Year-Long Trend in Glycated Hemoglobin Levels in Patients with Type 2 Diabetes during the COVID-19 Pandemic

It has been suggested that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on glycemic control in patients with type 2 diabetes mellitus (T2DM). However, no study has examined yearly trends in glycated hemoglobin (HbA1c) levels after the start of the COVID-19 outbreak. Here, we performed a retrospective analysis of HbA1c concentrations during the early period of the COVID-19 outbreak (COVID-19 cohort) and then compared the yearly trend in the mean HbA1c level, along with fluctuations in HbA1c levels, with those during previous years (non-COVID-19 cohorts). We observed that the mean HbA1c level in patients with T2DM increased during the first 6 months of the COVID-19 outbreak. After 6 months, HbA1c levels in the COVID-19 cohort returned to levels seen in the non-COVID-19 cohorts. The data suggest that vulnerable patients with T2DM should be monitored closely during the early period of a pandemic to ensure they receive appropriate care.

Kikuchi Disease Manifesting as Multifocal Lymphadenopathy and Splenomegaly: Ultrasonography, CT, and 18F-FDG PET/CT Findings Mimicking Lymphoma

Kikuchi disease is a type of benign, self-limiting necrotizing lymphadenitis that occurs most commonly in young women and usually manifests as palpable cervical lymph nodes and fever. Patients with an unusual location of lymph node involvement can be misdiagnosed with malignant disease. Here, we report a case of Kikuchi disease in a 15-year-old girl presenting with persistent fever for 2 weeks. Imaging studies, including ultrasonography, CT, and 18F-fluorodeoxyglucose PET/CT, revealed splenomegaly and enlarged lymph nodes in the neck, axilla, abdomen, retroperitoneum, and inguinal region. Laparoscopic excision of the celiac lymph nodes confirmed histiocytic necrotizing lymphadenitis, also known as Kikuchi disease. Conservative treatment with corticosteroids improved the patient's condition.

Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997–2016: a Nationwide Retrospective Cohort Study

Background@#Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. @*Methods@#We collected the data of a newly diagnosed pediatric HHA cohort (2007–2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997–2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. @*Results@#A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. @*Conclusion@#In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

Renal Tumors in Children / 임상소아혈액종양

Pediatric renal tumors represent a diverse group, which include Wilms' tumor (WT), renal cell carcinoma (RCC), clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma, malignant rhabdoid tumor of the kidney (MRTK) and primitive neuroectodermal tumor. WT (85%) and RCC (8%) are the most prevalent types. WT predominates among the 1- to 10-year age group, but RCC exceeds WT in children over age 10 years. Pediatric renal tumors are genetically, histologically and clinically heterogeneous. The overall survival for children with localized WT is currently more than 90%, whereas poorer survival rates are observed for anaplastic WT, metastatic WT, metastatic CCSK, MRTK, metastatic RCC and relapsed WT. Therefore risk-stratified treatment is important to minimize treatment morbidity while preserving survival. This review focuses on distinct characteristics of each tumor type and optimal stratified treatment.

Renal Tumors in Children / 임상소아혈액종양

Pediatric renal tumors represent a diverse group, which include Wilms' tumor (WT), renal cell carcinoma (RCC), clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma, malignant rhabdoid tumor of the kidney (MRTK) and primitive neuroectodermal tumor. WT (85%) and RCC (8%) are the most prevalent types. WT predominates among the 1- to 10-year age group, but RCC exceeds WT in children over age 10 years. Pediatric renal tumors are genetically, histologically and clinically heterogeneous. The overall survival for children with localized WT is currently more than 90%, whereas poorer survival rates are observed for anaplastic WT, metastatic WT, metastatic CCSK, MRTK, metastatic RCC and relapsed WT. Therefore risk-stratified treatment is important to minimize treatment morbidity while preserving survival. This review focuses on distinct characteristics of each tumor type and optimal stratified treatment.

