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International Journal of Molecular... Mar 2024Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer.... (Randomized Controlled Trial)
Randomized Controlled Trial
Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer. The number of studies on the predictive potential of the different components of the lipid profile with a predictive potential in breast cancer is quite low. The evaluation of the lipid profile was carried out for the 142 patients who benefited from neoadjuvant therapy (NAC) in order to identify a potential predictive biomarker. The serological sample collection was performed sequentially according to a standardized protocol, pre-NAC, post-NAC and 6 months post-NAC after a 6-h pre-collection fast. We also investigated in the general group the presence or absence of the p53 mutation (TP53) and of the mitotic index ki-67, respectively, in relation to the molecular subtypes. The menopausal status, tumor size, family history, grading, Ki-67, p53 and LN metastases have a predictive nature regarding overall survival (OS) ( < 0.05), while for disease free survival (DFS), only tumor size, tumor grading, Ki-67 > 14, and p53+ are of predictive nature. The genetic and molecular analysis carried out in our group indicates that 71.67% have a Ki-67 score higher than 14%, and 39% of the patients have the positive P53 mutation. The multivariate analysis in the case of patients included in the TNBC subtype showed that the increased tumor volume ( = 0.002) and increased level of HDL ( = 0.004) represent predictive factors for the tumor response rate to NAC. High HDL-C levels before NAC and increased LDL-C levels after NAC were associated with the better treatment response in ER-positive and HER2+ breast cancer patients. Increased HDL-C values and tumor volume represent predictive factors as to the response rate to NAC in the case of patients included in the TNBC subtype. Regarding the ER+ and HER2+ subtypes, increased levels of HDL-C pre-NAC and increased levels of LDL-C post-NAC were associated with a better therapeutic response rate. Tumor grading, Ki-67, p53, and LN metastases have a predictive nature for OS, while tumor size, tumor grading, and Ki-67 > 14, and p53+ are predictive for DFS.
Topics: Male; Humans; Ki-67 Antigen; Cholesterol, LDL; Triple Negative Breast Neoplasms; Tumor Suppressor Protein p53; Kidney Neoplasms
PubMed: 38612725
DOI: 10.3390/ijms25073911 -
Cancers Apr 2024Proliferation determined by Ki-67 immunohistochemistry has been proposed as a useful prognostic and predictive marker in breast cancer. However, the clinical validity of...
Proliferation determined by Ki-67 immunohistochemistry has been proposed as a useful prognostic and predictive marker in breast cancer. However, the clinical validity of Ki-67 is questionable. In this study, Ki-67 was retrospectively evaluated by three pathologists using two methods: a visual assessment of the entire slide and a quantitative assessment of the tumour margin in 411 early-stage breast cancer patients with a median follow-up of 26.8 years. We found excellent agreement between the three pathologists for both methods. The risk of recurrence for Ki-67 was time-dependent, as the high proliferation group (Ki-67 ≥ 30%) had a higher risk of recurrence initially, but after 4.5 years the risk was higher in the low proliferation group. In estrogen receptor (ER)-positive patients, the intermediate Ki-67 group initially followed the high Ki-67 group, but eventually followed the low Ki-67 group. ER-positive pN0-1 patients with intermediate Ki-67 treated with endocrine therapy alone had a similar outcome to patients treated with chemotherapy. A cut-off value of 20% appeared to be most appropriate for distinguishing between the high and low Ki-67 groups. To summarize, a simple visual whole slide Ki-67 assessment turned out to be a reliable method for clinical decision-making in early breast cancer patients. We confirmed Ki-67 as an important prognostic and predictive biomarker.
PubMed: 38611083
DOI: 10.3390/cancers16071405 -
International Journal of Biological... May 2024Here, the simultaneous effect of chemo- and photothermal therapy against epidermoid carcinoma (EC) was investigated. A novel hydrogel, termed bionanogel (BNG), was...
Here, the simultaneous effect of chemo- and photothermal therapy against epidermoid carcinoma (EC) was investigated. A novel hydrogel, termed bionanogel (BNG), was designed using psyllium mucilage polysaccharide and bacterial gellan gum, incorporated with nanocomplex carrying caffeic acid (CA) and IR-820, and further characterized. The dual effect of BNG and 808 nm laser (BNG + L) on EC was investigated. Staining and scratch assays were performed to analyze their therapeutic effect on EC. In vivo evaluations of BNG + L in xenograft models were performed. Rapid transition, limited swelling, degradability and high tensile strength indicated BNG stability and sustained drug release. Irradiation with 808 nm laser light at 1.25 W /cm for 4 min resulted in a temperature increase of 53 °C and facilitated cell ablation. The in vitro studies showed that BNG + L suppressed cancer progression via a late apoptotic effect. The in vivo study showed that the slow release of CA from BNG + L significantly attenuated EC with low mitotic index and downregulation of proteins involved in cancer proliferation such as EGFR, AKT, PI3K, ERK, mTOR and HIF-1α. Thus, BNG could be a novel medium for targeted and controlled drug delivery for the treatment of epidermoid cancer when triggered by NIR light.
