bims-netuvo 2023-12-24 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–12–24
seventeen papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Tumour-associated macrophages and Schwann cells promote perineural invasion via paracrine loop in pancreatic ductal adenocarcinoma.
Neurological adverse events of immune checkpoint inhibitors and the development of paraneoplastic neurological syndromes.
Clinical impact of perineural invasion encircled completely vs. incompletely by prostate cancer on needle core biopsy.
The Incidence of Lymphovascular and Perineural Invasion and their Impact on Survival in Patients with Rectal Cancer.
[Primary Malignant Peripheral Nerve Sheath Tumor of the Pulmonary Vein: A Case Report].
Spatial gene expression profiling unveils immuno-oncogenic programs of NF1-associated peripheral nerve sheath tumor progression.
Increased CD16a (FcγRIIIA) Expression in The Tumor Microenvironment of Atypical Neurofibromatous Neoplasms of Uncertain Biologic Potential May Be Associated with Progression from Neurofibromas to Atypical Neurofibromas.
Case Report of a Patient With Malignant Peripheral Nerve Sheath Tumor Treated With Wide Resection.
A Retrospective Analysis of High Resolution Ultrasound Evaluation of the "Split Fat Sign" in Peripheral Nerve Sheath Tumors.
Analysis of treatment sequence and outcomes in patients with relapsed malignant peripheral nerve sheath tumors.
Clinical Significance of SOX10 Expression in Human Pathology.
Drug Responses in Plexiform Neurofibroma Type I (PNF1) Cell Lines Using High-Throughput Data and Combined Effectiveness and Potency.
Trial watch: beta-blockers in cancer therapy.
Malignant triton tumor of uterus: A case report and literature review.
Association between stress, depression or anxiety and cancer: Rapid review of reviews.
GABA induced by sleep deprivation promotes the proliferation and migration of colon tumors through miR-223-3p endogenous pathway and exosome pathway.
Gene Signature Associated with Nervous System in an Experimental Radiation- and Estrogen-Induced Breast Cancer Model.

Br J Cancer. 2023 Dec 22.

Tumour-associated macrophages and Schwann cells promote perineural invasion via paracrine loop in pancreatic ductal adenocarcinoma.

Bin Zhang, Xiaofeng Guo, Leyi Huang, Yuting Zhang, Zhiguo Li, Dan Su, Longfa Lin, Peng Zhou, Huilin Ye, Yanan Lu, Quanbo Zhou.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently accompanied by perineural invasion (PNI), which is associated with excruciating neuropathic pain and malignant progression. However, the relationship between PNI and tumour stromal cells has not been clarified.
METHODS: The dorsal root ganglia or sciatic nerves nerve model was used to observe the paracrine interaction and the activation effect among Schwann cells, tumour-associated macrophages (TAMs), and pancreatic cancer cells in vitro. Next generation sequencing, enzyme-linked immunosorbent assay and chromatin immunoprecipitation were used to explore the specific paracrine signalling between TAMs and Schwann cells.
RESULTS: We demonstrated that more macrophages were expressed around nerves that have been infiltrated by pancreatic cancer cells compared with normal nerves in murine and human PNI specimens. In addition, high expression of CD68 or GFAP is associated with an increased incidence of PNI and indicates a poor 5-year survival rate in patients with PDAC. Mechanistically, tumour-associated macrophages (TAMs) activate Schwann cells via the bFGF/PI3K/Akt/c-myc/GFAP pathway. Schwann cells secrete IL-33 to recruit macrophages into the perineural milieu and facilitate the M2 pro-tumourigenic polarisation of macrophages.
CONCLUSIONS: Our study demonstrates that the bFGF/IL-33 positive feedback loop between Schwann cells and TAMs is essential in the process of PNI of PDAC. The bFGF/PI3K/Akt/c-myc/GFAP pathway would open potential avenues for targeted therapy of PDAC.

DOI: https://doi.org/10.1038/s41416-023-02539-w
Lancet Neurol. 2024 Jan;pii: S1474-4422(23)00369-1. [Epub ahead of print]23(1): 81-94

Neurological adverse events of immune checkpoint inhibitors and the development of paraneoplastic neurological syndromes.

Antonio Farina, Macarena Villagrán-García, Alberto Vogrig, Anastasia Zekeridou, Sergio Muñiz-Castrillo, Roser Velasco, Amanda C Guidon, Bastien Joubert, Jérôme Honnorat.

