Long-term influence of adjuvant breast radiotherapy on cognitive function in breast cancer patients treated with conservation therapy

Abstract

Background

The mechanisms underlying cognitive decline after radiotherapy not directed at brain areas remains unclear. We previously suggested that adjuvant breast radiotherapy in breast conservation therapy could lower memory function soon after therapy, and that the process might be partially mediated by plasma interleukin (IL)-6 levels. The present study investigated how that relationship changes longitudinally.

Methods

We performed the Wechsler Memory Scale-Revised (WMS-R) test and measured plasma IL-6 levels for 47 breast cancer surgical patients within 1 year after the initial therapy (study 1) and more than 2 years after study 1 (study 2). We also performed 2 × 2 mixed [the radiotherapy group (n = 25) or the no-radiotherapy group (n = 22) × study 1 or study 2] analysis of covariance on the WMS-R indices and plasma IL-6 levels. The association between changes in plasma IL-6 levels and changes in the WMS-R indices between the two studies was evaluated using Pearson's correlation coefficient.

Results

The Immediate Verbal Memory Index was significantly higher in study 2. The Delayed Recall Index was significantly higher in study 2 and significantly lower in the radiotherapy group only in study 1. There was a significant correlation between changes in plasma IL-6 levels and changes only in the Delayed Recall Index of the WMS-R.

Conclusions

Memory decline in breast cancer patients soon after adjuvant breast radiotherapy was restored approximately 3 years after treatment, and decreased plasma IL-6 levels might be involved in the recovery process.

https://ift.tt/2wAtgon

Video-assisted thoracoscopic right upper lobectomy in a patient with a right-sided aortic arch and Kommerell diverticulum

Abstract

Background

It is a very rare condition for a patient to have right lung cancer and a right-sided aortic arch simultaneously. Right lobectomy under video-assisted thoracoscopic surgery (VATS) in such a patient is a challenging procedure that is seldom reported. We successfully performed a VATS right upper lobectomy in a 77-year-old female with a right-sided aortic arch and Kommerell diverticulum.

Case presentation

A 77-year-old woman was referred to our division for a mixed ground-glass opacity lesion in the right upper lung. A right-sided aortic arch with Kommerell diverticulum was identified by preoperative 3D CT reconstruction. A VATS right upper lobectomy with radical mediastinal lymph node dissection was performed, and the final histological staging was Ia3 (pT1cN0M0). The patient was discharged without any complications.

Conclusions

We conclude that the video-assisted thoracic surgery can be safely performed in such conditions. It is difficult to determine the extent of upper mediastinal lymph node dissection in such cases.

https://ift.tt/2NBoq0B

The calcium-binding type III repeats domain of thrombospondin-2 binds to fibroblast growth factor 2 (FGF2)

Abstract

Thrombospondin (TSP)-1 and TSP-2 share similar structures and functions, including a remarkable antiangiogenic activity. We have previously demonstrated that a mechanism of the antiangiogenic activity of TSP-1 is the interaction of its type III repeats domain with fibroblast growth factor-2 (FGF2), affecting the growth factor bioavailability and angiogenic activity. Since the type III repeats domain is conserved in TSP-2, this study aimed at investigating whether also TSP-2 retained the ability to interact with FGF2. The FGF2 binding properties of TSP-1 and TSP-2 and their recombinant domains were analyzed by solid-phase binding and surface plasmon resonance assays. TSP-2 bound FGF2 with high affinity (Kd = 1.3 nM). TSP-2/FGF2 binding was inhibited by calcium and heparin. The FGF2-binding domain of TSP-2 was located in the type III repeats and the minimal interacting sequence was identified as the GVTDEKD peptide in repeat 3C, corresponding to KIPDDRD, the active sequence of TSP-1. A second putative FGF2 binding sequence was also identified in repeat 11C of both TSPs. Computational docking analysis predicted that both the TSP-2 and TSP-1-derived heptapeptides interacted with FGF2 with comparable binding properties. Accordingly, small molecules based on the TSP-1 active sequence blocked TSP-2/FGF2 interaction. Binding of TSP-2 to FGF2 impaired the growth factor ability to interact with its cellular receptors, since TSP-2-derived fragments prevented the binding of FGF2 to both heparin (used as a structural analog of heparan sulfate proteoglycans) and FGFR-1. These findings identify TSP-2 as a new FGF2 ligand that shares with TSP-1 the same molecular requirements for interaction with the growth factor and a comparable capacity to block FGF2 interaction with proangiogenic receptors. These features likely contribute to TSP-2 antiangiogenic and antineoplastic activity, providing the rationale for future therapeutic applications.

