Biomedical subjects

Jae-Sung Kim

Publications and source records attributed to Jae-Sung Kim.

23 records · Page 2Linked to original sources

PubMed2003

Hyperfractionated radiotherapy with concurrent chemotherapy for para-aortic lymph node recurrence in carcinoma of the cervix.

PURPOSE: To evaluate efficacy, toxicity, and patterns of relapse in patients treated with hyperfractionated radiotherapy (HFRT) with concurrent chemotherapy for para-aortic lymph node (PALN) recurrence of cervical carcinoma. METHODS AND MATERIALS: Between September 1997 and October 2000, 12 cervical carcinoma patients with isolated PALN recurrence who had previously received radical or postoperative radiotherapy were treated with HFRT and concurrent chemotherapy. The initial FIGO stage was Stage IB in 4 (33%) patients, Stage IIA in 2 (17%), and Stage IIB in 6 (50%). The radiation field encompassed the gross recurrent PALN with the superior margin at the upper end of the T12 body and the inferior margin between L5 and S1. The fractionated dose was 1.2 Gy in 2 daily fractions, and the median total dose was 60 Gy. The weekly concurrent chemotherapy consisted of paclitaxel in 11 patients and cisplatin in 1. The median number of cycles of chemotherapy was 5. RESULTS: The latent period to PALN recurrence from the time of initial treatment for all patients ranged from 2 to 92 months (median: 12 months). One month after treatment, the clinical tumor response evaluated was complete in 33% (4/12) and partial in 67% (8/12). The 3-year overall survival rate and median survival were 19% and 21 months, respectively. The latent period to PALN recurrence was the only significant prognostic factor; the median survival of patients who relapsed in < or =24 months from the initial treatment of cervical carcinoma was 13 months vs. 45 months for those relapsed at >24 months (p = 0.026). Grade 3-4 hematologic toxicity developed in 2 patients. Six (50%) patients experienced Grade 2 nausea. There were no late gastrointestinal or neurologic complications during the follow-up period. Subsequent distant metastases after PALN treatment developed in 58% (7/12). CONCLUSION: HFRT of 60 Gy to PALN with concurrent chemotherapy could be regarded as an effective treatment modality without significant acute or late toxicity. Patients with a latent period >24 months until PALN recurrence had a more favorable survival rate than those with a latent period </=24 months. Subsequent distant metastasis after PALN recurrence was the main cause of death and is a problem to overcome in the future.

Adult↗

PubMed2003

Potential radiation-sensitizing effect of semisynthetic epothilone B in human lung cancer cells.

BACKGROUND AND PURPOSE: To evaluate a semisynthetic epothilone B, BMS-247550, as a potential radiosensitizer in vitro and in vivo. MATERIALS AND METHODS: Human NCI-H460 lung cancer cells were treated with either BMS-247550 or paclitaxel and in combination with radiation at multiple doses for different time periods. Surviving fractions were then analyzed using a clonogenic assay. Cell cycle redistribution by BMS-247550 was measured with propidium iodide and flow cytometry. Percent apoptosis was also measured using 7-amino-actinomycin D staining with flow cytometry. For in vivo studies, the H460 xenograft model was used in athymic nude mice. Tumors were treated with BMS-247550 (5 mg/kg) i.p. injection on days 0, 2, and 4 and/or radiation (2 Gy/day, days 0-4). RESULTS: The in vitro radiation dose enhancement ratios (DER) of 1-h BMS-247550 and paclitaxel were 2.03 and 1.34, respectively. Treatment with BMS-247550 enhanced the G2/M block and induced apoptosis; whereas in combination with radiation, the induction of apoptosis was additive. BMS-247550 in combination with radiation in vivo enhanced the tumor growth delay when compared with either drug or radiation alone. CONCLUSIONS: These results demonstrated that BMS-247550 could enhance the effects of radiation in human lung cancer cells both in vitro and in vivo and that a G2/M block and increased apoptosis might be possible explanations for the enhancement.

Animals↗

PubMed2003

Mitochondrial permeability transition in the switch from necrotic to apoptotic cell death in ischemic rat hepatocytes.

