[Show abstract][Hide abstract] ABSTRACT: Leukemic promyelocytes have the unique ability to undergo differentiation after exposure to retinoic acid and both differentiation and apoptosis after exposure to arsenic trioxide (ATO). Recent studies have shown that inhibition of Src family kinases (SFKs) resulted in enhancement of retinoic acid-induced myeloid differentiation.
In this study, we investigated the question of whether the SFK inhibitor PP2 enhanced the differentiation of NB4 cells when combined with ATO as well as when combined with all-trans-retinoic acid (ATRA). In addition, we attempted to determine the difference in retinoic acid-induced gene expression between cells treated with PP2 in combination with ATRA and in combination with ATO.
SFK inhibitor PP2 induced significant enhancement of ATRA- or ATO-induced differentiation of NB4 cells. A significantly stronger synergistic effect was observed when PP2 was combined with ATRA than when combined with ATO. Flow cytometric analysis demonstrated a significant increase in CD11b-positive granulocytes up to 60.73% and 31.58%, respectively. These results were confirmed by nitroblue tetrazolium staining. These effects were not related to apoptosis. Results of Annexin-V-fluorescein staining revealed that PP2 combined with ATRA or PP2 combined with ATO did not induce apoptosis in NB4 cells. Retinoic acid-induced gene expression was different in both groups. Intercellular adhesion molecule-1 expression showed a significant increase in cells treated with PP2 in combination with ATRA, whereas cathepsin D expression showed a significant increase in cells treated with PP2 in combination with ATO.
Our data showed that SFK inhibitor PP2 enhanced acute promyelocytic leukemia cell differentiation when combined with either ATRA or ATO with difference in activation of retinoic acid-induced genes.
Cancer Research and Treatment 06/2013; 45(2):126-33. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we examined the efficacy and toxicity of S-1 with cisplatin as a second-line palliative chemotherapy for gemcitabine-refractory pancreatic cancer patients. Patients who had been previously treated with gemcitabine-based chemotherapy as palliative first-line chemotherapy received S-1/cisplatin [body surface area (BSA) <1.25 m(2), S-1 40 mg/day; BSA ≤1.25 to <1.5 m(2), 50 mg/day; BSA ≥1.5 m(2) 60 mg/day, orally, bid, daily on days 1-14 followed by a 7-day washout and cisplatin 60 mg/m(2)/day intravenously on day 1] every three weeks. The enrollment of 32 patients was planned, but the study was terminated early, prior to the first stage, following the enrollment of 11 patients. The median age of the patients was 56 (range, 42-74) years. Nine patients had a performance status (PS) of one. In total, there were 21 chemotherapy cycles and the median treatment duration was 21 (range, 7-96) days. Of the 11 patients, five could not be evaluated due to discontinuation prior to the response evaluation. One of the six evaluable patients achieved stable disease (9.1% in intention to treat analysis and 16.7% in per-protocol analysis), while five had progressive disease. Grade 3-4 hematological toxicities were anemia in one, neutropenia in one and thrombocytopenia in one cycle. Grade 3-4 nonhematological toxicities were fatigue in three, nausea in four, anorexia in two, diarrhea in one and peripheral neuropathy in two cycles. With a median follow-up period of 8.9 (range, 3.2-11.3) months, the median time to progression was 44 days [95% confidence interval (CI) 25.4-62.6] and the median overall survival was 81 days (95% CI 9.3-152.7). Combination chemotherapy with S-1 and cisplatin as applied in this study did not result in promising antitumor activity, a high degree of toxicity and poor compliance.
[Show abstract][Hide abstract] ABSTRACT: We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-α, IFN-γ, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-α, IFN-γ, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 ± 19.5 vs 80.9 ± 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.
Journal of Korean medical science 02/2012; 27(2):128-34. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prognosis of gastric cancer patients with bone marrow metastases is extremely poor. The current study was conducted to evaluate the clinical outcomes of advanced gastric cancer patients with bone marrow metastases.
We retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases who were treated at Soonchunhyang University Hospital between September 1986 and February 2009.
