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Article ; Online: Selective sensitization of tumors to chemotherapy by marine-derived lipids: a review.

Hajjaji, Nawale / Bougnoux, Philippe

2013 Volume 39, Issue 5, Page(s) 473–488

Abstract: Despite great improvements, a significant proportion of cancer patients still die, mainly because of the development of metastases. At this stage, current treatments still rely heavily on conventional chemotherapy for most cancers. The efficacy of ... ...

Abstract	Despite great improvements, a significant proportion of cancer patients still die, mainly because of the development of metastases. At this stage, current treatments still rely heavily on conventional chemotherapy for most cancers. The efficacy of chemotherapy is dose-dependent, which is limited by toxicity to non-tumor tissues, as a result of its poor tumor selectivity. To improve survival length and preserve quality of life, the challenge is to develop approaches aimed at increasing chemotherapy toxicity to tumor tissue while not affecting non-tumor tissues. Marine-derived lipids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have the potential to differentially sensitize tissues to chemotherapy. These lipids enhance the cytotoxicity of 15 anticancer drugs (antimetabolites, alkylating or intercalating agents, microtubule stabilizers, Abl tyrosine kinase inhibitor and arsenic trioxide) to a variety of cancer cell lines or tumors in animals, used as models for breast, prostate, colonic, lung, cervical, ovarian cancers, neuroblastomas, leukemia or lymphomas. However, DHA and EPA do not sensitize non-tumor tissues to anticancer drugs, which suggests that the effect of these lipids is tumor selective. Two phase II clinical trials already support these results, and randomized, phase III trials are ongoing. In this review, we discuss the double-faceted properties of these lipids, and then focus on their potential for transfer to the patient in the light of current therapeutic strategies. Should their beneficial effects be confirmed, the consequences could be considerable by opening up the prospect of systematic supplementation during cancer treatment, a significant shift in current cancer therapeutic paradigms.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Docosahexaenoic Acids/pharmacology ; Drug Synergism ; Eicosapentaenoic Acid/pharmacology ; Humans
Chemical Substances	Antineoplastic Agents ; Docosahexaenoic Acids (25167-62-8) ; Eicosapentaenoic Acid (AAN7QOV9EA)
Language	English
Publishing date	2013-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	125102-8
ISSN	1532-1967 ; 0305-7372
ISSN (online)	1532-1967
ISSN	0305-7372
DOI	10.1016/j.ctrv.2012.07.001
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Zs.A 1022: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Total long-chain polyunsaturated n-3 fatty acids level is an independent predictive factor of breast cancer multifocality in women with positive hormone-receptors tumors.

Ouldamer, Lobna / Goupille, Caroline / Vildé, Anne / Arbion, Flavie / Guimaraes, Cyrille / Jourdan, Marie-Lise / Bougnoux, Philippe / Body, Gilles / Chevalier, Stephan

Surgical oncology

2021 Volume 38, Page(s) 101597

Abstract: In a previous pilot study, we showed that polyunsaturated n-3 fatty acids of breast adipose tissues were associated with breast cancer multifocality. In the present study, we investigated biochemical, clinical and histological factors associated with ... ...

Abstract	In a previous pilot study, we showed that polyunsaturated n-3 fatty acids of breast adipose tissues were associated with breast cancer multifocality. In the present study, we investigated biochemical, clinical and histological factors associated with breast cancer focality in a large cohort of women with positive hormone-receptors tumors. One hundred sixty-one consecutive women presenting with positive hormone-receptors breast cancer underwent breast-imaging procedures including a Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during surgery of tumors. A biochemical profile of breast adipose tissue fatty acids was established by gas chromatography. Clinicopathologic characteristics were correlated with multifocality. We assessed whether these factors were predictive of breast cancer focality. We found that tumor size (OR = 1.06 95%CI [1.02-1.09], p < 0.001) and decreased levels in breast adipose tissue of long-chain polyunsaturated n-3 fatty acids (OR = 0.11 95%CI [0.01-0.98], p = 0.03), were independent predictive factors of multifocality. Low levels of long chain polyunsaturated n-3 fatty acids in breast adipose tissue appear to contribute to breast cancer multifocality. The present results reinforce the link between dietary habits and breast cancer clinical presentation.
MeSH term(s)	Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Fatty Acids, Omega-3/metabolism ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism
Chemical Substances	Fatty Acids, Omega-3 ; Receptors, Estrogen ; Receptors, Progesterone ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2021-04-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1107810-8
ISSN	1879-3320 ; 0960-7404
ISSN (online)	1879-3320
ISSN	0960-7404
DOI	10.1016/j.suronc.2021.101597
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Article ; Online: Evolution of characteristics of women with endometrial cancer during a 40 years study period.

