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https://www.readbyqxmd.com/read/28523098/incb24360-epacadostat-a-highly-potent-and-selective-indoleamine-2-3-dioxygenase-1-ido1-inhibitor-for-immuno-oncology
#1
Eddy W Yue, Richard Sparks, Padmaja Polam, Dilip Modi, Brent Douty, Brian Wayland, Brian Glass, Amy Takvorian, Joseph Glenn, Wenyu Zhu, Michael Bower, Xiangdong Liu, Lynn Leffet, Qian Wang, Kevin J Bowman, Michael J Hansbury, Min Wei, Yanlong Li, Richard Wynn, Timothy C Burn, Holly K Koblish, Jordan S Fridman, Tom Emm, Peggy A Scherle, Brian Metcalf, Andrew P Combs
A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 4f, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the in vitro ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28512413/two-cases-of-nivolumab-re-administration-after-pneumonitis-as-immune-related-adverse-events
#2
Keisuke Imafuku, Koji Yoshino, Kei Yamaguchi, Satoshi Tsuboi, Kuniaki Ohara, Hiroo Hata
Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs) associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD) pattern...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28506830/antibiotics-induced-gut-microbiota-dysbiosis-promotes-tumor-initiation-via-affecting-apc-th1-development-in-mice
#3
Chengming Xu, Banjun Ruan, Yinghao Jiang, Ting Xue, Zhenyu Wang, Huanyu Lu, Ming Wei, Shan Wang, Zicheng Ye, Dongsheng Zhai, Li Wang, Zifan Lu
Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35...
May 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28501764/open-label-multicentre-safety-study-of-vemurafenib-in%C3%A2-3219-patients-with-braf-v600-mutation-positive-metastatic-melanoma-2-year-follow-up-data-and-long-term-responders-analysis
#4
Christian U Blank, James Larkin, Ana M Arance, Axel Hauschild, Paola Queirolo, Michele Del Vecchio, Paolo A Ascierto, Ivana Krajsova, Jacob Schachter, Bart Neyns, Claus Garbe, Vanna Chiarion Sileni, Mario Mandalà, Helen Gogas, Enrique Espinosa, Geke A P Hospers, Wilson H Miller, Susan Robson, Martina Makrutzki, Vladan Antic, Michael P Brown
BACKGROUND: The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAF(V600) mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety. METHODS: This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas(®) 4800 BRAF V600 Mutation Test)...
May 11, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28501501/anti-tumor-effects-of-differentiation-inducing-factor-1-in-malignant-melanoma-gsk-3-mediated-inhibition-of-cell-proliferation-and-gsk-3-independent-suppression-of-cell-migration-and-invasion
#5
Masaki Arioka, Fumi Takahashi-Yanaga, Momoko Kubo, Kazunobu Igawa, Katsuhiko Tomooka, Toshiyuki Sasaguri
Differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium discoideum strongly inhibits the proliferation of various mammalian cells through the activation of glycogen synthase kinase-3 (GSK-3). To evaluate DIF-1 as a novel anti-cancer agent for malignant melanoma, we examined whether DIF-1 has anti-proliferative, anti-migratory, and anti-invasive effects on melanoma cells using in vitro and in vivo systems. DIF-1 reduced the expression levels of cyclin D1 and c-Myc by facilitating their degradation via GSK-3 in mouse (B16BL6) and human (A2058) malignant melanoma cells, and thereby strongly inhibited their proliferation...
May 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28499411/paraneoplastic-acral-vascular-syndrome-in-a-patient-with-metastatic-melanoma-under-immune-checkpoint-blockade
#6
Thilo Gambichler, Stefanie Strutzmann, Andrea Tannapfel, Laura Susok
BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested. CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla...
May 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28494532/risk-of-second-primary-cancer-in-people-with-non-melanoma-skin-cancer-a-nationwide-cohort-study
#7
Shu-Hui Wang, Ching-Chi Chi, Zi-Hao Zhao, Tao-Hsin Tung
Purpose: Previous western studies have found Caucasians with skin cancer, either melanoma or non-melanoma skin cancer (NMSC), have an elevated risk of second primary cancer. Our objective was to assess the risk of second primary cancer in Taiwanese with NMSC. Materials and Methods: By using data from Taiwan's National Health Insurance Research Database, we conducted a population-based cohort study to assess the risk of incident second primary cancer in Taiwanese affected by NMSC...