Immune checkpoint inhibitors, a class of oncological treatments that enhance antitumour immunity, can trigger neurological adverse events closely resembling paraneoplastic neurological syndromes. Unlike other neurological adverse events caused by these drugs, post-immune checkpoint inhibitor paraneoplastic neurological syndromes predominantly affect the CNS and are associated with neural antibodies and cancer types commonly found also in spontaneous paraneoplastic neurological syndromes. Furthermore, post-immune checkpoint inhibitor paraneoplastic neurological syndromes have poorer neurological outcomes than other neurological adverse events of immune checkpoint inhibitors. Early diagnosis and initiation of immunosuppressive therapy are likely to be crucial in preventing the accumulation of neurological disability. Importantly, the neural antibodies found in patients with post-immune checkpoint inhibitor paraneoplastic neurological syndromes are sometimes detected before treatment, indicating that these antibodies might help to predict the development of neurological adverse events. Experimental and clinical evidence suggests that post-immune checkpoint inhibitor paraneoplastic neurological syndromes probably share immunological features with spontaneous paraneoplastic syndromes. Hence, the study of post-immune checkpoint inhibitor paraneoplastic neurological syndromes can help in deciphering the immunopathogenesis of paraneoplastic neurological syndromes and in identifying novel therapeutic targets.

DOI: https://doi.org/10.1016/S1474-4422(23)00369-1
Hum Pathol. 2023 Dec 20. pii: S0046-8177(23)00248-4. [Epub ahead of print]

Clinical impact of perineural invasion encircled completely vs. incompletely by prostate cancer on needle core biopsy.

Julum Nwanze, Yuki Teramoto, Ying Wang, Hiroshi Miyamoto.

  The clinical significance of the pattern or degree of perineural invasion (PNI) by prostate cancer remains largely unknown. We herein assessed radical prostatectomy findings and postoperative oncologic outcomes in 125 patients who had undergone systematic sextant prostate biopsy exhibiting only a single focus of PNI encircled completely (n = 57; 46 %) vs. incompletely (n = 68; 54 %) by cancer. Between these two cohorts, there were no significant differences in clinicopathological features on biopsy or prostatectomy, including tumor grade, stage, and length or volume, and surgical margin status, as well as the need for adjuvant therapy immediately after prostatectomy. Similarly, survival analysis demonstrated no significant difference in the risk of disease progression following prostatectomy in patients with encircled vs. non-encircled PNI on biopsy (P = 0.679). When the non-encircled cases were further divided into four groups [i.e. 1-25 % enclosed (n = 12; 18 %), 26-50 % enclosed (n = 18; 26 %), 51-75 % enclosed (n = 10; 15 %), 76-99 % enclosed (n = 28; 41 %)], the rates of progression-free survival were comparable among the five groups (P = 0.954). In prostate biopsy specimens exhibiting PNI at only one focus, the degree of nerve involvement thus appears to have little clinical impact. Accordingly, PNI detected on prostate biopsy may need to be similarly taken into consideration irrespective of the degree of nerve involvement.

Keywords:  Perineural invasion; Prognosis; Prostate biopsy; Prostate cancer; Radical prostatectomy

DOI:  https://doi.org/10.1016/j.humpath.2023.12.001
Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2023 Dec 01. 44(3): 73-78

The Incidence of Lymphovascular and Perineural Invasion and their Impact on Survival in Patients with Rectal Cancer.

Shqipe Misimi, Dajana Cako, Ali İlbey Demirel, Andrej Nikolovski, Cemal Ulusoy, Mehmet Güray Duman.

