Survival analysis of breast cancer patients after diagnosis of second primary malignancies, focusing on the second primary hematologic malignancy

Purpose@#Although the overall survival (OS) of breast cancer patients is increasing with improved detection and therapies, so is the risk of breast cancer patients developing subsequent malignancies. We investigated the OS of breast cancer survivors according to sites of second primary malignancies (SPM). The OS of the second primary hematologic malignancy (SPHM) was then compared with that of metastatic breast cancer (MBC). @*Methods@#We retrospectively analyzed patients diagnosed with primary breast cancer between 1998 and 2019. Only those with SPM were eligible for analysis. First, the OS of patients with SPM diagnosed as the first event after the diagnosis of breast cancer was analyzed. Next, the OS of patients with SPHM, with or without breast cancer relapse, was compared with that of patients with MBC, matched using the propensity score. @*Results@#Patients diagnosed with SPM without breast cancer relapse as the first event had a significantly better OS than did patients with MBC, but the OS of those with SPHM as the first event did not differ significantly from that of patients with MBC (hazard ratio [HR], 1.558; 95% confidence interval [CI], 0.856–2.839; P = 0.147). The OS of patients with SPHM with or without breast cancer relapse was worse than that of the MBC group after propensity score matching (HR, 1.954; 95% CI, 1.045–3.654; P = 0.036). @*Conclusion@#Prognosis of SPM diagnosed as the first event was statistically better than that of MBC, except in case of SPHM. Patients with SPHM, with or without MBC, showed poor OS before and after propensity score matching.

Can chemotherapy be omitted for patients with N0 or N1 endocrine-sensitive breast cancer treated with gonadotropin-releasing hormone agonist and tamoxifen?

Purpose@#Whether administering chemotherapy followed by tamoxifen plus a gonadotropin-releasing hormone (GnRH) agonist to treat patients with lower-risk hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer provides a greater benefit than administering tamoxifen plus GnRH agonist alone remains unclear. This study aimed to compare the outcomes of propensity score-matched (PSM) patients who underwent these 2 types of treatment plans. @*Methods@#This retrospective study included patients treated at our institution between 2009 and 2019. Eligible patients had HR-positive, HER2-negative, invasive breast cancer who had undergone surgery. There were 579 patients with HR-positive, HER2-negative breast cancer who were treated with a GnRH agonist and tamoxifen; patients with pathologic N2 and those who received neoadjuvant chemotherapy were excluded. After 1:1 PSM of patients who underwent GnRH agonist treatment and tamoxifen with versus without chemotherapy, 122 patients from these 2 groups were analyzed. Survival rates were calculated using the Kaplan-Meier method and compared via the log-rank test. @*Results@#After PSM, there were no significant differences in several baseline characteristics between the 2 groups. After a median follow-up of 62.8 months, the patients in both groups demonstrated similar outcomes with no significant difference in disease-free survival (P = 0.596). @*Conclusion@#Patients derived no significant survival benefit from undergoing a chemotherapy regimen before receiving tamoxifen and GnRH agonist therapy compared to forgoing such chemotherapy.

Comparison of the Efficacy between First-Line Treatment Regimens for Patients with Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer

Purpose@#Endocrine therapy is the first-line treatment recommended for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer without visceral crisis. However, this recommendation has not been followed clinically because of efficacy issues. In this study, the survival of patients with HR-positive/HER2-negative metastatic breast cancer was evaluated based on the following first-line treatment regimens: the combination of palbociclib plus letrozole, conventional endocrine therapy, or chemotherapy. @*Methods@#Medical records were reviewed for this retrospective analysis. Patients with HR-positive/HER2-negative metastatic breast cancer were included. Progression-free survival (PFS) and overall survival (OS) were compared based on first-line treatment regimens. @*Results@#A total of 184 patients were included in the analysis. The first-line treatments were palbociclib plus letrozole in 46 patients (25.0%), endocrine therapy in 40 patients (21.7%), and chemotherapy in 98 patients (53.3%). The PFS of the palbociclib plus letrozole group was significantly longer than that of the endocrine therapy (hazard ratio=3.43, p<0.001) and chemotherapy (hazard ratio=2.88, p=0.001) groups. No significant difference was observed between the endocrine therapy and chemotherapy groups (p=0.430). The OS of the palbociclib plus letrozole group was significantly longer than that of the endocrine therapy (hazard ratio=5.34, p=0.009) and chemotherapy (hazard ratio 4.23, p=0.043) groups. No significant difference was observed between the endocrine therapy and chemotherapy groups (p=0.451). @*Conclusion@#The combination regimen of palbociclib and letrozole could be recommended as the first-line treatment of choice in patients with HR-positive/HER2-negative metastatic breast cancer.

