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Cureus Jan 2024Background and objective Gynecomastia is a benign proliferation of ductal epithelium in the retroareolar region in male patients. The aim of this study was to...
Background and objective Gynecomastia is a benign proliferation of ductal epithelium in the retroareolar region in male patients. The aim of this study was to investigate the frequency of gynecomastia in male patients who underwent thoracic computed tomography (CT) imaging at our clinic, assess possible causes, highlight the imaging characteristics of gynecomastia, and compare our findings with the literature. Materials and methods Male patients over 18 years of age who underwent thoracic CT imaging in our clinic were included in the study. Patients were initially assessed based on age and the presence of gynecomastia. The patients with gynecomastia were evaluated in terms of age, gynecomastia localization (right, left, and bilateral), gynecomastia type (nodular, dentritic, and diffuse), and possible etiology. Results The study included 1500 patients with a mean age of 45.6±21.7 years, and 470 (31.3%) patients had gynecomastia. Gynecomastia was on the right side in 11.3%, on the left side in 11.1%, and bilateral in 77.7% of the patients. Gynecomastia was nodular in 52.1%, dendritic in 35.3%, and diffuse in 17.2% of the patients. The causative factor could not be identified in 44.3% of the patients with gynecomastia. Among cases where the etiology was identified (56.7%), the most common factors were cancer (23.4%), chronic kidney disease (CKD) (13.2%), and chronic hepatitis B (10.7%). Conclusion When evaluating thoracic CT, the breast area, in addition to the lungs, chest wall, and bone structures, should also be evaluated carefully. With the increased use of thoracic CT scans, incidentally detected gynecomastia in patients is also on the rise. Knowing the presence of gynecomastia is very important for the clinician to determine the etiology and treat the underlying disease. Therefore, detecting and reporting gynecomastia on thoracic CT can prevent unnecessary advanced breast imaging methods and play a very important role in treating the underlying etiology.
PubMed: 38304650
DOI: 10.7759/cureus.51509 -
Frontiers in Oncology 2023Several breast cancer (BC) patients showed urinary tract infection after adjuvant trastuzumab plus paclitaxel, but no case of urothelial injury has been reported. In...
Several breast cancer (BC) patients showed urinary tract infection after adjuvant trastuzumab plus paclitaxel, but no case of urothelial injury has been reported. In this case, we report a 47-year-old female patient with stage I invasive ductal carcinoma in the left breast presenting with urothelial injury after the combination of trastuzumab and paclitaxel. Initially, the patient was highly suspected of having urinary tract infection as she showed abdominal and low back pain, as well as urinary irritation symptoms and hematuria. Unfortunately, the conditions were not attenuated after anti-infection therapy. Contrast-enhanced CT showed extensive exudation and edema in the bilateral renal pelvis, ureter, and bladder, together with dilatation and effusion in the renal pelvis and ureter. Cystoscopy showed extensive congestion, edema, and erosion in the bladder epithelium. Pathological analysis demonstrated slight thinning or even loss in the uroepithelial cell layer and interstitial congestion. In addition, there was growth arrest in the epithelial cells. Immunohistochemistry indicated HER2 expression in the urothelial cells. Finally, the patient was diagnosed with urothelial injury after combination of paclitaxel and trastuzumab. The symptoms were spontaneously cured with no administration of any antibiotics in the 3-month follow-up.
PubMed: 38304030
DOI: 10.3389/fonc.2023.1258474 -
Cell Discovery Jan 2024Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the...
Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cell dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis. While SMYD2 is overexpressed in aggressive breast cancers, we notice that it is not required for primary tumor growth. However, mammary-epithelium specific SMYD2 ablation increases mouse overall survival by blocking the primary tumor cell ability to metastasize. Mechanistically, we identify BCAR3 as a genuine physiological substrate of SMYD2 in breast cancer cells. BCAR3 monomethylated at lysine K334 (K334me1) is recognized by a novel methyl-binding domain present in FMNLs proteins. These actin cytoskeleton regulators are recruited at the cell edges by the SMYD2 methylation signaling and modulate lamellipodia properties. Breast cancer cells with impaired BCAR3 methylation lose migration and invasiveness capacity in vitro and are ineffective in promoting metastases in vivo. Remarkably, SMYD2 pharmacologic inhibition efficiently impairs the metastatic spread of breast cancer cells, PDX and aggressive mammary tumors from genetically engineered mice. This study provides a rationale for innovative therapeutic prevention of malignant breast cancer metastatic progression by targeting the SMYD2-BCAR3-FMNL axis.
