bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2022‒01‒02
six papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

  1. Cancer Metastasis Rev. 2021 Dec 27.
      Sleep is a basic need that is frequently set aside in modern societies. This leads to profound but complex physiological maladaptations in the body commonly referred to as circadian disruption, which recently has been characterized as a carcinogenic factor and reason for poor treatment outcomes, shortened survival, and reduced quality of life in cancer patients. As sleep and circadian physiology in cancer patients spans several disciplines including nursing science, neurology, oncology, molecular biology and medical technology, there is a lack of comprehensive and integrated approaches to deal with this serious and growing issue and at best a fractionated understanding of only part of the problem among researchers within each of these segments. Here, we take a multidisciplinary approach to comprehensively review the diagnosis and impact of sleep and circadian disruption in cancer patients. We discuss recent discoveries on molecular regulation of the circadian clock in healthy and malignant cells, the neurological and endocrine pathways controlling sleep and circadian rhythmicity, and their inputs to and outputs from the organism. The benefits and drawbacks of the various technologies, devices, and instruments used to assess sleep and circadian function, as well as the known consequences of sleep disruption and how sleep can be corrected in cancer patients, will be analyzed. We will throughout the review highlight the extensive crosstalk between sleep, circadian rhythms, and metabolic pathways involved in malignancy and identify current knowledge gaps and barriers for addressing the issue of sleep and circadian disruption in cancer patients. By addressing these issues, we hope to provide a foundation for further research as well as better and more effective care for the patients in the future.
    Keywords:  Cancer; Circadian clock; Metabolism; Patient care; Sleep; Treatment
  2. Front Oncol. 2021 ;11 781340
      Background: Brain metastasis (BM) is one of the most common failure patterns of pIIIA-N2 non-small cell lung cancer (NSCLC) after complete resection. Prophylactic cranial irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify the risk factors that are associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI.Methods and Materials: Between 2011 and 2014, patients with pIIIA-N2 NSCLC who underwent complete resection in our institution were reviewed and enrolled in the study. Clinical characteristics, pathological parameters, treatment mode, BM time, and overall survival were analyzed. A nomogram was built based on the corresponding parameters by Fine and Gray's competing risk analysis to predict the 1-, 3-, and 5-year probabilities of BM. Receiver operating characteristic curves and calibration curves were chosen for validation. A statistically significant difference was set as P <0.05.
    Results: A total of 517 patients were enrolled in our retrospective study. The median follow-up time for surviving patients was 53.2 months (range, 0.50-123.17 months). The median age was 57 (range, 25-80) years. Of the 517 patients, 122 (23.6%) had squamous cell carcinoma, 391 (75.6%) received adjuvant chemotherapy, and 144 (27.3%) received post-operative radiotherapy. The 1-, 3-, and 5-year survival rates were 94.0, 72.9, and 66.0%, respectively. The 1-, 3-, and 5-year BM rates were 5.4, 15.7, and 22.2%, respectively. According to the univariate analysis, female, non-smokers, patients with non-squamous cell carcinoma, bronchial invasion, perineural invasion, and patients who received adjuvant chemotherapy were more likely to develop BM. In a multivariate analysis, non-squamous cell carcinoma (subdistribution hazard ratios, SHR: 3.968; 95% confidence interval, CI: 1.743-9.040; P = 0.0010), bronchial invasion (SHR: 2.039, 95% CI: 1.325-3.139; P = 0.0012), perineural invasion (SHR: 2.514, 95% CI: 1.058-5.976; P = 0.0370), and adjuvant chemotherapy (SHR: 2.821, 95% CI: 1.424-5.589; P = 0.0030) were independent risk factors for BM. A nomogram model was established based on the final multivariable analysis result. The area under the curve was 0.767 (95% CI, 0.758-0.777).
    Conclusions: For patients with IIIA-N2 NSCLC after complete resection, a nomogram was established based on clinicopathological factors and treatment patterns for predicting the BM. Based on this nomogram, patients with a high risk of BM who may benefit from PCI can be screened.
