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PloS One 2024Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer...
Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer metastasis and a tumour-based Glasgow EMT score was associated with adverse clinical features and poor prognosis. In this study, the impact of using the established five tumour-based EMT markers consisting of E-cadherin (E-cad), β-catenin (β-cat), Snail, Zeb-1, and Fascin in combination with the stromal periostin (PN) on the prediction of CRC patients' prognosis were invesigated. Formalin-fixed paraffin-embedded tissues of 202 CRC patients were studies the expressions of E-cad, β-cat, Snail, Zeb-1, Fascin, and PN by immunohistochemistry. Individually, cytoplasmic Fascin (Fc), cytoplasmic Snail (Sc), nuclear Snail (Sn), stromal Snail (Ss), and stromal PN (Ps) were significantly associated with reduced survival. A combination of Ps with Fc, Fs, and Sn was observed in 2 patterns including combined Fc, Fs, and Ps (FcFsPs) and Fc, Sn, and Ps (FcSnPs). These combinations enhanced the prognostic power compared to individual EMT markers and were independent prognostic markers. As the previously established scoring method required five markers and stringent criteria, its clinical use might be limited. Therefore, using these novel combined prognostic markers, either FcFsPs or FcSnPs, may be useful in predicting CRC patient outcomes.
Topics: Humans; Colorectal Neoplasms; Snail Family Transcription Factors; Cell Adhesion Molecules; Prognosis; Female; Male; Middle Aged; Carrier Proteins; Microfilament Proteins; Epithelial-Mesenchymal Transition; Aged; Biomarkers, Tumor; Adult; Cadherins; Transcription Factors; beta Catenin; Aged, 80 and over; Periostin
PubMed: 38935747
DOI: 10.1371/journal.pone.0304666 -
PloS One 2024Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These...
Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These factors collectively interact in complex ways, influencing disease behavior, especially among highly admixed populations like Colombians. In this study, we assessed contributing factors to breast cancer health disparities according to genetic ancestry in Colombian patients from a national cancer reference center. We collected non-tumoral paraffin embedded (FFPE) blocks from 361 women diagnosed with breast cancer at the National Cancer Institute (NCI) to estimate genetic ancestry using a 106-ancestry informative marker (AIM) panel. Differences in European, Indigenous American (IA) and African ancestry fractions were analyzed according to potential sources of breast cancer health disparities, like etiology, tumor-biology, treatment administration, and socioeconomic-related factors using a Kruskal-Wallis test. Our analysis revealed a significantly higher IA ancestry among overweight patients with larger tumors and those covered by a subsidized health insurance. Conversely, we found a significantly higher European ancestry among patients with smaller tumors, residing in middle-income households, and affiliated to the contributory health regime, whereas a higher median of African ancestry was observed among patients with either a clinical, pathological, or stable response to neoadjuvant treatment. Altogether, our results suggest that the genetic legacy among Colombian patients, measured as genetic ancestry fractions, may be reflected in many of the clinical-pathological variables and socioeconomic factors that end up contributing to health disparities for this disease.
Topics: Humans; Female; Colombia; Breast Neoplasms; Middle Aged; Adult; Health Status Disparities; White People; Aged; Socioeconomic Factors
PubMed: 38935662
DOI: 10.1371/journal.pone.0306037 -
Micromachines Jun 2024Phase change materials (PCMs) are used to cool high-power-density electronic devices because of their high latent heat and chemical stability. However, their low thermal...
Phase change materials (PCMs) are used to cool high-power-density electronic devices because of their high latent heat and chemical stability. However, their low thermal conductivity limits the application of PCMs. To solve this problem, a double-porosity porous aluminum skeleton/paraffin phase change materials (DPAS/PCM) was prepared via additive manufacturing and the water-bath method. The thermal performance of the DPAS/PCM heat sink (HS) was experimentally investigated to examine the effects of the positive- and reverse-gradient porosity structures of the DPAS/PCM. The results show that a positive-gradient porosity arrangement is more conducive to achieving a low-temperature cooling target for LED operation. In particular, the temperature control time for the positive gradient porosity structure increased by 4.6-13.7% compared with the reverse gradient porosity structure. Additionally, the thermal performances of uniform porous aluminum skeleton/paraffin (UAS) and DPAS/PCMs were investigated. The temperature control effect of the DPAS/PCM was better than that of the UAS/PCM HS at high critical temperatures. Compared with the UAS/PCM HS, the temperature control time of the DPAS/PCM HS is increased by 7.8-12.5%. The results of this work show that the prepared DPAS/PCM is a high-potential hybrid system for thermal management of high-power electronic devices.
