Department of Biochemistry

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Lipid peroxidation and activity of some antioxidative enzymes in the root of maize (Zea mays) cultivated on cadmium contamination soil
(Journal / Scientia Africana / Vol. 20, 2021-04-23) Ugbeni, O.C.; Dania, Omoremime Elizabeth; Eruotor, H.
In this study, we examined the tolerance capacity of Zea mays to cadmium pollution. Soil was treated with varied concentrations of Cadmium; 5 mg, 10 mg, 20 mg and 30 mg/kg soil and Zea mays planted. Root samples were collected in weeks 3, 4, 5 and 6. Activities of Peroxidase, catalase superoxide dismutase, and lipid peroxidation were investigated. Decrease in peroxidase activity was extremely significant (p <0.05) in weeks 4 and 5 while that of week 6 was not significantly (p > 0.05) different from normal. The decrease correlated with increase in Cadmium concentration. However, at the highest concentration of 30 mg/kg of soil the trend was not significant. Increase in the activity of catalase was recorded in weeks 3 and 6. This increase didn’t follow a particular trend but at higher concentration of Cd and long term exposure, it became apparent. There was a negative correlation between catalase activity and lipid peroxidation. In week 3, catalase activity was not significant (p > 0.05) and lipid peroxidation was significant (p < 0.05) while at week 4, catalase activity was significant (p < 0.05) and lipid peroxidation was not significant (p = 0.8432). Catalase activity was not significant (p = 0.2753) at week 5 and lipid peroxidation was significant (p = 0.0030). At week 6 when catalase activity became extremely significant (p < 0.05), lipid peroxidation had a p value of 0.0128. Generally no significant activity (p > 0.05) was observed for superoxide dismutase. A significant increase in absorption of cadmium (p = 0.0374) at 30mg/kg soil was observed between weeks 5 and 6. It was also observed that cadmium had no significant effect (p > 0.05) on the root weight during the period of study. It’s suggestive therefore Cadmium contamination of soil could affect growth of maize and induce oxidative stress.
In silico molecular modeling and simulations of black tea theaflavins revealed theaflavin-3’-gallate as putative liver X receptor-beta agonist
(Journal of Biomolecular Structure and Dynamics Volume 41, 2023) Adigun, Temidayo O.; Danazum, Ammar U.; Umar, Haruna I.; Na’Allah, Asiat; Alabi, Mutiu A.; Cleanclay, Wisdom D.; Aberuagba, Adepeju; Alejolowo, Omokolade O.; Bamidele, Joy O.; Omotayo, Olakunle S.; Medayedupin, Oluwatobi A.
The low constitutive activation of Liver X receptor, an endogenous nuclear receptor with two subtypes (α and β), is a condition lying at the crossroad of cancer and cardiovascular disease. Both natural and synthetic Liver X receptor agonists have reportedly shown remarkable antiproliferative and atheroprotective effects but the repeated doses of its synthetic ones are also paradoxically associated with hyperlipidaemic effects and neurotoxicity, though attributed to the alpha subtype. This highlights the need for novel, safe, and potent LXR-beta-selective agonists. Hypocholesterolaemic effects of black theaflavins have been widely reported, but data on the exact theaflavin compound (s) responsible for these effects is currently lacking. Neither is information on the possible modulatory effects of the compound (s) on LXRbeta nor its possible implications in the context of drug development for cardiovascular diseases and cancers is explored. On this account, we investigated the potential interaction of four main theaflavin monomers (TF1, TF2A, TF2B & TF3) with human LXR-beta through robust computational modelling that entails molecular docking, free energy calculations and molecular dynamics simulations. The ligands were further profiled (in silico) for absorption, distribution, metabolism, excretion, and toxicological properties. Our result revealed theaflavin TF2B as a putative LXR-beta agonist, possibly responsible for the widely observed hypocholesterolaemic effect in black tea. This finding, while encouraging, needs to be experimentally verified in wet studies.
Bioactive Phytoconstituents and Their Therapeutic Potentials in the Treatment of Haematological Cancers: A Review
(MDPI, 2023-02) Iweala, Emeka J.; Oluwapelum, Adurosakin E.; Dania, Omoremime Elizabeth; Ugbogu, Eziuche A.