  Aim: Lymphovascular Invasion (LVI) and Perineural Invasion (PNI) represent undesirable but still realistic pathological features of rectal cancer, associated with poor prognosis and worse survival. The aim of this study is to assess the incidence of LVI and PNI in patients treated for rectal cancer and the impact of LVI and PNI on patient survival. Material and Methods: This retrospective single center observational study, conducted in the period of 2016-2019, includes patients with rectal cancer treated with/without long-course neoadjuvant chemoradiotherapy (nCRT). Data collection encompassed demographics, tumor characteristics, type of surgery (abdominal perineal rectal resection - APR and low anterior rectal resection - LAR), and LVI/PNI presence. Survival during follow-up was estimated and compared for patients with/without LVI and PNI involvement. Results: A total number of 234 patients (77 females and 157 males) with mean age of 61.3 enrolled in the study. Neoadjuvant CRT was conducted in 170 patients. APR procedure was performed in 67 of them and LAR in 167. LVI presence was noted in 55 (24.4%) and PNI in 77 (34.2%) patients. Mean survival during follow-up was 42.07 months. The use of nCRT influenced on survival (p < 0.033). Patients treated with LAR had better survival outcomes (p = 0.001). Presence of LVI and PNI was associated with a worse prognosis (p < 0.001). Conclusion: PNI was more frequent than the LVI in this study. Patients with nCRT conduction had better overall survival. LVI and PNI presence was associated with poor prognosis in terms of overall survival in patients with rectal cancer.

Keywords:  Rectal cancer; lymphovascular invasion; perineural invasion; prognosis; survival

DOI:  https://doi.org/10.2478/prilozi-2023-0049
J Korean Soc Radiol. 2023 Nov;84(6): 1384-1390

[Primary Malignant Peripheral Nerve Sheath Tumor of the Pulmonary Vein: A Case Report].

Hyun Woo, Hyeyoung Kwon, Jin Hwan Kim, Song Soo Kim, Hyung Kyu Park, Younju Rhee, Jae-Hyeong Park.

  Primary masses rarely originate from the heart and great vessels, and a malignant peripheral nerve sheath tumor (MPNST) is extremely rare. A 76-year-old male with pleural effusion underwent contrast-enhanced computed tomography, which revealed a hypoattenuating mass involving the right pulmonary vein and left atrium. Ultrasonography showed that the mass originated from the right pulmonary vein. Surgical resection confirmed an MPNST that originated from the pulmonary vein. We report the first Korean case of a primary MPNST originating from the pulmonary vein. We have also described the radiologic findings suggestive of a pulmonary vein mass.

Keywords:  Cardiac Neoplasm; Computed Tomography, X-Ray; Malignant Peripheral Nerve Sheath Tumor; Neoplasm; Pulmonary Vein

DOI:  https://doi.org/10.3348/jksr.2023.0001
Clin Cancer Res. 2023 Dec 21.

Spatial gene expression profiling unveils immuno-oncogenic programs of NF1-associated peripheral nerve sheath tumor progression.

Dana K Mitchell, Breanne Burgess, Emily White, Abbi E Smith, Elizabeth A Sierra Potchanant, Henry Mang, Brooke Rodriguez, Qingbo Lu, Shaomin Qian, Waylan Bessler, Xiaohong Li, Li Jiang, Kylee Brewster, Constance Temm, Andrew Horvai, Eric A Albright, Melissa L Fishel, Christine A Pratilas, Steven P Angus, D Wade Clapp, Steven D Rhodes.

PURPOSE: Plexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) associated with neurofibromatosis type 1 (NF1). Despite similar histological appearance, these neoplasms exhibit diverse evolutionary trajectories, with a subset progressing to malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathological features and CDKN2A copy number loss. While genomic studies have uncovered key driver events promoting tumor progression, the transcriptional changes preceding malignant transformation remain poorly defined.
EXPERIMENTAL DESIGN: Here we resolve gene expression profiles in PNSTs across the neurofibroma-to-MPNST continuum in NF1 patients and mouse models, revealing early molecular features associated with neurofibroma evolution and transformation.
RESULTS: Our findings demonstrate that ANF exhibit enhanced signatures of antigen presentation and immune response, which are suppressed as malignant transformation ensues. MPNSTs further displayed deregulated survival and mitotic fidelity pathways, and targeting key mediators of these pathways, CENPF and BIRC5, disrupted growth and viability of human MPNST cells lines and primary murine Nf1-Cdkn2a mutant Schwann cell precursors. Finally, neurofibromas contiguous with MPNST manifested distinct alterations in core oncogenic and immune surveillance programs, suggesting that early molecular events driving disease progression may precede histopathological evidence of malignancy.
CONCLUSIONS: If validated prospectively in future studies, these signatures may serve as molecular diagnostic tools to augment conventional histopathological diagnosis by identifying neurofibromas at high risk of undergoing malignant transformation, facilitating risk-adapted care.

