scholarly journals Mutational profiles of marker genes of cervical carcinoma in Bangladeshi patients

2020 ◽  
Author(s):  
Shahana Sharmin ◽  
Fatima Tuj Zohura ◽  
Md. Sajedul Islam ◽  
Anika Shimonty ◽  
Md. Abdullah-Al-Kamran Khan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hpv Vaccination ◽  
Gynecologic Cancer ◽  
Treatment Modalities ◽  
Nucleotide Sequence Analysis ◽  
Marker Genes ◽  
Cancer Tissue ◽  
Cancer Type ◽  
Tissue Samples ◽  
Cancer Subtypes

Abstract Background: Cervical cancer is a gynecologic cancer type that develops in the cervix, accounting for 8% mortality of all female cancer patients. Infection with specific human papillomavirus (HPV) types is considered the most severe risk factor for cervical cancer. In the context of our socioeconomic conditions, an increasing burden of this disease and high mortality rate prevail in Bangladesh. Although several researches related to the epidemiology, HPV vaccination, and treatment modalities were conducted, researches on the mutation profiles of marker genes in cervical cancer in Bangladesh remain unexplored. Methods: In this study, five different genomic regions within the top three most frequently mutated genes (EGFR, KRAS and PIK3CA) in COSMIC database with a key role in the development of cervical cancers were selected to study the mutation frequency in Bangladeshi patients. In silico analysis was done in two steps: nucleotide sequence analysis and its corresponding amino acid analysis.Results: DNA from 46 cervical cancer tissue samples were extracted and amplified by PCR, using 1 set of primers designed for EGFR and 2 sets of primers designed for two different regions of both PIK3CA and KRAS gene. In total, 39 mutations were found in 26 patient samples. Eleven different mutations (23.91%), twenty-four different mutations (52.17%) and four mutations (8.7%) were found in amplified EGFR, PIK3CA and KRAS gene fragments, among which 1 (EGFR) was common in seven patient samples and 2 (PIKCA) were found in more than 1 patient. Our study shows that except for KRAS, the frequency of observed mutations in our patients is higher than those reported earlier in other parts of the world. Most of the exonic mutations were found only in the PIK3CA and EGFR genes.Conclusions: The study can be used as a basis to build a mutation database for cervical cancer in Bangladesh with the possibility of targetable oncogenic mutations. Further exploration needs to establish future diagnostics, personalized medicine decisions, and other pharmaceutical applications for specific cancer subtypes.

scholarly journals Mutational Profiles of Marker Genes of Cervical Carcinoma in Bangladeshi patients

2020 ◽  
Author(s):  
Shahana Sharmin ◽  
Fatima Tuj Zohura ◽  
Md. Sajedul Islam ◽  
Anika Shimonty ◽  
Md. Abdullah-Al-Kamran Khan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hpv Vaccination ◽  
Gynecologic Cancer ◽  
Treatment Modalities ◽  
Nucleotide Sequence Analysis ◽  
Marker Genes ◽  
Cancer Tissue ◽  
Cancer Type ◽  
Tissue Samples ◽  
Cancer Subtypes

Abstract Background: Cervical cancer is a gynecologic cancer type that develops in the cervix, accounting for 8% mortality of all female cancer patients. Infection with specific human papillomavirus (HPV) types is considered the most severe risk factor for cervical cancer. In the context of our socioeconomic conditions, an increasing burden of this disease and high mortality rate prevail in Bangladesh. Although several researches related to the epidemiology, HPV vaccination, and treatment modalities were conducted, researches on the mutation profiles of marker genes in cervical cancer in Bangladesh remain unexplored. Methods: In this study, five different genomic regions within the top three most frequently mutated genes (EGFR, KRAS and PIK3CA) in COSMIC database with a key role in the development of cervical cancers were selected to study the mutation frequency in Bangladeshi patients. In silico analysis was done in two steps: nucleotide sequence analysis and its corresponding amino acid analysis.Results: DNA from 46 cervical cancer tissue samples were extracted and amplified by PCR, using 1 set of primers designed for EGFR and 2 sets of primers designed for two different regions of both PIK3CA and KRAS gene. In total, 39 mutations were found in 28 patient samples. Eleven different mutations (23.91%), twenty-four different mutations (52.17%) and four mutations (8.7%) were found in amplified EGFR, PIK3CA and KRAS gene fragments, among which 1 (EGFR) was common in seven patient samples and 2 (PIKCA) were found in more than 1 patient. Our study shows that except for KRAS, the frequency of observed mutations in our patients is higher than those reported earlier in other parts of the world. Most of the exonic mutations were found only in the PIK3CA and EGFR genes.Conclusions: The study can be used as a basis to build a mutation database for cervical cancer in Bangladesh with the possibility of targetable oncogenic mutations. Further exploration needs to establish future diagnostics, personalized medicine decisions, and other pharmaceutical applications for specific cancer subtypes.

