Charles C. Anunobi

Cell Proliferation (KI-67) Expression Is Associated with Poorer Prognosis in Nigerian Compared to British Breast Cancer Women

Background. Black women with breast cancer (BC) in Nigeria have higher mortality rate compared with British women. This study investigated prognostic features of cell proliferation biomarker (Ki-67) in Nigerian breast cancer women. Materials and Methods. The protein expression of Ki-67 was investigated in series of 308 Nigerian women, prepared as a tissue microarray (TMA), using immunohistochemistry. Clinic-pathological parameters, biomarkers, and patient outcome of tumours expressing Ki-67 in Nigerian women were correlated with UK grade-matched series. Results. A significantly larger proportion of breast tumours from Nigerian women showed high Ki-67 expression. Those tumours were significantly correlated with negative expression of the steroid hormone receptors (ER and PgR), p21, p27, E-cadherin, BRCA-1, and Bcl-2 (all P < 0.001), but positively associated with EGFR (P = 0.003), p53, basal cytokeratins: CK56, CK14, triple negative, and basal phenotype using Nielsens classification (all P < 0.001) compared to UK women. Multivariate analyses showed that race was also associated with BCSS independent of tumour size, lymph node status, and ER status. Conclusion. Ki-67 expression was observed to have contributed to the difference in the BCSS in Nigerian compared with British BC women. Therefore, targeting Ki-67 in the indigenous black women with BC might improve the patient outcome in the black women with BC.

Bromelain in the early phase of healing in acute crush Achilles tendon injury.

Bromelain, an enzyme extracted from the stem of the pineapple plant has been proposed as a treatment for reducing pain and swelling following acute muscle injuries but studies are yet to be done on its effect on tendon healing. This study therefore investigated the effects of bromelain on tenocyte proliferation and the tendon malondialdehyde (MDA) level in the early stage of healing in a crush injury to the Achilles tendon of Sprague‐Dawley rats.

Potential of Moringa oleifera in the Treatment of Benign Prostate Hyperplasia: Role of Antioxidant Defence Systems

Objective: This study sought to evaluate the protective effect of ethanolic leaf extract of Moringa oleifera on testosterone-induced benign prostatic hyperplasia (BPH) in male Sprague-Dawley rats. Materials and Methods: BPH was induced in rats by the administration of testosterone propionate (3 mg/kg, s.c., in olive oil) for 4 weeks. M. oleifera (50, 100, or 200 mg/kg), celecoxib (20 mg/kg), or M. oleifera (50 mg/kg) + celecoxib (20 mg/kg) were orally administered daily 15 min before testosterone. On day 29, blood was collected to measure the levels of serum testosterone and prostate-specific antigen before the animals were sacrificed. The prostates were weighed, assayed, and histologically examined. Results: M. oleifera significantly reduced the testosterone-induced increase in prostate weight (20.16%), prostate index (65.85%), serum testosterone (72.86%), and prostate-specific antigen (48.49%). Testosterone caused a significant increase in malondialdehyde (73%) as well as a reduction in glutathione (62.5%), superoxide dismutase (50%), and catalase (64%) activities which were attenuated by M. oleifera with a peak effect obtained at 100 mg/kg. The disruption of prostate histoarchitecture by testosterone was also ameliorated by M. oleifera. Conclusion: M. oleifera prevented testosterone-induced BPH through enhancement of antioxidant defence mechanisms, and hence could be used as an adjunct in the treatment of BPH.

Atorvastatin attenuates testosterone-induced benign prostatic hyperplasia in rats: role of peroxisome proliferator-activated receptor-γ and cyclo-oxygenase-2

Diabetes and obesity have been reported to alter sex steroid hormone metabolism. In this study, an attempt was made to investigate the protective effect of atorvastatin (ATR) in combination with celecoxib (CEL) or pioglitazone (PIO) on testosterone‐induced BPH in rats. Male Wistar rats (200–250 g) were randomly divided into nine groups (n = 8) and orally treated as follows for 28 consecutive days: group 1: vehicle control (10 mL/kg); group 2: vehicle testosterone (10 mL/kg); groups 3 ‐ 5: ATR (0.5, 2.5, and 5 mg/kg, respectively); group 6: CEL (20 mg/kg); group 7: PIO (20 mg/kg); and groups 8–9: ATR 0.5 mg/kg, and 15 min later, animals were given CEL (20 mg/kg) or PIO (20 mg/kg), respectively. One hour post‐treatment, animals in groups 2–9 were given testosterone propionate (3 mg/kg, s.c.). Twenty‐four hours after last treatment on day 28, blood was collected for serum testosterone and prostate‐specific antigen (PSA) analysis. Prostate was harvested for biochemical and histological assays. Subcutaneous injection of testosterone increased serum levels of testosterone and PSA which was ameliorated by pretreatments of rat with ATR, celecoxib, or pioglitazone. Similarly, testosterone‐induced increase in MDA and reduction in the activity of GSH, superoxide dismutase (SOD), and catalase were attenuated by ATR. Conversely, celecoxib or pioglitazone treatment failed to affect the activity of antioxidant enzymes. The histology of the prostate showed significant improvement in prostatic cells of ATR, celecoxib, or pioglitazone treated. Findings from the study showed that atorvastatin attenuated testosterone‐induced BPH. Moreover, synergistic effect was observed when atorvastatin was combined with celecoxib.

