scholarly journals Exploration of Binding Interaction of Steroidal Drugs with HMG-CoA Reductase for the Treatment of Breast Cancer Patients who suffer with Cardiovascular Problems: In-silico Studies

2020 ◽  
Vol 5 (1) ◽  
pp. 27-33
Author(s):  
Varish Ahmad
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Cholesterol Synthesis ◽  
Breast Cancer Patients ◽  
Binding Interaction ◽  
Hmg Coa Reductase ◽  
Study Results ◽  
In Silico Studies ◽  
Coa Reductase

Introduction: HMG-CoA reductase is widely used as a significant target to screen cardiovascular therapeutics molecules because of its involvement in cholesterol synthesis and cell proliferation. Steroidal drugs like anastrozole, exemestane, letrozole have been tested as potential inhibitors of cancer mediated aromatase enzyme and these could be inhibited to HMG-CoA reductase so that the link with cholesterol synthesis and cell proliferation can be utilized to control cancers in. Objective: To test the binding affinity and binding patterns using computational methods of these drugs and established them as a HMG-CoA reductase inhibitor due to the involvement of this enzyme with cholesterol synthesis and cell proliferation can be utilized to control the cancers. Materials and methods: Freely available docking tools like AutoDock and web resources like DrugBank and PDB were used to extract data and conduct the study. Results: The binding interaction of exemestane has shown significant docking interactions which are followed by anastrozole and letrozole. Exemestane has shown binding energy -8.74 kcal/mol, hydrogen bond length: 1.97513 Å, and interacting amino acid was analyzed as A: ASN658:HD21-: UNK1: O6. The positive control statin was used in this study has shown significant binding interaction but it was less than tested exemestane.Conclusion: Thus, exemestane can potentially inhibit to HMG-CoA reductase enzyme even stronger than the clinically tested drug statin and would be a good choice for cancer patients. Thus, in vitro laboratory experimentation and in vivo research are necessary to put forward therapeutic repositioning of these drugs so they could be established as a broad spectrum potential anticancer drugs including breast cancer especially for the patient with cardiovascular complications.  

scholarly journals Tumor-specific expression of HMG-CoA reductase in a population-based cohort of breast cancer patients

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Emma Gustbée ◽  
Helga Tryggvadottir ◽  
Andrea Markkula ◽  
Maria Simonsson ◽  
Björn Nodin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Specific Expression ◽  
Hmg Coa Reductase ◽  
Coa Reductase

scholarly journals USP1 Regulates TAZ Protein Stability Through Ubiquitin Modifications in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3090
Author(s):  
Ashley Mussell ◽  
He Shen ◽  
Yanmin Chen ◽  
Michalis Mastri ◽  
Kevin H. Eng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Protein Stability ◽  
Cancer Patients ◽  
Effector Proteins ◽  
Therapeutic Interventions ◽  
Hippo Signaling ◽  
Strong Positive Correlation ◽  
Breast Cancer Patients ◽  
Loss Of Function

The Hippo signaling pathway is an evolutionarily conserved pathway that was initially discovered in Drosophila melanogaster and was later found to have mammalian orthologues. The key effector proteins in this pathway, YAP/TAZ, are often dysregulated in cancer, leading to a high degree of cell proliferation, migration, metastasis and cancer stem cell populations. Due to these malignant phenotypes it is important to understand the regulation of YAP/TAZ at the protein level. Using an siRNA library screen of deubiquitinating enzymes (DUBs), we identified ubiquitin specific peptidase 1 (USP1) as a novel TAZ (WWTR1) regulator. We demonstrated that USP1 interacts with TAZ and increases TAZ protein stability. Conversely, loss of function of USP1 reduces TAZ protein levels through increased poly-ubiquitination, causing a decrease in cell proliferation and migration of breast cancer cells. Moreover, we showed a strong positive correlation between USP1 and TAZ in breast cancer patients. Our findings facilitate the attainment of better understanding of the crosstalk between these pathways and may lead to potential therapeutic interventions for breast cancer patients.

Prognostic value of vascular density and cell proliferation in breast cancer patients

1999 ◽  
Vol 195 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Olli Tynninen ◽  
Kristina von Boguslawski ◽  
Hannu J. Aronen ◽  
Timo Paavonen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Vascular Density ◽  
Breast Cancer Patients

scholarly journals Metformin Efficacy on Proliferation Indices of Tumoral Cells in Non-Diabetic Patients with Invasive Breast Cancer Referring to the Cancer Institute of Iran

2021 ◽  
Author(s):  
Sanambar Sadighi ◽  
Maasoumeh Saberian ◽  
Bita Behrouzi ◽  
Massoome Najafi ◽  
Issa Jahanzad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Intervention Group ◽  
P Value ◽  
Diabetic Patients ◽  
Tumor Cell Proliferation ◽  
Breast Cancer Patients ◽  
Metformin Therapy

