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Digestive Diseases and Sciences Jun 2024Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes could alter miRNA expression levels or processing and, thus, may contribute to colorectal cancer (CRC)...
BACKGROUND
Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes could alter miRNA expression levels or processing and, thus, may contribute to colorectal cancer (CRC) development. Therefore, this study aimed to examine whether the MIR181A1 genomic sequence possesses SNPs that can affect the expression of hsa-miR-181a-5p and, subsequently, impact its targets and associate with CRC risk.
METHODS
The NCBI dbSNP database was searched for possible SNPs associated with MIR181A1. One SNP with a minor allele frequency > 5%, rs12039395 G > T was identified. In silico analyses determined the effect of the SNP on the secondary structure of the miRNA and predicted the hsa-miR-181a-5p target genes. The SNP was genotyped using allelic discrimination assay, the relative hsa-miR-181a-5p expression level was determined using quantitative real-time PCR, and immunohistochemical staining was used to detect target genes in 192 paraffin-embedded specimens collected from 160 CRC patients and 32 healthy subjects.
RESULTS
The rs6505162 SNP conferred protection against CRC, and the G-allele presence provides may provide accessibility for the transcriptional machinery. Hsa-miR-181a-5p was significantly over-expressed in the CRC group compared to controls and in samples carrying the G-allele compared to those with T-allele. PTEN, identified as the only hsa-miR-181a-5p target implicated in CRC, was significantly diminished in the CRC group compared to controls and showed an inverse relationship with hsa-miR-181a-5p expression level as well as negatively associated with the G-allele presence in CRC.
CONCLUSION
This study highlights that rs12039395 G > T may protect against CRC by influencing the expression of hsa-mir-181a-5p and its target gene, PTEN.
PubMed: 38940971
DOI: 10.1007/s10620-024-08517-3 -
Przeglad Gastroenterologiczny 2024Colon adenocarcinoma (COAD) is one of the most frequently identified cancers of the digestive system. It is worth noting that the 5-year survival rates for patients...
INTRODUCTION
Colon adenocarcinoma (COAD) is one of the most frequently identified cancers of the digestive system. It is worth noting that the 5-year survival rates for patients diagnosed early are approximately 90%, whereas for patients with advanced diagnosis it is only 10%. It may indicate that metastasis is a critical cause of death for cancer patients.
AIM
The current study investigated the immunohistochemical expression of MnSOD in individuals living in Poland, who were diagnosed as colon adenocarcinoma patients, to assess its prognostic significance by correlating its expression with the clinicopathological factors and overall survival (OS).
MATERIAL AND METHODS
Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for MnSOD protein. The relationship between MnSOD immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated.
RESULTS
Immunohistochemical expression of MnSOD protein was detected in colon adenocarcinoma samples and non-pathological samples of colon tissues. As demonstrated, the level of the MnSOD immunohistochemical reactivity was not correlated with clinicopathological factors. A multivariate analysis demonstrated that the grade of tumour differentiation and MnSOD immunoexpression in healthy tissues were independent risk factors for worse survival of patients.
CONCLUSIONS
The high level of MnSOD immunoexpression in cancerous tissue was not associated with malignancy-related clinicopathological factors and 5-year overall survival of patients.
PubMed: 38939067
DOI: 10.5114/pg.2024.139238 -
Frontiers in Immunology 2024Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide, with human papillomavirus (HPV) infection contributing to cancer...
Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide, with human papillomavirus (HPV) infection contributing to cancer development. Conventional therapies achieve only limited efficiency, especially in recurrent or metastatic HNSCC. As the immune landscape decisively impacts the survival of patients and treatment efficacy, this study comprehensively investigated the immunological tumor microenvironment (TME) and its association with patient outcome, with special focus on several dendritic cell (DC) and T lymphocyte subpopulations. Therefore, formalin-fixed paraffin-embedded tumor samples of 56 HNSCC patients, who have undergone resection and adjuvant radiotherapy, were analyzed by multiplex immunohistochemistry focusing on the detailed phenotypic characterization and spatial distribution of DCs, CD8 T cells, and T-helper cell subsets in different tumor compartments. Immune cell densities and proportions were correlated with clinical characteristics of the whole HNSCC cohort and different HPV- or hypoxia-associated subcohorts. Tumor stroma was highly infiltrated by plasmacytoid DCs and T lymphocytes. Among the T-helper cells and CD8 T cells, stromal regulatory T cells and intraepithelial exhausted CD8 T cells expressing programmed cell death protein-1 (PD-1) and/or lymphocyte-activation gene-3 (LAG-3) were the predominant phenotypes, indicating an immunosuppressive TME. HPV-associated tumors showed significantly higher infiltration of type I and type II conventional DCs (cDC1, cDC2) as well as several CD8 T cell phenotypes including exhausted, activated, and proliferating T cells. On the contrary, tumors with hypoxia-associated gene signatures exhibited reduced infiltration for these immune cells. By multivariate Cox regression, immune-related prognostic factors were identified. Patient clusters defined by high infiltration of DCs and T lymphocytes combined with HPV positivity or low hypoxia showed significantly prolonged survival. Thereby, cDC1 and CD8 T cells emerged as independent prognostic factors for local and distant recurrence. These results might contribute to the implementation of an immune cell infiltration score predicting HNSCC patients' survival and such patient stratification might improve the design of future individualized radiochemo-(immuno)therapies.
