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drug resistant AND tumor

Seyedeh Alia Moosavian, Amirhossein Sahebkar
Accumulation of chemotherapeutic agents in the tumor tissue while reducing adverse effects and drug resistance are among the major goals in cancer therapy. Among nanocarriers, liposomes have been found to be more effective in the passive targeting of cancer cells. A promising recent development in targeted drug delivery is the use of aptamer-functionalized liposomes for cancer therapy. Aptamer-targeted liposomes have enhanced uptake in tumor cells as shown in vitro and in vivo. Here, we discuss the aptamer-functionalized liposome platforms and review functionalization approaches as well as the factors affecting antitumor efficiency of aptamer-targeted liposomal systems...
February 11, 2019: Cancer Letters
Di Jiang, Minjun Xu, Yuanyuan Pei, Yukun Huang, Yu Chen, Fenfen Ma, Huiping Lu, Jun Chen
Emergence of drug resistance in tumors causes therapeutic failure or tumor relapse. Combination of chemotherapy and photodynamic therapy holds significant promise to treat drug-resistant tumors. However, stubborn hydrophobicity of photosensitizer (PS), low encapsulation efficiency and leaking problem of PS in organic carrier, and disparate physicochemical properties of PS and chemotherapeutics make the combination unachievable. Thus how to efficiently co-deliver the two functional agents to enable photo-chemotherapy seems to be one of the key challenges...
February 11, 2019: Acta Biomaterialia
A Pompella, A Corti
No abstract text is available yet for this article.
July 2018: Journal of Biological Regulators and Homeostatic Agents
Ingeborg E de Kruijff, Anieta M Sieuwerts, Wendy Onstenk, Agnes Jager, Paul Hamberg, Felix E de Jongh, Marcel Smid, J Kraan, Mieke A Timmermans, John W M Martens, Stefan Sleijfer
The androgen receptor (AR) has potential clinical relevance in metastatic breast cancer (mBC) since it might be a treatment target and has been associated with endocrine resistance. A minimal-invasive way to determine AR expression on metastatic tumor cells is by characterization of circulating tumor cells (CTCs). Here, we assessed AR mRNA expression in CTCs (CTC-AR) and in matched primary tumor samples from mBC patients representing different breast cancer subtypes. In addition, we explored CTC-AR-status in relation to outcome on endocrine therapy...
February 13, 2019: International Journal of Cancer. Journal International du Cancer
Sam Donche, Jeroen Verhoeven, Benedicte Descamps, Julie Bolcaen, Karel Deblaere, Tom Boterberg, Caroline Van den Broecke, Christian Vanhove, Ingeborg Goethals
Glioblastoma is the most aggressive and malignant primary brain tumor in adults. Despite the current state-of-the-art treatment, which consists of maximal surgical resection followed by radiation therapy, concomitant, and adjuvant chemotherapy, progression remains rapid due to aggressive tumor characteristics. Several new therapeutic targets have been investigated using chemotherapeutics and targeted molecular drugs, however, the intrinsic resistance to induced cell death of brain cells impede the effectiveness of systemic therapies...
2019: Frontiers in Medicine
Vincenzo Carafa, Lucia Altucci, Angela Nebbioso
Sirtuins (SIRTs), class III histone deacetylases, are differentially expressed in several human cancers, where they display both oncogenic and tumor-suppressive properties depending on cellular context and experimental conditions. SIRTs are involved in many important biological processes and play a critical role in cancer initiation, promotion, and progression. A growing body of evidence indicates the involvement of SIRTs in regulating three important tumor processes: epithelial-to-mesenchymal transition (EMT), invasion, and metastasis...
2019: Frontiers in Pharmacology
Pengfei Liu, Yuchen Xiang, Xuewen Liu, Te Zhang, Rui Yang, Sen Chen, Li Xu, Qingqing Yu, Huzi Zhao, Liang Zhang, Ying Liu, Yuan Si
Non-small cell lung cancer (NSCLC) patients carrying an epidermal growth factor receptor (EGFR) mutation are initially sensitive to EGFR-tyrosine kinase inhibitors (TKIs) treatment, but soon develop an acquired resistance. The treatment effect of EGFR-TKIs-resistant NSCLC patients still faces challenges. Cucurbitacin B (CuB), a triterpene hydrocarbon compound isolated from plants of various families and genera, elicits anticancer effects in a variety of cancer types. However, whether CuB is a viable treatment option for gefitinib-resistant (GR) NSCLC remains unclear...
