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Κυριακή 14 Νοεμβρίου 2021

Effect of exercise on peritoneal microenvironment and progression of ovarian cancer

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Am J Cancer Res. 2021 Oct 15;11(10):5045-5062. eCollection 2021.

ABSTRACT

Ovarian cancer is one of the deadliest gynecological malignancies and lacks treatments that do not significantly impact patient health-related quality of life. Exercise has been associated with reduced cancer risk and improved clinical outcomes; however the underlying molecular mechanisms are unknown. In this study, we utilized a treadmill-running exercise model to investigate the effects of exercise on high-grade serous ovarian carcinoma (HGSOC) progression and chemotherapy outcomes. We found that treadmill-running suppressed peritoneal colonization of tumors in a syngeneic mouse ovarian cancer model. Acute exercise stimulated the production of CCL2 and IL-15 in the peritoneal microenvironment while downregulating CCL22, VEGF, and CCL12. Using a co-culture model, we demonstrated the role of CCL2 in mediating the activity of peritoneal cells to inhibit cancer cel l viability. We showed that the activation of M1 macrophages may contribute to the exercise-induced changes in the peritoneal microenvironment. We identified that chronic exercise modulates gene expression of intraperitoneal fat tissues related to lipid formation, thermogenesis, browning, and inflammation, which can contribute to inhibiting the colonization of metastatic ovarian cancer. Treadmill running also lowered blood urea nitrogen levels and reduced incidence of neutropenia and thrombocytopenia during chemotherapy in a mouse model, suggesting the potential beneficial effects of exercise in improving chemotherapy outcomes. Our data provided new insights into the acute and chronic effects of physical activity on ovarian cancer at the molecular and in vivo levels.

PMID:34765311 | PMC:PMC8569339

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Identification of potential immune-related circRNA-miRNA-mRNA regulatory network in cutaneous squamous cell carcinoma

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Am J Cancer Res. 2021 Oct 15;11(10):4826-4843. eCollection 2021.

ABSTRACT

Circulating RNAs (circRNAs) are involved in tumor development and progression by participating in immune regulation. Nevertheless, the circRNAs expression profiles and their roles on the immunomodulatory effects in cutaneous squamous cell carcinoma (cSCC) have rarely been studied. In our study, we identified the differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), mRNAs (DEmRNAs) in cSCC and established the circRNA competing endogenous RNAs (ceRNAs) network. Subsequently, the hub differentially expressed immune-related genes were identified and validated by immunochemistry as well as the GO and KEGG pathway analysis were performed. 54 differentially expressed circRNAs were identified and hub differentially expressed immune-related genes were identified and they were mostly associated with immune response in the progression of cSCC. Our results indic ated that the potential immune-related circRNA-miRNA-mRNA network may assist in understanding the molecular mechanisms underlying the carcinogenesis and progression in cSCC. Moreover, the immune-related genes may provide an insight into the pathogenesis, molecular biomarkers, and potential therapeutic targets for cSCC patients.

PMID:34765295 | PMC:PMC8569358

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Dickkopf-1 promotes angiogenesis by upregulating VEGF receptor 2-mediated mTOR/p70S6K signaling in hepatocellular carcinoma

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Am J Cancer Res. 2021 Oct 15;11(10):4788-4806. eCollection 2021.

ABSTRACT

The expression of Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling pathway, is upregulated in hepatocellular carcinoma (HCC). Here, we investigated the tumorigenic and angiogenic potential of DKK1 in HCC. Stable cell lines were established using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9)-based DKK1 knock-out system in Hep3B cells and the tetracycline-based DKK1 inducible system in Huh7 cells. Multicellular tumor spheroids (MCTSs) were cultured using Hep3B stable cells. We also employed xenografts generated using Hep3B stable cells and transgenic mouse models established using hydrodynamic tail vein injection. The angiogenic potential increased in HUVECs treated with CM from Huh7 stable cells with high DKK1 expression and Hep3B wild-type cells. DKK1 accelerated the downstream mo lecules of vascular endothelial growth factor receptor 2 (VEGFR2)-mediated mTOR/p70 S6 kinase (p70S6K) signaling. MCTSs generated using Hep3B wild-type cells promoted compact spheroid formation and increased the expression of CD31 and epithelial-mesenchymal transition (EMT) markers, and increased the VEGFR2-mediated mTOR/p70S6K signaling, compared to the controls (all P<0.01). Xenograft tumors generated using Hep3B cells with DKK1 knock-out (n=10) exhibited slower growth than, the controls (n=10) and the expression of Ki-67, VEGFR2, CD31 and EMT markers decreased (all P<0.05). In addition, forced DKK1 expression with HRAS in transgenic mouse livers (n=5) resulted in the formation of more tumors and increased expression of downstream molecules of VEGFR2-mediated mTOR/p70S6K signaling pathway as well as Ki67, CD31 and EMT markers (P<0.05), compared to that of the controls (n=5). Our findings indicate that DKK1 facilitates angiogenesis and tumorigenesis by upregulating VEGFR2-mediated mTOR/p70S6K signaling in HCC.