https://ift.tt/2LHlrSi

Understanding the evolving phenotype of vascular complications in telomere biology disorders

Abstract

Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications, hypotheses for the underlying biology and developed new collaborations to address the etiology and clinical management of vascular complications in TBDs.

https://ift.tt/2N1mGjV

Angiogenesis in pancreatic cancer: current research status and clinical implications

Abstract

Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of < 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors. However, clinical outcomes are far from satisfying for pancreatic cancer patients receiving anti-angiogenic therapies. In this review, we summarize the current status of angiogenesis in pancreatic cancer research and explore the reasons for the poor efficacy of anti-angiogenic therapies, aiming to identify some potential therapeutic targets that may enhance the effectiveness of anti-angiogenic treatments.

https://ift.tt/2PjhCVs

Community Pharmacists’ Knowledge, Attitudes, and Practice of Herbal Medicines in Asir Region, Kingdom of Saudi Arabia

Background. A dramatic increase in the use of natural products and herbal medicines has been observed globally. Simultaneously, there has been an increase in safety concerns regarding the extensive use of these herbal remedies among health care practitioners. The urban and rural populations of Saudi Arabia still rely on traditional Arabic herbal medicines for the treatment of various diseases. Objectives. This study aimed to evaluate community pharmacists' knowledge, attitudes, and practices of herbal medicines in the Asir region, Saudi Arabia. Methods. An online cross-sectional study was conducted among 233 community pharmacists using a structured questionnaire. Results. Pharmacists showed considerable knowledge of the indications of herbal products, with an average score of 84% correct answers, total P value

https://ift.tt/2LBQ6k0

Chitinase 3-like 1-CD44 interaction promotes metastasis and epithelial-to-mesenchymal transition through β-catenin/Erk/Akt signaling in gastric cancer

Abstract

Background

Enzymatically inactive chitinase-like protein CHI3L1 drives inflammatory response and promotes tumor progression. However, its role in gastric cancer (GC) tumorigenesis and metastasis has not yet been fully elucidated. We determined the significance of CHI3L1 expression in patients with GC. We also explored an as-yet unknown receptor of CHI3L1 and investigated the involved signaling in GC metastasis.

Methods

CHI3L1 expression was evaluated by immunoblotting, tissue microarray-based immunohistochemistry analysis (n = 100), and enzyme linked immunosorbent assay (ELISA) (n = 150). The interactions between CD44 and CHI3L1 or Interleukin-13 receptor alpha 2 (IL-13Rα2) were analyzed by co-immunoprecipitation, immunofluorescence co-localization assay, ELISA, and bio-layer interferometry. The roles of CHI3L1/CD44 axis in GC metastasis were investigated in GC cell lines and experimental animal model by gain and loss of function.

Results

CHI3L1 upregulation occurred during GC development, and positively correlated with GC invasion depth, lymph node status, and tumor staging. Mechanically, CHI3L1 binding to CD44 activated Erk and Akt, along with β-catenin signaling by phosphorylating β-catenin at Ser552 and Ser675. CD44 also interacted with IL-13Rα2 to form a complex. Notably, CD44v3 peptide and protein, but not CD44v6 peptide or CD44s protein, bound to both CHI3L1 and IL-13Rα2. Our in vivo and in vitro data further demonstrated that CHI3L1 promoted GC cell proliferation, migration, and metastasis.

Conclusions

CHI3L1 binding to CD44v3 activates Erk, Akt, and β-catenin signaling, therefore enhances GC metastasis. CHI3L1 expression is a novel biomarker for the prognosis of GC, and these findings have thus identified CHI3L1/CD44 axis as a vital pathway and potential therapeutic target in GC.

https://ift.tt/2C0clAI