bims-netuvo 2023-07-02 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–07–02
ten papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Carcinogenesis and Metastasis: Focus on TRPV1-Positive Neurons and Immune Cells.
Basal Cell Carcinoma Perineural Invasion and Suggestive Signs of Perineural Invasion-Findings and Perspectives.
Preoperative prediction of microvascular invasion and perineural invasion in pancreatic ductal adenocarcinoma with 18F-FDG PET/CT radiomics analysis.
Neuropeptide Y Peptide Family and Cancer: Antitumor Therapeutic Strategies.
The value of machine learning based radiomics model in preoperative detection of perineural invasion in gastric cancer: a two-center study.
Integrated Neurosurgical Management of Retroperitoneal Benign Nerve Sheath Tumors.
Norepinephrine/β2-Adrenergic Receptor Pathway Promotes the Cell Proliferation and Nerve Growth Factor Production in Triple-Negative Breast Cancer.
Clinicopathological Analysis of Complicated Colorectal Cancer: A Five-Year Retrospective Study from a Single Surgery Unit.
Schwannoma: A Rare Case of Submucosal Gastric Tumor.
Nerve Ultrasound of Peripheral Nerves in Patients Treated with Immune Checkpoint Inhibitors.

Biomolecules. 2023 06 13. pii: 983. [Epub ahead of print]13(6):

Carcinogenesis and Metastasis: Focus on TRPV1-Positive Neurons and Immune Cells.

Nuray Erin, Arpad Szallasi.

  Both sensory neurons and immune cells, albeit at markedly different levels, express the vanilloid (capsaicin) receptor, Transient Receptor Potential, Vanilloid-1 (TRPV1). Activation of TRPV1 channels in sensory afferent nerve fibers induces local effector functions by releasing neuropeptides (most notably, substance P) which, in turn, trigger neurogenic inflammation. There is good evidence that chronic activation or inactivation of this inflammatory pathway can modify tumor growth and metastasis. TRPV1 expression was also demonstrated in a variety of mammalian immune cells, including lymphocytes, dendritic cells, macrophages and neutrophils. Therefore, the effects of TRPV1 agonists and antagonists may vary depending on the prominent cell type(s) activated and/or inhibited. Therefore, a comprehensive understanding of TRPV1 activity on immune cells and nerve endings in distinct locations is necessary to predict the outcome of therapies targeting TRPV1 channels. Here, we review the neuro-immune modulation of cancer growth and metastasis, with focus on the consequences of TRPV1 activation in nerve fibers and immune cells. Lastly, the potential use of TRPV1 modulators in cancer therapy is discussed.

Keywords:  TRPV1; capsaicin; carcinogenesis; neuroimmune regulation; resiniferatoxin; thermoTRP

DOI:  https://doi.org/10.3390/biom13060983
Life (Basel). 2023 Jun 17. pii: 1406. [Epub ahead of print]13(6):

Basal Cell Carcinoma Perineural Invasion and Suggestive Signs of Perineural Invasion-Findings and Perspectives.

Elena Niculet, Carmen Bobeica, Cristian Onisor, Gabriela Gurau, Aurel Nechita, Diana Sabina Radaschin, Dana Tutunaru, Laura Bujoreanu-Bezman, Alin Laurentiu Tatu.

  Basal cell carcinoma (BCC) is a malignant tumor with a rising incidence and is the beneficiary of several innovative evaluation techniques. Histopathology remains the gold standard for assessment, having the possibility of addressing multiple high-risk factors such as perineural invasion (PNI). The current study included a number of 244 BCC patients and targeted the identification of positive PNI and its suggestive signs, and whether they correlated or not with other high-risk tumor signs. PNI was found in 20.1% of patients, with 30.7% of patients having perineural chronic inflammation (PCI), which is a suggestive sign of PNI. PNI was also found in larger tumors, with deeper Clark levels, in high-risk BCCs and high-grade tumors. PNI and PCI are both important for pathology reporting, aiding in treatment choice and further patient management, with possibly positive outcomes concerning morbidity and mortality.

Keywords:  basal cell carcinoma; perineural chronic inflammation; perineural inflammation; perineural invasion

DOI:  https://doi.org/10.3390/life13061406
Clin Radiol. 2023 Jun 02. pii: S0009-9260(23)00219-2. [Epub ahead of print]

Preoperative prediction of microvascular invasion and perineural invasion in pancreatic ductal adenocarcinoma with 18F-FDG PET/CT radiomics analysis.

C Jiang, Y Yuan, B Gu, E Ahn, J Kim, D Feng, Q Huang, S Song.

