• Archives of Pharmacal Research
• /
• v.29 no.10
• /
• pp.866-873
• /
• 2006

When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1 (MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of $10{\mu}M$ curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.

• Tuberculosis and Respiratory Diseases
• /
• v.51 no.4
• /
• pp.325-333
• /
• 2001

Background : This study aimed to estimate the clinical outcome and identify the characteristics of a group of patients with pulmonary tuberculosis who completed anti-tuberculosis therapy with the First-line drugs in spite of having positive smear results with negative sputum culture results over the previous six months. Method : A retrospective chart review of 21 patients who fulfilled the above criteria between 1995 and 1999 was performed. The laboratory data as well as the clinical data of the patients with positive smear results and negative culture results over a six months period were reviewed. Results : The negative conversion of sputum culture results was achieved within $1.3{\pm}1.2$ months and the negative conversion of the sputum smear results was accomplished during $9.5{\pm}3.3$ months. Chest X-rays at 5 months following the institution of anti-tuberculosis therapy from all patients revealed improvements. Four out of 21 patients(19%) relapsed during the follow up, $15.2{\pm}13.4$ months after administering anti-tuberculosis therapy for $13.3{\pm}3.1$ months. Relapses were confirmed from between 3 months and 4 months after the treatment completion. Only one of the four relapses had no past history of anti-tuberculosis therapy and the others had prior treatment twice (p<0.01). The period of anti-tuberculosis treatment was extended to a mean of $4.6{\pm}2.6$ months in 12 patients. However, prolongation of anti-tuberculosis therapy had no affect on the relapse rate (odds ratio, 95% CI 0.18, 2.15). Conclusion : Prolongation of therapy with the First-line drugs is not necessary for patients with persistently positive smear results over 6 months and negative culture results. A patient who has had prior anti-tuberculosis therapy more than twice should be paid the closest attention.

• Childhood Kidney Diseases
• /
• v.5 no.2
• /
• pp.117-124
• /
• 2001

Purpose : Since Mendoza(1990)'s report that long term methylprednisolone pulse therapy by Mendoza protocol (MP therapy) is a good treatment option in focal segmental glomerulosclerosis(FSGS), there have been reports of the effects of this therapy in steroid-resistant nephrotic syndrome. However, no studies have been performed on the effects of MP therapy in steroid- dependent nephrotic syndrome and secondary nephrotic syndrome. In this study, we investigated the effects of long term MP therapy in primary and secondary nephrotic syndrome in which previous treatment options were not effective. Methods : We chose 10 children who were diagnosed with steroid-dependent minimal change nephrotic syndrome(SD-MCNS), who had shown frequent relapse during the immunocompromised or cytotoxic therapy Period, and 6 children with FSGS and 5 children with secondary nephrotic syndrome children, who had shown no response during the previous therapy period. We treated these patients according to Mendoza protocol involving infusions of high doses of methylprednisolone, often in combination with oral cyclophosphamide for 82 weeks. Results : In all the 10 children with SD-MCNS, complete remission was visible on average of $18{\pm}9$ days after MP therapy was started. However, all these children relapsed during or after MP therapy. In these children, the mean relapse rate prior to MP therapy was $2.1{\pm}1.0$ relpases/year, which was reduced to $1.4{\pm}0.9$ relapses/year during MP therapy(P>0.05) and rose to $2.7{\pm}1.0$ relapse/year after MP therapy. Of the 6 children with FSGS, 4 children($67\%$) showed complete remission, of whom 3 children($50\%$) remained in the remission status during the follow up period, $1.2{\pm}0.7$ years, after the end of MP therapy. 2 children($33\%$) showed no response. All of the 5 children with secondary nephrotic syndrome showed remission and remained in the remissiom status during the follow up period, $1.7{\pm}0.6$ years The only side effect of MP therapy was transient hypertension in 10 children of ail subjects during the intravenous infusion of methylprednisolone. Conclusion : We conclude that although long term MP therapy is not effective in the treatment of SD-MCNS, it is an effective therapy against intractable FSGS and secondary nephrotic syndrome. (J Korean Soc Pediatr Nephrol 2001 ; 5 : 117-24)

