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Importance: While nipple-sparing mastectomy (NSM) for breast cancer was only performed using the open method in the past, its frequency using endoscopic and robotic surgical instruments has been increasing rapidly. However, there are limited studies regarding postoperative complications and the benefits and drawbacks of minimal access NSM (M-NSM) compared with conventional NSM (C-NSM). Objective: To examine the differences in postoperative complications between C-NSM and M-NSM. Design, Setting, Participants: This was a retrospective multicenter cohort study enrolling 1583 female patients aged 19 years and older with breast cancer who underwent NSM at 21 university hospitals in Korea between January 2018 and December 2020. Those with mastectomy without preserving the nipple-areolar complex (NAC), clinical or pathological malignancy in the NAC, inflammatory breast cancer, breast cancer infiltrating the chest wall or skin, metastatic breast cancer, or insufficient medical records were excluded. Data were analyzed from November 2021 to March 2024. Exposures: M-NSM or C-NSM. Main Outcomes and Measures: Clinicopathological factors and postoperative complications within 3 months of surgery were assessed. Statistical analyses, including logistic regression, were used to identify the factors associated with complications. Results: There were 1356 individuals (mean [SD] age, 45.47 [8.56] years) undergoing C-NSM and 227 (mean [SD] age, 45.41 [7.99] years) undergoing M-NSM (35 endoscopy assisted and 192 robot assisted). There was no significant difference between the 2 groups regarding short- and long-term postoperative complications (<30 days: C-NSM, 465 of 1356 [34.29%] vs M-NSM, 73 of 227 [32.16%]; P = .53; <90 days: C-NSM, 525 of 1356 [38.72%] vs M-NSM, 73 of 227 [32.16%]; P = .06). Nipple-areolar complex necrosis was more common in the long term after C-NSM than M-NSM (C-NSM, 91 of 1356 [6.71%] vs M-NSM, 5 of 227 [2.20%]; P = .04). Wound infection occurred more frequently after M-NSM (C-NSM, 58 of 1356 [4.28%] vs M-NSM, 18 of 227 [7.93%]; P = .03). Postoperative seroma occurred more frequently after C-NSM (C-NSM, 193 of 1356 [14.23%] vs M-NSM, 21 of 227 [9.25%]; P = .04). Mild or severe breast ptosis was a significant risk factor for nipple or areolar necrosis (odds ratio [OR], 4.75; 95% CI, 1.66-13.60; P = .004 and OR, 8.78; 95% CI, 1.88-41.02; P = .006, respectively). Conversely, use of a midaxillary, anterior axillary, or axillary incision was associated with a lower risk of necrosis (OR for other incisions, 32.72; 95% CI, 2.11-508.36; P = .01). Necrosis occurred significantly less often in direct-to-implant breast reconstruction compared to other breast reconstructions (OR, 2.85; 95% CI, 1.11-7.34; P = .03). Conclusions and Relevance: The similar complication rates between C-NSM and M-NSM demonstrates that both methods were equally safe, allowing the choice to be guided by patient preferences and specific needs.
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Three-dimensional (3D) cellular assemblies, such as cancer spheroids and organoids, are increasingly valued for their physiological relevance, and versatility in biological applications. Nanopatterns that mimic the extracellular matrix provide crucial topological cues, creating a physiologically relevant cellular environment and guiding cellular behaviors. However, the high cost and complex, time-consuming nature of the nanofabrication process have limited the widespread adoption of nanopatterns in diverse biological applications. In this study, we present a straightforward and cost-effective elastomer replica molding method utilizing commercially available optical discs to generate various nanopatterns, such as nanogroove/ridge, nanoposts, and nanopits, varying in spacing and heights. Using the nanopatterned well chips (NW-Chips), we demonstrated the efficient formation of 3D multicellular self-assemblies of three different types of cancer cells. Our findings highlight the accessibility and affordability of optical discs as tools for nanopattern generation, offering promising avenues for modulating cell behaviors and advancing diverse biological applications.
