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Scientific Reports Dec 2023Although the antioxidant properties of Melissa officinalis extract (Mox) are widely known, little work has focused on its protective capacity against heavy metal stress....
Although the antioxidant properties of Melissa officinalis extract (Mox) are widely known, little work has focused on its protective capacity against heavy metal stress. The primary objective of this study was to determine the potential of Mox to mitigate manganese (II) chloride (MnCI)-induced cyto-genotoxicity using the Allium and comet assays. Physiological, genotoxic, biochemical and anatomical parameters as well as the phenolic composition of Mox were examined in Allium cepa (L.). Application of 1000 µM MnCl reduced the rooting percentage, root elongation, weight gain, mitotic index and levels of chlorophyll a and chlorophyll b pigments compared to the control group. However, it increased micronuclei formation, chromosomal abnormality frequencies, tail DNA percentage, proline amount, lipid peroxidation level and meristematic damage severity. The activities of superoxide dismutase and catalase also increased. Chromosomal aberrations induced by MnCl were fragment, sticky chromosome, vagrant chromosome, unequal distribution of chromatin and bridge. Application of 250 mg/L Mox and 500 mg/L Mox along with MnCl significantly alleviated adverse effects dose dependently. The antioxidant activity bestowed by the phenolic compounds in Mox assisted the organism to combat MnCl toxicity. Consequently, Mox exerted remarkable protection against MnCl toxicity and it needs to be investigated further as a potential therapeutic option.
Topics: Onions; Manganese; Plant Roots; Chlorophyll A; Melissa; Allium; Antioxidants; DNA Damage; Chromosome Aberrations; Plant Extracts
PubMed: 38092949
DOI: 10.1038/s41598-023-49699-6 -
NMC Case Report Journal 2023Meningeal melanocytomas of the central nervous system, although typically benign, rarely undergo malignant transformations. A 46-year-old man presented with headache and...
Meningeal melanocytomas of the central nervous system, although typically benign, rarely undergo malignant transformations. A 46-year-old man presented with headache and nausea 4 years after gross total resection of a craniovertebral junction meningeal melanocytoma at another hospital. The initial clinical course was previously reported. Computed tomography revealed the presence of multiple intracranial mass lesions. Furthermore, magnetic resonance imaging showed multiple intracranial lesions and meningeal dissemination. A biopsy was performed for a circumflex lesion located in the right frontal lobe. Pathological examination showed anaplastic changes and a Ki-67 index of 33%. Based on the pleomorphic changes and high mitotic activity, the patient was diagnosed with primary cerebral malignant melanoma. The patient received four cycles of nivolumab (80 mg) and ipilimumab (165 mg), followed by whole-brain radiotherapy (37.5 Gy). However, the disease progressed after the third cycle. Genome analysis revealed Q209P and R625C mutations, but no treatments related to these gene mutations were available. Despite the seven cycles of nivolumab therapy, the patient eventually passed away 9 months after surgery. This case was a rare example of malignant transformation and leptomeningeal melanomatosis in a meningeal melanocytoma. It highlights the importance of careful follow up after gross total resection. Identification of molecular alterations can lead to better detection of melanocytic melanomas with poor prognosis and high risk of recurrence and metastasis. It can also facilitate the development of novel therapeutic options for these patients.
PubMed: 38076394
DOI: 10.2176/jns-nmc.2023-0109 -
Plants (Basel, Switzerland) Dec 2023Nitric oxide (NO) is a universal signaling molecule with important regulatory functions in the plant's life cycle and adaptation to a wide spectrum of environmental...
