bims-netuvo 2023-07-30 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–07–30
thirteen papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Targeting electrochemical communication between neurons and cancer.
Perineural invasion: A potential driver of cancer-induced pain.
Treatment of Cancer Pain: A Systematic Review.
Inflammation induced by tumor-associated nerves promotes resistance to anti-PD-1 therapy in cancer patients and is targetable by IL-6 blockade.
A Spectrum of Histomorphological and Immunohistochemical Expression Profiles of S-100, CD56 and Calretinin in Benign Peripheral Nerve Sheath Tumours.
Hybrid Peripheral Nerve Sheath Tumor of the Hand.
A case of intrascrotal extratesticular schwannoma.
Neurofibromatosis- and schwannomatosis- associated tumors: Approaches to genetic testing and counseling considerations.
The Conditioning of Adjuvant Chemotherapy for Stage II and III Rectal Cancer Determined by Postoperative Pathological Characteristics in Romania.
Clinical impact of perineural cancer invasion detected in prostate cores: Involvement of spatially contiguous versus separate biopsy sites.
Brain metastasis and intracranial leptomeningeal metastasis from malignant peripheral nerve sheath tumors: illustrative cases.
Involvement of the Opioid Peptide Family in Cancer Progression.
FOXM1 promotes neurofibromatosis type 1-associated malignant peripheral nerve sheath tumor progression in a NUF2-dependent manner.

Sci Transl Med. 2023 07 26. 15(706): eadi5170

Targeting electrochemical communication between neurons and cancer.

Humsa S Venkatesh.

Neuronal activity drives cancer progression through functional integration of malignant cell networks into neural circuitry.

DOI: https://doi.org/10.1126/scitranslmed.adi5170
Biochem Pharmacol. 2023 Jul 20. pii: S0006-2952(23)00283-6. [Epub ahead of print]215 115692

Perineural invasion: A potential driver of cancer-induced pain.

Rong-Jia Shi, Bo-Wen Ke, Ya-Ling Tang, Xin-Hua Liang.

  Perineural invasion (PNI) is the process through which tumors invade and interact with nerves. The dynamic changes in the nerves caused by PNI may induce disturbing symptoms. PNI-related cancer pain in neuro-rich tumors has attracted much attention because the occurrence of tumor-induced pain is closely related to the invasion of nerves in the tumor microenvironment. PNI-related pain might indicate the occurrence of PNI, guide the improvement of treatment strategies, and predict the unresectability of tumors and the necessity of palliative care. Although many studies have investigated PNI, its relationship with tumor-induced pain and its common mechanisms have not been summarized thoroughly. Therefore, in this review, we evaluated the relationship between PNI and cancer-associated pain. We showed that PNI is a major cause of cancer-related pain and that this pain can predict the occurrence of PNI. We also elucidated the cellular and molecular mechanisms of PNI-induced pain. Finally, we analyzed the possible targets for alleviating PNI-related pain or combined antitumor and pain management. Our findings might provide new perspectives for improving the treatment of patients with malignant tumors.

Keywords:  Cancer-associated pain; Nerve damage; Perineural invasion; Tumor innervation; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.bcp.2023.115692
Am J Clin Oncol. 2023 Jul 24.

Treatment of Cancer Pain: A Systematic Review.

Marcelen Rosenscheg, Julia Pedron, Lorena Pedroso.

CONTEXTUALIZATION: One of the biggest problems regarding the treatment of cancer patients is pain, whether due to the cancer or the treatment itself. Therefore, there is a search for treatments that aims to promote an effective treatment in this sense.
PURPOSE: This article aims to verify which are the recent methods used to treat pain in cancer patients in a multidisciplinary sense, and to evaluate their effectiveness.
METHODOLOGY: Systematic reviews, meta-analyses and randomized clinical trials utilizing the LILACS, NCBI, and MEDLINE platforms of the last 5 years were included. The descriptors were pain treatment in oncology, pain management, complementary therapies, and other synonyms, in Portuguese, English and Spanish. This included any technique that was effective in the treatment of cancer pain.
RESULTS: The initial search found 2246 articles, of which 22 were included in the systematic review. Most of these are acupuncture treatments, opioids versus anti-inflammatories versus analgesics, radiotherapy, behavioral therapies, among others. Most articles suggest benefits with these therapies, improved quality of life for patients and tolerable side effects.
CONCLUSION: This study demonstrates the effectiveness of the current methods used in the treatment of pain in cancer patients so that professionals in the area can have more options for treating cancer pain. Despite the important limitations, the guideline for further research and the situations in which treatments have shown effectiveness are present in it.

