem cells; neurogenesis; neurotransmitter; neurotrophin; reactive oxygen species; tissue remodeling

DOI:  https://doi.org/10.3390/cancers15061805
Biochim Biophys Acta Rev Cancer. 2023 Mar 27. pii: S0304-419X(23)00033-1. [Epub ahead of print] 188884

Vagus innervation in the gastrointestinal tumor: Current understanding and challenges.

Yan-Ting Li, Wen-Zhen Yuan, Wei-Lin Jin.

  The vagus nerve (VN) is the main parasympathetic nerve of the autonomic nervous system. It is widely distributed in the gastrointestinal tract and maintains gastrointestinal homeostasis with the sympathetic nerve under physiological conditions. The VN communicates with various components of the tumor microenvironment to positively and dynamically affect the progression of gastrointestinal tumors (GITs). The intervention in vagus innervation delays GIT progression. Developments in adeno-associated virus vectors, nanotechnology, and in vivo neurobiological techniques have enabled the creation of precisely regulated "tumor neurotherapies". Furthermore, the combination of neurobiological techniques and single cell sequencing may reveal more insights into VN and GIT. The present review aimed to summarize the mechanisms of communication between the VN and the gastrointestinal TME and to explore the potential and challenges of VN-based tumor neurotherapy in GITs.

Keywords:  Gastrointestinal tumor; Innervation; Neurotherapy; Vagotomy; Vagus nerve stimulation

DOI:  https://doi.org/10.1016/j.bbcan.2023.188884
Oncoimmunology. 2023 ;12(1): 2192098

Melanoma-associated repair-like Schwann cells suppress anti-tumor T-cells via 12/15-LOX/COX2-associated eicosanoid production.

Oleg Kruglov, Kavita Vats, Vishal Soman, Vladimir A Tyurin, Yulia Y Tyurina, Jiefei Wang, Li'an Williams, Jiying Zhang, Cara Donahue Carey, Erik Jaklitsch, Uma R Chandran, Hülya Bayir, Valerian E Kagan, Yuri L Bunimovich.

  Peripheral glia, specifically the Schwann cells (SCs), have been implicated in the formation of the tumor microenvironment (TME) and in cancer progression. However, in vivo and ex vivo analyses of how cancers reprogram SC functions in different organs of tumor-bearing mice are lacking. We generated Plp1-CreERT/tdTomato mice which harbor fluorescently labeled myelinated and non-myelin forming SCs. We show that this model enables the isolation of the SCs with high purity from the skin and multiple other organs. We used this model to study phenotypic and functional reprogramming of the SCs in the skin adjacent to melanoma tumors. Transcriptomic analyses of the peritumoral skin SCs versus skin SCs from tumor-free mice revealed that the former existed in a repair-like state typically activated during nerve and tissue injury. Peritumoral skin SCs also downregulated pro-inflammatory genes and pathways related to protective anti-tumor responses. In vivo and ex vivo functional assays confirmed immunosuppressive activities of the peritumoral skin SCs. Specifically, melanoma-reprogrammed SCs upregulated 12/15-lipoxygenase (12/15-LOX) and cyclooxygenase (COX)-2, and increased production of anti-inflammatory polyunsaturated fatty acid (PUFA) metabolites prostaglandin E2 (PGE2) and lipoxins A4/B4. Inhibition of 12/15-LOX or COX2 in SCs, or EP4 receptor on lymphocytes reversed SC-dependent suppression of anti-tumor T-cell activation. Therefore, SCs within the skin adjacent to melanoma tumors demonstrate functional switching to repair-like immunosuppressive cells with dysregulated lipid oxidation. Our study suggests the involvement of the melanoma-associated repair-like peritumoral SCs in the modulation of locoregional and systemic anti-tumor immune responses.

Keywords:  Cancer; Schwann cell; melanoma; neuroimmunology; tumor microenvironment

DOI:  https://doi.org/10.1080/2162402X.2023.2192098
J Pers Med. 2023 Mar 20. pii: 553. [Epub ahead of print]13(3):

Prognostic Factors and the Role of Adjuvant Chemotherapy in Pathological Node-Negative T3 Gastric Cancer.

