Childhood cancer survivors (CCS) are at increased risk of developing subsequent malignant neoplasms, including gastrointestinal (GI) cancer. We performed a systematic review to summarize all available literature on the risk of, risk factors for, and outcome after subsequent GI cancer among CCS.

Histone acetyltransferases and histone deacetylases (HDACs) are multifunctional enzymes that posttranslationally modify both histone and nonhistone acetylation sites, affecting a broad range of cellular processes (e.g., cell cycle, apoptosis, and protein folding) often dysregulated in cancer. HDAC inhibitors are small molecules that directly interact with HDAC catalytic sites preventing the removal of acetyl groups, thereby counteracting the effects of HDACs. Since the first HDAC inhibitor, valproic acid, was investigated as a potential antitumor agent, there have been a number of other HDAC inhibitors developed to improve efficacy and safety. Despite significant progress in the management of patients with hematologic malignancies, overall survival is still poor. The discovery that HDACs may play a role in hematologic malignancies and preclinical studies showing promising activity with HDAC inhibitors in various tumor types, led to clinical evaluation of HDAC inhibitors as potential treatment options for patients with advanced hematologic malignancies. The Food and Drug Administration has approved two HDAC inhibitors, vorinostat (2006) and romidepsin (2009), for the treatment of cutaneous T-cell lymphoma. This review highlights the safety of HDAC inhibitors currently approved or being investigated for the treatment of hematologic malignancies, with a specific focus on the safety experience with vorinostat in cutaneous T-cell lymphoma.

No 'gold standard' exists for single-agent chemotherapy of human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer (MBC) in the second-line. The objective of this systematic review is to identify and appraise overall survival (OS), progression-free survival (PFS), time to progression (TTP) and Grade ≥3 adverse event evidence for single-agent chemotherapy in this setting.

The androgen receptor (AR) plays a key role in progression to metastatic castration-resistant prostate cancer (mCRPC). Despite the recent progress in targeting persistent AR activity with the next-generation hormonal therapies (abiraterone acetate and enzalutamide), resistance to these agents limits therapeutic efficacy for many patients. Several explanations for response and/or resistance to abiraterone acetate and enzalutamide are emerging, but growing interest is focusing on importance of AR splice variants (AR-Vs) and in particular of AR-V7. Increasing evidences highlight the concept that variant expression could be used as a potential predictive biomarker and a therapeutic target in advanced prostate cancer. Therefore, understanding the mechanisms of treatment resistance or sensitivity can help to achieve a more effective management of mCRPC, increasing clinical outcomes and representing a promising and engaging area of prostate cancer research.

Along with anthracyclines, taxanes are the most active cytotoxics in breast cancer (BC). Balancing efficacy against toxicity in older patients with reduced physiological reserves and significant comorbidities is both important and difficult. This is especially so given the under-representation of elderly patients in major trials and a consequent lack of evidence for drug, dose and schedule. However, BC is frequent in elderly women, who are a growing proportion of the population. Careful consideration of their care is therefore imperative. Treatment that can cure or extend the duration and quality of life should not be restricted by age, but needs to be tailored to the circumstances of elderly patients. In adjuvant use, taxane toxicity in older women is greater than in their younger counterparts, limiting its sequential combination with anthracyclines for high-risk disease unless patients are in very good health. More frequently taxanes are used alone (weekly paclitaxel, three-weekly docetaxel) or combined with cytotoxics other than anthracyclines (e.g. docetaxel plus cyclophosphamide) to reduce cardiac risk, especially in HER-2-positive patients who may develop additional trastuzumab-related cardiac events. In elderly patients with metastases, weekly paclitaxel and three-weekly docetaxel are among the cornerstones of treatment, with generally acceptable toxicity. Three-weekly docetaxel at the approved dose of 100mg/m(2) is not appropriate for the elderly. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication but has been little studied in older BC patients. A head-to-head comparison with weekly paclitaxel favoured the solvent-free formulation for pathologic response, but those studied were a general adult population. Compared with early stage disease, choice of taxane and regimen in the metastatic setting relies even more on availability and preferences with regard to schedule, toxicity profile and cost, especially for recently developed formulations.

Sarcomas are a group of cancers that arise from transformed cells of mesenchymal origin. They can be classified into over 50 subtypes, accounting for approximately 1% of adult and 15% of pediatric cancers. Wide surgical resection, radiotherapy, and chemotherapy are the most common treatments for the majority of sarcomas. Among these therapies, chemotherapy can palliate symptoms and prolong life for some sarcoma patients. However, sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multidrug resistance (MDR). MDR attenuates the efficacy of anticancer drugs and results in treatment failure for sarcomas. Therefore, overcoming MDR is an unmet need for sarcoma therapy. Certain protein kinases demonstrate aberrant expression and/or activity in sarcoma cells, which have been found to be involved in the regulation of sarcoma cell progression, such as cell cycle, apoptosis, and survival. Inhibiting these protein kinases may not only decrease the proliferation and growth of sarcoma cells, but also reverse their resistance to chemotherapeutic drugs to subsequently reduce the doses of anticancer drugs and decrease drug side-effects. The discovery of novel strategies targeting protein kinases opens a door to a new area of sarcoma research and provides insight into the mechanisms of MDR in chemotherapy. This review will focus on the recent studies in targeting protein kinase to reverse chemotherapeutic drug resistance in sarcoma.

