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Research Article
Telomere Elongation and Mismatch Repair Deficiency Distinguish MSI Colorectal Cancer Cell Lines
Rajasekhar Moka*
,
Shreya Upadhya
Issue:
Volume 13, Issue 2, June 2025
Pages:
23-29
Received:
17 April 2025
Accepted:
29 April 2025
Published:
29 May 2025
Abstract: Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency and characterizes a distinct subset of colorectal cancers (CRC). In parallel, telomere length dynamics have emerged as important contributors to genomic stability and tumorigenesis. However, the relationship between MSI status, MMR protein expression, and telomere maintenance remains poorly defined. This study aimed to investigate the association between MSI status and telomere length in CRC cell lines and to evaluate the expression of key MMR proteins (MLH1, MSH2, MSH6, PMS2) to elucidate molecular differences between MSI and microsatellite stable (MSS) phenotypes. A panel of CRC cell lines with known MSI and MSS statuses was used. Telomere length was quantified using real-time quantitative PCR (qPCR) based on the T/S ratio method. MSI status was confirmed via PCR using mononucleotide repeat markers. Western blotting was performed to assess protein expressions of MLH1, MSH2, MSH6, and PMS2. β-actin served as a loading control. qPCR analysis revealed that MSI cell lines exhibited significantly longer telomeres compared to MSS lines (P < 0.05). Western blot results showed reduced or absent expression of MLH1 and PMS2 in MSI cell lines, confirming MMR deficiency. In contrast, MSS cell lines maintained normal expression of all tested MMR proteins. These findings suggest a link between defective MMR function and altered telomere dynamics in MSI-CRC. MSI CRC cell lines exhibit telomere elongation and loss of key MMR proteins, highlighting distinct molecular features compared to MSS counterparts. These insights may inform future strategies for personalized CRC diagnostics and therapeutics, particularly in the context of telomere-targeted or immunomodulatory treatments.
Abstract: Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency and characterizes a distinct subset of colorectal cancers (CRC). In parallel, telomere length dynamics have emerged as important contributors to genomic stability and tumorigenesis. However, the relationship between MSI status, MMR protein expression, and telomere ma...
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Research Article
Crocin and Flavocoxid Inhibit Tumor Growth, Alter Cytokine Levels of (IL-10/Tnf-α), and Promote Caspase-Induced Apoptosis, and Doxorubicin Efficacy
Issue:
Volume 13, Issue 2, June 2025
Pages:
30-45
Received:
28 August 2024
Accepted:
18 September 2024
Published:
6 June 2025
DOI:
10.11648/j.crj.20251302.12
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Abstract: Background: We assessed the differential sole and Doxorubicin-(Doxo)-combined chemotherapy of the phytomedicines Crocin and Flavocoxid-(flvcox), against the-mouse-Ehrlich-Ascites-Carcinoma-solid-tumor-model-(EAC). We further identified the underlying-molecular mechanisms of actions, interrelations of probed signals, as well as the relative-potency among all used drug modalities. Methods: Functional studies evaluated tumor-burden, animal-survival, serum/tumor redox-status, and levels of key-effectors coherent with tumorigenesis, inflammation, and host-immunity, namely (serum IL-10 and TNF-α) and with tumor-apoptosis (Caspase-3-expression). Furthermore, histopathological examinations were performed to envisage the associated structural changes. Results: EAC-bearing mice had significantly raised serum-TNF-α and tumor lipid-peroxide (MDA) levels, but lower serum IL-10-levels and total serum antioxidant-capacity-(TAC), thereby showing animal-fatalities after-3-weeks. Crocin administration significantly-shrank tumor-mass by (50%), -reduced tumor lipid-peroxide-(MDA) and serum-TNF-α levels; but raised serum-IL-10, TAC and tumor-caspase-3 levels; ultimately augmenting animal survival by (79%). Flvcox had weaker survival-effects (44%) than that of crocin. Correlation studies showed IL-10, contrary to TNF-α to boost animal-survival, and suppress tumor-size. Tumor caspase-3 levels augmented both animal-survival and the TAC-level, while opposed tumor-weight and tumor-MDA levels. Besides, tumor oxidative-stress boosted tumor growth, and reduced caspase-3 levels, thereby worsening animal survival. Histopathology analyses confirmed functional studies. Conclusions: 1)- The study reveals that Doxo confers superior cytotoxicity but inferior cytokine-balance, redox-status and animal-rescuing profiles; 2)- Crocin and Flvcox elicit prominent sole- and combined-cytotoxicity, and animal-rescuing potentials, by restoring the disrupted-balance of the cytokines (IL-10/TNF-α), optimizing serum/tumor redox-potentials and accelerating tumor-cell apoptosis; 3)- Cross-talk was evidently documented among (key-cytokines), (tumor-burden), (redox-status), and (tumor-apoptosis), in a manner that dictates the efficacy of sole (or) mutual-therapy, and their influence on animal-survival in response to cancer.