Yi-Fu Chen, Ming-Yang Chen, Puo-Hsien Le, Tsung-Hsing Chen, Chia-Jung Kuo, Shang-Yu Wang, Shih-Chiang Huang, Wen-Chi Chou, Ta-Sen Yeh, Jun-Te Hsu.

  The role of adjuvant chemotherapy in pathological T3N0M0 (pT3N0M0) gastric cancer (GC) remains unclear. The aim of this study was to analyze the prognostic factors of patients with pT3N0M0 GC and to clarify which ones could benefit from adjuvant chemotherapy. A total of 137 patients with pT3N0M0 GC were recruited between 1994 and 2020. Clinicopathological factors and adjuvant chemotherapy regimens were retrospectively collected. Prognostic factors of disease-free survival (DFS) and cancer-specific survival (CSS) were determined using univariate and multivariate analyses. The chemotherapy group was younger (p = 0.012), had had more lymph nodes retrieved (p = 0.042) and had higher percentages of vascular invasion (p = 0.021) or perineural invasion (p = 0.030) than the non-chemotherapy group. There were no significant differences in DFS (p = 0.222) and CSS (p = 0.126) between patients treated with or without adjuvant chemotherapy. Stump cancer, tumor size and perineural invasion were associated with higher rates of recurrence. Tumor size was an independent prognostic factor for DFS (hazard ratio, 4.55; confidence interval, 1.59-12.99; p = 0.005) and CSS (hazard ratio, 3.97; confidence interval, 1.38-11.43; p = 0.011). Tumor size independently influenced survival outcomes in pT3N0M0 patients who underwent radical surgery with and without adjuvant chemotherapy.

Keywords:  adjuvant chemotherapy; gastric cancer; node-negative; prognostic factor

DOI:  https://doi.org/10.3390/jpm13030553
Medicina (Kaunas). 2023 Mar 21. pii: 625. [Epub ahead of print]59(3):

Incidence and Predicting Factors of Histopathological Features at Robot-Assisted Radical Prostatectomy in the mpMRI Era: Results of a Single Tertiary Referral Center.

Ernesto Di Mauro, Francesco Di Bello, Gianluigi Califano, Simone Morra, Massimiliano Creta, Giuseppe Celentano, Marco Abate, Agostino Fraia, Gabriele Pezone, Claudio Marino, Simone Cilio, Marco Capece, Roberto La Rocca, Ciro Imbimbo, Nicola Longo, Claudia Colla' Ruvolo.

  Background and Objectives: To describe the predictors of cribriform variant status and perineural invasion (PNI) in robot-assisted radical prostatectomy (RARP) histology. To define the rates of upgrading between biopsy specimens and final histology and their possible predictive factors in prostate cancer (PCa) patients undergoing RARP. Material and Methods: Within our institutional database, 265 PCa patients who underwent prostate biopsies and consecutive RARP at our center were enrolled (2018-2022). In the overall population, two independent multivariable logistic regression models (LRMs) predicting the presence of PNI or cribriform variant status at RARP were performed. In low- and intermediate-risk PCa patients according to D'Amico risk classification, three independent multivariable LRMs were fitted to predict upgrading. Results: Of all, 30.9% were low-risk, 18.9% were intermediate-risk and 50.2% were high-risk PCa patients. In the overall population, the rates of the cribriform variant and PNI at RARP were 55.8% and 71.1%, respectively. After multivariable LRMs predicting PNI, total tumor length in biopsy cores (>24 mm [OR: 2.37, p-value = 0.03], relative to <24 mm) was an independent predictor. After multivariable LRMs predicting cribriform variant status, PIRADS (3 [OR:15.37], 4 [OR: 13.57] or 5 [OR: 16.51] relative to PIRADS 2, all p = 0.01) and total tumor length in biopsy cores (>24 mm [OR: 2.47, p = 0.01], relative to <24 mm) were independent predicting factors. In low- and intermediate-risk PCa patients, the rate of upgrading was 74.4% and 78.0%, respectively. After multivariable LRMs predicting upgrading, PIRADS (PIRADS 3 [OR: 7.01], 4 [OR: 16.98] or 5 [OR: 20.96] relative to PIRADS 2, all p = 0.01) was an independent predicting factor. Conclusions: RARP represents a tailored and risk-adapted treatment strategy for PCa patients. The indication of RP progressively migrates to high-risk PCa after a pre-operative assessment. Specifically, the PIRADS score at mpMRI should guide the decision-making process of urologists for PCa patients.