Haematological (blood) cancers are the cancers of the blood and lymphoid forming tissues which represents approximately 10% of all cancers. It has been reported that approximately 60% of all blood cancers are incurable. Despite substantial improvement in access to detection/diagnosis, chemotherapy and bone marrow transplantation, there is still high recurrence and unpredictable but clearly defined relapses indicating that effective therapies are still lacking. Over the past two decades, medicinal plants and their biologically active compounds are being used as potential remedies and alternative therapies for the treatment of cancer. This is due to their anti-oxidant, anti-inflammatory, anti-mutagenic, anti-angiogenic, anti-cancer activities and negligible side effects. These bioactive compounds have the capacity to reduce proliferation of haematological cancers via various mechanisms such as promoting apoptosis, transcription regulation, inhibition of signalling pathways, downregulating receptors and blocking cell cycle. This review study highlights the mechanistic and beneficial effects of nine bioactive compounds (quercetin, ursolic acid, fisetin, resveratrol, epigallocatechin gallate, curcumin, gambogic acid, butein and celastrol) as potential remedies for chemoprevention of haematological cancers. The study provides useful insights on the effectiveness of the use of bioactive compounds from plants for chemoprevention of haematological cancers.
Utilizing Mitracarpus scaber extracts for green synthesis of silver nanoparticles: Exploring physicochemical properties and potential chemopreventive activity against N-methyl-nitrosourea- induced prostate carcinoma in rats
(Nano-Structures & Nano-Objects Volume 40, 2024) Adesipe, Temitayo I.; Iweala, Emeka J.; Ishola, Ismail O.; Arotiba, Omotayo A.; Adebayo, Abiodun H.
This study evaluated the influence of silver nanoparticles (AgNPs) biosynthesized using Mitracarpus scaber (M. scaber) extracts on testosterone and n-methyl-nitrosourea (MNU)-induced prostate carcinoma in rat. AgNPs were synthesized from 0.1 M solution using the aqueous and ethanol extracts of M. scaber (AMS and EMS) as reducing as well as capping agents. The AgNPs produced using AMS (ANP) and EMS (ENP) were then analyzed via various spectroscopic experiments. Later on, the biological effects of ANP and ENP were evaluated on testosterone and n-methyl nitrosourea (MNU)-induced prostate carcinoma in rat. The study found that ANP and ENP have characteristic crystalline structures, with particle sizes ranging from ∼5 20 nm and prominent absorbance peak at 425 nm was observed for ANP while absorption peaks at 410 and 675 nm were observed for ENP indicating that ANP is isotropic in nature while ENP is anisotropic in nature. The findings regarding chemopreventive effects on prostate carcinogenesis revealed that ANP caused a significant (p < 0.05) reduction in prostate weight. However, both ANP and ENP, ameliorated prostatic hypertrophy (i.e., decreased prostate enlargement and acini proliferation) in rats induced with high-grade prostatic intraepithelial neoplasia. In comparison to the PCa group as well as other groups, ENP significantly (p < 0.05) decreased the mean concentrations of prostate-specific antigen (PSA), interleukin-6 (IL 6), and tumor necrosis factor-alpha (TNF-). Also, ENP significantly restored depleted activities levels of superoxide dismutase (SOD) and catalase caused by prostate carcinogenesis. Furthermore, ENP caused a significant (p < 0.05) reduction in glutathione (GSH) levels, an upregulation of DNA methyltransferase (DNMT1 and DNMT3b) expression, and activation of caspase 7. The results of the present study showed the potential anti-inflammatory, antioxidant and anti-neoplastic effects of AgNPs of M. scaber ethanol extract which implies that it could be used as an adjunct in the treatment of prostate cancer.
Anticancer Activity of Ethyl Acetate Fraction and Ethanol Leaf Extract of Olax subscorpioidea against DMBA-Induced Female Rats
(Tropical Journal of Natural Product Research, 2024) Adelegan, Ayodeji A.; Talabi, Azeem A.; Dokunmu, Titilope M; Iweala, Emeka Eze Joshua
Breast cancer continues to be a major contributor to cancer-related deaths in developing nations. Olax subscorpioidea is used in Nigerian traditional medicine as a treatment for cancer. The study examined the effects of Olax subscorpioidea's ethyl acetate fraction (OSEA) and ethanol leaf extract (OSE) on 7,12-Dimethylbenz(α)anthracene (DMBA)-induced breast cancer in female Sprague-Dawley rats. The anticancer, antioxidant and anti-inflammatory activities of the extracts were evaluated using established procedures. The study involved 40 female Sprague-Dawley rats with an average weight of 110 ± 20 g. The rats were given a dose of 80 mg/kg of DMBA to stimulate proliferation. Subsequently, OSEA, OSE (250 mg/kg BW), and tamoxifen (6.6 mg/kg BW) were administered. The trial spanned a duration of 22 weeks. The study evaluated the impact of the treatment on various aspects such as body weight, organ weight, liver and kidney function, oxidative stress indicators, oestrogen levels, Interleukin 6 (IL-6), Cancer antigen 153 (CA-153), and mammary tissue histology. It was found that body weight, Superoxide dismutase (SOD), Reduced glutathione (GSH), liver enzymes, and renal function increased significantly with OSEA and OSE therapy. The levels of oestrogen, IL-6, CA-153, and Malondialdehyde (MDA) decreased significantly. The histological study revealed that OSEA and OSE had a positive impact on acini normalisation and the inhibition of breast ductal cell growth. The study found that OSEA and OSE demonstrated promising effects against cancer, as well as antioxidant and anti-inflammatory properties, in rats with DMBA-induced breast cancer. The results offer scientific support for the traditional use of Olax subscorpioidea as a potential natural remedy for breast cancer.
