• Journal of Chest Surgery
• /
• v.50 no.5
• /
• pp.382-385
• /
• 2017

A 47-year-old man with myasthenia gravis (MG) was admitted for a lung transplant. He had bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation due to acute myeloid leukemia. MG developed after stem cell transplantation. Bilateral sequential lung transplantations and a total thymectomy were performed. The patient underwent right diaphragmatic plication simultaneously due to preoperatively diagnosed right diaphragmatic paralysis. A tracheostomy was performed and bilevel positive airway pressure (BiPAP) was applied on postoperative days 8 and 9, respectively. The patient was transferred to the general ward on postoperative day 12, successfully weaned off BiPAP on postoperative day 18, and finally discharged on postoperative day 62.

• Journal of Gastric Cancer
• /
• v.7 no.4
• /
• pp.237-241
• /
• 2007

Purpose: Patients with hematologic diseases such as chronic myeloid leukemia (CML) or chronic lymphoid leukemia (CLL) are known to have an increased chance of acquiring a secondary neoplasm. Stomach cancer is one of the most common malignant diseases in Korea, and we investigated whether the incidence of secondary stomach cancer in patients with a hematologic disease increases, in order to determine if a more intensive screening program for detecting secondary gastric cancer was required. We also investigated the safety of performing a gastrectomy in hematologic disease patients. Materials and Methods: From 1992 to 2006, the medical records of 8376 patients diagnosed with one of the six common hematologic diseases were reviewed. Results: Nine secondary stomach cancers were found among the 8376 patients during the 15-year observation period. No surgical-related complications occurred, and there was no recurrence of stomach cancer if detected early. Conclusion: It seems that a more intensive screening program for detecting secondary gastric cancer in hematologic disease patients is not required, and surgery is not risky in these patients.

• IMMUNE NETWORK
• /
• v.5 no.1
• /
• pp.36-44
• /
• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.9
• /
• pp.4827-4834
• /
• 2012

Tumor suppressor genes have received much attention for their roles in the development of human malignancies. Gelsolin has been found to be down-regulated in several types of human cancers, including leukemias. It is, however, expressed in macrophages, which are the final differentiation derivatives for the monocytic myeloid lineage, implicating this protein in the differentiation process of such cells. In order to investigate the role of gelsolin in leukaemic cell differentiation, stable clones over-expressing ectopic gelsolin, and a control clone were established from U937 leukaemia cells. Unlike the control cells, both gelsolin-overexpressing clones displayed retarded growth, improved monocytic morphology, increased NADPH and NSE activities, and enhanced surface expression of the ${\beta}$-integrin receptor, CD11b, when compared with the parental U937 cells. Interestingly, RT-PCR and western blot analysis also revealed that gelsolin enhanced p21CIP1 mRNA and protein expression in the overexpressing clones. Moreover, transient transfection with siRNA silencing P21CIP1, but not the control siRNA, resulted in a reduction in monocytic differentiation, accompanied by an increase in proliferation. In conclusion, our work demonstrates that gelsolin, by itself, is capable of inducing monocytic differentiation in U937 leukaemia cells, most probably through p21CIP1 activation.

• Proceedings of the Korean Society of Developmental Biology Conference
• /
• 2003.10a
• /
• pp.107-107
• /
• 2003

The activation of protooncogenes or the inactivation of their gene products may be a specific and effective functional study for human neoplasia. To examine this possibility, we have used the tetracycline regulatory system to generate transgenic mice that conditionally express the HccR-2 protooncogene in vivo. The new human cervical cancer protooncogene (HccR-2) was detected from cervical cancer cell line. To elucidate its biological functions, we generated transgenic mice that expressed the HccR-2 gene. The sustained expression of the HccR-2 transgene culminated chronic neutrophilic leukemia (CNL). CNL is a rare chronic myeloproliferative disorder that presents as a sustained, mature neutrophilic leukocytosis with few or no circulating immature granulocytes, the absence of peripheral blood monocytosis, basophilia, or eosinophilia, and infiltration of neutrophils at the liver, spleen and kidney. Mice expressing the HccR-2 and tetracycline-transactivating protein (tTa) transgene were found to have altered myeloid development that was characterized by increased percentages of mature neutrophil and band form neutrophil in the peripheral blood, liver and spleen. Activation of the transgene causes CNL. In our model, expression of HccR-2 transgene mice was similar in many respects to the human CNL. This model will be valuable not only for investigating the biological properties of the HccR-2 and other protooncogenes in vivo but also for analyzing the mechanism involved in the progression of CNL.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2002.07a
• /
• pp.113-113
• /
• 2002

