Unexpected heat shock element binding ability and tumor-killing activity of the combinatorial function domain of apoptin
In this study, we investigated the HSE-binding properties of the minimal functional region of apoptin. We showed that apoptin’s nuclear localization signals 1 and nuclear localization signals 2 represented functional regions that could bind with HSE and that this binding capacity was increased by polymers formed through the introduction of a leucine-rich stretch. Our data also showed that truncated combinatorial apoptin peptide has greater tumor-specific cell-killing activity and could be a potential antitumor agent. (Source: Anti-Cancer Drugs)
Source: Anti-Cancer Drugs - March 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

A novel STAT3 inhibitor HO-3867 induces cell apoptosis by reactive oxygen species-dependent endoplasmic reticulum stress in human pancreatic cancer cells
Pancreatic cancer is the most commonly diagnosed malignancy among solid tumors and has shown an increasing trend year by year. Thus, there is an urgent need for the discovery of new anticancer drugs for the treatment of pancreatic cancer. In recent years, it has been reported that the compound HO-3867, a novel analog of the natural product curcumin, showed antitumor activity with low toxicity. However, the underlying mechanism of this compound’s attack on cancer cells is not very clear. In the present study, it was found that HO-3867 showed good antitumor activity at the concentration of 2 μmol/l in PANC-1 ...
Source: Anti-Cancer Drugs - March 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Effect of dihydroartemisinin on UHRF1 gene expression in human prostate cancer PC-3 cells
This study aimed to investigate the effects of DHA, a novel anticancer agent, by inhibiting the expression of ubiquitin like containing PHD and ring finger 1 (UHRF1) in PC-3 cells. The apoptosis and cell-cycle distribution were detected by flow cytometry. Quantitative real-time PCR was performed to examine both UHRF1 and DNA methyltransferase 1 (DNMT1) expressions at mRNA levels, whereas the expressions of UHRF1, DNMT1, and p16INK4A proteins at protein levels were detected by Western blotting. Methylation levels of p16INK4A CpG islands were determined by bisulfite genomic sequencing. We showed that DHA induced the downregu...
Source: Anti-Cancer Drugs - March 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Nitroxoline shows antimyeloma activity by targeting the TRIM25/p53 axle
This study indicated that the long-term use of anti-infective NXQ has potential for MM treatment by targeting the TRIM25/p53 axle. (Source: Anti-Cancer Drugs)
Source: Anti-Cancer Drugs - March 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Hypothesis: ROBOPHERA, a phosphatase and tensin homolog-targeted antineoplastic therapy
Phosphatase and tensin homolog (PTEN) is a protein that regulates cellular response to growth/antigrowth signals, cell survival, apoptosis, proliferation, angiogenesis, and cellular migration. Impairments in these processes are the main hallmarks of cancer, and reduced expression, activity, or stability of PTEN are among the most common etiologies of diverse types of sporadic cancers. Rosiglitazone (RO), bortezomib (BO), phosphatidylserine (PH), ethanol (E), and radiotherapy (RA) (ROBOPHERA) stimulate the expression and increase the activity of PTEN. Here, it is hypothesized that the synergistic effects of these medication...
Source: Anti-Cancer Drugs - March 17, 2017 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Chemotherapy for localized head and neck squamous cell cancers
Concomitant chemotherapy with cisplatin (100 mg/m2 every 3 weeks) improves outcome for high-risk patients in the postoperative setting and for inoperable disease. Toxicity is increased. Other schemes of potentiation are sometimes used to reduce toxicity, but efficiency is diminished. Cetuximab also improves outcome, but there has been no direct comparison with cisplatin. Immunotherapy is currently being evaluated in association with radiation therapy. Trials are ongoing to evaluate the impact of de-escalation for human papillomavirus-positive patients. The association of docetaxel, cisplatin, and 5-fluorouracil is t...
Source: Anti-Cancer Drugs - March 17, 2017 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Chemotherapy for recurrent/metastatic head and neck cancers
Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this protocol in ongoing trials and the association of cisplatin, docetaxel, and cetuximab appears to be the most efficient. The human papilloma virus is very likely a favorable prognostic factor. Immunotherapy with nivolumab or pembrolizumab is now a new standard of treatment in second line after yielding an improve...