DOI: https://doi.org/10.1158/1078-0432.CCR-23-2548
J Pers Med. 2023 Dec 17. pii: 1720. [Epub ahead of print]13(12):

Increased CD16a (FcγRIIIA) Expression in The Tumor Microenvironment of Atypical Neurofibromatous Neoplasms of Uncertain Biologic Potential May Be Associated with Progression from Neurofibromas to Atypical Neurofibromas.

Min-Kyung Yeo, Yeong Jun Koh, Jong-Il Park, Kyung-Hee Kim.

  Neurofibroma (NF) is a benign tumor in the peripheral nervous system, but it can infiltrate around structures and cause functional impairment and disfigurement. We incidentally found that the expression of CD16a (Fc gamma receptor IIIA) was increased in NFs compared to in non-neoplastic nerves and hypothesized that CD16 could be relevant to NF progression. We evaluated the expressions of CD16a, CD16b, CD68, TREM2, Galectin-3, S-100, and SOX10 in 38 cases of neurogenic tumors (NF, n = 18; atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP), n = 14; and malignant peripheral nerve sheath tumor (MPNST), n = 6) by immunohistochemical staining. In the tumor microenvironment (TME) of the ANNUBPs, CD16a and CD16b expression levels had increased more than in the NFs or MPNSTs. CD68 and Galectin-3 expression levels in the ANNUBPs were higher than in the MPNSTs. Dual immunohistochemical staining showed an overlapping pattern for CD16a and CD68 in TME immune cells. Increased CD16a expression was detected in the ANNUBPs compared to the NFs but decreased with malignant progression. The CD16a overexpression with CD68 positivity in the ANNUBPs potentially reflects that the TME immune modulation could be associated with NF progression to an ANNUBP. Further studies should explore the role of CD16a in immunomodulation for accelerating NF growth.

Keywords:  CD16; immunomodulation; neurofibroma; tumor microenvironment

DOI:  https://doi.org/10.3390/jpm13121720
Cureus. 2023 Nov;15(11): e49055

Case Report of a Patient With Malignant Peripheral Nerve Sheath Tumor Treated With Wide Resection.

Arın Celayir, Mete Özer, Şeyhmus Kavak, Mahmut Kursat Ozsahin, Huseyin Botanlioglu.

  Malignant peripheral nerve sheath tumors are soft tissue sarcomas originating from peripheral nerves. They are more frequently diagnosed in individuals with neurofibromatosis and tend to affect young men more often than women. The most common sites for these tumors within the peripheral nerve sheath are in the pelvis and the distal femur. Although chemotherapy and radiotherapy are not frequently used, it should be noted that in some cases, postoperative radiotherapy and chemotherapy may be beneficial. The primary treatment approach typically involves the complete surgical removal of the tumor. Here, we discuss the case of our patient whom we successfully treated with extensive resection and followed up with postoperative radiotherapy at our clinic.

Keywords:  malignant peripheral nerve sheath tumor (mpnst); malignant schwannoma; marble-like pattern; radiotherapy; wide resection

DOI:  https://doi.org/10.7759/cureus.49055
Healthcare (Basel). 2023 Dec 12. pii: 3147. [Epub ahead of print]11(24):

A Retrospective Analysis of High Resolution Ultrasound Evaluation of the "Split Fat Sign" in Peripheral Nerve Sheath Tumors.

Jeena B Deka, Ritu Shah, Miguel Jiménez, Nidhi Bhatnagar, Alfredo Bravo-Sánchez, Inés Piñas-Bonilla, Javier Abián-Vicén, Fernando Jiménez.

  Peripheral nerve sheath tumors (PNST) comprise schwannomas and neurofibromas. The finding of increased adipose tissue around benign PNSTs has been described as the "split fat sign" on magnetic resonance imaging exams, which is suggestive of an intramuscular or intermuscular location of the tumor. However, few studies have described this sign as a salient ultrasound feature of PNSTs. The main purpose of this study was to retrospectively evaluate the presence of increased fatty tissue deposition around benign PNSTs diagnosed by high-resolution ultrasound. In addition, we aimed to corroborate the presence of vascularization around the affected area. A retrospective analysis of ten cases of PNSTs and two cases of post-traumatic neuromas diagnosed by high-resolution ultrasound was performed with a Logiq® P8 ultrasound with a 2-11 MHz multifrequency linear probe L3-12-D (central frequency: 10 MHz). Localized types of neurofibromas and schwannomas in any location were seen as predominantly hypoechoic tumors with an oval or fusiform shape. Exiting and entering nerves (tail sign) were observed in six cases, showing localized lesions both in intermuscular and subcutaneous locations. The presence of increased hyperechoic tissue (the split fat sign) was noted in cases of solitary intermuscular and intramuscular peripheral nerve sheath tumors, mainly the schwannomas. Though small tumors did not demonstrate the tail sign, the increase in adipose tissue and vascularity on US was well demonstrated. In conclusion, the nerve in continuity forms the basis of the ultrasonographic diagnosis of PNSTs. However, high-resolution US can convincingly demonstrate the increased presence of fat in the upper and lower poles as well as circumferentially in intermuscular or intramuscular benign PNSTs.

