RESUMO
PURPOSE: The tumor-stroma ratio (TSR) is a common histological parameter that measures stromal abundance and is prognostic in breast cancer (BC). However, more evidence is needed on the predictive value of the TSR for the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). The purpose of this study was to determine the importance of the TSR in predicting pCR in NAC settings. METHOD: We evaluated the TSR on pretreatment biopsies of 912 BC patients from four independent Chinese hospitals and investigated the potential value of the TSR for predicting pCR. Meanwhile, stromal tumor-infiltrating lymphocytes (sTILs) were assessed, and we evaluated the predictive value of the combination of sTILs and TSR (TSRILs). RESULTS: Patients with low stroma showed a higher pCR rate than those with high stroma among the four independent hospitals, and in multivariate analysis, the TSR was proven to be an independent predictor for pCR to NAC with an odds ratio of 1.945 (95% CI 1.230-3.075, P = 0.004). Moreover, we found that TSRILs could improve the area under the curve (AUC) for predicting pCR from 0.750 to 0.785 (P = 0.039); especially in HER2-negative BCs, the inclusion of TSRILs increased the AUC from 0.801 to 0.835 in the discovery dataset (P = 0.048) and 0.734 to 0.801 in the validation dataset (P = 0.003). CONCLUSION: TSR and sTILs can be easily measured in pathological routines and provide predictive information without additional cost; with more evidence from clinical trials, TSRILs could be a candidate to better stratify patients in NAC settings.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linfócitos do Interstício Tumoral/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Terapia NeoadjuvanteRESUMO
BACKGROUND: Collecting duct carcinoma (CDC) is a rare renal tumor, originating from the distal collecting duct. CDC rarely presents as a primary tumor outside the renal system. CASE PRESENTATION: In this study, we report a rare case of collecting duct carcinoma, with an initial presentation of retroperitoneal lymph node metastasis, and no identifiable primary renal tumor on CT, at the time of diagnosis. The patient was a 64-year-old man presenting with lower back pain. Preoperative CT showed a round, soft tissue mass, measuring 6.7 × 4.4 × 3.3 cm, in the left retroperitoneum with no exact occupying lesion in the left kidney. Clinically, ectopic pheochromocytoma was considered to be a differential diagnosis, and tumor resection was performed. Postoperative pathological results demonstrated that the mass was a fused lymph node, and the tumor cells were destroying the structure. The final diagnosis was lymph node metastatic collecting duct carcinoma, by histology and immunohistochemistry. No further treatment was performed as no space occupying lesion was found in the kidney. Three months later, CT was reexamined, and a mass of 3.6 cm in diameter, was found in the lower left kidney, along with multiple soft tissue masses, in the left renal hilum. Considering recurrence or metastasis, the patient was recommended to undergo surgical treatment, but the patient refused. Four months later, CT was re-examined. The tumor had rapidly progressed but the patient refused treatment again. As per the author's press release (eleven months after the first discovery), the patient is still alive. CONCLUSION: CDC is a rare malignant renal carcinoma, with a high chance of rapid progress, regional lymph nodes involvement and metastasis. It presents diagnostic challenges to clinicians and pathologists, particularly, in the absence of radiographically detectable intrarenal lesions. Definite diagnosis is based on pathological examination combined with immunohistochemical staining.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Espaço Retroperitoneal , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Espaço Retroperitoneal/patologiaRESUMO
BACKGROUND: Multiple factors including host-microbiota interaction could contribute to the conversion of healthy mucosa to sporadic precancerous lesions. An imbalance of the gut microbiota may be a cause or consequence of this process. AIM: The goal was to investigate and analyze the composition of gut microbiota during the genesis of precancerous lesions of colorectal cancer. METHODS: To analyze the composition of gut microbiota in the genesis of precancerous lesions, a rat model of 1, 2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) was established. The feces of these rats and healthy rats were collected for 16S rRNA sequencing. RESULTS: The diversity and density of the rat intestinal microbiota were significantly different between ACF-bearing and non-bearing group. ACF were induced in rats treated with DMH and showed increased expression of the inflammatory cytokines IL-6, IL-8, and TNF-α. Firmicutes was the most predominant phylum in both ACF-bearing and non-bearing group, followed by Bacteroidetes. Interestingly, although the density of Bacteroidetes decreased from the fifth week to the 17th week in both groups, it was significantly reduced in ACF-bearing group at the 13th week (P < 0.01). At the genus level, no significant difference was observed in the most predominant genus, Lactobacillus. Instead, Bacteroides and Prevotella were significantly less abundant (P < 0.01), while Akkermansia was significantly more abundant (P < 0.05) in ACF-bearing group at the 13th week. CONCLUSION: Imbalance of the intestinal microbiota existed between ACF-bearing and non-bearing rats, which could be used as biomarker to predict the genesis of precancerous lesions in the gut.
