Tumor growth inhibition modeling of individual lesion dynamics and inter‐organ variability in HER2‐negative breast cancer patients treated with docetaxel

e12575 Background: The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii. Methods: We performed the 16S rDNA sequencing of gut bacteria and the LC-MS metabolomics analysis of blood samples in 25 breast cancer patients and 25 benign breast disease controls. Correlation analysis of significant flora and metabolites were processed, including correlation coefficient calculation, matrix heat map analysis, cluster analysis, correlation network analysis, and scatter plot analysis. We screened for intestinal flora that may participate in breast cancer development and try to test and verify. CCK-8, apoptosis and transwell assays were explored to detect the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii. Western blot was used to analyze the changes of IL-6/STAT3 pathway by Faecalibacterium prausnitzii. Results: Total 49 significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobacteria was increased in breast cancer group. Differentially expressed metabolites were mainly enriched in pathways such as linoleic acid metabolism, retrograde endocannabinoid signaling, biosynthesis of unsaturated fatty acids, choline metabolism in cancer and arachidonic acid metabolism. Lipid upregulation was found in breast cancer patients, especially phosphorocholine. The abundance of Faecalibacterium was reduced in breast cancer patients, which was negatively correlated with various phosphorylcholines. Moreover, Faecalibacterium prausnitzii, the most well-known species in Faecalibacterium genus, could inhibit the secretion of IL-6 and the phosphorylation of JAK2/STAT3 in breast cancer cells. Faecalibacterium prausnitzii also suppressed the proliferation and invasion and promoted the apoptosis of breast cancer cells, while these effects disappeared after adding recombinant human IL-6. Conclusions: Flora-metabolites combined with the flora-bacteria (such as Faecalibacterium combined with phosphorocholine) might a new detection method for breast cancer. Faecalibacterium may be helpful for prevention of breast cancer. Faecalibacterium prausnitzii suppresses the growth of breast cancer cells through inhibition of IL-6/STAT3 pathway.

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Overexpression of ubiquitous mitochondrial creatine kinase (uMtCK) accelerates tumor growth by inhibiting apoptosis of breast cancer cells and is associated with a poor prognosis in breast cancer patients

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2012.08.147 ◽

2012 ◽

Vol 427 (1) ◽

pp. 60-66 ◽

Cited By ~ 16

Author(s):

Xiao-Long Qian ◽

Ya-Qing Li ◽

Feng Gu ◽

Fang-Fang Liu ◽

Wei-Dong Li ◽

...

Keyword(s):

Breast Cancer ◽

Creatine Kinase ◽

Tumor Growth ◽

Cancer Cells ◽

Cancer Patients ◽

Poor Prognosis ◽

Breast Cancer Cells ◽

Breast Cancer Patients ◽

Mitochondrial Creatine Kinase

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EXTH-02. AAV MEDIATED BRAIN DELIVERY OF AN ADCC-ENHANCED ANTIBODY OBVIATES XENOGRAFT GROWTH IN MOUSE MODELS OF HER2+ BREAST CANCER BRAIN METASTASIS

Neuro-Oncology ◽

10.1093/neuonc/noab196.641 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi163-vi163

Author(s):

Dan Laks ◽

Kenny Chen ◽

Xiaoqin Ren ◽

Ishan Shah ◽

Usman Hameedi ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Tumor Growth ◽

Cancer Patients ◽

Breast Cancer Cell Lines ◽

Breast Cancer Patients ◽

Aav Vector ◽

Orthotopic Xenograft ◽

Her2 Breast Cancer ◽

Breast Cancer Brain Metastasis

Abstract BACKGROUND HER2+ tumors constitute approximately 20% of breast cancer patients and are characterized by overexpression of the growth factor receptor HER2 (ERBB2), a cell proliferation driver. Effective anti-HER2 therapies confer prolonged patient survival necessitating the need for transformative treatments targeting brain metastases, a major cause of mortality in ~30-50% of HER2+ metastatic breast cancer patients. HER2-directed antibody immunotherapy, while efficacious for peripheral disease, has limited central nervous system exposure (CNS). To overcome these challenges, we transduced CNS cells with a novel AAV vector carrying an anti-HER2 antibody payload. METHODS We assessed the biochemical equivalence and functional effectiveness of AAV vector-encoded antibodies using in vitro assays. After selecting promising vector-encoded antibody candidates, a novel, blood-brain barrier penetrant AAV capsid was administered via i.v. dosing to an orthotopic xenograft mouse model of HER2+ brain metastases. Bioluminescent imaging provided a longitudinal measure of brain tumor burden. At study termination, we measured antibody biodistribution in cerebrospinal fluid (CSF), serum, and brain homogenates with AlphaLISA assays. RESULTS Using HER2+ breast cancer cell lines, we determined that an antibody-dependent cell cytotoxicity (ADCC) enhanced anti-HER2 antibody was most effective and demonstrated that AAV-vector encoded forms of the antibody performed comparably to recombinant reference antibodies. Following i.v. administration of a HER2 antibody encoding AAV vector, we measured >1 ug/mL of the antibody in CSF. Importantly, AAV-mediated expression of the ADCC-enhanced HER2-directed antibody significantly abrogated tumor growth in orthotopic xenograft models. CONCLUSIONS Peripheral administration of an AAV vector was able to transduce brain tissue such that efficacious levels of HER2-directed antibodies were produced. This strategy was successful at preventing tumor growth in our physiologically relevant model of breast cancer brain metastases. Such a treatment modality should be further evaluated in patient derived PDX models to validate translational efficacy for human patients.

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Effective tumor growth inhibition of MX1 and MDA-MB-231 estrogen receptor negative human breast cancer xenografts by treatment with LHRH antagonist cetrorelix.

