Human basal-like breast cancer (BLBC) is an enigmatic and aggressive malignancy with a poor prognosis. There is an urgent need to identify therapeutic targets for BLBC, because current treatment ...modalities are limited and not effective. The forkhead box transcription factor FOXC1 has recently been identified as a critical functional biomarker for BLBC. However, how it orchestrates BLBC cells was not clear. Here we show that FOXC1 activates the transcription factor nuclear factor-κB (NF-κB) in BLBC cells by increasing p65/RelA protein stability. High NF-κB activity has been associated with estrogen receptor-negative breast cancer, particularly BLBC. The effect of FOXC1 on p65/RelA protein stability is mediated by increased expression of Pin1, a peptidyl-prolyl isomerase. FOXC1 requires NF-κB for its regulation of cell proliferation, migration and invasion. Notably, FOXC1 overexpression renders breast cancer cells more susceptible to pharmacological inhibition of NF-κB. These results suggest that BLBC cells may rely on FOXC1-driven NF-κB signaling. Interventions of this pathway may provide modalities for the treatment of BLBC.
The experimental work, particularly the SEM study, presented in “Magnetic properties of electroformed Ni and Ni-Fe for Micromagnetic MEMS Applications”.
This paper reports a new technique which is based on electroforming process for high permeability Ni and Ni-Fe alloy. The magnetic properties of Ni and Ni-Fe alloy are investigated as a function of ...plating current density via scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and vibrating sample magnetometer (VSM). Concentration-dependent kinetics is used to formulate the deposition rate and also the same is verified by using finite element analysis tool COMSOL Multiphysics. Several experiments are performed to derive the relation between electroplating parameters and magnetic properties. The process conditions are optimized to develop high permeability (∼16000) Ni-Fe alloy (85.71–14.29 %). The higher current density shows a monotonically increasing behavior of relative permeability (μ
r
). In addition, the B-H curves indicate that the saturation magnetization (
B
s
a
t
) increases and coercivity decreases with increasing plating current density. Our experimental data confirms that the higher current density increase the softness of Ni. The observed properties of Ni and Ni-Fe based on experimental results can be used to study the magnetic behavior of micromagnetic sensors and large force actuators.
In this review, we summarize ongoing clinical trials involving liquid biopsies (LB) for colorectal cancer (CRC), outlining the current landscape and the future implementation of this technology. We ...also describe the current use of LB in CRC treatment at our institution, the Mayo Clinic Enterprise.
The use of LB in CRC treatment merits close attention. Their role is being evaluated in the screening, non-intervention, intervention, and surveillance settings through many active trials. This, coupled with the technique's rapid integration into clinical practice, creates constant evolution of care.
Review of ClinicalTrials.gov was performed identifying relevant and active trials involving LB for CRC. "Colorectal cancer" plus other terms including "liquid biopsies" and "ctDNA" were used as search terms, identifying 35 active trials.
LB use for the CRC is actively being investigated and requires close attention. Based on current evidence, Mayo Clinic Enterprise currently uses LB in the non-interventional, interventional and surveillance setting, but not for screening. Results of these trials may further establish the use of LB in the management of CRC.
Background
Schwannomas are rare tumours that pose a significant management challenge in the abdomen, retroperitoneum and pelvis. No data are available to inform management strategy.
Methods
A ...collaborative international cohort study, across specialist sarcoma units, was conducted to include adults presenting between 2000 and 2017 with histopathologically confirmed schwannomas within the abdomen, retroperitoneum or pelvis.
Results
Of 485 patients across 12 centres, 38 (7·8 per cent) were discharged without follow‐up, 199 (41·0 per cent) underwent early resection and 248 (51·1 per cent) had radiological monitoring. Of these 248 patients, 96 (38·7 per cent) eventually had surgery, giving an overall resection rate of 60·8 per cent (295 of 485). At baseline, median tumour volume was 90·1 (i.q.r. 26·5–262·0) cm3. The estimated growth rate was 10·5 (95 per cent c.i. 9·4 to 11·6) per cent per year, and was consistent in the short term (within 2 years of diagnosis) and long term (beyond 2 years) (ρ = 0·405, P = 0·021). A decision to operate was more common in symptomatic patients (P < 0·001) and for rapidly growing tumours (growth rate more than 20 per cent per year) (P = 0·025). R0/R1 resection was achieved in 91·6 per cent of patients (263 of 287). Kaplan–Meier long‐term recurrence rates after R0/R1 resection were 2·3 and 6·7 per cent at 3 and 5 years respectively.
Conclusion
Specific recommendations include: indications for early surgery, prediction of growth from radiological monitoring, promotion of selective submacroscopic resection and cessation of postoperative imaging surveillance.
Antecedentes
Los schwannomas son tumores raros que plantean un importante desafío para su tratamiento en el abdomen, retroperitoneo y pelvis. No existen datos disponibles que informen de la estrategia de tratamiento.
Métodos
Se llevó a cabo un estudio de cohortes colaborativo internacional, entre unidades especializadas en sarcomas, que incluía a pacientes adultos con schwannomas de la cavidad abdominal, retroperitoneo o pelvis con confirmación histológica que se presentaron entre 2000 y 2017.
