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1.
Nanotechnology ; 33(23)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35193121

RESUMO

We combined phosphoinositol-3-kinin inhibitor IPI-549 and photodynamic Chlorin e6 (Ce6) on carboxymethyl chitosan to develop a novel drug delivery nanoparticle (NP) system (Ce6/CMCS-DSP-IPI549) and evaluate its glutathione (GSH) sensitivity and targeting ability for breast cancer treatment. The NPs were spherical with a uniform size of 218.8 nm, a stable structure over 7 days. The maximum encapsulation efficiency was 64.42%, and NPs drug loading was 8.05%. The NPs released drugs within tumor cells due to their high GSH concentration, while they maintained structural integrity in normal cells, which have low GSH concentration. The cumulative release rates of IPI-549 and Ce6 at 108 h were 70.67% and 40.35% (at GSH 10 mM) and 8.11% and 2.71% (at GSH 2µM), respectively. The NPs showed a strong inhibitory effect on 4T1 cells yet did not affect human umbilical vein endothelial cells (HUVECs). After irradiation by a 660 nm infrared laser for 72 h, the survival rate of 4T1 cells was 15.51%. Cellular uptake studies indicated that the NPs could accurately release drugs into tumor cells. In addition, the NPs had a good photodynamic effect and promoted the release of reactive oxygen species to damage tumor cells. Overall, the combination therapy of IPI-549 and Ce6 is safe and effective, and may provide a new avenue for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Clorofilídeos , Nanopartículas , Fotoquimioterapia , Porfirinas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Clorofilídeos/uso terapêutico , Células Endoteliais/patologia , Feminino , Glutationa , Humanos , Isoquinolinas , Nanopartículas/química , Fármacos Fotossensibilizantes , Porfirinas/química , Pirazóis , Pirimidinas
2.
Clin. transl. oncol. (Print) ; 24(7): 1290-1310, julio 2022. ilus
Artigo em Inglês | IBECS | ID: ibc-203829

RESUMO

Bone metastases are very common complications associated with certain types of cancers that frequently negatively impact the quality of life and functional status of patients; thus, early detection is necessary for the implementation of immediate therapeutic measures to reduce the risk of skeletal complications and improve survival and quality of life. There is no consensus or universal standard approach for the detection of bone metastases in cancer patients based on imaging. Endorsed by the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) a group of experts met to discuss and provide an up-to-date review of our current understanding of the biological mechanisms through which tumors spread to the bone and describe the imaging methods available to diagnose bone metastasis and monitor their response to oncological treatment, focusing on patients with breast and prostate cancer. According to current available data, the use of next-generation imaging techniques, including whole-body diffusion-weighted MRI, PET/CT, and PET/MRI with novel radiopharmaceuticals, is recommended instead of the classical combination of CT and bone scan in detection, staging and response assessment of bone metastases from prostate and breast cancer.


Assuntos
Humanos , Masculino , Feminino , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Próstata , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Qualidade de Vida , Compostos Radiofarmacêuticos
3.
Clin. transl. oncol. (Print) ; 24(7): 1395-1402, julio 2022.
Artigo em Inglês | IBECS | ID: ibc-203838

RESUMO

PurposeTumor-associated macrophages (TAM) may participate to antitumor activity of anti-HER2-targeted therapies (Pertuzumab, Trastuzumab) in breast cancers harbouring HER-2 overexpression through antibody-dependent phagocytosis. Additive antitumor effect of concurrent cytotoxic chemotherapies, including Paclitaxel, may be counterbalanced by alteration in TAM infiltrate. The aim of this study is to evaluate the role of TAM in tumor response to anti-HER2-targeted therapies and chemotherapy in an experimental model of HER2-amplified breast cancer.MethodsA xenograft mouse model was built by subcutaneous injection of the SKBR-3 human HER2-amplified breast cancer cell line in Hu-CD34+ mice. Animals were randomized to receive weekly administration of Cremophor (control), Trastuzumab+Pertuzumab (TP), and Paclitaxel+Trastuzumab+Pertuzumab (PTP) with or without macrophage depletion with clodronate (C). At week 4, mice were euthanised and tumors were harvested for immunohistochemical analysis of TAM infiltration (RBP-J CD163 and CD68 for M1, M2, and overall TAM, respectively).ResultsTumor size was significantly lower in mice treated with TP, PTP, and PTP+C as compared to control, while no meaningful difference was observed in the TP+C arm. Analysis of TAM infiltrate showed significantly lower CD68 and CD163 expression in PTP, TP+C, and PTP+C as compared to TP and control arm. RBP-J expression was significantly decreased in mice treated with clodronate depletion.ConclusionsActivity of TP is modulated by TAM infiltrate, that is inhibited by concurrent administration of Paclitaxel. To enhance the effect of anti-HER2-targeted therapies and minimize chemotherapy-related side effects, modulation of TAM should be considered in novel therapeutic combinations.


