ABSTRACT
No abstract available.
Subject(s)
Atherosclerosis , Inflammation , Lymphoma, B-Cell, Marginal Zone , Renal Artery , UreterABSTRACT
BACKGROUND AND OBJECTIVES: To compare the effectiveness of monitoring cisplatin-induced ototoxicity in adult patients using extended high-frequency pure-tone audiometry (EHF-PTA) or distortion-product otoacoustic emission (DP-OAE) and to evaluate the concurrence of ototoxicity and nephrotoxicity in cisplatin-treated patients. SUBJECTS AND METHODS: EHF-PTA was measured at frequencies of 0.25, 0.5, 1, 2, 3, 4, 6, 8, 9, 11.2, 12.5, 14, 16, 18, and 20 kHz and DP-OAE at frequencies of 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 8 kHz in cisplatin-treated patients (n=10). Baseline evaluations were made immediately before chemotherapy and additional tests were performed before each of six cycles of cisplatin treatment. Laboratory tests to monitor nephrotoxicity were included before every cycle of chemotherapy. RESULTS: Four of 10 patients showed threshold changes on EHF-PTA. Five of 10 patients showed reductions in DP-OAE, but one was a false-positive result. The results of EHF-PTA and DP-OAE were consistent in two patients. Only one patient displayed nephrotoxicity on laboratory tests after the third cycle. CONCLUSIONS: In our study, the incidence rate of cisplatin-induced ototoxicity was 40% with EHF-PTA or DP-OAE. Although both EHF-PTA and DP-OAE showed the same sensitivity in detecting ototoxicity, they did not produce the same results in all patients. These two hearing tests could be used to complement one another. Clinicians should use both tests simultaneously in every cycle of chemotherapy to ensure the detection of ototoxicity.
Subject(s)
Adult , Humans , Audiometry, Pure-Tone , Cisplatin , Complement System Proteins , Drug Therapy , Hearing Tests , IncidenceABSTRACT
A 50-year-old male patient presented with a right scrotal mass that had been growing rapidly for more than one year. A heterogeneous enhancing right scrotal mass (12x9 cm) with para-aortic and peri-caval lymphadenopathies was found on abdominal computed tomography (CT). Right orchiectomy was performed and the gross finding had shown intact testis with a well-defined, huge, whitish solid mass adjacent to the testis. According to pathology, the mass was characterized as a leiomyosarcoma, grade 3 (by National Cancer Instituted [NCI] system). Therefore, the diagnosis was stage III, grade 3 paratesticular leiomyosarcoma. The patient underwent additional systemic chemotherapy using ifosfamide and adriamycin. After nine cycles of chemotherapy, positron emission tomography-CT was performed and no FDP uptake was observed. The patient has been followed up for 12 months after systemic chemotherapy, and he has maintained a complete response. We report here on a rare case of paratesticular leiomyosarcoma treated successfully with orichiectomy and additional systemic chemotherapy.
Subject(s)
Humans , Male , Middle Aged , Doxorubicin , Electrons , Formycins , Ifosfamide , Leiomyosarcoma , Orchiectomy , Ribonucleotides , TestisABSTRACT
Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.
Subject(s)
Female , Humans , Middle Aged , CD5 Antigens/metabolism , Antineoplastic Agents/therapeutic use , B-Lymphocytes/immunology , Bone Marrow/pathology , Cryoglobulinemia/diagnosis , Cyclophosphamide/therapeutic use , Diagnosis, Differential , Doxorubicin/therapeutic use , Drug Therapy, Combination , Glomerulonephritis/diagnosis , Kidney/pathology , Paraproteinemias/diagnosis , Prednisolone/therapeutic use , Vincristine/therapeutic use , Waldenstrom Macroglobulinemia/diagnosisABSTRACT
We report a rare case of multiple myeloma with biclonal gammopathy (IgG kappa and IgA lambda type) in a 58-year-old man with prostate cancer who presented with lower back pain. Through computed tomography (CT) imaging, an osteolytic lesion at the L3 vertebra and an enhancing lesion of the prostate gland with multiple lymphadenopathies were found. In the whole body positron emission tomography-computed tomography (PET-CT), an additional osteoblastic bone lesion was found in the left ischial bone. A prostate biopsy was performed, and adenocarcinoma was confirmed. Decompression surgery of the L3 vertebra was conducted, and the pathologic result indicated that the lesion was a plasma cell neoplasm. Immunofixation electrophoresis showed the presence of biclonal gammopathy (IgG kappa and IgA lambda). Bone marrow plasma cells (CD138 positive cells) comprised 7.2% of nucleated cells and showed kappa positivity. We started radiation therapy for the L3 vertebra lesion, with a total dose of 3,940 cGy, and androgen deprivation therapy as treatment for the prostate cancer.
