In Keun Choi

The cutoff value of serum ferritin for the diagnosis of iron deficiency in community-residing older persons

The serum ferritin assay is the best single blood test for the diagnosis of iron deficiency. Previous studies with elderly anemic patients have suggested that ferritin level less than 45xa0μg/L is indicative of iron deficiency. The subjects of these studies were hospitalized patients with anemia, however. We thus conducted a prospective study to determine the normal minimum level of serum ferritin of community-dwelling older adults by assessing the ratio of serum transferrin receptor to the log ferritin level (sTfR-F index). We conducted the anemia survey between October and November 2002. A total of 1,254 apparently healthy older adults, aged between 60 and 95 years, from three urban community dwellings participated in the survey. Among these individuals, 156 subjects who were anemic or whose serum ferritin level was less than 100xa0μg/L were selected. The soluble transferrin receptor assay was performed and the sTfR-F index was calculated. The receiver operating characteristic curve analysis was performed. Based on the data, serum ferritin level of 22xa0μg/L was selected as the cutoff value for the diagnosis of iron deficiency in community-dwelling older adults. Applying the serum ferritin cutoff of 22xa0μg/L and the sTfR-F index cutoff of 1.5, the sensitivity of the assay was 89.5% (34 of 38) and the specificity was 89.0% (105 of 118). In conclusion, for the diagnosis of iron deficiency of community-residing older adults, we suggest the serum ferritin cutoff value of 22xa0μg/L obtained by use of the sTfR-F index. The value is lower than the previous value established for hospitalized and anemic older adults.

Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma

Purpose: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. Patients and methods: All 53 patients received epirubicin (50xa0mg/m2 i.v.) on day 1 and cisplatin (60xa0mg/m2 i.v.) after epirubicin administration. Oral UFT 400–600xa0mg/day, determined by body surface area, and leucovorin 75xa0mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. Results: Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0–26.8%) with median response duration of 17.1xa0weeks (95% CI; 5.0–29.3xa0weeks, range; 7.1–51.7xa0weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6xa0weeks (95% CI; 17.3–31.9xa0weeks, range; 3.0–131.3xa0weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). Conclusion: The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC.

Mitomycin‐C, 5‐fluorouracil, and leucovorin as a salvage therapy in patients with metastatic colorectal adenocarcinoma

Aim:u2003 There is no further treatment option for metastatic colon patients who are refractory to standard chemotherapy and to whom novel biological agents are not available. We evaluated the outcomes of mitomycin‐C, 5‐fluorouracil (5‐FU) and leucovorin in patients with metastatic colon cancer previously treated with oxaliplatin/5‐FU/leucovorin and irinotecan/5‐FU/leucovorin.

Ulmus davidiana Nakai induces apoptosis and autophagy on non-small cell lung cancer cells ☆

ETHNOPHARMACOLOGICAL RELEVANCEnUlmus davidiana Nakai (UDN) is frequently used in the treatment of cancer in traditional oriental medicine. Although several reports indicate that UDN has inhibitory effects in some cancers, there has been no report on the inhibitory effects of UDN via both autophagy and apoptosis.nnnMATERIALS AND METHODSnCytotoxicity induced by UDN in human non-small cell lung cancer (NSCLC) H-1299 and H-460 cell lines was evaluated using the 2, 3-Bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay and trypan blue exclusion assay. Induction of apoptosis was also investigated using Hoechst staining and annexin-V binding assay and was confirmed with western blot analysis. Induction of autophagy was investigated through observation of autophagy vacuoles under inverted phase-contrast microscopy and was confirmed by observing the formation of autophagy vacuoles under a fluorescence microscope using monodansylcadaverine (MDC) staining and western blot analysis. The in vivo anti-tumorigenic effect of UDN was investigated in an athymic nude mouse xenograft model using H-1299 NSCLC cells.nnnRESULTSnUDN exhibited a marked inhibitory effect on cell growth in H-1299 and H-460 human NSCLC cell lines in a dose- and time-dependent manner in vitro and in vivo. It induced not only apoptosis, but also autophagy in both H-1299 and H-460 cells in a dose-dependent manner. UDN-mediated autophagy led to the accumulation of autophagosome, resulting in apoptosis induction and cell death.nnnCONCLUSIONSnFrom our current knowledge, we are the first to demonstrate that UDN has the potential to induce both autophagy and apoptosis in H-1299 and H-460 human NSCLC cell lines. We suggest that UDN can be considered a potential candidate for lung cancer-specific chemotherapy with efficacy as a cytotoxic agent.

Prevalence of iron deficiency anemia in community-dwelling older persons as measured by the transferrin receptor-ferritin index

community-dwelling older adults using the sTfR-F index. We conducted the anemia survey in three urban districts (Guro, Yangcheon and Gwanak) located in the southwestern part of Seoul in 2002. In this survey, a total of 1,254 subjects over the age of 60 years were selected from a cross-sectional study, the results of which have been published previously [2] . In brief, all the subjects lived in their own homes and were fully ambulatory with unlimited activities of daily living. Informed consent was obtained from all subjects, and then a complete medical history was taken and laboratory testing including a complete blood cell count with a reticulocyte count and iron profi les was performed. Anemia was defi ned according to the World Health Organization criteria, i.e. a hemoglobin level of ! 13 g/dl in men and ! 12 g/dl in women. In case of anemia, we performed the sTfR assay using a commercial kit based on a polyclonal antibody in a sandwich enzyme immunoassay (R&D Systems, Minneapolis, Minn., USA). According to the manufacturer, the central 95th percentile of the reference distribution of the sTfR concentration is 8.7–28.1 nmol/l. We then calculated the sTfR-F index (ratio of sTfR and log ferritin level). All the sTfR assays were performed in duplicate. IDA was considered present if the subject had anemia and the sTfR-F index was 1 1.5. Anemia is the most common hematologic problem encountered in older adults, and its prevalence increases with age [1, 2] . The common causes of anemia among older persons are anemia of chronic disease, iron defi ciency caused by gastrointestinal bleeding, cobalamin defi ciency, folate defi ciency and the myelodysplasia. Among these causes, the diagnosis of iron defi ciency anemia (IDA) is important because proper iron therapy can improve the symptoms, and treatment may help indicate an occult gastrointestinal pathology such as malignancy [3, 4] . There are few reports regarding the prevalence of IDA in older persons, and epidemiologic studies on East Asian populations are scarce. Moreover, the results of such studies have been variable according to the diagnostic criteria used. Previously published reports have used serum ferritin levels to diagnose IDA, but the cutoff levels were different in the various studies. The interpretation of the serum ferritin level in older adults is sometimes complicated because its level increases with age and with concomitant chronic illnesses [5, 6] . Therefore, we measured the soluble transferrin receptor (sTfR), which is not infl uenced by ageing or chronic diseases [7, 8] , and we calculated the ratio of sTfR to the log ferritin level (sTfR-F index) to make the test more specifi c. An index value of