Bispecific anti-CD3  x anti-B7-H3 antibody mediates T cell cytotoxic ability to human melanoma in vitro and in vivo
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. The cytotoxic capacity of activated T cells (ATCs) armed with an anti-CD3  x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) to melanoma cells was measured using a bioluminescent signal through a luciferase reporter on tumor cells. In contrast to unarmed ATCs, B7-H3Bi-Ab-armed ATCs exhibited increased cytotoxicity against melanoma cells at effector/target ratios from 1:1 to 20:...
Source: Investigational New Drugs - February 1, 2019 Category: Drugs & Pharmacology Source Type: research

The influence of prior ramucirumab treatment on the clinical activity of FOLFIRI as third-line therapy in patients with metastatic gastric Cancer
Conclusions Our findings suggest a poor efficacy of the FOLFIRI regimen in metastatic gastric or gastroesophageal junction cancer patients whose disease progressed during a ramucirumab-based second line of treatment. However, FOLFIRI could be an option for patients who responded to prior ramucirumab. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 28, 2019 Category: Drugs & Pharmacology Source Type: research

The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model
SummaryObtustatin, 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 de rmal microvascular endothelial cells (HMVEC-D) in vitro, and tested anti-angiogenic activity in vivo using the chick ...
Source: Investigational New Drugs - January 25, 2019 Category: Drugs & Pharmacology Source Type: research

Nifuroxazide induces apoptosis, inhibits cell migration and invasion in osteosarcoma
In this study, the anticancer effects and potential mechanisms of nifuroxazide, an oral nitrofuran antibiotic, on two osteosarcoma cell lines were investigated. The results of the antiproliferative activity in vitro showed that nifuroxazide inhibited cell proliferation of UMR106 and MG63 cells in a dose- and time-dependent manner. Interestingly, nifuroxazide showed low toxicity to non-tumor cells (HEK 293  T). In addition, ROS-mitochondrial mediated apoptosis was observed after treatment of nifuroxazide. Moreover, nifuroxazide could significantly inhibit osteosarcoma cells migration and invasion via p-Stat3, MMP-2 and...
Source: Investigational New Drugs - January 25, 2019 Category: Drugs & Pharmacology Source Type: research

In vitro and in vivo cytotoxic activity and human serum albumin interaction for a methoxy-styryl-thiosemicarbazone
SummaryThiosemicarbazone 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 evaluatedin 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. Treat...
Source: Investigational New Drugs - January 19, 2019 Category: Drugs & Pharmacology Source Type: research

Acknowledgement of Reviewers 2018
(Source: Investigational New Drugs)
Source: Investigational New Drugs - January 16, 2019 Category: Drugs & Pharmacology Source Type: research

The cellular effects of novel triazine nitrogen mustards in glioblastoma LBC3, LN-18 and LN-229 cell lines
In conclusion, this research provides novel information concerning cellular effects of apoptosis in LBC3, LN-18 and LN-229 cell lines. Moreover, we suggest that12f compound may be a candidate for further evaluation as an effective chemotherapeutic agent for human glioblastoma cells. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 15, 2019 Category: Drugs & Pharmacology Source Type: research

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
SummaryThe 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. We compared the inhibitory effects of Re-diSe and of its di selenide ligand (di-Se) on MDA-MB23...
Source: Investigational New Drugs - January 11, 2019 Category: Drugs & Pharmacology Source Type: research

Inhibition of AKT signalling by benzoxazine derivative LTUR6 through the modulation of downstream kinases
This study provides a deeper insight into the key proteins involved and presents a novel molecular pathway. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 10, 2019 Category: Drugs & Pharmacology Source Type: research

