• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7025-7029
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• 2015

Background: The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. Materials and Methods: Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. Results: The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. Conclusions: The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4699-4711
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• 2016

Background: In the last decade, it has become clear that change of gene expression may alter the hematopoietic cell quiescent state and consequently play a major role in leukemogenesis. WT1 is known to be a player in acute myeloid leukemia (AML) and FOXP3 has a crucial role in regulating the immune response. Objectives: To evaluate the impact of overexpression of WT1and FOXP3 genes on clinical course in adult and pediatric AML patients in Egypt. Patients and methods: Bone marrow and peripheral blood samples were obtained from 97 de novo non M3 AML patients (63 adult and 34 pediatric). Real-time quantitative PCR was used to detect overexpression WT1 and FOXP3 genes. Patient follow up ranged from 0.2 to 39.0 months with a median of 5 months. Results: In the pediatric group; WT1 was significantly expressed with a high total leukocyte count median 50X109/L (p=0.018). In the adult group, WT1 had an adverse impact on complete remission induction, disease-free survival and overall survival (p=0.02, p=0.035, p=0.019 respectively). FOXP3 overexpression was associated with FAB subtypes AML M0 +M1 vs. M2, M4+M5 (p =0.039) and the presence of hepatomegaly (p=0.005). Conclusions: WT1 and FOXP3 overexpression has an adverse impact on clinical presentation, treatment response and survival of pediatric and adult Egyptian AML patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6663-6668
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• 2015

Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Materials and Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong. Results: The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive cases were in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05). Conclusions: Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.

• Clinical and Experimental Pediatrics
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• v.53 no.3
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• pp.437-441
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• 2010

Toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) are rare, life-threatening mucocutaneous -diseases, usually attributable to drugs and infections. Corticosteroids have been used in the management of TEN for the last 30 years. This remains controversial and is still much debated. TEN can occur despite administration of high doses of systemic corticosteroids. The psychiatric side effects of corticosteroids can include headache, insomnia, depression, and mood disorders with or without psychotic episodes. Steroid-induced psychosis is dealt with by tapering or discontinuing the steroid; antipsychotics are also sometimes used. We report a case of an 11-year-old boy who was admitted with TEN. He had also been diagnosed as having nephrotic syndrome in the past. Remission was achieved through induction therapy and by maintaining the use of steroids. After a full-dose intravenous dexamethasone for TEN, he showed psychotic symptoms. We diagnosed him as having steroid-induced psychosis. We tapered the steroid use and initiated an atypical antipsychotic medication, olazapine and intravenous immunoglobulin (IV-IG). His symptoms dramatically improved and he was discharged.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.79-86
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• 2001

Recent clinical studies have shown that a high proportion of patients with acute promyelocytic leukemia (APL) achieve complete remission after treatment with all-trans retinoic acid (ATRA). However, most patients who receive continuous treatment with ATRA relapse and develop ATRA-resistant leukemia. Dendritic cells (DCs) are important antigen-presenting cells in the development of antileukemic T-cell responses. In this study, we investigated the strategies to overcome ATRA resistance of APL cells by inducing the differentiation of DCs from human leukemic cell lines for the developtment of adoptive immunotherapy. CD83 was used as a mature DC marker in this study and the expression of CD83 mRNA was determined by RT-PCR method. The promyelocytic leukemic cell line HL-60, B lymphoblast cell lines RPMI 7666 and NC-37 could be induced to dendritic cells in vitro. Treatment of HL-60 with phorbol 12-myristate 13-acetate (PMA) resulted in the expression of myeloid-related DC phenotypes, while treatment of RPMI 7666 with fms-like tyrosine kinase 3 ligand (Flt3-ligand, FL) and treatment of NC-37 with PMA and FL led to the expression of lymphoid-related DC phenotypes. In conclusion, myeloid-related DC phenotypes and lymphoid-related DC phenotypes could be generated from HL-60, NC-37 and RPMI 7666 cell lines, respectively. These DC phenotypes can potentially be used to generate antileukemic T cells in vitro for adoptive immunotherapy.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1478-1487
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• 2019

