bims-netuvo 2024-07-28 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–07–28
sixteen papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Perineural Invasion in Cervical Cancer: A Hidden Trail for Metastasis.
The Intersection of the Nervous System and Breast Cancer.
Development and Validation of a Biparametric MRI Deep Learning Radiomics Model with Clinical Characteristics for Predicting Perineural Invasion in Patients with Prostate Cancer.
Squamous Metaplasia in a Schwannoma: A Unique Histologic Finding.
Rapid Progression of a T3-T4 Paraspinal Schwannoma in a Young Female.
A rare presentation of thyroid malignant peripheral nerve sheath tumor in neurofibromatosis type 1 delineated by FDG PET/CT: A case report and literature review.
Collection of Rare Peripheral Nerve Tumors-Insights from the German Registry.
Schwannoma of Common Bile Duct: A Clinico-Radiologic Diagnostic Quagmire - A Case Report.
Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.
Schwann cells and enteric glial cells: Emerging stars in colorectal cancer.
Nerve Sheath Myxoma in Pregnancy: A Case Report.
Tumor microenvironment (Part I): Tissue integrity in a rat model of peripheral neural cancer.
Clinicopathologic characteristics and prognostic factors of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study.
Rare primary intrapulmonary malignant peripheral nerve sheath tumor showing significant response to sintilimab: A case report and literature review.
A retrospective study at a single center examining risk factors associated with central nervous system involvement in individuals diagnosed with diffuse large B-cell lymphoma.
Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress.

Diagnostics (Basel). 2024 Jul 14. pii: 1517. [Epub ahead of print]14(14):

Perineural Invasion in Cervical Cancer: A Hidden Trail for Metastasis.

Guoqiang Chen, Hao Sun, Yunxia Chen, Li Wang, Ouyi Song, Jili Zhang, Dazhi Li, Xiaojun Liu, Lixia Feng.

  Perineural invasion (PNI), the neoplastic invasion of nerves, is an often overlooked pathological phenomenon in cervical cancer that is associated with poor clinical outcomes. The occurrence of PNI in cervical cancer patients has limited the promotion of Type C1 surgery. Preoperative prediction of the PNI can help identify suitable patients for Type C1 surgery. However, there is a lack of appropriate preoperative diagnostic methods for PNI, and its pathogenesis remains largely unknown. Here, we dissect the neural innervation of the cervix, analyze the molecular mechanisms underlying the occurrence of PNI, and explore suitable preoperative diagnostic methods for PNI to advance the identification and treatment of this ominous cancer phenotype.

Keywords:  Schwann cells; Type C1 surgery; cervical cancer; neurotrophic factors; perineural invasion

DOI:  https://doi.org/10.3390/diagnostics14141517
Cancer Lett. 2024 Jul 24. pii: S0304-3835(24)00527-5. [Epub ahead of print] 217132

The Intersection of the Nervous System and Breast Cancer.

Yutong Liu, Shiqi Yin, Guanyu Lu, Ye Du.

  Breast cancer (BC) represents a paradigm of heterogeneity, manifesting as a spectrum of molecular subtypes with divergent clinical trajectories. It is fundamentally characterized by the aberrant proliferation of malignant cells within breast tissue, a process modulated by a myriad of factors that govern its progression. Recent endeavors outline the interplay between BC and the nervous system, illuminate the complex symbiosis between neural structures and neoplastic cells, and elucidate nerve dependence as a cornerstone of BC progression. This includes the neural modulations on immune response, neurovascular formation, and multisystem interactions. Such insights have unveiled the critical impact of neural elements on tumor dynamics and patient prognosis. This revelation beckons a deeper exploration into the neuro-oncological interface, potentially unlocking novel therapeutic vistas. This review endeavors to delineate the intricate mechanisms between the nervous system and BC, aiming to accentuate the implications and therapeutic strategies of this intersection for tumor evolution and the formulation of innovative therapeutic approaches.

Keywords:  cancer neuroscience; innervation; neural microenvironment; neuro-dependence; peripheral nerve damage

DOI:  https://doi.org/10.1016/j.canlet.2024.217132
Acad Radiol. 2024 Jul 22. pii: S1076-6332(24)00447-1. [Epub ahead of print]

Development and Validation of a Biparametric MRI Deep Learning Radiomics Model with Clinical Characteristics for Predicting Perineural Invasion in Patients with Prostate Cancer.