Assuntos
Focos de Criptas Aberrantes/microbiologia , Carcinogênese , Neoplasias Colorretais/microbiologia , Microbioma Gastrointestinal , Animais , Modelos Animais de Doenças , Masculino , Ratos Sprague-DawleyAssuntos
Linfangioleiomiomatose , Neoplasias , Feminino , Humanos , Ovário , Linfangioleiomiomatose/complicações , LinfonodosRESUMO
Breast cancer (BC) is the most common tumor in women worldwide. TRIM28 (RNF96) plays pleiotropic biological functions, such as silencing target genes, facilitating DNA repair, stimulating cellular proliferation and differentiation, and contributing to cancer progression. TRIM28 plays an increasingly crucial role in cancer, but its impact on BC, including breast invasive carcinoma, remains poorly understood. In the current study, analyses of online databases, quantitative real-time quantitative PCR, immunohistochemistry, and western blotting were performed on patients with breast invasive carcinoma (BRCA). Cordycepin (CD) was used to monitor BC progression and TRIM28 expression in vivo. As a result, we observed that TRIM28 is highly expressed in breast invasive carcinoma tissues compared with the corresponding normal tissues and is correlated with metastatic / invasive progression. High expression of TRIM28 might serve as a prognostic marker for long-term survival in triple-negative BC, advanced BC, or breast invasive carcinoma. Although TRIM28 methylation in tumor tissues of breast invasive carcinoma is not significantly changed compared to the matched normal tissues, the expressions and methylation of TRIM28 are significantly reversely correlated. TRIM28 expression was inhibited by CD in the mouse model, indicating its role in preventing BC progression. Thus, TRIM28 might be a potentially valuable molecular target for forecasting the progression / prognosis of patients with breast invasive carcinoma. CD, which represses BC growth/metastasis, may be involved partially through suppressing TRIM28 expression.
RESUMO
Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL's inhibitory effects on breast cancer using both in vitro (MCF7 and MDA-MB-468 cells) and in vivo (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL's anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and in vivo studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.
Assuntos
Autofagia , Neoplasias da Mama , Piperazinas , Piridinas , Piridonas , Pirimidinonas , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Animais , Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Piridinas/farmacologia , Piridinas/uso terapêutico , Piridonas/farmacologia , Piridonas/uso terapêutico , Feminino , Pirimidinonas/farmacologia , Pirimidinonas/uso terapêutico , Camundongos , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camundongos Nus , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Células MCF-7RESUMO
Primary small bowel adenocarcinoma (SBA) is a rare gastrointestinal cancer with a low incidence of ovarian metastasis. Differential diagnosis of metastatic and primary ovarian cancer is often challenging. The present study reported the case of a 45-year-old woman with jejunal adenocarcinoma who presented with right ovarian, left ovarian, abdominopelvic implant and local recurrent bowel wall metastases successively after primary tumor resection. The ovarian masses of the patient originated from SBA, which was confirmed by immunohistochemical results. Following four comprehensive evaluations by an experienced multidisciplinary team (MDT) during the disease period, the patient underwent four operations, 28 cycles of chemotherapy, 24 cycles of targeted therapy and maintenance therapy for 8 months. As of February 2023, the patient has survived for 73 months and has a high quality of life. It is suggested that when a patient with SBA presents with an ovarian mass, the differential diagnosis between metastatic ovarian cancer and primary ovarian cancer mainly relies on immunohistochemistry. After a comprehensive evaluation by an experienced MDT, surgical resection is the primary treatment for advanced SBA, thus demonstrating some benefits for patients.
RESUMO
Purpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD). Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test. Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23±6.17 VS 7.89±2.38). The difference between the two groups had statistical significance (P < 0.05). Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.