Pro-estrogenic and anti-inflammatory effects of Corchorus olitorius and Amaranthus hybridus leaves in DMBA-induced breast cancer
(Phytomedicine Plus, 2024) Dania, Omoremime E.; Dokunmu, Titilope M.; Adegboye, Bose E.; Adeyemi, Alaba O.; Chibuzor, Favour C.; Iweala, Emeka Eze Joshua
Background: Breast cancer is the world’s most prevalent cancer and accounts for the most lost disability-adjusted life years in women worldwide. Tumour-promoting inflammation and sustained proliferative signaling are some hallmarks of cancer which can be activated by environmental carcinogens that induce oxidative stress and inflammation via increased interleukin-6 (IL-6) secretion. Increased binding of estrogen promotes the develop ment and proliferation of breast cancer. Phytochemicals have been reported to promote health by combating oxidative stress. Purpose: This study aims to assess the potential of crude hydroethanolic extract of C. olitorius (CO) and A. hybridus (AH) singly and in combination on IL-6 and estrogen in DMBA-induced breast cancer in rats. Study design: A 9 × 6 animal model made up of three groups each of control (normal, negative, positive), che mopreventive, and therapeutic (CO, AH, CO + AH mix). Methods: Phytochemical analyses were carried out on the plants, and breast cancer (BCa) was induced in female Sprague-Dawley rats by administering 80 mg/Kg BW DMBA single dose orally. ELISA kits were used to determine the levels of IL-6 and estradiol in plasma. Results: The group administered Tamoxifen and a combination of both plants recorded significantly higher plasma levels of estradiol (p = 0.0005 and p = 0.0242) respectively. Chemopreventive AH and CO + AH mix (39.46 ± 3.167; 39.69 ± 1.837) respectively had IL-6 levels similar to the normal control (38.03 ± 2.334) and less than in the corresponding therapeutic groups (60.75 ± 13.08;57.88 ± 15.32) suggesting synergistic effect of both plants. Conclusion: A. hybridus can better prevent inflammation. We propose that the plants possess pro-estrogenic and anti-inflammatory potentials.
Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies
(Current Research in Pharmacology and Drug Discovery, 2024) Iweala, Emeka Eze Joshua; Amuji, Doris Nnenna; Oluwajembola, Abimbola Mary; Ugbogu, Eziuche Amadike
Breast cancer presents a significant challenge due to its heterogeneity and propensity for developing chemo resistance, particularly in the triple-negative subtype. c-Mesenchymal epithelial transition factor (c-Met), a re ceptor tyrosine kinase, presents a promising target for breast cancer therapy due to its involvement in disease progression and poor prognosis. However, the heterogeneous expression of c-Met within breast cancer subtypes and individual tumors complicates targeted therapy. Also, cancer cells can develop resistance to c-Met inhibitors through various mechanisms, including bypass signaling pathways and genetic mutations. The off-target effects of c-Met inhibitors further limit their clinical utility, necessitating the development of more selective agents. To overcome these challenges, personalized treatment approaches and combination therapies are being explored to improve treatment efficacy while minimizing adverse effects. Novel c-Met inhibitors with improved selectivity and reduced off-target toxicity show promise in preclinical studies. Additionally, targeted delivery systems aim to enhance drug localization and reduce systemic toxicity. Future directions involve refining inhibitor design and integrating c-Met inhibition into personalized treatment regimens guided by molecular profiling. This review explores the mechanisms by which c-Met contributes to chemoresistance in breast cancer and current challenges in targeting c-Met for breast cancer therapy. It discusses strategies to optimize treatment outcomes, ultimately improving patient prognosis and reducing mortality rates associated with this devastating disease
Chemical profiling, toxicity assessment, anti-diarrhoeal, anti-inflammatory and antinociceptive activities of Canarium schweinfurthii Engl. (Burseraceae) bark in rats
(Journal of Ethnopharmacology Volume 333, 2024) Umeh, lNkiruka Edith; Onuorah, Remigius Tochukwu; Ekweogu, Celestine Nwabu; Ijioma, Solomon Nnah; Egeduzu, Ozioma Glory; Nwaru, Ezeibe Chidi; Iweala, Emeka Eze Joshua; Ugbogu, Eziuche Amadike
