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BMJ Open Jun 2024The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was performed to identify the precise value of Ki-67 in predicting the prognosis of ESCC.
DESIGN
The current meta-analysis was carried out in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
DATA SOURCES
Electronic databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched until 26 September 2023.
STATISTICAL METHODS
Pooled HRs and corresponding 95% CIs were calculated to estimate the role of Ki-67 in predicting overall survival (OS) and disease-free survival (DFS) in ESCC. Between-study heterogeneity was evaluated using Cochrane's Q test and I statistics. Specifically, significant heterogeneities were identified based on p<0.10 on the Q statistic test or I>50% so the random-effects model should be used; otherwise, the fixed-effects model should be used. The relationship between Ki-67 and clinicopathological characteristics of ESCC was evaluated by combining ORs with their corresponding 95% CIs.
RESULTS
11 articles with 1124 patients were included in the present meta-analysis. Based on our analysis, increased Ki-67 expression was markedly associated with poor OS (HR 1.62, 95% CI 1.15 to 2.28, p=0.006) and DFS (HR 1.72, 95% CI 1.22 to 2.43, p=0.002) in ESCC. Moreover, subgroup analysis revealed that Ki-67 upregulation significantly predicted OS and DFS when a Ki-67 threshold of >30% was used. Nonetheless, Ki-67 was not significantly associated with sex, T stage, N stage, TNM stage, tumour differentiation or tumour location.
CONCLUSIONS
In the present meta-analysis, high Ki-67 expression significantly predicted OS and DFS in patients with ESCC, especially when Ki-67>30% was used as the threshold. These results suggest that Ki-67 could serve as an effective and reliable prognostic indicator for ESCC.
Topics: Humans; Ki-67 Antigen; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Prognosis; Biomarkers, Tumor; Disease-Free Survival
PubMed: 38839387
DOI: 10.1136/bmjopen-2023-083637 -
Discover Oncology Jun 2024The role of mast cells in malignancies remains unclear, and there is no clear correlation between mast cells and tumor microvessels, tumor growth, or lung adenocarcinoma...
BACKGROUND
The role of mast cells in malignancies remains unclear, and there is no clear correlation between mast cells and tumor microvessels, tumor growth, or lung adenocarcinoma (LUAD) prognosis. This study aims to explore the association between mast cell density (MCD) and intratumoral microvessel density (MVD), clinicopathological parameters, and prognosis in LUAD, by evaluating mast cell infiltration characteristics and their prognostic significance.
METHODS
This retrospective investigation involved 238 patients with LUAD undergoing complete resection. Tumor and normal lung tissue sections outside the tumor were immunohistochemically stained for MCD in the intratumoral and outside regions, respectively. CD34 polyclonal antibody was used to measure intratumoral MVD.
RESULTS
Intratumoral regions of LUAD had a higher MCD (P < 0.001) than normal lung tissue. In the intratumoral region, MCD and CD34-MVD were positively correlated (r = 0.411, P < 0.001). Intratumoral MCD correlated with sex, smoking history, tumor differentiation, pathological subtype, and tumor size. Female sex (P = 0.012), no smoking history (P = 0.002), acinar predominant type (P = 0.012), and tumor size ≤ 3 cm (P = 0.009) were associated with a higher MCD, whereas poorly differentiated (P = 0.039) and solid/micropapillary predominant types (P = 0.001) were associated with a lower MCD. Higher intratumoral MCD exhibited a marginally improved overall survival, and individuals with higher MCD infiltration ratios (intratumoral MCD/outside the MCD) had higher disease-free and overall survival rates (log-rank P < 0.001). A high MCD infiltration ratio was associated with decreased risk of tumor progression and death following complete resection.
CONCLUSION
The tumor microenvironment controls mast cell infiltration in LUAD, and patients with increased intratumoral mast cell infiltration have better prognosis.
PubMed: 38834833
DOI: 10.1007/s12672-024-01062-5 -
Cancer Immunology, Immunotherapy : CII Jun 2024There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results,... (Observational Study)
Observational Study
BACKGROUND
There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking.
METHOD
This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy.
RESULTS
A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008).
CONCLUSIONS
Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.
