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https://www.readbyqxmd.com/read/28335045/-imaging-of-metastastic-renal-cell-carcinoma-under-therapy-with-immune-checkpoint-inhibitors
#1
Mike Notohamiprodjo, Hans-Georg Kopp, Jens Bedke
No abstract text is available yet for this article.
April 2017: RöFo: Fortschritte Auf Dem Gebiete der Röntgenstrahlen und der Nuklearmedizin
https://www.readbyqxmd.com/read/28334791/isolated-acth-deficiency-probably-induced-by-autoimmune-related-mechanism-evoked-with-nivolumab
#2
Keiko Kitajima, Kenji Ashida, Naoko Wada, Ryoko Suetsugu, Yukina Takeichi, Shohei Sakamoto, Hiroshi Uchi, Takamitsu Matsushima, Motoaki Shiratsuchi, Keizo Ohnaka, Masutaka Furue, Masatoshi Nomura
Nivolumab, an anti-programmed death-1 antibody, is a breakthrough treatment for several malignancies. Its specific adverse effects caused by autoimmunity are termed immune-related adverse events, which involve several endocrine dysfunctions. Herein, we report two cases of isolated adrenocorticotropic hormone (ACTH) deficiency induced by nivolumab for the treatment of metastatic malignant melanoma. Case 1 was a 39-year-old man and Case 2 was a 50-year-old woman, both of whom presented with progressive melanoma...
February 18, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28334731/characterisation-of-cct271850-a-selective-oral-and-potent-mps1-inhibitor-used-to-directly-measure-in-vivo-mps1-inhibition-vs-therapeutic-efficacy
#3
Amir Faisal, Grace W Y Mak, Mark D Gurden, Cristina P R Xavier, Simon J Anderhub, Paolo Innocenti, Isaac M Westwood, Sébastien Naud, Angela Hayes, Gary Box, Melanie R Valenti, Alexis K De Haven Brandon, Lisa O'Fee, Jessica Schmitt, Hannah L Woodward, Rosemary Burke, Rob L M vanMontfort, Julian Blagg, Florence I Raynaud, Suzanne A Eccles, Swen Hoelder, Spiros Linardopoulos
BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28331614/sudden-hearing-loss-in-a-melanoma-patient-on-pembrolizumab-an-etiology-not-to-be-omitted-in-the-differential-diagnosis
#4
EDITORIAL
Marc-Elie Nader, Jeffrey N Myers, Paul W Gidley
Immune checkpoint inhibitors have emerged as a promising therapeutic option for metastatic cancers. However, they have been associated with inflammatory adverse reactions in various organ systems. A recent article reported a case of sudden bilateral hearing loss that occurred in a patient with metastatic melanoma being treated with pembrolizumab. The authors attributed that complication to an autoimmune reaction secondary to the treatment. This commentary discusses the importance of considering the diagnosis of leptomeningeal metastasis in patients with metastatic melanoma who present with new cranial nerve deficits...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331612/utility-of-pd-l1-immunohistochemistry-assays-for-predicting-pd-1-pd-l1-inhibitor-response
#5
REVIEW
Laurence P Diggs, Eddy C Hsueh
We have seen a notable increase in the application of PD-1/PD-L1 inhibitors for the treatment of several solid and hematogenous malignancies including metastatic melanoma, non-small-cell lung cancer and lymphoma to name a few. The need for biomarkers for identification of a suitable patient population for this type of therapy is now pressing. While specific biomarker assays have been developed for these checkpoint inhibitors based on their respective epitopes, the available studies suggested the clinical utility of these biomarker assays is for response stratification and not patient selection...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28331049/achieving-precision-death-with-cell-cycle-inhibitors-that-target-dna-replication-and-repair
#6
Aimee Bence Lin, Samuel C McNeely, Richard P Beckmann
All cancers are characterized by defects in the systems that ensure strict control of the cell cycle in normal tissues. The consequent excess tissue growth can be countered by drugs that halt cell division and, indeed, the majority of chemotherapeutics developed during the last century work by disrupting processes essential for the cell cycle, particularly DNA synthesis, DNA replication, and chromatid segregation. In certain contexts the efficacy of these classes of drugs can be impressive but, because they indiscriminately block the cell cycle of all actively dividing cells, their side effects severely constrain the dose and duration with which they can be administered, allowing both normal and malignant cells to escape complete growth arrest...
March 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#7
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28328001/cancer-vaccines-at-the-age-of-immune-checkpoint-inhibitors-reasonable-approach-as-combination-therapy-in-advanced-urothelial-carcinoma
#8
Petros Grivas, Vadim S Koshkin, Sumanta K Pal
No abstract text is available yet for this article.
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28326837/checkpoint-inhibitors-in-the-treatment-of-brain-metastases-of-non-small-cell-lung-cancer-and-melanoma
#9
Hampig Raphael Kourie, Hassan Kanaan, Gil Awada, Ahmad Hussein Awada
Brain metastases (BMs) are representing a new challenge for the oncologist; their incidence is increasing due to the better overall survival and systemic disease control in many malignancies, consequent to new potent cytotoxic and targeted therapies. In the era of immunotherapies, checkpoint inhibitors are representing a new therapeutic option in different solid tumors and settings; preliminary results showed potential activity of these agents in patients with BM, when administered as single agent or in combination with radiation therapy...