Esthesioneuroblastoma in a boy with 47, XYY karyotype / 소아과

Neuroblastomas are sometimes associated with abnormal constitutional karyotypes, but the XYY karyotype has been rarely described in neuroblastomas. Here, we report a case of an esthesioneuroblastoma in a boy with a 47, XYY karyotype. A 6-year-old boy was admitted to our hospital because of nasal obstruction and palpable cervical lymph node, which he first noticed several days previously. A polypoid mass in the right nasal cavity was detected through sinuscopy. Biopsy of the right nasal polyp was performed. Based on the result, the patient was diagnosed with a high-grade esthesioneuroblastoma. Nuclear imaging revealed increased uptake in both the right posterior nasal cavity and the right cervical IB-II space, suggesting metastatic lymph nodes. Cytogenetic analysis revealed a 47, XYY karyotype. Twelve courses of concurrent chemotherapy were administered. Three years after the completion of chemotherapy, the patient had had no disease recurrence. He manifested behavioral violence and temper tantrums, so we started methylphenidate for correction of the behavior.

Clinical Characteristics and Treatment Outcomes of Non-anaplastic Peripheral T-Cell Lymphoma in Children and Adolescents: A Single-center Experience / 임상소아혈액종양

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a rare form of non-Hodgkin's lymphoma (NHL), and it is usually associated with poor outcome. Here, we report our experience in treating this disease over 19 years, with the aim of helping to establish better treatment methods.METHODS: We retrospectively investigated 18 non-anaplastic PTCL cases that were diagnosed at a medical center in Seoul between October 1995 and October 2014. The clinical characteristics, treatments, and outcomes were reviewed.RESULTS: According to the World Health Organization (WHO) classifications for PTCL, 11 patients had PTCL, not otherwise specified (PTCL-NOS), 6 patients had extranodal natural killer/T-cell lymphoma, nasal type (ENKL), and 1 patient had subcutaneous panniculitis-like T-cell lymphoma. Patients were treated with various chemotherapeutic regimens. Of these 18 patients, 5 (27.7%) relapsed and 7 (38.9%) died from disease progression. Two relapsed patients received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). The 5-year event-free and overall survival rates were 43.2% and 66.7% in all cases, 45.5% and 54.5% in PTCL-NOS, and, 25.0% and 83.3% in ENKL, respectively.CONCLUSION: PTCL-NOS showed a suboptimal outcome. Among 6 ENKL patients, 3 relapsed, but 2 of 3 relapsed patients were salvaged. For better prognosis, HDCT-ASCT in relapsing and refractory PTCL and chemo-radiotherapy in ENKL could be considered as a salvage treatment. Larger studies are needed to confirm the outcome. Furthermore, an effort should be made to develop more efficient initial therapies through collaborative research.

Clinical Characteristics and Treatment Outcomes of Non-anaplastic Peripheral T-Cell Lymphoma in Children and Adolescents: A Single-center Experience / 임상소아혈액종양

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a rare form of non-Hodgkin's lymphoma (NHL), and it is usually associated with poor outcome. Here, we report our experience in treating this disease over 19 years, with the aim of helping to establish better treatment methods. METHODS: We retrospectively investigated 18 non-anaplastic PTCL cases that were diagnosed at a medical center in Seoul between October 1995 and October 2014. The clinical characteristics, treatments, and outcomes were reviewed. RESULTS: According to the World Health Organization (WHO) classifications for PTCL, 11 patients had PTCL, not otherwise specified (PTCL-NOS), 6 patients had extranodal natural killer/T-cell lymphoma, nasal type (ENKL), and 1 patient had subcutaneous panniculitis-like T-cell lymphoma. Patients were treated with various chemotherapeutic regimens. Of these 18 patients, 5 (27.7%) relapsed and 7 (38.9%) died from disease progression. Two relapsed patients received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). The 5-year event-free and overall survival rates were 43.2% and 66.7% in all cases, 45.5% and 54.5% in PTCL-NOS, and, 25.0% and 83.3% in ENKL, respectively. CONCLUSION: PTCL-NOS showed a suboptimal outcome. Among 6 ENKL patients, 3 relapsed, but 2 of 3 relapsed patients were salvaged. For better prognosis, HDCT-ASCT in relapsing and refractory PTCL and chemo-radiotherapy in ENKL could be considered as a salvage treatment. Larger studies are needed to confirm the outcome. Furthermore, an effort should be made to develop more efficient initial therapies through collaborative research.