Yue-Yue Zhang, Hui-Min Mao, Chao-Gang Wei, Tong Chen, Wen-Lu Zhao, Liang-Yan Chen, Jun-Kang Shen, Wan-Liang Guo.

   RATIONALE AND OBJECTIVES: Perineural invasion (PNI) is an important prognostic biomarker for prostate cancer (PCa). This study aimed to develop and validate a predictive model integrating biparametric MRI-based deep learning radiomics and clinical characteristics for the non-invasive prediction of PNI in patients with PCa.
MATERIALS AND METHODS: In this prospective study, 557 PCa patients who underwent preoperative MRI and radical prostatectomy were recruited and randomly divided into the training and the validation cohorts at a ratio of 7:3. Clinical model for predicting PNI was constructed by univariate and multivariate regression analyses on various clinical indicators, followed by logistic regression. Radiomics and deep learning methods were used to develop different MRI-based radiomics and deep learning models. Subsequently, the clinical, radiomics, and deep learning signatures were combined to develop the integrated deep learning-radiomics-clinical model (DLRC). The performance of the models was assessed by plotting the receiver operating characteristic (ROC) curves and precision-recall (PR) curves, as well as calculating the area under the ROC and PR curves (ROC-AUC and PR-AUC). The calibration curve and decision curve were used to evaluate the model's goodness of fit and clinical benefit.
RESULTS: The DLRC model demonstrated the highest performance in both the training and the validation cohorts, with ROC-AUCs of 0.914 and 0.848, respectively, and PR-AUCs of 0.948 and 0.926, respectively. The DLRC model showed good calibration and clinical benefit in both cohorts.
CONCLUSION: The DLRC model, which integrated clinical, radiomics, and deep learning signatures, can serve as a robust tool for predicting PNI in patients with PCa, thus aiding in developing effective treatment strategies.

Keywords:  Deep learning; Perineural invasion; Prediction model; Prostate cancer; Radiomics

DOI:  https://doi.org/10.1016/j.acra.2024.07.013
Cureus. 2024 Jun;16(6): e62720

Squamous Metaplasia in a Schwannoma: A Unique Histologic Finding.

John Grove, Rana Naous.

  Schwannomas are benign peripheral nerve sheath tumors that originate from Schwann cells and characteristically display a biphasic appearance of compact hypercellular and myxoid hypocellular areas, named Antoni A and Antoni B areas, respectively. While most schwannomas arise sporadically, they can be associated with familial tumor syndromes such as neurofibromatosis type 2 and Carney complex. Herein, we report a case of a 61-year-old female who had a schwannoma resected from her upper extremity that later revealed a focus of squamous metaplasia associated with the schwannoma, a finding that has not yet been reported in the literature. This unique finding may aid pathologists in the future when confronted with such an atypical presentation in a schwannoma.

Keywords:  histologic; metaplasia; nerve sheath; schwannoma; squamous

DOI:  https://doi.org/10.7759/cureus.62720
Cureus. 2024 Jun;16(6): e62773

Rapid Progression of a T3-T4 Paraspinal Schwannoma in a Young Female.

Riya Rupareliya, Monica Khadka, Devaun M Reid, Scott Taylor.

  This case report presents an unusual incidence of a T3-T4 paraspinal schwannoma in a 22-year-old female, highlighting its clinical significance due to its atypical presentation and growth rate. Schwannomas, benign peripheral nerve sheath tumors, are typically slow-growing and present with minimal or no neuropathic symptoms. However, this case deviated from the norm, with the patient experiencing significant neuropathic pain and rapid tumor growth from 37 mm to 55 mm over a period of six months, necessitating surgical intervention. Unique to this case was the presence of a positive Tinel sign and localized neuropathic back pain, features not commonly associated with paraspinal schwannomas. Through MRI and histological evaluation, the diagnosis of schwannoma was confirmed, underlining the necessity of considering paraspinal schwannomas in differential diagnoses for patients presenting similar symptoms. This case contributes to the medical literature by emphasizing the variability in presentation and growth rates of schwannomas, reinforcing the need for a thorough evaluation and an individualized approach to management in young patients presenting with neuropathic pain and positive neurological signs.