PMID:34765293 | PMC:PMC8569356

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The past, present and future of conversion therapy for liver cancer

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Am J Cancer Res. 2021 Oct 15;11(10):4711-4724. eCollection 2021.

ABSTRACT

Primary liver cancer is one of the world's most common malignant tumors, as well as the malignant tumor with the third highest mortality rate in China. Most Chinese patients with liver cancer already have intermediate or advanced stage disease at initial diagnosis and have lost the opportunity for surgery. Following recent advances in treatments for advanced liver cancer, the associated treatment efficacy and response rates have continuously improved. As a result, the application of preoperative treatments can lead to tumor downstaging in a high proportion of patients and consequently provide initially ineligible patients with opportunities for surgical intervention, representing a breakthrough treatment strategy for liver cancer. Since conversion study is still in its infancy, there remain controversies in terms of patient selection, choice of treatment method, and postoperative management. In this review, we collect and summarize current evidence and clinical experience of conversion therapy, highlight remaining problems and challenges and provide a foundation for further research and development of HCC treatment in clinical practice.

PMID:34765289 | PMC:PMC8569342

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The effects of endovascular clot retrieval and thrombolysis on dysphagia in an Australian quaternary hospital: A retrospective review

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Int J Lang Commun Disord. 2021 Nov 12. doi: 10.1111/1460-6984.12681. Online ahead of print.

ABSTRACT

Dysphagia (impaired swallowing) is known to contribute to decreased quality of life, and increased length of hospital stay and mortality post-stroke. Despite the advancements in stroke treatment with the introduction of thrombolysis and endovascular clot retrieval (ECR), patients continue to present with high rates of dysphagia. Speech and language therapists and stroke teams should consider the presence of haemorrhagic transformation, success of reperfusion and presence of communication deficits as risk factors for dysphagia post-ECR and/or thrombolysis.

PURPOSE: To establish incidence rates and patterns of dysphagia following the administration of reperfusion therapies in acute ischaemic stroke management.

METHOD: A retrospective review of 193 patients admitted with acute ischaemic stroke to a quaternary stroke unit in Australia over a three year period was completed. Clinical information extracted included demographics, type (thrombolysis and/or endovascular clot retrieval) and success of reperfusion therapy, and the progression of dysphagia and related factors.

RESULTS: Over half of all patients treated with reperfusion therapies presented with dysphagia on initial assessment by speech-language pathology (SLP). The type of reperfusion therapy administered was not significantly correlated with the presence of dysphagia. Dysphagia on initial assessment was significantly correlated with the presence of aphasia on initial assessment, the presence of haemorrhagic transformation, and the success of reperfusion. Increased rates of enteral feeding were also found in this study compared to figures reported in literature.

CONCLUSION: This study identified ongoing high rates of dysphagia amongst this patient population regardless of treatment type, demonstrating the need for ongoing SLP management post s troke. Further research is required in this area to develop an evidence-base for SLPs and the wider medical team and to inform clinical practice guidelines.