Resultados
De 485 pacientes de los 12 centros, 38 (7,8%) fueron dados de alta sin seguimiento, 199 (41,0%) fueron sometidos a resección precoz y 248 (51,1%) pacientes se incluyeron en seguimiento radiológico, de estos últimos 96 pacientes (38,7%) fueron sometidos finalmente a cirugía, con una tasa global de resección del 60,8% (295/485). Al inicio, la mediana del volumen tumoral fue 90,1 cm3 (rango intercuartílico: 26,5‐262,0). La tasa media de crecimiento fue 10,5% por año (i.c. del 95%: 9,4%‐11,6%), siendo uniforme en el seguimiento a corto (durante los 2 años del diagnóstico) y largo plazo (más allá de los 2 años, rho: 0,405, P = 0,021). La decisión de establecer la indicación quirúrgica fue más frecuente en pacientes sintomáticos (P < 0,001) y en tumores con crecimiento rápido (> 20% por año, P = 0,025). Se consiguió una resección R0/R1 en el 91,6%. Las tasas de recidiva a largo plazo de Kaplan‐Meier tras resección R0/R1 fueron 2% y 7% a 3 y 5 años, respectivamente.
Conclusión
Las recomendaciones específicas incluyen: indicaciones para la cirugía precoz, predicción del crecimiento en el seguimiento radiológico, fomentar la resección submacroscópica selectiva, y cese del seguimiento postoperatorio con pruebas de imagen.
Schwannomas present a significant management challenge, and surgery can result in morbidity. Individualized growth rates predicted after a period of radiological monitoring can help guide decision‐making. There is no role for surveillance after resection.
Practical guidelines
Sex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well ...reported. We provide a comprehensive analysis of sexual dimorphism in human cancers.
We analyzed four sets of cancer incidence data from the SEER (USA, 1975-2015), from the Cancer Registry at Mayo Clinic (1970-2015), from Sweden (1970-2015), and from the World Cancer Report in 2012.
We found that all human cancers had statistically significant sexual dimorphism with male dominance in the United States and mostly significant in the Mayo Clinic, Sweden, and the world data, except for thyroid cancer, which is female-dominant.
Sexual dimorphism is a clear but mostly neglected phenotype for most human cancers regarding the clinical practice of cancer. We expect that our study will facilitate the mechanistic studies of sexual dimorphism in human cancers. We believe that fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of individualized precision medicine beginning from the sex-specific diagnosis, prognosis, and treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gender differences in the incidences of cancers have been found in almost all human cancers. However, the mechanisms that underlie gender disparities in most human cancer types have been ...under-investigated. Here, we provide a comprehensive overview of potential mechanisms underlying sexual dimorphism of each cancer regarding sex hormone signaling. Fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of precision medicine. Our discussions of potential mechanisms underlying sexual dimorphism in each cancer will be instructive for future cancer research on gender disparities.
•Sex differences in the incidences of cancers have been found in almost all human cancers.•A comprehensive overview of potential mechanisms of sexual dimorphism in each cancer regarding sex hormone signaling.•Fully addressing sexual dimorphism in human cancers will greatly benefit current development of precision medicine.•Our discussions of potential mechanisms of sexual dimorphism in each cancer will be instructive for future cancer research.
Human basal-like breast cancer (BLBC) is an enigmatic and aggressive malignancy with a poor prognosis. There is an urgent need to identify therapeutic targets for BLBC, because current treatment ...modalities are limited and not effective. The forkhead box transcription factor FOXC1 has recently been identified as a critical functional biomarker for BLBC. However, how it orchestrates BLBC cells was not clear. Here we show that FOXC1 activates the transcription factor nuclear factor-κB (NF-κB) in BLBC cells by increasing p65/RelA protein stability. High NF-κB activity has been associated with estrogen receptor-negative breast cancer, particularly BLBC. The effect of FOXC1 on p65/RelA protein stability is mediated by increased expression of Pin1, a peptidyl-prolyl isomerase. FOXC1 requires NF-κB for its regulation of cell proliferation, migration and invasion. Notably, FOXC1 overexpression renders breast cancer cells more susceptible to pharmacological inhibition of NF-κB. These results suggest that BLBC cells may rely on FOXC1-driven NF-κB signaling. Interventions of this pathway may provide modalities for the treatment of BLBC. PUBLICATION ABSTRACT
Abstract only
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Background: In the last decade there has been an increase in the incidence of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. Although many factors have ...been proposed to explain this trend, the impact of breast reconstruction on the decision to undergo CPM has not been extensively studied.
Methods: A retrospective review of breast cancer patients from Surveillance, Epidemiology and End Results (SEER) registry data (2004-2008) was conducted. Characteristics of patients undergoing CPM were evaluated.
Results: 71,176 patients with a diagnosis of stage I-III infiltrating ductal or lobular breast cancer underwent mastectomy for their primary lesion. Among these, 10,558 patients (15%) underwent a CPM. A significantly higher proportion of women undergoing CPM had reconstruction performed (44%) than those patients not undergoing CPM (13%), p<0.001. On multivariate analysis (Table), significant variables predicting CPM included age <50 years (OR 10.12), breast reconstruction (OR 3.58), and lobular histology (OR 1.41), all p<0.001. Of the 12,466 patients (18%) who underwent reconstruction, 4,636 (37%) had implant reconstruction, 4,498 (36%) had tissue reconstruction, and 1,122 (9%) had combined tissue/implant reconstruction (no data for 18%). On multivariate analysis, predictors of reconstruction included age <50 years (OR 20.5; CI 18.5-22.7), year of surgery (2008 vs. 2004; OR 1.60; CI 1.49-1.71), low tumor grade (OR 1.19; CI 1.13-1.25) and ER+ status (OR 1.16; 95% CI 1.10-1.23). The use of radiation therapy was associated with a lower likelihood of pursuing reconstruction (OR 0.61; CI 0.58-0.65).
Conclusions: Apart from age, the factor most strongly associated with CPM is the decision to have reconstructive surgery performed. This suggests that CPM may not be purely associated with risk-reduction but also with treatment factors such as cosmesis.
Table: see text
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