2,998 results match your criteria Investigational new drugs[Journal]


A preclinical evaluation of thiostrepton, a natural antibiotic, in nasopharyngeal carcinoma.

Invest New Drugs 2019 Apr 16. Epub 2019 Apr 16.

Department of Otolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, No.201, Sec.2, Shipai Road, Taipei, 112, Taiwan.

Background Thiostrepton, a natural antibiotic, has recently been shown to be a potential anticancer drug for certain cancers, but its study in nasopharyngeal carcinoma (NPC) is still limited. The aims of this study were to investigate the anticancer effect of thiostrepton on NPC cells and to explore its underlying mechanism. Methods The effects of thiostrepton on the proliferation, migration, and invasion of NPC cells were investigated by a WST-1 assay, wound healing assay, and cell invasion assay, respectively. Read More

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http://link.springer.com/10.1007/s10637-019-00779-3
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http://dx.doi.org/10.1007/s10637-019-00779-3DOI Listing
April 2019
1 Read

A phase 2, open-label study of brentuximab vedotin in patients with CD30-expressing solid tumors.

Invest New Drugs 2019 Apr 16. Epub 2019 Apr 16.

Indiana University Division of Hematology and Oncology, 535 Barnhill Dr, Indianapolis, IN, 46202, USA.

Purpose Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate used in the treatment of several types of lymphomas. Expression of the target antigen has also been reported on a variety of malignant tumors of nonlymphoid origin. This phase 2, open-label study evaluated the safety and antitumor activity of BV in patients with CD30-expressing nonlymphomatous malignancies. Read More

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http://link.springer.com/10.1007/s10637-019-00768-6
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http://dx.doi.org/10.1007/s10637-019-00768-6DOI Listing
April 2019
3 Reads

Midkine silencing enhances the anti-prostate cancer stem cell activity of the flavone apigenin: cooperation on signaling pathways regulated by ERK, p38, PTEN, PARP, and NF-κB.

Invest New Drugs 2019 Apr 16. Epub 2019 Apr 16.

Department of Histology and Embryology, School of Medicine, Istanbul Aydin University, Istanbul, Turkey.

Prostate cancer (PCa) is the most common cancer in men worldwide. Midkine (MK) is overexpressed in PCa, as well as in tumor-initiating cells termed cancer stem cells (CSCs). Apigenin is a dietary flavone with considerable anti-tumor activities. Read More

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http://dx.doi.org/10.1007/s10637-019-00774-8DOI Listing

Emodin, a natural anthraquinone, suppresses liver cancer in vitro and in vivo by regulating VEGFR and miR-34a.

Invest New Drugs 2019 Apr 11. Epub 2019 Apr 11.

Department of Hepatobiliary Surgery, the Fourth Hospital of Hebei Medical University, NO.12, Jiankang Road, Shijiazhuang, 050011, Hebei Province, People's Republic of China.

The pharmacokinetic (PK) and potential effects of Emodin on liver cancer were systematically evaluated in this study. Both the intragastric administration (i.g. Read More

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http://dx.doi.org/10.1007/s10637-019-00777-5DOI Listing

Safety and clinical activity of the Notch inhibitor, crenigacestat (LY3039478), in an open-label phase I trial expansion cohort of advanced or metastatic adenoid cystic carcinoma.

Invest New Drugs 2019 Apr 6. Epub 2019 Apr 6.

Drug Development Department (DITEP), Institut Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, 94800, Villejuif Cedex, France.

Background Deregulated Notch signaling is implicated in multiple cancers. The phase I trial (I6F-MC-JJCA) investigated the safety and anti-tumor activity of crenigacestat (LY3039478), a selective oral Notch inhibitor, in an expansion cohort of patients with adenoid cystic carcinoma (ACC) who received the dose-escalation-recommended phase 2 dose (RP2D), established previously (Massard C, et al., Annals Oncol 2018, 29:1911-17). Read More

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http://link.springer.com/10.1007/s10637-019-00739-x
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http://dx.doi.org/10.1007/s10637-019-00739-xDOI Listing
April 2019
9 Reads

Correction to: A novel histone deacetylase inhibitor, CG200745, potentiates anticancer effect of docetaxel in prostate cancer via decreasing Mcl-1 and Bcl-.

Invest New Drugs 2019 Apr 2. Epub 2019 Apr 2.

Department of Urology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea.

The blots of control and docetaxel for caspase-9, caspase-3, caspase-8, Bcl-, and tubulin in the Figure 4f were reused from Figure 4 of our previous paper published in Journal of Urology in 2010 ( https://doi.org/10.1016/j. Read More

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http://dx.doi.org/10.1007/s10637-019-00746-yDOI Listing
April 2019
2.919 Impact Factor

Early depth of tumor shrinkage and treatment outcomes in non-small cell lung cancer treated using Nivolumab.