PubMed: 38296970
DOI: 10.1038/s41421-023-00644-x -
Clinical Proteomics Jan 2024Omics characterization of pancreatic adenocarcinoma tissue is complicated by the highly heterogeneous and mixed populations of cells. We evaluate the feasibility and...
BACKGROUND
Omics characterization of pancreatic adenocarcinoma tissue is complicated by the highly heterogeneous and mixed populations of cells. We evaluate the feasibility and potential benefit of using a coring method to enrich specific regions from bulk tissue and then perform proteogenomic analyses.
METHODS
We used the Biopsy Trifecta Extraction (BioTExt) technique to isolate cores of epithelial-enriched and stroma-enriched tissue from pancreatic tumor and adjacent tissue blocks. Histology was assessed at multiple depths throughout each core. DNA sequencing, RNA sequencing, and proteomics were performed on the cored and bulk tissue samples. Supervised and unsupervised analyses were performed based on integrated molecular and histology data.
RESULTS
Tissue cores had mixed cell composition at varying depths throughout. Average cell type percentages assessed by histology throughout the core were better associated with KRAS variant allele frequencies than standard histology assessment of the cut surface. Clustering based on serial histology data separated the cores into three groups with enrichment of neoplastic epithelium, stroma, and acinar cells, respectively. Using this classification, tumor overexpressed proteins identified in bulk tissue analysis were assigned into epithelial- or stroma-specific categories, which revealed novel epithelial-specific tumor overexpressed proteins.
CONCLUSIONS
Our study demonstrates the feasibility of multi-omics data generation from tissue cores, the necessity of interval H&E stains in serial histology sections, and the utility of coring to improve analysis over bulk tissue data.
PubMed: 38291365
DOI: 10.1186/s12014-024-09450-3 -
Microbiology Spectrum Mar 2024Despite the established concept of the human mammary gland (MG) as a habitat with its own microbiota, the exact mechanism of MG colonization is still elusive and a...
Despite the established concept of the human mammary gland (MG) as a habitat with its own microbiota, the exact mechanism of MG colonization is still elusive and a well-characterized model would reinforce studies of the MG microbiota development. We aimed to establish and characterize an cell model for studying MAmmary Gland mIcrobial Colonization (MAGIC) model. We used the immortalized cell line MCF10A, which expresses the strong polarized phenotype similar to MG ductal epithelium when cultured on a permeable support (Transwell). We analyzed the surface properties of the MAGIC model by gene expression analysis of E-cadherin, tight junction proteins, and mucins and by scanning electron microscopy. To demonstrate the applicability of the model, we tested the adhesion capability of the whole human milk (HM) microbial community and the cellular response of the model when challenged directly with raw HM samples. MCF10A on permeable supports differentiated and formed a tight barrier, by upregulation of CLDN8, MUC1, MUC4, and MUC20 genes. The surface of the model was covered with mucins and morphologically diverse with at least two cell types and two types of microvilli. Cells in the MAGIC model withstood the challenge with heat-treated HM samples and responded differently to the imbalanced HM microbiota by distinctive cytokine response. The microbial profile of the bacteria adhered on the MAGIC model reflected the microbiological profile of the input HM samples. The well-studied MAGIC model could be useful for studies of bacterial attachment to the MG and for studies of biofilm formation and microbiota development.IMPORTANCEThe MAGIC model may be particularly useful for studies of bacterial attachment to the surface of the mammary ducts and for studies of biofilm formation and the development of the human mammary gland (MG) microbiota. The model is also useful for immunological studies of the interaction between bacteria and MG cells. We obtained pioneering information on which of the bacteria present in the raw human milk (HM) were able to attach to the epithelium treated directly with raw HM, as well as on the effects of bacteria on the MG epithelial cells. The MAGIC cell model also offers new opportunities for research in other areas of MG physiology, such as the effects of bioactive milk components on microbial colonization of the MG, mastitis prevention, and studies of probiotic development. Since resident MG bacteria may be an important factor in breast cancer development, the MAGIC tool also offers new opportunities for cancer research.
