bims-netuvo 2024-01-07 papers

Issue of 2024‒01‒07
seven papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Neuroscience. 2023 Dec 27. pii: S0306-4522(23)00554-7. [Epub ahead of print]

Activation of transient receptor potential vanilloid 1 is involved in both pain and tumor growth in a mouse model of cancer pain.

Akari Yoshida, Masayuki Nishibata, Tomoyuki Maruyama, Shogo Sunami, Kyoichi Isono, Tomoyuki Kawamata.

Activation of calcitonin gene-related peptide (CGRP)-positive sensory neurons in the tumor microenvironment has been shown to be involved in tumor growth. However, how CGRP-positive sensory neurons are activated requires elucidation. In this study, we focused on transient receptor potential vanilloid 1 (TRPV1) and examined the contribution of TRPV1 to tumor growth and cancer pain in a mouse cancer model in which Lewis lung carcinoma was subcutaneously inoculated in the left plantar region. Tumor inoculation gradually increased the volumes of the hind paws of wild type (WT) mice over time, but those of both αCGRP knockout mice and TRPV1 knockout mice were significantly smaller than those of WT mice after tumor inoculation. Both TRPV1 and CGRP are therefore suggested to be involved in tumor growth. In an immunohistochemical study, the percentage of phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB)-positive profiles in CGRP-positive dorsal root ganglion (DRG) neurons in WT mice was significantly increased after tumor inoculation. The percentage of p-CREB-positive profiles in CGRP-positive DRG neurons in TRPV1 knockout mice was also increased after tumor inoculation, but was significantly lower than that in WT mice, indicating the contribution of TRPV1 to activation of CGRP-positive DRG neurons. Cancer pain in TRPV1 knockout mice was significantly lower than that in WT mice. In conclusion, TRPV1 is involved in both tumor growth and cancer pain, potentially leading to a novel strategy for the treatment of cancer pain and cancer development. Cancer pain is also suggested to facilitate tumor growth.

Keywords: calcitonin gene-related peptide; dorsal root ganglion; hyperalgesia; pain; tumor growth

DOI: https://doi.org/10.1016/j.neuroscience.2023.12.012

Clin Exp Metastasis. 2024 Jan 05.

Beta-blocker adjunct therapy as a prospective anti-metastatic with cardio-oncologic regulation.

Sachin G Nair, Sonu Benny, Wesley M Jose, Aneesh T P.

The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an anti-metastatic agent demands a significant focus to overrule the incidence of treatment failures. Adrenergic stimulation underlying the metastatic spread paved the way for beta blockers as a breakthrough in repurposing as an anti-metastatic agent. However, the current treatment approach fails to fully harness the versatile potential of the drug in inhibiting probable metastasis. The beta blockers were seen to show a myriad of grip over the pro-metastatic and prognostic parameters of the patient. Novel interventions in immune therapy, onco-hypertension, surgery-induced stress, induction of apoptosis and angiogenesis inhibition have been used as evidence to interpret our objective of discussing the potential adjuvant role of the drug in the existing anti-cancer regimens. Adding weight to the relative incidence of onco-hypertension as an unavoidable side effect from chemotherapy, the slot for an anti-hypertensive agent is necessitated, and we try to suggest beta-blockers to fill this position. However, pointing out the paucity in the clinical study, we aim to review the current status of beta blockers under this interest to state how the drug should be included as a drug of choice in every patient undergoing cancer treatment.

Keywords: Angiogenesis; Apoptosis; Beta blockers; Cardio-oncology; Hypertension; Metastasis

DOI: https://doi.org/10.1007/s10585-023-10258-y

J Cancer Res Ther. 2023 Dec 01. 19(6): 1552-1559

Development and validation of a combined nomogram for predicting perineural invasion status in rectal cancer via computed tomography-based radiomics.

Jiaxuan Liu, Lingling Sun, Xiang Zhao, Xi Lu.

AIM: This study aimed to create and validate a clinic-radiomics nomogram based on computed tomography (CT) imaging for predicting preoperative perineural invasion (PNI) of rectal cancer (RC).MATERIAL AND METHODS: This study enrolled 303 patients with RC who were divided into training (n = 242) and test datasets (n = 61) in an 8:2 ratio with all their clinical outcomes. A total of 3,296 radiomic features were extracted from CT images. Five machine learning (ML) models (logistic regression (LR)/K-nearest neighbor (KNN)/multilayer perceptron (MLP)/support vector machine (SVM)/light gradient boosting machine (LightGBM)) were developed using radiomic features derived from the arterial and venous phase images, and the model with the best diagnostic performance was selected. By combining the radiomics and clinical signatures, a fused nomogram model was constructed.
RESULTS: After using the Mann-Whitney U-test and least absolute shrinkage and selection operator (LASSO) to remove redundant features, the MLP model proved to be the most efficient among the five ML models. The fusion nomogram based on MLP prediction probability further improves the ability to predict the PNI status. The area under the curve (AUC) of the training and test sets was 0.883 and 0.889, respectively, which were higher than those of the clinical (training set, AUC = 0.710; test set, AUC = 0.762) and radiomic models (training set, AUC = 0.840; test set, AUC = 0.834).
CONCLUSIONS: The clinical-radiomics combined nomogram model based on enhanced CT images efficiently predicted the PNI status of patients with RC.

DOI: https://doi.org/10.4103/jcrt.jcrt_2633_22

J Orthop Case Rep. 2023 Dec;13(12): 53-57

Successful Outcome Following Limb Conservation Surgery for a Recurrent Malignant Peripheral Nerve Sheath Tumour: A Case Report.

Marlon M Mencia, Reena Moonsie.

