journal
MENU ▼
Read by QxMD icon Read
search

Investigational New Drugs

journal
https://www.readbyqxmd.com/read/28920157/mechanisms-of-cancer-cell-killing-by-sea-cucumber-derived-compounds
#1
REVIEW
Teresa Liliana Wargasetia, Widodo
The aim of cancer therapy is to specifically eradicate tumor cells while causing minimal damage to normal tissues and minimal side-effects. Because of this, the use of natural substances with low toxicity is a good option. Sea cucumbers are one of many potential marine animals that contain valuable nutrients and medicinal properties. The medicinal value of sea cucumbers is attributed to the presence of bioactive agents with promising biological and pharmacological properties that include cytotoxic activity, induction of apoptosis, cell cycle arrest, inhibition of tumor growth, anti-metastatic and anti-angiogenic properties, and inhibition of drug resistance...
September 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28905282/comparison-of-reporting-phase-i-trial-results-in-clinicaltrials-gov-and-matched-publications
#2
REVIEW
D Shepshelovich, H Goldvaser, L Wang, A R Abdul Razak, P L Bedard
Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile...
September 14, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28905188/novel-inhibitors-of-lysine-k-specific-demethylase-4a-with-anticancer-activity
#3
Hyo Jeong Lee, Bo-Kyoung Kim, Kyoung Bin Yoon, Yong-Chul Kim, Sun-Young Han
Lysine (K)-specific demethylase 4A (KDM4A) is a histone demethylase that removes methyl residues from trimethylated or dimethylated histone 3 at lysines 9 and 36. Overexpression of KDM4A is found in various cancer types. To identify KDM4A inhibitors with anti-tumor functions, screening with an in vitro KDM4A enzyme activity assay was carried out. The benzylidenehydrazine analogue LDD2269 was selected, with an IC50 of 6.56 μM of KDM4A enzyme inhibition, and the binding mode was investigated using in silico molecular docking...
September 14, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28891038/characteristics-of-patients-with-sorafenib-treated-advanced-hepatocellular-carcinoma-eligible-for-second-line-treatment
#4
Sadahisa Ogasawara, Tetsuhiro Chiba, Yoshihiko Ooka, Eiichiro Suzuki, Takahiro Maeda, Masayuki Yokoyama, Toru Wakamatsu, Masanori Inoue, Tomoko Saito, Kazufumi Kobayashi, Soichiro Kiyono, Masato Nakamura, Shingo Nakamoto, Shin Yasui, Akinobu Tawada, Makoto Arai, Tatsuo Kanda, Hitoshi Maruyama, Osamu Yokosuka, Naoya Kato
Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child-Pugh A and ECOG-PS ≤1 at the time of sorafenib failure...
September 11, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28884410/an-7-a-butyric-acid-prodrug-sensitizes-cutaneous-t-cell-lymphoma-cell-lines-to-doxorubicin-via-inhibition-of-dna-double-strand-breaks-repair
#5
Lilach Moyal, Neta Goldfeiz, Batia Gorovitz, Ada Rephaeli, Efrat Tal, Nataly Tarasenko, Abraham Nudelman, Yael Ziv, Emmilia Hodak
We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the mechanism underlying the effect of AN-7 on Dox-induced double-strand DNA breaks (DSBs) in CTCL, MyLa and Hut78 cell lines. The following markers/assays were employed: comet assay; western blot of γH2AX and p-KAP1; immunofluorescence of γH2AX nuclear foci; Western blot of repair protein; quantification of DSBs-repair through homologous recombination...
September 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28879519/safety-tolerability-and-pharmacokinetic-profile-of-dabrafenib-in-japanese-patients-with-braf-v600-mutation-positive-solid-tumors-a-phase-1-study
#6
Yutaka Fujiwara, Naoya Yamazaki, Yoshio Kiyohara, Shusuke Yoshikawa, Noboru Yamamoto, Arata Tsutsumida, Hiroshi Nokihara, Kenjiro Namikawa, Akihira Mukaiyama, Fanghong Zhang, Tomohide Tamura
Background Dabrafenib is a BRAF inhibitor that has demonstrated clinical activity with a good tolerability profile in patients with BRAF (V600E) mutated metastatic melanoma. This study evaluated the safety and tolerability, pharmacokinetics and preliminary efficacy of dabrafenib in Japanese patients. Methods This phase I, open-label, dose escalation study was conducted in 12 Japanese patients with BRAF (V600) mutation positive solid tumours. Primary endpoint was safety, assessed by monitoring and recording of all adverse events (AEs), serious AEs, drug-related AEs; secondary endpoints were pharmacokinetic profiles and efficacy measured by tumour response...