Subject(s)
Humans , Male , Middle Aged , Adenocarcinoma/complications , Antineoplastic Agents/therapeutic use , Bone Marrow Cells/metabolism , Combined Modality Therapy , Immunoelectrophoresis , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Multiple Myeloma/complications , Neoplasm Staging , Positron-Emission Tomography , Prostatic Neoplasms/complications , Spine/pathology , Syndecan-1/metabolism , Tomography, X-Ray ComputedABSTRACT
Multiple primary cancers are the occurrence of more than two cancers of different origin in an individual. Penile cancer is a rare disease, and finding it combined with other cancers is even rarer. A 64-year-old man with a painful penile mass was referred to us from a primary urological clinic. We performed a biopsy of the penile mass and the histology revealed a well-differentiated squamous cell carcinoma. Abdominal computed tomography showed a localized bladder tumor with inguinal lymphadenopathy. The patient underwent a partial penectomy, transurethral resection of the bladder tumor and inguinal lymph node dissection. The histology of the bladder tumor was high-grade papillary carcinoma, and that of the lymph node was squamous cell carcinoma. The penile and bladder tumors were in stage II (T1N1M0) and stage I (T1N0M0), respectively. We successfully treated the patient with adjuvant radiotherapy and systemic chemotherapy.
Subject(s)
Humans , Male , Middle Aged , Biopsy , Carcinoma, Papillary , Carcinoma, Squamous Cell , Lymph Node Excision , Lymph Nodes , Lymphatic Diseases , Penile Neoplasms , Radiotherapy, Adjuvant , Rare Diseases , Urinary Bladder , Urinary Bladder NeoplasmsABSTRACT
Niemann-Pick disease (NPD) is an inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase coded by SMPD1 gene. In contrast with type A NPD, a severe neurodegenerative disease of infancy, type B NPD patients have little or no neurodegeneration, and frequently survive into adulthood. Although over 100 mutations have been found within the SMPD1 gene causing NPD, there was only one report about SMPD1 mutation status of a Korean NPD patient. We report a case of a 32-yr-old female, who presented with thrombocytopenia without any neurologic involvement. Hepatosplenomegaly was detected by both physical examination and imaging studies, and a thoracic radiograph examination showed a pattern of interstitial lung disease. Biochemical tests revealed increased liver enzymes, cholesterol, triglyceride, and LDL-cholesterol, and decreased HDL-cholesterol. Sea-blue or foamy vacuolated histiocytes occurred in bone marrow and liver. Sequencing analysis of SMPD1 using genomic DNA from peripheral leukocytes identified a compound heterozygote of two mutations at exon 2: p.E246K and p.A357V. The former is a known mutation in an Italian patient, and the latter has not been reported yet. She has received oral rosuvastatin to treat hyperlipidemia at a dose of 10 mg per day for 4 months. This is the second report in which the mutation of SMPD1 gene was detected in a Korean NPD patient. The active genetic analysis of SMPD1 gene in patients with typical findings of type B NPD would enable us to facilitate diagnosis as well as to accumulate data on molecular characteristics of Korean NPD patients.
Subject(s)
Adult , Female , Humans , Pregnancy , Base Sequence , Bone Marrow Cells/pathology , Korea , Liver/pathology , Niemann-Pick Disease, Type B/diagnosis , Sea-Blue Histiocyte Syndrome/diagnosis , Sequence Analysis, DNA , Sphingomyelin Phosphodiesterase/genetics , Tomography, X-Ray ComputedABSTRACT
Two structural protein genes, VP19 and VP466, of white spot syndrome virus (WSSV) were cloned and expressed in Sf21 insect cells using a baculovirus expression system for the development of injection and oral feeding vaccines against WSSV for shrimps. The cumulative mortalities of the shrimps vaccinated by the injection of rVP19 and rVP466 at 15 days after the challenge with WSSV were 50.2% and 51.8%, respectively. For the vaccination by oral feeding of rVP19 and rVP466, the cumulative mortalities were 49.2% and 89.2%, respectively. These results show that protection against WSSV can be generated in the shrimp, using the viral structural protein as a protein vaccine.