Predicting the Benefit of Adjuvant Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer Patients with Phosphorylated S6K1 Expression Status / 한국유방암학회지

PURPOSE: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer.METHODS: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis.RESULTS: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1–90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16–0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188).CONCLUSION: pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation of Transcription 3 Signaling / 한국유방암학회지

PURPOSE: The chemical structure of tubulosine has been known since the mid-1960s. However, little is known about its biological and pharmacological functions. The aim of this study was to investigate the novel functions of tubulosine in cancer treatment, specifically in breast cancer. METHODS: An Unpaired (Upd)-induced Drosophila cell line and interleukin (IL)-6-stimulated human breast cancer cell lines were used to investigate the biological and pharmacological activities of tubulosine in vitro. To investigate the activities of tubulosine, we performed molecular and cellular experiments such as Western blot and reverse transcription polymerase chain reaction analyses, immunoprecipitation and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunofluorescence staining using breast cancer cell lines. RESULTS: Tubulosine exhibited anticancer activity in IL-6-stimulated human breast cancer cells. Moreover, tubulosine reduced the tyrosine phosphorylation level and transcriptional activity of signal transducer and activator of transcription (STAT) protein at 92E in Upd-induced Drosophila cells. Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. Interestingly, inhibition of IL-6-induced JAK2/STAT3 signaling by tubulosine was associated with the blocking of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) binding. CONCLUSION: Tubulosine exhibits anticancer activity through functional inhibition of IL-6-induced JAK2/STAT3 signaling by targeting IL-6Rα/gp130 binding in breast cancer cells. These findings suggest that tubulosine may hold promise for the treatment of inflammation-associated cancers, including breast cancer.

Factors Associated with Metastatic Breast Cancer in Patients Who Show Long-Term Stable Disease Status

PURPOSE: This study aimed to analyze the basic clinical characteristics and survival of patients with breast cancer whose disease had been stably maintained for more than 24 months after systemic therapy. METHODS: We retrospectively reviewed the medical records of patients with primary breast cancer who underwent surgery. Among these patients, patients with stage IV disease at diagnosis or those who developed distant metastasis during the follow-up period after surgery were included in this analysis. Patients whose disease remained stable for more than 24 months were classified as the long-term stable disease group. The remaining patients were classified as the control group. RESULTS: A total of 245 patients were eligible for this analysis. Patients in the long-term stable disease group showed a lower rate of histologic type III, a higher rate of hormone receptor positivity, and received less adjuvant chemotherapy. In the long-term stable disease group, the most frequent site of metastasis was the lungs, whereas in the control group, it was the bones. Overall survival was significantly better in the long-term stable disease group than in the control group (p<0.001). In univariate analysis, factors affecting the overall survival rate were the duration from diagnosis to metastasis, the absence of lymphatic infiltration, and the presence of hormone receptors. In multivariate analysis, the duration from diagnosis to metastasis and the absence of lymphatic infiltration were significant factors affecting the overall survival rate. CONCLUSION: Disease progression was observed in many patients even after the disease had been stable for more than 24 months after systemic therapy. Although these patients had better outcomes compared with the others, continuous observation and possible additional treatment might be helpful for some patients.

Evaluation of plasma N-terminal pro-brain natriuretic peptide and troponin I concentrations in dogs with congenital ventricular outflow tract stenosis

This study evaluated the levels of cardiac biomarkers in dogs with either pulmonic stenosis or aortic stenosis and the correlation between biomarkers and the severity of stenosis assessed by the echocardiography. To achieve this study goal, 38 dogs (10 healthy control dogs, 15 dogs with pulmonic stenosis and 13 dogs with aortic stenosis) were examined. The jet velocity and pressure gradient in this study population were measured by echocardiographic estimation, after which the study group was subdivided by the severity of stenosis. The plasma cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in this study group. The median concentrations of cTnI and NT-proBNP of the disease group were significantly higher than those of the control group, and these increased gradually as stenosis worsened. The severity of stenosis and the concentrations of cTnI and NT-porBNP were also found to be significantly correlated. Finally, the plasma cTnI and NT-proBNP tests were found to beneficial for differentiating clinical patients, predicting the progression of disease, and monitoring the outcome of interventional therapy for stenosis.

