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https://www.readbyqxmd.com/read/28529638/cxcr4-directed-endoradiotherapy-induces-high-response-rates-in-extramedullary-relapsed-multiple-myeloma
#1
Constantin Lapa, Ken Herrmann, Andreas Schirbel, Heribert Hänscheid, Katharina Lückerath, Margret Schottelius, Malte Kircher, Rudolf A Werner, Martin Schreder, Samuel Samnick, Saskia Kropf, Stefan Knop, Andreas K Buck, Hermann Einsele, Hans-Juergen Wester, K Martin Kortüm
C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM). Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival...
2017: Theranostics
https://www.readbyqxmd.com/read/28507794/a-novel-nanobody-based-target-module-for-retargeting-of-t-lymphocytes-to-egfr-expressing-cancer-cells-via-the-modular-unicar-platform
#2
Susann Albert, Claudia Arndt, Anja Feldmann, Ralf Bergmann, Dominik Bachmann, Stefanie Koristka, Florian Ludwig, Pauline Ziller-Walter, Alexandra Kegler, Sebastian Gärtner, Marc Schmitz, Armin Ehninger, Marc Cartellieri, Gerhard Ehninger, Hans-Jürgen Pietzsch, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
Recent treatments of leukemias with chimeric antigen receptor (CAR) expressing T cells underline their impressive therapeutic potential. However, once adoptively transferred into patients, there is little scope left to shut them down after elimination of tumor cells or in case adverse side effects occur. This becomes of special relevance if they are directed against commonly expressed tumor associated antigens (TAAs) such as receptors of the ErbB family. To overcome this limitation, we recently established a modular CAR platform technology termed UniCAR...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#3
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28498481/comparison-of-three-different-methods-for-the-detection-of-circulating-tumor-cells-in-mice-with-lung-metastasis
#4
Weifeng Xu, Bing Wu, Lengxi Fu, Junying Chen, Zeng Wang, Fei Huang, Jinrong Chen, Mei Zhang, Zhenhuan Zhang, Jingan Lin, Ruilong Lan, Ruiqing Chen, Wei Chen, Long Chen, Jinsheng Hong, Weijian Zhang, Yuxiong Ding, Paul Okunieff, Jianhua Lin, Lurong Zhang
Circulating tumor cells (CTCs) represent the key step of cancer cell dissemination. The alteration of CTCs correlates with the treatment outcome and prognosis. To enrich and identify CTCs from billions of blood cells renders a very challenging task, which triggers development of several methods, including lysis of RBC plus negative or positive enrichment using antibodies, and filter membrane or spiral microfluidics to capture CTCs. To compare the advantages of different enrichment methods for CTCs, we utilized the 4T1 breast cancer cells transfected with both green fluorescent protein (GFP) and luciferase to trace CTCs in the experimental lung metastasis model...
May 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28492339/venetoclax-for-the-treatment-of-patients-with-chronic-lymphocytic-leukemia
#5
Jennifer Crombie, Matthew S Davids
Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2 with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia (CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to tumor lysis syndrome in some patients with a large tumor burden, but this risk was subsequently mitigated by a revised study design that included lower initial dosing with intrapatient dose ramp-up and close tumor lysis syndrome monitoring and prophylaxis...
May 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28478879/tumor-lysis-syndrome-a-unique-solute-disturbance
#6
REVIEW
Penelope Z Strauss, Shannan K Hamlin, Johnny Dang
Tumor lysis syndrome (TLS) is a life-threatening disorder that is an oncologic emergency. Risk factors for TLS are well-known, but the current literature shows case descriptions of unexpected acute TLS. Solid tumors and untreated hematologic tumors can lyse under various circumstances in children and adults. International guidelines and recommendations, including the early involvement of the critical care team, have been put forward to help clinicians properly manage the syndrome. Advanced practice nurses may be in the position of triaging and initiating treatment of patients with TLS, and need a thorough understanding of the syndrome and its treatment...
June 2017: Nursing Clinics of North America
https://www.readbyqxmd.com/read/28477372/adcc-employing-an-nk-cell-line-hank-expressing-the-high-affinity-cd16-allele-with-avelumab-an-anti-pd-l1-antibody
#7
Caroline Jochems, James W Hodge, Massimo Fantini, Kwong Y Tsang, Amanda J Vandeveer, James L Gulley, Jeffrey Schlom
NK-92 cells, and their derivative, designated aNK, were obtained from a patient with non-Hodgkin lymphoma. Prior clinical studies employing adoptively transferred irradiated aNK cells have provided evidence of clinical benefit and an acceptable safety. aNK cells have now been engineered to express IL-2 and the high affinity (ha) CD16 allele (designated haNK). Avelumab is a human IgG1 anti-PD-L1 monoclonal antibody, which has shown evidence of clinical activity in a range of human tumors. Prior in vitro studies have shown that avelumab has the ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of human tumor cells when combined with NK cells...