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.6
• /
• pp.1143-1153
• /
• 1998

Background : Recent outbreaks of pulmonary disease due to drug-resistant strains of Mycobacterium Tuberculosis have resulted in significant morbidity and mortality in patients worldwide. We reviewed our experience to evaluate the effects of pulmonary resection on the management of multidrug-resistant tuberculosis. Method : A retrospective review was performed of 41 patients undergoing pulmonary resection for multidrug-resistant tuberculosis between January 1993 and December 1997. We divided these into 3 groups according to the radiologic findings : (1) patients who have reasonably localized lesion (Localized Lesion Group ; LLG) (2) patients who have cavitary lesions after pulmonary resection on chest roentgenogram (Remained Cavity Group : RCG) (3) patients who have Remained infiltrative lesions postoperatively (Remained infiltrative group : RIG). We evaluated the negative conversion rate after resection and overall response rate of the groups. Then they were compared with the results of the chemotherapy on the multi drug-resistant tuberculosis which has been outcome by Goble et al. Goble et al reported that negative conversion rate was 65% and overall response rate, 56% over a mean period of 5.1 months. Results : Seventy five point six percent were men and 24.4% women with a median age of 31 years (range, 16 to 60 years). Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 22 of 41 were still sputum culture positive at the time of surgery. 20 of 22 patients(90.9%, p<0.01) responded which is defined as negative sputum cultures within 2 months postoperative. Of 26 patients with the sufficient follow up data, 19 have Remained sputum culture negative for a mean duration of 25.7 months (73.1%, p<0.05). The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 15, consisted of 8 in RIG and 7 in RCG, of 41. 12 of 12 patients (100%, p<0.01) who were sputum positive at the time of surgery in LLG converted successfully. 14 of 15 patients (93.3%, p<0.05) with the follow up have completed treatment and not relapsed for a mean period of 25. 7 months. The mean length of postoperative drug therapy of LLG was 12.2 months. In RIG, postoperative negative conversion rate was 83.3% which was not significant statistically. There was a statistical significance in overall response rate (100%, p<0.05) of RIG for a mean period of 24.4 months with a mean length of postoperative chemotherapy, 11.8 months. In RCG a statistically lower overall response rate (14.3%, p<0.01) has been revealed for a mean duration of follow up, 24.2 months. A negative conversion rate of RCG was 75% which was not significant statistically. Conclusion : Surgery plays an important role in the management of patients with multidrug-resistant Mycobacterium tuberculosis infection. Aggressive pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection to avoid treatment failure or relapse. Especially all cavitary lesions on preoperative chest roentgenogram should be resected completely. If all of them could not be resected perfectly, you should not open the thorax.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.1 no.1
• /
• pp.79-89
• /
• 1998

Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

• Journal of Chest Surgery
• /
• v.30 no.10
• /
• pp.991-1000
• /
• 1997

Closed thoracostomy with UWSD* which is the most utilized procedure in chest surgery applies general thoracic disorders, trauma and after-thoracic surgery. The University hospital was involved on operating 2341 cases of closed thoracostomy with UWSD except chest tubing after-thoracic surgery for a full six years from January, 1991 to December, 1996. The rate of men and women out of the total 2341 cases was 3.5 : 1, the distribution by age showed that men were 36.6 $\pm21.0$ years old, women were $47.0\pm20.2$ years old and so that the total were 40.0 $\pm$ 20.5 years old. As for indication, spontaneous, secondary and traumatic pneumothorax were the most common, in addition to hemothorax hemopneumothorax, hydrothorax, hydropneumothorax, empyema, chylothorax. The most indwelling period of chest tubing is between eight and fourteen days for 974 cases and the average is 13.7 $\pm$ 6.3 days, The average drainage amount immediately after thoracostomy was 537 $\pm$ 88m1, and in 694 cases(46.0%), the drain amount was 201 ~ 500 ml. The rate of right and left tubing was 52.4 47.6, in 2071 cases(88.5%), the thoracostomy was the first chance and 2210 cases(94.4%) were treated with a single tube drainage. Almost all the patients complained of tube site pain, besides tube site infection, intercostal neuralgia, loss of tube function by the pleural adhesion, intrathoracic infection, incomplete reexpansion of defective lung, hemorrhage caused by the rupture of a blood vessel, subcutaneous emphysema, lung parenchymal rupture, diaphragmatic and intraabdominal trauma, reexpansionary pulmonary edema of one side lung and cellulitis were relapsed. 84.6% of all patients recovered with only clo ed thoracostomy and the rest of patient needed additional some necessary managements and so on to have successful results. There were two deaths(0.1%), caused by reexpansionary pulmonary edema, the cellulitis were complicated by thoracostomy with UWSD on an empyema patients to come to death(due to sepsis). t UWSD = under water seal drainage