PubMed: 38930776
DOI: 10.3390/mi15060806 -
Materials (Basel, Switzerland) Jun 2024Among the different types of phase change materials, paraffin is known to be the most widely used type due to its advantages. However, paraffin's low thermal...
Among the different types of phase change materials, paraffin is known to be the most widely used type due to its advantages. However, paraffin's low thermal conductivity, its limited operating temperature range, and leakage and stabilization problems are the main barriers to its use in applications. In this research, a thermal energy storage unit (TESU) was designed using a cylindrical macroencapsulation technique to minimize these problems. Experimental and numerical analyses of the storage unit using a tubular heat exchanger were carried out. The Ansys 18.2-Fluent software was used for the numerical analysis. Two types of paraffins with different thermophysical properties were used in the TESU, including both encapsulated and non-encapsulated forms, and their thermal energy storage performances were compared. The influence of the heat transfer fluid (HTF) inlet conditions on the charging performance (melting) was investigated. The findings demonstrated that the heat transfer rate is highly influenced by the HTF intake temperature. When the effect of paraffin encapsulation on heat transfer was examined, a significant decrease in the total melting time was observed as the heat transfer surface and thermal conductivity increased. Therefore, the energy stored simultaneously increased by 60.5% with the encapsulation of paraffin-1 (melting temperature range of 52.9-60.4 °C) and by 50.7% with the encapsulation of paraffin-2 (melting temperature range of 32.2-46.1 °C), thus increasing the charging rate.
PubMed: 38930175
DOI: 10.3390/ma17122804 -
Medicina (Kaunas, Lithuania) May 2024Lung adenocarcinoma is a leading cause of cancer-related mortality despite recent therapeutic advances. Cancer stem cells have gained increasing attention due to their...
Lung adenocarcinoma is a leading cause of cancer-related mortality despite recent therapeutic advances. Cancer stem cells have gained increasing attention due to their ability to induce cancer cell proliferation through self-renewal and differentiation into multiple cell lineages. OCT4 and LIN28 (and their homologs A and B) have been identified as key regulators of pluripotency in mammalian embryonic (ES) and induced stem (IS) cells, and they are the crucial regulators of cancer progression. However, their exact role in lung adenocarcinoma has not yet been clarified. The aim of this study was to explore the role of the pluripotency factors OCT4 and LIN28 in a cohort of surgically resected human lung adenocarcinomas to reveal possible biomarkers for lung adenocarcinoma prognosis and potential therapeutic targets. The expressions of OCT4, LIN28A and LIN28B were analyzed in formalin-fixed, paraffin-embedded tissue samples from 96 patients with lung adenocarcinoma by immunohistochemistry. The results were analyzed with clinicopathologic parameters and were related to the prognosis of patients. Higher OCT4 expression was related to an improved 5-year overall survival (OS) rate ( < 0.001). Nuclear LIN28B expression was lower in stage I and II tumors ( < 0.05) compared to advanced stage tumors. LIN28B cytoplasmic expression was associated with 5-year OS rates not only in univariate ( < 0.005), but also in multivariate analysis (where age, gender, histopathological subtype and stage were used as cofactors, < 0.01 HR = 2.592). Patients with lower LIN28B expression showed improved 5-year OS rates compared to patients with increased LIN28B expression. Our findings indicate that OCT4 and LIN28B are implicated in lung adenocarcinoma progression and prognosis outcome; thus, they serve as promising prognostic biomarkers and putative therapeutic targets in lung adenocarcinomas.
Topics: Humans; Octamer Transcription Factor-3; Male; Female; RNA-Binding Proteins; Middle Aged; Lung Neoplasms; Adenocarcinoma of Lung; Aged; Adenocarcinoma; Prognosis; Biomarkers, Tumor; Adult; Survival Analysis; Immunohistochemistry; Aged, 80 and over
PubMed: 38929487
DOI: 10.3390/medicina60060870 -
International Journal of Molecular... Jun 2024It is known that V-set and immunoglobulin domain containing 1 (VSIG1) is a cell-cell adhesion molecule that can serve as an indicator of better survival in patients with...
