Abstract Human papilloma-virus (HPV) infection is the major cause of cervical cancer. HPV18 is the most prevalent high-risk HPV after type 16 that accounts for the largest number of cervical cancer ...cases worldwide. Currently, although prophylactic vaccines have been developed, there is still an urgent need to develop therapeutic HPV vaccines for targeting tumors post-infection. In this study, we utilize a novel multi-phase strategy for HPV18 antigen development with the goal of increasing anti-HPV18 cellular immunity. Our data show that this construct can induce strong cellular immune responses against HPV18 E6 and E7 antigens in a murine model. Moreover, when applied to rhesus monkeys, this construct is also able to elicit cellular immunity. These data suggest such DNA immunogens are candidates for further study in the eventual context of immunotherapy for HPV-associated cancers.
•Postprostate brachytherapy bladder cancers (BC) present with aggressive pathology.•Postbrachytherapy BC and postprostate cancer BC have similar 5-year overall survival and cancer-specific ...survival.•Radical cystoprostectomies are effective in treating postbrachytherapy muscle-invasive bladder cancer.
To characterize the clinical course and prognosis of bladder malignancies associated with prior prostate brachytherapy
We queried our institutional database for patients with bladder cancer (BC) diagnosed between January 2005 and April 2019 who had previously undergone low dose rate (LDR) prostate brachytherapy. Patients diagnosed with BC at least 1 year following LDR prostate brachytherapy with or without external beam radiation therapy were included. Clinical and disease-specific characteristics were abstracted from chart review and survival outcomes were estimated using Kaplan-Meier estimates. We compared the pathologic characteristics and prognosis of secondary BCs in our study cohort to those of BCs diagnosed after prostate cancer managed without radiation reported by the Surveillance, Epidemiology, and End Results (SEER) populational database from 2005 to 2018.
Three hundred seventy-five patients were identified with combined diagnosis of prostate cancer and BC, 51 of whom met inclusion criteria in the study cohort. Median times from brachytherapy to BC diagnosis for the study and SEER cohort were 9.5 ± 4.5 and 6.3 ± 4.1 years, respectively. Compared to the SEER cohort, significantly greater proportion of BC from the study cohort presented with high-grade (study: 78.4%, SEER: 52.3%, P = 0.0008) and with MIBC (Study BC 35.3%, SEER BC: 17.5%, P = 0.0009). The study and the SEER cohort had similar 5-year overall survival (study: 67.9%, SEER: 58.0%, P = 0.1099), and 5-year cancer-specific survival (study: 81.0%, SEER: 82.8%, P = 0.5559). The 5-year progression-free survival for the study cohort was 43.7% (95% CI: 28.8–57.7).
Compared to bladder cancers following prostate cancer managed without radiation, bladder malignancies following prostate LDR brachytherapy present with higher grade and are more likely to be muscle invasive. Despite the aggressive presenting features of postprostate brachytherapy BC, there were no differences in overall and cancer-specific survival between the groups.
Chemical wood property traits were analyzed for the presence of quantitative trait loci (QTLs) in a three-generation outbred pedigree of loblolly pine ( Pinus taeda L.). These traits were assayed ...using pyrolysis molecular beam mass spectrometry and include mass spectrum peak intensities associated with carbohydrates, alpha-cellulose and hemicellulose sugars, and lignin. Models for projection to latent structures (PLS) were used to also estimate the chemical composition of cell walls (i.e., alpha-cellulose, galactan and lignin) from mass spectrum data using multivariate regression. Both earlywood and latewood fractions from the fifth annual ring were analyzed for each trait. An interval mapping approach designed for an outbred pedigree was used to estimate the number of QTLs, the magnitude of QTL effects, and their genomic position. Eight unique QTLs influencing cell wall chemistry were detected from multiple peak intensities and/or PLS estimates using the one- and two-QTL models. Significant differences in chemical contents were observed among the populations from North Carolina vs Oklahoma, and results from QTLxenvironment analyses suggest that QTLs interact with environmental location. QTLs should be verified in larger experiments and in different genetic and environmental backgrounds. QTL mapping will help towards eventually identifying genes having a major effect on chemical wood properties.