RESUMO
Context: TFE3 translocation renal cell carcinoma (RCC) is a rare tumor that represents approximately 1% of RCC. It was classifed as a member of MiT family translocation RCCs by the World Health Organization in 2016. It is characterized by Xp11 translocation gene fusions involving TFE3. The diagnosis of TFE3 translocation RCC is based on immunohistochemical analysis and TFE3 break apart probes in FISH analysis, rather than histological characteristics and imaging examination. Aims: To determine the clinico-pathological, immuno-phenotypic, and cytogenetic characteristics of TFE3 translocation RCC. Methods and Materials: The clinical data of a 52-year-old-female patient with TFE3 translocation RCC exhibiting rare morphological characteristics was analyzed, and the tumor tissues were probed using histopathological staining, immunohistochemistry, and fluorescence in situ hybridization (FISH). In addition, the relevant literature was reviewed. Results: This case is a TFE3 translocation RCC with rare morphological features. It composed of two types of tumor cells. TFE3 and pax-8 were diffusely and strongly expressed in both tumor cells, and they were partially positive for CAIX, RCC, CK, EMA, CD10, Vim, Melan-A, and p504s. Only 2% of the cells were positive for the proliferation marker Ki-67, and the tumor was negative for CK7, CD117, Inhibin-α, HBM45, and p53. FISH showed a positive signal for TFE3 translocation. Conclusions: This case was a TFE3 translocation RCC with rare morphological features. Through this case report, we emphasize the importance of in situ detection of TFE3 gene translocation and protein in TFE3 translocation RCC.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Feminino , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Hibridização in Situ Fluorescente/métodos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Cromossomos Humanos X/genética , Cromossomos Humanos X/química , Cromossomos Humanos X/metabolismo , Translocação GenéticaRESUMO
Objective: To explore the effective response strategies for infections in infants with short bowel syndrome and solid abdominal tumours, treated with totally implantable venous access ports (TIVAPs). Methods: A total of 210 children who were treated with a TIVAP in our department from 2020 to 2021 were selected for this retrospective study. Eight of these children diagnosed with a catheter-related bloodstream infection were studied in this study; antibiotic lock therapy (ALT) and cluster nursing management were used for treatment, and their effects on the infection outcome were observed. Results: Among the eight children, seven access ports were successfully protected, and one catheter was removed from the right chest wall port due to repeated infection. In this one child, the left side was re-implanted. Conclusion: The use of the ALT combined with cluster-based nursing can better treat infections of TIVAPs, improve the children's healing time, and has important clinical significance in the prevention of complications from the infection and improving the treatment and nursing of the patients diagnosed with these infections.
RESUMO
BACKGROUND: Breast-conserving therapy (BCT) is an accepted therapeutic option for most breast cancer patients. However, mastectomy is still performed in 30-50% of patients undergoing surgeries. There is increasing interest in preservation of the nipple and/or areola in hopes of achieving improved cosmetic and functional outcomes; however, the oncologic safety of nipple-areolar complex (NAC) preservation is a major concern. We sought to identify the predictive factors for NAC involvement in breast cancer patients. METHODS: We analyzed the rates and types of NAC involvement by breast carcinoma, and its association with other clinicopathologic features of the tumors in 787 consecutive therapeutic mastectomies performed at our institution between 1997 and 2009. RESULTS: Among these, 75 cases (9.5%) demonstrated NAC involvement. Only 21 (28%) of 75 of cases with NAC involvement could be identified grossly by inspection of the surgical specimen (seven of these had been clinically identified). NAC involvement was most significantly associated with tumors located in all four quadrants (P<0.0001), tumors>5 cm in size (P=0.0014 for invasive carcinoma and P=0.0032 for in-situ carcinoma), grade 3 tumors (P=0.0192), tumors with higher nuclear grades (P=0.0184), and tumors with HER2 overexpression (P=0.0137). CONCLUSIONS: On the basis of our findings, we have developed a mathematical model that is based on the extent and location of the tumor, HER2 expression, and nuclear grade that predicts the probability of NAC involvement by breast cancer. This model may aid in preoperative planning in selecting appropriate surgical procedures based on an individual patient's relative risk of NAC involvement.