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Nanoestruturas , Humanos , Nanoestruturas/química , Esferoides Celulares/citologia , Linhagem Celular Tumoral , Propriedades de SuperfícieRESUMO
Sorafenib (BAY 43-9006) was developed as a multi-kinase inhibitor to treat advanced renal cell, hepatocellular, and thyroid cancers. The cytotoxic effect of sorafenib on cancer cells results from not only inhibiting the MEK/ERK signaling pathway (the on-target effect) but also inducing oxidative damage (the off-target effect). The inhibitory effect of sorafenib on system Xc- (xCT), a cystine/glutamate antiporter, promotes ferroptosis induction and accounts for oxidative damage. While emerging studies on ferroptosis in cancers have garnered increasing attention, the lack of consideration for ferroptosis inducers (FINs) with favorable pharmacokinetics could be problematic. Herein, we remodeled the chemical structure of sorafenib, of which pharmacokinetics and safety are already assured, to customize the off-target effect (i.e., ferroptosis induction) to on-target by disrupting the adenine-binding motif. JB3, a sorafenib derivative (i.e., JB compounds), with a tenfold higher IC50 toward RAF1 because of chemical remodeling, induced strong cytotoxicity in the elastin-sensitive lung cancer cells, while it was markedly reduced by ferrostatin-1. The 24% oral bioavailability of JB3 in rats accounted for a significant anti-tumor effect of orally administrated JB3 in xenograft models. These results indicate that JB3 could be further developed as an orally bioavailable FIN in novel anti-cancer therapeutics.
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Antineoplásicos , Ferroptose , Neoplasias Pulmonares , Sorafenibe , Sorafenibe/farmacologia , Sorafenibe/administração & dosagem , Ferroptose/efeitos dos fármacos , Humanos , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Administração Oral , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Linhagem Celular Tumoral , Camundongos , Ratos , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/farmacocinética , Camundongos NusRESUMO
PURPOSE: Satisfaction should be prioritized to maximize the value of education for trainees. This study was conducted with professors, fellows, and surgical residents in the Department of general surgery (GS) to evaluate the importance of various educational modules to surgical residents. METHODS: A questionnaire was administered to professors (n = 28), fellows (n = 8), and surgical residents (n = 14), and the responses of the three groups were compared. Four different categories of educational curricula were considered: instructor-led training, clinical education, self-paced learning, and hands-on training. RESULTS: The majority of surgeons regarded attending scrubs as the most important educational module in the training of surgical residents. However, while professors identified assisting operators by participating in surgery as the most important, residents assessed the laparoscopic training module with animal models as the most beneficial. CONCLUSIONS: The best educational training course for surgical residents was hands-on training, which would provide them with several opportunities to operate and perform surgical procedures themselves.
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Currículo , Cirurgia Geral , Internato e Residência , Humanos , Cirurgia Geral/educação , Inquéritos e Questionários , Cirurgiões/educação , Masculino , Feminino , Atitude do Pessoal de Saúde , Educação de Pós-Graduação em Medicina , Docentes de Medicina , Competência ClínicaRESUMO
INTRODUCTION: Immune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival. METHODS: Clinical and radiologic data from 121 non-small cell lung cancer (NSCLC) patients with 136 immunotherapy cases were reviewed retrospectively. Three HPD definitions (Champiat et al., HPDc; Saâda-Bouzid et al., HPDs; and Ferrara et al., HPDf) were employed. Additionally, all new measurable lesions on the post-treatment CT scan were incorporated in measuring the sum of longest diameters (SLD) to define modified HPD (mHPD). RESULTS: Among the 121 patients, 4 (3.3%) had HPDc, 11 (9.1%) had HPDs, and none had HPDf. Adding all new measurable lesions increased HPD incidence by 5%-10% across definitions. Multivariate analysis revealed significantly lower progression-free survival (PFS) and overall survival (OS) for patients with HPDc (HR 5.25, P = .001; HR 3.75, P = .015) and HPDs (HR 3.74, P < .001; HR 3.46, P < .001) compared to those without. Patients with mHPD showed similarly poor survival outcomes as HPD patients. Liver metastasis at diagnosis was associated with HPDs, and a high tumor burden correlated with HPDc. CONCLUSIONS: The incidence and risk factors of HPD varied with different definitions, but mHPD identified more cases with poor outcomes. This comprehensive approach may enhance the identification of at-risk patients and lead to a better understanding of HPD in lung cancer during immunotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Progressão da Doença , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Feminino , Fatores de Risco , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Imunoterapia/métodos , Incidência , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Taxa de Sobrevida , PrognósticoRESUMO
Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG.
