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ABSTRACT: Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models.
We characterized the angiogenic factors, such as VEGF, heparanase, and MMPs, of murine squamous cell carcinoma (SCC7), melanoma (B16F10) or lung carcinoma (LLC1). Two weeks after oral administration of LHD into these cancer-cell-bearing mice, we evaluated the antiangiogenic activity of LHD.
Although all cancer cells expressed the angiogenic factors, SCC7 cells had much higher angiogenic potential and grew rapidly after implantation into mice. When orally administered, LHD delayed tumor graft growth regardless of cancer types. Particularly, LHD powerfully diminished the SCC7-derived tumor growth. Also, the expression of angiogenic factors in all kinds of tumor tissues was decreased, thereby attenuating the neovascularization in tumor tissue.
Our study shows that LHD has potent anticancer and antiangiogenic effect on at least three kinds of tumor cells. LHD can be specifically used for preventing neovascularization in tumor tissue because it has therapeutical potential as an antiangiogenic drug and can be orally absorbed.
Pharmaceutical Research 10/2009; 26(12):2667-76. · 4.09 Impact Factor
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ABSTRACT: High-dose chemotherapy supported by autologous stem cell transplantation (ASCT) after combined chemotherapy with infusional vincristine/doxorubicin plus dexamethasone is effective in multiple myeloma (MM). Outpatient treatment with bolus vincristine/doxorubicin infusion plus dexamethasone is convenient and has acceptable efficacy and toxicity for MM. Thalidomide has recently been shown to have significant antimyeloma activity. We assessed the efficacy and toxicity of the combination of bolus vincristine/doxorubicin and reduced dose dexamethasone with thalidomide (T-bVAd), administered on an outpatient basis, in untreated MM.
Twenty-six patients prospectively received T-bVAd, consisting of intravenous (i.v.) vincristine 0.4 mg plus doxorubicin 9 mg/m(2), administered as a single bolus on days 1 to 4, dexamethasone 20 mg per os daily for 4 days, and thalidomide 200 mg/day at bedtime. Response assessment was conducted after each 4-week treatment cycle. Patients who achieved response were allowed to proceed to high-dose chemotherapy with ASCT.
On an intention-to-treat basis, 23 of the 26 patients (88%) responded to treatment, with 16 (61%) achieving complete response (CR), 2 (8%) very good partial response (VGPR) and 5 (19%) partial response. Only three patients (12%) were rated as non-responders. Grade 3 and 4 hematologic toxicities consisted of neutropenia (13%), febrile neutropenia (6%), and thrombocytopenia (4%), without significant nonhematologic events. Of the 23 patients who showed response, 7 proceeded to single ASCT and 9 to tandem ASCT. With median follow-up time of 15.3 months (range, 9-25 months), median event free survival (EFS) and overall survival (OS) have not been reached yet, and OS and EFS rates for patients who achieved complete response after T-bVAd regimen were significantly higher than patients not.
Induction therapy with T-bVAd, administered as an outpatient regimen, was efficient and relatively well tolerated in the treatment of MM.
Investigational New Drugs 10/2009; 29(1):175-81. · 3.36 Impact Factor
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Sung Gyu Lee,
Gi Won Song,
Shin Hwang,
Tae Yong Ha,
Deok Bog Moon,
Dong Hwan Jung,
Ki Hun Kim,
Chul Soo Ahn,
Myung Hwan Kim, Sung Koo Lee,
Kyu Bo Sung,
Gi Young Ko
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ABSTRACT: Both curative resection and minimized in-hospital mortality offer the only chance of long-term survival in patients with hilar cholangiocarcinoma. The reported resectability rates for hilar cholangiocarcinoma have increased by virtue of combined major hepatectomy, but this procedure is technically demanding and still associated with a significant morbidity and mortality that must be carefully balanced against the chances of long-term survival.
Between January 2001 and December 2008, 350 patients with hilar cholangiocarcinoma underwent exploration for the purpose of potentially curative resection, of whom 302 (86.3%) were resected in the Department of Hepato-Biliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine. Combined hepatectomy was carried out in 268 (88.7%) of 302 resected patients. Major hemihepatectomy and parenchyma-preserving hepatectomy were performed in 257 and 11 patients, respectively. Portal vein resection was associated in 40 (14.9%) of 268 hepatectomized patients. To control preoperative cholangitis and reduce risk of postoperative hepatic failure, biliary decompression through endoscopic and/or percutaneous transhepatic drainage and portal vein embolization were preoperatively applied in 329 (94.0%) of 350 explored patients and in 91 (54.2%) of 168 extended hepatectomized patients (154 right hemihepatectomy, 9 right trisectionectomy, 5 left trisectionectomy), respectively. Liver transplantation was not performed as primary treatment for hilar cholangiocarcinoma.
