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1.
BMC Psychol ; 10(1): 2, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980291

RESUMO

BACKGROUND: Psycho-oncology literature pointed out that individual health outcomes may depend on patients' propensity to adopt approach or, conversely, avoidant coping strategies. Nevertheless, coping factors associated with postoperative distress remain unclear, unfolding the lack of tailored procedures to help breast cancer patients manage the psychological burden of scheduled surgery. In view of this, the present study aimed at investigating: 1. pre-/post-surgery distress variations occurring among women diagnosed with breast cancer; 2. the predictivity of approach and avoidant coping strategies and factors in affecting post-surgery perceived distress. METHODS: N = 150 patients (mean age = 59.37; SD = ± 13.23) scheduled for breast cancer surgery were administered a screening protocol consisting of the Distress Thermometer (DT) and the Brief-COPE. The DT was used to monitor patients' distress levels before and after surgery (± 7 days), whereas the Brief-COPE was adopted only preoperatively to evaluate patients' coping responses to the forthcoming surgical intervention. Non-parametric tests allowed for the detection of pre-/post-surgery variations in patients' perceived distress. Factor analysis involved the extraction and rotation of principal components derived from the Brief-COPE strategies. The predictivity of such coping factors was investigated through multiple regression (Backward Elimination). RESULTS: The Wilcoxon Signed-Rank Test yielded a significant variation in DT mean scores (TW = -5,68 < -zα/2 = -1,96; p < .001) indicative of lower perceived distress following surgery. The four coping factors extracted and Varimax-rotated were, respectively: 1. cognitive processing (i.e., planning + acceptance + active coping + positive reframing); 2. support provision (i.e., instrumental + emotional support); 3. emotion-oriented detachment (i.e., self-blame + behavioral disengagement + humor + denial); 4. goal-oriented detachment (i.e., self-distraction). Among these factors, support provision (B = .458; ß = - .174; t = - 2.03; p = .045), encompassing two approach coping strategies, and goal-oriented detachment (B = .446; ß = - .176; t = - 2.06; p = .042), consisting of one avoidant strategy, were strongly related to post-surgery distress reduction. CONCLUSION: The present investigation revealed that the pre-surgery adoption of supportive and goal-oriented strategies led to postoperative distress reduction among breast cancer patients. These findings highlight the importance of timely psychosocial screening and proactive interventions in order to improve patients' recovery and prognosis.


Assuntos
Neoplasias da Mama , Adaptação Psicológica , Neoplasias da Mama/cirurgia , Análise Fatorial , Feminino , Objetivos , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estresse Psicológico
2.
J Coll Physicians Surg Pak ; 32(1): 86-91, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34983154

RESUMO

OBJECTIVE: To evaluate the prognostic role of pan immune-inflammation value (PIV) in young breast cancer patients. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Afyon University of Health Sciences, School of Medicine Hospital, Turkey, between January 2010 and December 2020. METHODOLOGY: Patients who were under the age of 40 years at the time of diagnosis were included. Patients' characteristics and disease parameters were recorded. PIV was calculated according to (neutrophil x platelet x monocyte/lymphocyte, i.e. NxPxM/L) formula. Since a cut-off value with max sensitivity and specificity could not be obtained with ROC analysis, the median value of PIV was used as cut-off value. The relationship between PIV and pathological parameters was evaluated by ROC curves. The Kaplan-Meier method was used for OS and the log-rank test was used to evaluate the survival differences between the two groups, according to the optimal cut-off point. RESULTS: Based on the PIV cut-off value of 121 (49.8%) patients were in the low PIV and 122 (50.2%) patients were in the high PIV group. The patients in the high PIV group had a statistically significantly more advanced AJCC stage, and were younger patients. In the survival analysis, it was observed that the survival was worse in the high PIV group but this difference did not reach statistical significance (p=0.112). CONCLUSION: Higher PIV levels at the time of diagnosis can be another prognostic marker. However, to clarify the PIV prognostic value, it needs to be validated in larger, multi-centre prospective clinical studies. Key Words: Breast cancer, Pan immune-inflammation value (PIV), Prognosis, Young women.


