scholarly journals Successful Treatment by Mistletoe Viscum Album Extract of a Patient with Recurrent Triple Negative Breast Cancer who declined Chemotherapy

2021 ◽  
Vol 11 (03) ◽  
Author(s):  
Hancock Mark J ◽  
Parameswara Vinay K
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Complementary Therapy ◽  
Viscum Album ◽  
Full Spectrum ◽  
Breast Masses ◽  
High Incidence ◽  
Aggressive Breast Cancer

Triple negative breast cancer (TNBC) is an aggressive breast cancer with a high incidence of recurrence and poor prognosis even with the full spectrum of standard oncology treatments. Ever since its introduction about 100 years ago for cancer therapy, mistletoe viscum album extract (VAE) has been widely used in Europe as a popular complementary therapy for many cancers. We present a case of a patient diagnosed with stage 3c (T3N3bM0(i+)) TNBC who declined chemotherapy after a recurrence 2 years later. The patient received subcutaneous, intratumoral as well as intravenous VAE therapy for her recurrence. Her breast masses and lymph node sizes dramatically decreased under ultrasound examination within 2 months. After nearly three years since the tumor resolution, she is currently being managed on weekly subcutaneous VAE as well as intravenous VAE once in 6-8 weeks. She has excellent quality of life, no sign of tumor recurrence or other adverse side effects from her treatments. Though we believe the best outcomes in oncology are by integrating complementary and conventional care together, this case shows that VAE can have standalone effectiveness at least in some cases. Use of VAE to augment conventional treatments should be considered to bolster breast cancer care.

Machine Learning-based Virtual Screening Strategy Reveals Some Natural Compounds As Potential PAK4 Inhibitors In Triple Negative Breast Cancer

2020 ◽  
Vol 18 ◽  
Author(s):  
Opeyemi Iwaloye ◽  
Olusola Olalekan Elekofehinti ◽  
Babatomiwa Kikiowo ◽  
Emmanuel Ayo Oluwarotimi ◽  
Toyin Mary Fadipe
Keyword(s):  
Breast Cancer ◽  
Virtual Screening ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Binding Free Energy ◽  
Natural Compounds ◽  
Energy Calculation ◽  
Reference Drug ◽  
Predictive Quality

Background: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many cancers, especially in the progression of Triple Negative Breast Cancer (TNBC). The present study was aimed at designing some potential drug candidates as PAK4 inhibitors for breast cancer therapy. Objective: This study aimed to finding novel inhibitors of PAK4 from natural compounds using computational approach. Methods: An e-pharmacophore model was developed from docked PAK4-coligand complex and used to screen over a thousand natural compounds downloaded from BIOFACQUIM and NPASS databases to match a minimum of 5 sites for selected (ADDDHRR) hypothesis. The robustness of the virtual screening method was accessed by well-established methods including EF, ROC, BEDROC, AUAC, and the RIE. Compounds with fitness score greater than one were filtered by applying molecular docking (HTVS, SP, XP and Induced fit docking) and ADME prediction. Using Machine learningbased approach QSAR model was generated using Automated QSAR. The computed top model kpls_des_17 (R2= 0.8028, RMSE = 0.4884 and Q2 = 0.7661) was used to predict the pIC50 of the lead compounds. Internal and external validations were accessed to determine the predictive quality of the model. Finally the binding free energy calculation was computed. Results: The robustness/predictive quality of the models were affirmed. The hits had better binding affinity than the reference drug and interacted with key amino acids for PAK4 inhibition. Overall, the present analysis yielded three potential inhibitors that are predicted to bind with PAK4 better than reference drug tamoxifen. The three potent novel inhibitors vitexin, emodin and ziganein recorded IFD score of -621.97 kcal/mol, -616.31 kcal/mol and -614.95 kcal/mol, respectively while showing moderation for ADME properties and inhibition constant. Conclusion: It is expected that the findings reported in this study may provide insight for designing effective and less toxic PAK4 inhibitors for triple negative breast cancer.

