Localized prostate cancer genotyping: Another step towards personalized therapy

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Genomic organization and recombinational unit duplication-driven evolution of ovine and bovine T cell receptor gamma loci

<p>Abstract</p> <p>Background</p> <p>In humans and mice ("γδ low species") less than 5% of the peripheral blood T lymphocytes are gamma/delta T cells, whereas in chicken and artiodactyls ("γδ high species") gamma/delta T cells represent about half of the T cells in peripheral blood. In cattle and sheep (Bovidae) two paralogous T cell receptor gamma loci (TRG1 and TRG2) have been found. TRG1 is located on 4q3.1, within a region of homology with the human TRG locus on chromosome 7, while TRG2 localizes on 4q2.2 and appears to be unique to ruminants. The purpose of this study was the sequencing of the genomic regions encompassing both loci in a "γδ high" organism and the analysis of their evolutionary history.</p> <p>Results</p> <p>We obtained the contiguous genomic sequences of the complete sheep TRG1 and TRG2 loci gene repertoire and we performed cattle/sheep sequence analysis comparison using data available through public databases. Dot plot similarity matrix comparing the two sheep loci with each other has shown that variable (V), joining (J) and constant (C) genes have evolved through a series of duplication events involving either entire cassettes, each containing the basic V-J-J-C recombinational unit, or single V genes. The phylogenetic behaviour of the eight enhancer-like elements found in the sheep, compared with the single copy present in the human TRG locus, and evidence from concordant insertions of repetitive elements in all analyzed TRGJ blocks allowed us to infer an evolutionary scenario which highlights the genetic "flexibility" of this region and the duplication-driven evolution of gene cassettes. The strong similarity of the human and Bovidae intergenic J-J-C regions, which display an enhancer-like element at their 3' ends, further supports their key role in duplications.</p> <p>Conclusion</p> <p>We propose that only duplications of entire J-J-C regions that possessed an enhancer-like element at their 3' end, and acquired at least one V segment at their 5' end, were selected and fixed as functional recombinational units.</p

Evolution of the T-cell receptor (TR) Loci in the adaptive immune response: The tale of the TRG locus in mammals

T lymphocytes are the principal actors of vertebrates’ cell-mediated immunity. Like B cells, they can recognize an unlimited number of foreign molecules through their antigen-specific heterodimer receptors (TRs), which consist of αβ or γδ chains. The diversity of the TRs is mainly due to the unique organization of the genes encoding the α, β, γ, and δ chains. For each chain, multi-gene families are arranged in a TR locus, and their expression is guaranteed by the somatic recombination process. A great plasticity of the gene organization within the TR loci exists among species. Marked structural differences affect the TR γ (TRG) locus. The recent sequencing of multiple whole genome provides an opportunity to examine the TR gene repertoire in a systematic and consistent fashion. In this review, we report the most recent findings on the genomic organization of TRG loci in mammalian species in order to show differences and similarities. The comparison revealed remarkable diversification of both the genomic organization and gene repertoire across species, but also unexpected evolutionary conservation, which highlights the important role of the T cells in the immune response

Comparing the first and the second waves of COVID-19 in Italy: differences in epidemiological features and CT findings using a semi-quantitative score

Purpose: CT findings of hospitalized COVID-19 patients were analyzed during both the first and the second waves of the pandemic, in order to detect any significant differences between the two groups. Methods: In this observational, retrospective, monocentric study, all hospitalized patients who underwent CT for suspected COVID-19 pneumonia from February 27 to March 27, 2020 (first wave) and from October 26 to November 24, 2020 (second wave) were enrolled. Epidemiological data, radiological pattern according to the RSNA consensus statement and visual score extension using a semi-quantitative score were compared. Results: Two hundred and eleven patients (mean age, 64.52&nbsp;years ± 15.14, 144 males) were evaluated during the first wave while 455 patients (mean age, 68.26&nbsp;years ± 16.34, 283 males) were studied during the second wave. The same prevalence of patterns was documented in both the first and the second waves (p = 0.916), with non-typical patterns always more frequently observed in elderly patients, especially the “indeterminate” pattern. Compared to those infected during the first wave, the patients of the second wave were older (64.52 vs.68.26, p = 0.005) and presented a slightly higher mean semi-quantitative score (9.0 ± 2.88 vs. 8.4 ± 3.06, p = 0.042). Age and semi-quantitative score showed a positive correlation (r = 0.15, p = 0.001). Conclusions: There was no difference regarding CT pattern prevalence between the first and the second waves, confirming both the validity of the RSNA consensus and the most frequent radiological COVID-19 features. Non-typical COVID-19 features were more frequently observed in older patients, thus should not be underestimated in the elderly population

Multiparametric magnetic resonance imaging for the differential diagnosis between granulomatous prostatitis and prostate cancer: a literature review to an intriguing diagnostic challenge

