Search Results (350)

Background/Objectives: Tamoxifen, a selective estrogen receptor modulator widely used as an adjunct in the treatment of breast cancer, has known effects on bone metabolism, although its impact on osseointegration and cellular responses during early bone healing remains unclear. Understanding these effects is essential given the increasing use of dental implants in cancer survivors. The study aimed to observe the influence of tamoxifen on human osteosarcoma (SAOS-2) cells lines, as well on the osseointegration of titanium implants in ovariectomized female rats. Methods: SAOS-2 cells were incubated with Dulbecco’s modified growth medium. Six titanium (Ti) disks were used at each time point. The samples were divided into groups with the presence (TAM, n = 36) or not (CTR, n = 36) of tamoxifen in a concentration of 2 μM. In vivo, 72 animals were divided in groups with bilateral ovariectomy or SHAM and tamoxifen administration or not (15 mg/kg). Cell viability, mineralization rate, and collagen synthesis were assessed, as well as bone/implant contact (BIC) and bone ingrowth (BIN). Results: Tamoxifen caused a decrease in SAOS-2 viability, although an increase in the mineralization rate was observed. In vivo, the TAM groups presented higher BIC and BIN when compared to their control, but a lower percentage of mature collagen cells. Conclusions: Based on our findings, in vitro, the therapy with TAM slightly reduced the viability of SAOS-2 cells while significantly increasing the mineralization rate. In vivo, the therapy positively influenced BIC and BIN during the osseointegration phase. Full article

Objectives: To investigate the efficacy and underlying mechanisms of IBCar’s biological activity in breast cancer models, both in cell culture and in mice, and to compare its effects on cancer versus normal cells. Methods: The cytotoxicity of IBCar was evaluated using the MTS assay to assess metabolic activity and the clonogenic assay to determine reproductive integrity. The impact of IBCar on microtubule integrity, mitochondrial function, and multiple signaling pathways was analyzed using Western blotting, microarray analysis, and live cell imaging. The therapeutic effectiveness of orally administered IBCar was assessed in a transgenic mouse model of Luminal B breast cancer and in mice implanted with subcutaneous triple-negative breast cancer xenografts. Results: IBCar demonstrated potent cytotoxicity across a diverse panel of breast cancer cell lines, including those with mutant or wild-type TP53, and cell lines with short and long doubling times. Comparative analysis revealed distinct responses between normal and cancer cells, including differences in IBCar’s effects on the mitochondrial membrane potential, endoplasmic reticulum stress and activation of cell death pathways. In breast cancer cells, IBCar was cytotoxic at nanomolar concentrations, caused irreversible microtubule depolymerization leading to sustained mitochondrial dysfunction, endoplasmic reticulum stress, and induced apoptosis. In normal cells, protective mechanisms included reversible microtubule depolymerization and activation of pro-survival signaling via the caspase-8 and riptosome pathways. The therapeutic potential of IBCar was confirmed in mouse models of Luminal B and triple negative BC, where it exhibited strong antitumor activity without detectable toxicity. Conclusions: These findings collectively support IBCar as a promising, effective, and safe therapeutic candidate for breast cancer treatment. Full article