    Keywords:  brain metastasis; competing risk analysis; complete resection; nomogram; non-small cell lung cancer
  3. Acta Gastroenterol Belg. 2021 Oct-Dec;84(4):84(4): 607-617
      Background and study aims: The prognostic value of H. pylori, which infects more than half of the human population living in the world and plays a role in gastric cancer pathogenesis, is controversial. Our aim is to investigate the relationship between H. pylori and prognostic factors in gastric cancer.Patients and methods: The data of 110 patients (38 females and 72 males) that underwent surgeries due to gastric cancer between 2014 and 2017 were retrospectively analyzed. The relationships between survival (disease-free and overall) and factors such as p53, HER2/neu, Ki-67, neutrophil and platelet lymphocyte ratio (NLR / PLR), histopathological and demographic characteristics were examined. In addition, the results of H. pylori positive and negative groups were compared.
    Results: Sixty-one (55%) patients were H. pylori negative and 49 (45%) were positive. In multivariate analysis, TNM stage, lymph node capsule invasion and NLR were determined as independent prognostic factors in both disease-free and overall survival. Age>62 and PLR>14.3 were determined as independent predictive factors of poor prognosis in overall survival. In univariate analysis, tumor diameter of >4.3 cm, lymphovascular and perineural invasion, and diffuse p53 expression were determined as predictive factors of poor prognosis in disease-free and overall survival. The effectiveness of these markers in prognosis was not different between H. pylori negative and positive groups.
    Conclusion: While age, tumor diameter, TNM stage, lymph node capsule invasion, perineural and lymphovascular invasion, diffuse p53, PLR, and NLR were determined as prognostic factors in gastric cancer, these factors were not affected by the presence of H. pylori.
    Keywords:  H. pylori; HER2; gastric cancer; neutrophil lymphocyte ratio; p53; platelet lymphocyte ratio
  4. World J Gastroenterol. 2021 Dec 07. 27(45): 7813-7830
      BACKGROUND: Surgical resection is a treatment of choice for gallbladder cancer (GBC) patients but only 10% of patients have a resectable disease at presentation. Even after surgical resection, overall survival (OS) has been poor due to high rates of recurrence. Combination of surgery and systemic therapy can improve outcomes in this aggressive disease.AIM: To summarize our single-center experience with multimodality management of resectable GBC patients.
    METHODS: Data of all patients undergoing surgery for suspected GBC from January 2012 to December 2018 was retrieved from a prospectively maintained electronic database. Information extracted included demographics, operative and perioperative details, histopathology, neoadjuvant/adjuvant therapy, follow-up, and recurrence. To know the factors associated with recurrence and OS, univariate and multivariate analysis was done using log rank test and cox proportional hazard analysis for categorical and continuous variables, respectively. Multivariate analysis was done using multiple regression analysis.
    RESULTS: Of 274 patients with GBC taken up for surgical resection, 172 (62.7%) were female and the median age was 56 years. On exploration, 102 patients were found to have a metastatic or unresectable disease (distant metastasis in 66 and locally unresectable in 34). Of 172 patients who finally underwent surgery, 93 (54%) underwent wedge resection followed by anatomical segment IVb/V resection in 66 (38.4%) and modified extended right hepatectomy in 12 (7%) patients. The postoperative mortality at 90 d was 4.6%. During a median follow-up period of 20 mo, 71 (41.2%) patients developed recurrence. Estimated 1-, 3-, and 5-years OS rates were 86.5%, 56%, and 43.5%, respectively. Estimated 1- and 3-year disease free survival (DFS) rates were 75% and 49.2%, respectively. On multivariate analysis, inferior OS was seen with pT3/T4 tumor (P = 0.0001), perineural invasion (P = 0.0096), and R+ resection (P = 0.0125). However, only pT3/T4 tumors were associated with a poor DFS (P < 0.0001).
