2,964 results match your criteria Investigational new drugs[Journal]


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

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
1 Read

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
2 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
1 Read

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://dx.doi.org/10.1007/s10637-019-00736-0DOI Listing
February 2019

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
1 Read

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
3 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

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
2 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

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

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
16 Reads

Inhibition of AKT signalling by benzoxazine derivative LTUR6 through the modulation of downstream kinases.

Invest New Drugs 2019 Jan 10. Epub 2019 Jan 10.

Faculty of Science Technology and Engineering, School of Pharmacy and Applied Science, Latrobe Institute of Molecular Sciences, La Trobe University, Bendigo, Australia.

Many compounds structurally similar to chromones have been developed to enhance the sensitizing effect of cancer cells to chemotherapeutic agents. Most of these compounds have been shown to promote this sensitization by targeting the repair pathways. One such compound is LTUR6, which enhances the sensitization of doxorubicin to colon cancer cells HT29, by inhibiting the phosphorylation of the double stranded break (DSB) repair enzyme AKT. Read More

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http://dx.doi.org/10.1007/s10637-019-00726-2DOI Listing
January 2019

A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors.

Invest New Drugs 2019 Jan 9. Epub 2019 Jan 9.

Eisai Co. Ltd., Tokyo, Japan.

Background We conducted a first-in-Japanese, phase I study of ontuxizumab, a humanized, anti-endosialin monoclonal antibody, to confirm its tolerability, safety, and pharmacokinetics, and identify exploratory efficacy. Methods This was a multicenter, multiple-dose, open-label study in Japanese patients aged ≥20 years with solid tumors, including gastric cancer (GC) or advanced hepatocellular carcinoma (HCC), who had failed standard chemotherapy. The study comprised two parts: part 1 (dose-escalation; ontuxizumab 2-12 mg/kg weekly) and part 2 (cohort-expansion; 4 or 8 mg/kg weekly, or 12 mg/kg biweekly). Read More

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http://dx.doi.org/10.1007/s10637-018-0713-7DOI Listing
January 2019
1 Read

IMRT combined with S-1 concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a prospective phase II study.

Invest New Drugs 2019 Jan 8. Epub 2019 Jan 8.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Purpose The current standard treatment for locally advanced nasopharyngeal carcinoma (LANPC) is intensity-modulated radiation therapy (IMRT) plus cisplatin concurrent chemoradiotherapy (CCRT). However, this regimen has well-known hematological and gastrointestinal toxicities. Many studies have reported that S-1 was effective in the treatment of multiple solid cancers with mild toxicities. Read More

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http://link.springer.com/10.1007/s10637-018-00720-0
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http://dx.doi.org/10.1007/s10637-018-00720-0DOI Listing
January 2019
1 Read

Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib.

Invest New Drugs 2019 Jan 5. Epub 2019 Jan 5.

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

Intended to explore synthetic lethality and develop better combinatorial regimens, we screened colorectal cancer (CRC) cells using poly ADP-ribose (PAR) polymerase (PARP) inhibitors and cytotoxic agents. We studied four PARP inhibitors and three DNA-damaging agents, and their combinations using sulforhodamine B assay. Rucaparib demonstrated the greatest synergy with irinotecan, followed by olaparib and PJ34. Read More

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http://dx.doi.org/10.1007/s10637-018-00717-9DOI Listing
January 2019
4 Reads

Significant differences on submission lag following regulation reform for registration of novel therapeutic drugs in Taiwan.

Authors:
I-Chen Sun

Invest New Drugs 2019 Jan 5. Epub 2019 Jan 5.

Division of Pharmaceutical Science, Center for Drug Evaluation, Taipei, Taiwan, Republic of China.

Drug lag, which delays patients' access to medicinal products, is typically associated with pharmaceutical regulations. To shorten drug lag, health authorities may establish new policies to liberalize the regulations, a step that is important in countries, such as Taiwan, with consumer demand for imported novel therapeutic agents. Taiwan's government enacted Articles 38-1 and 38-2 of Regulations for Registration of Medicinal Products to relax the regulatory barriers for new drug submission, thus conditionally exempting the requirement for the Certificate of Pharmaceutical Product (CPP). Read More

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http://dx.doi.org/10.1007/s10637-018-00715-xDOI Listing
January 2019

Human antigen R and drug resistance in tumors.