Topics: Humans; Carcinoma, Renal Cell; Female; Male; Middle Aged; Kidney Neoplasms; Adult; Aged; Young Adult; Adolescent; Sex Factors; Immune Checkpoint Inhibitors; Prognosis; Immunotherapy; Antineoplastic Combined Chemotherapy Protocols; Survival Rate; Aged, 80 and over
PubMed: 38832989
DOI: 10.1007/s00262-024-03719-0 -
BMC Veterinary Research Jun 2024Neutering dogs is a widespread method and is carried out for various behavioural and husbandry reasons. This study's main objective is to investigate the behavioural...
Neutering dogs is a widespread method and is carried out for various behavioural and husbandry reasons. This study's main objective is to investigate the behavioural correlations between neutering and the breed of male dogs. In order to possibly find breed-dependent differences in the behaviour of intact and castrated dogs, a differentiation between two clades - the "Huskies"(chow chow, shar pei, akita/shiba inu, alaskan malamute, siberian/alaskan husky) and the "Bulldogs" (german boxer, english/french bulldog, old english mastiff, boston terrier, english bull terrier, staffordshire bull terrier, american staffordshire terrier), based on Parker et al. [1], was made.Using an online questionnaire,, 31 neutered and 37 intact male dogs from the clade "Huskies" and 30 neutered and 38 intact male dogs from the clade "Bulldogs", participated in the study (N = 136).The survey included detailed questions on the dogs' personality and any associated issues as well as a behavioural anamnesis. Further questions relating to four of the "big five" personality dimensions based on the "Budapest questionnaire" by Turcsán et al. from 2011 [2] were also added.The results show, that neutered males from both breed clades more frequently displayed aggression toward humans than intact males (multinomial logistic regression, p = 0.002). When it came to aggression towards other dogs, it was the "Huskies" that differed significantly from the "Bulldogs"(multinomial logistic regression, p = 0.04) with being more aggressive. There were also significant differences in stress-related behaviour depending on castration status and breed (multinomial logistic regression, p < 0.001; Cramer's V = 0.33) and only the castration status had an impact on the significance (multinomial logistic regression, p < 0.001). The analysis also revealed significance for stress-indicating behaviour with dependence on neutering status (multinomial logistic regression, p < 0.001) and showed that stress as well as uncertainty are significantly more common in neutered dogs depending on breed and neutering status (multinomial logistic regression, p < 0.001; Cramer's V = 0.42), in that only neutered "Bulldogs" were stressed, but more "Huskies" overall.According to the Budapest questionnaire data, the "Bulldog" clade had considerably greater extraversion scores overall (ordinal regression, p < 0.001) than the "Huskies".Our findings highlight the risks and potential negative effects of neutering. Gonadectomy in no way substitutes for the dog receiving the necessary socialization, training, or bonding. Although in some circumstances it might have a favourable impact on the dog's behaviour, it should not be seen as a panacea for unwanted behaviour. Given that not all behaviours are influenced by sex hormones, every castration decision must be weighed up individually.
Topics: Animals; Dogs; Male; Behavior, Animal; Orchiectomy; Surveys and Questionnaires; Aggression
PubMed: 38831350
DOI: 10.1186/s12917-024-04097-6 -
Cell Death & Disease Jun 2024Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms...
Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.
Topics: Humans; Mesenchymal Stem Cells; Obesity; Mitochondria; Epigenesis, Genetic; Adipose Tissue; Cell Differentiation; Female; Male; 5-Methylcytosine; Adult; Middle Aged; Cell Proliferation
PubMed: 38824145
DOI: 10.1038/s41419-024-06774-8 -
Scientific Reports May 2024Adult vertebrate cartilage is usually quiescent. Some vertebrates possess ocular scleral skeletons composed of cartilage or bone. The morphological characteristics of...