Abstract: Background: We assessed the differential sole and Doxorubicin-(Doxo)-combined chemotherapy of the phytomedicines Crocin and Flavocoxid-(flvcox), against the-mouse-Ehrlich-Ascites-Carcinoma-solid-tumor-model-(EAC). We further identified the underlying-molecular mechanisms of actions, interrelations of probed signals, as well as the relative-potency ...
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Research Article
Polymorphism and Genetic Diversity in Senegalese Patients with Oral Cancers
Issue:
Volume 13, Issue 2, June 2025
Pages:
46-55
Received:
23 April 2025
Accepted:
7 May 2025
Published:
12 June 2025
DOI:
10.11648/j.crj.20251302.13
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Abstract: Cancer is the leading cause of death and a major obstacle to increasing life expectancy worldwide in the 21st century. Oral cavity cancers are the most common type of head and neck cancers. This study aimed to determine the polymorphism and genetic diversity of the tumor protein P53 (TP53) in oral cavity cancers in Senegal. From a total of 40 patients with oral cavity cancer, we collected 40 cancerous tissue samples, 20 adjacent healthy tissue samples, and 15 blood samples. Blood samples were collected from participants in the control group. Tissue samples were obtained from each patient during a biopsy after obtaining informed consent. DNA extraction, polymerase chain reaction (PCR), and sequencing were performed. MEGA, BioEdit, and DnaSP software were used to analyze polymorphisms and genetic diversity. A total of 36.80%, 22.27%, and 7.74% polymorphic sites were found in cancerous tissues, healthy tissues, and blood samples, respectively. Nine amino acids showed significant differences in distribution between participants in the control group and patients. Significant differences were also observed within and between populations. This study revealed an increasing number of oral cancer cases in Senegal. Moreover, healthy tissues exhibited the same genetic alterations as cancerous tissues.
Abstract: Cancer is the leading cause of death and a major obstacle to increasing life expectancy worldwide in the 21st century. Oral cavity cancers are the most common type of head and neck cancers. This study aimed to determine the polymorphism and genetic diversity of the tumor protein P53 (TP53) in oral cavity cancers in Senegal. From a total of 40 patie...