Invest New Drugs 2019 Jan 5. Epub 2019 Jan 5.

Department of Urology, Gansu Provincial Hospital, 204 Donggang West Road, Chengguan District, 730000, Lanzhou, Gansu, People's Republic of China.

The human embryonic lethal abnormal visual protein, HuR, belongs to the Hu family of RNA-binding proteins. Over the past two decades, HuR has been extensively associated with multiple biological characteristics of tumors, including tumor development and progression, angiogenesis, invasion, migration and prognosis, since this protein regulates the stability of cancer-associated target mRNAs due to its posttranscriptional regulatory mechanisms. A recent investigation of the multiple functions of HuR has provided emerging evidence of its role in drug resistance in various tumors. Read More

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http://link.springer.com/10.1007/s10637-018-00723-x
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http://dx.doi.org/10.1007/s10637-018-00723-xDOI Listing
January 2019
6 Reads

Biodistribution, pharmacokinetics and radioimmunotherapy of Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice.

Invest New Drugs 2019 Jan 5. Epub 2019 Jan 5.

Institute of Nuclear Energy Research, 1000 Wenhua Rd, Longtan District, Taoyuan City, Taiwan.

Background Cetuximab is a fully humanized IgG1 subclass monoclonal that binds specifically to the human epidermal growth factor receptor (EGFR). Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, such as colon, rectum and lung tumors. In this study, cetuximab with a combination of radiotherapy nuclear Re achieved better therapeutic effect on lung cancer. Read More

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http://dx.doi.org/10.1007/s10637-018-00718-8DOI Listing
January 2019

Efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal patients with metastatic, hormone receptor-positive, HER2-negative breast cancer: a phase II study.

Invest New Drugs 2019 Jan 5. Epub 2019 Jan 5.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1354, Houston, TX, 77030, USA.

Background Increased adiposity is thought to result in worse clinical outcomes in patients with breast cancer through increased estrogen production, hyperinsulinemia, insulin resistance, and activation of the phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin (mTOR) pathway. Thus, we hypothesized that the addition of metformin to everolimus and exemestane, could lead to better outcomes in overweight and obese patients with metastatic, hormone receptor-positive, HER2-negative breast cancer. We conducted a phase II trial to evaluate the efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal women with metastatic, hormone receptor-positive, HER2-negative breast cancer. Read More

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http://dx.doi.org/10.1007/s10637-018-0700-zDOI Listing
January 2019
2 Reads

Screening, identification of prostate cancer urinary biomarkers and verification of important spots.

Invest New Drugs 2019 Jan 4. Epub 2019 Jan 4.

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

Prostate-specific antigen (PSA) has been widely used as the unique serum biomarker for the diagnosis of prostate cancer (PCa). When PSA is moderately increased (e.g. Read More

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http://dx.doi.org/10.1007/s10637-018-0709-3DOI Listing
January 2019

MiR-181a, a new regulator of TGF-β signaling, can promote cell migration and proliferation in gastric cancer.

Invest New Drugs 2019 Jan 4. Epub 2019 Jan 4.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, 300060, China.

Transforming growth factor-beta (TGF-β) signaling pathway plays pivotal roles in various types of cancer. TGF-β receptor 2 (TGFβR2) contains a kinase domain that phosphorylates and activates the downstream of the TGF-β signaling pathway. Our previous microarray analysis revealed marked changes in miR-181a expression in gastric cancers, and the bioinformatics analysis suggested that miR-181a negatively regulated TGFβR2. Read More

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http://dx.doi.org/10.1007/s10637-018-0695-5DOI Listing
January 2019

A phase 1 dose escalation and expansion study of Tarextumab (OMP-59R5) in patients with solid tumors.

