Efficacy of the granisetron transdermal system for the control of nausea and vomiting induced by highly emetogenic chemotherapy: a multicenter, randomized, controlled trial

Background/Aims@#We compared the efficacy of the granisetron transdermal system (GTS) with that of ondansetron for controlling chemotherapy-induced nausea and vomiting (CINV) in patients treated with highly emetogenic chemotherapy (HEC). @*Methods@#We randomized a total of 389 patients to groups treated by GTS and ondansetron before HEC. The primary endpoint was the percentage of patients achieving complete response (CR; no retching/vomiting/rescue medication) of CINV from the time of chemotherapy initiation to 24 hours after the last administration of chemotherapy (prespecified non-inferiority margin of 15%). Quality of life (QoL) was also assessed using the Functional Living Index-Emesis (FLIE). @*Results@#The per protocol analysis included 152 (47.80%) and 166 patients (52.20%) in the GTS and ondansetron groups, respectively. In the full analysis set, the most common diagnosis, regimen, and period of chemotherapy were lung cancer (149 patients, 40.27%), cisplatin-based regimen (297 patients, 80.27%), and 1 day chemotherapy (221 patients, 59.73%). The CR rates were 86.84% and 90.36% in the GTS and ondansetron groups, respectively; the treatment difference was −3.52% (95% confidence interval, −10.52 to 3.48) and met the primary endpoint, indicating that GTS was not inferior to ondansetron. Patient satisfaction, assessed on the FLIE, showed significantly higher scores in the GTS group compared to the ondansetron group (mean ± standard deviation, 1,547.38 ± 306.00 and 1,494.07 ± 312.05 mm, respectively; p = 0.0449). @*Conclusions@#GTS provided effective, safe, and well-tolerated control of CINV and improved the QoL in HEC.

Mesenchymal Stem Cells Derived from Wharton’s Jelly Can Differentiate into Schwann Cell-Like Cells and Promote Peripheral Nerve Regeneration in Acellular Nerve Grafts

BACKGROUND@#Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton’s Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCsladen acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury. @*METHODS@#The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining. @*RESULTS@#Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100b, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs.WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury. @*CONCLUSION@#WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.

Mesenchymal Stem Cells Derived from Wharton’s Jelly Can Differentiate into Schwann Cell-Like Cells and Promote Peripheral Nerve Regeneration in Acellular Nerve Grafts

BACKGROUND@#Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton’s Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCsladen acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury. @*METHODS@#The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining. @*RESULTS@#Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100b, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs.WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury. @*CONCLUSION@#WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.

Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined. MATERIALS AND METHODS: A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13mRNA expression levels using a NanoString assay (NanoString Technologies). RESULTS: The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate. CONCLUSION: MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.

Small Cell Lung Cancer with Mutation of Epidermal Growth Factor Receptor in Patients with Lung Adenocarcinoma Resistant to Gefitinib / 대한내과학회지

Most epidermal growth factor receptor (EGFR) gene mutations are detected in lung adenocarcinomas. In contrast, these mutations have rarely been reported in small cell lung cancer (SCLC). We herein report two cases of EGFR-mutant SCLC transformed from and combined with lung adenocarcinoma. In one case, SCLC appeared to be transformed from EGFR mutant 19-del adenocarcinoma when the patient became resistant to gefitinib. The other patient had combined EGFR-mutant 19-del SCLC and adenocarcinoma at the initial diagnosis, which was resistant to gefitinib at multiple sites. Further comparative molecular analyses of these histologically distinct tumors would provide useful information regarding the role of EGFR mutation in the pathogenesis of SCLC. In conclusion, despite the presence of the same EGFR mutation, gefitinib was not effective in treatment of SCLC. Therefore, confirmation of SCLC cell morphology may become an important means of predicting resistance to EGFR tyrosine kinase inhibitors in addition to common secondary genetic alterations.

A Case of Patient with Lung Adenocarcinoma with Double Rare EGFR Mutation of G719C and L861Q / 계명의대학술지

The vast majority of epidermal growth factor receptor (EGFR) gene mutations are detected in lung adenocarcinoma. EGFR mutations are the strongest predictor of response to EGFR tyrosine kinase inhibitor (TKI) treatment in patient with advanced non-small cell lung cancer. Of these, exon 19 deletions and exon 21 L858R point mutations account for more than 80% of mutations detected in tumor with EGFR mutations, which called classical EGFR mutations, and double mutations mainly composed of classical and uncommon EGFR mutations are reported to be present in 13% of total EGFR mutations. But there has been no report to date of patient with double mutation of TKI sensitive uncommon EGFR mutations (G719C and L861Q). We experienced a case of patient with lung adenocarcinoma with double mutation of G719C and L861Q, the first case on our literature review, and showing partial response to TKI treatment.