Lorphelin, Henri / Rossard, Lauranne / Rua, Carina / Arbion, Flavie / Bougnoux, Philippe / Body, Gilles / Ouldamer, Lobna

Journal of gynecology obstetrics and human reproduction

2019 Volume 48, Issue 7, Page(s) 489–494

Abstract: Objectives: The aim of our work was to investigate changes in presentation and endometrial cancer (EC) types frequencies thorough a 40 years study period.: Patients and methods: The patient group consisted of consecutive women undergoing surgery for ... ...

Abstract	Objectives: The aim of our work was to investigate changes in presentation and endometrial cancer (EC) types frequencies thorough a 40 years study period. Patients and methods: The patient group consisted of consecutive women undergoing surgery for endometrial cancer in our institution between 1975, and 2014. Clinical data included age, BMI (Kg/m2), histological data from surgical staging and survival data. Results: 842 patients with the final diagnosis of endometrial cancer were enrolled. BMI was overweight rising through study decades. Age of diagnosis was also in constant augmentation since 1975. Type II EC proportion was 9.2% in the seventies and 27.9% after 2000. Overall survival was stable over time. Women with BMI < 18 kg/m Discussion and conclusion: An analysis on a larger population of underweight women with EC is needed to identify specific factors. A trend to develop more type II EC can partly explain these results. We identified a clear trend of augmentation of type II EC, known to have a poor prognosis while necessitating specific surgical management. Histologic analysis standardisation, surgical strategy and amelioration of adjuvant treatments permitted to maintain a stable overall survival for the whole population despite this augmentation.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cancer Care Facilities/statistics & numerical data ; Carcinoma, Endometrioid/epidemiology ; Carcinoma, Endometrioid/mortality ; Carcinoma, Endometrioid/pathology ; Endometrial Neoplasms/epidemiology ; Endometrial Neoplasms/mortality ; Endometrial Neoplasms/pathology ; Female ; France/epidemiology ; Gynecology/statistics & numerical data ; Gynecology/trends ; Humans ; Medical Oncology/statistics & numerical data ; Medical Oncology/trends ; Middle Aged ; Registries/statistics & numerical data ; Retrospective Studies ; Survival Analysis ; Tertiary Care Centers/statistics & numerical data
Language	English
Publishing date	2019-04-12
Publishing country	France
Document type	Journal Article
ISSN	2468-7847
ISSN (online)	2468-7847
DOI	10.1016/j.jogoh.2019.04.006
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Article ; Online: Endogenous ether lipids differentially promote tumor aggressiveness by regulating the SK3 channel.

Journal of lipid research

2024 Volume 65, Issue 5, Page(s) 100544

Abstract: SK3 channels are potassium channels found to promote tumor aggressiveness. We have previously demonstrated that SK3 is regulated by synthetic ether lipids, but the role of endogenous ether lipids is unknown. Here, we have studied the role of endogenous ... ...

Abstract	SK3 channels are potassium channels found to promote tumor aggressiveness. We have previously demonstrated that SK3 is regulated by synthetic ether lipids, but the role of endogenous ether lipids is unknown. Here, we have studied the role of endogenous alkyl- and alkenyl-ether lipids on SK3 channels and on the biology of cancer cells. Experiments revealed that the suppression of alkylglycerone phosphate synthase or plasmanylethanolamine desaturase 1, which are key enzymes for alkyl- and alkenyl-ether-lipid synthesis, respectively, decreased SK3 expression by increasing micro RNA (miR)-499 and miR-208 expression, leading to a decrease in SK3-dependent calcium entry, cell migration, and matrix metalloproteinase 9-dependent cell adhesion and invasion. We identified several ether lipids that promoted SK3 expression and found a differential role of alkyl- and alkenyl-ether lipids on SK3 activity. The expressions of alkylglycerone phosphate synthase, SK3, and miR were associated in clinical samples emphasizing the clinical consistency of our observations. To our knowledge, this is the first report showing that ether lipids differentially control tumor aggressiveness by regulating an ion channel. This insight provides new possibilities for therapeutic interventions, offering clinicians an opportunity to manipulate ion channel dysfunction by adjusting the composition of ether lipids.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	80154-9
ISSN	1539-7262 ; 0022-2275
ISSN (online)	1539-7262
ISSN	0022-2275
DOI	10.1016/j.jlr.2024.100544
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Zs.A 175: Show issues

