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Genetics vascular tumors

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https://www.readbyqxmd.com/read/28920957/klf4-dependent-perivascular-cell-plasticity-mediates-pre-metastatic-niche-formation-and-metastasis
#1
Meera Murgai, Wei Ju, Matthew Eason, Jessica Kline, Daniel W Beury, Sabina Kaczanowska, Markku M Miettinen, Michael Kruhlak, Haiyan Lei, Jack F Shern, Olga A Cherepanova, Gary K Owens, Rosandra N Kaplan
A deeper understanding of the metastatic process is required for the development of new therapies that improve patient survival. Metastatic tumor cell growth and survival in distant organs is facilitated by the formation of a pre-metastatic niche that is composed of hematopoietic cells, stromal cells and extracellular matrix (ECM). Perivascular cells, including vascular smooth muscle cells (vSMCs) and pericytes, are involved in new vessel formation and in promoting stem cell maintenance and proliferation. Given the well-described plasticity of perivascular cells, we hypothesized that perivascular cells similarly regulate tumor cell fate at metastatic sites...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28917530/overcoming-key-biological-barriers-to-cancer-drug-delivery-and-efficacy
#2
Susy M Kim, Peggy H Faix, Jan E Schnitzer
Poor delivery efficiency continues to hamper the effectiveness of cancer therapeutics engineered to destroy solid tumors using different strategies such as nanocarriers, targeting agents, and matching treatments to specific genetic mutations. All contemporary anti-cancer agents are dependent upon passive transvascular mechanisms for their delivery into solid tumors. The therapeutic efficacies of our current drug arsenal could be significantly improved with an active delivery strategy. Here, we discuss how drug delivery and therapeutic efficacy is greatly hindered by barriers presented by the vascular endothelial cell layer and by the aberrant nature of tumor blood vessels in general...
September 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28916654/biallelic-dicer1%C3%A2-loss-mediated-by-ap2-cre-drives-angiosarcoma
#3
Jason A Hanna, Catherine J Drummond, Matthew R Garcia, Jonathan C Go, David Finkelstein, Jerold E Rehg, Mark E Hatley
Angiosarcoma is an aggressive vascular sarcoma with an extremely poor prognosis. Due to the relative rarity of this disease, its molecular drivers and optimal treatment strategies are obscure. DICER1 is an RNase III endoribonuclease central to microRNA biogenesis, and germline DICER1 mutations result in a cancer predisposition syndrome, associated with an increased risk of many tumor types. Here we show that biallelic Dicer1 deletion with aP2-Cre drives aggressive and metastatic angiosarcoma independent of other genetically engineered oncogenes or tumor suppressor loss...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28903735/foxp3-is-a-hcc-suppressor-gene-and-acts-through-regulating-the-tgf-%C3%AE-smad2-3-signaling-pathway
#4
Jie-Yi Shi, Li-Jie Ma, Ji-Wei Zhang, Meng Duan, Zhen-Bin Ding, Liu-Xiao Yang, Ya Cao, Jian Zhou, Jia Fan, Xiaoming Zhang, Ying-Jun Zhao, Xiao-Ying Wang, Qiang Gao
BACKGROUND: FOXP3 has been discovered to be expressed in tumor cells and participate in the regulation of tumor behavior. Herein, we investigated the clinical relevance and biological significance of FOXP3 expression in human hepatocellular carcinoma (HCC). METHODS: Expression profile of FOXP3 was analyzed using real-time RT-PCR, western blotting and immunofluorescence on HCC cell lines, and immunostaing of a tissue microarray containing of 240 primary HCC samples...
September 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28902337/multimodal-imaging-of-astrocytic-hamartomas-associated-with-tuberous-sclerosis
#5
Stephen G Schwartz, J William Harbour
An 11-year-old patient was diagnosed with tuberous sclerosis complex based on retinal and cutaneous findings and confirmed by genetic testing. Spectral-domain optical coherence tomography (OCT) demonstrated subtle solid intraretinal tumors that focally replaced the inner retina and displaced the outer retinal layers. OCT angiography demonstrated prominent intrinsic vascularity but no feeder vessels. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:756-758.].