May 6, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28475775/autocrine-activation-of-the-ifn-signaling-pathway-may-promote-immune-escape-in-glioblastoma
#8
Manuela Silginer, Sara Nagy, Caroline Happold, Hannah Schneider, Michael Weller, Patrick Roth
Background.: Interferons (IFNs) are cytokines typically induced upon viral infection but are constitutively expressed also in the absence of acute infection. The physiological role of autocrine and paracrine IFN signaling, however, remains poorly understood, and its function in glioblastoma has not been explored in depth. Methods.: Using RNA interference-mediated gene silencing, we characterized constitutive type I IFN signaling and its role in human glioma cells...
May 5, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28473665/anti-tumor-activity-of-an-immunotoxin-tgf%C3%AE-pe38-delivered-by-attenuated-salmonella-typhimurium
#9
Daejin Lim, Kwang Soo Kim, Hyunju Kim, Kyong-Cheol Ko, Jae Jun Song, Jong Hyun Choi, Minsang Shin, Jung-Joon Min, Jae-Ho Jeong, Hyon E Choy
The anticancer strategy underlying the use of immunotoxins is as follows: the cancer-binding domain delivers the toxin to a cancer cell, after which the toxin enters and kills the cell. TGFα-PE38 is an immunotoxin comprising transforming growth factor alpha (TGFα), a natural ligand of epidermal growth factor receptor (EGFR), and a modified Pseudomonas exotoxin A (PE38) lacking N terminal cell-binding domain, a highly potent cytotoxic protein moiety. Tumor cells with high level of EGFR undergo apoptosis upon treatment with TGFα-PE38...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28473408/lysis-of-human-neutrophils-by-community-associated-methicillin-resistant-staphylococcus-aureus
#10
Mallary C Greenlee-Wacker, Silvie Kremserová, William M Nauseef
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) cause infections associated with extensive tissue damage and necrosis. In vitro, human neutrophils fed CA-MRSA lyse by an unknown mechanism that is inhibited by necrostatin-1, an allosteric inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK-1). RIPK-1 figures prominently in necroptosis, a specific form of programmed cell death dependent on RIPK-1, RIPK-3 and the mixed lineage kinase-like protein (MLKL). We previously reported that necrostatin-1 inhibits lysis of human neutrophils fed CA-MRSA and attributed the process to necroptosis...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28468826/neuropilin-1-mediates-neutrophil-elastase-uptake-and-cross-presentation-in-breast-cancer-cells
#11
Celine Kerros, Satyendra C Tripathi, Dongxing Zha, Jennifer M Mehrens, Anna Sergeeva, Anne V Philips, Na Qiao, Haley L Peters, Hiroyuki Katayama, Pariya Sukhumalchandra, Kathryn E Ruisaard, Alexander A Perakis, Lisa S St John, Sijie Lu, Elizabeth A Mittendorf, Karen Clise-Dwyer, Amanda C Herrmann, Gheath Alatrash, Carlo Toniatti, Samir M Hanash, Qing Ma, Jeffrey J Molldrem
Neutrophil elastase (NE) can be rapidly taken up by tumor cells that lack endogenous NE expression, including breast cancer, which results in cross-presentation of PR1, an NE-derived HLA-A2-restricted peptide that is an immunotherapy target in hematological and solid tumor malignancies. The mechanism of NE uptake, however, remains unknown. Using the mass spectometry-based approach, we identify neuropilin-1 (NRP1) as a NE receptor that mediates uptake and PR1 cross-presentation in breast cancer cells. We demonstrated that soluble NE is a specific, high-affinity ligand for NRP1 with a calculated Kd=38...
May 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28464762/cancer-targeted-oncolytic-adenoviruses-for-modulation-of-the-immune-system
#12
Vincenzo Cerullo, Cristian Capasso, Markus Vähä-Koskela, Otto Hemminki, Akseli Hemminki
Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen-presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit...
May 2, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28461998/detection-of-early-dj-stent-encrustation-by-sonographic-twinkling-artifacts-a-pilot-study
#13
Roman A Blaheta, Anton Oertl, Hans-Joachim Freisleben, Karen Nelson, Hanns Ackermann, Axel Haferkamp, Tobias Engl
INTRODUCTION: Ureter obstruction caused by a retro-peritoneal tumor is treated by inserting an indwelling ureter splint (DJ-stent). Indwelling duration is limited by cumulative crystalline deposits into the splint, eventually causing the repeated impairment of urine flow. Deciding when a DJ-stent must be replaced is important since belated removal can be accompanied by severe complications. X-ray or conventional sonography do not allow satisfactory evaluation of early incrustation, therefore, the use of sonographic twinkling artifacts (TA) to provide accurate stent surveillance was investigated...
