bims-netuvo 2024-06-16 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–06–16
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Perineural invasion: An independent risk factor for cervical cancer prognosis and a possible pathway for a future targeted treatment?
The TREK-1 potassium channel is involved in both the analgesic and anti-proliferative effects of riluzole in bone cancer pain.
Melan-A-Positive Granular Cell Tumor With Extensive Intraneural and Perineural Spread: A Rare Case Report.
Radiotherapy and surgery remain effective treatment options for retroperitoneal MPNST: a retrospective study based on SEER database.
Chemotherapy-induced neuropathy and pain in pediatric oncology patients: impact of combination therapies.
Role of Endorphins in Breast Cancer Pathogenesis and Recovery.
Sexual dimorphism in colorectal cancer: molecular mechanisms and treatment strategies.
Outcomes of initial therapy for synchronous brain metastases from small cell lung cancer: a single-institution retrospective analysis.

Eur J Surg Oncol. 2024 Jun 01. pii: S0748-7983(24)00501-8. [Epub ahead of print]50(7): 108449

Perineural invasion: An independent risk factor for cervical cancer prognosis and a possible pathway for a future targeted treatment?

Christos Iavazzo, Helen J Trihia, Ioannis D Gkegkes.

DOI: https://doi.org/10.1016/j.ejso.2024.108449
Biomed Pharmacother. 2024 Jun 07. pii: S0753-3322(24)00771-6. [Epub ahead of print]176 116887

The TREK-1 potassium channel is involved in both the analgesic and anti-proliferative effects of riluzole in bone cancer pain.

Mélissa Delanne-Cuménal, Sylvain Lamoine, Mathieu Meleine, Youssef Aissouni, Laetitia Prival, Mathilde Fereyrolles, Julie Barbier, Christine Cercy, Ludivine Boudieu, Julien Schopp, Michel Lazdunski, Alain Eschalier, Stéphane Lolignier, Jérôme Busserolles.

   BACKGROUND: The metastasis of tumors into bone tissue typically leads to intractable pain that is both very disabling and particularly difficult to manage. We investigated here whether riluzole could have beneficial effects for the treatment of prostate cancer-induced bone pain and how it could influence the development of bone metastasis.
METHODS: We used a bone pain model induced by intratibial injection of human PC3 prostate cancer cells into male SCID mice treated or not with riluzole administered in drinking water. We also used riluzole in vitro to assess its possible effect on PC3 cell viability and functionality, using patch-clamp.
RESULTS: Riluzole had a significant preventive effect on both evoked and spontaneous pain involving the TREK-1 potassium channel. Riluzole did not interfere with PC3-induced bone loss or bone remodeling in vivo. It also significantly decreased PC3 cell viability in vitro. The antiproliferative effect of riluzole is correlated with a TREK-1-dependent membrane hyperpolarization in these cells.
CONCLUSION: The present data suggest that riluzole could be very useful to manage evoked and spontaneous hypersensitivity in cancer-induced bone pain and has no significant adverse effect on cancer progression.

Keywords:  Bone cancer pain; Prostate cancer; Riluzole; TREK-1 potassium channel

DOI:  https://doi.org/10.1016/j.biopha.2024.116887
Cureus. 2024 May;16(5): e59903

Melan-A-Positive Granular Cell Tumor With Extensive Intraneural and Perineural Spread: A Rare Case Report.

Svetlana Bobkova, Eli Oldham, Igor Shendrik.

  Cutaneous granular cell tumors (GCTs) are rare tumors that typically exhibit benign clinical behavior and are likely of Schwann cell origin. Some histologic and immunohistochemical variants of GCTs may present challenges due to infiltrative growth patterns, perineural invasion, and expression of Melan-A. In this case report, we present a 27-year-old male who had previously been diagnosed with a typical GCT on the back a few years ago. The current biopsy from the proximal palm demonstrated a cytologically similar tumor with extensive perineural spread and notable positivity for Melan-A. Although uncommon, these features are consistent with the histological appearances of GCTs. The current views on the histogenesis of GCTs, clinical associations, differential diagnosis with melanoma, and histological criteria for malignant GCTs are discussed. A panel of immunohistochemical stains, including Inhibin-α and preferentially expressed antigen in melanoma (PRAME), is proposed for use in rare instances of Melan-A-positive GCTs.

Keywords:  dermatopathology; granular cell tumor; hmb-45; immunohistochemistry; inhibin-α; melan-a; s-100; tumor

DOI:  https://doi.org/10.7759/cureus.59903
Front Surg. 2024 ;11 1339170

Radiotherapy and surgery remain effective treatment options for retroperitoneal MPNST: a retrospective study based on SEER database.

Zhe Xi, Zhuang Aobo, Xi Li, Wang Yue, Guangting Yan, Zhenhang Lin, Geng Zhang, Xiaogang Xia, Lanlan Lian, Wengang Li.

