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Δευτέρα 28 Φεβρουαρίου 2022

Transoral robotic surgery for the identification of unknown primary head and neck squamous cell carcinomas: Its effect on the wait and the weight

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Abstract

Background

Neck carcinoma of unknown primary (CUP) is a frequent scenario. Transoral robotic mucosectomies (TORM) of pharynx have increased rate of primary identification, but come with cost of treatment delay.

Methods

We reviewed patients who underwent CUP protocol from 2014 to 2020. Patients with cervical nodes carcinoma and failure to localize a primary source were classified as CUP. We determined primary identification rate and postoperative complications.

Results

We included 65 patients underwent TORM. Surgical approach consisted of lingual and/or palatine tonsillectomies. The primary detection rate was 49.2%. Average weight reduction was 2.5 ± 4.3 kg. The average number of days from consultation to definitive treatment was 52.2 ± 18.3.

Conclusion

A systematic approach to patients with CUP showed a promising primary identification rate compared to panendoscopy alone. TORM carries a small risk of complications. The benefits of primary identification must be weighed with the morbidity and delay to definitive treatment.

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Cancer stem cell markers CD44v9+/CD133- are associated with low apoptosis in both sporadic and ulcerative colitis-associated colorectal cancers

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Histol Histopathol. 2022 Feb 28:18445. doi: 10.14670/HH-18-445. Online ahead of print.

ABSTRACT

OBJECTIVE: To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)-associated colorectal tumors.

METHODS: A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53.

RESULTS: CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer.

CONCLUSION: CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.

PMID:35224715 | DOI:10.14670/HH-18-445

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Application of a three-dimensional printed model to localize a cranial cerebrospinal fluid leak: a case report

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J Int Med Res. 2022 Feb;50(2):3000605221078412. doi: 10.1177/03000605221078412.

ABSTRACT

Localization of defect sites is a major challenge for surgical repair of cerebrospinal fluid (CSF) leaks. Here, we report a case in which we applied a 3-dimensional (3D) printed model to accurately identify the defect sites and facilitate the successful repair of a cranial CSF leak. A 37-year-old female patient diagnosed with recurrent nasopharyngeal carcinoma suffered CSF rhinorrhea and severe bacterial meningitis. Lumbar drainage and antibiotic administration failed to control the condition. In addition to high resolution computed tomography and magnetic resonance imaging, we applied a 3D printed model of the skull to improve the understanding of the osseous destruction at the skull base and aid in accurately localizing the defect sites of the right middle fossa. Accordingly, a right temporalis pedicled flap combined with an autogenous fascia lata flap was applied to cover the defect sites. The leak stopped postoperatively, and meningitis was relieved by enhanced antibacterial treatment. As a complement to high resolution computed tomography and magnetic resonance imaging, a 3D printed model may improve localization of complex defect sites and surgical planning by allowing preoperative visualization of the skull condition.

PMID:35220787 | DOI:10.1177/03000605221078412

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Eyelid carcinomas: Tumor aggressiveness tendencies for smokers compared to non-smokers

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Exp Ther Med. 2022 Mar;23(3):234. doi: 10.3892/etm.2022.11159. Epub 2022 Jan 21.

ABSTRACT

During the past few years, several studies have demonstrated that head and neck carcinomas present more aggressive forms for smokers, relative to non-smokers. Our aim was to investigate the tumor aggressiveness for patients with eyelid carcinomas, in relation to tobacco consumption, as well as other demographic and clinical data. For 98 patients with eyelid carcinomas, we studied the relationship between the duration of their symptoms and their tumor stage at first diagnosis, trying to determine potential correlations with smoking status and several other clinical parameters. Our data revealed that, for the same duration of symptoms, tobacco consumers tended to have higher tumor stages, which did not correlate with other variables. For early diagnosed tumors, within the first year of symptoms, smokers presented 6.044 times higher odds to exhibit m ore advanced tumor stages, compared to non-smokers, and this value decreased to 4.501, up to 5 years of the presence of symptoms (P<0.05). We also noted that, for smokers, an increased age was associated with increased tumor stages, which was opposed to non-smokers, regardless of their symptom duration [average odds ratio (OR) 1.122, P<0.05]. Tumor aggressiveness was therefore associated with tobacco consumption, leading to an increased risk of developing more aggressive forms of eyelid carcinomas for smokers, compared to non-smokers.