There were 5 cases (1.7%) of in-hospital death after resection and 1 postoperative liver failure that was successfully treated with liver transplantation. Major complications were encountered in 23 patients (7.0%), and the overall morbidity rate was 43%. In 302 resections, 214 (70.9%) were curative resections (R0) and 88 (29.1%) were palliative resections (R1). The overall 1-, 3- and 5-year survival rates after resection, including in-hospital deaths, were 84.6, 50.7 and 47.3% in the R0 group and 69.9, 33.3 and 7.5% in the R1 group, respectively. The 5-year survival rate of extended hemihepatectomy of 36.4% was better than that of parenchyma-preserving hepatectomy at 10.5%. Two significant predictive factors adversely affecting survival after resection were lymph node metastasis and incurability of surgery (P < 0.001). Two patients with vascular involvement who underwent concomitant hepatic artery and portal vein reconstruction are alive after more than 3 years.
Preoperative biliary decompression and portal vein embolization enabled us to reduce in-hospital deaths associated with extended hepatectomy for hilar cholangiocarcinoma. Major hemihepatectomy offers an increased survival because of the higher possibility of curative resection than bile duct resection alone and parenchyma-preserving hepatectomy, but it still carries a certain mortality. Less extensive procedures can be conducted safely and are beneficial for aged patients in poor condition with a less advanced tumor stage if tumor-free resectional margins are obtained.
Journal of hepato-biliary-pancreatic sciences. 10/2009; 17(4):476-89.
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ABSTRACT: This study was carried out to evaluate the clinical significance of ascitic fluid carcinoembryonic antigen (CEA) in advanced gastric cancer patients with ascites.
From November 2001 to February 2008, 119 gastric cancer patients with concurrent ascites who were clinically diagnosed with carcinomatosis, were retrospectively reviewed with regard to ascitic fluid cytology and clinicopathological parameters. Serum CEA (sCEA) and ascitic fluid CEA (aCEA) were measured using a chemiluminescent enzyme immunoassay.
The patients' median age was 50 years (range 23-80 years). The median value of aCEA was significantly higher than sCEA [130.5 ng/ml (range 0.2-12.211 ng/ml) vs. 2.1 ng/ml (range 0.02-8.152 ng/ml), p < 0.001]. Sixty-five patients (54.6%) had positive ascitic fluid cytology. The median overall survival of all patients was 3.0 months (95% CI 2.0-4.0 months). The patients with low aCEA (<5 ng/ml) had a significantly longer overall survival compared to patients with high aCEA (>or=5 ng/ml) (7.4 months vs. 2.3 months, p = 0.003). However, we found no difference in overall survival according to ascitic fluid cytology (median, 3.0 months vs. 2.5 months, p = 0.530). Multivariate analysis also demonstrated that aCEA levels of more than 5 ng/ml were associated with poor prognosis (HR = 2.88; 95% CI 1.45-5.74; p = 0.003), while sCEA levels were not associated with poor prognosis (HR = 1.15; 95% CI 0.67-2.03; p = 0.622).
These results suggest that aCEA levels can be used as a prognostic marker for advanced gastric cancer patients with ascites.
Journal of Cancer Research and Clinical Oncology 09/2009; 136(4):517-26. · 2.56 Impact Factor
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Inkeun Park,
Jae-Lyun Lee,
Min-Hee Ryu,
Heung Moon Chang,
Tae-Won Kim,
Sun-Jin Sym, Sung Sook Lee,
Geundoo Jang,
Changhoon Yoo,
Kyun-Seop Bae,
Yoon-Koo Kang
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ABSTRACT: We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced gastric cancer (AGC).
Oxaliplatin was fixed at a dose of 130 mg/m2 on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m2 per day from 70 mg/m2 per day up to 100 mg/m2 per day. Pharmacokinetic analyses were performed following a single dose of S-1 on D-5 and D1 of the first cycle.