September 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28875433/crucial-micrornas-and-genes-in-metformin-s-anti-pancreatic-cancer-effect-explored-by-microrna-mrna-integrated-analysis
#7
Yilong Li, Le Li, Guangquan Zhang, Yongwei Wang, Hua Chen, Rui Kong, Shangha Pan, Bei Sun
Despite great improvements in surgical procedures and chemotherapy, pancreatic cancer remains one of the most aggressive and fatal human malignancies, with a low 5-year survival rate. Therefore, novel therapeutic strategies for the prevention and treatment of pancreatic cancer are urgently needed. The present study aimed to investigate the mechanisms by which metformin exerts its anticancer effects on the microRNA-mRNA interactions in human pancreatic cancer. Microarray and systematic analyses revealed that the anti-pancreatic cancer effects of metformin were correlated with 3 up-regulated microRNAs and 4 of their target mRNAs...
September 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28868573/phase-i-dose-escalation-and-pharmacokinetic-study-on-the-nanoparticle-formulation-of-polymeric-micellar-paclitaxel-for-injection-in-patients-with-advanced-solid-malignancies
#8
Meiqi Shi, Jing Sun, Jinsong Zhou, Hao Yu, Shaorong Yu, Guohao Xia, Li Wang, Yue Teng, Gangyi Liu, Chen Yu, Yaling Shen, Jifeng Feng
Background Polymeric micellar paclitaxel (PM-paclitaxel) is a novel Cremophor EL-free, nanoparticle-encapsulated paclitaxel formulation administered through intravenous injection. The primary objective of this phase I trial was to determine the first cycle dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PM-paclitaxel. Secondary objectives included the evaluation of the safety, antitumor activity, and pharmacokinetic (PK) profile of PM-paclitaxel in patients with advanced malignancies. Methods The PM-paclitaxel dose was escalated from 175 mg/m(2) (level 1) to 435 mg/m(2) (level 5)...
September 4, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28864978/phase-ii-basket-trial-of-perifosine-monotherapy-for-recurrent-gynecologic-cancer-with-or-without-pik3ca-mutations
#9
Kosei Hasegawa, Masahiro Kagabu, Mika Mizuno, Katsutoshi Oda, Daisuke Aoki, Seiji Mabuchi, Shoji Kamiura, Satoshi Yamaguchi, Yoichi Aoki, Toshiaki Saito, Mayu Yunokawa, Kazuhiro Takehara, Aikou Okamoto, Kazunori Ochiai, Tadashi Kimura
Objective Perifosine exhibits anti-tumor activity by inhibiting AKT phosphorylation. The purpose of this phase II basket trial was to evaluate the efficacy and safety of perifosine monotherapy for ovarian, endometrial, and cervical cancers. Methods Recurrent or persistent ovarian, endometrial, or cervical cancer patients were assigned to PIK3CA wild-type or mutant groups. Each patient received 600 mg oral perifosine on day 1 followed by a maintenance dose of 100 mg daily. The primary endpoint was disease control rate; secondary endpoints included response rate, progression-free survival, overall survival, and safety...
September 2, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28852909/effects-of-rifampin-itraconazole-and-esomeprazole-on-the-pharmacokinetics-of-alisertib-an-investigational-aurora-a-kinase-inhibitor-in-patients-with-advanced-malignancies
#10
Xiaofei Zhou, Shubham Pant, John Nemunaitis, A Craig Lockhart, Gerald Falchook, Todd M Bauer, Manish Patel, John Sarantopoulos, Michael Bargfrede, Andreas Muehler, Lakshmi Rangachari, Bin Zhang, Karthik Venkatakrishnan
Aim Two studies investigated the effect of gastric acid reducing agents and strong inducers/inhibitors of CYP3A4 on the pharmacokinetics of alisertib, an investigational Aurora A kinase inhibitor, in patients with advanced malignancies. Methods In Study 1, patients received single doses of alisertib (50 mg) in the presence and absence of either esomeprazole (40 mg once daily [QD]) or rifampin (600 mg QD). In Study 2, patients received single doses of alisertib (30 mg) in the presence and absence of itraconazole (200 mg QD)...