Source: Anti-Cancer Drugs - March 17, 2017 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Association between adjuvant docetaxel-based chemotherapy and breast cancer-related lymphedema
In conclusion, adjuvant docetaxel-based chemotherapy significantly increased the risk of breast cancer-related lymphedema. (Source: Anti-Cancer Drugs)
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Phase I dose-escalation study of plitidepsin in combination with sorafenib or gemcitabine in patients with refractory solid tumors or lymphomas
This phase I trial evaluated the combination of the marine-derived cyclodepsipeptide plitidepsin (trade name Aplidin) with sorafenib or gemcitabine in advanced cancer and lymphoma patients. The study included two treatment arms: a sorafenib/plitidepsin (S/P) and a gemcitabine/plitidepsin (G/P) arm. In the S/P arm, patients were treated orally with sorafenib continuous dosing at two dose levels (DL1: 200 mg twice daily and DL2: 400 mg twice daily) combined with plitidepsin (1.8 mg/m2, day 1, day 8, day 15, and, q4wk, intravenously). In the G/P arm, patients with solid tumors or lymphoma were treated at ...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Final results of the phase III URO-BCG 4 multicenter study: efficacy and tolerance of one-third dose BCG maintenance in nonmuscle invasive bladder cancer
The objective of this study was to assess at 3 years bacillus Calmette–Guerin (BCG) maintenance treatment for NMIBC using one-third dose schedule and fewer instillations every 3 or 6 months. This was a phase III randomized study including patients with intermediate-risk or high-risk NMIBC, who received, after a full-dose induction schedule, three-weekly instillations of one-third dose BCG every 6 months (group I) and two-weekly instillations every 3 months (group II) during 3 years. We assessed oncological efficacy, BCG side effects, leukocyturia, and prostate-specific antigen. No tumor recurrence was reported at 36 ...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Optimal multidisciplinary treatment of oral cavity mucosal melanoma: outcome analysis in a case series
Oral cavity mucosal melanomas (OCMM) represent only 3% of all malignant melanomas. Surgery is the mainstay of treatments and it is often followed by adjuvant radiotherapy. The role of adjuvant immunotherapy and/or chemotherapy is still debated and to date neither treatment is routinely used. From January 1990 to January 2010, we have collected from our database data of 20 patients with a histologically proven diagnosis of OCMM. Upfront surgery, followed by adjuvant radiotherapy was performed in 16/20 (80%) patients. Immunohistochemical analysis was carried out on all tissue samples and the following markers were assessed: ...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

5-Fluorouracil degradation rate could predict toxicity in stages II–III colorectal cancer patients undergoing adjuvant FOLFOX
5-Fluorouracil is commonly used for gastrointestinal cancer treatment in an adjuvant setting; however, the toxicity can lead to a reduction, delay, or discontinuation of treatment. We retrospectively investigated the association between the 5-fluorouracil degradation rate (5-FUDR) and genetic polymorphisms of TSER, DPYD, and MHTFR with toxicity in colorectal cancer patients treated with adjuvant FOLFOX. Pretreatment 5-FUDR and MTHFR A1298T or C677T, TSER, and DPYD gene polymorphisms were characterized in stages II–III colorectal cancer patients. Patients were classified into three metabolic classes according to the 5...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Poly ADP-ribose polymerase inhibition suppresses cisplatin toxicity in chronic myeloid leukemia cells
Cancer cells may acquire drug resistance by activating DNA repair signaling. Poly ADP-ribose polymerase (PARP) plays an important role in DNA repair and it is overexpressed in many cancers including chronic myeloid leukemia (CML). PARP inhibitors have been used either alone or with other drugs to augment cancer cell death. However, whether PARP inhibitors may also augment cell death induced by chemotherapeutic agents in CML cells has not been studied. K562 cells with or without PARP-1 knockdown were treated with cisplatin alone or together with olaparib. The cell death was investigated by propidium iodide staining and apop...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Autophagy inhibitors chloroquine and LY294002 enhance temozolomide cytotoxicity on cutaneous melanoma cell lines in vitro
In this study, we showed that the combination of autophagy inhibitors chloroquine or LY294002 and TMZ induced enhanced cytotoxicity of alkylating agents on human melanoma cell lines. All assays were performed on patient-derived melanoma cell lines. The effectiveness of the combined treatment of TMZ and autophagy inhibitors was determined using an MTT assay. Next, we analyzed the expression mRNA level of Beclin 1, LC3B, and p62/STSQM1 and the relative expression of LC3B protein under combined treatment. Autophagic flux was determined by analysis of colocalization of Lysotracker Red and LC3B puncta. Apoptosis was measured by...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

