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https://www.readbyqxmd.com/read/30342077/successful-intracranial-delivery-of-trastuzumab-by-gene-therapy-for-treatment-of-her2-positive-breast-cancer-brain-metastases
#1
Inbal Zafir-Lavie, Shay Sherbo, Haim Goltsman, Felix Badinter, Eilam Yieni, Paula Ofek, Reem Miari, Osnat Tal, Atar Liran, Tamar Shatil, Simi Krispel, Nir Shapir, Garry A Neil, Itai Benhar, Amos Panet, Ronit Satchi Fainaro
BACKGROUND: Trastuzumab is a monoclonal antibody which demonstrates efficacy for HER2 positive breast cancer patients. Recently, an increased incidence of brain metastasis in trastuzumab-treated patients has been reported. The reason for this may be the effectiveness of systemic trastuzumab allowing patients to survive longer thus providing time for brain metastases to develop, along with the lack of penetration of systemic therapies through the blood brain barrier. In recent years, several administration routes to the brain have been evaluated...
October 17, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30341914/cyclooxygenase-2-in-cancer-a-review
#2
REVIEW
Nasser Hashemi Goradel, Masoud Najafi, Eniseh Salehi, Bagher Farhood, Keywan Mortezaee
Cyclooxygenase-2 (COX-2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo- and radiotherapy. COX-2 is released by cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells...
October 20, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30341066/tgf%C3%AE-activated-usp27x-deubiquitinase-regulates-cell-migration-and-chemoresistance-via-stabilization-of-snail1
#3
Guillem Lambies, Martina Miceli, Catalina Martínez-Guillamon, Ruben Olivera-Salguero, Raúl Peña, Carolina-Paola Frías, Irene Calderón, Boyko S Atanassov, Sharon Y R Dent, Joaquin Arribas, Antonio García de Herreros, Víctor M Díaz
In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability...
October 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/30333912/mitochondria-as-oncotarget-a-comparison-between-the-tetracycline-analogs-doxycycline-and-col-3
#4
Margherita Protasoni, Albert M Kroon, Jan-Willem Taanman
Tetracyclines have anticancer properties in addition to their well-known antibacterial properties. It has been proposed that tetracyclines slow metastasis and angiogenesis through inhibition of matrix metalloproteinases. However, we believe that the anticancer effect of tetracyclines is due to their inhibition of mitochondrial protein synthesis, resulting in a decrease of the mitochondrial energy generating capacity. Several groups have developed analogs that are void of antibacterial action. An example is COL-3, which is currently tested for its anticancer effects in clinical trials...
September 18, 2018: Oncotarget
https://www.readbyqxmd.com/read/30333314/molecular-mechanisms-of-il-33-mediated-stromal-interactions-in-cancer-metastasis
#5
Patrik Andersson, Yunlong Yang, Kayoko Hosaka, Yin Zhang, Carina Fischer, Harald Braun, Shuzhen Liu, Guohua Yu, Shihai Liu, Rudi Beyaert, Mayland Chang, Qi Li, Yihai Cao
Molecular mechanisms underlying the cancer stroma in metastasis need further exploration. Here, we discovered that cancer-associated fibroblasts (CAFs) produced high levels of IL-33 that acted on tumor-associated macrophages (TAMs), causing them to undergo the M1 to M2 transition. Genomic profiling of metastasis-related genes in the IL-33-stimulated TAMs showed a >200-fold increase of MMP9. Signaling analysis demonstrated the IL-33-ST2-NF-κB-MMP9-laminin pathway that governed tumor stroma-mediated metastasis...
October 18, 2018: JCI Insight
https://www.readbyqxmd.com/read/30323895/ssecks-akap12-suppresses-metastatic-melanoma-lung-colonization-by-attenuating-src-mediated-pre-metastatic-niche-crosstalk
#6
Masashi Muramatsu, Shin Akakura, Lingqiu Gao, Jennifer Peresie, Benjamin Balderman, Irwin H Gelman
SSeCKS/Gravin/AKAP12 (SSeCKS) controls metastasis-associated PKC and Src signaling through direct scaffolding activity. SSeCKS is downregulated in the metastases of many human cancer types, and its forced re-expression suppresses the metastatic behavior of prostate cancer cells. SSeCKS is also downregulated in breast and prostate cancer stroma, and SSeCKS-null mice (KO) are metastasis-prone, suggesting a role in suppressing formation of the pre-metastatic niche. Here, we show that lung colonization and metastasis formation by B16F10 and SM1WT1[ Braf V600E ] mouse melanoma cells is 9-fold higher in syngeneic KO compared to WT hosts, although there is no difference in orthotopic tumor volumes...
