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Three Cases of Synchronous Solid Tumor and Multiple Myeloma.

Sang Hoon JI ; Joon Oh PARK ; Jeeyun LEE ; Mi Jung OH ; Do Hyoung LIM ; Byeong Bae PARK ; Keun Woo PARK ; Se Hoon LEE ; Kihyun KIM ; Won Seog KIM ; Chul Won JUNG ; Young Suk PARK ; Young Hyuck IM ; Won Ki KANG ; Mark H LEE ; Keunchil PARK

Cancer Research and Treatment.2004;36(5):338-340.

The association between a multiple myeloma and a secondary solid tumor is not well established. Some reports showed an increased risk of secondary solid neoplasms in multiple myeloma patients, but others have not. Three cases of the synchronous occurrence of multiple myelomas and solid tumors, namely, a small cell carcinoma of the lung, an adenocarcinoma of the colon and a squamous carcinoma of the pyriform sinus were experienced at our hospital. Therefore, herein is reported the clinical courses and treatment results. The stage of multiple myeloma was Durie-Salmon stage I in all of three cases; therefore, the solid tumors were treated as a primary target because the prognosis of early stage multiple myeloma is generally better than that of advanced solid tumor, while a smoldering or stage I myeloma do not need primary therapy until progression of the multiple myeloma. Two patients died of their solid tumors, but one patient is alive.
Adenocarcinoma ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Colon ; Humans ; Lung ; Multiple Myeloma* ; Neoplasms, Multiple Primary ; Neoplasms, Second Primary ; Prognosis ; Pyriform Sinus

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Dexamethasone Inhibits TRAIL- and Anti-cancer Drugs-induced Cell Death in A549 Cells through Inducing NF-kappaB-independent cIAP2 Expression.

Youn Seup KIM ; Jae Seuk PARK ; Young Koo JEE ; Kye Young LEE

Cancer Research and Treatment.2004;36(5):330-337.

PURPOSE: We have examined that dexamethasone inhibits apoptotic cell death of A549 lung epithelial cells through TRAIL and anti-cancer drugs. The purpose of the study is to determine the roles of GR, cIAP and NF- kappaB in this mechanism. MATERIALS AND METHODS: In the A549 lung epithelial cell line, TRAIL, taxol, doxorubicine & gemcitabine were used to investigate cell toxicity. Cells were pretreated 12 hours in advance with dexamethasone. RU486 was pretreated 30 minutes before dexamethasone. Crystal violet assay was used for cell toxicity tests. Apoptosis assay was performed by taking morphologic surveys with fluorescent microscopy after double staining with Hoechst 33342 & propium iodide. RT-PCR was used to investigate the gene expression of cIAP1 & cIAP2 by dexamethasone. Ad-IkappaBalpha-SR transduction study was used for the role of NF-kappaB. RESULTS: TRAIL and anti-cancer drug-induced apoptosis was partially suppressed in A549 cells pretreated with dexamethasone. The inhibitory effect on cell death disappeared in A549 cells pretreated with RU486. Using RT-PCR, changes of cIAP1 and cIAP2 genes manifestation in A549 cells subsequent to pretreatment with dexamethasone were examined. The results showed an increase in cIAP2 expression during a course of time which was suppressed by RU486 pretreatment. Induction of cIAP2 expression changes by dexamethasone was uniquely observed despite the blockade of NF-kappa by Ad-IkappaB alpha-SR transduction. CONCLUSIONS: These results suggest that dexametha sone inhibits TRAIL- and anti-cancer drug-induced apoptosis in A549 cells by inducing cIAP2 gene expression through a GR-mediated, NF-kappa-independent pathway.
Apoptosis ; Cell Death* ; Dexamethasone* ; Doxorubicin ; Epithelial Cells ; Gene Expression ; Gentian Violet ; Lung ; Microscopy ; Mifepristone ; NF-kappa B ; Paclitaxel ; Prednisone ; Toxicity Tests

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Phenylacetate Induces Growth Inhibition and Apoptosis of Human Osteosarcoma Cells.

Jong Hyuk PARK ; Min Young PARK ; Ho Sung PARK ; Kyu Yun JANG ; Myoung Ja CHUNG ; Woo Sung MOON ; Dong Geun LEE ; Myoung Jae KANG

Cancer Research and Treatment.2004;36(5):324-329.