Stomach and Colon Metastasis from Breast Cancer / 이화의대지

Gastric metastasis from breast cancer is rare and only six cases have been reported in Korea. Colon metastasis is more rare than gastric metastasis. We report a 63-year-old woman with gastric and colon metastases of invasive lobular carcinoma of breast. She was diagnosed as right breast cancer, received right modified radical mastectomy 10 years ago and has been treated with chemotherapy and hormone therapy. Investigating for melena and a small caliber of stool, we found gastric and colon metastases. The diagnosis of metastatic breast cancer was made through gross pathologic and immunohistochemistry staining. We report a case with gastric and colon metastases from breast cancer and a review of the associated six case reports in Korea.

A Case of Pneumatosis Intestinalis Associated with Sunitinib Treatment for Renal Cell Carcinoma / 대한소화기학회지

Sunitinib as a multitarget tyrosine kinase inhibitor is one of the anti-tumor agents, approved by the United States Food and Drug Administration to use treat gastrointestinal stromal tumor and metastatic renal cell carcinoma. The agent is known to commonly induce adverse reactions such as fatigue, nausea, diarrhea, stomatitis, esophagitis, hypertension, skin toxicity, reduciton in cardiac output of left ventricle, and hypothyroidism. However, it has been reported to rarely induce adverse reactions such as nephrotic syndrome and irreversible reduction in renal functions, and cases of intestinal perforation or pneumatosis interstinalis as such reactions have been consistently reported. In this report, a 66-year old man showing abdominal pain had renal cell carcinoma and history of sunitinib at a dosage of 50 mg/day on a 4-weeks-on, 2-weeks-off schedule. Seven days after the third cycle he was referred to the hospital because of abdominal pain. Computed tomography showed pneumoperitoneum with linear pneumatosis intestinalis in his small bowel. The patient underwent surgical exploration that confirmed the pneumatosis intestinalis at 100 cm distal to Treitz's ligament. We report a rare case of intestinal perforation with pneumatosis intestinalis after administration of sunitinib to a patient with metastatic renal cell carcinoma.

A Multicenter Retrospective Analysis of the Clinical Features of Pernicious Anemia in a Korean Population

To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B12 deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.

Neurolymphomatosis in a patient with T-cell non-Hodgkin's lymphoma / 대한내과학회지

Neurolymphomatosis, defined as a selective infiltration of lymphoma cells into cranial nerves, peripheral nerves and nerve roots, is a rarely recognized manifestation of lymphoma. Its characteristic symptoms are often overlooked or mistaken for other conditions, such as a peripheral polyneuropathy, due to chemotherapeutic agents or clinical findings of metastatic lesions in the central nervous system. Recently, neurolymphomatosis has been increasingly recognized using magnetic resonance imaging and positron emission tomography-computed tomography. We present a case of neurolymphomatosis manifesting as peripheral mononeuropathy in a patient with T-cell non-Hodgkin's lymphoma.

A Case of Gastrointestinal Stromal Tumor with Recurrent Hypoglycemia

Non-islet cell tumor induced hypoglycemia (NICTH) is attributable to overproduction of insulin-like growth factor-II (IGF-II) by solid tumors, and these tumors usually originate from mesenchymal or epithelial cells. Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor and most commonly find in the gastrointestinal tract. It is usually expresses the CD117 (stem cell factor receptor, c-kit) detected by immunohistochemistry. Hypoglycemia associated with GIST is very rare and this has not yet been reported in Korea. A 72-year-old man was hospitalized due to frequent episodes of confusion. It was observed that non-hyperinsulinemic hypoglycemia, an elevated serum IGF-II level and a huge liver mass. The histology of liver mass showed c-kit (CD117) positivity, which was consistent with GIST, but it was surgically unresectable. He was treated with imatinib mesylate. Although he recieved palliative treatment, he still experienced intermittent fasting hypoglycemia. After 2 months, the serum IGF-II level was even higher than before. We changed imatinib mesylate to sunitinib malate and performed radiotherapy on the liver mass. Although the change of the liver mass was not significant, he did not suffer from hypoglycemia for three months afterwards.

