PURPOSE Anal cancer risk is substantially higher among HIV-infected men who have sex with men (MSM) as compared with other reproductive-age adults, but screening is rare across sub-Saharan Africa. We report the use of high-resolution anoscopy (HRA) as a first-line screening tool and the resulting early outcomes among MSM in Abuja, Nigeria. METHODS From August 2016 to August 2017, 424 MSM enrolled in an anal cancer screening substudy of TRUST/RV368, a combined HIV prevention and treatment cohort. HRA-directed biopsies were diagnosed by histology, and ablative treatment was offered for high-grade squamous intraepithelial lesions (HSIL). HRA proficiency was assessed by evaluating the detection of squamous intraepithelial lesions (SIL) over time and the proportion biopsied. Prevalence estimates of low-grade squamous intraepithelial lesions and HSIL with 95% CIs were calculated. Multinomial logistic regression was used to identify those at the highest risk of SIL. RESULTS Median age was 25 years (interquartile range [IQR], 22-29), median time since sexual debut was 8 years (IQR, 4-12), and 59% (95% CI, 54.2% to 63.6%) were HIV infected. Rate of detection of any SIL stabilized after 200 screenings, and less than 20% had two or more biopsies. Preliminary prevalence estimates of low-grade squamous intraepithelial lesions and HSIL were 50.0% (95% CI, 44.7% to 55.3%) and 6.3% (95% CI, 4.0% to 9.3%). HIV infection, at least 8 years since anal coital debut, concurrency, and external warts were independently statistically associated with SIL. CONCLUSION Proficiency with HRA increased with experience over time. However, HSIL detection rates were low, potentially affected by obstructed views from internal warts and low biopsy rates, highlighting the need for ongoing evaluation and mentoring to validate this finding. HRA is a feasible first-line screening tool at an MSM-friendly health care facility. Years since anal coital debut and external warts could prioritize screening.
IntroductionDiagnosis of prostatic diseases with Immunohistochemistry still faces challenges because of the peculiar histology of the prostate and difference(s) in reactivity of Monoclonal antibodies (MoAb) to benign and malignant changes.MethodsThirty (30) archived paraffin embedded tissue samples from primary prostate tumors (15 Benign Prostatic Hyperplasia (BPH) and 15 Cancer of the prostate (CaP)) were sectioned at thickness of 5µm and confirmed as BPH or CaP. Sections from each sample were stained by Immunohistochemistry using the Streptavidin-biotin method and using CK5/6, CK7, CK8,CK20 and Ki67 antibodies (Zymed Antibody products). Appropriate positive and negative controls for each antibody were setup alongside the test slides.ResultsBPH samples were reactive to Ck5/6 (93.3%), Ck7 (80%) and Ck8 (100%). Only 13.3% of BPH samples were reactive to Ki67. The reactivity of Ck5/6, 7, 8 in CaP is a contrast with only 3(20%) of samples positive with Ck5/6, 2(13.3%) positive with Ck7 and 14(93.3%) with Ck8. While reactivity of Ck 8 is similar in BPH and CaP, no reaction was recorded in Ck 20 in both BPH and CaP. Ki67 was only reactive in 2(13.3) of BPH samples and 15(100%) of CaP. Only Ck 8 was expressed in both BPH and CaP. There was co-expression of Ck5/6, 7,8 and Ki67 in13.3%; Ck7and Ki67 in 13.3% in both BPH and CaP.ConclusionThe various cytokeratins are individually expressed in both BPH and CaP. Ck5/6 and Ck7 are co-expressed and may be used in the diagnosis of BPH, Ck5/6,7,8 and Ki67 are co-expressed in Prostatic adenocarcinoma and squamous cell carcinoma of the prostate while Ck8 and Ki67 are co-expressed and may be used for diagnosis of Prostatic adenocarcinoma alone.
Background: PIK3CA mutations have been reported to be associated with resistance to therapy in HER2+ breast cancers. This study, therefore, became imperative to determine the expression pattern of this mutant protein together with ER, PR and KI67 in order to serve as a useful predictive tool in the management of HER2 breast cancers.Methods: A total of 53 archived formalin-fixed, paraffin-embedded HER2+ breast cancer tissue blocks from 2015 to 2019 were used for the study in NAUTH Nnewi. The selected blocks were sectioned and stained with haematoxylin and eosin staining techniques. HER2, ER and PR status confirmation as well as PIK3CA and KI67 protein expressions were evaluated using immunohistochemistry (Avidin-biotin complex method). PIK3CA and KI67 expressions in the tissue were scored based on proportion and intensity of immune-labelling using the semi-quantitative method.Result: The mean age of subjects was 47 years and the breast cancers were all invasive ductal carcinoma. Twenty-nine (54.7%) were ER+ while 24 (45.3%) were ER-. Twenty-one (39.6%) were PR+ while 32 (60.4%) were PR-. Twenty-one (39.6%) were PIK3CA negative, 9(35.8%) showed low PIK3CA, while 13(24.5%) showed high PIK3CA. Thirty-four (64.2%) were negative for KI67, 11(20.8%) showed low KI67, while 8(15.5%) showed high KI67. There was weak and moderate positive relationship between ER/PR status and PIK3CA (r=-0.032; p=0.822) and KI67 (r=0.050; p=0.721) respectively. A weak negative correlation between KI67 and PIK3CA (r=-0.118; p=0.401) were observed with 12 (22.4%) of the 13 highly positive PIK3CA cases showing either negative or low for KI67 immunoreactivity while 7(13.2%) of the 8 highly positive KI67 cases showed either negative or low PIK3CA immunoreactivity.Conclusion: This study established a moderate expression of PIK3CA mutant protein. It also pointed out an existing interesting relationship between PIK3CA and KI67, which can be further revealed in future studies.
This article presents silica nanoparticles for the sustained release of AMACR antibody-conjugated and free doxorubicin (DOX) for the inhibition of prostate cancer cell growth. Inorganic MCM-41 silica nanoparticles were synthesized, functionalized with phenylboronic acid groups (MCM-B), and capped with dextran (MCM-B-D). The nanoparticles were then characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, zeta potential analysis, nitrogen sorption, X-ray diffraction, and thermogravimetric analysis, before exploring their potential for drug loading and controlled drug release. This was done using a model prostate cancer drug, DOX, and a targeted prostate cancer drug, α-Methyl Acyl-CoA racemase (AMACR) antibody-conjugated DOX, which attaches specifically to AMACR proteins that are overexpressed on the surfaces of prostate cancer cells. The kinetics of sustained drug release over 30 days was then studied using zeroth order, first order, second order, Higuchi, and the Korsmeyer-Peppas models, while the thermodynamics of drug release was elucidated by determining the entropy and enthalpy changes. The flux of the released DOX was also simulated using the COMSOL Multiphysics software package. Generally, the AMACR antibodyconjugated DOX drug-loaded nanoparticles were more effective than the free DOX drug-loaded formulations in inhibiting the growth of prostate cancer cells in vitro over a 96 h period. The implications of the results are then discussed for the development of drug-eluting structures for the localized and targeted treatment of prostate cancer.
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