Background: Because of the decreasing effect of metformin on insulin resistance, it has been suggested as an anti-obesity and anti-cancer drug. So, we aimed to study the effect of metformin therapy on tumor cell proliferation in non-diabetic breast cancer patients. Methods: We conducted a prospective clinical trial and studied the effect of metformin therapy on the level of Ki67 as a measure of tumor cell proliferation. Our primary endpoint was to evaluate the changes in Ki67. The intervention group consisted of 25 non-diabetic breast cancer patients with no indication for neoadjuvant chemo- therapy. They were followed up from the time of biopsy to operation. Metformin (1500 mg/day) was prescribed in the intervention group from the date of diagnosis until the surgery (2.8 weeks). Controls were 20 early breast cancer patients who had been followed up with no prescription from biopsy until operation. Results: We could not find any statistically significant difference between the two groups regarding baseline clinical or tumor characteristics such as age, stage, grade, estrogen receptor, HER2 status or time, and type of surgery. However, the immuno- histochemistry (IHS) study showed a decrease in median Ki67 from 35.14 to 29.6 in the intervention group (P-value= 0.02). While an increase from 24.5 to 30.6 was detected in the control group (P-value= 0.02). Both of these changes were statistically significant. Although mild gastrointestinal symptoms were seen in approximately 50% of cases, generally, patients tolerated metformin well. There was a correlation between the score of HOMA, a metabolic factor, and the changes in KI67. Conclusion: Metformin prescription in a short period of time between biopsy and definitive surgery leads to the inhibition of breast cancer cell growth. We found a relationship between metformin anti-proliferative effect and glucose and insulin metabolism.

scholarly journals Spectrum of breast cancer patients: twin institutional study

2017 ◽  
Vol 4 (9) ◽  
pp. 3077 ◽  
Author(s):  
Prabhat B. Nichkaode ◽  
Aditya Parakh
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Urban Population ◽  
Disease Stage ◽  
Rural India ◽  
Breast Cancer Patients ◽  
Female Population ◽  
Receptor Status ◽  
Common Cancer ◽  
Study Results

Background: Breast cancer is emerging as one of the most common cancer occurring in urban female population of India. It has become the second most common cancer in rural India, after cancer of uterine cervix. One must understand the diversity of presentation of breast cancer patients in the rural and urban population. Author is a surgeon working in a hospital which caters health care to both, rural as well as urban population. The present study is meant to review the data of various types of presentation, of cancer breast in two Institutes in different states. We also would like to compare our data with a few major cancer centers in metropolitan cities. The aim of the study was to present a data of patients with breast cancer at two institutes.Methods: This is a retrospective observational study carried out at two different medical teaching Institutes, CCM Medical College, Kachandur, Durg, Chhattisgarh and other at NKP Salve Institute of Medical Sciences Nagpur, Maharashtra. Study was carried out from 2009 till 2016 and total of 167 patients were included in the study. Data like age, menstrual status, size of lump, stage of disease, grade of disease (Bloom Richardson Elliston Index) and ER, PR, HER/neu receptor status of tumor, presence or absence of metastasis, and follow up records related to outcome, are presented in this study. Results: Out of 167 patients included in the study, two patients were males, and were excluded from our study. It becomes a study of 165 patients. Average age of patients at presentation was between 35 to 65 years. Majority of patients belong to stage III a (bulky operable disease) or III b, (locally advanced breast cancer) Stage II, and stage IV -metastatic disease. No patient of stage I disease reported in the present study. Most common pathological type was infiltrating ductal carcinoma.Conclusions: Breast cancer has emerged as the commonest cancer in urban India, with second most common cancer in rural India. Majority of our patients present with advanced disease stage with numerous poor prognostic factors such as young age, larger tumor size, lymph node metastasis, high pathological grade and poor hormone receptor status. These factors are a reflection of poor health awareness for breast cancer, general indifference towards women’s health, poor financial resources, unavailability of multimodality treatment facilities.

scholarly journals Targeted Inhibition of Fibroblast Growth Factor Receptor 1-GLI Through AZD4547 and GANT61 Modulates Breast Cancer Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Syeda Kiran Riaz ◽  
Walizeb Khan ◽  
Fen Wang ◽  
Tanwir Khaliq ◽  
Amber Malik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Breast Cancer Patients ◽  
Shh Pathway

The underlying mechanism of fibroblast growth factor receptor 1 (FGFR1) mediated carcinogenesis is still not fully understood. For instance, FGFR1 upregulation leads to endocrine therapy resistance in breast cancer patients. The current study aimed to identify FGFR1-linked genes to devise improved therapeutic strategies. RNA-seq and microarray expression data of 1,425 breast cancer patients from two independent cohorts were downloaded for the analysis. Gene Set Enrichment Analysis (GSEA) was performed to identify differentially expressed pathways associated with FGFR1 expression. Validation was done using 150 fresh tumor biopsy samples of breast cancer patients. The clinical relevance of mRNA and protein expression of FGFR1 and its associated genes were also evaluated in mouse embryonic fibroblasts (MEFs) and breast cancer cell line (MDA-MB-231). Furthermore, MDA-MB-231 cell line was treated with AZD4547 and GANT61 to identify the probable role of FGFR1 and its associated genes on cells motility and invasion. According to GSEA results, SHH pathway genes were significantly upregulated in FGFR1 patients in both discovery cohorts of breast cancer. Statistical analyses using both discovery cohorts and 150 fresh biopsy samples revealed strong association of FGFR1 and GLI1, a member of SHH pathway. The increase in the expression of these molecules was associated with poor prognosis, lymph node involvement, late stage, and metastasis. Combined exposures to AZD4547 (FGFR1 inhibitor) and GANT61 (GLI1 inhibitor) significantly reduced cell proliferation, cell motility, and invasion, suggesting molecular crosstalk in breast cancer progression and metastasis. A strong positive feedback mechanism between FGFR1–GLI1 axis was observed, which significantly increased cell proliferation and metastasis. Targeting FGFR1–GLI1 simultaneously will significantly improve the prognosis of breast cancer in patients.