The median age was 46 years (range, 24 to 61 years). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas. The majority of the patients had thrombocytopenia, anemia, and elevated lactate dehydrogenase levels. Sixteen patients (61.5%) received palliative chemotherapy (median, 4 cycles; range, 1 to 13 cycles). The median overall survival after detection of bone marrow metastases for the cohort of patients was 37 days (95% confidence interval, 12.5 to 61.5 days). The median overall survival after detection of bone marrow involvement was 11 days in the best supportive care group (range, 2 to 34 days) and 121 days (range, 3 to 383 days) in the palliative chemotherapy group (p<0.001). The causes of death were tumor progression (11 patients, 45%), brain hemorrhage (6 patients, 25%), infection (5 patients, 21%), and disseminated intravascular coagulation (1 patient, 4%). There were no chemotherapy-related deaths.
Palliative chemotherapy could be considered in advanced gastric cancer patients with bone marrow metastases as a treatment option.
Cancer Research and Treatment 12/2011; 43(4):244-9. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the considerable advances in the treatment of colorectal cancer, substantial changes in treatment strategies are required to overcome the problems of drug resistance and toxicity.
Combinations of Pan-deacetylase inhibitor LBH589 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were studied in three colon cancer cell lines, HCT116, colo205, and HT29 (HCT116 and colo205 are TRAIL sensitive, whereas HT29 is TRAIL resistant).
It was found that TRAIL-induced cytotoxicity was enhanced by LBH589 cotreatment in the TRAIL-sensitive cell lines, and in the TRAIL-resistant HT29 cell line. The cytotoxicity of low-dose TRAIL plus LBH589 was found to be comparable to that of high-dose TRAIL plus LBH589. Additionally, TRAIL and LBH589 were significantly less toxic to normal UCB mononuclear cells than to the three colon cancer cell lines examined.
LBH589 enhances TRAIL-induced apoptosis in human colon cancer cell lines, especially those resistant to TRAIL-induced apoptosis.
Anticancer research 10/2011; 31(10):3385-94. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We retrospectively determined the efficacy and safety of the combination of oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line chemotherapy for patients with metastatic or recurrent gastric cancer.
Between January 2006 and August 2009, 39 patients with histologically-confirmed, metastatic or recurrent gastric cancer underwent chemotherapy, and the results were retrospectively investigated. The chemotherapy regimen consisted of oxaliplatin (100 mg/m(2)) and FA (200 mg/m(2); 2-hour infusion), then 5-FU (2,400 mg/m(2); 46-hour continuous infusion) every 2 weeks.
Thirty-nine patients received a total of 210 treatment cycles. The median number of cycles was 6 (range, 1 to 16). Of the 32 evaluable patients, zero patients achieved a complete response and 11 patients achieved a partial response (response rate, 28.2%). The median time-to-progression and overall survival were 4.3 months (95% confidence interval [CI], 2.0 to 6.5 months) and 9.8 months (95% CI, 3.5 to 16.0 months), respectively. The main hematologic toxicity was anemia, which was observed in 119 cycles (56.7%). Grade 3/4 neutropenia was observed in 32 cycles (15.2%). The main non-hematologic toxicity was constipation, which was observed in 91 cycles (46.2%). Peripheral neuropathy occurred in 71 cycles (33.8%); all cases were grade 1 or 2. No treatment-related deaths were reported.
This study showed that combination chemotherapy with oxaliplatin, 5-FU, and FA is an active and well-tolerated regimen as first-line treatment in patients with metastatic or recurrent gastric cancer.
Cancer Research and Treatment 09/2011; 43(3):154-9. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This phase II clinical trial was conducted to evaluate the activity and safety of a combination treatment of paclitaxel (Genexol®) plus carboplatin in patients with advanced non-small cell lung cancer.
Chemotherapy-naïve patients having histologically confirmed advanced or metastatic non-small cell lung cancer were enrolled. Genexol® was administered at 225 mg/m(2) intravenous (IV) infusion over 3 hours, followed by carboplatin (area under the concentration-time curve=6) IV on day 1 every 3 weeks.
Twenty-eight patients were enrolled between January 2003 and January 2005. A total of 110 cycles of chemotherapy were given. The median number of chemotherapy cycles was 4. A total of 25 study patients were evaluable. On an intent-to-treat basis, there were ten partial responses (response rate 35.7%). The median time-to-progression was 3.2 months (95% confidence interval [CI], 1.5 to 4.9) and the median overall survival was 8.2 months (95% CI, 4.1 to 12.3). The main hematologic grade 3/4 toxicity was neutropenia, which was observed in 14 (50.0%) patients. The main non-hematologic toxicity was peripheral neuropathy, which was observed in 12 patients (42.9%). Grade 3/4 neuropathy occurred in 8 patients (28.6%) and three patients discontinued treatment because of neuropathy.