Ethnopharmacological relevance The bark of Canarium schweinfurthii is used in ethnomedicine for the treatment of diabetes, pain, malaria, fever and diarrhoea. Aim of the study The chemical phytoconstituents, antidiarrheal, anti-inflammatory and antinociceptive effects and safety profile of the aqueous extract of Canarium schweinfurthii bark (AECSB) were investigated. Materials and methods Gas chromatography-mass spectrometry (GC-MS) was used to analyse the phytochemical composition. In the acute toxicity test, AECSB were administered up to 2 g/kg by oral gavage. For the subacute toxicity test (28 days), rats in group 1 (control) received no AECSB, while rats in groups 2–4 were administered different doses of AECSB. Charcoal meal transit and castor oil-induced diarrhoea models were used to study the antidiarrheal effect, while egg albumin/carrageenan and acetic acid/tail immersion models were used for the anti-inflammatory and antinociceptive studies, respectively. With the exception of the acute toxicity experiment, AECSB was administered orally at doses of 200, 400 and 800 mg/kg. Results Bioactive phytoconstituents identified include p-cymene, δ-terpinene, linalool and phytol. No adverse effects or mortality were observed in acute and subacute studies. Treatment with AECSB (28 days) had no significant effect on organ weight, biochemical, hematologic and histopathologic parameters compared to the control groups (p > 0.05). Comparable antidiarrheal and antinociceptive effects were observed in both AECSB- and standard drug-treated groups, while the 400 and 800 mg/kg AECSB-treated groups showed remarkable anti-inflammatory effects compared to the standard drug-treated and control groups (p < 0.05). Conclusion AECSB has antidiarrheal, antinociceptive and anti-inflammatory effects and can be safely used for therapeutic purposes.
Advancements in Biomarkers of Prostate Cancer: A Review
(2024) Agbetuyi-Tayo, Praise; Gbadebo, Mary; Rotimi, OluwakemiA.; Rotim, Solomon O
Prostate cancer (PCa) is one of the most prevalent and deadly cancers among men, particularly affecting men of African descent and contributing significantly to cancer-related morbidity and mortality worldwide. The disease varies widely, from slow-devel oping forms to highly aggressive or potentially fatal variants. Accurate risk stratification is crucial for making therapeutic decisions and designing adequate clinical trials. This review assesses a broad spectrum of diagnostic and prognostic biomarkers, many of which are incorporated into clinical guidelines, including the Prostate Health Index (PHI), 4Kscore, STHLM3, PCA3, SelectMDx, ExoDx Prostate Intelliscore (EPI), and MiPS. It also highlights emerging biomarkers with preclinical support, such as urinary non-coding RNAs and DNA methylation patterns. Additionally, the review explores the role of tumor-associated microbiota in PCa, offering new insights into its potential contributions to disease understanding. By examining the latest advance ments in PCa biomarkers, this review enhances understanding their roles in disease management.
Photosensitizers in photodynamic therapy: An advancement in cancer treatment
(Results in Chemistry (Elsevier), 2024) Oluwajembola, Abimbola Mary; Cleanclay, Wisdom D.; Onyia, Abimbola F.; Chikere, Bruno N.; Zakari, Suleiman; Ndifreke, Ebong; De Campos, Opeyemi C.
Photodynamic therapy (PDT) is a clinically proven advancement in cancer treatment that has progressively gained consideration as a possible method of cancer treatment over time. This therapy, which involves the administration of a photosensitizing drug before activation of the drug with light from a source such as a laser to produce a cytotoxic effect, is minimally invasive and could increase the life expectancy of cancer patients. Cancer has been a major threat to human health, and it affects the quality of life of cancer patients as it is one of the topmost causes of mortality worldwide. The burden of cancer has been projected to increase to 2.1 million new cases and 1.4 million deaths in Africa by 2040. It is therefore expedient to put in more effort in proffering preventive measures, more efficient treatments, and possible cures for this disease. Recent studies have shown that many types of tumors can be destroyed using PDT. Tumor cells are destroyed via apoptosis, necrosis, and autophagy through some mechanisms in PDT. The successful outcome of this therapy depends greatly on three components which are photosensitizer (PS), light and molecular oxygen. Out of these three, photosensitizer is the most essential. Among the characteristics of a potent PS are the presence of a tetrapyrrole structure and the ability to initiate a photodynamic reaction when irradiated typically at a wavelength between 600 nm and 800 nm, although some PS can function effectively outside this range. This review highlights the effectiveness of PDT in the treatment of cancer and emphasizes the importance of PS, with more focus on those derived from natural sources, in determining the outcome of the therapy.