Invest New Drugs 2019 Apr 1. Epub 2019 Apr 1.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.

Background It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated associations between early depth of response and survival outcomes among patients receiving nivolumab for NSCLC. Read More

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http://dx.doi.org/10.1007/s10637-019-00770-yDOI Listing
April 2019
3 Reads

MicroRNA-101-3p suppresses proliferation and migration in hepatocellular carcinoma by targeting the HGF/c-Met pathway.

Invest New Drugs 2019 Mar 30. Epub 2019 Mar 30.

Department of Pathology, Infectious Diseases Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.

MicroRNAs are involved in each stage of tumor development. Activation of the hepatocyte growth factor (HGF)/c-Met axis facilitates the proliferation and migration of cancer cells, and the HGF/c-MET pathway provides potential targets for anticancer treatment. However, the interaction between HGF and miRNAs in hepatocellular carcinoma (HCC) remains unknown. Read More

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http://dx.doi.org/10.1007/s10637-019-00766-8DOI Listing
March 2019
2 Reads

Cellular uptake evaluation of pentagamaboronon-0 (PGB-0) for boron neutron capture therapy (BNCT) against breast cancer cells.

Invest New Drugs 2019 Mar 30. Epub 2019 Mar 30.

Departement of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, 55281, Indonesia.

Pentagamaboronon-0 (PGB-0), a curcumin analog compound, has been synthesized as a candidate of boron-carrier pharmaceutical (BCP) for boron neutron capture therapy (BNCT); however, this compound is poorly soluble in water. To improve its solubility, aqueous formulations of PGB-0 with a monosaccharide, fructose or sorbitol, were successfully synthesized, namely PGB-0-F and PGB-0-So, respectively. The cytotoxicity study showed that PGB-0-F and PGB-0-So exerted low cytotoxicity against MCF-7 and MDA-MB 231 breast cancer cells. Read More

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http://dx.doi.org/10.1007/s10637-019-00765-9DOI Listing
March 2019
3 Reads

Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells.

Invest New Drugs 2019 Mar 30. Epub 2019 Mar 30.

Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy based on the natural product formononetin. Read More

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http://dx.doi.org/10.1007/s10637-019-00767-7DOI Listing
March 2019
2 Reads

A first-in-human study of the novel metabolism-based anti-cancer agent SM-88 in subjects with advanced metastatic cancer.

Invest New Drugs 2019 Mar 30. Epub 2019 Mar 30.

Tyme Technologies, Inc., 17 State St. 7th floor, New York, NY, 10004, USA.

Purpose SM-88 (D,L-alpha-metyrosine; racemetyrosine) is a novel anti-cancer agent, used with melanin, phenytoin, and sirolimus (SMK Therapy). This pilot first-in-human study characterized the safety, tolerability, and efficacy of SMK Therapy in subjects with advanced metastatic cancer. Methods All subjects (n = 30) received SMK Therapy for an initial 6 week Cycle (5 days on, 2 off per week) and continued if well tolerated. Read More

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http://dx.doi.org/10.1007/s10637-019-00758-8DOI Listing
March 2019
1 Read

Emodin induced necroptosis in the glioma cell line U251 via the TNF-α/RIP1/RIP3 pathway.

Invest New Drugs 2019 Mar 28. Epub 2019 Mar 28.

Department of Neurosurgery, Affiliated Hospital of Jining Medical University, & Shandong Provincial Key Laboratory of Stem Cells and Neuro-oncology, Jining, Shandong, 272029, People's Republic of China.

Emodin, an anthraquinone compound extracted from rhubarb and other traditional Chinese medicines, has been proven to have a wide range of pharmacological effects, such as anti-inflammatory, antiviral, and antitumor activities. Previous studies have confirmed that emodin has inhibitory effects on various solid tumors, such as osteosarcoma, liver cancer, prostate cancer and glioma. This study aimed to investigate the effects and mechanisms of emodin-induced necroptosis in the glioma cell line U251 by targeting the TNF-α/RIP1/RIP3 signaling pathway. Read More

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http://dx.doi.org/10.1007/s10637-019-00764-wDOI Listing

Discovery of a pyrimidine compound endowed with antitumor activity.

Invest New Drugs 2019 Mar 21. Epub 2019 Mar 21.

Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy.

Recently, some synthetic nitrogen-based heterocyclic molecules, such as PJ34, have shown pronounced antitumor activity. Therefore, we designed and synthesized new derivatives characterized by a nitrogen-containing scaffold and evaluated their antiproliferative properties in tumor cells. We herein report the effects of three newly synthesized compounds on cell lines from three different human cancers: triple-negative breast cancer, colon carcinoma and glioblastoma. Read More

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http://link.springer.com/10.1007/s10637-019-00762-y
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http://dx.doi.org/10.1007/s10637-019-00762-yDOI Listing
March 2019
5 Reads

The exosome secretion inhibitor neticonazole suppresses intestinal dysbacteriosis-induced tumorigenesis of colorectal cancer.