Assuntos
Humanos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ácido Clodrônico/uso terapêutico , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Camundongos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico
5.
Sci Rep ; 12(1): 9495, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681031

RESUMO

Breast cancer is the most common cancer type among women worldwide. The majority of breast cancer expresses estrogen receptor (ER) and endocrine therapy is a standard treatment of ER-positive breast cancer. However, development of the therapy resistance is still a major challenge and thus new therapeutic approaches are needed. Here we show that an RNA-binding protein, PSPC1, play a crucial role in ER-positive breast cancer growth through post-transcriptional gene regulation. We showed that siRNA-mediated PSPC1 silencing suppressed the proliferation of ER-positive breast cancer cells. Strong immunoreactivity (IR) of PSPC1 was correlated with poor prognosis for ER-positive breast cancer patients. Using immunoprecipitation, RNA-immunoprecipitation (RIP) and quantitative PCR (qPCR) experiments, we showed that PSPC1 interacted with PSF and was involved in post-transcriptional regulation of PSF target genes, ESR1 and SCFD2. Strong SCFD2 IR was correlated with poor prognosis for ER-positive breast cancer patients and combinations of PSPC1, PSF, and SCFD2 IRs were potent prognostic factors. Moreover, we identified DDIAS and MYBL1 as SCFD2 downstream target genes using microarray analysis, and finally showed that SCFD2 silencing suppressed tamoxifen-resistant breast tumor growth in vivo. These results indicated that PSPC1 and SCFD2 axis could be a promising target in the clinical management of the disease.


Assuntos
Neoplasias da Mama , Receptor alfa de Estrogênio , Proteínas de Ligação a RNA , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Hormônios , Humanos , Prognóstico , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/metabolismo , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico
6.
Nat Genet ; 54(6): 850-860, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35681052

RESUMO

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Genômica , Humanos , Recidiva Local de Neoplasia/genética
7.
Biomed Res Int ; 2022: 4239500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692593

RESUMO

A large number of facts have shown that epigenetic modification and metabolic reprogramming represented by noncoding RNA play an important role in the invasion and metastasis of breast cancer, but the mechanism is not clear. The purpose of our study is to find a new biomarker of breast cancer and to provide a new perspective for regulating glucose metabolism and aerobic glycolysis of BC. In this paper, by downregulating C-myc protein, our team found that the expression of long-chain noncoding RNATSPAR-AS2 was significantly downregulated. However, the expression of long-chain noncoding RNASPAR-AS2 in BC is relatively high, and the prognosis is poor. TSPEAR-AS2 can promote the malignant phenotype of BC cells, including proliferation, apoptosis, invasion and metastasis, and glycolysis. At the same time, TSPEAR-AS2 can also upregulate the expression of GLUT1, an important regulator of glycolysis, thus promoting the metabolic reprogramming of BC. Molecular mechanism experiments show that TSPEAR-AS2 may promote the expression of GLUT1 by participating in IGF2BP2 modified by the GLUT1 gene. Our results suggest that the C-myc/TSPEAR-AS2/GLUT1 axis promotes the invasion and metastasis of BC by inducing glucose metabolism reprogramming. However, more phenotypic and molecular mechanism results need to be further verified.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glicólise/genética , Humanos , MicroRNAs/genética , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética
8.
J Exp Clin Cancer Res ; 41(1): 203, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701840