BACKGROUND & AIMS: Ischemia/reperfusion can initiate both necrotic and apoptotic death of hepatocytes. Previous work showed that onset of the mitochondrial permeability transition (MPT) can initiate necrotic cell death after reperfusion, but the MPT is also implicated in apoptosis. Here, we investigated factors regulating how cell death switches from necrosis to apoptosis after ischemia/reperfusion injury. METHODS: Overnight cultured rat hepatocytes were incubated in anoxia at pH 6.2 for 4 hours and reoxygenated at pH 7.4 to simulate ischemia/reperfusion. Some cells were incubated with fructose plus glycine just before and then continuously after reperfusion. Development of apoptosis was evaluated by examining chromatin condensation, nuclear DNA fragmentation, and caspase 3 activity. RESULTS: Reperfusion with the glycolytic substrate fructose plus the cytoprotective amino acid glycine prevented necrotic cell killing. Instead, apoptosis developed within 12 hours as shown by nuclear chromatin changes, TUNEL staining, and caspase 3 activation. This apoptotic cell killing was prevented by cyclosporin A, an MPT blocker, and by pancaspase and caspase 3 inhibition, but not by caspase 8 inhibition. Cyclosporin A also blocked caspase-3 activation. Reperfusion with glycine alone prevented necrotic cell death but did not induce apoptosis and only poorly promoted recovery of ATP, whereas fructose alone during reperfusion promoted both ATP recovery and apoptosis. CONCLUSIONS: Glycolytic ATP generation after reperfusion prevents necrotic killing of hepatocytes after simulated ischemia/reperfusion despite onset of the MPT. Instead, the MPT promotes caspase-and ATP-dependent apoptosis. Thus, the MPT is a common mechanism responsible for both necrosis and apoptosis after ischemia/reperfusion.

Animals↗

PubMed2002

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer.

PURPOSE: Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS: Between July 1999 and March 2001, 45 patients with locally advanced rectal cancer (cT3/T4 or N+) were treated with preoperative chemoradiation. Radiation of 45 Gy/25 fractions was delivered to the pelvis, followed by a 5.4 Gy/3 fractions boost to the primary tumor. Chemotherapy was administered concurrent with radiotherapy and consisted of 2 cycles of 14-day oral capecitabine (1650 mg/m(2)/day) and leucovorin (20 mg/m(2)/day), each of which was followed by a 7-day rest period. Surgery was performed 6 weeks after the completion of chemoradiation. RESULTS: Thirty-eight patients received definitive surgery. Primary tumor and node downstaging occurred in 63% and 90% of patients, respectively. The overall downstaging rate, including both primary tumor and nodes, was 84%. A pathologic complete response was achieved in 31% of patients. Twenty-one patients had tumors located initially 5 cm or less from the anal verge; among the 18 treated with surgery, 72% received sphincter-preserving surgery. No Grade 3 or 4 hematologic toxicities developed. Other Grade 3 toxicities were as follows: hand-foot syndrome (7%), fatigue (4%), diarrhea (4%), and radiation dermatitis (2%). CONCLUSION: These preliminary results suggest that preoperative chemoradiation with capecitabine is a safe, well-tolerated, and effective neoadjuvant treatment modality for locally advanced rectal cancer. In addition, this preoperative treatment has a considerable downstaging effect on the tumor and can increase the possibility of sphincter preservation in distal rectal cancer.

Adenocarcinoma↗

PubMed2002

Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy.

Inhibition of mitochondrial oxidative phosphorylation progresses to uncoupling when opening of cyclosporin A-sensitive permeability transition pores increases permeability of the mitochondrial inner membrane to small solutes. Involvement of the mitochondrial permeability transition (MPT) in necrotic and apoptotic cell death is implicated by demonstrations of protection by cyclosporin A against oxidative stress, ischemia/reperfusion, tumor necrosis factor-alpha exposure, Fas ligation, calcium overload, and a variety of toxic chemicals. Confocal microscopy directly visualizes the MPT in single mitochondria within living cells from the translocation of impermeant fluorophores, such as calcein, across the inner membrane. Simultaneously, mitochondria release potential-indicating fluorophores. Subsequently, mitochondria swell, causing outer membrane rupture and release of cytochrome c and other proapoptotic proteins from the intermembrane space. In situ a sequence of decreased NAD(P)H, increased free calcium, and increased reactive oxygen species formation within mitochondria promotes the MPT and subsequent cell death. Necrotic and apoptotic cell death after the MPT depends, in part, on ATP levels. If ATP levels fall profoundly, glycine-sensitive plasma membrane permeabilization and rupture ensue. If ATP levels are partially maintained, apoptosis follows the MPT. The MPT also signals mitochondrial autophagy, a process that may be important in removing damaged mitochondria. Cellular features of necrosis, apoptosis, and autophagy frequently occur together after death signals and toxic stresses. A new term, necrapoptosis, describes such death processes that begin with a common stress or death signal, progress by shared pathways, but culminate in either cell lysis (necrosis) or programmed cellular resorption (apoptosis), depending on modifying factors such as ATP.

Animals↗