Invest New Drugs 2019 Mar 19. Epub 2019 Mar 19.

Department of General Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301 Middle Yanchang Road, Shanghai, 200072, China.

Colorectal cancer (CRC) is the most frequently encountered malignancy associated with the rectum or colon, and accumulating evidences have implicated intestinal dysbacteriosis (IDB, disruption of gut microbiome) and exosomes in the pathology of CRC. We aimed to investigate the effect of IDB on exosome secretion in a CRC xenograft mouse model. An IDB mouse model was established and was inoculated with the CRC cell line SW480 as a xenograft tumor. Read More

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http://link.springer.com/10.1007/s10637-019-00759-7
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http://dx.doi.org/10.1007/s10637-019-00759-7DOI Listing
March 2019
10 Reads

Tubulin colchicine site binding agent LL01 displays potent antitumor efficiency both in vitro and in vivo with suitable drug-like properties.

Invest New Drugs 2019 Mar 18. Epub 2019 Mar 18.

Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.

Through rational drug design, we previously identified an indenoprazole derivative, 2-(6-ethoxy-3-(3-ethoxyphenylamino)-1-methyl-1,4-dihydroindeno[1,2-c]pyrazol-7-yloxy)acetamide (LL01), as a potent tubulin polymerization inhibitor targeting the tubulin colchicine binding site. In this study, we further demonstrated that LL01 was not a P-gp substrate. It potently inhibited the growth of a variety of tumor cells, including those with multidrug resistance, with GI values in the low nanomole ranges. Read More

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http://link.springer.com/10.1007/s10637-019-00753-z
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http://dx.doi.org/10.1007/s10637-019-00753-zDOI Listing
March 2019
3 Reads

Cytotoxicity of [HuArgI (co)-PEG5000]-induced arginine deprivation to ovarian Cancer cells is autophagy dependent.

Invest New Drugs 2019 Mar 18. Epub 2019 Mar 18.

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, 1102 2801, Lebanon.

In this study, we assess arginine auxotrophy in ovarian cancer cells and attempt to target them using arginine deprivation induced by a pegylated recombinant human Arginase I cobalt [HuArgI (Co)-PEG5000]. Ovarian cancer cells were sensitive to [HuArgI (Co)-PEG5000]-induced arginine deprivation with IC values in the low pM range. Addition of excess L-citrulline rescued only one of three cell lines tested, indicating that the majority of cell lines are completely auxotrophic for arginine. Read More

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http://link.springer.com/10.1007/s10637-019-00756-w
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http://dx.doi.org/10.1007/s10637-019-00756-wDOI Listing
March 2019
12 Reads

Knockdown of FBXO22 inhibits melanoma cell migration, invasion and angiogenesis via the HIF-1α/VEGF pathway.

Invest New Drugs 2019 Mar 18. Epub 2019 Mar 18.

Department of Plastic Surgery, The Affiliated Friendship Plastic Surgery Hospital with Nanjing Medical University, 149 Hanzhong Road, Nanjing, 210029, Jiangsu Province, China.

F-box proteins, a type of substrate-recognition complexes consisting of SKP1-cullin 1-F-box protein (SCF) E3 ligase, can critically affect many cellular processes because of the ubiquitylation and subsequent degradation of target proteins. This study investigated the effect of FBXO22 on melanoma angiogenesis, migration, and invasion. Results showed that FBXO22 staining intensity was increased in malignant melanoma (MM) compared with that in skin tissue (P˂0. Read More

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http://dx.doi.org/10.1007/s10637-019-00761-zDOI Listing
March 2019
3 Reads
2.919 Impact Factor

A phase I, dose-escalation study of PF-06650808, an anti-Notch3 antibody-drug conjugate, in patients with breast cancer and other advanced solid tumors.

Invest New Drugs 2019 Mar 18. Epub 2019 Mar 18.

START Center for Cancer Care, 4383 Medical Dr., San Antonio, TX, 78229, USA.

Background PF-06650808 is a novel anti-Notch3 antibody-drug conjugate (ADC) able to deliver an auristatin-based cytotoxic payload to target cells. In this first-in-human, dose-finding, phase I study (NCT02129205), we investigated safety, pharmacokinetics, immunogenicity, and preliminary antitumor activity of single-agent PF-06650808 in 40 patients with advanced breast cancer (BC) and other solid tumors unselected for Notch3 expression. Primary endpoint was dose-limiting toxicity (DLT). Read More

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http://dx.doi.org/10.1007/s10637-019-00754-yDOI Listing
March 2019
3 Reads

Ramucirumab as a second line therapy for advanced HCC: a significant achievement or a wasted opportunity for personalised therapy?

