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https://www.readbyqxmd.com/read/29449898/targeted-therapy-of-brain-metastases-latest-evidence-and-clinical-implications
#1
REVIEW
Rodica Di Lorenzo, Manmeet S Ahluwalia
Brain metastases (BM) occur in 20-40% of patients with cancer and 60-75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients are living longer and are more likely to experience complications from BM. The diagnosis of BM drastically worsens long-term survival rates, with multiple metastases being a poor prognostic factor. Until recently, the mainstay of treatment consisted of stereotactic radiosurgery (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination of these modalities...
December 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29449659/using-immunotherapy-to-boost-the-abscopal-effect
#2
REVIEW
Wilfred Ngwa, Omoruyi Credit Irabor, Jonathan D Schoenfeld, Jürgen Hesser, Sandra Demaria, Silvia C Formenti
More than 60 years ago, the effect whereby radiotherapy at one site may lead to regression of metastatic cancer at distant sites that are not irradiated was described and called the abscopal effect (from 'ab scopus', that is, away from the target). The abscopal effect has been connected to mechanisms involving the immune system. However, the effect is rare because at the time of treatment, established immune-tolerance mechanisms may hamper the development of sufficiently robust abscopal responses. Today, the growing consensus is that combining radiotherapy with immunotherapy provides an opportunity to boost abscopal response rates, extending the use of radiotherapy to treatment of both local and metastatic disease...
February 16, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29449532/senescence-associated-secretory-factors-induced-by-cisplatin-in-melanoma-cells-promote-non-senescent-melanoma-cell-growth-through-activation-of-the-erk1-2-rsk1-pathway
#3
Xuerong Sun, Benyan Shi, Huiling Zheng, Ling Min, Jie Yang, Xiaoyi Li, Xiaoxin Liao, Weixing Huang, Mingmeng Zhang, Shun Xu, Zhe Zhu, Hongjing Cui, Xinguang Liu
Although targeted therapy and immunotherapy greatly improve the outcome of melanoma, drug resistance and low response rates still maintain the unsubstitutability of traditional chemotherapy. Cisplatin (CDDP) is widely used in different types of tumours with high response rates, but it generally has low efficiency in melanoma. The mechanisms underpinning the phenomena are not sufficiently understood. Here we demonstrated that various melanoma cell lines adopted senescence phenotype after CDDP treatment in contrast to the other types of tumour cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449192/association-of-body-mass-index-and-outcomes-in-patients-with-metastatic-melanoma-treated-with-targeted-therapy-immunotherapy-or-chemotherapy-a-retrospective-multicohort-analysis
#4
Jennifer L McQuade, Carrie R Daniel, Kenneth R Hess, Carmen Mak, Daniel Y Wang, Rajat R Rai, John J Park, Lauren E Haydu, Christine Spencer, Matthew Wongchenko, Stephen Lane, Dung-Yang Lee, Mathilde Kaper, Meredith McKean, Kathryn E Beckermann, Samuel M Rubinstein, Isabelle Rooney, Luna Musib, Nageshwar Budha, Jessie Hsu, Theodore S Nowicki, Alexandre Avila, Tomas Haas, Maneka Puligandla, Sandra Lee, Shenying Fang, Jennifer A Wargo, Jeffrey E Gershenwald, Jeffrey E Lee, Patrick Hwu, Paul B Chapman, Jeffrey A Sosman, Dirk Schadendorf, Jean-Jacques Grob, Keith T Flaherty, Dana Walker, Yibing Yan, Edward McKenna, Jeffrey J Legos, Matteo S Carlino, Antoni Ribas, John M Kirkwood, Georgina V Long, Douglas B Johnson, Alexander M Menzies, Michael A Davies
BACKGROUND: Obesity has been linked to increased mortality in several cancer types; however, the relation between obesity and survival outcomes in metastatic melanoma is unknown. The aim of this study was to examine the association between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma who received targeted therapy, immunotherapy, or chemotherapy. METHODS: This retrospective study analysed independent cohorts of patients with metastatic melanoma assigned to treatment with targeted therapy, immunotherapy, or chemotherapy in randomised clinical trials and one retrospective study of patients treated with immunotherapy...
February 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29449085/the-simultaneous-isolation-of-multiple-high-and-low-frequent-t-cell-populations-from-donor-peripheral-blood-mononuclear-cells-using-the-major-histocompatibility-complex-i-streptamer-isolation-technology
#5
Marthe C J Roex, Lois Hageman, Matthias T Heemskerk, Sabrina A J Veld, Ellis van Liempt, Michel G D Kester, Lothar Germeroth, Christian Stemberger, J H Frederik Falkenburg, Inge Jedema
BACKGROUND: Adoptive transfer of donor-derived T cells can be applied to improve immune reconstitution in immune-compromised patients after allogeneic stem cell transplantation. The separation of beneficial T cells from potentially harmful T cells can be achieved by using the major histocompatibility complex (MHC) I-Streptamer isolation technology, which has proven its feasibility for the fast and pure isolation of T-cell populations with a single specificity. We have analyzed the feasibility of the simultaneous isolation of multiple antigen-specific T-cell populations in one procedure by combining different MHC I-Streptamers...