Background: Lysosomal-associated membrane protein 1 (LAMP1), typically localized to the lysosomal membrane, is increasingly implicated as a marker of cancer aggressiveness and metastasis when expressed on the cell surface. This study aimed to develop a LAMP1-targeted antibody-based PET tracer and assess its efficacy in mouse models of human breast and colon adenocarcinoma. Methods: To determine the source of LAMP1 expression, we utilized human single-cell RNA sequencing and spatial transcriptomics, complemented by in-house flow cytometry on xenografted mouse models. Tissue microarrays of multiple epithelial cancers and normal tissue were stained for LAMP-1, and staining was quantified. An anti-LAMP1 monoclonal antibody was conjugated with desferrioxamine (DFO) and labeled with zirconium-89 (⁸⁹Zr). Human triple-negative breast cancer (MDA-MB-231) and colon cancer (Caco-2) cell lines were implanted in nude mice. PET/CT imaging was conducted at 24, 72, and 168 h post-intravenous injection of ⁸⁹Zr-DFO-anti-LAMP1 and ⁸⁹Zr-DFO-IgG (negative control), followed by organ-specific biodistribution analyses at the final imaging time point. Results: Integrated single-cell and spatial RNA sequencing demonstrated that LAMP1 expression was localized to myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in addition to the cancer cells. Tissue microarray showed significantly higher staining for LAMP-1 in tumor tissue compared to normal tissue (3986 ± 2635 vs. 1299 ± 1291, p < 0.001). Additionally, xenograft models showed a significantly higher contribution of cancer cells than the immune cells to cell surface LAMP1 expression. In vivo, PET imaging with ⁸⁹Zr-DFO-anti-LAMP1 PET/CT revealed detectable tumor uptake as early as 24 h post-injection. The ⁸⁹Zr-DFO-anti-LAMP1 tracer demonstrated significantly higher uptake than the control ⁸⁹Zr-DFO-IgG in both models across all time points (MDA-MB-231 SUV_max at 168 h: 12.9 ± 5.7 vs. 4.4 ± 2.4, p = 0.003; Caco-2 SUV_max at 168 h: 8.53 ± 3.03 vs. 3.38 ± 1.25, p < 0.01). Conclusions: Imaging of cell surface LAMP-1 in breast and colon adenocarcinoma is feasible by immuno-PET. LAMP-1 imaging can be expanded to adenocarcinomas of other origins, such as prostate and pancreas. Full article

Dark sweet cherries (DSC) phytochemicals have emerged as a promising dietary strategy to combat triple-negative breast cancer (TNBC). This study explored the effects of DSC extract rich in anthocyanins (ACN) as a chemopreventive agent and as a complement to doxorubicin (DOX) in treating TNBC tumors and metastasis using a 4T1 syngeneic animal model. Initiating ACN intake as a chemopreventive one week before 4T1 cell implantation significantly delayed tumor growth without any signs of toxicity. Both DOX treatment and the combination of DOX-ACN effectively delayed tumor growth rate, but DOX-ACN allowed for body weight gain, which was hindered by DOX alone. As a chemopreventive, ACN downregulated metastasis- and immune-suppression-related genes, including STAT3, Snail1, mTOR, SIRT1, TGFβ1, IKKβ, and those unaffected by DOX alone, such as HIF, Cd44, and Rgcc32. Correlations between mRNA levels seen in control and DOX groups were absent in ACN and/or DOX-ACN groups, indicating that Cd44, mTOR, Rgcc32, SIRT1, Snail1, and TGFβ1 may be ACN targets. The DOX-ACN treatment showed a trend toward enhanced efficacy involving CREB, PI3K, Akt-1, and Vim compared to DOX alone. Particularly, ACN significantly suppressed lung metastasis compared to the other groups. ACN also decreased the frequency and incidence of metastasis in the liver, heart, kidneys, and spleen, while their metastatic area (%) and number of breast cancer (BC) metastatic tumor nodules were lowered without reaching significance. Further research is needed to explore the efficacy of combining ACN with drug therapy in the context of drug resistance. Full article

