bims-netuvo 2023-09-17 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–09–17
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Pancreatic cancer cell-derived semaphorin 3A promotes neuron recruitment to accelerate tumor growth and dissemination.
Role of stress in the pathogenesis of cancer (Review).
Circadian rhythms and cancer.
Different oncological features of colorectal cancer codon-specific KRAS mutations: Not codon 13 but codon 12 have prognostic value.
Case Report Of A Rare Incidentaloma Of The Adrenal Gland-Schwannoma.
Schwannomatosis manifesting as multiple schwannomas in a single intercostal nerve.
Plexiform neurofibroma (Hamartoma) of the median nerve: A two-case report.
Effect of baseline cancer pain on the efficacy of immunotherapy in lung cancer patients.

Am J Cancer Res. 2023 ;13(8): 3417-3432

Pancreatic cancer cell-derived semaphorin 3A promotes neuron recruitment to accelerate tumor growth and dissemination.

Yu-Hsuan Hung, Ya-Chin Hou, Shih-Han Hsu, Li-Yun Wang, Ya-Li Tsai, Yan-Shen Shan, Yung-Yeh Su, Wen-Chun Hung, Li-Tzong Chen.

Perineural invasion and neurogenesis are frequently observed in pancreatic ductal adenocarcinoma (PDAC), and they are associated with a poor prognosis. Axon guidance factor semaphorin 3A (SEMA3A) is upregulated in PDAC. However, it remains unclear whether cancer-derived SEMA3A influences nerve innervation and pancreatic tumorigenesis. In silico analyses were performed using PROGgene and NetworkAnalyst to clarify the importance of SEMA3A and its receptors, plexin A1 (PLXNA1) and neuropilin 2 (NRP2), in pancreatic cancer. In vitro assays, including migration, neurite outgrowth, and 3D recruitment, were performed to study the effects of SEMA3A on neuronal behaviors. Additionally, an orthotopic animal study using C57BL/6 mice was performed to validate the in vitro findings. Expression of SEMA3A and its receptors predicted worse prognosis for PDAC. Cancer-derived SEMA3A promoted neural migration, neurite outgrowth, and neural recruitment. Furthermore, SEMA3A-induced effects depended on PLXNA1, NRP2, and MAPK activation. Trametinib, an approved MAPK kinase (MEK) inhibitor, counteracted SEMA3A-enhanced neuronal activity in vitro. Inhibition of SEMA3A by shRNA in pancreatic cancer cells resulted in decreased neural recruitment, tumor growth, and dissemination in vivo. Our results suggested that cancer-secreted SEMA3A plays an important role in promoting neo-neurogenesis and progression of PDAC.

Keywords: Neuron; neuropilin; pancreatic ductal adenocarcinoma; plexin A1; semaphorin 3A
Int J Oncol. 2023 Nov;pii: 124. [Epub ahead of print]63(5):

Role of stress in the pathogenesis of cancer (Review).

Ioannis G Lempesis, Vasiliki Epameinondas Georgakopoulou, Petros Papalexis, Georgios P Chrousos, Demetrios A Spandidos.

  Stress is a state of disrupted homeostasis, triggered by intrinsic or extrinsic factors, the stressors, which are counteracted by various physiological and behavioural adaptive responses. Stress has been linked to cancer development and incidence for decades; however, epidemiological studies and clinical trials have yielded contradictory results. The present review discusses the effects of stress on cancer development and the various underlying mechanisms. Animal studies have revealed a clear link between stress and cancer progression, revealing molecular, cellular and endocrine processes that are implicated in these effects. Thus, stress hormones, their receptor systems and their intracellular molecular pathways mediate the effects of stress on cancer initiation, progression and the development of metastases. The mechanisms linking stress and cancer progression can either be indirect, mediated by changes in the cancer microenvironment or immune system dysregulation, or direct, through the binding of neuroendocrine stress‑related signalling molecules to cancer cell receptors. Stress affects numerous anti‑ and pro‑cancer immune system components, including host resistance to metastasis, tumour retention and/or immune suppression. Chronic psychological stress through the elevation of catecholamine levels may increase cancer cell death resistance. On the whole, stress is linked to cancer development and incidence, with psychological stressors playing a crucial role. Animal studies have revealed a better link than human ones, with stress‑related hormones influencing tumour development, migration, invasion and cell proliferation. Randomized controlled trials are required to further evaluate the long‑term cancer outcomes of stress and its management.