scholarly journals Update Breast Cancer 2019 Part 3 – Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel

2019 ◽  
Vol 79 (05) ◽  
pp. 470-482 ◽  
Author(s):  
Hans-Christian Kolberg ◽  
Andreas Schneeweiss ◽  
Tanja N. Fehm ◽  
Achim Wöckel ◽  
Jens Huober ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Checkpoint Inhibitors ◽  
Local Therapy ◽  
Breast Cancer Patients ◽  
Long Term Effects ◽  
Cancer Review ◽  
Therapeutic Decisions ◽  
Study Results

AbstractThe treatment of breast cancer patients in a curative situation is special in many ways. The local therapy with surgery and radiation therapy is a central aspect of the treatment. The complete elimination of tumour cells at the site of the primary disease must be ensured while simultaneously striving to keep the long-term effects as minor as possible. There is still focus on the continued reduction of the invasiveness of local therapy. With regard to systemic therapy, chemotherapies with taxanes, anthracyclines and, in some cases, platinum-based chemotherapies have become established in the past couple of decades. The context for use is being continually further defined. Likewise, there are questions in the case of antihormonal therapy which also still need to be further defined following the introduction of aromatase inhibitors, such as the length of therapy or ovarian suppression in premenopausal patients. Finally, personalisation of the treatment of early breast cancer patients is also being increasingly used. Prognostic tests could potentially support therapeutic decisions. It must also be considered how the possible use of new therapies, such as checkpoint inhibitors and CDK4/6 inhibitors could look in practice once study results in this regard are available. This overview addresses the backgrounds on the current votes taken by the international St. Gallen panel of experts in Vienna in 2019 for current questions in the treatment of breast cancer patients in a curative situation.

Natural HPV58 E6 and E7 Variants Detected in Thai Breast Cancer Patients Cooperate to Induce Loss of p53 and Increase Cell Growth

2021 ◽  
Vol 104 (6) ◽  
pp. 902-910
Keyword(s):  
Breast Cancer ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Human Papillomavirus ◽  
Cell Growth ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Breast And Cervical Cancer ◽  
Cervical Cancer Cells ◽  
Hpv Oncoproteins

Background: Detection of human papillomavirus (HPV) in breast cancer patients has suggested a possible contributing role of the virus in cancer progression in this population. Objective: To investigate the presence of HPVs in Thai breast cancer patients and examine the potential activities of HPVs identified in both breast and cervical cancer cells. Materials and Methods: Fifty-five breast cancer tissues from Thai patients were subjected to HPV detection using PCR-EIA and DNA sequencing. Detection of HPV E6 proteins in sample tissues was examined by fluorescence immunohistochemistry. Cervical and two types of breast cancer cell lines expressing HPV oncogenes were established. The separate and combination of HPV oncoproteins activity for p53 degradation and specific gene regulation were investigated using western blot analysis and qPCR. Cell proliferation was assessed by MTT assay. Results: Twenty-two percent (10/45) of invasive breast cancers were found infected with various high-risk HPV types, with HPV58 E6D4G/E7T20IG63S being the most common variant. The percentage of HPV58 alone was approximately 50% (5/10) of all HPV positive samples. Similar potential oncogenic activity for this variant was observed in breast and cervical cancer cells. A separate analysis of single or combination of 58E6 (prototype or E6D4G) with 58E7 (prototype or E7T20IG63S) demonstrated that co-expression of 58E7T20IG63S with 58E6 (either prototype or E6D4G) significantly promoted cell proliferation compared to prototype 58E6/E7. Enhanced proliferation was mediated through elevated p53 degradation and reduced p21 expression. While p53 degradation activity was greatly diminished from E6 with D4G mutation, co-expression with E7T20IG63S cooperated to enhance degradation of p53 and promoted cell growth. Conclusion: HPV58 E6D4G/E7T20IG63S was the most HPV oncogene variant detected in Thai breast cancer patients. This variant exhibited in promoting cell proliferation and p53 degradation. A cooperative effect was observed in combination of HPV oncoproteins. Keywords: Human papillomavirus type 58; oncogene variant; breast cancer; Thai patients; altered cell growth

Sign in / Sign up

Export Citation Format

Share Document