Like cervical cancer, anal cancer is often caused by a human papillomavirus and has a premalignant stage called high-grade squamous intraepithelial lesion or anal intraepithelial neoplasia. A ...randomized trial showed that treating HSIL led to a 57% reduction in progression to anal cancer as compared with active surveillance.
The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous ...intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n = 34), HSIL (n = 30), and SCC (n = 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH.
Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging ...agents that can be used to measure tissue and tumor proliferation. We have developed and tested F-18FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Highlights • Acute binge-pattern cocaine-induced region-specific effects in the striatum. • Cell counts revealed differential patterns in D1-r versus D2-r labeled cells. • Drd1 -eGFP mice had more ...labeled cells in the dorsolateral striatum. • Drd2 -eGFP mice had fewer labeled cells in the dorsolateral striatum. • Drd2 -eGFP mice also showed fewer labeled cells in the NAc core.
Purpose
We conducted a pilot trial utilizing
18
FFMAU 1-(2′-deoxy-2′-
18
Ffluoro-β-
d
-arabinofuranosyl thymine as a tumor tracer in positron emission tomography (PET) and evaluated its ...reproducibility, and changes in maximum and peak standardized uptake value (SUVmax and SUVpeak) with zoledronic acid treatment in castrate resistant prostate cancer (CRPC) patients with bone metastases (BM).
Procedures
Eligible patients had CRPC with radiographic evidence of BM and creatinine clearance >30 ml/min. Two baseline
18
FFMAU-PET scans (about 1 week apart, range 2–12 days) were obtained for testing reproducibility. Zoledronic acid 4 mg was infused over 15 min within 1 week after second scan and a third PET scan was obtained 7 days later. The bony lesion with the highest uptake on the first scan was compared with later scans. Bone turnover markers and prostate-specific antigen (PSA) were obtained pre- and post-therapy. PET response was defined as decline in SUVmean of ≥15 % after zoledronic acid.
Results
Eleven patients were evaluated, median age was 65 years, five were African-American and six were Caucasian, and median PSA level was 36.3 ng/ml (range 1.0–1209.3). Notably, the range of absolute percent SUVmax changes varied between 0.77 and 54.7, and only nine measurements were greater than one (1.09–2.19). Zoledronic acid did not appreciably change FMAU uptake. No clinical response was noted. Urine N-telopeptide (NTx) was markedly decreased in all patients after zoledronic acid and serum bone-specific alkaline phosphatase (BSAP) registered a modest change. Urine NTx correlated more closely with SUV max than serum BSAP.
Conclusions
FMAU tracer was able to detect bone metastases in CRPC patients but uptake was highly variable in bony lesions. Zoledronic acid did not produce an appreciable change in scans. Future investigations of FMAU tracer as a marker of early response in CRPC is recommended.
The kinetics of 1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)thymine (FMAU) were studied using PET to determine the most appropriate and simplest approach to image acquisition and analysis. The ...concept of tumor retention ratio (TRR) is introduced and validated.
Ten patients with brain (n = 4) or prostate (n = 6) tumors were imaged using (18)F-FMAU PET (mean dose, 369 MBq). Sixty-minute dynamic images were obtained; this was followed by whole-body images. Mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) of each tumor were determined as the mean over 3 planes of each time interval. For kinetic analyses, blood activity was measured in 18 samples over 60 min. Samples were analyzed by high-performance liquid chromatography at 3 selected times to determine tracer metabolites. FMAU kinetics were measured using a 3-compartment model yielding the flux (K1 x k3/(k2 + k3)) (K1, k2, and k3 are rate constants) and compared with TRR measurements. TRR was calculated as the tumor (18)F-FMAU uptake area under the curve divided by the product of blood (18)F-FMAU AUC and time. A similar analysis was performed using muscle to estimate (18)F-FMAU delivery.
SUVmean measurements obtained from 5 to 11 min correlated with those obtained from 30 to 60 min (r(2) = 0.92, P < 0.0001) and 50 to 60 min (r(2) = 0.92, P < 0.0001) due to the rapid clearance of (18)F-FMAU. Similar results were obtained using SUVmax measurements (r(2) = 0.93, P < 0.0001; r(2) = 0.88, P < 0.0001, respectively). The measurement of TRR using either blood or muscle activity over 11 min provided results comparable to those of 60-min dynamic imaging and a 3-compartment model. This analysis required only 5 blood samples drawn at 1, 2, 3, 5, and 11 min without metabolite correction to produce comparable results.