10.1158/0008-5472.sabcs-2137 ◽

2009 ◽

Author(s):

S Seitz ◽

AV Schally ◽

A Papadia ◽

S Glueck ◽

C Calfa ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Tumor Growth ◽

Growth Inhibition ◽

Human Breast Cancer ◽

Tumor Growth Inhibition ◽

Human Breast ◽

Lhrh Antagonist ◽

Estrogen Receptor Negative ◽

Breast Cancer Xenografts

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Hubungan Kadar Vitamin D Plasma dengan Indeks Mitosis pada Pasien Kanker Payudara

SRIWIJAYA JOURNAL OF MEDICINE ◽

10.32539/sjm.v1i3.29 ◽

2018 ◽

Vol 1 (3) ◽

pp. 143-148

Author(s):

Astrid Siska Pratiwi ◽

Yahwardiah Siregar

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Tumor Growth ◽

Cancer Patients ◽

Active Form ◽

Plasma Vitamin ◽

Breast Cancer Patients ◽

Breast Cancer Outcome ◽

Vitamin D Levels ◽

Anatomical Pathology

Breast cancer is the most common cancer suffered by women and one of the biggest causes of death for women worldwide. Later, nutrition became one of the risk factors in breast cancer outcome, one of them is vitamin D. Calcitriol is the active form of vitamin D as an anti-proliferation, and inhibits tumor growth. Uncontrolled proliferation is one of the characteristics of cancer cells. Tumor growth rates become prognostic markers that can be evaluated by correlating at cellular levels such as mitosis. The aimed of this study was to analyze the relationship between vitamin D levels and mitosis index in breast cancer patients. Research with cross sectional design gathered 50 breast cancer patients who were newly diagnosed and had never received chemotherapy. The study was conducted from January 2017 - August 2018 at the Department of Surgical Oncology, RSUPH. Adam Malik Medan. Examination of plasma vitamin D levels is done by ELISA technique at the Lab. Faculty of Medicine Universitas Sumatera Utara. The mitosis index data was obtained from the medical record of the research subjects reviewed by anatomical pathology specialists at the Lab. Anatomical Pathology of Faculty of Medicine Universitas Sumatera Utara. Statistical test uses Fisher Exact. The results of the study 48% of subjects had vitamin D sufficiency, 38% insufficiency and 14% had deficiency. The mean vitamin D levels in all of the study subjects were insufficiency (27.93ng / ml). In this study there was no significant relationship between plasma vitamin D levels and mitosis index in breast cancer patients p = 0.062. The insignificant relationship between vitamin D levels and mitotic index in this study shows that vitamin D not a single factors to influence the mitosis index in breast cancer patients.

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Effects of melatonin and doxorubicin on primary tumor and metastasis in breast cancer model

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666211213094258 ◽

2021 ◽

Vol 21 ◽

Author(s):

Gamze Tanriover ◽

Sayra Dilmac ◽

Gunes Aytac ◽

Ammad Ahmad Farooqi ◽

Muzaffer Sindel

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Cancer Patients ◽

Primary Tumor ◽

Metastatic Breast ◽

Suppressor Cells ◽

Metastatic Tumor ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Ample Evidence

Background: Melatonin exerts oncostatic effects on breast cancer via immunomodulation and anti-oxidation. Doxorubicin is an effective chemotherapeutic agent, but parallel studies also provide ample evidence of an off-target effect of Doxorubicin in breast cancer patients. Objective: Combinatorial use of doxorubicin and melatonin has not been comprehensively analyzed in breast cancer models. We hypothesized that the anti-oxidative, anti-proliferative and anti-inflammatory effects of melatonin could ameliorate the off-target effects of doxorubicin in breast cancer patients and enhance the anti-tumoral effects of doxorubicin. The goal of the study is to test this hypothesis in cancer cell lines and xenografted mice. Methods: The effects of Melatonin and doxorubicin on the cell viability were evaluated in 4T1-Brain Metastatic Tumor (4TBM). Furthermore, the effects of melatonin and doxorubicin on the primary tumors and systemic metastasis were evaluated in the xenografted mice. Lung and liver tissues were removed and metastasis analyses were performed. The levels of p65, phospho-STAT3, CD11b+, GR1+, Ki67, and cleaved caspase-3 proteins were determined with immunohistochemistry and western blot analysis. We examined the effects of melatonin and Melatonin+Doxorubicin combination therapy on 4TBM cells. Results: Our results showed that doxorubicin inhibited the proliferation of metastatic breast cancer cells while melatonin did not affect cells. Tumor growth and metastasis were markedly suppressed in melatonin alone and combination with doxorubicin. The expression of CD11b+ and GR1+ proteins which are indicators of myeloid-derived suppressor cells (MDSCs) were noted to be reduced in both primary tumor and metastatic tissues in melatonin and doxorubicin groups. Conclusion: The combination of melatonin with doxorubicin reduced primary tumor growth and distant metastasis. Based on these results, melatonin is a promising candidate for combinatory use with conventional chemotherapeutics for breast cancer treatment.

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Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer

Cells ◽

10.3390/cells8070750 ◽

2019 ◽

Vol 8 (7) ◽

pp. 750 ◽

Cited By ~ 1

Author(s):

Angela Maselli ◽

Stefania Parlato ◽

Rossella Puglisi ◽

Carla Raggi ◽

Massimo Spada ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Cancer Patients ◽

Tamoxifen Resistance ◽

Breast Cancer Patients ◽

Hormone Receptor Positive ◽

Molecular Events ◽

Therapeutic Decisions ◽

Er Positive ◽

Positive Breast Cancer

Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients.

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