EGFR and HER2 expression in cervical cancer patients in Ibadan, Nigeria.

Cervical cancer is a leading cause of cancer-related deaths in developing countries, including Nigeria where it is the second most common female malignancy. Studies from elsewhere have demonstrated the relationship between epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and advanced cervical cancer. However, we are not aware of such studies in Nigerian patients. The main objective of the study was to determine the prevalence of EGFR or HER1 and HER2 protein expression in cervical cancers and to determine their impact on overall survival. Clinical data and formalin-embedded tissue blocks of 124 patients who presented in the Radiation Oncology Department, University College Hospital (UCH), from 2006 to 2015 and had their histological diagnosis at the Pathology Department, UCH were retrieved and analysed for EGFR and HER2 expression using immunohistochemistry. EGFR expression was analysed using the immunoreactivity score by Remmele and Stegner. HER2 was analysed using the Hercep® test kit guidelines. Survival analysis was done using Kaplan-Meier and Cox regression analysis. Missing data were reported as missing, not documented. EGFR (immunoreactivity score > 4) was overexpressed in 26.6% of the 124 cervical tissue samples tested. Most patients whose samples were positive for EGFR were young, had squamous cell carcinoma and advanced diseases. HER2 was overexpressed in two samples (1.6%). The 5-year overall survival rate of the patients was 28.3%. The 5-year survival rate of patients who were EGFR positive was 9.5% and 34.1% for those who were EGFR negative. Screening for EGFR should be considered in cervical cancer patients. HER2 was overexpressed in two cervical tissue samples in this study and may be of poor interest as a potential target in the management of cervical cancer patients. Large prospective multi-institutional studies should be considered to further explore the relationship between EGFR and survival in cervical cancer patients.

ARETTA: Assessing Response to Neoadjuvant Taxotere and Subcutaneous Trastuzumab in Nigerian Women With HER2-Positive Breast Cancer: A Study Protocol.

Human epidermal growth factor receptor 2 (HER2) subtype of breast cancer is aggressive, leading to a poor outcome. Targeted therapy with trastuzumab has been shown to be effective in the treatment of HER2-positive breast cancer. Cardiotoxicity is a specific adverse effect associated with trastuzumab. The initial formulation of trastuzumab was intravenous, but presently, a subcutaneous formulation (Herceptin SC) is available. Insufficient data on the response rate and cardiotoxic effects of trastuzumab among indigenous Black populations exist. In all studies evaluating the efficacy and toxicity of trastuzumab alone or in combination with chemotherapy, indigenous Black populations in Africa were not included, yet they are the ones most likely to benefit from highly effective cancer medicines. This is partly due to poor oncology clinical trial infrastructure in sub-Saharan Africa. The ARETTA study protocol (ClinicalTrials.gov identifier: NCT03879577) is a phase II multicenter feasibility study to evaluate the efficacy and toxicity of docetaxel given every 3 weeks for 4 cycles plus trastuzumab in 60 previously untreated women with nonmetastatic breast cancer. The primary endpoint is to assess the proportion of patients with complete pathologic response. Secondary endpoints include the number of patients who require dose delays in docetaxel and trastuzumab attributed to hematologic, GI, and cardiac toxicity. Pharmacokinetic profiles of subcutaneous trastuzumab will also be determined. The ARETTA study will provide important information on the clinical response and cardiac safety of subcutaneous trastuzumab in combination with docetaxel among indigenous African women with nonmetastatic breast cancer. It can also be used as a blueprint for conducting biomarker-driven oncology clinical trials in low-resource settings such as sub-Saharan Africa.

Epidemiology and Risk Factors of Osteosarcoma.

Osteosarcoma is a rare tumor diagnosed at any age; however younger age is a common risk factor. In addition, multiple factors are believed to contribute to higher rates of osteosarcoma, particularly race and gender. Although diagnosed worldwide, osteosarcoma is found to be more prevalent in Africa with high numbers of cases reported in Nigeria, Uganda, and Sudan. Additionally, higher rates are detected in African Americans, suggesting a genetic predisposition linked to race. This review focuses on identifying high risk factors of osteosarcoma with an emphasis on sarcoma epidemiology and risk factors in African countries.

Infrastructural Challenges Lead to Delay of Curative Radiotherapy in Nigeria.