Secondary Adrenal Insufficiency Associated with Megestrol Acetate in a Patient with Lung Cancer / 결핵및호흡기질환

Loss of appetite is an important factor in the quality of life for advanced cancer patients. Megestrol acetate is used to stimulate appetite, but it can cause suppression of the pituitary adrenal axis due to the affinity of the glucocorticoid receptor. Adrenal insufficiency is a life threatening disorder if left, untreated, but the initial clinical symptoms of the patients are vague. Awareness of the glucocorticoid-like activity of megestrol acetate and its side effects are important for the diagnosis of adrenal insufficiency. We present a case of secondary adrenal insufficiency associated with megestrol acetate in a patient with lung cancer.

Effect of Octreotide on Patients with Malignant Bowel Obstruction / 한국호스피스완화의료학회지

PURPOSE: Malignant bowel obstruction causes gastrointestinal symptoms and leads to diminished quality of life in patients with advanced cancer. Several studies have shown the efficacy of octreotide for the relief of malignant bowel obstruction-related symptoms. The aim of this study is to assess the efficacy and safety of octreotide in patients with malignant bowel obstruction. METHODS: We retrospectively reviewed medical records of twenty nine patients who had suffered from malignant bowel obstruction without clinical improvement of conservative care and subsequently, received octreotide treatment. Initial dosage of octreotide was 0.1 mg/day, and dose was escalated depending on the clinical effect. For each patient, we assessed visual analogue scale (VAS) of pain, number of vomiting episode, and amount of nasogastric tube drainage. RESULTS: Median dosage of octreotide was 0.2 mg/day (range 0.1~0.6), and median duration from initial medication to death was 20 days (range 2~103). VAS before and after octreotide treatment were 5.6+/-1.24, and 2.7+/-0.96, respectively. The numbers of vomiting episode before and after octreotide treatment were 3.6/day+/-2.5, and 0.4/day+/-0.8, respectively. The mean amounts of nasogastric tube drainage before and after octreotide treatment were 975+/-1,083 cc/day and 115+/-196 cc/day, respectively. Statistically significant reduction in VAS, the number of vomiting episode and the amount of nasogastric tube drainage were observed after octreotide treatment (P<0.05). CONCLUSION: Administration of octreotide in patients with malignant bowel obstruction, which is uncontrolled by other medication, was effective and safe. In such clinical situations, physicians should consider to add of octreotide for symptomatic control.

A Case of Post-transplant Lymphoproliferative Disorder Manifested as Native Kidney Mass / 대한신장학회지

Post-transplant lymphoproliferative disorder (PTLD) following solid organ transplantation is an important form of post-transplant malignancy. PTLD is typically associated with Epstein-Barr virus (EBV) and occurs in the setting of immunosuppression resulting in a deficiency of EBV-specific cytotoxic T lymphocytes. PTLD encompasses heterogeneous lymphoproliferative diseases, from polyclonal proliferation resembling infectious mononucleosis to aggressive monomorphic proliferation such as diffuse large B-cell lymphoma. Clinically, PTLD is usually manifested as lymph nodal mass or extranodal mass of solid organs such as liver, transplanted kidney, tonsil, bone marrow or spleen. The authors experienced very rare case of PTLD manifested as a single mass in a native kidney. According to a review of the literature, this is a rare case of PTLD which developed in a native kidney after kidney transplantation. Initially under the impression of renal cell carcinoma, unilateral nephrectomy of the native kidney had performed, and after confirmed as PTLD by histologic diagnosis the patient had treated with reduction of immunosuppressants and chemotheraphy for PTLD, and eventually has got in complete remission.

Characterization of the Expression of PKCalpha(Isoform) in DMH-induced Vascular Endothelial Proliferation