Tissue retention ratio measurements obtained over 11 min can replace flux measurements in (18)F-FMAU imaging. The SUVmean and the SUVmax in 5-11 min images correlated well with those of images obtained at 50-60 min. The quality of the images and tissue kinetics in 11 min of imaging makes it a desirable and shorter tumor imaging option.
Abstract
Background
Women living with human immunodeficiency virus (WLHIV) have disproportionately high rates of squamous cell carcinoma of the anus compared with the general population of women. ...Anal high-grade squamous intraepithelial lesions (HSILs) precede anal cancer, and accurate studies of HSIL prevalence among WLHIV in the United States are lacking.
Methods
The AIDS Malignancy Consortium 084 study was a multicenter national trial to evaluate the prevalence of and risk factors for anal HSIL in a US cohort. Eligible participants were WLHIV aged ≥18 years with no history of anal HSIL. Study participants had an examination including collection of cervical/vaginal and anal specimens, followed by high-resolution anoscopy with biopsy.
Results
We enrolled 256 women with evaluable anal pathology. The mean age was 49.4 years, 64% women were non-Hispanic black, 67% were former or current smokers, and 56% reported ever having anal sex with a man. The median CD4 T-cell count was 664 cells/μL. The prevalence of anal histologic HSIL (hHSIL) was 27% (95% confidence interval CI, 22%–33%). There was a strong concordance (240/254) between local and consensus pathologists for hHSIL vs less than hHSIL (κ = 0.86 95% CI, .79–.93). Current CD4 count of ≤200 cells/μL was the strongest predictor of consensus anal hHSIL diagnosis (adjusted odds ratio aOR, 10.34 95% CI, 3.47–30.87). History of anoreceptive intercourse was also associated with hHSIL (aOR, 2.44 95% CI, 1.22–4.76).
Conclusions
The prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy.
To determine the true prevalence of anal high-grade squamous intraepithelial lesions in women living with human immunodeficiency virus in the United States, we conducted high-resolution anoscopy and biopsies on all participants in the study. The prevalence was 27%, and substantially higher than previous reports.
► h of 5μm Fused-Core particles is lower than smaller Fused-Core particles. ► The thinner shell for the Fused-Core particles results in flatter van Deemter plots. ► Thinner shells have reduced ...surface area producing reduced loading and retention. ► Columns of 5μm Fused-Core particles have twice the plates of 5μm porous particles. ► A 5μm Fused-core column provides 3μm performance without the higher pressure.
Superficially porous particles (also called Fused-Core, core shell or porous shell particles) show distinct advantages over comparable totally porous particles for separating small molecules. Columns of Fused-Core particles exhibit very high efficiency because of superior eddy dispersion properties (smaller van Deemter A term). The efficiency for columns of 2.7μm Fused-Core particles actually rivals that for sub-2μm totally porous particles with only about one-half the back pressure. These Fused-Core particles show special advantages with larger molecules for fast separations at high mobile phase velocities because of superior mass transfer (kinetic) properties (smaller van Deemter C term). This report describes the effect of different particle size and porous shell thicknesses on chromatographic performance for Fused-Core particles. Particle characteristics can significantly affect factors of separation importance. For example, the reduced plate height of packed columns is affected by particle diameter. Interestingly, larger Fused-Core particles show smaller reduced plate heights than smaller Fused-Core particles. Also, porous shell thickness has a strong effect on solute retention as well as separation efficiency, and particle surface area has a direct influence on sample loading characteristics. Fused-Core particles with a wide range of physical characteristics have been developed that allows the preparation of stable, efficient packed columns.
Background: Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSILs). The incidence of anal cancer is ...highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years old, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). Setting: We enrolled MSM who were aged 50+ during 2018–2022 in San Francisco, CA. Methods: One hundred twenty-nine MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with a biopsy of visible lesions. Results: Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (odds ratio: 45.1, 95% confidence interval: 15.8–129); other oncogenic HPV types (odds ratio: 5.95, 95% confidence interval: 2.74–12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. Conclusion: The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remains very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening.
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