AIM: To develop and validate a predictive model based on 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) radiomics features and clinicopathological parameters to preoperatively identify microvascular invasion (MVI) and perineural invasion (PNI), which are important predictors of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC).
MATERIALS AND METHODS: Preoperative 18F-FDG PET/CT images and clinicopathological parameters of 170 patients in PDAC were collected retrospectively. The whole tumour and its peritumoural variants (tumour dilated with 3, 5, and 10 mm pixels) were applied to add tumour periphery information. A feature-selection algorithm was employed to mine mono-modality and fused feature subsets, then conducted binary classification using gradient boosted decision trees.
RESULTS: For MVI prediction, the model performed best on a fused subset of 18F-FDG PET/CT radiomics features and two clinicopathological parameters, with an area under the receiver operating characteristic curve (AUC) of 83.08%, accuracy of 78.82%, recall of 75.08%, precision of 75.5%, and F1-score of 74.59%. For PNI prediction, the model achieved best prediction results only on the subset of PET/CT radiomics features, with AUC of 94%, accuracy of 89.33%, recall of 90%, precision of 87.81%, and F1 score of 88.35%. In both models, 3 mm dilation on the tumour volume produced the best results.
CONCLUSIONS: The radiomics predictors from preoperative 18F-FDG PET/CT imaging exhibited instructive predictive efficacy in the identification of MVI and PNI status preoperatively in PDAC. Peritumoural information was shown to assist in MVI and PNI predictions.

DOI: https://doi.org/10.1016/j.crad.2023.05.007
Int J Mol Sci. 2023 Jun 09. pii: 9962. [Epub ahead of print]24(12):

Neuropeptide Y Peptide Family and Cancer: Antitumor Therapeutic Strategies.

Manuel Lisardo Sánchez, Francisco D Rodríguez, Rafael Coveñas.

  Currently available data on the involvement of neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) and their receptors (YRs) in cancer are updated. The structure and dynamics of YRs and their intracellular signaling pathways are also studied. The roles played by these peptides in 22 different cancer types are reviewed (e.g., breast cancer, colorectal cancer, Ewing sarcoma, liver cancer, melanoma, neuroblastoma, pancreatic cancer, pheochromocytoma, and prostate cancer). YRs could be used as cancer diagnostic markers and therapeutic targets. A high Y1R expression has been correlated with lymph node metastasis, advanced stages, and perineural invasion; an increased Y5R expression with survival and tumor growth; and a high serum NPY level with relapse, metastasis, and poor survival. YRs mediate tumor cell proliferation, migration, invasion, metastasis, and angiogenesis; YR antagonists block the previous actions and promote the death of cancer cells. NPY favors tumor cell growth, migration, and metastasis and promotes angiogenesis in some tumors (e.g., breast cancer, colorectal cancer, neuroblastoma, pancreatic cancer), whereas in others it exerts an antitumor effect (e.g., cholangiocarcinoma, Ewing sarcoma, liver cancer). PYY or its fragments block tumor cell growth, migration, and invasion in breast, colorectal, esophageal, liver, pancreatic, and prostate cancer. Current data show the peptidergic system's high potential for cancer diagnosis, treatment, and support using Y2R/Y5R antagonists and NPY or PYY agonists as promising antitumor therapeutic strategies. Some important research lines to be developed in the future will also be suggested.

Keywords:  NPY; NPY receptor antagonist; PP; PYY; Y receptor; apoptosis; cancer progression; metastasis; neuropeptide Y; pancreatic polypeptide; peptide YY

DOI:  https://doi.org/10.3390/ijms24129962
Front Oncol. 2023 ;13 1205163

The value of machine learning based radiomics model in preoperative detection of perineural invasion in gastric cancer: a two-center study.

Xujie Gao, Jingli Cui, Lingwei Wang, Qiuyan Wang, Tingting Ma, Jilong Yang, Zhaoxiang Ye.

