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Kuntal Kanti Goswami, Madhurima Sarkar, Sarbari Ghosh, Akata Saha, Tithi Ghosh, Ipsita Guha, Subhasis Barik, Saptak Banerjee, Soumyabrata Roy, Anamika Bose, Parthasarathi Dasgupta, Rathindranath Baral
Heterogeneous tumor microenvironment (TME), broadly divided into tumor core and peripheral sub-microenvironments, differentially polarize normal macrophages into a different form known as tumor associated M2 macrophages (M2TAMs) to promote tumor growth. In view of the extensive immune-editing role of NLGP, here, we have observed that NLGP is effective to convert M2TAMs (CD11b(+)F4/80(high)) to M1 (CD11b(+)F4/80(low)) more prominently in tumor core, along with downregulation of other M2 associated markers, like, ManR, Ym1, Fizz1...
October 21, 2016: Molecular Immunology
Famke Aeffner, Nathan T Martin, Mirza Peljto, Joshua C Black, Justin K Major, Maryam Jangani, Michael O Ports, Joseph S Krueger, G David Young
Tissue image analysis (tIA) is emerging as a powerful tool for quantifying biomarker expression and distribution in complex diseases and tissues. Pancreatic ductal adenocarcinoma (PDAC) develops in a highly complex and heterogeneous tissue environment and, generally, has a very poor prognosis. Early detection of PDAC is confounded by limited knowledge of the pre-neoplastic disease stages and limited methods to quantitatively assess disease heterogeneity. We sought to develop a tIA approach to assess the most common PDAC precursor lesions, pancreatic intraepithelial neoplasia (PanIN), in tissues from Kras(LSL-G12D/+); Trp53(LSL-R172H/+); Pdx-Cre (KPC) mice, a validated model of PDAC development...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
E Hain, L Maggiori, G Manceau, C Mongin, J Prost À la Denise, Y Panis
BACKGROUND: The effect of anastomotic leakage on oncological outcomes after total mesorectal excision (TME) is controversial. This study aimed to assess the influence of symptomatic and asymptomatic anastomotic leakage on oncological outcomes after laparoscopic TME. METHODS: All patients who underwent restorative laparoscopic TME for rectal adenocarcinoma with curative intent from 2005 to 2014 were identified from an institutional database. Asymptomatic anastomotic leakage was defined by CT performed systematically 4-8 weeks after rectal surgery, with no relevant clinical symptoms or laboratory examination findings during the postoperative course...
October 20, 2016: British Journal of Surgery
Peter Bailey, David K Chang, Marie-Andrée Forget, Francis A San Lucas, Hector A Alvarez, Cara Haymaker, Chandrani Chattopadhyay, Sun-Hee Kim, Suhendan Ekmekcioglu, Elizabeth A Grimm, Andrew V Biankin, Patrick Hwu, Anirban Maitra, Jason Roszik
Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases...
October 20, 2016: Scientific Reports
Azhar Z Abbasi, Claudia R Gordijo, Mohammad Ali Amini, Azusa Maeda, Andrew M Rauth, Ralph S DaCosta, Xiao Yu Wu
Hypoxia in the tumor microenvironment (TME) mediates resistance to radiotherapy (RT) and contributes to poor prognosis in patients receiving RT. Here we report the design of clinically suitable formulations of hybrid manganese dioxide (MnO2) nanoparticles (MDNP) using biocompatible materials to re-oxygenate the TME by reacting with endogenous H2O2. MDNP containing hydrophilic terpolymer-protein-MnO2 or hydrophobic polymer-lipid-MnO2 provided different oxygen generation rates in the TME relevant to different clinical settings...
October 6, 2016: Cancer Research
Sounik Saha, Xunhao Xiong, Prabir K Chakraborty, Khader Shameer, Rochelle R Arvizo, Rachel A Kudgus, Shailendra Kumar Dhar Dwivedi, Md Nazir Hossen, Elizabeth M Gillies, J David Robertson, Joel T Dudley, Raul A Urrutia, Russell G Postier, Resham Bhattacharya, Priyabrata Mukherjee
Altered tumor microenvironment (TME) arising from a bidirectional crosstalk between the pancreatic cancer cells (PCCs) and the pancreatic stellate cells (PSCs) is implicated in the dismal prognosis in pancreatic ductal adenocarcinoma (PDAC), yet effective strategies to disrupt the crosstalk is lacking. Here, we demonstrate that gold nanoparticles (AuNPs) inhibit proliferation and migration of both PCCs and PSCs by disrupting the bidirectional communication via alteration of the cell secretome. Analyzing the key proteins identified from a functional network of AuNP-altered secretome in PCCs and PSCs, we demonstrate that AuNPs impair secretions of major hub node proteins in both cell types and transform activated PSCs toward a lipid-rich quiescent phenotype...