A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors
Conclusions Ontuxizumab, up to a dosage of 12  mg/kg weekly, was generally safe and well tolerated in this population, with no dose-limiting toxicities. The maximum tolerated dose was not reached; 8 mg/kg weekly or 12 mg/kg biweekly were the recommended dosages. We observed long-term disease stabilization in GC and extraskeletal chondrosarco ma, and tumor shrinkage in gastrointestinal stromal tumor and HCC.Trial registration: NCT01773434 (ClinicalTrials.gov). (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 9, 2019 Category: Drugs & Pharmacology Source Type: research

IMRT combined with S-1 concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a prospective phase II study
Conclusion The results demonstrated that IMRT plus S-1 CCRT was effective with mild toxicity for patients with LANPC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 8, 2019 Category: Drugs & Pharmacology Source Type: research

Biodistribution, pharmacokinetics and radioimmunotherapy of 188 Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice
Conclusion The tumor targeting and localization of 188Re-cetuximab were confirmed in this study. Synergistic therapeutic efficacy was demonstrated for the radioimmunotherapy of188Re-cetuximab. The results of this study reveal the potential advantage and benefit obtained from188Re-cetuximab for diagnosis and therapy of oncology applications in the future. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 5, 2019 Category: Drugs & Pharmacology Source Type: research

Significant differences on submission lag following regulation reform for registration of novel therapeutic drugs in Taiwan
This study examined whether t he enacted regulations reduce submission lag by analyzing the time gap of submission between Taiwan and the United States during 2014–2017. The results indicated that the enacted regulations substantially affected submission lag. Submission lag was significantly shorter for applications not requir ing a CPP than those requiring one CPP, which in turn was significantly shorter than those requiring two CPPs. This conclusion can be applied to biological, chemical, non-orphan, and oncology drugs and also applications filed by subsidiary companies, but not orphan drugs and applications filed ...
Source: Investigational New Drugs - January 5, 2019 Category: Drugs & Pharmacology Source Type: research

Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib
In conclusion, among the various combinations studied, rucaparib plus irinotecan was the most synergistic one. Alterations in cell cycle arrest and apoptosis were dependent on MSI status in CRC cells. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 5, 2019 Category: Drugs & Pharmacology Source Type: research

Human antigen R and drug resistance in tumors
SummaryThe 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. Herein, we demonstrate the roles of HuR...
Source: Investigational New Drugs - January 5, 2019 Category: Drugs & Pharmacology Source Type: research

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
Conclusion The combination of metformin, everolimus and exemestane was safe and had moderate clinical benefit in overweight and obese with patients metastatic, hormone receptor-positive, HER2-negative breast cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 5, 2019 Category: Drugs & Pharmacology Source Type: research

Screening, identification of prostate cancer urinary biomarkers and verification of important spots
SummaryProstate-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., 4 –10 ng/ml), it is difficult to differentiate benign prostatic hyperplasia (BPH) from cancer. The diagnostic test (i.e., prostate biopsy) is invasive, adding pain and economic burden to the patient. Urine samples are more convenient, non-invasive and readily available than blood. We sought to dete rmine whether ferritin might be the potential urinary biomarker in prostate cancer diagnosis. Using two-dimensional electrophoresis (2DE) followe...
Source: Investigational New Drugs - January 4, 2019 Category: Drugs & Pharmacology Source Type: research

MiR-181a, a new regulator of TGF- β signaling, can promote cell migration and proliferation in gastric cancer
SummaryTransforming 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 canc ers, and the bioinformatics analysis suggested that miR-181a negatively regulated TGFβR2. In order to verify the effect of miR-181a on TGFβR2 and clarify the influence of miR-181a on the migration and proliferation of gastric cancer, studies in gastric cance...
Source: Investigational New Drugs - January 4, 2019 Category: Drugs & Pharmacology Source Type: research

A phase 1 dose escalation and expansion study of Tarextumab (OMP-59R5) in patients with solid tumors
Conclusion Tarextumab was generally well-tolerated at doses
Source: Investigational New Drugs - December 28, 2018 Category: Drugs & Pharmacology Source Type: research

