Brain Metastases from Colorectal Cancer: Microenvironment and Molecular Mechanisms

Zang, Yiwen; Gu, Xiaodong; Xiang, Jianbin; Chen, Zongyou

doi:10.3390/ijms131215784

Cited by 26 publications

(24 citation statements)

References 99 publications

(95 reference statements)

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“…The impact of other somatic mutations on the development of brain metastases in the mCRC context is currently unclear. Some authors have proposed mutations in phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and v-raf murine sarcoma viral oncogene homologe B1 (BRAF) as predictors of CNS involvement in mCRC patients; however, the evidence is scarce and even contradictory 20,22,23 . BRAF and PIK3CA statuses were not available in our registry for the brain metastasis group, again based on small numbers.…”

Section: Discussionmentioning

confidence: 96%

“…Other authors have proposed an opposite theory whereby different molecular features of the cancer explain the pattern of brain metastases. Across the literature, KRAS mutations in mCRC correlate with poor OS and increased incidence of both lung and brain metastases [20][21][22] . In our study, noting the small number in whom the KRAS mutation status was known, 55% of patients with brain metastases presented with KRASmutated cancers compared to 43% of the overall population, in keeping with this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

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Brain metastasis in advanced colorectal cancer: Results from the South Australian metastatic colorectal cancer (SAmCRC) registry

et al. 2016

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Objective: Brain metastasis is considered rare in metastatic colorectal cancer (mCRC); thus, surveillance imaging does not routinely include the brain. The reported incidence of brain metastases ranges from 0.6% to 3.2%. Methods:The South Australian mCRC Registry (SAmCRC) was analyzed to assess the number of patients presenting with brain metastasis during their lifetime. Due to small numbers, a descriptive analysis is presented. Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis (1.4%). The clinical characteristics of those with brain metastasis were as follows: the median age was 65.3 years and 51% were female. Where the VKi-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status of the tumor was known, the majority harbored a KRAS mutation (55%); 31 (53%) underwent craniotomy and 55 (93%) underwent whole-brain radiotherapy. The median survival time from diagnosis of brain metastasis was 4.2 months (95% confidence interval 2.9-5.5). Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy (8.5 months vs. 2.2 months, respectively). Data from the SAmCRC (a population-based registry) confirm that brain metastases are rare and the median time to development is approximately 2 years. Conclusions: Brain metastasis is a rare outcome in advanced CRC. Patients within the registry tended to be female, young in age, and harbored with higher rates of KRAS mutations. Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately, most patients with central nervous system involvement die from their extracranial disease.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Brain metastasis in advanced colorectal cancer: Results from the South Australian metastatic colorectal cancer (SAmCRC) registry

et al. 2016

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“…2011 120 miR-483-3p Protein Kinase-α, Zang Y-W et al. 2012 114 miR-503 CUG-binding protein 1, Occludin Yang et al. 2014 123 miR-595 Cell-polarity protein-6 Veltman et al.…”

Section: Mirna and Barrier Functionmentioning

confidence: 99%

“… 112,113 In esophageal carcinoma cells the displacement of claudin-7 induces the loss of E-cadherin expression and therefore the destabilization of tight junctions. 114 …”

Section: Mirna and Blood Brain Barriermentioning

confidence: 99%

MicroRNAs regulate tight junction proteins and modulate epithelial/endothelial barrier functions

et al. 2014

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Tightly controlled epithelial and endothelial barriers are a prerequisite for life as these barriers separate multicellular organisms from their environment and serve as first lines of defense. Barriers between neighboring epithelial cells are formed by multiple intercellular junctions including the ‘apical junctional complex—AJC’ with tight junctions (TJ), adherens junctions (AJ), and desmosomes. TJ consist of tetraspan transmembrane proteins like occludin, various claudins that directly control paracellular permeability, and the ‘Junctional Adhesion Molecules’ (JAMs). For establishing tight barriers TJ are essential but at the same time have to allow also selective permeability. For this, TJ need to be tightly regulated and controlled. This is organized by a variety of adaptor molecules, i.e., protein kinases, phosphatases and GTPases, which in turn are regulated and fine-tuned involving microRNAs (miRNAs). In this review we summarize available data on the role and targeting of miRNAs in the maintenance of epithelial and/or endothelial barriers.

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“…In this sense we believe that the model of patients with CNS metastasis could be interesting for the development of biomarkers and understanding the mechanisms of metastasis, as has been suggested by other research groups [21]. …”

Section: Discussionmentioning

confidence: 81%

Central nervous system metastasis secondary to colorectal cancer: a retrospective cohort study of 20 cases

Mondaca¹,

Hornig²,

Muñoz-Schuffenegger³

et al. 2016

ecancer

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IntroductionInvolvement of the central nervous system (CNS) secondary to colorectal cancer is infrequent and associated with a poor prognosis. Its treatment is extrapolated from metastases of other origins as the information available on this scenario is limited. The goal of this study is to assess the clinical characteristics of a series of patients and determine the results in terms of progression-free survival (PFS) and global survival.MethodThe records of patients with CNS metastasis of colorectal origin who were treated in this facility between the years 2001 and 2016 were reviewed retrospectively.Results20 patients with CNS lesions of this origin were identified. Of these, 45% were male and 55% were female (average age 65.5 years). The histology corresponded to tubular adenocarcinoma in 95% of cases. Around 85% of the patients showed a neurological deficit, and their recursive partitioning analysis (RPA) classifications were 1 in 20%, 2 in 55%, and 3 in 25% of the cases studied. The treatments provided were: holocerebral radiotherapy (45%), stereotactic radiosurgery (25%), surgery followed by holocerebral radiotherapy (25%), and exclusively palliative care (5%). The PFS was 2.6 months from treatment of the CNS lesion, while the median survival was 3.8 months. The survival times for patients receiving different treatments were as follows: surgery plus holocerebral radiotherapy 16.2 months, stereotactic radiotherapy 12 months, and holocerebral radiotherapy 2.4 months (p = 0.003).ConclusionThe prognosis for patients with metastasis of colorectal origin is poor. The patients treated with surgery or stereotactic radiotherapy can have a greater survival.

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Brain Metastases from Colorectal Cancer: Microenvironment and Molecular Mechanisms

Cited by 26 publications

References 99 publications

Brain metastasis in advanced colorectal cancer: Results from the South Australian metastatic colorectal cancer (SAmCRC) registry

Brain metastasis in advanced colorectal cancer: Results from the South Australian metastatic colorectal cancer (SAmCRC) registry

MicroRNAs regulate tight junction proteins and modulate epithelial/endothelial barrier functions

Central nervous system metastasis secondary to colorectal cancer: a retrospective cohort study of 20 cases

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