A Case of Secondary Primary Malignancy after Lenalidomide Therapy for Multiple Myeloma / 대한내과학회지

Lenalidomide, an orally administered immune-modulating drug, has several mechanisms of action against multiple myeloma (MM). However, the mechanisms of action of immune-modulating drugs are not understood completely. Lenalidomide maintenance therapy prolongs the time to progression and increases the overall survival in patients with MM. However, secondary primary malignancy (SPM) has been noted as a serious adverse event in patients with MM treated with lenalidomide. Lenalidomide treatment is not covered by insurance. Consequently, physicians have little experience with the adverse events of lenalidomide treatment in patients with MM. Here, we describe a case of breast cancer after lenalidomide treatment for MM. To our knowledge, this is the first report of a lenalidomide-associated SPM in Korea. The risk factors associated with lenalidomide-associated SPM should be considered carefully when implementing chemotherapy regimens in patients with MM.

Serial Serum HER2 Measurements for the Detection of Breast Cancer Recurrence in HER2-Positive Patients / 한국유방암학회지

PURPOSE: The measurement of serum human epidermal growth factor receptor 2 (HER2) extracellular domain levels is a well-established method for evaluating whether a metastatic HER2-positive breast cancer patient will respond to HER2-targeted treatment. However, little is known about the value of serum HER2 for detecting disease relapse following curative surgical treatment in breast cancer patients. The purpose of this study was to evaluate the sensitivity of serum HER2, carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the detection of disease recurrence in postoperative breast cancer patients with a primary HER2-positive tumor. METHODS: Serial measurements were taken of serum HER2, CEA, and CA 15-3 levels in patients with primary invasive HER2-positive breast cancer who underwent curative surgical treatment between January 2008 and December 2010. Following treatment, serum HER2 levels were monitored every 6 months using a chemiluminescence immunoassay. RESULTS: Overall, 264 patients were analyzed in this retrospective study. The median follow-up period was 27.7 months, and 24 patients relapsed during follow-up. The sensitivity of serum HER2, CEA, and CA 15-3 for the detection of disease recurrence was 37.5%, 25.1%, and 12.5%, respectively. Sensitivity increased to 45.8% when all three tumor markers were combined in the analysis. In a subgroup of patients without liver disease, the sensitivity of serum HER2, CEA, and CA 15-3 was 57.1%, 21.4%, and 14.3%, respectively. Of the 264 patients in this study, 80 patients had chronic hepatitis, liver cirrhosis, or abnormal aspartate aminotransferase or alanine aminotransferase levels during the follow-up period. Following the exclusion of these patients, the sensitivity of serum HER2 for the detection of disease recurrence increased to 57.1%. CONCLUSION: Serial serum HER2 measurement may be useful for the detection of disease relapse in patients with HER2-positive breast cancer. Abnormal liver function can result in elevated serum HER2 in the absence of disease recurrence.

A Case of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in an Adult Presenting with an Extramedullary Bone Tumor / 대한내과학회지

Acute lymphoblastic leukemia (ALL) is a lymphoid malignancy characterized by impaired differentiation and proliferation of leukemic myeloblasts. Normal hematopoietic cells are replaced by excess myeloblasts, causing bone marrow failure. Therefore, patients with ALL typically present with symptoms related to infection, anemia, and thrombocytopenia. Extramedullary involvement of ALL as an initial presenting symptom has rarely been reported in adults, although several such cases of relapse have been described. Isolated extramedullary manifestations may lead to a late diagnosis of ALL. We describe herein a patient with Philadelphia chromosome-positive ALL presenting with an extramedullary bone tumor.

A Case of von Hippel-Lindau Disease with Aortic Valve Insufficiency / 영남의대학술지

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary disorder caused by a germline mutation of the VHL gene. It is a multi-systemic disorder that is predisposed to benign or malignant tumors of visceral organs such as hemangioblastoma of the central nervous system, renal cell carcinoma, retinal angioma and pheochromocytoma. We report herein a case of VHL disease that initially manifested with aortic valve insufficiency.