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Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan-Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.
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Neoplasias da Mama , Movimento Celular , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Tamoxifeno , Feminino , Humanos , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/genética , Células MCF-7 , Invasividade Neoplásica , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA-based MRD detection to predict recurrence in a real-world cohort of primarily early-stage non-small cell lung cancer (NSCLC) patients treated with curative intent. METHODS: Longitudinal plasma samples were collected post curative-intent treatment from 36 patients with stage I-IV NSCLC. A personalized, tumor-informed assay was used to detect and quantify ctDNA in plasma samples. RESULTS: Of the 24 patients with plasma samples available during the MRD window (within 6 months of curative surgery and before adjuvant therapy), ctDNA was detectable in two patients. Patients with ctDNA-positivity during the MRD window were 15 times more likely to recur compared to ctDNA-negative patients (HR: 15.0, 95% CI: 1.0-253.0, p = 0.010). At any time post-curative intent treatment, ctDNA-positivity was associated with significantly poorer recurrence-free survival compared to persistently ctDNA-negative patients (p < 0.0001). CONCLUSION: Our real-world data indicate that longitudinal, personalized, tumor-informed ctDNA monitoring is a valuable tool in patients with NSCLC receiving curative treatment to identify patients at high risk for recurrence.
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Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Neoplasia Residual , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Masculino , Feminino , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Medicina de Precisão/métodos , Prognóstico , Idoso de 80 Anos ou mais , AdultoRESUMO
Purpose: Endoscopic nipple-sparing mastectomy (E-NSM) is a minimally invasive surgical technique that shows good results in patients with breast cancer. The authors compared 3 different types of commercial energy devices to examine their efficacy and safety in E-NSM performed with breast reconstruction. Methods: A total of 36 cases of E-NSM were conducted with either Sonicision (S group, n = 11), Harmonic (H group, n = 6), or Thunderbeat (T group, n = 19). The clinicopathologic factors and postoperative complications, including nipple or skin necrosis and surgical site seroma volume, were evaluated for 3 months after surgery. Results: The surgical duration of E-NSM was significantly shorter in the S group than in the H group (P = 0.043) and T group (P = 0.037). However, the total surgical duration including E-NSM and breast reconstruction, and the total and daily drainage volume of postoperative seroma did not differ significantly among the 3 groups. Even when the energy devices were compared according to their working principle, i.e., ultrasonic (S and H) vs. hybrid (T), the total breast surgery duration and total and daily drainage volume of seroma showed no difference between the 2 groups. Although surgeon satisfaction did not significantly differ when using 3 devices for E-NSM (P = 0.428), surgeon's fatigue was found to be lowest in the S group, though it was not significant (P = 0.064). Conclusion: Any energy device can be safely used for E-NSM with breast reconstruction without causing any major complications. However, cordless ultrasonic energy devices allow greater mobility for the surgeon and, therefore, may shorten surgical time in breast surgery.