Phylogenetically conserved Bcl-2 family proteins play a pivotal role in the regulation of apoptosis from virus to human. Members of the Bcl-2 family consist of antiapoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w, and proapoptotic proteins such as BAD, Bax, BOD, and Bok. It has been proposed that anti- and proapoptotic Bcl-2 proteins regulate cell death by binding to each other and forming heterodimers. A delicate balance between anti- and proapoptotic Bcl-2 family members exists in each cell and the relative concentration of these two groups of proteins determines whether the cell survives or undergoes apoptosis. Mcl-1 (Myeloid cell :leukemia-1) is a member of the Bcl-2 family proteins and was originally cloned as a differentiation-induced early gene that was activated in the human myeloblastic leukemia cell line, ML-1 . Mcl-1 is expressed in a wide variety of tissues and cells including neoplastic ones. We recently identified a short splicing variant of Mcl-1 short (Mcl-IS) and designated the known Mcl-1 as Mcl-1 long (Mcl-lL). Mcl-lL protein exhibits antiapoptotic activity and possesses the BH (Bcl-2 homology) 1, BH2, BH3, and transmembrane (TM) domains found in related Bcl-2 proteins. In contrast, Mcl-1 S is a BH3 domain-only proapoptotic protein that heterodimerizes with Mcl-lL. Although both Mc1-lL and Mcl-lS proteins contain BH domains fecund in other Bcl-2 family proteins, they are distinguished by their unusually long N-terminal sequences containing PEST (proline, glutamic acid, serine, and threonine) motifs, four pairs of arginine residues, and alanine- and glycine-rich regions. In addition, the expression pattern of Mcl-1 protein is different from that of Bcl-2 suggesting a unique role (or Mcl-1 in apoptosis regulation. Tankyrasel (TRF1-interacting, ankyrin-related ADP-related polymerasel) was originally isolated based on its binding to TRF 1 (telomeric repeat binding factor-1) and contains the sterile alpha motif (SAM) module, 24 ankyrin (ANK) repeats, and the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP). Previous studies showed that tankyrasel promotes telomere elongation in human cells presumably by inhibiting TRFI though its poly(ADP-ribosyl)action by tankyrasel . In addition, tankyrasel poly(ADP-ribosyl)ates Insulin-responsive amino peptidase (IRAP), a resident protein of GLUT4 vesicles, and insulin stimulates the PARP activity of tankyrase1 through its phosphorylation by mitogen-activated protein kinase (MAPK). ADP-ribosylation is a posttranslational modification that usually results in a loss of protein activity presumably by enhancing protein turnover. However, little information is available regarding the physiological function(s) of tankyrase1 other than as a PARP enzyme. In the present study, we found tankyrasel as a specific-binding protein of Mcl-1 Overexpression of tankyrasel led to the inhibition of both the apoptotic activity of Mel-lS and the survival action of Mcl-lL in mammalian cells. Unlike other known tankyrasel-interacting proteins, tankyrasel did not poly(ADP-ribosyl)ate either of the Mcl-1 proteins despite its ability to decrease Mcl-1 proteins expression following coexpression. Therefore, this study provides a novel mechanism to regulate Mcl-1-modulated apoptosis in which tankyrasel downregulates the expression of Mcl-1 proteins without the involvement of its ADP-ribosylation activity.