Relationships between serum vitamin D levels and clinical characteristics of drug reaction with eosinophilia and systemic symptoms syndrome

PURPOSE: Vitamin D deficiency (VDD) is widely spread and on the increase throughout the world. Although vitamin D is essential for skeletal mineralization, VDD or vitamin D insufficiency (VDI) has been associated with nonskeletal disorders including cardiovascular disease, cancer, allergic disease and skin disease. However, a few reports showed the association of vitamin D and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Thereafter, we evaluated the association between vitamin D and DRESS syndrome. METHODS: We conducted a retrospective study on 45 patients with DRESS syndrome. Four hundred and ninty-eight healthy people who visited the health screening center were enrolled in the study as a control group. We investigated the clinical characteristics, the causative drugs and treatments in the patients with DRESS syndrome, and also analyzed the associations with serum 25-hydroxyvitamin D (25(OH)D3). RESULTS: Forty-four patients (97.8%) had low serum vitamin D levels; 21 patients were VDD (serum 25(OH)D3 <10 ng/mL), and 23 patients were VDI (serum 25(OH)D3 10 to 30 ng/mL). There were no significant differences in clinical parameters between two groups. Serum 25(OH)D3 level of the study patients was significantly lower that of the controls (12.3+/-9.6 ng/mL vs. 17.3+/-5.5 ng/mL, P<0.001). Serum 25(OH)D3 level showed a significant negative correlation with admission days (r=-0.377, P=0.011). CONCLUSION: The majority of the patients with DRESS syndrome showed low vitamin D levels. Serum 25(OH)D3 was inversely correlated with admission days.

Development of a New Index for Mortality Prediction Due to Hemorrhagic Shock using Lactate Concentration and Perfusion in S-D Rats

PURPOSE: We proposed a new index for predicting death resulting from hemorrhagic shock, which was calculated by dividing measured lactate concentration by perfusion. METHODS: Using 24 Sprague-Dawley (S-D) rats, we induced uncontrolled hemorrhage and then measured blood lactate concentration and perfusion in addition to vital signs such as heart rate, blood pressure, respiration rate and temperature. Perfusion and lactate concentration were measured by laser Doppler flowmetry and a lactate concentration meter, respectively. We collected the data for 15 min, which consisted of 3 intervals after homeostasis, and thus obtained a new index. RESULTS: The proposed index revealed an earlier death prediction than lactate concentration alone with the same timing as perfusion. The new index showed generally better sensitivity, specificity and accuracy than lactate concentration and perfusion. Using a receiver operating characteristic curve method, the mortality prediction with the proposed index resulted in a sensitivity of 98.0%, specificity of 90.0%, and accuracy of 93.7%. The mortality prediction with the proposed index resulted in a sensitivity of 98.0%, specificity of 90.0% and accuracy of 93.7%. CONCLUSION: This index could provide physicians, in emergency situations, with early and accurate mortality predictions for cases of human hemorrhagic shock.

Development of a New Index for Mortality Prediction Due to Hemorrhagic Shock using Lactate Concentration and Perfusion in S-D Rats

PURPOSE: We proposed a new index for predicting death resulting from hemorrhagic shock, which was calculated by dividing measured lactate concentration by perfusion. METHODS: Using 24 Sprague-Dawley (S-D) rats, we induced uncontrolled hemorrhage and then measured blood lactate concentration and perfusion in addition to vital signs such as heart rate, blood pressure, respiration rate and temperature. Perfusion and lactate concentration were measured by laser Doppler flowmetry and a lactate concentration meter, respectively. We collected the data for 15 min, which consisted of 3 intervals after homeostasis, and thus obtained a new index. RESULTS: The proposed index revealed an earlier death prediction than lactate concentration alone with the same timing as perfusion. The new index showed generally better sensitivity, specificity and accuracy than lactate concentration and perfusion. Using a receiver operating characteristic curve method, the mortality prediction with the proposed index resulted in a sensitivity of 98.0%, specificity of 90.0%, and accuracy of 93.7%. The mortality prediction with the proposed index resulted in a sensitivity of 98.0%, specificity of 90.0% and accuracy of 93.7%. CONCLUSION: This index could provide physicians, in emergency situations, with early and accurate mortality predictions for cases of human hemorrhagic shock.

Ultrasonographic evaluation of renal dimension and resistive index in clinically healthy Korean domestic short-hair cats