PURPOSE: Phenylacetate has potent antiproliferative effects in many malignant tumors. However, the exact mechanism as to how phenylacetate induces cell growth arrest remains unclear and very little is known about its effects on human osteosarcoma cells. In this study, we investigated whether phenylacetate is effective against two osteosarcoma cell lines (HOS and U-2 OS) in vitro. MATERIALS AND METHODS: The viability of phenylacetate- treated cell lines was assessed by trypan blue exclusion assay, and the cell cycle distribution was measured by flow cytometry. To measure cell apoptosis, poly (ADP- ribose) polymerase cleavage assay and flow cytometry were employed. The expressions of cell cycle-regulatory proteins and the apoptosis-related genes were evaluated by western blot analysis. RESULTS: Phenylacetate was found to inhibit the growth of osteosarcoma cells, induce cell cycle arrest in the G1 phase, and induce apoptosis. A significant decrease in Bcl-2 expression and a mild up-regulation of Bax were also observed in both phenylacetate-treated cell lines. Reduced phosphorylation of the pRb and the increased expression of p21Cip1 were observed subsequent to treatment with phenylacetate. CONCLUSION: These findings support the idea that pheny lacetate may be an effective chemotherapeutic agent to be employed in the future against osteosarcoma, because phenylacetate acts to inhibit the growth of osteosarcoma cells through cell cycle arrest and apoptosis.
Apoptosis* ; Blotting, Western ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Flow Cytometry ; G1 Phase ; Humans* ; Osteosarcoma* ; Phosphorylation ; Trypan Blue ; Up-Regulation

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Activity of Green Tea Polyphenol Epigallocatechin-3-gallate Against Ovarian Carcinoma Cell Lines.

Yong Wook KIM ; Su Mi BAE ; Joon Mo LEE ; Sung Eun NAMKOONG ; Sei Jun HAN ; Byoung Rai LEE ; Insu P LEE ; Sang Hee KIM ; Young Joo LEE ; Chong Kook KIM ; Yong Wan KIM ; Woong Shick AHN

Cancer Research and Treatment.2004;36(5):315-323.

PURPOSE: A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG), is known to possess anti-cancer properties. In this study, the time-course of the anticancer effects of EGCG on human ovarian cancer cells were investigated to provide insights into the molecular-level understanding of the growth suppression mechanism involved in EGCG-mediated apoptosis and cell cycle arrest. MATERIALS AND METHODS: Three human ovarian cancer cell lines (p53 negative, SKOV-3 cells; mutant type p53, OVCAR-3 cells; and wild type p53, PA-1 cells) were used. The effect of EGCG treatment was studied via a cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay. RESULTS: EGCG exerts a significant role in suppressing ovarian cancer cell growth, showed dose dependent growth inhibitory effects in each cell line and induced apoptosis and cell cycle arrest. The cell cycle was arrested at the G1 phase by EGCG in SKOV-3 and OVCAR-3 cells. In contrast, the cell cycle was arrested in the G1/S phase in PA-1 cells. EGCG differentially regulated the expression of genes and proteins (Bax, p21, Retinoblastoma, cyclin D1, CDK4 and Bcl-XL) more than 2 fold, showing a possible gene regulatory role for EGCG. The continual expression in p21WAF1 suggests that EGCG acts in the same way with p53 proteins to facilitate apoptosis after EGCG treatment. Bax, PCNA and Bcl-X are also important in EGCG-mediated apoptosis. In contrast, CDK4 and Rb are not important in ovarian cancer cell growth inhibition. CONCLUSION: EGCG can inhibit ovarian cancer cell growth through the induction of apoptosis and cell cycle arrest, as well as in the regulation of cell cycle related proteins. Therefore, EGCG-mediated apoptosis could be applied to an advanced strategy in the development of a potential drug against ovarian cancer.
Apoptosis ; Blotting, Western ; Cell Count ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line* ; Cyclin D1 ; G1 Phase ; Humans ; Ovarian Neoplasms ; Proliferating Cell Nuclear Antigen ; Retinoblastoma ; Tea*

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Effective Inhibition of Cancer Cell Growth by a Novel Tripartite Transfection Complex Containing Ribbon Antisense Molecules to hTR.

Jong Gu PARK

Cancer Research and Treatment.2004;36(5):308-314.

PURPOSE: In the present study, ribbon antisense to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. MATERIALS AND METHODS: Ribbon antisense molecules to the human hTR gene (hTR-RiAS) were constructed and complexed with a short modified peptide and cationic liposomes to improve the cellular uptake of the antisense molecules. The DPL complexes containing hTR-RiAS were transfected into target cancer cells. Various assays were performed to confirm the effects of the hTR-RiAS on the gene expression and cell proliferation. RESULTS: When cancer cells were treated with hTR-RiAS, the cellular level of hTR mRNA was reduced by more than 95%, as shown by RT-PCR. Further, the telomerase activity was also affected by the antisense treatment. In contrast, both mismatched and scrambled oligonucleotides failed to reduce the levels of hTR mRNA and telomerase activity. When checked for cancer cell viability, hTR- RiAS inhibited cell growth by more than 70%, in a very rapid manner. The reduced cell viability was found to be due to apoptosis of cancer cells. CONCLUSION: These results show that hTR-RiAS is a powerful anticancer reagent, with the potential for broad efficacy to diverse malignant tumors.
Apoptosis ; Cell Proliferation ; Cell Survival ; Gene Expression ; Humans ; Liposomes ; Oligonucleotides ; RNA ; RNA, Messenger ; Telomerase ; Transfection*

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Expression of Caspase-3 and c-myc in Non-Small Cell Lung Cancer.