WHAT THIS PAPER ADDS: What is already known on the subject Stroke is one of the leading causes of disability and death internationally. Dysphagia (impaired swallowing), a common sequalae of stroke, is known to contribute to decreased quality of life, increased length of hospital stay and mortality. With advancements in technology, treatments for acute ischaemic stroke (endovascular clot retrieval and thrombolysis) are increasing in popularity. However, limited research exists exploring the impact of these therapies on dysphagia. What this paper adds Despite the advancements in stroke treatment, patients continue to present with high rates of dysphagia. Dysphagia following thrombolysis and/or ECR was found to be significantly correlated to the presence of aphasia, haemorrhagic transformation, and the success of reperfusion (regardless of treatment type). Additionally, increased rates of enteral feeding were found amongst this patient population compared to figures reported in the literature for patients following traditional stroke management. Clinical implications of this study Speech-language pathologists and the wider medical team should consider dysphagia as an ongoing consequence of stroke following reperfusion therapies, with consideration for success of reperfusion and adverse outcomes i.e., haemorrhagic transformation. Further research is required to provide an evidence-base and specific guidelines for the management of dysphagia post reperfusion therapies, including use of enteral feeding.

PMID:34767286 | DOI:10.1111/1460-6984.12681

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The stroma in oral potentially malignant disorders: An overlooked denominator?

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Message:

Review Tumori
Jan-Feb 2018;104(1):9-14. doi: 10.5301/tj.5000673.
Significance of stroma in biology of oral squamous cell carcinoma
Vanja Vucicevic Boras 1 2, Aleksandra Fucic 3, Mihajlo Virag 4 5, Dragana Gabric 1, Igor Blivajs 4, Cedna Tomasovic-Loncaric 6, Zoran Rakusic 7 8, Vesna Bisof 7 9, Nicolas Le Novere 10, Danko Velimir Vrdoljak 11
Affiliations collapse
Affiliations
11 Department of Oral Medicine, School of Dentistry, University of Zagreb, Zagreb - Croatia.
22 Dental Department, Clinical Hospital Centre "Zagreb", Zagreb - Croatia.
33 Independent Researcher, Institute for Medical Research and Occupational Health, Zagreb - Croatia.
44 Department of Oral and Maxillofacial Surgery, Clinical Hospital Centre "Dubrava", Zagreb - Croatia.
55 Department of Maxillofacial Surgery and Dentistry, Medical Faculty, University of Zagreb, Zagreb - Croatia.
66 Department of Pathology, Clinical Hospital Centre Dubrava, Zagreb - Croatia.
77 Department of Oncology, Clinical Hospital Centre "Zagreb", Zagreb - Croatia.
88 Department of Clinical Oncology, Medical Faculty, University of Zagreb, Zagreb - Croatia.
99 Department for Nuclear Medicine and Oncology, Medical Faculty, University of Osijek, Osijek - Croatia.
1010 Biomathematics, Babraham Institute, Cambridge - UK.
1111 Department for Oncoplastic and Reconstructive Surgery, Clinic for Tumours, Clinical Hospital Centre "Sisters of Mercy", Zagreb - Croatia.
PMID: 28885677 DOI: 10.5301/tj.5000673
Abstract
The worldwide annual incidence of oral squamous cell carcinoma (OSCC) is over 300,000 cases with a mortality rate of 48%. This cancer type accounts for 90% of all oral cancers, with the highest incidence in men over 50 years of age. A significantly increased risk of developing OSCC exists among smokers and people who consume alcohol daily. OSCC is an aggressive cancer that metastasizes rapidly. Despite the development of new therapies in the treatment of OSCC, no significant increase in 5-year survival has been recorded in the past decades. The latest research suggests focus should be put on examining tumor stroma activation within OSCC, as the stroma may contain cells that can produce signal molecules and a microenvironment crucial for the development of metastases. The aim of this review is to provide an insight into the factors that activate OSCC stroma and hence faciliate neoplastic progression. It is based on the currently available data on the role and interaction between metal loproteinases, cytokines, growth factors, hypoxia factor and extracellular adhesion proteins in the stroma of OSCC and neoplastic cells. Their interplay is additionally presented using the Systems Biology Graphical Notation in order to sublimate the collected knowledge and enable the more efficient recognition of possible new biomarkers in the diagnostics and follow-up of OSCC or in finding new therapeutic targets.

Keywords: Biomarker; Cytokines; Estrogen receptor; OSCC; Stroma androgen receptor.

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Increased body mass index predicts prolonged survival in patients with head and neck squamous cell carcinoma

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Abstract

Background

Higher body mass index (BMI) may have a protective effect on survival in patients with head and neck cancer. The aim of this study was to determine the effect of BMI on overall survival (OS) in veterans with head and neck squamous cell carcinoma (HNSCC).