September 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28892049/membrane-mucin-muc4-promotes-blood-cell-association-with-tumor-cells-and-mediates-efficient-metastasis-in-a-mouse-model-of-breast-cancer
#6
A R Rowson-Hodel, J H Wald, J Hatakeyama, W K O'Neal, J R Stonebraker, K VanderVorst, M J Saldana, A D Borowsky, C Sweeney, K L Carraway
Mucin-4 (Muc4) is a large cell surface glycoprotein implicated in the protection and lubrication of epithelial structures. Previous studies suggest that aberrantly expressed Muc4 can influence the adhesiveness, proliferation, viability and invasiveness of cultured tumor cells, as well as the growth rate and metastatic efficiency of xenografted tumors. Although it has been suggested that one of the major mechanisms by which Muc4 potentiates tumor progression is via its engagement of the ErbB2/HER2 receptor tyrosine kinase, other mechanisms exist and remain to be delineated...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28881585/c-ebp-%C3%AE-positively-regulates-mdsc-expansion-and-endothelial-vegfr2-expression-in-tumor-development
#7
Yongfen Min, Jingdong Li, Peng Qu, P Charles Lin
Vascular endothelial cells and Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) are two important components that constitute the tumor microenvironment. Targeting these cells offers the potential to halt tumor growth. In this study, we report a common mediator in C/EBP-δ that regulates both components and aids in tumor development. C/EBP-δ is elevated in tumor derived MDSCs. Interestingly, genetic deletion of C/EBP-δ in mice significantly impaired MDSC expansion in response to tumor progression, but it had no effect on Gr-1+CD11b+ cell production in normal development...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880889/loss-of-kaiso-expression-in-breast-cancer-cells-prevents-intra-vascular-invasion-in-the-lung-and-secondary-metastasis
#8
Jacek M Kwiecien, Blessing I Bassey-Archibong, Wojciech Dabrowski, Lyndsay G Rayner, Alexandra R Lucas, Juliet M Daniel
The metastatic activity of breast carcinomas results from complex genetic changes in epithelial tumor cells and accounts for 90% of deaths in affected patients. Although the invasion of the local lymphatic vessels and veins by malignant breast tumor cells and their subsequent metastasis to the lung, has been recognized, the mechanisms behind the metastatic activity of breast tumor cells to other distal organs and the pathogenesis of metastatic cancer are not well understood. In this study, we utilized derivatives of the well-established and highly metastatic triple negative breast cancer (TNBC) cell line MDA-MB-231 (MDA-231) to study breast tumor metastasis in a mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28877060/clinicopathologic-diversity-of-undifferentiated-sarcoma-with-bcor-ccnb3-fusion-analysis-of-11-cases-with-a-reappraisal-of-the-utility-of-immunohistochemistry-for-bcor-and-ccnb3
#9
Atsuji Matsuyama, Eisuke Shiba, Yoshihisa Umekita, Kanae Nosaka, Takihiro Kamio, Hiroyuki Yanai, Chika Miyasaka, Reiko Watanabe, Ichiro Ito, Tomoko Tamaki, Shinichi Hayashi, Masanori Hisaoka
Undifferentiated sarcoma harboring the BCOR-CCNB3 fusion is characterized by its predilection to affect skeletons of adolescent males, cellular small round/spindle cell morphology, and CCNB3 immunoreactivity. We analyzed 11 cases of BCOR-CCNB3 sarcoma, 10 of which were identified in a reverse transcription-polymerase chain reaction-based screen of 85 patient samples recorded in our database as unclassified small round or spindle cell sarcomas. BCOR rearrangements were confirmed by fluorescence in situ hybridization in 8 tumors...