   Introduction: The proportion of retroperitoneal malignant peripheral nerve sheath tumours (RMPNST) in retroperitoneal tumors is less than 5%, but the mortality rate is very high. However, there is no relevant research focused on RMPNST only.
Methods: We retrospectively analyzed data from the SEER database of patients with primary RMPNST from 2000 to 2019, by leveraging the advantages of the Seer database, we can explore the prognosis of such rare diseases. Kaplan-Meier method was used to construct the survival curve, and cox regression model was used to analyze the factors affecting the prognosis of patients. In addition, a model was developed to distinguish high-risk and low-risk patients.
Results: This study included a total of 52 patients, with a median survival time of 39 months (95% CI 12.740-65.260) and a 5-year survival rate of 44.2% (95% CI 0.299-0.565). Radiotherapy (p = 0.004, OR: 1.475, 95% CI 0.718-3.033), metastasis disease (p = 0.002, OR: 5.596, 95% CI 2.449-47.079) and surgery (p = 0.003, OR: 5.003, 95% CI 0.011-0.409) were associated with overall survival (OS). The 5-year distant metastasis rate was 36% (95% CI 0.221-0.499). We used the above risk factors to separate patients into high and low groups and evaluate the results through the receiver operating characteristic (ROC) curve. This model is beneficial for guiding the selection of treatment strategies.
Conclusion: The majority of RMPNST patients have a good prognosis after surgery, and the establishment of high-low group is helpful for clinical decision-making.

Keywords:  SEER database; malignant peripheral nerve sheath tumours; radiotherapy; retroperitoneal tumors; retrospective study

DOI:  https://doi.org/10.3389/fsurg.2024.1339170
Eur J Pediatr. 2024 Jun 10.

Chemotherapy-induced neuropathy and pain in pediatric oncology patients: impact of combination therapies.

Delia Soriano, Gisella Santos Chocler, Mariana Alejandra Varela, María Florencia Coronel.

  Chemotherapy-induced peripheral neuropathy (CIPN) and associated pain are prevalent adverse effects of pediatric cancer treatment, significantly affecting the patient's quality of life. Their impact and risk factors have yet to be assessed in our country. This study aimed to assess the prevalence and clinical characteristics of CIPN, as well as to explore associations with patient- and treatment-related variables, within a cohort of Argentinean pediatric oncology patients. Sixty-six patients diagnosed with malignant hematopoietic tumors and receiving the neurotoxic agent vincristine were included in this observational study. Variables analyzed included age, gender, anthropometric measurements, tumor type, chemotherapy treatment, development of pain and other symptoms, severity, and analgesic treatment. The study population consisted of 39 boys and 27 girls. Most patients received two or three neurotoxic drugs. Symptoms consistent with CIPN were identified in 15 children, reflecting a prevalence of 23%. The main symptom was pain in the lower limbs, with some patients reporting jaw or generalized body pain. Pain was categorized as moderate or severe in 60% and 27% of cases, respectively. NSAIDs, anticonvulsants, and/or opioids were prescribed. Among the patient- and treatment-related variables analyzed as potential risk factors, the use of vincristine in conjunction with cytarabine and the administration of a higher number of neurotoxic drugs demonstrated significant association with the development of CIPN.
CONCLUSIONS: Combination therapy stands out as a risk factor for clinical CIPN. The high prevalence of moderate/severe pain underscores the importance of close vigilance given its potential to compromise the patient's overall well-being.
WHAT IS KNOWN: • Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect and dose-limiting factor in pediatric cancer treatment. • Prevalence varies among regions and risk factors are still under study.
WHAT IS NEW: • Prevalence of symptomatic CIPN is 23% among pediatric patients undergoing treatment for hematopoietic tumors in a referral hospital in Argentina. Most patients report moderate or severe pain. • Combining vincristine with cytarabine and using a higher number of neurotoxic drugs in combination therapies exhibit significant association with the development of CIPN-related symptoms.

Keywords:  Chemotherapy-induced neuropathy; Life-threatening illness; Palliative care; Pediatric oncology patients; Quality of life; Severe pain

DOI:  https://doi.org/10.1007/s00431-024-05638-9
Adv Neurobiol. 2024 ;35 87-106

Role of Endorphins in Breast Cancer Pathogenesis and Recovery.

David H Nguyen.

  Understanding the relationship between stress and breast cancer development is essential to preventing and alleviating the cancer. Recent research has shed light on the cognitive, physiological, cellular, and molecular underpinnings of how the endorphin pathway and stress pathway affect breast cancer. This chapter consists of two parts. Part 1 will discuss the role of endorphins in breast cancer development. This includes a discussion of three topics: (1) the neurophysiological effect of endorphins on breast tumor growth in vivo, along with further experiments that will deepen our knowledge of how β-endorphin affects breast cancer; (2) how both the opioid receptor and somatostatin receptor classes alter intracellular signaling in breast cancer cells; and (3) genetic alleles in the opioid signaling pathway that are correlated with increased breast cancer risk. Part 2 will discuss the role of endorphins in recovery from breast cancer. This includes a discussion of three topics: (1) the relationship between breast cancer diagnosis and depression; (2) the effectiveness of cognitive behavioral therapy in reducing stress in breast cancer patients; and (3) the effect of psychotherapy and exercise on preserving telomere length in breast cancer patients.

