Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct ...clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14⁺ cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14⁺ epithelial tumor cell clusters disseminate collectively to colonize distant organs.
Abstract Background A growing body of retrospective literature is emerging regarding active surveillance (AS) for patients with small renal masses (SRMs). There are limited prospective data ...evaluating the effectiveness of AS compared to primary intervention (PI). Objective To determine the characteristics and clinical outcomes of patients who chose AS for management of their SRM. Design, setting, and participants From 2009 to 2014, the multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry prospectively enrolled 497 patients with solid renal masses ≤4.0 cm who chose PI or AS. Intervention AS versus PI. Outcome measurements and statistical analysis The registry was designed and powered as a noninferiority study based on historic recurrence rates for PI. Analyses were performed in an intention-to-treat manner. Primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Results and limitations Of the 497 patients enrolled, 274 (55%) chose PI and 223 (45%) chose AS, of whom 21 (9%) crossed over to delayed intervention. AS patients were older, had worse Eastern Cooperative Oncology Group scores, total comorbidities, and cardiovascular comorbidities, had smaller tumors, and more often had multiple and bilateral lesions. OS for PI and AS was 98% and 96% at 2 yr, and 92% and 75% at 5 yr, respectively (log rank, p = 0.06). At 5 yr, CSS was 99% and 100% for PI and AS, respectively ( p = 0.3). AS was not predictive of OS or CSS in regression modeling with relatively short follow-up. Conclusions In a well-selected cohort with up to 5 yr of prospective follow-up, AS was not inferior to PI. Patient summary The current report is among the first prospective analyses of patients electing for active surveillance of a small renal mass. Discussion of active surveillance should become part of the standard discussion for management of small renal masses.
Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical ...biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization.
Background
The rapidly expanding clinical adaptation of prostate-specific membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with prostate cancer has placed an increasing onus ...on understanding both the potential pearls of interpretation as well as limitations of this new technique. As with any new molecular imaging modality, accurate characterization of abnormalities on PSMA-targeted PET imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants of radiotracer uptake, and potential sources of false-positive and false-negative imaging findings. In recent years, a growing number of reports have come to light describing incidental non-prostatic benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In this review, we have summarized the published literature regarding the potential pearls and technical and interpretive pitfalls of this imaging modality. Knowledge of these limitations can increase the confidence of interpreting physicians and thus improve patient care.
Conclusions
As PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance.
The oligometastatic state has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastases. With improvements in diagnostic modalities such as ...functional imaging, oligometastatic prostate cancer is being diagnosed with greater frequency than ever before. Furthermore, the paradigm for treatment of advanced prostate cancers is shifting toward a more aggressive approach. Many questions surround the understanding of the process and consequences of oligometastasis, meaning that the contemporary literature offers a wide variety of definitions of oligometastatic prostate cancer. Until genomic data exist to provide a biological component to the definition of oligometastatic disease, a clinical diagnosis made on the basis of up to five extrapelvic lesions is reasonable for use. Retrospective studies suggest that interventions such as radical prostatectomy and local or metastasis-directed radiotherapy can be performed in the metastatic setting with minimal risk of toxic effects. These therapies seem to decrease the need for subsequent palliative interventions, but insufficient data are available to draw reliable conclusions regarding their effect on survival. Thus, a protocol for clinicians to manage the patient presenting with oligometastatic prostate cancer would be a useful clinical tool.
Calcium carbonate (CaCO3) has attracted scientific attention due to its essential role in both inorganic and bioorganic chemistry. Vaterite is the least thermodynamically stable CaCO3 polymorph and ...has elicited great interest as an advanced biomaterial for tissue engineering, drug delivery, and a broad range of personal care products. Numerous methods of vaterite particle synthesis with different sizes and morphologies have highlighted the submicron porous particles of spherical or ellipsoidal shape as the most useful ones. In this regard, the current study is aimed at development of a reliable method for synthesis of such structures. Herein, submicron vaterite particles are synthesized by dropwise precipitation from saturated sodium carbonate and calcium chloride solutions in the presence of ethylene glycol while manipulating the concentration ratios of reagents. We demonstrate that our novel technique named “dropwise precipitation” leads to changing calcium concentrations in the reaction solution at each moment affecting the crystallization process. The proposed technique allows routine obtainment of vaterite particles of a required shape, either spherical or ellipsoidal, and a controlled size in the range from 0.4 to 2.7 μm and (0.4 × 0.7) to (0.7 × 1.1) μm, respectively. The key parameters influencing the size, shape, and percent of vaterite fraction for synthesized CaCO3 particles are discussed.
