Nanocage-incorporated engineered destabilized 3'UTR ARE of ERBB2 inhibits tumor growth and liver and lung metastasis in EGFR T790M osimertinib- and trastuzumab-resistant and ERBB2-expressing NSCLC via the reduction of ERBB2.

Non-small cell lung cancer (NSCLC) caused more deaths in 2017 than breast cancer, prostate, and brain cancers combined. This is primarily due to their aggressive metastatic nature, leading to more fatal rates of cancer patients. Despite this condition, there are no clinically approved drugs that can target metastasis. The NSCLC with EGFR T790M-overexpressing HER2 shows the resistance to osimertinib and trastuzumab starting 10-18 months after the therapy, and thus prospects are grim to these patients. To target the recalcitrant ERBB2 driver oncogene, we developed two engineered destabilizing 3'UTR ERBB2 constructs that degrade the endogenous ERBB2 transcript and proteins by overwriting the encoded endogenous ERBB2 mRNA with the destabilizing message. When iron oxide nanocages (IO nanocages) were used as vehicles to deliver them to tumors and whole tissues in mice bearing tumors, it was well tolerated and safe and caused no genome rearrangement whereas they were integrated into genome deserts (non-coding regions). We achieved significant reduction of the primary tumor volume with desARE3'UTRERBB2-30, achieving 50% complete tumor lysis and inhibiting 60%-80% of liver metastasis, hepatomegaly, and 90% of lung metastasis, through ERBB2 downregulation. These constructs were distributed robustly into tumors, livers, lungs, kidneys, and spleen and mildly in the brain and not in the heart. They caused no abnormality in both short- and long-term administrations as well as in healthy mice. In summary, we accomplished significant breakthrough for the therapeutics of intractable lung cancer patients whose cancers become resistant and metastasize.

Predictive and prognostic relevance of immunohistochemical testing of estrogen and progesterone receptors in breast cancer in South East Nigeria: A review of 417 cases.

ER/PgR testing are now routinely performed in breast cancer evaluation in Southeastern Nigeria. ER is predictive to show beneficiaries of hormonal therapy and a prognostic marker to establish tumors that will resist paclitaxel induced apoptosis so a cost effective combination of anthracylines can be used as treatment in our low resource setting thus improving survival, reducing recurrence, and cost. Four hundred seventeen cases of breast cancer seen over a period of 3 years were routinely tested for ER/PgR. ER positivity was defined as nuclear positivity of 1% in the presence of internal and external controls. Four hundred seventeen patients with Ductal Carcinoma participated. Majority were females 98.3%. Majority 60.2% were between 31 and 50 years old. Mean age was 33.5 ± 6.4 years. Two hundred fifty-seven (61.6%) were positive both for ER/PgR. 70.3% of age group 41-50 years had positive ER, age groups 20-30, and >70 years had positive ER also. ER positive cancer was 60.2%. Fifty-seven were 1%-9% positive. Most positive estrogen receptors were seen between 41 and 50 years at 70.3%. Least was seen at 31-40 years at 51.4%. Study provides an objective basis for using hormonal manipulation and makes cost affordable with appropriate chemotherapeutic agents in our low resource setting. Presentations were typically late. Seventy-six percent of stage 2 disease survived after 6 years compared with only 56% of stage 2 disease prior to immunotyping and radiotherapy in 2007. Both stage 3 and 4 had remarkable survival too at 55% and 33% respectively when compared with 2007 figures at 33% for stage 3 and 9.2% at stage 4.

The Challenges of Management of High-grade Gliomas in Nigeria.

BACKGROUND: High-grade gliomas (HGG) are among the most challenging brain tumors despite many research efforts worldwide. AIM: The aim of this study was to evaluate the local challenges that may influence outcome of HGG managed in a neurosurgical center in Nigeria. METHODOLOGY: Retrospective analysis of prospectively recorded data of patients managed for intracranial HGG at Memfys Hospital for Neurosurgery, Enugu, Nigeria, between the year 2006 and 2015. Only cases with conclusive histology following surgery were analyzed. RESULTS: Glioma was 60 (23.8%) of 252 histology confirmed brain tumors. HGG represented 53.8% of gliomas with male:female ratio of 2.2:1.0 and peaked from fifth decade of life. Glioblastoma multiforme accounted for 69% of HGG. At 1-year postsurgery, 53% of HGGs were dead and 88% of these deaths were in the World Health Organization Grade IV group. Only 40% of cases could receive adjuvant treatment with only 15% mortality at 1 year in this subgroup that received adjuvant therapy. In addition, 19% of cases had surgery at Karnofsky score (Ks) of ≥70%. However, 94% of mortality at 1 year was related to surgery at Ks of ≤60%. Only four patients had a tumor volume of ≤50 cm3, and among these cases, three patients were independent at 1 year. Patients with tumor volume above 50 cm3 accounted for 94% of mortality. CONCLUSION: The peak age incidence for HGG seems to be lower than in Caucasians. Most cases present late with poor Ks and big tumor volume. The proportion with access to adjuvant treatment is still poor. Preoperative Karnofsky, extent of resection, duration of hospital, and Intensive Care Unit stay have impact on outcome.