In phase I (n=18), MTD was not defined. In phase II (n=47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0-9.2 months) and the median overall survival was 12.5 months (95% CI 9.2-15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle.
The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.
Cancer Chemotherapy and Pharmacology 07/2009; 65(3):473-80. · 2.83 Impact Factor
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Eun Kwang Choi,
Myung-Hwan Kim,
Se Jin Jang,
Keun-Hwa Lee,
Chang Yun Hwang,
Sung-Hoon Moon,
Tae Yoon Lee,
Chang Ok Koh,
Do Hyun Park,
Sang Soo Lee,
Dong Wan Seo, Sung Koo Lee
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ABSTRACT: Tumor growth factor beta (TGF-beta) is an immunosuppressive cytokine and has been implicated in a variety of disease processes, including those in autoimmune disease. Tumor growth factor beta is also involved in fibrosis by regulating matrix metalloproteinases (MMPs) and the tissue inhibitor of MP (TIMP). The purpose of this study was to compare the expression patterns of TGF-beta1, MMP-2, and TIMP-2 between autoimmune chronic pancreatitis (AIP) and alcoholic chronic pancreatitis (ACP) by immunohistochemical staining of pancreatic tissue specimens.
Pancreatic tissue specimens were obtained from 16 of 57 patients who had a diagnosis of AIP at the Asan Medical Center. Pancreatic tissue specimens of ACP were obtained from 10 patients who were surgically treated. Immunohistochemical staining was performed with antibodies specific for TGF-beta1, MMP-2, and TIMP-2.
The degree of immunohistochemical staining for TGF-beta1 was significantly weaker in AIP than in ACP in the pancreatic ductal epithelial and mononuclear cells (P = 0.029 and P = 0.018, respectively).
This finding suggests that there may be a defect in the function of regulatory T (Treg) cells, which normally prevents autoimmune disease progression via a suppressor mechanism. Further studies are needed to identify the type of regulatory T cell involved in this process.
Pancreas 07/2009; 38(7):739-45. · 2.39 Impact Factor
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ABSTRACT: Numerous electronic devices have been introduced into operating rooms. Although little is known about the relationship between exposure to electromagnetic fields and health hazards, several studies have demonstrated causal relationships between electromagnetic fields exposure and various symptoms, cancers, and other diseases.
This study was approved by the Institutional Review Board. The intensity of extremely low-frequency electromagnetic fields was measured during surgery with the extremely low-frequency electromagnetic field strength measurement system at the standing position of anesthesiologists in 18 operating rooms and analyzed with EMDEX analysis and graphical program (EMCALC 95; ENERTECH, Campbell, CA).
The average measurement duration per operating room per day was 7.41 +/- 0.70 h (mean +/- SD). The average sample number of measurements was 888.11 +/- 82.75 per operating room. The average magnetic field was 5.83 +/- 5.23 milliGuass (mG) (range, 0.10-33.80 mG), with 70% of these levels 2 mG or greater.
The authors' results indicate that anesthesiologists in operating rooms are exposed to extremely low-frequency electromagnetic field levels that exceed magnetic field intensity of 2 mG recommended by the Swedish Board for Technical Accreditation for production by computer monitors and detected 30 cm from them. It currently is not clear if this exposure has health effects on anesthesiologists and other operating room personnel.
Anesthesiology 07/2009; 111(2):275-8. · 5.36 Impact Factor
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ABSTRACT: Double balloon endoscopy (DBE) is a new endoscopic method with the capability for complete observation of whole small bowel. This study evaluated the feasibility and usefulness of DBE for the diagnosis and therapy of small bowel diseases in patients with distorted intestinal anatomy by previous surgeries.
From January 2005 to August 2007, 15 patients with Roux-en-Y anastomosis underwent DBE in Asan Medical Center. Eight were men and the median age was 57 years (range, 40 to 68 y). Indications of DBE were suspected small bowel bleeding, chronic diarrhea, and recurrent acute pancreatitis. The main outcome measurements included completeness of the observation of afferent loop and DBE findings.