DOI: https://doi.org/10.1097/COC.0000000000001029
Res Sq. 2023 Jul 18. pii: rs.3.rs-3161761. [Epub ahead of print]

Inflammation induced by tumor-associated nerves promotes resistance to anti-PD-1 therapy in cancer patients and is targetable by IL-6 blockade.

Moran Amit, Erez Baruch, Priyadahrshini Nagarajan, Frederico Gleber-Netto, Xiayu Rao, Tongxin Xie, Shamima Akhter, Adebayo Adewale, Shajedul Islam, Brandi Mattson, Renata Ferrarotto, Michael Wong, Michael Davies, Sonali Jindal, Sreyashi Basu, Catherine Harwood, Irene Leigh, Nadim Ajami, Andrew Futreal, Micah Castillo, Preethi Gunarante, Ryan Goepfert, Nikhil Khushalani, Jing Wang, Stephanie Watowich, George Calin, Michael Migden, Paola Vermeer, Nisha D'Silva, Dan Yaniv, Jared Burks, Javier Gomez, Patrick Dougherty, Kenneth Tsai, James Allison, Padmanee Sharma, Jennifer Wargo, Jeffrey Myers, Neil Gross.

While the nervous system has reciprocal interactions with both cancer and the immune system, little is known about the potential role of tumor associated nerves (TANs) in modulating anti-tumoral immunity. Moreover, while peri-neural invasion is a well establish poor prognostic factor across cancer types, the mechanisms driving this clinical effect remain unknown. Here, we provide clinical and mechniastic association between TANs damage and resistance to anti-PD-1 therapy. Using electron microscopy, electrical conduction studies, and tumor samples of cutaneous squamous cell carcinoma (cSCC) patients, we showed that cancer cells can destroy myelin sheath and induce TANs degeneration. Multi-omics and spatial analyses of tumor samples from cSCC patients who underwent neoadjuvant anti-PD-1 therapy demonstrated that anti-PD-1 non-responders had higher rates of peri-neural invasion, TANs damage and degeneration compared to responders, both at baseline and following neoadjuvant treatment. Tumors from non-responders were also characterized by a sustained signaling of interferon type I (IFN-I) - known to both propagate nerve degeneration and to dampen anti-tumoral immunity. Peri-neural niches of non-responders were characterized by higher immune activity compared to responders, including immune-suppressive activity of M2 macrophages, and T regulatory cells. This tumor promoting inflammation expanded to the rest of the tumor microenvironment in non-responders. Anti-PD-1 efficacy was dampened by inducing nerve damage prior to treatment administration in a murine model. In contrast, anti-PD-1 efficacy was enhanced by denervation and by interleukin-6 blockade. These findings suggested a potential novel anti-PD-1 resistance drived by TANs damage and inflammation. This resistance mechanism is targetable and may have therapeutic implications in other neurotropic cancers with poor response to anti-PD-1 therapy such as pancreatic, prostate, and breast cancers.

DOI: https://doi.org/10.21203/rs.3.rs-3161761/v1
Cureus. 2023 Jun;15(6): e40751

A Spectrum of Histomorphological and Immunohistochemical Expression Profiles of S-100, CD56 and Calretinin in Benign Peripheral Nerve Sheath Tumours.

Poornima Jaiswal, Anand Cd, Jaison Jacob John.

   INTRODUCTION: Peripheral nerve sheath tumours comprise benign tumours; namely schwannomas and neurofibromas, and only rarely comprise hybrid benign tumours and their malignant counterpart, malignant peripheral nerve sheath tumours (MPNST). There may be diagnostic difficulties in histopathology analysis, especially in core needle biopsies where there is a limited amount of tissue. Immunohistochemistry (IHC) can play a beneficial role, especially in atypical and cellular histological variants and rarely hybrid tumours.
METHODS: A total of 45 cases of benign peripheral nerve sheath tumours were included in the study; there were 27 cases of neurofibroma including variants like plexiform and cellular neurofibromas and 18 cases of schwannomas including variants like ancient schwannoma and cellular schwannoma. Immunohistochemical staining (IHC) on these tumour tissues using S-100, CD56 and calretinin was done and scoring was done based on extent and intensity.
RESULTS AND DISCUSSION: No significant differences were observed between neurofibromas and schwannomas on patient age and anatomical locations of these tumours. IHC results did not show statistically significant patterns of expression of S-100 protein between the schwannoma and neurofibromas groups (p=0.75). CD56 protein was expressed strongly (3+) in 90% of cases of schwannoma and negative in 86% of neurofibromas, the differential expression between the two groups was found to be statistically significant (p <0.0001). Calretinin was positive in 39% of schwannomas including one case of cellular schwannoma and negative in all (100%) cases of neurofibroma while the differential expression of calretinin between schwannoma and neurofibroma groups was found to be statistically significant (p < 0.005).
CONCLUSION: Our study shows that S-100 does not show differential expression between schwannomas and neurofibromas. CD56 could be a potentially useful IHC marker to aid in the diagnosis of peripheral nerve sheath tumours with significantly higher expression in schwannomas compared to neurofibromas. Calretinin was also found to be preferentially expressed in schwannomas, though the difference is statistically significantly lower compared to CD56. A panel of all these markers could be used for accurate diagnosis.

