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https://www.readbyqxmd.com/read/29774126/autophagy-deficient-breast-cancer-shows-early-tumor-recurrence-and-escape-from-dormancy
#1
Hussein F Aqbi, Liliya Tyutyunyk-Massey, Rebecca C Keim, Savannah E Butler, Theresa Thekkudan, Supriya Joshi, Timothy M Smith, Dipankar Bandyopadhyay, Michael O Idowu, Harry D Bear, Kyle K Payne, David A Gewirtz, Masoud H Manjili
Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773200/lithium-chloride-attenuates-mitomycin-c-induced-necrotic-cell-death-in-mda-mb-231-breast-cancer-cells-via-hmgb1-and-bax-signaling
#2
Mahdieh Razmi, Azra Rabbani-Chadegani, Fatemeh Hashemi-Niasari, Parinaz Ghadam
The clinical use of potent anticancer drug mitomycin C (MMC) has limited due to side effects and resistance of cancer cells. The aim of this study was to investigate whether lithium chloride (LiCl), as a mood stabilizer, can affect the sensitivity of MDA-MB-231 breast cancer cells to mitomycin C. The cells were exposed to various concentrations of mitomycin C alone and combined with LiCl and the viability determined by trypan blue and MTT assays. Proteins were analyzed by western blot and mRNA expression of HMGB1 MMP9 and Bcl-2 were analyzed by RT-PCR...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29572797/clinical-usefulness-of-the-histoculture-drug-response-assay-for-breast-cancer
#3
Robert M Hoffman, Hirokazu Tanino
The histoculture drug response assay (HDRA) was used to compare drug sensitivity of recurrent and primary breast cancer in vitro as well as in the clinic. The HDRA utilizes 3-dimensional culture of human tumors on Gelfoam® . The evaluation rate was 98.8%. The HDRA mean inhibition rate of primary tumors vs. recurrent tumors was, respectively, 57.9% and 38.6% for doxorubicin (DOX); 59.9% and 42.8% for mitomycin C (MMC); 49.0% and 33.4% for 5-fluorouracil (5-FU); and 34.5% and 16.0% for cisplatinum (CDDP). The recurrent cases were pretreated clinically with CAF (cyclophosphamide [CTX], DOX, and 5-FU), CEF (CTX, epirubicin [EPN], and 5-FU), or CMF (CTX, methotrexate [MTX], and 5-FU)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29231814/a-homozygous-fancm-mutation-underlies-a-familial-case-of-non-syndromic-primary-ovarian-insufficiency
#4
Baptiste Fouquet, Patrycja Pawlikowska, Sandrine Caburet, Celine Guigon, Marika Mäkinen, Laura Tanner, Marja Hietala, Kaja Urbanska, Laura Bellutti, Bérangère Legois, Bettina Bessieres, Alain Gougeon, Alexandra Benachi, Gabriel Livera, Filippo Rosselli, Reiner A Veitia, Micheline Misrahi
Primary Ovarian Insufficiency (POI) affects ~1% of women under forty. Exome sequencing of two Finnish sisters with non-syndromic POI revealed a homozygous mutation in FANCM, leading to a truncated protein (p.Gln1701*). FANCM is a DNA-damage response gene whose heterozygous mutations predispose to breast cancer. Compared to the mother's cells, the patients' lymphocytes displayed higher levels of basal and mitomycin C (MMC)-induced chromosomal abnormalities. Their lymphoblasts were hypersensitive to MMC and MMC-induced monoubiquitination of FANCD2 was impaired...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29053672/sample-extraction-and-simultaneous-chromatographic-quantitation-of-doxorubicin-and-mitomycin-c-following-drug-combination-delivery-in-nanoparticles-to-tumor-bearing-mice
#5
Rui Xue Zhang, Tian Zhang, King Chen, Ji Cheng, Paris Lai, Andrew M Rauth, K Sandy Pang, Xiao Yu Wu
Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28959140/curcumin-reduces-mitomycin-c-resistance-in-breast-cancer-stem-cells-by-regulating-bcl-2-family-mediated-apoptosis
#6
Qian-Mei Zhou, Yang Sun, Yi-Yu Lu, Hui Zhang, Qi-Long Chen, Shi-Bing Su
BACKGROUND: Curcumin, a natural compound derived from the turmeric rhizome Curcuma longa Linn, has anticancer and chemoresistance reduction biological activities. We evaluated the efficacy of curcumin in sensitizing chemotherapy drugs through regulation of Bcl-2-mediated apoptosis in breast cancer stem-like cells (BCSCs). METHODS: Cell survival was measured using MTT assay. Apoptosis-related proteins were observed using western blot analysis. Apoptosis was detected with flow cytometric analysis and by Hoechst 33258 staining...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28216624/dual-targeted-hybrid-nanoparticles-of-synergistic-drugs-for-treating-lung-metastases-of-triple-negative-breast-cancer-in-mice
#7
Tian Zhang, Preethy Prasad, Ping Cai, Chunsheng He, Dan Shan, Andrew Michael Rauth, Xiao Yu Wu
Lung metastasis is the major cause of death in patients with triple negative breast cancer (TNBC), an aggressive subtype of breast cancer with no effective therapy at present. It has been proposed that dual-targeted therapy, ie, targeting chemotherapeutic agents to both tumor vasculature and cancer cells, may offer some advantages. The present work was aimed to develop a dual-targeted synergistic drug combination nanomedicine for the treatment of lung metastases of TNBC. Thus, Arg-Gly-Asp peptide (RGD)-conjugated, doxorubicin (DOX) and mitomycin C (MMC) co-loaded polymer-lipid hybrid nanoparticles (RGD-DMPLN) were prepared and characterized...