RESUMO

BACKGROUND: Breast cancer is the leading female cancer type and the cause of cancer-related mortality worldwide. Adipocytes possess important functions of energy supply, metabolic regulation, and cytokine release, and are also the matrix cell that supports mammary gland tissue. In breast cancer tumor microenvironment (TME), adipocytes are the prominent stromal cells and are implicated in inflammation, metastatic formation, metabolic remodeling, and cancer susceptibility. MAIN BODY: It is well-established that adipocyte secretome is a reservoir engaged in the regulation of tumor cell behavior by secreting a large number of cytokines (IL-6, IL-8, and chemokines), adipokines (leptin, adiponectin, autotaxin, and resistin), lipid metabolites (free fatty acids and ß-hydroxybutyrate), and other exosome-encapsulated substances. These released factors influence the evolution and clinical outcome of breast cancer through complex mechanisms. The progression of breast cancer tumors revolves around the tumor-adipose stromal network, which may contribute to breast cancer aggressiveness by increasing the pro-malignant potential of TME and tumor cells themselves. Most importantly, the secretome alterations of adipocytes are regarded as distinctly important targets for breast cancer diagnosis, treatment, and drug resistance. CONCLUSION: Therefore, this review will provide a comprehensive description of the specific adipocyte secretome characteristics and interactions within TME cell populations, which will enable us to better tailor strategies for tumor stratification management and treatment.


Assuntos
Neoplasias da Mama , Adipócitos/patologia , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Neoplasias da Mama/patologia , Citocinas/metabolismo , Feminino , Humanos , Microambiente Tumoral
9.
Nanoscale ; 14(23): 8474-8483, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35661186

RESUMO

Immunomagnetic nanoparticles (IMNs) have been widely developed as a detection tool to isolate rare circulating tumor cells (CTCs) from whole blood as a potential method for early cancer diagnosis, metastasis examination, and treatment guidance. However, a spontaneous interaction between nanoparticles and proteins results in the formation of a protein corona that reduces the performance of IMNs when they enter body fluids. To address this issue, the protein corona was precoated onto magnetic nanoparticles (C-MNs), and then their surfaces were conjugated with an immuno-antibody. The adsorption of proteins on C-MNs was decreased 6-fold and non-specific cell binding was reduced 5-fold, compared with magnetic nanoparticles (MNs). Furthermore, the immuno-antibody functionalized C-MNs (IC-MNs) maintained highly specific CTC capture performance when exposed to blood plasma. By using artificial spiked blood samples, IC-MNs exhibited 90.2% CTC isolation efficiency, compared with 60.3% by using IMNs. IC-MNs also successfully captured CTCs with high purity in 24 out of 26 female breast cancer patient blood samples. This work demonstrated that a novel preformed protein corona strategy can provide a useful clinically applicable diagnostic tool.


Assuntos
Neoplasias da Mama , Nanopartículas , Células Neoplásicas Circulantes , Coroa de Proteína , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Separação Celular , Feminino , Humanos , Separação Imunomagnética/métodos , Células Neoplásicas Circulantes/metabolismo
10.
J Investig Med High Impact Case Rep ; 10: 23247096221105249, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712858

RESUMO

Postmenopausal patients with metastatic breast cancer (mBC) may live years with their disease on therapies with minimal toxicities but they will eventually progress on first-line therapy. For those eligible for second-line therapy, PIK3CA mutation testing is recommended in estrogen receptor-positive, her2-negative disease. If present, alpelisib, a PI3K inhibitor, has been shown to improve progression-free survival. Hyperglycemia is a common side effect of alpelisib. We describe a case of diabetic ketoacidosis (DKA) necessitating treatment in the intensive care unit (ICU) in a woman with type 2 diabetes mellitus (T2DM) started on alpelisib. A 76-year-old female with diet-controlled T2DM and mBC was placed on second-line treatment with alpelisib after progression on first-line therapy. After more than 2 weeks of treatment, the patient presented to the emergency department with nausea and vomiting. Lab results showed DKA and she was admitted to the ICU for further management. This case highlights the need for a multidisciplinary approach to caring for patients who are started on a PI3K inhibitor. We propose 5 guidelines to prevent hyperglycemia in those started on apelisib: (1) strict criteria for initiating alpelisib, (2) understand the steps needed to prevent hyperglycemia, (3) get help from a multidisciplinary team, (4) act immediately when hyperglycemia is noted, and (5) record blood glucose values. By implementing these steps, we hope to prevent critical hyperglycemic episodes in vulnerable patients on alpelisib.