Suprasellar Clear Cell Meningioma in an Infant: Case report

Clear cell meningiomas are an uncommon subtype of meningioma rarely seen in infancy. We report a case of clear cell meningioma in an 8-month-old male infant. He presented at the Lagos University Teaching Hospital, Lagos, Nigeria, in 2015 with persistent vomiting, poor feeding and failure to thrive over a four month period. Generalised hypertonia and hyperreflexia were noted on examination. Computed tomography of the brain revealed a huge largely isodense suprasellar mass with a hypodense core. The tumour, which measured 6 × 5 × 4 cm, enhanced non-uniformly with contrast injection and extended to occlude the third ventricle. The patient underwent a bifrontal craniotomy with subtotal tumour excision. Six hours postoperatively, he went into cardiac arrest and could not be resuscitated. A histological diagnosis of clear cell meningioma was made as the tumour cells were immunoreactive to epithelial membrane antigen, S100 protein and vimentin. This case of clear cell meningioma was unusual due to its early occurrence and supratentorial location.

Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms

The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). The specific SIBLING-MMP pairing reported in some cancers have not been reported in prostate neoplasms. In this study, we investigated SIBLING-MMP expression and potential interaction in prostate neoplasms. Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). MEPE was significantly upregulated in benign prostate hyperplasia (BPH; X2=44.153/p<0.001). There were no significant differences in MMP expression between BPH and pAdC. Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. Our reports provide evidence that SIBLING-MMP interaction may play a role in the progression of BPH to pAdC.

Histomorphological changes in induced benign prostatic hyperplasia with exogenous testosterone and estradiol in adult male rats treated with aqueous ethanol extract of Secamone afzelii

Abstract Secamone afzelii (S. afzelii) used locally to manage benign prostatic hyperplasia (BPH) was used to treat exogenously induced BPH in adult male Wister rats. Male rats weighing 200 ± 10 g kg−1 had exogenous administration of testosterone and estradiol in staggered doses (three times weekly) for three weeks. The induced animals were in five groups (6 rats per group). Groups 1 and 2 received extract at 200 and 400 mg kg−1 body weight (bwt) by gavages for thirty days; group 3, finasteride (0.1 mg kg−1); group 4, untreated for thirty days; group 5, negative control, which was sacrificed twenty-one days after induction. Group 6 received extract (400 mg kg−1) and steroid hormones simultaneously; group 7, normal control. The extract caused marked decrease in prostate weight of BPH induced rats with the photomicrograph of the prostate showing extensive shrinkage of glandular tissue whereas glandular hyperplasia occurred in the negative control. Prostate specific antigen (PSA) level significantly (p < 0.05) decreased in the treated groups compared to negative control. Treatment with the extract/finasteride caused significant decrease in testosterone to a level comparable to normal. The BPH induced rats treated with S. afzelii/finasteride recorded marked increase in the levels of antioxidant enzymes compared to the negative control. S. afzelii effectively ameliorated prostatic hyperplasia exogenously induced by causing extensive shrinkage of glands and stroma. It also exhibited antioxidant properties and showed to be a good prophylaxis.

Synoptic Versus Narrative Reporting of Prostate Biopsies at a Tertiary Healthcare Institution : Challenges, successes and expectations

OBJECTIVES Cancer pathology reports are expected to contain all information required for patient management and disease surveillance. Moreover, reports for patients with prostate cancer have become increasingly complex with the addition of more pathological details. This study aimed to compare narrative and synoptic prostate cancer reports for core needle biopsies received at a tertiary hospital in Nigeria in order to determine which form was most complete according to international standards. METHODS This study was conducted from January 2010 to December 2015 at the Lagos University Teaching Hospital, Lagos, Nigeria. All malignant prostate cancer histopathology reports received during this period were analysed for the presence of important clinicopathological parameters, including the numbers of cores taken and those involved by the tumour, percentage of tumour involvement, Gleason score and the presence of high-grade prostatic intraepithelial neoplasms (HGPINs) and perineural and lymphovascular invasion. RESULTS A total of 83 reports were reviewed, of which 27 were in narrative and 56 in synoptic format. The documentation of clinicopathological characteristics in narrative reports was significantly incomplete compared to synoptic reports in recording the number of cores (33.3% versus 96.4%), number of cores involved by the tumour (11.1% versus 94.6%), percentage of cores involved by the tumour (3.7% versus 100.0%) and the presence of HGPINs (7.4% versus 100.0%) and perineural (59.3% versus 98.2%) and lymphovascular (48.1% versus 100.0%) invasion (P <0.001 each). CONCLUSION Synoptic reports of malignant prostate cancer biopsies received at the Lagos University Teaching Hospital were found to contain more complete information than narrative reports.

