Terminal Cyclohexane-Type Meroterpenoids from the Fruiting Bodies of Ganoderma cochlear

Eleven new cyclohexane-type meroterpenoids (1, 3–5, 7, 8, 11–15) and four known similar meroterpenoids (2, 6, 9, and 10) were isolated from Ganoderma cochlear. Their structures and absolute configurations at stereogenic centers were elucidated by using HRESIMS, NMR spectroscopy and computational methods. In addition, the structure of the known meroterpenoid, cochlearol G (2), was revised, and the absolute configurations at the stereogenic centers of known meroterpenoids 9 and 10 were determined. All the isolated meroterpenoids were evaluated for their activities against renal fibrosis and triple negative breast cancer, and their insulin resistance. The results of the renal fibrosis study showed that meroterpenoid 11 inhibits over-expression of fibronectin, collagen I and α-SMA. Results of the wound healing study revealed that 4, 6 and 8 significantly inhibit migration of BT549 cells. Observations made in Western blotting experiments showed that 6 decreases the levels of TWIST1 and ZEB1, and increases the level of E-cadherin. Finally, meroterpenoids 7, 9, 11, and 15 significantly up-regulate p-AMPK protein expression in normal L6 myotubes cells.

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Pathogenesis and Potential Therapeutic Targets for Triple-Negative Breast Cancer

Cancers ◽

10.3390/cancers13122978 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2978

Author(s):

Chia-Jung Li ◽

Yen-Dun Tony Tzeng ◽

Yi-Han Chiu ◽

Hung-Yu Lin ◽

Ming-Feng Hou ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

High Efficiency ◽

Early Recurrence ◽

New Developments ◽

Great Progress ◽

Low Toxicity ◽

Made In

Triple negative breast cancer (TNBC) is a heterogeneous tumor characterized by early recurrence, high invasion, and poor prognosis. Currently, its treatment includes chemotherapy, which shows a suboptimal efficacy. However, with the increasing studies on TNBC subtypes and tumor molecular biology, great progress has been made in targeted therapy for TNBC. The new developments in the treatment of breast cancer include targeted therapy, which has the advantages of accurate positioning, high efficiency, and low toxicity, as compared to surgery, radiotherapy, and chemotherapy. Given its importance as cancer treatment, we review the latest research on the subtypes of TNBC and relevant targeted therapies.

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A Molecular and Morphological Deep-Dive Into Metaplastic Breast Cancers

Cancer Informatics ◽

10.1177/1176935119850155 ◽

2019 ◽

Vol 18 ◽

pp. 117693511985015

Author(s):

Amy E McCart Reed ◽

Sunil R Lakhani

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Breast Cancer Mortality ◽

Progesterone Receptors ◽

Breast Cancers ◽

Her2 Expression ◽

Deep Dive ◽

Whole Exome ◽

Morphological Assessment ◽

Made In

Metaplastic breast cancers (MBC) are relatively rare but account for significant global breast cancer mortality. Typically presenting without oestrogen and progesterone receptors or HER2 expression, these triple negative breast cancers are the archetypal ‘stem cell-like’ tumours that show a variety of metaplastic elements, including squamous, spindle, and chondroid. Given the vast heterogeneity in MBC by definition, large cohort studies are needed to draw conclusions. Together with our consortium colleagues, a cohort of 347 MBC was established, and a detailed morphological assessment made in an effort to understand the clinical relevance of the current diagnostic guidelines. Biomarker expression was investigated, and whole exome sequencing was performed. Herein, we provide an overview and contextualisation of the study.

