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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.
J. Health Biol. Sci. (Online) ; 10(1): 1-4, 01/jan./2022. tab
Artigo em Inglês | LILACS | ID: biblio-1379702

RESUMO

Objectives: to describe and examine oral hygiene habits and self-reported gingival bleeding in women with breast cancer undergoing chemotherapy. Methods: in an observational and prospective study, 140 women were evaluated during chemotherapy between 2017 and 2019. Results and Conclusion: more than 40% of participants reported gingival bleeding at some point during chemotherapy. Flossing was unsatisfactory at baseline and in the intermediate cycle as well as did not affect self-reported gingival bleeding. The amount of tooth brushing per day was a predictor of self-reported gingival bleeding at the end of chemotherapy.


Objetivos: descrever e examinar os hábitos de higiene bucal e o autorrelato de sangramento gengival em mulheres com câncer de mama em quimioterapia. Métodos: em um estudo observacional prospectivo, foram avaliadas 140 mulheres ao longo da quimioterapia, entre 2017 e 2019. Resultados e Conclusão: mais de 40% das participantes relataram sangramento gengival em algum momento da quimioterapia. O uso de fio dental foi insatisfatório no baseline e ciclo intermediário, bem como não afetou o autorrelato de sangramento gengival. A quantidade de escovação dentária por dia foi um preditor para o autorrelato de sangramento gengival ao fim da quimioterapia.


Assuntos
Neoplasias da Mama , Tratamento Farmacológico , Higiene Bucal , Dispositivos para o Cuidado Bucal Domiciliar , Autorrelato
3.
Psychooncology ; 31(1): 54-61, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34498358

RESUMO

OBJECTIVES: To examine the impact of breast reconstruction on women's perceptions of body image over time and to assess the influence of sociodemographic variables on body image. METHODS: A prospective, longitudinal cohort study, using validated breast cancer-specific questionnaires, to compare patient-reported outcomes in women choosing immediate (n = 61), delayed (n = 16) or no (n = 23) breast reconstruction. RESULTS: One hundred women completed baseline questionnaires that included items on body image; 30 women completed all four annual follow-up sets, while 20 women completed baseline only. The three groups were well matched at baseline and similar trajectories in body image measures were identified over 48 months in all groups. At 12 months post-mastectomy, significant changes were seen in eight of the 10 subscales; this reduced to seven subscales at 24 months and four at 36 months. By 48 months, only three subscales remained significantly different to baseline scores: women remained less vulnerable and had fewer limitations (improved outcomes); the one worse outcome was persistently higher levels of arm concern. Three of the sociodemographic variables (health insurance, age and employment status) showed significant inter-group differences at some time points. CONCLUSION: These findings suggest women recover from the negative impact of mastectomy on body image within four years of surgery, whether they have immediate, delayed or no reconstruction. Our results provide some indirect evidence that having a choice of BR options is important, regardless of the choice made. Four years appears to be a suitable follow-up period for future studies in this area.


Assuntos
Neoplasias da Mama , Mamoplastia , Imagem Corporal , Neoplasias da Mama/cirurgia , Feminino , Humanos , Estudos Longitudinais , Mamoplastia/métodos , Mastectomia , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida
4.
Clin. transl. oncol. (Print) ; 24(9): 1732–1743, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-506

RESUMO

PurposeTo evaluate treatment outcomes in patients with early-stage breast cancer (ESBC) treated with targeted intraoperative radiation therapy (IORT) administered as accelerated partial breast irradiation (APBI).MethodsBetween December 2014 and May 2019, 50 patients diagnosed with ESBC were treated with a 50 kilovoltage (kV) X-ray source with a single dose of 20 Gy using the Intrabeam® radiotherapy delivery system. All patients were followed prospectively to assess local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), radiation-induced toxicity, and cosmetic outcomes. We also evaluated the prognostic implications of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).ResultsMedian follow-up was 53 months. Mean patient age was 70 years. The mean duration of radiation delivery was 22.25 min. Two patients developed a recurrence. One death was recorded. Elevated pretreatment NLR levels were a significant risk factor for mortality (p = 0.0026). The most common treatment-related toxicities were breast induration (30%) and seroma (18%). Five-year LC, DFS, CSS, and OS rates were 97.1%, 93.9%, 100%, and 94.4%, respectively. Cosmesis was excellent or good in most cases (94%).ConclusionThese findings confirm the effectiveness of a single dose of 20 Gy of IORT with the Intrabeam device as APBI. The toxicity profile was good with excellent cosmesis. These results provide further support for the clinical use of APBI in well-selected patients. (AU)