Introduction: A malignant peripheral nerve sheath tumor (MPNST) is a rare soft-tissue sarcoma with a high recurrence rate and poor prognosis. Early diagnosis and complete surgical excision are the fundamental principles of treatment. A benign presentation and low clinical suspicion often delay definitive diagnosis, and en bloc excision may not be feasible depending on the size and location of the tumor. We describe a rare case of a recurrent MPNST successfully treated by surgical excision.Case Report: A 35-year-old woman presented with a rapidly growing painful mass 3 months following incomplete removal of a MPNST from her forearm. Staging investigations showed no evidence of metastasis. The patient underwent en-bloc surgical excision, split skin grafting, and adjuvant radiation therapy. Histology and immunohistochemical analysis confirmed a MPNST. Five years after having surgery, the patient shows no evidence of recurrence and has excellent function.
Conclusion: MPNST are rare soft tissue sarcomas that can masquerade as benign lumps. There is a paucity of literature on the outcome of surgically-treated recurrent disease. Notwithstanding local recurrence of the tumor, complete surgical excision can yield excellent clinical results.

Keywords: Malignant peripheral nerve sheath tumor; en bloc excision; radiation therapy; recurrence; soft-tissue sarcoma

DOI: https://doi.org/10.13107/jocr.2023.v13.i12.4076

Clin Epigenetics. 2024 Jan 04. 16(1): 9

Malignant peripheral nerve sheath tumor (MPNST) and MPNST-like entities are defined by a specific DNA methylation profile in pediatric and juvenile population.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) account for 3-10% of pediatric sarcomas, 50% of which occur in neurofibromatosis type 1 (NF1). Sporadic MPNSTs diagnosis may be challenging due to the absence of specific markers, apart from immunohistochemical H3K27me3 loss. DNA methylation (DNAm) profiling is a useful tool for brain and mesenchymal neoplasms categorization, and MPNSTs exhibit a specific DNAm signature. An MPNST-like group has recently been recognized, including pediatric tumors with retained H3K27me3 mark and clinical/histological features not yet well explored. This study aims to characterize the DNAm profile of pediatric/juvenile MPNSTs/MPNST-like entities and its diagnostic/prognostic relevance.RESULTS: We studied 42 tumors from two groups. Group 1 included 32 tumors histologically diagnosed as atypical neurofibroma (ANF) (N = 5) or MPNST (N = 27); group 2 comprised 10 tumors classified as MPNST-like according to Heidelberg sarcoma classifier. We performed further immunohistochemical and molecular tests to reach an integrated diagnosis. In group 1, DNAm profiling was inconclusive for ANF; while, it confirmed the original diagnosis in 12/27 MPNSTs, all occurring in NF1 patients. Five/27 MPNSTs were classified as MPNST-like: Integrated diagnosis confirmed MPNST identity for 3 cases; while, the immunophenotype supported the change to high-grade undifferentiated spindle cell sarcoma in 2 samples. The remaining 10/27 MPNSTs variably classified as schwannoma, osteosarcoma, BCOR-altered sarcoma, rhabdomyosarcoma (RMS)-MYOD1 mutant, RMS-like, and embryonal RMS or did not match with any defined entity. Molecular analysis and histologic review confirmed the diagnoses of BCOR, RMS-MYOD1 mutant, DICER1-syndrome and ERMS. Group 2 samples included 5 high-grade undifferentiated sarcomas/MPNSTs and 5 low-grade mesenchymal neoplasms. Two high-grade and 4 low-grade lesions harbored tyrosine kinase (TRK) gene fusions. By HDBSCAN clustering analysis of the whole cohort we identified two clusters mainly distinguished by H3K27me3 epigenetic signature. Exploring the copy number variation, high-grade tumors showed frequent chromosomal aberrations and CDKN2A/B loss significantly impacted on survival in the MPNSTs cohort.
CONCLUSION: DNAm profiling is a useful tool in diagnostic work-up of MPNSTs. Its application in a retrospective series collected during pre-molecular era contributed to classify morphologic mimics. The methylation group MPNST-like is a 'hybrid' category in pediatrics including high-grade and low-grade tumors mainly characterized by TRK alterations.

Keywords: DNA methylation; H3K27 trimethylation; Malignant peripheral nerve sheath tumors; Sarcoma classifier

DOI: https://doi.org/10.1186/s13148-023-01621-7

IJU Case Rep. 2024 Jan;7(1): 56-59

Prostatic schwannoma discovered after laparoscopic radical prostatectomy: A case report with literature review.

Tanan Bejrananda, Nattawit Jakjaroenrit.

Background: Schwannomas originating in the prostate are extremely rare. We present a case of prostatic schwannoma in a 66-year-old male with lower urinary tract symptoms. Preoperative evaluation revealed a prostatic mass, and the definitive diagnosis was made through laparoscopic radical prostatectomy.Case presentation: A 66-year-old male presented with persistent lower urinary tract symptoms for 5 years and a prostate-specific antigen level of 0.63 ng/mL. MRI showed a well-defined solid cystic mass in the posterolateral basal right peripheral zone, causing superior displacement of the right seminal vesicle. Laparoscopic radical prostatectomy was performed, confirming a periprostatic schwannoma.
Conclusion: This case highlights the rarity of prostatic schwannomas and their association with lower urinary tract symptoms. MRI plays a crucial role in identifying prostatic masses, while laparoscopic radical prostatectomy can serve as a diagnostic and therapeutic approach for prostatic schwannomas. Increased awareness of this rare entity is essential for accurate diagnosis and optimal management.

Keywords: case report; laparoscopic radical prostatectomy; prostate; schwannoma

DOI: https://doi.org/10.1002/iju5.12667