The impact of chemotherapy in cancer patients: reflection on traditional Chinese symptom complex, cancer-related fatigue, and quality of life.

Traditional Chinese medicine is a trend in cancer holistic care. We found that patients undergoing chemotherapy had more traditional Chinese medicine symptom complexes with qi and blood deficiency and led poor quality of life and experienced fatigue. The traditional Chinese medicine theory based on qi and blood supply in cancer care deserves further research.

What really matters in pain management for terminally ill cancer patients in Taiwan.

The paradox of patients who are in pain yet satisfied with their pain management has been documented repeatedly. Pain relief constitutes only one part of patient satisfaction with pain management. The quality of cancer pain management in Taiwan has not been evaluated from the patient's perspective. A cross-sectional design was used to survey 1,370 terminally ill cancer patients in Taiwan to characterize the status of, and satisfaction with cancer pain management by investigating the relative importance of pain intensity, pain relief experiences, and clinicians' pain management practices. Cancer patients with pain had unsatisfactory pain relief within one week of admission (47.4 percent) and inadequate pain medication (23.6 percent). However, these patients perceived that clinicians adequately informed them about pain treatment. Patient satisfaction with pain management was primarily determined by examining the perceptions that medication dose was just right, responses to requests for pain medication were prompt, and understandable and consistent information about pain treatment was offered. In conclusion, Taiwanese cancer patients' satisfaction with pain management was influenced more by perceived pain management practices than by pain relief itself.

Downregulation of c-Myc determines sensitivity to 2-methoxyestradiol-induced apoptosis in human acute myeloid leukemia.

OBJECTIVE: 2-Methoxyestradiol (2ME2) has been shown to induce apoptosis in leukemic cells, but its exact mechanism remains unclear. Because c-Myc plays a critical role in leukemogenesis, we evaluated whether 2ME2 acts on acute myeloid leukemia (AML) through modulation of c-Myc activity. MATERIALS AND METHODS: AML cell lines and primary AML leukemia were treated with 2ME2 and the relationship between 2ME2-induced apoptosis and changes in c-Myc activity was examined. RESULTS: 2ME2 induced mitochondrial apoptosis of human AML cells through increased reactive oxygen species. Further investigation showed that 2ME2 downregulated c-Myc expression in a time-dependent manner. Increased oxidative stress led to downregulation of c-Myc mRNA and protein, but did not affect the stability of c-Myc protein. To demonstrate the role of c-Myc in 2ME2-induced apoptosis, we ectopically expressed wild-type c-Myc in AML cells and found that ectopic expression of c-Myc abrogated the 2ME2-induced apoptosis. In addition, we showed that 2ME2 treatment inhibited phosphorylation of Akt and binding of nuclear factor-kappaB p65/p50 heterodimers to its DNA targets. As with results from cell lines studied, 2ME2 also induced cytotoxicity to primary AML cells and downregulated their c-Myc expression and induced apoptosis. CONCLUSION: Downregulation of c-Myc is critical for 2ME2-induced oxidative stress and apoptosis in AML cells. Our results might be extended to other types of cancers overexpressing c-Myc.

The cytotoxicity of arsenic trioxide to normal hematopoietic progenitors and leukemic cells is dependent on their cell-cycle status.

Arsenic trioxide (ATO) is a novel agent to treat acute promyelocytic leukemia (APL). ATO can degrade chimeric PML-RAR proteins and induce apoptosis in various cancer cells. However, its effects on primary hematopoietic CD34+ have not been examined. In this study, we compared the effects of ATO on HL60 leukemic cells and primary umbilical cord blood (UCB) CD34+ cells. HL60 cells and UCB CD34+ cells were cultured with different concentrations of ATO for up to three weeks and examined for changes of cell cycle. We found that ATO (< or = 5 microM) caused prolongation of G1/S and G2/M phase in a dose-dependent manner. The percentage of cells in G2/M increased significantly (from 8.6 to 53.8%). High-dose ATO (> or = 25 microM) caused non-specific cell death in HL60 cells without any changes in cell cycle. In contrast to HL60 cells, UCB CD34+ cells were more resistant to high-dose ATO and most ATO-resistant CD34+ cells remained in G0/G1 phase. Primary cells that were resistant to ATO were rich in CD34+ cells. We further show that the ATO resistance was not related to the expression of P-glycoprotein (MDR-1). Our results suggest that the resistance to ATO in primitive UCB CD34+ cells is most likely related to its cell-cycle status. These results could be useful to design treatments for non-APL malignancies and to enrich hematopoietic stem cells in clinically applicable settings.

The correlation of traditional chinese medicine deficiency syndromes, cancer related fatigue, and quality of life in breast cancer patients.

BACKGROUND: To evaluate the correlation between the different traditional chinese medicine (TCM) deficiency syndromes, cancer related fatigue (CRF), and quality of life (QoL) in breast cancer patients. PATIENTS AND METHODS: Ninety-five breast cancer patients were categorized into different qi ( qì), blood ( xuè), yin ( yin), and yang ( yáng) TCM deficiency syndrome groups (DSGs). We used the ICD-10 for diagnosing CRF. The QoL was assessed by the WHO-BREF and Short Form Health Survey (SF12) questionnaires. The major outcome was to compare the QoL scores between the different TCM DSGs. The second outcome was the intergroup analysis between the CRF and different TCM DSGs in breast cancer patients. RESULTS: The patients with qi deficiency ( qì xu) had a higher correlation with CRF (p=0.001) and poorer QoL both in the WHO-BREF and SF12 survey (p<0.001), whereas the patients with yin deficiency ( yin xu) had poorer QoL in the psychological (p=0.02) and social aspects (p=0.04). The qi deficiency ( qì xu) syndrome was closely associated with yin deficiency syndrome ( yin xu). (p=0.03). CONCLUSION: Our study confirmed the concept of Qi-deficiency ( qì xu) in TCM was associated with CRF as identified in cancer care in western medicine. The breast cancer patients with qi deficiency ( qì xu) have poorer QoL. Treatment of CRF and improving QoL by supplying qi ( qì) may warrant further investigation.

