bims-netuvo 2024-08-04 papers

Issue of 2024‒08‒04
four papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

J Anus Rectum Colon. 2024 ;8(3): 195-203

Does Colorectal Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer Increase Perineural Invasion?

Hiroki Kato, Kazushige Kawai, Daisuke Nakano, Akira Dejima, Ichiro Ise, Soichiro Natsume, Misato Takao, Satomi Shibata, Toshiro Iizuka, Tetsuo Akimoto, Yuichiro Tsukada, Masaaki Ito.

Objectives: To clarify whether self-expandable metallic stent (SEMS) placement for obstructive colorectal cancer (CRC) increases perineural invasion (PNI), thereby worsening the prognosis.Methods: In total, 1022 patients with pathological T3 or T4 colon or rectosigmoid cancer who underwent resection were retrospectively reviewed. The study patients were divided into a no obstruction group (n=693), obstruction without stent group (n=251), and obstruction with stent group (n=78), and factors demonstrating an independent association with PNI, the difference in PNI incidence and severity between groups, and the association between PNI and the duration from SEMS placement to surgery were investigated. Survival analysis was performed for each group.
Results: On multivariate analysis, SEMS placement (hazard ratio [HR]: 2.08) was independently associated with PNI whereas SEMS placement was not. PNI occurred in 39%, 45%, and 68% of the no obstruction, obstruction without stent, and obstruction with stent group, respectively. In the obstruction with stent group, the proportion of PNI was not associated with the duration from SEMS placement to surgery. Extramural PNI, an advanced form of PNI, demonstrated no increase with increasing interval. The five-year OS was 86.3%, 76.7%, and 73.1% in no obstruction, obstruction without stent, and obstruction with stent group, respectively. On multivariate analysis, obstruction was an independent risk factor of decreased OS (HR: 1.57) whereas SEMS placement was not.
Conclusions: The prognosis was comparable between patients with SEMS placement and those with an obstruction who did not undergo SEMS placement, thus demonstrating that SEMS is a viable, therapeutic option for BTS.

Keywords: bridge to surgery; colon cancer; obstruction; perineural invasion; self-expanding metallic stent

DOI: https://doi.org/10.23922/jarc.2023-057

Eur J Pharmacol. 2024 Jul 25. pii: S0014-2999(24)00549-1. [Epub ahead of print] 176860

Efficacy of GluN2B-Containing NMDA Receptor Antagonist for Antitumor and Antidepressant Therapy in Non-small Cell Lung Cancer.

Weiming Bian, Ye Chen, Yanjie Ni, Bihua Lv, Bo Gong, Kaiyuan Zhu, Wei Gao, Linghui Zeng, Wen Lu, Bin Zhang.

Non-small cell lung cancer (NSCLC) is the predominant subtype of lung cancer. Evidence suggests that the ionotropic glutamate receptor N-methyl-D-aspartate (NMDA) receptor, a critical molecule in the central nervous system, is expressed in NSCLC. However, the specific expression patterns, subcellular localization, functional modulation, and pathological implications of NMDA receptor subtypes in NSCLC have not been fully elucidated. In this study, we employed a multi-disciplinary approach, combining biochemical and molecular biology with electrophysiological recordings and behavioral assays, to investigate these aspects. We reveal the expression of GluN2B-containing NMDA receptors in A549 and H460 NSCLC cell lines and the induction of NMDA receptor-mediated currents by glutamate in A549 cells. Furthermore, the GluN2B-specific inhibitors ifenprodil and Ro 25-6981 significantly reduced cell viability and migration, while promoting apoptosis. Importantly, intraperitoneal administration of ifenprodil in nude mice inhibited the growth of subcutaneous tumors derived from A549 and H460 cells and ameliorated depression-like behaviors. These findings underscore the potential antiproliferative effects of ifenprodil and Ro 25-6981 and suggest that GluN2B-containing NMDA receptors may represent novel therapeutic targets for NSCLC, with the added benefit of potential antidepressant action.

Keywords: A549; GluN2B; H460; NMDA receptors; Non-small cell lung cancer; antidepressant

DOI: https://doi.org/10.1016/j.ejphar.2024.176860

Clin Cancer Res. 2024 Aug 02.

Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics.

PURPOSE: Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of PNST in cancer predisposition syndrome NF1.EXPERIMENTAL DESIGN: cfDNA was isolated from plasma samples of a novel cohort of 101 NF1 patients and 21 healthy controls and underwent whole genome sequencing. We investigated diagnosis-specific signatures of copy number alterations (CNA) with in silico size selection as well as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end-motifs, and fragment non-negative matrix factorization (NMF) signatures.
RESULTS: The novel cohort of NF1 patients validated that our previous cfDNA CNA-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management.
CONCLUSIONS: Novel cfDNA fragmentomic signatures distinguish atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 and provides a blueprint for de-centralizing non-invasive cancer surveillance in hereditary cancer syndromes.

DOI: https://doi.org/10.1158/1078-0432.CCR-24-0797

Cureus. 2024 Jun;16(6): e63295

Ancient Schwannoma Along the Patellar Tendon: Unveiling a Rare Clinical Phenomenon With Literature Review.

Siddhant Pundalik Pol, Sunil K Bhosale, Jigar Desai, Dipen Ariwala, Chintan Vaidya, Shahrukh Azad, Falgun Dhawale, Navnath Jawale.

Ancient schwannoma, a rare subtype of schwannoma, a benign tumor originating from nerve sheaths, can arise from various nerves, except for the optic, olfactory, spinal, and autonomic nervous systems. Schwannomas are typically characterized by the presence of neoplastic Schwann cells and tend to develop eccentrically. Malignant transformations of schwannomas are exceptionally uncommon. In this case report, a 42-year-old male presented with a painful lump on the front of his left knee. The lump was described as an extra-articular swelling below the kneecap, situated over the patellar tendon. Initially, ultrasonography (USG) indicated the presence of a slow-flow vascular malformation in the infrapatellar region of the left knee. However, subsequent magnetic resonance imaging (MRI) revealed a well-defined mass in the subcutaneous plane below the knee, with minimal septations, leading to an initial suspicion of a large sebaceous cyst. Further investigation through histopathological analysis confirmed the diagnosis of an extra-articular schwannoma. This finding highlights the importance of thorough examination and diagnostic techniques in differentiating between various types of soft tissue masses. Schwannomas, although uncommon in certain locations, should be considered in the differential diagnosis of painful lumps, even in atypical anatomical sites such as the knee.

Keywords: extra-articular tumor; infra-patellar swelling; knee joint schwannoma; orthopedics surgery; schwannoma

DOI: https://doi.org/10.7759/cureus.63295