Our study explores the role of cancer-derived extracellular exosomes (EXs), particularly focusing on collagen alpha-3 (VI; COL6A3), in facilitating tumor dissemination and metastasis in epithelial ovarian cancer (EOC). We found that COL6A3 is expressed in aggressive ES2 derivatives, SKOV3 overexpressing COL6A3 (SKOV3/COL6A3), and mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs), as well as their EXs, but not in less aggressive SKOV3 cells or ES2 cells with COL6A3 knockdown (ES2/shCOL6A3). High COL6A3 expression correlates with worse overall survival among EOC patients, as evidenced by TCGA and GEO data analysis. In vitro experiments showed that EXs from MSC-OCSPCs or SKOV3/COL6A3 cells significantly enhance invasion ability in ES2 or SKOV3/COL6A3 cells, respectively (both, p <0.001). In contrast, ES2 cells with ES2/shCOL6A3 EXs exhibited reduced invasion ability (p < 0.001). In vivo, the average disseminated tumor numbers in the peritoneal cavity were significantly greater in mice receiving intraperitoneally injected SKOV3/COL6A3 cells than in SKOV3 cells (p < 0.001). Furthermore, mice intravenously (IV) injected with SKOV3/COL6A3 cells and SKOV3/COL6A3-EXs showed increased lung colonization compared to mice injected with SKOV3 cells and PBS (p = 0.007) or SKOV3/COL6A3 cells and PBS (p = 0.039). Knockdown of COL6A3 or treatment with EX inhibitor GW4869 or rapamycin-abolished COL6A3-EXs may suppress the aggressiveness of EOC.

BACKGROUND: Ki-67 immunostaining is commonly used in neuroendocrine tumors to estimate the proliferative index and for grading. This study investigates its association with the invasiveness of follicular-derived thyroid carcinomas (TCs).
METHODS: A retrospective analysis of patients with TC at three McGill University teaching hospitals between January 2018 and November 2023 was conducted. The inclusion criteria included patients with malignant thyroid tumors and accessible Ki-67 LI data from final pathology specimens. The data collected included patient demographics, Ki-67 LI values, and different invasiveness attributes, such as molecular mutations, the histological subtype, lymphovascular invasion (LVI), extrathyroidal extension (ETE), and positive lymph nodes (LNs).
RESULTS: In total, 212 patients met the inclusion criteria, of which 80.7% were females and 19.3% were males. The Ki-67 LI ranged from 1% to 30%, with the majority of the cases within the range of 1-15%. A significant association was observed between higher Ki-67 LI and high-risk histological subtypes of thyroid carcinoma (p < 0.001). Similarly, Ki-67 LI was significantly associated with LVI and positive LN metastasis (p < 0.001 and p = 0.036, respectively). However, no significant association was found between the Ki-67 LI and gene mutations or ETE (p = 0.133 and p = 0.190, respectively). Using percentiles to establish a cutoff, patients with a Ki-67 LI higher than 6.7 showed a higher likelihood of being associated with invasive features.
CONCLUSIONS: Elevated Ki-67 LI can serve as an indicator of aggressiveness in follicular-derived TC, especially when associated with distinct histological subtypes, LVI and positive LNs.