Favorable outcome of allogeneic hematopoietic stem cell transplantation followed by post-transplant treatment with imatinib in children with Philadelphia chromosome-positive acute lymphoblastic leukemia

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the preferred curative therapy for children with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We evaluated the treatment outcomes of children with Ph+ ALL who underwent allogeneic HSCT. METHODS: Fifteen children diagnosed with Ph+ ALL in Asan Medical Center Children's Hospital between 1998 and 2012 were retrospectively analyzed. RESULTS: Of 521 children diagnosed with ALL during the study period, 15 had a Philadelphia chromosome. Among these 15 patients, 13 attained complete remission (CR) following induction chemotherapy, and two died of intracerebral hemorrhage during leukapheresis and induction chemotherapy, respectively. Of the 13 patients who attained CR, 12 received allogeneic HSCT, mainly from unrelated donors. Of the 12 patients who received HSCT, one died of a transplant-related cause, one died of relapse after HSCT, and 10 remain in continuous CR. Of the 10 patients who remained in CR longer than six months after HSCT, seven received post-HSCT imatinib. For all 15 patients, the 5-year overall survival, event-free survival, and cumulative incidence of relapse were 60.0%, 48.6%, and 38.8%, respectively, with a median follow-up of 70 months. For the HSCT group, the 5-year overall survival, event-free survival, and cumulative incidence of relapse were 80.2%, 72.9%, and 29.3%, respectively, with a median follow-up of 100 months. CONCLUSION: Allogeneic HSCT cures a significant proportion of Ph+ ALL patients. Because the use of imatinib appears to be a promising approach, strategies that include tyrosine kinase inhibitors before and after HSCT require further evaluation.

Clinical Significance of Previously Cryptic Copy Number Alterations and Loss of Heterozygosity in Pediatric Acute Myeloid Leukemia and Myelodysplastic Syndrome Determined Using Combined Array Comparative Genomic Hybridization plus Single-Nucleotide Polymo

The combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH+SNP microarray) platform can simultaneously detect copy number alterations (CNA) and copy-neutral loss of heterozygosity (LOH). Eighteen children with acute myeloid leukemia (AML) (n=15) or myelodysplastic syndrome (MDS) (n=3) were studied using CGH+SNP microarray to evaluate the clinical significance of submicroscopic chromosomal aberrations. CGH+SNP microarray revealed CNAs at 14 regions in 9 patients, while metaphase cytogenetic (MC) analysis detected CNAs in 11 regions in 8 patients. Using CGH+SNP microarray, LOHs>10 Mb involving terminal regions or the whole chromosome were detected in 3 of 18 patients (17%). CGH+SNP microarray revealed cryptic LOHs with or without CNAs in 3 of 5 patients with normal karyotypes. CGH+SNP microarray detected additional cryptic CNAs (n=2) and LOHs (n=5) in 6 of 13 patients with abnormal MC. In total, 9 patients demonstrated additional aberrations, including CNAs (n=3) and/or LOHs (n=8). Three of 15 patients with AML and terminal LOH>10 Mb demonstrated a significantly inferior relapse-free survival rate (P=0.041). This study demonstrates that CGH+SNP microarray can simultaneously detect previously cryptic CNAs and LOH, which may demonstrate prognostic implications.

