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Article ; Online: Epigenetic Modulators as Therapeutic Agents in Cancer.

Patnaik, Eshaan / Madu, Chikezie / Lu, Yi

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: Epigenetics play a crucial role in gene regulation and cellular processes. Most importantly, its dysregulation can contribute to the development of tumors. Epigenetic modifications, such as DNA methylation and histone acetylation, are reversible ... ...

Abstract	Epigenetics play a crucial role in gene regulation and cellular processes. Most importantly, its dysregulation can contribute to the development of tumors. Epigenetic modifications, such as DNA methylation and histone acetylation, are reversible processes that can be utilized as targets for therapeutic intervention. DNA methylation inhibitors disrupt DNA methylation patterns by inhibiting DNA methyltransferases. Such inhibitors can restore normal gene expression patterns, and they can be effective against various forms of cancer. Histone deacetylase inhibitors increase histone acetylation levels, leading to altered gene expressions. Like DNA methylation inhibitors, histone methyltransferase inhibitors target molecules involved in histone methylation. Bromodomain and extra-terminal domain inhibitors target proteins involved in gene expression. They can be effective by inhibiting oncogene expression and inducing anti-proliferative effects seen in cancer. Understanding epigenetic modifications and utilizing epigenetic inhibitors will offer new possibilities for cancer research.
MeSH term(s)	Humans ; Histones/metabolism ; Neoplasms/drug therapy ; Neoplasms/genetics ; DNA Methylation ; Epigenesis, Genetic ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Acetylation
Chemical Substances	Histones ; Antineoplastic Agents ; Histone Deacetylase Inhibitors
Language	English
Publishing date	2023-10-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241914964
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Article: Phytochemicals in Chemoprevention: A Cost-Effective Complementary Approach.

Jain, Aayush / Madu, Chikezie O / Lu, Yi

Journal of Cancer

2021 Volume 12, Issue 12, Page(s) 3686–3700

Abstract: Cancer is one of the leading causes of death across the world. Although conventional cancer treatments such as chemotherapy and radiotherapy have effectively decreased cancer progression, they come with many dose-limiting side-effects. Phytochemicals ... ...

Abstract	Cancer is one of the leading causes of death across the world. Although conventional cancer treatments such as chemotherapy and radiotherapy have effectively decreased cancer progression, they come with many dose-limiting side-effects. Phytochemicals that naturally occur in spices, fruits, vegetables, grains, legumes, and other common foods are surprisingly effective complements to conventional cancer treatments. These biologically active compounds demonstrate anticancer effects via cell signaling pathway interference in cancerous cells. In addition, phytochemicals protect non-cancerous cells from chemotherapy-induced side-effects. This paper addresses the not only the potential of phytochemicals quercetin, isoflavones, curcumin, catechins, and hesperidin in terms of cancer treatment and protection against side-effects of chemotherapy, but also methods for increasing phytochemical bioavailability.
Language	English
Publishing date	2021-04-30
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.57776
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Article: The Impact of Hormonal Imbalances Associated with Obesity on the Incidence of Endometrial Cancer in Postmenopausal Women.

Ding, Sarah / Madu, Chikezie O / Lu, Yi

Journal of Cancer

2020 Volume 11, Issue 18, Page(s) 5456–5465

Abstract: Obesity has long been associated with endometrial cancer amongst postmenopausal women; in fact, obese women are more than twice as likely to develop endometrial cancer as women of normal weight. The risk of developing this type of cancer increases with ... ...

Abstract	Obesity has long been associated with endometrial cancer amongst postmenopausal women; in fact, obese women are more than twice as likely to develop endometrial cancer as women of normal weight. The risk of developing this type of cancer increases with weight gains in adulthood, especially among women who did not use hormonal therapy for menopause. Thus, with an association between menopause, obesity, and endometrial cancer established, it prompts the following question: what specific factors could cause higher risk levels for endometrial cancer in this cohort of women? In this paper, the factor of hormonal changes and imbalances associated with both obesity and menopause will be examined. The hormones that will be discussed are insulin and insulin-like factors, estrogen, and adipokines (specifically adiponectin, visfatin, and leptin).
Language	English
Publishing date	2020-07-11
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.47580
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Article ; Online: Role of HSP90 in Cancer.