Assuntos
Neoplasias da Mama , Diabetes Mellitus Tipo 2 , Hiperglicemia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hiperglicemia/tratamento farmacológico , Fosfatidilinositol 3-Quinases/uso terapêutico , Receptor ErbB-2 , Tiazóis
11.
Carbohydr Polym ; 291: 119554, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35698382

RESUMO

Efficient delivery systems for co-delivery of P-glycoprotein (P-gp) inhibitors and chemotherapeutic drugs are essential for inhibiting multi-drug resistance (MDR) breast cancers. Herein, we present a multi-functional carboxymethyl chitosan (CMC) based core-shell nanoplatform to co-deliver MDR1 gene-silenced small interfering RNA (siMDR1) and doxorubicin (DOX) for optimal combinatorial therapy. DOX is linked to CMC through a disulfide bond to model redox-responsive prodrug (CMC-DOX) as the inner core. siMDR1 is encapsulated in oligoethylenimine (OEI), which is electrostatically adsorbed on CMC-DOX as the pH-responsive sheddable shielding shell. AS1411 aptamer and GALA peptide functionalised hyaluronic acid (AHA/GHA) are provided on the surface for tumour-targeting and endo/lysosomal escape. The nanoplatform could stepwise release payloads with acid/redox triggered fashion. AHA effectively improves nanoplatform intracellular uptake and tumour accumulation. GHA facilitates cargos escape from endo/lysosomes to cytoplasm. The multi-functional nanoplatform provides 86.3 ± 2.2% siMDR1 gene silencing and significantly downregulates P-gp expression. Moreover, it ensures 55.7 ± 1.6% MCF-7/ADR cell apoptosis at a low concentration of DOX (30 µg/mL) in vitro and performs synergistic therapeutic effects suppressing tumour growth in vivo. Overall, the multi-functional CMC-based biopolymers can be efficient siRNA/drug co-delivery carriers for cancer chemotherapy.


Assuntos
Neoplasias da Mama , Quitosana , Nanopartículas , Neoplasias da Mama/patologia , Quitosana/farmacologia , Doxorrubicina , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Células MCF-7 , Nanopartículas/química , RNA Interferente Pequeno/química
12.
Comput Math Methods Med ; 2022: 8066289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693263

RESUMO

This research was aimed at investigating the role of ultrasound elastography (UE) in evaluating the properties of axillary lymph nodes in breast cancer and exploring the influencing factors of lymph node metastasis in breast cancer patients. Routine ultrasonography (US) and UE were performed for 160 breast cancer patients. 80 cases were in the group with lymph node metastasis, and the other 80 were in the nonlymph node metastasis group. The sensitivity, specificity, and accuracy of the two ultrasound examinations were compared, the receiver-operator characteristic (ROC) curves were drawn, and the influencing factors of lymph node metastasis were analyzed. The sensitivity, specificity, and accuracy of UE in diagnosing axillary lymph nodes of breast cancer were 97.22%, 95.45%, and 96.25%, respectively, which were markedly higher than those of routine US (P < 0.05). Cortical thickness, blood flow grade, blood flow type, and elasticity score had a greater impact on axillary lymph node metastasis of breast cancer. When cortical thickness ≥ 3 cm, blood flow was of 2-3 grades, blood flow was the peripheral/mixed type, and elasticity score was 3-4 points, these became risk factors for lymph node metastasis in breast cancer patients. UE was effective in diagnosing the property of lymph nodes and could evaluate lymph node metastasis in breast cancer patients. It had a good clinical value and was worthy of popularization and application.


