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Cancer inflamation

Mark Owyong, Gizem Efe, Michael Owyong, Aamna J Abbasi, Vaishnavi Sitarama, Vicki Plaks
There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT) mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME) and specifically, those directly affecting critical players to ensure CIT efficacy...
2018: Frontiers in Cell and Developmental Biology
David A Schaer, Richard P Beckmann, Jack A Dempsey, Lysiane Huber, Amelie Forest, Nelusha Amaladas, Yanxia Li, Ying Cindy Wang, Erik R Rasmussen, Darin Chin, Andrew Capen, Carmine Carpenito, Kirk A Staschke, Linda A Chung, Lacey M Litchfield, Farhana F Merzoug, Xueqian Gong, Philip W Iversen, Sean Buchanan, Alfonso de Dios, Ruslan D Novosiadly, Michael Kalos
Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), has recently been approved for the treatment of hormone receptor-positive breast cancer. In this study, we use murine syngeneic tumor models and in vitro assays to investigate the impact of abemaciclib on T cells, the tumor immune microenvironment and the ability to combine with anti-PD-L1 blockade. Abemaciclib monotherapy resulted in tumor growth delay that was associated with an increased T cell inflammatory signature in tumors. Combination with anti-PD-L1 therapy led to complete tumor regressions and immunological memory, accompanied by enhanced antigen presentation, a T cell inflamed phenotype, and enhanced cell cycle control...
March 13, 2018: Cell Reports
Lucia Negri, Napoleone Ferrara
The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility...
April 1, 2018: Physiological Reviews
Q B Tran, R Mizumoto, S Ratnayake, B Strekozov
INTRODUCTION: Silent metastatic gastric adenocarcinoma presenting as appendicitis is very rare. Rare pathologies may be encountered during common operations such as appendicectomy and an awareness of possible alternative pathological entities would be helpful in a surgeon's wealth of knowledge. PRESENTATION OF CASE: A 63-year-old man presented with a three-day history of acute abdominal pain suggestive of appendicitis. Intra-operatively, a macroscopically inflamed and perforated appendix was found...
February 16, 2018: International Journal of Surgery Case Reports
Yared Hailemichael, Amber Woods, Tihui Fu, Qiuming He, Michael C Nielsen, Farah Hasan, Jason Roszik, Zhilan Xiao, Christina Vianden, Hiep Khong, Manisha Singh, Meenu Sharma, Faisal Faak, Derek Moore, Zhimin Dai, Scott M Anthony, Kimberly S Schluns, Padmanee Sharma, Victor H Engelhard, Willem W Overwijk
Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control...
February 26, 2018: Journal of Clinical Investigation
Jun-Bin Li, Lanlan Chen, Qianqian Wang, Hong-Wen Liu, Xiao-Xiao Hu, Lin Yuan, Xiaobing Zhang
Peroxynitrite (ONOO-), an extremely reactive nitrogen species (RNS), is implicated in diverse pathophysiological conditions, including cancer, neurodegenerative diseases and inflammation. Sensing and imaging of ONOO- in living systems remains challenging due to the high autofluorescence and the limited light penetration depth. In this work, we developed a bioluminescent probe BP-PN, based on luciferase-luciferin pairs and the ONOO--responded group α-ketoamide, for highly sensitive detection and imaging of endogenous ONOO- in living cells and mice for the first time...
February 22, 2018: Analytical Chemistry
Chithra Devi Palani, Lalitha Ramanathapuram, Aroonwan Lam-Ubol, Zoya B Kurago
Patient treatment for oral squamous cell carcinoma (OSCC) not associated with Human papillomavirus remains problematic. OSCC microenvironment is typically inflamed and colonized by microorganisms, providing ligands for toll-like receptors (TLR). In immune cells TLR2 and TLR4 activate NF-kB and extracellular signal regulated kinase (ERK)1/2 pathways, leading to upregulation of inhibitory adenosine receptors A2a and A2b, and reduction in stimulatory A1 and A3. How TLR and adenosine receptors function in SCC cells is not understood...