Assuntos
Humanos , Tórax/efeitos da radiação , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Raios X , Radioterapia
5.
Clin. transl. oncol. (Print) ; 24(9): 1744–1754, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-507

RESUMO

PurposeWe conducted a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) after the neoadjuvant chemotherapy, compared to axillary lymph-node dissection, in terms of false-negative rate (FNR) and sentinel lymph-node identification rate (SLNIR), sensitivity, negative predictive value (NPV), need for axillary lymph-node dissection (ALND), morbidity, preferences, and costs.MethodsMEDLINE, Embase, Scopus, and The Cochrane Library were searched. We assessed the quality of the included systematic reviews using AMSTAR2 tool, and estimated the degree of overlapping of the individual studies on the included reviews.ResultsSix systematic reviews with variable quality were selected. We observed a very high overlapping degree across the included reviews. The FNR and the SLNIR were quite consistent (FNR 13–14%; SLNIR ~ 90% or higher). In women with initially clinically node-negative breast cancer, the FNR was better (6%), with similar SLNIR (96%). The included reviews did not consider the other prespecified outcomes.ConclusionsIt would be reasonable to suggest performing an SLNB in patients treated with NACT, adjusting the procedure to the previous marking of the affected lymph node, using double tracer, and biopsy of at least three sentinel lymph nodes. More well-designed research is needed. (AU)


Assuntos
Humanos , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Pacientes
6.
Clin. transl. oncol. (Print) ; 24(9): 1764–1775, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-509

RESUMO

PurposeTo explore the roles and underlying mechanisms of miR-1290 in determining the sensitivity of triple-negative breast cancer (TNBC) to radiation therapy.MethodsELISA was performed to detect the levels of IL-18 and IL-1β in radiosensitive cells and serum samples. The level of miR-1290 in radiosensitive cells and tissues was assessed by qRT–PCR assay. A luciferase reporter assay was performed to confirm NLRP3 as the target of miR-1290. Functionally, the roles of miR-1290 in TNBC radioresistance were analyzed by transfection of either miR-1290 mimic or miR-1290 inhibitor. Moreover, the involvement of the miR-1290/NLRP3 axis in TNBC radioresistance was analyzed by experiments with a miR-1290 mimic and NLRP3 overexpression. MTT and colony formation assays were used to detect radiation-induced cell viability and proliferation. qRT–PCR and western blot assays were used to detect pyroptosis markers (NLRP3, ACS and caspase-1).ResultsThe results showed that radioresistance in TNBC cells was associated with a reduction in pyroptosis. miR-1290 expression was increased in radioresistant cells, and it had higher expression levels in the radioresistant tumor tissues of TNBC patients compared to the radiosensitive samples. The miR-1290 mimic suppressed radiation-induced pyroptosis and reduced the radiosensitivity of TNBC cells. Moreover, we found that NLRP3 was a potential target of miR-1290. Overexpression of NLRP3 partly reversed the effects of miR-1290 on pyroptosis and radioresistance. The mouse models showed that miR-1290 suppressed tumor size, tumor weight and pyroptosis.ConclusionsmiR-1290/NLRP3-mediated pyroptosis may play an important role in determining radioresistance in TNBC and serve as a novel therapeutic option. (AU)


Assuntos
Humanos , Camundongos , MicroRNAs/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/radioterapia , Piroptose , Tolerância a Radiação/genética
7.
Clin. transl. oncol. (Print) ; 24(9): 1800–1808, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-512