Ulcerative colitis (UC), a chronic inflammatory bowel disease, substantially impacts patients' health-related quality of life. In this study, an effective strategy for discovering high-efficiency probiotics has been developed. First, in order to survive in the conditions of the stomach and intestine, high bile salt-resistant and strong acid-resistant strains were screened out from the fecal flora of healthy adults. Next, the probiotic candidates were rescreened by examining the induction ability of IL-10 (anti-inflammatory factor) production in dextran sodium sulfate (DSS)-induced colitis mice, and Lactobacillus sakei 07 (L07) was identified and selected as probiotic P. In the end, fourteen bifidobacterium strains isolated from stools of healthy males were examined for their antimicrobial activity. Bifidobacterium bifidum B10 (73.75% inhibition rate) was selected as probiotic B. Moreover, the colonic IL-6 and $TNF-{\alpha}$ expression of the DSS-induced colitis mice treated with L. sakei 07 (L07) - B. bifidum B10 combination (PB) significantly decreased and the IL-10 expression was up-regulated by PB compared to the DSS group. Furthermore, Bacteroidetes and Actinobacteria decreased and Firmicutes increased in the DSS group mice, significantly. More interestingly, the intestinal flora biodiversity of DSS colitis mice was increased by PB. Of those, the level of B. bifidum increased significantly. The Bacteriodetes/Firmicutes (B/F) ratio increased, and the concentration of homocysteine and LPS in plasma was down-regulated by PB in the DSS-induced colitis mice. Upon administration of PB, the intestinal permeability of the the DSS-induced colitis mice was decreased by approximately 2.01-fold. This method is expected to be used in high-throughput screening of the probiotics against colitis. In addition, the L. sakei 07 - B. bifidum B10 combination holds potential in UC remission by immunomodulatory and gut microbiota modulation.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.331-338
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• 1995

Purpose : To evaluate our clinical experience with the combination of teletherapy and intraluminal brachytherapy in patients with unresectable or inoperable esophageal cancers. Materials and Methods : From Nov 1989 to Mar 1993, twenty patients with esophageal cancer were treated with radical radiotherapy and intraluminal brachytherapy at Yonsei Cancer Center. All patients had squamous histolgy and stage distribution was as follows: stage II, 4($20{\%}$)patients; III, 15 ($75{\%}$)patients; IV, 1($5{\%}$)patients. A dose of S-12Gy/1-3weeks with intraluminal brachytherapy (3-5Gy/fraction) to 5mm from the outside of the esophageal tube using high dose rate Iridium-192 remotely afterloading brachytherapy machine was given 2 weeks after a total dose of 59-64Gy with external radiotherapy. Induction chemotherapy using cisplatin and 5-FU was performed in 13 patients with median 3 cycles(1-6 cycles), Response rate, local control rate, survival and complications were analysed retrospectively. Results : Two-year overall survival rate and median survival were $15.8{\%}$ and 13.5 months. Response rates were as follows complete remission(CR) 5($25{\%}$): partial remission a(PRa) 7($35{\%}$): partial remission b(PRb) 7($35{\%}$), no response(NR) 1($5{\%}$). Patterns of failure were as follows; local failure 13($65{\%}$), local and distant failure 3($15{\%}$), distant failure 0($0{\%}$). Ultimate local control rate was $20{\%}$. Treatment related complications included esophageal ulcer in two patients and esophageal stricture in one. Conclusion : Though poor local conrol rate, median survival was improved as compared with previous results of radiation therapy alone(8months) and chemoradiation combined treatment(11 months) in Yonsei Cancer Center High-dose-rate intraluminal brachytherapy following external irradiation is an effective treatment modality with acceptable toxicity in esophageal cancer.