Invest New Drugs 2018 Dec 28. Epub 2018 Dec 28.

START, San Antonio, TX, USA.

Purpose This Phase I trial evaluated the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of tarextumab (OMP-5948), a novel cross-reactive antibody which binds and selectively inhibits signaling via both Notch2 and Notch3, in adult patients with advanced malignancies. Methods Standard 3 + 3 design with tarextumab 0.5, 1, 2. Read More

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http://link.springer.com/10.1007/s10637-018-0714-6
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http://dx.doi.org/10.1007/s10637-018-0714-6DOI Listing
December 2018
13 Reads

Safety, tolerability, and pharmacology of AB928, a novel dual adenosine receptor antagonist, in a randomized, phase 1 study in healthy volunteers.

Invest New Drugs 2018 Dec 19. Epub 2018 Dec 19.

Arcus Biosciences, Inc., 3928 Point Eden Way, Hayward, CA, USA.

Adenosine suppresses antitumor immune responses via A and A receptors expressed on intratumoral immune cells. This effect is mediated by increased cyclic adenosine 5'-monophosphate (AMP) levels and phosphorylation of cyclic AMP response element binding protein (CREB). We conducted a phase 1, placebo-controlled, single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study to assess the safety, tolerability, pharmacokinetics (PK), including food effect (FE), and pharmacodynamics (PD) of oral AB928, a novel dual AR/AR antagonist, in healthy volunteers. Read More

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http://dx.doi.org/10.1007/s10637-018-0706-6DOI Listing
December 2018
2 Reads

A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma.

Invest New Drugs 2018 Dec 19. Epub 2018 Dec 19.

Hematology-Medical Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), Columbus, OH, USA.

Purpose Vorinostat is a potent HDAC inhibitor that sensitizes head and neck squamous cell carcinoma (HNSCC) to cytotoxic therapy while sparing normal epithelium. The primary objective of this Phase I study was to determine the maximally tolerated dose (MTD) and safety of Vorinostat in combination with standard chemoradiation therapy treatment in HNSCC. Patients and Methods Eligible patients had pathologically confirmed Stage III, IVa, IVb HNSCC, that was unresectable or borderline resectable involving the larynx, hypopharynx, nasopharynx, and oropharynx. Read More

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http://link.springer.com/10.1007/s10637-018-0696-4
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http://dx.doi.org/10.1007/s10637-018-0696-4DOI Listing
December 2018
11 Reads

MICONIDINE acetate, a new selective and cytotoxic compound with synergic potential, induces cell cycle arrest and apoptosis in leukemia cells.

Invest New Drugs 2018 Dec 19. Epub 2018 Dec 19.

Experimental Oncology and Hemopathies Laboratory, Clinical Analysis Department, Federal University of Santa Catarina, Florianópolis, SC, CEP: 88040-900, Brazil.

Plants are important sources of biologically active compounds and they provide unlimited opportunities for the discovery and development of new drug leads, including new chemotherapeutics. Miconidin acetate (MA) is a hydroquinone derivative isolated from E. hiemalis. Read More

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http://dx.doi.org/10.1007/s10637-018-0694-6DOI Listing
December 2018
6 Reads

Cyclodextrin polymers decorated with RGD peptide as delivery systems for targeted anti-cancer chemotherapy.

Invest New Drugs 2018 Dec 17. Epub 2018 Dec 17.

Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, 95125, Catania, Italy.

Polymeric cyclodextrin-based nanoparticles are currently undergoing clinical trials as nanotherapeutics. Using a non-covalent approach, we decorated two cross-linked cyclodextrin polymers of different molecular weights with an RGD peptide derivative to construct a novel carrier for the targeted delivery of doxorubicin. RGD is the binding sequence for the integrin receptor family that is highly expressed in tumour tissues. Read More

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http://link.springer.com/10.1007/s10637-018-0711-9
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http://dx.doi.org/10.1007/s10637-018-0711-9DOI Listing
December 2018
8 Reads

Phase I dose-escalation study of F14512, a polyamine-vectorized topoisomerase II inhibitor, in patients with platinum-refractory or resistant ovarian cancer.