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PURPOSE: In total mastectomy (TM), sentinel lymph node biopsy (SLNB) is recommended but can be omitted for breast-conserving surgery (BCS) in patients with ductal carcinoma in situ (DCIS). However, concerns regarding SLNB-related complications and their impact on quality of life exist. Consequently, further research is required to evaluate the role of axillary surgeries, including SLNB, in the treatment of TM. We aimed to explore the clinicopathological factors and outcomes associated with axillary surgery in patients with a final diagnosis of pure DCIS who underwent BCS or TM. METHODS: We retrospectively analyzed large-scale data from the Korean Breast Cancer Society registration database, highlighting on patients diagnosed with pure DCIS who underwent surgery and were categorized into two groups: BCS and TM. Patients were further categorized into surgery and non-surgery groups according to their axillary surgery status. The analysis compared clinicopathological factors and outcomes according to axillary surgery status between the BCS and TM groups. RESULTS: Among 18,196 patients who underwent surgery for DCIS between 1981 and 2022, 11,872 underwent BCS and 6,324 underwent TM. Both groups leaned towards axillary surgery more frequently for large tumors. In the BCS group, clinical lymph node status was associated with axillary surgery (odds ratio, 11.101; p = 0.003). However, in the TM group, no significant differences in these factors were observed. Survival rates did not vary between groups according to axillary surgery performance. CONCLUSION: The decision to perform axillary surgery in patients with a final diagnosis of pure DCIS does not affect the prognosis, regardless of the breast surgical method. Furthermore, regardless of the breast surgical method, axillary surgery, including SLNB, should be considered for high-risk patients, such as those with large tumors. This may reduce unnecessary axillary surgery and enhance the patients' quality of life.
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PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.
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While the human gut microbiota has a significant impact on gut health and disease, understanding of the roles of gut microbes, interactions, and collective impact of gut microbes on various aspects of human gut health is limited by the lack of suitable in vitro model system that can accurately replicate gut-like environment and enable the close visualization on causal and mechanistic relationships between microbial constitutents and the gut. , In this study, we present a scalable Gut Microbiome-on-a-Chip (GMoC) with great imaging capability and scalability, providing a physiologically relevant dynamic gut-microbes interfaces. This chip features a reproducible 3D stratified gut epithelium derived from Caco-2 cells (µGut), mimicking key intestinal architecture, functions, and cellular complexity, providing a physiolocially relevant gut environment for microbes residing in the gut. Incorporating tumorigenic bacteria, enterotoxigenic Bacteroides fragilis (ETBF), into the GMoC enable the observation of pathogenic behaviors of ETBF, leading to µGut disruption and pro-tumorigenic signaling activations. Pre-treating the µGut with a beneficial gut microbe Lactobacillus spp., effectively prevent ETBF-mediated gut pathogenesis, preserving the healthy state of the µGut through competition-mediated colonization resistance. The GMoC holds potential as a valuable tool for exploring unknown roles of gut microbes in microbe-induced pathogenesis and microbe-based therapeutic development.
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Microbioma Gastrointestinal , Dispositivos Lab-On-A-Chip , Microbioma Gastrointestinal/fisiologia , Humanos , Células CACO-2RESUMO
This study thoroughly explores the quality and safety aspects of saeu-jeot, a popular salt-fermented shrimp in South Korea, with a specific focus on products fermented in underground tunnels. In this study, an extensive analysis of key quality factors (pH, salinity, total nitrogen [TN], and amino nitrogen [AN]), along with detailed investigation into chemical hazards (volatile basic nitrogen [VBN] and biogenic amines [BAs]), and microbiological hazards (total aerobic bacteria [TAB], fecal indicator bacteria, halophilic bacteria, and foodborne pathogens) were performed. The results indicate that the shrimp grade did not dramatically affect the quality and safety of the saeu-jeot. However, given the prevalent small-scale production of saeu-jeot, the study strongly underscores the pressing need for the establishment of a standardized manufacturing process. The absence of grade-dependent variations in quality highlights the critical importance of implementing standardized procedures to ensure the consistent quality and safety of saeu-jeot, particularly in the context of its frequent small-scale production. These findings provide crucial insights for the industry to enhance practices and meet quality and safety standards effectively.