YM155 induces apoptosis in p53-deficient T-acute lymphoblastic leukemia cells independent of survivin inhibition
T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer that arises from the malignant transformation of T-cell progenitors. Despite the significant progress in current treatment, challenges remain the lifelong morbidity after current chemotherapy regimens and postrelapse survival. In addition, patients with T-ALL have inferior outcomes compared with those with B-cell precursor; consequently, novel therapeutic approaches are still necessary to improve the outcome in this cohort. YM155 is an imidazolium derivative originally discovered as a suppressant of survivin expression. It has been reported that Y...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Inhibitory effect of a redox-silent analogue of tocotrienol on hypoxia adaptation in prostate cancer cells
In this report, we investigated the inhibitory effect of a redox-silent analogue of tocotrienol on the survival of a human androgen-independent PCa cell line (PC3) under hypoxia. We found that the redox-silent analogue exerted a cytotoxic effect on PC3 cells in a dose-dependent manner irrespective of either hypoxia or normoxia. Moreover, under hypoxia, the analogue dose dependently reduced the protein levels of hypoxia-inducible factor (HIF)-1α and HIF-2α. In addition, a specific inhibitor toward HIF-1α induced cytotoxicity on PC3 cells, whereas selective inhibition of HIF-2α exerted no effect. Furt...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Dihydromyricetin reverses MRP2-mediated MDR and enhances anticancer activity induced by oxaliplatin in colorectal cancer cells
Dihydromyricetin (DMY), extracted from the Chinese herbal medicine Ampelopsis grossedentata, possesses antitumor potential in different types of human cancer cells. Hence, its effects on drug resistance and molecular mechanisms in colorectal cancer (CRC) are still unknown. In our present study, we observed that DMY enhanced the chemosensitivity to oxaliplatin (OXA). DMY increased OXA-induced apoptosis and reduced 5(6)-carboxy-2′,7′-dichlorofluorescein accumulation in OXA-resistant CRC HCT116/L-OHP cells. Our mechanistic study suggested that DMY treatment inhibited multidrug resistance protein 2 (MRP2) expressio...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Enhanced anticancer activity of drug nanoparticles formulated with β-cyclodextrin
Camptothecin (CPT) is a potent chemotherapeutic agent that shows a broad spectrum of anticancer activities. However, it is clinically inactive because of poor aqueous solubility, rapid aqueous hydrolysis, and unexpected side effects. Three strategies have extensively been adopted to improve its dissolution rate including reduction of drug particle size to a nanoscale, use of an amorphous state, and the formation of inclusion compounds. In our study, we combined these three strategies together by constructing CPT nanoparticles by creating an inclusion complex with β-cyclodextrin (BCD). This new CPT formulation showed a...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Construction, expression, and activity of a novel immunotoxin comprising a humanized antiepidermal growth factor receptor scFv and modified Pseudomonas aeruginosa exotoxin A
In conclusion, the results of this study indicated that huscFv-PE25 can recognize and exert an inhibitory effect on EGFR-overexpressing cancer cells, despite its smaller size and lower immunogenicity. This may provide a basis for the development of novel clinical therapeutic agents against EGFR-overexpressing tumor cells. (Source: Anti-Cancer Drugs)
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Potential anticancer role of colchicine-based derivatives: an overview
Colchicine, the main alkaloid of the poisonous plant meadow saffron (Colchicum autumnale L.), is a classical drug used for the treatment of gout and familial Mediterranean fever. Although colchicine is not clinically used to treat cancer because of toxicity, it exerts antiproliferative effects through the inhibition of microtubule formation by blocking the cell cycle at the G2/M phase and triggering apoptosis. Colchicine can still be used as a lead compound for the generation of potential anticancer drugs. Thus, numerous analogues of colchicine have been synthesized in the hope of developing novel, useful drugs with more f...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Reversal effects of local anesthetics on P-glycoprotein-mediated cancer multidrug resistance
The existence of multidrug resistance (MDR) is the main reason for failure in cancer chemotherapy. The main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). P-gp, a 170 kDa transmembrane phosphorylated glycoprotein encoded by ABCB1 belonging to a member of the ATP-binding cassette (ABC) super-family of the membrane transporters, is also known as the MDR protein. Local anesthetics (LAs) are a major contributor to medical practice. As a cornerstone of analgesia, LAs provides myriad benefits. Recent studies have shown that the LAs can interfere with receptors other than the traditional sodium channel. L...