Methods

A cohort of 702 patients diagnosed with HNSCC between 1995 and 2019 were identified at the Washington DC Veterans Affairs Medical Center, and 342 patients were included for analysis. Records were queried for clinical-demographic data, BMI, and outcomes.

Results

HNSCC patients categorized as overweight or obese at time of diagnosis had a lower 3-year risk of death (p = 0.033) and improved OS (p < 0.001) compared to patients who were underweight or normal weight. The majority of locoregional recurrences occurred in patients with low or normal pretreatment BMI.

Conclusions

Higher BMI at diagnosis may have a protective effect on OS in veterans with HNSCC.

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Medical analysis of the contribution of sialendoscopy in managing non-tumoral main salivary gland pathology in Reunion Island: Observational study following STROBE guidelines

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Eur Ann Otorhinolaryngol Head Neck Dis. 2021 Nov 9:S1879-7296(21)00253-2. doi: 10.1016/j.anorl.2021.10.005. Online ahead of print.

ABSTRACT

GOALS: To perform a medical analysis of the contribution of sialendoscopy in the treatment of non-tumoral pathologies of the main salivary glands, in Reunion Island, a French overseas territory.

MATERIAL AND METHOD: A multicenter retrospective observational study was conducted for an 8-year period, before and after introduction of sialendoscopy (2011-2014 and 2015-2018), following STROBE guidelines.

OBJECTIVES: To compare populations treated before (period A) and after (period B) the introduction of sialendoscopy in terms of clinical characteristics, and analyze the characteristics of patients treated by sialendoscopy.

RESULTS: Two hundred and sixty-five patients were included: 74 in 2011-2014 and 191 in 2015-2018; 139 had sialendoscopy. Populations A and B were comparable except for the proportion of parotids treated (9% vs. 31%, respectively; P<0.0001), and smaller stones (11mm vs. 7.4mm, respectively; P=0.003). One hundred and ten pure sialendoscopies and 29 combined routes (20.8%) were performed: 63% submandibular and 37% parotid. Median age was 46 years. The M/F sex ratio was 0.96. Thirty-seven patients presented stenosis. There were 10 cases of papillary catheterization failure (7.1%), and 16 false routes or creation of false channels (11.5%), including 9 during the learning period. The rate of crossover to gland resection decreased: 10.45% for 2015-2016 and 5.56% for 2017-2018.

CONCLUSION: Although follow-up ranged between 12 and 55months (median, 30months), sialendoscopy appeared to be a useful and reliable technique, with a role in therapeutic strategy for the management of non-tumoral salivary pathologies in Reunion Island.

PMID:34772641 | DOI:10.1016/j.anorl.2021.10.005

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Relations Between Dysphonia and Personality: An Approximation From Gray' Theories.

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Our study sought to show the relation between dysphonia and personality traits as explained by Gray's theories. Personality traits were analyzed in a patient group of 141 patients who showed functional and congenital voice disorders. The results were compared to the control group made up of 99 vocally healthy individuals. Their objective voice quality was measured by using the Dysphonia Severity Index, Voice Handicap level was measured using the VHI-10, and a perceptive analysis was conducted with a listening jury.
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Pretreatment tumor sampling and prognostic factors in patients with soft-tissue sarcoma of the head and neck

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Eur Arch Otorhinolaryngol. 2021 Nov 12. doi: 10.1007/s00405-021-07162-0. Online ahead of print.

ABSTRACT

BACKGROUND: Insufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common.

METHODS: This retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival.

RESULTS: The lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS.

CONCLUSIONS: Diagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size.

PMID:34773167 | DOI:10.1007/s00405-021-07162-0

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Open wound management following pull‐through resection for oral cancer: A case series of 14 patients

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Abstract

●Following pull-through resection for oral cancer, primary closure of the oral defect is sometimes difficult. Incompletely closed defects may result in surgical site infection (SSI). ●We investigated the occurrence of SSI during and after open wound management following pull-through resection, other surgical outcomes, and postoperative quality of life (QOL). ●Open wound management was performed when the resection range was preoperatively expected to be half or less of the tongue and the defect was difficult to close primarily. ●The defect was left open, and drains were placed through the defect. The wound was cleansed after surgery, and the drains were removed as the wound healed. ●Open wound management was a simple and safe method with no occurrence of SSI. Postoperative QOL was acceptable when the oral defects were contained within half of the mobile tongue or less than half of the tongue base.

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