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1.
Gan To Kagaku Ryoho ; 48(9): 1133-1137, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34521791

RESUMO

We conducted a questionnaire survey of patients with breast cancer who underwent implantation of a subcutaneous central venous port system for chemotherapy; we aimed to evaluate their satisfaction with the port and difficulties in daily life. Overall, 130 patients with breast cancer who underwent port implantation for chemotherapy between 2016 and 2018 responded to our survey. Although the overall satisfaction was high(78.5%), 82(63.1%)patients reported difficulties in daily life, such as"pain or discomfort,""irritation over the implanted area while wearing a seat belt,"and"unable to wear a bag across their bodies."Some patients(10.8%)responded that these negative factors were associated with difficulties in carrying out social roles. The proportion of patients who understood the explanation provided before port implantation was 80.0%, and the satisfaction of these patients tended to be high(85.6%).


Assuntos
Neoplasias da Mama , Cateterismo Venoso Central , Neoplasias da Mama/tratamento farmacológico , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora , Feminino , Humanos , Satisfação do Paciente , Satisfação Pessoal , Inquéritos e Questionários
2.
Gan To Kagaku Ryoho ; 48(9): 1153-1155, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34521794

RESUMO

A 44-years-old woman who underwent bilateral mastectomy was treated with chemotherapy after axillary lymph nodes and liver metastases recurrence. She was referred to our hospital for BRCA1/2 germline test and the test revealed BRCA2 pathogenic mutation. Before the administration of olaparib as the fourth-line therapy, liver dysfunction, caused by extensive liver metastasis, was observed. The liver damage improved, and tumor markers decreased immediately as shown in the blood test and CT examination results after 2 months; indicating marked reduction of liver metastasis. In the OlympiAD trial, the patients received olaparib as either the first-, second- or third-line treatment; however, few data on the efficacy of olaparib in the patients, as a late line treatment, were reported. In this article, we report a case of a woman in whom olaparib was used as the fourth-line treatment for metastatic recurrent breast cancer. A high therapeutic effect was obtained and the quality of life has been maintained in her for the past 1 year.


Assuntos
Neoplasias da Mama , Adulto , Neoplasias da Mama/tratamento farmacológico , Feminino , Mutação em Linhagem Germinativa , Humanos , Mastectomia , Recidiva Local de Neoplasia , Ftalazinas , Piperazinas , Qualidade de Vida
3.
Talanta ; 235: 122796, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517654

RESUMO

Bone metastasis of malignant solid tumors has become one of the most serious complications, especially in breast cancer, which was particularly challenging for early detection and treatment in clinical practice. In this work, we reported a new fluorescently labeled bisphosphonate for bone metastasis detection of breast cancer. The designed probes were based on Rhodamine B and bisphosphonate as recognition group, which can specifically target hydroxyapatite (HA) existed in bone tissue. After the osteoclasts were adsorbed on the bone surface, the surrounding microenvironment was acidified, causing the HA to locally dissolve. The probe bound to the HA was then released, and realized the fluorescence turn on under acidic conditions. In vitro experiments showed that G0 was more excellent than G2 owing to shorter connecting arm. Subsequently, we proved that G0 could combine with HA rapidly and exhibit excellent response in solid state. More importantly, we established a model of bone metastasis with MDA-MB-231 cells which was similar to the clinical cases and evaluated the theranostics value of G0 prospectively, which provide the potential application prospect in clinical.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Neoplasias Ósseas/tratamento farmacológico , Osso e Ossos , Neoplasias da Mama/tratamento farmacológico , Difosfonatos , Feminino , Humanos , Osteoclastos , Medicina de Precisão , Microambiente Tumoral
4.
Mater Sci Eng C Mater Biol Appl ; 128: 112258, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474818

RESUMO

A novel polyelectrolyte nanocarrier was synthesized via layer-by-layer self-assembly of polycationic and polyanionic chains. The nanocarrier is composed of polyglutamate grafted chitosan core, dextran sulfate as a complexing agent, and polyethyleneimine shell decorated with folic acid. This polyelectrolyte complex has unique physicochemical properties so that the core is considered as an efficient carrier for LTX-315 and melittin peptides, and the shell is suitable for delivery of miR-34a. The spherical nanocarriers with an average size of 123 ± 5 nm and a zeta potential of -36 ± 1 mV demonstrated controlled-release of gene and peptides ensured a synergistic effect in establishing multiple cell death pathways on chemoresistance human breast adenocarcinoma cell line, MDA-MB-231. In vitro cell viability assays also revealed no cytotoxicity for the nanocarriers, and an IC50 of 15 µg/mL and 150 µg/mL for melittin and LTX-315, respectively, after 48 h, whereas co-delivery of melittin with miR-34a increased smart death induction by 54%.