RESUMO

BackgroundBreast cancer (BC) prevalence steadily increases in older patients but their treatment is based on the geriatric evaluations of comorbidities and potential benefits proved in clinical trials with younger patients. The lack of better decision-making tools urges to promote the search for new prognostic markers. The association between inflammation, aging and cancer may be crucial for better treatment selection. We sought to analyze its impact on the survival of older BC patients, evaluating the interaction with age and comorbidities.MethodsWe evaluated the relationship between inflammatory biomarkers at BC diagnosis (circulating blood cell counts and inflammatory indexes) and BC-related and not related mortality rate, evaluating the influence of comorbidities and age through the competitive risks assessment.ResultsWe analyzed 148 consecutive BC patients aged ≥ 70 years old, diagnosed with BC and regional lymph node metastases. After the median follow-up of 51.5 months, 59 patients died (28 due to breast cancer progression and 31 because of other causes). Increased levels of circulating monocytes, neutrophils and neutrophil-to-lymphocytes ratio and decreased level of eosinophils and eosinophil multiple by neutrophils-to-lymphocytes ratio were associated with higher probability of BC-related death but not with death related to other causes.ConclusionOur data suggest a role of inflammatory parameters as a possible prognostic tool in therapeutic decision-making process in older patients with BC, as increased level of inflammation was associated with cancer-specific mortality. Prospective studies may give the possibility of refining the geriatric evaluation for BC treatment in elderly. (AU)


Assuntos
Humanos , Mama/patologia , Neoplasias da Mama/patologia , Inflamação/patologia , Prognóstico , Estudos Retrospectivos
8.
BMJ Open ; 12(8): e055324, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914919

RESUMO

INTRODUCTION: Within the value-based healthcare framework, outcome data can be used to inform patients about (treatment) options, and empower them to make shared decisions with their health care professional. To facilitate shared decision-making (SDM) supported by outcome data, a multicomponent intervention has been designed, including patient decision aids on the organisation of post-treatment surveillance (breast cancer); discharge location (stroke) and treatment modality (advanced kidney disease), and training on SDM for health care professionals. The SHared decision-making supported by OUTcome information (SHOUT) study will examine the effectiveness of the intervention and its implementation in clinical practice. METHODS AND ANALYSIS: Multiple interrupted time series will be used to stepwise implement the intervention. Patients diagnosed with either breast cancer (N=630), stroke (N=630) or advanced kidney disease (N=473) will be included. Measurements will be performed at baseline, three (stroke), six and twelve (breast cancer and advanced kidney disease) months. Trends on outcomes will be measured over a period of 20 months. The primary outcome will be patients' perceived level of involvement in decision-making. Secondary outcomes regarding effectiveness will include patient-reported SDM, decisional conflict, role in decision-making, knowledge, quality of life, preferred and chosen care, satisfaction with the intervention, healthcare utilisation and health outcomes. Outcomes regarding implementation will include the implementation rate and a questionnaire on the health care professionals' perspective on the implementation process. ETHICS AND DISSEMINATION: The Medical research Ethics Committees United in Nieuwegein, the Netherlands, has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. Bureau Onderzoek & Innovatie of Santeon, the Netherlands, approved this study. The results will contribute to insight in and knowledge on the use of outcome data for SDM, and can stimulate sustainable implementation of SDM. TRIAL REGISTRATION NUMBER: NL8374, NL8375 and NL8376.


Assuntos
Neoplasias da Mama , Nefropatias , Acidente Vascular Cerebral , Neoplasias da Mama/terapia , Tomada de Decisões , Técnicas de Apoio para a Decisão , Feminino , Humanos , Análise de Séries Temporais Interrompida , Participação do Paciente , Qualidade de Vida , Acidente Vascular Cerebral/terapia
9.
JAMA Netw Open ; 5(8): e2225118, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35917122

RESUMO

Importance: In response to an increase in COVID-19 infection rates in Ontario, several systemic treatment (ST) regimens delivered in the adjuvant setting for breast cancer were temporarily permitted for neoadjuvant-intent to defer nonurgent breast cancer surgical procedures. Objective: To examine the use and compare short-term outcomes of neoadjuvant-intent vs adjuvant ST in the COVID-19 era compared with the pre-COVID-19 era. Design, Setting, and Participants: This was a retrospective population-based cohort study in Ontario, Canada. Patients with cancer starting selected ST regimens in the COVID-19 era (March 11, 2020, to September 30, 2020) were compared to those in the pre-COVID-19 era (March 11, 2019, to March 10, 2020). Patients were diagnosed with breast cancer within 6 months of starting systemic therapy. Main Outcomes and Measures: Estimates were calculated for the use of neoadjuvant vs adjuvant ST, the likelihood of receiving a surgical procedure, the rate of emergency department visits, hospital admissions, COVID-19 infections, and all-cause mortality between treatment groups over time. Results: Among a total of 10 920 patients included, 7990 (73.2%) started treatment in the pre-COVID-19 era and 7344 (67.3%) received adjuvant ST; the mean (SD) age was 61.6 (13.1) years. Neoadjuvant-intent ST was more common in the COVID-19 era (1404 of 2930 patients [47.9%]) than the pre-COVID-19 era (2172 of 7990 patients [27.2%]), with an odds ratio of 2.46 (95% CI, 2.26-2.69; P < .001). This trend was consistent across a range of ST regimens, but differed according to patient age and geography. The likelihood of receiving surgery following neoadjuvant-intent chemotherapy was similar in the COVID-19 era compared with the pre-COVID-19 era (log-rank P = .06). However, patients with breast cancer receiving neoadjuvant-intent hormonal therapy were significantly more likely to receive surgery in the COVID-19 era (log-rank P < .001). After adjustment, there were no significant changes in the rate of emergency department visits over time between patients receiving neoadjuvant ST, adjuvant ST, or ST only during the ST treatment period or postoperative period. Hospital admissions decreased in the COVID-19 era for patients who received neoadjuvant ST compared with adjuvant ST or ST alone (P for interaction = .01 for both) in either setting. Conclusions and Relevance: In this cohort study, patients were more likely to start neoadjuvant ST in the COVID-19 era, which varied across the province and by indication. There was limited evidence to suggest any substantial impact on short-term outcomes.