Keywords:  fatty tissue; high resolution ultrasound; neurofibromas; peripheral nerve sheath tumors; schwannomas

DOI:  https://doi.org/10.3390/healthcare11243147
Neurooncol Adv. 2023 Jan-Dec;5(1):5(1): vdad156

Analysis of treatment sequence and outcomes in patients with relapsed malignant peripheral nerve sheath tumors.

Lindy Zhang, Kathryn M Lemberg, Ana Calizo, Ravi Varadhan, Alan H Siegel, Christian F Meyer, Jaishri O Blakeley, Christine A Pratilas.

   Background: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas originating from cellular components within the nerve sheath. The incidence of MPNST is highest in people with neurofibromatosis type 1 (NF1), and MPNST is the leading cause of death for these individuals. Complete surgical resection is the only curative therapeutic option, but is often unfeasible due to tumor location, size, or presence of metastases. Evidence-based choices of chemotherapy for recurrent/refractory MPNST remain elusive. To address this gap, we conducted a retrospective analysis of our institutional experience in treating patients with relapsed MPNST in order to describe patient outcomes related to salvage regimens.
Methods: We conducted a retrospective electronic health record analysis of patients with MPNST who were treated at Johns Hopkins Hospital from January 2010 to June 2021. We calculated time to progression (TTP) based on salvage chemotherapy regimens.
Results: Sixty-five patients were included in the analysis. Upfront therapy included single or combined modalities of surgery, chemotherapy, or radiotherapy. Forty-eight patients received at least 1 line of chemotherapy, which included 23 different regimens (excluding active clinical studies). Most patients (n = 42, 87.5%) received a combination of doxorubicin, ifosfamide, or etoposide as first-line chemotherapy. Salvage chemotherapy regimens and their TTP varied greatly, with irinotecan/temozolomide-based regimens having the longest average TTP (255.5 days, among 4 patients).
Conclusions: Patients with advanced or metastatic MPNST often succumb to their disease despite multiple lines of therapy. These data may be used as comparative information in decision-making for future patients and clinical trials.

Keywords:  chemotherapy; malignant peripheral nerve sheath tumors; neurofibromatosis type 1; salvage therapy; soft tissue sarcoma

DOI:  https://doi.org/10.1093/noajnl/vdad156
Curr Issues Mol Biol. 2023 Dec 15. 45(12): 10131-10158

Clinical Significance of SOX10 Expression in Human Pathology.

Hisham F Bahmad, Aran Thiravialingam, Karthik Sriganeshan, Jeffrey Gonzalez, Veronica Alvarez, Stephanie Ocejo, Alvaro R Abreu, Rima Avellan, Alejandro H Arzola, Sana Hachem, Robert Poppiti.

  The embryonic development of neural crest cells and subsequent tissue differentiation are intricately regulated by specific transcription factors. Among these, SOX10, a member of the SOX gene family, stands out. Located on chromosome 22q13, the SOX10 gene encodes a transcription factor crucial for the differentiation, migration, and maintenance of tissues derived from neural crest cells. It plays a pivotal role in developing various tissues, including the central and peripheral nervous systems, melanocytes, chondrocytes, and odontoblasts. Mutations in SOX10 have been associated with congenital disorders such as Waardenburg-Shah Syndrome, PCWH syndrome, and Kallman syndrome, underscoring its clinical significance. Furthermore, SOX10 is implicated in neural and neuroectodermal tumors, such as melanoma, malignant peripheral nerve sheath tumors (MPNSTs), and schwannomas, influencing processes like proliferation, migration, and differentiation. In mesenchymal tumors, SOX10 expression serves as a valuable marker for distinguishing between different tumor types. Additionally, SOX10 has been identified in various epithelial neoplasms, including breast, ovarian, salivary gland, nasopharyngeal, and bladder cancers, presenting itself as a potential diagnostic and prognostic marker. However, despite these associations, further research is imperative to elucidate its precise role in these malignancies.