Keywords:  cancer; hormones; pathogenesis; pathophysiology; stress

DOI:  https://doi.org/10.3892/ijo.2023.5572
Adv Protein Chem Struct Biol. 2023 ;pii: S1876-1623(23)00064-0. [Epub ahead of print]137 135-159

Circadian rhythms and cancer.

Chandrabose Selvaraj, Sher Zaman Safi, Rajendran Vijayakumar.

  Circadian rhythms are autonomous oscillators developed by the molecular circadian clock, essential for coordinating internal time with the external environment in a 24-h daily cycle. In mammals, this circadian clock system plays a major role in all physiological processes and severely affects human health. The regulation of the circadian clock extends beyond the clock genes to involve several clock-controlled genes. Hence, the aberrant expression of these clock genes leads to the downregulation of important targets that control the cell cycle and the ability to undergo apoptosis. This may lead to genomic instability and promotes carcinogenesis. Alteration in the clock genes and their modulation is recognized as a new approach for the development of effective treatment against several diseases, including cancer. Until now, there has been a lack of understanding of circadian rhythms and cancer disease. For that, this chapter aims to represent the core components of circadian rhythms and their function in cancer pathogenesis and progression. In addition, the clinical impacts, current clock drugs, and potential therapeutic targets have been discussed.

Keywords:  Cancer; Circadian rhythms; Clock gene; Jetlag; Melatonin; Sleep; Time

DOI:  https://doi.org/10.1016/bs.apcsb.2023.05.001
World J Gastroenterol. 2023 Aug 28. 29(32): 4883-4899

Different oncological features of colorectal cancer codon-specific KRAS mutations: Not codon 13 but codon 12 have prognostic value.

Hong-Min Ahn, Duck-Woo Kim, Hyeon Jeong Oh, Hyung Kyung Kim, Hye Seung Lee, Tae Gyun Lee, Hye-Rim Shin, In Jun Yang, Jeehye Lee, Jung Wook Suh, Heung-Kwon Oh, Sung-Bum Kang.

   BACKGROUND: Approximately 40% of colorectal cancer (CRC) cases are linked to Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. KRAS mutations are associated with poor CRC prognosis, especially KRAS codon 12 mutation, which is associated with metastasis and poorer survival. However, the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear.
AIM: To evaluate the clinicopathological characteristics and prognostic value of codon-specific KRAS mutations, especially in codon 13.
METHODS: This retrospective, single-center, observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019. Patients with KRAS mutation status confirmed by molecular pathology reports were included. The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed. Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.
RESULTS: Among the 2203 patients, the incidence of KRAS codons 12, 13, and 61 mutations was 27.7%, 9.1%, and 1.3%, respectively. Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics, but only codon 12 was associated with pathological features, such as stage of primary tumor (T stage), lymph node involvement (N stage), vascular invasion, perineural invasion, tumor size, and microsatellite instability. KRAS codon 13 mutation showed no associations (77.2% vs 85.3%, P = 0.159), whereas codon 12 was associated with a lower 5-year recurrence-free survival rate (78.9% vs 75.5%, P = 0.025). In multivariable analysis, along with T and N stages and vascular and perineural invasion, only codon 12 (hazard ratio: 1.399; 95% confidence interval: 1.034-1.894; P = 0.030) among KRAS mutations was an independent risk factor for recurrence.
CONCLUSION: This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.

Keywords:  Codon; Colonic neoplasms; Genes; Ras; Rectal neoplasms

DOI:  https://doi.org/10.3748/wjg.v29.i32.4883
J Pak Med Assoc. 2023 Aug;73(8): 1726-1728

Case Report Of A Rare Incidentaloma Of The Adrenal Gland-Schwannoma.

Usama Muhammad Kathia, Azfar Ali, Ammar Tariq Alvi, Ali Waqar Chaudhry, Hamid Elahi, Khizar Hayat Gondal.

  The Schwannoma is a benign growth of the nerve sheath cells most commonly seen in the vestibulocochlear nerve. Its prevalence in the adrenal gland is 1-3%. Here we discuss a case that presented as an incidentaloma of the right adrenal gland in a young male patient who had vague abdominal symptoms and a normal hormonal profile. He underwent an excisional biopsy of the right adrenal gland due to the large size of the lesion (more than 4cm). The histopathology report helped to establish the diagnosis of Schwannoma. Incidentaloma is defined as a lesion of the adrenal gland encountered on any radiological investigation carried out for symptoms that are not associated with adrenal pathologies. After discovering such lesions, it is imperative to perform radiological and hormonal investigations in an organised manner to plan further management of such cases.