Keywords:  calretinin; cd56; ihc; immunohistochemistry; neurofibroma; peripheral nerve sheath; s-100; schwannoma

DOI:  https://doi.org/10.7759/cureus.40751
Dtsch Arztebl Int. 2023 May 05. pii: arztebl.m2023.0019. [Epub ahead of print]120(18): 323

Hybrid Peripheral Nerve Sheath Tumor of the Hand.

Inga Langner, Matthias Mühler, Matthias Mühler, Henry Schroeder.

DOI: https://doi.org/10.3238/arztebl.m2023.0019
Radiol Case Rep. 2023 Oct;18(10): 3380-3385

A case of intrascrotal extratesticular schwannoma.

Ryo Takaji, Satoki Abe, Toshitaka Shin, Tsutomu Daa, Ryuichi Shimada, Yoshiki Asayama.

  Schwannomas are benign tumors arising from Schwann cells, which compose the myelin sheath covering peripheral nerves. Although schwannomas can develop in various locations throughout the human body, the scrotum is a rare site for development of a schwannoma. Furthermore, to the best of our knowledge, no study to date has focused on the detailed imaging findings of intrascrotal schwannoma.

Keywords:  Magnetic resonance imaging; Schwannoma; Scrotal tumor; Tunica albuginea

DOI:  https://doi.org/10.1016/j.radcr.2023.07.029
Am J Med Genet A. 2023 Jul 24.

Neurofibromatosis- and schwannomatosis- associated tumors: Approaches to genetic testing and counseling considerations.

Allison Goetsch Weisman, Shelly Weiss McQuaid, Heather B Radtke, Jessica Stoll, Bryce Brown, Alicia Gomes.

  Neurofibromatosis (NF) and schwannomatosis (SWN) are genetic conditions characterized by the risk of developing nervous system tumors. Recently revised diagnostic criteria include the addition of genetic testing to confirm a pathogenic variant, as well as to detect the presence of mosaicism. Therefore, the use and interpretation of both germline and tumor-based testing have increasing importance in the diagnostic approach, treatment decisions, and risk stratification of these conditions. This focused review discusses approaches to genetic testing of NF- and SWN-related tumor types, which are somewhat rare and perhaps lesser known to non-specialized clinicians. These include gastrointestinal stromal tumors, breast cancer, plexiform neurofibromas with or without transformation to malignant peripheral nerve sheath tumors, gliomas, and schwannomas, and emphasizes the need for inclusion of genetic providers in patient care and appropriate pre- and post-test education, genetic counseling, and focused evaluation by a medical geneticist or other healthcare provider familiar with clinical manifestations of these disorders.

Keywords:  breast cancer; gastrointestinal stromal tumor; genetic counseling; genetic testing; glioma; neurofibromatosis; plexiform neurofibroma; schwannoma; schwannomatosis

DOI:  https://doi.org/10.1002/ajmg.a.63346
Medicina (Kaunas). 2023 Jun 29. pii: 1224. [Epub ahead of print]59(7):

The Conditioning of Adjuvant Chemotherapy for Stage II and III Rectal Cancer Determined by Postoperative Pathological Characteristics in Romania.

Horia-Dan Liscu, Bogdan-Radu Liscu, Ruxandra Mitre, Ioana-Valentina Anghel, Ionut-Lucian Antone-Iordache, Andrei Balan, Simona Coniac, Andreea-Iuliana Miron, Georgian Halcu.

  The management of locally advanced rectal cancer (LARC) suffered changes thanks to the development of improved surgical procedures, radiation delivery, and chemotherapy. Although treatment options improved individually, the optimal order is still debated. Neoadjuvant chemo-radiotherapy followed by total mesorectal excision (TME) has been the "golden standard" for locally advanced rectal cancer. There is no common ground in international guidelines on the indications of adjuvant chemotherapy (ADJCHT), with differences between the American, European, and Japanese guidelines. This paper studies the preferences of Romanian oncologists in prescribing ADJCHT. We conducted a single-institution, retrospective study of all nonmetastatic, ECOG 0-1 LARC patients staged II-III who underwent TME and were admitted to the Oncology or Radiotherapy Department of Colțea Clinical Hospital, Bucharest between January 2017 and March 2021. A total of 186 patients were included in the study. A positive correlation was found between ADJCHT and each of the following: (y)pT > 2, (y)pN > 0, and the presence of perineural invasion (PNI+). A strong positive correlation was found between ADJCHT and the presence of at least one risk factor: (y)pT > 2, (y)pN > 0, PNI+, lymphovascular invasion, positive margins, or tumor grade > 1. Tumor downstaging decreased the risk of metastases in the first 2 years and was associated with the use of neoadjuvant radiotherapy, while adding neoadjuvant chemotherapy increased the chance of nodal downstaging. ADJCHT practice for LARC in Romania follows either NCCN or ESMO guidelines, at the discretion of the oncologist, due to the lack of national guideline.