Assuntos
Neoplasias da Mama , Adulto , Feminino , Humanos , Linfócitos , Neutrófilos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
3.
J Coll Physicians Surg Pak ; 32(1): 122-124, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34983165

RESUMO

This study sought to investigate the efficacy and safety of eribulin in advanced breast cancer patients. Eighteen patients with advanced breast cancer were retrospectively included. The previous use of taxanes, and the use of eribulin in subsequent treatment was reviewed. Progression- free survival(PFS)and the efficacy of eribulin, influencing factors, and adverse reactions were analysed. For patients who were previously treated with taxanes were more resistant, subsequent eribulin treatment chemotherapy PFS was generally for two months. However, for patients who chose eribulin combined with anlotinib for the latter-line regimen, PFS reached for five months, and these patients were in continuous remission. Among the 18 patients, 17 patients (94.4%) had different degrees of bone marrow suppression. Patients who have not been treated with taxanes or who have been treated with taxanes for a long response time, experience better effects when eribulin was used as subsequent treatment. Eribulin combined with anlotinib is the preferred combination therapy. Key Words: Breast cancer, Eribulin, Efficacy, Safety.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Feminino , Furanos/efeitos adversos , Humanos , Cetonas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
5.
In Vivo ; 36(1): 40-48, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972698

RESUMO

BACKGROUND: Aromatase inhibitor therapy is currently the preferred choice in postmenopausal women with estrogen receptor positive breast cancer. This article reviews the ocular side effects of treatment with aromatase inhibitors (AIs) in patients with breast cancer. MATERIALS AND METHODS: A comprehensive search was performed on PubMed, Web of Science and Google scholar. RESULTS: After duplication removal, 14 clinical studies and 5 case reports, published between 2008 and 2021, were identified. Most frequently, AI treatment resulted in minor to moderate dry eye symptoms. "De novo" onset of Sjogren syndrome during AI therapy was also reported. Retinal and optic nerve side effects varied from mild, subclinical anatomic and functional impairment to severe decreased vision, secondary to hemi-central retinal artery occlusion, bilateral optic neuritis or uveitis with bilateral macular edema. CONCLUSION: Visual disturbances encountered during AI treatment may be underestimated. Ophthalmic screening is important for early detection and appropriate treatment.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos
6.
In Vivo ; 36(1): 314-324, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972728

RESUMO

BACKGROUND/AIM: Post-operative radiotherapy for breast cancer can increase cardiac disease in a dose-dependent manner. In this study we show the reduction of dose to heart and left anterior descending artery (LAD) which can be achieved by using "Deep inspiration breath-hold" (DIBH) technique. PATIENTS AND METHODS: Tangential 3D-planned radiation was delivered to 357 patients with left-sided breast cancer, 159 of them with the DIBH technique. A distinction was made according to fractionation scheme. RESULTS: The mean heart dose was significantly reduced by DIBH from 2.64 Gy to 1.39 Gy (p<0.001). The mean dose to the LAD was significantly reduced from 5.68 Gy to 3.88 Gy (p<0.001). Mean dose and volume receiving 5, 10 and 15 Gy of ipsilateral lung were higher with both hypofractionated schedule and conventional fractionation in the DIBH group. CONCLUSION: DIBH in left-sided breast irradiation is an effective method of reducing the radiogenic heart dose.


Assuntos
Neoplasias da Mama , Neoplasias Unilaterais da Mama , Neoplasias da Mama/radioterapia , Suspensão da Respiração , Feminino , Coração , Humanos , Pulmão , Órgãos em Risco , Dosagem Radioterapêutica , Neoplasias Unilaterais da Mama/radioterapia
7.
In Vivo ; 36(1): 336-340, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972731

RESUMO

BACKGROUND/AIM: Breast cancer is the most common cancer in Sudan. The p16 protein plays a vital role in the regulation of the cell cycle. PATIENTS AND METHODS: This study analysed the protein expression of p16 in 202 paraffin blocks from Sudanese women with breast cancer using immunohistochemistry. RESULTS: This study included 168 (83.2%), 16 (7.9%), and 18 (8.9%) patients with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. There were 95 cases (47.0%) with grade III, 70 cases (34.6%) with grade II, and 23 cases (11.4%) with grade I breast cancer. The hormone receptor status was available for 119 of the cases, and 31 (15.3%), 25 (12.4%), and 63 (31.2%) cases were positive for oestrogen, progesterone, and HER2 receptors, respectively. CONCLUSION: p16 protein expression was associated with high histologic grade, lymph node metastasis, and poor prognosis. p16 protein expression may potentially be used as a prognostic marker.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Feminino , Humanos , Prognóstico , Receptor ErbB-2/genética , Receptores de Progesterona/genética
8.
In Vivo ; 36(1): 398-408, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972741