Invest New Drugs 2019 Mar 16. Epub 2019 Mar 16.

Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, via Padre Pio 1, 85028, Rionero, Vulture, PZ, Italy.

The second line treatment of hepatocellular carcinoma (HCC) has recently become an exciting area of interest since new emerging options have demonstrated survival benefits versus placebo. Unfortunately, predictive biomarkers are unavailable for these treatments. Ramucirumab, a monoclonal antibody against VEGFR-2, has demonstrated overall survival superiority against placebo as a second line therapy for patients with AFP > 400 ng/ml in the recent REACH-2 trial. Read More

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http://dx.doi.org/10.1007/s10637-019-00760-0DOI Listing

Identification of inhibitors of the polo-box domain of polo-like kinase 1 from natural and semisynthetic compounds.

Invest New Drugs 2019 Mar 15. Epub 2019 Mar 15.

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, 55128, Mainz, Germany.

PLK1 has an important role in the regulation of cell cycle and represents an important target for cancer treatment. This enzyme belongs to the Polo-like kinases family, which is characterized by a regulatory domain named Polo-box domain (PBD). Rather than regular kinase inhibitors, this domain provides high selectivity to PLK1. Read More

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http://dx.doi.org/10.1007/s10637-019-00752-0DOI Listing
March 2019
2 Reads

Novel palladium (II) complexes with tetradentate thiosemicarbazones. Synthesis, characterization, in vitro cytotoxicity and xanthine oxidase inhibition.

Invest New Drugs 2019 Mar 14. Epub 2019 Mar 14.

Department of Chemistry, Engineering Faculty, Istanbul University-Cerrahpasa, 34320, Avcilar, Istanbul, Turkey.

In vitro cytotoxicity and xanthine oxidase inhibition capabilities were investigated for five palladium (II) chelate complexes. The palladium complexes were synthesized by starting from S-alkyl-thiosemicarbazones where the alkyl component is methyl, ethyl, propyl or butyl. The solid complexes are characterized by elemental analysis and spectroscopic techniques (UV-visible, IR and 1H NMR). Read More

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http://link.springer.com/10.1007/s10637-019-00751-1
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http://dx.doi.org/10.1007/s10637-019-00751-1DOI Listing
March 2019
5 Reads

Eribulin, trastuzumab, and pertuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer: a phase II, multicenter, collaborative, open-label, single-arm clinical trial.

Invest New Drugs 2019 Mar 8. Epub 2019 Mar 8.

Department of Breast Surgery, Saitama Red Cross Hospital, Saitama, Japan.

Purpose To examine the efficacy and safety of triple therapy with eribulin, trastuzumab, and pertuzumab in patients with HER2-positive metastatic breast cancer (MBC) who never received any prior therapy in the first-line metastatic/advanced setting. Methods Eribulin 1.4 mg/m (days 1 and 8), trastuzumab 8 mg/kg over 90 min and 6 mg/kg over 30 min, and pertuzumab 840 mg/body over 60 min and 420 mg/body over 30 min were administered intravenously in 21-day cycles. Read More

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http://dx.doi.org/10.1007/s10637-019-00755-xDOI Listing
March 2019
2 Reads

Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion.

Invest New Drugs 2019 Mar 7. Epub 2019 Mar 7.

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 211100, Jiangsu Province, China.

The dyskeratosis congenita 1 (DKC1) gene is located on the X chromosome at Xq28. Dyskerin encoded by the DKC1 gene is associated with the formation of certain small RNAs and the telomerase activity. Inherited mutations in DKC1 inactivate the dyskerin and causes dyskeratosis congenital, which is characterized by skin defects, hematopoiesis failure, and increased susceptibility to cancer. Read More

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http://dx.doi.org/10.1007/s10637-019-00748-wDOI Listing
March 2019
2 Reads

A phase I study to determine the maximum tolerated dose of trifluridine/tipiracil and oxaliplatin in patients with refractory metastatic colorectal cancer: LUPIN study.

Invest New Drugs 2019 Mar 6. Epub 2019 Mar 6.

Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Background The effectiveness of reintroducing oxaliplatin for metastatic colorectal cancer (mCRC) refractory to both oxaliplatin and irinotecan was previously reported in a phase II study (RE-OPEN). We conducted a phase I study to determine the maximum tolerated dose of oxaliplatin plus trifluridine/tipiracil (FTD/TPI) in patients with refractory mCRC. Patients and Methods Three dosages of intravenous oxaliplatin (50, 65 and 85 mg/m) on days 1 and 15 and a fixed dose of FTD/TPI 35 mg/m twice daily (bid) on days 1-5 and 15-19 every 4 weeks were investigated in patients with refractory mCRC using a 3 + 3 design. Read More

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http://dx.doi.org/10.1007/s10637-019-00749-9DOI Listing
March 2019
1 Read

A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer.