Assuntos
Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Modelos Biológicos , Mamilos/patologia , Adulto , Neoplasias da Mama/química , Neoplasias da Mama/cirurgia , Carcinoma in Situ/química , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/química , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Feminino , Humanos , Modelos Logísticos , Metástase Linfática , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Gradação de Tumores , Receptor ErbB-2/análiseRESUMO
Re-epithelialization is a crucial step towards wound healing. The traditional Chinese medicine, Astragalus membranaceus (Fisch) Bge, has been used for hundreds of years for many kinds of ulcerated wounds. Recent research has identified the active compound in this drug as astragaloside IV (AS-IV), but the underlying molecular mechanisms of its therapeutic action on keratinocytes remain poorly understood. In this study, we used an in vitro model of ulcer-like wound processes, lithium chloride (LiCl)-induced cultured mouse keratinocytes, to investigate the effects of AS-IV treatment. The effects on cell proliferation were evaluated by the MTS/PMS colorimetric assay, effects on cell migration were determined by a wound-healing scratch experiment, effects on the cell cycle were analyzed by flow cytometry, and effects on protein expression were analyzed by immunoblotting and immunofluorescence. LiCl strongly inhibited cell proliferation and migration, up-regulated ß-catenin expression, and down-regulated proliferating cell nuclear antigen (PCNA) expression. AS-IV treatment attenuat the inhibition of proliferation and migration, significantly reducing the enhanced ß-catenin expression, and recovering PCNA and ß-tubulin expression. Thus, AS-IV mediates mouse keratinocyte proliferation and migration via regulation of the Wnt signaling pathway. Down-regulating ß-catenin to increase keratinocyte migration and proliferation is one mechanism by which AS-IV can promote ulcerated wound healing.
RESUMO
Cholangiocarcinoma (CCA) is a fatal tumor associated with chronic inflammation. Circular RNAs (circRNAs) have been evidenced to be involved in tumorigenesis and tumor progression. This study aimed to explore the effects and potential molecular mechanism of circSETD3 in CCA progression. Levels of CircSETD3 and microRNA (miR)-421 in CCA tissue and cell lines were measured using quantitative real-time polymerase-chain reaction (qRT-PCR). A direct target of miR-421 was predicted using TargetScan and further confirmed by a dual-luciferase reporter assay. Cell proliferation and apoptosis were measured using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry, respectively. The activity of caspase-3 was also examined using caspase-3 activity detection kits. Moreover, the levels of B-cell lymphoma-2 modifying factor (BMF), B-cell lymphoma 2 (BCL2), and Bcl-2-associated X protein (BAX) in TFK1 cells were assessed using qRT-PCR and western blot analysis. We found that circSETD3 was downregulated, while miR-421 was upregulated in CCA tissues and cell lines. CircSETD3 negatively regulated miR-421 levels in TFK1 cells. Functional assays revealed that circSETD3-plasmid inhibited cell proliferation, induced apoptosis, promoted caspase-3 activity, enhanced Bax and cleaved-Caspase 3 expression, and reduced Bcl-2 levels, and these effects were reversed by miR-421 mimic. Meanwhile, similar results were observed in miR-421 inhibitor-transfected TFK1 cells, and these results were abolished by BMF-siRNA. BMF, a direct target of miR-421, was downregulated in CCA tissues and cell lines. These findings demonstrate that circSETD3 inhibits proliferation and induces apoptosis in CCA cells by regulating the miR-421/BMF axis, indicating its potential as a promising candidate for CCA therapy.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , Apoptose/genética , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Colangiocarcinoma/genética , Regulação para Baixo/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Neoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced breast cancer. However, not all patients benefit from NAC; some even obtain worse outcomes after therapy. Hence, predictors of treatment benefit are crucial for guiding clinical decision-making. Here, we investigated the predictive potential of breast cancer stromal histology via a deep learning (DL)-based approach and proposed the tumor-associated stroma score (TS-score) for predicting pathological complete response (pCR) to NAC with a multicenter dataset. The TS-score was demonstrated to be an independent predictor of pCR, and it not only outperformed the baseline variables and stromal tumor-infiltrating lymphocytes (sTILs) but also significantly improved the prediction performance of the baseline variable-based model. Furthermore, we discovered that unlike lymphocytes, collagen and fibroblasts in the stroma were likely associated with a poor response to NAC. The TS-score has the potential to better stratify breast cancer patients in NAC settings.