Assuntos
Neoplasias da Mama , COVID-19 , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , COVID-19/epidemiologia , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Ontário/epidemiologia , Estudos Retrospectivos
10.
Praxis (Bern 1994) ; 111(10): 550-556, 2022 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-35920011

RESUMO

Endocrine Treatments in Breast Cancer Abstract. Breast cancer, the most common cancer in women, expresses estrogen and/or progesterone receptors in about 75% of patients. This allows for the use of endocrine treatments. Adjuvant therapy with tamoxifen for 5 years reduces the mortality by about 33%; the residual risk can be lowered by using aromatase inhibitors and by prolonging the treatment. In patients with advanced disease, the median duration of response to first-line therapy is about twelve months, and the median survival time is 20 to 40 months. The use of the various substances differs in terms of duration, sequence, and combinations, particularly with CDK4/6-inhibitors, depending on the clinical situation. Endocrine therapies are prescribed over a long period of time. Treatment adherence is improved by optimal control of side effects.


Assuntos
Neoplasias da Mama , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Tamoxifeno/efeitos adversos
11.
Int J Oncol ; 61(4)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35920189

RESUMO

Proviral integration of Moloney virus 2 (PIM2) is a pro­survival factor of cancer cells and a possible therapeutic target in hematological malignancies. However, the attempts at inhibiting PIM2 have yielded underwhelming results in early clinical trials on hematological malignancies. Recently, a novel pan­PIM inhibitor, JP11646, was developed. The present study examined the utility of targeting PIM2 in multiple solid cancers and investigated the antitumor efficacy and the mechanisms of action of JP11646. When PIM2 expression was compared between normal and cancer tissues in publicly available datasets, PIM2 was found to be overexpressed in several types of solid cancers. PIM2 ectopic overexpression promoted tumor growth in in vivo xenograft breast cancer mouse models. The pan­PIM inhibitor, JP11646, suppressed in vitro cancer cell proliferation in a concentration­dependent manner in multiple types of cancers; a similar result was observed with siRNA­mediated PIM2 knockdown, as well as an increased in cell apoptosis. By contrast, another pan­PIM inhibitor, AZD1208, suppressed the expression of downstream PIM2 targets, but not PIM2 protein expression, corresponding to no apoptosis induction. As a mechanism of PIM2 protein degradation, it was found that the proteasome inhibitor, bortezomib, reversed the apoptosis induced by JP11646, suggesting that PIM2 degradation by JP11646 is proteasome­dependent. JP11646 exhibited significant anticancer efficacy with minimal toxicities at the examined doses and schedules in multiple in vivo mice xenograft solid cancer models. On the whole, the present study demonstrates that PIM2 promotes cancer progression in solid tumors. JP11646 induces apoptosis at least partly by PIM2 protein degradation and suppresses cancer cell proliferation in vitro and in vivo. JP11646 may thus be a possible treatment strategy for multiple types of solid cancers.