Assuntos
Neoplasias da Mama , Quitosana , MicroRNAs/administração & dosagem , Nanopartículas , Neoplasias da Mama/tratamento farmacológico , Morte Celular , Linhagem Celular Tumoral , Feminino , Humanos , Meliteno/farmacologia , MicroRNAs/genética , Oligopeptídeos , Polieletrólitos
5.
Mater Sci Eng C Mater Biol Appl ; 128: 112305, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474856

RESUMO

In spite of established evidence of the synergistic combination of hydrophobic anticancer molecule and microRNA for breast cancer treatment, their in vivo delivery has not been realized owing to their instability in the biological milieu and varied physicochemical properties. The present work reports folate targeted hybrid lipo-polymeric nanoplexes for co-delivering DTX and miR-34a. These nanoplexes exhibited a mean size of 129.3 nm with complexation efficiency at an 8:1 N/P ratio. The obtained nanoplexes demonstrated higher entrapment efficiency of DTX (94.8%) with a sustained release profile up to 85% till 48 h. Further, an improved transfection efficiency in MDA-MB-231 and 4T1 breast cancer cells was observed with uptake primarily through lipid-raft and clathrin-mediated endocytosis. Further, nanoplexes showed improved cytotoxicity (~3.5-5 folds), apoptosis (~1.6-2.0 folds), and change in expression of apoptotic genes (~4-7 folds) compared to the free treatment group in breast cancer cells. In vivo systemic administration of FA-functionalized DTX and FAM-siRNA-loaded nanoplexes showed an improved area under the curve (AUC) as well as circulation half-life compared to free DTX and naked FAM-labelled siRNA. Acute toxicity studies of the cationic polymer showed no toxicity at a dose equivalent to 10 mg/kg based on the hematological, biochemical, and histopathological examination.


Assuntos
Antineoplásicos , Neoplasias da Mama , MicroRNAs/administração & dosagem , Nanopartículas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Docetaxel/farmacologia , Portadores de Fármacos/uso terapêutico , Feminino , Ácido Fólico , Humanos , MicroRNAs/genética , Polímeros/uso terapêutico
6.
Anticancer Res ; 41(9): 4535-4542, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475080

RESUMO

BACKGROUND/AIM: Due to the SARS-CoV-2 pandemic, many scientific committees proposed neoadjuvant therapy (NACT) bridging treatment as a novel strategy and indication. The aim of the study was to evaluate the impact of COVID-19 pandemic on breast cancer patients undergoing NACT. PATIENTS AND METHODS: All breast cancer patients referred to two Breast Units during COVID-19-pandemic were enrolled. RESULTS: Out of 814 patients, 43(5.3%) were enrolled in the COVID-19-group and compared with 94 (7.9%) similar Pre-COVID-19 patients. We observed a reduction in the number of patients undergoing NACT, p=0.0019. No difference was reported in terms of clinical presentation, indications, and tumor response. In contrast, a higher number of vascular adverse events was reported (6.9% vs. 0% p=0.029). Immediate breast cancer reconstructions following invasive surgery suffered a significant slowdown (5.9% vs. 47.7%, p=0.019). CONCLUSION: COVID-19 caused a reduction in the number of patients undergoing NACT, with no changes in terms of indications, clinical presentation, and tumor response. Furthermore, there was an increased incidence of vascular events.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , COVID-19/epidemiologia , Mamoplastia/estatística & dados numéricos , Terapia Neoadjuvante/estatística & dados numéricos , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , COVID-19/complicações , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Pandemias , Estudos Retrospectivos , Resultado do Tratamento
7.
Medicine (Baltimore) ; 100(35): e26878, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477121