Because 1 patient underwent DBE twice separately owing to recurrent bleeding, a total of 16 cases were analyzed. The observation of afferent loop was complete in 13 (81%) of 16 cases. The overall diagnostic yield of DBE was 69% (11/16). Out of 11 cases in which DBE detected abnormalities, 6 (55%) showed definite lesions and 5 (45%) probable lesions. Of the 11 cases in which abnormalities were found, 7 (64%) showed lesions in afferent loop. Of the 6 cases in which definite lesions were found, 4 (67%) showed lesions in afferent loop. Therapeutic endoscopic procedures were performed in 4 cases, which include argon plasma coagulation, foreign body removal, and endoscopic nasobiliary drainage.
DBE in patients with distorted intestinal anatomy such as Roux-en-Y anastomosis is a useful tool for the management of small bowel lesions, especially those in the afferent loop.
Journal of clinical gastroenterology 04/2009; 43(8):737-42. · 2.21 Impact Factor
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ABSTRACT: Biotic signaling molecules including abscisic acid (ABA) are involved in signal transduction pathways that mediate the defense response of plants to environmental stresses. The antimicrobial protein gene CaAMP1, previously isolated from pepper (Capsicum annuum), was strongly induced in pepper leaves exposed to ABA, NaCl, drought, or low temperature. Because transformation is very difficult in pepper, we overexpressed CaAMP1 in Arabidopsis. CaAMP1-overexpressing (OX) transgenic plants exhibited reduced sensitivity to ABA during the seed germination and seedling stages. Overexpression of CaAMP1 conferred enhanced tolerance to high salinity and drought, accompanied by altered expression of the AtRD29A gene, which is correlated with ABA levels and environmental stresses. The transgenic plants were also highly tolerant to osmotic stress caused by high concentrations of mannitol. Together, these results suggest that overexpression of the CaAMP1 transgene modulates salt and drought tolerance in Arabidopsis through ABA-mediated cell signaling.
Planta 11/2008; 229(2):383-91. · 3.00 Impact Factor
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ABSTRACT: The petroleum ether extract of Viola websteri Hemsl. (Violaceae) was investigated for its activity against chloroquine-sensitive strains of Plasmodium falciparum using the parasite lactate dehydrogenase assay method. The main antiplasmodial principles, 6-(8'Z-pentadecenyl)-salicylic acid (1) and 6-(8'Z, 11'Z, 14'Z-heptadecatrienyl)-salicylic acid (2), have been isolated from V. websteri for the first time. This is the first report on the antiplasmodial activity of the compounds from V. websteri.
Parasitology Research 11/2008; 104(2):463-6. · 2.15 Impact Factor
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ABSTRACT: To report long-term visual outcomes and complications of a new foldable, one-piece, acrylic posterior chamber intraocular lens with closed-loop haptics (C-flex, Rayner, UK) for scleral fixation.
Retrospective interventional case series of 29 eyes of 29 patients who underwent scleral fixation with the C-flex intraocular lens in the absence of capsular support.
Review of 29 consecutive cases from January 2001 to December 2005 in which scleral fixation was performed with the C-flex intraocular lens. All cases were performed by a single surgeon (S.J.L.) and with an ab externo two-point scleral fixation technique. Preoperative status, intraoperative complications, and postoperative outcomes were analyzed.
Mean best corrected visual acuity improved from 20/150 to 20/40 (P < 0.001) at 1 month and to 20/50 (P < 0.001) at mean follow-up of 41 months. Complications included clinically insignificant decentration [1 (3%)], mild intraoperative vitreous hemorrhage [1 (3%)], postoperative hyphema [2 (7%)], and transient elevated intraocular pressure [2 (7%)]. All complications were mild and resolved without the need for reoperation.
Scleral fixation of the closed-loop, foldable, acrylic C-flex intraocular lens appeared to reduce operative time, was associated with minimal postoperative complications, and resulted in long-term visual improvement.
Retina (Philadelphia, Pa.) 10/2008; 29(1):91-7. · 2.93 Impact Factor
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ABSTRACT: PRSS1 and SPINK1 are 2 important genes in the defense mechanism guarding against the development of pancreatitis. This study aimed to evaluate the prevalence of PRSS1 and SPINK1 mutations and to explore the presence of any ethnic specificity in Korean patients.
A total of 47 patients from 40 families including 37 patients with idiopathic pancreatitis and 10 patients with familial pancreatitis were prospectively enrolled. Fifty healthy controls were included for analysis of SPINK1 IVS3+2T site.
