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https://www.readbyqxmd.com/read/29790899/advances-in-the-systemic-treatment-of-melanoma-brain-metastases
#1
I C Glitza Oliva, G Schvartsman, H Tawbi
Of the solid tumor types that metastasize to the brain, melanoma has the highest propensity to form brain metastases. In addition, much remains unknown regarding the pathophysiology involved in melanoma cell extravasation through the blood-brain barrier, which enables interactions with the microenvironment, and melanoma cell transcriptomic responses to brain-specific cues. However, recent developments in targeted therapy and immunotherapy have generated considerable optimism regarding the treatment of metastatic melanoma...
May 22, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29790867/fluorine-18-fluorocholine-pet-ct-parameters-predictive-for-hematological-toxicity-to-radium-223-therapy-in-castrate-resistant-prostate-cancer-patients-with-bone-metastases-a-pilot-study
#2
Lavinia Vija Racaru, Mathieu Sinigaglia, Salim Kanoun, Fayçal Ben Bouallègue, Ilan Tal, Sévérine Brillouet, Mathilde Bauriaud-Mallet, Slimane Zerdoud, Lawrence Dierickx, Delphine Vallot, Olivier Caselles, Erwan Gabiache, Pierre Pascal, Frederic Courbon
PURPOSE: This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. PATIENTS AND METHODS: F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra...
May 21, 2018: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/29789890/surveillance-magnetic-resonance-imaging-for-isolated-optic-pathway-gliomas-is-gadolinium-necessary
#3
Ezekiel Maloney, A Luana Stanescu, Francisco A Perez, Ramesh S Iyer, Randolph K Otto, Sarah Leary, Lotte Steuten, Amanda I Phipps, Dennis W W Shaw
BACKGROUND: Pediatric optic pathway gliomas are typically indolent but have a variable clinical course. Treatment is dictated by symptoms and changes on contrast-enhanced MRI examinations. Gadolinium retention in children has motivated parsimonious use of gadolinium-based contrast agents. OBJECTIVES: To determine surveillance MR factors that motivate changes in tumor-directed therapies and extrapolate cost-efficacy of a non-contrast follow-up protocol. MATERIALS AND METHODS: Using an imaging database search we identified children with isolated optic pathway gliomas and ≥3 follow-up contrast-enhanced MRIs...
May 22, 2018: Pediatric Radiology
https://www.readbyqxmd.com/read/29789416/macrophage-derived-granulin-drives-resistance-to-immune-checkpoint-inhibition-in-metastatic-pancreatic-cancer
#4
Michael C Schmid, Valeria Quaranta, Carolyn Rainer, Sebastian Rune Nielsen, Meirion Llŷr Raymant, Muhammad S Ahmed, Dannielle D Engle, Arthur Taylor, Trish Murray, Fiona Campbell, Daniel H Palmer, David A Tuveson, Ainhoa Mielgo
The ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumor microenvironment that suppresses and excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immunoprotective role of the metastatic tumor microenvironment in pancreatic cancer is not completely understood. In this study we find that macrophage-derived granulin contributes to cytotoxic CD8+ T cell exclusion in metastatic livers...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29788730/afp-role-in-predicting-recurrence-of-hepatocellular-carcinoma-after-living-donor-liver-transplantation-in-hcv-patients
#5
A Lech Komorowski, C C Hsu, K D Julka, B Vasavada, C C Lin, C C Wang, C L Chen
HCC is one of the leading causes of death worldwide. Liver transplantation including living donor transplantation is the best available treatment. We have analyzed our experience with LDLT in patients with HCC and HCV in order to determine if alpha feto-protein (AFP) is a better predictor of recurrence than the tumor burden. We have identified all patients with HCV related liver disease and HCC who have undergone LDLT in one center during the period from December 2000 to December 2014. Outcomes from the prospective database were compared for patients who met Milan criteria (single tumor ≤5 cm, maximum of 3 total tumors with none >3 cm) or not...
March 14, 2018: Neoplasma
https://www.readbyqxmd.com/read/29785515/prostate-specific-antigen-flare-induced-by-223-racl-2-in-patients-with-metastatic-castration-resistant-prostate-cancer
#6
Angelo Castello, H A Macapinlac, E Lopci, E B Santos
PURPOSE: Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer, but its impact during radium-223 dichloride (223 RaCl2 ) therapy is still unclear. This radioisotope has shown to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC). We sought to evaluate the impact of PSA flare on survival and its relation with metabolic parameters on 18 F-labeled sodium fluoride PET/CT. METHODS: We conducted a retrospective study of 168 patients with mCRPC (median age 69; median PSA 29...