• Radiation Oncology Journal
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• v.14 no.2
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• pp.137-147
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• 1996

Purpose : This report is the result f retrospective analysis for children who received prophylactic cranial irradiation combined with intrathecal chemotherapy. Materials and Methods : Ninety children with ALL who had got bone marrow remission after induction chemotherapy received PCI. All but 3 children were treated with a dose of 1800 cGy as a standard regimen. While the PCI was given, all patients received intrathecal chemotherapy. Results : Nine of 90 patients experienced CNS relapse during the duration of follow-up ranged from 36 to 96 months (median 60 months). Three children experienced BM relapse prior to CNS relapse. Therefore, CNS relapse rate as the first adverse event was $6.7\%$. Median time interval of CNS relapse was 16 months from the first day of hematologic complete remission. Eighty-nine percent of patients who had CNS relapse were associated with hematologic relapse. and $78\%$ of CNS relpase occurred during maintenance chemotherapy (on-therapy relapse). The CNS RFS at 2 and 5 years are $68\%$ and $42\%$, respectively with median of 43 months. The Prognostic factors affecting CNS RFS are initial WBC count (cut-off point of 50,000/ul), FAB subtype and CALGB risk criteria. The DFS at 2 and 5 years are 61 and $39\%$, respectively with median of 34 months. The prognostic factors affecting DFS are initial WBC count (cut-off point of 50,000/ul), FAB subtype, POG and CALGB risk criteria. Conclusions : In our study, $6.7\%$ of CNS relapse rate as a first adverse event was comparable with other studies. Various risk criteria was based on age at diagnosis and initial WBC count such as POG and CALGB criteria, had prognostic significance for CNS RFS and DFS. Prospective randomized trial according to prognostic subgroup based on risk criteria and systematic study about neuropsychologic function for long term survivors, are essential to determine the most effective and least toxic form of CNS prophylaxis.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.359-368
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• 2001

Purpose : To determine the long-term results of bladder-preserving approach by transurethral resection of the bladder (TURB), systemic chemotherapy, and radiation therapy for muscle-invasive bladder cancer Methods and materiaals : From 1991 Jan. through 1994 Dec., 25 patients with muscle invading clinical stage T2 to T4NxM0 bladder cancer were treated with induction by maximal TURB and (arm 1, n=4) three cycles of chemotherapy [MVAC(methotrexate, vincristine, adriamycin, ciplatin)] followed by 64.8 Gy of radiation with concomitant cisplatin, or two cycles of chemotherapy [MCV (methotrexate, ciplatin, vincristine)] after irradiation with concomitant cisplatin (arm 2, n=14), or concurrent chemoradiation only (arm 3, n=7). Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. Those with less than a CR underwent cystectomy. The median follow-up of all patients was 70 months. Resulst : Most treatment toxicities were mild to moderate. Grade 3 acute hematologic toxicity and chronic cystitis were observed in only 1 and 2 patients, respectively. Overall 5 year survival was $67.3\%$. Complete remission rate was $80\%$ (20/25). Sixty-three percent of all survivors retained their bladders. In multivariate analysis, prognostic factors that significantly affect survival were T-stage (p=0.013) and Complete remission (p=0.002). Conclusion : Combined modality therapy with TURB, chemotherapy, and radiation has a $67.3\%$ overall 5 year survival rate. This result is similar to cystectomy-based studies for patients of similar clinical stages.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.9 no.2
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• pp.210-217
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• 2006

Purpose: Crohn disease (CD) in children is frequently complicated by malnutrition and growth retardation. Conventional treatment with corticosteroid may also affect the growth of children, which may be alleviated by nutritional therapy. Therefore, we performed this study to evaluate the role of nutritional therapy in the treatment of CD in children. Methods: The study cohort consisted of thirty children under the age of 17 years, admitted to the Asan Medical Center from 2001 to 2005. While 11 children received nutritional therapy (NT) with an elemental diet, 19 received conventional corticosteroid therapy (ST). Comparative analysis was performed for the rate of the induction of remission, recurrence, disease activity index of pre and post-treatment, and changes of the growth using mean standard deviation score for weight (zW) and height (zH). Results: Ten of 11 children with NT and 18 of 19 children with ST completed the therapy. Two of them were lost to follow-up during the treatment. All 10 children with NT and 15 of 18 children with ST achieved remission. While there was no recurrence in children with NT, 7 with ST showed recurrence within 1 year. Pre- and post treatment Pediatric Crohn disease Activity Index (PCDAI) did not show a difference between the two groups. There were no differences in zW and zH between the two groups after 1 year of follow-up. Conclusion: This study showed that nutritional therapy could be considered instead of steroid therapy for treatment of children with CD. However, a long-term study will be needed to determine the long-term efficacy.