PMID:35222711 | PMC:PMC8815059 | DOI:10.3892/etm.2022.11159

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Long non-coding RNA ATB is associated with metastases and promotes cell invasion in colorectal cancer via sponging miR-141-3p

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Exp Ther Med. 2022 Mar;23(3):238. doi: 10.3892/etm.2022.11163. Epub 2022 Jan 24.

ABSTRACT

[This corrects the article DOI: 10.3892/etm.2020.9391.].

PMID:35222715 | PMC:PMC8815047 | DOI:10.3892/etm.2022.11163

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Vitamin D3 promotes autophagy in THP-1 cells infected with Mycobacterium tuberculosis

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Exp Ther Med. 2022 Mar;23(3):240. doi: 10.3892/etm.2022.11165. Epub 2022 Jan 25.

ABSTRACT

Tuberculosis (TB) is a major disease that causes mortality worldwide. The lethality of this disease is a result of the contagious bacteria Mycobacterium tuberculosis (M.tb). Infection can inhibit phagosomal maturation, with M.tb mainly attacking macrophages and inhibiting autophagy and apoptosis. Vitamin D has been used to treat tuberculosis, whereby the active metabolite, 1,25-dihydroxyvitamin D, may enhance the immune response to M.tb. Moreover, macrophages infected with M.tb have a high demand for Ca2+. However, the mechanisms by which vitamin D3 protects against and treats TB remain unclear. In the present study, MTT assay showed that vitamin D3 decreased the viability of THP-1 cells in a dose- and time-dependent manner. Autophagy-related factors in THP-1 cells infected with M.tb were analyzed by w estern blotting and RT-qPCR and the results demonstrated that vitamin D3 significantly increased the expression level of p62, LC3Ⅱ/LC3Ⅰ, Beclin-1, ATG-5 and AMPK in THP-1 cells following M.tb infection. The Ca2+ concentration assay demonstrated that vitamin D3 may promoted cellular autophagy by inhibiting the concentration of Ca2+. Furthermore, the effect of vitamin D3 on M.tb infection was also assessed using Balb/c mice; pulmonary injury was assessed by H&E staining of the lungs tissue. The results demonstrated that vitamin D3 markedly attenuated cellular damage caused by M.tb infection. In conclusion, the present study indicated that vitamin D3 may activate cell autophagy signals by inhibiting the concentration of Ca2+. These data may improve understanding of the effect of vitamin D3 on M.tb infection and help determine the underlying mechanism of vitamin D3 to alleviate and treat the inflammatory response cause d by TB.

PMID:35222717 | PMC:PMC8815057 | DOI:10.3892/etm.2022.11165

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Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation

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Exp Ther Med. 2022 Mar;23(3):222. doi: 10.3892/etm.2022.11146. Epub 2022 Jan 17.

ABSTRACT

Osteoarthritis (OA) is an age-related degenerative disease, and its incidence is increasing with the ageing of the population. Metformin, as the first-line medication for the treatment of diabetes, has received increasing attention for its role in OA. The purpose of the present study was to confirm the therapeutic effect of metformin in a mouse model of OA and to determine the mechanism underlying the resultant delay in OA progression. The right knees of 8-week-old C57BL/6 male mice were subjected to destabilization of the medial meniscus (DMM). Metformin (200 mg/kg) was then administered daily for 4 or 8 weeks. Safranin O-fast green staining, H&E staining and micro-CT were used to analyse the structure and morphological changes. Immunohistochemical staining was used to detect type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), NO D-like receptor protein 3 (NLRP3), caspase-1, gasdermin D (GSDMD) and IL-1β protein expression. Reverse transcription-quantitative PCR was used to detect the mRNA expression of NLRP3, caspase-1, GSDMD and IL-1β. Histomorphological staining showed that metformin delayed the progression of OA in the DMM model. With respect to cartilage, metformin decreased the Osteoarthritis Research Society International score, increased the thickness of hyaline cartilage and decreased the thickness of calcified cartilage. Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP-13, NLRP3, caspase-1, GSDMD and IL-1β. In addition, in subchondral bone, metformin inhibited osteophyte formation, increased the bone volume fraction (%) and the bone mineral density (g/cm3), decreased the trabecular separation (mm) in early stage of osteoarthritis (4 weeks) but the opposite in an advanced stage of osteoarthritis (8 weeks). Overall, metformin inhibited the activation of NLRP3 inflammasome, decreased cartilage degradation, reversed subchondral bone remodelling and inhibited chondrocyte pyroptosis.