   Purpose: To establish and validate a machine learning based radiomics model for detection of perineural invasion (PNI) in gastric cancer (GC).
Methods: This retrospective study included a total of 955 patients with GC selected from two centers; they were separated into training (n=603), internal testing (n=259), and external testing (n=93) sets. Radiomic features were derived from three phases of contrast-enhanced computed tomography (CECT) scan images. Seven machine learning (ML) algorithms including least absolute shrinkage and selection operator (LASSO), naïve Bayes (NB), k-nearest neighbor (KNN), decision tree (DT), logistic regression (LR), random forest (RF), eXtreme gradient boosting (XGBoost) and support vector machine (SVM) were trained for development of optimal radiomics signature. A combined model was constructed by aggregating the radiomic signatures and important clinicopathological characteristics. The predictive ability of the radiomic model was then assessed with receiver operating characteristic (ROC) and calibration curve analyses in all three sets.
Results: The PNI rates for the training, internal testing, and external testing sets were 22.1, 22.8, and 36.6%, respectively. LASSO algorithm was selected for signature establishment. The radiomics signature, consisting of 8 robust features, revealed good discrimination accuracy for the PNI in all three sets (training set: AUC = 0.86; internal testing set: AUC = 0.82; external testing set: AUC = 0.78). The risk of PNI was significantly associated with higher radiomics scores. A combined model that integrated radiomics and T stage demonstrated enhanced accuracy and excellent calibration in all three sets (training set: AUC = 0.89; internal testing set: AUC = 0.84; external testing set: AUC = 0.82).
Conclusion: The suggested radiomics model exhibited satisfactory prediction performance for the PNI in GC.

Keywords:  computed tomography; gastric cancer; nomogram; perineural invasion; radiomics

DOI:  https://doi.org/10.3389/fonc.2023.1205163
Cancers (Basel). 2023 Jun 10. pii: 3138. [Epub ahead of print]15(12):

Integrated Neurosurgical Management of Retroperitoneal Benign Nerve Sheath Tumors.

Alberto Benato, Quintino Giorgio D'Alessandris, Marino Murazio, Fabio Pacelli, Pier Paolo Mattogno, Eduardo Fernández, Liverana Lauretti.

  Peripheral nerve sheath tumors (PNST) of the retroperitoneum are rare and are often treated by general surgeons dealing with retroperitoneal cancers. However, resection without the correct microsurgical technique can cause permanent neurological deficits and pain. Here, we discuss our interdisciplinary approach based on the integration of expertise from neurosurgery and abdominal surgery, allowing for both safe exposure and nerve-sparing microsurgical resection of these lesions. We present a series of 15 patients who underwent resection of benign retroperitoneal or pelvic PNST at our institution. The mean age of patients was 48.4 years; 67% were female. Tumors were 14 schwannomas and 1 neurofibroma. Eight patients (53%) reported neurologic symptoms preoperatively. The rate of complete resection was 87% (n = 13); all symptomatic patients showed improvement of their preoperative symptoms. There were no postoperative motor deficits; one patient (7%) developed a permanent sensory deficit. At a mean postoperative follow-up of 31 months, we observed no recurrences. To our best knowledge, this is the second-largest series of benign retroperitoneal PNST consistently managed with microsurgical techniques. Our experience confirms that interdisciplinary management allows for safe treatment of these tumors with good neurological and oncological outcomes.

Keywords:  exoscope; nerve sheath tumor; neurosurgery; peripheral nerve surgery; retroperitoneal

DOI:  https://doi.org/10.3390/cancers15123138
J Breast Cancer. 2023 Jun;26(3): 268-285

Norepinephrine/β2-Adrenergic Receptor Pathway Promotes the Cell Proliferation and Nerve Growth Factor Production in Triple-Negative Breast Cancer.

Meihua Jin, Yan Wang, Tingting Zhou, Wenzhe Li, Qingping Wen.

   PURPOSE: Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC.
METHODS: The expression levels of the β2-adrenergic receptor (β2-AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2-AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2-AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis.
RESULTS: The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2-AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the co-culture assay, the sympathetic adrenergic NE/β2-AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth.
CONCLUSION: These results suggest that NE/β2-AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.

Keywords:  Nerve Growth Factors; Norepinephrine; Receptor, trkA; Receptors, Adrenergic, beta-2; Triple Negative Breast Neoplasms

DOI:  https://doi.org/10.4048/jbc.2023.26.e25
Diagnostics (Basel). 2023 Jun 09. pii: 2016. [Epub ahead of print]13(12):

Clinicopathological Analysis of Complicated Colorectal Cancer: A Five-Year Retrospective Study from a Single Surgery Unit.

Elena Savu, Liviu Vasile, Mircea-Sebastian Serbanescu, Dragos Ovidiu Alexandru, Ioana Andreea Gheonea, Daniel Pirici, Stefan Paitici, Stelian Stefanita Mogoanta.