Assuntos
Neoplasias da Mama , Técnicas de Imagem por Elasticidade , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia
13.
J Surg Oncol ; 126(1): 57-67, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35689588

RESUMO

The Brazilian Society of Surgical Oncology organized a group of oncological surgeons to discuss surgical aspects associated with locally advanced breast carcinoma. This article reviews the indications, different surgeries (thoracoabdominal or myocutaneous flaps), and associated complications. It discusses special conditions such as invasion of the chest wall and interscapular thoracic disarticulation. It makes recommendations based on the literature regarding clinical findings, tumor conditions, response to neoadjuvant therapy, choice of flaps in surgery, and tumor biology.


Assuntos
Neoplasias da Mama , Oncologia Cirúrgica , Parede Torácica , Brasil , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/cirurgia , Retalhos Cirúrgicos , Parede Torácica/cirurgia
14.
Cell Host Microbe ; 30(6): 875-877, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35679824

RESUMO

In a recent Cell paper, Fu et al. bridge descriptive cancer microbiome research with mechanistic and functional insight. With savvy use of antibiotics, the authors demonstrate divergent roles of the gut and intratumoral microbiome in breast tumor growth and metastasis, providing potentially actionable tools for better breast cancer management.


Assuntos
Neoplasias da Mama , Melanoma , Microbiota , Neoplasias Cutâneas , Neoplasias da Mama/patologia , Feminino , Humanos
15.
Integr Biol (Camb) ; 14(3): 62-75, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35652485

RESUMO

Macrophages are white blood cells that play disparate roles in homeostasis and immune responses. They can reprogram their phenotypes to pro-inflammatory (M1) or anti-inflammatory (M2) states in response to their environment. About 8-15% of the macrophage transcriptome has circadian oscillations, including genes closely related to their functioning. As circadian rhythms are associated with cellular phenotypes, we hypothesized that polarization of macrophages to opposing subtypes might differently affect their circadian rhythms. We tracked circadian rhythms in RAW 264.7 macrophages using luminescent reporters. Cells were stably transfected with Bmal1:luc and Per2:luc reporters, representing positive and negative components of the molecular clock. Strength of rhythmicity, periods and amplitudes of time series were assessed using multiple approaches. M1 polarization decreased amplitudes and rhythmicities of Bmal1:luc and Per2:luc, but did not significantly affect periods, while M2 polarization increased periods but caused no substantial alterations to amplitudes or rhythmicity. As macrophage phenotypes are also altered in the presence of cancer cells, we tested circadian effects of conditioned media from mouse breast cancer cells. Media from highly aggressive 4T1 cells caused loss of rhythmicity, while media from less aggressive EMT6 cells yielded no changes. As macrophages play roles in tumors, and oncogenic features are associated with circadian rhythms, we tested whether conditioned media from macrophages could alter circadian rhythms of cancer cells. Conditioned media from RAW 264.7 cells resulted in lower rhythmicities and periods, but higher amplitudes in human osteosarcoma, U2OS-Per2:luc cells. We show that phenotypic changes in macrophages result in altered circadian characteristics and suggest that there is an association between circadian rhythms and macrophage polarization state. Additionally, our data demonstrate that macrophages treated with breast cancer-conditioned media have circadian phenotypes similar to those of the M1 subtype, and cancer cells treated with macrophage-conditioned media have circadian alterations, providing insight to another level of cross-talk between macrophages and cancer.


Assuntos
Ritmo Circadiano , Macrófagos , Animais , Neoplasias da Mama/patologia , Meios de Cultivo Condicionados , Feminino , Macrófagos/citologia , Camundongos , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Células RAW 264.7
16.
Medicina (Kaunas) ; 58(6)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35743961