Keywords:  active surveillance; cribriform variant; perineural invasion; tumor length; upgrading

DOI:  https://doi.org/10.3390/medicina59030625
Life (Basel). 2023 Mar 15. pii: 794. [Epub ahead of print]13(3):

In Vitro Effects of Photon Beam and Carbon Ion Radiotherapy on the Perineural Invasion of Two Cell Lines of Neurotropic Tumours.

Alexandra Charalampopoulou, Amelia Barcellini, Giuseppe Emanuele Frittitta, Giorgia Fulgini, Giovanni Battista Ivaldi, Giuseppe Magro, Marco Liotta, Ester Orlandi, Marco Giuseppe Pullia, Paola Tabarelli de Fatis, Angelica Facoetti.

  Primary mucosal melanoma (PMM) and pancreatic ductal adenocarcinoma (PDAC) are two aggressive malignancies, characterized by intrinsic radio-chemoresistance and neurotropism, a histological feature resulting in frequent perineural invasion (PNI), supported by neurotrophic factors secreted in the tumour microenvironment (TME), such as neurotrophin-3 (NT-3). Carbon-ion radiotherapy (CIRT) could represent an effective option in unresectable PMM and PDAC. Only a few data about the effects of CIRT on PNI in relation to NT-3 are available in the literature, despite the numerous pieces of evidence revealing the peculiar effects of this type of radiation on tumour cell migration. This in vitro study investigated for the first time the response of PMM and PDAC cells to NT-3 and evaluated the effects of conventional photon beam radiotherapy (XRT) and CIRT on cell viability, proliferation, and migration. Our results demonstrated the greater capacity of C-ions to generally decrease cell viability, proliferation, and migration, while the addition of NT-3 after both types of irradiation determined an increase in these features, maintaining a dose-dependent trend and acting more effectively as a chemoattractant than inductor in the case of migration.

Keywords:  NT-3; carbon ions; hadrontherapy; migration; neurotropism; perineural invasion; radiobiology

DOI:  https://doi.org/10.3390/life13030794
Urol Int. 2023 Mar 29. 1-20

Predictive Factors for Gleason Score Upgrading in Patients with Prostate Cancer after Radical Prostatectomy: A Systematic Review and Meta-Analysis.

Yang Wang, Xiaoke Chen, Kun Liu, Ruijuan Liu, Liangliang Li, Chaoshan Yin, Peixing Song.

   INTRODUCTION: Previous studies have revealed that Gleason score upgrading (GSU) was closely related to an increased biochemical recurrence rate and adverse oncologic outcomes in patients with prostate cancer (PC). Therefore, we performed a meta-analysis to determine the predictive factors for GSU following radical prostatectomy (RP).
METHODS: We performed an extensive literature search using PubMed, Embase, and Cochrane in September 2022. In order to calculate the pooled odds ratio (OR), standardized mean difference (SMD), and 95% confidence intervals, a fixed effect or a DerSimonian and Laird random effect was applied.
RESULTS: Twenty-six studies included 18,745 PC patients that were available for further analysis. Our results revealed that GSU was significantly correlated with age (summary SMD = 0.13; p = 0.004), prostate volume (PV) (summary SMD = -0.19;p < 0.001), preoperative PSA (p-PSA) (summary SMD = 0.18; p < 0.001), PSA density (PSAD) (summary SMD = 0.40; p < 0.001), number of positive cores (summary SMD = 0.28; p = 0.001), percentage of positive cores (summary SMD = 0.36; p < 0.001), Prostate Imaging Reporting and Data System (PI-RADS) scores (>3/≤3) (summary OR = 2.27; p = 0.001), clinical T stage (>T2/≤T2) (summary OR = 1.73; p < 0.001), positive surgical margins (PSM) (summary OR = 2.12; p < 0.001), extraprostatic extension (EPE) (summary OR = 2.73; p < 0.001), pathological T stage (>T2/≤T2) (summary OR = 3.45; p < 0.001), perineural invasion (PNI) (summary OR = 2.40; p = 0.008), and neutrophil to lymphocyte ratio (NLR) (summary SMD = 0.50; p < 0.001). However, we found that GSU was not significantly correlated with body mass index (BMI) (summary SMD = -0.02; p = 0.602). Moreover, our sensitivity and subgroup analyses showed that the findings were reliable.
CONCLUSIONS: Age, PV, p-PSA, PSAD, number of positive cores, percentage of positive cores, PI-RADS score, clinical T stage, PSM, EPE, pathological T stage, PNI, and NLR are independent factors predicting GSU following RP. The findings may be helpful in risk stratification and personalized treatment in PC patients.