It is known that V-set and immunoglobulin domain containing 1 (VSIG1) is a cell-cell adhesion molecule that can serve as an indicator of better survival in patients with gastric cancer. Its interaction with cytoplasmic thyroid transcription factor 1 (TTF-1) has been hypothesized to characterize gastric-type HCC, but its clinical importance is far from understood. As VSIG1 has also been supposed to be involved in the epithelial-mesenchymal transition (EMT) phenomenon, we checked for the first time in the literature the supposed interaction between VSIG1, TTF-1, and Vimentin (VIM) in HCCs. Immunohistochemical (IHC) stains were performed on 217 paraffin-embedded tissue samples that included tumor cells and normal hepatocytes, which served as positive internal controls. VSIG1 positivity was seen in 113 cases (52.07%). In 71 out of 217 HCCs (32.71%), simultaneous positivity for VSIG1 and TTF-1 was seen, being more specific for G1/G2 carcinomas with a trabecular architecture and a longer OS ( = 0.004). A negative association with VIM was revealed ( < 0.0001). Scirrhous-type HCC proved negative for all three examined markers. The present paper validates the hypothesis of the existence of a gastric-type HCC, which shows a glandular-like architecture and is characterized by double positivity for VSIG1 and TTF-1, vimentin negativity, and a significant OS.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Middle Aged; Vimentin; Aged; Adult; Biomarkers, Tumor; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Aged, 80 and over; Thyroid Nuclear Factor 1; Transcription Factors; Immunohistochemistry
PubMed: 38928294
DOI: 10.3390/ijms25126588 -
International Journal of Molecular... Jun 2024Since transcription factor Forkhead Box P3 (FoxP3) was identified as a specific regulatory T cell (Treg) marker, researchers have scrutinized its value as a potential...
Since transcription factor Forkhead Box P3 (FoxP3) was identified as a specific regulatory T cell (Treg) marker, researchers have scrutinized its value as a potential novel therapeutic target or a prognostic factor in various types of cancer with inconsistent results. The present analysis was performed to assess the influence of Treg FoxP3 expression on the prognosis of primary melanoma and to evaluate the correlations with various clinicopathological prognostic factors. We analyzed all eligible patients with stage pT3 primary malignant melanomas treated in a tertiary cancer center. Immunohistochemical staining for Treg FoxP3 expression was performed on retrospectively identified paraffin blocks and subsequently correlated with the outcomes of the patients. A total of 81% of the patients presented a positive Treg FoxP3 expression, being correlated with a higher risk of lymph node metastasis, tumor relapse, and death. Moreover, positive expression was statistically associated with a shorter OS. The tumor relapse rate was estimated at 36.7%. A positive expression of Treg FoxP3 and lymph node metastasis were associated with a higher risk of death based on multivariate analysis. Treg FoxP3 expression may be used as an independent prognostic factor in patients with malignant melanoma to evaluate tumor progression and survival.
Topics: Humans; Forkhead Transcription Factors; Melanoma; Male; T-Lymphocytes, Regulatory; Female; Middle Aged; Prognosis; Aged; Adult; Lymphatic Metastasis; Biomarkers, Tumor; Retrospective Studies; Skin Neoplasms; Aged, 80 and over; Neoplasm Recurrence, Local
PubMed: 38928083
DOI: 10.3390/ijms25126377 -
Biomedicines Jun 2024Poorly differentiated cancer (PDC) and anaplastic thyroid cancer (ATC) have an aggressive course of disease with limited treatment options. The expression of programmed...
IMPORTANCE
Poorly differentiated cancer (PDC) and anaplastic thyroid cancer (ATC) have an aggressive course of disease with limited treatment options. The expression of programmed cell death ligand-1 (PD-L1) has been used to determine the responses of many cancers to immunotherapy. The aim of the study was to investigate the expression of PD-L1 in a cohort of patients with PDC and ATC to assess their suitability for immunotherapy. Data, settings, and participants: This study is a retrospective cohort review of patients treated for PDC and ATC treated at a tertiary referral institution during the period 2000-2020. PD-L1 22C3 pharmDx qualitative immunohistochemistry was performed on formalin-fixed, paraffin-embedded (FFPE) specimens of tumours to detect the presence of the PD-L1 protein.
MAIN OUTCOME MEASURES
The percentage of tumours that were positive for PD-L1 immunohistochemistry and the PD-L1 protein expression as measured by using the Tumour Proportion Score (TPS). Secondary outcomes studied were the associations between demographic, clinicopathological, treatment and disease outcomes and PD-L1 expression.