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Article: N-3 Fatty Acid Supplementation Impacts Protein Metabolism Faster Than it Lowers Proinflammatory Cytokines in Advanced Breast Cancer Patients: Natural

Mantha, Olivier L / Hankard, Régis / Tea, Illa / Schiphorst, Anne-Marie / Dumas, Jean-François / Berger, Virginie / Goupille, Caroline / Bougnoux, Philippe / De Luca, Arnaud

Metabolites

2022 Volume 12, Issue 10

Abstract: While clinical evidence remains limited, an extensive amount of research suggests a beneficial role of n-3 polyunsaturated fatty acid supplementation in cancer treatment. One potential benefit is an improvement of protein homeostasis, but how protein ... ...

Abstract	While clinical evidence remains limited, an extensive amount of research suggests a beneficial role of n-3 polyunsaturated fatty acid supplementation in cancer treatment. One potential benefit is an improvement of protein homeostasis, but how protein metabolism depends on proinflammatory cytokines in this context remains unclear. Here, using the natural abundance of the stable isotopes of nitrogen as a marker of changes in protein metabolism during a randomized, double-blind, controlled clinical trial, we show that protein homeostasis is affected way faster than proinflammatory cytokines in metastatic breast cancer patients supplemented with n-3 polyunsaturated fatty acids. We provide some evidence that this response is unrelated to major changes in whole-body substrate oxidation. In addition, we demonstrate that more fatty acids were impacted by metabolic regulations than by differences in their intake levels during the supplementation. This study documents that the percentage of patients that complied with the supplementation decreased with time, making compliance assessment crucial for the kinetic analysis of the metabolic and inflammatory responses. Our results highlight the time-dependent nature of metabolic and inflammatory changes during long-chain n-3 fatty acid supplementation.
Language	English
Publishing date	2022-09-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo12100899
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Article ; Online: Natural isotopic abundances as markers of compliance in clinical trials.

Mantha, Olivier L / Goupille, Caroline / Dumas, Jean-François / Robins, Richard / Bougnoux, Philippe / Hankard, Régis / De Luca, Arnaud

The American journal of clinical nutrition

2020 Volume 111, Issue 5, Page(s) 1109–1110

MeSH term(s)	Animals ; Carbon ; Carbon Isotopes/analysis ; Humans ; Inpatients ; Meat ; Nitrogen Isotopes/analysis ; Sugar-Sweetened Beverages
Chemical Substances	Carbon Isotopes ; Nitrogen Isotopes ; Carbon (7440-44-0)
Language	English
Publishing date	2020-04-22
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.1093/ajcn/nqaa053
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Article ; Online: Prolonged complete response after treatment withdrawal in HER2-overexpressed, hormone receptor-negative breast cancer with liver metastases: the prospect of disappearance of an incurable disease.

Viel, Erika / Arbion, Flavie / Barbe, Catherine / Bougnoux, Philippe

BMC cancer

2014 Volume 14, Page(s) 690

Abstract: Background: Metastatic breast cancer has consistently been viewed as a non-curable disease. Specific palliative treatments such as chemotherapy and hormone therapy have resulted in a mean overall survival of approximately 30 months. While cases of ... ...