    CONCLUSION: Multimodality treatment significantly improves the 5-year survival rate of patients with GBC up to 43%. R+ resection, higher T stage, and perineural invasion adversely affect the outcome and should be considered for systemic therapy in addition to surgery to optimize the outcomes. Multimodality treatment of GBC has potential to improve the survival of GBC patients.
    Keywords:  Adjuvant; Chemoradiotherapy; Chemotherapy; Gallbladder cancer; Multimodality; Surgical resection
  5. Front Endocrinol (Lausanne). 2021 ;12 766463
      Objective: Our study aims to clarify the role of estradiol and leptin in breast cancer risk and prognostic assessment in postmenopausal Chinese women.Design: The serum circulating estradiol and leptin level was detected by ELISA. Then the correlation between estradiol, leptin level, and clinical characteristics was analyzed using Fisher's exact test. Next, the Kaplan-Meier model was used to analyze the association between estradiol, leptin, and prognosis of postmenopausal breast cancer patients in our cohort and the TCGA dataset.
    Setting: The study was conducted at the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College.
    Patients: A total of 182 postmenopausal breast cancer patients and 111 healthy subjects from January 2010 to August 2010 were included in the analysis. Another 702 cases with breast cancer were retrieved from The Cancer Genome Atlas (TCGA) database for subsequent analysis.
    Main Outcome Measure: Serum circulating estradiol and leptin level.
    Results: The level of estradiol was significantly higher (P<0.001) but the level of leptin had no significant difference (P = 0.764) in postmenopausal breast cancer patients compared with healthy subjects. The level of estradiol and leptin was not significantly different between estrogen receptor (ER) positive and ER-negative groups (P>0.05). Estradiol was significantly correlated with tumor T stage (P = 0.002) and leptin was significantly associated with perineural invasion (P = 0.014). In addition, the disease-free survival of patients with a high level of estradiol was significantly shorter (P = 0.025) but leptin tended to be a protective factor for overall survival in TCGA analysis (P = 0.038).
    Conclusion: Circulating estradiol and leptin played important roles in the risk of postmenopausal breast cancer even in low-estrogen nations with an independent expression of ER status. High circulating estradiol was a poor prognostic factor and leptin may be a protection signal in Chinese postmenopausal patients with breast cancer.
    Keywords:  breast cancer; elderly patients; estradiol; leptin; postmenopausal
  6. Med Res Rev. 2021 Dec 29.
      The role of the β-adrenoceptors (β-ARs) in hypoxia-driven diseases has gained visibility after the demonstration that propranolol promotes the regression of infantile hemangiomas and ameliorates the signs of retinopathy of prematurity (ROP). Besides the role of β2-ARs, preclinical studies in ROP have also revealed that β3-ARs are upregulated by hypoxia and that they are possibly involved in retinal angiogenesis. In a sort of figurative round trip, peculiarities typical of ROP, where hypoxia drives retinal neovascularization, have been then translated to cancer, a disease equally characterized by hypoxia-driven angiogenesis. In this step, investigating the role of β3-ARs has taken advantage of the assumption that cancer growth uses a set of strategies in common with embryo development. The possibility that hypoxic induction of β3-ARs may represent one of the mechanisms through which primarily embryo (and then cancer, as an astute imitator) adapts to grow in an otherwise hostile environment, has grown evidence. In both cancer and embryo, β3-ARs exert similar functions by exploiting a metabolic shift known as the Warburg effect, by acquiring resistance against xenobiotics, and by inducing a local immune tolerance. An additional potential role of β3-AR as a marker of stemness has been suggested by the finding that its antagonism induces cancer cell differentiation evoking that β3-ARs may help cancer to grow in a nonhospital environment, a strategy also exploited by embryos. From cancer, the round trip goes back to neonatal diseases for which new possible interpretative keys and potential pharmacological perspectives have been suggested.
    Keywords:  oxygen sensing receptor; oxygen-related prematurity diseases; treatment approach; vessel proliferation/regression; β-adrenergic system