Birbo, Bereket / Madu, Elechi E / Madu, Chikezie O / Jain, Aayush / Lu, Yi

International journal of molecular sciences

2021 Volume 22, Issue 19

Abstract: HSP90 is a vital chaperone protein conserved across all organisms. As a chaperone protein, it correctly folds client proteins. Structurally, this protein is a dimer with monomer subunits that consist of three main conserved domains known as the N- ... ...

Abstract	HSP90 is a vital chaperone protein conserved across all organisms. As a chaperone protein, it correctly folds client proteins. Structurally, this protein is a dimer with monomer subunits that consist of three main conserved domains known as the N-terminal domain, middle domain, and the C-terminal domain. Multiple isoforms of HSP90 exist, and these isoforms share high homology. These isoforms are present both within the cell and outside the cell. Isoforms HSP90
MeSH term(s)	Animals ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Molecular Chaperones/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology ; Protein Isoforms/metabolism
Chemical Substances	HSP90 Heat-Shock Proteins ; Molecular Chaperones ; Protein Isoforms
Language	English
Publishing date	2021-09-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms221910317
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Article: Angiogenesis in Breast Cancer Progression, Diagnosis, and Treatment.

Madu, Chikezie O / Wang, Stephanie / Madu, Chinua O / Lu, Yi

Journal of Cancer

2020 Volume 11, Issue 15, Page(s) 4474–4494

Abstract: Angiogenesis is a significant event in a wide range of healthy and diseased conditions. This process frequently involves vasodilation and an increase in vascular permeability. Numerous players referred to as angiogenic factors, work in tandem to ... ...

Abstract	Angiogenesis is a significant event in a wide range of healthy and diseased conditions. This process frequently involves vasodilation and an increase in vascular permeability. Numerous players referred to as angiogenic factors, work in tandem to facilitate the outgrowth of endothelial cells (EC) and the consequent vascularity. Conversely, angiogenic factors could also feature in pathological conditions. Angiogenesis is a critical factor in the development of tumors and metastases in numerous cancers. An increased level of angiogenesis is associated with decreased survival in breast cancer patients. Therefore, a good understanding of the angiogenic mechanism holds a promise of providing effective treatments for breast cancer progression, thereby enhancing patients' survival. Disrupting the initiation and progression of this process by targeting angiogenic factors such as vascular endothelial growth factor (Vegf)-one of the most potent member of the VEGF family- or by targeting transcription factors, such as Hypoxia-Inducible Factors (HIFs) that act as angiogenic regulators, have been considered potential treatment options for several types of cancers. The objective of this review is to highlight the mechanism of angiogenesis in diseases, specifically its role in the progression of malignancy in breast cancer, as well as to highlight the undergoing research in the development of angiogenesis-targeting therapies.
Language	English
Publishing date	2020-05-18
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.44313
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Article ; Online: Phenotypic characterisation and associations of leg ulcers in adult sickle cell patients.

Madu, Anazoeze / Madu, Kenechi / Anigbogu, Ikechukwu / Ugwu, Angela Ogechukwu / Okwulehie, Vincent A / Ololo, Uchenna / Ugwu, Chioma / Chikezie, Kelechi

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

2021 Volume 30, Issue 1, Page(s) 126–131

Abstract: Sickle leg ulcer (SLU) occurs as a result chronic occlusion of the vasculature with consequent necrosis of the skin and subcutaneous tissue usually in proximity of the malleoli. The description of clinical associations and the simultaneous occurrence of ... ...