Clinical characteristics and treatment outcomes of children with anaplastic large cell lymphoma: a single center experience

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is uncommon in children, accounting for approximately 15% of all cases of childhood non-Hodgkin lymphoma. Despite many studies attempting new treatment strategies, treatment outcomes have not significantly improved, and the optimal treatment for pediatric ALCL has not been established. METHODS: The records of newly diagnosed ALCL patients at our institute between July 1998 and April 2013 were reviewed. We evaluated the general characteristics of the patients, chemotherapy regimens, overall survival (OS) rates, and event-free survival (EFS) rates. RESULTS: Twenty-eight ALCL patients were eligible. The median age at diagnosis was 10.8 years. Lymph node involvement was the most common presentation (79%). CCG-5941, a multi-agent T-cell lineage chemotherapy, was the predominant treatment regimen (57%). The five-year OS and EFS rates were 88% and 69%, respectively. Stage, the presence of B symptoms, lung involvement, and bone marrow involvement were significant prognostic factors for EFS (P=0.02, 0.01, 0.01, and 0.02, respectively). Eight patients relapsed, and three died during the study period. Four of the eight patients who relapsed were treated with high-dose chemotherapy and autologous stem cell transplantation (HDCT-ASCT). Two of the four who had undergone HDCT-ASCT developed secondary relapses and were subsequently treated with allogeneic SCT or brentuximab. CONCLUSION: We found that treatment outcomes with multi-agent chemotherapy in children with ALCL were similar to those of previous reports, and that relapsed patients could be salvaged with HDCT-ASCT or allogeneic SCT. A prospective, larger cohort study is warranted to define the optimal treatment for pediatric ALCL.

Polyomavirus Activation in Pediatric Patients with Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation / 임상소아혈액종양

BACKGROUND: Reactivation of the polyomavirus and the use of conditioning regimen may be the causes of hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT). However, there are only a few reports on the clinical characteristics of viral reactivation in HC following HSCT in Korea, especially in pediatric population.METHODS: 51 patients who received HSCT in Ajou University Hospital from January 2006 to June 2012 were investigated retrospectively. 16 patients were diagnosed with HC following HSCT and were enrolled in this study. Confirmation of polyomavirus was done by polymerase chain reaction (PCR) method.RESULTS: Out of the 16 patients diagnosed with HC following HSCT, there were 5 early type HC patients and 11 late type HC patients. Positive PCR results for the BK virus (BKV) and the JC virus were found on 13 and 5 patients, respectively. 4 patients showed positive results for both viruses. For the late type HC, there were 10 patients with positive PCR results for the BKV. Cyclophosphamide was used in 33 patients, and 13 patients eventually developed HC. There was no statistical significance between the incidence of hematuria and the reactivation of the BKV or the conditioning regimens. Most patients were treated conservatively but 4 patients who showed severe hematuria or poor general condition received intravenous cidofovir. After the infusion of cidofovir, hematuria disappeared on average of 65 days and the BKV was undetectable on average of 53 days.CONCLUSION: In our study, activation of the BKV was common in patients who were diagnosed with HC following HSCT. All patients recovered from HC with conservative management and the BKV became undetectable in the majority of patients who were treated with intravenous cidofovir.

Polyomavirus Activation in Pediatric Patients with Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation / 임상소아혈액종양

BACKGROUND: Reactivation of the polyomavirus and the use of conditioning regimen may be the causes of hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT). However, there are only a few reports on the clinical characteristics of viral reactivation in HC following HSCT in Korea, especially in pediatric population. METHODS: 51 patients who received HSCT in Ajou University Hospital from January 2006 to June 2012 were investigated retrospectively. 16 patients were diagnosed with HC following HSCT and were enrolled in this study. Confirmation of polyomavirus was done by polymerase chain reaction (PCR) method. RESULTS: Out of the 16 patients diagnosed with HC following HSCT, there were 5 early type HC patients and 11 late type HC patients. Positive PCR results for the BK virus (BKV) and the JC virus were found on 13 and 5 patients, respectively. 4 patients showed positive results for both viruses. For the late type HC, there were 10 patients with positive PCR results for the BKV. Cyclophosphamide was used in 33 patients, and 13 patients eventually developed HC. There was no statistical significance between the incidence of hematuria and the reactivation of the BKV or the conditioning regimens. Most patients were treated conservatively but 4 patients who showed severe hematuria or poor general condition received intravenous cidofovir. After the infusion of cidofovir, hematuria disappeared on average of 65 days and the BKV was undetectable on average of 53 days. CONCLUSION: In our study, activation of the BKV was common in patients who were diagnosed with HC following HSCT. All patients recovered from HC with conservative management and the BKV became undetectable in the majority of patients who were treated with intravenous cidofovir.