Nitric oxide (NO) is a universal signaling molecule with important regulatory functions in the plant's life cycle and adaptation to a wide spectrum of environmental stresses including drought. The effect of pre-sowing seed treatment with the donor of NO sodium nitroprusside (SNP, 200 μM) on wheat L. plants subjected to dehydration (PEG-8000, 12%) was investigated. SNP pretreatment stimulated germination and seedling growth in normal conditions and protected them under dehydration. These effects were confirmed by percentage of seed germination, changes in fresh and dry weight of 5-6-day-old seedlings, as well as by seedlings' linear dimensions, visual appearance, and mitotic index of the root apical meristem. Assessment of the transpiration intensity (TI) and relative water content (RWC) showed that SNP pretreatment helped to maintain the water status of seedlings subjected to dehydration stress. The data obtained by enzyme-linked immunosorbent assay (ELISA) suggested that the positive effects of SNP may be due to its influence on the phytohormonal system. SNP pretreatment induced an increase in the level of indolylacetic acid (IAA) and especially cytokinins (CK), while essential changes in ABA content were not detected. Water deficiency caused a substantial increase in ABA content and a decrease in the levels of CK and IAA. Pre-sowing SNP treatment decreased stress-induced fluctuations in the content of all studied phytohormones. Using reverse-transcription PCR (RT-PCR), we obtained data on the increase in expression of the dehydrin gene in SNP-pretreated seedlings under normal and, especially, under dehydration conditions. These findings may indicate the participation of dehydrins in NO-induced defense reactions in wheat plants under water stress. Furthermore, exogenous NO had a stabilizing effect on membrane cellular structures, as evidenced by the reduction of electrolyte leakage (EL) levels and malondialdehyde (MDA) content in dehydrated wheat seedlings under the influence of pre-sowing SNP treatment.
PubMed: 38068687
DOI: 10.3390/plants12234051 -
Radiology Case Reports Jan 2024Neuroendocrine breast carcinoma (NEBC) is an uncommon and malignant breast lesion. The absence of proper testing for this type of breast cancer carcinoma exacerbates...
Neuroendocrine breast carcinoma (NEBC) is an uncommon and malignant breast lesion. The absence of proper testing for this type of breast cancer carcinoma exacerbates this paucity. Additionally, only scant evidence of these tumors is present because of the repeated revisions in their diagnostic criteria throughout time. This case report highlights the importance of the correlation between histological and radiological findings in the diagnosis and treatment of neuroendocrine breast cancer. We describe the clinical, radiological, and histological characteristics of a patient diagnosed with neuroendocrine carcinoma. The breast parenchyma was penetrated by a carcinomatous tumor growth that contained trabeculae and lobules, exhibiting mild cytonuclear atypia, and having a low mitotic index. This report emphasizes the value of a multidisciplinary strategy for precise diagnosis and treatment planning.
PubMed: 38046918
DOI: 10.1016/j.radcr.2023.10.047 -
Frontiers in Genetics 2023Histone deacetylation is an important mechanism involved in human breast cancer tumorigenesis and recent veterinary oncology studies also demonstrate a similar...
Histone deacetylation is an important mechanism involved in human breast cancer tumorigenesis and recent veterinary oncology studies also demonstrate a similar relationship in some canine neoplasms. The use of HDAC inhibitors and has demonstrated antitumor action on several strains of human and animal cancers. The present study aims to correlate the expression of H3K9Ac, H4K12Ac, HDAC1, HDAC2 and HDAC6 in simple mammary carcinomas in dogs with clinicopathological parameters and overall survival time. To this end, 61 samples of simple breast carcinomas were analyzed by the immunohistochemistry technique with subsequent validation of the antibodies by the Western Blot technique. The expressions obtained via a semi-quantitative way were categorized by assigning scores and classified into high or low expressions according to the given score, except for HDAC6, when the marking percentage was considered and subdivided into high and low expressions using the median value. For statistical analysis, the chi-square test or Fisher exact test were used as univariate analysis and correspondence analysis as a multivariate test, in addition to the Kaplan-Meier survival analysis. In the studied samples, the highest frequencies were determined for the high expression proteins H4K12Ac (88.5%), HDAC2 (65.6%) and HDAC6 (56.7%) and the low expression proteins H3K9Ac (73.8%) and HDAC1 (54.1%). An association between the low expression of HDAC1 and the presence of lymph node metastasis ( = 0.035) was indicated by univariate analysis while the high expression of HDAC1 was associated with favorable prognostic factors, such as the absence of lymph node metastasis and low mitotic index by multivariate analysis. Also, by multivariate analysis, the low expression of HDAC6 was correlated with the low expression of Ki67, smaller tumors, and better prognosis factors as well. Protein expression was not correlated with patients' overall survival time ( > 0.05). The high expressions of HDAC2 and HDAC6 in mammary carcinomas in female dogs may be useful information for research involving therapeutic targets with iHDACs since their inhibition favors hyperacetylation and transcription of tumor suppressor genes.