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Conditioned media from MCF7 and BT474 breast cancer cells induce insulin resistance in skeletal muscle myotubes

10.1101/2020.01.27.921262 ◽

2020 ◽

Author(s):

Mona S. Ali ◽

Xiuqing Han ◽

Jingwen Li ◽

Marja Jäättelä ◽

Lykke Sylow

Keyword(s):

Breast Cancer ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Metabolic Disorders ◽

Breast Cancer Mortality ◽

Conditioned Media ◽

Glut4 Translocation ◽

L6 Myotubes

AbstractBackgroundMetabolic disorders are prevalent in women with breast cancer and breast cancer survivors. Such disorders increase breast cancer mortality and likelihood of relapse 2- and 3-fold, respectively. However, there is a severe lack of research into the physiological sequelae of breast cancer, including the metabolic health consequences. The aim of the present study was to provide novel insights into the causes of metabolic disturbances associated with breast cancer by investigating the effects of breast cancer on insulin sensitivity in skeletal muscle.MethodL6 myotubes stably expressing GLUT4 were incubated for 72 hours in normal growth medium or medium supplemented with 25% conditioned media (CM) from either MCF7 or BT474 breast cancer cells. Basal and insulin- (100nM) stimulated GLUT4 translocation, 2-deoxyglucose (2DG) uptake, and intracellular insulin signaling was determined in day 7 myotubes.ResultsBasal- and insulin-stimulated GLUT4 translocation was reduced in L6 myotubes incubated with MCF7 (basal: −7%, insulin: −14%, p<0.01) or BT474 (basal: −16%, insulin: −8%, p<0.01) breast cancer CM. Insulin-stimulated 2DG uptake in L6 myotubes was also reduced by MCF7 (−5%, p<0.05) and BT474 (−10%, p<0.05) breast cancer CM. Insulin-stimulated p-AktThr308 (but not p-AktSer473) phosphorylation tended to be reduced (−25%, p<0.1) in L6 myotubes incubated with MCF7 or BT474 breast cancer CM, while p-TBC1D4Thr642 phosphorylation was enhanced (+34%, p<0.05) by MCF7 breast cancer CM.ConclusionWe conclude that breast cancer reduces muscle insulin responsiveness, evidenced as reduced insulin-stimulated GLUT4 translocation, downregulated glucose uptake, and blunted intracellular insulin sigaling in L6 myotubes incubated with breast cancer cell CM. Thus, skeletal muscle insulin resistance might contribute to metabolic disorders prevalent in women with breast cancer and could be a potential treatment target.

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Caveolin-1: Oncogenic role in breast cancer? Clues from molecular profiling.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.134 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 134-134 ◽

Cited By ~ 3

Author(s):

Rebecca Feldman ◽

Zoran Gatalica ◽

Sandeep K. Reddy ◽

Michael Castro ◽

Jasgit C. Sachdev

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Analysis Tool ◽

Breast Cancer Patients ◽

P53 Expression ◽

P Values ◽

Over Expression ◽

Caveolin 1

134 Background: Caveolin-1 (CAV1) is the structural component of caveolae, compartments within the plasma membrane that sequester signaling molecules, thus facilitating molecular “hot spots”. The role of CAV1 in breast cancer is an active area of investigation. We sought to understand the clinical and pathological characteristics of CAV1 positive tumors (CAV 1+) through a retrospective analysis of molecularly-profiled breast cancer patients. Methods: 2,728 breast cancer patients molecularly profiled with a commercial assay (Caris Life Sciences) were evaluated retrospectively for expression of various biomarkers by immunohistochemistry (IHC) and in situ hybridization. JMP statistical analysis tool was used to ascertain distributional differences. Results: Using a threshold of 2+ and 30%, 121/2728 (4%) of patients exhibited CAV1 over-expression by IHC. To observe clinicopathologic differences in the CAV1 + and CAV1- tumors, distribution by age, metastatic disease, and triple negative histology (TNBC) were analyzed. Average age for both groups was 55. 39% vs. 54% were metastatic and 74% vs. 26% were TNBC (p = 0.0001) among CAV1+ and CAV1- groups, respectively. To evaluate the potential oncogenic associations of CAV1, we evaluated the relationship between CAV1+ and various oncogenic pathways. Positive EGFR protein expression and presence of EGFR gene amplification, as well as cKIT over-expression associated with CAV1+ (all p-values < 0.001), whereas HER2 expression and amplification were associated with CAV1- (p = 0.001 for both). In addition, higher Ki67, p53 and TOP2A expression by IHC were observed in CAV1+ patients compared to the CAV1- subgroup (90% vs. 66%, 50% vs. 36%, 84% vs. 65% ; all p-values < 0.0001). Biomarker expression differences that did not meet statistical significance: ERCC1, MGMT, PDGFRA, RRM1, SPARC, TS and TOPO1. Conclusions: The majority of CAV1+ breast cancers are comprised of triple negative, higher proliferative tumors, with aberrant p53 expression as well as expression of other growth factor signaling proteins. This data supports the potential role of CAV1 in fostering molecular hubs for signaling and CAV-1 being a potential target for future therapeutic investigation in TNBC.