Keywords:  SOX10; melanoma; mesenchymal tumors; neural crest cells; neuroectodermal tumors

DOI:  https://doi.org/10.3390/cimb45120633
Cancers (Basel). 2023 Dec 12. pii: 5811. [Epub ahead of print]15(24):

Drug Responses in Plexiform Neurofibroma Type I (PNF1) Cell Lines Using High-Throughput Data and Combined Effectiveness and Potency.

Paul O Zamora, Gabriel Altay, Ulisses Santamaria, Nathan Dwarshuis, Hari Donthi, Chang In Moon, Dana Bakalar, Matthew Zamora.

  Background: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by heterozygous germline NF1 gene mutations that predispose patients to developing plexiform neurofibromas, which are benign but often disfiguring tumors of the peripheral nerve sheath induced by loss of heterozygosity at the NF1 locus. These can progress to malignant peripheral nerve sheath tumors (MPNSTs). There are no approved drug treatments for adults with NF1-related inoperable plexiform neurofibromas, and only one drug (selumetinib), which is an FDA-approved targeted therapy for the treatment of symptomatic pediatric plexiform neurofibromas, highlighting the need for additional drug screening and development. In high-throughput screening, the effectiveness of drugs against cell lines is often assessed by measuring in vitro potency (AC50) or the area under the curve (AUC). However, the variability of dose-response curves across drugs and cell lines and the frequency of partial effectiveness suggest that these measures alone fail to provide a full picture of overall efficacy. Methods: Using concentration-response data, we combined response effectiveness (EFF) and potency (AC50) into (a) a score characterizing the effect of a compound on a single cell line, S = log[EFF/AC50], and (b) a relative score, ΔS, characterizing the relative difference between a reference (e.g., non-tumor) and test (tumor) cell line. ΔS was applied to data from high-throughput screening (HTS) of a drug panel tested on NF1-/- tumor cells, using immortalized non-tumor NF1+/- cells as a reference. Results: We identified drugs with sensitivity, targeting expected pathways, such as MAPK-ERK and PI3K-AKT, as well as serotonin-related targets, among others. The ΔS technique used here, in tandem with a supplemental ΔS web tool, simplifies HTS analysis and may provide a springboard for further investigations into drug response in NF1-related cancers. The tool may also prove useful for drug development in a variety of other cancers.

Keywords:  NF1; concentration–response; drug evaluation; high-throughput; in vitro; neurofibromatosis; plexiform; web tool

DOI:  https://doi.org/10.3390/cancers15245811
Oncoimmunology. 2023 ;12(1): 2284486

Trial watch: beta-blockers in cancer therapy.

Killian Carnet Le Provost, Oliver Kepp, Guido Kroemer, Lucillia Bezu.

  Compelling evidence supports the hypothesis that stress negatively impacts cancer development and prognosis. Irrespective of its physical, biological or psychological source, stress triggers a physiological response that is mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic adrenal medullary axis. The resulting release of glucocorticoids and catecholamines into the systemic circulation leads to neuroendocrine and metabolic adaptations that can affect immune homeostasis and immunosurveillance, thus impairing the detection and eradication of malignant cells. Moreover, catecholamines directly act on β-adrenoreceptors present on tumor cells, thereby stimulating survival, proliferation, and migration of nascent neoplasms. Numerous preclinical studies have shown that blocking adrenergic receptors slows tumor growth, suggesting potential clinical benefits of using β-blockers in cancer therapy. Much of these positive effects of β-blockade are mediated by improved immunosurveillance. The present trial watch summarizes current knowledge from preclinical and clinical studies investigating the anticancer effects of β-blockers either as standalone agents or in combination with conventional antineoplastic treatments or immunotherapy.

Keywords:  Beta-adrenoreceptors; beta-blockers; cancer; catecholamines; stress

DOI:  https://doi.org/10.1080/2162402X.2023.2284486
J Clin Ultrasound. 2023 Dec 21.

Malignant triton tumor of uterus: A case report and literature review.