WNT/β–catenin pathway activation correlates with the increase of tumor-associated macrophages in triple negative breast cancer (TNBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12564-e12564
Author(s):  
Eleonora Timperi ◽  
Mengliang Ye ◽  
Thierry Dubois ◽  
Didier Meseure ◽  
Anne Vincent- Salomon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Immune Checkpoint Blockade ◽  
Tumor Associated Macrophages ◽  
T Cell Exclusion

e12564 Background: Triple negative breast cancer (TNBC) occurs in about 20% of all breast carcinomas. Because only a fraction of TNBCs responding to immune checkpoint blockade show a pre-existing T cell-inflamed tumor microenvironment (TME), it is critical to understand the mechanisms of T-cell exclusion. Tumor-cell intrinsic activation of the WNT/β–catenin pathway, overexpressed in 30% of human breast cancers, is linked to a T-cell excluded TME. In β–cateninhigh TNBC, however, the quality of the myeloid compartment has not been evaluated. Methods: A total of seventy-five, early-stage, untreated, TNBC patients was assessed (patient cohorts approved by IRB). β–catenin expression was detected by IHC and scored as high, intermediate, and low. The presence of T cells, tumor-associated macrophages (TAMs) and LAMP-expressing dendritic cells (LAMP+ DCs) was assessed by IHC using aCD3, aCD68, aCD163, and aLAMP, respectively. Public TNBC datasets TCGA (N = 157) and METABRIC (N = 319) were interrogated for correlations between β–catenin- and immune-associated genes. Results: Three patient groups (N = 25/group) were identified according to the negative, medium and high intracellular expression of β–catenin. As opposed to β–cateninlow TNBC, the β–cateninhigh group displayed significantly lower CD3+ T cells (median 5% ±7.37 SD vs median 30% ± 18.28 SD, p < 0.0001) and LAMP+ DCs (median 1% ± 2.515 SD vs median 10% ± 7.038 SD, p < 0.0001). The β–cateninlow group was enriched in lymphocyte-predominant TNBC. For the first time, we show that the immune-suppressive, CD68+CD163+ TAMs were strongly accumulated in the β–cateninhigh group (median 20% ± 12.20 SD vs median 5% ± 6.831 SD, p < 0.0001). The interrogation of the public TNBC datasets TCGA and METABRIC confirmed that – after patient statification according to the expression level of a WNT/β–catenin gene-signature (i.e. MMP7, SFRP1, WNT10A, WNT16, WNT9B) – multiple TAM-associated genes – identified by our group in a single-cell RNAseq dataset – were strongly upregulated in WNT/β–cateninhigh signature, highlighting the role of the WNT/β–catenin signaling pathway not only in T-cell exclusion but also in selective TAM accumulation. Conclusions: Immune-suppressive TAMs are accumulated in β–cateninhigh, T-cell excluded TNBCs emphasizing the importance of tumor-intrinsic factors in shaping the quality of the immune infiltrate.

scholarly journals Elicitation of Health-Related Quality-of-Life Concepts Associated With Triple-Negative Breast Cancer

2015 ◽  
Vol 18 (3) ◽  
pp. A212
Author(s):  
S Holmstrom ◽  
NA Hawken ◽  
S Dam ◽  
S Aballea ◽  
N Oestreicher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related

scholarly journals Non-Coding RNAs Associated With Radioresistance in Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Alberto Aranza-Martínez ◽  
Julio Sánchez-Pérez ◽  
Luis Brito-Elias ◽  
César López-Camarillo ◽  
David Cantú de León ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Metabolism ◽  
Breast Cancer Subtype ◽  
Damage Response ◽  
Non Coding Rnas ◽  
Regulatory Rnas ◽  
Cycle Regulation ◽  
Aggressive Breast Cancer

The resistance that Triple-Negative Breast Cancer (TNBC), the most aggressive breast cancer subtype, develops against radiotherapy is a complex phenomenon involving several regulators of cell metabolism and gene expression; understanding it is the only way to overcome it. We focused this review on the contribution of the two leading classes of regulatory non-coding RNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), against ionizing radiation-based therapies. We found that these regulatory RNAs are mainly associated with DNA damage response, cell death, and cell cycle regulation, although they regulate other processes like cell signaling and metabolism. Several regulatory RNAs regulate multiple pathways simultaneously, such as miR-139-5p, the miR-15 family, and the lncRNA HOTAIR. On the other hand, proteins such as CHK1 and WEE1 are targeted by several regulatory RNAs simultaneously. Interestingly, the study of miRNA/lncRNA/mRNA regulation axes increases, opening new avenues for understanding radioresistance. Many of the miRNAs and lncRNAs that we reviewed here can be used as molecular markers or targeted by upcoming therapeutic options, undoubtedly contributing to a better prognosis for TNBC patients.