Keywords:  neuropathic pain; paraspinal schwannoma; peripheral nerve sheath tumors; rapid-growing tumor; tinel test

DOI:  https://doi.org/10.7759/cureus.62773
Asia Ocean J Nucl Med Biol. 2024 ;12(2): 174-178

A rare presentation of thyroid malignant peripheral nerve sheath tumor in neurofibromatosis type 1 delineated by FDG PET/CT: A case report and literature review.

Serin Moghrabi, Nabeela Al-Hajaj, Fatimah Abu Aljaaz, Omar Jaber, Akram Al-Ibraheem.

  Malignant peripheral nerve sheath tumors (MPNST) are rare, aggressive soft tissue sarcomas that arise from peripheral nerves and often present a diagnostic and therapeutic challenge. They can occur sporadically or in association with neurofibromatosis type 1 (NF1), a genetic disorder caused by mutations in the NF1 gene. This report presents the unique case of a 33-year-old male with progressive dry cough, hoarseness, and neck swelling who underwent a total thyroidectomy, revealing a high-grade malignant peripheral nerve sheath tumor invading the thyroid. FDG PET/CT led to the additional diagnosis of NF1. This case stands out due to the rarity of finding an MPNST within the thyroid and the simultaneous identification of NF1. It underscores the importance of screening MPNST patients for NF1 and vice versa, spotlighting the expanding role of FDG PET/CT in comprehensive evaluations. To our knowledge, this report presents the first case of NF1-associated MPNST with thyroid involvement worldwide.

Keywords:  Malignant peripheral nerve; Neurofibromatosis type 1; PET/CT A B S T R A C T; Thyroid; sheath tumor

DOI:  https://doi.org/10.22038/AOJNMB.2024.76555.1539
Cancers (Basel). 2024 Jul 20. pii: 2599. [Epub ahead of print]16(14):

Collection of Rare Peripheral Nerve Tumors-Insights from the German Registry.

Peripheral Nerve Tumor Study

  The most common peripheral nerve tumors are of a benign nature and include schwannoma or neurofibroma. In rare cases, other tumors or non-tumorous lesions can mimic peripheral nerve tumors clinically or radiologically. Based on data from the multicentric German Peripheral Nerve Tumor Registry (PNTR), which encompasses current information on 315 surgically treated patients from three high-volume centers, we present 61 cases of rare tumors and lesions that mimic tumors associated with peripheral nerves. This cohort displays considerable heterogeneity, featuring a broad spectrum of morphological features and biological potentials. Histopathological diagnoses include various intrinsic peripheral nerve tumors such as malignant peripheral nerve tumors (MPNSTs) (n = 13), perineurioma (n = 17), and hybrid nerve sheath tumors (HPNSTs, comprising schwannoma/perineurioma and schwannoma/neurofibroma) (n = 14), as well as atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) (n = 1). Additionally, the cohort encompasses extrinsic tumorous lesions like lymphoma (n = 3), lymphangioma (n = 2), hemangioma (n = 2), solitary fibrous tumor (n = 2), metastatic disease (n = 1), and single cases of other rare tumor entities (n = 6). An overview of the underlying pathology, imaging features, and clinical presentation is provided, with a brief description of each entity. A definitive preoperative differentiation between benign peripheral nerve tumors and rare intrinsic and extrinsic tumors is often not possible. Clinical examination and subtle imaging clues can at least indicate the possibility of a rare entity. The basic requirement is close cooperation between radiologists, neurologists, neuropathologists, and neurosurgeons at a specialized center to develop a multidisciplinary concept and offer the patient the best therapeutic approaches.

Keywords:  hybrid nerve sheath tumor; malignant nerve sheath tumor; neurofibromatosis; perineurioma; rare peripheral nerve tumor

DOI:  https://doi.org/10.3390/cancers16142599
GE Port J Gastroenterol. 2023 Oct 25. 1-8

Schwannoma of Common Bile Duct: A Clinico-Radiologic Diagnostic Quagmire - A Case Report.

Shilpi Thakur, Nihar Ranjan Dash, Adarsh Barwad, Prasenjit Das, Kumble S Madhusudhan, Rajni Yadav.