Ti-Ling Jiang, Yan Liu, Bo Ji, Dong-Hua Sheng, Qi-Can He, Jia-Chun Song, Gong Wang, Kai Wang.

  Malignant triton tumor (MTT) is a highly aggressive malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation. There are few reports that MTT occurred in urogenital system. In the present study, we report the first MTT occurring in the uterus. A 57-year-old woman came to the emergency department due to persistent vaginal bleeding for 2 months. The gynecological palpation found that a club-shaped excrescence existed in the vagina about 7 cm × 3 cm × 3 cm. The mass located in the lower segment of the uterus and the cervix was confirmed by gynecological vaginal ultrasound and magnetic resonance imaging, which was preliminarily diagnosed as cervical carcinoma. After neoplasm punch biopsy, the pathological diagnosis was malignant triton tumor. The patient finally lost follow-up. This is the first report about MTT in the uterus and suggests that pathological biopsy combined with imaging examination is necessary for the diagnosis of rarely MTT.

Keywords:  diagnosis; malignant peripheral nerve sheath tumor; malignant triton tumor; ultrasound; uterus

DOI:  https://doi.org/10.1002/jcu.23630
Compr Psychoneuroendocrinol. 2023 Nov;16 100215

Association between stress, depression or anxiety and cancer: Rapid review of reviews.

Katy Cooper, Fiona Campbell, Sue Harnan, Anthea Sutton.

   Background: Several studies have suggested links between psychological stress, depression or anxiety, and cancer incidence or outcomes. Existing systematic reviews have addressed this question, with differing results.
Aims: This rapid systematic umbrella review summarises existing reviews assessing the association between psychological stress, depression or anxiety and cancer incidence or cancer outcomes.
Methods: Systematic reviews assessing stress, depression or anxiety and cancer were identified via searches of MEDLINE, PsycInfo and Cochrane Database of Systematic Reviews from 2010 to November 2020.
Results: Twelve systematic reviews were included, summarising cohort and case-control studies, most of which adjusted for confounders. Regarding cancer incidence, one large meta-analysis reported a significant association between depression/anxiety and cancer incidence, while another showed a non-significant trend. Two further meta-analyses reported significant associations between stressful life events and cancer incidence. Conversely, two meta-analyses of work stress showed no significant association with cancer incidence. Regarding outcomes among cancer patients, three meta-analyses reported significant associations between depression/anxiety and cancer mortality, while another reported a non-significant trend for depression and cancer recurrence. One meta-analysis reported a significant association between partner bereavement and cancer mortality, while another showed no significant association between work stress and cancer mortality.
Conclusions: There is consistent evidence for an association between psychological stress, depression or anxiety and cancer incidence in general populations, and some evidence for an association with mortality in cancer populations. Future research may focus on confirmation of these findings, as well as the role of social support and stress-reducing interventions in buffering against these effects.

Keywords:  Cancer; Psychological; Stress; Systematic review

DOI:  https://doi.org/10.1016/j.cpnec.2023.100215
J Exp Clin Cancer Res. 2023 Dec 18. 42(1): 344

GABA induced by sleep deprivation promotes the proliferation and migration of colon tumors through miR-223-3p endogenous pathway and exosome pathway.

Haijun Bao, Zuojie Peng, Xukai Cheng, Chenxing Jian, Xianguo Li, Yongping Shi, Wenzhong Zhu, Yuan Hu, Mi Jiang, Jia Song, Feifei Fang, Jinhuang Chen, Xiaogang Shu.