Cerebellar Liponeurocytoma: A Novel Report from Nigeria in a 6-Year-Old Girl, and Review of Literature.

Liponeurocytoma is a newly defined clinical entity predominantly seen in the cerebellum as a slow-growing tumor. In this report, we present the case of a 6-year-old Nigerian girl with a liponeurocytoma, and review of literature.

Testicular Schistosomiasis Mimicking Malignancy in a Child: A Case Report.

Schistosomiasis is an important communicable disease in the developing world. However, testicular schistosomiasis is an extremely rare condition. We report a case of testicular schistosomiasis mimicking testicular tumour in a 13 year old who presented with huge unilateral testicular mass. The dilemma encountered in the diagnosis and treatment of this child is presented to highlight the need for high index of suspicion of this pathology in children with testicular mass presenting from schistosomiasis-endemic areas.

Metaplastic breast carcinoma; melanocytic variant, a very rare tumour.

Metaplastic breast carcinoma (MBC) is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Melanocytic variant was first described by Ruffolo et al. in 1997. We report a case of MBC, melanocytic variant, in a 57-year-old Nigerian female who presented with a left breast mass 8 cm in diameter in the upper outer quadrant, hard and gradually increase in size to become painful. Breast examination showed gross asymmetry. Left breast was oedematous and shiny with extensive peau d'orange. No palpable axillary nodes were seen. Chest X-ray and abdominal ultrasound scan showed no involvement. Breast biopsy revealed an invasive metaplastic ductal carcinoma with melanocytic differentiation.

Prevalence, morbidity, and mortality patterns of typhoid ileal perforation as seen at the University of Nigeria Teaching Hospital Enugu Nigeria: an 8-year review.

BACKGROUND: Some recent studies have reported a decrease in mortality from typhoid ileal perforation. The present report aims to determine the prevalence, morbidity, and mortality of this disease in patients mostly drawn from a rural area. METHODS: This is a retrospective study of 50 patients treated between January 1999 and December 2007 at the University of Nigeria Teaching Hospital, Enugu, Nigeria. The variables studied included patient demographics, clinical features, intraoperative findings, complications, and mortality. Statistical analysis was done with SPSS version 13. RESULTS: Of the 50 patients included in the study, 22 were males with the highest rate in patients aged 20 years and younger. Fever was the commonest symptom and at initial presentation, the mean pulse and respiratory rates were significantly higher in the patients who subsequently died than in those who survived (P < 0.05). All the perforations occurred in the ileum; 62 % of the patients had solitary perforations, 28 % had double perforations, and 10 % had three or more. Fifty-eight perforations were treated by simple closure in two layers, 4 patients had ileal resection and anastomosis, and 2 underwent right hemicolectomy. The mean interval between operation and death was 1.7 days. The overall mortality rate was 30 %, but among those with three or more perforations, mortality was 100 %. CONCLUSIONS: Typhoid ileal perforation still carries a high mortality especially in rural areas. Those with tachycardia and tachypnea at presentation and those with three or more perforations are at a higher risk of dying from the disease.

A case of vulval swelling secondary to female circumcision posing a diagnostic dilemma.

INTRODUCTION: The practice of FGM is most prevalent in the African countries such as Nigeria, Ethiopia, Sudan, Egypt, and some area of the Middle East. It is not restricted to any ethnic, religious or socioeconomic class. There are many reasons for perpetuation of this practice; the most common are cultural and religious beliefs. The aim of this paper is to highlight the diagnostic dilemma associated with this type of case and the psychological trauma of a patient following her unfortunate genital mutilations. PRESENTATION OF CASE: We present the case of epidermal inclusion dermoid cyst in an 18-year-old teenage girl referred to us from the gynecologist as a case of hydrocoele of the canal of Nuck involving the left labia majora. Patient was previously seen by general practitioner who diagnosed a left Bartholins cyst. Excision of the mass, revealed a well encapsulated cystic mass containing serous fluid with no extension to the inguinal area, measured 10cm×8cm. Histology showed epidermoid inclusion dermoid cyst probably related to circumcision (female genital mutilation). DISCUSSION: Implantation dermoid cyst though a recognized complication of FGM is rare in our environment and a high index of suspicion is required any time a girl presents with a vulval swelling. Cosmesis still remains the watchword to assuage the psychological impact on the patient. CONCLUSION: There is need for more public health campaigns to educate communities about the harms of circumcision with the goal of eradicating the practice.

Death patterns among Nigerian leaders.