Topics: Female; Humans; Milk, Human; Mammary Glands, Human; Cytokines; Bacteria; Mucins; Microbiota
PubMed: 38289112
DOI: 10.1128/spectrum.02369-23 -
Oncogene Mar 2024
PubMed: 38263250
DOI: 10.1038/s41388-024-02941-5 -
MedRxiv : the Preprint Server For... Jan 2024Determine the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs).
OBJECTIVE
Determine the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs).
DESIGN
This is a cross-sectional study.
SETTING
TMIs (n=444) underwent chest-contouring surgeries to treat their gender dysphoria between 2013 and 2019 at an urban medical center.
PARTICIPANTS
Of the 444 TMIs, 425 had pathology images analyzed by our deep-learning algorithm to extract breast tissue composition. A subset of 42/444 TMIs had mammography prior to surgery; mammography files were available for 25/42 TMIs and analyzed using a breast density software, LIBRA.
MAIN OUTCOMES AND MEASURES
The first outcome was the association of duration of TT and breast tissue composition assessed by pathologists (categories of lobular atrophy and stromal composition) or by our algorithm (% epithelium, % fibrous stroma, and % fat). The second outcome is the association of TT and breast density as assessed by a radiologist (categorical variable) or by LIBRA (percent density, absolute dense area, and absolute non-dense area).
RESULTS
Length of TT was associated with increasing degrees of lobular atrophy ( <0.001) but not fibrous content ( =0.821) when assessed by the pathologists. Every six months of TT was associated with decreased amounts of both epithelium (exp(β)=0.97, 95% CI 0.95-0.98, adj =0.005) and stroma (exp(β)=0.99, 95% CI 0.98-1.00, adj =0.051), but not fat (exp(β)=1.01, 95%CI 0.98-1.05, =0.394) in fully adjusted models. There was no association between TT and radiologist's breast density assessment ( =0.575) or LIBRA measurements ( >0.05).
CONCLUSIONS
TT decreases breast epithelium and fibrous stroma, thus potentially reducing the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.
SUMMARY BOX
Very little is known about the effect of gender-affirming testosterone therapy on cancer risks, such as breast cancer.Epidemiological studies had different conclusions about the association between testosterone and breast cancer in cisgender women (positive association) and trans masculine individuals (inverse association).More laboratory-based research are needed to understand the effect of testosterone on breast cancer risk in the understudied trans masculine population.Our study provides quantitative histological evidence to support prior epidemiological reports that testosterone may reduce breast cancer risk in trans masculine individuals.
PubMed: 38260574
DOI: 10.1101/2024.01.09.24300987 -
Colloids and Surfaces. B, Biointerfaces Feb 2024Most of the malignancies detected within the brain parenchyma are of metastatic origin. As the brain lacks classical lymphatic circulation, the primary way for...
Most of the malignancies detected within the brain parenchyma are of metastatic origin. As the brain lacks classical lymphatic circulation, the primary way for metastasis relies on hematogenous routes. Dissemination of metastatic cells to the brain implies attachment to the luminal surface of brain endothelial cells, transmigration through the vessel wall, and adhesion to the brain surface of the vasculature. During this process, tumor cells must interact with brain endothelial cells and later on with pericytes. Physical interaction between tumor cells and brain vascular cells might be crucial in the successful extravasation of metastatic cells through blood vessels and later in their survival within the brain environment. Therefore, we applied single-cell force spectroscopy to investigate the nanoscale adhesive properties of living breast adenocarcinoma cells to brain endothelial cells and pericytes. We found target cell type-dependent adhesion characteristics, i.e. increased adhesion of the tumor cells to pericytes in comparison to endothelial cells, which underlines the existence of metastatic potential-related nanomechanical differences relying partly on membrane tether dynamics. Varying adhesion strength of the tumor cells to different cell types of brain vessels presumably reflects the transitory adhesion to endothelial cells before extravasation and the long-lasting strong interaction with pericytes during survival and proliferation in the brain. Our results highlight the importance of specific mechanical interactions between tumor cells and host cells during metastasis formation.
