Κυριακή 6 Μαρτίου 2022

Investigation of the Mechanism of Impaired Skin Barrier Function in Dogs With Malignant Tumors

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In Vivo. 2022 Mar-Apr;36(2):743-752. doi: 10.21873/invivo.12761.

ABSTRACT

BACKGROUND/AIM: No study has investigated skin barrier dysfunction with systemic diseases in veterinary medicine. We investigated the mechanism of disturbed skin barrier function in dogs with internal diseases.

MATERIALS AND METHODS: Healthy controls and dogs with systemic diseases were enrolled in three different disease groups: malignant tumor, hyperadrenocorticism and kidney disease. Transepidermal water loss (TEWL), serum levels of five selective pro-inflammatory cytokines and claudin-1, and complete blood count were measured.

RESULTS: TEWL was significantly increased in the malignant tumor group while serum claudin-1 concentrations were significantly lower compared to controls. Tumor necrosis factor-α was also significantly increased in the cancer group. In addition, the malignant tumor group showed significantly higher monocyte chemotactic prot ein-1 after chemotherapy, but lower interleukin-6 levels, compared to dogs with no chemotherapy.

CONCLUSION: Skin barrier function was decreased in dogs with malignant tumors compared to dogs with other systemic diseases by oxidative stress and a reduction in tight junction proteins.

PMID:35241530 | DOI:10.21873/invivo.12761

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Tremella fuciformis Inhibits Melanogenesis in B16F10 Cells and Promotes Migration of Human Fibroblasts and Keratinocytes

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In Vivo. 2022 Mar-Apr;36(2):713-722. doi: 10.21873/invivo.12757.

ABSTRACT

BACKGROUND/AIM: Natural skin whiteners have been investigated for centuries. The development of preparations that safely achieve whitening of hyper-pigmented skin lesions is a challenge for the cosmetics industry. Furthermore, promoting rapid wound healing and minimizing inflammation in injured skin are key to prevent from abnormal pigmentation in scar tissue. Natural products, including the fungus Tremella fuciformis (TF), are attracting attention as potential sources of lead compounds for these applications.

MATERIALS AND METHODS: We investigated the in vitro effects of TF on melanogenesis in murine B16F10 cells. Melanin and tyrosinase levels were measured after treatment with TF. Wound healing in human keratinocytes (HaCaT) and fibroblasts (Detroit 551) was also determined via cell migration assay prior to TF exposure.

RESULTS: TF significantly dec reased melanin content and tyrosinase expression in a concentration-dependent manner in B16F10 cells. Furthermore, TF promoted wound healing in human HaCaT keratinocytes and Detroit 551 fibroblasts.

CONCLUSION: TF proved effectively on inhibiting melanogenesis and promoting wound healing in vitro, demonstrating its potential as a novel skin-whitening agent. However, further clinical studies of safety and efficacy are required.

PMID:35241526 | DOI:10.21873/invivo.12757

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Cisplatin Versus Carboplatin and Paclitaxel in Radiochemotherapy for Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

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In Vivo. 2022 Mar-Apr;36(2):821-832. doi: 10.21873/invivo.12769.

ABSTRACT

BACKGROUND/AIM: The implementation of a platinum-containing regimen is recommended for definitive and adjuvant therapy of patients with locally advanced head and neck tumour. We compared the conditions for the use of cisplatin or carboplatin/paclitaxel or for changing between these two regimens on a clinic-specific basis.

PATIENTS AND METHODS: We evaluated 150 patients with advanced head and neck squamous cell carcinoma who received simultaneous radiochemotherapy at our institution between 2012 and 2017. Chemotherapy with weekly doses of cisplatin (40 mg/m2, group 1) or, in cases of impaired renal and/or cardiac function, with weekly doses of carboplatin AUC2 and paclitaxel (45 mg/m2, group 2), was performed as a first-choice therapy. If toxicities occurred in group 1, treatment was switched to the carboplatin/paclitaxel regimen (group 3). Patient- and therapy-related parameters, toxicity and survival data were compared across groups.