BACKGROUND: The aim of this study is to establish the patterns of death amongst Nigerian leaders since independence, thus providing a feasible avenue to avoid their recurrence if possible especially amongst the political elite who currently hold power. METHODS: Using available unclassified authentic public information, all leaders who had ruled Nigeria since her independence on 1 October, 1960 until her 45th birthday on 1 October 2005, irrespective of whether they are dead or alive were included. Data was extracted and analyzed. RESULTS: On 1 October 2005, Nigeria celebrated 45 years as a sovereign nation. Within this period, the country has had eleven leaders, all of whom were men. Only three (27.3%) were civilians, while eight (72.7%) were army generals. Of the eleven leaders, four (36.4%) had died before Nigeria reached its 45th birthday and all of these four (100%) died while still in office. Three of the dead leaders (75%) were assassinated, while one (25%) died suddenly in mysterious circumstances, believed to be the result of poisoning by unknown external powerful interest groups. Three of the deaths (75%) occurred during violent periods of Nigeria's checkered history (1966-1970 and 1993-1999), showing that periods of national and international strife appeared to be the weakest link in chains of events that led to their death while in office. Autopsies were neither requested nor performed on any of the dead leaders, signifying an entrenched culture of nonchalance, a lack of a coordinated national coroner's law and contempt for accurate and detailed death records. Worse still, no valid tenable death certificate has ever been issued. In other words, no attempt has been made to determine the cause of death of four of the nation's former leaders. Only hurried national burials were accorded two (50%) of them while the other two (50%), who died in the coup and revenge coup of 1966, were completely neglected, and not even given a decent national burial. CONCLUSIONS: The facts identified above will serve as a landmark to highlight an existing problem, and thus bring the issue to the attention of policy-makers and the political elite. The overall expected benefit is that nations like Nigeria can focus on the issue of orderly succession and the peaceful handing-over of government to duly transparently elected national leaders and all efforts should be made to avoid holding on to power unnecessarily. The tenets of democracy shall be upheld and transparent elections take place so as to reduce national tension and strife to the barest minimum. We also strongly recommend a review and improvement of Nigeria's national coroner's laws.

Neuroblastoma occurring in a 38-year old Nigerian man: a rare finding.

Neuroblastoma (NB) is a common malignancy in children, but rarely occurs in adults. Accepted unfavorable prognostic factors include age over one year, low histological grade and advanced stage, MYCN amplification, chromosomal aberrations, elevations of neuron specific enolase and lactate dehydrogenase, and increased catecholamine metabolites in urine or serum. In adults, abdomen/retroperitoneum are the primary sites and in children the adrenal gland. We report a 38-year old civil servant who presented at our urology clinic on the 21(st) of December 2007 with a six month history of right flank dull pain which was worse on walking and relieved by rest, hypertension and a large right retroperitoneal mass. Tumor resection revealed a grade III NB. Chemotherapy using a combination of vincristine, adriamycin and cyclophosphamide was started. Follow-up showed regression of the mass initially with a relapse after patient absconded for three months. He resurfaced with new masses and he had a repeat chemotherapy with disappearance of the masses and is currently undergoing further treatment. To our knowledge this is the only report of NB in an adult registered so far in Nigeria and perhaps the whole of Africa. Currently, there are no standard treatment guidelines for patients with NB in adulthood. This study emphasizes the need for a standard treatment regime for adult onset neuroblastoma and its recognition as a possible differential in intra-abdominal mass in adults.

Benign breast lesions in Eastern Nigeria.

OBJECTIVE: To characterize benign breast diseases in Eastern Nigeria and to highlight the age variations of these lesions as base line data. METHODS: The Department of Morbid Anatomy, University of Nigeria Teaching Hospital, Enugu caters for over 30 million African blacks and receives 2000 surgical pathology specimens yearly. Seven hundred and twenty-two benign breast specimens were analyzed over 5 years from 1st January 2000 to 31st December 2004, out of 1050 breast samples received. RESULTS: Of 1050 breast specimens received, 722 (68.8%) were benign. Fibroadenoma was the most common lesion with 318 cases (44%), occurring at a mean age of 16-32 years. Next was fibrocystic changes with 165 cases (22.9%) at a mean age of 23-45 years. Normal breast in the axillary tail region was seen in 32 cases (4.4%), represented as no pathology, with a mean presentation age of 20-46 years. Low grade Phyllodes tumor had 28 cases (3.9%), presenting at an average mean age of 17-32 years. Lactating adenoma had 19 (2.6%) cases. Other lesions made up less than 3% each. Benign breast lesions peaked at the 20-24 age range and then declined. Most were females. CONCLUSION: Benign breast lesions occur more frequently than malignant breast lesions with a ratio of 2.3:1 and were presented 20 years earlier than their malignant counterparts. Fibroadenoma was the most common benign lesion followed by fibrocystic disease, similar to the findings in Western Nigeria. In Northern Nigeria, fibrocystic breast disease was more common.