Invest New Drugs 2019 Mar 2. Epub 2019 Mar 2.

High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, Anhui, People's Republic of China.

Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput drug screen strategy to identify new drugs that can enhance the sensitivity of chemo-drug cisplatin in SCLC. Read More

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http://dx.doi.org/10.1007/s10637-019-00750-2DOI Listing
March 2019
2 Reads
2.919 Impact Factor

A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors.

Invest New Drugs 2019 Mar 2. Epub 2019 Mar 2.

National Taiwan University Hospital, 7 Chung Shan S Rd, Taipei, 10002, Taiwan.

Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600 mg/d; cohort 2, 1000 mg/d for 2 weeks, then 800 mg/d. Read More

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http://dx.doi.org/10.1007/s10637-019-00745-zDOI Listing
March 2019
5 Reads

Population pharmacokinetic analysis of AR-67, a lactone stable camptothecin analogue, in cancer patients with solid tumors.

Invest New Drugs 2019 Feb 28. Epub 2019 Feb 28.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone St., Lexington, KY, 40536, USA.

Background AR-67 is a novel camptothecin analogue at early stages of drug development. The phase 1 clinical trial in cancer patients with solid tumors was completed and a population pharmacokinetic model (POP PK) was developed to facilitate further development of this investigational agent. Methods Pharmacokinetic data collected in the phase 1 clinical trial were utilized for the development of a population POP PK by implementing the non-linear mixed effects approach. Read More

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http://link.springer.com/10.1007/s10637-019-00744-0
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http://dx.doi.org/10.1007/s10637-019-00744-0DOI Listing
February 2019
16 Reads

Axitinib pharmacologic therapeutic monitoring reveals severe under-exposure despite titration in patients with metastatic renal cell carcinoma.

Invest New Drugs 2019 Feb 26. Epub 2019 Feb 26.

Department of Medical Oncology, Hôpitaux Universitaires Henri Mondor, 51 avenue du Mal-de-Lattre-de-Tassigny, 94010, Créteil, France.

Introduction New therapeutic strategies combining axitinib and immune checkpoint blockers are ongoing in metastatic renal cell carcinoma (mRCC). These strategies do not consider the pharmacokinetic variability of axitinib. We aimed to describe the risk of axitinib under-exposure using routine pharmacologic therapeutic monitoring (PTM). Read More

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http://dx.doi.org/10.1007/s10637-019-00743-1DOI Listing
February 2019
1 Read

A phthalimidoalkanamide derived novel DNMT inhibitor enhanced radiosensitivity of A549 cells by inhibition of homologous recombination of DNA damage.

Invest New Drugs 2019 Feb 22. Epub 2019 Feb 22.

College of Pharmacy, Daegu Catholic University, Gyeongsan-si, Gyeongbuk, South Korea.

Purpose To elucidate the radiosensitizing effect and underlying mechanism of a new kind of DNA methyltransferase (DNMT) inhibitor with biological availability. Methods A novel non-nucleoside compound, designated as MA-17, was recently derived from a phthalimido alkanamide structure. DNMT expressions were confirmed in cultured human lung cancer (A549) and normal astrocyte (NHA) cells, radiosensitivity was measured using clonogenic assay, and assays of cell cycle alteration, apoptosis, DNA damage repair, and differential gene expression were undertaken. Read More

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http://link.springer.com/10.1007/s10637-019-00730-6
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http://dx.doi.org/10.1007/s10637-019-00730-6DOI Listing
February 2019
5 Reads
2.919 Impact Factor

Phase I study of TAS-121, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with non-small-cell lung cancer harboring EGFR mutations.

Invest New Drugs 2019 Feb 21. Epub 2019 Feb 21.

Thoracic Center, St. Luke's International Hospital, 9-1 Akashicho, Chuo-ku, Tokyo, 104-0045, Japan.

Purpose We investigated the safety, tolerability, pharmacokinetics, and efficacy of TAS-121, a novel, potent, and highly selective third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in Japanese patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC) previously treated with EGFR-TKI. Methods This was an open-label, non-randomized, multi-center, dose escalation, phase I study conducted in three phases (dose escalation, expansion, and extension phases). TAS-121 was administered orally once daily (QD) or twice daily (BID) under fasting conditions in a 21-day treatment cycle. Read More

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http://link.springer.com/10.1007/s10637-019-00732-4
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http://dx.doi.org/10.1007/s10637-019-00732-4DOI Listing
February 2019
3 Reads

Synergistic effect and reduced toxicity by intratumoral injection of cytarabine-loaded hyaluronic acid hydrogel conjugates combined with radiotherapy on lung cancer.

