bims-netuvo 2024-02-18 papers

Dis Model Mech. 2024 Feb 01. pii: dmm050533. [Epub ahead of print]17(2):

Stem cell modeling of nervous system tumors.

Frank B Furnari, Corina Anastasaki, Shan Bian, Howard A Fine, Tomoyuki Koga, Lu Q Le, Fausto J Rodriguez, David H Gutmann.

Nervous system tumors, particularly brain tumors, represent the most common tumors in children and one of the most lethal tumors in adults. Despite decades of research, there are few effective therapies for these cancers. Although human nervous system tumor cells and genetically engineered mouse models have served as excellent platforms for drug discovery and preclinical testing, they have limitations with respect to accurately recapitulating important aspects of the pathobiology of spontaneously arising human tumors. For this reason, attention has turned to the deployment of human stem cell engineering involving human embryonic or induced pluripotent stem cells, in which genetic alterations associated with nervous system cancers can be introduced. These stem cells can be used to create self-assembling three-dimensional cerebral organoids that preserve key features of the developing human brain. Moreover, stem cell-engineered lines are amenable to xenotransplantation into mice as a platform to investigate the tumor cell of origin, discover cancer evolutionary trajectories and identify therapeutic vulnerabilities. In this article, we review the current state of human stem cell models of nervous system tumors, discuss their advantages and disadvantages, and provide consensus recommendations for future research.

Keywords: Brain tumor; CRISPR engineering; Nerve sheath tumors; human embryonic stem cells (hESCs); human induced pluripotent stem cells (hiPSCs)

DOI: https://doi.org/10.1242/dmm.050533

Am J Case Rep. 2024 Feb 13. 25 e942083

Robotic-Assisted Resection of a Benign Schwannoma of the Obturator Nerve: A Rare Case.

Bruno Mirandola Bulisani, Marina Ströher, Felipe Martin Bianco Rossi, Milena Arruda de Oliveira Leite, Murilo Rocha Rodrigues, Luiz Guilherme Lisboa Gomes, Jaques Waisberg.

BACKGROUND Neurilemmomas are rare tumors derived from the Schwann cells that comprise the peripheral nerve sheaths. They have a slow growth and rarely display malignancy. Early diagnosis is rare, and the treatment consists by surgical resection. Although robotic-assisted surgery is commonly used for treating retroperitoneal diseases, there are few reports of resection of retroperitoneal and pelvic schwannoma through robotic-assisted surgery. In the present study, we reported a case of complete excision of a benign retroperitoneal schwannoma of the obturator nerve by robotic-assisted surgery. CASE REPORT A 51-year-old woman was referred by her gynecologist for left pelvic discomfort of a 3-month duration. The physical examination was normal, but a computerized tomography scan of the abdomen and pelvis showed an expansive pelvic lesion in the topography of the left iliac vessels, a hypodense contrast enhancement measuring 4.6×3.4 cm. Magnetic resonance imaging showed an extraperitoneal lesion located medially and inferiorly to the left external iliac vessels, with a size of 4.9×3.7 cm, and of probable neural etiology. Surgical resection of the tumor was recommended because of the diagnostic hypothesis of obturator nerve schwannoma. CONCLUSIONS This case showed that retroperitoneal neurilemmomas are difficult to diagnose owing to a lack of specific symptoms, and the best treatment is complete tumor resection. The use of robotic techniques gives greater dexterity to the surgeon, since it provides high-definition 3-dimensional vision, which can make the removal of retroperitoneal tumors susceptible to minimally invasive resection in a safe and effective way.

DOI: https://doi.org/10.12659/AJCR.942083

Cureus. 2024 Jan;16(1): e52356

Synchronous Pelvic Schwannoma With Metastatic Prostate Cancer: A Rare Case and Pathology Review.

Hagar Attia, John O Agboola, Gyuhee Seong, Aye Thida, Edwin Chiu, Maksim Agaronov.