RNA Mapping of Mutant Myotonic Dystrophy Protein Kinase 3'-Untranslated Region Transcripts

Myotonic dystrophy type 1 (DM1), which is a dominantly inherited neurodegenerative disorder, results from a CTG trinucleotide repeat expansion in the 3'-untranslated region (3'-UTR) of the myotonic dystrophy protein kinase (DMPK) gene. Retention of mutant DMPK (mDMPK) transcripts in the nuclei of affected cells has been known to be the main cause of pathogenesis of the disease. Thus, reducing the RNA toxicity through elimination of the mutant RNA has been suggested as one therapeutic strategy against DM1. In this study, we suggested RNA replacement with a trans -splicing ribozyme as an alternate genetic therapeutic approach for amelioration of DM1. To this end, we identified the regions of mDMPK 3'-UTR RNA that were accessible to ribozymes by using an RNA mapping strategy based on a trans - splicing ribozyme library. We found that particularly accessible sites were present not only upstream but also downstream of the expanded repeat sequence. Repair or replacement of the mDMPK transcript with the specific ribozyme will be useful for DM1 treatment through reduction of toxic mutant transcripts and simultaneously restore wild-type DMPK or release nucleus-entrapped mDMPK transcripts to the cytoplasm.

In Vivo Target RNA Specificity of Trans-Splicing Phenomena by the Group I Intron

The Tetrahymena group I intron has been shown to employ a trans-splicing reaction and has been modified to specifically target and replace human telomerase reverse transcriptase (hTERT) RNA with a suicide gene transcript, resulting in the induction of selective cytotoxicity in cancer cells that express the target RNA, in animal models as well as in cell cultures. In this study, we evaluated the target RNA specificity of trans -splicing phenomena by the group I intron in mice that were intraperitoneally inoculated with hTERT-expressing human cancer cells to validate the anti-cancer therapeutic applicability of the group I intron. To this end, an adenoviral vector that encoded for the hTERT-targeting group I intron was constructed and systemically injected into the animal. 5'-end RACE-PCR and sequencing analyses of the trans-spliced cDNA clones revealed that all of the analyzed products in the tumor tissue of the virus-infected mice resulted from reactions that were generated only with the targeted hTERT RNA. This study implies the in vivo target specificity of the trans - splicing group I intron and hence suggests that RNA replacement via a trans -splicing reaction by the group I intron is a potent anti-cancer genetic approach.

An RNA Mapping Strategy to Identify Ribozyme-Accessible Sites on the Catalytic Subunit of Mouse Telomerase

Telomerase reverse transcriptase (TERT) is an enzymatic ribonucleoprotein that prolongs the replicative life span of cells by maintaining protective structures at the ends of eukaryotic chromosomes. Telomerase activity is highly up-regulated in 85-90% of human cancers, and is predominately regulated by hTERT expression. In contrast, most normal somatic tissues in humans express low or undetectable levels of telomerase activity. This expression profile identifies TERT as a potential anticancer target. By using an RNA mapping strategy based on a trans-splicing ribozyme library, we identified the regions of mouse TERT (mTERT) RNA that were accessible to ribozymes. We found that particularly accessible sites were present downstream of the AUG start codon. This mTERTspecific ribozyme will be useful for validation of the RNA replacement as cancer gene therapy approach in mouse model with syngeneic tumors.