RESULTS: We examined 99, 30, and 21 patients in each group who received at least 1 course of chemotherapy. Group 3 patients switched from cisplatin to carboplatin/paclitaxel after a median of 3 courses due to nephrotoxicity (95.2%). The target of at least 5 chemotherapy courses was most frequently achieved by patients in group 1 (69.7%), followed by group 3 (61.9%) and then group 2 (40.0%). Multivariate analysis revealed that patients who switched groups were more likely to be over 60 years old (p=0.021), undergo definitive radiochemotherapy (p=0.049) and develop higher nephrotoxicity (p=0.036) than group 1 patients. Outcomes did not differ between groups.

CONCLUSION: When cisplatin application is contraindicated due to renal- or cardiotoxicity, carboplatin/paclitaxel is an appropriate option.

PMID:35241538 | DOI:10.21873/invivo.12769

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Background Parenchymal Enhancement in Contrast-enhanced Spectral Mammography: A Retrospective Analysis and a Pictorial Review of Clinical Cases

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In Vivo. 2022 Mar-Apr;36(2):853-858. doi: 10.21873/invivo.12773.

ABSTRACT

BACKGROUND/AIM: Despite the popularity of contrast enhanced spectral mammography (CESM), univocal classification of the background parenchymal enhancement (BPE), a bilateral enhancement of the normal breast parenchyma after contrast administration, is lacking. The present study aimed to evaluate the application of BPE Breast Imaging Reporting and Data System Magnetic Resonance (BI-RADS-MR) score for the CESM BPE. Moreover, a pictorial review of four different cases with CESM is provided.

PATIENTS AND METHODS: A single-center, retrospective study from a prospectively maintained database of all women undergoing digital mammography (DM) and CESM in our institution between 2016 and 2019. DM and CESM were classified by two experienced radiologists.

RESULTS: No statistically significant difference between DM breast density and BPE CESM classification was fo und. Agreement between readers ranged from substantial to almost perfect.

CONCLUSION: BIRADS-RM score for the CESM BPE represents a handy option for radiologists with high inter-reader and DM agreement.

PMID:35241542 | DOI:10.21873/invivo.12773

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Recurrent Metastatic Parotid Acinic Cell Carcinoma Responsive to Pembrolizumab

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In Vivo. 2022 Mar-Apr;36(2):1047-1051. doi: 10.21873/invivo.12801.

ABSTRACT

BACKGROUND: No clear chemotherapy regimen for recurrent or metastatic parotid cancer exists. We describe our experience with pembrolizumab to treat recurrent or metastatic parotid cancer.

CASE REPORT: A 73-year-old woman with swelling in the lower part of the right ear for 10 years before surgery was diagnosed with right parotid cancer, underwent total right parotidectomy, and reported recurrence. She requested treatment due to diminished quality of life caused by neurological symptoms. Tissue was collected from the recurrent lesion and its combined positive score was >20; pembrolizumab was started 9 years postoperatively.

RESULTS: To date, the patient has received 14 cycles of pembrolizumab. Evaluation by computed tomography showed a partial response to treatment. The only immune-related adverse event was grade 1 pneumonia in both lungs.

C ONCLUSION: Significant response to pembrolizumab in recurrent or metastatic parotid cancer is rarely reported, making this a remarkable case. We plan to continue pembrolizumab administration.

PMID:35241570 | DOI:10.21873/invivo.12801

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Predictive Value of Circulating Tumor Cells in Prognosis of Stage III/IV Colorectal Cancer After Oxaliplatin-based First-line Chemotherapy

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In Vivo. 2022 Mar-Apr;36(2):806-813. doi: 10.21873/invivo.12767.

ABSTRACT

BACKGROUND/AIM: Insufficient data exist to support the concept of the circulating tumor cell (CTC) level as a prognostic factor for platinum-based first-line chemotherapy. This study investigated the impact of CTCs on the prognosis of patients with advanced colorectal cancer (CRC) after receiving platinum-based chemotherapy. Analyses were carried out of clinicopathological features and molecular phenotypes to clarify independent risk factors for a high CTC count.

