Predicting nedaplatin sensitivity of cervical cancer using the histoculture drug response assay.

PURPOSE: There are currently no clinically available chemosensitivity assays for cervical cancer. In this study we evaluated whether the histoculture drug response assay (HDRA) could be used to predict chemosensitivity to nedaplatin (NDP) in cervical cancer. METHODS: Fifty-four surgical specimens and biopsies from patients with squamous cell carcinoma of the cervix were tested with the HDRA. The results were used to calculate the concentration resulting in 50% inhibition of tumor growth (IC50). We then determined the cut-off concentration for NDP, and investigated the chemosensitivity of NDP for each patient. Moreover, the correlations between chemosensitivity and the clinical response of NDP-containing chemotherapy, and the clinical outcomes of the patients with Stage I and II disease were also investigated. RESULTS: Fifty-one of 54 specimens (94.0%) were evaluable with this assay. The optimal cutoff concentration of NDP was determined to be 48 microg/ml. In 18 patients with measurable lesions, all nine patients in the high sensitive group by HDRA were judged as partial response (PR) to NDP containing chemotherapy. In contrast five of nine patients in the low sensitive group were classified as stable disease, and four were PR. The true positive rate was 100%, the true negative rate was 55.6%, and the accurate prediction rate was 77.8%. Furthermore, the disease-free survival of the high sensitive group tended to be better than that of the low sensitive group in the patients who received postoperative adjuvant chemotherapy with NDP. CONCLUSIONS: In the current study, the sensitivity of cervical tumors to nedaplatin was predicted by the HDRA.

Inhibition of eukaryotic dna polymerase alpha by persimmon (Diospyros kaki) extract and related polyphenols.

The effects of persimmon extract (Diospyros kaki) and related polyphenols on eukaryotic DNA polymerase alpha were examined. It was found that persimmon extract, epigallocatechin gallate, and epicatechin gallate strongly inhibited the activity of DNA polymerase alpha purified from calf thymus. Among these polyphenols, persimmon extract had the most potent effect on DNA polymerase alpha activity and the concentration of persimmon extract producing 50% inhibition of the activity was 0.191 microM. Persimmon extract showed a weaker effect on DNA polymerase beta and slightly inhibited primase and DNA polymerase I. The inhibition of DNA polymerase alpha by persimmon extract was competitive with the template-primer and noncompetitive with dTTP substrate. The Ki value of DNA polymerase alpha for persimmon extract was estimated to be 70 nM. Moreover, persimmon extract inhibited [3H]thymidine incorporation of human peripheral lymphocyte cells stimulated by PHA.

Honokiol induces apoptosis in human lymphoid leukemia Molt 4B cells.

The exposure of human lymphoid leukemia Molt 4B cells to honokiol led to both growth inhibition and the induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with honokiol. The fragmentation by honokiol of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. These findings suggest that growth inhibition by honokiol of Molt 4B cells results from the induction of apoptosis in the cells.

Black tea theaflavins induce programmed cell death in cultured human stomach cancer cells.

The exposure of human stomach cancer KATO III cells to black tea theaflavin extract, free theaflavin, and theaflavin digallate that are main components of the extract, led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological changes showing apoptotic bodies were observed in the cells treated with black tea theaflavin extract, theaflavin and theaflavin digallate. The fragmentations by these theaflavin compounds of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis were observed to be concentration- and time-dependent. These data suggest that drinking of black tea in large amounts is recommended to protect humans from stomach cancer.

Induction of apoptosis in human stomach cancer cells by green tea catechins.

The exposure of human stomach cancer KATO III cells to green tea catechin extract and epigallocatechin gallate (EGCG), a main component of the extract led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological changes showing apoptotic body were observed in the cells treated with green tea catechin extract and EGCG. The fragmentation of DNA to oligonucleosomal-sized fragments, characteristic of apoptosis was determined to be concentration- and time-dependent. These data suggest that drinking of green tea in large amounts is recommended possibly to protect humans from stomach cancer.

Inhibitory effects of persimmon (Diospyros kaki) extract and related polyphenol compounds on growth of human lymphoid leukemia cells.

We have investigated the effects of persimmon (Diospyros kaki) extract (PS) and related polyphenol compounds such as catechin (C), epicatechin (EC), epicatechingallate (ECG), epigallocatechin (EGC), and epigallocatechingallate (EGCG) on the growth of human lymphoid leukemia Molt 4B cells. We found that PS, ECG, EGC, and EGCG strongly inhibited the growth of the cells in a dose-dependent manner, while C and EC inhibited the growth of the cells only moderately. Ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, was inhibited by 10-20% by these polyphenol compounds. The morphology of the Molt 4B cells indicated severe damage 3 days after treatment with PS, ECG, EGC, and EGCG. Irregular shape of the cells and DNA fragmentation were observed in PS, ECG, EGC, or EGCG-treated cells. These results suggest that PS, ECG, EGC, and EGCG induce apoptosis (programmed cell death) of Molt 4B cells.

Induction of programmed cell death (apoptosis) in human lymphoid leukemia cells by catechin compounds.

The need for antitumor compounds with novel mechanisms of action is great. The exposure of human lymphoid leukemia Molt 4B cells to epigallocatechin (EGC), epigallocatechin gallate (EGCG), and persimmon extract (PS) led to both growth inhibition and the induction of programmed cell death (apoptosis). The fragmentation of DNA to oligonucleosomal-sized fragments, characteristic of programmed cell death, was determined to be concentration- and time-dependent. These data provide the first evidence that catechin compounds and persimmon extract containing all these catechin compounds induce programmed cell death.

[Calcifying mucinous adenocarcinoma of the stomach--case report].

In a patient with mucinous adenocarcinoma of the stomach and metastatic lesions in the lung and lymph nodes , X-ray films demonstrated multiple punctuate calcifications. We collected reported cases of gastric cancers with radiographically visualized calcium deposits and discussed their characteristics.