Potential of telmisartan in the treatment of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a common health problem in ageing men. This study was carried out to investigate the protective effect of telmisartan on testosterone‐induced BPH in rats. Fifty‐four male Wistar rats (200–250 g) were randomly divided into nine groups (n = 6) and orally treated for 28 consecutive days: group 1 – vehicle normal, olive oil (10 mL/kg); group 2 – BPH model control (10 mL/kg); groups 3–5 – telmisartan (5, 10 or 20 mg/kg, respectively); group 6 – pioglitazone (20 mg/kg); group 7 – celecoxib (20 mg/kg); group 8 – combination of telmisartan (5 mg/kg) and pioglitazone (20 mg/kg); group 9 – combination of telmisartan (5 mg/kg) and celecoxib (20 mg/kg). Animals in groups 2–9 were given testosterone propionate in olive oil (3 mg/kg) subcutaneously 15 min after pretreatments. On day 29, blood was collected for the estimation of serum testosterone and prostate‐specific antigen (PSA). The prostates were excised, weighed and subjected to biochemical and histological studies. Testosterone injection induced significant increase in prostatic index, serum testosterone and PSA suggesting BPH as well as increased prostate oxidative stress which were ameliorated with the pretreatment of rats with telmisartan or co‐administration of celecoxib and pioglitazone. Histological examination showed that testosterone disrupted the morphology of the prostate epithelial cells evidenced in the involution of the epithelial lining of the acini into the lumen indicating BPH which was reversed by telmisartan. Findings from this study showed that telmisartan alone or in combination with pioglitazone prevented the development of testosterone‐induced prostatic hyperplasia.

3 Intrasound Therapy Reverses The Effects Of Alcohol Consumption On The Healing Tendon And Augments Healing

Functional abnormalities in wound structure has been identified as a potential complication if a patient consumes alcohol prior to injury and studies suggest that even a single incidence of acute ethanol exposure can perturb the tissue response to trauma significantly. Ethanol ingestion has been shown to result in delayed and abnormal tendon healing 3 weeks after injury. This study investigated the effects of low intensity intrasound therapy (LITR) given twice daily on the morphology and antioxidant parameters in the healing tendon following an acute injury in rats exposed to prior ethanol consumption. Fifteen male rats, randomised into three groups all underwent induced crush injury to the Achilles tendon. Groups 2 and 3 had prior administration of 30% ethanol for six days. The three groups were allocated to: serve as controls (Group 1), received no treatment (Group 2), LITR twice daily (Group 3). LITR was commenced immediately post-injury and was given twice daily over the first 6 days. The animals were sacrificed on day 20 post-injury and the tendons were excised, and processed for histology and anti-oxidant and MDA assay. The tendons in group 2 showed disordered and haphazard collagen formation with neutrophilic infiltrates and high tenoblast population at 20 days post-injury while the LITR treated tendon had dense, well-ordered, parallel collagen deposits with fewer tenoblasts. LITR also significantly improved the antioxidant parameters and lowered the MDA compared with the alcohol-exposed untreated tendon (p < 0.05). LIRT thus reverses the deleterious effect of ethanol on the healing tendon and resulted in near-normal morphology of the healing tendon 20 days post-injury. Abstract 3 Figure 1 L/S of tendon of rat. A: control, B: alcohol fed with no treatment and C: alcohol fed and treated with LITR. (H&E) X200. A shows moderately aligned collagen fibres (C), B shows disorganized collagen fibres (C) with neutrophilic infiltrates (N) while C shows orderly and parallel collagen deposits (C) and elongated tenocytes (T) Abstract 3 Table 1 Correlation of antioxidants with MDA Spearman’s Correlation (r) Groups SOD Catalase GRP 1 -0.63 -0.63 GRP 2 0.37 0.37 GRP 3 -0.98 -0.97 Group 1: Control (Nil alcohol, nil treatment) Group 2: Alcohol, nil treatment Group 3: Alcohol, LITR twice daily Abstract 3 Table 2 Population of tendon cells Total number of cells (N)/Unit Area Groups TB TC Ratio of TB to TC p-value X ± SD X ± SD GRP 1 710 ± 353 334 ± 120 2 : 1 0.12 GRP 2 693 ± 206 210 ± 52 3 : 1 0.02* GRP 3 572 ± 385 445 ± 76 1: 1 0.59 TB: Tenoblasts; TC: Tenocytes Group 1: Control (Nil alcohol, nil treatment) Group 2: Alcohol, nil treatment Group 3: Alcohol, LITR twice daily * Significant at p < 0.05 References Aiyegbusi et al . Connective Tissue Research. 2012;53(6):478–484 Novasonic. www.novasonicwest.com/novasonic. 2007 Molina et al. Alcohol Clin Exp Res. 2002;26(1):120–8 Sommers MS. Crit Care Nurse. 1994;14:82–86, 88–93