PubMed: 38028583
DOI: 10.3389/fgene.2023.1257932 -
Frontiers in Veterinary Science 2023Primary renal neoplasia is rare in humans and dogs, with renal cell carcinoma (RCC) being the most common form of this cancer. As RCC is often diagnosed at an advanced...
Primary renal neoplasia is rare in humans and dogs, with renal cell carcinoma (RCC) being the most common form of this cancer. As RCC is often diagnosed at an advanced stage, pulmonary metastasis is frequently observed. Tyrosine kinase inhibitors (TKIs) are the standard adjuvant treatments for metastatic RCC in humans. Similarly, in veterinary medicine, recent trials have employed TKIs for early-stage RCC patients who underwent complete surgical resection and showed no distant metastasis. However, the use of TKIs has not yet been reported commonly in cases of advanced RCC with metastasis. This case study presents the first clinical outcomes of TKI therapy in a dog with incompletely resected RCC and metastasis. A 5-year-old spayed female Chihuahua was referred to our hospital with a right renal mass and multiple pulmonary nodules suspected to be metastases. A portion of the renal mass was surgically removed, and histopathological examination revealed RCC with a high mitotic index. Adjuvant chemotherapy was administered, owing to incomplete resection with suspected pulmonary metastasis. An anticancer drug response prediction test was conducted using patient tissues. Since toceranib showed the most favorable responsiveness, it was selected as a therapeutic agent. Toceranib was orally administered at a dosage of 2.27 mg/kg every 48 h. Regular medical records for potential adverse effects were obtained, including systemic blood pressure, complete blood count, serum biochemical examination, and urinalysis. After 2 weeks of toceranib therapy, partial remission of pulmonary nodules continued for 2 months. The patient did not experience any adverse effects of the anticancer drug during the 4-month follow-up period. However, the patient died from an unidentified cause 6 months after the initial detection of the renal mass. This report describes the use of toceranib in dogs with RCC. In the present case, the patient showed an initial response to chemotherapy, and despite the presence of several poor prognostic factors, the dog survived beyond the expected 3-month lifespan to 6 months. Notably, no adverse events were observed during treatment.
PubMed: 38026615
DOI: 10.3389/fvets.2023.1287185 -
Cureus Oct 2023Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently identified, infrequent, low-grade mesenchymal neoplasm, first identified in 2014. Although it is...
Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently identified, infrequent, low-grade mesenchymal neoplasm, first identified in 2014. Although it is relatively new to the field, SCPFT has been gaining prominence in surgical pathology practice because of its distinctive features. As of now, there are limited reported cases of SCPFT, with fewer than 100 instances documented in scientific literature. This distinctive blend of rarity and intriguing variability in presentation emphasizes the significance of identifying and understanding this uncommon entity, facilitating precise diagnosis and optimal management. In this article, we aimed to present a notable case of SCPFT in a male in his 20s who presented with a distinct subcutaneous mass measuring 2.4 × 1.8 cm at the medial aspect of the knee joint. The patient reported no significant medical history or trauma to the affected area. MRI of the knee showed a well-defined 2.4 × 1.8 cm subcutaneous mass with no definite communication with the underlying ligament or meniscus. The histopathological examination revealed spindle cell neoplasm arranged in intersecting fascicles, accompanied by arborizing blood vessels. Neoplastic spindle cells exhibited marked nuclear pleomorphism, and abundant and eosinophilic cytoplasm, with focal areas of granular, glassy, and lipidized cytoplasm. Nuclear pseudo inclusions and a few mitotic figures (1-2 per high-power field) were noted. Inflammatory infiltrates were identified within the neoplasm, comprising eosinophils and lymphocytes, highlighting an immune response within the tumor microenvironment. The surgical margin exhibited involvement with the tumor infiltrates, with the neoplastic cells extending into the adjacent fat tissue. This finding indicates local tumor spread and potential challenges in achieving complete resection. Immunohistochemical staining showed positive staining for CD34, corroborating the diagnosis of a CD34-positive fibroblastic tumor. Focal positive staining for pan-CK was noted. Staining for CD31, smooth muscle actin (SMA), desmin, S100, and anaplastic lymphoma kinase (ALK) was negative, supporting the diagnosis. The Ki67 proliferation index was low.