January 23, 2018: Oncotarget
Flavia Merigo, Alessandro Brandolese, Sonia Facchin, Silvia Missaggia, Paolo Bernardi, Federico Boschi, Renata D'Incà, Edoardo Vincenzo Savarino, Andrea Sbarbati, Giacomo Carlo Sturniolo
AIM: To investigate by immunostaining glucose transporter expression in human colorectal mucosa in controls and patients with inflammatory bowel disease (IBD). METHODS: Colorectal samples were obtained from patients undergoing lower endoscopic colonoscopy or recto-sigmoidoscopy. Patients diagnosed with ulcerative colitis ( n = 18) or Crohn's disease ( n = 10) and scheduled for diagnostic colonoscopy were enrolled. Patients who underwent colonoscopy for prevention screening of colorectal cancer or were followed-up after polypectomy or had a history of lower gastrointestinal symptoms were designated as the control group (CTRL, n = 16)...
February 21, 2018: World Journal of Gastroenterology: WJG
Bedia Begum Karakocak, Jue Liang, Pratim Biswas, Nathan Ravi
For targeted delivery with nanoparticles (NPs) as drug carriers, it is imperative that the NPs are internalized into the targeted cell. Surface properties of NPs influence their interactions with cells. We examined the responses of retinal pigment epithelial cells, NIH 3T3 fibroblast cells, and Chinese hamster ovary cells to gold nanoparticles (Au NPs) in their nascent form as well as coated with end-thiolated hyaluronate (HS-HA). The grafting density of HS-HA on Au NPs was calculated based on total organic carbon measurements and thermal gravimetric analysis...
April 15, 2018: Carbohydrate Polymers
Zongshan Shen, Jiancheng Wang, Qiting Huang, Yue Shi, Zhewei Wei, Xiaoran Zhang, Yuan Qiu, Min Zhang, Yi Wang, Wei Qin, Shuheng Huang, Yinong Huang, Xin Liu, Kai Xia, Xinchun Zhang, Zhengmei Lin
Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting...
February 14, 2018: Cell Death & Disease
Curtis J Perry, Andrés R Muñoz-Rojas, Katrina M Meeth, Laura N Kellman, Robert A Amezquita, Durga Thakral, Victor Y Du, Jake Xiao Wang, William Damsky, Alexandra L Kuhlmann, Joel W Sher, Marcus Bosenberg, Kathryn Miller-Jensen, Susan M Kaech
Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state...
February 7, 2018: Journal of Experimental Medicine
Shalin Shah, Kevin Wood, Brian Labadie, Brian Won, Ryan Brisson, Theodore Karrison, Thomas Hensing, Mark Kozloff, Riyue Bao, Jyoti D Patel, Jason J Luke
Hypothesis: The majority of non-small cell lung cancer (NSCLC) patients treated with anti-PD-1/PD-L1 therapy develop either innate or acquired resistance. Across tumor types, the "T cell-inflamed" tumor microenvironment correlates with clinical response to immunotherapy. We hypothesize that clinical characteristics may be predictive of resistance and that "T cell-inflamed" NSCLC tumors can be identified by gene expression profiling. Results: Of 93 patients, 36 (38...
January 12, 2018: Oncotarget
Iris Hecht, Amir Toporik, Joseph R Podojil, Ilan Vaknin, Gady Cojocaru, Anat Oren, Elizabeta Aizman, Spencer C Liang, Ling Leung, Yosef Dicken, Amit Novik, Nadav Marbach-Bar, Aziza Elmesmari, Clare Tange, Ashley Gilmour, Donna McIntyre, Mariola Kurowska-Stolarska, Kay McNamee, Judith Leitner, Shirley Greenwald, Liat Dassa, Zurit Levine, Peter Steinberger, Richard O Williams, Stephen D Miller, Iain B McInnes, Eyal Neria, Galit Rotman
The B7-like protein family members play critical immunomodulatory roles and constitute attractive targets for the development of novel therapies for human diseases. We identified Ig-like domain-containing receptor (ILDR)2 as a novel B7-like protein with robust T cell inhibitory activity, expressed in immune cells and in immune-privileged and inflamed tissues. A fusion protein, consisting of ILDR2 extracellular domain with an Fc fragment, that binds to a putative counterpart on activated T cells showed a beneficial effect in the collagen-induced arthritis model and abrogated the production of proinflammatory cytokines and chemokines in autologous synovial-like cocultures of macrophages and cytokine-stimulated T cells...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
George C Prendergast, William J Malachowski, Arpita Mondal, Peggy Scherle, Alexander J Muller
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8+ T effector cells and natural killer cells and induces CD4+ T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers...