Invest New Drugs 2018 Dec 14. Epub 2018 Dec 14.

Institut Claudius Regaud, IUCT-Oncopole, Departement d'Oncologie Medicale, Toulouse, France.

Purpose To determine the maximum tolerated dose (MTD) of F14512, a topoisomerase II inhibitor designed to target cancer cells through the polyamine transport system, (three-hour daily infusion given for 3 consecutive days every 3 weeks) in platinum-refractory or resistant ovarian cancer. Other objectives were safety, pharmacokinetics (PK), PK/pharmacodynamics relationship, and efficacy. Methods This was an open-label, dose-escalation, multicenter phase I study. Read More

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http://dx.doi.org/10.1007/s10637-018-0688-4DOI Listing
December 2018
1 Read

The availability of drug by liposomal drug delivery : Individual kinetics and tissue distribution of encapsulated and released drug in mice after administration of PEGylated liposomal prednisolone phosphate.

Invest New Drugs 2018 Dec 13. Epub 2018 Dec 13.

Department of Clinical Pharmacy, Division of Laboratory Medicine & Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.

Lately, the usefulness of liposomal drug delivery systems has been debated. To better understand the underlying pharmacokinetics of the targeted drug delivery by liposomes, individual encapsulated and non-encapsulated drug concentrations in blood, tumor, liver, spleen and kidneys were quantified after i.v. Read More

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http://link.springer.com/10.1007/s10637-018-0708-4
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http://dx.doi.org/10.1007/s10637-018-0708-4DOI Listing
December 2018
10 Reads

Modulator of the PI3K/Akt oncogenic pathway affects mTOR complex 2 in human adenocarcinoma cells.

Invest New Drugs 2018 Dec 13. Epub 2018 Dec 13.

College of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA, 30341, USA.

Chaetoglobosin K (ChK) is a natural product that has been shown to promote F-actin capping, inhibit growth, arrest cell cycle G2 phase, and induce apoptosis. ChK also has been shown to downregulate two important kinases involved in oncogenic pathways, Akt and JNK. This report investigates how ChK is involved in the receptor tyrosine kinase pathway (RTK/PI3K/mTORC2/Akt) to the centrally located protein kinase, Akt. Read More

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http://link.springer.com/10.1007/s10637-018-0705-7
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http://dx.doi.org/10.1007/s10637-018-0705-7DOI Listing
December 2018
7 Reads

Multicenter retrospective analysis of the safety and efficacy of regorafenib after progression on sorafenib in Korean patients with hepatocellular carcinoma.

Invest New Drugs 2018 Dec 7. Epub 2018 Dec 7.

Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background The pivotal RESORCE trial showed that regorafenib was effective as second-line therapy for patients with advanced HCC who progressed on first-line sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice. Methods Between April 2017 and August 2017, the Named Patient Program (NPP) was activated to provide controlled, pre-approval access of regorafenib in Korea. Read More

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http://link.springer.com/10.1007/s10637-018-0707-5
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http://dx.doi.org/10.1007/s10637-018-0707-5DOI Listing
December 2018
5 Reads

Efficacy and safety of lanreotide in Korean patients with metastatic, well-differentiated gastroenteropancreatic-neuroendocrine tumors: a retrospective analysis.

Invest New Drugs 2018 Dec 10. Epub 2018 Dec 10.

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

Lanreotide autogel is a long-acting somatostatin analogue with proven efficacy and safety in patients with well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) in a prior randomized phase III trial (CLARINET). However, the CLARINET study only enrolled patients with Ki-67 index <10%, and few patients of Asian ethnicity were included. We retrospectively analyzed the efficacy and safety of lanreotide in Korean patients with GEP-NETs in the daily practice setting. Read More

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http://link.springer.com/10.1007/s10637-018-0710-x
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http://dx.doi.org/10.1007/s10637-018-0710-xDOI Listing
December 2018
5 Reads

A novel tetravalent bispecific antibody targeting programmed death 1 and tyrosine-protein kinase Met for treatment of gastric cancer.