Multiparametric magnetic resonance imaging (mpMRI) is currently the most effective diagnostic tool for detecting prostate cancer (PCa) and evaluating adenocarcinoma-mimicking lesions of the prostate gland, among which granulomatous prostatitis (GP) represents the most interesting diagnostic challenge. GP consists of a heterogeneous group of chronic inflammatory lesions that can be differentiated into four types: idiopathic, infective, iatrogenic, and associated with systemic granulomatous disease. The incidence of GP is growing due to the increase in endourological surgical interventions and the adoption of intravesical instillation of Bacillus Calmette-Guerin in patients with non-muscle invasive bladder cancer; therefore, the difficulty lies in identifying specific features of GP on mpMRI to avoid the use of transrectal prostate biopsy as much as possible

Inside the 2016 American Society of Clinical Oncology Genitourinary Cancers Symposium: Part 1 - Kidney cancer

The American Society of Clinical Oncology Genitourinary Cancers Symposium, Moscone West Building, San Francisco, CA, USA, 7-9 January 2016 The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held in San Francisco (CA, USA), from 7 to 9 January 2016, focused on 'patient-centric care: translating research to results'. Every year, this meeting is a must for anyone studying genitourinary tumors to keep abreast of the most recent innovations in this field, exchange views on behaviors customarily adopted in daily clinical practice, and discuss future topics of scientific research. This two-part report highlights the key themes presented at the 2016 ASCO Genitourinary Cancers Symposium, with part 1 reporting the main novelties of kidney cancer and part 2 discussing the most relevant issues which have emerged for bladder and prostate tumors

The t cell receptor (Trb) locus in tursiops truncatus: From sequence to structure of the alpha/beta heterodimer in the human/dolphin comparison

The bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic envi-ronment. Here we report a genomic, evolutionary, and expression study of T. truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3’ end, its unique-ness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rear-ranged T cell receptor α (TRA) and TRB cDNA from the peripheral blood of one of the two speci-mens, and the human/dolphin amino acids multi-sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the com-plementarity-determining region according to IMGT numbering (CDR-IMGT) of the dolphin variable V-alpha and beta domains were identified. According to comparative modelization, the atom pair contact sites analysis between the human MH1 grove (G) domains and the T cell receptor (TR) V domains confirms conservation of the structure of the dolphin TR/pMH

PD-1 blockade therapy in renal cell carcinoma: current studies and future promises

RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway

Response of a radiology department to the SARS-CoV-2 pandemic: the experience of the hospital “Policlinico Tor Vergata” in Rome

The dissemination of severe acute respiratory syndrome linked to the novel coronavirus, SARS-CoV-2, prompted all health services to provide adequate measures to limit new cases that could affect healthcare professionals. Due to the large number of suspected patients subjected to CT scans and the proximity of radiologists to the patient during exams, radiologists as well as the entire staff of the radiology department are particularly exposed to SARS-CoV-2. This article includes the emergency management procedures, the use of personal protective devices, and the rearrangement of exam rooms and of human resources in the department of radiology at “Policlinico Tor Vergata” in Rome performed during the SARS-CoV-2 pandemic. We introduce the management measures that our department has taken to cope with the influx of patients while still ensuring the proper management of other emergencies and time-sensitive exams

Transverse prostate maximum sectional area can predict clinically significant prostate cancer in PI-RADS 3 lesions at multiparametric magnetic resonance imaging

BackgroundTo evaluate multiparametric magnetic resonance imaging (mpMRI) parameters, such as TransPA (transverse prostate maximum sectional area), TransCGA (transverse central gland sectional area), TransPZA (transverse peripheral zone sectional area), and TransPAI (TransPZA/TransCGA ratio) in predicting prostate cancer (PCa) in prostate imaging reporting and data system (PI-RADS) 3 lesions. MethodsSensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), the area under the receiver operating characteristic curve (AUC), and the best cut-off, were calculated. Univariate and multivariate analyses were carried out to evaluate the capability to predict PCa. ResultsOut of 120 PI-RADS 3 lesions, 54 (45.0%) were PCa with 34 (28.3%) csPCas. Median TransPA, TransCGA, TransPZA and TransPAI were 15.4cm(2), 9.1cm(2), 5.5cm(2) and 0.57, respectively. At multivariate analysis, location in the transition zone (OR=7.92, 95% CI: 2.70-23.29, P&lt;0.001) and TransPA (OR=0.83, 95% CI: 0.76-0.92, P&lt;0.001) were independent predictors of PCa. The TransPA (OR=0.90, 95% CI: 0.082-0.99, P=0.022) was an independent predictor of csPCa. The best cut-off of TransPA for csPCa was 18 (Sensitivity 88.2%, Specificity 37.2%, PPV 35.7%, NPV 88.9%). The discrimination (AUC) of the multivariate model was 0.627 (95% CI: 0.519-0.734, P&lt;0.031). ConclusionsIn PI-RADS 3 lesions, the TransPA could be useful in selecting patients requiring biopsy