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https://www.readbyqxmd.com/read/28636293/-treatment-of-advanced-hepatocellular-carcinoma-novel-agents-and-role-of-local-therapy
#1
Louis Parisod, Rafael Duran, Alban Denys, Antonia Digklia
The incidence of hepatocellular carcinoma (HCC) is increasing in Switzerland and its treatment is a challenge. The purpose of this article is to summarize the different therapeutic approaches in the metastatic stage, as well as the perspectives of targeted treatments and immunotherapy. Until recently, the only recognized therapeutic standard for these patients with metastatic CHC was sorafenib, a tyrosine kinase inhibitor. If the patient was to progress under sorafenib, no other recognized therapeutic option was available as second line...
May 17, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28634084/drug-delivery-to-melanoma-brain-metastases-can-current-challenges-lead-to-new-opportunities
#2
Gautham Gampa, Shruthi Vaidhyanathan, Jann N Sarkaria, William F Elmquist
Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease...
June 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#3
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28633362/human-papillomavirus-related-oropharyngeal-cancer
#4
M Taberna, M Mena, M A Pavón, L Alemany, M L Gillison, R Mesía
High-risk (HR) human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some parts of the world.The primary risk factor for developing HPV-related OPSCC is oral HPV-infection and the majority of oral HPV-infections are acquired by oral sex. Progression into a OPSCC includes persistent infection with evasion of immune response in the microenvironment, the activation of viral early genes (E6, E7) in basal epithelial cells, the deregulation of cell cycle and the accumulation of chromosomal instability...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#5
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28630682/overexpressed-prame-is-a-potential-immunotherapy-target-in-sarcoma-subtypes
#6
Jason Roszik, Wei-Lien Wang, John A Livingston, Christina L Roland, Vinod Ravi, Cassian Yee, Patrick Hwu, Andrew Futreal, Alexander J Lazar, Shreyaskumar R Patel, Anthony P Conley
BACKGROUND: PRAME (preferentially expressed antigen in melanoma), a member of the cancer-testis antigen family, has been shown to have increased expression in solid tumors, including sarcoma, and PRAME-specific therapies are currently in development for other cancers such as melanoma. METHODS: To map the landscape of PRAME expression in sarcoma, we used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) projects and determined which sarcoma subtypes and subsets are associated with increased PRAME expression...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28628776/3d-printed-lattices-as-an-activation-and-expansion-platform-for-t-cell-therapy
#7
Bahman Delalat, Frances Harding, Batjargal Gundsambuu, Elena M De-Juan-Pardo, Felix M Wunner, Marie-Luise Wille, Marek Jasieniak, Kristen A L Malatesta, Hans J Griesser, Antonio Simula, Dietmar W Hutmacher, Nicolas H Voelcker, Simon C Barry
One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation...
June 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#8
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28627410/current-and-upcoming-mitochondrial-targets-for-cancer-therapy
#9
REVIEW
Hyoung Kyu Kim, Yeon Hee Noh, Bernd Nilius, Kyung Soo Ko, Byoung Doo Rhee, Nari Kim, Jin Han
Mitochondria are essential intracellular organelles that regulate energy metabolism, cell death, and signaling pathways that are important for cell proliferation and differentiation. Therefore, mitochondria are fundamentally implicated in cancer biology, including initiation, growth, metastasis, relapse, and acquired drug resistance. Based on these implications, mitochondria have been proposed as a major therapeutic target for cancer treatment. In addition to classical view of mitochondria in cancer biology, recent studies found novel pathophysiological roles of mitochondria in cancer...
June 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28625798/melanoma-patient-imaging-in-the-era-of-effective-systemic-therapies
#10
M Stodell, J F Thompson, L Emmett, R F Uren, R Kapoor, R P M Saw
Imaging plays a critical role in the current multi-disciplinary management of patients with melanoma. It is used for primary disease staging, surgical planning, and surveillance in high-risk patients, and for monitoring the effects of systemic or loco-regional therapies. Several different imaging modalities have been utilised in the past. Contemporary imaging practises vary geographically depending on clinical guidelines, physician preferences, availability and cost. Targeted therapies and immunotherapies have revolutionised the treatment of patients with metastatic melanoma over the last few years...
May 25, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28625477/challenges-and-advances-in-the-diagnosis-biology-and-treatment-of-urothelial-upper-tract-and-bladder-carcinomas
#11
REVIEW
Jeanny B Aragon-Ching
Urothelial carcinomas span the bladder, ureter, and renal pelvis, and while there had been stagnation in the field of drug approval for the past two decades, there is now accelerated and regular US FDA approval of 5 immunotherapy agents. However, patients who inherently do not respond or progress on such therapies still represent an area of increased unmet need. In this special Seminars issue, we explore varying aspects of bladder urothelial carcinoma treatment with targeted therapies, the unique presentation and challenges in the treatment of upper tract and renal pelvis tumors, as well as new and emerging diagnostic imaging tools for varying genitourinary cancers...
July 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28623714/can-the-co-dependence-of-the-immune-system-and-angiogenesis-facilitate-pharmacological-targeting-of-tumours
#12
REVIEW
Lorenzo Mortara, Andrew V Benest, David O Bates, Douglas M Noonan
Tumours elicit a number of mechanisms to induce a reprogramming of innate and adaptive immune cells to their advantage, inducing a pro-angiogenic phenotype. Investigation of these events is now leading to the identification of specific myeloid and lymphoid cell-targeted therapies, as well as of unexplored off-target activities of clinically relevant chemotherapeutic and metabolic drugs. It is also leading to an enhanced understanding of the interplay between angiogenesis and the immune system, and the value of novel co-targeting approaches using both immunotherapy and anti-angiogenic therapy...