With the purpose to replace expensive and significantly cytotoxic positively charged polypeptides in biodegradable capsules formed via Layer-by-Layer (LbL) assembly, multilayers of bovine serum ...albumin (BSA) and tannic acid (TA) are obtained and employed for encapsulation and release of model drugs with different solubility in water: hydrophilic-tetramethylrhodamine-isothiocyanate-labeled BSA (TRITC-BSA) and hydrophobic 3,4,9,10-tetra-(hectoxy-carbonyl)-perylene (THCP). Hydrogen bonding is proposed to be predominant within thus formed BSA/TA films. The TRITC-BSA-loaded capsules comprising 6 bilayers of the protein and polyphenol are benchmarked against the shells composed of dextran sulfate (DS) and poly-l-arginine (PARG) on degradability by two proteolytic enzymes with different cleavage site specificity (i.e., α-chymotrypsin and trypsin) and toxicity for murine RAW264.7 macrophage cells. Capsules of both types possess low cytotoxicity taken at concentrations equal or below 50 capsules per cell, and evident susceptibility to α-chymotrypsin resulted in release of TRITC-BSA. While the BSA/TA-based capsules clearly display resistance to treatment with trypsin, the assemblies of DS/PARG extensively degrade. Successful encapsulation of THCP in the TRITC-BSA/TA/BSA multilayer is confirmed, and the release of the model drug is observed in response to treatment with α-chymotrypsin. The thickness, surface morphology, and enzyme-catalyzed degradation process of the BSA/TA-based films are investigated on a planar multilayer comprising 40 bilayers of the protein and polyphenol deposited on a silicon wafer. The developed BSA/TA-based capsules with a protease-specific degradation mechanism are proposed to find applications in personal care, pharmacology, and the development of drug delivery systems including those intravenous injectable and having site-specific release capability.
Focal therapy (FT) and partial gland ablation (PGA) are quickly adopted by urologists and radiologists as an option for the management of localized prostate cancer.
To find consensus on a ...standardized nomenclature and to define a follow-up guideline after FT and PGA for localized prostate cancer in clinical practice.
A review of the literature identified controversial topics in the field of FT. Online questionnaires were distributed to experts during three rounds, with the goal to achieve consensus on debated topics. The consensus project was concluded with a face-to-face meeting in which final conclusions were formulated.
Controlled feedback of responses of previous rounds were summarized and returned to the participants allowing them to re-evaluate their decisions. The level of agreement to achieve consensus on a topic was set at 80%.
Sixty-five experts participated in this interdisciplinary consensus study (72% urologists; 28% radiologists). The experts propose the use of the herein standardized nomenclature for ablative procedures. After FT/PGA, the following tests should be performed to assess treatment outcomes: prostate-specific antigen (PSA), imaging, biopsies, and functional outcome assessment. Although not a reliable marker for treatment failure, PSA should be measured every 3 mo in the 1st year and every 6 mo thereafter. Magnetic resonance imaging is the preferred image modality and should be performed at 6 and 18 mo after treatment. A systematic 12-core transrectal ultrasound-guided biopsy combined with a targeted biopsy of the treated area should be performed 6–12 mo after treatment. Functional outcomes should be obtained 3–6 mo after treatment for the first time and until stability is attained.
The panel recommends the use of the proposed nomenclature and follow-up protocols to generate reliable data supporting a broader implementation of FT as a standard of care for select patients with localized prostate cancer.
In this report, we present expert opinion on the use of a standardized nomenclature, and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer.
In this report, we present expert opinion on the use of a standardized nomenclature and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer. The panel recommends the use of the proposed nomenclature and follow-up protocols to generate reliable data supporting a broader implementation of focal therapy as a standard of care for select patients with localized prostate cancer.
The good in social media Gorin, Michael A.
BJUI compass,
November 2022, Letnik:
3, Številka:
6
Journal Article
Recenzirano
Odprti dostop
There is no doubt that this is something that social media can benefit from seeing more of, as in recent years, there has been no shortage of stories about how social media has had a negative impact ...on society. The use of this platform has been shown to improve the dissemination of clinical practice guidelines, 2 promote physician engagement in journal club, 3 enable input from other doctors on complex clinical cases 4 and facilitate the exchange of information between healthcare organizations, patients, and providers. 5 In my own experience, I have found social media to be a rich source of information on the latest medical news. Since joining Twitter in 2015 (@michael_gorin), I can say that there have been few, if any, major clinical trial results that I did not know about within a day or so of their reporting at a conference or within a journal. Of these contributions, perhaps the most important one relates to defining the journal's mission of being home to any publication in the field of urology that adheres to ‘sound science’ principles, regardless of the overall impact of a paper. 6 Even negative studies or those that are only confirmatory in nature are welcome for publication at BJUI Compass, so long as the methods used are scientifically valid.
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