OBJECTIVE: The association between Papillary Thyroid Carcinoma (PTC) and coexistent Hashimoto\'s Thyroiditis (HT) was controversial. The purpose of this study was to evaluate the presence of HT exerts any influence on the aggressiveness of PTC, and to establish a nomogram for predicting the possibility of aggressiveness in PTC.
METHODS: 373 consecutive PTC patients with/without coexistent HT from January 2017 to December 2020 were retrospective reviewed. Patients\' clinicopathologic and sonographic characteristics were collected for univariate and multivariate analyses. A nomogram was established based on the risk factors for aggressiveness in PTC.
RESULTS: Male (p = 0.001), tumor size >1.0 cm (p = 0.046) and lymph node metastasis (p = 0.018) were negatively associated with PTC coexisted with HT, while it was significantly positively associated with the frequence of multifocality (p = 0.010). Univariate and multivariate analyses suggested that age ≥55 years (p = 0.000), male (p = 0.027), HT (p = 0.017), tumor size >1.0 cm (p = 0.015), multifocality (p = 0.041), distance to capsular ≤0 cm (p = 0.050) and blood flow (Grade I: p = 0.044) were independent risk factors for predicting the aggressiveness in PTC. A nomogram according to these predictors was further developed and validated. The receiver operating characteristic curve (AUC = 0.734 and 0.809 for training and validation cohorts, respectively) and decision curve analyses indicated that the nomogram model was clinically useful. The calibration curve revealed that the nomogram exhibited an excellent consistency.
CONCLUSIONS: In this study, the coexistent HT might play a protective role in preventing the proliferation of PTC. Dispensable aggressive treatment may be reduced in PTC by pre-operative identification of sonographic and clinical characteristics and incorporating with the predicted nomogram model.

BACKGROUND: This study aimed to investigate the trends of aggressive care at the end-of-life (EoL) for patients with advanced cancer in Korea and to identify factors affecting such care analyzing nationwide data between 2012 to 2018.
METHODS: This was a population-based, retrospective nationwide study. We used administrative data from the National Health Insurance Service and the Korea Central Cancer Registry to analyze 125,350 patients aged 20 years and above who died within one year of a stage IV cancer diagnosis between 2012 and 2018.
RESULTS: The overall aggressiveness of EoL care decreased between 2012 and 2018. In patients\' last month of life, chemotherapy use (37.1% to 32.3%; p < 0.05), cardiopulmonary resuscitation (13.2% to 10.4%; p < 0.05), and intensive care unit admission (15.2% to 11.1%; p < 0.05) decreased during the study period, although no significant trend was noted in the number of emergency room visits. A steep increase was seen in inpatient hospice use in the last month of life (8.6% to 26.6%; p < 0.05), while downward trends were observed for hospice admission within three days prior to death (13.9% to 11%; p < 0.05). Patients were more likely to receive aggressive EoL care if they were younger, women, had treatment in tertiary hospitals, or had hematologic malignancies. In the subgroup analysis, the overall trend of aggressive EoL care decreased for all five major cancer types.
CONCLUSIONS: The aggressiveness of EoL care in stage IV cancer patients showed an overall decrease during 2012-2018 in Korea.

Complex cannibalism (CxC) is an emerging new seeming entity in oral squamous cell carcinoma (OSCC) embody as a prime metabolic event in determining the aggressive potential. Owing to paucity in literature regarding it, the aim of the present study to deciphering the occurrence of CxC in OSCC. Further, the expression of cluster of differentiation 68 (CD68) was studied in tumor cells and correlated with CxC to ascertain the biological behaviour of OSCC. 30 Hematoxylin and Eosin stained sections of various grades of OSCC were scanned for CxC and correlated with clinicopathological parameters. Immunohistochemical analysis using CD68 was performed. While observing CxC in OSCC, statistically significant in age (p-0.048) and histological grades (p-0.004). CD68 expression in tumor cells was statistically significant in histopathological grades (p < 0.001) whereas on correlating with CxC (p - 0.171) was non-significant. The analogous rise in CxC and CD68 with increasing histopathological grades could aid in recognising CxC as a precise histopathological parameter to assess the aggressive biological potential in OSCC.

BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk.
METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics.
RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade.
CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Squamous cell carcinoma (SCC) stands as the second most prevalent skin cancer in dogs, primarily attributed to UV radiation exposure. Affected areas typically include regions with sparse hair and pale or depigmented skin. The significance of spontaneous canine cutaneous SCC as a model for its human counterpart is underscored by its resemblance. This study assesses the expression of key markers-Epidermal Growth Factor Receptor (EGFR), Cyclooxygenase-2 (Cox-2), and Ki-67-in canine cutaneous SCC. Our objective is to investigate the association between their expression levels and classical clinicopathological parameters, unraveling the intricate relationships among these molecular markers. In our retrospective analysis of 37 cases, EGFR overexpression manifested in 43.2% of cases, while Cox-2 exhibited overexpression in 97.3%. The EGFR, Cox-2 overexpression, and Ki-67 proliferation indices, estimated through immunohistochemistry, displayed a significant association with the histological grade, but only EGFR labeling is associated with the presence of lymphovascular emboli. The Ki-67 labeling index expression exhibited an association with EGFR and Cox-2. These findings propose that EGFR, Cox-2, and Ki-67 hold promise as valuable markers in canine SCC. EGFR, Cox-2, and Ki-67 may serve as indicators of disease progression, offering insights into the malignancy of a lesion. The implications extend to the potential therapeutic targeting of EGFR and Cox-2 in managing canine SCC. Further exploration of these insights is warranted due to their translational relevance and the development of targeted interventions in the context of canine SCC.

暂无摘要。

Rhabdomyosarcoma is a pediatric cancer associated with aggressiveness and a tendency to develop metastases. Fusion-negative rhabdomyosarcoma (FN-RMS) is the most commonly occurring subtype of RMS, where metastatic disease can hinder treatment success and decrease survival rates. RMS-derived exosomes were previously demonstrated to be enriched with miRNAs, including miR-1246, possibly contributing to disease aggressiveness. We aimed to decipher the functional impact of exosomal miR-1246 on recipient cells and its role in promoting aggressiveness. Treatment of normal fibroblasts with FN-RMS-derived exosomes resulted in a significant uptake of miR-1246 paired with an increase in cell proliferation, migration, and invasion. In turn, delivery of miR-1246-mimic lipoplexes promoted fibroblast proliferation, migration, and invasion in a similar manner. Conversely, when silencing miR-1246 in FN-RMS cells, the resulting derived exosomes demonstrated reversed effects on recipient cells\' phenotype. Delivery of exosomal miR-1246 targets GSK3β and promotes β-catenin nuclear accumulation, suggesting a deregulation of the Wnt pathway, known to be important in tumor progression. Finally, a pilot clinical study highlighted, for the first time, the presence of high exosomal miR-1246 levels in RMS patients\' sera. Altogether, our results demonstrate that exosomal miR-1246 has the potential to alter the tumor microenvironment of FN-RMS cells, suggesting its potential role in promoting oncogenesis.

It remains unclear if pre-diagnostic factors influence the developmental pathways of colorectal cancer (CRC) that could enhance tumor aggressiveness. This study used prospective data from 205,489 cancer-free US health professionals to investigate the associations of 31 known or putative risk factors with the risk of aggressive CRC. Tumor aggressiveness was characterized by three endpoints: aggressive CRC (cancer that causes death within 5 years of diagnosis), fatal CRC, and tumor stage at diagnosis. The data augmentation method was used to assess the difference in the associations between risk factors and endpoints. We documented 3201 CRC cases, of which 899 were aggressive. The protective associations of undergoing lower endoscopy (hazard ratios [HR] 0.43, 95% confidence interval (CI) 0.37, 0.49 for aggressive versus HR 0.61, 95% CI 0.56, 0.67 for non-aggressive) and regular use of aspirin (HR 0.70, 95% CI 0.61, 0.81 versus HR 0.84, 95% CI 0.77, 0.92) were stronger for aggressive than non-aggressive CRC (pHeterogeneity <0.05). Lower intake of whole grains or cereal fiber and greater dietary inflammatory potential were associated with a higher risk of aggressive but not non-aggressive CRC. The remaining risk factors showed comparable associations with aggressive CRC and non-aggressive CRC. Aggressive cases were more likely to have KRAS-mutated tumors but less likely to have distal or MSI-high tumors (p < .007). Similar results were observed for fatal CRC and advanced tumor stages at diagnosis. These findings provide initial evidence for the role of pre-diagnostic risk factors in the pathogenesis of aggressive CRC and suggest research priorities for preventive interventions.