Invest New Drugs 2019 Feb 21. Epub 2019 Feb 21.

Department of Oncology, Affiliated Hospital of Southwest Medical University, 25 TaiPing Rd, Luzhou, 646000, China.

The aim of this study was to explore the synergistic anti-tumor effects of cytarabine hyaluronic acid-tyramine (Ara-HA-Tyr) hydrogel conjugates and radiotherapy (RT) in the Lewis lung cancer (LLC) xenograft model, and the mechanisms involved. The radiotherapy sensitization ratio (SER) of 0.5 μg cytarabine (Ara-C) was 1. Read More

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http://dx.doi.org/10.1007/s10637-019-00740-4DOI Listing
February 2019

Durable response to the ALK inhibitor alectinib in inflammatory myofibroblastic tumor of the head and neck with a novel SQSTM1-ALK fusion: a case report.

Invest New Drugs 2019 Feb 21. Epub 2019 Feb 21.

Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.

An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that typically develops in the lungs and seldom in the head and neck region. It is often related to the anaplastic lymphoma kinase (ALK) fusion gene. Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in patients with ALK-positive IMT. Read More

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http://dx.doi.org/10.1007/s10637-019-00742-2DOI Listing
February 2019
5 Reads

Switch maintenance therapy with S-1 after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel in advanced lung squamous cell carcinoma.

Invest New Drugs 2019 Feb 21. Epub 2019 Feb 21.

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan.

Background Optimal maintenance therapy for lung squamous cell carcinoma (SCC) has not been established. The aim of this study was to evaluate the efficacy and safety of switch maintenance therapy with S-1, an oral fluoropyrimidine, after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in chemotherapy-naïve patients with advanced SCC. Methods Chemotherapy-naïve patients with advanced SCC received induction therapy with four cycles of carboplatin (at an area under the curve of 6, day 1 of a 28-day cycle) and nab-paclitaxel (100 mg/kg, days 1, 8, and 15). Read More

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http://dx.doi.org/10.1007/s10637-019-00747-xDOI Listing
February 2019
2 Reads

GNS561, a new lysosomotropic small molecule, for the treatment of intrahepatic cholangiocarcinoma.

Invest New Drugs 2019 Feb 19. Epub 2019 Feb 19.

Genoscience Pharma, 10 Rue d'Iéna, Marseille, France.

Among the acquired modifications in cancer cells, changes in lysosomal phenotype and functions are well described, making lysosomes a potential target for novel therapies. Some weak base lipophilic drugs have a particular affinity towards lysosomes, taking benefits from lysosomal trapping to exert anticancer activity. Here, we have developed a new lysosomotropic small molecule, GNS561, and assessed its activity in multiple in vitro intrahepatic cholangiocarcinoma models (HuCCT1 and RBE cell lines and patient-derived cells) and in a chicken chorioallantoic membrane xenograft model. Read More

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http://dx.doi.org/10.1007/s10637-019-00741-3DOI Listing
February 2019
1 Read

An orally antitumor chalcone hybrid inhibited HepG2 cells growth and migration as the tubulin binding agent.

Invest New Drugs 2019 Feb 11. Epub 2019 Feb 11.

Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Liver cancer is a kind of high mortality cancer due to the difficulty of early diagnosis. It is necessary to develop the anticancer agents to treat liver cancer. Here, a novel chalcone derivative was synthesized and evaluated for anticancer activity in vitro against liver cancer cell lines (HepG2, SNU-423, SMMC7221, and SNU-398). Read More

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http://dx.doi.org/10.1007/s10637-019-00737-zDOI Listing
February 2019
3 Reads
2.919 Impact Factor

LEF1-AS1 contributes to proliferation and invasion through regulating miR-544a/ FOXP1 axis in lung cancer.

Invest New Drugs 2019 Feb 8. Epub 2019 Feb 8.

Departments of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, No.287 Changhuai Road, Bengbu City, Anhui Province, 233004, People's Republic of China.

Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulators in tumor development. This study aims to investigate the potential role oflncRNALEF1-AS1, in the progression of lung cancer. Quantitative real-time PCR (qRT-PCR) and western blot assays showed that LEF1-AS1 was upregulated while miR-544a was downregulated in lung cancer specimens and cells. Read More

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http://dx.doi.org/10.1007/s10637-018-00721-zDOI Listing
February 2019

Delineation of proapoptotic signaling of anthracene-shelled ML metallacapsules and their synergistic activity with curcumin in cisplatin-sensitive and resistant tumor cell lines.

Invest New Drugs 2019 Feb 8. Epub 2019 Feb 8.

Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000, Sofia, Bulgaria.