Topics: Caffeic Acids; Animals; Humans; Polysaccharides, Bacterial; Carcinoma, Squamous Cell; Mice; Psyllium; Cell Line, Tumor; Polysaccharides; Hydrogels; Xenograft Model Antitumor Assays; Drug Delivery Systems
PubMed: 38582464
DOI: 10.1016/j.ijbiomac.2024.131166 -
Glia Jul 2024Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA...
Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA profile of diseased microglia have been well documented, the actual microglia proteome remains poorly characterized. Here we performed a functional characterization together with proteome analyses of microglial cells at different stages of disease in the SOD1-G93A model of ALS. Functional analyses of microglia derived from the lumbar spinal cord of symptomatic mice revealed: (i) remarkably high mitotic index (close to 100% cells are Ki67+) (ii) significant decrease in phagocytic capacity when compared to age-matched control microglia, and (iii) diminished response to innate immune challenges in vitro and in vivo. Proteome analysis revealed a development of two distinct molecular signatures at early and advanced stages of disease. While at early stages of disease, we identified several proteins implicated in microglia immune functions such as GPNMB, HMBOX1, at advanced stages of disease microglia signature at protein level was characterized with a robust upregulation of several unconventional proteins including rootletin, major vaults proteins and STK38. Upregulation of GPNMB and rootletin has been also found in the spinal cord samples of sporadic ALS. Remarkably, the top biological functions of microglia, in particular in the advanced disease, were not related to immunity/immune response, but were highly enriched in terms linked to RNA metabolism. Together, our results suggest that, over the course of disease, chronically activated microglia develop unconventional protein signatures and gradually lose their immune identity ultimately turning into functionally inefficient immune cells.
Topics: Amyotrophic Lateral Sclerosis; Microglia; Animals; Proteome; Mice; Mice, Transgenic; Spinal Cord; Disease Models, Animal; Phagocytosis; Humans; Female; Mice, Inbred C57BL; Male
PubMed: 38577970
DOI: 10.1002/glia.24531 -
Journal of Cancer Research and... Jan 2024Despite the growing advances in molecular research and therapeutics, glioblastomas are still considered highly invasive aggressive tumors with a median survival of 15...
BACKGROUND
Despite the growing advances in molecular research and therapeutics, glioblastomas are still considered highly invasive aggressive tumors with a median survival of 15 months. Genetic alterations have been studied in detail; however, additionally, there is now growing evidence on the role of epigenetic alterations in glioblastoma. Recently, histone modification patterns have been found to have a significant part in gene expression and prognosis. However, further research in this field is warranted to establish its role for the betterment of these patients with the deadly disease.
AIMS
To determine the immunohistochemical expression of histone modifications like histone-3-lysine-18 acetylation (H3K18Ac) and histone-4-lysine 20 trimethylation (H4K20triMe) in glioblastoma patients.
MATERIALS AND METHODS
This is a retrospective study of 48 glioblastoma patients who underwent surgery. Immunohistochemistry (IHC) for tri-methyl-histone-H4 (Lys20) (H4K20triMe) and acetyl-histone-H3 (Lys18) (H3K18Ac) was performed in paraffin-embedded tissues manually, and the expression was noted. Data on the mitotic index and overall survival was collected and statistically analyzed.
RESULTS
The mean age was 50 years with a M: F ratio of 1.6:1. Out of 48 cases, 60% (28 cases) demonstrated positivity for H3K18Ac and 98% (46 cases) for H4K20triMe. The pattern of expression was nuclear with increased expression adjacent to necrosis and at the invasive front. The overall median Q score for H3K18Ac was 1/12 and for H4K20triMe was 6/12. No significant statistical significance was observed between histone expression, Ki67%, and overall survival.
CONCLUSION
Histone modification patterns are being explored in detail in an array of tumors. They also have a potential role in glioblastoma for risk stratification and instituting appropriate treatment based on the prognosis. Epigenetic changes like histone modification patterns, in addition to genetics, can pave the way for a better molecular understanding of glioblastomas and provide hope in the future to improve the survival of these patients with deadly diseases.