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BACKGROUND: Postoperative scar formation is inevitable, and a gold standard management has not been established to date. Due to the fact long and large scar formation occurs in reconstructive surgery, this study analyzed the relationship between various factors in patients who received breast reconstruction using latissimus dorsi (LD) flap to investigate appropriate and effective management approaches. PATIENTS AND METHODS: Twenty-seven patients who underwent breast reconstruction between June 2014 and January 2015 received laser therapy on their LD donor site at the Kyungpook National University Chilgok Hospital. Scar evaluation was performed on both the surgical scar and intact skin on the contralateral side. Scar evaluation was conducted at five specific points, 2 cm from the midpoint of the scar on each side. Laser treatment was performed at 4-week intervals, and patients were then followed-up for 6 months. To assess scars, gross images were taken using the same settings. In addition, spectrophotometry was used for color assessment, durometer for texture and pressure evaluation, and Vernier calipers and height gauges for a more precise and objective approach. RESULTS: The mean age of the participants was 45.7 years, and the mean body mass index was 22.1 kg/m2 The operator-evaluated scar scale scores were 107.2 and 97.3 in the experimental and control groups, respectively. In the patient-rated questionnaire, the scores were 62.3 and 59.4 in the experimental and control groups, respectively. CONCLUSION: When analyzing early-stage postoperative scars based on various factors, laser therapy is considered a very useful scar management approach. Additionally, when performing reconstructive surgery, tension force is regarded as a significant factor to take into account since it affects scar widening.
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Terapia a Laser , Mamoplastia , Músculos Superficiais do Dorso , Humanos , Pessoa de Meia-Idade , Cicatriz/etiologia , Cicatriz/cirurgia , Músculos Superficiais do Dorso/cirurgia , Retalhos Cirúrgicos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Terapia a Laser/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: In our previous study, Developmental endothelial locus-1 (Del-1) was a promising predictive marker for breast cancer. However, the downstream targets of Del-1 remain unknown. Here, we sought to discover a druggable target downstream of Del-1 and investigate the mechanism by which it regulates the course of breast cancer. METHODS: To investigate Del-1 downregulation effect on breast cancer, we performed transcriptome analysis using RNA sequencing of Del-1 knockdowned MDA-MB-231 cell line Plus, to investigate the expression of Del-1 and Maternal embryonic leucine zipper kinase (MELK), mRNA levels in eight different triple-Negative Breast Cancer (TNBC) cell lines were analyzed. High-throughput sequencing was performed on total RNA isolated. OTS167 was used for MELK inhibition. The effects of MELK on cell proliferation and invasion were determined using the MTT and Matrigel transwell assays. Furthermore, we examined MELK expression in breast cancer tissue. RESULTS: Del-1 and MELK mRNA expression levels were significantly higher in the TNBC cell lines, MDA-MB-468, HCC-1806, and MBA-MB-231. Knocking down Del-1 with siRNA in HCC-1806 and MBA-MB-231 cells significantly decreased MELK expression and thus suggested a possible relationship between Del-1 and MELK. In MDA-MB-468 cells, a basal-like 1 TNBC cell line, OTS167 significantly inhibited breast cancer cell proliferation and promoted cell apoptosis. To further investigate the relationship between Del-1 and MELK, dual inhibition of both Del-1 and MELK was performed, which significantly reduced the viability of MDA-MB-468 and MBA-MB-231 cells. CONCLUSION: We found that MELK acts downstream of Del-1 and is a promising druggable target, especially in basal-like and mesenchymal stem-like subtype.
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Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Feminino , Linhagem Celular Tumoral , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Movimento Celular , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , Perfilação da Expressão Gênica , ApoptoseRESUMO
BACKGROUND To evaluate the role of double-lung transplantation (DLT) for lung cancer, the survival outcomes of patients who underwent DLT for lung cancer and the incidence of de novo lung cancer after DLT were assessed. MATERIAL AND METHODS Data from all cases reported in the literature were pooled for analysis and additional data were collected from the Organ Procurement Transplantation Network (OPTN) registry. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) of patients who underwent DLT for lung cancer were determined. Moreover, the incidence of de novo lung cancer and associated OS in lung transplant recipients were examined. RESULTS Of the 20 cases series and 15 cases from the OPTN registry, the 5-year RFS was 55.0% and 66.7% and the 5-year OS was 55.0% and 26.7%, respectively, and the median CSS was 48.0 (range, 2.0-144.0) and 27.7 (range, 0.2-66.6) months, respectively. In the OPTN data, the incidence of post-transplant lung cancer in patients who underwent DLT for the non-cancerous disease was 0.8% and the 5-year OS was 47.3%. CONCLUSIONS In conclusion, our integrated analysis of the case series and the OPTN registry demonstrated promising survival outcomes for patients with refractory bilateral lung cancer who underwent DLT. Although there are limitations to consider, the results of this study underscore the potential benefits of DLT in managing refractory lung-limited lung cancer.