The Relationship between Qi Deficiency, Cancer-related Fatigue and Quality of Life in Cancer Patients.

BACKGROUND: Qi ( qì) refers to the vital energy of the body in Traditional Chinese medicines (TCM). Qi deficiency ( qì xu) is the most common symptom in cancer patients according to the concept of TCM. We hypothesized that cancer patients with Qi deficiency suffer from poor quality of life (QOL) and fatigue. METHOD: Among the 256 registered cancer patients screened at our outpatient clinic, a total of 198 were enrolled. The inclusion criteria were (1) age between 18 and 70 years, (2) cancer diagnosis confirmed by the professional physician, (3) being Chinese, and (4) Eastern Cooperative Oncology Group (ECOG) performance status rating (PSR) ≤ 3. The major outcome is the difference in QOL score in cancer patients with and without Qi deficiency. RESULTS: The initial results showed statistically significant differences in WHO-QOL scores in physical, psychological, and social domains between the groups with and without Qi deficiency as well as the groups with and without cancerrelated fatigue (CRF). All patients with CRF present were also diagnosed as Qi deficient. In addition, among the patients with no CRF, 39.9% (69/173) were diagnosed as suffering from Qi deficiency, which led to poor QOL. CONCLUSIONS: The present study showed statistically significant difference in WHO-QOL scores in physical, psychological, and social domains between the groups with and without Qi deficiency as well as the groups with and without CRF. Cancer patients diagnosed with Qi deficiency or CRF have poor QOL. The concept of Qi deficiency in TCM might be applied to cancer health care.

Targeting c-Myc as a novel approach for hepatocellular carcinoma.

Hepatocelluar carcinoma (HCC) is the most lethal cancer in the world. Most HCC over-express c-Myc, which plays a critical role in regulating cellular growth, differentiation and apoptosis in both normal and neoplastic cells. c-Myc is among the most frequently overexpressed genes in human cancers. Overexpression of c-Myc in hepatic cells leads to development of hepatocellular carcinoma. Here, we review the current progress in understanding physiologic function and regulation of c-Myc as well as its role in hepatic carcinogenesis and discuss the association of c-Myc activation in chronic hepatitis B infection and the upregulation of HIF-1/VEGF. We also explore the possibility of treating HCC by inhibiting c-Myc and examine the pros and cons of such an approach. Although this strategy is currently not available in clinics, with recent advances in better drug design, pharmacokinetics and pharmacogenetics, inhibition of c-Myc might become a novel therapy for HCC in the future.

Meisoindigo is a promising agent with in vitro and in vivo activity against human acute myeloid leukemia.

Meisoindigo, a derivative of Indigo naturalis, has been used in China for chronic myeloid leukemia. In vitro cell line studies have shown that this agent might induce apoptosis and myeloid differentiation of acute myeloid leukemia (AML). In this study, we explored its mechanisms and potential in AML. NB4, HL-60, and U937 cells and primary AML cells were used to examine its effects and the NOD/SCID animal model was used to evaluate its in vivo activity. Meisoindigo inhibited the growth of leukemic cells by inducing marked apoptosis and moderate cell-cycle arrest at the G(0)/G(1) phase. It down-regulated anti-apoptotic Bcl-2, and up-regulated pro-apoptotic Bak and Bax and cell-cycle related proteins, p21and p27. Furthermore, it induced myeloid differentiation, as demonstrated by morphologic changes, up-regulation of CD11b, and increased nitroblue tetrazolium reduction activity in all cell lines tested. In addition, meisoindigo down-regulated the expression of human telomerase reverse transcriptase and enhanced the cytotoxicity of conventional chemotherapeutic agents, cytarabine and idarubicin. As with the results from cell lines, meisoindigo also induced apoptosis, up-regulated p21 and p27, and down-regulated Bcl-2 in primary AML cells. The in vivo anti-leukemic activity of meisoindigo was also demonstrated by decreased spleen size in a dose-dependent manner. Taking these results together, meisoindigo is a potential agent for AML.

Small-molecule c-Myc inhibitor, 10058-F4, inhibits proliferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells.

c-Myc oncogene is critical for the development of hepatocellular carcinoma. Given the successful use of small-molecule inhibitors on cancers, targeting c-Myc with small-molecule inhibitors represents a promising approach. The potential of using small-molecule c-Myc inhibitor, 10058-F4, was evaluated on hepatocellular carcinoma cell lines, HepG2 and Hep3B cells. HepG2 cells were more sensitive to 10058-F4 than Hep3B cells, as demonstrated by reduced cell viability, marked morphological changes and decreased c-Myc levels. 10058-F4 arrested the cell cycle (at G0/G1 phase) and induced apoptosis upon extended treatment. These observations might be attributable to the increased cyclin-dependent kinase inhibitor, p21, and decreased cyclin D3 levels. Besides, 10058-F4 also significantly decreased the alpha-fetoprotein levels, an indicator for hepatocellular carcinoma differentiation. We further found that 10058-F4 inhibited the transactivation of human telomerase reverse transcriptase, downregulated human telomerase reverse transcriptase expression and abrogated telomerase activity. In addition, pretreatment with 10058-F4 increased the chemosensitivity of HepG2 cells to low-dose doxorubicin, 5-fluorouracil and cisplatin. Therefore, small-molecule c-Myc inhibitors might represent a novel agent, alone or in combination with conventional chemotherapeutic agents, for anti-hepatocellular carcinoma therapy.