Assuntos
Neoplasias da Mama , Neoplasias Hematológicas , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Inibidores de Proteassoma , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas/metabolismo
12.
Clin Nucl Med ; 47(9): e605-e606, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35930715

RESUMO

ABSTRACT: Dysregulation of the cyclin D-CDK4/6-INK4-RB pathway, which leads to uncontrolled cell proliferation, is frequently observed in breast cancer. Recently, 3 CDK4/6 inhibitors have been FDA approved as first-line treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Despite promising clinical results, the metabolic response to treatment with these new drugs has not been elaborately demonstrated yet. Herein, we presented a patient with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who demonstrated a complete metabolic response on 18F-FDG PET/CT to treatment with a CDK4/6 inhibitor (ribociclib).


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Quinase 4 Dependente de Ciclina/uso terapêutico , Quinase 6 Dependente de Ciclina/uso terapêutico , Ciclinas/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2
13.
Sci Rep ; 12(1): 13482, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931718

RESUMO

The frozen section (FS) diagnoses of pathology experts are used in China to determine whether sentinel lymph nodes of breast cancer have metastasis during operation. Direct implementation of a deep neural network (DNN) in clinical practice may be hindered by misdiagnosis of the algorithm, which affects a patient's treatment decision. In this study, we first obtained the prediction result of the commonly used patch-DNN, then we present a relative risk classification and regression tree (RRCART) to identify the misdiagnosed whole-slide images (WSIs) and recommend them to be reviewed by pathologists. Applying this framework to 2362 WSIs of breast cancer lymph node metastasis, test on frozen section results in the mean area under the curve (AUC) reached 0.9851. However, the mean misdiagnosis rate (0.0248), was significantly higher than the pathologists' misdiagnosis rate (p < 0.01). The RRCART distinguished more than 80% of the WSIs as a high-accuracy group with an average accuracy reached to 0.995, but the difference with the pathologists' performance was not significant (p > 0.01). However, the other low-accuracy group included most of the misdiagnoses of DNN models. Our research shows that the misdiagnosis from deep learning model can be further enriched by our method, and that the low-accuracy WSIs must be selected for pathologists to review and the high-accuracy ones may be ready for pathologists to give diagnostic reports.


Assuntos
Neoplasias da Mama , Segunda Neoplasia Primária , Neoplasias da Mama/patologia , Erros de Diagnóstico , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Segunda Neoplasia Primária/patologia , Redes Neurais de Computação , Biópsia de Linfonodo Sentinela
14.
Sci Rep ; 12(1): 13487, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931753

RESUMO

Psoralen derivatives are well known for their unique phototoxicity and also exhibits promising anti-breast cancer activity both in the presence and the absence of UVA irradiation. However, the structure-activity relationship on this scaffold remains lacking. Herein, a series of psoralen derivatives with various C-5 substituents were synthesized and evaluated for their in vitro dark and light-activated cytotoxicity against three breast cancer cell lines: MDA-MB-231, T47-D, and SK-BR-3. The type of substituents dramatically impacted the activity, with the 4-bromobenzyl amide derivative (3c) exhibiting the highest dark cytotoxicity against T47-D (IC50 = 10.14 µM), with the activity comparable to those of the reference drugs (doxorubicin, 1.46 µM; tamoxifen citrate, 20.86 µM; lapatinib 9.78 µM). On the other hand, the furanylamide 3g exhibits the highest phototoxicity against SK-BR-3 cells with the IC50 of 2.71 µM, which is almost tenfold increase compared to the parent compound, methoxsalen. Moreover, these derivatives showed exceptional selectivity towards HER2+ (SK-BR-3) over the HER2- (MDA-MB-231) breast cancer cell lines, which correlates well with the results from the molecular docking study, revealing that 3g formed favorable interactions within the active site of the HER2. Additionally, the cell morphology of SK-BR-3 cells suggested that the significant phototoxicity was related to induction of cell apoptosis. Most of the synthesized psoralen derivatives possess acceptable physicochemical properties and are suitable for being further developed as a novel anti-breast cancer agent in the future.