PMID:35222699 | PMC:PMC8812147 | DOI:10.3892/etm.2022.11146

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MicroRNA-4722-5p and microRNA-615-3p serve as potential biomarkers for Alzheimer's disease

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Exp Ther Med. 2022 Mar;23(3):241. doi: 10.3892/etm.2022.11166. Epub 2022 Jan 26.

ABSTRACT

The aim of the present study was to investigate the expression levels of microRNA(miR)-4722-5p and miR-615-3p in Alzheimer's disease (AD) and their diagnostic value. Blood samples were collected from 33 patients with AD and 33 healthy controls, and an β-amyloid (Aβ)25-35-induced PC12 cell model was also established. The relative mRNA expression levels of miR-4722-5p and miR-615-3p were detected using reverse transcription-quantitative PCR. The correlations between the mRNA expression levels of the two miRNAs and the mini-mental state examination (MMSE) scores were analyzed, and the receiver operating characteristic curve was used to assess the diagnostic value of miR-4722-5p and miR-615-3p in AD. Functional enrichment analysis of the miRNA target genes was performed using The Database for Annotation, Visualization and Integrated Discovery databa se and the R language analysis package. The mRNA expression levels of miR-4722-5p and miR-615-3p were increased in patients with AD and the Aβ25-35-induced PC12 cell model. The mRNA expression levels of miR-4722-5p and miR-615-3p were negatively correlated with MMSE scores, and the combination of the two miRNAs for AD had an improved diagnostic value than that of each miRNA alone. The results of Gene Ontology (GO) enrichment analysis showed that the target genes of miR-4722-5p were found in the cytoplasm and cytosol, and were mainly involved in protein folding and cell division. The molecular functions included protein binding and GTPase activator activity. The results of Kyoto Encyclopedia of Genes and Genomes analysis showed that miR-4722-5p was associated with the regulation of dopaminergic synapses and mTOR signaling pathways. GO enrichment analysis also revealed that the target genes of miR-615-3p were located in the nucleus and cytoplasm, were involved in the regulation of tr anscription and protein phosphorylation, and were associated with protein binding, metal ion binding and transcription factor activity. The target genes of miR-615-3p played important roles in the regulation of the Ras and FoxO signaling pathways. In conclusion, miR-4722-5p and miR-615-3p may be potential biomarkers in the early diagnosis of AD.

PMID:35222718 | PMC:PMC8815048 | DOI:10.3892/etm.2022.11166

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Circular RNA, hsa_circRNA_102049, promotes colorectal cancer cell migration and invasion via binding and suppressing miRNA-455-3p

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Exp Ther Med. 2022 Mar;23(3):244. doi: 10.3892/etm.2022.11169. Epub 2022 Jan 27.

ABSTRACT

Colorectal cancer (CRC) is the second most prevalent malignant gastrointestinal tumor type worldwide, displaying poor prognosis. Accumulating studies have reported the significance of circular RNAs (circRNAs) and microRNAs (miRNAs) in CRC carcinogenesis and development. At present, the functions and mechanisms of action underlying the circular RNA, hsa_circRNA_102049, in CRC are not completely understood. The present study aimed to establish the involvement of hsa_circRNA_102049 in CRC, as well as the associated mechanisms. The expression levels of hsa_circRNA_102049 and miRNA-455-3p were measured in CRC cell lines and tissues via reverse transcription-quantitative PCR. CRC progression was evaluated by performing Cell Counting Kit-8, flow cytometry, wound healing and Transwell invasion assays. The results demonstrated that hsa_circRNA_102049 was h ighly expressed in both CRC tissues and cell lines, which was associated with enhanced CRC cell proliferation, migration and invasion. Furthermore, miR-455-3p expression was downregulated in CRC cells and served as a target of has_circRNA_102049, which was validated by performing the dual luciferase reporter assay. hsa_circRNA_102049 knockdown significantly increased miR-455-3p expression, which was significantly reversed by co-transfection with the miR-455-3p inhibitor. Notably, miRNA-455-3p overexpression alleviated hsa_circRNA_102049-mediated induction of CRC cell proliferation, migration and invasion. The present study clearly demonstrated that miRNA-455-3p was a target of hsa_circRNA_102049. Moreover, the results indicated that the circular RNA, hsa_circRNA_102049, may function as a tumor promoter in CRC via directly sponging miRNA-455-3p.