• Korean Journal of Veterinary Research
• /
• v.27 no.2
• /
• pp.269-275
• /
• 1987

Radiation-induced life shortening, carcinogenesis and other pathological changes were investigated in NIH(GP) mice after $^{60}Co-{\gamma}$ ray irradiation(100~700rads). The results were summarized as follows: 1. There were little difference in body weights, hematological examination and other clinical findings between normal and irradiated groups. 2. Mean survival time of the mice after irradiation were decreased dose-dependently. 3. Main gross findings of the mice irradiated were appeared as enlargement of spleen, thymus and lymph nodes, tumorous nodules of lung and cyst of ovary. Especially, enlargement of thymus was promineort in high dose group. 4. Microscopically, there were various findings including myeloid leukemia, thymic lymphoma, lung adenoma, adenosquamous cell carcinoma of pancreas, pneumonia and other pathological changes. Especially thymic lymphoma was highly frequent in the 700 rads group.

• Parasites, Hosts and Diseases
• /
• v.48 no.1
• /
• pp.1-7
• /
• 2010

Neutrophils play an important role in the human immune system for protection against such microorganisms as a protozoan parasite, Trichomonas vaginalis; however, the precise role of neutrophils in the pathogenesis of trichomoniasis is still unknown. Moreover, it is thought that trichomonal lysates and excretory-secretory products (ESP), as well as live T. vaginalis, could possibly interact with neutrophils in local tissues, including areas of inflammation induced by T. vaginalis in humans. The aim of this study was to investigate the influence of T. vaginalis lysate on the fate of neutrophils. We found that T. vaginalis lysate inhibits apoptosis of human neutrophils as revealed by Giemsa stain. Less altered mitochondrial membrane potential (MMP) and surface CD16 receptor expression also supported the idea that neutrophil apoptosis is delayed after T. vaginalis lysate stimulation. In contrast, ESP stimulated-neutrophils were similar in apoptotic features of untreated neutrophils. Maintained caspase-3 and myeloid cell leukemia-1 (Mcl-1) in neutrophils co-cultured with trichomonad lysate suggest that an intrinsic mitochondrial pathway of apoptosis was involved in T. vaginalis lysate-induced delayed neutrophil apoptosis; this phenomenon may contribute to local inflammation in trichomoniasis.

• Bulletin of the Korean Chemical Society
• /
• v.35 no.7
• /
• pp.2097-2108
• /
• 2014

Chemical feature based quantitative pharmacophore models were generated using the HypoGen module implemented in DS2.5. The best hypothesis, Hypo1, which was characterized by the highest correlation coefficient (0.96), the highest cost difference (61.60) and the lowest RMSD (0.74), consisted of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic and one ring aromatic. The reliability of Hypo1 was validated on the basis of cost analysis, test set, Fischer's randomization method and GH test method. The validated Hypo1 was used as a 3D search query to identify novel inhibitors. The screened molecules were further refined by employing ADMET, docking studies and visual inspection. Three compounds with novel scaffolds were selected as the most promising candidates for the designing of Mcl-1 antagonists. Finally, a 10 ns molecular dynamics simulation was carried out on the complex of receptor and the retrieved ligand to demonstrate that the binding mode was stable during the MD simulation.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.5945-5950
• /
• 2015

A 6-year retrospective cohort study was conducted among Thai hematologic malignancy (HM) patients receiving intensive chemotherapy. Of the 145 eligible patients receiving 893 chemotherapy sessions, 46.9% were female, median age was 52 years, and the most common HM diagnosis was diffuse large B-cell lymphoma (46.2%). Febrile neutropenia (FN) occurred in 14.9% of chemotherapy sessions with an incidence of 24.8 per 1,000 chemotherapy cycles per year. Independent factors associated with FN were receiving the first chemotherapy cycle [adjusted hazard ratio (aHR) 4.1], having hemoglobin ${\leq}100g/L$ (aHR 3.7) and platelet ${\leq}140,000/{\mu}L$ (aHR 2.7) on chemotherapy day and receiving acute myeloid leukemia regimens (aHR 20.8). Granulocyte colony stimulating factor was significantly associated with reduced rate of FN when given in those receiving CHOP regimen. With the median follow-up time of 16 months, the overall survival time was significantly longer in patients without FN than those with FN (61.7 vs. 20.8 months; p<0.001).