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Hormone-replacement therapy may be associated with increased incidence of luminal breast cancer: Results from a large-scale health maintenance organization (HMO) analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13599 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13599-e13599

Author(s):

Nava Siegelmann-Danieli ◽

Vered Rosenberg ◽

Avital Bareket-Samish ◽

Gabriel Chodick ◽

Varda Shalev

Keyword(s):

Breast Cancer ◽

Hormone Replacement Therapy ◽

Replacement Therapy ◽

Large Scale ◽

Triple Negative ◽

Hormone Replacement ◽

Luminal Breast Cancer ◽

Luminal A ◽

Health Maintenance ◽

Over Expression

e13599 Background: Trends in breast cancer (BC) incidence may be impacted by potentially competing variables (e.g., mammography rates, hormone-replacement therapy [HRT] use). Methods: This observational retrospective study examined trends/associations between BC incidence, mammography rates, and HRT use among female members of the Maccabi Healthcare Services (the second largest HMO in Israel).BC subtypes were determined based on therapies received by patients diagnosed after 2006 (following trastuzumab approval in the adjuvant setting). Results: Between 2002 and 2014, 14,092 BC cases (88% invasive, 12% in-situ) were identified. The age-adjusted incidence rate of invasive BC peaked in 2005, consistent with increased mammography screening that year, and decreased thereafter. HRT use among all female members aged≥45 years decreased from 13.2% in 2002 to 4.6% in 2014, consistent with the global trend after the Women's Health Initiative publication. Analysis by BC subtype involved 6,218 invasive BC patients diagnosed between 2007 and 2014 (luminal A, 47.5%; luminal B1 without human epidermal growth factor receptor 2 [HER2] over-expression, 25.7%; luminal B2 with HER2 over-expression, 7.7%; estrogen receptor [ER]-negative/HER2+, 4.9%; triple negative, 8.3%; unknown, 6.0%). Overall, 75-86% of patients across all subtypes did not have any HRT exposure vs 14-25% who were current users (within 1 year before the BC diagnosis), recent users (within 2-5 years), or past users ( > 5 years). Current and recent use of HRT was statistically significantly higher in luminal BC vs ER-negative tumors: rates in luminal A/B1/B2, 15.3%/12.1%/11.1% vs ER-negative HER2+/triple-negative/unknown, 8.9%/9.7%/7.7% ( P< 0.001). In BC patients (≥45 years) with HRT exposure, the preparations used were estrogen plus progesterone (62%), estrogen alone (24%), and tibolone (14%). In non-BC cases (≥45 years), the respective values were similar: 61%, 26%, and 13%. Conclusions: HRT current/recent exposure may contribute to increased incidence of luminal BC tumors.