PRSS1 mutations were observed in 6 patients from 2 families and SPINK1 mutations in 13 patients from 11 families, respectively. In case of SPINK1 mutations, N34S and IVS3+2T>C were identified in 3 and 11 patients, respectively, including one with compound N34S/IVS3+2T>C heterozygote. The prevalence of SPINK1 IVS3+2T>C mutations was 26.8% among 41 patients without PRSS1 mutations, whereas the prevalence among 50 healthy controls was 0%. Only PRSS1 R122H was identified. Late onset of symptoms at the age of 36 years and absence of symptoms at the age of 47 years were observed in 2 patients with PRSS1 mutations.
PRSS1 and SPINK1 mutations were not rare in Korean patients with idiopathic and familial pancreatitis. SPINK1 IVS3+2T>C was a prevalent mutation in this population.
Pancreas 10/2008; 38(2):180-3. · 2.39 Impact Factor
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Je Hyeong Kim,
Min Hyun Suk,
Dae Wui Yoon,
Hye Young Kim,
Ki Hwan Jung,
Eun Hae Kang, Sung Yong Lee,
Sang Yeub Lee,
In Bum Suh,
Chol Shin,
Jae Jeong Shim,
Kwang Ho In,
Se Hwa Yoo,
Kyung Ho Kang
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ABSTRACT: Poly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-kappaB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung.
Male C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-kappaB DNA-binding activity in tissue homogenates were measured.
The VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-alpha and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-kappaB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05).
Overactivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.
Critical care (London, England) 09/2008; 12(4):R108. · 4.61 Impact Factor
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ABSTRACT: Despite recent advances in laparoscopic pancreatic surgery, few studies have compared laparoscopic distal pancreatic resection (LDPR) with open distal pancreatic resection (ODPR). This study aimed to compare clinical outcomes for LDPR and ODPR performed at a single institution.
For this study, 93 patients with benign pancreatic disease underwent LDPR, and 35 patients with benign pancreatic disease underwent ODPR. Patient demographic characteristics, operative times, perioperative complications, length of hospital stay, and return to normal diet were compared retrospectively between the two groups.
The LDPR and ODPR groups had the same demographic characteristics. The median operative time was 195 min in the LDPR group and 190 min in the ODPR group (p>0.05). The rate of spleen preservation was higher in the LDPR group (40.8%) than in the ODPR group (5.7%) (p<0.05) No operative mortality occurred in either group. The overall complication rate was 24.7% in the LDPR group and 29% in the ODPR group (p>0.05). The rate of pancreas-related complications was 11.8% in the LDPR group and 17.2% in the ODPR group (p>0.05). Pancreatic fistula developed in 8.6% of the LDPR group and in 14.3% of the ODPR group (p>0.05). Bowel movement return to normal and resumption of normal diet were achieved 2.8+/-1.3 days after the operation in the LDPR group and 4.5+/-1.6 days after the operation in the ODPR group (p<0.05). The median duration of hospital stay was 10 days for the LDPR group, which was significantly shorter than the 16 days for the ODPR group (p<0.01).
The use of LDPR for benign lesions of the distal pancreas is feasible and safe. The LDPR procedure is associated with operative times and complication rates similar to those for ODPR, but LDPR has the advantages of an earlier return to normal bowel movements and normal diet and shorter hospital stays than ODPR.
Surgical Endoscopy 06/2008; 22(10):2261-8. · 4.01 Impact Factor
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ABSTRACT: To evaluate the prognostic factors for visual outcome after intravitreal bevacizumab injection to treat macular edema due to branch retinal vein occlusion (BRVO).
Fifty eyes of 50 consecutive patients treated with intravitreal bevacizumab for macular edema due to BRVO with minimum follow-up of 3 months were retrospectively reviewed. Patients were categorized into two groups according to the final visual acuity. Group 1 consisted of eyes with 5 or more ETDRS letters gain, and group 2 consisted of eyes with less than 5 letters improvement or which had worsened at last follow-up visit. Comparative clinical and fluorescein angiographic characteristics were analyzed between the two groups.
Of 50 eyes, 28 (56%) had improved vision after intravitreal bevacizumab injections and were categorized as group 1; 22 eyes (44%) were categorized as group 2. The number of early VA gainers, who showed visual improvement at 1 month after bevacizumab injection, was significantly higher in group 1 (P < 0.001, chi-square test). The early gainers tend to maintain significantly better visual outcome until last follow-up. The number of eyes with angiographically documented macular ischemia was significantly higher in group 2 (P < 0.001). In group 2, the decrease in central macular thickness was not accompanied by visual acuity improvement.