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Neoplasias Pulmonares , Transplante de Pulmão , Transplante de Órgãos , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/cirurgia , Incidência , Transplante de Pulmão/métodos , Pulmão , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: The tongue is an important anatomical structure, playing an significant role in natural speech, swallowing, and sense of taste. Immediate reconstruction using autologous tissue must be performed following glossectomy for tongue cancer to improve patient quality of life. This study aimed to demonstrate the usefulness of a surgical technique using the free vertical latissimus dorsi flap (FvLDF) for tongue reconstructions using autologous tissue. PATIENTS AND METHODS: Among patients who underwent total glossectomy for tongue cancer from November 2014 to February 2023, we selected 10 patients who underwent immediate tongue reconstruction with a radial free forearm flap (RFFF) or free anterolateral thigh flap and four patients who underwent FvLDF. The patients were compared regarding postoperative function (width of oropharyngeal space in computed tomography, language-speech evaluation), aesthetic results, and features. RESULTS: All four patients who underwent FvLDF showed successful flap survival, with no severe complications. Because vertical incision was made during flap harvest with primary closure possible with the mid-axillary line, donor morbidity was significantly lower in patients who underwent reconstruction with FvLDF than in those who underwent reconstruction with RFFF, and good aesthetic results were obtained. In comparing the oropharyngeal space of patients on neck CT preoperatively and postoperatively, the width increase rate of patients who underwent reconstruction with FvLDF was significantly smaller. FvLDF patients demonstrated good speech and swallowing functions. CONCLUSION: Considering the advantages of reconstruction with FvLDF in terms of features and aesthetic results, this surgical technique may be a reliable alternative technique for tongue defects after glossectomy.
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Retalhos de Tecido Biológico , Músculos Superficiais do Dorso , Neoplasias da Língua , Humanos , Glossectomia/métodos , Neoplasias da Língua/cirurgia , Qualidade de Vida , Língua/cirurgiaRESUMO
Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.
Assuntos
Terapia de Imunossupressão , Transplante de Pulmão , Neoplasias , Incidência , Risco , Terapia de Imunossupressão/efeitos adversos , Neoplasias/classificação , Neoplasias/epidemiologia , Neoplasias/mortalidade , Humanos , Masculino , Adulto , Pessoa de Meia-IdadeRESUMO
Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.
RESUMO
The clinical features and prognosis of breast cancer can vary widely, depending on the molecular subtype. Luminal B breast cancers are usually either estrogen receptor-positive and/or progesterone receptor-positive with high proliferation of Ki67 index, or HER2 positive (HER2+). The authors compared the clinicopathologic factors and survival rates of different subtypes of luminal B breast cancer according to HER2 status. Between 2009 and 2013, 1131 cases of breast cancer were reviewed and characterized as 1 of 4 different molecular subtypes based on their immunohistochemical results: luminal A, luminal B, HER2+, or triple-negative breast cancer. From these, luminal B breast cancers were extracted and the clinical features and prognosis of the HER2- and the HER2â +â subtypes were compared. Survival differed significantly based on the molecular subtype regardless of whether or not the patient received treatment with neoadjuvant chemotherapy. While patients with HER2- luminal B breast cancer who received neoadjuvant chemotherapy had better prognoses, patients with HER2â +â luminal B breast cancer who did not receive neoadjuvant chemotherapy had better prognoses. Luminal B breast cancers showed different clinical outcomes and survival rates according to HER2 gene overexpression type. Physicians should consider these results when they establish a treatment strategy.