Gene expression responses in vivo by human telomerase reverse transcriptase (hTERT)-targeting trans-splicing ribozyme

A trans-splicing ribozyme which can specifically reprogram human telomerase reverse transcriptase (hTERT) RNA was previously suggested as a useful agent for tumor-targeted gene therapy. In this study, we evaluated in vivo function of the hTERT-targeting trans-splicing ribozymes by employing the molecular analysis of expression level of genes affected by the ribozyme delivery into peritoneal carcinomatosis mice model. To this effect, we constructed adenoviral vector encoding the specific ribozyme. Noticeably, more than four-fold reduction in the level of hTERT RNA was observed in tumor nodules by the systemic infection of the ribozyme-encoding virus. Such hTERT RNA knockdown in vivo induced changes in the global gene expression profile, including the suppression of specific genes associated with anti-apoptosis including bcl2, and genes for angiogenesis and metastasis. In addition, specific trans-splicing reaction with the targeted hTERT RNA took place in the tumors established as peritoneal carcinomatosis in mice by systemic delivery of the ribozyme. In conclusion, this study demonstrates that an hTERT-specific RNA replacement approach using trans-splicing ribozyme represents a potential modality to treat cancer.

Specificity of Intracellular Trans-Splicing Reaction by hTERT-Targeting Group I Intron

Recent anti-cancer approaches have been based to target tumor-specifically associated and/or causative molecules such as RNAs or proteins. As this specifically targeted anti-cancer modulator, we have previously described a novel human cancer gene therapeutic agent that is Tetrahymena group I intron-based trans-splicing ribozyme which can reprogram and replace human telomerase reverse transcriptase (hTERT) RNA to selectively induce tumor-specific cytotoxicity in cancer cells expressing the target RNA. Moreover, the specific ribozyme has been shown to efficiently retard tumor tissues in xenograft mice which had been inoculated with hTERT-expressing human cancer cells. In this study, we assessed specificity of trans-splicing reaction in cells to evaluate the therapeutic feasibility of the specific ribozyme. In order to analyze the trans-spliced products by the specific ribozyme in hTERT-positive cells, RT, 5'-end RACE-PCR, and sequencing reactions of the spliced RNAs were employed. Then, whole analyzed products resulted from reactions only with the hTERT RNA. This study suggested that the developed ribozyme perform highly specific RNA replacement of the target RNA in cells, hence trans-splicing ribozyme will be one of specific agents for genetic approach to revert cancer.

Massive Identification of Cancer-Specific Nucleic Acid Ligands

Targeting of complex system such as human cells rather than biochemically pure molecules will be a useful approach to massively identify ligands specific for the markers associated with human disease such as cancer and simultaneously discover the specific molecular markers. In this study, we developed in vitro selection method to identify nuclease-resistant nucleic acid ligands called RNA aptamers that are specific for human cancer cells. This method is based on the combination of the cell-based selection and subtractive systematic evolution of ligands by exponential enrichment (SELEX) method. These aptamers will be useful for cancer-specific ligands for proteomic research to identify cancer-specific molecular markers as well as tumor diagnosis and therapy.

Functional Modification of a Specific RNA with Targeted Trans-Splicing

The self-splicing group I intron from Tetrahymena thermophila has been demonstrated to perform splicing reaction with its substrate RNA in the trans configuration. In this study, we explored the potential use of the trans-splicing group I ribozymes to replace a specific RNA with a new RNA that exerts any new function we want to introduce. We have chosen thymidine phosphorylase (TP) RNA as a target RNA that is known as a valid cancer prognostic factor. Cancer-specific expression of TP RNA was first evaluated with RT-PCR analysis of RNA from patients with gastric cancer. We determined next which regions of the TP RNA are accessible to ribozymes by employing an RNA mapping strategy, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. A specific ribozyme recognizing the most accessible sequence in the TP RNA with firefly luciferase transcript as a 3' exon was then developed. The specific trans-splicing ribozyme transferred an intended 3' exon tag sequence onto the targeted TP transcripts, resulting in a more than two fold induction of the reporter activity in the presence of TP RNA in mammalian cells, compared to the absence of the target RNA. These results suggest that the Tetrahymena ribozyme can be a potent anti-cancer agent to modify TP RNAs in tumors with a new RNA harboring anti-cancer activity.