August 30, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28852916/vinblastine-and-antihelmintic-mebendazole-potentiate-temozolomide-in-resistant-gliomas
#11
Franciele Cristina Kipper, Andrew Oliveira Silva, André Luis Marc, Gláucia Confortin, Augusto Valadão Junqueira, Eliseu Paglioli Neto, Guido Lenz
Glioblastoma (GBM) is a very aggressive tumor that has not had substantial therapeutic improvement since the introduction of temozolomide (TMZ) in combination with radiotherapy. Combining TMZ with other chemotherapeutic agents is a strategy that could be further explored for GBM. To search for molecular predictors of TMZ resistance, the TCGA (The Cancer Genome Atlas) database was utilized to assess the impact of specific genes on TMZ response. Patients whose tumors expressed low levels of FGFR3 and AKT2 responded poorly to TMZ...
August 29, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28819760/effect-of-alisertib-an-investigational-aurora-a-kinase-inhibitor-on-the-qtc-interval-in-patients-with-advanced-malignancies
#12
Xiaofei Zhou, John Nemunaitis, Shubham Pant, Todd M Bauer, Manish Patel, John Sarantopoulos, A Craig Lockhart, Daniel Goodman, Dirk Huebner, Diane R Mould, Karthik Venkatakrishnan
Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 mg twice daily [BID] for 7 days in 21-day cycles). Methods Patients received a single dose of alisertib (50 mg) on Day 1, and multiple doses of alisertib (50 mg BID) on Days 4 through to the morning of Day 10 of the first cycle of treatment...
August 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28819699/cudc-907-a-dual-hdac-and-pi3k-inhibitor-reverses-platinum-drug-resistance
#13
Kenneth K W To, Li-Wu Fu
Platinum (Pt)-based anticancer drugs are the mainstay of treatment for solid cancers. However, resistance to Pt drugs develops rapidly, which can be caused by overexpression of multidrug resistance transporters and activation of DNA repair. CUDC-907 is a potent molecular targeted anticancer agent, rationally designed to simultaneously inhibit histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K). We investigated the potentiation effect of CUDC-907 on Pt drugs in resistant cancer cells. ABCC2 stably-transfected HEK293 cells and two pairs of parental and Pt-resistant cancer cell lines were used to test for the circumvention of resistance by CUDC-907...
August 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28808818/first-in-human-study-of-the-epichaperome-inhibitor-pu-h71-clinical-results-and-metabolic-profile
#14
Giovanna Speranza, Larry Anderson, Alice P Chen, Khanh Do, Michelle Eugeni, Marcie Weil, Larry Rubinstein, Eva Majerova, Jerry Collins, Yvonne Horneffer, Lamin Juwara, Jennifer Zlott, Rachel Bishop, Barbara A Conley, Howard Streicher, Joseph Tomaszewski, James H Doroshow, Shivaani Kummar
Background Molecular chaperone targeting has shown promise as a therapeutic approach in human cancers of various histologies and genetic backgrounds. The purine-scaffold inhibitor PU-H71 (NSC 750424), selective for Hsp90 in epichaperome networks, has demonstrated antitumor activity in multiple preclinical cancer models. The present study was a first in-human trial of PU-H71 aimed at establishing its safety and tolerability and characterizing its pharmacokinetic (PK) profile on a weekly administration schedule in human subjects with solid tumors refractory to standard treatments...
August 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28782087/germline-brca-mutations-in-asian-patients-with-pancreatic-adenocarcinoma-a-prospective-study-evaluating-risk-category-for-genetic-testing
#15
Kyoungmin Lee, Changhoon Yoo, Kyu-Pyo Kim, Kyoung-Jin Park, Heung-Moon Chang, Tae Won Kim, Jae-Lyun Lee, Woochang Lee, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Sang Hyun Shin, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Song Cheol Kim, Baek-Yeol Ryoo
Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy...