Keywords:  Romanian oncologists; adjuvant chemotherapy; neoadjuvant radiochemotherapy; neoadjuvant radiotherapy; rectal cancer; tumor downstage

DOI:  https://doi.org/10.3390/medicina59071224
Pathol Int. 2023 Jul 26.

Clinical impact of perineural cancer invasion detected in prostate cores: Involvement of spatially contiguous versus separate biopsy sites.

Yuki Teramoto, Numbereye Numbere, Hiroshi Miyamoto.

DOI: https://doi.org/10.1111/pin.13356
J Neurosurg Case Lessons. 2023 Jul 17. pii: CASE23148. [Epub ahead of print]6(3):

Brain metastasis and intracranial leptomeningeal metastasis from malignant peripheral nerve sheath tumors: illustrative cases.

Masasuke Ohno, Shoichi Haimoto, Satoshi Tsukushi, Waki Hosoda, Fumiharu Ohka, Ryuta Saito.

   BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft-tissue tumors. Intracranial metastasis from MPNSTs is quite rare.
OBSERVATIONS: The authors report on a 73-year-old male whose MPNST metastasized to the brain and a 32-year-old male with leptomeningeal metastasis from MPNST and review 41 cases of MPNST that developed intracranial metastasis, as reported in the literature.
LESSONS: Brain metastasis and leptomeningeal metastasis of MPNSTs show different clinical courses and require pathology-specific treatment.

Keywords:  brain metastasis; leptomeningeal metastasis; malignant peripheral nerve sheath tumor

DOI:  https://doi.org/10.3171/CASE23148
Biomedicines. 2023 Jul 14. pii: 1993. [Epub ahead of print]11(7):

Involvement of the Opioid Peptide Family in Cancer Progression.

Manuel Lisardo Sánchez, Francisco D Rodríguez, Rafael Coveñas.

  Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins) in cancer development. Anticancer therapeutic strategies targeting the opioid peptidergic system and the main research lines to be developed regarding the topic reviewed are suggested. There is much to investigate about opioid peptides and cancer: basic information is scarce, incomplete, or absent in many tumors. This knowledge is crucial since promising anticancer strategies could be developed alone or in combination therapies with chemotherapy/radiotherapy.

Keywords:  angiogenesis; apoptosis; cancer progression; dynorphin; endorphin; enkephalin; metastasis; opioid receptor; tumor cell

DOI:  https://doi.org/10.3390/biomedicines11071993
Cancer Gene Ther. 2023 Jul 24.

FOXM1 promotes neurofibromatosis type 1-associated malignant peripheral nerve sheath tumor progression in a NUF2-dependent manner.

Rehanguli Aimaier, Man-Hon Chung, Yihui Gu, Qingxiong Yu, Chengjiang Wei, Haibo Li, Zizhen Guo, Manmei Long, Yuehua Li, Wei Wang, Qingfeng Li, Zhichao Wang.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas characterized by poor prognosis and low drug response rates. Traditional chemo/radiotherapies show only mild benefits for patients with MPNSTs, and no targeted therapy is available in the clinic. A better understanding of the molecular background of MPNSTs is critical for the development of effective targeted therapies. Forkhead box M1 (FOXM1) has been implicated in the progression of many human malignancies, though its role in MPNSTs is unclear. In this study, using four Gene Expression Omnibus (GEO) datasets and a tissue microarray, we demonstrated that FOXM1 upregulation was associated with poor prognosis in patients with MPNSTs. FOXM1 overexpression and knockdown regulated the proliferation and colony formation of MPNST cells. Using bioinformatics analysis and luciferase reporter assays, we identified NUF2 as a direct downstream target of FOXM1. Both in vitro and in vivo experiments demonstrated that the induction of MPNST cell proliferation by FOXM1 was dependent on elevated NUF2 expression, as NUF2 knockdown abolished the FOXM1-induced proliferation of MPNST cells. Our study showed that the FOXM1-NUF2 axis mediates human MPNST progression and could be a potential therapeutic target.

DOI: https://doi.org/10.1038/s41417-023-00645-8