In recent years, significant progress has been made in breast reconstructive surgery, particularly with the use of three-dimensional (3D) disassemblable scaffolds. Reconstructive plastic surgery aimed at restoring the shape and size of the mammary gland offers medical, psychological, and social benefits. Using autologous tissues allows surgeons to recreate the appearance of the mammary gland and achieve tactile sensations similar to those of a healthy organ while minimizing the risks associated with implants; 3D disassemblable scaffolds are a promising solution that overcomes the limitations of traditional methods. These constructs offer the potential for patient-specific anatomical adaptation and can provide both temporary and long-term structural support for regenerating tissues. One of the most promising approaches in post-mastectomy breast reconstruction involves the use of autologous cellular and tissue components integrated into either synthetic scaffolds—such as polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL)—or naturally derived biopolymer-based matrices, including alginate, chitosan, hyaluronic acid derivatives, collagen, fibrin, gelatin, and silk fibroin. In this context, two complementary research directions are gaining increasing significance: (1) the development of novel hybrid biomaterials that combine the favorable characteristics of both synthetic and natural polymers while maintaining biocompatibility and biodegradability; and (2) the advancement of three-dimensional bioprinting technologies for the fabrication of patient-specific scaffolds capable of incorporating cellular therapies. Such therapies typically involve mesenchymal stromal cells (MSCs) and bioactive signaling molecules, such as growth factors, aimed at promoting angiogenesis, cellular proliferation, and lineage-specific differentiation. In our review, we analyze existing developments in this area and discuss the advantages and disadvantages of 3D disassemblable scaffolds for mammary gland reconstruction, as well as prospects for their further research and clinical use. Full article

Background and Clinical Significance: Breast reconstruction following mastectomy is a critical aspect of treatment for many patients, offering both physical and psychological benefits. Traditional methods include autologous tissue flaps and implants, with implant-based techniques being the most prevalent in the Western world. However, complications such as capsular contracture remain a concern. Acellular dermal matrices (ADM) have emerged as a valuable alternative, improving outcomes by reducing capsular contracture rates and enhancing tissue integration. Case Presentation: This case report presents the first use of a novel ADM, biocade^® (biotrics bioimplants AG, Berlin, Germany) in breast reconstruction following a mastectomy. A 55-year-old female patient underwent a left-sided nipple-sparing mastectomy, followed by prepectoral direct-to-implant reconstruction using an ADM-wrapped implant. The patient tolerated the procedure well, with no immediate complications observed. Postoperative monitoring focused on wound healing and assessing for signs of complications related to the implant. The use of the ADM resulted into satisfactory aesthetic and functional outcomes. Conclusions: The successful outcome of this case highlights the potential benefits of using collagen matrices in breast reconstruction, particularly in preserving mastectomy scenarios. The immediate results and improved aesthetics offered by prepectoral direct-to-implant reconstruction with ADM align well with patient expectations for a more natural appearance and faster recovery. However, this case report also highlights the need for ongoing research to fully explore the potential of these biomaterials and address associated challenges. Full article

The endocannabinoid system (ECS) is a complex neuromodulatory network involved in maintaining physiological balance through interactions with various neurotransmitter and hormonal pathways. Its key components—cannabinoid receptors (CBRs)—are activated by endogenous ligands and exogenous cannabinoids such as those found in the Cannabis sativa plant. Although cannabinoids like cannabidiol (CBD) have garnered interest for their potential therapeutic effects, evidence regarding their safety, particularly for reproductive health, remains limited. This review summarizes the structure and molecular mechanisms of the ECS, its role in reproductive physiology—including its interactions with the hypothalamic–pituitary–gonadal axis (HPG axis), gametogenesis, implantation, and lactation—and the possible consequences of cannabinoid exposure for fertility. In addition, we focus on the involvement of the ECS and cannabinoids in breast cancer, highlighting emerging evidence on their dual role in tumor progression and therapy. These insights emphasize the need for further research to better define the therapeutic potential and risks associated with cannabinoid use in reproductive health and breast cancer. Full article