September 4, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28832416/targeted-therapy-and-imaging-findings
#10
Girish S Shroff, Marcelo F Benveniste, Patricia M de Groot, Carol C Wu, Chitra Viswanathan, Vassiliki A Papadimitrakopoulou, Mylene T Truong
Non-small cell lung cancer (NSCLC) is usually diagnosed when it is not amenable to curative surgery or radiation. Many of these patients are candidates for systemic therapy. Median survival is only approximately 10 months, and, accordingly, treatment in advanced NSCLC is evolving toward a more personalized approach with the identification of genetic abnormalities based on biomarkers. For example, gene mutations in EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase) lead to a cascade of pathways resulting in uncontrolled growth, proliferation, and survival of tumor cells...
September 2017: Journal of Thoracic Imaging
https://www.readbyqxmd.com/read/28818770/hereditary-multiple-exostoses-as-a-novel-cause-of-bilateral-popliteal-artery-aneurysms-in-the-elderly
#11
Eliza J Ferrari, Rory K Crotty, Katharina Eikermann-Haerter, James R Stone
Hereditary multiple exostoses (HME) is a genetic condition characterized by the development of multiple osteochondromas during childhood and adolescence. On rare occasions, these bony tumors can be associated with vascular injury, most commonly involving the popliteal artery. Such patients typically present with vascular complications in adolescence and young adulthood. We report an autopsy study of an elderly man who presented with bilateral popliteal artery pseudoaneurysms in the setting of HME at age 81...
July 8, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#12
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28802504/cutaneous-malignant-vascular-neoplasms
#13
REVIEW
Wonwoo Shon, Steven D Billings
Accurate diagnosis of cutaneous malignant vascular tumors, including angiosarcoma and epithelioid hemangioendothelioma, is critical for determination of appropriate clinical management and prognosis. Although there have been significant advances in understanding genetic aspects of cutaneous vascular biology, differential diagnosis of malignant vascular tumor involving skin and superficial soft tissue is a frequent source of difficulty. This brief overview highlights the clinicopathologic features of primary and secondary cutaneous angiosarcoma and epithelioid hemangioendothelioma and also provides a short summary of newer molecular data...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28801584/differences-of-protein-expression-profiles-kras-and-braf-mutation-and-prognosis-in-right-sided-colon-left-sided-colon-and-rectal-cancer
#14
Xian Hua Gao, Guan Yu Yu, Hai Feng Gong, Lian Jie Liu, Yi Xu, Li Qiang Hao, Peng Liu, Zhi Hong Liu, Chen Guang Bai, Wei Zhang
To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, β-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796347/clinicopathological-analysis-of-atrx-daxx-and-notch-receptor-expression-in-angiosarcomas
#15
Gauri Panse, John S A Chrisinger, Cheuk H Leung, Davis R Ingram, Samia Khan, Khalida Wani, Heather Lin, Alexander J Lazar, Wei-Lien Wang
AIMS: Multiple genetic alterations including alternative lengthening of telomeres (ALT) and NOTCH mutations have been described in angiosarcoma. Loss of ATRX (α-thalessemia/mental retardation syndrome X-linked) and DAXX (death domain-associated 6) expression is frequently associated with the ALT phenotype. Additionally, inhibition of NOTCH signaling induces malignant vascular tumors in mice, indicating a tumor suppressive role of the NOTCH pathway in the pathogenesis of angiosarcoma...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28794363/renal-cell-carcinoma-and-a-pancreatic-neuroendocrine-tumor-a-coincidence-or-instance-of-von-hippel-lindau-disease
#16
Hiroyuki Matsubayashi, Masashi Niwakawa, Katsuhiko Uesaka, Keiko Sasaki, Yoshimi Kiyozumi, Hirotoshi Ishiwatari, Kinichi Hotta, Kenichiro Imai, Sayo Ito, Kohei Takizawa, Masaki Tanaka, Noboru Kawata, Naomi Kakushima, Hiroyuki Ono
We herein report a rare case of a 79-year-old man who presented with the simultaneous occurrence of pancreatic neuroendocrine tumors (PNET) and renal cell carcinomas (RCC), without any other Von Hippel-Lindau (VHL)-associated lesions or any pertinent family history. Computed tomography showed vascular-rich solid lesions in the left kidney and the pancreatic tail, measuring 72 mm and 15 mm in size, respectively. Preoperatively, RCC with pancreatic metastasis was suspected and laparotomy was performed. However, the resected specimens revealed a different tumor histology, namely renal clear cell carcinoma (G2, pT3) and PNET (G1, pT3)...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28756566/pten-hamartoma-of-the-soft-tissue-the-initial-manifestation-of-an-underlying-pten-hamartoma-tumor-syndrome-in-a-4-year-old-female
#17
Charles B Chism, Lindsay Crawford, Amanda Tchakarov, Alyaa Al-Ibraheemi, Nicholas M Beckmann
A 4-year-old female was referred to pediatric orthopedic surgery for left leg pain and limping for 3 months following a motor vehicle collision. Recently, the patient's mother had noted left knee swelling and dragging of the left leg when walking. Past medical history was significant for hip dysplasia with slight leg length discrepancy. The patient was otherwise healthy. Physical examination was remarkable for left pre-patellar soft tissue fullness with normal range of motion. There was no warmth or tenderness...