• Journal of Gastric Cancer
• /
• v.4 no.4
• /
• pp.257-262
• /
• 2004

Purpose: We reported our preliminary result in 2001. At that time, the follow-up period was too short to evaluate the survival benefit of adjuvant chemotherapy in gastric cancer without serosal invasion. Therefore, we followed those patients for 66 months to determine the long-term effects of adjuvant chemotherapy. Materials and Methods: We analyzed the recurrence pattern, the survival rate, and the disease-specific survival of 135 patients by reviewing their medical records and calling the patients or their relatives. All enrolled patients were included in the intention-to-treat analysis of efficacy. Results: The follow-up rate was $89.6\%$ (121/135), and the median follow-up duration was 66 months. Among the 135 patients, 4 relapsed in group 1 (5-FU+cisplatin), 7 in group 2 (mitomycin C+oral 5-FU), and 6 in group 3 (oral 5-FU only). The overall survival rate was $89\%$ in group 1, $84\%$ in group 2, and $82\%$ in group 3. There were no differences in the overall survival rates and the disease-specific survival rates among the three groups. Conclusion: Oral chemotherapeutic agents have an acceptable effect for adjuvant chemotherapy compared with intravenous agent. However, a large-scale, prospective, randomized study, including a control group, is needed for an exact evaluation.

• Clinical and Experimental Pediatrics
• /
• v.52 no.5
• /
• pp.538-543
• /
• 2009

Purpose : To report the clinical experience with amitriptyline for managing children with cyclic vomiting syndrome (CVS). Methods : Totally, eleven children (eight males) were diagnosed with CVS. Of these, medical records were reviewed for eight children treated with amitriptyline; three children were not treated because one was not followed up and two were kept under observation to study the natural course without medication, because the frequency of vomiting had recently decreased to less than one episode per year. The eight amitriptyline-treated children were divided into three groups by the therapeutic response: (1) complete remission (CR), with no recurrence of symptoms after treatment; 2) partial remission (PR), in which the frequency of symptoms decreased by almost 50% after treatment; and (3) no response. Results : For the eight amitriptyline-treated children, the mean age of symptom onset was 4.7 (0.3-7) yr and mean age at diagnosis was 8.9 (6.0-11.3) yr. The mean number of vomiting episodes was 8.8 (2-25) per year, and the duration of vomiting in each episode ranged from 3 hours to 5 days. CR was achieved in five (62.5%) of the eight amitriptyline-treated children (0.2-0.8 mg/kg/day orally, at night) and PR was achieved in three children (37.5%). Two children relapsed on discontinuation of amitriptyline by their parents decision but showed improvement on remedication. No adverse effects were noted throughout the study period. Conclusion : Amitriptyline can be used in long-term prophylaxis for the management of children with CVS aged over 6 yr. However, a large-scale study is needed to ascertain its effects.