   Background: Schwannomas are benign nerve sheath tumors that are extremely rare in the biliary tract. A comprehensive review of literature enumerated approximately 30 case reports of schwannoma in the biliary tract tree and porta hepatis region.
Case Presentation: We report a case of a 40-year-old female who presented with abdominal pain. Imaging revealed a mass at the porta hepatis extending from the portal bifurcation till the hilum encasing the main portal vein and abutting the right portal vein. Differentials of carcinoma, lymphoma, and mesenchymal tumor were kept. Ultrasound-guided biopsy of the mass showed a benign nerve sheath tumor, immunopositive for S100. The histopathological evaluation of the excised mass confirmed the origin of mass in the common bile duct.
Conclusions: Our case highlights that schwannomas, though benign, can mimic a carcinoma or lymphoma if present at a rare site such as bile ducts. An exhaustive clinical and radiological workup with diligent histopathological evaluation is mandatory in dealing with such rare cases as radical surgery and chemotherapy can be avoided in such patients.

Keywords:  Benign nerve sheath tumor; Common bile duct; Porta hepatis; Schwannoma

DOI:  https://doi.org/10.1159/000534300
Front Immunol. 2024 ;15 1384623

Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.

Siddhi N Paudel, Brian J Hutzen, Katherine E Miller, Elizabeth A R Garfinkle, Chun-Yu Chen, Pin-Yi Wang, Andrea M Glaspell, Mark A Currier, Emily M Ringwalt, Louis Boon, Elaine R Mardis, Mitchell S Cairo, Nancy Ratner, Rebecca D Dodd, Kevin A Cassady, Timothy P Cripe.

   Introduction: Malignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness.
Methods: Here we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy's antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others.
Results: Myelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment.
Discussion: In summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.

Keywords:  T-VEC; immunotherapy; macrophage targeting; malignant peripheral nerve sheath tumors; oncolytic virotherapy; pexidartinib; trabectedin; tumor microenvironment

DOI:  https://doi.org/10.3389/fimmu.2024.1384623
Biochim Biophys Acta Rev Cancer. 2024 Jul 24. pii: S0304-419X(24)00091-X. [Epub ahead of print] 189160

Schwann cells and enteric glial cells: Emerging stars in colorectal cancer.

Kexin He, Hao Wang, Ruixue Huo, Shu-Heng Jiang, Junli Xue.

  Cancer neuroscience, a promising field dedicated to exploring interactions between cancer and the nervous system, has attracted growing attention. The gastrointestinal tracts exhibit extensive innervation, notably characterized by intrinsic innervation. The gut harbors a substantial population of glial cells, including Schwann cells (SCs) wrapping axons of neurons in the peripheral nervous system and enteric glial cells (EGCs) intricately associated with intrinsic innervation. Glial cells play a crucial role in maintaining the physiological functions of the intestine, encompassing nutrient absorption, barrier integrity, and immune modulation. Nevertheless, it has only been in recent times that the significance of glial cells within colorectal cancer (CRC) has begun to receive considerable attention. Emerging data suggests that glial cells in the gut contribute to the progression and metastasis of CRC, by interacting with cancer cells, influencing inflammation, and modulating the tumor microenvironment. Here, we summarize the significant roles of glial cells in the development and progression of CRC and discuss the latest technologies that can be integrated into this field for in-depth exploration, as well as potential specific targeted strategies for future exploration to benefit patients.

Keywords:  Colorectal carcinoma; Enteric glia; Microenvironment; Neuroglia

DOI:  https://doi.org/10.1016/j.bbcan.2024.189160
Diseases. 2024 Jul 18. pii: 164. [Epub ahead of print]12(7):

Nerve Sheath Myxoma in Pregnancy: A Case Report.

Elena De Chiara, Valerio Gaetano Vellone, Jacopo Ferro, Chiara Trambaiolo Antonelli, Liliana Piro, Stefano Avanzini, Valentina Prono, Andrea Beccaria, Monica Muraca, Ramona Tallone.