Background/Objective: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has affected more than 1700 women with textured breast implants. About 80% of patients present with fluid (seroma) around their implant. BIA-ALCL can be cured by surgery alone when confined to the seroma and lining of the peri-implant capsule. To address the need for early detection, we developed a rapid point of care (POC) lateral flow assay (LFA) to identify lymphoma in seromas. Methods: We compared 28 malignant seromas to 23 benign seromas using both ELISA and LFA. LFA test lines (TL) and control lines (CL) were visualized and measured with imaging software and the TL/CL ratio for each sample was calculated. Results: By visual exam, the sensitivity for detection of CA9 was 93% and specificity 78%, while the positive predictive value was 84% and negative predictive value 90%. Quantitative image analysis increased the positive predictive value to 96% while the negative predictive value reduced to 79%. Conclusions: We conclude that CA9 is a sensitive biomarker for detection and screening of patients for BIA-ALCL in patients who present with seromas of unknown etiology. The CA9 LFA can potentially replace ELISA, flow cytometry and other tests requiring specialized equipment, highly trained personnel, larger amounts of fluid and delay in diagnosis of BIA-ALCL. Full article

Background: Immediate direct-to-implant (DTI) breast reconstruction is associated with high patient satisfaction and faster recovery. However, concerns remain for patients requiring post-mastectomy radiation therapy (PMRT). While PMRT improves overall survival for breast cancer patients, it has been associated with increased implant-specific complications such as capsular contracture, infection, and implant loss. As the impact of PMRT on pre-pectoral DTI specifically is not well understood, the goal of this systematic review was to evaluate the impact of PMRT on outcomes in this growing patient population. Methods: PubMed, EMBASE, and Web of Science were systematically reviewed for articles published from 1 January 2000 to 23 December 2024 investigating outcomes after prepectoral DTI reconstruction with exposure to PMRT. Demographic, clinical, and post-operative variables were recorded for PMRT and non-PMRT cohorts, and primary outcomes included infection, capsular contracture, implant loss, and wound healing complications. Meta-analysis was performed for key outcomes using the Mantel-Haenszel method. Results: Of 472 initially identified records, seven studies met inclusion criteria with a combined total of 343 prepectoral DTI reconstructions exposed to PMRT and 1385 reconstructions not exposed to PMRT. PMRT significantly increased the odds of any complication (OR 2.11, p = 0.01), implant loss (OR 1.88, p = 0.02), infection (OR 2.76, p = 0.004), and capsular contracture (OR 8.88, p < 0.001). However, PMRT was not associated with significantly increased odds of wound healing complications (OR 1.5, p = 0.36). Conclusions: PMRT after pre-pectoral DTI reconstruction significantly increases odds of complications, including infection, capsular contracture, and reconstructive failure. Plastic surgeons should be mindful of the sequelae of PMRT with prepectoral DTI reconstruction to improve pre-operative counseling and shared decision-making. Full article

Deciphering the spatiotemporal distribution of bacteria during breast cancer progression may provide critical insights for developing bacterial-based therapeutic strategies. Using a murine breast cancer model, we longitudinally profiled the microbiota in breast tumor tissue, mammary gland, spleen, and cecal contents at 3-, 5-, and 7- weeks post-tumor implantation through 16S rRNA gene sequencing. Breast tumor progression was associated with lung metastasis and splenomegaly, accompanied by distinct tissue-specific microbial dynamics. While alpha diversity remained stable in tumors, mammary tissue, and cecal contents, it significantly increased in the spleen (p < 0.05). Longitudinal analysis revealed a progressive rise in Firmicutes and a decline in Proteobacteria abundance within tumors, mammary tissue, and cecum, whereas the spleen microbiota displayed unique phylum-level compositional shifts. Tissue- and time-dependent microbial signatures were identified at phylum, genus, and species levels during breast tumor progression. Strikingly, the spleen microbiota integrated nearly all genera enriched in other sites, suggesting its potential role as a microbial reservoir. Gut-associated genera (Lactobacillus, Desulfovibrio, Helicobacter) colonized both cecal contents and the spleen, with Lactobacillus consistently detected across all tissues, suggesting microbial translocation. The spleen exhibited uniquely elevated diversity and compositional shifts, potentially driving splenomegaly. These results delineated the trajectory of microbiota translocation and colonization, and demonstrated tissue-specific microbial redistribution during breast tumorigenesis, offering valuable implications for advancing microbiome-targeted cancer therapies. Full article