RESUMO

Background and objectives: Breast cancer is the most commonly diagnosed cancer in women and its mortality is increasing. Therefore, research to improve treatment is of paramount importance. One method of treatment is photodynamic therapy. Photodynamic therapy selectively stimulates apoptosis in photosensitizer-treated neoplastic breast cells as a result of cytotoxic singlet oxygen generation via collisions between triplet excited state photosensitizer and triplet ground state oxygen upon tissue irradiation. The aim of this study was to evaluate the effects of photodynamic action on cancerous breast tissue samples as a model of photodynamic therapy. Materials and Methods: Breast cancer tissue samples were obtained from post-operative material and the patterns of histopathological changes in breast cancer tissue before and after photodynamic action on post-chemotherapy tissue were evaluated. Excised tissue samples were obtained from 48 female breast cancer patients who had previously undergone chemotherapy. Breast cancer tissues for this study were taken from macroscopically visible tumors larger than 10 mm. Histopathological analysis was performed to evaluate any morphological changes prior to and after photodynamic action on the post-chemotherapy tissue samples. Eighteen breast cancer tissue samples were analyzed before chemotherapy, fifteen after chemotherapy, and fifteen samples were analyzed after chemotherapy and application of photodynamic action. The photosensitizer Rose Bengal was applied to the samples subjected to photodynamic action. Results: Photodynamic action on post-chemotherapy neoplastic tissue showed histological changes under a light microscope. The results showed that morphological changes in breast cancer tissues after chemotherapy and photodynamic action were dependent on the concentration of Rose Bengal. In all cases, follow-up imaging showed tumor shrinkage of an average of 35% from baseline size. Conclusions: Histopathological examination revealed photosensitizer-concentration-dependent changes after photodynamic action in excised post-chemotherapy tissue. The effects of photodynamic action observed in this study suggest that the application of photodynamic therapy after chemotherapy can aid in breast cancer cell eradication.


Assuntos
Neoplasias da Mama , Fotoquimioterapia , Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Rosa Bengala/uso terapêutico
17.
Diagn Interv Radiol ; 28(3): 217-225, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35748203

RESUMO

PURPOSE We aimed to evaluate digital breast tomosynthesis (DBT)-based radiomics in the differentiation of benign and malignant breast lesions in women. METHODS A total of 185 patients who underwent DBT scans were enrolled between December 2017 and June 2019. The features of handcrafted and deep learning-based radiomics were extracted from the tumoral and peritumoral regions with different radial dilation distances outside the tumor. A 3-step method was used to select discriminative features and develop the radiomics signature. Discriminative clinical factors were identified by univariate logistic regression. The clinical fac- tors with P < .05 were used to build a clinical model with multivariate logistic regression. The radiomics nomogram was developed by integrating the radiomics signature and discriminative clinical factors. Discriminative performance of the radiomics signature, clinical model, nomo- gram, and breast imaging reporting and data system assessment were evaluated and compared with the receiver operating characteristic and decision curves analysis (DCA). RESULTS A total of 2 handcrafted and 2 deep features were identified as the most discriminative features from the peritumoral regions with 2 mm dilation distances and used to develop the radiomics signature. The nomogram incorporating the radiomics signature, age, and menstruation status showed the best discriminative performance with area under the curve (AUC) values of 0.980 (95% CI, 0.960 to 1.000; sensitivity =0.970, specificity =0.946) in the training cohort and 0.985 (95% CI, 0.960 to 1.000; sensitivity = 0.909, specificity = 0.966) in the validation cohort. DCA con- firmed the potential clinical usefulness of our nomogram. CONCLUSION Our results illustrate that the radiomics nomogram integrating the DBT imaging features and clinical factors (age and menstruation status) can be considered as a useful tool in aiding the clinical diagnosis of breast cancer.


Assuntos
Neoplasias da Mama , Mamografia , Área Sob a Curva , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Nomogramas , Curva ROC , Estudos Retrospectivos
18.
Zhonghua Zhong Liu Za Zhi ; 44(6): 523-530, 2022 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-35754226