July 29, 2017: Skeletal Radiology
https://www.readbyqxmd.com/read/28753786/tumor-xenografts-of-human-clear-cell-renal-cell-carcinoma-but-not-corresponding-cell-lines-recapitulate-clinical-response-to-sunitinib-feasibility-of-using-biopsy-samples
#18
Yiyu Dong, Brandon J Manley, Maria F Becerra, Almedina Redzematovic, Jozefina Casuscelli, Daniel M Tennenbaum, Ed Reznik, Song Han, Nicole Benfante, Ying-Bei Chen, Maria E Arcila, Omer Aras, Martin H Voss, Darren R Feldman, Robert J Motzer, Nicola Fabbri, John H Healey, Patrick J Boland, Mohit Chawla, Jeremy C Durack, Chung-Han Lee, Jonathan A Coleman, Paul Russo, A Ari Hakimi, Emily H Cheng, James J Hsieh
BACKGROUND: Parallel development of preclinical models that recapitulate treatment response observed in patients is central to the advancement of personalized medicine. OBJECTIVE: To evaluate the use of biopsy specimens to develop patient-derived xenografts and the use of corresponding cell lines from renal cell carcinoma (RCC) tumors for the assessment of histopathology, genomics, and treatment response. DESIGN, SETTING, AND PARTICIPANTS: A total of 74 tumor specimens from 66 patients with RCC were implanted into immunocompromised NOD-SCID IL2Rg(-/-) mice...
August 25, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28749108/snp-and-haplotype-analysis-of-vascular-endothelial-growth-factor-vegf-gene-in-lung-cancer-patients-of-kashmir
#19
Niyaz A Naikoo, Dil Afroze, Roohi Rasool, Sonaullah Shah, A G Ahangar, Imtiyaz A Bhat, Iqbal Qasim, Mushtaq A Siddiqi, Zafar A Shah
Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. In this large case-control study, we investigated whether functional polymorphisms (+405C>G, +936C>T) in the VEGF gene are associated with the risk of lung cancer. The study investigates the association between variants of VEGF gene and lung cancer. We performed single nucleotide polymorphism (SNP), haplotype and linkage disequilibrium studies on 100 patients and 128 healthy controls with 2 SNPs in the VEGF gene...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28745442/modification-of-pedicle-lengthening-through-perforator-transposition-in-free-anterolateral-thigh-flaps-with-pedicle-size-discrepancy-a-case-report
#20
Hyun Ho Han, Daiwon Jun, Goo Hyun Mun, Suk-Ho Moon
In spite of thorough presurgical planning, emergency situations requiring longer pedicle length may arise during anterolateral thigh (ALT) free flap surgeries. While performing vessel graft for pedicle lengthening, discrepancy may occur because of a certain genetic predisposition or vascular variation at the anastomosis site of the graft vessel and the flap pedicle. A 76-year-old male patient with neurofibromatosis type I had a 15 x 10 cm defect, which was caused by radical excision of a malignant peripheral nerve sheath tumor on his back...
July 26, 2017: Microsurgery
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