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https://www.readbyqxmd.com/read/29164052/development-of-novel-patient-derived-xenografts-from-breast-cancer-brain-metastases
#1
María J Contreras-Zárate, D Ryan Ormond, Austin E Gillen, Colton Hanna, Nicole L Day, Natalie J Serkova, Britta M Jacobsen, Susan M Edgerton, Ann D Thor, Virginia F Borges, Kevin O Lillehei, Michael W Graner, Peter Kabos, Diana M Cittelly
Brain metastases are an increasing burden among breast cancer patients, particularly for those with HER2(+) and triple negative (TN) subtypes. Mechanistic insight into the pathophysiology of brain metastases and preclinical validation of therapies has relied almost exclusively on intracardiac injection of brain-homing cells derived from highly aggressive TN MDA-MB-231 and HER2(+) BT474 breast cancer cell lines. Yet, these well characterized models are far from representing the tumor heterogeneity observed clinically and, due to their fast progression in vivo, their suitability to validate therapies for established brain metastasis remains limited...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29163806/interferon-inducible-cxc-chemokines-are-crucial-immune-modulators-and-survival-predictors-in-colorectal-cancer
#2
Larissa Kistner, Dietrich Doll, Anne Holtorf, Ulrich Nitsche, Klaus-Peter Janssen
Tumor-infiltrating T-cells are strongly associated with prognosis in colorectal cancer, but the mechanisms governing intratumoral lymphocyte recruitment are unclear. We investigated the clinical relevance and functional contribution of interferon-regulated CXC-chemokines CXCL9, CXCL10, and CXCL11, described as T-cells attractants. Their expression was significantly elevated in tumors as compared to normal colon in 163 patients with colon cancer, represented an independent positive predictor of post-operative survival, and was highly significantly correlated with the presence of tumor-infiltrating cytotoxic CD8(+) T-cells and CD4(+) TH1-effector cells...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29160412/exosomes-promote-cetuximab-resistance-via-the-pten-akt-pathway-in-colon-cancer-cells
#3
S Zhang, Y Zhang, J Qu, X Che, Y Fan, K Hou, T Guo, G Deng, N Song, C Li, X Wan, X Qu, Y Liu
Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt...
November 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29157662/evaluation-of-guideline-adherence-in-colorectal-cancer-treatment-in-the-netherlands-a-survey-among-medical-oncologists-by-the-dutch-colorectal-cancer-group
#4
Lotte Keikes, Martijn G H van Oijen, Valery E P P Lemmens, Miriam Koopman, Cornelis J A Punt
BACKGROUND: Clinical guidelines are generated to preserve high-quality evidence-based care. Data on the implementation of guidelines into clinical practice are scarce, despite that guideline adherence prevents over- and undertreatment and correlates with survival. Therefore, we investigated guideline adherence for the systemic treatment in high-risk stage II and stage III colon cancer and metastatic colorectal cancer. PATIENTS AND METHODS: In all Dutch hospitals (n = 88) 1 medical oncologist involved in colorectal cancer care was approached to participate...
November 17, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29157147/a-case-of-aseptic-meningitis-in-a-cetuximab-experienced-patient-with-metastatic-colon-cancer
#5
Chelsea L Rohrer, Zunilda Grullon, Sarah K George, Raul Castillo, Kelli Karasiewicz
Cetuximab is a monoclonal antibody against epidermal growth factor receptor and is used in the treatment of head and neck cancer, non-small cell lung cancer, and colorectal cancer. This case report describes a rare (<1% incidence) side effect of cetuximab administration: aseptic meningitis. We report a case which is, to our knowledge, the only case at the time of submission of this manuscript of aseptic meningitis in a patient being treated for metastatic colon cancer who was not cetuximab-naïve. This case report may help inform clinicians about the identification and outcome of this adverse event...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29156800/comparative-molecular-analyses-of-left-sided-colon-right-sided-colon-and-rectal-cancers
#6
Mohamed E Salem, Benjamin A Weinberg, Joanne Xiu, Wafik S El-Deiry, Jimmy J Hwang, Zoran Gatalica, Philip A Philip, Anthony F Shields, Heinz-Josef Lenz, John L Marshall
Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156792/liquid-biopsy-in-colon-cancer-comparison-of-different-circulating-dna-extraction-systems-following-absolute-quantification-of-kras-mutations-using-intplex-allele-specific-pcr
#7
Vera Kloten, Nadine Rüchel, Nadina Ortiz Brüchle, Janina Gasthaus, Nils Freudenmacher, Florian Steib, Jolein Mijnes, Julian Eschenbruch, Marcel Binnebösel, Ruth Knüchel, Edgar Dahl
Non-invasive molecular analysis of circulating tumor DNA (ctDNA) is a promising application in personalized cancer management, although there is still much to learn about the biological characteristics of ctDNA. The present study compared absolute amounts of KRAS mutated ctDNA and total circulating cell-free DNA (cfDNA) in colorectal cancer (CRC) patients (n=50) from various stages and healthy controls (n=8) by Intplex allele-specific and digital droplet PCR. In addition, the impact of two prominent extraction techniques (silica-based membrane vs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156704/ackr3-expression-on-diffuse-large-b-cell-lymphoma-is-required-for-tumor-spreading-and-tissue-infiltration
#8
Viola Puddinu, Sabrina Casella, Egle Radice, Sylvia Thelen, Stefan Dirnhofer, Francesco Bertoni, Marcus Thelen
Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma accounting for more than the 30% of the cases. Involvement of extranodal sites, such as bone marrow and central nervous system, is associated with poor prognosis. A contribution of the chemokine system in these processes is assumed as it is known as a critical regulator of the metastatic process in cancer. The atypical chemokine receptor 3 (ACKR3), which does not couple to G-proteins and does not mediate cell migration, acts as a scavenger for CXCL11 and CXCL12, interfering with the tumor homing CXCL12/CXCR4 axis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29153095/circulating-cell-free-dna-mutation-patterns-in-early-and-late-stage-colon-and-pancreatic-cancer
#9
Eveline E Vietsch, Garrett T Graham, Justine N McCutcheon, Aamir Javaid, Giuseppe Giaccone, John L Marshall, Anton Wellstein
Cancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level without the need for invasively acquired samples from primary or metastatic lesions. This potential for molecular analysis makes ccfDNA attractive for the study of clonal evolution and for uncovering emerging therapeutic resistance or sensitivity...
