Synergic chemoprevention with dietary carbohydrate restriction and supplementation of AMPK-activating phytochemicals: the role of SIRT1.

Calorie restriction or a low-carbohydrate diet (LCD) can increase life span in normal cells while inhibiting carcinogenesis. Various phytochemicals also have calorie restriction-mimetic anticancer properties. We investigated whether an isocaloric carbohydrate-restriction diet and AMP-activated protein kinase (AMPK)-activating phytochemicals induce synergic tumor suppression. We used a mixture of AMPK-activating phytochemical extracts including curcumin, quercetin, catechins, and resveratrol. Survival analysis was carried out in a B16F10 melanoma model fed a control diet (62.14% kcal carbohydrate, 24.65% kcal protein and 13.2% kcal fat), a control diet with multiple phytochemicals (MP), LCD (16.5, 55.2, and 28.3% kcal, respectively), LCD with multiple phytochemicals (LCDmp), a moderate-carbohydrate diet (MCD, 31.9, 62.4, and 5.7% kcal, respectively), or MCD with phytochemicals (MCDmp). Compared with the control group, MP, LCD, or MCD intervention did not produce survival benefit, but LCDmp (22.80±1.58 vs. 28.00±1.64 days, P=0.040) and MCDmp (23.80±1.08 vs. 30.13±2.29 days, P=0.008) increased the median survival time significantly. Suppression of the IGF-1R/PI3K/Akt/mTOR signaling, activation of the AMPK/SIRT1/LKB1pathway, and NF-κB suppression were the critical tumor-suppression mechanisms. In addition, SIRT1 suppressed proliferation of the B16F10 and A375SM cells under a low-glucose condition. Alterations in histone methylation within Pten and FoxO3a were observed after the MCDmp intervention. In the transgenic liver cancer model developed by hydrodynamic transfection of the HrasG12V and shp53, MCDmp and LCDmp interventions induced significant cancer-prevention effects. Microarray analysis showed that PPARα increased with decreased IL-6 and NF-κB within the hepatocytes after an MCDmp intervention. In conclusion, an isocaloric carbohydrate-restriction diet and natural AMPK-activating agents induce synergistic anticancer effects. SIRT1 acts as a tumor suppressor under a low-glucose condition.

Therapeutic strategies for well-differentiated papillary mesothelioma of the peritoneum.

OBJECTIVE: Well-differentiated papillary mesothelioma is an uncommon subtype of mesothelioma with a frequently indolent course, although it occasionally manifests in a more aggressive form. To establish a treatment strategy for this rare disease, we report the clinical characteristics and outcomes of 15 patients with well-differentiated papillary mesothelioma. METHODS: All pathologically diagnosed well-differentiated papillary mesothelioma cases were reviewed between 1998 and 2012. RESULTS: Of the 15 cases, 8 and 7 presented with single and multiple lesions, respectively. All cases with single lesions were asymptomatic, while 4 out of the 7 cases with multiple lesions were symptomatic. After tumor excision, none of the eight single-lesion cases experienced tumor recurrence. Among the other seven cases with multiple lesions, only one patient with disseminated lesions died due to disease burden. Five patients with multiple lesions received cisplatin-based intravenous or intraperitoneal chemotherapy, with a mix of complete (n= 2) and partial (n= 2) responses observed. Of particular note, one patient receiving cisplatin and pemetrexed combination chemotherapy experienced complete tumor resolution without any serious toxicity. CONCLUSIONS: We recommend different treatment strategies based on the disease status. If the tumor is completely resectable, an excisional biopsy seems to be sufficient. If complete resection is unavailable for the asymptomatic patient with a localized tumor extent, close follow-up is an appropriate option. When the tumor is extensive or accompanied by symptoms, chemotherapy should be strongly considered.

The clinical outcome of chemotherapy-induced amenorrhea in premenopausal young patients with breast cancer with long-term follow-up.

BACKGROUND: We investigated the factors that predict chemotherapy-induced amenorrhea (CIA) and the prognostic significance of CIA after long-term follow-up. METHODS: We reviewed data from 241 premenopausal patients with breast cancer who underwent adjuvant CMF or FAC chemotherapy after breast cancer surgery between January 1995 and December 2000. RESULTS: The median follow-up duration was 109.8 (range, 16.6-193.1) months. The age of CIA patients was older than non-CIA patients (median, 44 (range, 28-53) years and 36 (range, 25-49) years, respectively; P < 0.001). The addition of tamoxifen to the chemotherapy increased the incidence of CIA from 48% to 63.6% (P = 0.015). The 10-year disease-free survival (DFS) rate was higher in the CIA group compared with the non-CIA group in hormonal receptor-positive patients (78.4% vs. 67%, respectively; P = 0.022), and the 10-year overall survival (OS) rate also was higher in the CIA group compared with the non-CIA group (90.8% vs. 79.7%, respectively; P = 0.041). CONCLUSIONS: The most important predictors of CIA are age and the addition of tamoxifen to the chemotherapy. CIA is likely to have an influence on DFS and OS in premenopausal patients with breast cancer with a positive hormone receptor, and it might be used as a surrogate marker for effective chemotherapy in these young Asian patients.

Treatment outcome of localized Helicobacter pylori-negative low-grade gastric MALT lymphoma.

AIM: To investigate treatment outcome of Helicobacter pylori (H. pylori)-negative low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: In this study, we retrospectively reviewed the clinical outcome and clinicopathologic factors of stage IE H. pylori-negative low-grade gastric MALT lymphoma cases from August 1998 to June 2009. RESULTS: A total of eleven patients with H. pylori-negative low-grade gastric MALT lymphoma were enrolled in the study and received anti-H. pylori eradication treatment and/or radiotherapy or excisional therapy. Complete remission (CR) of gastric MALT lymphoma was achieved in all patients. The time to CR was 1-66 mo (median, 1 mo). CONCLUSION: Eradication therapy may be offered as an initial treatment option even in cases of localized H. pylori-negative gastric MALT lymphoma.