RESUMO

BACKGROUND/AIM: To provide data regarding relationships between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE MRI) and prognostic factors in breast cancer (BC). PATIENTS AND METHODS: Data from 4 Centers (200 female patients, mean age, 51.2±11.5 years) were acquired. The following data were collected: histopathological diagnosis, tumor grade, stage, hormone receptor status, KI 67, and DCE MRI values including Ktrans (volume transfer constant), Ve (volume of the extravascular extracellular leakage space (EES) and Kep (diffusion of contrast medium from the EES back to the plasma). DCE MRI values between different groups were compared using the Mann-Whitney U-test and by the Kruskal-Wallis H test. The association between DCE MRI and Ki 67 values was calculated by the Spearman's rank correlation coefficient. RESULTS: DCE MRI values of different tumor subtypes overlapped significantly. There were no statistically significant differences of DCE MRI values between different tumor grades. All DCE MRI parameters correlated with KI-67: Ktrans, r=0.44, p=0.0001; Ve, r=0.34, p=0.0001; Kep, r=0.28, p=0.002. ROC analysis identified a Ktrans threshold of 0.3 min-1 for discrimination of tumors with low KI-67 expression (<25%) and high KI-67 expression (≥25%): sensitivity, 75.5%, specificity, 73.0%, accuracy, 74.0%, AUC, 0.78. DCE MRI values overlapped between tumors with different T and N stages. CONCLUSION: Ktrans, Kep, and Ve cannot be used as reliable a surrogate marker for hormone receptor status, tumor stage and grade in BC. Ktrans may discriminate lesions with high and lower proliferation activity.


Assuntos
Neoplasias da Mama , Adulto , Biomarcadores , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Curva ROC
9.
In Vivo ; 36(1): 473-481, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972751

RESUMO

BACKGROUND/AIM: It can be difficult to establish the origin of a tumor in metastatic breast cancer (MBC), especially with triple-negative breast cancer (TNBC) or high-grade features. We evaluated the diagnostic utility of GATA3, SOX10, and PAX8 panels in MBC by comparing their expression in each molecular subtype of MBC. PATIENTS AND METHODS: We evaluated 84 MBC and 37 primary TNBC cases using GATA3, SOX10, and PAX8 staining in whole tissue sections. RESULTS: GATA3 was least sensitive in the detection of metastatic TNBC (metastatic non-TNBC, 0.95; metastatic TNBC, 0.37). SOX10 had the lowest overall sensitivity (0.12) but was elevated in metastatic TNBC, even higher than GATA3 (0.59 vs. 0.37). The combination of GATA3, SOX10, and PAX8 expression showed the highest detection rate (MBC, 0.94; metastatic non-TNBC, 0.95; metastatic TNBC, 0.93). CONCLUSION: We recommend combining GATA3, SOX10, PAX8 expression profiling to confirm breast as the site of origin in metastatic MBC.


Assuntos
Neoplasias da Mama , Segunda Neoplasia Primária , Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais/genética , Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Fator de Transcrição GATA3/genética , Humanos , Fator de Transcrição PAX8/genética , Fatores de Transcrição SOXE/genética
10.
In Vivo ; 36(1): 522-527, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972757

RESUMO

BACKGROUND: Breast cancer often metastasizes to the lungs, bones, liver, and brain, colon metastasis from breast cancer (CMBC) is extremely rare. CASE REPORT: The patient was a 63-year-old female. Mastectomy had been performed for breast cancer (pStage IIB) 15 years earlier at another hospital. Metastasis to the lumbar spine had been detected 4 years prior to referral to us and the patient had undergone hormonal therapy with an aromatase inhibitor. Furthermore, early primary sigmoid colon cancer had been endoscopically resected 2 years before referral. The patient was diagnosed with cancer recurrence in the colon at follow-up examinations performed 2 years after that endoscopic resection. After referral to our hospital, laparoscopic sigmoidectomy was performed. Based on the histopathological examination and immunohistological staining results (positive for cytokeratin 7, GATA-binding protein 3, estrogen receptor and human epidermal growth factor receptor-related 2 (2+); negative for cytokeratin 20, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15 and caudal-related homeobox 2) the final pathological diagnosis was CMBC. CONCLUSION: Although extremely rare, the possibility of CMBC should be considered in the case of colonic tumors in patients with a history of breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias do Colo Sigmoide , Neoplasias da Mama/cirurgia , Colo Sigmoide , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias do Colo Sigmoide/cirurgia
11.
Trials ; 23(1): 25, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34998436