scholarly journals Simvastatin induced ferroptosis for triple-negative breast cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xianxian Yao ◽  
Ruihong Xie ◽  
Yongbin Cao ◽  
Jing Tang ◽  
Yongzhi Men ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Blood Circulation ◽  
Triple Negative ◽  
Breast Cancer Therapy ◽  
Mva Pathway ◽  
Zwitterionic Polymer ◽  
Aggressive Breast Cancer ◽  
Mcf 7

AbstractTriple-negative breast cancer (TNBC), a management of aggressive breast cancer, remains an unmet medical challenge. Although a wave of efforts had spurred to design novel therapeutic method of TNBC, unpredictable prognosis with lacking effective therapeutic targets along with the resistance to apoptosis seriously limited survival benefits. Ferroptosis is a non-apoptotic form of cell death that is induced by excessive lipid peroxidation, which provide an innovative way to combat cancer. Emerging evidence suggests that ferroptosis plays an important role in the treatment of TNBC cells. Herein, a novel ferroptosis nanomedicine was prepared by loading simvastatin (SIM), a ferroptosis drug, into zwitterionic polymer coated magnetic nanoparticles (Fe3O4@PCBMA) to improve the therapeutic effect of TNBC. The as-obtained Fe3O4@PCBMA-SIM nanoparticles demonstrated more cytotoxicity against MDA-MB-231 than MCF-7 due to the higher expression of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), which demonstrated that statins could effectively kill TNBC. Further experiments showed that SIM could inhibit the expression of HMGCR to downregulate the mevalonate (MVA) pathway and glutathione peroxidase 4 (GPX4), thereby inducing cancer cell ferroptosis. What’s more, PCBMA endows Fe3O4@PCBMA longer blood circulation performance to enhance their accumulation at tumor sites. Given that Fe3O4 have proven for clinical applications by the U.S. Food and Drug Administration (FDA) and SIM could induce cancer cell ferroptosis, the developed Fe3O4@PCBMA-SIM nanosystem would have great potential in clinics for overcoming the drug resistance brought about by apoptotic drugs to cancer cells.

scholarly journals Bilateral Choroidal Metastases In Triple-Negative Breast Cancer: Radiotherapy And Eribulin For Vision Preservation And Prolong Survival

2021 ◽  
Vol 15 (4) ◽  
pp. 226
Author(s):  
Harissa Husainy Hasbullah ◽  
Zulia Zulkiffli ◽  
Han Albert Dicken
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Bone Metastases ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Continuous Administration ◽  
Breast Cancer Radiotherapy ◽  
Short Course ◽  
Pleural Metastases

Introduction: Choroidal metastases are infrequent in breast cancer, but if they present, they usually signify the disseminated disease and poor prognosis. The challenges in treating choroidal metastases are not only to prolong survival but also to preserve vision, improving the quality of life. Case Presentation: Our patient was firstly diagnosed with stage-three triple-negative breast cancer at the age of 32 years. She had surgery, adjuvant chemotherapy with anthracycline regime, as well as adjuvant radiotherapy. Her disease firstly recurred two years later with pleural effusion, but it was controlled with six cycles of docetaxel. She was in remission until ten years later when she presented with a worsening dry cough and progressive blurring of vision in both eyes. CT restaging showed multiple sub-centimeter bilateral lung nodules, singular pleural metastases, and multiple bone metastases. Choroidal metastases were also confirmed with the ophthalmological assessment which includes CT of the orbit. She received short-course palliative radiotherapy followed immediately by eribulin. Then, she started monthly bisphosphonates. She was able to read again four months after radiotherapy, and her vision remains normal to date. The latest PET scans showed no FDG avid disease in the lungs with pleural metastases significantly reduced in size. Bone metastases remain stable and asymptomatic. It has been nearly four years since the diagnosis of choroidal metastases. She is still on eribulin at an adjusted dose and interval. She remains asymptomatic from her bone, lung, and choroidal metastases. Conclusions: Short-course radiotherapy to the orbit, followed by continuous administration of eribulin, can lead to prolonged survival with a good quality of life in triple-negative breast cancer with choroidal metastases

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