Invest New Drugs 2018 Dec 4. Epub 2018 Dec 4.

Department of Biochemistry and Molecular Biology, School of Basic Medicine, Fudan University, P.O. Box #238 No. 138 Yi Xue Yuan Road, Shanghai, China.

Background Redirecting T cells to tumor cells using bispecific antibodies (BsAbs) is emerging as a potent cancer therapy. The main concept of this strategy is to cross-link tumor cells and T cells by simultaneously binding to cell surface tumor-associated antigen (TAA) and the CD3ƹ chain. However, immune checkpoint programmed cell death ligand-1 (PD-L1) on tumor cells or other myeloid cells upreglulated remarkablely after the treatment of CD3-binding BsAbs, leads to the generation of suppressed microenvironment for immune evasion and tumor progression. Read More

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http://link.springer.com/10.1007/s10637-018-0689-3
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http://dx.doi.org/10.1007/s10637-018-0689-3DOI Listing
December 2018
15 Reads

First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors.

Invest New Drugs 2018 Dec 4. Epub 2018 Dec 4.

Department of Medical Oncology, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.

Background This first-in-human phase 1 study assessed the safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 to determine its maximum tolerated dose (MTD) and recommended dose (RD). Methods In this dose-escalation study with a 3 + 3 design, TAS-114 and S-1 were concurrently administered orally under fasting conditions at 5-240 mg/m and 30-36 mg/m, respectively, in patients with advanced solid tumors. Safety, efficacy, and pharmacokinetics (PK) were evaluated. Read More

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http://dx.doi.org/10.1007/s10637-018-0697-3DOI Listing
December 2018
2 Reads

The role of oxidative stress in 63 T-induced cytotoxicity against human lung cancer and normal lung fibroblast cell lines.

Invest New Drugs 2018 Nov 29. Epub 2018 Nov 29.

Department of Medicinal Chemistry, University of Vienna, Vienna, Austria.

It has been shown previously that molecules built on benzanilide and thiobenzanilide scaffolds possess differential biological properties including selective anticancer activity. In our previous study, we examined the cytotoxic activity and mechanism of action of the thiobenzanilide derivative N,N'-(1,2-phenylene)bis3,4,5-trifluorobenzothioamide (63 T) as a potential chemotherapeutic compound in an experimental model employing A549 lung adenocarcinoma cells and CCD39Lu non-tumorigenic lung fibroblasts. Since the results suggested oxidative stress as a co-existing mechanism of the cytotoxic effect exerted by 63 T on tested cells, studies involving the analysis of reactive oxygen species (ROS) generation and markers of oxidative stress in cells incubated with 63 T were carried out. Read More

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http://link.springer.com/10.1007/s10637-018-0704-8
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http://dx.doi.org/10.1007/s10637-018-0704-8DOI Listing
November 2018
2 Reads

A mediator of phosphorylated Smad2/3, evodiamine, in the reversion of TAF-induced EMT in normal colonic epithelial cells.

Invest New Drugs 2018 Nov 29. Epub 2018 Nov 29.

Central Laboratory, Affiliated Bao'an Hospital of Shenzhen, Southern Medical University, Shenzhen, Guangdong, 518000, People's Republic of China.

Purpose Transdifferentiation exists within stromal cells in the tumour microenvironment. Transforming growth factor-β (TGF-β) secreted by tumour-associated fibroblasts (TAFs) affects the differentiation states of epithelial cells, including epithelial-mesenchymal transition (EMT). Evodiamine, a natural drug, can regulate differentiation. Read More

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http://dx.doi.org/10.1007/s10637-018-0702-xDOI Listing
November 2018
1 Read

Caffeic acid phenethyl ester exerts apoptotic and oxidative stress on human multiple myeloma cells.

Invest New Drugs 2018 Nov 22. Epub 2018 Nov 22.

Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine-Georgia Campus, 625 Old Peachtree Road NW, Suwanee, GA, 30024-2937, USA.