Topics: Adult; Humans; Middle Aged; Histones; Glioblastoma; Histone Code; Lysine; Retrospective Studies; Acetylation
PubMed: 38554298
DOI: 10.4103/jcrt.jcrt_257_22 -
Annals of Diagnostic Pathology Aug 2024The Ki-67 proliferative index plays a pivotal role in the subclassification of neuroendocrine neoplasm (NEN) according to the WHO Classification of Digestive System...
The Ki-67 proliferative index plays a pivotal role in the subclassification of neuroendocrine neoplasm (NEN) according to the WHO Classification of Digestive System Tumors (5th edition), which designates neuroendocrine tumor (NET) grades 1, 2, and 3 for Ki-67 proliferative index of <3 %, 3-20 %, and >20 %, respectively. Proliferative index calculation must be performed in the hotspot, traditionally selected by visual scanning at low-power magnification. Recently, gradient map visualization has emerged as a tool for various purposes, including hotspot selection. This study includes 97 cases of gastrointestinal neuroendocrine neoplasms, with hotspots selected by bare eye and gradient map visualization (GM). Each hotspot was analyzed using three methods: eye estimation (EE), digital image analysis (DIA), and manual counting. Of the NENs studied, 91 % were NETs (26 % for G1, 55 % for G2, and 10 % for G3). Only 9 cases were neuroendocrine carcinoma (NEC). Between two hotspot selection methods, GM resulted in a higher grade in 14.77 % of cases, primarily upgrading from NET G1 to G2. Among the counting methods, DIA demonstrated substantial agreement with manual counting, both for pathologist and resident. Grading by other methods tended to result in a higher grade than MC (26.99 % with EE and 8.52 % with DIA). Given its clinical and statistical significance, this study advocates for the application of GM in hotspot selection to identify higher-grade tumors. Furthermore, DIA provides accurate grading, offering time efficiency over MC.
Topics: Humans; Ki-67 Antigen; Neuroendocrine Tumors; Pancreatic Neoplasms; Image Processing, Computer-Assisted; Neoplasm Grading; Intestinal Neoplasms; Female; Male; Middle Aged; Aged; Stomach Neoplasms; Adult; Mitotic Index; Carcinoma, Neuroendocrine; Gastrointestinal Neoplasms
PubMed: 38547761
DOI: 10.1016/j.anndiagpath.2024.152295 -
Computers in Biology and Medicine May 2024The functional relevance of cyclic adenosine monophosphate (cAMP)-response element-binding protein 5 (CREB5) in cancers remains elusive, despite its significance as a...
BACKGROUND
The functional relevance of cyclic adenosine monophosphate (cAMP)-response element-binding protein 5 (CREB5) in cancers remains elusive, despite its significance as a member of the CREB family. The current research aims to explore the role of CREB5 in multiple cancers.
METHODS
Pan-cancer analysis was performed to explore the expression patterns, prognostic value, mutational landscape as well as single-cell omic, immunologic, and drug sensitivity profiles of CREB5. Furthermore, we incorporated five distinct machine learning algorithms and determined that the least absolute shrinkage and selection operator-COX (LASSO-COX) algorithm, which exhibited the highest C index, was the optimal selection. Subsequently, we constructed a prognostic model centered around CREB5-associated genes. To elucidate the biological function of CREB5 in glioma cells, several assays including cell counting kit-8 (CCK-8), wound healing, transwell, flow cytometric were performed.
RESULTS
CREB5 was overexpressed in pan-cancer and was linked to unfavorable prognosis, particularly in glioma. Furthermore, genetic alterations were determined in various types of cancer, and modifications in the CREB5 gene were linked to the prognosis. The single-cell omics and enrichment analyses showed that CREB5 was predominantly expressed in malignant glioma cells and was critically involved in the regulation of various oncogenic processes. Elevated levels of CREB5 were strongly linked with the infiltration of cancer-associated fibroblasts and the Th1 subset of CD4 T cells. The validated CREB5-associated prognostic model reliably predicted the prognosis and drug response of glioma patients. The in vitro experiments showed that CREB5 promoted glioma cell proliferation, invasion, migration, and gap phase 2/mitotic (G2/M) phase arrest and recruited M2 macrophages into glioma cells.
CONCLUSION
CREB5 has the potential to act as an oncogene and a biological marker in multiple cancers, particularly glioma.
Topics: Humans; Biomarkers; Cyclic AMP Response Element-Binding Protein A; Glioma; Immunotherapy; Multiomics; Prognosis
PubMed: 38547657
DOI: 10.1016/j.compbiomed.2024.108307 -
Journal of Dentistry (Shiraz, Iran) Mar 2024Fibro-osseous lesions (FLs), may rarely exhibit malignant features likewise undergo malignant transformation. Awareness of these features can assist in screening for...