Source: Anti-Cancer Drugs - February 17, 2017 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Plerixafor mobilization of peripheral blood hematopoietic progenitors to support further high-dose chemotherapy cycles in a patient with germ-cell tumor relapsing after previous tandem high-dose chemotherapy and hematopoietic cell transplantation: report of a case
Salvage high-dose chemotherapy (HDC) and autologous hematopoietic stem cell (HSC) transplantation represents a curative treatment option for patients with relapsed/refractory germ-cell tumors (GCTs). However, an appreciable proportion of these fail to mobilize adequate numbers of hematopoietic progenitors; thus, plerixafor is applied for that purpose. Limited data exist on remobilization of HSCs after previous autografting. Here, we report a unique case that had undergone successful previous tandem HDC for relapsed GCT, and 1 year later required remobilization of HSCs to support two further cycles of HDC after subsequent m...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Case Report Source Type: research

Efficacy and safety of recombinant human adenovirus p53 combined with chemoradiotherapy in the treatment of recurrent nasopharyngeal carcinoma
This study aims to explore the efficacy and safety of recombinant human adenovirus p53 (rAd-p53) combined with chemoradiotherapy (CRT) in the treatment of recurrent nasopharyngeal carcinoma (NPC). A total of 162 recurrent NPC patients were selected and divided randomly into the rAd-p53+CRT, CRT, and rAd-p53 groups. An electrochemical luminescence immune analyzer was used to detect serum levels of tumor markers (carcinoembryonic antigen, cancer antigen 199, and cancer antigen 153). Efficacy evaluation was in accordance with Response Evaluation Criteria in Solid Tumor. Toxicity evaluation was performed according to the WHO g...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Comparison of survival with somatostatin analog and chemotherapy and prognostic factors for treatment in 165 advanced neuroendocrine tumor patients with Ki-67 20% or less
The objectives of this study were to compare progression-free survival (PFS) with somatostatin analog (SSA) versus chemotherapy (CTx) in first-line therapy and to determine the patient group in which these treatments were more effective in neuroendocrine tumors (NETs) with a Ki-67 index of 20% or less. Patients who received SSA or CTx and had unresectable locally advanced and metastatic NETs with a Ki-67 index of 20% or less were retrospectively selected from 13 centers in the Turkish database between 2000 and 2015. One hundred and sixty-five patients were enrolled. The median age was 56 years and the male-to-female ratio ...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Exclusive concurrent radiochemotherapy for advanced head and neck cancers with ‘fractionated’ 5-fluorouracil and cisplatin
We report the safety and efficacy of CRC with daily fractionated 5-fluorouracil and cisplatin (‘F’ 5FU–CDDP) in a monocentric retrospective cohort. From January 2006 to August 2012, all patients with unresectable (or inoperable) nonmetastatic locoregionally advanced ENT cancer treated curatively by means of radiotherapy (normal fractionated 70 Gy to the macroscopic tumor and prophylactic 50 Gy) with three courses (week 1–week 4–week 7) of ‘F’ 5FU–CDDP regimen (800 mg/m2/day of 5-fluorouracil and 20 mg/m2/day of CDDP from day 1 to day 4) were includ...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Prognostic role of the cumulative toxicity in patients affected by metastatic renal cells carcinoma and treated with first-line tyrosine kinase inhibitors