September 11, 2018: Oncotarget
https://www.readbyqxmd.com/read/30323586/prior-anti-cafs-break-down-the-cafs-barrier-and-improve-accumulation-of-docetaxel-micelles-in-tumor
#7
Ning Pang, Ji Li, Aning Sun, Zhenzhen Yang, Shixuan Cheng, Xian-Rong Qi
Background: Abnormal expression of stromal cells and extracellular matrix in tumor stroma creates a tight barrier, leading to insufficient extravasation and penetration of therapeutic agents. Cancer-associated fibroblasts (CAFs) take on pivotal roles encouraging tumor progression. Method: To surmount the refractoriness of stroma, we constructed a multi-targeting combined scenario of anti-CAFs agent tranilast and antitumor agent docetaxel micelles (DTX-Ms). Tranilast cut down crosstalk between tumor cells and stromal cells, ameliorated the tumor microenvironment, and enhanced the antiproliferation efficacy of DTX-Ms on cancer cells...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30321496/fgf-represses-metastasis-of-neuroblastoma-regulated-by-mycn-and-tgf-%C3%AE-1-induced-lmo1-via-control-of-let-7-expression
#8
Xiao-Hui Wang, Hai-Ying Wu, Jian Gao, Xu-Hui Wang, Tian-Hui Gao, Shu-Feng Zhang
BACKGROUND: MYCN and LMO1 amplification are commonly observed in neuroblastoma (NB), which was often accompanied by genetic loss of let-7 microRNA (miRNA). Fibroblast growth factor (FGF) was found to regulate let-7 miRNA expression via FGF receptor substrate 2 (FRS2), which then activates transforming growth factor beta (TGF-β) signaling. METHODS: Expression of MYCN, LMO1, FRS2, let-7, and TGF-β receptor I (TGFβRI) was selectively knocked-down or enhanced in NB cells...
October 12, 2018: Brain Research
https://www.readbyqxmd.com/read/30319254/cationic-graphene-oxide-nanoplatform-mediates-mir-101-delivery-to-promote-apoptosis-by-regulating-autophagy-and-stress
#9
Akram Assali, Omid Akhavan, Fatemeh Mottaghitalab, Mohsen Adeli, Rassoul Dinarvand, Shayan Razzazan, Ehsan Arefian, Masoud Soleimani, Fatemeh Atyabi
Introduction: MicroRNA-101 (miR-101) is an intense cancer suppressor with special algorithm to target a wide range of pathways and genes which indicates the ability to regulate apoptosis, cellular stress, metastasis, autophagy, and tumor growth. Silencing of some genes such as Stathmin1 with miR-101 can be interpreted as apoptotic accelerator and autophagy suppressor. It is hypothesized that hybrid microRNA (miRNA) delivery structures based on cationized graphene oxide (GO) could take superiority of targeting and photothermal therapy to suppress the cancer cells...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30317612/contribution-of-regulatory-t-cells-to-cancer-a-review
#10
REVIEW
Masoud Najafi, Bagher Farhood, Keywan Mortezaee
Regulatory T cells (Tregs) represent a low number of T-cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross-talks with other immunosuppressive cells including cancer-associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid-derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells...
October 14, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30317122/obesity-activated-adipose-derived-stromal-cells-promote-breast-cancer-growth-and-invasion
#11
Lauren E Hillers, Joseph V D'Amato, Tamara Chamberlin, Gretchen Paderta, Lisa M Arendt
Obese women diagnosed with breast cancer have an increased risk for metastasis, and the underlying mechanisms are not well established. Within the mammary gland, adipose-derived stromal cells (ASCs) are heterogeneous cells with the capacity to differentiate into multiple mesenchymal lineages. To study the effects of obesity on ASCs, mice were fed a control diet (CD) or high-fat diet (HFD) to induce obesity, and ASCs were isolated from the mammary glands of lean and obese mice. We observed that obesity increased ASCs proliferation, decreased differentiation potential, and upregulated expression of α-smooth muscle actin, a marker of activated fibroblasts, compared to ASCs from lean mice...