RESUMO
Epithelial-mesenchymal transition (EMT) inducing transcription factor TWIST1 plays a vital role in cancer metastasis. How the tumor-suppressive E3 ligase, speckle-type POZ protein (SPOP), regulates TWIST1 in breast cancer remains unknown. In this study, we report that SPOP physically interacts with, ubiquitinates, and destabilizes TWIST1. SPOP promotes K63-and K48-linked ubiquitination of TWIST1, predominantly at K73, thereby suppressing cancer cell migration and invasion. Silencing SPOP significantly enhances EMT, which accelerates breast cancer cell migration and invasiveness in vitro and lung metastasis in vivo. Clinically, SPOP is negatively correlated with the levels of TWIST1 in highly invasive breast carcinomas. Reduced SPOP expression, along with elevated TWIST1 levels, is associated with poor prognosis in advanced breast cancer patients, particularly those with metastatic triple-negative breast cancer (TNBC). Taken together, we have disclosed a new mechanism linking SPOP to TWIST1 degradation. Thus SPOP may serve as a prognostic marker and a potential therapeutic target for advanced TNBC patients.
RESUMO
We report a case of combined large cell neuroendocrine carcinoma of the lung associated with low-grade fetal adenocarcinoma (L-FLAC) without ß-catenin mutation in exon 3. A 33-year-old man presented at the hospital with a more than 5-month history of cough with no obvious cause. Computed tomography revealed a large, solid, round mass located in the upper lobe of the right lung. Microscopic examination showed two tumor components: large cell neuroendocrine carcinoma and low-grade fetal adenocarcinoma. Immunohistochemistry ofthe fetal adenocarcinoma showed abnormal nuclear/cytoplasmic expression of ß-catenin, but no exon 3 mutation in ß-catenin. Our findings provide further insight into the pathologic mechanism of FLAC.
RESUMO
Breast mucoepidermoid carcinoma (MEC) is clinically rare, with an estimated incidence of 0.2-0.3% of all primary breast tumors. To date, only 41 cases have been reported in the literature. Herein, we present a case of breast MEC diagnosed at our hospital. The clinicopathologic features were preliminarily discussed by reviewing the literature. A 42-year-old Chinese woman presented with a lump in her right breast that was detected approximately three months prior. A microscopic examination showed that the breast MEC was composed of different proportions of mucinous cells, intermediate cells, and epidermoid cells. Most mucinous cells were positive for cytokeratin 7, while the epidermoid and intermediate cells were positive for p63 and cytokeratin 5/6. All tumor cells were negative for other myoepithelial markers, such as calponin. Tumor cells did not express estrogen, progesterone, or the HER-2/neu protein. After the patient underwent mastectomy, she was diagnosed with a low-grade mucoepidermoid carcinoma based on the clinical, histologic, and immuno-phenotypic characteristics. Our findings provide further insight into the pathologic mechanism of MEC, as correct diagnosis is essential for patient management.