February 12, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Nazanin Rohani, Liangliang Hao, Maria S Alexis, Brian A Joughin, Konstantin Krismer, Mira N Moufarrej, Anthony R Soltis, Douglas A Lauffenburger, Michael B Yaffe, Christopher B Burge, Sangeeta N Bhatia, Frank B Gertler
Acidosis is a fundamental feature of the tumor microenvironment that directly regulates tumor cell invasion by affecting immune cell function, clonal cell evolution, and drug resistance. Despite the important association of tumor microenvironment acidosis with tumor cell invasion, relatively little is known regarding which areas within a tumor are acidic and how acidosis influences gene expression to promote invasion. Here we injected a labeled pH-responsive peptide to mark acidic regions within tumors. Surprisingly, acidic regions were not restricted to hypoxic areas and overlapped with highly proliferative, invasive regions at the tumor-stroma interface, which were marked by increased expression of matrix metalloproteinases and degradation of the basement membrane...
February 12, 2019: Cancer Research
Anna Visa, Marta C Sallán, Oscar Maiques, Lía Alza, Elisabet Talavera, Ricard López-Ortega, Maria Santacana, Judit Herreros, Carles Cantí
T-type Ca2+ channels (TTCC) have been identified as key regulators of cancer cell cycle and survival. In vivo studies in glioblastoma (GBM) murine xenografts have shown that drugs able to block TTCC in vitro (such as tetralol derivatives mibefradil/NNC-55-096, or different 3,4-dihydroquinazolines) slow tumor progression. However, currently available TTCC pharmacological blockers have limited selectivity for TTCC, and are unable to distinguish between TTCC isoforms. Here we analyzed the expression of TTCC transcripts in human GBM cells and show a prevalence of Cav3...
February 12, 2019: Cancer Research
Miro K Viitala, Reetta Virtakoivu, Sina Tadayon, Jenna Rannikko, Sirpa Jalkanen, Maija Hollmén
PURPOSE: As foremost regulators of cancer-related inflammation and immunotherapeutic resistance, tumor-associated macrophages have garnered major interest as immunotherapeutic drug targets. However, depletory strategies have yielded little benefit in clinical studies to date. An alternative approach is to exploit macrophage plasticity and "reeducate" tumorigenic macrophages towards an immunostimulatory phenotype to activate the host's antitumor immunity. EXPERIMENTAL DESIGN: We investigated the role of macrophage scavenger receptor Clever-1 on tumor growth in multiple mouse cancer models with inflammatory and non-inflammatory characteristics by using conditional knockouts, bone marrow chimeras and cell depletion experiments...
February 12, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Wipa Chantarawong, Supakarn Chamni, Khanit Suwanborirux, Naoki Saito, Pithi Chanvorachote
Lung cancer is one of the most significant cancers as it accounts for almost 1 in 5 cancer deaths worldwide, with an increasing incident rate. Management of the cancer has been shown to frequently fail due to the ability of the cancer cells to resist therapy as well as metastasis. Recent evidence has suggested that the poor response to the current treatment drugs and the ability to undergo metastasis are driven by cancer stem cells (CSCs) within the tumor. The discovery of novel compounds able to suppress CSCs and sensitize the chemotherapeutic response could be beneficial to the improvement of clinical outcomes...
February 11, 2019: Marine Drugs
Tian Tian, Xiaoyi Li, Jinhua Zhang
The mammalian or mechanistic target of rapamycin (mTOR) pathway plays a crucial role in regulation of cell survival, metabolism, growth and protein synthesis in response to upstream signals in both normal physiological and pathological conditions, especially in cancer. Aberrant mTOR signaling resulting from genetic alterations from different levels of the signal cascade is commonly observed in various types of cancers. Upon hyperactivation, mTOR signaling promotes cell proliferation and metabolism that contribute to tumor initiation and progression...
February 11, 2019: International Journal of Molecular Sciences
Tuba N Gide, Camelia Quek, Alexander M Menzies, Annie T Tasker, Ping Shang, Jeff Holst, Jason Madore, Su Yin Lim, Rebecca Velickovic, Matthew Wongchenko, Yibing Yan, Serigne Lo, Matteo S Carlino, Alexander Guminski, Robyn P M Saw, Angel Pang, Helen M McGuire, Umaimainthan Palendira, John F Thompson, Helen Rizos, Ines Pires da Silva, Marcel Batten, Richard A Scolyer, Georgina V Long, James S Wilmott
Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments...
February 11, 2019: Cancer Cell
Asma Begum, Ross H McMillan, Yu-Tai Chang, Vesselin R Penchev, N V Rajeshkumar, Anirban Maitra, Michael G Goggins, James R Eshelman, Christopher L Wolfgang, Zeshaan A Rasheed, William Matsui
OBJECTIVE: Cancer-associated fibroblasts (CAFs) play an important role in the progression of pancreatic ductal adenocarcinoma (PDAC) by promoting tumor cell migration and drug resistance. We determined the impact of CAFs on PDAC cancer stem cells (CSCs). METHODS: Fibroblast cell lines from patients' tumors were cocultured with PDAC cells and examined for clonogenic growth and self-renewal using colony-forming assays and migration in vitro. Changes in the frequency of CSCs was determined by flow cytometry...