RESUMO

ABSTRACT: Many free radicles are implicated to activate a number of oncogenic signaling, cause damage to deoxyribonucleic acid and tumor suppressor genes, or promote expression of proto-oncogenes. Reduced level of antioxidants and increases oxidative stress markers are associated with the development of various types of cancer.This prospective study included 60 women who were grouped into equal groups. Patients group included 30 breast cancer women and control group consisting of 30 apparently healthy women. Both groups were compared regarding the serum levels of antioxidants biomarkers (vitamin C, ceruloplasmin, glutathione) and oxidative stress biomarkers, malondialdehyde (MDA), peroxynitrite, and gamma-glutamyl transferase.In regard to the antioxidant biomarkers, there was a significant difference between the patients and the controls regarding the levels of serum ceruloplasmin and glutathione, (P values .000) for each while vitamin C showed no significant correlation (P value .053), while regarding oxidative stress biomarkers, the correlation was significant for both peroxynitrite and MDA (P value .000 and .001) respectively, and not significant for gamma-glutamyl transferase (P value 1.00).Reduced level both ceruloplasmin and glutathione is seen in patients with breast cancer while vitamin C is not associated. Elevated levels of both peroxynitrite and MDA is seen in patients with breast cancer which may be used as serum markers for the early detection of breast cancer.


Assuntos
Antioxidantes/análise , Neoplasias da Mama/tratamento farmacológico , Adulto , Antioxidantes/uso terapêutico , Estudos de Casos e Controles , Correlação de Dados , Feminino , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Prospectivos
8.
Chin J Physiol ; 64(4): 202-209, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34472451

RESUMO

Gamma-linolenic acid (GLA), a natural fatty acid obtained from oils of various vegetables and seeds, has been demonstrated as an anticancer agent. In this work, we investigated the anticancer effects of GLA on breast cancer BT-474 cells. GLA at 30 µM, a concentration reportedly within the range of circulating concentrations in clinical studies, caused apoptotic cell death. GLA caused an elevation in mitochondrial Ca2+ level and a decrease in mitochondrial membrane potential. GLA treatment depleted cyclopiazonic acid (CPA)-sensitive Ca2+ store and triggered substantial Ca2+ influx. Intracellular Ca2+ release triggered by GLA was suppressed by 3 µM xestospongin C (XeC, IP3 receptor-channel blocker) and 100 µM ryanodine (ryanodine receptor-channel blocker), suggesting that the Ca2+ release was via IP3 receptor-channel and ryanodine receptor-channel. Increased expressions of p-eIF2α and CHOP were observed in GLA-treated cells, suggesting GLA-treated cells had increased expressions of p-eIF2α and CHOP, which suggest endoplasmic reticulum (ER) stress. In addition, GLA elicited increased production of reactive oxygen species. Taken together, our results suggest a basal level of GLA induced apoptotic cell death by causing Ca2+ overload, mitochondrial dysfunction, Ca2+ store depletion, ER stress, and oxidative stress. This is the first report to show that GLA caused Ca2+ store depletion and ER stress. GLA-induced Ca2+ store depletion resulted from opening of IP3 receptor-channel and ryanodine receptor-channel.


Assuntos
Neoplasias da Mama , Ácido gama-Linolênico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Feminino , Humanos , Estresse Oxidativo , Ácido gama-Linolênico/metabolismo
9.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479891

RESUMO

Ado-trastuzumab emtansine (T-DM1) is a monoclonal antibody drug conjugate approved for the treatment of HER2-positive breast cancers. Presented here is a case report of a patient who developed fatal pulmonary toxicity in the form of acute eosinophilic pneumonia while undergoing treatment with T-DM1. Prior to beginning T-DM1 therapy, this patient had been treated with two HER2-targeted agents (trastuzumab, pertuzumab) per National Comprehensive Cancer Network (NCCN) guidelines. This case represents a novel presentation of toxicity associated with T-DM1 while perhaps demonstrating additive toxicity associated with multiple lines of HER2 targeted therapies.