Background/Objectives: The aim of this case series is to evaluate the outcomes and safety of video-assisted mastectomy, illustrating the harmonious collaboration of oncologic and plastic surgery. This novel minimally invasive technique allows immediate prosthetic reconstruction and represents a cost-effective alternative to robotic breast surgery. Methods: Video-assisted, single-port nipple-sparing mastectomies were performed in patients with small to medium-sized breasts, followed by immediate direct-to-implant reconstruction with either prepectoral or dual plane implant placement. The patients’ electronic medical records were analyzed, including demographic characteristics, operative times and histopathology reports. Results: A total of 18 patients underwent successful video-assisted mastectomy, without conversion to traditional open procedure. Fifteen of the operations were risk-reducing mastectomies. Twelve patients had complementary procedures performed concurrently on the previously operated contralateral breast (delayed reconstruction/expander-to-implant exchange). Moreover, three patients benefited from additional minimally invasive techniques during the same surgery (prophylactic laparoscopic hysterectomy). Immediate breast reconstruction with polyurethane or microtextured breast implants up to 450 cc was performed, with satisfactory aesthetic outcomes and no cancer recurrences at 6 to 12 months postoperative follow-up. Early complications included transient hypercapnia, areolar congestion and cellulitis. No skin necrosis or implant-related complications were reported. The most frequently encountered late issues were contour irregularities. Conclusions: Video-assisted mastectomy facilitates the safe removal of proven pathologic or healthy breast tissue with minimal damage to the breast’s skin envelope, facilitating single-stage breast reconstruction. Full article

Background/Objectives: Autologous fat grafting (AFT) has become a widely used technique in breast reconstruction, offering natural aesthetics, tissue integration, and patient satisfaction. However, its clinical outcomes require comparison with implant-based reconstruction (IBR), the most common method in clinical practice. While AFT provides a more natural appearance and avoids foreign body-related complications, issues such as fat resorption, procedural variability, and oncological concerns necessitate further investigation. Additionally, artificial intelligence (AI) has been increasingly integrated into breast imaging and reconstructive planning, improving diagnostic accuracy, procedural optimization, and complication prevention. This study aims to compare AFT and IBR while exploring AI’s role in enhancing breast reconstruction outcomes. Methods: A comprehensive review of clinical studies was conducted to evaluate the advantages, limitations, and oncological implications of AFT versus IBR. AI-driven applications in breast imaging and reconstructive planning were examined for their potential in predicting fat graft retention and optimizing implant selection. Data from systematic reviews and meta-analyses were incorporated to refine reconstruction strategies. Results: AFT offers superior aesthetic outcomes with better tissue integration but presents variability in fat resorption. IBR remains the preferred approach due to its predictability but carries risks of implant-related complications. AI technologies contribute to improved reconstruction planning, enhancing surgical precision and long-term patient outcomes. Conclusions: Optimized patient selection and long-term follow-up are essential for improving breast reconstruction techniques. AI-driven approaches provide valuable tools for enhancing procedural predictability and personalized treatment strategies. Future research should focus on refining AI algorithms and establishing standardized protocols for reconstructive decision-making. Full article