Assuntos
Antineoplásicos , Neoplasias da Mama , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Ficusina/farmacologia , Humanos , Simulação de Acoplamento Molecular
15.
J Coll Physicians Surg Pak ; 32(8): 1014-1019, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35932125

RESUMO

OBJECTIVE: To determine the efficacy of trastuzumab-based treatment in patients with HER2/neu-positive metastatic gastric cancer. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Istanbul University, Institute of Oncology, Istanbul, Turkey, between January 2014 and December 2020. METHODOLOGY: The clinicopathological characteristic and treatment data of patients with HER2/neu-positive metastatic gastric cancer were recorded retrospectively. Kaplan-Meier analysis was performed to compare the chemotherapy regimens. RESULTS: Sixty-three patients were included in the study. The average age was 61. Female patients accounted for 27% of the total, while male patients accounted for 73%. De novo metastatic cases accounted for 44 (69.8%) of the total number of patients. The median survival time was 13.6 (8-19.3) months. Complete response was 6.3%, partial response was 39.7%, and the stable response was 9.5% with trastuzumab-based chemotherapy. The overall survival (p= 0.45) and progression-free survival (p=0.893) were similar for different chemotherapy regimens. The grade 1-2 to grade 3-4 toxicity ratio was 79.6% and 20.6%, respectively. The patients' performance (p<0.001) and the number of metastatic sites (p=0.001) were both shown to be unfavourable predictive variables for OS in multivariate analysis. CONCLUSION: The addition of taxane to trastuzumab-based combinations (with platinum and fluoropyrimidine) did not affect overall and progression-free survival in this research. Three or more metastatic sites and poor performance status were found as the unfavourable prognostic variables for overall survival. KEY WORDS: Gastric cancer, Trastuzumab, Chemotherapy, Prognostic factors.


Assuntos
Neoplasias da Mama , Neoplasias Gástricas , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2 , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Trastuzumab/uso terapêutico
16.
Perm J ; 26(2): 54-63, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35933666

RESUMO

Introduction The COVID-19 pandemic drove rapid, widespread adoption of telehealth (TH). We evaluated surgical telehealth utilization and outcomes for newly diagnosed breast cancer patients during the initial pandemic period. Methods We identified patients with breast cancer diagnosed March 17, 2020 through May 17, 2020 who underwent surgery as the initial treatment. Clinicodemographic characteristics were collected. Initial consultation types (office, telephone, or video) were categorized. Outcomes included time to consultation, surgeon touchpoints, time to surgery, surgery types, and reexcision rates. Continuous variables were compared using Mann-Whitney tests or t-tests, and categorical variables were compared using χ2 or Fisher's exact tests. Results Of 158 patients, 56% had initial telehealth consultations (21% telephone, 35% video) and 42% did not have a preoperative physical examination. Age, race/ethnicity, and stage distributions were similar between initial visit types. Median time to consultation was lower in the initial telehealth group than the office group (6 days vs 9 days, p = 0.01). Other outcomes (surgeon touchpoints, time to surgery, surgery type, reconstruction) were similar between visit types. We observed higher reexcision rates in patients with initial telehealth visits (20% telehealth vs 4% office, p = 0.01), but evaluation was limited by small numbers. The reexcision rate was 13% for patients with telehealth visits and no preoperative physical exam. Discussion During the initial pandemic period, the majority of new breast cancer patients had an initial telehealth surgical consultation. Office and telehealth consultation visits had comparable numbers of postconsultation surgeon touchpoints and most outcomes. Our findings suggest that telehealth consultations may be feasible for preoperative breast cancer consultations.


Assuntos
Neoplasias da Mama , COVID-19 , Telemedicina , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pandemias , SARS-CoV-2 , Telemedicina/métodos
17.
Perm J ; 26(2): 158-161, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35933669

RESUMO

Introduction Apocrine carcinoma, a cancer of sweat glands, is very rare, with a global incidence of 0.0049 to 0.0173 cases per 100,000 persons annually. It is usually found in axilla and anogenital areas. The intraductal apocrine variety of salivary duct carcinoma in the parotid gland is very rare and aggressive and may be due to ectopic sweat glands in the parotid gland duct or metaplastic change of the salivary duct epithelium. It usually presents in an advanced stage. Even though surgery is the standard of care in most head and neck cancers, there are no standard guidelines for the treatment of intraductal apocrine parotid carcinoma, which is different from other head and neck cancers due to its rare incidence, aggressive behavior, and poor prognosis. Case presentation We present a rare case of intraductal apocrine salivary duct carcinoma of the left parotid gland, presented in a locally advanced stage with very high chances of recurrence after surgery, and discuss the role of volumetric modulated arc technique radiotherapy in its management. Conclusion Intraductal apocrine salivary duct carcinoma usually has androgen receptor expression, and lack of expression is associated poor prognosis. Even with complete resection, it has a high recurrence rate. Volumetric modulated arc technique radiotherapy (VMAT) decreases recurrence and increases survival by irradiating the areas more likely of recurrence, with minimal toxicity to surrounding normal tissues.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Neoplasias de Cabeça e Pescoço , Neoplasias das Glândulas Salivares , Feminino , Humanos , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia
18.
Anal Chim Acta ; 1221: 340084, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934341