RESUMO

Breast cancer is the most common cancer in the world, and 5-year survival rate of metastatic breast cancer is about 20%. The treatment of metastatic breast cancer is mainly chemotherapy, endocrine therapy and targeted therapy. However, after multiline treatment, patients with MBC especially the triple negative breast cancer face the problem of drug resistance. Tumor angiogenesis theory suggests that blocking angiogenesis can inhibit tumor growth and migration. Based on this, angiogenesis treatment strategy is proposed. Antiangiogenic drugs mainly include biological macromolecular drugs targeting vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) and small molecule VEGFR inhibitors. Angiogenesis is known to play a key role in the growth and metastasis of breast cancer. Therefore, anti-angiogenetic therapy has potential in metastatic breast cancer patients. Since the approval of tumor drug indications by NPMA in China is often later than the release of the latest research data, the National Health Commission issued "the guiding principles for the clinical application of new antitumor drugs" in 2020. The principle pointed out that under special circumstances such as the absence of better treatment, medical institutions should manage the usage of drugs that are not clearly defined in the instructions but have evidence-based data. Based on the latest research progress in breast cancer, the consensus writing expert group collated published reports, international academic conferences, conducted analysis, discussion and summary, collected data on the use of small molecule anti-vascular targeting drugs for advanced breast cancer, and formulated "expert consensus on the application of small molecule anti-angiogenic drugs in the treatment of advanced breast cancer" . For clinicians' reference only.


Assuntos
Inibidores da Angiogênese , Neoplasias da Mama , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neoplasias da Mama/patologia , Consenso , Feminino , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Uso Off-Label , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Medicine (Baltimore) ; 101(25): e29371, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35758368

RESUMO

ABSTRACT: Deciding if patients with small (≤1 cm), node-negative, human epidermal growth factor receptor 2 (HER2) positive breast cancer should receive adjuvant systemic therapy remains a challenge. No randomized clinical trials have examined the efficacy of trastuzumab in this setting. This prospective observational study aimed to investigate the choice of adjuvant systemic therapy in clinical practice in China.We prospectively collected data from patients with HER-2 positive breast cancer (less than 1 cm and node negative) patients who underwent breast cancer surgery at Shanxi Provincial People's Hospital Breast Center from January 1, 2017 to December 31, 2019, and retrospectively investigated the association between baseline clinicopathological features and treatment strategy, cardiotoxicity, and disease outcome.Of 168 eligible patients, 102 (60.7%) received adjuvant systemic therapy with trastuzumab (AST+T), 47 (28%) received adjuvant systemic therapy without trastuzumab (AST) and 19 (11.3%) did not receive adjuvant systemic therapy. Multivariate logistic regression analysis demonstrated that age, tumor size and hormone receptor status were significantly associated with treatment choice. Three-year invasive disease-free survival probability was 100%, 97.9% and 89.5% with AST+T, AST, and no therapy, respectively (P < .001).The majority of patients (60.7%) with pT1a-b pN0 HER2 positive breast cancer received adjuvant systemic therapy with trastuzumab, whereas only 11.3% did not receive any adjuvant systemic therapy. Tumor size, age and hormone receptor status influenced treatment choice. The 3-year invasive disease-free survival probability was significantly higher for patients who received adjuvant systemic therapy with trastuzumab compared with those who did not receive adjuvant systemic therapy. Cardiac adverse events were rare.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Hormônios/uso terapêutico , Humanos , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Trastuzumab
20.
Biomater Sci ; 10(13): 3637-3646, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35648436

RESUMO

Despite the great progress in the control of primary tumor growth, metastasis remains the major challenge of breast cancer therapy in clinics, which is highly related to the upregulation of reactive oxygen species (ROS) and overexpression of its relevant pro-survival miR-155 gene. Therefore, we fabricated a poly-antioxidant (FTP) to deliver anti-miR-155 for synergistic treatment of metastatic breast cancer by ROS scavenging and miR-155 inhibition. FTP was synthesized by the polymerization of fluorated-polyethyleneimine (FPEI) and antioxidants (TEMPOL), using a glutathione (GSH) responsive linker for controlled drug release. Notably, the poly-drug strategy could not only promote the tumoral accumulation of small molecular antioxidants but also enhance the transfection efficiency of anti-miR-155 owing to the hydrophobic property of TEMPOL. After synergistic treatment, the NF-κB pathway was significantly blocked, thereby generating strong anti-metastatic ability both in vitro and in vivo. The poly-antioxidant could be a new type of nanoplatform for highly efficient and safe miRNA delivery, which also provides a promising strategy for the synergistic treatment of metastatic breast cancer.


Assuntos
Neoplasias da Mama , MicroRNAs , Antagomirs/uso terapêutico , Antioxidantes/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Glutationa/metabolismo , Humanos , MicroRNAs/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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