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1.
Niger Med J ; 63(4): 282-287, 2022.
Article in English | MEDLINE | ID: mdl-38863473

ABSTRACT

Background: HCC is a common cancer worldwide and one of the leading causes of cancer death. This aim of this study is to determine the age and gender characteristics of the HCC patients in our center and to determine the contribution of viral hepatitis (B and C) and alcohol to the etiology of HCC among our patients. Methodology: This is a retrospective study of HCC patients seen at the gastroenterology unit of ABUTH between April 2015 and September 2018. Data on age, gender, HBsAg, and HCV antibody status and alcohol consumption were recorded from the case files of all eligible patients. Results: A total of 87 patients were included in the study. They consisted of 68 males (78.2%) and 19 females (21.8%) with male to female ratio of 4:1. The mean age of the study subjects was 46.7 years (SD ± 12.5), with a range of 22 and maximum age of 80 years. Majority of the patients were within the age group 40-49 (32.2%). HBsAg was present in 48 patients (55.2%), HCV antibody was positive in 14 patients (16.1%) and 3 patients (3.4%) were positive for both HBsAg and HCV antibody. Four (4.6%) had significant alcohol ingestion and in 18 patients (20.7%), the etiology was undetermined. Conclusion: In our study, HCC was found predominantly among male patients in the age group 40-49 years. Viral hepatitis particularly HBV is the most important etiological factor for HCC among our patients.

2.
PLoS One ; 16(1): e0245581, 2021.
Article in English | MEDLINE | ID: mdl-33465114

ABSTRACT

Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatment in vivo in rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p = 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatments in vivo (p <0.05). The mechanistic rational of these effects underscores the importance of expanded concept of possible aspirin combination therapy with FOLFOX sequentially in future CRC management. Validation of our findings through randomized clinical trials of aspirin plus FOLFOX sequentially in patients with CRC is therefore warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Aspirin/pharmacology , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Animals , Annexin A5/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , B7-H1 Antigen/metabolism , Cell Line, Tumor , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology , DNA Mismatch Repair/drug effects , Drug Interactions , Duffy Blood-Group System/metabolism , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Humans , Inhibitor of Apoptosis Proteins/metabolism , Leucovorin/pharmacology , Leucovorin/therapeutic use , Male , Mismatch Repair Endonuclease PMS2/metabolism , MutS Homolog 2 Protein/metabolism , Neoplasm Proteins/metabolism , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/therapeutic use , Prognosis , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Receptors, Cell Surface/metabolism , Tumor Suppressor Protein p53/metabolism , Xenograft Model Antitumor Assays
3.
JCO Glob Oncol ; 6: 1647-1655, 2020 10.
Article in English | MEDLINE | ID: mdl-33141623

ABSTRACT

PURPOSE: Colorectal cancer (CRC) incidence rates are increasing among individuals < 50 years of age (early-onset CRC) globally with causes unknown. Racial/ethnic disparities in early-onset CRC have also grown more pronounced, because Black individuals have higher early-onset CRC incidence and poorer survival compared with White individuals. We describe the prevalence and burden of early-onset CRC among Africans in Nigeria and African Americans (AAs) in the United States. PATIENTS AND METHODS: We identified Black individuals diagnosed with a first primary CRC ages 18 to 49 years between 1989 and 2017 at Ahmadu Bello University Teaching Hospital in Zaria, Nigeria (Nigerians), and in the United States (AAs) using the National Institutes of Health/National Cancer Institute's SEER program of cancer registries. Multivariable logistic regression models were used to investigate clinical and demographic differences between Nigerians and AAs with early-onset CRC, adjusted for age, sex, tumor site, and histology. RESULTS: A total of 5,019 Black individuals were diagnosed with early-onset CRC over the study period (379 Nigerians; 4,640 AAs). Overall, approximately one third of young Black patients were diagnosed with rectal tumors (35.8%). Nigerian individuals with early-onset CRC were eight-fold more likely to be diagnosed with rectal tumors (odds ratio [OR], 8.14; 95% CI, 6.23 to 10.62; P < .0001) and more likely to be diagnosed at younger ages (OR, 0.87; 95% CI, 0.86 to 0.89; P < .0001) compared with young African Americans in adjusted models. CONCLUSION: Compared with AA individuals diagnosed with early-onset CRC, Nigerian individuals harbor distinct features of early-onset CRC. Additional investigation of the histopathologic and biologic heterogeneity of early-onset CRCs among Black individuals is critical for understanding racial disparities in susceptibility and outcomes, which may have implications for tailored early-onset CRC prevention, detection, and treatment strategies.


Subject(s)
Black or African American , Colorectal Neoplasms , Adolescent , Adult , Colorectal Neoplasms/epidemiology , Humans , Middle Aged , Nigeria/epidemiology , SEER Program , United States/epidemiology , White People , Young Adult
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