Adult vertebrate cartilage is usually quiescent. Some vertebrates possess ocular scleral skeletons composed of cartilage or bone. The morphological characteristics of the spotted wolffish (Anarhichas minor) scleral skeleton have not been described. Here we assessed the scleral skeletons of cultured spotted wolffish, a globally threatened marine species. The healthy spotted wolffish we assessed had scleral skeletons with a low percentage of cells staining for the chondrogenesis marker sex-determining region Y-box (Sox) 9, but harboured a population of intraocular cells that co-express immunoglobulin M (IgM) and Sox9. Scleral skeletons of spotted wolffish with grossly observable eye abnormalities displayed a high degree of perochondrial activation as evidenced by cellular morphology and expression of proliferating cell nuclear antigen (PCNA) and phosphotyrosine. Cells staining for cluster of differentiation (CD) 45 and IgM accumulated around sites of active chondrogenesis, which contained cells that strongly expressed Sox9. The level of scleral chondrogenesis and the numbers of scleral cartilage PCNA positive cells increased with the temperature of the water in which spotted wolffish were cultured. Our results provide new knowledge of differing Sox9 spatial tissue expression patterns during chondrogenesis in normal control and ocular insult paradigms. Our work also provides evidence that spotted wolffish possess an inherent scleral chondrogenesis response that may be sensitive to temperature. This work also advances the fundamental knowledge of teleost ocular skeletal systems.
Topics: Animals; Chondrogenesis; SOX9 Transcription Factor; Sclera; Temperature; Immunoglobulin M; Eye; Water; Proliferating Cell Nuclear Antigen; Cartilage
PubMed: 38822021
DOI: 10.1038/s41598-024-63370-8 -
PloS One 2024Genetic sex-determining mechanisms have been extensively elucidated in mammals; however, the sex chromosomes, sex-determining genes, and gene regulatory networks...
Genetic sex-determining mechanisms have been extensively elucidated in mammals; however, the sex chromosomes, sex-determining genes, and gene regulatory networks involved in sex differentiation remain poorly understood in amphibians. In this study, we investigated the sex-determining mechanism in the Hyla eximia treefrog based on karyotypic analysis and identification of H-Y antigen, a sex-linked peptide that is present in the gonads of the heterogametic sex (XY or ZW) in all vertebrates. Results show a diploid chromosome number 2n = 24 with homomorphic sex chromosomes. The heterogametic sex, ZW-female, were hypothesized based on H-Y antigen mRNA expression in female gonads (24,ZZ/24,ZW). The treefrog H-Y peptide exhibited a high percentage of identity with other vertebrate sequences uploaded to GenBank database. To obtain gene expression profiles, we also obtained the coding sequence of the housekeeping Actb gene. High H-Y antigen expression levels were further confirmed in ovaries using real-time polymerase chain reaction (RT-PCR) during non-breeding season, we noted a decrease in the expression of the H-Y antigen during breeding season. This study provides evidence that sex hormones might suppress H-Y antigen expression in the gonads of heterogametic females 24,ZW during the breeding season. These findings suggest that H-Y gene expression is a well-suited model for studying heterogametic sex by comparing the male and female gonads.
Topics: Animals; Female; Male; Sex Determination Processes; Anura; Ovary; Sex Chromosomes; Gonads; Amino Acid Sequence
PubMed: 38820287
DOI: 10.1371/journal.pone.0304554 -
BMC Ecology and Evolution May 2024Ctenoluciidae is a Neotropical freshwater fish family composed of two genera, Ctenolucius (C. beani and C. hujeta) and Boulengerella (B. cuvieri, B. lateristriga, B....
Ctenoluciidae is a Neotropical freshwater fish family composed of two genera, Ctenolucius (C. beani and C. hujeta) and Boulengerella (B. cuvieri, B. lateristriga, B. lucius, B. maculata, and B. xyrekes), which present diploid number conservation of 36 chromosomes and a strong association of telomeric sequences with ribosomal DNAs. In the present study, we performed chromosomal mapping of microsatellites and transposable elements (TEs) in Boulengerella species and Ctenolucius hujeta. We aim to understand how those sequences are distributed in these organisms' genomes and their influence on the chromosomal evolution of the group. Our results indicate that repetitive sequences may had an active role in the karyotypic diversification of this family, especially in the formation of chromosomal hotspots that are traceable in the diversification processes of Ctenoluciidae karyotypes. We demonstrate that (GATA)n sequences also accumulate in the secondary constriction formed by the 18 S rDNA site, which shows consistent size heteromorphism between males and females in all Boulengerella species, suggesting an initial process of sex chromosome differentiation.