May 10, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28492033/cutaneous-melanoma-in-women
#8
REVIEW
Mi Ryung Roh, Philip Eliades, Sameer Gupta, Jane M Grant-Kels, Hensin Tsao
BACKGROUND: Gender disparity in melanoma outcome is consistently observed, suggesting that gender is as an important prognostic factor. However, the source of this gender disparity in melanoma remains unclear. OBJECTIVE: This article reviews advances in our understanding of gender differences in melanoma and how such differences may contribute to outcomes. METHODS: A broad literature search was conducted using the PubMed database, with search terms such as 'gender differences in melanoma' and 'sex differences in melanoma...
March 2017: International Journal of Women's Dermatology
https://www.readbyqxmd.com/read/28489985/preclinical-evaluation-of-the-imipridone-family-analogues-of-clinical-stage-anti-cancer-small-molecule-onc201-reveals-potent-anti-cancer-effects-of-onc212
#9
Jessica Wagner, Christina Leah Kline, Marie D Ralff, Avital Lev, Amriti Lulla, Lanlan Zhou, Gary L Olson, Bhaskara Rao Nallaganchu, Cyril H Benes, Joshua E Allen, Varun V Prabhu, Martin Stogniew, Wolfgang Oster, Wafik S El-Deiry
Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogues to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives...
May 10, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28486417/extensions-to-multivariate-space-time-mixture-modeling-of-small-area-cancer-data
#10
Rachel Carroll, Andrew B Lawson, Christel Faes, Russell S Kirby, Mehreteab Aregay, Kevin Watjou
Oral cavity and pharynx cancer, even when considered together, is a fairly rare disease. Implementation of multivariate modeling with lung and bronchus cancer, as well as melanoma cancer of the skin, could lead to better inference for oral cavity and pharynx cancer. The multivariate structure of these models is accomplished via the use of shared random effects, as well as other multivariate prior distributions. The results in this paper indicate that care should be taken when executing these types of models, and that multivariate mixture models may not always be the ideal option, depending on the data of interest...
May 9, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28479936/presage-of-oncolytic-virotherapy-for-oral-cancer-with-herpes-simplex-virus
#11
REVIEW
Yoshiaki Yura
A virus is a pathogenic organism that causes a number of infectious diseases in humans. The oral cavity is the site at which viruses enter and are excreted from the human body. Herpes simplex virus type 1 (HSV-1) produces the primary infectious disease, gingivostomatitis, and recurrent disease, labial herpes. HSV-1 is one of the most extensively investigated viruses used for cancer therapy. In principle, HSV-1 infects epithelial cells and neuronal cells and exhibits cytotoxicity due to its cytopathic effects on these cells...
May 2017: Japanese Dental Science Review
https://www.readbyqxmd.com/read/28477020/genetic-association-between-tnf-%C3%AE-promoter-polymorphism-and-susceptibility-to-squamous-cell-carcinoma-basal-cell-carcinoma-and-melanoma-a-meta-analysis
#12
Ning Liu, Guang-Jing Liu, Juan Liu
Tumor necrosis factor-alpha (TNF-α) is a multifunctional pro-inflammatory cytokine that plays an important role in cancer development. We performed a meta-analysis to assess the relationship between single nucleotide polymorphisms in the TNF-α promoter region (rs1800629 and rs361525) and susceptibility to squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma. After database retrieval, article selection, data extraction, and quality assessment, 20 articles comprising 4865 cases and 6329 controls were included in this study...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468915/combining-dna-vaccine-and-aida-1-in-attenuated-salmonella-activates-tumor-specific-cd4-and-cd8-t-cell-responses
#13
Yu Mei, Lixiang Zhao, Yonghao Liu, Huanle Gong, Yuan Song, Lei Lei, Ying Zhu, Ziqi Jin, Shoubao Ma, Bo Hu, Qing Sun, Haiyan Liu
Stimulation of tumor-specific responses in both CD4(+) and CD8(+) T cells has been a challenge for effective tumor vaccines. We designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated Salmonella strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the Salmonella tumor vaccine. The vaccine activated tumor-specific CD4(+) and CD8(+) T-cell responses, with increased T-cell proliferation, tumor antigen-specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity...