February 28, 2017: Future Oncology
https://www.readbyqxmd.com/read/28323658/changing-face-of-metastatic-prostate-cancer-the-law-of-diminishing-returns-holds-true
#10
Ulka N Vaishampayan
PURPOSE OF REVIEW: Prostate cancer presents with a multitude of faces. It ranges from localized cancers staying quiescent for many years during active surveillance to the raging diffuse liver metastases causing terminal disease. The incidence of metastatic disease is increasing. This review will highlight some of the recent developments as well as ongoing challenges of managing advanced prostate cancer. RECENT FINDINGS: Significant strides are being made in managing metastatic prostate cancer...
March 18, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28323141/mechanistic-and-pharmacologic-insights-on-immune-checkpoint-inhibitors
#11
REVIEW
Randy F Sweis, Jason J Luke
The concept of augmenting the immune system to eradicate cancer dates back at least a century. A major resurgence in cancer immunotherapy has occurred over the past decade since the identification and targeting of negative regulators with antibody therapies to augment the anti-tumor immune response. Unprecedented responses across a broad array of cancer types elevated this class of therapies to the forefront of cancer treatment. The most successful drugs to date target the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28322974/current-modalities-in-cancer-immunotherapy-immunomodulatory-antibodies-cars-and-vaccines
#12
REVIEW
Jason Lohmueller, Olivera J Finn
Successes of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy in curing patients with otherwise lethal cancers have validated immunotherapy as a treatment for cancer and have inspired excitement for its broader potential. Most promising is the ability of each approach to eliminate bulky and advanced-stage cancers and to achieve durable cures. Despite this success, to date only a subset of cancer patients and a limited number of cancer types respond to these therapies. A major goal now is to expand the types of cancer and number of patients who can be successfully treated...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28321818/skin-reactions-to-immune-checkpoint-inhibitors
#13
Anisha B Patel, Omar Pacha
The novelty of immune checkpoint inhibitors has only recently led to the characterization of cutaneous adverse events (AEs). This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat. In the following chapter, we will review the categories of these drugs, common cutaneous effects, their grading, and management options.
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321817/adverse-events-in-cancer-immunotherapy
#14
Noha Abdel-Wahab, Anas Alshawa, Maria E Suarez-Almazor
Cancer immunotherapy has resulted in durable responses in patients with metastatic disease, unseen with traditional chemotherapy. Several therapies have been approved by the Food and Drug Administration for the treatment of various cancers, including: immune checkpoint inhibitors, cytokines - interleukin 2 (IL-2) and interferon alpha (IFN), and the cancer vaccine sipuleucel-T. These therapies upregulate the immune system to enhance antitumor responses. As a consequence, they can cause inflammatory and immune-related adverse events that can affect one or more organs, can be serious, and on occasion lifethreatening...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321812/optimizing-radiotherapy-with-immunotherapeutic-approaches
#15
Jonathan E Schoenhals, Tijana Skrepnik, Ugur Selek, Maria A Cortez, Ailin Li, James W Welsh
Several factors must be considered to successfully integrate immunotherapy with radiation into clinical practice. One such factor is that concepts arising from preclinical work must be tested in combination with radiation in preclinical models to better understand how combination therapy will work in patients; examples include checkpoint inhibitors, tumor growth factor-beta (TGF-β) inhibitors, and natural killer (NK) cell therapy. Also, many radiation fields and fractionation schedules typically used in radiation therapy had been standardized before the introduction of advanced techniques for radiation planning and delivery that account for changes in tumor size, location, and motion during treatment, as well as uncertainties introduced by variations in patient setup between treatment fractions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#16
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28318492/-brain-tumor-immunotherapy-illusion-or-hope
#17
REVIEW
Denis Migliorini, Valérie Dutoit, Paul R Walker, Pierre-Yves Dietrich
Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials...
March 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28318345/novel-agents-in-classical-hodgkin-lymphoma
#18
Sven Borchmann, Bastian von Tresckow
Classical Hodgkin lymphoma (cHL) is the most common hematological malignancy in young adults and can be cured in most cases. However, relapsed and refractory Hodgkin lymphoma, certain patient groups, such as elderly patients, and toxicity of first-line treatment still pose significant challenges. Consequently, new treatment options are needed. Recently, many new treatment concepts have been evaluated in clinical trials. Targeted drug-antibody conjugates and immune checkpoint inhibitors have decisively changed treatment approaches...
March 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28318336/are-tumor-infiltrating-lymphocytes-protagonists-or-background-actors-in-patient-selection-for-cancer-immunotherapy
#19
Federica Zito Marino, Paolo Antonio Ascierto, Giulio Rossi, Stefania Staibano, Marco Montella, Daniela Russo, Roberto Alfano, Alessandro Morabito, Gerardo Botti, Renato Franco
Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of ''cancer immunoediting''. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response...
March 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#20
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
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