October 19, 2016: ACS Nano
Jae Hwan Oh, Sung Chan Park, Min Jung Kim, Byung Kwan Park, Jong Hee Hyun, Hee Jin Chang, Kyung Su Han, Dae Kyung Sohn
PURPOSE: To evaluate the feasibility of transanal total mesorectal excision (TME) in patients with rectal cancer. METHODS: This study enrolled 12 patients with clinically node negative rectal cancer located 4-12 cm from the anal verge who underwent transanal endoscopic TME with the assistance of single port laparoscopic surgery between September 2013 and August 2014. The primary endpoint was TME quality; secondary endpoints included number of harvested lymph nodes and postoperative complications within 30 days (NCT01938027)...
October 2016: Annals of Surgical Treatment and Research
Zhen Wang, Jun-Qiang Chen, Jin-Lu Liu, Lei Tian
Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small vesicles formed in vesicular bodies with a diameter of 30-100 nm and a classic "cup" or "dish" morphology. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donor cell to recipient cells. Exosomes secreted from tumor cells are called tumor-derived (TD) exosomes. There is emerging evidence that TD exosomes can construct a fertile environment to support tumor proliferation, angiogenesis, invasion and premetastatic niche preparation...
October 19, 2016: Journal of Translational Medicine
Vanessa Verdin, Joseph Weerts, David Francart, Constant Jehaes, David Magis, Paul Magotteaux, Laurine Mattart, Benoit Monami, Christian Wahlen, Serge Markiewicz
BACKGROUND: Rectal adenocarcinomas surgery morbidity and mortality might be impaired by neoadjuvant therapy. We performed this retropsective study to be compared with the PROCARE study running afterwards. METHODS: We performed a retrospective study of 95 patients operated on for rectal adenocarcinoma in a single institution during the period of 2007-2009. We used logistic regression to estimate the relationship between possible predictive parameters of anastomotic leakage (AL)...
October 17, 2016: Acta Chirurgica Belgica
Marta Penna, Roel Hompes, Steve Arnold, Greg Wynn, Ralph Austin, Janindra Warusavitarne, Brendan Moran, George B Hanna, Neil J Mortensen, Paris P Tekkis
OBJECTIVE: This study aims to report short-term clinical and oncological outcomes from the international transanal Total Mesorectal Excision (taTME) registry for benign and malignant rectal pathology. BACKGROUND: TaTME is the latest minimally invasive transanal technique pioneered to facilitate difficult pelvic dissections. Outcomes have been published from small cohorts, but larger series can further assess the safety and efficacy of taTME in the wider surgical population...
October 4, 2016: Annals of Surgery
Atsushi Ogura, Takashi Akiyoshi, Toshiya Nagasaki, Tsuyoshi Konishi, Yoshiya Fujimoto, Satoshi Nagayama, Yosuke Fukunaga, Masashi Ueno, Hiroya Kuroyanagi
BACKGROUND: The feasibility of additional lateral pelvic lymph node dissection (LPLND) compared with total mesorectal excision (TME) alone in patients treated with preoperative chemoradiotherapy (CRT) is controversial, especially in laparoscopic surgery. This study was performed to evaluate the feasibility of adding laparoscopic LPLND to TME in patients with advanced lower rectal cancer and swollen LPLNs treated with preoperative CRT. METHODS: We reviewed 327 patients with lower rectal cancer without distant metastasis who underwent preoperative CRT followed by laparoscopic TME...
October 11, 2016: World Journal of Surgery
Chi-Cheng Chen, Chi-Ping Huang, Teng-Fu Hsieh, Wei-Kai Chiu, Wen-Ling Chang, Chih-Rong Shyr
Interactions between infiltrating macrophages in the tumor microenvironment (TME) and tumor cells contribute to tumor progression. The potential impacts of recruited macrophages to the upper urinary tract urothelial cell carcinomas (UUTUCs) progression remain unclear. Here we found human UUTUCs might recruit more macrophages than surrounding normal urothelial cells in human clinical specimens and in in vitro co-culture experiments with UUTUC cells and macrophages. The consequences of recruiting more macrophages to UUTUCs might then enhance UUTUC cell growth, migration and invasion...
2016: American Journal of Cancer Research
Elisabeth Naschberger, Andrea Liebl, Vera S Schellerer, Manuela Schütz, Nathalie Britzen-Laurent, Patrick Kölbel, Ute Schaal, Lisa Haep, Daniela Regensburger, Thomas Wittmann, Ludger Klein-Hitpass, Tilman T Rau, Barbara Dietel, Valérie S Méniel, Alan R Clarke, Susanne Merkel, Roland S Croner, Werner Hohenberger, Michael Stürzl
Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs...