PMID:35222721 | PMC:PMC8815054 | DOI:10.3892/etm.2022.11169

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HMBOX1 attenuates LPS-induced periodontal ligament stem cell injury by inhibiting CXCL10 expression through the NF-κB signaling pathway

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Exp Ther Med. 2022 Mar;23(3):224. doi: 10.3892/etm.2022.11148. Epub 2022 Jan 17.

ABSTRACT

Homeobox containing 1 (HMBOX1) is a member of the homeobox transcription factor family that has been reported to serve an important role in numerous biological processes. The present study aimed to determine the role of HMBOX1 in the pathogenesis of periodontitis. Human periodontal ligament stem cells (hPDLSCs) were treated with liposaccharide (LPS) and transfected with a HMBOX1 overexpression (Ov-HMBOX1) plasmid or small interfering (si)-C-X-C motif chemokine ligand 10 (CXCL10) plasmids. The effects of Ov-HMBOX1 on cell proliferation, inflammation and apoptosis were subsequently investigated using Cell Counting Kit-8, ELISA for analysis of IL-6, TNF-α and IL-1β levels, TUNEL and western blotting assays for analysis of Bcl-2, Bax, cleaved caspase-3 and caspase-3 levels, respectively. Furthermore, the potential effects of HMBOX1 on the mRNA and p rotein levels of CXCL10 and the NF-κB signaling pathway were investigated by using reverse transcription-quantitative PCR and western blotting. Finally, the physiological processes of lipopolysaccharide (LPS)-induced hPDLSCs overexpressing HMBOX1 were assessed following treatment with phorbol 12-myristate 13-acetate (PMA), a NF-κB agonist. The results revealed that Ov-HMBOX1 transfection promoted proliferation whilst alleviating inflammation and apoptosis in LPS-induced hPDLSCs. Ov-HMBOX1 reduced the expression of CXCL10 by suppressing the NF-κB signaling pathway. PMA treatment inhibited the proliferation of LPS-induced hPDLSCs transfected with Ov-HMBOX1, which was reversed by transfection with si-CXCL10. In conclusion, results of the present study provided evidence that HMBOX1 can attenuate LPS-induced hPDLSC injury by downregulating CXCL10 expression via the NF-κB signaling pathway, which may provide a novel insight into the development of potentially novel treatment strategie s for periodontitis.

PMID:35222701 | PMC:PMC8812104 | DOI:10.3892/etm.2022.11148

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Managing Cachexia in Head and Neck Cancer: a Systematic Scoping Review

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Adv Ther. 2022 Feb 27. doi: 10.1007/s12325-022-02074-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Patients with head and neck cancer (HNC) are usually confronted with functional changes due to the malignancy itself or its treatment. These factors typically affect important structures involved in speech, breathing, chewing, swallowing, and saliva production. Consequently, the intake of food will be limited, which further contributes to loss of body weight and muscle mass, anorex ia, malnutrition, fatigue, and anemia. This multifactorial condition can ultimately lead to cancer cachexia syndrome. This study aims to examine the treatment of cachexia in HNC patients.

METHODS: We systematically searched OvidMedline, PubMed, Scopus, and Web of Science for articles examining the treatment of cachexia in HNC.

RESULTS: A total of nine studies were found, and these suggested interventions including nutritional, pharmacologic, therapeutic exercise, and multimodal approaches. The nutritional intervention includes essential components such as dietary counseling, oral nutritional supplements, and medical nutritional support. Individualized nutritional interventions include oral, enteral (feeding tubes i.e., percutaneous endoscopic gastrostomy [PEG], nasogastric tube [NGT]) and parenteral nutrition. The pharmacologic interventions aim at increasing the appetite and weight of cachectic patients. Therapeutic exercise and increased physical activity can help to e nhance the synthesis of muscle protein, reducing inflammation and the catabolic effects of cachexia syndrome.

CONCLUSION: Owing to the multifactorial nature of this syndrome, it is expected that the management approach should be multi-interventional. Early implementation of these interventions may help to improve survival and quality of health and life of cachectic HNC patients.

PMID:35224702 | DOI:10.1007/s12325-022-02074-9

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