Although outcomes for women with breast cancers may vary by biologic subtype, patients with T1a,b N0M0 tumors have an excellent prognosis across all subgroups. HER2 overexpression occurs in 15-20% of primary breast tumors, and is associated with diminished disease-free and overall survival. The anti-HER2 monoclonal antibody trastuzumab in combination with chemotherapy is an effective treatment for all stages of HER2 positive breast cancer (bc). However, the absolute benefit decreases as the risk of recurrence lessens and no available randomized adjuvant trial has evaluated the role of trastuzumab in women with pT1a,b N0M0, HER2-positive breast tumors. These findings may explain the debate about the appropriate indication for adjuvant chemotherapy plus trastuzumab in this setting of patients. The aim of this review was to describe known and novel prognostic risk factors to be used for tailored treatment decision in pT1a,b N0M0 HER2-positive tumors. Whether patients with small HER2-positive bc may be suitable for (chemo)therapy reduction strategies, the current available data cannot exclude the need for a more aggressive treatment in a small subset of these subjects. Novel clinical prognostic factors such as interval cancer (IC) detection may help to address this clinically important controversy. A multicenter population-based cancer registry study is currently evaluating whether IC detection may identify patients with pT1a N0M0 HER2-positive tumors in whom the rate of recurrence justifies consideration for use of conventional, trastuzumab-based chemotherapy regimens.

In the experiments on the rabbits the disturbances of cardio and systemic hemodynamic after 5-fluorouracilum administration have been shown. Yakton administercd intravenously in dose 560 mg/ kg one hour before 5-fluorouracilum protects the disturbances of cardio- and systemic hemodynamic data in animals.

The use of modern chemotherapy (CT) allowed to achieve significant progress in the treatment of many malignant tumors that were previously considered fatal. Improving the efficiency of the treatment was achieved by the intensification of chemotherapy. However, intensification of chemotherapy regimes provoked increase in the number of side effects of anticancer therapy,which often lead to a decrease in the intensity of the selected mode, the additional financial costs of treating the complications and the formation of the negative attitude of the patient to treatment. Thus, the side effects of chemotherapy are the actual problem of modern oncology. The purpose of this literature review was to investigate the frequency, symptoms and ways to prevent and treat various types of toxicity of chemotherapy.

Both EGFR and VEGFR-2 are important targets for cancer therapy, the combined inhibition of both EGFR and VEGFR-2 signaling pathway represents a promising approach to the treatment of cancers with a synergistic effect. In this study, a series of novel 4-anilinoquinazoline-acylamino derivatives designed as EGFR and VEGFR-2 dual inhibitors were synthesized and evaluated for biological activities. Most of them exhibited interesting inhibitory potencies against EGFR and VEGFR-2 as well as good antiproliferative activities. Compounds 15a, 15b and 15e exhibited the most potent inhibitory activity against EGFR (IC50 = 0.13 μM, 0.15 μM and 0.69 μM, respectively) and VEGFR-2 (IC50 = 0.56 μM, 1.81 μM and 0.87 μM, respectively), among them, compound 15b showed the highest antiproliferative activities against three cancer cell lines (HT-29, MCF-7 and H460) with IC50 of 5.27 μM, 4.41 μM and 11.95 μM, respectively. Molecular docking established the interaction of 15a with the DFG-out conformation of VEGFR-2, suggesting that they might be type II kinase inhibitors.

Attention must be paid to chemotherapy for cancer patients in a hyperglycemia state. It is difficult for chemotherapy to cure cancer in patients in a hyperglycemia state. This study was carried out to determine the change in cell viability after treatment with bromopyruvate, which is an alkylating drug with anti-tumor activity, in a high glucose condition.

Tamoxifen is a widely used in anti-oestrogen treatment of breast cancer. Previous reports showed that tamoxifen is associated with proliferative endometrial lesions. We herein reported an unusual case of concurrent hyperplastic lesions in the uterine cavity and right ovary in a 45-year-old woman with tamoxifen therapy. Regular vaginal ultrasonography showed the progressive endometrial thickening and right ovary enlargement during the period of drug use. Both lesions in the uterine cavity and right ovary showed characteristics resembling that of Müllerian adenofibroma. There were also foci of endometriosis in her bilateral ovarian surfaces. We suggest that women taking tamoxifen with a known history of endometriosis should be followed with transvaginal ultrasonography periodically.

In this study, we screened the different human osteosarcoma cell line MG-63 miRNAs after the treatment of curcumin and explored the effects of curcumin on MG-63 cells and its mechanism.