Keywords:  Breast cancer; Endorphin; Stress; Telomeres

DOI:  https://doi.org/10.1007/978-3-031-45493-6_5
Biol Sex Differ. 2024 Jun 12. 15(1): 48

Sexual dimorphism in colorectal cancer: molecular mechanisms and treatment strategies.

Yair Rodríguez-Santiago, Claudia Angelica Garay-Canales, Karen Elizabeth Nava-Castro, Jorge Morales-Montor.

   INTRODUCTION: Sexual dimorphism significantly influences cancer incidence and prognosis. Notably, females exhibit a lower risk and favorable prognosis for non-reproductive cancers compared to males, a pattern observable beyond the scope of risk behaviors such as alcohol consumption and smoking. Colorectal cancer, ranking third in global prevalence and second in mortality, disproportionately affects men. Sex steroid hormones, particularly estrogens and androgens, play crucial roles in cancer progression, considering epidemiological in vivo and in vitro, in general estrogens imparting a protective effect in females and androgens correlating with an increasing risk of colorectal cancer development.
MAIN BODY: The hormonal impact on immune response is mediated by receptor interactions, resulting in heightened inflammation, modulation of NF-kB, and fostering an environment conducive to cancer progression and metastasis. These molecules also influence the enteric nervous system, that is a pivotal in neuromodulator release and intestinal neuron stimulation, also contributes to cancer development, as evidenced by nerve infiltration into tumors. Microbiota diversity further intersects with immune, hormonal, and neural mechanisms, influencing colorectal cancer dynamics. A comprehensive understanding of hormonal influences on colorectal cancer progression, coupled with the complex interplay between immune responses, microbiota diversity and neurotransmitter imbalances, underpins the development of more targeted and effective therapies.
CONCLUSIONS: Estrogens mitigate colorectal cancer risk by modulating anti-tumor immune responses, enhancing microbial diversity, and curbing the pro-tumor actions of the sympathetic and enteric nervous systems. Conversely, androgens escalate tumor growth by dampening anti-tumor immune activity, reducing microbial diversity, and facilitating the release of tumor-promoting factors by the nervous system. These findings hold significant potential for the strategic purposing of drugs to fine-tune the extensive impacts of sex hormones within the tumor microenvironment, promising advancements in colorectal cancer therapies.

Keywords:  Androgen receptor; Colon cancer; Estrogen receptor; Neuroimmunoendocrine network; Sex steroids; Sexual dimorphism

DOI:  https://doi.org/10.1186/s13293-024-00623-1
Transl Lung Cancer Res. 2024 May 31. 13(5): 1110-1120

Outcomes of initial therapy for synchronous brain metastases from small cell lung cancer: a single-institution retrospective analysis.

Kevin V Chaung, Michael Z Kharouta, Andrew J Gross, Pingfu Fu, Mitchell Machtay, Tiffany R Hodges, Andrew E Sloan, Tithi Biswas, Afshin Dowlati, Serah Choi.

  Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases at the time of initial SCLC diagnosis. A total of 107 SCLC patients with synchronous brain metastases treated at a single institution were included in this retrospective analysis. These patients had brain lesions present on initial staging imaging. Survival was estimated using the Kaplan-Meier method with log-rank test. Factors predictive of OS and bPFS were analyzed using Cox proportional hazards regression model. Median OS for the entire cohort was 9 months (interquartile range, 4.2-13.8 months) and median bPFS was 7.3 months (interquartile range, 3.5-11.1 months). OS was 30.3% at 1 year and 14.4% at 2 years, while bPFS was 22.0% at 1 year and 6.9% at 2 years. The median number of brain lesions at diagnosis was 3 (interquartile range, 2-8), and the median size of the largest metastasis was 2.0 cm (interquartile range, 1.0-3.3 cm). Increased number of brain lesions was significantly associated with decreased OS. Patients who received both chemotherapy and whole brain radiation therapy (WBRT) had improved OS (P=0.02) and bPFS (P=0.005) compared to those who had either chemotherapy or WBRT alone. There was no significant difference in OS or bPFS depending on the sequence of therapy or the dose of WBRT. Thirteen patients underwent upfront brain metastasis resection, which was associated with improved OS (P=0.02) but not bPFS (P=0.09) compared to those who did not have surgery. The combination of chemotherapy and WBRT was associated with improved OS and bPFS compared to either modality alone. Upfront brain metastasis resection was associated with improved OS but not bPFS compared to those who did not have surgery.

Keywords:  Small cell lung cancer (SCLC); brain metastases; chemotherapy; craniotomy; radiation therapy

DOI:  https://doi.org/10.21037/tlcr-23-641