Keywords:  Gleason score upgrading; Meta-analysis; Prostate cancer; Risk factors

DOI:  https://doi.org/10.1159/000528873
Zhonghua Bing Li Xue Za Zhi. 2023 Apr 08. 52(4): 353-357

[Concordance between three integrated scores based on prostate biopsy and grade-grouping of radical prostatectomy specimen].

Y Fu, J Cai, Y Chen, Q Zhou, Y M Xu, J Shi, X S Fan.

Objective: To analyze three different integrated scoring schemes of prostate biopsy and to compare their concordance with the scoring of radical prostatectomy specimens. Methods: A retrospective analysis of 556 patients with radical prostatectomy performed in Nanjing Drum Tower Hospital, Nanjing, China from 2017 to 2020. In these cases, whole organ sections were performed, the pathological data based on biopsy and radical prostatectomy specimens were summarized, and 3 integrated scores of prostate biopsy were calculated, namely the global score, the highest score and score of the largest volume. Results: Among the 556 patients, 104 cases (18.7%) were classified as WHO/ISUP grade group 1, 227 cases (40.8%) as grade group 2 (3+4=7); 143 cases (25.7%) as grade group 3 (4+3=7); 44 cases (7.9%) as grade group 4 (4+4=8) and 38 cases (6.8%) as grade group 5. Among the three comprehensive scoring methods for prostate cancer biopsy, the consistency of global score was the highest (62.4%). In the correlation analysis, the correlation between the scores of radical specimens and the global scores was highest (R=0.730, P<0.01), while the correlations of the scores based on radical specimens with highest scores and scores of the largest volume based on biopsy were insignificant (R=0.719, P<0.01; R=0.631, P<0.01, respectively). Univariate and multivariate analyses showed tPSA group and the three integrated scores of prostate biopsy were statistically correlated with extraglandular invasion, lymph node metastasis, perineural invasion and biochemical recurrence. Elevated global score was an independent prognostic risk factor for extraglandular invasion and biochemical recurrence in patients; increased serum tPSA was an independent prognostic risk factor for extraglandular invasion; increased hjighest score was an independent risk factor for perineural invasion. Conclusions: In this study, among the three different integrated scores, the overall score is most likely corresponded to the radical specimen grade group, but there is difference in various subgroup analyses. Integrated score of prostate biopsy can reflect grade group of radical prostatectomy specimens, thereby providing more clinical information for assisting in optimal patient management and consultation.

DOI: https://doi.org/10.3760/cma.j.cn112151-20221125-00992
STAR Protoc. 2023 Mar 27. pii: S2666-1667(23)00156-9. [Epub ahead of print]4(2): 102198

Generation of human iPSC-derived neurofibromaspheres for in vitro and in vivo uses.

Helena Mazuelas, Itziar Uriarte-Arrazola, Juana Fernández-Rodríguez, Miriam Magallón-Lorenz, Alberto Villanueva, Conxi Lázaro, Bernat Gel, Eduard Serra, Meritxell Carrió.

  Neurofibromas are benign peripheral nervous system tumors associated with neurofibromatosis type 1, which originate from NF1(-/-) Schwann cell precursors. We describe a protocol to generate neurofibromaspheres by differentiating NF1(-/-) Schwann cells from induced pluripotent stem cells and combining them with neurofibroma primary fibroblasts. We also describe the development of neurofibroma-like tumors when neurofibromaspheres are engrafted in the sciatic nerve of nude mice. This model constitutes a versatile platform for drug screening and the study of neurofibroma biology. For complete details on the use and execution of this protocol, please refer to Mazuelas et al. (2022).1.