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The effect of miR-340 over-expression on cell-cycle-related genes in triple-negative breast cancer cells

European Journal of Cancer Care ◽

10.1111/ecc.12496 ◽

2016 ◽

Vol 26 (6) ◽

pp. e12496 ◽

Cited By ~ 8

Author(s):

S. Mohammadi Yeganeh ◽

M. Vasei ◽

R. Tavakoli ◽

V. Kia ◽

M. Paryan

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Over Expression

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Metabolic Syndrome and Triple-Negative Breast Cancer: A New Paradigm

International Journal of Breast Cancer ◽

10.1155/2012/809291 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 41

Author(s):

Andrew A. Davis ◽

Virginia G. Kaklamani

Keyword(s):

Breast Cancer ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Growth Factor ◽

Triple Negative ◽

Growth Factor Receptor ◽

Breast Cancers ◽

New Paradigm ◽

Cancer Subtypes ◽

The Metabolic Syndrome

Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angiogenesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC.

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Biological Subtypes of Triple-Negative Breast Cancer

Breast Care ◽

10.1159/000455820 ◽

2017 ◽

Vol 12 (1) ◽

pp. 8-14 ◽

Cited By ~ 21

Author(s):

Michael Hubalek ◽

Theresa Czech ◽

Hannes Müller

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Treatment Options ◽

Breast Cancers ◽

Great Progress ◽

Her 2 ◽

Disproportionate Number ◽

New Treatment ◽

Routine Clinical Application ◽

Made In

Triple-negative breast cancers (TNBCs) are defined as tumors that are negative for estrogen, progesterone and HER-2 receptor. At a percentage of 10-20% TNBCs represent a minority in all breast cancers. However, because of the poor prognosis this particular subtype, triple negative disease accounts for a disproportionate number of metastatic cases and breast cancer deaths. Identification of its subtypes is essential for understanding the biological characteristics and clinical behavior of TNBC, as well as for developing personalized treatments. This review will focus on the great progress that has been made in the past few years on identifying new targets in TNBC subtypes and a variety of new treatment options that are on the verge of routine clinical application.

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Survival Analysis Based on Clinicopathological Data from a Single Institution: Chemotherapy Intensity Would Be Enhanced in Patients with Positive Hormone Receptors and Positive HER2 in China Who Cannot Afford the Target Therapy

ISRN Oncology ◽

10.1155/2013/606398 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8

Author(s):

Jianyi Li ◽

Shi Jia ◽

Wenhai Zhang ◽

Yang Zhang ◽

Xiang Fei ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Progression ◽

Triple Negative ◽

Her2 Overexpression ◽

Luminal A ◽

Luminal B ◽

Over Expression ◽

Risk Of Death ◽

Systemic Treatments ◽

Increased Risk

Background. Immunohistochemical markers were often used to classify breast cancer into subtypes. The aim of this study was to estimate death and tumor progression for patients with the major subtypes of breast cancer as classified using immunohistochemical assay and to investigate the patterns of benefit from the therapies over the past years. Methods. The study population included primary, operable 199 invasive ductal breast cancer patients, with the median age of 51.1 years old. All patients underwent local and/or systemic treatments. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. The expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki67 was analyzed by immunohistochemistry. All patients were classified into the following categories: luminal A, luminal B, HER2 overexpression, and triple-negative subtypes. Result. The median follow-up time was 33 months. Luminal A tumors had the lowest rate of tumor progression (0%, P=0.006), while luminal B, HER2 over-expression, and triple-negative subtypes were associated with an increased risk of tumor progression (15.4, 19.2, 15.4%). Clinicopathological subtypes retained independent prognostic significance (P=0.008). There were significant differences by Cox model analyzed in age, menopause, lymph node metastasis, and HER2 for the event of death and tumor progression (P<0.05), and there were significant differences only in chemotherapy for the event, respectively (P<0.05). Conclusion. Clinicopathological subtypes of breast cancer could robustly identify the risk of death and tumor progression and were significant in making therapeutic decision. HER2 was the important poor indicator. The chemotherapy intensity would be enhanced for patients with luminal B, especially for HER2 over-expression subgroup.

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