Caffeic acid phenethyl ester (CAPE) is a phenolic compound initially identified in bee glue. CAPE is reported to exhibit antitumor activity in many cancer models. However, the effect of CAPE on multiple myeloma (MM) is not well studied. Read More

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http://dx.doi.org/10.1007/s10637-018-0701-yDOI Listing
November 2018
14 Reads

A phase I study of the safety and tolerability of VLX600, an Iron Chelator, in patients with refractory advanced solid tumors.

Invest New Drugs 2018 Nov 21. Epub 2018 Nov 21.

Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ, USA.

Introduction VLX600 is a novel iron chelator designed to interfere with intracellular iron metabolism, leading to inhibition of mitochondrial respiration and bioenergetic catastrophe and resultant tumor cell death. Methods We conducted a multicenter, phase 1, dose escalation study to determine the safety and adverse event profile and the maximum tolerated dose and recommended phase 2 dose of VLX600. Other endpoints included pharmacokinetics, and preliminary evidence of anti-cancer efficacy as assessed according to RECIST 1. Read More

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http://dx.doi.org/10.1007/s10637-018-0703-9DOI Listing
November 2018
10 Reads

The novel PI3K inhibitor S1 synergizes with sorafenib in non-small cell lung cancer cells involving the Akt-S6 signaling.

Invest New Drugs 2018 Nov 19. Epub 2018 Nov 19.

China State Key Laboratory of New Drug & Pharmaceutical Process, Center for Pharmacological Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, 1111 Rd. Zhongshanbeiyi, Hongkou, Shanghai, 200437, China.

Non-small cell lung cancer (NSCLC) has been the major cause of cancer-related deaths worldwide. Targeted therapy has been available as an additive strategy for NSCLC patients, but the inevitable resistance to mono-targeted agents has largely hampered its usage in the clinic. We have previously designed and synthesized a novel small molecule compound S1, 2-methoxy-3-phenylsulfonamino-5-(quinazolin-6-yl) benzamides and demonstrated its inhibition of PI3K and mTOR as well as the anti-tumor potential. Read More

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http://dx.doi.org/10.1007/s10637-018-0698-2DOI Listing
November 2018
1 Read

Increasing complexity in oncology phase I clinical trials.

Invest New Drugs 2018 Nov 16. Epub 2018 Nov 16.

Cancer Therapy and Research Center (CTRC), University of Texas Health Science Center, San Antonio, TX, USA.

Clinical trials in oncology have become increasingly complex because of incorporation of predictive biomarkers and patient selection based on molecular profiling of tumors. We have examined the change in procedures and work intensity in phase 1 oncology trials over the years with several parameters used as surrogates of complexity. Categories that were included as events were clinical evaluations, pharmacokinetic (PK) laboratory tests, non-PK laboratory tests, specific molecular or histological characteristics, questionnaires and subjective assessments, routine clinical and physical examinations, imaging, invasive procedures and others. Read More

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http://link.springer.com/10.1007/s10637-018-0699-1
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http://dx.doi.org/10.1007/s10637-018-0699-1DOI Listing
November 2018
12 Reads

First-in-human phase I study of the microtubule inhibitor plocabulin in patients with advanced solid tumors.

Invest New Drugs 2018 Nov 9. Epub 2018 Nov 9.

Clinical Research Unit, Institut Claudius Regaud, IUCT- Oncopole, 1 avenue Joliot-Curie, Toulouse, 31059, France.

Background Plocabulin (PM060184) is a novel marine-derived microtubule inhibitor that acts as an antitumor agent. This first-in-human study evaluated dose-limiting toxicities (DLT) to define the maximum tolerated dose (MTD) and phase II recommended dose (RD) of plocabulin given as a 10-min infusion on Day (D) 1, D8 and D15 every four weeks. Patients and methods Forty-four patients with advanced solid tumors received plocabulin following an accelerated titration design. Read More

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http://link.springer.com/10.1007/s10637-018-0674-x
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http://dx.doi.org/10.1007/s10637-018-0674-xDOI Listing
November 2018
9 Reads

A phase II trial of gemcitabine, S-1 and LV combination (GSL) therapy in patients with advanced pancreatic cancer.

