Individualised Multimodal Treatment Strategies for Anaplastic and Poorly Differentiated Thyroid Cancer

Wächter, Sabine; Wunderlich, Annette; Roth, Silvia; Mintziras, Ioannis; Maurer, Elisabeth; Hoffmann, Sebastian; Verburg, Frederik A.; Fellinger, Sebastian A; Holzer, Katharina; Bartsch, Detlef K.; Fazio, Pietro Di

doi:10.3390/jcm7050115

Cited by 29 publications

(26 citation statements)

References 33 publications

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“…After behavioral analyses, the mice were anesthetized via a combination of ketamine and xylazine and euthanized, as previously described [6,38]. The brain parts were separated and homogenized in PRO-PREP TM extraction solution (iNtRON Biotechnology, Inc., Sungnam, South Korea) and centrifuged (13,000 RPM for 25 min at 4 • C).…”

Section: Immunoblotingmentioning

confidence: 99%

Oral Administration of Alpha Linoleic Acid Rescues Aβ-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice

Ali

Ikram

Park

et al. 2020

Cells

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In this work, we evaluated the effects of alpha linoleic acid (ALA), an omega-3 polyunsaturated fatty acid, on amyloid-beta-induced glial-cell-mediated neuroinflammation, amyloidogenesis, and cognitive dysfunction in mice. After an infusion of Aβ1–42 (Aβ1–42, 5 μL/5 min/mouse, intracerebroventricular injection (i.c.v), and respective treatments of ALA (60 mg/kg per oral for six weeks), neuroinflammation, apoptotic markers, and synaptic markers were evaluated by Western blot and immunofluorescence analyses. According to our findings, the infusion of Aβ1–42 activated Toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the frontal cortices and hippocampi of the Aβ1–42-injected mice to a greater extent than the Aβ1–42 + ALA-cotreated mice. Similarly, there was an elevated expression of phospho-c-Jun-N-terminal kinase (p-JNK), phospho-nuclear factor-kB p65 (p-NF-kB p65 (Ser536)), and tissue necrosis factor (TNF) in the Aβ1–42 infused mouse brains; interestingly, these markers were significantly reduced in the Aβ + ALA-cotreated group. The elevated expression of pro-apoptotic markers was observed during apoptotic cell death in the Aβ1–42-treated mouse brains, whereas these markers were markedly reduced in the Aβ + ALA-cotreated group. Moreover, Aβ1–42 infusion significantly increased amyloidogenesis, as assessed by the enhanced expression of the amyloid precursor proteins (APP) beta-amyloid cleaving enzyme-1 (BACE-1) and amyloid-beta (Aβ1–42) in the mouse brains, whereas these proteins were markedly reduced in the Aβ + ALA-cotreated group. We also checked the effects of ALA against Aβ-triggered synaptic dysfunction and memory dysfunction, showing that ALA significantly improved memory and synaptic functions in Aβ-treated mouse brains. These results indicated that ALA could be an applicable intervention in neuroinflammation, apoptotic cell loss, amyloidogenesis, and memory dysfunction via the inhibition of TLR4 and its downstream targets in Aβ + ALA-cotreated mouse brains.

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Section: Immunoblotingmentioning

confidence: 99%

Oral Administration of Alpha Linoleic Acid Rescues Aβ-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice

Ali

Ikram

Park

et al. 2020

Cells

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“…Poorly differentiated thyroid cancer (PDTC) remains one of the most aggressive cancers of the head and neck with a poor prognosis due to its radioiodine refractoriness, high metastatic potential and current limited armamentarium of effective treatment strategies. 1,2 The Walczyk retrospective study of 46 patients with PDTC Outcomes of this study showed that integration of AJCC stage, ATA risk and age group identifies six subgroups of patients with progressively worse DSS as AJCC stage, ATA risk and age increases, and in addition provides a more individualized estimate of DSS, especially in ATA high-risk patients. 4 From a histopathogenetic and clinical perspective, PDTCs are distinctive, and they have a risk of mortality, recurrence and metastasis that resides between that of well-differentiated thyroid cancers and anaplastic carcinomas.…”