June 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27793948/clinical-significance-of-the-histoculture-drug-response-assay-in-breast-cancer
#8
Yoshiaki Shinden, Yuko Kijima, Munetsugu Hirata, Hideo Arima, Akihiro Nakajyo, Kiyonori Tanoue, Kosei Maemura, Shoji Natsugoe
BACKGROUND/AIM: Despite the fact that breast cancer patients are generally administered systemic chemotherapy after surgical treatment, predictive factors that allow optimization of chemotherapy are needed. The histoculture drug response assay (HDRA) is a clinically practical in vitro drug-response assay for identifying optimal anticancer agents. PATIENTS AND METHODS: Thirty-eight primary breast cancer patients who underwent surgical treatment without receiving systemic neoadjuvant therapy were analyzed...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27721762/combination-chemotherapy-of-mitomycin-c-and-methotrexate-was-effective-on-metastatic-breast-cancer-resistant-to-eribulin-vinorelbine-and-bevacizumab-after-anthracycline-taxane-and-capecitabine
#9
Masahiko Tanabe
Complete cure of metastatic breast cancer (MBC) is still considered difficult even after the development of new drugs. While new drugs have been continuously developed, conventional drugs such as mitomycin C (MMC) and methotrexate (MTX) have become less used. Combination chemotherapy with MMC and MTX (MMC/MTX) was reported to be effective for 9.7-19.4% of 31 patients with human epidermal growth factor receptor type 2 (HER2)-negative MBC who were aggressively treated with anthracycline, taxane, capecitabine, and vinorelbine...
May 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27277787/coordination-of-the-recruitment-of-the-fancd2-and-palb2-fanconi-anemia-proteins-by-an-ubiquitin-signaling-network
#10
Gregory Bick, Fan Zhang, A Ruhikanta Meetei, Paul R Andreassen
Fanconi anemia (FA) is a chromosome instability syndrome and the 20 identified FA proteins are organized into two main arms which are thought to function at distinct steps in the repair of DNA interstrand crosslinks (ICLs). These two arms include the upstream FA pathway, which culminates in the monoubiquitination of FANCD2 and FANCI, and downstream breast cancer (BRCA)-associated proteins that interact in protein complexes. How, and whether, these two groups of FA proteins are integrated is unclear. Here, we show that FANCD2 and PALB2, as indicators of the upstream and downstream arms, respectively, colocalize independently of each other in response to DNA damage induced by mitomycin C (MMC)...
June 2017: Chromosoma
https://www.readbyqxmd.com/read/27232881/clinicopathological-characteristics-of-mucinous-breast-cancer-a-retrospective-analysis-of-a-10-year-study
#11
Lei Lei, Xingfei Yu, Bo Chen, Zhanhong Chen, Xiaojia Wang
BACKGROUND: Mucinous breast carcinoma (MC) is a special type of breast cancer that presents with a large amount of extracellular mucin. MC comprises approximately 4% of all invasive breast cancers. This type of tumor has a better prognosis and higher incidence in peri- and post-menopausal patients. Pathologically, there are two main subtypes of MC: pure and mixed. In this study, we describe 10 years of experience with MC at the Zhejiang Cancer Hospital in China, specifically, clinical data, histological findings and immunohistochemical features...