RESUMO

BACKGROUND: An often heard and justifiable concern of ethnic minorities is related to researchers' lack of attention to sharing the results of a study with participants after the study has concluded. Few studies have examined the effects of returning overall study results on participants' attitudes, especially among populations underrepresented in research. Among Latina research participants, providing a summary of study results could enhance participation in research. We assess Latina breast cancer survivors' reactions to receiving study results and their attitudes about participating in future studies. METHODS: For this cross-sectional survey study, all women who had participated in two behavioral randomized controlled trials (RCTs) were mailed a letter summarizing the study results (using written and graphic formats) and a questionnaire assessing problems and understanding the results, importance of sharing results, willingness to participate in future studies, and format preferences for receiving the results. A postage-paid envelope for returning the completed questionnaire was included. Logistic regression examined the associations of age, education, and rural/urban residence on format preferences and willingness to participate. The survey sample consisted of 304 low-income, predominantly Spanish-speaking Latina breast cancer survivors (151 from urban and 153 from rural communities) who had participated in two RCTs testing a stress management program designed for Latina breast cancer survivors. RESULTS: Ninety-two women returned the questionnaires (30.3%). Most of the women (91.1%) indicated that they had no trouble understanding the results of the study, and 97% agreed that it is very/extremely important for researchers to share the study result with the participants. The majority (60.2%) reported that receiving the results increased their willingness to participate in future studies. About half (51.7%) did not have a format preference, 37.4% preferred written summaries, and 10.9% preferred graphs. CONCLUSIONS: This study is an important first step to understanding the impact of returning study results among a population that is underrepresented in research. Returning the results of studies and understanding the impact of doing so is consistent with maintaining community involvement in all phases of research. The findings suggest that sharing aggregate research results in simple language yields few problems in participants' understanding of the results and is viewed as important by participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT02931552 Date registered: October 13, 2016 and NCT01383174 Date registered: June 28, 2011.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Estudos Transversais , Feminino , Humanos , Inquéritos e Questionários
12.
J Int Med Res ; 50(1): 3000605211070757, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35000471

RESUMO

OBJECTIVE: Breast cancer (BC) is the most common form of cancer among Asian females. Mutations in the BRCA1/BRCA2 genes are often observed in BC cases and largely increase the lifetime risk of having BC. Because of the paucity of high-quality data on the molecular spectrum of BRCA mutations in South Asian populations, we aimed to explore these mutations among South Asian countries. METHODS: A systematic literature search was performed for the BRCA1 and BRCA2 gene mutation spectrum using electronic databases such as PubMed, EMBASE, and Google Scholar. Twenty studies were selected based on specific inclusion and exclusion criteria. RESULTS: The 185delAG (c.68_69del) mutation in exon 2 of BRCA1 was the most common recurrent mutation and founder mutation found. Various intronic variants, variants of unknown significance, large genomic rearrangements, and polymorphisms were also described in some studies. CONCLUSIONS: The South Asian population has a wide variety of genetic mutations of BRCA1 and BRCA2 that differ according to countries and ethnicities. A stronger knowledge of various population-specific mutations in these cancer susceptibility genes can help provide efficient strategies for genetic testing.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Ásia/epidemiologia , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Feminino , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Mutação , Recidiva Local de Neoplasia , Neoplasias Ovarianas/genética , Análise Espectral
13.
J Egypt Natl Canc Inst ; 34(1): 2, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35001182

RESUMO

BACKGROUND: Breast conserving surgery (BCS) has been a standard procedure for the treatment of breast cancer instead of mastectomy whenever possible. Lateral chest wall perforator flaps are one of the volume replacement techniques that participate in increasing the rate of BCS especially in small- to moderate-sized breasts with good cosmetic outcome. In this study, we tried to evaluate the outcome of those flaps as an oncoplastic procedure instead of the conventional flaps. METHODS: This study included 26 patients who underwent partial mastectomy with immediate reconstruction using lateral chest wall perforator flaps in the period from October 2019 to November 2020. The operative time, techniques, and complications were recorded. The cosmetic outcome was assessed 3 months post-radiation therapy through a questionnaire and photographic assessment. RESULTS: Lateral intercostal artery perforator (LICAP), lateral thoracic artery perforator (LTAP) and combined flaps were performed in 24, 1, and 1 patients, respectively. The mean operative time was 129.6 ± 13.2 min. The flap length ranged from 10 to 20 cm and its width from 5 to 9 cm. Overall patients' satisfaction was observed to be 88.5% as either excellent or good and the photographic assessment was 96.2% as either excellent or good. CONCLUSIONS: Lateral chest wall perforator flaps are reliable and safe option for partial breast reconstruction with an acceptable aesthetic outcome. In the era of oncoplastic breast surgery, they deserve to gain attention especially with the advantages of some modifications added to the classic technique.