October 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/30288114/multidisciplinary-therapy-for-scirrhous-gastric-cancer-a-retrospective-analysis-and-proposal-of-new-treatment-strategy
#12
Sachio Fushida, Jun Kinoshita, Katsunobu Oyama, Takashi Fujimura, Tomoya Tsukada, Takahisa Yamaguchi, Itasu Ninomiya, Tetsuo Ohta
Background: Scirrhous gastric cancer (SGC) is highly invasive and metastatic because of its interactions with stromal cells, such as fibroblasts and macrophages, and extracellular matrix, leading to a higher incidence of peritoneal metastasis (PM) than other gastric cancers (GCs). Taxane-based intraperitoneal chemotherapy (IPC) is a promising therapy for PM. We retrospectively analyzed outcomes of multidisciplinary therapies that included IPC for SGC. Patients and therapy: Of 1,679 GC patients treated between 1990 and 2012, we analyzed 119 patients who underwent multidisciplinary therapy for SGC...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/30279173/remodeling-of-the-collagen-matrix-in-aging-skin-promotes-melanoma-metastasis-and-affects-immune-cell-motility
#13
Amanpreet Kaur, Brett L Ecker, Stephen M Douglass, Curtis H Kugel, Marie R Webster, Filipe V Almeida, Rajasekharan Somasundaram, James Hayden, Ehsan Ban, Hossein Ahmadzadeh, Janusz Franco-Barraza, Neelima Shah, Ian A Mellis, Frederick Keeney, Andrew Kossenkov, Hsin-Yao Tang, Xiangfan Yin, Qin Liu, Xiaowei Xu, Mitchell Fane, Patricia Brafford, Meenhard Herlyn, David W Speicher, Jennifer A Wargo, Michael T Tetzlaff, Lauren E Haydu, Arjun Raj, Vivek Shenoy, Edna Cukierman, Ashani T Weeraratna
Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited metastasis in an aged microenvironment, in 3D skin reconstruction models, and in vivo...
October 2, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30279172/age-related-changes-in-hapln1-increase-lymphatic-permeability-and-affect-routes-of-melanoma-metastasis
#14
Brett L Ecker, Amanpreet Kaur, Stephen M Douglass, Marie R Webster, Filipe V Almeida, Gloria Marino, Andrew J Sinnamon, Madalyn G Neuwirth, Gretchen M Alicea, Abibatou Ndoye, Mitchell Fane, Xiaowei Xu, Myung Shin Sim, Gary B Deutsch, Mark B Faries, Giorgos C Karakousis, Ashani T Weeraratna
Older melanoma patients have lower rates of sentinel lymph node (LN) metastases yet paradoxically have inferior survival. Patient age correlated with an inability to retain Technetium radiotracer during sentinel LN biopsy in over 1000 patients, and high technecium counts correlated to better survival. We hypothesized that loss of integrity in the lymphatic vasculature due to ECM degradation might play a role. We have implicated HAPLN1 in age-dependent ECM degradation in the dermis. Here we queried whether HAPLN1 could be altered in the lymphatic ECM...
October 2, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30275181/color-coded-imaging-of-the-circulating-tumor-cell-microenvironment
#15
Tomoyuki Satake, Atsushi Suetsugu, Miki Nakamura, Takahiro Kunisada, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M Hoffman
BACKGROUND/AIM: Circulating tumor cells (CTCs) may initiate metastasis. Some studies show that the number of CTCs and existence of CTC clusters can be prognostic. In the present study, our color-coded imaging nude mouse model of metastatic lymphoma was utilized to investigate the microenvironment of CTC clusters using fluorescent-protein imaging. MATERIALS AND METHODS: EL-4 mouse lymphoma cells expressing red fluorescent protein (RFP) were injected into the spleen of transgenic C57B/6-green fluorescent protein (GFP) mice...
