Tumor cells detach from the primary tumor or metastatic sites and enter the peripheral blood, often causing metastasis. These cells, named Circulating Tumor Cells (CTCs), display the same spatial and ...temporal heterogeneity as the primary tumor. Since CTCs are involved in tumor progression, they represent a privileged window to disclose mechanisms of metastases, while -omic analyses at the single-cell level allow dissection of the complex relationships between the tumor subpopulations and the surrounding normal tissue. However, in addition to reporting the proof of concept that we can query CTCs to reveal tumor evolution throughout the continuum of treatment for early detection of resistance to therapy, the scientific literature has also been highlighting the disadvantages of CTCs, which hampers a routine use of this approach in clinical practice. To date, an increasing number of CTC technologies, as well as -omics methods, have been employed, mostly lacking strong comparative analyses. The rarity of CTCs also represents a major challenge, because there is no consensus regarding the minimal criteria necessary and sufficient to define an event as CTC; moreover, we cannot often compare data from of one study with that of another. Finally, the availability of an individual tumor profile undermines the traditional histology-based treatment. Applying molecular data for patient benefit implies a collective effort by biologists, bioengineers, and clinicians, to create tools to interpret molecular data and manage precision medicine in every single patient. Herein, we focus on the most recent findings in CTC −omics to learn how far we have come.
Silver and gold salts and complexes mainly act as soft and carbophilic Lewis acids even if their use as σ-activators has been rarely reported. Recently, transformations involving Au(I)/Au(III)-redox ...catalytic systems have been reported in the literature. In this review we highlight all these aspects of silver and gold-mediated processes and their application in multicomponent reactions.
Image-guided vacuum-assisted breast biopsy (VABB) of the tumour bed, performed after neoadjuvant therapy, is increasingly being used to assess residual cancer and to potentially identify to identify ...pathological complete response (pCR). In this study, the accuracy of preoperative VABB specimens was assessed and compared with surgical specimens in patients with triple-negative or human epidermal growth factor receptor 2 (HER2)-positive invasive ductal breast cancer after neoadjuvant therapy. As a secondary endpoint, the performance of contrast-enhanced MRI of the breast and PET-CT for response prediction was assessed.
This single-institution prospective pilot study enrolled patients from April 2018 to April 2021 with a complete response on imaging (iCR) who subsequently underwent VABB before surgery. Those with a pCR at VABB were included in the primary analysis of the accuracy of VABB. The performance of imaging (MRI and PET-CT) was analysed for prediction of a pCR considering both patients with an iCR and those with residual disease at postneoadjuvant therapy imaging.
Twenty patients were included in the primary analysis. The median age was 44 (range 35-51) years. At surgery, 18 of 20 patients showed a complete response (accuracy 90 (95 per cent exact c.i. 68 to 99) per cent). Only two patients showed residual ductal intraepithelial neoplasia of grade 2 and 3 respectively. In the secondary analysis, accuracy was similar for MRI and PET-CT (77 versus 78 per cent; P = 0.76).
VABB in patients with an iCR might be a promising method to select patients for de-escalation of surgical treatment in triple-negative or HER2-positive breast cancer. The present results support such an approach and should inform the design of future trials on de-escalation of surgery.
Circulating tumor cells (CTCs) are cellular elements that can be scattered into the bloodstream from primary cancer, metastasis, and even from a disseminated tumor cell (DTC) reservoir. CTCs are ..."seeds", able to give rise to new metastatic lesions. Since metastases are the cause of about 90% of cancer-related deaths, the significance of CTCs is unquestionable. However, two major issues have stalled their full clinical exploitation: rarity and heterogeneity. Therefore, their full clinical potential has only been predicted. Finding new ways of studying and using such tremendously rare and important events can open new areas of research in the field of cancer research, and could drastically improve tumor companion diagnostics, personalized treatment strategies, overall patients management, and reduce healthcare costs.
The reactivity of vinyl‐/furoindole derivatives with gold‐activated π‐systems is the subject of extensive investigation. In the presence of these electrophilic partners, the realized transformations ...allow for the construction of different and fascinating architectures via cycloaddition and cyclization reactions often included in cascade processes. The reactions realized involving in these processes an external substituent at the indole moiety are the subject of the present minireview.
The use of substituted or polycyclic indoles in reactions with gold‐activated π‐systems allows for the synthesis of new classes of carbazole derivatives and highly functionalized indoles under mild conditions and with high level of regio diastereo and enantio selectivities.
Qualitative alterations or abnormal expression of microRNAs (miRNAs) in colon cancer have mainly been demonstrated in primary tumors. Poorly overlapping sets of oncomiRs, tumor suppressor miRNAs and ...metastamiRs have been linked with distinct stages in the progression of colorectal cancer. To identify changes in both miRNA and gene expression levels among normal colon mucosa, primary tumor and liver metastasis samples, and to classify miRNAs into functional networks, in this work miRNA and gene expression profiles in 158 samples from 46 patients were analysed.