Assuntos
Neoplasias da Mama , Mamoplastia , Retalho Perfurante , Parede Torácica , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Retalho Perfurante/cirurgia , Parede Torácica/cirurgia
14.
BMC Surg ; 22(1): 10, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34998369

RESUMO

BACKGROUND: Implant-based breast reconstruction is easy to be performed but has flaws that an unnatural appearance might be presented when no sufficient coverage existing. While autologous tissue reconstruction also has disadvantages like donor site scar and skin patch effect. There is a demand for a new method to obtain natural and aesthetic appearance while surmounting drawbacks of conventional breast reconstruction surgery. METHODS: A retrospective review of thirty-one patients undergoing tissue expander (TE)/implant two-stage breast reconstruction with latissimus dorsi muscle flap (LDMF) transfer through endoscopic approach in Peking University Third Hospital from April 2016 to August 2020 was performed. The LDMF harvest time, drain time, and complications were reviewed. The 3D volume was obtained to assess the volume symmetry of bilateral breasts. The BREAST-Q reconstruction module was used to evaluate the satisfaction. RESULTS: The mean endoscopic LDMF harvest time was 90.4 min. In the mean follow-up of 11.2 months, there were no severe capsular contracture happened. The reconstructed side achieved good volume symmetry to the contralateral side (P = 0.256). Based on the evaluation of the BREAST-Q scores, the outcome of Satisfaction with Breasts was excellent or good in 87.1% of the cases. CONCLUSIONS: The novel type of two-stage breast reconstruction protocol, which includes tissue expansion followed by implant insertion with endoscopy-assisted LDMF transfer, could effectively reduce visible scars, avoid the patch effect, while require short time for LDMF harvest and present low incidence of complications. It is a promising method for breast reconstruction because it achieves good outcomes in the mastectomy patients.


Assuntos
Neoplasias da Mama , Mamoplastia , Músculos Superficiais do Dorso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Estudos Retrospectivos , Expansão de Tecido
15.
FASEB J ; 36(1): e22068, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34918396

RESUMO

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) has been frequently overexpressed in many types of malignancy, suggesting its oncogenic function. It recognizes phosphorylated serine or threonine (pSer/Thr) of a target protein and isomerizes the adjacent proline (Pro) residue, thereby altering folding, subcellular localization, stability, and function of target proteins. The oncogenic transcription factor, Nrf2 harbors the pSer/Thr-Pro motif. This prompted us to investigate whether Pin1 could bind to Nrf2 and influence its stability and function in the context of implications for breast cancer development and progression. The correlation between Pin1 and Nrf2 in the triple-negative breast cancer cells was validated by RNASeq analysis as well as immunofluorescence staining. Interaction between Pin1 and Nrf2 was assessed by co-immunoprecipitation and an in situ proximity ligation assay. We found that mRNA and protein levels of Pin1 were highly increased in the tumor tissues of triple-negative breast cancer patients and the human breast cancer cell line. Genetic or pharmacologic inhibition of Pin1 enhanced the ubiquitination and degradation of Nrf2. In contrast, the overexpression of Pin1 resulted in the accumulation of Nrf2 in the nucleus, without affecting its transcription. Notably, the phosphorylation of Nrf2 at serine 215, 408, and 577 is essential for its interaction with Pin1. We also identified phosphorylated Ser104 and Thr277 residues in Keap1, a negative regulator of Nrf2, for Pin1 binding. Pin1 plays a role in breast cancer progression through stabilization and constitutive activation of Nrf2 by competing with Keap1 for Nrf2 binding.