scholarly journals Mutational profiles of marker genes of cervical carcinoma in Bangladeshi patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shahana Sharmin ◽  
Fatima Tuj Zohura ◽  
Md. Sajedul Islam ◽  
Anika Shimonty ◽  
Md. Abdullah-Al-Kamran Khan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hpv Vaccination ◽  
Gynecologic Cancer ◽  
Treatment Modalities ◽  
Nucleotide Sequence Analysis ◽  
Marker Genes ◽  
Cancer Tissue ◽  
Cancer Type ◽  
Tissue Samples ◽  
Cancer Subtypes

Abstract Background Cervical cancer is a gynecologic cancer type that develops in the cervix, accounting for 8% mortality of all female cancer patients. Infection with specific human papillomavirus (HPV) types is considered the most severe risk factor for cervical cancer. In the context of our socioeconomic conditions, an increasing burden of this disease and high mortality rate prevail in Bangladesh. Although several researches related to the epidemiology, HPV vaccination, and treatment modalities were conducted, researches on the mutation profiles of marker genes in cervical cancer in Bangladesh remain unexplored. Methods In this study, five different genomic regions within the top three most frequently mutated genes (EGFR, KRAS and PIK3CA) in COSMIC database with a key role in the development of cervical cancers were selected to study the mutation frequency in Bangladeshi patients. In silico analysis was done in two steps: nucleotide sequence analysis and its corresponding amino acid analysis. Results DNA from 46 cervical cancer tissue samples were extracted and amplified by PCR, using 1 set of primers designed for EGFR and 2 sets of primers designed for two different regions of both PIK3CA and KRAS gene. In total, 39 mutations were found in 26 patient samples. Eleven different mutations (23.91%), twenty-four different mutations (52.17%) and four mutations (8.7%) were found in amplified EGFR, PIK3CA and KRAS gene fragments, respectively; among which 1 (EGFR) was common in seven patient samples and 2 (PIKCA) were found in more than 1 patient. Our study shows that except for KRAS, the frequency of observed mutations in our patients is higher than those reported earlier in other parts of the world. Most of the exonic mutations were found only in the PIK3CA and EGFR genes. Conclusions The study can be used as a basis to build a mutation database for cervical cancer in Bangladesh with the possibility of targetable oncogenic mutations. Further explorations are needed to establish future diagnostics, personalized medicine decisions, and other pharmaceutical applications for specific cancer subtypes.

scholarly journals Diagonistic Value of ARFI in Breast Lesions

2021 ◽  
pp. 24-30
Author(s):  
J. Jayapriya ◽  
S. Arul Murugan
Keyword(s):  
Breast Cancer ◽  
Acoustic Radiation ◽  
Radiation Force ◽  
Acoustic Radiation Force Impulse ◽  
Stiffness Index ◽  
Cancer Tissue ◽  
Cancer Type ◽  
Tissue Samples ◽  
Biopsy Confirmation ◽  
Index Value

Breast cancer became the most prominent cancer type in women worldwide. Its prevalence increased in recent years due to changes in life style and relapse among the patients seemed to be higher. Acoustic radiation force impulse (ARFI) imaging in based on the principle of the ultrasonic elasticity and the elestography accurately predict and measure the changes in breast cancer tissue compared to the normal tissue. It is a technical alternative to the palpation and able to measure lesser than 10 mm size. In contrast to biopsy, where the reduced deformability would occur and lead to biopsy failing. In fibroadenoma, due to its complications, many false positives could be detected and the ARFI elastography serve as an effective alternative method for breast cancer confirmation. The tissue stiffness index value is used to differentiate the benign and malignant tissue samples. ARFI further, use B- mode elasticity and help in recommending the biopsy confirmation.

scholarly journals Immunotherapy Advances for Epithelial Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3733
Author(s):  
Erin G. Hartnett ◽  
Julia Knight ◽  
Mackenzy Radolec ◽  
Ronald J. Buckanovich ◽  
Robert P. Edwards ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Gynecologic Cancer ◽  
Single Agent ◽  
Standard Of Care ◽  
Treatment Modalities ◽  
Cancer Type ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Therapies