In this trial, the combination of Genexol® and carboplatin showed significant activity as first line treatment for patients with advanced or metastatic non-small cell lung cancer. However, a modest dose reduction of Genexol® is needed due to sensory neuropathy.
Cancer Research and Treatment 03/2011; 43(1):19-23. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catheterization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catheterization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P<0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P<0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC.
Journal of Korean medical science 12/2010; 25(12):1748-53. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: A central venous catheterization (CVC) is frequently used for delivering anti-cancer chemotherapeutic agents, blood products, parenteral nutrition, and other intravenous therapy in patients with cancer. Major complications of CVC use are thrombosis, infection, and mechanical complications. The aim of this study was to evaluate the frequency of CVC complications and related factors. Methods: The records of cancer patients who received a CVC at our university hospital from March 2001 to October 2006 were retrospectively investigated. Chi square test was used to determine whether there was a related factor for thrombosis or infection, and Kaplan-Meier analysis for univariate analysis, or Cox-regression analysis for multivariate analysis was used for catheter life span. Results: Three hundred and ten CVCs (235 nontunneled, 75 tunneled) were inserted in 310 patients (157 males, 153 females). Among them, 104 had hematologic cancers and 206 had solid cancers. The mean age of the patients was 52 years (range, 19~82 years). CVC complications occurred in 60 cases (19%). CVC-related thrombosis occurred frequently in patients with infection (P=0.003), whereas diagnosis, catheter type, transfusion, and TPN history did not affect infection or thrombosis. The mean duration of the catheter was 102 days (range, 2~1,330 days), and the duration was prolonged in patients with tunneled catheters (P=0.000), or without transfusion through CVC (P=0.030). Conclusion: The major complications for long-term use of a CVC were infectionand thrombosis. Tunneled catheter was effective tool for long term use, especially in cases without transfusion through CVC. The studies on the prevention or treatment ofthrombosis and infection are, therefore, warranted by using CVC for an extended period of time.
The Korean Journal of Hospice and Palliative Care. 01/2010; 13(1).
[Show abstract][Hide abstract] ABSTRACT: Choriocarcinoma in the testis is very rare, and it represents less than 1% (0.3%) of all the testicular germ cell tumors. It is a particularly aggressive variant of non-seminoma tumor, which is characterized by a high serum beta-HCG level and multiple lung metastases. The optimal management for this disease remains undefined. We report here on a case of choriocarcinoma with multiple lung metastases, and the patient has achieved continuous remission for 2 years after combination chemotherapy of BEP (bleomycin, etoposide and cisplatin) and sequential high-dose chemotherapy with autologous peripheral stem cell rescue.
Cancer Research and Treatment 12/2009; 41(4):229-32. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose The aim of this study is to investigate the efficacy and safety of gemcitabine and oxaliplatin combination chemotherapy as
first-line therapy in patients with inoperable biliary tract cancer (BTC).
Methods The treatment of this non-randomized phase II study consisted of gemcitabine 1,000mg/m2 intravenously (i.v.) on day 1 and oxaliplatin 85mg/m2 i.v. on day 2 every 2weeks until disease progression, unaccep toxicity or patients’ refusal.
Results From Sept 2006 to Oct 2007, 40 patients were enrolled. In the ITT analysis, the objective response rate was 15.0% and the
disease control rate was 52.5%. The median overall survival (95% CI) was 8.5months (6.4–10.7) and the time to progression
was 4.2months (0.5–7.9). For the 305 cycles, observed grade 3/4 toxicity was uncommon.
ConclusionsGemcitabine and dose adjusted oxaliplatin combination chemotherapy had moderate anti-tumor activity and was well tolerated
as a first-line treatment for patients with inoperable BTC.
Cancer Chemotherapy and Pharmacology 07/2009; 64(2):371-377. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.
Journal of Korean medical science 07/2009; 24(3):535-8. · 0.84 Impact Factor