Abstract	Sickle leg ulcer (SLU) occurs as a result chronic occlusion of the vasculature with consequent necrosis of the skin and subcutaneous tissue usually in proximity of the malleoli. The description of clinical associations and the simultaneous occurrence of SLU and other complications of SCD compared to the non-SLU patients was the aim of this work. A total of 272 (60.8% males and 39.2% females) patients were captured during this time period out of which 68 (51 males and 17 females) had SLU out of whom 20 patients had bilateral leg ulcers. Prevalence of SLU was 25% and the median age of patients was 25 years, frequency of crisis 2 per annum and 44 (74.6%) had been transfused in the past. Median Hb of the group was 7.6 g/dl and 25% had values lower than 6.5. The occurrence of other complications in SLU patients was as follows; 10 had AVN, 9 priapism, 8 had osteomyelitis, 6 nephropathy, stroke 2, osteoarthritis 4 and cholelithiasis 4. There was a significant relationship between the occurrence of SLU and gender of the patient being more in 67males-Likelihood ratio 4.610 (p = 0.032) and the occurrence of pulmonary hypertension-Likelihood ratio 4.762 (p = 0.029). There was no significant association between the occurrence of SLU and other complications of SCD. Leg ulcer patients have a median age of 25 years with a prevalence of 25% but do not necessarily show other features of severe disease phenotypes. SLU patients were more likely to develop pulmonary hypertension. Further studies on impact of environmental factors on the occurrence of SLU are needed to further evaluate its aetiology.
MeSH term(s)	Adult ; Anemia, Sickle Cell/complications ; Anemia, Sickle Cell/epidemiology ; Female ; Humans ; Leg Ulcer/epidemiology ; Leg Ulcer/etiology ; Male ; Phenotype ; Prevalence ; Wound Healing
Language	English
Publishing date	2021-11-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1174873-4
ISSN	1524-475X ; 1067-1927
ISSN (online)	1524-475X
ISSN	1067-1927
DOI	10.1111/wrr.12970
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Article ; Online: Role of HSP90 in Cancer

Bereket Birbo / Elechi E. Madu / Chikezie O. Madu / Aayush Jain / Yi Lu

International Journal of Molecular Sciences, Vol 22, Iss 10317, p

2021 Volume 10317

Abstract	HSP90 is a vital chaperone protein conserved across all organisms. As a chaperone protein, it correctly folds client proteins. Structurally, this protein is a dimer with monomer subunits that consist of three main conserved domains known as the N-terminal domain, middle domain, and the C-terminal domain. Multiple isoforms of HSP90 exist, and these isoforms share high homology. These isoforms are present both within the cell and outside the cell. Isoforms HSP90 α and HSP90 β are present in the cytoplasm; TRAP1 is present in the mitochondria; and GRP94 is present in the endoplasmic reticulum and is likely secreted due to post-translational modifications (PTM). HSP90 is also secreted into an extracellular environment via an exosome pathway that differs from the classic secretion pathway. Various co-chaperones are necessary for HSP90 to function. Elevated levels of HSP90 have been observed in patients with cancer. Despite this observation, the possible role of HSP90 in cancer was overlooked because the chaperone was also present in extreme amounts in normal cells and was vital to normal cell function, as observed when the drastic adverse effects resulting from gene knockout inhibited the production of this protein. Differences between normal HSP90 and HSP90 of the tumor phenotype have been better understood and have aided in making the chaperone protein a target for cancer drugs. One difference is in the conformation: HSP90 of the tumor phenotype is more susceptible to inhibitors. Since overexpression of HSP90 is a factor in tumorigenesis, HSP90 inhibitors have been studied to combat the adverse effects of HSP90 overexpression. Monotherapies using HSP90 inhibitors have shown some success; however, combination therapies have shown better results and are thus being studied for a more effective cancer treatment.
Keywords	HSP90 ; molecular chaperones ; GRP94 ; TRAP1 ; targeted therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570 ; 616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Selection, Analysis and Improvement of Anti-Angiogenesis Compounds Identified by an Anti-HIF-1α Screening and Validation System.

Madu, Chikezie / Li, Liyuan / Lu, Yi

Journal of Cancer

2016 Volume 7, Issue 14, Page(s) 1926–1938

Abstract: Cancer cells resort to activating hypoxia-inducible factor-1 (HIF-1) as one of several responses to hypoxic conditions. Overexpression of HIF-1, the transcriptional regulator for a group of malignant-pathway related genes including vascular endothelial ... ...

