bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2022–11–20
seven papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies.
  2. Circadian disruption and cancer- and treatment-related symptoms.
  3. Impact of adjuvant therapy on outcomes after curative-intent resection for distal cholangiocarcinoma.
  4. Factors influencing apparent diffusion coefficient value in extrahepatic cholangiocarcinoma: A retrospective study.
  5. Individualized conditional survival nomograms for stage I-III early onset colorectal cancer patients.
  6. Hybrid tumors with perineurioma components: a systematic review of the literature and illustrative case.
  7. Emerging roles of the P2X7 receptor in cancer pain.
  1. Cell Metab. 2022 Nov 11. pii: S1550-4131(22)00490-9. [Epub ahead of print]
    Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies.
    Yu Zhang, Chengzhong Lin, Zheqi Liu, Yiting Sun, Mingtao Chen, Yibo Guo, Wei Liu, Chenping Zhang, Wantao Chen, Jian Sun, Ronghui Xia, Yuhua Hu, Xi Yang, Jiang Li, Zhiyuan Zhang, Wei Cao, Shuyang Sun, Xu Wang, Tong Ji.
      Although nutrient-starvation therapies can elicit strong anti-tumor effects in multiple carcinomas, it has been convincingly demonstrated that cancer cells exploit the tumor microenvironment to thrive in nutrient-poor environments. Here, we reveal that cancer cells can co-opt nociceptive nerves to thrive in nutrient-poor environments. Initially examining the low-glucose environment of oral mucosa carcinomas, we discovered that cancer cells employ ROS-triggered activation of c-Jun to secrete nerve growth factor (NGF), which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP) production. The neurogenic CGRP subsequently induces cytoprotective autophagy in cancer cells through Rap1-mediated disruption of the mTOR-Raptor interaction. Both anti-glycolysis and anti-angiogenesis-based nutrient-starvation therapies aggravate the vicious cycle of cancer cells and nociceptive nerves and therapeutically benefit from blocking neurogenic CGRP with an FDA-approved antimigraine drug. Our study sheds light on the role of the nociceptive nerve as a microenvironmental accomplice of cancer progression in nutrient-poor environments and upon nutrient-starvation therapies.
    Keywords:  CGRP; angiogenesis; autophagy; cancer neuroscience; glycolysis; melanoma; nociceptive nerve; nutrient-starvation therapy; oral mucosa carcinomas; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.cmet.2022.10.012
  2. Front Oncol. 2022 ;12 1009064
    Circadian disruption and cancer- and treatment-related symptoms.
    Ali Amidi, Lisa M Wu.
      Cancer patients experience a number of co-occurring side- and late-effects due to cancer and its treatment including fatigue, sleep difficulties, depressive symptoms, and cognitive impairment. These symptoms can impair quality of life and may persist long after treatment completion. Furthermore, they may exacerbate each other's intensity and development over time. The co-occurrence and interdependent nature of these symptoms suggests a possible shared underlying mechanism. Thus far, hypothesized mechanisms that have been purported to underlie these symptoms include disruptions to the immune and endocrine systems. Recently circadian rhythm disruption has emerged as a related pathophysiological mechanism underlying cancer- and cancer-treatment related symptoms. Circadian rhythms are endogenous biobehavioral cycles lasting approximately 24 hours in humans and generated by the circadian master clock - the hypothalamic suprachiasmatic nucleus. The suprachiasmatic nucleus orchestrates rhythmicity in a wide range of bodily functions including hormone levels, body temperature, immune response, and rest-activity behaviors. In this review, we describe four common approaches to the measurement of circadian rhythms, highlight key research findings on the presence of circadian disruption in cancer patients, and provide a review of the literature on associations between circadian rhythm disruption and cancer- and treatment-related symptoms. Implications for future research and interventions will be discussed.
    Keywords:  cancer; circadian rhythms; cognitive impairment; depressed mood; fatigue; sleep
    DOI:  https://doi.org/10.3389/fonc.2022.1009064
  3. J Surg Oncol. 2022 Nov 17.
    Impact of adjuvant therapy on outcomes after curative-intent resection for distal cholangiocarcinoma.
    Jing-Jing Hou, Shishir K Maithel, Sharon M Weber, George Poultsides, Christopher L Wolfgang, Ryan C Fields, Jin He, Charles Scoggins, Kamron Idrees, Perry Shen, Xu-Feng Zhang, Timothy M Pawlik.