May 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28468736/prevention-of-non-melanoma-skin-cancers-with-nicotinamide-in-transplant-recipients-a-case-control-study
#14
Francesco Drago, Giulia Ciccarese, Ludovica Cogorno, Camillo Calvi, Luigina A Marsano, Aurora Parodi
Nicotinamide is the precursor of nicotinamide adenine dinucleotide (NAD+), an essential cofactor for adenosine triphosphate (ATP) production. It has recently been reported to be effective in reducing the rates of new non-melanoma skin cancers (NMSCs) and actinic keratosis (AKs). We studied the efficacy of oral nicotinamide as treatment for AKs in transplant recipients. We recruited 38 transplant (eight liver and 30 kidney) patients with single or multiple AKs. Nineteen patients were randomly assigned to Group 1 and took nicotinamide 500 mg/daily (cases); the other 19 patients were randomly assigned to Group 2 without nicotinamide (controls)...
May 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28462646/primary-giant-aggressive-amelanotic-duodenal-melanoma
#15
R Kilambi, A N Singh, N R Dash, K S Madhusudhan, P Das
Primary malignant melanoma of the gastrointestinal tract is extremely rare. A 35-year-old man presented with complaints of abdominal pain and weight loss. Contrast enhanced computed tomography showed a large mass involving the duodenum and the superior mesenteric vessels. Upper gastrointestinal endoscopy demonstrated a large, friable mass along the duodenal wall and biopsy was suggestive of malignant melanoma. A detailed physical examination and whole body imaging (positron emission tomography and computed tomography) did not reveal any other lesion...
May 2017: Annals of the Royal College of Surgeons of England
https://www.readbyqxmd.com/read/28445541/iqgap1-is-an-oncogenic-target-in-canine-melanoma
#16
Becky H Lee, Poornima H Neela, Michael S Kent, Ashley M Zehnder
Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%), human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans...
2017: PloS One
https://www.readbyqxmd.com/read/28439153/supraclavicular-metastases-from-distant-primary-solid-tumours-a-retrospective-study-of-41%C3%A2-years
#17
Keyvan Sagheb, Asina Manz, Stefan B Albrich, Katherine J Taylor, Georg Hess, Christian Walter
OBJECTIVES: Approximately 1 % of all malignant solid tumours of the head and neck area are metastases from primary tumours beneath the clavicles. The aim of this study was to analyse the distribution of primary tumours since meta-analyses might have been biased due to the usually extraordinary character of case reports. MATERIALS AND METHODS: All patient files from 1970 to 2012 from the Oral and Maxillofacial Surgery unit at a University Hospital were analysed regarding the existence of metastases to the head and neck area from distant primaries...
June 2017: Journal of Maxillofacial and Oral Surgery
https://www.readbyqxmd.com/read/28423984/congenital-amelanotic-melanoma-in-a-crossbred-heifer-calf
#18
Christine M Winslow, Jason Wood, John N Gilliam, Melanie A Breshears
A large, pedunculated cutaneous mass protruding from the left flank fold and an enlarged left prefemoral lymph node were found on examination of a 3-d-old crossbred Aberdeen Angus heifer. The calf was asymptomatic aside from peripheral lymphadenopathy, and the mass, along with the left prefemoral lymph node, was surgically excised. Histologic examination of the mass and the lymph node revealed a homogeneous population of neoplastic cells that stained positively with immunohistochemical stains S100 and melan A, supporting a diagnosis of congenital amelanotic melanoma with nodal metastasis...
April 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28421728/oral-pigmentations-in-physiologic-conditions-post-inflammatory-affections-and-systemic-diseases
#19
Martina Lambertini, Annalisa Patrizi, Giulia M Ravaioli, Emi Dika
Melanocytes are found throughout the oral mucosa but usually go unnoticed because of their relatively low level of pigment production. When focally or generally active in pigment production or proliferation they may be responsible for several affections in the oral mucosae ranging from physiologic pigmentation, systemic diseases to malignant neoplasms. The diagnosis of oral pigmentations (OP) is usually challenging for the physician, but a careful examination of the oral cavity may reveal the first manifestation of underlying systemic diseases...
April 19, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28418845/preclinical-development-of-g1t38-a-novel-potent-and-selective-inhibitor-of-cyclin-dependent-kinases-4-6-for-use-as-an-oral-antineoplastic-in-patients-with-cdk4-6-sensitive-tumors
#20
John E Bisi, Jessica A Sorrentino, Jamie L Jordan, David D Darr, Patrick J Roberts, Francis X Tavares, Jay C Strum
Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance...
March 15, 2017: Oncotarget
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