Most cancers arise in individuals over the age of 60. As the world population is living longer and reaching older ages, cancer is becoming a substantial public health problem. It is estimated that, by 2050, more than 20% of the world's population will be over the age of 60 - the economic, healthcare and financial burdens this may place on society are far from trivial. In this Review, we address the role of the ageing microenvironment in the promotion of tumour progression. Specifically, we discuss the cellular and molecular changes in non-cancerous cells during ageing, and how these may contribute towards a tumour permissive microenvironment; these changes encompass biophysical alterations in the extracellular matrix, changes in secreted factors and changes in the immune system. We also discuss the contribution of these changes to responses to cancer therapy as ageing predicts outcomes of therapy, including survival. Yet, in preclinical studies, the contribution of the aged microenvironment to therapy response is largely ignored, with most studies designed in 8-week-old mice rather than older mice that reflect an age appropriate to the disease being modelled. This may explain, in part, the failure of many successful preclinical therapies upon their translation to the clinic. Overall, the intention of this Review is to provide an overview of the interplay that occurs between ageing cell types in the microenvironment and cancer cells and how this is likely to impact tumour metastasis and therapy response.

How the ageing microenvironment influences tumour progression

The major current conventional types of metastatic breast cancer (MBC) treatments include surgery, radiation, hormonal therapy, chemotherapy, or immunotherapy. Introducing biological drugs, targeted treatment and gene therapy can potentially reduce the mortality and improve the quality of life in patients with MBC. However, combination of several types of treatment is usually recommended. Triple negative breast cancer (TNBC) accounts for 10–20% of all cases of breast carcinoma and is characterized by the low expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2). Consequently, convenient treatments used for MBC that target these receptors are not effective for TNBC which therefore requires special treatment approaches. This review discusses the occurrence of MBC, the prognosis and predictive biomarkers of MBC, and focuses on the novel advanced tactics for treatment of MBC and TNBC. Nanotechnology-based combinatorial approach for the suppression of EGFR by siRNA and gifitinib is described.

/pdf/metastatic-and-triple-negative-breast-cancer-challenges-and-1tdrraq0p1.pdf

Metastatic and triple-negative breast cancer: challenges and treatment options.

Magnetic particle imaging (MPI) is a novel imaging method that was first proposed by Gleich and Weizenecker in 2005. Applying static and dynamic magnetic fields, MPI exploits the unique characteristics of superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs’ response allows a three-dimensional visualization of their distribution in space with a superb contrast, a very high temporal and good spatial resolution. Essentially, it is the SPIONs’ superparamagnetic characteristics, the fact that they are magnetically saturable, and the harmonic composition of the SPIONs’ response that make MPI possible at all. As SPIONs are the essential element of MPI, the development of customized nanoparticles is pursued with the greatest effort by many groups. Their objective is the creation of a SPION or a conglomerate of particles that will feature a much higher MPI performance than nanoparticles currently available commercially. A particle’s MPI performance and suitability is characterized by parameters such as the strength of its MPI signal, its biocompatibility, or its pharmacokinetics. Some of the most important adjuster bolts to tune them are the particles’ iron core and hydrodynamic diameter, their anisotropy, the composition of the particles’ suspension, and their coating. As a three-dimensional, real-time imaging modality that is free of ionizing radiation, MPI appears ideally suited for applications such as vascular imaging and interventions as well as cellular and targeted imaging. A number of different theories and technical approaches on the way to the actual implementation of the basic concept of MPI have been seen in the last few years. Research groups around the world are working on different scanner geometries, from closed bore systems to single-sided scanners, and use reconstruction methods that are either based on actual calibration measurements or on theoretical models. This review aims at giving an overview of current developments and future directions in MPI about a decade after its first appearance.

/pdf/magnetic-particle-imaging-current-developments-and-future-3gqjm8tdgg.pdf

Magnetic particle imaging: current developments and future directions

Tomographic imaging has become a mandatory tool for the diagnosis of a majority of diseases in clinical routine. Since each method has its pros and cons, a variety of them is regularly used in clinics to satisfy all application needs. Magnetic particle imaging (MPI) is a relatively new tomographic imaging technique that images magnetic nanoparticles with a high spatiotemporal resolution in a quantitative way, and in turn is highly suited for vascular and targeted imaging. MPI was introduced in 2005 and now enters the preclinical research phase, where medical researchers get access to this new technology and exploit its potential under physiological conditions. Within this paper, we review the development of MPI since its introduction in 2005. Besides an in-depth description of the basic principles, we provide detailed discussions on imaging sequences, reconstruction algorithms, scanner instrumentation and potential medical applications.