PURPOSE: In low- and middle-income countries, there has been an exponential increase in cancer incidence. According to the International Atomic Energy Agency, the biggest gap in radiotherapy availability and need is in Nigeria, where each machine serves an estimated 25.7 million people. This study aimed to characterize the barriers to radiotherapy and to identify areas for intervention. METHODS: This was a cross-sectional study conducted at the University College Hospital in Ibadan, Nigeria, from June 2017 to August 2017. Demographic, sociocultural, and infrastructural factors relating to radiotherapy were collected through a questionnaire (N = 186). Ordinal logistic regression was used to identify the factors leading to delays in referral and delays in treatment initiation. RESULTS: Patients traveled from 20 of Nigeria's 36 states. The median age was 50 years (range, 19-79 years). The most common cancers treated were breast (37.5%), cervical (16.3%), head and neck (11.9%), and prostate (10.9%). In ordinal logistic regression, sociocultural factors, including the inability to pay (odds ratio [OR], 1.99; P = .034), a bad hospital experience (OR, 7.05; P = .001), and travel time (OR, 1.36; P = .001), increased the odds of referral delay to radiotherapy. In contrast, there was no significant relationship between time to treatment initiation and sociocultural factors including age, education, and inability to pay. Infrastructural barriers, including machine breakdown (OR, 2.92; P = .001), worker strikes (OR, 2.64; P = .001), and power outages (OR, 2.81; P = .022), increased the odds of treatment delay. CONCLUSION: Although delays caused by patient factors are reported extensively, patients overcame these barriers in the hopes of curative treatment. However, staff and equipment malfunctions prevented patients from receiving timely radiotherapy. Policies aimed at addressing machine maintenance, health care worker satisfaction, and the aging power grid in Nigeria must be implemented in the future to strengthen the health care system to care for patients with cancer.

Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells.

: The cytochalasin B-induced membrane vesicles (CIMVs) are suggested to be used as a vehicle for the delivery of therapeutics. However, the angiogenic activity and therapeutic potential of human mesenchymal stem/stromal cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown. OBJECTIVES: The objectives of this study were to analyze the morphology, size distribution, molecular composition, and angiogenic properties of CIMVs-MSCs. METHODS: The morphology of CIMVs-MSC was analyzed by scanning electron microscopy. The proteomic analysis, multiplex analysis, and immunostaining were used to characterize the molecular composition of the CIMVs-MSCs. The transfer of surface proteins from a donor to a recipient cell mediated by CIMVs-MSCs was demonstrated using immunostaining and confocal microscopy. The angiogenic potential of CIMVs-MSCs was evaluated using an in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix. RESULTS: Human CIMVs-MSCs retain parental MSCs content, such as growth factors, cytokines, and chemokines: EGF, FGF-2, Eotaxin, TGF-α, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFNα2, IFN-γ, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, IL-15, sCD40L, IL-17A, IL-1RA, IL-1a, IL-9, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP_1a, MIP-1b, TNF-α, TNF-ß, VEGF. CIMVs-MSCs also have the expression of surface receptors similar to those in parental human MSCs (CD90+, CD29+, CD44+, CD73+). Additionally, CIMVs-MSCs could transfer membrane receptors to the surfaces of target cells in vitro. Finally, CIMVs-MSCs can induce angiogenesis in vivo after subcutaneous injection into adult rats. CONCLUSIONS: Human CIMVs-MSCs have similar content, immunophenotype, and angiogenic activity to those of the parental MSCs. Therefore, we believe that human CIMVs-MSCs could be used for cell free therapy of degenerative diseases.

CD4 Count and Anti Retroviral Therapy for HIV Positive Patients With Cancer in Nigeria -A Pilot Study.

BACKGROUND: Highly Active Anti Retroviral Treatment (HAART) improves the outcome of HIV positive patients treated for cancer. In our center HAART is only commenced in HIV positive patients with malignancy if the CD4 T lymphocyte count is less than 200 cells/ul. Presently, the outcome of treatment in these patients is poor. OBJECTIVE: To evaluate the influence of CD4 T-cell count and HAART on treatment outcome of HIV positive patients with cancer managed at the oncology service of The University College Hospital, Ibadan-South West Nigeria. PATIENTS AND METHODS: Twenty two adult HIV positive patients with malignancies who presented for treatment at our hospital from 2007 to 2009 were closely monitored by the investigators. Relevant clinical data collected included age, sex, HIV status, type of malignancy, CD4 counts, history of ART, ECOG performance status, prescribed oncology treatment with regularity of treatment and to follow up conditions. RESULTS: Twenty two patients aged between 26 and 67 years were evaluated. The performance status of all patients was at least ECOG 2. Three ART naive patients with initial CD4 counts 450 cells/ul and above were able to complete oncology treatment without HAART with good malignant disease control. Five other patients on HAART before the diagnosis of malignancy with CD4 counts 350 cells/ul and above were also able to complete their treatments on schedule with good outcome. Eight HAART naive patients with initial CD4 counts less than 370 cells/ul had inconsistent treatments with poor outcome. CONCLUSION: Based on these observations, we propose that HAART should be commenced on all HIV positive patients diagnosed with malignancy with an initial CD4 count less than 450 cells/ul in our environment. Further studies in low resource settings with appropriate sample sizes are however needed to validate these findings.