The aim of the present study was to investigate the effects of matrine on proliferation and apoptosis in human breast cancer MCF-7 cells and its relevant molecular mechanisms.

Increasing evidences have indicated the role of garlicin in inhibiting the progression of various tumors including glioma, pulmonary carcinoma and pancreatic carcinoma, via mediating cell apoptosis or cell cycle. The regulatory effect and related molecular mechanism of garlicin in intrahepatic cholangiocarcinoma, however, remained unknown. This study thus aimed to investigate this scientific issue. HCCC-9810 cell line was treated with serially diluted garlicin, followed by cell proliferation assay using MTT approach. Transwell migration and invasion assays were further employed the regulatory effect of garlicin. The expression level of p-AKT and AKT proteins in tumor cells was quantified by Western blot. The growth of tumor cells was significantly inhibited by high concentration of garlicin (> 1.5 μM). Lower concentration of garlicin showed dose-dependent inhibition of tumor cell invasion and migration. After using specific agonist IGF-1 (50 ng/mL) of PI3K/AKT signaling pathway, such facilitating effects of garlicin were depressed (P < 0.05). Western blotting showed significantly decreased phosphorylation level of AKT after treated with gradient concentrations of garlicin, while leaving the total AKT protein level unchanged. Garlicin may inhibit the invasion and migration of intrahepatic cholangiocarcinoma cells via inhibiting PI3K/AKT signaling pathway.

Acute myeloid leukemia is known as one of the most malignant diseases. We aimed at exploring the effect of portulacerebroside A (PCA) on the apoptosis in human leukemia HL60 cells and clarify the possible mechanisms involved in. By MTT analysis, we found that PCA (1-100 μM) inhibited the cell viability in a time- and dose-dependent manner, and cell cycle was arrested at G0/G1 period. PCA treatment from 5 to 50 μM dose-dependently induced apoptosis from 12.7 ± 1.56% to 52.7 ± 6.214% of HL60 cells. Mitochondrial membrane potential (MMP) was decreased and reactive oxygen species (ROS) accumulated obviously. mRNA expressions and protein levels of Bax/Bcl-2, caspase-3 and caspase-9 were elevated significantly. ERK1/2, JNK1/2 and p38 MAPK pathway were blocked detected by western blot analysis. In conclusion, PCA can act as a new agent for leucocythemia treatment.

Accelerated progression of residual hepatocellular carcinoma (HCC) after incomplete radiofrequency ablation (RFA) has been reported more frequently. Recent data have redefined the concept of inflammation as a critical component of tumor progression. However, there has been little understanding regarding the relationship between progression of residual HCC and the inflammation induced by thermal destruction of the tumor after RFA. The present study was designed to determine whether inflammation facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms.

The present study was performed to investigate the effect of retinoic acid amide (RAA) on the expression of integrin α3β1, rate of cell proliferation and migration in p53-deficient glioma cell line, LN-308. The results revealed promotion of integrin α3 expression, reduction in proliferation and migration in RAA treated cells compared to the control LN-308 glioma cells. Promotion of RAA induced integrin α3β1 expression led to the enhancement in cyclin-dependent kinase nuclear localization and activation of Akt pathway. In addition, RAA treatment inhibited the expression of nuclear factor-κB, Bcl-2 and epidermal growth factor receptor (EGFR). These factors are responsible for promoting the rate of cell proliferation and survival in the carcinoma cells. Thus RAA treatment inhibits rate of LN-308 glioma cell proliferation and migration through increase in integrin α3β1 expression and activation of Akt pathway. Therefore, RAA can be of therapeutic importance for the treatment of glioma.

Oleanolic acid has significant pharmacological activities, such as anti-tumor, regulating blood sugar level and liver protection, which are more effective compared with free aglyconeoleanolic acid. However, it is still unknown if oleanolic acid affects the proliferation of human bladder cancer. We utilized T24 cells to study the effect of oleanolic acid on the proliferation and apoptosis of human bladder cancer. In this study, we found that the anti-cancer effect of oleanolic acid significantly suppressed cell proliferation and increased apoptosis and caspase-3 activity of T24 cells. Furthermore, Akt, mTOR and S6K protein expression was greatly inhibited in T24 cells under oleanolic acid treatment. Meanwhile, ERK1/2 of phosphorylation protein expression was significantly promoted by oleanolic acid treatment. Taken together, we provided evidences that oleanolic acid was Akt/mTOR/S6K and ERK1/2 signaling-targeting anti-tumor agent. These findings represent new evidences that oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling, and oleanolic acid may be used to prevent human bladder cancer.

The optimal concentration of individual vitamin D intake for preventing bladder cancer has not, to our knowledge, been defined. To evaluate the comparative efficacy of different serum 25-hydroxyvitamin D concentrations in preventing bladder cancer, we conducted a systematic search of the literature published up to April 2015.