Gene expression levels and inhibitory effect of 7-[(7-methoxy- 4,5-dihydro-1H-benzo[g]indazol-3-yl)carbonyl]-2-phenyl- 5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]Pyrimidin-9 (1H)-one (MCL) against AP2-I and BDP1 in malaria experimental models
(Scientific African, 2024) Oladejo, David O; Anzaku, Dorathy O; Mamudu, Collins O; Elugbadebo, Temitope; Dokunmu, Titilope M; Adebiyi, Ezekiel F; Iweala, Emeka Joshua
Resistance to antimalarial drugs leads a global recurrence of malaria, posing a significant challenge to malaria control. This study aimed to assess gene expression and resistance profiles in clinical isolates, and validate the inhibitory effect of MCL compound against PbAP2-I and PbBDP1 genes in vivo. Malaria prevalence rate throughout the clinical study period stood at 12.24%. Blood samples were obtained from 182 malaria outpatients and 30 P. berghei-infected mice treated with varying MCL concentrations. DNA and RNA were extracted. PfAP2-I, PfBDP1, PfMDR1, and PfK13 genes were amplified using Real-time qPCR and sequenced for mutation profiling. Relative gene expression of AP2-I and BDP1 genes in P. falciparum and P. berghei-treated mice was carried out by Reverse-transcription PCR. The data were analyzed using ANOVA at P<0.05 indicating a significant difference. Relative gene expression results from clinical isolates showed PfAP2-I and PfBDP1 are highly expressed in the trophozoite and schizont stages. The clinical isolates show conserved nucleotide sequences for PfAP2-I, PfBDP1, and PfK13 genes compared to the 3D7 strain. However, Asn86Tyr mutation implicated in antimalarial drug resistance and Leu1312Iso mutation not previously reported to be associated with antimalarial drug resistance were observed for the PfMDR1 gene. MCL inhibited the expression of PbAP2-I (by 4.52 and 8.08 folds) and PbBDP1 (by 37.92 and 79.07 folds) at 40μM and 50μM concentrations after a 7-day, single oral daily dose. Our findings validate MCL’s inhibitory activity against AP2-I and BDP1 genes, hence representing potential new targets of antimalarial therapy for controlling malaria parasite invasion.
Acute oral toxicity and antimalarial studies of 7-[(7-methoxy- 4,5-dihydro-1H-benzo[g]indazol-3-yl)carbonyl]-2-phenyl- 5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]pyrimidin-9 (1H)-one in mouse models
(Scientific African, 2024) Oladejo, David O; Dokunmu, Titilope M; Tebamifor, Mercy E; Omunagbe, Mercy B; Okafor, Esther O; Iweala, Emeka Joshua
Protein biomarkers for diagnosis of breast cancer
(Scientific African, 2024) Iweala, Emeka Joshua; Amuji, Doris Nnenna; Nnaji, Faith Chinasaokwu
Breast cancer remains a major global health challenge, demanding better diagnostic tools. Traditional methods like mammography have limitations, highlighting the need for specific, noninvasive approaches. Protein biomarkers offer a promising avenue for early and accurate detection, potentially leading to improved patient outcomes and personalized treatment. This review explores key protein biomarkers, including Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER-2), and Cancer Antigen 27.29(CA27.29), focusing on the proteomic methodologies used in their discovery and validation. However, challenges exist, such as variability in biomarker expression and limitations in abundance, stability, and specificity, which hinder clinical use. The review discusses innovative strategies to overcome these challenges, emphasizing the importance of translating biomarker research into practical applications for personalized medicine in breast cancer diagnosis and therapy. This exploration contributes to the evolving field of breast cancer diagnostics, paving the way for future discoveries and improved patient care.
Advancements in Biomarkers of Prostate Cancer: A Review
(Technology in Cancer Research & Treatment Volume 23, 2024) Agbetuyi-Tayo, Praise; Gbadebo, Mary; Rotimi, Oluwakemi A.; Rotimi, SolomonO.