Tyrosine kinase inhibitor-related toxicities have been reported to be predictive and/or prognostic factors in patients affected by metastatic renal cell carcinoma (mRCC). We aim to investigate the incidence of cumulative toxicity and its prognostic role in mRCC patients treated with sunitinib or pazopanib. mRCC patients treated with sunitinib or pazopanib at the European Institute of Oncology in Milan were reviewed for the incidence of adverse events. Cumulative toxicity was defined as the presence of more than one selected adverse event of any grade. Prognoses were evaluated by the International mRCC Database Consortium c...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Irradiated VEGF164-modified tumor cell vaccine protected mice from the parental tumor challenge
In this study, we established a VEGF164 overexpressing LL/2 lung cancer cell model and found that the postirradiated VEGF164-modified tumor cells protected the host against the challenge with LL/2 wild-type tumor cells. Histochemical assay showed that there were large areas of tumor necrosis with macrophage infiltration in the mice vaccinated with the VEGF164-modified tumor vaccine. T-cells isolated from the vaccinated mice showed cytotoxicity against the parental tumor cells in a dose-dependent manner. Meanwhile, sera from the mice vaccinated with LL/2-VEGF164 showed higher titers of antibodies against parental tumor cell...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Receptor for advanced glycation end product blockade enhances the chemotherapeutic effect of cisplatin in tongue squamous cell carcinoma by reducing autophagy and modulating the Wnt pathway
Tongue squamous cell carcinoma (TSCC) is one of the most severe types of cancer with poor outcomes. Cisplatin is used widely to treat cancer cells, but many patients develop acquired drug resistance. The receptor for advanced glycation end products (RAGE) is expressed widely in TSCC and associated with drug-induced chemotherapy resistance. However, the effect of RAGE and cisplatin on Tca-8113 cells remains unknown. We assayed the combined use of RAGE blockade and cisplatin effect on Tca-8113 cells’ viability by MTT and apoptosis rate of Tca-8113 cells on RAGE blockade+cisplatin treatment; cisplatin alone; or RAGE blo...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Enhancement of death receptor 4-mediated apoptosis and cytotoxicity in renal cell carcinoma cells by anisomycin
We examined the cytotoxicity of anisomycin alone and in combination with mapatumumab in human RCC cell lines and primary RCC cell cultures. RCC cells treated with anisomycin showed cytotoxicity in a dose-dependent manner. Anisomyin in combination with mapatumumab showed a synergistic effect not only in two human RCC cell lines but also in five primary RCC cell cultures. The synergy between anisomycin and mapatumumab for cytotoxicity was also observed for apoptosis. Interestingly, anisomycin significantly increased DR4 expression at both the mRNA and the protein level. Furthermore, the combination-induced cytotoxicity was s...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Pachymic acid inhibits the tumorigenicity of gastric cancer cells by the mitochondrial pathway
In this study, we aimed to explore the efficacy and mechanisms of PA in GC. The antiproliferative effect of PA was assessed by a growth assay and a colony formation assay. Flow cytometry was used to detect changes in cell cycle distribution. Apoptosis was assessed by an annexin V/propidium iodide double-staining assay. The expressions of the apoptosis-related proteins were measured by western blot. The mitochondrial capacity was observed by immunostaining of Mito Tracker Red and mitochondrial function protein MT. Xenograft models of GC were constructed by a subcutaneous injection of SGC-7901 and MKN-49P cells pretreated wi...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Regulator of G-protein signaling 3 targeted by miR-126 correlates with poor prognosis in gastric cancer patients