Assuntos
Neoplasias da Mama , Maitansina , Eosinofilia Pulmonar , Ado-Trastuzumab Emtansina , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Maitansina/efeitos adversos , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/diagnóstico , Receptor ErbB-2 , Trastuzumab/efeitos adversos
10.
Nanoscale ; 13(34): 14417-14425, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473184

RESUMO

The recurrence and metastasis of tumor after surgery is the main cause of death for patients with breast cancer. Systemic chemotherapy suffered from low delivery efficiency to tumors and the side effects of chemo drugs. Localized chemotherapy using drug-containing implants is an alternative, while the reconstruction of breast tissue is generally considered after chemotherapy, resulting in a second surgery for patients. Here, we describe a strategy using implantable drug-containing polymeric scaffolds to deliver chemo drugs directly to the post-resection site, and simultaneously provide mechanical support and regenerative niche for breast tissue reconstruction. When doxorubicin was loaded in mesoporous silica nanoparticles and subsequently incorporated into polycaprolactone scaffolds (DMSN@PCL), a 9-week sustained drug release was achieved post implantation in mice. The local recurrence of residual tumor after surgery was significantly inhibited within 4 weeks in a post-surgical mouse model bearing xenograft MDA-MB-231 tumor. DMSN@PCL scaffolds exhibited good biocompatibility in mice during the treatment. We believe our strategy holds great promise as an adjuvant localized chemotherapy in clinics for combating post-resection breast cancer recurrence.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Feminino , Humanos , Camundongos , Poliésteres
11.
Rozhl Chir ; 100(6): 271-276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465116

RESUMO

INTRODUCTION: The role of sentinel lymph node biopsy (SLNB) in patients with breast cancer after neoadjuvant chemotherapy (NAC) is currently under discussion. The aim of our study was to determine the false negativity rate (FNR) of SLNB, the accuracy of ultrasound examination in the evaluation of the status of lymph nodes and the accuracy of perioperative cryobiopsy of the sentinel lymph node (SLN). METHODS: Prospective multicentre study, which took place in years 20182020 at three centres in the Czech Republic. A total of 59 patients were evaluated. RESULTS: The FNR of SLNB in the group of patients with cN1 before NAC and ycN0 after NAC was 12.5%. The FNR of perioperative histological examination of the SLN was 38.5%. The FNR of ultrasound examination of axillary lymph nodes in patients after NAC was 35.5%, and the false positivity rate was 16.7%. The incidence of inflammatory complications in our cohort was 3.3%. CONCLUSION: The FNR of SLNB in the group of patients with cN1 before NAC and ycN0 after NAC exceeds the tolerable limit of 10%. The FNR of perioperative histological examination of the SLN is high; definitive histological examination of the SLN may change the original diagnostic-therapeutic plan. Ultrasound examination of the axillary lymph nodes in patients after NAC is a method with high false negativity and positivity and may not correspond with the perioperative finding. The incidence of inflammatory complications in our cohort in patients after NAC is comparable to literature data on the frequency of complications in patients without NAC.


Assuntos
Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Terapia Neoadjuvante , Estudos Prospectivos
12.
Rozhl Chir ; 100(6): 285-294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465118

RESUMO

INTRODUCTION: Neoadjuvant therapy (NT) is one of the possible oncological treatment strategies for breast cancer. Its aim is to achieve down-staging of the tumour in the breast and axilla and thus the possibility of converting mastectomy to a breast-conserving procedure, and also to allow for a less burdensome and more targeted operation of the axillary lymph nodes. The role of the radiologist is to utilise imaging procedures for precise local staging of the malignancy prior to NT, to evaluate the effect of treatment during its course and upon its completion, and to perform restaging of the cancer in the breast and axilla. CASE REPORTS: The authors present three case reports of female patients with breast cancer who underwent neoadjuvant chemotherapy (NCT). They describe the diagnostic procedure and imaging methods used to establish local staging of the cancer prior to treatment, to monitor the disease during the course of treatment, and to perform restaging of the cancer after completing NCT. The radiological response after NCT completion was correlated with the pathological response. CONCLUSION: Correct determination of the extent of the cancer in the breast and axilla by the radiologist before NT and precise histological analysis of the tumour by the pathologist are fundamental for selecting the appropriate treatment for patients at the multidisciplinary breast tumour board.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Axila/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Mastectomia , Estadiamento de Neoplasias , Radiologistas , Biópsia de Linfonodo Sentinela
13.
Breast ; 59: 301-307, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34385028