Background: Implant-based breast reconstruction (IBBR) is a widely adopted technique following mastectomy in breast cancer patients. However, the impact of chemotherapy type and duration on the development of capsular contracture remains unclear. Methods: This nationwide, retrospective, cohort study used Health Insurance Review and Assessment Service data to identify breast cancer patients who received chemotherapy and underwent immediate IBBR between January 2015 and December 2018. Follow-up continued until January 2024, with a median follow-up of 5.2 years. A total of 4303 patients (direct-to-implant [DTI], n = 2083; tissue expander insertion [TEI], n = 2220) were included. Results: Chemotherapy type and duration were not significantly associated with capsular contracture risk in either the DTI or TEI groups. In the DTI cohort, no significant difference in contracture incidence was found between neoadjuvant and adjuvant chemotherapy before or after matching (p = 0.056 and p = 0.121, respectively). In the TEI cohort, an initially significant difference (p = 0.019) was no longer observed after matching (p = 0.213). Similarly, chemotherapy duration (≤12 weeks vs. >12 weeks) did not impact contracture risk in either cohort. Multivariate analysis identified age, radiotherapy, lymphedema, and axillary lymph node dissection (ALND) as independent risk factors for contracture (p < 0.005). Comorbidities, such as diabetes and autoimmune diseases, also showed no significant association with contracture risk. Conclusions: These findings suggest that chemotherapy decisions should not be guided by contracture concerns. Instead, optimizing reconstruction outcomes should focus on modifiable factors, such as radiotherapy, lymphedema, and ALND. Full article

Anaplastic Large Cell Lymphoma (ALCL) represents a diverse group of mature T-Cell Lymphomas unified by strong CD30 expression but with different molecular and clinical subtypes. This review summarizes recent molecular advances in ALCL, highlighting key discoveries that have refined its classification, diagnosis, and therapeutic strategies. ALCL comprises four major entities: systemic ALK-positive ALCL, systemic ALK-negative ALCL, Breast Implant-Associated ALCL (BIA-ALCL), and primary cutaneous ALCL. Each subtype exhibits unique phenotypes, along with cytogenetic and molecular alterations that affect clinical outcomes. Nevertheless, different oncogenic mechanisms mediate STAT3 activation. In ALK-positive ALCL, ALK fusion proteins drive oncogenesis via constitutive activation of STAT3 and other signaling pathways. ALK-negative ALCL comprises heterogeneous genetic subtypes, in which JAK/STAT3 pathway alterations and novel gene fusions are gaining recognition as potential therapeutic targets. This review emphasizes the need for integrative molecular diagnostics to improve stratification of ALCL subtypes and targeted treatment approaches. Future research should focus on elucidating the biological mechanisms underlying these alterations and on translating molecular insights into clinical practice. Full article

Background: Nipple-sparing mastectomy (NSM), given demonstrated oncologic safety, is widely used for both therapeutic and prophylactic mastectomy. The popularity of NSM has spurred advancements by breast and plastic surgeons, liberalizing the indications for NSM and improving patient and aesthetic reconstructive outcomes. This review explores these developments and establishes up-to-date surgical tenets for successful NSM and reconstruction. Methods: A comprehensive literature review was conducted using the PubMed, Google Scholar, and Cochrane Library databases, focusing on peer-reviewed studies published up to 2024. Articles were selected based on relevance, quantity, and documentation of clinical outcomes and patient satisfaction. Results: NSM is utilized frequently for both invasive breast cancers and prophylactic mastectomy, with expanded criteria for candidacy by breast surgeons. Staged procedures such as adjunct reduction, mastopexy, or nipple delay allow patients with larger or ptotic breasts to undergo NSM with comparable outcomes. Long-term outcome studies have identified important risk factors for complications, including smoking history, higher mastectomy weight, certain medical comorbidities, and suboptimal mastectomy flaps. Evolutions in reconstructive decision making in direct-to-implant and staged tissue expander placement have improved aesthetic results while accounting for poor mastectomy flap quality or adjuvant therapy. Long-term outcomes show NSM remains safe and has comparable rates of local recurrence. Patient-reported outcomes demonstrate satisfaction with NSM, especially in sexual and psychological wellbeing metrics. Conclusions: NSM has been demonstrated to be safe in long-term oncologic outcomes. Its widespread popularity over the past ten years has helped identify methods to improve upon surgical and aesthetic outcomes, including decision-making in reconstruction; considerations for challenging patient-related characteristics such as macromastia, ptosis, and NAC asymmetry; and novel advances in areas such as neurotization. Full article