  Patients with primary colorectal cancer can present with obstructions, tumor bleeding, or perforations, which represent acute complications. This paper aimed to analyze and compare the clinical and pathological profiles of two patient groups: one with colorectal cancer and a related complication and another without any specific complication. We performed a five-year retrospective study on colorectal cancer patients admitted to a surgery unit and comparatively explored the main clinical and pathological features of the tumors belonging to the two groups. A total of 250 patients with colorectal cancer were included in the analysis. Of these, 117 (46.8%) had presented a type of complication. The comparative analysis that examined several clinical and pathological parameters showed a statistically significant difference for unfavorable prognosis factors in the group with complications. This was evident for features such as vascular and perineural invasion, lymph node involvement, pathological primary tumor stage, and TNM stage. Colorectal cancers with a related complication belonged to a group of tumors with a more aggressive histopathologic profile and more advanced stages. Furthermore, the comparable incidence of cases in the two groups of patients warrants further efforts to be made in terms of early detection and prognosis prediction of colorectal cancer.

Keywords:  adenocarcinoma; colorectal cancer; colorectal cancer complications; histopathology; lymph nodes; perineural invasion; vascular invasion

DOI:  https://doi.org/10.3390/diagnostics13122016
Diagnostics (Basel). 2023 Jun 15. pii: 2073. [Epub ahead of print]13(12):

Schwannoma: A Rare Case of Submucosal Gastric Tumor.

Cosmina Fugărețu, Cătalin Mișarca, Lucian Petcu, Raluca Șoană, Andrada Cîrnațiu, Marin Valeriu Surlin, Stefan Patrascu, Sandu Ramboiu.

  Schwannoma is a tumor that originates from the Schwann cells that surround a neuron's axon. This tumor is very rare in the gastrointestinal tract and develops submucosally from intestinal nerve plexuses. The most common location for gastrointestinal schwannomas is the stomach, where they account for only 0.2% of gastric tumors. We present the case of a 56-year-old asymptomatic patient who was diagnosed, following a routine ultrasound examination, with an abdominal tumor. An abdominal MRI confirmed the gastric origin of the tumor. Although a subsequent upper-digestive endoscopic ultrasound was performed, a definitive diagnosis could not be established. Thus, a laparoscopic wedge resection of the stomach was performed. The immunohistochemical examination of the tumor established the diagnosis of benign schwannoma. Despite the availability of advanced endoscopy and imaging techniques, the diagnosis of gastric schwannoma is very rarely preoperative. The immunohistochemical identification of S-100 on the surgical specimen confirmed the diagnosis.

Keywords:  gastric schwannoma; rare gastric tumors; submucosal gastric tumors

DOI:  https://doi.org/10.3390/diagnostics13122073
Medicina (Kaunas). 2023 May 23. pii: 1003. [Epub ahead of print]59(6):

Nerve Ultrasound of Peripheral Nerves in Patients Treated with Immune Checkpoint Inhibitors.

Katharina Kneer, Jan-Hendrik Stahl, Cornelius Kronlage, Paula Bombach, Mirjam Renovanz, Natalie Winter, Alexander Grimm.

  Background and Objectives: Immune checkpoint inhibitors (ICIs) have enriched tumor therapy, improving overall survival. Immunotherapy adverse events (irAEs) occur in up to 50% of patients and also affect the peripheral nervous system. The exact pathomechanism is unclear; however, an autoimmune process is implicated. Thus, the clinical evaluation of irAEs in the peripheral nervous system is still demanding. We retrospectively analyzed nerve ultrasound (NU) data of polyneuropathies (PNPs) secondary to checkpoint inhibitors. Materials and Methods: NU data of patients with PNP symptoms secondary to ICI therapy were retrospectively analyzed using the Ultrasound Pattern Sum Score (UPSS) as a quantitative marker. Our findings were compared with a propensity score match analysis (1:1 ratio) to NU findings in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and chemotherapy-associated PNP patients. Results: In total, 10 patients were included (4 female, mean age 66 ± 10.5, IQR 60-77), where NU was performed in 80%. The UPSS obtained ranged from 0 to 5 (mean 2 ± 1.6, IQR 1-2.5). The morphological changes seen in the NUs resembled sonographic changes seen in chemotherapy-associated PNP (n = 10, mean UPSS 1 ± 1, IQR 0-2) with little to no nerve swelling. In contrast, CIDP patients had a significantly higher UPSS (n = 10, mean UPSS 11 ± 4, IQR 8-13, p < 0.0001). Conclusions: Although an autoimmune process is hypothesized to cause peripheral neurological irAEs, NU showed no increased swelling as seen in CIDP. The nerve swelling observed was mild and comparable to ultrasound findings seen in chemotherapy-associated PNP.

Keywords:  UPSS; immune checkpoint inhibitors; nerve ultrasound; polyneuropathy

DOI:  https://doi.org/10.3390/medicina59061003