Topics: Animals; Characiformes; Male; Chromosome Mapping; Female; Retroelements; Repetitive Sequences, Nucleic Acid; Evolution, Molecular; Microsatellite Repeats; Karyotype; Chromosomes
PubMed: 38816840
DOI: 10.1186/s12862-024-02262-x -
Scientific Reports May 2024The current study aimed to investigate the effect of Sox9-Cre-directed Nr5a1-conditional knockout (Sox9-Cre;Nr5a1) on adrenal development. We showed that SOX9 is...
The current study aimed to investigate the effect of Sox9-Cre-directed Nr5a1-conditional knockout (Sox9-Cre;Nr5a1) on adrenal development. We showed that SOX9 is expressed by adrenocortical cells at E10.5-E11.5 but is extinguished no later than E12.5. The number of adrenocortical cells significantly reduced in Sox9-Cre;Nr5a1 mice while the number of cleaved caspase 3-positive cells increased compared to that in the controls at E11.5-E12.5, when the adrenal primordium (AP) is about to expand. This indicated that fetal adrenocortical cells are lost via apoptosis due to Nr5a1 ablation by E12.5. Both medulla formation and encapsulation were perturbed, accompanied by a smaller AP size, in Sox9-Cre;Nr5a1 mice during embryonic development. Adult Sox9-Cre;Nr5a1 adrenals were hypoplastic and exhibited irregular organization of the medulla with aberrant sex differentiation in the X zone. Additionally, there were histologically eosin-negative vacuolated cells, which were negative for both the X-zone marker 20αHSD and the steroidogenesis marker 3βHSD at the innermost cortex of Sox9-Cre;Nr5a1 adrenals. Although Nr5a1 adrenals were hypoplastic, a small number of chromaffin cells were properly located in the center, having normal sex differences in the X-zone. The results collectively provided in-vivo evidence that Nr5a1 plays a critical role in AP expansion and subsequent adrenal development.
Topics: Animals; SOX9 Transcription Factor; Mice; Steroidogenic Factor 1; Adrenal Glands; Integrases; Mice, Knockout; Female; Male
PubMed: 38811798
DOI: 10.1038/s41598-024-63264-9 -
Archives of Oral Biology Sep 2024This paper investigates whether deciduous upper molars and lower canines have sexual dimorphic features, exploring these teeth' dimensions and the presence of...
OBJECTIVE
This paper investigates whether deciduous upper molars and lower canines have sexual dimorphic features, exploring these teeth' dimensions and the presence of Zuckerkandl's tubercle and Carabelli's cusp on the first and second upper molars.
DESIGN
We analyzed 64 pairs of dental plaster casts from 34 females and 30 males aged between 3 and 12 years. We measured the first and second deciduous upper molars and the lower deciduous canines (maximum mesiodistal and buccolingual length), and we registered the presence of the Zuckerkandl's tubercle and the Carabelli's cusp on the first and second upper molars, respectively.
RESULTS
Regarding the differentiation between sexes using Carabelli's cusp and Zuckerkandl's tubercle, the classification was not independent of Carabelli's cusp presence only for tooth 65 (p = 0.035). In all other teeth, whether for Carabelli's cusp or Zuckerkandl's tubercle, their presence was similar for both sexes. There were statistically significant differences between sexes (p < 0.05) for the buccolingual measurements of both upper second molars, the first right upper molar, and the right canine. The developed model allowed for a 64.1% accuracy in sex estimation.
CONCLUSIONS
The study suggests that while Carabelli's cusp and Zuckerkandl's tubercle in upper deciduous molars don't consistently differ between sexes, tooth size, particularly the buccolingual measurements of certain teeth, including upper deciduous molars and lower canines, may provide a more reliable criterion for sex estimation. The developed model depicted moderate accuracy, underscoring the need for a multifactorial approach when estimating sex from skeletal remains. It suggests that while dental features can contribute to sex estimation, they should be used in conjunction with other skeletal or molecular markers to improve accuracy.
Topics: Humans; Male; Female; Cuspid; Tooth, Deciduous; Molar; Child; Child, Preschool; Models, Dental; Odontometry; Sex Characteristics
PubMed: 38810388
DOI: 10.1016/j.archoralbio.2024.106006