Abstract	Cancer cells resort to activating hypoxia-inducible factor-1 (HIF-1) as one of several responses to hypoxic conditions. Overexpression of HIF-1, the transcriptional regulator for a group of malignant-pathway related genes including vascular endothelial growth factor (VEGF), is associated with increased tumor growth, vascularization, and metastasis. HIF-1 is composed of an inducible subunit, HIF-1α and a constitutively expressed subunit, HIF-1ß. HIF-1 activity is mainly dependent on the level of HIF-1α protein, the inducible and regulatory subunit of the HIF-1 heterodimer complex; thus, identification of novel anti-HIF-1α agents will lead to effective blockage of the HIF-1 (HIF-1α)-mediated "switch-on" function for those malignant-pathway related genes and suppression of the HIF-1α/VEGF-mediated signaling pathway that promotes cancer progression and metastasis. While there is an extremely large number of small molecule compounds in the database (compound libraries), the currently existing screening system is inefficient and time-consuming; or, at best, the application of the existing screening system is very limited as it is usually not coupled with biological validation processes. The further development of potential drugs is partly hindered due to the cumbersome steps in between the primary screen and consequent validation: the slow, exhausted and sometimes lack of a linked biological validation process contributes to the dismal fate of scant compounds uncovered in the primary screen. To improve upon the status quo, we developed a prototype screening system that is coupled anti-HIF-1α primary screen with secondary anti-VEGF/anti-angiogenesis validation screens. We used breast cancer cells as the model to select potent anti-HIF-1α small-molecule compounds by their abilities to inhibit transactivation of a VEGF promoter fused to a luciferase reporter gene under hypoxia. Positive compounds were then validated by a series of assays that confirm compounds' anti-HIF-1α activities including measurement of their effects on HIF-1α downstream VEGF gene expression and angiogenic ability of breast cancer cells. Moreover, we demonstrated that we could further improve the compound's potency of anti-HIF-1α and anti-angiogenesis by modifying the identified lead to synthesize a superior (novel) drug.
Language	English
Publishing date	2016-09-27
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.15603
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Article ; Online: Viral-based gene delivery and regulated gene expression for targeted cancer therapy.

Lu, Yi / Madu, Chikezie O

Expert opinion on drug delivery

2010 Volume 7, Issue 1, Page(s) 19–35

Abstract: Importance of the field: Cancer is both a major health concern and a care-cost issue in the US and the rest of the world. It is estimated that there will be a total of 1,479,350 new cancer cases and 562,340 cancer deaths in 2009 within the US alone. One ...

Abstract	Importance of the field: Cancer is both a major health concern and a care-cost issue in the US and the rest of the world. It is estimated that there will be a total of 1,479,350 new cancer cases and 562,340 cancer deaths in 2009 within the US alone. One of the major obstacles in cancer therapy is the ability to target specifically cancer cells. Most existing chemotherapies and other routine therapies (such as radiation therapy and hormonal manipulation) use indiscriminate approaches in which both cancer cells and non-cancerous surrounding cells are treated equally by the toxic treatment. As a result, either the cancer cell escapes the toxic dosage necessary for cell death and consequently resumes replication, or an adequate lethal dose that kills the cancer cell also causes the cancer patient to perish. Owing to this dilemma, cancer- or organ/tissue-specific targeting is greatly desired for effective cancer treatment and the reduction of side effect cytotoxicity within the patient. Areas covered in this review: In this review, the strategies of targeted cancer therapy are discussed, with an emphasis on viral-based gene delivery and regulated gene expression. What the reader will gain: Numerous approaches and updates in this field are presented for several common cancer types. Take home message: A summary of existing challenges and future directions is also included.
MeSH term(s)	Blotting, Southern ; Gene Expression ; Genetic Vectors ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/therapy ; Polymerase Chain Reaction ; Prodrugs/therapeutic use ; Viruses/genetics
Chemical Substances	Prodrugs
Language	English
Publishing date	2010-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2167286-6
ISSN	1744-7593 ; 1742-5247
ISSN (online)	1744-7593
ISSN	1742-5247
DOI	10.1517/17425240903419608
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Article ; Online: Novel diagnostic biomarkers for prostate cancer.

Madu, Chikezie O / Lu, Yi

Journal of Cancer

2010 Volume 1, Page(s) 150–177

Abstract: Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the ...

Abstract	Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The purpose of this review is to examine the current status of prostate cancer biomarkers, with special emphasis on emerging markers, by evaluating their diagnostic and prognostic potentials. Both genes and proteins that reveal loss, mutation, or variation in expression between normal prostate and cancerous prostate tissues will be covered in this article. Along with the discovery of prostate cancer biomarkers, we will describe the criteria used when selecting potential biomarkers for further development towards clinical use. In addition, we will address how to appraise and validate candidate markers for prostate cancer and some relevant issues involved in these processes. We will also discuss the new concept of the biomarkers, existing challenges, and perspectives of biomarker development.
Language	English
Publishing date	2010-10-06
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2573318-7
ISSN	1837-9664 ; 1837-9664
ISSN (online)	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.1.150
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