2016: PloS One
https://www.readbyqxmd.com/read/26305906/curcumin-improves-the-tumoricidal-effect-of-mitomycin-c-by-suppressing-abcg2-expression-in-stem-cell-like-breast-cancer-cells
#12
Qianmei Zhou, Meina Ye, Yiyu Lu, Hui Zhang, Qilong Chen, Shuang Huang, Shibing Su
Cancer cells with stem cell-like properties contribute to the development of resistance to chemotherapy and eventually to tumor relapses. The current study investigated the potential of curcumin to reduce breast cancer stem cell (BCSC) population for sensitizing breast cancer cells to mitomycin C (MMC) both in vitro and in vivo. Curcumin improved the sensitivity of paclitaxel, cisplatin, and doxorubicin in breast cancer cell lines MCF-7 and MDA-MB-231, as shown by the more than 2-fold decrease in the half-maximal inhibitory concentration of these chemotherapeutic agents...
2015: PloS One
https://www.readbyqxmd.com/read/26217553/combination-chemotherapy-with-mitomycin-c-and-methotrexate-is-active-against-metastatic-her2-negative-breast-cancer-even-after-treatment-with-anthracycline-taxane-capecitabine-and-vinorelbine
#13
Takayo Fukuda, Masahiko Tanabe, Kokoro Kobayashi, Ippei Fukada, Shunji Takahashi, Takuji Iwase, Yoshinori Ito
BACKGROUND: Combination chemotherapy with mitomycin C and methotrexate (MM) was reported to be effective for 24% of patients with metastatic breast cancer (MBC) who had been treated with anthracycline and taxane. Antimetabolites such as capecitabine and antitubulins such as vinorelbine have been generally used for MBC treatment after anthracycline and taxane. A subsequent choice of chemotherapy should be offered to patients with MBC who have kept good performance status (PS) after being aggressively treated with anthracycline, taxane, capecitabine, and vinorelbine (ATCV), but is not well clear which treatment is superior to others after ATCV...
2015: SpringerPlus
https://www.readbyqxmd.com/read/25885449/yy1-suppresses-fen1-over-expression-and-drug-resistance-in-breast-cancer
#14
Jianwei Wang, Lina Zhou, Zhi Li, Ting Zhang, Wenpeng Liu, Zheng Liu, Yate-Ching Yuan, Fan Su, Lu Xu, Yan Wang, Xiaotong Zhou, Hong Xu, Yuejin Hua, Ying-Jie Wang, Li Zheng, Yue-E Teng, Binghui Shen
BACKGROUND: Drug resistance is a major challenge in cancer therapeutics. Abundant evidence indicates that DNA repair systems are enhanced after repetitive chemotherapeutic treatments, rendering cancers cells drug-resistant. Flap endonuclease 1 (FEN1) plays critical roles in DNA replication and repair and in counteracting replication stress, which is a key mechanism for many chemotherapeutic drugs to kill cancer cells. FEN1 was previously shown to be upregulated in response to DNA damaging agents...
February 13, 2015: BMC Cancer
https://www.readbyqxmd.com/read/25786718/a-novel-nanoparticle-formulation-overcomes-multiple-types-of-membrane-efflux-pumps-in-human-breast-cancer-cells
#15
Preethy Prasad, Ji Cheng, Adam Shuhendler, Andrew M Rauth, Xiao Yu Wu
Multidrug resistance (MDR) in cancer cells can involve overexpression of different types of membrane drug efflux pumps and other drug resistance mechanisms. Hence, inhibition of one resistance mechanism may not be therapeutically effective. Previously we demonstrated a new polymer lipid hybrid nanoparticle (PLN) system was able to circumvent drug resistance of P-glycoprotein (P-gp) overexpressing breast cancer cells. The objectives of the present study were 2-fold: (1) to evaluate the ability of the PLN system to overcome two other membrane efflux pumps-multidrug resistance protein 1 (MRP1+) and breast cancer resistance protein (BCRP+) overexpressed on human breast cancer cell lines MCF7 VP (MRP1+) and MCF7 MX (BCRP+); and (2) to evaluate possible synergistic effects of doxorubicin (Dox)-mitomycin C (MMC) in these cell lines...
