The immune effects of EGFR tyrosine kinase inhibitors (EGFR-TKIs) are poorly understood. Identifying immune biomarkers could guide patient selection and optimisation of EGFR-TKI-immunotherapy combinations.

This retrospective report evaluated the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) for life threatening patients with unresectable hepatic metastases.

To investigate the effects of dihydrofolate reductase (DHFR) gene expression up-regulating on cisplatin resistance in epithelial ovarian cancer cell lines.

To explore the effect and mechanism of glucose regulated protein 78 (GRP78) on autophagy and apoptosis in ovarian carcinoma, and to investigate the influence on the growth and sensitivity to cisplatin on the ovarian cancer cells.

To evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment.

To explore the differences in sensitivity to rapamycin of five esophageal squamous cell carcinoma cell lines with different differentiation and the changes of sensitivity of the cells after siRNA-interfered expression of p70S6K.

Suboptimal chemotherapy of anticancer drugs may be attributed to a variety of cellular mechanisms, which synergize to dodge the drug responses. Nearly 2 decades of heat-shock protein 90 (Hsp90)-targeted drug discovery has shown that the mono-therapy with Hsp90 inhibitors seems to be relatively ineffective compared with combination treatment due to several cellular dodging mechanisms. In this article, we have tried to analyze and review the Hsp90 and mammalian target of rapamycin (m-TOR)-mediated drug resistance mechanisms. By using this information we have discussed about the rationale behind use of drug combinations that includes both or any one of these inhibitors for cancer therapy. Currently, biodegradable nano vector (NV)-loaded novel drug delivery systems have shown to resolve the problems of poor bioavailability. NVs of drugs such as paclitaxel, doxorubicin, daunorubicin, and others have been successfully introduced for medicinal use. Hence, looking at the success of NVs, in this article we have also discussed the progress made in the delivery of biodegradable NV-loaded Hsp90 and m-TOR-targeted inhibitors in multiple drug combinations. We have also discussed the possible ways by which the market success of biodegradable NVs can positively impact the clinical trials of anti-Hsp90 and m-TOR combination strategy.

Primary liver cancer is a common cancer and the mortality of liver cancer ranks the second of all malignancy-related deaths in China. The most common primary liver cancer is hepatocellular carcinoma, accounting for approximately 90% of the total. Because liver is the largest parenchymatous organ in the body undertaking all kinds of important metabolic functions, liver cancer inevitably causes greater harms and its treatment is extremely difficult. Currently, there are still no effective drugs for the treatment of patients with advanced inoperable liver cancer. We observed the strong inhibitory activity of halofuginone on HepG2 cell growth and the cell cycle and apoptosis assays showed that halofuginone arrested the cell cycle and inhibited the induction. And we found that halofuginone inhibits tumor cell cycle possibly by up-regulating p15 and p21 of expression. Then, we found that the proportion of cleaved PARP, caspase-3, 8 and 9 in HepG2 cells increased after halofuginone treatment. And the results showed that halofuginone down-regulated Mcl-1 and c-IAP1 expression. Finally, our results showed halofuginone regulated the activities of JNK and MEK/ERK signaling pathways in hepatocellular carcinoma cells. In summary, this study shows that halofuginone can inhibit the in vitro growth, arrest the cell cycle and induce the apoptosis of HepG2 cells. Its mechanisms of action may be related to the regulation of associated protein expression, up-regulation of JNK, and inhibition of MEK/ERK signaling pathway.

Withaferin A, the principal bio-active component isolated from the Withaniasomnifera, has shown promising anti-leukemic activity in addition to anti-invasive and anti-metastatic activity. The present study demonstrates the effect of withaferin A on the cell cycle status and the phosphorylation/activation of proteins involved in signal transduction in t(4;11) and non-t(4;11) acute lymphoblastic leukemia (ALL) cell lines after treatment with withaferin A. The cells after treatment with the vehicle or 25 μM withaferin A for 1, 2, 4 and 8 h were examined using flow cytometric analysis. The results revealed that withaferin A treatment induced cell growth arrest at the S to G2/M phase transition of the cell cycle. Withaferin A treatment also induced the phosphorylation of stress signalling proteins, including the p38 mitogen-activated protein kinase, the c-Jun N-terminal kinase, c-Jun, the heat shock protein 27 and protein kinase B within 0 to 16 h. These results were observed using multiplex technology and Western blotting analysis. Thus withaferin A induces stress response leading to cell death. Therefore, withaferin A can be a potent therapeutic agent for the treatment of high risk ALL with chromosomal translocation t(4;11).

Deguelin, the main components from Mundulea sericea, was reported to suppress the growth of various cancer cells. However, the effect of Deguelin on tumor cell invasion and metastasis and its mechanism still unclear so far. In this study, we investigated the effects of Deguelin on the cell invasion in human lung cancer A549 and H460 cells. Our results demonstrate that Deguelin can significantly inhibited cell proliferation, cell migration and cell invasion. Moreover, Deguelin could also affected reorganization of the actin cytoskeleton and decreased filopodia and lamellipodia formation. Furthermore, deguelin-treated tumors showed decreased the tumor metastasis related genes such as CD44, MMP2 and MMP9 at protein and mRNA levels and the content of CEA, SCC, NSE, CYFAR21-1. In addition, Deguelin down-regulated protein expression of Rac1 and Rock1, which are impotent in actin cytoskeleton rearrangements and cell motility. Together, our results suggest that Deguelin inhibit tumor growth and metastasis of lung cancer cells and might be a candidate compound for curing lung cancer.