Keywords:  Cancer; Cell Biology; Cell Differentiation; Model Organisms

DOI:  https://doi.org/10.1016/j.xpro.2023.102198
Int J Surg. 2023 Apr 03.

Development and validation of prognostic model based on extra-gastric lymph nodes metastasis and lymph node ratio in node-positive gastric cancer: a retrospective cohort study based on a multicenter database.

Yi Zeng, Fenglin Cai, Pengliang Wang, Xinyu Wang, Yong Liu, Li Zhang, Rupeng Zhang, Luchuan Chen, Han Liang, Zaisheng Ye, Jingyu Deng.

BACKGROUND: Regional lymph node metastasis (LNM) is a competent and the most intensive predictor for prognostic evaluation of patients after curative surgery. This study is based on the databases of two large medical centers in North and South China. It aims to establish a prognostic model for prognosis based on extra-gastric LNM (ELNM) and lymph node ratio (LNR) in node-positive gastric cancer (GC).
METHODS: Clinical data of 874 GC patients with pathologically confirmed LNM in a large medical center in southern China, were included as the training cohort. In addition, clinical data of 674 patients with pathologically confirmed LNM from a large medical center in northern China, were used as the validation cohort.
RESULTS: In the training cohort, a modified N staging system (mNstage) based on ELNM and LNR was established; it has a significantly higher prognostic accuracy than the pN, LNR and ELNM staging system(AIC, pN stage vs. LNR stage vs. ELNM stage vs. mN stage= 5498.479 vs. 5537.815 vs. 5569.844 vs. 5492.123; BIC,pN stage vs. LNR stage vs. ELNM stage vs. mN stage= 5512.799 vs. 5547.361 vs. 5574.617 vs. 5506.896;likelihood-ratio X2,pN stage vs. LNR stage vs. ELNM stage vs. mN stage=177.7 vs. 149.8 vs. 115.79 vs. 183.5). In the external validation, mNstage also has higher prognostic accuracy than the pN, LNR and ELNM staging system. Cox multivariate regression analysis showed that age, mNstage, pT stage, and perineural invasion were independent factors. A nomogram model was established according to the four factors (age, mNstage, pT stage, and perineural invasion). The nomogram model was greater than the traditional TNM staging in the training cohort (one-year AUC, AJCC 8th TNM vs. Nomogram=0.692 vs. 0.746, three-year AUC: AJCC 8th TNM vs. Nomogram=0.684 vs. 0.758, five-year AUC: AJCC 8th TNM vs. Nomogram=0.725 vs. 0.762). In the external validation, the nomogram also shows better prognostic value and greater prediction accuracy than the traditional TNM staging.
CONCLUSION: The prognostic model based on ELNM and LNR has good prognostic prediction in patients with node-positive GC.

DOI: https://doi.org/10.1097/JS9.0000000000000308
Biochem Biophys Res Commun. 2023 Mar 21. pii: S0006-291X(23)00331-5. [Epub ahead of print]657 69-79

Sympathetic β2-adrenergic receptor blockade overcomes docetaxel resistance in prostate cancer.

Mi Zhang, Fangfang Chen, Xueqing Sun, Yanping Huang, Yan Zeng, Jinying Chen, Shiqi Wu, Chen Xu.