Prostate cancer (PCa) is one of the most prevalent and deadly cancers among men, particularly affecting men of African descent and contributing significantly to cancer-related morbidity and mortality worldwide. The disease varies widely, from slow-developing forms to highly aggressive or potentially fatal variants. Accurate risk stratification is crucial for making therapeutic decisions and designing adequate clinical trials. This review assesses a broad spectrum of diagnostic and prognostic biomarkers, many of which are incorporated into clinical guidelines, including the Prostate Health Index (PHI), 4Kscore, STHLM3, PCA3, SelectMDx, ExoDx Prostate Intelliscore (EPI), and MiPS. It also highlights emerging biomarkers with preclinical support, such as urinary non-coding RNAs and DNA methylation patterns. Additionally, the review explores the role of tumor-associated microbiota in PCa, offering new insights into its potential contributions to disease understanding. By examining the latest advancements in PCa biomarkers, this review enhances understanding their roles in disease management
Future directions in cervical cancer treatment
(Academic Press (Strategies for Overcoming Chemotherapy Resistance in Cervical Cancer), 2024-02) Damane, Botle Precious; Mulaudzi, Thanyani Victor; Kgokolo, Cordelia Mahlatse; Luvhengo, Thifhelimbilu; Skepu, Amanda; Rotim, Solomon O.; Dlamini, Zodwa
Immunotherapy has been a breakthrough in the treatment of several cancers with limited adverse effects compared to other therapies. Patients have experienced remission with undetectable cancers for an impressive number of years. However, the success rate is only observed in about 15%–20% of cases indicating that there is still a tremendous need for targeted therapies that are efficient in all cancers with limited or no adverse effects. The combination of immunotherapy with the existing chemotherapeutic regimens has shown improvement in several other cancers, but resistance is still a hindering factor. Thus, the application of nanomedicine, computational oncology, artificial intelligence (AI), and molecularly targeted therapies with the consideration of indigenous knowledge are reshaping the future development of cancer therapies. Together, these oncotherapeutic modalities could reshape cancer-preventative strategies, improve precision oncology, and decipher drug resistance. They offer the ability to deliver specific drugs/compounds to a specific location and ensure their efficaciousness whilst protecting the surrounding tissue. This effect takes place even in events where multiple therapeutic approaches are employed. Thus, the future of cancer therapies particularly that of the most common cancers such as cervical cancer is promising. Continual improvement of the golden standards of therapy such as radiotherapy with technologies that can detect and treat cancer simultaneously can potentially improve patient care and clinical outcomes.
Abstract 3455: Prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a Western Nigerian population
(Volume 84, Issue 6_Supplement POSTER PRESENTATIONS - PROFFERED ABSTRACTS, 2024-03-15) Vachon, Celine M; Allmer, Cristine; Moonen, Danelle; Norman, Aaron; Cook, Joselle; Slager, Susan; Rotimi, Oluwakemi A.; De Campos, Opeyemi C; Dokumu, Titilope M.; Murray, David; Kumar, Shaji; Brown, Elizabeth; Baughnm, Linda B; Rotimi, Solomon
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by plasma cell production of monoclonal (M) protein and is a requisite precursor to multiple myeloma (MM). African American (AA) individuals have a two-fold higher incidence of MGUS and MM compared to White individuals. However, data are limited on individuals from Africa, especially using sensitive MGUS detection methods. We examined the prevalence of MGUS in a sample of the general population in Nigeria. Individuals aged 40 and over (n=343) were recruited through health promotion events in Ado-Odo Ota Local Government Area of Ogun State, Nigeria, and provided informed consent, a blood sample, and a short questionnaire. Serum was screened at Mayo Clinic for heavy chain (HC)-MGUS using the matrix-assisted laser desorption/ionization-time of flight (Mass-Fix) assay, which has high sensitivity for detection of M-proteins; serum free light chains (FLC) were also measured. FLC was abnormal if the kappa (>0.26 mg/dL) or lambda (>0.33 mg/dL) light chain (LC) was elevated and FLC ratio (kappa/lambda) was outside the reference range (0.26-3.10). LC-MGUS was defined as an abnormal FLC in the absence of a HC. Age- and sex adjusted prevalence rates were directly standardized to 2010 United States (US) population for comparison to published studies. Logistic regression was used to examine the association of age, sex, and BMI with HC-MGUS. The mean age of participants was 55 years (SD=10.9), and 74.6% were female. Of these, 216 (63%) had both parents from the Yoruba tribe, 89 (26%) from the Igbo tribe and 38 (11%) from other tribes. Overall, 33 participants (9.6%) had HC-MGUS, with 8 (2.3%) having an M protein above 0.2 g/dL; 6 (1.7%) had LC-MGUS. HC-MGUS was predominantly IgG isotype (48.5%), followed by IgA (27.3%), biclonal (15.2%) and IgM (9.0%). Prevalence of HC-MGUS was 8.3% for ages 40-49, 7.7% ages 50-69 and 22% ages 70 and above. Standardized to the US population, age and sex adjusted MGUS prevalence ages 50 and older was 17.3% (95% CI: 9.8%-24.9%) and HC-MGUS was 14.7% (95% CI: 7.7% 21.8%), similar to previously published rates of HC-MGUS using Mass-Fix screening of AA individuals (16.5%, 95% CI: 12.2%-20.8%) (PMID: 35316833). In models that included age, sex and BMI, older age was positively associated with HC-MGUS (OR=3.1, 95% CI: 1.1-8.7 for ages 70+ compared to <50), while female sex (OR=0.53, 95% CI: 0.24-1.2) and overweight/obesity (OR=0.34, 95% CI: 0.16-0.75 for BMI > 25 vs. <25) were inversely associated with HC-MGUS. We observed similar prevalence of HC MGUS at ages 50 and above among Western Nigerian and AA populations when screened using mass-spectrometry. Older age was positively associated with HC MGUS while overweight and obesity were inversely associated. Studies of MGUS in indigenous African populations may provide insight to unique cancer risk factors compared to other populations.