February 12, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29448849/development-of-small-molecule-immune-checkpoint-inhibitors-of-pd-1-pd-l1-as-a-new-therapeutic-strategy-for-tumour-immunotherapy
#6
Kui Li, Tian Hongqi
Cancer immunotherapy has been increasingly utilized to treat advanced malignancies. The signalling network of immune checkpoints has attracted considerable attention. Immune checkpoint inhibitors are revolutionizing the treatment options and expectations for patients with cancer. The reported clinical success of targeting the T-cell immune checkpoint receptors PD-1/PD-L1 has demonstrated the importance of immune modulation. Indeed, antibodies binding to PD-1 or PD-L1 have shown remarkable efficacy. However, antibody drugs have many disadvantages, such as their production cost, stability, and immunogenicity, and therefore, small-molecule inhibitors of PD-1 and its ligand PD-L1 are being introduced...
February 16, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29446615/leveraging-engineering-of-cells-for-drug-delivery
#7
Zhaowei Chen, Quanyin Hu, Zhen Gu
Cell therapy has become a momentum-gathering treatment strategy for a variety of diseases, including cancer, diabetes, hemophilia, and cardiomyopathy. However, clinical applications of conventional cell therapies have often been compromised by rapid decline in viability and function of the transplanted cells due to host recognition and subsequent foreign body rejection. Along this line, cell engineering technologies such as cell encapsulation within microcapsules and immobilization in porous scaffolds have been implemented to address the immunosuppression concerns...
February 15, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#8
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina I Wikstrom, Pontus Blomberg, Bjorn E Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
PURPOSE: To evaluate the safety, efficacy and immunobiological correlates of allogeneic NK cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. EXPERIMENTAL DESIGN: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29444918/immunotherapy-a-new-standard-of-care-in-thoracic-malignancies-a-summary-of-the-european-respiratory-society-research-seminar-of-the-thoracic-oncology-assembly
#9
Adrien Costantini, Marta Grynovska, Francesca Lucibello, Jorge Moisés, Franck Pagès, Ming S Tsao, Frances A Shepherd, Hasna Bouchaab, Marina Garassino, Joachim G J V Aerts, Julien Mazières, Michele Mondini, Thierry Berghmans, Anne-Pascale Meert, Jacques Cadranel
In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in thoracic malignancies?" was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events...
February 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29444087/safety-and-efficacy-of-anti-pd-l1-therapy-in-the-woodchuck-model-of-hbv-infection
#10
Scott Balsitis, Volodymyr Gali, Pamela J Mason, Susan Chaniewski, Steven M Levine, Michael J Wichroski, Michael Feulner, Yunling Song, Karen Granaldi, James K Loy, Chris M Thompson, Jacob A Lesniak, Catherine Brockus, Narendra Kishnani, Stephan Menne, Mark I Cockett, Renuka Iyer, Stephen W Mason, Daniel J Tenney
Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters...
2018: PloS One
https://www.readbyqxmd.com/read/29443657/il-2-and-beyond-in-cancer-immunotherapy
#11
John M Wrangle, Alicia Patterson, C Bryce Johnson, Daniel J Neitzke, Shikhar Mehrotra, Chadrick E Denlinger, Chrystal M Paulos, Zihai Li, David J Cole, Mark P Rubinstein
The development of the T- and natural killer (NK) cell growth factor IL-2 has been a sentinel force ushering in the era of immunotherapy in cancer. With the advent of clinical grade recombinant IL-2 in the mid-1980s, oncologists could for the first time directly manipulate lymphocyte populations with systemic therapy. By itself, recombinant IL-2 can induce clinical responses in up to 15% of patients with metastatic cancer or renal cell carcinoma. When administered with adoptively transferred tumor-reactive lymphocytes, IL-2 promotes T cell engraftment and response rates of up to 50% in metastatic melanoma patients...
February 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29441454/chemotherapy-and-immunotherapy-for-recurrent-and-metastatic-head-and-neck-cancer-a-systematic-review
#12
REVIEW
Alessandro Guidi, Carla Codecà, Daris Ferrari
Head and neck cancer (HNC) is a fatal malignancy with an overall long-term survival of about 50% for all stages. The diagnosis is not rarely delayed, and the majority of patients present with loco-regionally advanced disease. The rate of second primary tumors after a diagnosis of HNC is about 3-7% per year, the highest rate among solid tumors. Currently, a single-modality or a combination of surgery, radiotherapy and chemotherapy (CHT), is the standard treatment for stage III-IV HNC. For the recurrent/metastatic setting, in the last 40 years great efforts have been made in order to develop a more effective CHT regimen, from the use of methotrexate alone, to the combination of cisplatin (CDDP) and 5-fluorouracile (5FU) or paclitaxel...
February 13, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29441437/immune-checkpoint-blockade-the-new-frontier-in-cancer-treatment
#13
Jeffrey M Clarke, Daniel J George, Stacey Lisi, April K S Salama
Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival...