Assuntos
Neoplasias da Mama/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Neoplasias da Mama/genética , Feminino , Células HEK293 , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Peptidilprolil Isomerase de Interação com NIMA/genética , Proteínas de Neoplasias/genética , Ligação Proteica , Estabilidade Proteica , Proteólise , Ubiquitinação
16.
Environ Res ; 204(Pt A): 111989, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34506784

RESUMO

Organophosphorus chlorpyrifos (CPF) is currently considered an endocrine disruptor (ED), as it can imitate hormone actions both in vitro and in vivo. We recently reported that CPF induces migration and invasion in 2D cultures and changes the expression of key molecular markers involved in epithelial mesenchymal transition in MCF-7 and MDA-MB-231 cell lines. In this study, we investigated whether CPF could behave as a predisposing factor for tumors to become more metastatic and aggressive using 3D culture models. In MCF-7 cells, 0.05 µM CPF induced an increase in the number and size of mammospheres via estrogen receptor alpha (ERα) and c-SRC. Furthermore, 0.05 µM CPF increased the area of spheroids generated from MCF-7 cells, induced invasion using both Matrigel® and type 1 collagen matrices, and increased cell migration capacity via ERα in this 3D model. In turn, 50 µM CPF increased cell migration capacity and invasion using type 1 collagen matrix. In monolayers, CPF increased the phosphorylation and membrane translocation of c-SRC at both concentrations assayed. CPF at 0.05 µM boosted p-AKT, p-GSK-3ß and p-P38. While p-AKT rose in a ERα-dependent way, p-GSK-3ß was dependent on ERα- and c-SRC, and p-P38 was only dependent on c-SRC. On the other hand, the increase in p-AKT and p-P38 induced by 50 µM CPF was dependent on the c-SRC pathway. We also observed that 0.05 µM CPF increased IGF-1R and IRS-1 expression and that 50 µM CPF induced IGF-1Rß phosphorylation. In the MDA-MB-231 cell line, 0.05 and 50 µM CPF increased p-c-SRC. Finally, p-AKT and p-GSK-3ß were also induced by CPF at 0.05 and 50 µM, and an increase in p-P38 was observed at 50 µM. Taken together, these data provide support for the notion that CPF may represent a risk factor for breast cancer development and progression.


Assuntos
Neoplasias da Mama , Clorpirifos , Disruptores Endócrinos , Linhagem Celular Tumoral , Proliferação de Células , Clorpirifos/toxicidade , Disruptores Endócrinos/toxicidade , Feminino , Glicogênio Sintase Quinase 3 beta , Humanos , Fenótipo , Fosforilação
17.
Cancer Lett ; 524: 121-130, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34687790

RESUMO

Chimeric antigen receptor (CAR) T cell therapy has been successful in treating hematological malignancy, but solid tumors remain refractory. Here, we demonstrated that knocking out transcription factor IKZF3 in HER2-specific CAR T cells targeting breast cancer cells did not affect CAR expression or CAR T cell differentiation, but markedly enhanced killing of the cancer cells in vitro and in a xenograft model, which was associated with increased T cell activation and proliferation. Furthermore, IKZF3 KO had similar effects on the CD133-specific CAR T cells targeting glioblastoma cells. AlphaLISA and RNA-seq analyses indicate that IKZF3 KO increased the expression of genes involved in cytokine signaling, chemotaxis and cytotoxicity. Our results suggest a general strategy for enhancing CAR T efficacy on solid tumors.


Assuntos
Neoplasias da Mama/terapia , Fator de Transcrição Ikaros/genética , Receptor ErbB-2/genética , Receptores de Antígenos Quiméricos/genética , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Inativação de Genes , Xenoenxertos , Humanos , Fator de Transcrição Ikaros/antagonistas & inibidores , Imunoterapia Adotiva/métodos , Camundongos , RNA-Seq , Receptores de Antígenos Quiméricos/antagonistas & inibidores , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia
18.
Cancer Lett ; 524: 245-258, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715250