PURPOSE: DMH(1,2-dimethylhydrazine) has been known to induce vascular neoplasm such as malignant endothelioma in animal experiment, through induction of abnormal proliferation of HUVECs. In our previous studies, 11 types of PKC isoenzymes were determined by RT-PCR and the expression of PKCalpha, and mu was more prominent than other PKC isoenzymes in the DMH-treated group. However, this result was not based on objective assessment. In this study, we further evaluated the role of PKCalpha on the DMH-induced abnormal proliferation of HUVECs by two different methods to identify its presence with high relevance in objective view. PKCmu will be investigated in further study. METHODS: The study was conducted with the cultured HUVECs group(control) and the 0.75x10(-9)M DMH-treated group. After processing protein extraction in 0 and 24 hour, extracted protein was treated of quantitative test through BCA protein assay. In the western blot analysis, electrophoresis was performed in the order of gel preparation, sample preparation, and gel running. Electrotransfer to nitrocellulose membrane and reaction with antibody were done. Detection of PKCalpha was achieved through "Gel Image Analysis System". In the fluorescence immunocytochemical analysis, the grading of radiance of the intracellular PKCalpha particles was detected with confocal microscope after treating with primary and fluorescent secondary antibody in 0 and 24 hours. RESULTS: The Western blot analysis showed increased PKCalpha expression from the specimen obtained in 24 hour of the DMH treatment group when compared to those in control group. Under confocal fluorescence microscope, the emitting radiance in the DMH treated group was brighter at 24 hours as well. CONCLUSION: We believe that PKCalpha plays a role in DMH-induced abnormal proliferation of the vascular endothelium, which may provide insights in understanding the vascular neoplasm.

Role of Protein Kinase C in Abnormal Proliferation of Vascular Endothelial Cell induced by 1,2-Dimethylhydrazine; Analysis of Isoform

PURPOSE: Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, have been known to take a role in signal transduction pathway of angiogenesis. The authors confirmed that PKC is the most noticeable mediator for abnormal proliferation of vascular endothelial cells through in vitro study model using the inhibitors, targeting the formation of three co-enzymes. In this study, we would investigate which isoform of PKC play an important role in abnormal angiogenesis of vascular endothelial cell. METHODS: In 96 well plates, 10(4) HUVECs(human umbilical vein endothelial cells) were evenly distributed. Two groups were established; the control group without administration of DMH(1,2-dimethylhydrazine) and the DMH group with administration of 7.5x10(-9)M DMH. RNA was extracted from vascular endothelial cell of each group and expression of the PKC isoform was analyzed by RT-PCR(reverse transcriptase-polymerase chain reaction) method. RESULTS: RT-PCR analysis showed that PKCalpha, -betaI, -betaII, -eta, -micron and -zeta were expressed in vascular endothelial cells of each group. DMH incresed the expression of PKCalpha and PKCmicron, and decreased PKCbetaI, PKCbetaII expression dominantly. CONCLUSION: Based on the result of this study, it was suggested that PKCalpha and PKCmicron may have significant role in abnormal proliferation of vascular endothelial cell.

Activity of Protein Kinase C in Abnormally Proliferated Vascular Endothelial Cells

PURPOSE: To understand the pathogenesis of the disease that presents abnormally proliferated vascular endothelial cells, a model of DMH(1,2-dimethylhydrazine)-induced abnormal proliferation of HUVECs(Human Umbilical Vein Endothelial Cells) was made. We indirectly determined that Protein Kinase C(PKC) restricts the cellular proliferation and inhibits the manifestation of growth factor by using several inhibiting substances of the transmitter through our previous studies. Thereupon, we attempted to observe direct enzymatic activities of PKC and its correlation with the abnormal proliferation of vascular endothelial cells. METHODS: 10(5) HUVECs cells were applied to 6 individual well plates in three different groups; A control group cultured without treatment, a group concentrated with 0.75x10(-8)M DMH only, and a group treated with DMH & 5x10(-9)M Calphostin C, inhibitor of PKC. In analyzing the formation of intracellular PKC enzyme, protein separation was performed, and separated protein was quantitatively measured. PKC enzyme reaction was analyzed through Protein Kinase C Assay System (Promega, USA), and the results were analyzed according to Beer's law. RESULTS: Enzymatic activity of PKC presented the highest in all reaction time of a group concentrated only with DMH, and the lowest in the control group. The group treated with DMH and the inhibitor revealed statistically lower enzymatic activity than group only with DMH in all reaction time, although higher than the control group. CONCLUSION: From the enzymatic aspect, most active and immediate reaction of the PKC was observed in the group concentrated with DMH only. The group treated with DMH & PKC inhibitor showed meaningful decrease. Accordingly, PKC holds a significant role in DMH-induced abnormal proliferation of vascular endothelial cells.