December 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29152287/acute-drop-of-platelets-in-metastatic-colon-cancer
#10
Ahmed-Tarig Ahmed, Shweta Gupta
Oxaliplatin is a platinum commonly used in the treatment of metastatic colon cancer. It can cause thrombocytopenia through different mechanism. Sudden isolated drop in platelets should raise the concern for oxaliplatin immune-induced thrombocytopenia and abrupt discontinuation of the drug. Patients should not be rechallenged with oxaliplatin once diagnosis of OIIT is confirmed.
November 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29152153/molecular-determinants-of-prostate-cancer-metastasis
#11
REVIEW
Kiera Rycaj, Dean G Tang
Metastatic cancer remains largely incurable and fatal. The general course of cancer, from the initiation of primary tumor formation and progression to metastasis, is a multistep process wherein tumor cells at each step must display specific phenotypic features. Distinctive capabilities required for primary tumor initiation and growth form the foundation, and sometimes may remain critical, for subsequent metastases. These phenotypic features must remain easily malleable during the acquisition of additional capabilities unique and essential to the metastatic process such as dissemination to distant tissues wherein tumor cells interact with foreign microenvironments...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147564/a-review-of-orexin-s-unprecedented-potential-as-a-novel-highly-specific-treatment-for-various-localized-and-metastatic-cancers
#12
REVIEW
Nicole L Graybill, Volkmar Weissig
A systematic review was conducted to categorize the types of cancerous tissues that express orexin receptors and also to examine the effect of in vitro administration of orexin A or B to corresponding cell samples. Comprehensive literature analyses of primary experimental studies were performed. The results of the review included an increased frequency of orexin receptor expression in many colon and prostate cancer tissues and an upward trend of pro-apoptotic activity in these aggressive cell types.
2017: SAGE Open Medicine
https://www.readbyqxmd.com/read/29146133/synthesis-and-bio-evaluation-of-indole-chalcone-based-benzopyrans-as-promising-antiligase-and-antiproliferative-agents
#13
Sampa Gupta, Pooja Maurya, Akanksha Upadhyay, Pragati Kushwaha, Shagun Krishna, Mohammad Imran Siddiqi, Koneni V Sashidhara, Dibyendu Banerjee
DNA replication and repair are complex processes accomplished by the concerted action of a network of enzymes and proteins. DNA ligases play a crucial role in these processes by catalyzing the nick joining between DNA strands. As compared to normal cells, elevated levels of human DNA ligase I (hLigI) is reported in some cancers. We studied the inhibition of hLigI mediated DNA nick sealing activity followed by the antiproliferative activity of novel indole-chalcone based benzopyran compounds on cancer cells...
November 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29142750/evaluation-of-epidermal-growth-factor-receptor-serum-levels-and-their-association-with-clinicopathological-characteristics-in-patients-with-colorectal-cancer
#14
Mehmet Karabulut, Cigdem Usul Afsar, Halil Alıs, Ebru Oran, Senem Karabulut, Cevher Akarsu, Nuri Alper Sahbaz, Alpen Yahya Gümüsoglu, Elif Bilgin, Nuri Faruk Aykan
Colorectal cancer (CRC) is a major public health concern and one of the leading causes of cancer-related mortality worldwide. The aim of the present study was to determine the serum epidermal growth factor receptor (sEGFR) levels in healthy volunteers and patients with CRC, to determine the association between tumor marker levels and clinicopathological findings, and investigate its prognostic value. A total of 140 patients with CRC were enrolled in the present study. Pre-treatment sEGFR levels were determined using ELISA...
