scholarly journals Breast cancer anti-hormonal therapy and rheumatic diseases: linking the clinical to molecular world

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Nadia Melillo ◽  
Francesco Paolo Cantatore
Keyword(s):  
Breast Cancer ◽  
Rheumatic Diseases ◽  
Hormonal Therapy ◽  
Molecular Mechanisms ◽  
Oestrogen Therapy ◽  
Future Studies ◽  
Biochemical Pathways ◽  
Clinical Relationship ◽  
Hormonal Therapies ◽  
The Relationship

Anti-hormonal therapies are used in the treatment of hormone dependent breast cancer. Their use may be complicated with the onset of arthralgia and autoimmune diseases. Recently a clinical relationship between oestrogen, anti-oestrogen therapy and rheumatic diseases has been reported in the literature, but, until now, experimental supporting data about the interacting biochemical pathways involved are still very limited. The understanding of this molecular link may provide important information to elucidate the relationship between autoimmunity and cancer mechanism and treatment. This review is intended to highlight the relationship between known common molecular mechanisms which explain this association and that probably need to be investigated in future studies.

Risk factors for fractures in patients on hormonal therapies for breast cancer and DCIS.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19627-e19627
Author(s):  
Abdullah Ladha ◽  
Josy Mathew
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Bone Mineral Density ◽  
Aromatase Inhibitors ◽  
Hormonal Therapy ◽  
Mineral Density ◽  
Risk Of Fracture ◽  
Increased Risk ◽  
Hormonal Therapies ◽  
Positive Breast Cancer

e19627 Background: Hormonal therapy with aromatase inhibitors (AI) or tamoxifen (TAM) is standard of care for hormone receptor positive breast cancer and DCIS. Fractures are a complication of treatment with AI due to accelerated bone loss. Risk factors for fracture in patients on hormonal therapy (HT) for breast cancer and DCIS are poorly defined. Methods: All 71 patients with breast cancer or DCIS seen in the bone and mineral clinic of our institution from 2000 to 2010 were analyzed. Data on demographics, pathology, type and duration of HT, bone mineral density studies (BMD), number and site of fractures were collected. Statistical analysis: t test, chi square test and Fisher’s exact test for categorical data. Results: The age of the patients ranged 40 to 97 years. 65 patients had ER positive breast cancer, 6 patients had DCIS. 9 patients had fractures.41 patients were on an AI alone, 8 were on TAM alone and 14 were on both sequentially. Fractures involved: vertebral compression, femur, hip, distal radioulnar, rib, hand and feet bones. Patients who had osteoporosis at the femur, osteoporosis or osteopenia in the lumbar spine or forearm in the initial BMD study were found to have an increased risk of fracture (P<0.05). Patients who were on TAM and AI sequentially had an increased risk of fracture (P<0.05) compared AI alone. The use of bisphosphonates and the duration of use were significantly associated with fracture (P<0.05) as these patients already had osteoporosis. The age, race, duration of AI use and the use of calcium and vitamin D were not found to be significantly different in patients who had fractures compared to those who did not. In the 24 patients who had two BMD studies, there was no significant change in the BMD overall. Conclusions: Patients with osteoporosis or osteopenia at baseline have an increased risk of fracture with the use of hormonal therapies for breast cancer and DCIS. This risk was not eliminated by the use of bisphosphonates. Sequential use of tamoxifen and aromatase inhibitors increase the risk of fractures. Bone mineral density studies done prior to the initiation of hormonal therapy for breast cancer maybe useful estimating the risk of fracture while on treatment.

scholarly journals Mechanism of Mutant p53 Using Three-Dimensional Culture on Breast Cancer Malignant Phenotype via SREBP-Dependent Cholesterol Synthesis Pathway

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1026-A1026
Author(s):  
Akitoshi Nakayama ◽  
Masataka Yokoyama ◽  
Hidekazu Nagano ◽  
Naoko Hashimoto ◽  
Kazuyuki Yamagata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Malignant Transformation ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
3D Culture ◽  
Breast Cancer Cell Lines ◽  
Mutant P53 ◽  
Gain Of Function ◽  
Mva Pathway ◽  
The Relationship

Abstract In many cancers, including hormone sensitive tumors such as breast cancer, the “gain of function” caused by mutations in the tumor suppressor gene p53 plays an important role in the acquisition of malignant phenotypes and the regulation of cancer stem cell characteristics. However, its action of molecular mechanisms, particularly in vivo conditions, has not been fully clarified. Therefore, we focused on the “gain of function” of mutant p53 and the cholesterol biosynthesis pathway, especially the mevalonate(MVA) pathway, using breast cancer cells, and clarified the interaction between them and the relationship with cancer malignancy using 3D-culture. Here, we generated knock out and knock in breast cancer cell lines for p53 using CRISPR-Cas9 system, and then confirmed malignant morphological changes by 3D-culture model. We found that the introduction of mutant p53 was solely able to mediate the malignant transformation of cancer. Next, focusing on the relationship between cancer malignant transformation and lipid metabolism pathway, we investigated the role of the MVA pathway in malignant transformation by mutation p53. When investigating the effects of the addition of HMG-CoA inhibitors and isoprenoids, intermediate metabolites were important for malignant transformation during 3D culture. Furthermore, knockdown of SREBP2, which controls the MVA pathway, suppressed malignant phenotypes, so we proceeded with analysis of the interaction between mutant p53 and SREBP2. As the result, we found that mutant p53 and SREBP2 co-localize in the nucleus and consistently mutant p53 was associated with mevalonate pathway genes in parallel with binding pattern of SREBP2. Thus, our results provide the novel insight into the potential therapeutic targets for breast cancer with poor prognosis.