Abstract 2230: Connecting Black men to point of prostate cancer diagnosis (PPCD) support using precision intervention based on Virtual Reality Assistant (ViRA)
(Volume 84, Issue 6_Supplement POSTER PRESENTATIONS - PROFFERED ABSTRACTS, 2024-03-15) Odedina, Folakemi T.; Ngufor, Che; Merriweather, Arnold; Pereira, Deidre; Dronca, Roxana S.; Kaninjing, Ernest; Ashing, Kimlin; Rotimi, Solomon; Gordon, Vinessa
Background: The point of prostate cancer (CaP) diagnosis (PPCD) instantly leads to a life changing experience for Black men, with diverse emotional reactions that includes fear, denial, overwhelmingness, cancer fatalism etc. Black men diagnosed with CaP expressed several needs at the PPCD, including time to reflect on the diagnosis, being comfortable, emotional support, psycho-oncology support and social determinants of health (SDOH) navigation. Given that Black men are diverse in terms of their needs at the PPCD, precision intervention is needed to support them. Aim: The aim was to develop, implement, and establish the acceptance and usability of a Virtual Reality Assistant (ViRA) that will provide precision intervention tailored to the needs of Black men at the PPCD. This study is one of the five iCCaRE for Black Men projects focused on survivorship care. Methodology: The development of the ViRA was guided by CaP survivors through qualitative study. Reflective, analytic, and interpretive memos were used to generate action plans for the development of the ViRA. Based on a comprehensive PPCD ViRA intervention guide created by the team, the ViRA prototype was developed with mobile immersive technologies that integrated SDOH navigation, standard CaP psycho oncology support and emotional support. The goal was to have the intervention personalized to everyone based on participant-provided information. Alpha testing of the ViRA is ongoing and will be completed on November 20, 2023. Participants are three prostate cancer survivors and three clinicians. The assessments will confirm the accuracy of the ViRA predictions and the functionality of the ViRA. Results: We developed the ViRA SDOH screening and navigation tool to identify participants’ needs and appropriately connect them with relevant support services and resources in their communities. The emotional support intervention was based on four CaP survivors as virtual reality avatars, providing empathetic rapport through self disclosure and sharing of survivorship stories in different settings (home, clinic, barbershop etc). The psycho-oncology support intervention was developed with the guidance of a psycho-oncologist, with her avatar providing psychoeducation about the PPCD experience, reify and concretize the PPCD experience, and foster hope using the basic tenets of Problem-Solving Therapy. The results of the alpha testing and the modified ViRA will be presented during the conference. Conclusion: Meeting the needs of Black men at the PPCD requires a personalized and decentralized approach, which would allow Black men to access support anywhere. The presentation will unveil the iCCaRE ViRA, a smart and connected personalized AR enabled intervention that will deliver SDOH navigation, CaP psycho-oncology support and emotional support tailored to the needs of Black men.
Abstract 819: Feasibility of patient centered home care (PCHC) to reduce disparities in high-risk black men with advanced prostate cancer
(Volume 84, Issue 6_Supplement POSTER PRESENTATIONS - PROFFERED ABSTRACTS, 2024-03-15) Dronca, Roxana S.; Odedina, Folakemi; Ngufor, Che; Ashing, Kimlin; Kaninjing, Ernest; Rotimi, Solomon
The objective of our study is to evaluate the feasibility, acceptance, and impact of patient-centered home care (PCHC) on patient reported outcomes (PROs) and health related quality of life (HQoL) of black men with advanced prostate cancer (CaP). Meeting patients where they are and offering treatment in or closer to their homes reduce psychological distress and increase treatment compliance, especially for disadvantaged patients in rural areas, those on low incomes, with poor access to transport, elderly and people with disabilities. In 2023, Mayo Clinic has developed the Cancer Care Beyond Walls (CCBW) program, a cancer care delivery model that integrates virtual with in facility treatment and provides a package of care to support administration of cancer-directed therapy (chemotherapy, immunotherapy, hormonal therapy) and/or supportive care in the patients’ homes. Our study will assess if patients and families are comfortable with cancer therapy at home, what factors influences their decision, and use this data to inform our understanding of the proportion of the black men with advanced CaP who would be willing to receive and would benefit from this level of care at home. Patients with advanced CaP from our practice requiring active anti-cancer therapy are administered a brief questionnaire regarding preference for location of therapy at the infusion center or in the home, with perceived difficulties and advantages of each approach. A focus group session with prostate cancer survivor advocates is also conducted to capture patients’ thoughts, feelings, attitudes, and questions towards cancer treatments being administered at home versus a hospital setting. In addition, we are conducting an observational study of 20 patients with advanced prostate cancer receiving supportive care/symptom management and/or anti cancer therapy in the home as part of the Mayo Clinic CCBW Program to assess the safety of cancer directed therapy when administered at home by a home health provider with remote patient monitoring and command center support, and establish the impact of home cancer treatment administration on patient-reported function and global health/quality of life, patient-reported symptoms, clinical outcomes, and cost of care. Successful completion of the project will deliver data on patient understanding and acceptability of cancer care at home, strategies for overcoming barriers to care for underserved communities, and the foundation from which we discover, translate and apply new knowledge in administering personalized care to vulnerable populations.