PubMed: 38021590
DOI: 10.7759/cureus.47831 -
Medicina (Kaunas, Lithuania) Oct 2023The careful selection of adequate SLNB candidates not only aims at reducing the surgical risk while identifying SLN metastasis, but also plays a crucial role in...
The careful selection of adequate SLNB candidates not only aims at reducing the surgical risk while identifying SLN metastasis, but also plays a crucial role in identifying the patients eligible for adjuvant therapy. Objectives: The purpose of our study was to investigate the clinical and histologic aspects of primary melanomas that correlate with the likelihood of a positive SLNB result. : A total of 101 primary melanoma patients who underwent sentinel lymph node biopsies were included in the study. General patient demographics were obtained as well as localization and melanoma-specific characteristics of primary melanoma from histologic reports in addition to data derived from SLNB melanoma histopathology reports. : The patients with positive SLN results had a statistically significant increased Breslow thickness (3.8 mm vs. 1.97 mm, = 0.002), higher mitotic index rate (5/mm vs. 2/mm, = 0.009), as well as the presence of ulceration (68.4% vs. 31.6%, = 0.007). Univariate regression analysis showed the Breslow thickness ( = 0.008), the mitotic index rate ( = 0.054), the presence of ulceration ( = 0.009), as well as the pT3-4 stage ( = 0.009) to be significant predictors of SLN positivity. The optimal cut-off values for Breslow thickness and the number of mitoses scores were determined based on ROC curve analysis. Using the Breslow thickness, mitotic index rate, presence of ulceration, and pT3-4 stage significant coefficients from the univariate regression model, a chance prediction score was developed. The newly developed and proposed scoring system can aid in patient selection for SLN biopsy by facilitating a more efficient risk assessment in the detection of lymph node metastases in melanoma patients.
Topics: Humans; Skin Neoplasms; Sentinel Lymph Node; Patient Selection; Prognosis; Retrospective Studies; Melanoma; Sentinel Lymph Node Biopsy; Risk Assessment
PubMed: 38003969
DOI: 10.3390/medicina59111921 -
Journal of Clinical Medicine Nov 2023Aquaporins (AQPs) are small transmembrane proteins able to facilitate the passive transport of water and small molecules throughout cells. Several studies have...
Aquaporins (AQPs) are small transmembrane proteins able to facilitate the passive transport of water and small molecules throughout cells. Several studies have demonstrated that modulation of AQPs' expression contributes to cancer development and progression. However, to date, very little is known about their involvement in malignant melanoma (MM) progression. In this retrospective observational study, we evaluated the correlation between AQP1, -8, and -9 expression and the clinical outcomes of 58 patients diagnosed with MM from 2014 to 2016, of which 14 were diagnosed as nodular melanoma (NM) and 44 as superficial spreading melanoma (SSM). In general, we found that AQPs were more highly expressed in SSM than NM, suggesting a potential correlation with prognosis. While analyzing the expression of each AQP, we discovered that AQP1 was associated with a specific body site and low mitotic index, AQP8 with a negative sentinel lymph node, and AQP9 with the Breslow thickness and lack of ulcerations. Together with the survival analysis performed in this study, our results suggest that the expression of AQP1, -8, and -9 could be correlated with a better prognosis for malignant melanoma.
PubMed: 38002749
DOI: 10.3390/jcm12227137 -
Biomolecules Nov 2023Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is...
Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior.
BACKGROUND
Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors.
METHODS
Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration.
RESULTS
The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration.
CONCLUSIONS
These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.
Topics: Humans; Animals; Mice; Polylactic Acid-Polyglycolic Acid Copolymer; Cetuximab; Lactic Acid; Polyglycolic Acid; Glycols; Tissue Distribution; Iodine Radioisotopes; Quality of Life; Cell Line, Tumor; Thyroid Neoplasms; ErbB Receptors; Nanoparticles; Drug Carriers
PubMed: 38002329
DOI: 10.3390/biom13111647