Topics: Humans; Endothelial Cells; Pericytes; Brain; Endothelium; Adenocarcinoma
PubMed: 38241889
DOI: 10.1016/j.colsurfb.2024.113751 -
Breast (Edinburgh, Scotland) Feb 2024Free dermal fat grafts (FDFG) are used for immediate breast defect repair in breast-conserving surgery (BCS), and have achieved satisfactory immediate postoperative...
BACKGROUND
Free dermal fat grafts (FDFG) are used for immediate breast defect repair in breast-conserving surgery (BCS), and have achieved satisfactory immediate postoperative cosmetic effects (Sawai et al., 2004) [1]. However, the oncologic safety and long-term cosmetic outcomes of these surgical procedures remain unknown. Therefore, t,in this study, we aim to investigate the oncological safety and long-term cosmetic outcomes of FDFG in patients with breast cancer.
METHODS
This matched retrospective case-control study included patients with non-special types of breast cancer who underwent FDFG for breast defect repair after BCS or BCS alone at two breast cancer research centers in Guangxi Province, China, from January 2016 to December 2019. The patients were divided into either the FDFG or BCS group. Control cases were screened using propensity score matching, and survival analysis and cosmetic evaluations were performed.
RESULTS
A total of 442 patients with breast cancer were included in the study. After 1:4 propensity score matching, 53 and 212 patients were included in the FDFG and BCS groups, respectively. The median follow-up time was 49.9 (9.0-76.0) months. The rate of local recurrence in the FDFG group (9.4 %) was significantly higher than that in the BCS group (1.9 %; p < 0.05). The total cosmetic evaluation score was significantly higher in the BCS group 18 months after surgery than in the FDFG group (p < 0.05).
CONCLUSIONS
In this retrospective study, FDFG was significantly associated with an increased risk of local recurrence. Further prospective studies are required to confirm these results. No significant difference in long-term cosmetic effects were observed for FDFG than for BCS alone for immediate breast defect repair.
Topics: Humans; Female; Mastectomy, Segmental; Retrospective Studies; Breast Neoplasms; Case-Control Studies; Treatment Outcome; Mammaplasty; China; Epidermis
PubMed: 38190791
DOI: 10.1016/j.breast.2023.103622 -
American Journal of Cancer Research 2023We examined associations of stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsy samples with subsequent breast cancer (BCa) risk and explored if these...
We examined associations of stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsy samples with subsequent breast cancer (BCa) risk and explored if these associations were mediated by mammographic breast density (MBD). We included 101 BCa cases/375 controls, all with previous biopsy-confirmed benign breast disease (BBD) within the Nurses' Health Study (NHS) and NHSII. The data on BCa risk factors were obtained from biennial questionnaires. MBD was assessed with computer-assisted techniques. Immunohistochemistry (IHC) was done on BBD tissue microarrays. For each core, the IHC expression was assessed using a semi-automated method, and expressed as % of cells that stained positive for a specific marker out of the total cell count. Logistic regression was used to examine the associations of each marker's expression of each (in epithelium and stroma) with BCa risk, adjusted for risk factors. Stromal CD44 expression was inversely associated with BCa risk (OR for ≥10% vs. <10%=0.58, 95% CI 0.34, 1.00). Combined stromal + epithelial CD24 expression was inversely associated with BCa risk (>50% vs. 0-10% OR=0.17, 95% CI 0.04-0.81, p-trend =0.03). Stromal CD24 and ALDH1A1 as well as epithelial expression of any of the three markers were not associated with BCa risk. In a smaller subset of women with available MBD, these observed associations did not appear to be mediated by MBD. Our findings suggest inverse associations of CD44 in stroma and combined stromal + epithelial CD24 with BCa risk. Future studies are warranted to confirm our findings and to examine these associations by BBD subtype.
PubMed: 38187066
DOI: No ID Found