In this study, we found that RGS3 is significantly upregulated in gastric cancer (GC) tumor samples compared with normal samples from the analysis of two independent GC mRNA microarray datasets in the NCBI public database. Further immunohistochemistry assay and western-blot experiments confirmed this finding on the basis of the results of our own 102 paired GC specimens and three GC cell lines. We found that a high expression of RGS3 is associated with advanced TNM stages and more aggressive malignant behaviors. In addition, the association of overexpression of RGS3 and poor overall survival and progression-free survival o...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Inhibition of IL-8 secretion on BxPC-3 and MIA PaCa-2 cells and induction of cytotoxicity in pancreatic cancer cells with marine natural products
Pancreatic cancer presents one of the most negative prognosis of all cancers as it has usually metastasized by the time a patient is diagnosed. The American Cancer Society estimates that 93% of patients will die within 5 years of diagnosis, highlighting the need for new drugs to treat this disease. Interleukin 8 (IL-8) mediates the angiogenesis of tumors arising from Ras mutations, which are present in about 90% of pancreatic adenocarcinomas. Overexpression of IL-8 in pancreatic tumors is believed to promote tumor angiogenesis and to activate survival signaling pathways. A 96-well cell-based enzyme-linked immunosorbent ass...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

YM155 inhibits topoisomerase function
In this study, YM155 did not behave like a typical DNA intercalator in viscosity, circular dichroism, and absorption spectroscopy studies. In addition, molecular modeling experiments ruled out YM155 DNA interaction to produce DNA intercalation. We show that YM155 inhibited topoisomerase 2α decatenation and topoisomerase 1-mediated cleavage of DNA, suggesting that YM155 inhibits the enzyme function. Consistent with these findings, DNA double-strand break repair was also inhibited by YM155. (Source: Anti-Cancer Drugs)
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Modified schedules of DCF chemotherapy for advanced gastric cancer: a systematic review of efficacy and toxicity
The objective of this systematic review was to evaluate overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade (G) greater than or equal to 3 adverse event of mDCF chemotherapy in this setting. MEDLINE, SCOPUS, Embase, Web of Science, LILACS, CINAHL, Google Scholar, and the Cochrane Library were searched for studies with mDCF schedules in advanced GC. Pooled median OS, PFS, ORR (the primary endpoints), and G3 or G4 adverse events (secondary endpoints) were presented according to random effect model. Twenty-four studies were included for a total of 1311 patients, with weekly or biweek...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Hypoxia-activated prodrugs in the treatment of advanced pancreatic adenocarcinoma
Pancreatic cancer is an aggressive malignancy with poor survival and high mortality rate with 250 000 deaths per year worldwide. The unique pancreatic cancer microenvironment serves as a major obstacle in the effective treatment of this malignancy. The microenvironment consists not only of pancreatic ductal adenocarcinoma cells but also comprises cells of pancreatic cancer stellate, vascular, and immune origin combined with a dense extracellular matrix containing collagen. The aforementioned pathology leads to an increased intratumor pressure combined with an erratic vascular proliferation within the tumor causing h...