• Radiation Oncology Journal
• /
• v.15 no.1
• /
• pp.11-18
• /
• 1997

Purpose : To evaluate the efficacy of combined treatment of surgery and chemoradiotherapy for supratentorial primitive neuroectodermal tumors (SPNET) and obtain the Prognostic factors and complications Materials and Methods .The a9e of 18 patients ranged from 1 to 27 years (median=5 years). There were 12 males and 6 females The extents of surgery were gross total (n:9), subtotal (n:8), biopsy only (n: 1). Craniospinal radiotherapy was delivered to all the patients except 2 patients who were treated only with the whole brain and primary lesion. Radiation dose were 3120-5800cGy (median=5460) to primary mass, 1500-4200cGy (median=3600cGy) to the whole brain and 1320-3600cGy (median= 2400 cGy) to the spinal axis. Chemotherapy was done in 13 patients. Median follow-up period was 45 months ranged from 1 to 89 months. Results : Patterns of failure were as follows; local recurrence (1), multiple intracranial recurrence (2), spinal seeding (3), craniospinal seeding (2) and multiple bone metastasis (1). Two of two patients who did not received craniospinal radiotherapy failed at spinal area. All the relapsed cases died at 1 to 13 months after diagnosis of progression. The 2- and 5-rear overall survival rates were $61\%\;and\;49\%$, respectively The a9e, sex, tumor location did not influence the survival but aggressive resection with combined chemotherapy showed better outcome. Among 9 survivors, complications were detected as radiation necrosis (n=1), hypopituitarism (n=2), cognitive defect(n=1), memory deficit (n=1), growth retardation (n=1). Conclusion : To improve the results of treatment of SPNET, maximal surgical resection followed by radiation therapy and chemotherapy is necessary. The extended radiation field including craniospinal axis may reduce the recurrence in spinal axis.

• Radiation Oncology Journal
• /
• v.17 no.3
• /
• pp.217-222
• /
• 1999

Purpose : To evaluate prognostic factors and survival rates of the patients who received radiation therapy for locally recurrent uterine cervical cancer after curative surgery. Materials and Methods : Between October 1983 and July 1990, fifty three patients who received radiation therapy for locally recurrent cervical cancer after curative surgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, The Catholic University of Korea were analysed retrospectively. Age at diagnosis ranged from 33 to 69 years (median 53 years). Pathological analysis showed that forty five ($84.9\%$) patients had squamous cell carcinoma, seven ($13.2\%$) patients had adenocarcinoma, and one (1.9%) patient had adenosquamous cell carcinoma. The interval between hysterectomy and tumor recurrence ranged from 2 months to 25 years (mean 34.4 months). The recurrent sites were vaginal stump in 41 patients ($77.4\%$) and pelvic side wall in 12 patients ($22.6\%$). Recurrent tumor size was devided into two groups : less than 3 cm in 43 patients ($81.1\%$) and more than 3 cm in 10 patients ($18.9\%$). External beam irradiation of whole pelvis was done first up to 46.8 Gy to 50.4 Gy in 5 weeks to 6 weeks, followed by either external beam boost to the recurrent site in 18 patients ($34\%$) or intracavitary irradiation in 24 patients ($45.3\%$). Total dose of radiation ranged from 46.8 Gy to 111 Gy (median 70.2 Gy). Follow up period ranged from 2 to 153 months with a median of 35 months. Results : Overall response rate was $66\%$ (35/53). Among them, six patients ($17.1\%$) relapsed between 7 months and 116 months after radiation therapy (mean 47.7 months), Therefore overall recurrence rate was $45.3\%$. Overall five-year actuarial survival rate was $78.9\%$ and distant failure rate was $10\%$ (5/50). The significant prognostic factors affecting survival rate were interval between primary surgery and tumor recurrence (p=0.0055), recurrent tumor size (p=0.0039), and initial response to radiation therapy (p=0.0428). Complications were observed in 10 ($20/%$) patients, which included mild to moderate lower gastrointestinal, genitourinary, or skin manifestations. One patient died of pulmonary embolism just after intracavitary irradiation. Conclustion : Radiation therapy is the effective treatment for the patients with locally recurrent cervical cancer after curative surgery. These results suggest that interval between primary surgery and tumor recurrence, recurrent tumor size, and initial response to radiation therapy were significant prognostic factors for recurrent cervical cancer.