Lung cancer and radiofrequency ablation Rose, Steven C; Thistlethwaite, Patricia A; Sewell, Patrick E ...
Journal of vascular and interventional radiology,
06/2006, Letnik:
17, Številka:
6
Journal Article
Recenzirano
Radiofrequency (RF) ablation is a recently developed technique for image-guided local destruction of selected tumors. Because the lung is a common site for cancer and usually has substantial ...functional reserve, RF ablation of lung cancers is an attractive option for minimally invasive treatment. The primary goal of the present review is to describe the natural history, staging systems, and conventional therapies for primary and secondary treatment of lung cancer, as well as the results of RF ablation in animal models and in humans for pulmonary applications, to clarify the appropriate role and limitations of this technology. The secondary goals are to review the principles of how RF works and to describe RF ablation techniques to familiarize interventionalists who may consider incorporating this technology into their practice and inform diagnostic radiologists of expected imaging findings and clinicians of their patients' anticipated courses and outcomes.
Psychometrics is a branch of psychology concerned with the measurement of mental attributes, behavior, and performance, in addition to the design and analysis of tests and other instruments. The ...origins of this field are rooted in the explorations of 18th century scientists concerned with capturing phenomena in empirical ways. Less discussed is the use of tests and assessments to validate racialization, which thrusts persons racialized as Black into the early discourse on psychometrics. Scholars, scientists, and psychometricians racialized as Black have long engaged psychometrics providing two major contributions: infrastructure via personnel and training programs built by persons racialized as Black; and interdisciplinarity, which include disciplinary standards and knowledge production. This commentary names these important figures and describes their contributions to the field of psychometrics.
Plain language summary
This commentary names these important Black figures and describes their contributions to the field of psychometrics.
Anchored reference loci provide a framework for comparative mapping. They are landmarks to denote conserved chromosomal segments, allowing the synthesis of genetic maps from multiple sources. We ...evaluated 90 expressed sequence tag polymorphisms (ESTPs) from loblolly pine (Pinus taeda L.) for this function. Primer sets were assayed for amplification and polymorphism in six pedigrees, representing two subgenera of Pinus and a distant member of the Pinaceae, Douglas-fir (Pseudotsuga menziesii Mirb. Franco). On average, 89% of primer sets amplified in four species of subgenus Pinus, 49% in one species of subgenus Strobus, and 22% in Douglas-fir. Polymorphisms were detected for 37-61% of the ESTPs within each pedigree. Comparative mapping in loblolly and slash pine (P. elliottii Englm.) revealed that ESTPs mapped to the same location. Disrupted synteny or significant disruptions in colinearity were not detected. Thirty-five ESTPs met criteria established for anchor loci. The majority of those that did not meet these criteria were excluded when map location was known in only a single species. Anchor loci provide a unifying tool for the community, facilitating the creation of a "generic" pine map and serving as a foundation for studies on genome organization and evolution.
Objectives
To assess the concordance between biopsy and radical prostatectomy (RP) specimens using the 2005 Gleason score (GS) and the International Society of Urological Pathology (ISUP) 2014/World ...Health Organization 2016 modified system, accounting for the introduction of transperineal biopsy and pre‐biopsy multiparametric magnetic resonance imaging (mpMRI).
Patients and Methods
Between 2002 and 2019, we identified 2431 patients with paired biopsy and RP histopathology from a prospectively recorded and maintained prostate cancer database. Biopsy specimens were graded according to the 2005 GS or ISUP 2014 modified system, according to the year of diagnosis. Multivariable logistic regression analysis was conducted to retrospectively assess the impact of prostate‐specific antigen (PSA), PSA density, age, pre‐biopsy mpMRI, and biopsy method, on the rate of upgraded disease. The kappa coefficient was used to establish the degree of change in concordance between groups.