A Study for the Mechanism of Abnormal Proliferation in Vascular Endothelial Cells using Inhibitors to the Signal Transduction Pathway

Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, take a significant role in signal transduction pathway of angiogenesis. The authors utilized the inhibitors, targeting the formation of three co-enzyme in signal transduction pathway in order to quantify the suppression of abnormal vascular endothelial cell proliferation induced by DMH, to compare the level suppression in each up-regulated growth factors, CTGF, CYR61, ITGbeta1, FHL2, and to identify the relationship between abnormal cell proliferation and signal transduction pathway. Five groups were established; Control group, Group of DMH, Group of DMH-mixed Herbimycin, inhibitor of protein tyrosine kinase, Group of DMH-mixed Calphostin C, inhibitor of protein kinase C, Group Of Dmh-Mixed 10U Catalase, Inhibitor Of oxidase. The rise of vascular endothelial cell was compared by MTT assay, and four growth factors were analysed with RT-PCR method, at pre-administration, 4, 8, 12, and 24 hours after administration. In comparison of abnormal proliferation of vascular endothelial cell induced by DMH, suppression was noticed in Herbimycin and Calphostin C group, and Calphostin C group revealed higher suppression effect. Nevertheless, Catalase group did not have any suppression. In manifestation of four growth factors, Herbimycin and Calphostin C group presented similar manifestation with control group, except in ITGbeta. Catalse group had similar manifestation with DMH group in all four growth factors. Abnormal proliferation of vascular endothelial cell induced by DMH have a direct relationship with PTK and PKC, more specifically to PKC. Oxidase was confirmed not to have any relevance.

RT-PCR of Up-Regulated Factors in Abnormally Proliferated Vascular Endothelial Cells by 1,2- Dimethylhydrazine

Many studies for verifying angiogenesis have been in progress, especially in the field of abnormal vascular proliferation to explain the pathogenesis and to develop a treatment of several diseases. In our previous experiments, endothelial cell proliferations were induced by DMH stimulation in vitro, and the 177 factors(142 up- regulated and 35 down-regulated factors) were identified. Among the up-regulated factors, 9 substances (EFEMP1, CTGF, CYR61, ITGbeta1, FHL2, SERPINE1, MYC, PTTG1 and MSH6) were selected, which were related to cell proliferation and showed high signal intensities. The RNA was isolated from HUVECs at the time of 0, 6, 12, 24 hours after the DMH treatment, and RNA of control group HUVECs was also isolated. Genetic information of selected molecules was used to make primer for each, and RT-PCR was performed to analyze both groups. In control and treatment groups, each substance presented variety of manifestation degree according to time differences. EFEMP1, CTGF, CYR61, ITGbeta1, FHL2 and MYC were related to abnormal vascular proliferation steadily and SERPINE1, PTTG1 and MSH6 were related secondarily. CTGF was related to both normal and abnormal proliferation, but it played a more significant role in abnormal proliferation from earlier stage. EFEMP1, CYR61, ITGbeta1, FHL2 and MYC were similar to CTGF, although the relation appeared lately. Further study should be performed to analyze the expressions and the interactions of growth factors, which could be utilized in the new therapeutic development.

Intrapleural Chemotherapy with Cisplatin and Cytarabine in the Management of Malignant Pleural Effusion / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate the efficacy of intrapleural chemotherapy (IPC) with cisplatin and cytarabine in the management of malignant pleural effusion (MPE) from non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: A prospective analysis was carried out on 40 patients with pathologically proven MPE from NSCLC who had received IPC. A single dose of cisplatin 100 mg/m2 plus cytarabine 1200 mg/m2 in 250 ml normal saline was instilled into the pleural space via a chest tube and drained 4 hours later. Patients were evaluated for toxicities and responses at 1, 2, & 3 weeks and then at monthly intervals if possible. Systemic chemotherapy was administered, if the patient agreed to receive it, after achieving complete control (CC) of MPE. RESULTS: The median duration of chest tube insertion for drainage was 7 (3~32) days. Among the assessable 37 patients, CC and partial control (PC) were 32 (86.5%) and 4 (10.8%) patients, respectively (overall response rate 97.3%). The median duration of response was 12 months (2~23) and there were only two relapses of IPC after achieving CC. Among the 35 patients who were assessable until they died, 28 patients (80.0%) maintained CC until the last follow-up. There was only one toxic death and the toxicities of IPC, versus the results obtained, were deemed acceptable. CONCLUSION: The procedures were tolerable to the patients and chemotherapy-induced complications were at an acceptable level. The outcome of this trial indicates that IPC has a superior and long lasting treatment response in the management of patients with MPE from NSCLC.