Since the introduction of cisplatin into clinical practice a few decades ago, the topic of metal-based drugs has expanded significantly. Recent examples emphasize on metallosupramolecules as an emerging class of compounds with diverse properties. They can trigger unique cellular events in malignant cells or serve as molecular hosts for various biologically active compounds, including anticancer agents. Read More

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http://link.springer.com/10.1007/s10637-019-00738-y
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http://dx.doi.org/10.1007/s10637-019-00738-yDOI Listing
February 2019
7 Reads

A phase I study of the antibody drug conjugate ASG-5ME, an SLC44A4-targeting antibody carrying auristatin E, in metastatic castration-resistant prostate cancer.

Invest New Drugs 2019 Feb 6. Epub 2019 Feb 6.

Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 353 E 68th St, New York, NY, 10065, USA.

Background Antibody drug conjugates (ADC) offer the potential of maximizing efficacy while minimizing systemic toxicity. ASG-5ME, an SLC44A4-targeting antibody carrying monomethyl auristatin E (MMAE), a microtubule-disrupting agent, was investigated in men with metastatic castration resistant prostate cancer. Methods The primary objective of this phase I study was to determine maximum tolerated dose (MTD) and recommended phase II dose. Read More

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http://dx.doi.org/10.1007/s10637-019-00731-5DOI Listing
February 2019
5 Reads

Clinical outcomes of advanced stage cancer patients treated with sequential immunotherapy in phase 1 clinical trials.

Invest New Drugs 2019 Feb 6. Epub 2019 Feb 6.

Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.

Background Given the increasing number of available immunotherapeutic agents, more patients are presenting after failing immunotherapy in need of new treatment options. In this study, we investigated the clinical outcomes of patients treated with sequential immunotherapy. Methods We performed a retrospective review of 90 advanced stage cancer patients treated on immunotherapy-based phase 1 clinical trials at Winship Cancer Institute from 2009 to 2017. Read More

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http://link.springer.com/10.1007/s10637-019-00736-0
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http://dx.doi.org/10.1007/s10637-019-00736-0DOI Listing
February 2019
1 Read

Modified ingenol semi-synthetic derivatives from Euphorbia tirucalli induce cytotoxicity on a large panel of human cancer cell lines.

Invest New Drugs 2019 Feb 1. Epub 2019 Feb 1.

Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, CEP 14784 400, Barretos, São Paulo, Brazil.

The latex from Euphorbia tirucalli is used in Brazil as a folk medicine for several diseases, including cancer. Recently, we showed a cytotoxic activity of E. tirucalli euphol in a wide range of cancer cell lines. Read More

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http://dx.doi.org/10.1007/s10637-019-00728-0DOI Listing
February 2019

Apatinib, a novel VEGFR inhibitor plus docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR: a phase I trial.

Invest New Drugs 2019 Feb 1. Epub 2019 Feb 1.

State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

Background This phase I trial was primarily conducted to determine the maximum tolerated dose (MTD) of apatinib combined with docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR who have failed to first-line platinum-based chemotherapy, and to evaluate the safety and tolerability of apatinib plus docetaxel. Methods This was a single-center, open-label, dose-escalating phase I trial. The study used a standard 3 + 3 dose escalation design with the primary aim of determining the MTD. Read More

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http://dx.doi.org/10.1007/s10637-019-00735-1DOI Listing
February 2019
2 Reads

Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.

Invest New Drugs 2019 Feb 1. Epub 2019 Feb 1.

Department of Immunology, Institute for Biological Research "Sinisa Stankovic", Belgrade University, Belgrade, Serbia.

We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. Read More

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http://link.springer.com/10.1007/s10637-019-00733-3
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http://dx.doi.org/10.1007/s10637-019-00733-3DOI Listing
February 2019
9 Reads

Bispecific anti-CD3 x anti-B7-H3 antibody mediates T cell cytotoxic ability to human melanoma in vitro and in vivo.

Invest New Drugs 2019 Feb 1. Epub 2019 Feb 1.

Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing, 100038, China.

Inhibition of the B7-H3 immune checkpoint is reported to limit the tumor growth of B7-H3 tumors. In this study, we demonstrated B7-H3 expression in human melanoma cells, including a primary culture and several cell lines. Furthermore, we investigated whether B7-H3 could serve as a target for T cell-mediated immunotherapy against melanoma. Read More

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http://dx.doi.org/10.1007/s10637-018-00719-7DOI Listing
February 2019
1 Read

The influence of prior ramucirumab treatment on the clinical activity of FOLFIRI as third-line therapy in patients with metastatic gastric Cancer.

Invest New Drugs 2019 Jan 28. Epub 2019 Jan 28.

Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, via Padre Pio 1, 85028, Rionero, Vulture (PZ), Italy.