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confidence: 96%

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confidence: 99%

“…

Please see related paper on pages [331][332][333][334][335][336][337][338][339] of this issue.Poorly differentiated thyroid cancer (PDTC) remains one of the most aggressive cancers of the head and neck with a poor prognosis due to its radioiodine refractoriness, high metastatic potential and current limited armamentarium of effective treatment strategies. 1,2 The Walczyk retrospective study of 46 patients with PDTC treated in a single tertiary referral centre from 2000 to 2017 focused on the clinical usefulness of the recent 2015 American Thyroid Association (ATA) guidelines and the updated 8th edition of AJCC staging system in patients with this rare and aggressive endocrine malignancy. 3 This Polish study emphasized a comprehensive approach to management of PDTC including clinical and pathological factors, initial risk stratification, response to therapy, and follow-up data including re-evaluation of initial risk estimates.

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confidence: 99%

“…1 Future research in this area should be based on studies aimed at resolving existing controversies and development of the new, personalized multimodal treatment options to improve patient outcomes. 2,5,6 O RCI D…”

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Commentary on the study of Walczyk et al. Poorly differentiated thyroid cancer in the context of the revised 2015 American Thyroid Association Guidelines and the Updated American Joint Committee on Cancer/Tumor‐Node‐Metastasis Staging System (eighth edition).

Barczyński

2019

Clinical Endocrinology

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M2‐like tumor‐associated macrophages‐secreted Wnt1 and Wnt3a promotes dedifferentiation and metastasis via activating β‐catenin pathway in thyroid cancer

Feng

Chen

et al. 2020

Molecular Carcinogenesis

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BackgroundThyroid carcinoma (TC) has been a global issue for its rapid increasing incidence worldwide. Although most TC was not so aggressive with a good prognosis, treatment against anaplastic TC was relatively limited and the mechanisms are not well elucidated yet.MethodsTC cell lines (IHH4 and TPC‐1) were used. Flow cytometry was used to identify the surface marker of M2‐like tumor‐associated macrophages (TAMs) from cell culture. Quantitative real‐time polymerase chain reaction, western blot analysis, immunostaining, and immunohistochemistry were used to detect the expression of Wnt1, Wnt3a, components of Wnt/β‐catenin pathway, and proliferation/epithelial–mesenchymal transition (EMT)‐related proteins. Alkaline phosphatase activity assay, colony formation assay, and transwell assay were used to examine the roles of Wnt1, Wnt3a, and β‐catenin pathway in cell dedifferentiation, proliferation, migration, and invasion of TC cells, respectively. Subcutaneous tumor growth was monitored in nude mice.ResultsCoculture with M2‐like TAMs facilitated dedifferentiation, proliferation, migration, and invasion in TC cells. EMT and proliferation‐related proteins were also promoted in cocultured TC cells. The level of Wnt1 and Wnt3a was increased in the coculture system. Block of Wnt1 or Wnt3a suppressed malignant behaviors in cocultured tumor cells. Furthermore, Wnt1 or Wnt3a knockdown inhibited Wnt/β‐catenin signaling pathway, and suppressed EMT and proliferation‐related signals in cocultured tumor cells. Knockdown of Wnt1 or Wnt3a inhibited tumor growth in xenograft model.ConclusionM2‐like TAMs promoted dedifferentiation, proliferation, and metastasis of TC by Wnt1 and Wnt3a secretion and ensuing β‐catenin activation.

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Individualised Multimodal Treatment Strategies for Anaplastic and Poorly Differentiated Thyroid Cancer

Cited by 29 publications

References 33 publications

Oral Administration of Alpha Linoleic Acid Rescues Aβ-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice

Oral Administration of Alpha Linoleic Acid Rescues Aβ-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice

Commentary on the study of Walczyk et al. Poorly differentiated thyroid cancer in the context of the revised 2015 American Thyroid Association Guidelines and the Updated American Joint Committee on Cancer/Tumor‐Node‐Metastasis Staging System (eighth edition).

M2‐like tumor‐associated macrophages‐secreted Wnt1 and Wnt3a promotes dedifferentiation and metastasis via activating β‐catenin pathway in thyroid cancer

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