Results
Overall, 24% of patients had upgraded disease and 8% of patients had downgraded disease when using the modified ISUP 2014 criteria. Agreement in the updated ISUP 2014 cohort was 68%, compared with 55% in the 2005 GS group, which was validated by a kappa coefficient that was good (k = 0.5 ± 0.4) and poor (k = 0.3 ± 0.1), respectively. In multivariable models, a change in grading system independently improved overall disease concordance (P = 0.02), and there were no other co‐segregated patient or pathological factors such as PSA, total number of cores, maximum cancer length, biopsy route or the use of mpMRI that impacted this finding.
Conclusion
The 2014 ISUP modifed system improves overall concordance between biopsy and surgical specimens, and thus allows more accurate prognostication and management in high‐grade disease, independent of more extensive prostate sampling and the use of mpMRI.
The use of recombinant T cell receptors (TCRs) to target therapeutic interventions has been hindered by the naturally low affinity of TCR interactions with peptide major histocompatibility complex ...ligands. Here, we use multimeric forms of soluble heterodimeric αβ TCRs for specific detection of target cells pulsed with cognate peptide, discrimination of quantitative changes in antigen display at the cell surface, identification of virus-infected cells, inhibition of antigen-specific cytotoxic T lymphocyte activation, and identification of cross-reactive peptides. Notably, the A6 TCR specific for the immunodominant HLA A2-restricted human T cell leukemia virus type 1 Tax11–19 epitope bound to HLA A2-HuD87–95 (KD 120 μm by surface plasmon resonance), an epitope implicated as a causal antigen in the paraneoplastic neurological degenerative disorder anti-Hu syndrome. A mutant A6 TCR that exhibited dramatically increased affinity for cognate antigen (KD 2.5 nm) without enhanced cross-reactivity was generated; this TCR demonstrated potent biological activity even as a monomeric molecule. These data provide insights into TCR repertoire selection and delineate a framework for the selective modification of TCRs in vitro that could enable specific therapeutic intervention in vivo.
Water vapor thermal therapy (WVTT, i.e., Rezum
) and prostatic urethral lift (PUL, i.e., Urolift
) are minimally invasive surgical therapy (MIST) options for benign prostatic hyperplasia (BPH). Few ...studies have directly compared the two procedures. We examined the clinical characteristics and postoperative outcomes of patients undergoing WVTT and PUL at our high-volume urban academic center.
We reviewed our institutional MIST database to identify patients with prostate sizes ≥30 and ≤80 cc who underwent WVTT or PUL for treatment of BPH between January 2017 and September 2021. Pre- and postoperative outcomes, including retreatment rates, American Urological Association symptom score (AUA-SS), maximum flow (Qmax), postvoid residual (PVR), medication usage, trial of void success rates, catheterization requirements, and postoperative complications within 90 days were extracted and compared between procedures.
Three hundred seven patients received WVTT and 110 patients received PUL with average follow-up times of 11.3 and 12.8 months, respectively. WVTT patients showed significant improvements in AUA-SS, Qmax, and PVR, whereas PUL patients showed improvements in only AUA-SS and Qmax. Both WVTT and PUL patients with longitudinal follow-up demonstrated improvements in AUA-SS, Qmax, and PVR. Postoperatively, alpha-blocker utilization was significantly decreased following both WVTT and PUL (WVTT: 73.9%-46.6%, PUL: 76.4%-38.2%, both
< 0.001). Compared to patients receiving PUL, WVTT patients more frequently reported postoperative dysuria (22.8%
8.3%,
= 0.001) and nonclot-related retention (18.9%
7.3%,
= 0.005); PUL patients more frequently experienced postoperative clot retention (7.3%
2.6%,
= 0.027). There were no differences in rates of postoperative bladder spasm, trial of void success, urinary tract infections, or emergency department visits. Postoperative erectile dysfunction and retrograde ejaculation were rare and occurred at similar rates.
In the real-world setting, WVTT and PUL have similar medium-term efficacy in improving symptoms and decreasing medication utilization for patients with BPH. Differences in postoperative complication profiles should inform patient counseling.
PDF