Topics: Humans; Dendritic Cells; Squamous Cell Carcinoma of Head and Neck; Male; Female; CD8-Positive T-Lymphocytes; Middle Aged; Tumor Microenvironment; Head and Neck Neoplasms; Aged; Lymphocytes, Tumor-Infiltrating; Prognosis; Adult; Papillomavirus Infections
PubMed: 38938577
DOI: 10.3389/fimmu.2024.1414298 -
Journal of Ovarian Research Jun 2024Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC....
PURPOSE
Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC. We investigated the differences in clinical genomic profiles between the primary and platinum-sensitive recurrent OC (PSROC), focusing on HRD status.
MATERIALS AND METHODS
A total of 40 formalin-fixed paraffin-embedded (FFPE) tissues of primary tumors and their first platinum-sensitive recurrence from 20 OC patients were collected, and comprehensive genomic profiling (CGP) analysis of FoundationOneCDx (F1CDx) was applied to explore the genetic (dis)similarities of the primary and recurrent tumors.
RESULTS
By comparing between paired samples, we found that genomic loss of heterozygosity (gLOH) score had a high intra-patient correlation (r = 0.79) and that short variants (including TP53, BRCA1/2 and NOTCH1 mutations), tumor mutational burden (TMB) and microsatellite stability status remained stable. The frequency of (likely) pathological BRCA1/2 mutations was 30% (12/40) in all samples positively correlated with gLOH scores, but the proportion of gLOH-high status (score > 16%) was 50% (10/20) and 55% (11/20) in the primary and recurrent samples, respectively. An additional 20% (4/20) of patients needed attention, a quarter of which carried the pathological BRCA1 mutation but had a gLOH-low status (gLOH < 16%), and three-quarters had different gLOH status in primary-recurrent pairs. Furthermore, we observed the PSROC samples had higher gLOH scores (16.1 ± 9.24 vs. 19.4 ± 11.1, p = 0.007), more CNVs (36.1% vs. 15.1% of discordant genomic alternations), and significant enrichment of altered genes in TGF-beta signaling and Hippo signaling pathways (p < 0.05 for all) than their paired primaries. Lastly, mutational signature and oncodrive gene analyses showed that the computed mutational signature similarity in the primary and recurrent tumors were best matched the COSMI 3 signature (Aetiology of HRD) and had consistent candidate cancer driver genes of MSH2, NOTCH1 and MSH6.
CONCLUSION
The high genetic concordance of the short variants remains stable along OC recurrence. However, the results reveal significantly higher gLOH scores in the recurrent setting than in paired primaries, supporting further clinically instantaneity HRD assay strategy.
Topics: Humans; Female; Ovarian Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Genomics; Aged; Mutation; Loss of Heterozygosity; Adult; Biomarkers, Tumor; Gene Expression Profiling
PubMed: 38937827
DOI: 10.1186/s13048-024-01455-8 -
BMC Women's Health Jun 2024Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral... (Review)
Review
BACKGROUND
Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously.
CASE PRESENTATION
We report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment.
CONCLUSIONS
This is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians' understanding of this disease for early detection, diagnosis and treatment.
Topics: Humans; Female; Peutz-Jeghers Syndrome; Metaplasia; Genital Neoplasms, Female; Adenocarcinoma, Mucinous; Ovarian Neoplasms; Adult; Uterine Cervical Neoplasms; Neoplasms, Multiple Primary
PubMed: 38937781
DOI: 10.1186/s12905-024-03184-y -
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 -
Endocrine Jun 2024To evaluate the role of intraoperative frozen biopsy of central lymph nodes in central neck dissection and thyroidectomy in patients of unilateral, clinically negative...
PURPOSE
To evaluate the role of intraoperative frozen biopsy of central lymph nodes in central neck dissection and thyroidectomy in patients of unilateral, clinically negative nodes (cN0) papillary thyroid microcarcinoma (PTMC) without extra-glandular invasion.
METHODS
The clinical data of 465 patients were collected retrospectively. Part of prelaryngeal, pretracheal and ipsilateral paratracheal lymph nodes were taken for frozen pathological examination during the operation. Then the thyroid lobe on the tumor side and isthmus were excised, and central neck dissection of the affected side was performed in all patients. The number of metastases in entire central lymph nodes of the affected side can be obtained by postoperative paraffin pathology. If the number of positive lymph nodes during surgery is ≥3, contralateral gland resection was performed.
RESULTS
In this group of 465 patients, there were 186 cases with central lymph node metastasis. The Kappa coefficient of consistency between frozen pathology and paraffin pathology in central lymph nodes was 0.605. The ROC curve for the number of intraoperative frozen metastases-postoperative pathological metastases over 5 showed that the AUC of the curve was 0.793, while the maximum Youden index was 0.5259, whose corresponding number of positive lymph nodes was 3.
CONCLUSION
Intraoperative central lymph nodes biopsy can be used as an important indicator for the status of central lymph node metastasis in unilateral cN0 PTMC patients without extra-glandular invasion and a determinant for central lymph node dissection. While the number of positive lymph nodes intraoperatively is ≥3, total thyroidectomy should be considered.
PubMed: 38935297
DOI: 10.1007/s12020-024-03851-y -
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