February 8, 2019: Pancreas
Malgorzata Maj, Anna Kokocha, Anna Bajek, Tomasz Drewa
Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. They are also considered as a preferred cell source for urinary tract reconstruction. However, as MSCs exhibit affinity to tumor microenvironment, possible activation of tumor-initiating cells remains a major concern in the application of stem cell-based therapies for patients with a bladder cancer history. To analyze the influence of adipose-derived stem cells (ASCs) on bladder cancer cells with stem cell-like properties, we isolated CD133-positive bladder cancer cells and cultured them in conditioned medium from ASCs (ASC-CM)...
February 11, 2019: Journal of Cellular Biochemistry
Zhuoying Wang, Chongren Wang, Dongqing Zuo, Tao Zhang, Fei Yin, Zifei Zhou, Hongsheng Wang, Jing Xu, Min Mao, Gangyang Wang, Yingqi Hua, Wei Sun, Zhengdong Cai
Osteosarcoma (OS) is the most common primary bone malignancy in adolescents. One major obstacle for current OS treatment is drug-resistance. Raddeanin A (RA), an oleanane-type triterpenoid saponin, exerts anti-tumor effects in several tumor models, but the effect of RA in human drug-resistant OS remained to be elucidated. In the present study, we investigated the anti-tumor effects of RA in both drug-sensitive and drug-resistant OS cells and its underlying mechanism. RA inhibited cell proliferation and colony formation and induced apoptotic cell death in a dose-dependent manner in both drug-sensitive and drug-resistant cells...
2019: International Journal of Biological Sciences
Yanhui Liu, Pingchong Lei, Hong Qiao, Kai Sun, Xiling Lu, Fengchang Bao, Runhong Yu, Cheng Lian, Yao Li, Wei Chen, Fei Xue
Daunorubicin (Dnr) is at the forefront of acute myeloid leukemia (AML) therapy, but drug resistance poses a major threat to treatment success. MicroRNA (miR)-9 has been shown to have a pivotal role in AML development. However, little is known about the role of miR-9 in Dnr resistance in AML. We explored the potential role of miR-9 in Dnr resistance in AML cells and its mechanism of action. AML cell lines with high half-maximal inhibitory concentration to Dnr in vivo had significantly low miR-9 expression. miR-9 overexpresssion sensitized AML cells to Dnr, inhibited cell proliferation, and enhanced the ability of Dnr to induce apoptosis; miR-9 knockdown had the opposite effects...
2019: International Journal of Biological Sciences
Yinjie Su, Weiping Yang, Ning Jiang, Juanyi Shi, Luping Chen, Guangzheng Zhong, Junming Bi, Wei Dong, Qiong Wang, Chunhui Wang, Tianxin Lin
Hypoxia plays a critical role in cancer biology. It induces genomic instability, which in turn helps cancer cells respond adaptively to meet the needs of carcinogenesis, cancer progression and relapse. Circular RNA has not been reported among the variety of downstream factors in this adaptive response. Although a few studies have demonstrated the important role of circular RNAs in driving human bladder cancer progression, their carcinogenic roles are still under investigated. Here, we identified a hypoxia-elevated circular RNA, circELP3, that contributes to bladder cancer progression and cisplatin resistance...
2019: International Journal of Biological Sciences
Jixian Xiong, Shaoxiang Wang, Tie Chen, Xingsheng Shu, Xianming Mo, Gang Chang, Jia-Jie Chen, Chenyang Li, Hui Luo, Jiing-Dwan Lee
Gastric cancer stem cell (GCSC) is implicated in gastric cancer relapse, metastasis and drug resistance. However, the key molecule(s) involved in GCSC survival and the targeting drugs are poorly understood. We discovered increased secreted clusterin (S-Clu) protein expression during the sphere-forming growth of GCSC via mass spectrometry. Overexpression of clusterin was detected in 69/90 (77%) of primary GC tissues and significantly associated with T stage, lymph node metastasis and TNM stage. Depletion of clusterin (Clu, the full-length intracellular clusterin) led to the declustering of GCSC tumorspheres and apoptosis of GCSC...
2019: International Journal of Biological Sciences
Guillaume Rieunier, Xiaoning Wu, Valentine M Macaulay, Adrian V Lee, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Bone metastases are a frequent complication of cancer that are associated with considerable morbidity. Current treatments may temporarily palliate the symptoms of bone metastases, but often fail to delay their progression. Bones provide a permissive environment because they are characterized by dynamic turnover, secreting factors required for bone maintenance but also stimulating the establishment and growth of metastases. Insulin-like growth factors (IGFs) are the most abundant growth factors in bone and are required for normal skeletal development and function...
February 11, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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