October 10, 2016: Journal of Clinical Investigation
Q Denost, C Kontovounisios, S Rasheed, R Chevalier, R Brasio, M Capdepont, E Rullier, P P Tekkis
BACKGROUND: Rectal cancer involving at least one adjacent organ (mrT4b) requires multi-visceral resection to achieve clear resection margin (R0). Performing pelvic compartment preservation according to the tumour response has not been considered. This study assesses the impact of changing the surgical strategy according to tumour response in rectal cancer mrT4b. METHODS: Patients with non-metastatic T4b rectal cancer at two tertiary referral centres between 2008 and 2013 were grouped as "Responders" ypT0-3abNx versus "Non-responders" ypT3cd-4Nx and divided into three surgical procedures: total mesorectal excision (TME), extended-TME (eTME) and beyond-TME (b-TME)...
September 17, 2016: European Journal of Surgical Oncology
Cara C Schafer, Yong Wang, Kenneth P Hough, Anandi Sawant, Stefan C Grant, Victor J Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S Deshane
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival...
September 26, 2016: Oncotarget
W Xu, Z Xu, H Cheng, J Ying, F Cheng, W Xu, J Cao, J Luo
AIM: The objective of this meta-analysis was to evaluate the feasibility, safety, and short-term clinical outcomes of transanal total mesorectal excision (TaTME) comparing with laparoscopy total mesorectal excision (LapTME) for mid and low rectal cancer. METHODS: Relevant studies were searched from the databases of Pubmed, Embase, and the Cochrane Library. The qualities of all of the included studies were evaluated using Newcastle-Ottawa Scale (NOS). The synthesized outcomes were pooled using fixed-effects models or random-effects models, which weighted the odds ratio (OR) or mean difference (MD) with 95% confidence intervals (95% CI)...
September 19, 2016: European Journal of Surgical Oncology
Peter Bondeven
Rectal cancer constitutes one-third of all colorectal cancers, and the incidence in Denmark increasing. In 2012, 1.400 cases were registered, and of these 38% were located in the upper rectum. There have been several key advances in the optimal management of rectal cancer during the past decades, primarily by standardisation and improvement of the surgical procedure. There is now general agreement that the optimal surgical treatment involves the concept of total mesorectal excision and that a resection with tumour-free margins is crucial...
October 2016: Danish Medical Journal
M-P Bernardi, A L A Bloemendaal, M Albert, M Whiteford, A R L Stevenson, R Hompes
PURPOSE: Transanal total mesorectal excision (taTME) requires specific technical expertise, as it is often difficult to ascertain the correct dissection plane. Consequently, one can easily enter an incorrect plane, potentially resulting in bleeding (sidewall or presacral vessels), autonomic nerve injury and urethral injury. We aim to demonstrate specific visual features, which may be encountered during surgery and can guide the surgeon to perform the dissection in the correct plane. METHOD: Specific features of dissection in the correct and incorrect planes are demonstrated in the accompanying video...
October 1, 2016: Techniques in Coloproctology
Paul Kuria, Muhammad Ilyas, Elijah Ateka, Douglas Miano, Justus Onguso, James C Carrington, Nigel J Taylor
Mitigation of cassava mosaic disease (CMD) focuses on the introgression of resistance imparted by the polygenic recessive (CMD1), dominant monogenic (CMD2) and CMD3 loci. The mechanism(s) of resistance they impart, however, remain unknown. Two CMD susceptible and nine CMD resistant cassava genotypes were inoculated by microparticle bombardment with infectious clones of African cassava mosaic virus Cameroon strain (ACMV-CM) and the Kenyan strain K201 of East African cassava mosaic virus (EACMV KE2 [K201]). Genotypes carrying the CMD1 (TMS 30572), CMD2 (TME 3, TME 204 and Oko-iyawo) and CMD3 (TMS 97/0505) resistance mechanisms showed high levels of resistance to ACMV-CM, with viral DNA undetectable by PCR beyond 7days post inoculation (dpi)...
September 29, 2016: Virus Research
Marta Penna, Nicolas C Buchs, Alexander L Bloemendaal, Roel Hompes
The surgical approach to total mesorectal excision (TME) for rectal cancer has undergone a substantial evolution with the adoption of more minimally invasive procedures. Transanal TME (taTME) is the latest advanced technique pioneered to tackle difficult pelvic dissections. Areas covered: The evolution of TME surgery from open to laparoscopic, robotic and transanal techniques was explored in this review. The outcomes to date on the latest approach, taTME, are reviewed and the future direction of rectal cancer surgery proposed...
October 3, 2016: Expert Review of Anticancer Therapy
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