MICONIDINE acetate, a new selective and cytotoxic compound with synergic potential, induces cell cycle arrest and apoptosis in leukemia cells
This study indicates thatMA may be a new agent for AL and highlights its potential as a new source of anticancer drugs.Graphical abstractMA blocks G2/M phase with PML expression and KI67 inhibition, ROS generation and intrinsic and extrinsic apoptosis, leading to mitochondrial damage, caspase 3 and PARP cleavage and DNA fragmentation. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 19, 2018 Category: Drugs & Pharmacology Source Type: research

A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma
Conclusion Vorinostat in combination with concurrent chemoradiation therapy is a safe and highly effective treatment regimen in HNSCC. There was a high rate of complete response to therapy with toxicity rates comparable, if not favorable to existing therapies. Further investigation in Phase II and III trials is strongly recommended. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 19, 2018 Category: Drugs & Pharmacology Source Type: research

Safety, tolerability, and pharmacology of AB928, a novel dual adenosine receptor antagonist, in a randomized, phase 1 study in healthy volunteers
SummaryAdenosine suppresses antitumor immune responses via A2a and A2b 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 A2aR/A2bR antagonist, in healthy volunteers. AB928 doses between 10 and 200  mg once...
Source: Investigational New Drugs - December 19, 2018 Category: Drugs & Pharmacology Source Type: research

Cyclodextrin polymers decorated with RGD peptide as delivery systems for targeted anti-cancer chemotherapy
SummaryPolymeric 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. The assembled host–guest systems were investigated using NMR and DLS techniques. We found that, in comparison with free doxorubicin or the binary complex doxorubicin/cyclodextrin polym...
Source: Investigational New Drugs - December 17, 2018 Category: Drugs & Pharmacology Source Type: research

Phase I dose-escalation study of F14512, a polyamine-vectorized topoisomerase II inhibitor, in patients with platinum-refractory or resistant ovarian cancer
Conclusion Although there was some encouraging efficacy signal, grade 4 neutropenia led to complications and it was decided to stop the study. A DL below 5  mg/m2/day was not tested as this would not allow reaching the minimum serum concentration needed for the pharmacological activity of the drug. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 14, 2018 Category: Drugs & Pharmacology Source Type: research

The availability of drug by liposomal drug delivery
SummaryLately, 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. administration of liposomal prednisolone phosphate in mice. Kinetic analysis shows that the tumor influx of encapsulated drug is not dominant compared to the uptake by the other tissues. Further, from a quantitative point of view, the availability of non-encapsulated drug in the tumor tissue after liposomal delive...
Source: Investigational New Drugs - December 13, 2018 Category: Drugs & Pharmacology Source Type: research

Modulator of the PI3K/Akt oncogenic pathway affects mTOR complex 2 in human adenocarcinoma cells
This report investigates how ChK is involved in the receptor tyrosine kinase pathway (RTK/PI3K/mTORC2/Akt) to the centrally located protein kinase, Akt. Studies have reported that ChK does not inhibit PI3K comparable to wortmannin and does not affect PDK1 activation. PDK1 is responsible for phosphorylation on Akt T308, while mTORC2 phosphorylates Akt S473. Yet, Akt ’s two activation sites, T308 and S473, are known to be affected by ChK treatment. It was our hypothesis that ChK acts on the mTORC2 complex to inhibit the phosphorylation seen at Akt S473. This inhibition at mTORC2 should decrease phosphorylation at both ...
Source: Investigational New Drugs - December 13, 2018 Category: Drugs & Pharmacology Source Type: research

Efficacy and safety of lanreotide in Korean patients with metastatic, well-differentiated gastroenteropancreatic-neuroendocrine tumors: a retrospective analysis
SummaryLanreotide 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  25% and prior systemic therapy were significantly associated with poorer PFS in the multivariate analysis. Lanreotide is well-tolerated and effective for Korean patients with GEP-NETs in the daily practice setting. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 10, 2018 Category: Drugs & Pharmacology Source Type: research