Invest New Drugs 2018 Nov 9. Epub 2018 Nov 9.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose Our previous phase I trial suggested feasibility of addition of leucovorin (LV) to S-1 and gemcitabine therapy in advanced pancreatic cancer. The aim of this phase II trial was to assess the efficacy and toxicity of gemcitabine, S-1 and LV (GSL) combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naïve patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Read More

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http://link.springer.com/10.1007/s10637-018-0691-9
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http://dx.doi.org/10.1007/s10637-018-0691-9DOI Listing
November 2018
8 Reads

Phase I/II study evaluating the safety and clinical efficacy of temsirolimus and bevacizumab in patients with chemotherapy refractory metastatic castration-resistant prostate cancer.

Invest New Drugs 2018 Nov 7. Epub 2018 Nov 7.

Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave/CA60, Cleveland, OH, 44195, USA.

Background Mammalian target of rapamycin (mTOR) pathway and angiogenesis through vascular endothelial growth factor (VEGF) have been shown to play important roles in prostate cancer progression. Preclinical data in prostate cancer has suggested the potential additive effect dual inhibition of VEGF and mTOR pathways. In this phase I/II trial we assessed the safety and efficacy of bevacizumab in combination with temsirolimus for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). Read More

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http://link.springer.com/10.1007/s10637-018-0687-5
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http://dx.doi.org/10.1007/s10637-018-0687-5DOI Listing
November 2018
14 Reads
2.920 Impact Factor

Mass balance, routes of excretion, and pharmacokinetics of investigational oral [C]-alisertib (MLN8237), an Aurora A kinase inhibitor in patients with advanced solid tumors.

Invest New Drugs 2018 Nov 6. Epub 2018 Nov 6.

Quantitative Clinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.

Aims This two-part, phase I study evaluated the mass balance, excretion, pharmacokinetics and safety of the investigational aurora A kinase inhibitor, alisertib, in three patients with advanced malignancies. Methods Part A; patients received a single 35-mg dose of [C]-alisertib oral solution (~80 μCi total radioactivity [TRA]). Serial blood, urine, and fecal samples were collected up to 336 h post-dose for alisertib mass balance and pharmacokinetics in plasma and urine by liquid chromatography-tandem mass spectrometry, and mass balance/recovery of [C]-radioactivity in urine and feces by liquid scintillation counting. Read More

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http://link.springer.com/10.1007/s10637-018-0693-7
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http://dx.doi.org/10.1007/s10637-018-0693-7DOI Listing
November 2018
11 Reads

Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma.

Invest New Drugs 2018 Nov 5. Epub 2018 Nov 5.

Department of Internal Medicine, Division of Hematology/Oncology, Ann Arbor, MI, USA.

Background Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM): <400 cal and < 20% fat or 10 g per meal. Methods A single arm study of pazopanib with a LFM in 16 adult patients with metastatic RCC with a clear cell component, RECIST 1. Read More

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http://link.springer.com/10.1007/s10637-018-0692-8
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http://dx.doi.org/10.1007/s10637-018-0692-8DOI Listing
November 2018
9 Reads

A phase I study of the vascular endothelial growth factor inhibitor Vatalanib in combination with Pemetrexed disodium in patients with advanced solid tumors.

Invest New Drugs 2018 Oct 31. Epub 2018 Oct 31.

Department of Oncology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, United States.

Introduction Vatalanib is an oral receptor tyrosine kinase inhibitor that blocks all known VEGF, PDGF, and c-Kit receptors. This phase I study evaluated the safety, tolerability, and biologic activity of the combination of vatalanib with pemetrexed disodium in patients with advanced solid tumors. Methods Patients were administered escalating twice daily doses of vatalanib in combination with pemetrexed disodium in 21-day cycles. Read More

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http://dx.doi.org/10.1007/s10637-018-0690-xDOI Listing
October 2018