Keywords:   Schwannoma, Adrenal Incidentaloma, Adrenocortical Adenoma, Adrenocortical Carcinoma, Adrenalectomy

DOI:  https://doi.org/10.47391/JPMA.7310
Asian J Surg. 2023 Sep 09. pii: S1015-9584(23)01388-X. [Epub ahead of print]

Schwannomatosis manifesting as multiple schwannomas in a single intercostal nerve.

Min-Li Lv, Jian-Quan Zhong, Hao Feng.



Keywords:  3-D reconstruction; CT; Neurogenic tumor; Schwannomatosis

DOI:  https://doi.org/10.1016/j.asjsur.2023.08.224
Hand Surg Rehabil. 2023 Sep 13. pii: S2468-1229(23)00166-4. [Epub ahead of print]

Plexiform neurofibroma (Hamartoma) of the median nerve: A two-case report.

Ali Murat Başak, Derya Özçelik, Gupse Turan.

  Plexiform neurofibroma is a benign peripheral nerve-sheath tumor, rarely involving major nerves of the extremities. In the literature, there are no clear treatment strategies for plexiform neurofibroma of major peripheral nerves. Our experience encountered two patients with plexiform neurofibroma of the median nerve, presenting with a palmar mass and symptoms of carpal tunnel compression. Preoperatively, plexiform neurofibroma was diagnosed on MRI and clinical examination. Both patients also experienced significant neurological deterioration, with finger numbness and increased nerve/tumor size. Potential malignant transformation was also considered. For these reasons, resection of the involved area of the nerve and repair were indicated. In both patients, intraoperative pathological diagnosis was plexiform neurofibroma. The 45-year-old male patient refused further surgery after carpal tunnel release, which was performed under axillary block. One year postoperatively, nerve compression symptoms decreased moderately. In the other patient, a 7-year-old boy, a significantly enlarged area of the median nerve was resected, and neurorrhaphy was performed. One year postoperatively, median nerve motor-sensory functions recovered completely. Four years postoperatively, no enlargement of the residual tumor was observed.

Keywords:  Hamartoma; Hand; Median nerve; Nerve; Plexiform neurofibroma; Tumor

DOI:  https://doi.org/10.1016/j.hansur.2023.08.007
J Thorac Dis. 2023 Aug 31. 15(8): 4314-4323

Effect of baseline cancer pain on the efficacy of immunotherapy in lung cancer patients.

Huan Zhou, Jingwen Wei, Wei Sun, Zhengbo Song.

   Background: Cancer pain is a common symptom in cancer patients. However, few reports have evaluated the effect of baseline cancer pain on the efficacy of immunotherapy in lung cancer patients. The aim of this retrospective study is to reveal the effect of baseline cancer pain on the prognosis of lung cancer patients receiving immunotherapy.
Methods: We retrospectively reviewed the medical records of lung cancer patients who received immunotherapy at Zhejiang Cancer Hospital and were included 280 patients with or without baseline cancer pain. Propensity score matching (PSM) was used to minimize potential selection bias. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier estimation and log-rank tests. Cox proportional hazard regression analysis was performed to identify factors associated with survival independence.
Results: The median PFS and OS of the patients with baseline cancer pain were significantly shorter than that of patients without baseline cancer pain (PFS: 3.1 vs. 6.5 months, P=0.001; OS: 16.5 vs. 31.2 months, P<0.001). PSM also included 27 patients with or without breakthrough pain. Patients with breakthrough pain had significantly shorter median PFS and OS than those without breakthrough pain (PFS: 1.9 vs. 4.2 months, P=0.001; OS: 9.9 vs. 18.7 months, P=0.012). Cox analysis results implicated breakthrough pain as an independent prognostic factor for immunotherapy.
Conclusions: Baseline cancer pain is a negative prognostic factor for lung cancer patients receiving immunotherapy. Patients with baseline cancer pain may have a worse survival prognosis if they develop breakthrough pain.

Keywords:  Baseline cancer pain; breakthrough pain; efficacy; immune checkpoint inhibitors (ICIs); lung cancer

DOI:  https://doi.org/10.21037/jtd-23-375