Multicenter retrospective analysis of the safety and efficacy of regorafenib after progression on sorafenib in Korean patients with hepatocellular carcinoma
Conclusion Regorafenib was well-tolerated and effective in patients with advanced HCC who progressed on first-line sorafenib, with efficacy and safety outcomes consistent with those of the previous RESORCE trial. TTP on first-line sorafenib may predict the efficacy of subsequent regorafenib. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 7, 2018 Category: Drugs & Pharmacology Source Type: research

First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors
Conclusion TAS-114 plus S-1 showed tolerable, safe, and potentially effective results. To confirm safety and efficacy, two phase 2 studies are ongoing in NSCLC and gastric cancer patients.Clinical trial registration ClinicalTrials.gov (NCT01610479) . (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 4, 2018 Category: Drugs & Pharmacology Source Type: research

A novel tetravalent bispecific antibody targeting programmed death 1 and tyrosine-protein kinase Met for treatment of gastric cancer
Conclusion The engagement of the PD-1/PD-L1 blockade to c-Met-overexpressing cancer cells is a promising strategy for the treatment of gastric cancer and potentially other malignancies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 4, 2018 Category: Drugs & Pharmacology Source Type: research

Phase I dose-escalation trial of afatinib, an irreversible ErbB family blocker, in combination with gemcitabine or docetaxel in patients with relapsed or refractory solid tumors
Conclusions Afatinib/gemcitabine and afatinib/docetaxel demonstrated manageable safety profiles, with evidence of clinical efficacy at the MTDs. For afatinib/docetaxel, a dose level of afatinib 30  mg/docetaxel 75 mg/m2 produced higher response rates.Trial registration: NCT01251653 (ClinicalTrials.gov). (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2018 Category: Drugs & Pharmacology Source Type: research

Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer
Conclusion Binimetinib was well tolerated and showed promising evidence of activity in patients with BTC. Correlative studies suggested the potential for binimetinib to promote muscle gain in patients with BTC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2018 Category: Drugs & Pharmacology Source Type: research

Acquired resistance to an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in an uncommon G719S EGFR mutation
Discussion The newly established G719S-GR cell line may be useful for investigating the mechanism underlying the development of AR in the G719X mutation; the loss ofPTEN may be one such mechanism. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2018 Category: Drugs & Pharmacology Source Type: research

First-in-human phase I study of the microtubule inhibitor plocabulin in patients with advanced solid tumors
Conclusion The main DLT of plocabulin was PSN, as anticipated for a tubulin-binding agent. Since encouraging antitumor activity was observed, efforts to improve toxicity and to find the RD were planned in other trials evaluating D1&D8 and D1-D3 plus D15-D17 schedules. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 9, 2018 Category: Drugs & Pharmacology Source Type: research

A phase II trial of gemcitabine, S-1 and LV combination (GSL) therapy in patients with advanced pancreatic cancer
Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 9, 2018 Category: Drugs & Pharmacology Source Type: research

Phase I/II study evaluating the safety and clinical efficacy of temsirolimus and bevacizumab in patients with chemotherapy refractory metastatic castration-resistant prostate cancer
Conclusions The combination of temsirolimus and bevacizumab showed limited clinical activity in mCRPC patients previously treated with chemotherapy and was associated with significant adverse events (AEs). Transient decrease in CTC levels was independent from PSA response. NCT01083368. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 7, 2018 Category: Drugs & Pharmacology Source Type: research

Mass balance, routes of excretion, and pharmacokinetics of investigational oral [ 14 C]-alisertib (MLN8237), an Aurora A kinase inhibitor in patients with advanced solid tumors
Conclusions Findings suggest that alisertib is eliminated mainly via feces, consistent with hepatic metabolism and biliary excretion of drug-related material. Further investigation of alisertib pharmacokinetics in patients with moderate-severe hepatic impairment is warranted to inform dosing recommendations in these patient populations. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 6, 2018 Category: Drugs & Pharmacology Source Type: research

Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma
SummaryBackground Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM):
Source: Investigational New Drugs - November 5, 2018 Category: Drugs & Pharmacology Source Type: research

A phase I study of the vascular endothelial growth factor inhibitor Vatalanib in combination with Pemetrexed disodium in patients with advanced solid tumors
Conclusion The combination of vatalanib with pemetrexed disodium was feasible, but not well tolerated. The modest efficacy results are consistent with other results obtained from combinations of chemotherapy and a large number of VEGF tyrosine kinase inhibitors. This combination should not be developed further unless predictive biomarkers can be identified. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 31, 2018 Category: Drugs & Pharmacology Source Type: research

Lurbinectedin (PM01183), a selective inhibitor of active transcription, effectively eliminates both cancer cells and cancer stem cells in preclinical models of uterine cervical cancer
Conclusions Lurbinectedin is highly effective on uterine cervical cancer because it eliminates CSCs, and lurbinectedin is a promising agent to overcome platinum resistance in cervical cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 30, 2018 Category: Drugs & Pharmacology Source Type: research

The bispecific anti-CD3  × anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer
SummaryExpression of CD155 differs between tumor and normal tissues, and high expression of this molecule can promote tumor metastasis. Here, we investigate whether CD155 can serve as a target for T cell-mediated immunotherapy of human prostate cancer. We first demonstrate that prostate cancer cells, including PC-3, PC-3  M, and LNCAP cells, express CD155 at high levels. Next, the specific cytotoxic activity of activated T cells (ATCs) armed with a novel anti-CD3 × anti-CD155 bispecific antibody (CD155Bi-Ab) against tumor cells was evaluated by flow cytometry, lactate dehydrogenase assay (LDH), and ELI...
Source: Investigational New Drugs - October 29, 2018 Category: Drugs & Pharmacology Source Type: research

A novel humanized anti-PD-1 monoclonal antibody potentiates therapy in oral squamous cell carcinoma
In this study, the role of our novel mAb was tested in the treatment of OSCC in vitro and in vivo. We found that our novel mAb can significantly augment T cell mediated cytokine secretion, target cellular lytic and apoptotic abilities, and inhibit tumor growth and inflammation in vivo. The PD-L1 blockade was accompanied by the inhibition of AKT and ERK1/2, thus suggesting that the PD-L1/PD-1 signaling pathway may play an important immunopreventive role in the tumorigenic properties of OSCC cells by modulating the AKT and ERK1/2 pathways. Additionally, PD-L1 staining was observed both in human OSCC tissues and normal oral m...
Source: Investigational New Drugs - October 27, 2018 Category: Drugs & Pharmacology Source Type: research

Chemotherapy in pregnancy: exploratory study of the effects of paclitaxel on the expression of placental drug transporters
Discussion Paclitaxel modulates the expression of placental drug transporters involved in the disposition of various anticancer agents. Further studies will be needed to assess the impact of repeated or prolonged exposure to paclitaxel on the expression and function of placental drug transporters. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 26, 2018 Category: Drugs & Pharmacology Source Type: research

Advanced development of ErbB family-targeted therapies in osteosarcoma treatment
SummaryOsteosarcoma (OS) is the most common primary aggressive and malignant bone tumor. Newly diagnostic OS patients benefit from the standard therapy including surgical resection plus radiotherapy and neoadjuvant chemotherapy (MAP chemotherapy: high-dose methotrexate, doxorubicin and cisplatin). However, tumor recurrence and metastasis give rise to a sharp decline of the 5-year overall survival rate in OS patients. Little improvement has been made for decades, urging the development of more effective therapeutic approaches. ErbB receptor family including EGFR, HER2, HER3 and HER4, being important to the activation of PI3...
Source: Investigational New Drugs - October 24, 2018 Category: Drugs & Pharmacology Source Type: research