RESULTS
Nineteen patients (12F:7M) with a mean age of 65.4 (±14.3 SD) years were diagnosed with PDC in 4 (21%) and fifteen were diagnosed with ATC (79%) during the study period. Fifteen (79%) patients underwent some form of surgery, with R0 resection achieved in only three of the fifteen (20%) patients. Overall, PD-L1 expression was seen in seven of the fifteen (47%) of the patients with ATC, with no positivity seen in the patients with PDC. PD-L1 expression had no impact on treatment modality and positive expression was not significantly associated with stage of disease, metastasis, or survival.
CONCLUSION
Nearly half of patients with ATC express PD-L1 and may be amenable to immunotherapy with pembrolizumab.
PubMed: 38927511
DOI: 10.3390/biomedicines12061304 -
Scientific Reports Jun 2024Identifying novel epigenetic biomarkers is a promising way to improve the clinical management of patients with breast cancer. Our study aimed to determine the...
Identifying novel epigenetic biomarkers is a promising way to improve the clinical management of patients with breast cancer. Our study aimed to determine the methylation pattern of 25 tumor suppressor genes (TSG) and select the best methylation biomarker associated with clinicopathological features in the cohort of Slovak patients diagnosed with invasive ductal carcinoma (IDC). Overall, 166 formalin-fixed, paraffin-embedded (FFPE) tissues obtained from patients with IDC were included in the study. The methylation status of the promoter regions of 25 TSG was analyzed using semiquantitative methylation-specific MLPA (MS-MLPA). We identified CDH13 as the most frequently methylated gene in our cohort of patients. Further analysis by ddPCR confirmed an increased level of methylation in the promoter region of CDH13. A significant difference in CDH13 methylation levels was observed between IDC molecular subtypes LUM A versus HER2 (P = 0.0116) and HER2 versus TNBC (P = 0.0234). In addition, significantly higher methylation was detected in HER2+ versus HER2- tumors (P = 0.0004) and PR- versus PR+ tumors (P = 0.0421). Our results provide evidence that alteration in CDH13 methylation is associated with clinicopathological features in the cohort of Slovak patients with IDC. In addition, using ddPCR as a methylation-sensitive method represents a promising approach characterized by higher precision and technical simplicity to measure the methylation of target CpGs in CDH13 compared to other conventional methods such as MS-MLPA.
Topics: Humans; Cadherins; Female; DNA Methylation; Breast Neoplasms; Middle Aged; Carcinoma, Ductal, Breast; Aged; Promoter Regions, Genetic; Slovakia; Biomarkers, Tumor; Adult; Polymerase Chain Reaction
PubMed: 38926485
DOI: 10.1038/s41598-024-65580-6 -
Journal of Clinical and Experimental... 2024In the new WHO classifications of haematolymphoid tumours (WHO-HAEM5), classic Hodgkin lymphoma (cHL) is categorized into B-cell lymphoid proliferations and lymphomas....
In the new WHO classifications of haematolymphoid tumours (WHO-HAEM5), classic Hodgkin lymphoma (cHL) is categorized into B-cell lymphoid proliferations and lymphomas. Although the majority of Hodgkin Reed-Sternberg (HRS) cells are of germinal center B-cell origin with some defects of B-cell transcription factors, they rarely express T-cell antigens or cytotoxic molecules. Clonality analyses on cHL samples using BIOMED-2 have been reported by several groups; however, those studies were only focused on Ig regions, including IgH, Ig-kappa, and Ig-lambda, and TCR-γ clonality analysis of cHL has not yet been explored. Here, we investigated TCR-γ gene rearrangement for one hundred cases using a PCR-based method. Four of one hundred (4%) cases showed TCR-γ clonal peaks. Of these, three were at an advanced stage and one patient died of the disease. To clarify whether HRS cells showed T-cell clonality or not, we performed PCR analysis using DNAs of microdissected HRS cells. Three samples showed identical clonal peaks with bulk specimens. Our results indicate that cHL is a heterogeneous disease of mainly B-cell and rarely T-cell origin with a special phenotype. Further molecular studies are warranted.
Topics: Humans; Hodgkin Disease; Male; Adult; Female; Middle Aged; Aged; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; Paraffin Embedding; Aged, 80 and over; Adolescent; Receptors, Antigen, T-Cell, gamma-delta; Reed-Sternberg Cells; Young Adult; Polymerase Chain Reaction
PubMed: 38925974
DOI: 10.3960/jslrt.24027