Source: Anti-Cancer Drugs - January 13, 2017 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Docetaxel and mitoxantrone before radical prostatectomy in men with high-risk prostate cancer: 10-year follow-up and immune correlates
The aims of this study were to report the clinical outcomes in a cohort of men with high-risk prostate cancer treated with neoadjuvant docetaxel and mitoxantrone 10 years after treatment, identify pretreatment clinical parameters that may be predictors of recurrence, and describe tumor-infiltrating leukocytes present in radical prostatectomy specimens. We conducted a phase I/II study of neoadjuvant docetaxel and mitoxantrone before radical prostatectomy in high-risk localized prostate cancer to determine the feasibility of this combination and predictors of prostate cancer recurrence after cytotoxic chemotherapy. After 10 ...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Trabectedin in advanced desmoplastic round cell tumors: a retrospective single-center series
Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy that occurs with unpredictable chemosensitivity and limited treatment options in the advanced setting. Prognosis is poor, and exploring new treatment options for such diseases is difficult because of its rarity. Clinical activity of trabectedin for advanced DSRCT was scarcely reported in the literature. Here, we report a series of six patients treated with trabectedin for an unresectable DSRCT. After receiving trabectedin, two patients had stable disease with a time to progression of 3 and 3.5 months; four patients experienced disease progressi...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Duration of response to first androgen deprivation therapy, time to castration resistance prostate cancer, and outcome of metastatic castration resistance prostate cancer patients treated with abiraterone acetate
The objective of this retrospective study was to assess whether or not a correlation between duration of response to first androgen deprivation therapy (ADT), time to castration-resistant prostate cancer (TTCRPC), and outcome of AA therapy exists. A retrospective analysis of clinical data of mCRPC patients treated with AA at two Italian cancer centers was carried out. The Kaplan–Meier method and Cox proportional hazard model were used to analyze survival data. Correlation between median duration of response to first ADT or median TTCRPC and the outcome of patients treated with AA was analyzed. From January 2015 to No...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Predictive Comprehensive Geriatric Assessment in elderly prostate cancer patients: the prospective observational scoop trial results
The Comprehensive Geriatric Assessment (CGA) represents the future of the geriatric oncology to reduce toxicities and treatment-related hospitalization in the elderly. Most patients receiving docetaxel for metastatic castration-resistant prostate cancer are in their seventies or older. We explored the efficacy of the CGA in predicting chemotherapy feasibility and response to docetaxel in a cohort of 24 patients aged at least 70. This was an observational, prospective study involving 24 patients who were 70 years of age or older and about to start chemotherapy with docetaxel for metastatic castration-resistant prostate canc...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Clinical effects of single nucleotide polymorphisms on drug-related genes in Japanese metastatic renal cell carcinoma patients treated with sunitinib
In conclusion, our data showed that the ABCB1 rs2032582 GG genotype was associated with individual adverse events’ susceptibility among Japanese patients treated with sunitinib in routine clinical settings. (Source: Anti-Cancer Drugs)
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Lentivirus-mediated p21/Waf-1 short hairpin RNA enhances the cytotoxic effects and replicative potential of a bladder cancer-specific oncolytic adenovirus in vitro
In this study, we investigated the effect of the cell cycle-dependent kinase inhibitor p21/Waf-1 on an adenovirus. We used lentivirus-mediated short hairpin RNA to knock down p21/Waf-1 in two bladder cancer cell lines EJ and 5637. The p21/Waf-1 knockdown not only induced stronger cytopathic effects but also augmented apoptosis, which was closely associated with the enhancement of Fas and the subsequent significant activation of caspase-3. A replicative assay showed that p21/Waf-1 knockdown increased the viral particle production. Western blot analysis confirmed that p21/Waf-1 knockdown upregulated the expression of androge...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Differential receptor dependencies: expression and significance of muscarinic M1 receptors in the biology of prostate cancer
This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways’ homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selecti...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Tunicamycin enhances human colon cancer cells to TRAIL-induced apoptosis by JNK-CHOP-mediated DR5 upregulation and the inhibition of the EGFR pathway
Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively induces apoptosis in many tumor cells while leaving normal cells intact and is thus an attractive candidate for antitumor therapies. This paper reports that the combination of tunicamycin plus TRAIL produced a strong synergistic effect in TRAIL-sensitive human colon cancer HCT116 cells and TRAIL-resistant HT-29 cells. On a cellular mechanistic level, tunicamycin-enhanced TRAIL-induced apoptosis by death receptor (DR) 5 upregulation and DR4 deglycosylation. Knockdown of DR5 but not DR4 expression by specific shRNAs or siRNAs signi...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Chlorogenic acid induces reactive oxygen species generation and inhibits the viability of human colon cancer cells