STATEMENT OF THE PROBLEM
Fibro-osseous lesions (FLs), may rarely exhibit malignant features likewise undergo malignant transformation. Awareness of these features can assist in screening for potentially malignant cases and identifying low-grade central osteogenic sarcoma (LGCOS) that may mimic FLs.
PURPOSE
The objective of this study was to determine the usability of an index in predicting malignant changes in jaw FLs.
MATERIALS AND METHOD
This was a retrospective study where hematoxylin and eosin (H&E) slides and archival records of fibrous dysplasia (FD) and ossifying fibroma (OF) cases were reviewed. The sections were assessed for permeation of marrow spaces, stromal growth pattern, cytologic atypia, mitotic activity, and pattern of bone growth, which are parameters for diagnosing LGCOS. The predictive histologic index of malignancy (PHIM) was determined by a sum of the scores and graded as 0=nil, 1=low, 2 & 3=moderate, and 4 & 5=high. Data were presented using descriptive analysis.
RESULTS
Ninety-three cases of FLs met the inclusion criteria, consisting of 40(43%) cases of FD and 53(57%) cases of OF. The peak age of presentation for FD and OF was 2 and 3 decade. There was a female preponderance of 1:1.6. The maxilla was the most common site affected by FD, while the mandible was most commonly affected by OF. For FD cases, the PHIM was moderate in 10(25%) cases and low in 21(52.5%) cases. Similarly, for OF cases, 30(56.6%) cases had low grade PHIM while 10(17%) cases had moderate grade PHIM.
CONCLUSION
The PHIM depicted low to moderate malignancy grade in some of the cases studied. Follow up studies would be necessary to assess the PHIM.
PubMed: 38544774
DOI: 10.30476/dentjods.2023.96389.1935 -
Toxics Mar 2024Indigo carmine has a variety of uses in foods, textiles, medicine, pharmaceuticals, and cosmetics. There are studies reporting the toxic potential of indigo carmine on...
Indigo carmine has a variety of uses in foods, textiles, medicine, pharmaceuticals, and cosmetics. There are studies reporting the toxic potential of indigo carmine on human health and the environment. In this study, we investigated the cytogenotoxic effects of indigo carmine using apical root cells of . bulbs were subjected to four treatments with indigo carmine (0.0032, 0.0064, 0.0125, and 0.2 mg/mL) and to ultrapure water as a control. After 5 days, root growth, root length, mitotic index, mitotic inhibition, chromosomal anomalies, and cell morphology were analyzed. According to our results, a decrease in root length and mitotic index was observed at all concentrations of indigo carmine. Additionally, several types of chromosomal abnormalities were observed, such as disturbed metaphase, sticky chain metaphase, anaphase bridge, and laggard chromosomes. Moreover, histological observation indicated that indigo carmine induces alterations in various components of root tip tissue, such as deformation and alteration of the cell wall, progressive condensation of chromatin, shrinkage of the nuclei, and an increase in the number of irregularly shaped nuclei and nuclear fragments. Our results indicate that the tested concentrations of indigo carmine may have toxic effects and raise concerns about its intensive use in many fields.
PubMed: 38535927
DOI: 10.3390/toxics12030194 -
Veterinary Pathology Mar 2024One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The...
One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review was to analyze the methods and prognostic relevance of histologically measuring mitotic activity that have been reported for canine tumors in the literature. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and nonsystematic (Google Scholar) literature search and eligibility screening process. Mitotic activity methods encompassed the mitotic count (MC, number of mitotic figures per tumor area) in 126 studies, presumably the MC (method not specified) in 6 studies, and the mitotic index (MI, number of mitotic figures per number of tumor cells) in 5 studies. A particularly high risk of bias was identified based on the available details of the MC methods and statistical analyses, which often did not quantify the prognostic discriminative ability of the MC and only reported values. A significant association of the MC with survival was found in 72 of 109 (66%) studies. However, survival was evaluated by at least 3 studies in only 7 tumor types/groups, of which a prognostic relevance is apparent for mast cell tumors of the skin, cutaneous melanoma, and soft tissue tumor of the skin and subcutis. None of the studies using the MI found a prognostic relevance. This review highlights the need for more studies with standardized methods and appropriate analysis of the discriminative ability to prove the prognostic value of the MC and MI in various tumor types. Future studies are needed to evaluate the influence of the performance of individual pathologists on the appropriateness of prognostic thresholds and investigate methods to improve interobserver reproducibility.
PubMed: 38533804
DOI: 10.1177/03009858241239565