Jin young YOO ; Chi Hong KIM ; So Hyang SONG ; Byoung Yong SHIM ; Youn Ju JEONG ; Meyung Im AHN ; Suji KIM ; Deog Gon CHO ; Min Seop JO ; Kyu Do CHO ; Hong Joo CHO ; Seok Jin KANG ; Hoon Kyo KIM

Cancer Research and Treatment.2004;36(5):303-307.

PURPOSE: Caspase-3 is a cysteine protease that plays an important role in the process of apoptotic cell death, but little has been studied clinically on caspase-3 in lung cancer. Increased c-myc expression can result in mitosis or apoptosis, and its contribution to the pathogenesis and prognosis of lung cancer has gained interest. In the present study, the expressions of caspase-3 and c-myc, along with their possible correlations with prognostic variables, were analyzed in resected non-small cell lung carcinomas (NSCLC). MATERIALS AND METHODS: Archival tumor tissues from 147 previously untreated NSCLC patients were examined by immunohistochemistry for the expressions of caspase-3 and c-myc proteins. Clinical information was obtained through the computerized retrospective database from the tumor registry. RESULTS: The expressions of caspase-3 and c-myc were detected in 60 (88/147) and 16% (24/147) of tumors, respectively. No association was found between caspase-3 and c-myc expressions. A multivariate analysis demonstrated the N status and pathologic stage to be significantly correlated with poor survival (p-value=.018 and .002, respectively), but positive expression of caspase-3 was associated with a good prognosis (p=.03). CONCLUSION: Our data suggest the involvement of caspase-3 in the tumorigenesis of NSCLC. It is also noteworthy that caspase-3 expression might be a favorable prognostic indicator in these tumors.
Apoptosis ; Carcinogenesis ; Carcinoma, Non-Small-Cell Lung* ; Caspase 3* ; Cell Death ; Cysteine Proteases ; Humans ; Immunohistochemistry ; Lung ; Lung Neoplasms ; Mitosis ; Multivariate Analysis ; Prognosis ; Proto-Oncogene Proteins c-myc ; Retrospective Studies

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Prognostic Significance of CD24 Expression in Gastric Carcinoma.

Nevine S DARWISH ; Min A KIM ; Mee Soo CHANG ; Hye Seung LEE ; Byung Lan LEE ; Yong Il KIM ; Woo Ho KIM

Cancer Research and Treatment.2004;36(5):298-302.

PURPOSE: The human CD24 antigen is a small heavily glycosylated cell surface protein, which is expressed in hematological malignancies, as well as in a large variety of solid tumors. Its expression is now known to be related to the prognosis of several kinds of tumors. This study is designed to examine the prognostic significance of CD24 in Korean gastric cancer patients. MATERIALS AND METHODS: In the present study, we examined CD24 expression in 300 consecutive cases of gastric carcinoma by immunohistochemical staining using the tissue-array method. We also investigated the clinicopathological profiles related to CD24 expression. RESULTS: One hundred and three cases out of 300 (34.3%) showed the positive expression of CD24. The altered expression of CD24 was significantly associated with differentiated cancer (p=0.003), the intestinal subtype according to the Lauren classification (p<0.001), the advanced stage cancer (p=0.027), with lymphatic invasion (p=0.038) and with vascular invasion (p=0.006). The survival analysis revealed that the patients with CD24 positive expression showed significantly poorer survival than those without CD24 expression. Moreover, a combined evaluation revealed that PTEN /CD24 cases showed the best survival compared to other groups (p=0.01). CONCLUSION: Positive CD24 expression occurs in a subset of gastric carcinomas and it correlates significantly with lymphatic invasion, blood vessel invasion and poor survival.
Antigens, CD24 ; Blood Vessels ; Classification ; Hematologic Neoplasms ; Humans ; Immunohistochemistry ; Prognosis ; Stomach Neoplasms ; Survival Analysis

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A Phase II Study of Weekly Paclitaxel, Cisplatin and Concurrent Radiation Therapy for Locally-Advanced Unresectable Non-Small Cell Lung Cancer: Early Closure due to Lack of Efficacy.

Se Hoon PARK ; Mi Kyung KIM ; Sun Young KYUNG ; Young Hee LIM ; Chang Hyeok AN ; Jeong Woong PARK ; Seong Hwan JEONG ; Jae Woong LEE ; Kyu Chan LEE ; Eun Kyung CHO ; Soo Mee BANG ; Dong Bok SHIN ; Jae Hoon LEE

Cancer Research and Treatment.2004;36(5):293-297.