November 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29138850/role-of-mitochondrial-function-in-the-invasiveness-of-human-colon-cancer-cells
#15
Chen-Sung Lin, Li-Tzu Liu, Liang-Hung Ou, Siao-Cian Pan, Chia-I Lin, Yau-Huei Wei
We investigated the role of mitochondrial function in the invasiveness of human colorectal cancer (CRC) cell lines, using paired primary SW480 and metastatic SW620 cells, and appraised the clinical relevance of the alteration of mtDNA copy number in 33 pairs of CRC specimens after surgical resection. Suppression of mitochondrial function was achieved by the exposure of cells to oligomycin A (OA) or by knockdown of mitochondrial transcriptional factor A (TFAM) to evaluate their effects on energy metabolism, reactive oxygen species, protein expression levels of epithelial-mesenchymal transition (EMT) markers and invasive activity of CRC cells...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29138417/association-of-predicted-pathogenic-mutations-in-mitochondrial-nd-genes-with-distant-metastasis-in-nsclc-and-colon-cancer
#16
Nobuko Koshikawa, Miho Akimoto, Jun-Ichi Hayashi, Hiroki Nagase, Keizo Takenaga
Cancer cells have more mutations in their mitochondrial DNA (mtDNA) than do normal cells, and pathogenic mutations in the genes encoding mitochondrial NADH dehydrogenase (ND) subunits have been found to enhance the invasive and metastatic ability of various tumour cells in animal experiments. However, it is unknown whether single-nucleotide variants (SNVs) of the ND genes that decrease complex I activity are involved in distant metastasis in human clinical samples. Here, we demonstrated the enhancement of the distant metastasis of Lewis lung carcinoma cells by the ND6 13885insC mutation, which is accompanied by the overexpression of metastasis-related genes, metabolic reprogramming, the enhancement of tumour angiogenesis and the acquisition of resistance to stress-induced cell death...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137623/analysis-of-factors-influencing-molecular-testing-at-diagnostic-of-colorectal-cancer
#17
Quentin Thiebault, Gautier Defossez, Lucie Karayan-Tapon, Pierre Ingrand, Christine Silvain, David Tougeron
BACKGROUND: The aim of the study was to evaluate the current rate of molecular testing prescription (KRAS codons 12/13, BRAF and microsatellite instability (MSI)) in newly diagnosed colorectal cancer (CRC) patients and to determine which factors influence testing. METHODS: All incident CRC cases in 2010 were identified in the Poitou-Charentes General Cancer Registry. The exhaustive molecular testing performed was accessed in the French molecular genetics platform...
November 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29137351/microrna-200-associated-with-metastatic-breast-cancer-promotes-traits-of-mammary-luminal-progenitor-cells
#18
Lourdes Sánchez-Cid, Mònica Pons, Juan José Lozano, Nuria Rubio, Marta Guerra-Rebollo, Aroa Soriano, Laia Paris-Coderch, Miquel F Segura, Raquel Fueyo, Judit Arguimbau, Erika Zodda, Raquel Bermudo, Immaculada Alonso, Xavier Caparrós, Marta Cascante, Arash Rafii, Yibin Kang, Marian Martínez-Balbás, Stephen J Weiss, Jerónimo Blanco, Montserrat Muñoz, Pedro L Fernández, Timothy M Thomson
MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137281/hic-5-regulates-epithelial-to-mesenchymal-transition-in-ovarian-cancer-cells-in-a-tgf%C3%AE-1-independent-manner
#19
Razan Sheta, Zhi-Qiang Wang, Magdalena Bachvarova, Marie Plante, Jean Gregoire, Marie-Claude Renaud, Alexandra Sebastianelli, Stephane Gobeil, Chantale Morin, Elizabeth Macdonald, Barbara Vanderhyden, Dimcho Bachvarov
The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. We have previously identified the hydrogen peroxide-inducible clone-5 (Hic-5) gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. Hic-5 is a focal adhesion scaffold protein and has been primarily studied for its role as a key mediator of TGF-β-induced epithelial-to-mesenchymal transition (EMT) in epithelial cells of both normal and malignant origin; however, its role in EOC has been never investigated...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133416/rsk2-phosphorylates-t-bet-to-attenuate-colon-cancer-metastasis-and-growth
#20
Ke Yao, Cong Peng, Yuwen Zhang, Tatyana A Zykova, Mee-Hyun Lee, Sung-Young Lee, Enyu Rao, Hanyong Chen, Joohyun Ryu, Lei Wang, Yi Zhang, Ge Gao, Wei He, Wei-Ya Ma, Kangdong Liu, Ann M Bode, Ziming Dong, Bing Li, Zigang Dong
Metastasis is a major cause of cancer-related deaths. Approximately 80% of patients with colorectal cancer develop liver metastasis and 20% develop lung metastasis. We found that at different stages of colon cancer, IFNγ secretion from peripheral blood mononuclear cells was decreased compared with healthy controls. The ribosomal S6 kinase (RSK) family of kinases has multiple cellular functions, and we examined their roles in this observed IFNγ decrease. Flow cytometry analysis of wild-type (WT) and RSK2 knockout (KO) mice revealed significantly lower levels of IFNγ in the RSK2 KO mice compared with the WT mice...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
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