New treatment modalities are needed in order to improve the prognosis of women diagnosed with epithelial ovarian cancer (EOC), the most aggressive gynecologic cancer type. Most ovarian tumors are infiltrated by immune effector cells, providing the rationale for targeted approaches that boost the existing or trigger new anti-tumor immune mechanisms. The field of immuno-oncology has experienced remarkable progress in recent years, although the results seen with single agent immunotherapies in several categories of solid tumors have yet to extend to ovarian cancer. The challenge remains to determine what treatment combinations are most suitable for this disease and which patients are likely to benefit and to identify how immunotherapy should be incorporated into EOC standard of care. We review here some of the most promising immune therapies for EOC and focus on those currently tested in clinical trials.

Genetic diversity of HPV in tissues of tumors of the reproductive organs in women.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17001-e17001
Author(s):  
Galina Andreevna Nerodo ◽  
Oleg Ivanovich Kit ◽  
Tatiana Zykova ◽  
Victoria A. Ivanova ◽  
Vera P. Nikitina ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Cervical Cancer ◽  
Vulvar Cancer ◽  
Uterine Cancer ◽  
Reproductive Organs ◽  
Cancer Tissue ◽  
Hpv 16 ◽  
Tissue Samples ◽  
Tumor Tissues ◽  
Cancer Tissues

e17001 Background: The purpose of the study was to determine the rate of various HPV genotypes detection in tissues of tumors of the female reproductive organs. Methods: FFPE and frozen tissue samples of cervical cancer (n=126), vulvar cancer (n=113) and uterine cancer (n=29) were studied. DNAs of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 were determined by the Real-Time PCR. Results: HPV DNAs were found in 94.4% of samples of cervical cancer tissue, 65.5% - uterine cancer tissue and 28.3% - vulvar cancer tissue. HPV 16 and 18 were the most frequent (78.8%). HPV 16 in cervical cancer was detected in 60.9%, vulvar cancer – 59.0% and uterine cancer – 54.5%. On the contrary, HPV 18 was more frequent in uterine cancer (40.9%) and less frequent in cervical cancer (18.4%) and vulvar cancer (2.7%). Besides HPV 16 and 18, genotypes 31, 33, 35, 39, 45, 51, 52, 56 and 59 were found in tumor tissues as well (21.2% in total). HPV 35, 52 and 56 were the most frequently detected. Cervical cancer tissues showed the greatest genetic diversity of HPV and uterine cancer tissues – the lesser one (HPV 35 only, besides HPV 16 and 18). Combination of several HPV types was also more frequent in cervical cancer (37.0% of positive samples); in vulvar cancer – 18.8% and in uterine cancer – 15.8%. Conclusions: The results confirm HPV significance in carcinogenesis of cervical cancer, vulvar cancer and probably uterine cancer and show genetic diversity of HPV in different localizations of tumors of the female reproductive system.

scholarly journals Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Nicole J. Chew ◽  
Terry C. C. Lim Kam Sian ◽  
Elizabeth V. Nguyen ◽  
Sung-Young Shin ◽  
Jessica Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Therapeutic Target ◽  
Breast Cancer Subtype ◽  
Breast Cancer Subtypes ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Luminal A ◽  
Tissue Samples ◽  
Cancer Subtypes ◽  
Luminal B