       BACKGROUND: The benefit of adjuvant therapy (AT) after curative resection of distal cholangiocarcinoma (DCC) remains unclear. The objective of the current study was to investigate the impact of AT on long-term survival of patients who underwent curative-intent resection for DCC.
    METHODS: Patients who underwent curative-intent resection for DCC between 2000 and 2020 were identified from a multi-institutional database. The primary outcomes included overall (OS) and recurrence-free survival (RFS).
    RESULTS: Among 245 patients, 150 (61.2%) patients received AT (chemotherapy alone: n = 43; chemo- and radiotherapy: n = 107) after surgical resection, whereas 95 (38.8%) patients underwent surgery only. Patients who received AT were younger, and more likely to have an advanced tumor with the presence of perineural invasion (PNI), lymph node metastasis (LNM), lymph-vascular invasion, and higher T categories (all p < 0.05). Overall, there was no difference in OS (median, surgery + AT 25.5 vs. surgery alone 24.5 months, p = 0.27) or RFS (median, surgery + AT 15.8 vs. surgery alone 18.9 months, p = 0.24) among patients who did versus did not receive AT. In contrast, AT was associated with improved long-term survival among patients with PNI (median OS, surgery + AT 25.9 vs. surgery alone 17.8 months, p = 0.03; median RFS, surgery + AT 15.9 vs. surgery alone 11.9 months, p = 0.04) and LNM (median, surgery + AT 20.0 vs. surgery alone 17.8 months, p = 0.03), but not among patients with no PNI or LNM (all p > 0.1).
    CONCLUSIONS: AT was commonly utilized among patients with DCC. Patients with more advanced disease, including the presence of PNI or LNM, benefited the most from AT with improved long-term outcomes among this subset of patients.
    Keywords:  adjuvant therapy; distal cholangiocarcinoma; lymph node metastasis; perineural invasion; recurrence
    DOI:  https://doi.org/10.1002/jso.27146
  4. Eur J Radiol. 2022 Nov 10. pii: S0720-048X(22)00453-3. [Epub ahead of print]157 110603
    Factors influencing apparent diffusion coefficient value in extrahepatic cholangiocarcinoma: A retrospective study.
    ChunMei Yang, Xin Quan, XinQiao Huang, ZhuoYue Tang, Jian Shu.
       BACKGROUND: Most cases of extrahepatic cholangiocarcinoma (ECC) show various degrees of hyperintensity on diffusion-weighted imaging (DWI) and hypointensity on apparent diffusion coefficient (ADC). However, the factors influencing ADC values in ECC have not yet been explored extensively. Therefore, this study explored the independent factors influencing ADC values in ECC.
    METHODS: A total of 88 patients with ECC confirmed by surgical pathology were retrospectively assessed. All patients underwent abdominal magnetic resonance imaging (MRI) at 3.0 T and ADC values of the tumor were measured. The correlation between ADC values and multiple clinicopathological features in ECC was analyzed, and independent factors influencing the ADC values in ECC were explored further.
    RESULTS: The ADC value of the tumor showed a significant difference in different perineural invasion group (p = 0.048), microvascular invasion group (p = 0.001), vascular endothelial growth factor expression group (p < 0.001), lymphatic status group (p = 0.003), and differentiation degree (DD) group (p < 0.001). However, there were no significant differences in different sex (p = 0.715), tumor location (p = 0.659), and degree of T stage (p = 0.879). Moreover, ADC value was negatively correlated with microvascular density (r = -0.725, p < 0.001) and lesion size (r = -0.244, p = 0.023). Nevertheless, there was no correlation between ADC value and patient age (r = 0.026, p = 0.812). Further regression analysis indicated that ADC value was independently associated with pathological DD of ECC (R2 = 0.678, p < 0.001) but not with other clinicopathological factors (p > 0.05).
    CONCLUSION: ADC value of ECC is independently correlated with pathological DD of ECC, indicating that ADC value is a potential imaging biomarker for predicting the degree of ECC malignancy.
    Keywords:  Apparent diffusion coefficient; Differentiation degree; Extrahepatic cholangiocarcinoma; Influencing factors
    DOI:  https://doi.org/10.1016/j.ejrad.2022.110603
  5. Jpn J Clin Oncol. 2022 Nov 16. pii: hyac169. [Epub ahead of print]
    Individualized conditional survival nomograms for stage I-III early onset colorectal cancer patients.
    Min Chen, Ting Chen.
       OBJECTIVE: Conditional survival accounts for the time already survived after surgery and provides additional survival information. The aim was to assess conditional survival in stages I-III early onset colorectal cancer patients and to create nomograms predicting the conditional overall survival and cancer-specific survival after surgery.