April 2012: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/25777376/yy1-suppresses-fen1-over-expression-and-drug-resistance-in-breast-cancer
#16
Jianwei Wang, Lina Zhou, Zhi Li, Ting Zhang, Wenpeng Liu, Zheng Liu, Yate-Ching Yuan, Fan Su, Lu Xu, Yan Wang, Xiaotong Zhou, Hong Xu, Yuejin Hua, Ying-Jie Wang, Li Zheng, Yue-E Teng, Binghui Shen
BACKGROUND: Drug resistance is a major challenge in cancer therapeutics. Abundant evidence indicates that DNA repair systems are enhanced after repetitive chemotherapeutic treatments, rendering cancers cells drug-resistant. Flap endonuclease 1 (FEN1) plays critical roles in DNA replication and repair and in counteracting replication stress, which is a key mechanism for many chemotherapeutic drugs to kill cancer cells. FEN1 was previously shown to be upregulated in response to DNA damaging agents...
2015: BMC Cancer
https://www.readbyqxmd.com/read/25447153/alpha-momorcharin-%C3%AE-mmc-exerts-effective-anti-human-breast-tumor-activities-but-has-a-narrow-therapeutic-window-in-vivo
#17
Dongliang Cao, Yun Sun, Ling Wang, Qianchuan He, Juecun Zheng, Fei Deng, Shanshan Deng, ShuChing Chang, XiaoPing Yu, Minhui Li, Yao Meng, Jiagui Jin, Fubing Shen
Alpha-momorcharin (α-MMC), a ribosome inactivating protein (RIP) extracted from the seeds of Momordica charantia, exerts anti-tumor, antiviral, and anti-fungal activities. However, α-MMC has an obvious toxicity that limits its clinical application. We examined the effect of α-MMC on the inhibition of human breast cancer and assessed its general toxicity to find the therapeutic window in vivo for its potential clinical use. It was purified using column chromatography, and then injected into the xenograft nude mouse model induced by MDA-MB-231 and MCF-7...
January 2015: Fitoterapia
https://www.readbyqxmd.com/read/25226537/synergistic-effect-of-combinatorial-treatment-with-curcumin-and-mitomycin-c-on-the-induction-of-apoptosis-of-breast-cancer-cells-a-cdna-microarray-analysis
#18
Qian-Mei Zhou, Qi-Long Chen, Jia Du, Xiu-Feng Wang, Yi-Yu Lu, Hui Zhang, Shi-Bing Su
In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic mechanisms of combinatorial treatment using curcumin and MMC on the inhibition of tumor growth were explored by differential gene expression profile, gene ontology (GO), ingenuity pathway analysis (IPA) and Signal-Net network analysis...
2014: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/24830351/synergistic-nanoparticulate-drug-combination-overcomes-multidrug-resistance-increases-efficacy-and-reduces-cardiotoxicity-in-a-nonimmunocompromised-breast-tumor-model
#19
Adam J Shuhendler, Preethy Prasad, Rui Xue Zhang, Mohammad Ali Amini, Mei Sun, Peter P Liu, Robert G Bristow, Andrew M Rauth, Xiao Yu Wu
Anthracyclines, commonly employed for cancer chemotherapy, suffer from dose-limiting cardiotoxicity and poor efficacy due to multidrug resistance (MDR). We previously demonstrated that simultaneous delivery of the synergistic drugs doxorubicin (DOX) and mitomycin C (MMC) by polymer-lipid hybrid nanoparticles (PLN) circumvented MDR, increased efficacy, and reduced cardiotoxicity in immuncompromised mice superior to poly(ethylene glycol)-coated (PEGylated) lipososmal DOX (PLD). Herein it is shown that the DOX-MMC combination was also synergistic in MDR EMT6/AR1 murine breast cancer cells and that their nanoparticle formulations were able to overcome the MDR phenotype...
August 4, 2014: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/24789349/the-fanconi-anemia-pathway-sensitizes-to-dna-alkylating-agents-by-inducing-jnk-p53-dependent-mitochondrial-apoptosis-in-breast-cancer-cells
#20
Lin Zhao, Yanlin Li, Miao He, Zhiguo Song, Shu Lin, Zhaojin Yu, Xuefeng Bai, Enhua Wang, Minjie Wei
The Fanconi anemia/BRCA (FA/BRCA) DNA damage repair pathway plays a pivotal role in the cellular response to DNA alkylating agents and greatly influences drug response in cancer treatment. However, the molecular mechanisms underlying the FA/BRCA pathway reversed resistance have received limited attention. In the present study, we investigated the effect of Fanconi anemia complementation group F protein (FANCF), a critical factor of the FA/BRCA pathway, on cancer cell apoptosis induced by DNA alkylating agents such as mitomycin c (MMC)...
July 2014: International Journal of Oncology
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