May 21, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29784674/clinically-relevant-cytotoxic-immune-cell-signatures-and-clonal-expansion-of-t-cell-receptors-in-high-risk-mycn-not-amplified-human-neuroblastoma
#7
Jun S Wei, Igor B Kuznetsov, Shile Zhang, Young K Song, Shahab Asgharzadeh, Sivasish Sindiri, Xinyu Wen, Rajesh Patidar, Sushma Nagaraj, Ashley Walton, Jaime M Guidry Auvil, Daniela S Gerhard, Aysen Yuksel, Daniel R Catchpoole, Stephen M Hewitt, Paul M Sondel, Robert C Seeger, John M Maris, Javed Khan
PURPOSE: High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease including a focus on tumor-infiltrating lymphocytes (TILs). EXPERIMENTAL DESIGN: We performed deep RNA-seq on pre-treatment diagnostic tumors from 129 high-risk and 21 low- or intermediate-risk patients with neuroblastomas...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29783803/-application-of-sentinel-lymph-node-biopsy-in-patients-with-melanoma
#8
M Ren, Y Y Kong, X Cai, X X Shen, J J Lyu
Objective: To investigate the difference between routine hematoxylin-eosin (HE) staining and immunohistochemistry in diagnosing metastatic melanoma in sentinel lymph node (SLN) metastases, and to evaluate the association of SLN tumor burden with the status of non-sentinel lymph nodes (NSLN). Methods: 126 melanoma patients were treated with SLN biopsy and further examined with immunohistochemistry at Fudan University Shanghai Cancer Center between 2010 and 2016, and the status of SLN was respectively estimated by HE stain and immunohistochemistry (S-100 protein, HMB45, Melan A and SOX10)...
May 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29783020/immune-modulation-of-a-novel-lipid-soluble-extract-of-pinellia-pedatisecta-schott-in-the-tumor-microenvironment-of-an-hpv-tumor-burdened-mouse-model
#9
Haixia Huang, Mingxing Zhang, Meng Zhang, Jing Peng, Guiling Li, Congjian Xu, Suiqi Gui
ETHNOPHARMACOLOGICAL RELEVANCE: Pinellia pedatisecta Schott extract (PE), a traditional Chinese medicine, has been used to reduce swelling, dry dampness and suppress cervical tumors. AIMS: To evaluate the roles of PE in the regulation of anti-tumor effects and the cellular immune response in the tumor microenvironment. METHODS: The immune microenvironment of HPV+ TC-1 tumors was examined by immunohistochemistry, real-time PCR and flow cytometry...
May 18, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29782924/emerging-biomarkers-for-immune-checkpoint-inhibition-in-lung-cancer
#10
REVIEW
George Cyriac, Leena Gandhi
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker...
May 18, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29781343/issues-and-promises-of-bevacizumab-in-prostate-cancer-treatment
#11
Vittore Cereda, Vincenzo Formica, Mario Roselli
There is general agreement that increased angiogenesis is an important factor in determining prostate cancer development and prognosis. Vascular Endothelial Growth Factor (VEGF) is thought to play a primary role in the molecular events that lead to prostate cancer progression, from androgen-dependency to castration-resistance until dissemination to the skeleton. Bevacizumab is a recombinant anti-VEGF monoclonal antibody that has exhibited clinical activity in different cancer types. Areas covered: In this review we summarize the data of clinical trials, investigating the effects of bevacizumab in prostate cancer patients...
May 21, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29780819/a-comprehensive-review-of-the-pharmacologic-management-of-uterine-leiomyoma
#12
REVIEW
Terrence D Lewis, Minnie Malik, Joy Britten, Angelo Macapagal San Pablo, William H Catherino
Uterine leiomyomata are the most common benign tumors of the gynecologic tract impacting up to 80% of women by 50 years of age. It is well established that these tumors are the leading cause for hysterectomy with an estimated total financial burden greater than $30 billion per year in the United States. However, for the woman who desires future fertility or is a poor surgical candidate, definitive management with hysterectomy is not an optimal management plan. Typical gynecologic symptoms of leiomyoma include infertility, abnormal uterine bleeding (AUB)/heavy menstrual bleeding (HMB) and/or intermenstrual bleeding (IMB) with resulting iron-deficiency anemia, pelvic pressure and pain, urinary incontinence, and dysmenorrhea...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29779406/inhalation-delivery-of-topotecan-is-superior-to-intravenous-exposure-for-suppressing-lung-cancer-in-a-preclinical-model
#13
Philip J Kuehl, Marcie J Grimes, Devon Dubose, Michael Burke, David A Revelli, Andrew P Gigliotti, Steven A Belinsky, Mathewos Tessema
Intravenous (IV) topotecan is approved for the treatment of various malignancies including lung cancer but its clinical use is greatly undermined by severe hematopoietic toxicity. We hypothesized that inhalation delivery of topotecan would increase local exposure and efficacy against lung cancer while reducing systemic exposure and toxicity. These hypotheses were tested in a preclinical setting using a novel inhalable formulation of topotecan against the standard IV dose. Respirable dry-powder of topotecan was manufactured through spray-drying technology and the pharmacokinetics of 0...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29777404/randomized-trial-comparing-resection-of-primary-tumor-with-no-surgery-in-stage-iv-breast-cancer-at-presentation-protocol-mf07-01
#14
Atilla Soran, Vahit Ozmen, Serdar Ozbas, Hasan Karanlik, Mahmut Muslumanoglu, Abdullah Igci, Zafer Canturk, Zafer Utkan, Cihangir Ozaslan, Turkkan Evrensel, Cihan Uras, Erol Aksaz, Aykut Soyder, Umit Ugurlu, Cavit Col, Neslihan Cabioglu, Betül Bozkurt, Ali Uzunkoy, Neset Koksal, Bahadir M Gulluoglu, Bulent Unal, Can Atalay, Emin Yıldırım, Ergun Erdem, Semra Salimoglu, Atakan Sezer, Ayhan Koyuncu, Gunay Gurleyik, Haluk Alagol, Nalan Ulufi, Uğur Berberoglu, Mustafa Dulger, Omer Cengiz, Efe Sezgin, Ronald Johnson
BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group...