August 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28776290/synthesis-characterization-and-evaluation-of-cd-l-proline-2-a-novel-histone-deacetylase-inhibitor-that-induces-epigenetic-modification-of-histone-deacetylase-isoforms-in-a549-cells
#16
Anusha Chidambaram, Arunachalam Sekar, Kavya S H, Ramesh Kumar Chidambaram, Kalaiarasi Arunachalam, Senthilkumar G P, Ravikumar Vilwanathan
Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we synthesized cadmium-proline complexes using both the D- and L-isomers of proline and evaluated their biological activities by observing the efficiency of their inhibition of HDAC activity, ability to reduce the expression of HDAC isoforms in A549 cells and effect on apoptosis...
August 3, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28762171/addition-of-an-antiangiogenic-therapy-bevacizumab-to-gemcitabine-plus-oxaliplatin-improves-survival-in-advanced-biliary-tract-cancers
#17
Marie Bréchon, Marie Dior, Johann Dréanic, Bertrand Brieau, Marie-Anne Guillaumot, Catherine Brezault, Olivier Mir, François Goldwasser, Romain Coriat
Background The prognosis of patients with metastatic carcinoma of the biliary tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based is the gold standard. The addition of bevacizumab to the chemotherapy might increase patients' survival. Our aim was to assess and compare the efficacy of GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32; Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were compared...
August 1, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28752433/a-phase-i-study-to-determine-safety-pharmacokinetics-and-pharmacodynamics-of-anf-rho%C3%A2-a-novel-pegylated-granulocyte-colony-stimulating-factor-in-healthy-volunteers
#18
Hemant Misra, John Berryman, Ronald Jubin, Abraham Abuchowski
Patients receiving pegfilgrastim (Neulasta®) for the treatment of neutropenia can experience bone pain following the injections required to achieve effective neutrophil levels. The safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of ANF-RHO™, a novel pegylated granulocyte colony stimulating factor, were assessed in a randomized, controlled, double-blind Phase 1 clinical study in healthy volunteers. Subjects received a single subcutaneous dose of ANF-RHO over a range of 6 doses (5-50 μg/kg), placebo (saline), or the recommended clinical dose of pegfilgrastim administered at the labeled fixed 6 mg dosage (equivalent to 80-100 μg/kg)...
July 28, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733703/induction-of-accelerated-senescence-by-the-microtubule-stabilizing-agent-peloruside-a
#19
Ariane Chan, Connie Gilfillan, Nikki Templeton, Ian Paterson, Peter T Northcote, John H Miller
Chemotherapeutic agents can induce accelerated senescence in tumor cells, an irreversible state of cell cycle arrest. Paclitaxel, a microtubule-stabilizing agent used to treat solid tumors of the breast, ovary, and lung and discodermolide, another stabilizing agent from a marine sponge, induce senescence in cultured cancer cells. The aim of this study was to determine if the microtubule-stabilizing agent peloruside A, a polyketide natural product from a marine sponge, can induce accelerated senescence in a breast cancer cell line MCF7...
July 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733702/anti-invasive-effects-of-cxcr4-and-fak-inhibitors-in-non-small-cell-lung-carcinomas-with-mutually-inactivated-p53-and-pten-tumor-suppressors
#20
Miodrag Dragoj, Jasna Bankovic, Evangelia Sereti, Sofija Jovanovic Stojanov, Konstantinos Dimas, Milica Pesic, Tijana Stankovic
Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. At the time of diagnosis, a large percentage of NSCLC patients have already developed metastasis, responsible for extremely high mortality rates. CXCR4 receptor and focal adhesion kinase (FAK) are known to regulate such invasive cancer behavior. Their expression is downregulated by p53 and PTEN tumor suppressors which are commonly co-inactivated in NSCLC patients and contribute to metastasis. Therefore, targeting CXCR4 or FAK seems to be a promising strategy in suppressing metastatic spread of p53/PTEN deficient NSCLCs...
July 22, 2017: Investigational New Drugs
journal
journal
28658
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"