2018: International Review of Cell and Molecular Biology
Guinever Eustaquio do Imperio, Enrrico Bloise, Mohsen Javam, Phetcharawan Lye, Andrea Constantinof, Caroline Dunk, Fernando Marcos Dos Reis, Stephen James Lye, William Gibb, Tania M Ortiga-Carvalho, Stephen Giles Matthews
BACKGROUND/AIMS: The ATP-binding cassette (ABC) transporters mediate drug biodisposition and immunological responses in the placental barrier. In vitro infective challenges alter expression of specific placental ABC transporters. We hypothesized that chorioamnionitis induces a distinct pattern of ABC transporter expression. METHODS: Gene expression of 50 ABC transporters was assessed using TaqMan® Human ABC Transporter Array, in preterm human placentas without (PTD; n=6) or with histological chorioamnionitis (PTDC; n=6)...
January 29, 2018: Cellular Physiology and Biochemistry
Adrian Frick, Vineeta Khare, Gregor Paul, Michaela Lang, Franziska Ferk, Siegfried Knasmueller, Andrea Beer, Georg Oberhuber, Christoph Gasche
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated-cancer (CAC), however, the underlying processes of disease progression are not completely understood. Here, the molecular processes of inflammation-driven colon carcinogenesis were investigated using IL-10 deficient mice (IL-10- KO). IL-10- KO mice were euthanized after development of colitis and dysplasia. Immunohistochemistry (IHC) was performed for markers of colitis-induced DNA damage (CIDD): oxidative-DNA-lesions (8-oxoG), double-strand breaks (DSB; γH2AX) and DSB-repair...
January 29, 2018: Molecular Cancer Research: MCR
Rondell P Graham, Bita V Naini, Sejal S Shah, Christina A Arnold, Rajesh Kannangai, Michael S Torbenson, Dora M Lam-Himlin
BACKGROUND: Human intestinal spirochetosis (IS) has been recognized for decades, but whether it represents commensalism or a pathogenic process remains controversial. IS is diagnosed on routine stains with confirmation by silver stains but these stains are labor intensive and slow to read. We evaluated the Treponema pallidum immunostain as a diagnostic adjunct for IS. METHODS: We retrieved biopsies from 33 patients with IS for this study. Each case was tested by Warthin-Starry (WS) and T...
January 22, 2018: Diagnostic Pathology
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
Conventional cancer treatments such as surgery, radiotherapy, chemotherapy and targeted therapy, not only destruct tumors, but also injure the normal tissues, resulting in limited efficacy. Recent advances in cancer therapy have aimed at changing the host milieu of cancer against its development and progression by targeting tumor microenvironment and host immune system to eradicate tumors. To the host body, tumors arise in tissues. They impair the normal healthy tissue physiological function, become chronically inflamed and develop non-healing or overhealing wounds as well as drive immuno-suppressive activity to escape immunity attack...
2018: Cancer Cell International
Thomas Ian Whitehead-Clarke, Farag Smew, Ahsan Zaidi, Dimitrios Pissas
After a positive faecal occult blood test, a 60-year-old woman underwent a screening colonoscopy which identified a malignant-looking ulcer in the ascending colon. Biopsies from the lesion were inconclusive. A subsequent CT scan of the abdomen and pelvis commented on a polypoid lesion in the ascending colon. A colorectal cancer multidisciplinary team discussion concluded that a right hemicolectomy was indicated as the lesion was suspicious for malignancy. Intraoperatively, there was a firm ascending colon mass adherent to the abdominal wall, which was resected with clear margins...
January 24, 2018: BMJ Case Reports
Mikihiro Fujiya
Inflammatory bowel disease (IBD) is a major risk factor for colorectal cancer. Surveillance colonoscopy is presumably important for the early detection of colitis-associated cancer/dysplasia (CC/Ds). However, it is not easy to detect certain lesions in the inflamed mucosa using white-light endoscopy (WLE), even during the remission phase. Therefore, WLE with random biopsies has been the traditional approach for dysplasia detection. Recent advances in endoscopic technologies, including high-definition endoscopy and image-enhanced endoscopy, have improved the visibility of dysplastic lesions, suggesting that novel endoscopic procedures with a target biopsy are suitable for the surveillance of CC/Ds[1]...
January 23, 2018: Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society
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