Abstract	Background: Metastatic breast cancer has consistently been viewed as a non-curable disease. Specific palliative treatments such as chemotherapy and hormone therapy have resulted in a mean overall survival of approximately 30 months. While cases of prolonged complete response have been reported with hormone or trastuzumab monotherapy, rendering metastatic breast cancer a chronic disease, any treatment withdrawal has ineluctably led to relapse. Prolonged remission without any anti-cancer treatment has never been reported to our knowledge. Case presentation: We report here the unique observation of the spontaneous evolution of two breast cancer patients with synchronous liver metastases who decided to stop trastuzumab after achieving complete response. They were Caucasian women with synchronous liver metastatic breast carcinoma. Both breast cancers reached skin and regional lymph nodes. There were several liver metastases in both patients. They received surgery, radiotherapy and chemotherapy combined with trastuzumab. They decided to stop their treatment, despite guidelines. After a follow-up longer than 20 months, they did not relapse clinically, radiologically, and biologically. Conclusion: This findings question the belief of the unavoidability of recurrence of metastatic breast cancer, specifically in the liver. It opens up the unprecedented possibility of a cure-like state in exceptional and probably special cases.
MeSH term(s)	Aged ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Female ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Liver Neoplasms/secondary ; Middle Aged ; Receptor, ErbB-2/metabolism ; Trastuzumab ; Treatment Outcome ; Withholding Treatment
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2014-09-22
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/1471-2407-14-690
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Article: NMR-Based Lipidomic Approach To Evaluate Controlled Dietary Intake of Lipids in Adipose Tissue of a Rat Mammary Tumor Model

Ouldamer, Lobna / Nadal-Desbarats Lydie / Chevalier Stephan / Body Gilles / Goupille Caroline / Bougnoux Philippe

Journal of Proteome Research. 2016 Mar. 04, v. 15, no. 3

2016

Abstract: The fatty acids composition of adipose tissue may provide information on the nutritional part of the risk or evolution of breast cancer. To determine whether ¹H NMR of adipose tissue provides information on the nature of the diet consumed, a dietary ... ...

Abstract	The fatty acids composition of adipose tissue may provide information on the nutritional part of the risk or evolution of breast cancer. To determine whether ¹H NMR of adipose tissue provides information on the nature of the diet consumed, a dietary intervention with increasing percentage of polyunsaturated n-3 docosahexaenoic acid (DHA 22:6n-3, provided as DHASCO oil) was applied to a rat model of N-nitroso-N-methylurea-induced mammary tumors. Spectra of the lipid extracts were obtained from adipose tissues in five groups of Sprague–Dawley rats fed with a diet containing 7% peanut/rapeseed enriched with 8% (w/w) of an oil without (palm oil) or with low (1%), moderate (3%), or high (8%) DHASCO content. A control group received a basal diet with 15% peanut/rapeseed representative of the “Western” diet. After 5 months of those five controlled diets, adipose tissue was collected for analysis of the lipid extract using both ¹H NMR analysis on an 11.7 T spectrometer and gas chromatography considered as gold standard. ¹H NMR analysis showed a dose-dependent increase in DHA in the lipid extract of adipose tissues and a commensurate decrease in n-6 polyunsaturated fatty acids in the three DHA groups, which allowed one to follow n-6/n-3 ratio changes. The highest n-6/n-3 ratio was observed in the control Western diet group compared to the other diet groups. The integrated spectral regions showed separation between groups, thereby documenting a specific NMR lipid profile corresponding to each dietary intervention. Those diet-dependent NMR lipid profiles were consistent with that obtained with gas chromatography analyses of the same samples. This study is a proof of concept highlighting the potential use of the ¹H NMR approach to evaluate dietary intervention in biopsies of adipose tissues.
Keywords	Western diets ; adipose tissue ; animal models ; biopsy ; docosahexaenoic acid ; dose response ; evolution ; food intake ; gas chromatography ; lipid composition ; mammary neoplasms (animal) ; nuclear magnetic resonance spectroscopy ; nutritional intervention ; oils ; omega-6 fatty acids ; peanuts ; proteome ; rapeseed ; rats ; risk ; spectrometers
Language	English
Dates of publication	2016-0304
Size	p. 868-878.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021%2Facs.jproteome.5b00788
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Zs.A 6189: Show issues

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Article ; Online: Low eicosapentaenoic acid and gamma-linolenic acid levels in breast adipose tissue are associated with inflammatory breast cancer.