Purpose Few data described the activity of chemotherapy after ramucirumab plus paclitaxel progression in metastatic gastric cancer patients. The aim of this phase II study is to assess the efficacy and safety of the FOLFIRI regimen as a third-line of treatment. Methods The study enrolled patients with histologically proven metastatic gastric cancer or gastroesophageal junction carcinoma whose disease had progressed after ramucirumab-based second line of treatment. Read More

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http://dx.doi.org/10.1007/s10637-019-00725-3DOI Listing
January 2019

Nifuroxazide induces apoptosis, inhibits cell migration and invasion in osteosarcoma.

Invest New Drugs 2019 Jan 25. Epub 2019 Jan 25.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, Sichuan Province, 610041, People's Republic of China.

Osteosarcoma is the most common primary malignancy of bone and characterized by an appendicular primary tumor with a high rate of metastasis to the lungs. Unfortunately, there is no effective strategy to treat osteosarcoma in current clinical practice. In this study, the anticancer effects and potential mechanisms of nifuroxazide, an oral nitrofuran antibiotic, on two osteosarcoma cell lines were investigated. Read More

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http://dx.doi.org/10.1007/s10637-019-00724-4DOI Listing
January 2019
8 Reads

The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model.

Invest New Drugs 2019 Jan 25. Epub 2019 Jan 25.

Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.

Obtustatin, isolated from the Levantine Viper snake venom (Macrovipera lebetina obtusa -MLO), is the shortest known monomeric disintegrin shown to specifically inhibit the binding of the α1β1 integrin to collagen IV. Its oncostatic effect is due to the inhibition of angiogenesis, likely through α1β1 integrin inhibition in endothelial cells. To explore the therapeutic potential of obtustatin, we studied its effect in S-180 sarcoma-bearing mice model in vivo as well as in human dermal microvascular endothelial cells (HMVEC-D) in vitro, and tested anti-angiogenic activity in vivo using the chick embryo chorioallantoic membrane assay (CAM assay). Read More

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http://dx.doi.org/10.1007/s10637-019-00734-2DOI Listing
January 2019

In vitro and in vivo cytotoxic activity and human serum albumin interaction for a methoxy-styryl-thiosemicarbazone.

Invest New Drugs 2019 Jan 19. Epub 2019 Jan 19.

Instituto de Química, Departamento de Química Orgânica, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Rodovia BR-465, Km 7, Seropédica, RJ, 23890-000, Brazil.

Thiosemicarbazone is a class of compounds with potential applications in medicine, presenting high capacity to inhibit the growth of cancer cells as well as low toxicity. Because of high interest in anticancer studies involving thiosemicarbazones as new chemotherapeutic agents, a synthetic thiosemicarbazone derivative, 4-N-(2'-methoxy-styryl)-thiosemicarbazone (MTSC) was evaluated in vivo against Ehrlich carcinoma in an animal model. In vivo results demonstrated that MTSC treatment induced the survival of mice and altered significantly the body weight of the surviving mice 12 days after tumor inoculation. Read More

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http://dx.doi.org/10.1007/s10637-018-00722-yDOI Listing
January 2019
1 Read

The cellular effects of novel triazine nitrogen mustards in glioblastoma LBC3, LN-18 and LN-229 cell lines.

Invest New Drugs 2019 Jan 15. Epub 2019 Jan 15.

Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Bialystok, Poland.

1,3,5-triazine is an important heterocyclic skeleton for mono, two or three 2-chloroethylamine groups. The study presented here provides novel information on cellular effects of 1,3,5-triazine with mono, two or three 2-chloroethylamine groups in glioblastoma LBC3, LN-18 and LN-229 cell lines. In our study, the most cytotoxic effect was observed in 1,3,5-triazine with three 2-chloroethylamine groups (12f compound). Read More

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http://dx.doi.org/10.1007/s10637-018-0712-8DOI Listing
January 2019
1 Read

The rhenium(I)-diselenoether anticancer drug targets ROS, TGF-β1, VEGF-A, and IGF-1 in an in vitro experimental model of triple-negative breast cancers.

Invest New Drugs 2019 Jan 11. Epub 2019 Jan 11.

Institut Galien, Université Paris-Saclay, 92296, Châtenay-Malabry, France.

The rhenium(I)-diselenoether complex (Re-diSe) is a rhenium tricarbonyl-based drug chelated by a diselenoether ligand. In this work, we compared its inhibitory effects on the hormone-independent MDA-MB231cancer line and other different cancer cell lines after an exposure time of 72 h by MTT assays. The sensitivity of MDA-MB231 was in the same range than the hormone-dependent MCF-7 breast cancer, the PC-3 prostate and HT-29 colon cancer cells, while the A549 lung and the HeLa uterine cancer cells were less sensitive. Read More

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http://link.springer.com/10.1007/s10637-019-00727-1
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http://dx.doi.org/10.1007/s10637-019-00727-1DOI Listing
January 2019
22 Reads