RESUMO

PURPOSE: To examine clinicodemographic determinants associated with breast cancer survivorship follow-up during COVID-19. METHODS: We performed a retrospective, population-based cohort study including early stage (Stage I-II) breast cancer patients who underwent resection between 2006 and 2018 in a New York City hospital system. The primary outcome was oncologic follow-up prior to and during the COVID-19 pandemic. Secondary analyses compared differences in follow-up by COVID-19 case rates stratified by ZIP code. RESULTS: A total of 2942 patients with early-stage breast cancer were available for analysis. 1588 (54%) of patients had attended follow-up in the year prior to the COVID-19 period but failed to continue to follow-up during the pandemic, either in-person or via telemedicine. 1242 (42%) patients attended a follow-up appointment during the COVID-19 pandemic. Compared with patients who did not present for follow-up during COVID-19, patients who continued their oncologic follow-up during the pandemic were younger (p = 0.049) more likely to have received adjuvant radiation therapy (p = 0.025), and have lower household income (p = 0.031) on multivariate modeling. When patients who live in Bronx, New York, were stratified by ZIP code, there was a modest negative association (r = -0.56) between COVID-19 cases and proportion of patients who continued to follow-up during the COVID-19 period. CONCLUSION: We observed a dramatic disruption in routine breast cancer follow-up during the COVID-19 pandemic. Providers and health systems should emphasize reintegrating patients who missed appointments during COVID-19 back into regular surveillance programs to avoid significant morbidity and mortality from missed breast cancer recurrences.


Assuntos
Neoplasias da Mama/mortalidade , COVID-19/psicologia , Sobreviventes de Câncer/psicologia , Sobrevivência , Adolescente , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , COVID-19/epidemiologia , Estudos de Coortes , Feminino , Hospitais Urbanos , Humanos , Masculino , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Cidade de Nova Iorque/epidemiologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
14.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3249-3256, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396744

RESUMO

Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people's health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Diterpenos , Fenantrenos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Diterpenos/farmacologia , Compostos de Epóxi , Feminino , Humanos , Microambiente Tumoral
15.
Int J Mol Sci ; 22(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34445277

RESUMO

Breast cancer (BC) is the leading cause of death in women all over the world. Currently, combined chemotherapy with two or more agents is considered a promising anti-cancer tool to achieve better therapeutic response and to reduce therapy-related side effects. In our study, we demonstrated an antagonistic effect of cytostatic agent-cisplatin (CDDP) and histone deacetylase inhibitor: cambinol (CAM) for breast cancer cell lines with different phenotypes: estrogen receptor positive (MCF7, T47D) and triple negative (MDA-MB-231, MDA-MB-468). The type of pharmacological interaction was assessed by an isobolographic analysis. Our results showed that both agents used separately induced cell apoptosis; however, applying them in combination ameliorated antiproliferative effect for all BC cell lines indicating antagonistic interaction. Cell cycle analysis showed that CAM abolished cell cycle arrest in S phase, which was induced by CDDP. Additionally, CAM increased cell proliferation compared to CDDP used alone. Our data indicate that CAM and CDDP used in combination produce antagonistic interaction, which could inhibit anti-cancer treatment efficacy, showing importance of preclinical testing.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cisplatino , Antagonismo de Drogas , Inibidores de Histona Desacetilases/farmacologia , Modelos Biológicos , Naftalenos , Pirimidinonas , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Cisplatino/antagonistas & inibidores , Cisplatino/farmacologia , Feminino , Humanos , Células MCF-7 , Naftalenos/antagonistas & inibidores , Naftalenos/farmacologia , Pirimidinonas/antagonistas & inibidores , Pirimidinonas/farmacologia
16.
In Vivo ; 35(5): 2675-2685, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410956

RESUMO

BACKGROUND/AIM: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells. MATERIALS AND METHODS: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays. RESULTS: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G2/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death. CONCLUSION: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.


Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Sobrevivência Celular , Feminino , Humanos , Isoniazida/uso terapêutico , Isoniazida/toxicidade , Células MCF-7 , Espécies Reativas de Oxigênio
17.
Ann Surg Oncol ; 28(10): 5730-5741, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34342757

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer. METHODS: Based on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010-2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0). RESULTS: Of 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson-Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET. CONCLUSIONS: Although the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Hormônios , Humanos , Mastectomia , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Ann Surg Oncol ; 28(10): 5495-5506, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34374914

RESUMO

OBJECTIVE: We aim to delineate the relationship between breast and axillary pathologic complete response (pCR) in patients receiving neoadjuvant chemotherapy for breast cancer. METHODS: We performed a retrospective cohort study of patients with clinical T1-4N0-3M0 breast cancer receiving neoadjuvant chemotherapy followed by surgical therapy at Sunnybrook Health Sciences Centre in Toronto, Canada between 2014 and 2019. Clinicopathologic data were abstracted from the electronic medical record. Women were stratified into receptor subtypes as follows: hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-), HR+/HER2+, HR-/HER2+ and HR-/HER2- (triple negative) and compared with Fisher's exact test. Our primary outcome was to assess the positive predictive value of breast pCR for determining axillary pCR, and vice versa. RESULTS: There were 374 breast cancers, with 109 (29.1%) achieving breast pCR (ypT0/Tis). Amongst node-positive tumours achieving breast pCR, rates of associated axillary pCR (ypN0/0i+) were as follows: HR+/HER2- (2/6, 33.3%), HR+/HER2+ (12/13, 92.3%), HR-/HER2+ (15/17, 88.2%) and triple negative (15/17, 88.2%) (P = 0.02). Conversely, amongst node-positive tumours achieving axillary pCR, rates of associated breast pCR were: HR+/HER2- (2/10, 20.0%), HR+/HER2+ (12/23, 52.2%), HR-/HER2+ (15/24, 62.5%) and triple negative (15/26, 57.7%) (P = 0.1). CONCLUSIONS: Breast pCR is a strong predictor of axillary pCR in women with HER2-positive and triple-negative breast cancers. Conversely, axillary pCR is a modest predictor of breast pCR for these subtypes. There is a poor relationship between breast and axillary pCR in women with hormone receptor-positive disease. These data may inform future de-escalation of surgery in women with HER2-positive and triple-negative disease.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila , Neoplasias da Mama/tratamento farmacológico , Canadá , Feminino , Humanos , Terapia Neoadjuvante , Receptor ErbB-2 , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
19.
Ann Surg Oncol ; 28(10): 5788-5797, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34379251

RESUMO

BACKGROUND: Surgical axillary staging demonstrating positive nodal disease before neoadjuvant chemotherapy (NAC) necessitates axillary lymph node dissection (ALND) post-NAC. Despite evidence supporting post-NAC surgical staging, we hypothesized that there is persistent use of pre-NAC staging and that it is associated with aggressive clinicopathologic features and a higher rate of subsequent ALND. PATIENTS AND METHODS: Stage I-III breast cancer patients who underwent lymph node staging surgery and received NAC between 2013 and 2017 in the National Cancer Database were included. Sequence of staging surgery and chemotherapy administration was determined. Multivariable regression was used to assess characteristics associated with pre-NAC staging. Rate of ALND was compared between those who had pre- and post-NAC surgical axillary staging. RESULTS: In total, 120,538 met inclusion; 68% received NAC first and 32% had pre-NAC staging. Pre-NAC staging surgery was associated with younger age (age < 30 versus 40-49 years, HR 1.1) and decreased with older age (ages 70-79/80+ versus 40-49 years, HR 0.86 and 0.73). Advancing clinical T stage, lobular subtype, higher grade, and HR+/HER2- subtype were also associated with pre-NAC surgical staging. Women who underwent pre-NAC surgical staging were more likely to undergo ALND. CONCLUSIONS: Over 30% of women underwent surgical axillary staging prior to NAC, resulting in higher rates of ALND in this cohort. While certain features suggestive of aggressive behavior (grade and T stage) were associated with pre-NAC surgical axillary staging, women with more aggressive tumor subtypes (triple negative/HER2+) were less likely to undergo pre-NAC surgical axillary staging. Pre-NAC surgical axillary staging should be performed only in rare circumstances to avoid unnecessary ALND.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Adulto , Idoso , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela
20.
Am J Nurs ; 121(9): 24-25, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438426

RESUMO

The newest indications for monoclonal antibodies are as treatment for homozygous familial hypercholesterolemia, advanced triple-negative breast cancer, advanced urothelial cancer, relapsed or refractory large B-cell lymphoma, and non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Humanos
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