Schwannomas are benign tumors arising from well-differentiated Schwann cells of peripheral nerves. They are usually found on the limbs, head, and neck. It is uncommon for schwannoma to occur in the pelvis and when it does, it is often diagnosed late. Pelvic schwannoma when diagnosed are often bigger in size (>5 cm) and may present with local symptoms such as constipation and bladder outlet obstruction. We hereby present a patient with concurrent metastatic prostate carcinoma and pelvic schwannoma. The patient is a 57-year-old man initially diagnosed with prostate cancer and was lost to follow-up. One year later, he presented with metastatic prostate disease and bladder outlet obstruction. Further evaluation revealed a concurrent pelvic mass that was increasing in size. The biopsy of this mass was suggestive of schwannoma. It was decided at the multidisciplinary tumor board conference to offer treatment for his metastatic prostate disease and observe the schwannoma. His obstructive symptoms worsened in the face of clinical evidence of regression of his prostatic disease, and it was decided to resect the pelvic mass. The surgery revealed a huge soft tissue mass within the pelvis that was adherent to the bladder, prostate, and rectum. Morphology and immunohistochemistry studies of the pelvic mass confirmed the diagnosis of ancient schwannoma. We hereby highlight the clinical importance of this presentation and the diagnostic and therapeutic dilemma involved in the management of this patient who presented with two pathologic conditions causing similar symptoms but of different prognostic and therapeutic significance.

Keywords: immunohistochemistry (ihc); oncology; pelvic schwannoma; prostate adenocarcinoma; surgical pathology

DOI: https://doi.org/10.7759/cureus.52356

Cureus. 2024 Jan;16(1): e52194

Beta-Adrenergic Blockade in Advanced Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Multicentric Study.

Ana Duarte Mendes, Ana Rita Freitas, Rodrigo Vicente, Ricardo Ferreira, Telma Martins, Maria João Ramos, Carlota Baptista, Bruno Miguel Silva, Inês Margarido, Marina Vitorino, Michelle Silva, Sofia Braga.

Introduction The standard treatment of cancer has dramatically improved with immune checkpoint inhibitors (ICIs). Despite their proven advantage, many patients fail to exhibit a meaningful and lasting response. The beta-adrenergic signalling pathway may hold significant promise due to its role in promoting an immunosuppressive milieu within the tumour microenvironment. Inhibiting β-adrenergic signalling could enhance ICI activity; however, blocking this pathway for this purpose has yielded conflicting results. The primary objective of this study was to evaluate the effect of beta-blocker use on overall survival and progression-free survival during ICI therapy. Methods A multicentric, retrospective, observational study was conducted in four Portuguese institutions. Patients with advanced non-small cell lung cancer treated with ICIs between January 2018 and December 2019 were included. Those using beta blockers for non-oncological reasons were compared with non-users. Results Among the 171 patients included, 36 concomitantly received beta blockers and ICIs. No significant increase was found in progression-free survival among patients who took β-blockers (HR 0.74, 95% confidence interval (CI) 0.48-1.12, p = 0.151), and no statistically significant difference was found in overall survival. An apparent trend was observed towards better outcomes in the beta-blocker group, with a median overall survival of 9.93 months in the group not taking β-blockers versus 14.90 months in the β-blocker group (p = 0.291) and a median progression-free survival of 5.37 in the group not taking β-blockers versus 10.87 months in the β-blocker group (p = 0.151). Nine (25%) patients in the beta-blocker group and 16 (12%) in the non-beta-blocker group were progressive disease-free at the end of follow-up. This difference between the two groups is statistically significant (p = 0.047). Conclusion Our study found no statistically significant evidence that beta blockers enhance the effectiveness of immunotherapy. Using adrenergic blockade to modulate the immune system shows promise, warranting the need to develop prospective clinical studies.

Keywords: beta-adrenergic signaling; immune checkpoint inhibitor; immune response; immunotherapy; lung cancer

DOI: https://doi.org/10.7759/cureus.52194