Preoperative presence of macular ischemia can be useful in predicting the outcome of visual acuity after intravitreal bevacizumab for macular edema due to BRVO. The early gainers who favorably responded to the initial intravitreal bevacizumab injection are most likely to benefit from the bevacizumab treatment.
Albrecht von Graæes Archiv für Ophthalmologie 06/2008; 246(9):1241-7. · 2.17 Impact Factor
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ABSTRACT: The purpose of this retrospective study was to analyze the overall survival of patients with brain metastases due to breast cancer and to identify prognostic factors that affect clinical outcome.
Of the 7,872 breast cancer patients histologically diagnosed with breast cancer between January 1990 and July 2006 at the Asan Medical Center, 198 patients with solitary or multiple brain metastases were included in this retrospective study. Central nervous system (CNS) lesions were diagnosed by computed tomography (CT) or magnetic resonance imaging (MRI). Patients with leptomeningeal or dural metastases without co-existent parenchymal metastatic lesions were excluded in this study. We reviewed the medical records and pathologic data of these 198 patients to characterize the clinical features and outcomes.
The median age of the patients at the diagnosis of brain metastases was 45 years (range 26-78 years). Fifty-five patients (28%) had a single brain metastasis, whereas 143 (72%) had more than two metastases. A total of 157 (79.2%) patients received whole-brain radiation therapy (WBRT). A total of 7 (3.6%) patients underwent resection of solitary brain metastases, 22 (11%) patients underwent gamma-knife surgery, three patients underwent intrathecal chemotherapy (1.5%) and 9 (4.6%) patients received no treatment. The overall median survival time was 5.6 months (95% confidence interval (CI), 4.7-6.5 months) and 23.1% of the patients survived for more than 1 year. The median overall survival time was 5.4 months for patients treated with WBRT, 14.9 months for patients treated with surgery or gamma-knife surgery only, and 2.1 months for patients who received no treatment (P < 0.001). Multivariate analysis demonstrated that Eastern Cooperative Oncology Group (ECOG) performance status (relative risk (RR) = 0.704, 95% CI 0.482-1.028, P = 0.069), number of brain metastases (RR = 0.682, 95% CI 0.459-1.014, P = 0.058), treatment modalities (RR = 1.686, 95% CI 1.022-2.781, P = 0.041), and systemic chemotherapy after brain metastases (RR = 1.871, 95% CI 1.353-2.586, P < 0.001) were independent factors associated with survival.
Although survival of breast cancer patients with brain metastases was generally short, the performance status, number of brain metastases, treatment modalities and systemic chemotherapy after brain metastases were significantly associated with survival. Patients with single-brain metastasis and good performance status deserve aggressive treatment. The characteristics of initial primary breast lesions did not affect survival after brain metastasis.
Breast Cancer Research and Treatment 11/2007; 111(3):523-30. · 4.43 Impact Factor
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ABSTRACT: The degree of chromosomal losses and the presence of microsatellite instability (MSI) in gastric carcinomas have been categorized into low-risk (low-level loss and MSI) and high-risk (baseline- and high-level losses) genotypes. With the aim of making a preoperative diagnosis, this study confirmed the stem line genotype that is common over an entire tumor as well as in a single biopsy specimen. Biopsy specimens were obtained from 91 gastric carcinoma patients and examined for their microsatellite genotypes using a panel of 41 microsatellite markers on 8 cancer-associated chromosomes. The genotype of the biopsy specimens was compared with that of a surgical specimen, which had been multifocally examined for its intratumoral heterogeneity. Of the 91 pairs of biopsy and surgical specimens, 87 (96%) containing either the same (60 cases) or a similar (17 cases) number of chromosomal losses were categorized into the same microsatellite genotype, and the remaining 4 pairs (4%) were classified into a different genotype. The surgical specimens showed that an extraserosal invasion and lymph node metastasis are frequently associated with either a high-level (4 or more) of chromosomal losses irrespective of the tumor size (73% and 85%) or the large carcinomas > 5 cm in diameter irrespective of the tumor genotype (76% and 83%). The status of the extraserosal invasion and lymph node metastasis (0.691 and 0.802 receiver operating characteristic areas, respectively) predicted by the biopsy genotype and the tumor size corresponded closely to the surgical pathology results. Therefore, the extent of chromosomal losses and the presence of an MSI determined on a biopsy specimen will provide valuable information for making a preoperative genetic diagnosis of a gastric carcinoma.