2017: Central European Journal of Urology
https://www.readbyqxmd.com/read/28451002/-costal-metastasis-revealing-esophageal-squamous-cell-carcinoma
#14
Mamadou Ngoné Gueye, Gnagna Diouf, Daouda Dia, Awa Boye, Thierno Fall, Jean Louis Diémé, Oumar Ba, Mouhamadou Mbengue
Esophageal cancer is associated with poor prognosis. Its severity is linked to delayed diagnosis which is most often made once a cancer has metastasized, in Africa. Costal metastases are rare. We report a case of a 38-year old Senegalese patient with squamous cell carcinoma of the lower esophagus with lytic metastases to the ribs. Mrs. TD, aged 38, was admitted with painful swelling in right hemithorax associated with weight loss. The patient also reported mechanical dysphagia evolving during 4 months which had not motivated consultation...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28450695/hyperphosphatemia-a-cause-of-high-anion-gap-metabolic-acidosis-report-of-a-case-and-review-of-the-literature
#15
Seyed Ali Sadjadi, Alexander Pi
BACKGROUND Hyperphosphatemia is a common problem in patients with kidney failure. It is usually mild and rarely severe enough to cause metabolic acidosis on its own. Besides kidney failure, use of phosphate containing enemas, rhabdomyolysis, and tumor lysis syndrome are common causes of severe hyperphosphatemia. CASE REPORT A 74-year-old man with a history of diabetes mellitus type II, arterial hypertension, and end stage renal disease, who was on hemodialysis and who had undergone hemicolectomy for ischemic bowel disease, and had not eaten for several days, developed severe metabolic acidosis, with an anion gap (AG) of 31 meq/L, -uncorrected for serum albumin...
April 28, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28429138/prothrombotic-state-in-asthma-is-related-to-increased-levels-of-inflammatory-cytokines-il-6-and-tnf%C3%AE-in-peripheral-blood
#16
Stanislawa Bazan-Socha, Lucyna Mastalerz, Agnieszka Cybulska, Lech Zareba, Romy Kremers, Michal Zabczyk, Grazyna Pulka, Teresa Iwaniec, Coenraad Hemker, Anetta Undas
Recently, we have reported that asthma is associated with enhanced plasma thrombin formation and impaired fibrinolysis. The mechanisms underlying the prothrombotic state in this disease are unknown. Our aim was to investigate whether prothrombotic alterations in asthmatics are associated with inflammation. We studied 164 adult, white, stable asthmatics and 72 controls matched for age, sex, body mass index (BMI), and smoking. Plasma tumor necrosis factor α (TNFα), interleukin (IL)-6, and serum periostin were evaluated using ELISAs, and their associations with thrombin generation, fibrinolytic capacity, expressed as clot lysis time (CLT), and platelet markers were later analyzed...
April 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28428785/interferon-gamma-induces-changes-in-natural-killer-nk-cell-ligand-expression-and-alters-nk-cell-mediated-lysis-of-pediatric-cancer-cell-lines
#17
Arianexys Aquino-López, Vladimir V Senyukov, Zlatko Vlasic, Eugenie S Kleinerman, Dean A Lee
Natural killer (NK) cells have therapeutic potential for cancer due to their capacity for targeting tumor cells without prior sensitization. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion that secret 20 times the amount of interferon gamma (IFNγ) than resting NK cells. IFNγ can upregulate major histocompatibility complex (MHC)-class I, an inhibitory ligand for NK cells, but can also upregulate intercellular adhesion molecule 1 (ICAM-1) which promotes NK:target cell interaction for an efficient lysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#18
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423623/melanoma-associated-fibroblasts-decrease-tumor-cell-susceptibility-to-nk-cell-mediated-killing-through-matrix-metalloproteinases-secretion
#19
Linda Ziani, Thouraya Ben Safta-Saadoun, Johanne Gourbeix, Andrea Cavalcanti, Caroline Robert, Gilles Favre, Salem Chouaib, Jerome Thiery
Cancer-associated fibroblasts (CAFs) play a central role in the complex process of tumor-stroma interaction and promote tumor growth. Emerging evidences also suggest that these fibroblasts are involved in the alteration of the anti-tumor immune response by impacting several immune cell populations, especially through their secretion of pro-inflammatory and immunosuppressive factors in the tumor microenvironment. However, the underlying immuno-modulating mechanisms triggered by these fibroblasts are still only partially defined...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413674/spontaneous-tumor-lysis-syndrome-in-a-patient-with-metastatic-prostate-cancer
#20
Naomi Serling-Boyd, Zoe Quandt, Nazima Allaudeen
Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, with most cases occurring in hematological malignancies following the initiation of treatment. However, on rare occasions, TLS may occur in solid tumors as well. In the present case study, the case is reported of a 56-year-old African-American man who presented with a recent diagnosis of prostate cancer, abdominal pain, elevated transaminases, renal insufficiency, hyperkalemia, and hyperuricemia, consistent with spontaneous TLS in the setting of metastatic prostate cancer...
April 2017: Molecular and Clinical Oncology
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