Abstract 1310: Social determinants of migrant health factors impacting prostate cancer care and survivorship among sub-Saharan African immigrant men diagnosed with prostate cancer
(Volume 84, Issue 6_Supplement POSTER PRESENTATIONS - PROFFERED ABSTRACTS, 2024-03-15) Kaninjing, Ernest; Asiedu, Gladys; Voorhis, Kaitlin Va; Young, Mary Ellen; Erefah, Ebenezer; Agboola, Emmanuel; Odedina, Folakemi; Dronca, Roxana S.; Ashing, Kimlin; Rotimi, Solomon; Ngufor, Che; Merriweather, Arnola; McCall, John; Hill, Anthony
Abstract 4343: Revealing ovarian cancer copy number variation in single cells
(American Association for Cancer Research Cancer Res (2024) 84 (6_Supplement): 4343, 2024-03-15) Jin, Yuxin; Bassiouni, Rania; Rania, Lee D.; Qian, Jing; Rotimi, Solomon; Webb, Michelle G.; Rajpara, Seeta; Craig, David W.; Roman, Lynda D.; Carpten, John D.
The mortality rate associated with ovarian cancer (OvCa) is disproportionately high in comparison to its incidence rate. This is partly due to the heterogeneous nature of the disease, which reduces treatment efficacy and contributes to high rates of relapse and chemotherapy resistance. Most OvCa are epithelial in origin and can be classified into four main subtypes: serous, mucinous, endometrioid, and clear cell. Of these, high grade serous ovarian cancer (HGSOC) is the deadliest. Epithelial ovarian carcinomas (EOC) typically exhibit widespread chromosomal and arm-level copy number abnormalities across most of the genome; in HGSOC, focal amplifications and microdeletions are especially prevalent and indicative of high genomic instability. To understand the heterogeneity of aneuploidy in EOC and HGSOC, we performe single-cell whole genome sequencing on four EOC samples: two HGSOC, one clear cell, and one mixed clear cell and endometrioid. All samples were late stage and treatment naïve, and one sample had a known BRCA2 mutation. Sequencing data was processed by two complementary methods to call copy number alterations. First, we used the Cell Ranger DNA pipeline (10x Genomics) to align cell-identified sequencing reads to human reference genome GRCh38 for coverage-based copy number estimation. Resulting copy number calls were cleaned up for mappability, quality, and noisiness. Each sample was then subject to clustering and subclustering analysis using maximum likelihood genetic clustering algorithms. All samples exhibited a high level of aneuploidy, including characteristic alterations known to be associated with EOC. Two tumors contained readily distinguishable clonal populations, and all samples contained main tumor clones that could be further divided by unique subclonal characteristics. Evidence of polyploidy was also seen in all four specimens, with some tumor clusters exhibiting triploid and tetraploid baselines. In parallel, sequencing data was analyzed by the Copy-number Haplotype Inference in Single-cell by Evolutionary Links (CHISEL) algorithm. CHISEL utilizes both binned read depth ratio and B-allele frequency data to determine allele- and haplotype-specific copy numbers in single cells. Results from CHISEL confirmed the copy number calls from Cell Ranger DNA, and revealed widespread loss of heterozygosity in all samples. These findings were corroborated with allele-specific copy number data derived from matched tumor-normal whole exome sequencing. Furthermore, CHISEL detected polyploidy in one-third of the tumor cells with no preference for the A or B alleles. Overall, our findings highlight that the known heterogeneity of ovarian cancer extends to the level of aneuploidy and CNAs, shedding light on factors which pose significant barriers to effective personalized medicine implementation.