Abstract Background Particular breast cancer subtypes pose a clinical challenge due to limited targeted therapeutic options and/or poor responses to the existing targeted therapies. While cell lines provide useful pre-clinical models, patient-derived xenografts (PDX) and organoids (PDO) provide significant advantages, including maintenance of genetic and phenotypic heterogeneity, 3D architecture and for PDX, tumor–stroma interactions. In this study, we applied an integrated multi-omic approach across panels of breast cancer PDXs and PDOs in order to identify candidate therapeutic targets, with a major focus on specific FGFRs. Methods MS-based phosphoproteomics, RNAseq, WES and Western blotting were used to characterize aberrantly activated protein kinases and effects of specific FGFR inhibitors. PDX and PDO were treated with the selective tyrosine kinase inhibitors AZD4547 (FGFR1-3) and BLU9931 (FGFR4). FGFR4 expression in cancer tissue samples and PDOs was assessed by immunohistochemistry. METABRIC and TCGA datasets were interrogated to identify specific FGFR alterations and their association with breast cancer subtype and patient survival. Results Phosphoproteomic profiling across 18 triple-negative breast cancers (TNBC) and 1 luminal B PDX revealed considerable heterogeneity in kinase activation, but 1/3 of PDX exhibited enhanced phosphorylation of FGFR1, FGFR2 or FGFR4. One TNBC PDX with high FGFR2 activation was exquisitely sensitive to AZD4547. Integrated ‘omic analysis revealed a novel FGFR2-SKI fusion that comprised the majority of FGFR2 joined to the C-terminal region of SKI containing the coiled-coil domains. High FGFR4 phosphorylation characterized a luminal B PDX model and treatment with BLU9931 significantly decreased tumor growth. Phosphoproteomic and transcriptomic analyses confirmed on-target action of the two anti-FGFR drugs and also revealed novel effects on the spliceosome, metabolism and extracellular matrix (AZD4547) and RIG-I-like and NOD-like receptor signaling (BLU9931). Interrogation of public datasets revealed FGFR2 amplification, fusion or mutation in TNBC and other breast cancer subtypes, while FGFR4 overexpression and amplification occurred in all breast cancer subtypes and were associated with poor prognosis. Characterization of a PDO panel identified a luminal A PDO with high FGFR4 expression that was sensitive to BLU9931 treatment, further highlighting FGFR4 as a potential therapeutic target. Conclusions This work highlights how patient-derived models of human breast cancer provide powerful platforms for therapeutic target identification and analysis of drug action, and also the potential of specific FGFRs, including FGFR4, as targets for precision treatment.

scholarly journals The E545 Mutation of PIK3CA in Cervical Cancer Promotes the Survival by Several Different Pathways

2021 ◽  
Author(s):  
Yan Chen ◽  
Ma-Chi Yuan ◽  
Jia-Zhen Shi ◽  
Xia Zhao ◽  
Nan He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Differential Expression ◽  
Bioinformatics Analysis ◽  
Cancer Tissue ◽  
Ppi Network ◽  
Tissue Samples ◽  
Cervical Cancer Tissue ◽  
Differential Expression Genes ◽  
High Degree

Abstract Backgroud: The E545 mutation of PIK3CA in Cervical cancer is frequently happened. But the role of E545 mutation of PIK3CA in Cervical cancer is not clear.Methods: In this study, we analysised the molecular signatures of E545 mutation Cervical cancer by bioinformatics methods.Results: We collected transcriptome sequencing results of 227 no mutation cervical cancer tissue samples and 36 mutation cervical cancer tissue samples, then analyzed the data combining bioinformatics methods. A total of 5 differential expression miRNAs were obtained, including 3 up-regulated miRNAs, 1 down-rugulated miRNA. A total of 174 differential expression genes were obtained, including 132 up-regulated genes, 40 down-rugulated genes. GO analysis suggested that the up-regulated DEGs were mainly enriched in transcription factor activity, leukotriene signaling pathway and so on. Besides, we constructed a PPI network with DEGs to screen the top hub genes with a relatively high degree of connectivity. Among them CAV1, KRT20, FOS, had a degree of connectivity larger than 5 and functioned as hub module genes to promote the survival of E545 mutation cervical cancer. We also identified different miRNA-DEG axis, including hsa-mir-449a-AXL, hsa-mir-508-CGA, COL15A1, NNMT, hsa-mir-552-CHST6, NWD1. These axis regulated the survival of E545 mutation cervical cancer togetherly. Conclusions: In conclusion, this study identified DEGs and screened the key genes and pathways closely related to E545 mutation in Cervical cancer by bioinformatics analysis, These results might hold promise for finding potential therapeutic targets of cervical cancer harboring E545 mutation of PI3KCA.

scholarly journals A high yield gold nanoparticle-based DNA isolation method for human papillomaviruses genotypes from cervical cancer tissue samples

2019 ◽  
Author(s):  
Noorossadat Seyyedi ◽  
Fatemeh Farjadian ◽  
Ali Farhadi ◽  
Gholamreza Rafiei Dehbidi ◽  
Reza Ranjbaran ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Sequences ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
High Yield ◽  
Cancer Tissue ◽  
Purification Method ◽  
Tissue Samples ◽  
Hpv Dna ◽  
Cervical Cancer Tissue