Chas, Marie / Goupille, Caroline / Arbion, Flavie / Bougnoux, Philippe / Pinault, Michelle / Jourdan, Marie Lise / Chevalier, Stephan / Ouldamer, Lobna

Breast (Edinburgh, Scotland)

2019 Volume 45, Page(s) 113–117

Abstract: Objective: Since it is thought that breast adipose tissue could influence breast cancer clinical presentation, we wanted to characterize specifically the relationship between breast adipose tissue fatty acid profile and Inflammatory Breast cancer (IBC).! ...

Abstract	Objective: Since it is thought that breast adipose tissue could influence breast cancer clinical presentation, we wanted to characterize specifically the relationship between breast adipose tissue fatty acid profile and Inflammatory Breast cancer (IBC). Methods: Two hundred thirty-four women presenting with breast cancer were managed in our centre between January 2009 and December 2011. Breast adipose tissue specimens were collected during breast surgery. We established the biochemical profile of adipose tissue fatty acids (FA) by gas chromatography and assessed whether there were differences in function of the presence of breast inflammation or not. Results: We found that IBC was associated with decreased levels in breast adipose tissue of eicosapentaenoic acid (EPA), one of the two main polyunsaturated n-3 fatty acids (n-3 PUFA) of marine origin, but also with decreased levels of Gamma Linolenic acid (GLA). Inversely, an increase in palmitic acid levels was associated with IBC. Conclusion: These differences in lipid content may contribute to the occurrence of breast cancer inflammation.
MeSH term(s)	Adipose Tissue/metabolism ; Adult ; Aged ; Aged, 80 and over ; Breast/metabolism ; Breast Neoplasms/metabolism ; Chromatography, Gas ; Eicosapentaenoic Acid/metabolism ; Female ; Humans ; Inflammatory Breast Neoplasms/metabolism ; Middle Aged ; Retrospective Studies ; gamma-Linolenic Acid/metabolism
Chemical Substances	gamma-Linolenic Acid (78YC2MAX4O) ; Eicosapentaenoic Acid (AAN7QOV9EA)
Language	English
Publishing date	2019-04-01
Publishing country	Netherlands
Document type	Evaluation Studies ; Journal Article
ZDB-ID	1143210-x
ISSN	1532-3080 ; 0960-9776
ISSN (online)	1532-3080
ISSN	0960-9776
DOI	10.1016/j.breast.2019.04.001
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Article: DHA Effect on Chemotherapy-Induced Body Weight Loss: An Exploratory Study in a Rodent Model of Mammary Tumors

Hajjaji, Nawale / Couet, Charles / Besson, Pierre / Bougnoux, Philippe

Nutrition and cancer. 2012 Oct. 1, v. 64, no. 7

2012

Abstract: Body weight loss during the course of cancer disease has been associated with poor prognosis. Beside cancer-associated cachexia, weight loss can also result from chemotherapy. This work explored whether a model of mammary tumors in female Sprague Dawley ... ...

Abstract	Body weight loss during the course of cancer disease has been associated with poor prognosis. Beside cancer-associated cachexia, weight loss can also result from chemotherapy. This work explored whether a model of mammary tumors in female Sprague Dawley rats could be appropriate to study the effect of doxorubicin on body weight, described weight change in this model, and assessed the effect of DHA on weight during chemotherapy. After tumor induction, rats were randomly assigned to a control or a DHA-enriched diet, and treated with doxorubicin or placebo twice a week for 2.5 wk (n = 6 in each group). Body weight, food intake, and tumor growth were monitored. Neither the induction of tumors nor their initial development impaired body weight gain. No reduction in food intake was observed. Tumor growth was similar between groups from day 1 to day 11. Although doxorubicin induced body weight loss from day 4 compared to placebo (P< 0.01) in rats fed the control diet, it did not induce body weight loss in rats fed the DHA-enriched diet (P = 0.02), indicating that DHA had a protective effect. These results indicate that doxorubicin can induce body weight loss in this model and that a DHA-enriched diet can prevent this effect.
Keywords	cachexia ; chemotherapy ; doxorubicin ; food intake ; mammary neoplasms (animal) ; models ; prognosis ; protective effect ; rats ; weight gain ; weight loss
Language	English
Dates of publication	2012-1001
Size	p. 1000-1007.
Publishing place	Taylor & Francis Group
Document type	Article
ZDB-ID	2025822-7
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2012.714832
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