PATIENTS AND METHODS: Patients diagnosed with stage III/IV CRC (n=76) were included in the study. The blood samples of patients were evaluated for CTCs using the CellRich™ platform system. Immunohistochemistry (Ias used to analyze epithelial-mesenchymal transition-associated biomarkers E-cadherin and vimentin. Univariate and logistic regression analyses were then conducted to analyze the risk fac tors for CTC expression. Additionally, the influence of oxaliplatin on disease-free survival after first-line chemotherapy or during chemotherapy was analyzed through a 2-year follow-up.

RESULTS: Patients in the CTC+ group experienced shorter DFS after receiving oxaliplatin first-line chemotherapy than patients in the CTC- group (p<0.01). In addition, univariate analysis revealed that the tumor M-stage, tumor location, RAS mutation, high expression of vimentin, and deletion of E-cadherin expression were correlated with a high CTC count. Multivariate analysis suggested that the presence of RAS gene mutations and high vimentin expression were independent risk factors for high CTC loads (p<0.01).

CONCLUSION: CTC positivity can indicate the efficacy of first-line chemotherapy with oxaliplatin in stage III/IV colorectal cancer. This may be linked to tumor epithelial-mesenchymal transition in patients with CTCs. Moreover, RAS gene mutation and high expression of vimentin were identified as independent risk factors for a high CTC count.

PMID:35241536 | DOI:10.21873/invivo.12767

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The Geriatric Nutritional Risk Index Predicts Tolerability of Lenvatinib in Patients With Hepatocellular Carcinoma

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In Vivo. 2022 Mar-Apr;36(2):865-873. doi: 10.21873/invivo.12775.

ABSTRACT

BACKGROUND/AIM: We aimed to investigate the association between The Geriatric Nutritional Risk Index (GNRI) and the tolerability of lenvatinib in patients with hepatocellular carcinoma (HCC).

PATIENTS AND METHODS: We retrospectively evaluated 61 HCC patients treated with lenvatinib and compared those with low GNRI (≤98, n=26) to those with high GNRI (>98, n=35).

RESULTS: The discontinuation of lenvatinib due to adverse events was more frequent in the low GNRI group (46.2%) than in the high GNRI group (17.1%) (p=0.014). Multivariate analysis revealed that low GNRI (p=0.014), hypothyroidism (model 1 p=0.021, model 2 p=0.013), and advanced age (p=0.026) were independently associated with the discontinuation of lenvatinib. The progression-free survival in the low GNRI group was significantly shorter than that in the high GNRI group (p=0.047).

C ONCLUSION: The GNRI might be independently associated with the tolerability of lenvatinib in patients with HCC.

PMID:35241544 | DOI:10.21873/invivo.12775

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Optimization of Culture Conditions for the Generation of Canine CD20-CAR-T Cells for Adoptive Immunotherapy

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In Vivo. 2022 Mar-Apr;36(2):764-772. doi: 10.21873/invivo.12763.

ABSTRACT

BACKGROUND/AIM: Chimeric antigen receptor (CAR) T cell therapy targeting CD20 has the potential to become a promising novel treatment for canine B cell lymphoid malignancy. However, the optimal approach for producing potent CAR-T cells with favorable phenotype for dogs remains unknown. In this study, we assessed several culture conditions and their effects on the phenotypic characteristics of CD20-CAR-T cells.

MATERIALS AND METHODS: Canine CAR-T cells were generated by incubating with several mitogens in the presence or absence of Akt inhibitor. Gene transduction efficiency and phenotypic characteristics were determined by flow cytometry.

RESULTS: Comparison of several kinds of mitogens revealed that stimulation with phytohemagglutinin has high transduction efficacy, whereas stimulation with concanavalin A was superior in memory T cell formation. Akt inhibition at the initial stage of CAR-T production tended to enhance transduction efficiency and memory T cell formation.

CONCLUSION: This study provides a significant insight into the understanding of the ex vivo expansion of canine T cells in adoptive immunotherapy.