RESUMO
Trillium tschonoskii Maxim (TTM), a traditional Chinese medicine, has been demonstrated to have a potent anti-tumor effect. Recently, polyphyllin VI (PPVI), a main saponin isolated from TTM, was reported by us to significantly suppress the proliferation of non-small cell lung cancer (NSCLC) via the induction of apoptosis and autophagy in vitro and in vivo. In this study, we further found that the NLRP3 inflammasome was activated in PPVI administrated A549-bearing athymic nude mice. As is known to us, pyroptosis is an inflammatory form of caspase-1-dependent programmed cell death that plays an important role in cancer. By using A549 and H1299 cells, the in vitro effect and action mechanism by which PPVI induces activation of the NLRP3 inflammasome in NSCLC were investigated. The anti-proliferative effect of PPVI in A549 and H1299 cells was firstly measured and validated by MTT assay. The activation of the NLRP3 inflammasome was detected by using Hoechst33324/PI staining, flow cytometry analysis and real-time live cell imaging methods. We found that PPVI significantly increased the percentage of cells with PI signal in A549 and H1299, and the dynamic change in cell morphology and the process of cell death of A549 cells indicated that PPVI induced an apoptosis-to-pyroptosis switch, and, ultimately, lytic cell death. In addition, belnacasan (VX-765), an inhibitor of caspase-1, could remarkably decrease the pyroptotic cell death of PPVI-treated A549 and H1299 cells. Moreover, by detecting the expression of NLRP3, ASC, caspase-1, IL-1ß, IL-18 and GSDMD in A549 and h1299 cells using Western blotting, immunofluorescence imaging and flow cytometric analysis, measuring the caspase-1 activity using colorimetric assay, and quantifying the cytokines level of IL-1ß and IL-18 using ELISA, the NLRP3 inflammasome was found to be activated in a dose manner, while VX-765 and necrosulfonamide (NSA), an inhibitor of GSDMD, could inhibit PPVI-induced activation of the NLRP3 inflammasome. Furthermore, the mechanism study found that PPVI could activate the NF-κB signaling pathway via increasing reactive oxygen species (ROS) levels in A549 and H1299 cells, and N-acetyl-L-cysteine (NAC), a scavenger of ROS, remarkably inhibited the cell death, and the activation of NF-κB and the NLRP3 inflammasome in PPVI-treated A549 and H1299 cells. Taken together, these data suggested that PPVI-induced, caspase-1-mediated pyroptosis via the induction of the ROS/NF-κB/NLRP3/GSDMD signal axis in NSCLC, which further clarified the mechanism of PPVI in the inhibition of NSCLC, and thereby provided a possibility for PPVI to serve as a novel therapeutic agent for NSCLC in the future.
RESUMO
OBJECTIVE: To observe the effects of Fuhuang Shengji Yuchuang (FHSJYC) Ointment, a compound traditional Chinese herbal medicine, on the expressions of types I and III collagens in granulation tissue of wound in rats with diabetes. METHODS: Fifty-four male Wistar rats were randomly divided into three groups: wound control group, normal saline (NS) group and FHSJYC Ointment group. Diabetes was induced by injection of 1.5% alloxan and oral gavage of 5% glucose, and skin wound was made in rats of the NS group and the FHSJYC Ointment group. Skin wounds of the rats in the FHSJYC Ointment group were treated with FHSJYC Ointment gauze dressing, while those in the NS group were treated with NS gauze dressing once daily. The rats were executed in turn on the third day and the eleventh day of the treatment, and the changes of the content of types I and III collagens in the wound granulation tissue were observed by immunohistochemical technology. RESULTS: Compared with the NS group, the wound closure index in the FHSJYC Ointment group was increased (P<0.05). After 3-day treatment, the expression of type I collagen showed no significant differences among the three groups, while the expression of type III collagen in the FHSJYC Ointment group was higher than that in the NS group (P<0.05), similar with that in the wound control group. After 11-day treatment, the expressions of both types I and type III collagens in the FHSJYC Ointment group were higher than those in the NS group (P<0.05), similar with those in the wound control group. CONCLUSION: FHSJYC Ointment can affect the process of wound healing by promoting and regulating the expressions of types I and III collagens.
Assuntos
Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Diabetes Mellitus/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Tecido de Granulação/metabolismo , Animais , Masculino , Ratos , Ratos Wistar , Cicatrização/efeitos dos fármacosRESUMO
The purpose of this report is to determine the clinicopathological and immuno-phenotypical characteristics of myoid hamartoma of the breast (MHB). The clinical data, histological morphology, and immunohistochemical results of 2 patients diagnosed with MHB were analyzed, and 15 cases of MHB reported in China were reviewed. Both patients were female, aged 28 and 35 years old, and their lesions were located in the upper outer quadrant of the left breast and the right breast respectively. The lesions measured 3 cm × 3 cm × 2.5 cm and 6.5 cm × 6 cm × 4.5 cm. A gross examination indicated a grayish solid block with clear boundaries. A microscopic examination showed different proportions of ducts and acini, beam myoid cells, adipose tissue, and fibrous stroma. The myoid cell bundles of both specimens were positive for vimentin, SMA, h-caldesmon and desmin, but negative for ER, PR, PCK, s-100, Calponin, and P63. Both cases were confirmed as MHB based on their clinical, histological and immuno-phenotypical characteristics. Our findings provide further insights into the pathological basis of MHB, which can help avoid both misdiagnosis and missed diagnosis.