Subject(s)
Penaeidae/immunology , Viral Structural Proteins/immunology , Viral Vaccines/immunology , White spot syndrome virus 1/immunology , Animals , Cell Line , Gene Expression , Penaeidae/virology , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Spodoptera , Vaccination , Viral Structural Proteins/genetics , Viral Structural Proteins/metabolism , Viral Vaccines/genetics , Viral Vaccines/metabolism , White spot syndrome virus 1/genetics , White spot syndrome virus 1/metabolismABSTRACT
Primary lymphoma arising from the uterine cervix has been rarely encountered, and breast involvement is rare because of the relative paucity of lymphoid tissue in the breast. A 32-year-old woman with a primary malignant lymphoma of the uterine cervix and breast involvement is reported. The patient presented with post-coital vaginal bleeding, and punch biopsy of the cervix revealed the diffuse large B cell type of malignant lymphoma. PET-scan was done for staging, and abnormal FDP uptakes were detected in a uterine cervical mass and breast nodule. Ultrasonography-guided needle biopsy was done for the breast mass, and 2 biopsied nodules revealed fibroadenoma and diffuse large B cell lymphoma. The patient (Ann Arbor stage IV) was treated with 6 cycles of combination chemotherapy with CHOP plus rituximab. The patient went into complete remission. Thereafter, 4500cGy pelvic irradiation was done for adjuvant therapy.
Subject(s)
Adult , Female , Humans , Antibodies, Monoclonal, Murine-Derived , Biopsy , Biopsy, Needle , Breast , Cervix Uteri , Drug Therapy, Combination , Fibroadenoma , Formycins , Lymphoid Tissue , Lymphoma , Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Ribonucleotides , Uterine Hemorrhage , RituximabABSTRACT
Uterine cervical cancer is the 5(th) most common malignancy in Korean women. With the development of new diagnostic and therapeutic modalities, earlier stage cancers are being diagnosed with longer survival rates being anticipated. Accordingly, recurrent cancers are being encountered more often in clinical practice. Most recurrent uterine cervical cancer patients, have intra-pelvic lesions and adjacent lymph node involvement, while a distant metastasis alone is extremely rare. A mediastinal recurrence of uterine cervical cancer is not common with most manifesting as small lymph node enlargements. We report a case of a 46-year-old woman with recurrent uterine cervical cancer presenting only as a huge mediastinal mass without a local recurrence.
Subject(s)
Female , Humans , Middle Aged , Lymph Nodes , Neoplasm Metastasis , Recurrence , Survival Rate , Uterine Cervical NeoplasmsABSTRACT
Glucocorticoids (GCs) are the most effective group of medications available to treat inflammation. Although most patients with inflammation respond to GC, a small group of patients exhibit persistent GC-resistance with prolonged inflammation. Previously, it was proposed that the GC-resistance is caused by low amount of human GC receptor (hGR alpha) and/or excessive presence of a GC receptor isoform, hGR beta that was generated from alternative splicing of the hGR message. We have tested this hypothesis by investigating correlation between the expression pattern of hGR mRNAs in patients with inflammatory nasal polyps and the effectiveness of GC treatment.? We have performed reverse transcription PCR analysis of mRNAs coding each hGR alpha and hGR beta in nasal tissues.? hGR alpha mRNA was more expressed in patients with nasal polyps than in normal subjects. However, the elevated hGR alpha mRNA expression was decreased after GC treatment. Compared with hGR alpha mRNA expression, level of hGR beta mRNA expression was very low in all groups. In patients, hGR beta mRNA was expressed at a similar level regardless of GC efficacy, indicating that there is no correlation between the GC sensitivity and the expression level of hGR beta mRNA. Thus, persistent GC-resistance is not associated with low expression of hGRa or over- expression of hGR beta.
Subject(s)
Middle Aged , Male , Humans , Female , Child , Aged , Adult , Adolescent , Treatment Failure , Reverse Transcriptase Polymerase Chain Reaction , Receptors, Glucocorticoid/metabolism , RNA, Messenger/metabolism , Nasal Polyps/drug therapy , Glucocorticoids/pharmacology , Gene Expression , Drug ResistanceABSTRACT
PURPOSE: Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factor such as uPAR and growth factor. So we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients. MATERIALS AND METHODS: Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients. RESULTS: The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg and 4.8+-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between T stage (p >0.05). In nodal stage, there was also no difference in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesteron receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.0023) and TNM stage (p=0.0004) were significantly associated with overall survival. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). CONCLUSION: These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.
