Variations in the human gut microbiome might reflect an individual’s lifestyle and influence their blood levels of disease biomarkers. Understanding the connections between gut microbes and host ...phenotypes is crucial for determining health and disease. The gastrointestinal tract has the largest reservoir of microbes, both in the lumen, where they aid primary and secondary metabolism, and on the mucosal surfaces, where they communicate with host immune cells. Here, we present a review of the interactions between the human microbiota and the host, to provide an overview of the role of the gut microbiome in the development and progression of major human diseases, with specific focus on cancer.
Avenues to Precision Oncology Meisel, Alexander
Healthbook TIMES. Oncology Hematology,
3/2020, Volume:
1, Issue:
3
Journal Article
Peer reviewed
Open access
Until recently, the clinical management of cancer heavily relied on anatomical and histopathological criteria, with ad hoc guidelines directing the therapeutic choices in specific indications. In the ...last years, the development and therapeutic implementation of novel anticancer therapies significantly improved the clinical outcome of cancer patients. Nonetheless, such cutting-edge approaches revealed the limitation of the one-size-fits-all paradigm. The newly discovered molecular targets can be exploited either as bona fide targets for subsequent drug development, or as tools to precision medicine, in the form of prognostic and/or predictive biomarkers. This article provides an overview of some of the most recent advances in precision medicine in oncology, with a focus on novel tissue-agnostic anticancer therapies. The definition and implementation of biomarkers and companion diagnostics in clinical trials and clinical practice are also discussed, as well as the changing landscape in clinical trial design.
ABSTRACT
In general, advanced prostate cancer is initially treated with androgen deprivation therapy (ADT). Despite high response rates to this treatment, the response is not durable and most of the ...patients eventually develop metastatic castration-resistant prostate cancer (mCRPC). The treatment strategies for mCRPC usually include a combination of different approaches, such as hormone therapy, chemotherapy, or radiation. Here, we discuss the case of a 78-year old patient with advanced prostate cancer who developed mCRPC after 4 years of continuous therapy with ADT. The patient was subsequently treated with analgesic radiotherapy, followed by chemotherapy, including docetaxel and cabazitaxel. The patient responded well to the treatment, with acceptable treatment-related toxicity. Three years later, however, the disease progressed, and the patient received anti-hormonal therapy with enzalutamide. In conclusion, this case report discusses the different therapy selections and outcomes. Finally, a literature overview offers a comprehensive insight into the current systemic therapies for mCRPC.
Early diagnosis and the detection of distant metastases and recurrences in patients with prostate cancer (PCa) have been notably improved in recent decades through advances in imaging techniques. ...More recently, positron emission tomography (PET) hybrid imaging (PET/computed tomography \CT and PET/magnetic resonance imaging \MRI) using small molecule radiopharmaceuticals to selectively bind targets unique to PCa has permitted more accurate staging of patients with localized, locally advanced and metastatic disease. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in most PCa cells, has emerged as one of many specific targets for PCa imaging. Since its introduction in Switzerland in 2016, PSMA-targeted PET/CT with ^68^Gallium(^68^Ga)-labeled and, less commonly, ^18^Flourine(^18^F) -labelled radiotracers, has shown unparalleled precision in detecting metastatic PCa compared with conventional imaging techniques. Furthermore, radioligand therapies such as lutetium-177 (^177^Lu)-PSMA-617 can selectively deliver β-radiation to PSMA-expressing cells. The phase III VISION trial showed that this treatment significantly improved survival outcomes in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). This article discusses the value and impact of ^68^Ga/^18^F-PSMA PET/CT imaging compared with conventional imaging modalities for accurately detecting PCa lesions in a primary setting and for local recurrence or metastases. In addition, an overview of the PSMA ligand therapy, a treatment modality for patients with advanced PCa is presented.
The G protein-coupled estrogen receptor (GPER) is a novel estrogen receptor that mediates proliferative effects induced by estrogen but also by tamoxifen. The aim of our study was to analyze the ...frequency of GPER in a large collective of primary invasive breast carcinomas, with special emphasis on the subcellular expression and to evaluate the association with clinicopathological parameters and patient overall survival.
The tissue microarrays from formalin-fixed, paraffin embedded samples of primary invasive breast carcinomas (n = 981) were analyzed for GPER expression using immunohistochemistry. Expression data were compared to the clinicopathological parameters and overall survival. GPER localization was also analyzed in two immortalized breast cancer cell lines T47D and MCF7 by confocal immunofluorescence microscopy.
A predominantly cytoplasmic GPER expression was found in 189 carcinomas (19.3%), whereas a predominantly nuclear expression was observed in 529 cases (53.9%). A simultaneous comparable positive expression of both patterns was found in 32 of 981 cases (3.2%), and negative staining was detected in 295 cases (30%). Confocal microscopy confirmed the occurrence of cytoplasmic and nuclear GPER expression in T47D and MCF7. Cytoplasmic GPER expression was significantly associated with non-ductal histologic subtypes, low tumor stage, better histologic differentiation, as well as Luminal A and B subtypes. In contrast, nuclear GPER expression was significantly associated with poorly differentiated carcinomas and the triple-negative subtype. In univariate analysis, cytoplasmic GPER expression was associated with better overall survival (p = 0.012).
Our data suggest that predominantly cytoplasmic and/or nuclear GPER expression are two distinct immunohistochemical patterns in breast carcinomas and may reflect different biological features, reason why these patterns should be clearly distinguished in histological evaluations. Prospective studies will be needed to assess whether the expression status of GPER in breast carcinomas should be routinely observed by clinicians, for instance, before implementing endocrine breast cancer treatment.
Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. ...However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models. ACE-2 and TMPRSS-2 expression was analyzed by immunostaining in a variety of tissues obtained from FVB/N mice undergoing either gonadectomy or sham-surgery and being subjected to ischemia-reperfusion injury or transverse aortic constriction surgery. In lung tissues sex did not have a significant impact on the expression of ACE-2 and TMPRSS-2. On the contrary, following myocardial injury, female sex was associated to a lower expression of ACE-2 at the level of the kidney tubules. In addition, after myocardial injury, a significant correlation between younger age and higher expression of both ACE-2 and TMPRSS-2 was observed for lung alveoli and bronchioli, kidney tubules, and liver sinusoids. Our experimental data indicate that gonadal hormones and biological sex do not alter ACE-2 and TMPRSS-2 expression in the respiratory tract in mice, independent of disease state. Thus, sex differences in ACE-2 and TMPRSS-2 protein expression observed in mice may not explain the higher disease burden of COVID-19 among men.
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