   PURPOSE: Due to the limited effective therapies, resistance to docetaxel is ordinarily fatal and remains a critical clinical challenge.β2-adrenergic receptor(β2-AR)can promote the metastasis and invasion of prostate cancer, but the role in chemotherapy-resistant prostate cancer remains unclear.
METHODS: By downloading the GEO database in NCBI, the expression of β2-AR in different prostate tissues was analyzed. We constructed docetaxel-resistant prostate cancer cell lines by the method of dose-escalation. LC3B-labeled stable cells and shAtg5 knockdown stable cells were constructed by lentivirus infection. The molecular mechanism of β2-AR affecting docetaxel sensitivity through apoptosis and autophage were investigated by flow cytometry, mitochondrial membrane potential and western blot. Then we detected the interaction between autophagy and apoptotic by performing immunoprecipitation assay.
RESULTS: We show that restraining the activity of β2-AR sensitized the cell response and reduced the resistance to docetaxel. The mechanism involves the regulation of β2-AR in the cellular response to docetaxel through apoptosis and autophagy via caspase signaling and Atg5/AMPK/mTOR pathway as well as the effect of β2-AR on the crosstalk between apoptosis and autophagy via p38 MAPK and JNK/c-Jun/FOXO3a signaling pathways.
CONCLUSION: Our data demonstrate that β2-AR inhibitor-induced autophagy and apoptosis contribute to the effectiveness responses to docetaxel in castration-resistant prostate cancer, and in combination with pharmacological agents of β2-AR and autophagy inhibitors may provide a potential therapeutic strategy to enhance the limited capacity of docetaxel to control castration-resistant prostate cancer.

Keywords:  Apoptosis and autophagy; Chemotherapy resistance; Prostate cancer; β(2)-adrenergic receptor

DOI:  https://doi.org/10.1016/j.bbrc.2023.03.046
Curr Opin Anaesthesiol. 2023 Mar 07.

Anaesthesia and cancer recurrence: the influence of perioperative anaesthetic technique on cancer recurrence after surgery.

Lua S Rahmani, Ahmed Abdelaatti, Thomas P Wall, Donal J Buggy.

PURPOSE OF REVIEW: Cancer is a leading cause of death worldwide, and incidence is increasing. Excisional surgery is essential in approximately 70% of solid organ tumours. Emerging research in onco-anaesthesiology suggests that perioperative anaesthetic and analgesic techniques might influence long-term oncologic outcomes.
RECENT FINDINGS: Prospective, randomized control trials (RCTs) demonstrate that perioperative regional and neuraxial anaesthetic techniques do not affect cancer recurrence. Ongoing trials are investigating the potential outcome benefits of systemic lidocaine. Retrospective studies indicate improved postoperative oncologic outcomes for certain types of breast cancer with higher intraoperative opioid dosage, nuancing available evidence on the effect of opioids. RCT evidence suggests that propofol has no beneficial effect compared with volatiles on breast cancer recurrence, although it remains unclear whether this applies to other cancer types.
SUMMARY: Although regional anaesthesia definitively does not affect cancer recurrence, ongoing prospective RCTs with oncological outcomes as primary endpoints are awaited to establish if other anaesthetic or analgesic techniques influence cancer recurrence. Until such trials conclusively identify a causal relationship, insufficient evidence exists to recommend specific anaesthetic or analgesic techniques for tumour resection surgery based on altering the patient's risk of recurrence.

DOI: https://doi.org/10.1097/ACO.0000000000001261
Curr Gene Ther. 2023 Mar 28.

Anesthesia and Cancer: Something More than Avoid Stress Response.

Aida Raigon Ponferrada, Salvador Romero Molina, Juan Carlos Molina Ruiz, Gomez Maldonado J, Jose Luis Guerrero Orriach.

  Currently, patients with tumor pathologies have become the most numerous patients in operating rooms. The influence of anesthetics drugs has been the subject of numerous studies, they have shown that the use of certain drugs may have impact on prognosis and survival. By investigating the action of these drugs on different metabolic pathways and their mechanisms of action, we can better understand how they influence various hallmarks of carcinogenesis and determine their potential impact on cancer progression. Some of the pathways of action are widely known within oncology, being targets of specific treatments such as PI3k/AKT/mTOR, EGFR and Wnt/ β-catenin. This review performs a thorough dissection of the interaction between anesthetic drugs and oncological cell lines through cell signaling pathways, genetic, immune and transcriptomic pathways. Through these underlying mechanisms, it aims to clarify the effect of the choice of anesthetic drug and its potential influence on the prognosis of oncological surgery.

Keywords:  anesthesia; cancer; mirnas; propofol; halogenated; opioids; local anaesthetics.

DOI:  https://doi.org/10.2174/1566523223666230328165109