PMID:35241532 | DOI:10.21873/invivo.12763

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PKM2 Is Overexpressed in Glioma Tissues, and Its Inhibition Highly Increases Late Apoptosis in U87MG Cells With Low-density Specificity

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In Vivo. 2022 Mar-Apr;36(2):694-703. doi: 10.21873/invivo.12755.

ABSTRACT

BACKGROUND/AIM: Pyruvate kinase M2 (PKM2) functions as an important rate-limiting enzyme in aerobic glycolysis and is involved in tumor initiation and progression. However, there are few studies on the correlation between PKM2 expression and its role in glioma.

MATERIALS AND METHODS: PKM2 expression was immunohistochemically examined in human brain tumor samples. Furthermore, we studied the effects of two PKM2 inhibitors (shikonin and compound 3K) on the U87MG glioma cell line.

RESULTS: PKM2 was overexpressed in most glioma tissues when compared to controls. Interestingly, glioma-adjacent tissues from showed slight PKM2 overexpression. This suggests that PKM2 overexpression maybe an important trigger factor for glioma tumorigenesis. We found that the PKM2 inhibitor shikonin was effective against U87MG cells at a relatively low dose and was largely dep endent on low cellular density compared to the effects of the anticancer drug vincristine. Shikonin highly increased late-apoptosis of U87MG cells. We also demonstrated that autophagy was involved in the increase in late-apoptosis levels caused by shikonin. Although vincristine treatment led to a high level of G2-phase arrest in U87MG cells, shikonin did not increase G2 arrest. Co-treatment with two PKM2 inhibitors, shikonin and compound 3K, increased the inhibitory effects.

CONCLUSION: Combination therapy with PKM2 inhibitors together might be more effective than combination therapy with anticancer drugs. Our findings encourage the application of PKM2-targeting in gliomas, and lay the foundation for the development of PKM2 inhibitors as promising antitumor agents for glioma.

PMID:35241524 | DOI:10.21873/invivo.12755

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A Deep Learning Framework for Real‐Time 3D Model Registration in Robot‐Assisted Laparoscopic Surgery

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Abstract

Introduction

The current study presents a Deep Learning framework to determine, in real-time, position and rotation of a target organ from an endoscopic video. These inferred data are used to overlay the 3D model of patient's organ over its real counterpart. The resulting augmented video flow is streamed back to the surgeon as a support during laparoscopic Robot-Assisted procedures.

Methods

This framework exploits semantic segmentation and, thereafter, two techniques, based on Convolutional Neural Networks and motion analysis, were used to infer the rotation.

Results

The segmentation shows optimal accuracies, with a mean IoU score greater than 80% in all tests. Different performance levels are obtained for rotation, depending on the surgical procedure.

Discussion

Even if the presented methodology has various degrees of precision depending on the testing scenario, this work sets the first step for the adoption of Deep Learning and Augmented Reality to generalize the automatic registration process.

This article is protected by copyright. All rights reserved.

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Submandibular gland transfer for the prevention of radiation‐induced xerostomia in oropharyngeal cancer: Dosimetric impact in the intensity modulated radiotherapy era

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Abstract

Background

Submandibular gland (SMG) transfer decreased radiation-associated xerostomia in the 2/3-dimensional radiotherapy era. We evaluated the dosimetric implications of SMG transfer on modern intensity modulated radiotherapy (IMRT) plans.

Methods

Eighteen oropharynx cancer patients underwent SMG transfer followed by IMRT; reoptimized plans using the baseline SMG location were generated. Mean salivary gland, oral cavity, and larynx doses were compared between clinical plans and reoptimized plans.

Results

No statistically significant difference in mean SMG dose (27.53 Gy vs. 29.61 Gy) or total salivary gland dose (26.12 Gy vs. 26.41 Gy) was observed with or without SMG transfer (all p > 0.05). Mean oral cavity and larynx doses were not statistically different. Neither tumor site, target volume crossing midline, stage, nor salivary gland volumes were associated with mean doses.

Conclusions

Salivary gland doses were similar with or without SMG transfer. IMRT likely decreases the benefit of SMG transfer on the risk of radiation-associated xerostomia.

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