To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival.

It has been reported that the hypermethylation of APAF-1, DAPK-1 and other tumor suppressive genes (TSGs) correlates with progression of renal cell carcinoma and exerts prognostic and diagnostic relevance in renal cell carcinoma. A recent study has confirmed that demethylation regulates the TSGs expression and proliferation of various types of cancer cells. The present study was to recognize a potential anti-tumor effect of 5-aza-2'-deoxycytidine (DAC), a demethylation agent.

This review is to describe synergistic effects of various combinations of dietary natural products including curcumin, quercetin, soybean isoflavones, silibinin, and EGCG that have potential for the treatment of prostate cancer. These data can provide valuable insights into the future rational design and development of synergistic and/or hybrid agents for potential treatment of prostate cancer.

Prostate cancer is the most common diagnosed invasive cancer in American men and is the second leading cause of cancer-related deaths. Although there are several therapies successful in treating early, localized stage prostate cancer, current treatment of advanced metastatic castration-resistant prostate cancer remains ineffective due to inevitable progression of resistance to first-line treatment with docetaxel. The natural product quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid compound ubiquitous in dietary plants, possesses evidenced potential in treating advanced metastatic castration-resistant prostate cancer. However, its poor bioavailability and moderate potency hinder its advancement into clinical therapy. In order to engineer quercetin derivatives with improved potency and pharmacokinetic profiles for the treatment of advanced metastatic prostate cancer, we started this study with creating a small library of alkylated derivatives of quercetin for in vitro evaluation. The biological data and chemical reactivity of quercetin and its derivatives reported in literature directed us to design 3,4',7-O-trialkylquercetins as our first batch of targets. Consequently, nine 3,4',7-O-trialkylquercetins, together with four 3,7-O- dialkylquercetins, four 3,3',4',7-tetraalkylquercetins, and one 3,3',4'-O-trialkylquercetin, were prepared by one step O-alkylation of commercially available quercetin mediated by potassium carbonate. Their structures were determined by ID and 2D NMR data, and HRMS. Their anti-proliferative activities towards both androgen-refractory and androgen-sensitive prostate cancer cells were evaluated using WST-1 cell proliferation assay. The acquired structure-activity relationships indicate that 3,7-O-dialkylquercetins rather than 3,4',7-O-trialkylquercetins were much more potent than quercetin towards prostate cancer cells.

Basal cell carcinoma represents is most common tumor in fair-skinned individuals. In Germany, age-standardized incidence rates are 63 (women) and 80 (men) per 100,000 population per year. Early lesions may be difficult to diagnose merely on clinical grounds. Here, noninvasive diagnostic tools such as optical coherence tomography and confocal laser scanning microscopy may be helpful. The clinical diagnosis is usually confirmed by histology. Standard therapy consists of complete excision with thorough histological examination, either by means of micrographic surgery or, depending on tumor size and location as well as infiltration, using surgical margins of 3-5 mm or more. In particular, multiple basal cell carcinomas (such as in Gorlin-Goltz syndrome) and locally advanced as well as rarely also metastatic basal cell carcinoma may pose a therapeutic challenge. In superficial basal cell carcinoma, nonsurgical therapies such as photodynamic therapy or topical agents may be considered. In case of locally advanced or metastatic basal cell carcinoma, an interdisciplinary tumor board should issue therapeutic recommendations. These include radiation therapy as well as systemic therapy with a hedgehog inhibitor.

Drop metastases from glioblastoma multiforme (GBM) to the spinal cord are extremely rare in clinical practice. We report herewith multiple drop metastases to the cervical and thoracic spinal cord presenting as paraplegia in a patient treated initially with tumor resection followed by chemoradiation and later with temozolomide-.based adjuvant chemotherapy.

A 75-year-old male was diagnosed with central squamous cell carcinoma of the left lung, who has been given 3-dimensional conformal radiotherapy of total dose with 60 Gy in 30 fractions. Three years later, the tumor relapsed in situ and he received another stereotactic radiotherapy with a total dose of 40 Gy at a margin of planning target volume (PTV) in 10 (5 fractions/week) at 4 Gy/fraction. Gefitinib (250 mg/day) was initiated immediately after radiotherapy. Obstructive atelectasis in the left lung and increased pleural effusion occurred at the fourth month after radiotherapy. As this patient has been detected with deletion in exon 19 of the EGFR gene, gefitinib was continuous administered without interruption. After another 4 months, the atelectasis in the left lung reexpanded significantly. To the best of our knowledge, this is the first report in the literature that EGFR tyrosine kinase inhibitors (EGFR-TKI) reversed the radiation atelectasis of pulmonary in the nonsmall cell lung cancer (NSCLC) patient.

Severe hyponatremia with seizure owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral/renal salt wasting syndrome related with high mortality. The correct diagnosis of the hyponatremia for each case is important because of the alteration of the treatment approach. SIADH is an important clinical manifestation that does not occur after all chemotherapy courses. We cannot estimate whether the disease will occur on, which course of the chemotherapy in this case.