Renal length, height, width, resistive index (RI), size of cortex, and medulla were determined by renal ultrasonography in 50 healthy Korean domestic short-hair cats. In the sagittal plane, the renal length was 3.83 +/- 0.51 cm (mean +/- SD) in the left kidney and 3.96 +/- 0.48 cm in the right kidney, whereas the renal height was 2.42 +/- 0.27 cm in the left kidney and 2.36 +/- 0.28 cm in the right kidney. In the transverse plane, the renal height was 2.42 +/- 0.28 cm in the left kidney and 2.38 +/- 0.27 cm in the right kidney, whereas the renal width was: 2.65 +/- 0.35 cm in the left kidney and 2.63 +/- 0.31 cm in the right kidney. In the dorsal plane, the renal length was 3.84 +/- 0.53 cm in the left kidney and 3.97 +/- 0.54 cm in the right kidney, whereas the renal width was 2.65 +/- 0.34 cm in the left kidney and 2.66 +/- 0.33 cm in the right kidney. There were no significant differences (p > 0.05) among the same structure sizes measured in different planes. In the sagittal plane, the size of the renal cortex was 0.47 +/- 0.08 cm in the left kidney and 0.47 +/- 0.08 cm in the right kidney, whereas of the size of the renal medulla was 0.55 +/- 0.30 cm in the left kidney and 0.50 +/- 0.07 cm in the right kidney. RI evaluated by pulsed wave Doppler sonography was 0.52 +/- 0.05 in the left kidney and 0.55 +/- 0.05 in the right kidney. The actual renal dimensions determined by gross examination were not statistically different from those determined by ultrasonography. Furthermore the renal dimensions and RI were statistically correlated to the body weight of cats.

Effect of Induced and Spontaneous Hypothermia on Survival Time of Uncontrolled Hemorrhagic Shock Rat Model

We examined the hypothesis that mild hypothermia (rectal temperature 34 degrees C) results in the same survival time, whether induced spontaneously or intentionally, during untreated, lethal, uncontrolled hemorrhagic shock in rats. Sixty-four Sprague-Dawley male rats were randomly assigned to normothermia (Nth) (n=19), spontaneous mild hypothermia (Sp.Hth) (n=25) or controlled mild hypothermia (Con.Hth) (n=20) groups. After blood withdrawal of 3 mL/100 g over 15 minutes, followed by 75% tail amputation under spontaneous breathing and light anesthesia by i.p. injection of pentobarbital sodium, rats were observed without fluid resuscitation or hemostasis for 180 minutes or until death. The initial temperature of the Nth group was artificially maintained throughout the experiment. For the mild hypothermia groups, the Sp.Hth group was exposed to ambient temperature while the Con. Hth group was actively cooled to a target rectal temperature of 34 degrees C. In the Con.Hth group, all rats except one died before 180 minutes. All rats in the Nth group died within 38 minutes, and within 67 minutes in the Sp.Hth group. The average survival time was shortest in the Nth group at 20.3 +/- 5.3 minutes, followed by the Sp.Hth group at 30.1 +/- 13.5 minutes, and the Con.Hth group at 81.9 +/- 39.8 minutes (p 0.01). Tail bleed out volume was 0.51 +/- 0.19, 0.26 +/- 0.15 and 0.19 +/- 0.12 mL/100 g in the Nth, Sp.Hth and Con.Hth groups, respectively (p 0.05). In conclusion, spontaneous mild hypothermia did not prolong the survival time as much as controlled mild hypothermia in the rat model for untreated, lethal, uncontrolled hemorrhagic shock.

Matrix metalloproteinases in human gliomas: activation of matrix metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix metalloproteinase (MT1-MMP) expression

To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.

Matrix metalloproteinases in human gliomas: activation of matrix metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix metalloproteinase (MT1-MMP) expression

To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.

Growth Suppression by Adenovirus-mediated Gene Transfer of p16/INK4a in Glioma Cell Lines

No abstract available.

Cormeal Endothelial Cell Loss in Phacoemulsifications of Sup. & Temporal Scleral Pocket Incisions

Recently, phacoemulsification is a widely used technique gor extraction of opaque lens. Phacoemulsification thorugh a small incision prvides early visual rehabilitation. However, the side effects of phacoemulsification such as endothelial cell loss have been reported continuously. The aim of this study was to analyze the influence of incision site on corneal endotheliu. Central corneal endothlial cell loss(ECL) was compared following insertion of posterior chamber PMMA intraocular lens with 5.5mm superior scleral pocket incision in 30 eyes and 5.5mm temporal scleral poket incision in 31 eyes. Cell density of the corneal endothelium in all eyes was examed by auto-focus Non Contact Specular Microscopy preoperatively and 2 months postoperatively. The average cell loss was 7.41+/-6.9% and 6.61+/-7.1%, respectively. Phacoemulsification with temporal 5.5mm scleral pocket incisions produced slightly less endothelial cell loss(ECL) than superior incisions. But, there was no statistically significant difference between the eyes with temporal 5.5mm scleral pocket incisions and those with superior 5.5mm scleral pocket incisions. The endothelial cell loss(ECL) is not associated with the direction of corneal incision. If the appropriate direction of corneal incision is chosen by pre-poerative corneal astigmatism, it seems that we will find the better results.