PURPOSE: In this phase II study, the efficacy and safety of weekly paclitaxel concomitant with cisplatin and thoracic radiotherapy (TRT) was evaluated in patients with locally-advanced unresectable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with stage III NSCLC (without pleural effusion or cervical lymphadenopathy) received TRT (63 Gy in 35 fractions over 7 weeks) with concurrent weekly cisplatin 20 mg/m2 and paclitaxel 40 mg/m2/week infused over 3 hours. In patients without evidence of disease progression, the administration of a further 2 cycles of consolidation chemotherapy, consisting of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2, were planned after completion of the TRT. RESULTS: Between Feb 2000 and Dec 2002, 20 patients were entered into the study; 13 completed all 7 weeks of treatment (median 7.6 weeks; range 3.3 to 9.4). Seven out of 16 (43.8%) objective responses were observed, with 15 (75%) patients experiencing at least one episode of grade 3/4 toxicity. The main toxicities were moderate to severe neutropenia and gastrointestinal toxicity. CONCLUSION: The unsatisfactory response rate and the high incidence of grade 3/4 hematologic and non-hematologic toxicities, including 7 early discontinuations of treatment and exceeding the study stopping rules, prompted the early closure of the study. In view of the activity observed, the protocol was amended to protracted continuous infusion paclitaxel, cisplatin and concurrent TRT.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Consolidation Chemotherapy ; Disease Progression ; Humans ; Incidence ; Neutropenia ; Paclitaxel* ; Pleural Effusion ; Radiotherapy

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A Phase II Trial of Docetaxel and Ifosfamide for Patients with Platinum-Resistant or Refractory Non-Small Cell Lung Cancer in a Salvage Setting.

Gyeong Won LEE ; Jung Hun KANG ; Seok Hyun KIM ; Hea Yong LEE ; Ho Cheol KIM ; Won Sup LEE ; Jong Duk LEE ; Young Sil HWANG ; Joung Soon JANG ; Jong Seok LEE

Cancer Research and Treatment.2004;36(5):287-292.

PURPOSE: We conducted a phase II study of docetaxel and ifosfamide chemotherapy for patients with platinum- resistant or refractory non-small-cell lung cancer (NSCLC) to evaluate the response and toxicity profiles as a salvage treatment. MATERIALS AND METHODS: Between July 2000 and July 2004, 40 patients who had previously received platinum- based regimen as the first-line or second-line therapy were enrolled in this study. The treatment consisted of a docetaxel 75 mg/m2 intravenous infusion on day 1 and intravenous ifosfamide 3 g/m2 with Mesna(R) uroprotectione on day 1 through 3. This regimen was repeated every 3 weeks. RESULTS: One hundred thirty cycles of treatment were given, with a median of 3 cycles (range: 2~6 cycles). All the patients were evaluable for the response rate and toxicity profile. The major toxicity was myelosuppression. Grade 3~4 neutropenia occurred in 30 patients (75%) during treatment. Febrile neutropenia occurred in 16 patients (40%). Five of 40 patients (12.5%) had a partial response (95% confidence interval, 3.3~21.7%). The median time to disease progression was 2.65 months (range: 2.02~3.20 months), and the median survival was 5.24 months (range: 2.99~7.49 months). CONCLUSION: Salvage chemotherapy with docetaxel and ifosfamide showed a low efficacy and a high proportion of severe neutropenia in patients with platinum-resistant or refractory advanced NSCLC.
Carcinoma, Non-Small-Cell Lung* ; Disease Progression ; Drug Therapy ; Febrile Neutropenia ; Humans ; Ifosfamide* ; Infusions, Intravenous ; Lung Neoplasms ; Neutropenia ; Salvage Therapy

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Transcription Factors in the Cellular Signaling Network as Prime Targets of Chemopreventive Phytochemicals.

Young Joon SURH

Cancer Research and Treatment.2004;36(5):275-286.

Accumulating evidence from epidemiologic and laboratory studies support an inverse relationship between a regular consumption of fruits and vegetables and the risk of specific cancers. Numerous phytochemicals derived from edible plants have been reported to possess ability to interfere with a specific stage of carcinogenic process. Multiple mechanisms have been proposed to account for the anti-carcinogenic actions of dietary constituents, but more attention has recently focussed on intracellular signaling cascades as common molecular targets of a wide variety of chemopreventive phytochemicals.
Chemoprevention ; Fruit ; Mitogen-Activated Protein Kinases ; Phytochemicals* ; Plants, Edible ; Signal Transduction ; Transcription Factor AP-1 ; Transcription Factors* ; Vegetables

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