Gold nanoparticles (AuNPs) are commonly used in biosensors of various kinds. The purification of DNA from cancer tissues is an important step in diagnostic and therapeutic development, but current methods are not optimal. Many cervical cancer patients are also susceptible to high-risk human papillomavirus (HR-HPV) infection. Accurate viral diagnosis has so far relied on the extraction of adequate amounts of DNA from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Since the sensitivity and specificity of commercially available purification kits are not optimal, we designed a DNA purification method based on AuNPs to purify sufficient amounts of HR-HPV DNA from cervical cancer tissue samples. AuNPs were coated with a series of oligonucleotide probes to hybridize to specific DNA sequences of HR-HPV genotypes. With this method, we recovered 733 out of 800 copies of type-specific HPV DNA with complete specificity, compared to 36 copies with a standard commercial kit (Qiagen FFPE).

scholarly journals HOTAIR contributes to cell proliferation and metastasis of cervical cancer via targetting miR-23b/MAPK1 axis

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Qin Li ◽  
Yanhong Feng ◽  
Xu Chao ◽  
Shuai Shi ◽  
Man Liang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Downstream Target ◽  
Cervical Cancer Cells

The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) has been found to be overexpressed in many human malignancies and involved in tumor progression and metastasis. Although the downstream target through which HOTAIR modulates tumor metastasis is not well-known, evidence suggests that miR-23b might be involved in this event. In the present study, the expressions of HOTAIR and miR-23b were detected by real-time PCR in 33 paired cervical cancer tissue samples and cervical cell lines. The effects of HOTAIR on the expressions of miR-23b and mitogen-activated protein kinase 1 (MAPK1) were studied by overexpression and RNAi approaches. We found that HOTAIR expression was significantly increased in cervical cancer cells and tissues. In contrast, the expression of miR-23b was obviously decreased. We further demonstrated that HOTAIR knockdown promoted apoptosis and inhibited cell proliferation and invasion in vitro and in vivo. Moreover, our data indicated that HOTAIR may competitively bind miR-23b and modulate the expression of MAPK1 indirectly in cervical cancer cells. Taken together, our study has identified a novel pathway through which HOTAIR exerts its oncogenic role, and provided a molecular basis for potential applications of HOTAIR in the prognosis and treatment of cervical cancer.

Quantitative Analysis of Heparanase Gene Expression in Normal Cervical, Cervical Intraepithelial Neoplastic, and Cervical Carcinoma Tissues

2009 ◽  
Vol 19 (9) ◽  
pp. 1614-1619 ◽  
Author(s):  
Eugene Varchalama ◽  
Alexander Rodolakis ◽  
Areti Strati ◽  
Theocharis Papageorgiou ◽  
Christos Valavanis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Heparan Sulfate ◽  
Mrna Expression ◽  
Tumor Size ◽  
Invasive Cervical Cancer ◽  
Cancer Tissue ◽  
Low Grade ◽  
Tissue Samples ◽  
Cervical Cancer Tissue

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans, the major proteoglycans in the extracellular matrix and cell surfaces. Traditionally, heparanase activity was implicated in cellular invasion associated with angiogenesis, inflammation, and cancer metastasis. More recently, heparanase up-regulation was documented in an increasing number of primary human tumors. Ιn this study, we sought to investigate the expression of heparanase messenger RNA (mRNA) in normal cervical tissue and intraepithelial cervical lesion and its clinicopathologic importance in invasive cervical cancer. Gene expression of heparanase was assessed by quantitative real-time reverse transcriptase polymerase chain reaction in 28 normal cervical, 26 intraepithelial neoplastic, and 48 cervical cancer tissue samples. Heparanase mRNA expression was different between the 3 groups and lower in normal cervical specimens in relationship with intraepithelial cervical lesions and invasive cervical cancer tissue samples (P = 0.048). Gradually increasing expression of heparanase was evident as the cells progressed from low-grade to high-grade squamous intraepithelial lesions (P = 0.002). In invasive cervical cancer cases, there was a direct correlation between heparanase expression and tumor size (P = 0.002). In cases treated with radical hysterectomy and pelvic lymphadenectomy, the heparanase mRNA expression was significantly higher in tumors exhibiting lymph vascular space invasion (P = 0.044) and in cases with big tumor size (P = 0.005). In our study, we did not find any significant correlation between disease-free and overall survival rates and expression of heparanase (P = 0.396 and P = 0.712, respectively). The results of this study suggest that the gene expression of heparanase in cervical cancer enhances growth, invasion, and angiogenesis of the tumor and may have therapeutic applications.

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