Survivin is expressed in many cancers but not in normal adult tissues and is transcriptionally regulated. To test the feasibility of using the survivin promoter to induce cancer-specific transgene expression in lung cancer gene therapy, a vector expressing a luciferase gene driven by the survivin promoter was constructed and evaluated in vitro and in vivo. We found that the survivin promoter was generally more highly activated in cancer cell lines than in normal and immortalized normal cell lines. When delivered intravenously by DNA:liposome complexes, the survivin promoter was more than 200 times more cancer specific than the cytomegalovirus promoter in vivo. To identify lung cancer patients who may benefit from gene therapy with the survivin promoter, we measured survivin protein expression in surgical specimens of 75 non-small-cell lung cancers and 10 normal lung tissues by immunohistochemical staining and found that survivin is expressed in most of the non-small-cell lung cancers tested (81%, 61 of 75) but none of the normal lung tissues. The survivin promoter also induced transgene expression of a mutant Bik in cancer cells, which suppressed the growth of cancer cells in vitro and in vivo. These results indicate that the survivin promoter is a cancerspecific promoter for various cancers and that it may be useful in cancer gene therapy.

Breast and prostate cancer are the most well-characterized cancers of the type that have their development and growth controlled by the endocrine system. These cancers are the leading causes of cancer death in women and men, respectively, in the United States. Being hormone-dependent tumors, antihormone therapies usually are effective in prevention and treatment. However, the emergence of resistance is common, especially for locally advanced tumors and metastatic tumors, in which case resistance is predictable. The phenotypes of these resistant tumors include receptorpositive, ligand-dependent; receptor-positive, ligand-independent; and receptor-negative, ligandindependent. The underlying mechanisms of these phenotypes are complicated, involving not only sex hormones and sex hormone receptors, but also several growth factors and growth factor receptors, with different signaling pathways existing alone or together, and with each pathway possibly linking to one another. In this review, we will discuss the potential mechanisms of antihormonetherapy resistance in breast and prostate cancers, especially focusing on the similarities and differences of these two cancers. We will also discuss novel agents that have been applied in clinical practice or with clinical potential in the future.Endocrine-Related Cancer (2005) 12 511-532

Background: Many patients with advanced cancer will develop physical and psychological symptoms related to their disease. These symptoms are infrequently treated by conventional care. Palliative care programs have been developed to fill this gap in care. However, there are limited beds in hospice units. To allow more terminal cancer patients to receive care from a hospice team, a combined hospice care system was recently developed in Taiwan. This study is a report of our experiences with this system. Patients and Methods: From January to December 2009, terminal cancer patients who accepted consultation from a hospice team for combined hospice care were enrolled in the study. Demographic data, clinical symptoms, referring department, type of cancer, and outcome were analyzed. Results: A total of 354 terminal cancer patients in acute wards were referred to a hospice consulting team. The mean patient age was 61 years, and the proportion of males was 63.28%. After combined hospice care, there was a significant improvement in the sign rate of do-not-resuscitate (DNR) orders from 41.53% to 71.47% ( p < 0.0001), and awareness of disease prognosis from 46.05% to 57.69% ( p ¼ 0.0006). Combined hospice care also enabled 64.21% of terminal cancer patients who were not transferred to hospice ward to receive combined care by a hospice consulting team while in acute wards, thus increasing the hospice utilization of terminal cancer patients. The major symptoms presented by the patients were pain (58%), dyspnea (52%), constipation (45%), and fatigue (23%). Conclusions: Through the hospice consulting system, hospice combined care has a positive effect on the utilization of hospice care, rate of DNR signing and quality of end-of-life care for terminal cancer patients.

Background: Paclitaxel is wildly used in chemotherapy, however, the adverse drug reactions (ADRs) occurred frequently. Various novel nano-based paclitaxel delivery systems were developed. The aim performed systemically review and meta-analyses to evaluate the effect adverse drug reactions (ADRs) of paclitaxel and its nano-based delivery systems. Methods: Systematically searched PubMed, Embase, Web of Science, Cochrane, Clinicalkey, Clinicaltrial.com, ASCO and ESMO. Data of adverse effect were analyzed to odds ratio (ORs) with 95% confidence interval (CI). The quality of studies was assessed with CASP Randomised Controlled Trial Checklist. Statistical analysis was used WinBUGS software (version 1.4.3) with the NetMetaXL interface (version 1.6.1). Results: Twenty-one studies, including 7011 patients and 6 paclitaxel formulations fulfilled the inclusion criteria. In all grade hypersensitivity reactions, comparing to SB-P, people with Lip-P had 0.19 times (95% CI= 0.02, 1.3) of chance, with Nab-P had 0.47 times (95% CI= 0.11, 1.40) of chance, with PPX had 0.44 times (95% CI= 0.03, 5.7) of chance for all grade adverse effect. In All grad neutropenia, comparing to Lip-P, people with SB-P had 0.83 times (95% CI= 0.15, 4.81) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.73 times (95% CI= 0.22, 2.42) of chance for all grade adverse effect. In leucopenia, comparing to Nab-P, people with SB-P had 0.66 times (95% CI= 0.50, 0.87) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.64 times (95% CI= 0.32, 1.16) of chance for all grade adverse effect. The rate of incidence in peripheral sensory neuropathy, myalgias and arthralgias tend to no significant differences between different formulations. Conclusion: Nano-based paclitaxel delivery resulted in fewer hypersensitivity reactions than solvent-based delivery. However, the incidence of neutropenia and leucopenia was higher in nano-based than solvent-based paclitaxel delivery. Dose-dependent ADRs were more frequent in paclitaxel anticancer treatment.