International Journal of Cancer 01/2005; 113(2):249-58. · 5.44 Impact Factor
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ABSTRACT: Pepper (Capsicum annuum L.) SAR8.2 genes, designated CASAR82A, B and C, which are induced by all the biotic and abiotic stresses, were isolated from a pepper cDNA library constructed with the mRNAs from pepper plants infected with Xanthomonas campestris pv. vesicatoria. The pepper CASAR82A, B and C gene products, which are very similar to each other in amino acid sequences, have 43-50% homology with those of tobacco SAR8.2 genes. The CASAR8.2 genes were not constitutively expressed in any of the organs of healthy pepper plants. In contrast, the CASAR82A gene was locally or systemically induced in pepper plants infected by X. campestris pv. vesicatoria, Colletotrichum coccodes or Phytophthora capsici. Strong induction of the CASAR82A gene also was found in pepper leaves treated with ethylene, methyl jasmonate, indole-3-acetic acid, abscisic acid, salicylic acid, benzothiadiazole, DL-#-n-amino butyric acid or hydrogen peroxide. Interestingly, the transcription of the CASAR82A gene was rapidly triggered by high salinity, drought or low-temperature stresses, but not by mechanical wounding. In situ hybridization results revealed that the CASAR82A mRNAs were localized in phloem and epidermal cells of pepper leaf and stem tissues infected by C. coccodes and P. capsici, or treated with salicylic acid. These results thus suggest that pepper SAR8.2 genes may be valuable as a molecular marker for the detection of various pathogen infections, abiotic elicitors and environmental stresses.
Planta 12/2002; 216(3):387-396. · 3.00 Impact Factor
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ABSTRACT: A total of 48 subjects harbouring Trichuris trichiura, Ascaris lumbricoides, hookworm and/or Enterobius vermicularis were treated with oxantel/pyrantel pamoate tablets (100 mg of each) in a single dose of 20 mg base per kg of body weight. In all 37 cases of A. lumbricoides and 8 cases of A. duodenale infections cured completely, and the mean recovered worm-load was 3.8 with a range of 1-21 and 5.8 with a range of 3-9 respectively. In T. trichiura infection, 32(71.1%) of 45 cases cured completely and the average egg reduction rate was 90.8 per cent. The mean recovered worm-load was 14.6 with a rnage of 1-77 worms. On the other hand, in E. vermicularis infection, 37 (84.1%) of 44 patients were negative eggs by anal swab tests on the 10 to 11th days and 27 (61.4%) on the 20 to 21st days after treatment. The mean recovered worm-load was 17.7 with a range of 1-62. Only one patient with Trichostrongylus orientalis treated with this drug showed no eggs in his stools throughout the post-treatment examinations. Side effects were not noted in all treated cases. These findings demonstrate that a single dose of oxantel/pyrantel pamoate tablets can be considered a drug of choice for multiple infections with these nematodes.
Kisaengch'unghak chapchi. The Korean journal of parasitology. 07/1978; 16(1):14-20.
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ABSTRACT: A total of 56 subjects with multiple nematode infections with T. trichiura, Ascaris, hookworms and Enterobius were treated with oxantel and pyrantel pamoate mixture in a paratable suspension(50 mg of each per ml). A single dose of 10 mg per kg body weight in each cured 100 per cent of 54 subjects with Ascaris, 97.1 per cent of 35 subjects with hookworms, 77.8 per cent of 36 with Enterobius and 73.2 per cent of 56 subjects with T. trichiura infestation. The mean egg per gram stool reduction rate in T. trichiura infection was 91.9%. Of the 31 subjects infected with Ancylostoma doudenale 96.8% were cured with a single dose and 4 infected with Necator americanus showed a 100% cure rate with a similar daily dose on 3 consecutive days. Side effects were few and mild. There was no clinical or laboratory evidence of drug toxicity. These findings show a single dose of oxantel and pyrantel pamoate mixture to be a highly effective and acceptable treatment for multiple infections with these nematodes.
Kisaengch'unghak chapchi. The Korean journal of parasitology. 01/1976; 13(2):97-101.