    METHODS: A total of 7058 patients who underwent surgical resection of early onset colorectal cancer were identified from surveillance, epidemiology and end results database. The formula used for conditional survival calculation was conditional survival(x|y) = S(x + y)/S(x), where S(x) represents the survival at x years. Conditional survival nomograms were then developed to predict the 5-year conditional overall survival and cancer-specific survival.
    RESULTS: The 5-year overall survival and cancer-specific survival after surgery increases gradually with additional survival time. Race, tumour site, grade, histology, T stage, N stage, lymph node ratio, preoperative carcinoma embryonic antigen level and perineural invasion status were independent predictors of cancer-specific survival, while age and sex were another two independent risk factors for overall survival. The nomograms based on these factors were successfully developed to predict 5-year overall survival and cancer-specific survival given 1-4 years already survived.
    CONCLUSION: The probability of achieving postoperative 5-year overall survival and cancer-specific survival for early onset colorectal cancer increases gradually with additional time survived. The developed nomograms are fairly valuable and informative in facilitating clinical treatment and follow-up schemes.
    Keywords:  cancer-specific survival; conditional survival; early onset colorectal cancer; nomogram; overall survival
    DOI:  https://doi.org/10.1093/jjco/hyac169
  6. Acta Neurochir (Wien). 2022 Nov 18.
    Hybrid tumors with perineurioma components: a systematic review of the literature and illustrative case.
    Karina A Lenartowicz, Dileep D Monie, Kimberly K Amrami, Christopher J Klein, Caterina Giannini, Robert J Spinner.
       PURPOSE: Hybrid peripheral nerve sheath tumors (HPNST) are a newly recognized class of peripheral nerve sheath tumor, composed of at least two areas characteristic of perineurioma, schwannoma, or neurofibroma. The literature consists only of case reports and small series; therefore, we present an illustrative case and an analysis of all reported cases of HPNST with a perineurioma component in the literature.
    METHODS: A systematic search of the literature was performed to identify all reported cases of hybrid perineurioma-schwannoma or perineurioma-neurofibroma in the world's literature. Individual cases were analyzed for demographics, clinical features, imaging, and outcomes.
    RESULTS: A total of 159 cases were identified across 41 studies. Hybrid tumors tended to present in mid-adulthood (median 38.5 years), predominantly affected females (57%, 89/156), as a painless (63%, 63/100) mass, or swelling. Ten patients (10/74, 14%) had a history of neurofibromatosis 1, and 2 patients a history of neurofibromatosis 2 (2/74, 3%). The majority (78%, 122/157) of cases occurred superficially, most commonly in the lower extremity (25%, 39/157). Perineurioma-schwannoma was the most reported (86%, 137/159) pathologic diagnosis, with 3 cases presenting with malignant features. Two cases reocurred after resection.
    CONCLUSION: HPNST tend to occur in mid-adulthood and present as slowly progressive, painless, superficial masses, with a heterogeneous appearance on imaging. These entities pose a unique diagnostic challenge and likely remain under-recognized in the literature and current clinical practice. They pose low risk of recurrence or malignant transformation, and future work regarding the association with neurofibromatosis and genetic profiles is needed.
    Keywords:  Hybrid tumor; Neurofibroma; Perineurioma; Peripheral nerve sheath; Schwannoma
    DOI:  https://doi.org/10.1007/s00701-022-05413-5
  7. Purinergic Signal. 2022 Nov 19.
    Emerging roles of the P2X7 receptor in cancer pain.
    Ping Wu, Yin Wang, Yansong Liu, Yan Liu, Guohua Zhou, Xiaoqi Wu, Qingping Wen.
      Cancer pain is the most prevalent symptom experienced by cancer patients. It substantially impacts a patient's long-term physical and emotional health, making it a pressing issue that must be addressed. Purinergic receptor P2X7 (P2X7R) is a widely distributed and potent non-selective ATP-gated ion channel that regulates tumor proliferation, chronic pain, and the formation of inflammatory lesions in the central nervous system. P2X7R plays an essential role in cancer pain and complications related to cancer pain including depression and opioid tolerance. This review focuses on the structure and distribution of P2X7R, its role in diverse tissues in cancer pain, and the application of P2X7R antagonists in the treatment of cancer pain to propose new ideas for cancer pain management.
    Keywords:  Cancer pain; Depression; P2X7 receptor; P2X7 receptor antagonist
    DOI:  https://doi.org/10.1007/s11302-022-09902-1
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