Most changes in miRNA and gene expression levels had already manifested in the primary tumors while these levels were almost stably maintained in the subsequent primary tumor-to-metastasis transition. In addition, comparing normal tissue, tumor and metastasis, we did not observe general impairment or any rise in miRNA biogenesis. While only few mRNAs were found to be differentially expressed between primary colorectal carcinoma and liver metastases, miRNA expression profiles can classify primary tumors and metastases well, including differential expression of miR-10b, miR-210 and miR-708. Of 82 miRNAs that were modulated during tumor progression, 22 were involved in EMT. qRT-PCR confirmed the down-regulation of miR-150 and miR-10b in both primary tumor and metastasis compared to normal mucosa and of miR-146a in metastases compared to primary tumor. The upregulation of miR-201 in metastasis compared both with normal and primary tumour was also confirmed. A preliminary survival analysis considering differentially expressed miRNAs suggested a possible link between miR-10b expression in metastasis and patient survival. By integrating miRNA and target gene expression data, we identified a combination of interconnected miRNAs, which are organized into sub-networks, including several regulatory relationships with differentially expressed genes. Key regulatory interactions were validated experimentally. Specific mixed circuits involving miRNAs and transcription factors were identified and deserve further investigation. The suppressor activity of miR-182 on ENTPD5 gene was identified for the first time and confirmed in an independent set of samples.
Using a large dataset of CRC miRNA and gene expression profiles, we describe the interplay of miRNA groups in regulating gene expression, which in turn affects modulated pathways that are important for tumor development.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by the uncontrolled activation of cytotoxic T lymphocytes, NK cells, and macrophages, resulting in an ...overproduction of pro-inflammatory cytokines. A primary and a secondary form are distinguished depending on whether or not it is associated with hematologic, infectious, or immune-mediated disease. Clinical manifestations include fever, splenomegaly, neurological changes, coagulopathy, hepatic dysfunction, cytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis. In adults, therapy, although aggressive, is often unsuccessful. We report the case of a 41-year-old man with no apparent history of previous disease and an acute onset characterized by fever, fatigue, and weight loss. The man was from Burkina Faso and had made trips to his home country in the previous five months. On admission, leukopenia, thrombocytopenia, increased creatinine and transaminases, LDH, and CRP with a normal ESR were found. The patient also presented with hypertriglyceridemia and hyperferritinemia. An infectious or autoimmune etiology was ruled out. A total body CT scan showed bilateral pleural effusion and hilar mesenterial, abdominal, and paratracheal lymphadenopathy. Lymphoproliferative disease with HLH complication was therefore suspected. High doses of glucocorticoids were then administered. A cytologic analysis of the pleural effusion showed anaplastic lymphoma cells and bone marrow aspirate showed hemophagocytosis. An Epstein–Barr Virus (EBV) DNA load of more than 90000 copies/mL was found. Bone marrow biopsy showed a marrow localization of peripheral T lymphoma. The course was rapidly progressive until the patient died. HLH is a rare but usually fatal complication in adults of hematologic, autoimmune, and malignant diseases. Very early diagnosis and treatment are critical but not always sufficient to save patients.
A gold(I)‐catalyzed cascade 3,3‐propargylic rearrangement and 4+2 cycloaddition reaction of 2‐vinylindoles with propargylic esters is reported. The reaction leads to the synthesis of highly ...substituted tetrahydrocarbazole derivatives in high yields and diasteroselectivities. Furthermore, a preliminary screening for an asymmetric version of this reaction is described.
The peculiar features of gold(III) and gold(I) species include exceptional carbophilicity and, at the same time, lone pair affinity. Such a combination offers many advantages for the development of ...more sustainable approaches to the synthesis of indole derivatives from readily available 2‐alkynylanilines. This mini‐review critically summarizes the literature reports in this field, with the aim to encourage further research activities in this promising area.
Abstract Background Troponins may be elevated in patients with pneumonia, but associations with myocardial infarction (MI) and with platelet activation are still undefined. Objectives The aim of this ...study was to investigate the relationship between troponin elevation and in vivo markers of platelet activation in the early phase of hospitalization of patients affected by community-acquired pneumonia. Methods A total of 278 consecutive patients hospitalized for community-acquired pneumonia, who were followed up until discharge, were included. At admission, platelet activation markers such as plasma soluble P-selectin, soluble CD40 ligand, and serum thromboxane B2 (TxB2 ) were measured. Serum high-sensitivity cardiac troponin T levels and electrocardiograms were obtained every 12 and 24 h, respectively. Results Among 144 patients with elevated high-sensitivity cardiac troponin T, 31 had signs of MI and 113 did not. Baseline plasma levels of soluble P-selectin and soluble CD40 ligand and serum TxB2 were significantly higher in patients who developed signs of MI. Logistic regression analysis showed plasma soluble CD40 ligand (p < 0.001) and soluble P-selectin (p < 0.001), serum TxB2 (p = 0.030), mean platelet volume (p = 0.037), Pneumonia Severity Index score (p = 0.030), and ejection fraction (p = 0.001) to be independent predictors of MI. There were no significant differences in MI rate between the 123 patients (45%) taking aspirin (100 mg/day) and those who were not aspirin treated (12% vs. 10%; p = 0.649). Aspirin-treated patients with MIs had higher serum TxB2 compared with those without MIs (p = 0.005). Conclusions MI is an early complication of pneumonia and is associated with in vivo platelet activation and serum TxB2 overproduction; aspirin 100 mg/day seems insufficient to inhibit thromboxane biosynthesis. (MACCE in Hospitalized Patients With Community-acquired Pneumonia; NCT01773863 )
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