https://iopscience.iop.org/article/10.1088/1361-6560/aa6c99/pdf

Magnetic particle imaging: from proof of principle to preclinical applications

To investigate the effects of age at diagnosis on metastatic breast cancer and patients’ prognosis, we collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. We finally identified 4932 eligible metastatic breast cancer patients diagnosed between 2010–2013, including 850 younger patients ( 69 years). The results revealed that in stage IV patients, elder patients were more likely to have lung metastasis (P < 0.001) and less likely to have only distant lymphatic spread (P = 0.004). Higher proportion of younger (34.9%) and middle-aged (36.2%) patients had multiple metastatic sites than elder patients (28.3%) (P < 0.001). In survival analysis, younger patients presented the best prognosis, while elder patients had the worst both in overall survival (χ2 = 121.9, P < 0.001) and breast cancer-specific survival (χ2 = 69.8, P < 0.001). Age at diagnosis was an independent prognostic factor for metastatic breast cancer patients. Moreover, patients with bone metastasis only had superior survival compared to other metastatic patients (P < 0.001). Brain metastasis only group and multiple sites metastasis group had the poorest prognosis (P < 0.05). We hope the results will provide insights into a better understanding of distant metastatic breast cancer.

/pdf/comparison-of-patterns-and-prognosis-among-distant-ybqfww4r4c.pdf

Comparison of patterns and prognosis among distant metastatic breast cancer patients by age groups: a SEER population-based analysis

Gynecomastia is defined as a unilateral or bilateral persistent benign mammary gland enlargement in men. Prevalence of asymptomatic gynecomastia is up to 65%. True gynecomastia must be distinguished from pseudogynecomastia. Typically, in true gynecomastia, a solid tissue mass is palpable below the nipple-areolar complex. Malignant changes such as male mammary carcinoma must always be ruled out. The causes of gynecomastia are diverse. An imbalance of female to male hormones triggers the onset of the disease. This imbalance can be caused by endogenous diseases like hyperthyroidism, chronic liver disease, primary or secondary gonadal failure, androgen resistance syndromes, medication, and drug abuse. A series of heart or hypertension medications can also trigger gynecomastia. A basic requirement of proper therapy planning is knowledge of the triggers and possible drug therapy options. Inquiring about the patient's lifestyle and medication history is essential. Drug therapy with tamoxifen may be considered at an early stage. For gynecomastia persisting over 12 months, surgical excision is the treatment of choice, and there are several surgical options available depending on the grade of the gynecomastia. A thoughtful approach to managing this condition can lead to high patient satisfaction.

/pdf/gynecomastia-conservative-and-surgical-management-zh7n8tlmsv.pdf

Gynecomastia - Conservative and Surgical Management.

Background

We analysed the prevalence of the most common hereditary thrombophilia (hTP) – factor V Leiden (FVL) mutation, prothrombin 20210 G>A substitution (PT) – and the 677 C>T replacement in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in Caucasian patients with a history of two and more consecutive recurrent miscarriages (RMs) as compared to healthy controls with an identical ethnic background and at least one live birth.



Methods

A multicenter analysis of three hTP was performed in 641 RM patients identically screened at specialized university centres.



Results

The study groups consisted of 240 patients with 2 (1) and 401 patients with >2 miscarriages (2) and were compared with 157 controls. There was no significant difference in the prevalence of the hTP between RM patients and controls nor within the two study groups. Subgroup analysis showed that the homozygous MTHFR polymorphism was significantly more prevalent in the study group 2 as compared to study group 1 (13.9 versus 7.9%, P = 0.02).



Conclusion

In Caucasians, maternal FVL or PT mutations do not seem to contribute to the pathophysiology of RM, irrespective of the number of miscarriages. However, the role of the homozygous MTHFR polymorphism merits further investigation.

Maternal factor V Leiden and prothrombin mutations do not seem to contribute to the occurrence of two or more than two consecutive miscarriages in Caucasian patients.