RESUMO

The stiffening of the extracellular matrix (ECM) during tumor progression results in an increase in cancer cell motility. In cell migration, two major isoforms of non-muscle myosin II (NMII), NMIIA and NMIIB, are expressed and assembled into the cytoskeleton. However, the isoform-specific regulatory roles of NMIIA and NMIIB as well as the underlying mechanisms in response to mechanical cues of the ECM are still elusive. Here, based on polyacrylamide (PAA) gels with tunable elastic modulus, we mimicked the mechanical properties of tumor tissue at different stages of breast cancer in vitro and investigated the distinct roles of NMII isoforms in the regulation of substrate stiffness. We demonstrate that NMIIA is engaged in establishing cell polarity by facilitating lamellipodia formation, focal adhesion turnover, and actin polymerization at the cell leading edge, while NMIIB is recruited to the cell perinuclear region and contributes to traction force generation and polarized distribution, both in a substrate stiffness-dependent manner. We further validated that substrate stiffness modulates the distribution and activation of NMII isoforms via the Rac1/p-PAK1/pS1916-NMIIA and PKCζ/pS1935-NMIIB signaling pathways in a site- and kinase-specific phosphoregulation manner. Our study is helpful for understanding the mechanotransduction of cancer cells and provides inspiration for molecular targets in antimetastatic therapy.


Assuntos
Neoplasias da Mama/genética , Matriz Extracelular/genética , Miosina não Muscular Tipo IIA/genética , Miosina não Muscular Tipo IIB/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Polaridade Celular/genética , Feminino , Humanos , Mecanotransdução Celular/genética , Isoformas de Proteínas/genética , Transdução de Sinais/genética , Especificidade por Substrato , Quinases Ativadas por p21/genética , Proteínas rac1 de Ligação ao GTP/genética
19.
Int J Cancer ; 150(1): 73-79, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34460111

RESUMO

Polygenic risk scores (PRS) for disease risk stratification show great promise for application in general populations, but most are based on data from individuals of White European origin. We assessed two well validated PRS (SNP18, SNP143) in the Predicting-Risk-of-Cancer-At-Screening (PROCAS) study in North-West England for breast cancer prediction based on ethnicity. Overall, 9475 women without breast cancer at study entry, including 645 who subsequently developed invasive breast cancer or ductal carcinoma in situ provided DNA. All were genotyped for SNP18 and a subset of 1868 controls were genotyped for SNP143. For White Europeans both PRS discriminated well between individuals with and without cancer. For n = 395 Black (n = 112), Asian (n = 119), mixed (n = 44) or Jewish (n = 120) women without cancer both PRS overestimated breast cancer risk, being most marked for women of Black and Jewish origin (P < .001). SNP143 resulted in a potential mean 40% breast cancer risk overestimation in the combined group of non-White/non-European origin. SNP-PRS that has been normalized based on White European ethnicity for breast cancer should not be used to predict risk in women of other ethnicities. There is an urgent need to develop PRS specific for other ethnicities, in order to widen access of this technology.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/epidemiologia , Polimorfismo de Nucleotídeo Único , /genética , Adulto , Idoso , Densidade da Mama , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Estudos de Casos e Controles , Inglaterra/epidemiologia , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
20.
Int J Cancer ; 150(1): 124-131, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34460112

RESUMO

In August 2017, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have been reimbursed in the Netherlands for patients with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer (ABC). This study evaluates the implementation of CDK4/6 inhibitors and changes in treatment choices in the Netherlands. All patients diagnosed with HR+/HER2- ABC in 2009 to 2018 in seven hospitals were selected from the Southeast Netherlands Advanced Breast cancer (SONABRE) registry. The 2-year cumulative use of CDK4/6 inhibitors since reimbursement date (August 2017) was assessed using competing-risk methodology in two cohorts. The first cohort included patients with ABC diagnosis between August 2017 and December 2018. The second cohort included patients with ABC diagnosis between 2009 and August 2017, and still alive on August 1, 2017. In addition, treatment choices in the first three lines of therapy in calendar years 2009 to 2018 were evaluated for the total study population. Among patients diagnosed since August 2017 (n = 214), 50% (95% confidence interval [CI] = 43-57) received CDK4/6 inhibitors within 2 years beyond diagnosis. Of eligible patients diagnosed before August 2017 (n = 417), 31% (95% CI = 27-36) received CDK4/6 inhibitors within 2 years following reimbursement. Another 20% of both cohorts are still CDK4/6 inhibitor naïve and on first-line therapy. The use of chemotherapy decreased in first two lines of therapy between 2009 and 2018 (first-line: 29%-13%; second-line: 26%-19%). The implementation rate of CDK4/6 inhibitors since reimbursement is currently 50% within 2 years beyond diagnosis and is expected to increase further. The implementation of targeted therapy decreased the use of chemotherapy as first-line therapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Seleção de Pacientes , Prognóstico , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Taxa de Sobrevida
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