May 17, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29777137/enhanced-efficacy-of-combined-temozolomide-and-bromodomain-inhibitor-therapy-for-gliomas-using-targeted-nanoparticles
#15
Fred C Lam, Stephen W Morton, Jeffrey Wyckoff, Tu-Lan Vu Han, Mun Kyung Hwang, Amanda Maffa, Elena Balkanska-Sinclair, Michael B Yaffe, Scott R Floyd, Paula T Hammond
Effective treatment for glioblastoma (GBM) is limited by the presence of the blood-brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29774030/changes-in-the-tcr%C3%AE-repertoire-and-tumor-immune-signature-from-a-cutaneous-melanoma-patient-immunized-with-the-csf-470-vaccine-a-case-report
#16
Mariana Aris, Alicia Inés Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
The allogeneic therapeutic vaccine CSF-470 has demonstrated a significant benefit over medium-dose IFNα2b in the distant metastasis-free survival for stages IIB-IIC-III cutaneous melanoma patients in a randomized phase II/III clinical trial (CASVAC-0401, NCT01729663). At the end of the 2-year CSF-470 immunization protocol, patient #006 developed several lung and one subcutaneous melanoma metastases; this later was excised. In this report, we analyzed the changes throughout vaccination of immune populations in blood and in the tumor tissue, with special focus on the T-cell repertoire...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773595/therapeutic-effects-of-the-novel-subtype-selective-histone-deacetylase-hdac-inhibitor-chidamide-on-myeloma-associated-bone-disease
#17
Jingsong He, Qingxiao Chen, Huiyao Gu, Jing Chen, Enfan Zhang, Xing Guo, Xi Huang, Haimeng Yan, DongHua He, Yang Yang, Yi Zhao, Gang Wang, Huang He, Qing Yi, Zhen Cai
Histone deacetylases are promising therapeutic targets in hematological malignancies. In the present work, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins, including p21 and p27, among others...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29772266/pten-pdz-binding-domain-suppresses-mammary-carcinogenesis-in-the-mmtv-pymt-breast-cancer-model
#18
Mingfei Yan, Yubing Wang, Chi Wai Wong, Penelope Mei-Yu Or, Kin Lok Wong, Lisha Li, Alexander M Many, Hong Guan, Ui Soon Khoo, Andrew M Chan
Phosphatase and tension homolog (PTEN) is a potent tumor suppressor that possesses a PDZ-binding domain (PDZ-BD) at the end of its carboxyl terminus, whose functions during tumorigenesis remains unclear. Here, we crossed a mouse strain with germline deletion of PTEN PDZ-BD with MMTV-PyMT breast cancer model, and found that knockout (KO) mice display normal development of mammary glands, but have both increased breast tumorigenicity and lung metastasis. Orthotopic allograft experiments suggest the loss of PTEN PDZ-BD in breast cancer cells rather than in tumor microenvironment plays a prominent role in increasing tumor burden...
May 14, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#19
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29770327/-in-vitro-cytotoxicity-and-in-vivo-antimammary-tumor-effects-of-the-hydroethanolic-extract-of-acacia-seyal-mimosaceae-stem-bark
#20
Stephane Zingue, Amstrong Nang Njuh, Alain Brice Tueche, Jeremie Tamsa, Edwige Nana Tchoupang, Stanislas Djaouli Kakene, Marius Trésor Kemegne Sipping, Dieudonné Njamen
The present study was designed to evaluate the in vitro and in vivo antitumor effects of A. seyal hydroethanolic extract on breast cancer. The cytotoxicity of A. seyal extract was evaluated using resazurin reduction assay in 9 cell lines. Further, the protective effect of the hydroethanolic extract of A. seyal stem barks was evaluated on 7,12-dimethylbenz(a)anthracene- (DMBA-) induced breast cancer rat model. Incidence, burden, volume, and histological analysis of mammary tumors were measured. The Acacia seyal extract exhibited CC50 of 100 in MCF-7 cells after 24 h...
2018: BioMed Research International
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