  Nerve sheath myxoma (NSM) is a rare benign peripheral nerve sheath tumor that affects young adults. NSMs are asymptomatic, slow-growing swellings located in the upper extremities, more rarely in the lower extremities. Given the high risk of recurrence, it is recommended to perform a complete exeresis. To our knowledge, the evolution and management of NMS during pregnancy have not been described yet. We report the first case of recurrent pretibial NSM in a pregnant girl and its follow-up and outcome during and after pregnancy. NSM is difficult to diagnose clinically or using imaging. The final diagnosis remains histopathological. It is known how various types of benign and malignant skin tumors can develop or change during pregnancy. With our case, however, we documented that pregnancy does not affect the growth and evolution of NSM. Given the benign nature of the lesions and their tendency to grow slowly, during pregnancy, follow-up of NSMs can be conducted through ultrasonography and surgical treatment postponed after delivery. Our case highlights the importance of careful monitoring and individualized decision making, especially in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Our case highlights the importance of a careful monitoring and a tailored treatment in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Considering the benign nature of the lesions and their tendency to grow slowly, follow-up of NSMs during pregnancy can be conducted through ultrasonography, and surgical treatment can be postponed after delivery.

Keywords:  immunohistochemistry; leg soft tissue tumor; nerve sheath myxoma; neurothekeoma; peripheral nerve sheath tumor; pregnancy

DOI:  https://doi.org/10.3390/diseases12070164
Heliyon. 2024 Jul 15. 10(13): e33932

Tumor microenvironment (Part I): Tissue integrity in a rat model of peripheral neural cancer.

Ahmad Maqboul, Bakheet Elsadek.

  ICAM-1 (intercellular adhesion molecule 1) and MPZ (myelin protein zero) are thought to be a factor in the integrity of nerve tissues. In this report, we attempted to trace the expression of ICAM-1, responsible for cell-to-cell adhesion, and of MPZ, the main constituent of myelin sheath, in malignant tissues of the sciatic nerve (SN) in inbred male Copenhagen rats. AT-1 Cells (anaplastic tumor 1) were injected in the perineurial sheath, and tissues of the SNs were collected after 7, 14 and 21 days and compared to a sham-operated group of rats (n = 6 each). Tissues were sectioned and histologically examined, under light microscope, and stained for measuring the immunoreactivity of ICAM-1 and MPZ under laser scanning microscope. The cancer model was established, and the tumor growth was confirmed. ICAM-1 showed severe decreases, proportional to the growing anaplastic cells, as compared to the sham group. MPZ revealed, however, a distinct defensive pattern before substantially decreasing in a comparison with sham. These results support the notion that malignancies damage peripheral nerves and cause severe axonal injury and loss of neuronal integrity, and clearly define the role of ICAM-1 and MPZ in safeguarding the nerve tissues.

Keywords:  AT-1; Anaplastic tumor 1; CD54; Cancer cells; Copenhagen rat; ICAM-1; Intercellular adhesion molecule 1; MPZ; Myelin protein zero; Neural cancer; P0; Protein 0; TME; Tissue integrity; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.heliyon.2024.e33932
Int J Gynaecol Obstet. 2024 Jul 19.

Clinicopathologic characteristics and prognostic factors of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study.

Yan-Hong Lyu, Hai-Xia Liu, Xue Han, Peng Yuan, Ming-Yi Wang, Yuan-Yuan He, Jun-Li Ge, Wei Zou, Ru Jing, Cai-Shi Xin, Hong Yang, Bi-Liang Chen, Gao-Wen Chen, Jia Li.

   OBJECTIVE: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC).
METHODS: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis.
RESULTS: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022).
CONCLUSION: Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.

Keywords:  high grade; mixed histology; neuroendocrine carcinoma of the cervix; perineural invasion; prognosis; treatment

DOI:  https://doi.org/10.1002/ijgo.15771
Oncol Lett. 2024 Sep;28(3): 423

Rare primary intrapulmonary malignant peripheral nerve sheath tumor showing significant response to sintilimab: A case report and literature review.

Yunqi Chen, Ting Chen, Wanshan Zhu, Luzhen Li, Cantu Fang, Huatang Zhang.