February 13, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29440290/a-spatio-temporal-model-of-macrophage-mediated-drug-resistance-in-glioma-immunotherapy
#14
Yongjiang Zheng, Jiguang Bao, Qiyi Zhao, Tianshou Zhou, Xiaoqiang Sun
The emergence of drug resistance is often an inevitable obstacle that limits the long-term effectiveness of clinical cancer chemotherapeutics. Although various forms of cancer cell-intrinsic mechanisms of drug resistance have been experimentally revealed, the role and the underlying mechanism of tumor microenvironment in driving the development of acquired drug resistance remain elusive, which significantly impedes effective clinical cancer treatment. Recent experimental studies have revealed a macrophage-mediated drug resistance mechanism in which the tumor microenvironment undergoes adaptation in response to macrophage-targeted colony-stimulating factor-1 receptor (CSF1R) inhibition therapy in gliomas...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29438186/peanut-allergy-reduction-in-high-risk-pediatric-patients
#15
Jaime Hopper, Courtney Hopp, Jessica Durbin
The prevalence of food allergies has doubled in the past 10 years. Peanut allergies are a significant public health issue and are the primary reason for food-related anaphylactic reactions that result in death. Evidence supports that early introduction of the peanut protein (or in combination with immunotherapy) to the highly allergic may safely desensitize patients, which could lead to less adverse allergic reactions and alter allergy management overall.
March 12, 2018: Nurse Practitioner
https://www.readbyqxmd.com/read/29437535/safety-and-clinical-activity-of-pembrolizumab-and-multisite-stereotactic-body-radiotherapy-in-patients-with-advanced-solid-tumors
#16
Jason J Luke, Jeffrey M Lemons, Theodore G Karrison, Sean P Pitroda, James M Melotek, Yuanyuan Zha, Hania A Al-Hallaq, Ainhoa Arina, Nikolai N Khodarev, Linda Janisch, Paul Chang, Jyoti D Patel, Gini F Fleming, John Moroney, Manish R Sharma, Julia R White, Mark J Ratain, Thomas F Gajewski, Ralph R Weichselbaum, Steven J Chmura
Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1-treatment outcomes may be improved with lower disease burden. In this context, we conducted a phase I study to evaluate the safety of pembrolizumab with multisite SBRT in patients with metastatic solid tumors. Patients and Methods Patients progressing on standard treatment received SBRT to two to four metastases...
February 13, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29436395/myeloid-targeted-immunotherapies-act-in-synergy-to-induce-inflammation-and-antitumor-immunity
#17
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
https://www.readbyqxmd.com/read/29435842/perspectives-in-head-and-neck-medical-oncology
#18
Idoroenyi Amanam, Rohan Gupta, Alain Mita, Kevin Scher, Erminia Massarelli
The modern treatment of locoregionally advanced disease often requires a multimodality combination approach. A number of chemotherapeutic agents can be combined with radiation, but the platinum agent cisplatin, a potent radiation sensitizer, is best studied in head and neck cancer. Newer agents such as cetuximab can be used in combination with radiation therapy for those patients who cannot tolerate cisplatin. For chemotherapy-naïve patients with metastatic head and neck cancer who demonstrate a good performance status, platinum doublet regimens are commonly used...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29435154/efficacy-of-granulocyte-macrophage-colony-stimulating-factor-combined-with-metronomic-paclitaxel-in-the-treatment-of-lewis-lung-carcinoma-transplanted-in-mice
#19
Nengping Zhu, Rongsheng Qin, Qin Zhang, Shaozhi Fu, Shanshan Liu, Yue Chen, Juan Fan, Yunwei Han
Metronomic chemotherapy in combination with immunotherapy is an attractive approach in cancer therapy. The purpose of the present study was to investigate the anti-tumor effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with metronomic paclitaxel (MET PTX) on Lewis lung carcinoma transplanted in mice. In the present study, tumor-bearing mice survival time and tumor growth were monitored. The day after the end of the treatment, white blood cells were counted, and the number and maturation of dendritic cell were determined by flow cytometry...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434859/silencing-of-suppressor-of-cytokine-signaling-1-enhances-the-immunological-effect-of-mucin-1-calreticulin-primed-4t1-cell-treated-dendritic-cells-in-breast-cancer-treatment
#20
Song Qin, Zhipeng Gao, Yu Liu, Changbai Liu, Jun Wang, Li Li Zou
In cancer immunotherapy, dendritic cell (DC)-based vaccines represent a promising, yet challenging, treatment method. In addition to overcoming the low expression levels of antigenic epitopes on cancer cells, it is also necessary to overcome the inhibitory effect of suppressor of cytokine signaling 1 (SOCS1) on DC self-antigen presentation. Our group previously demonstrated that calreticulin (CRT) translocated type I transmembrane glycoprotein mucin 1 (MUC1), a breast cancer antigen, to the surface of 4T1 cells, and that treatment with MUC1-CRT-primed 4T1 cell-treated DCs induced apoptosis in a breast cancer cell line...
February 2018: Oncology Letters
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