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Research Article
A Hospital-Based Matched Case Control Study Examined the Breast Cancer Risk Factors for Women Who Visit the Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia
Issue:
Volume 13, Issue 2, June 2025
Pages:
56-70
Received:
15 January 2025
Accepted:
23 April 2025
Published:
18 June 2025
DOI:
10.11648/j.crj.20251302.14
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Abstract: Breast cancer is a type of cancer that is distinguished by the uncontrolled and abnormal growth of breast cells. Globally, it remained the most frequently diagnosed neoplastic disease in women and the leading cause of cancer-related death. Despite the increasing incidence of breast cancer in Ethiopia, there has been a limited study that determines the risk factors for breast cancer. This study employed a hospital-based matched case-control design to analyze breast cancer risk factors for women seeking care at the Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia. A hospital-based, unmatched case-control study design was employed from March 1 to April 30, 2022, among 131 cases and 257 control women attending Hawassa University Comprehensive Specialized Hospital. Data were collected using a standardized, pre-tested questionnaire. SPSS version 20 was used for the statistical analysis of the data. Descriptive statistics were used to summarize the socio-demographic, reproductive, and other characteristics of respondents. The bivariable and multivariable logistic regression analyses were used to assess variables associated with breast cancer and were presented with a 95% confidence interval. The final result was displayed using text figures and tables. In this study, age [AOR=5.79, 95%CI (2.11, 12.75)], family history of cancer (AOR=6.05, 95% CI (1.92 19.03), not consuming fruits (AOR=3.34, 955; CI 1.32, 8.48), eating sea foods (fish) (AOR=.24, 95% CI 0.1, 0.60), using packed food or drink (AOR= 4.10 95% CI, 1.23, 13.67), hormonal contraceptive use (AOR= 3.86 95%, CI 1.62, 9.24), having history of breast injury (AOR= 3.29 95% CI 1.20 9.01), history of abortion (AOR=3.16, 95% CI 1.11 9.00), exposure of radiation (AOR= 2.64 95% CI, 1.14 6.15) were risk factors associated with breast cancer. Having a family history of cancer, not eating fruits, not eating sea foods (fish), using packed foods or drinks, using hormonal contraception, having a history of breast injury, a history of abortion, and previous radiation exposure were all risk factors for breast cancer. Health professionals should deliver health education on the importance of a fruit and fish diet and its association with lower breast cancer risk.
Abstract: Breast cancer is a type of cancer that is distinguished by the uncontrolled and abnormal growth of breast cells. Globally, it remained the most frequently diagnosed neoplastic disease in women and the leading cause of cancer-related death. Despite the increasing incidence of breast cancer in Ethiopia, there has been a limited study that determines ...
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Research Article
Cancers Are Derived from the Disruption of Cell Differentiation
Maojin Li*
Issue:
Volume 13, Issue 2, June 2025
Pages:
71-80
Received:
26 May 2025
Accepted:
9 June 2025
Published:
23 June 2025
DOI:
10.11648/j.crj.20251302.15
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Abstract: The mechanisms of cancer are discussed by analyzing the characteristics of the functional state and biological behavior of the abnormal nuclear cells. The abnormal nuclear cells with abnormal nuclear structure and function are a kind of sick cell or functional defect cells having existed in human body for a long time. The abnormal nuclear cells are resulted from the nuclear damage caused by the radiation, viruses and various carcinogenic compounds. Some of genes in human body are expressed, some are not expressed for life. The expressional genes are functional genes, the genes never expressed for life in human body are dormant genes or sealed genes. The nuclear damages destroy cell state of differentiation, affect gene expressional regulation and change gene expressional profiling, resulting in loss of expression of the functional genes and reactivation of the sealed genes; which finally leads to cancer, aging and other chronic refractory diseases. The cancer is not resulted from the genetic mutations or chromosomal aberrations, but rather the reactivation of genes involved in proliferation due to the nuclear damage. The biological characteristics of the cancer cells, such as the shedding and metastasis, immune tolerance, uncontrolled, loss of contact inhibition function and so on, all originate from the nuclear aberrant cells. The nuclear damage can trigger the genes that drive mitosis, leading to cancer. Thus, re-sealing the several genes that trigger the proliferation may completely prevent or cure cancers.
Abstract: The mechanisms of cancer are discussed by analyzing the characteristics of the functional state and biological behavior of the abnormal nuclear cells. The abnormal nuclear cells with abnormal nuclear structure and function are a kind of sick cell or functional defect cells having existed in human body for a long time. The abnormal nuclear cells are...
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