  Primary pulmonary malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with a low incidence, poor prognosis and limited treatment options. The present study reported a case of lung MPNST in a 63-year-old male patient without any pulmonary symptoms. Immunohistochemical analysis of the tumor indicated a programmed death-ligand 1 (PD-L1) expression tumor proportion score of 60%. A total of six courses of sintilimab were used in this patient and a remarkable response was achieved. In summary, sintilimab single-agent immunotherapy may be a novel treatment for pulmonary MPNST. When encountering analogous cases in the future, oncologists can test for the expression of PD-L1 in patients to guide the therapy's design.

Keywords:  immunotherapy; lung; malignant peripheral nerve sheath tumor; programmed death-ligand 1 expression; sintilimab

DOI:  https://doi.org/10.3892/ol.2024.14556
Clin Neurol Neurosurg. 2024 Jul 14. pii: S0303-8467(24)00341-X. [Epub ahead of print]244 108454

A retrospective study at a single center examining risk factors associated with central nervous system involvement in individuals diagnosed with diffuse large B-cell lymphoma.

Wei Chen, Hu Liu, Shu-Ling Hou, Xi Li, Li Li, Ke Lian, Xiao-Bo Wu, Xiao Zhang.

   OBJECTIVE: The aim of this study is to identify risk factors contributing to central nervous system (CNS) invasion and to validate the suitability of the Central Nervous System International Prognostic Index (CNS-IPI) for individuals afflicted with diffuse large B-cell lymphoma (DLBCL).
METHODS: Based on the presence or absence of CNS invasion, 365 patients were stratified into two groups: the CNS group and the non-CNS group. The clinical data of the patients were retrospectively analyzed using univariate and multivariate analysis, and the differences in survival curves were compared. The dependent variable in this study was the presence or absence of CNS invasion, while the independent variables included age, stage, extranodal involvement, renal/adrenal involvement, and others. Statistical methods included the chi-squared test and Fisher's exact test for intergroup comparison and binary logistic regression for multi-factor analysis. The related risk factors were modeled using the Cox proportional hazards model. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to compare the differences between survival curves. The optimal cutoff value of beta-2 (β2)-microglobulin was determined through the utilization of a receiver operating characteristic (ROC) curve. All P values were bidirectional, and P < 0.05 was considered statistically significant. Both SPSS 23.0 (IBM Inc., Armonk, NY, USA) and RStudio (R software version 4.0.2, R Project for Statistical Computing) software were used for data processing RESULTS: The five factors of the CNS-IPI were related to the prognosis of patients with CNS invasion. Bone involvement, albumin < 40 g/L, and P53 protein (+) were the risk factors for CNS invasion in patients with DLBCL. However, prognostic factors such as double strike, testicular involvement, breast involvement, uterine involvement, and bone marrow involvement did not apply to these patients. It was also discovered that elderly patients with DLBCL with reduced albumin levels were more susceptible to CNS invasion. Furthermore, extranodal involvement at multiple sites and elevated beta-2 (β2) microglobulin were independent prognostic factors CONCLUSION: Patients older than 60 years with DLBCL and decreased albumin are at increased risk for CNS invasion. In addition to the five factors in the CNS-IPI, bone involvement, albumin levels < 40 g/L, and P53 protein expression are risk factors affecting the prognosis of CNS invasion in patients with DLBCL.

Keywords:  Diffuse large B-cell lymphoma; Prognosis; Risk factor; Secondary central nervous system invasion

DOI:  https://doi.org/10.1016/j.clineuro.2024.108454
Cell Commun Signal. 2024 Jul 25. 22(1): 375

Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress.

Jinxin Lu, Xiaoyu Zhang, Keyu Su, Huandong Luo, Congcong Liu, Yuqing Yang, Bin He, Cenxin Wang, Zhuoran Zhao, Xianxian Liu, Xu Wang, Peixuan Meng, Dekang Lv, Chunli Wang, Keith W Kelley, Ling Wang, Bai Cui, Quentin Liu, Fei Peng.

   BACKGROUND: Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive.
METHODS: KrasLSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines.
RESULTS: In this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both KrasLSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients.
CONCLUSION: We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

Keywords:  CLOCK transcription; Cancer stemness; Chronic stress; Gemcitabine resistance; Norepinephrine; Olanzapine; mPFC activity

DOI:  https://doi.org/10.1186/s12964-024-01747-y