The relationship between adherence to adjuvant hormonal therapy and survival among low-income, insured women with primary breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11522-e11522
Author(s):  
G. G. Kimmick ◽  
F. Camacho ◽  
W. Hwang ◽  
R. T. Anderson
Keyword(s):  
Breast Cancer ◽  
Hormonal Therapy ◽  
Low Income ◽  
Hormone Receptor ◽  
Adjuvant Hormonal Therapy ◽  
Cancer Specific Survival ◽  
Comorbidity Score ◽  
Regional Stage ◽  
Charlson Comorbidity Score ◽  
The Relationship

e11522 Background: Clinical trials and meta-analyses show that adjuvant hormonal therapy for hormone receptor positive breast cancer significantly decreases risk of death. We explored the relationship between adherence to adjuvant hormonal therapy and death in a low-income, Medicaid-insured population. Methods: Using a Medicaid claims-tumor registry linked database and National Death Index data (NDI), we evaluated adherence to adjuvant hormonal therapy [defined as >80% Medication Possession Ratio (MPR)] and mean six-year overall and cancer-specific survival by local versus regional stage for all female breast cancer diagnosed in years 2000–2002, in North Carolina. The Kaplan-Meier and Cox Proportional Hazards models were used to determine the role of adherence on cancer-specific survival. Models were adjusted for age, race, Charlson comorbidity score, number of prescription medications, type of surgery, use of radiation therapy, prior chemotherapy, hormone receptor status (positive or unknown). Results: The final sample consisted of 1,042 cases [ages range 29–97 years (mean 65.9 years; 56% Caucasian; mean Charlson comorbidity score 4.1 (SD 2.9); 680 local and 362 regional stage], of which 732 filled a prescription for adjuvant hormonal therapy within the year after breast cancer diagnosis. Filling a prescription for adjuvant hormonal therapy, versus not, was not significantly associated with cancer-related death: HR 1.04 (95% CI 0.66 - 1.64) overall; HR 0.75 (95% CI 0.39 - 1.43) for local stage and HR 1.01 (95% CI 0.51 - 2.00) for regional stage. However, adherence in the highest quartile (MPR>95) is associated with an increase in mortality risk. Conclusions: In this low income insured group of breast cancer patients, no statistically significant association was found between death rates and use of adjuvant hormonal therapy. However, an unexpected association between very high adherence and increase in mortality was found. This may reflect methodological limitations of claims data involving bias and unidentified patient risk. More research is needed to explore reasons for higher mortality among low-income women with high medication adherence. [Table: see text]

scholarly journals Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2839 ◽  
Author(s):  
Laetitia Delort ◽  
Lauriane Bougaret ◽  
Juliette Cholet ◽  
Marion Vermerie ◽  
Hermine Billard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Hormonal Therapy ◽  
Breast Cancer Cells ◽  
Hormonal Therapies ◽  
The Impact

Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- and hormonal therapies. Residual cancer stem cells could also have a key role in this process. To understand the mechanisms involved in the reduced efficacy of hormonal therapy on breast cancer cells in the presence of adipose secretome, human adipose stem cells (hMAD cell line) differentiated into mature adipocytes were co-cultured with mammary breast cancer cells and treated with hormonal therapies (tamoxifen, fulvestrant). Proliferation and apoptosis were measured (fluorescence test, impedancemetry, cytometry) and the gene expression profile was evaluated. Cancer stem cells were isolated from mammospheres made from MCF-7. The impact of chemo- and hormonal therapies and leptin was evaluated in this population. hMAD-differentiated mature adipocytes and their secretions were able to increase mammary cancer cell proliferation and to suppress the antiproliferative effect of tamoxifen, confirming previous data and validating our model. Apoptosis and cell cycle did not seem to be involved in this process. The evaluation of gene expression profiles suggested that STAT3 could be a possible target. On the contrary, leptin did not seem to be involved. The study of isolated cancer stem cells revealed that their proliferation was stimulated in the presence of anticancer therapies (tamoxifen, fulvestrant, doxorubicine) and leptin. Our study confirmed the role of adipocytes and their secretome, but above all, the role of communication between adipose and cancer cells in interfering with the efficiency of hormonal therapy. Among the pathophysiological mechanisms involved, leptin does not seem to interfere with the estrogenic pathway but seems to promote the proliferation of cancer stem cells.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

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