Primary hyperparathyroidism in pregnant women is a rare antenatal complication. Maternal symptoms include nephrolithiasis, bone disease, pancreatitis, hyperemesis, muscle weakness, mental status changes, and hypercalcemic crisis. Fetal complications comprise intrauterine growth retardation, low birth weight, preterm delivery, intrauterine fetal death, postpartum neonatal titanic crisis, and permanent hypoparathyroidism. A 23-year-old gravida was referred to our clinic with severe hyperemesis and weight loss at 32 gestational weeks. She was diagnosed with primary hyperparathyroidism because of parathyroid adenoma and treated with surgery where a synchronous thyroid papillary carcinoma was detected. After right parathyroidectomy and right subtotal lobectomy of the thyroid, the patient was stable and laboratory and clinical findings normalized. The fetus’ state was monitored via reassuring non-stress cardiotocography and repeated sonographic exams until birth. Delivery was induced at 35 weeks of gestation because of preeclampsia. Parathyroid adenoma in pregnancy is a rare maternal condition with potential impact on the advancing pregnancy. Generally, a surgical approach is recommended with thorough inspection of the thyroid gland so that any irregular structure might be removed during the same surgical intervention for diagnostic reasons. In this reported case, a coexistent papillary carcinoma of the thyroid was detected accidentally and removed successfully.

Coexistent parathyroid adenoma and thyroid papillary carcinoma in pregnancy

Fragestellung: Die radikale axillare Lymphonodektomie (ALN) ist mit hoher Morbiditat und Lebensqualitatsverlust verbunden. Die Sentinellymphonodektomie (SNLB) verringert diese Folgen unter Verwendung von Farbstoff und Radionukliden. Superparamagnetische Eisenoxid-Nanopartikel (SPIOs) ersetzen diese unter Anwendung des neuen Magnetic Partilce Imaging (MPI)-Verfahrens. Die personelle Belastung mit ionisierenden Strahlen (Patientin und am SNLB-Prozess beteiligte) entfallt. Qualitative und quantitative Anreicherung von SPIOs im Lymphgewebe der Axilla sind bislang unerforscht. Zudem wurde das MPI-Verfahren bisher nicht in vivo angewandt. Durch die hier vorgestellten Versuche werden erstmals Ergebnisse in den genannten Fragestellungen im Mausmodel generiert. Methodik: Beim MPI werden SPIOs durch Anlegen magnetischer Wechselfelder im Gewebe dreidimensional darstell- und damit exakt lokalisierbar. Nach Injektion von Resovist® in die Milchdruse der lebenden Maus wird die Ausbreitung des Tracers nach Sacrifice im Gewebe histologisch, immunhistochemisch und elektronenmikroskopisch verfolgt. Dabei erfolgt eine Festlegung der optimalen Dosis und Laufzeit des Tracers in das Zielgebiet. Die Detektion des SNL erfolgt durch parallele Injektion mit Patentblau und wiederum durch Histologie/Iimmunhistochemie. Spektrometrische Untersuchungen dienen der Evaluation des MPI am isolierten axillaren Gewebe. Die Sicherheit des Verfahrens wird im Tumormodell der Maus mit zwei Mammakarzinomlinien am metastasierten Lymphknoten untersucht. Ergebnisse: Dieser Mausversuch ist Teil eines umfangreichen Versuchsprogramms zur Entwicklung eines neuen und gegenuber dem Standard der SNLB deutlich weniger aufwandigen und weniger belastenden Diagnoseverfahrens. Hierbei soll eine neuartige MPI-Handsonde mit einseitiger Magnetspulenanordnung zur Anwendung im Operationssaal entwickelt werden. Schlussfolgerung: Bei der konventionellen SNLB muss die Axilla komplett exploriert und der SNL im Gewebe identifiziert werden. Die intraoperative dreidimensionale Darstellung der SNL mittels MPI-Handsonde erleichtert das Auffinden der SNL im Gewebe. Die intensive operative Exploration der Axilla entfallt und die Morbiditat wird deutlich verringert. Die beim MPI eingesetzten Tracer sind leicht zu beschaffen, wodurch die Methode einem grosen Patientinnenkreis zuganglich wird. Das Konzept der SNLB durch MPI kann prinzipiell bei allen soliden Tumoren angewendet werden. Dieses Projekt wird durch das Bundesministerium fur Bildung und Forschung (BMBF) unterstutzt („Magnetic-Particle-Imaging fur die Wachterlymphknoten-Biopsie beim Mammakarzinom“, ID 91). Es ist auserdem Teil des universitaren Forschungsschwerpunktes „Bildgebung bei Krankheitsprozessen“ der Universitat zu Lubeck.

Magnetic Particle Imaging durch Superparamagnetische Nanopartikel zur Sentinellymphknotendetektion beim Mammakarzinom

https://www.degruyter.com/downloadpdf/j/bmte.2013.58.issue-s1-L/bmt-2013-4262/bmt-2013-4262.xml

Lymphatic Tissue and Superparamagnetic Nanoparticles - Magnetic Particle Imaging for Detection and Distribution in a Breast Cancer Model.

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