   BACKGROUND: Research has indicated that long-term sleep deprivation can lead to immune dysfunction and participate in the occurance and progression of tumors. However, the relationship between sleep deprivation and colon cancer remains unclear. This study explored the specific mechanism through which sleep deprivation promotes the proliferation and migration of colon cancer, with a focus on the neurotransmitter GABA.
METHODS: Chronic sleep deprivation mice model were used to investigate the effect of sleep disorder on tumors. We detected neurotransmitter levels in the peripheral blood of mice using ELISA. CCK-8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the effect of GABA on colon cancer cells, while immunofluorescence showed the distribution of macrophages in lung metastatic tissues. We isolated exosomes from a GABA-induced culture medium to explore the effects of GABA-induced colon cancer cells on macrophages. Gain- and loss-of-function experiments, luciferase report analysis, immunohistochemistry, and cytokine detection were performed to reveal the crosstalk between colon cancer cells and macrophages.
RESULTS: Sleep deprivation promote peripheral blood GABA level and colon cancer cell proliferation and migration. Immunofluorescence analysis revealed that GABA-induced colon cancer metastasis is associated with enhanced recruitment of macrophages in the lungs. The co-culture results showed that GABA intensified M2 polarization of macrophage induced by colon cancer cells. This effect is due to the activation of the macrophage MAPK pathway by tumor-derived exosomal miR-223-3p. Furthermore, M2-like macrophages promote tumor proliferation and migration by secreting IL-17. We also identified an endogenous miR-223-3p downregulation of the E3 ligase CBLB, which enhances the stability of cMYC protein and augments colon cancer cells proliferation and migration ability. Notably, cMYC acts as a transcription factor and can also regulate the expression of miR-223-3p.
CONCLUSION: Our results suggest that sleep deprivation can promote the expression of miR-223-3p in colon cancer cells through GABA, leading to downregulation of the E3 ligase CBLB and inhibition of cMYC ubiquitination. Simultaneously, extracellular miR-223-3p promotes M2-like macrophage polarization, which leads to the secretion of IL-17, further enhancing the proliferation and migration of colon cancer cells.

Keywords:  Colon cancer cells; Exosomes; GABA; Macrophages; Sleep deprivation; miRNA

DOI:  https://doi.org/10.1186/s13046-023-02921-9
Biomedicines. 2023 Nov 22. pii: 3111. [Epub ahead of print]11(12):

Gene Signature Associated with Nervous System in an Experimental Radiation- and Estrogen-Induced Breast Cancer Model.

Gloria M Calaf, Debasish Roy, Lilian Jara, Francisco Aguayo, Leodan A Crispin.

  Breast cancer is frequently the most diagnosed female cancer in the world. The experimental studies on cancer seldom focus on the relationship between the central nervous system and cancer. Despite extensive research into the treatment of breast cancer, chemotherapy resistance is an important issue limiting the efficacy of treatment. Novel biomarkers to predict prognosis or sensitivity to chemotherapy are urgently needed. This study examined nervous-system-related genes. The profiling of differentially expressed genes indicated that high-LET radiation, such as that emitted by radon progeny, in the presence of estrogen, induced a cascade of events indicative of tumorigenicity in human breast epithelial cells. Bioinformatic tools allowed us to analyze the genes involved in breast cancer and associated with the nervous system. The results indicated that the gene expression of the Ephrin A1 gene (EFNA1), the roundabout guidance receptor 1 (ROBO1), and the kallikrein-related peptidase 6 (KLK6) was greater in T2 and A5 than in the A3 cell line; the LIM domain kinase 2 gene (LIMK2) was greater in T2 than A3 and A5; the kallikrein-related peptidase 7 (KLK7), the neuroligin 4 X-linked gene (NLGN4X), and myelin basic protein (MBP) were greater than A3 only in T2; and the neural precursor cell expressed, developmentally down-regulated 9 gene (NEDD9) was greater in A5 than in the A3 and E cell lines. Concerning the correlation, it was found a positive correlation between ESR1 and EFNA1 in BRCA-LumA patients; with ROBO1 in BRCA-Basal patients, but this correlation was negative with the kallikrein-related peptidase 6 (KLK6) in BRCA-LumA and -LumB, as well as with LIMK2 and ROBO1 in all BRCA. It was also positive with neuroligin 4 X-linked (NLGN4X) in BRCA-Her2 and BRCA-LumB, and with MBP in BRCA-LumA and -LumB, but negative with KLK7 in all BRCA and BRCA-LumA and NEDD9 in BRCA-Her2. The differential gene expression levels between the tumor and adjacent tissue indicated that the ROBO1, KLK6, LIMK2, KLK7, NLGN4X, MBP, and NEDD9 gene expression levels were higher in normal tissues than in tumors; however, EFNA1 was higher in the tumor than the normal ones. EFNA1, LIMK2, ROBO1, KLK6, KLK7, and MBP gene expression had a negative ER status, whereas NEDD9 and NLGN4X were not significant concerning ER status. In conclusion, important markers have been analyzed concerning genes related to the nervous system, opening up a new avenue of studies in breast cancer therapy.

Keywords:  axon guidance; breast cancer; neural precursors; neuronal markers; neurotransmitter; radiation

DOI:  https://doi.org/10.3390/biomedicines11123111