June 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28623233/structural-and-functional-analyses-of-pyroglutamate-amyloid-%C3%AE-specific-antibodies-as-a-basis-for-alzheimer-immunotherapy
#13
Anke Piechotta, Christoph Parthier, Martin Kleinschmidt, Kathrin Gnoth, Thierry Pillot, Inge Lues, Hans-Ulrich Demuth, Stephan Schilling, Jens-Ulrich Rahfeld, Milton T Stubbs
Alzheimers disease is associated with deposition of the amyloidogenic peptide Aβ in the brain. Passive immunization using Aβ-specific antibodies has been demonstrated to reduce amyloid deposition both in vitro and in vivo. As N terminally truncated pyroglutamate (pE)-modified Aβ species (AβpE3) exhibit enhanced aggregation potential and propensity to form toxic oligomers, they represent particularly attractive targets for antibody therapy. Here we present three separate monoclonal antibodies that specifically recognize AβpE3 with affinities of 1-10 nM and inhibit AβpE3 fibril formation in vitro...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28622169/molecular-aspects-of-allergens-in-atopic-dermatitis
#14
Raffaela Campana, Sheron Dzoro, Irene Mittermann, Elena Fedenko, Olga Elisyutina, Musa Khaitov, Alexander Karaulov, Rudolf Valenta
PURPOSE OF REVIEW: Molecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens...
June 15, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28621802/glypican-3-a-promising-biomarker-for-hepatocellular-carcinoma-diagnosis-and-treatment
#15
REVIEW
Fubo Zhou, Wenting Shang, Xiaoling Yu, Jie Tian
Liver cancer is the second leading cause of cancer-related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis...
June 16, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28621442/dendritic-cell-based-immunotherapy-evokes-potent-anti-tumor-immune-responses-in-cd105-human-renal-cancer-stem-cells
#16
Xiao-Fei Zhang, De-Sheng Weng, Ke Pan, Zi-Qi Zhou, Qiu-Zhong Pan, Jing-Jing Zhao, Yan Tang, Shan-Shan Jiang, Chang-Long Chen, Yong-Qiang Li, Hong-Xia Zhang, Alfred E Chang, Max S Wicha, Yi-Xin Zeng, Qiao Li, Jian-Chuan Xia
Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma(RCC) CSCs against renal cancer cells in vitro and in vivo...
June 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28620578/surgical-management-of-advanced-and-metastatic-renal-cell-carcinoma-a-multidisciplinary-approach
#17
REVIEW
Brian M Shinder, Kevin Rhee, Douglas Farrell, Nicholas J Farber, Mark N Stein, Thomas L Jang, Eric A Singer
The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy (predominantly high-dose interleukin 2) has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoadjuvant systemic therapy may increase the feasibility of resecting the primary tumor, which may be beneficial for patients with locally advanced or metastatic disease...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28619999/pd-l2-expression-in-human-tumors-relevance-to-anti-pd-1-therapy-in-cancer
#18
Jennifer H Yearley, Christopher Gibson, Ni Yu, Christina Moon, Erin Murphy, Jonathan Juco, Jared Lunceford, Jonathan Cheng, Laura Q M Chow, Tanguy Y Seiwert, Masahisa Handa, Joanne E Tomassini, Terrill McClanahan
Purpose: Tumor-associated PD-L1 expression is predictive of clinical response to PD-1-directed immunotherapy. However, PD-L1-negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. The prevalence of PD-L2, the other known ligand of PD-1, and its relationship to response to anti-PD-1 therapy were evaluated.Experimental Design: PD-L2 expression was assessed in archival tumor tissue from seven indications using a novel immunohistochemical assay...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28618924/expression-and-clinical-significance-of-placenta-specific-1-in-pancreatic-ductal-adenocarcinoma
#19
Yin Yin, Xu Zhu, Shanshan Huang, Jiawei Zheng, Mengyun Zhang, Wencui Kong, Qun Chen, Yan Zhang, Xiong Chen, Kerong Lin, Xuenong Ouyang
The limited efficacy of conventional therapies for pancreatic ductal adenocarcinoma has led to the growing interest for identifying potential antigenic targets for immunotherapy. Placenta-specific 1 (PLAC1) is a new member of cancer-testis antigens with restricted expression in normal tissues. Ectopic activation of PLAC1 has been found in different types of cancers, but its role in pancreatic ductal adenocarcinoma remains unknown. This study evaluated the protein expression of PLAC1 and its clinical significance in pancreatic ductal adenocarcinoma...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617920/milestone-analyses-of-immune-checkpoint-inhibitors-targeted-therapy-and-conventional-therapy-in-metastatic-non-small-cell-lung-cancer-trials-a-meta-analysis
#20
Gideon M Blumenthal, Lijun Zhang, Hui Zhang, Dickran Kazandjian, Sean Khozin, Shenghui Tang, Kirsten Goldberg, Rajeshwari Sridhara, Patricia Keegan, Richard Pazdur
Importance: Novel intermediate end points may be useful to detect signals of early activity and prioritize new therapies to treat patients with advanced malignant neoplasms, including metastatic non-small cell lung cancer (mNSCLC). Objective: To explore milestone rate, a proposed intermediate end point for immunotherapy trials. Data Sources: Trials submitted to the US Food and Drug Administration with more than 150 patients and in which the intention-to-treat population was assessed were identified...
June 15, 2017: JAMA Oncology
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