Corticosteroid switch in heavily pre-treated castration-resistant prostate cancer patients progressed on abiraterone acetate plus prednisone
SummaryThe aim of this retrospective study is to evaluate the activity and safety of a steroidal switch from prednisone to dexamethasone in patients with advanced, heavily pre-treated, castration-resistant prostate cancer (CRPC) who progressed on abiraterone acetate. Treatment consisted of oral daily abiraterone plus dexamethasone (0.5 mg once daily) administered until disease progression or unacceptable toxicity. Thirty-six patients were evaluated: all men underwent a prior treatment with enzalutamide. A PSA decrease ≥50% was observed in 11% of patients; median progression-free survival was 10.8 weeks (95% CI: 9.2&ndas...
Source: Investigational New Drugs - October 22, 2018 Category: Drugs & Pharmacology Source Type: research

Antitumor evaluation of novel phenothiazine derivatives that inhibit migration and tubulin polymerization against gastric cancer MGC-803 cells
SummaryTwo novel series of 1,2,3-triazole −phenothiazine hybrids and dithiocarbamate−phenothiazine hybrids were designed and synthesized by molecular hybridization strategy. Their antiproliferative activity against three gastric cancer cell lines (MKN28, MGC-803 and MKN45) were evaluated. Among them, hybrid13h displayed the most potent inhibitory activity against gastric cancer MGC-803 cells with an IC50 value of 1.2  μM. Hybrid13h could inhibit migration by regulating the expression level of N-cadherin, E-cadherin, Vimentin, and actived-MMP2. Furthermore, it could regulate wnt/ β-catenin signaling...
Source: Investigational New Drugs - October 22, 2018 Category: Drugs & Pharmacology Source Type: research

Correction to: Phase I study combining the aurora kinase a inhibitor alisertib with mFOLFOX in gastrointestinal cancer
The authors would like to note that the investigator affiliations have been corrected to reflect the actual affiliations of each author. The authors would also like to note an amendment to the first name of the second author. Nilo Azad was changed to reflect the full name of the author, which is Nilofer S. Azad as shown above. The original article has been corrected. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 18, 2018 Category: Drugs & Pharmacology Source Type: research

Relationship between expression of XRCC1 and tumor proliferation, migration, invasion, and angiogenesis in glioma
In this study, we investigated whether XRCC1 plays a role in glioma pathogenesis. Using the tissue microarray technology, we found that XRCC1 expression is significantly decreased in glioma compared with tumor adjacent normal brain tissue (P 
Source: Investigational New Drugs - October 17, 2018 Category: Drugs & Pharmacology Source Type: research

Prognostic factors in patients with metastatic or recurrent pancreatic cancer treated with first-line nab -paclitaxel plus gemcitabine: implication of inflammation-based scores
Conclusion Among the inflammation based prognostic scores, mGPS was a reliable prognostic indicator that could stratify survival outcomes in patients with recurrent or mPC who received AG as first-line chemotherapy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 16, 2018 Category: Drugs & Pharmacology Source Type: research

Second-line chemotherapy in patients with advanced or recurrent biliary tract cancer: a single center, retrospective analysis of 294 cases
SummaryPurpose The survival benefit of first-line chemotherapy (CT1) for biliary tract cancer (BTC) is now established but the role of second-line chemotherapy (CT2) has not been fully elucidated yet.Methods Consecutive advanced BTC patients receiving CT1 between 2000 and 2016 were retrospectively studied. We investigated the safety and efficacy of CT2, prognostic factors for residual survival after CT1, and explored subgroups who would benefit from CT2.Results Among 294 patients receiving CT1 for advanced BTC, CT2 was given in 139 patients (47%). CT2 provided a response rate of 4%, a disease control rate of 52%, a median ...
Source: Investigational New Drugs - October 15, 2018 Category: Drugs & Pharmacology Source Type: research