RESUMO

The development of new diagnostic tools in tumor pathology allows the optimization of individualized therapies in cancer patients. The functional optical image provides a unique opportunity to identify the pathophysiological characteristics of each tumor in a non-invasive way. Although fluorescent recombinant affibodies and nanobodies, capable of detecting certain membrane proteins present in tumor cells, has been described, the use of bioluminescent molecules is gaining a great impact in this field due to its high sensitivity. In this work, we characterize a new luciferase from the Metridia lucens copepod (MlLuc) and develop a novel bioluminescent recombinant affibody (MlLuc-aff) capable of recognizing the HER2 receptors that are overexpressed in breast cancer tumors. For this purpose, the thermostability and pH sensitivity of MlLuc1.1 were determined, showing no significant changes in the activity among temperatures between 4 and 70 °C, and with a maximum of brightness at pH 8.0. Furthermore, MlLuc-aff was able to accurately detect HER2 receptors expressed in the SK-BR-3 cells. Future applications of this new tracer can contribute to the early diagnosis of breast cancer patients and the assessment of the efficacy of the treatment.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Neoplasias da Mama/patologia , Feminino , Humanos , Luciferases , Receptor ErbB-2/metabolismo , Proteínas Recombinantes de Fusão/química
19.
Sleep ; 45(4)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35934507

RESUMO

Rest-activity rhythm (RAR) disruptions are frequently associated with chemotherapy in breast cancer (BC), but they are less known in BC with endocrine therapy (ET). The aim of this ancillary study was to characterize the RAR and estimated sleep characteristics from actigraphy in BC patients either treated (ET+) or untreated with ET (ET-), compared to healthy controls (HC) and using a cross-sectional design. Eighteen ET+, 18 ET-, and 16 HC completed questionnaires and wore wrist actigraphs at home for 2 weeks. Parametric and nonparametric RAR, sleep parameters, and quality of life were compared between groups (p < .05). BC groups presented lower daytime activity than HC according to RAR analysis (mesor and M10 parameters). Compared to HC, ET- had lower inter-daily stability and ET+ had greater sleep complaints. Compared to ET-, ET+ had lower sleep efficiency, more time awake, and higher activity levels at night, as assessed with actigraphy. Our results suggest an effect of cancer independent of treatment on RAR in BC, highlighting the need for further investigation of this topic. In contrast, sleep as assessed with actigraphy seems modified only during ET which matches with patients' sleep complaints. Further longitudinal studies would aid in confirming the latter hypothesis.


Assuntos
Neoplasias da Mama , Ritmo Circadiano , Actigrafia/métodos , Neoplasias da Mama/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Qualidade de Vida , Descanso , Sono
20.
J Immunol Res ; 2022: 9529114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935587

RESUMO

Objective: To identify trastuzumab-resistant genes predicting drug response and poor prognosis in human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Methods: Gene expression profiles from the GEO (Gene Expression Omnibus) database were obtained and analyzed. Differentially expressed genes (DEGs) between the pathological complete response (pCR) group and non-pCR group in a trastuzumab neoadjuvant therapy cohort and DEGs between Herceptin-resistant and wild-type cell lines were detected and evaluated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed to select the functional hub genes. The hub genes' prognostic power was validated by another trastuzumab adjuvant treatment cohort. Results: Fifty upregulated overlapping DEGs were identified by analyzing two trastuzumab resistance-related GEO databases. Functional analysis picked out ten hub genes enriched in mitochondrial function and metabolism pathways: ASCL1, CPT2, DLD, ELVOL7, GAMT, NQO1, SLC23A1, SPR, UQCRB, and UQCRQ. These hub genes could distinguish patients with trastuzumab resistance from the sensitive ones. Further survival analysis of hub genes showed that DLD overexpression was significantly associated with an unfavorable prognosis in HER2+ breast cancer patients. Conclusion: Ten novel trastuzumab resistance-related genes were discovered, of which DLD could be used for trastuzumab response prediction and prognostic prediction in HER2+ breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Receptor ErbB-2 , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico
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