October 2018: Anticancer Research
https://www.readbyqxmd.com/read/30267883/directing-fibroblast-self-assembly-to-fabricate-highly-aligned-collagen-rich-matrices
#16
Benjamin T Wilks, Elisabeth B Evans, Morcos N Nakhla, Jeffrey R Morgan
Extracellular matrix composition and organization play a crucial role in numerous biological processes ranging from cell migration, differentiation, survival and metastasis. Consequently, there have been significant efforts towards the development of biomaterials and in vitro models that recapitulate the complexity of native tissue architecture. Here, we demonstrate an approach to fabricating highly aligned cell-derived tissue constructs via the self-assembly of human dermal fibroblasts. By optimizing mold geometry, cell seeding density, and media composition we can direct human dermal fibroblasts to adhere to one another around a non-adhesive agarose peg to facilitate the development of cell-mediated circumferential tension...
September 26, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/30263873/human-adipose-derived-stem-cell-conditioned-media-and-exosomes-containing-malat1-promote-human-dermal-fibroblast-migration-and-ischemic-wound-healing
#17
Denise R Cooper, Chunyan Wang, Rehka Patel, Andrea Trujillo, Niketa A Patel, Jamie Prather, Lisa J Gould, Mack H Wu
Objective: Chronically ill patients heal recalcitrant ulcerative wounds more slowly. Human adipose-derived stem cells (hADSCs) play an important role in tissue regeneration and exosomes secreted by hADSC contribute to their paracrine signaling. In addition to cytokines, lipids and growth factors, hADSC secrete mRNA, miRNA, and long noncoding (lnc) RNA into exosomes. In this study we examined the role of lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), an abundant lncRNA in exosomes from conditioned media (CM), on cell migration and ischemic wound healing...
September 1, 2018: Advances in Wound Care
https://www.readbyqxmd.com/read/30257985/cd151-regulates-expression-of-fgfr2-in-breast-cancer-cells-via-pkc-dependent-pathways
#18
Rafal Sadej, Xiaohong Lu, Lukasz Turczyk, Vera Novitskaya, Andrea F Lopez-Clavijo, Radzisław Kordek, Piotr Potemski, Michael J O Wakelam, Hanna Romanska, Fedor Berditchevski
Expression of the tetraspanin CD151 is frequently upregulated in epithelial malignancies and correlates with poor prognosis. Here we report that CD151 is involved in regulation of the expression of fibroblast growth factor receptor 2 (FGFR2). Depletion of CD151 in breast cancer cells resulted in an increased level of FGFR2. Accordingly, an inverse correlation between CD151 and FGFR2 was observed in breast cancer tissues. CD151-dependent regulation of the FGFR2 expression relies on post-transcriptional mechanisms involving HuR/ELAVL1, a multifunctional RNA binding protein, and the assembly of processing bodies (P-bodies)...
September 26, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/30254454/podoplanin-positive-cancer-associated-fibroblasts-predict-poor-prognosis-in-lung-cancer-patients
#19
Guoming Hu, Kefang Zhong, Wei Chen, Shimin Wang, Liming Huang
Background: Cancer-associated fibroblasts (CAFs) are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin-positive CAFs in human lung cancer still remains controversial. Methods: Herein, we performed a meta-analysis including 12 published studies with 1,802 patients identified from PubMed and EBSCO to assess the prognostic impact of podoplanin-positive CAFs in lung cancer patients...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/30243489/cancer-associated-fibroblasts-contribute-to-oral-cancer-cells-proliferation-and-metastasis-via-exosome-mediated-paracrine-mir-34a-5p
#20
Yao-Yin Li, Yi-Wei Tao, Shuo Gao, Pei Li, Jian-Mao Zheng, Si-En Zhang, Jianfeng Liang, Yuejiao Zhang
BACKGROUND: Cancer-associated fibroblasts (CAFs) play an important role in regulating tumor progression by transferring exosomes to neighboring cells. Our aim was to clarify the role of microRNA encapsulated in the exosomes derived from CAFs in oral squamous cell carcinoma (OSCC). METHODS: We examined the microRNA expression profiles of exosomes derived from CAFs and donor-matched normal fibroblasts (NFs) from patients with OSCC. We used confocal microscopy to examine the transportation of exosomal miR-34a-5p between CAFs and OSCC cells...
September 19, 2018: EBioMedicine
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