Chlorogenic acid (CGA) is one of the polyphenols identified in the human diet. Previous studies have shown that CGA plays a protective role against liver diseases. The colon plays a pivotal role in CGA metabolism. However, little is known about the direct effects and the underlying molecular mechanisms of CGA in colon cancer. Here, we investigate these mechanisms of CGA activity in human colon cancer cells. The effects of CGA on the viability of two human colon cancer cell lines, HCT116 and HT29, were determined using the MTT assay. The intracellular reactive oxygen species (ROS) were detected using fluorescence microscopy...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

PRIMA-1 induces caspase-mediated apoptosis in acute promyelocytic leukemia NB4 cells by inhibition of nuclear factor-κB and downregulation of Bcl-2, XIAP, and c-Myc
Restoration of p53 function triggers cell death and eliminates tumors in vivo. Identification of p53-reactivating small molecules such as PRIMA-1 holds promise for effective new anticancer therapies. Here, we investigated the effects of small molecule PRIMA-1 on cell viability and expression of p53-regulated genes and proteins in the acute promyelocytic leukemia-derived NB4 cell line. Our results showed that PRIMA-1 had antileukemic properties in acute promyelocytic leukemia-derived NB4 cells. PRIMA-1-triggered apoptosis in a dose-dependent and time-dependent manner as indicated by the MTT assay and annexin-V staining. Apo...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Chamaejasmine induces apoptosis in HeLa cells through the PI3K/Akt signaling pathway
Chamaejasmine is one of the major bioactive components of Stellera chamaejasme L, which is a Chinese traditional herbal medicine that has been used widely in the treatment of cancer. The aim of this study is to investigate the potential effect of chamaejasmine on cervical cancer cells and elucidate the underlying mechanisms of action. We first examined the antitumor activity of chamaejasmine both in vitro and in vivo. In the following experiments with HeLa cells, cell apoptosis and ultrastructure changes were assessed by flow cytometry and transmission electron microscopy, respectively. The effects of chamaejasmine on reac...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Antitumor activity of recombinant RGD-IFN-α2a-core fusion protein in vitro
In this study, we expressed recombinant RGD-IFN-α2a-core fusion proteins and assessed their antitumor activity in vitro. Two RGD-IFN-α2a-core fusion proteins and a negative control protein were expressed in vitro. These two RGD-IFN-α2a-core fusion proteins could bind the tumor cell surface specifically and did not bind to normal cells. RGD-IFN-α2a-core fusion protein treatment of tumor cells significantly reduced cell viability and induced apoptosis in a dose-dependent manner. At the ‘mRNA’ level, both proteins could upregulate CASP3 expression. These data indicate that both laboratory-e...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Penicillium spp.: prolific producer for harnessing cytotoxic secondary metabolites
Secondary metabolites from fungal endophytes have become an interesting, attractive, and alternative source for novel pharmaceuticals. Several novel compounds with diversified chemical structures have been isolated from endophytic fungi. The genus Penicillium has been exploited worldwide for its biosynthetic potential for producing highly versatile cytotoxic secondary metabolites. Many of the compounds isolated from various species of the genus Penicillium have shown promising in-vitro as well as in-vivo growth-inhibitory properties against different human cancers. Thus, in relation to this genus, Penicillium represents th...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Review Articles Source Type: research

Clinical mutation assay of tumors: new developments
Mutation detection in tumors started with classical cytogenetics as the method of choice more than 50 years ago. Karyotyping proved to be sensitive enough to detect deletions or duplications of large chromosome segments, and translocations. Over time, new techniques were developed to detect mutations that are much smaller in scope. The availability of Sanger sequencing and the invention of the PCR improved the discriminatory power of mutation detection to just one base change in the genomic DNA sequence. Techniques derived from PCR (allele-specific PCR, qPCR) and improved or modified sequencing methods (capillary electroph...
Source: Anti-Cancer Drugs - December 1, 2016 Category: Cancer & Oncology Tags: Review Articles Source Type: research

The TYMS-TSER polymorphism is associated with toxicity of low-dose capecitabine in patients with advanced gastrointestinal cancer
Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of different genes involved in fluoropyrimidine metabolism and 5-fluorouracil (5-FU) degradation rate were associated with the outcome of a low-dose capecitabine schedule. Genotyping of DPYD IVS14+1 G>A, MTHFR C677T, and A1298C single-nucleotide polymorphisms was performed by pyrosequencing technology. A PCR ...
Source: Anti-Cancer Drugs - September 27, 2016 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research