Sorafenib has been recommended as a new palliative therapy for advanced hepatocellular carcinoma (HCC). However, the clinical outcome of patients receiving sorafenib therapy varies. This study sought to identify which clinical method could be used to predict clinical outcome of sorafenib monotherapy in patients with advanced HCC. A total of 146 advanced HCC patients with Child-Pugh A liver function were enrolled from June 2011 to September 2015. Sorafenib doses ranged from 200 mg once daily to 400 mg twice daily. Clinical and pathological parameters were collected. There was no predefined primary endpoint. Tumor response rate, adverse events, overall survival (OS), and progression-free survival (PFS) were analyzed. The follow-up period was 1718 days (median: 859 days). The median dosage of sorafenib was 562.35 mg.Forty patients (27.4%) had stable disease and 106 patients (72.6%) had progression disease. The OS was 432.21 ± 360.52 days (median: 329 days) and PFS was 167.05 ± 166.50 days (median: 102.5 days). No sorafenib toxic effect-related mortality was encountered. The most common severe adverse events (≧grade 3) were hand-foot skin reactions (HFSR) (16, 11.0%), diarrhea (7, 4.8%), and alopecia (1, 0.7%). The following patients had longer median PFS (mPFS): those receiving total dosage > 55000 mg (217 vs.63 days; HR = 0.20,95%CI = 0.11-0.38; p < 0.001), those receiving daily dosage <562 mg (140 vs.69 days; HR = 0.27, 95%CI = 0.17-0.46; p < 0.001), those with treatment durations > 112 days (231vs.64 days; HR = 0.37, 95%CI = 0.19-0.74; p < 0.001), and those with HFSR (105 vs.75 days; HR = 0.60,95% CI = 0.6-0.98; p = 0.04). In conclusion, increased cumulative doses of sorafenib as well as the appearance of HFSR were indicators of prolonged mPFS in sorafenib-treated advanced HCC patients.

Hepatocellular carcinoma (HCC) is among the most common causes of cancer death in men. Whether or not a longitudinal follow-up of circulating tumor cells (CTCs) before and at different time points during systemic/targeted therapy is useful for monitoring the treatment response of patients with locally advanced or metastatic HCC has been evaluated in this study. Blood samples (n = 104) were obtained from patients with locally advanced or metastatic HCC (n = 30) for the enrichment of CTCs by a negative selection method. Analysis of the blood samples from patients with defined disease status (n = 81) revealed that those with progressive disease (PD, n = 37) had significantly higher CTC counts compared to those with a partial response (PR) or stable disease (SD; n = 44 for PR + SD, p = 0.0002). The median CTC count for patients with PD and for patients with PR and SD was 50 (interquartile range 21–139) and 15 (interquartile range 4–41) cells/mL of blood, respectively. A longitudinal analysis of patients (n = 17) after a series of blood collections demonstrated that a change in the CTC count correlated with the patient treatment response in most of the cases and was particularly useful for monitoring patients without elevated serum alpha-fetoprotein (AFP) levels. Sequential CTC enumeration during treatment can supplement standard medical tests and benefit the management of patients with locally advanced or metastatic HCC, in particular for the AFP-low cases.

To ensure the success of systemic gene therapy, it is critical to enhance the tumor specificity and activity of the promoter. In the current study, we determined that topoisomerase IIa promoter is selectively activated in breast cancer cells. An element containing an inverted CCAAT box (ICB) was shown to be responsible for the breast cancer specificity. When the ICB-harboring topoisomerase IIa minimal promoter was linked with an enhancer sequence from the cytomegalovirus immediate early gene promoter (CMV promoter), this composite promoter, CT90, exhibited activity comparable to or higher than the CMV promoter in breast cancer cells in vitro and in vivo, yet expresses much lower activity in normal cell lines and normal organs than the CMV promoter. A CT90-driven construct expressing BikDD, a potent proapoptotic gene, was shown to selectively kill breast cancer cells in vitro, and to suppress mammary tumor development in an animal model of intravenously administrated, liposome-delivered gene therapy. Expression of BikDD was readily detectable in the tumors but not in the normal organs (such as heart) of CT90-BikDD-treated animals. The results indicate that liposomal CT90-BikDD is an effective systemic breast cancer-targeting gene therapy.

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