Subject(s)
Humans , Basement Membrane , Breast Neoplasms , Breast , Cytosol , Enzyme-Linked Immunosorbent Assay , Estrogens , Extracellular Matrix , Multivariate Analysis , Plasminogen Activators , Plasminogen , Urokinase-Type Plasminogen ActivatorABSTRACT
PURPOSE: We measured and compared the uPA, plasminogen activator inhibitor-1 (PAI-1) and uPA receptor (uPAR) levels in breast cancer tissues and blood of the patients to evaluate their clinical relevance for biotherapy. MATERIALS AND METHODS: uPA, PAI-1 (Monozyme, Netherland), uPAR (American Diagnostics, USA) levels were measured by ELISA assay in 192 breast cancer tissues, in 18 normal breast tissues and in 163 blood from breast cancer patients. RESULTS: There was a tendency of uPA increment from ductal carcinoma in situ while increment of PAI-1 and uPAR occurred from Ti. With the progression of cancer, uPA, PAI-1, uPAR tended to decrease; however, the uPA/uPAR, uPA/PAI-1 ratios remained unchanged. There was a correlation of uPA expression between normal and cancer tissues ( r(2)= 0.49). Correlation of uPA and PAI-1 was found in normal tissue and stage I cancer tissue while correlation of uPAR and PAI-1 was found with cancer progression. Between cancer tissue and blood significant correlations were found in uPA, PAI-1, uPAR levels. CONCLUSION: uPA, PAI-1, uPAR levels in cancer tissue elevated from the early stage maintaining correlative expressions with cancer progression. A positive correlation between cancer tissue and blood level suggested the applicability of the levels of uPA, PAI-1 or uPAR for detecting patients for biotherapy.
Subject(s)
Humans , Biological Therapy , Breast Neoplasms , Breast , Carcinoma, Intraductal, Noninfiltrating , Enzyme-Linked Immunosorbent Assay , Plasminogen Activator Inhibitor 1 , Plasminogen Activators , Plasminogen , Urokinase-Type Plasminogen ActivatorABSTRACT
PURPOSE: Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy. MATERIALS AND METHODS: Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. RESULTS: Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care. CONCLUSION: Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.
Subject(s)
Female , Humans , Male , Cisplatin , Disease-Free Survival , Doxorubicin , Drug Therapy , Etoposide , Extremities , Femur , Follow-Up Studies , Humerus , Infusions, Intravenous , Korea , Limb Salvage , Lung , Mortality , Nausea , Necrosis , Osteosarcoma , Quality of Life , Recurrence , Sepsis , Survival Rate , Tibia , VomitingABSTRACT
PURPOSE: Brain metastasis is estimated to occur in 20 to 40% of cancer patients, and meningeal involvement has been reported in 5% to 8% of cancer patients. Even if the prognosis is grave, standard treatment modality of brain metastasis or leptomeningeal carcinomatosis has not been established. We evaluated the prognosis and the clinical features of the brain and leptomeningeal metastasis of the breast cancer. MATERIALS AND METHODS: The 43 patients who was diagnosed as brain parenchymal metastasis or leptomeningeal carcinomatosis clinically, radiologically and/or cytologically were included in this study. The median age was 44(range: 27-61) years. RESULTS: The median duration from brain metastasis to death was 181 days(range: 8~1599), and the median duration from leptomeningeal carcinomatosis to death was 39 days(range: 25~152). Age(p=0.7174) and number of brain metastatic lesion(p=0.4097) did not influence the survival, but the presence of other systemic metastatic lesion affected the survival(p 0.0224). When we compared the survival rates of patients according to treatment modality, the patients with systemic chemotherapy versus patients without systemic chemotherapy showed differences(p= 0.0009). Patients treated with whole brain radiation only versus patients with whole brain radiation and other systemic management also showed different survival rate(p=0.0009). But intrathecal chemotherapy had no effect on survival. Well differentiated, solitary lesions were treated by operation and/or gamma-knife surgery, and their effects were good. CONCLUSION: Prolongation of survival was suggested with whole brain radiotherapy combined with systemic treatment in brain or leptomeningeal metastasis. Further study is expected to confirm this finding.
Subject(s)
Humans , Brain , Breast Neoplasms , Breast , Drug Therapy , Meningeal Carcinomatosis , Neoplasm Metastasis , Prognosis , Radiotherapy , Survival RateABSTRACT
Vitamin B12 deficiency anemia is a disorder caused by impaired DNA synthesis. Vitamin B12 binds to the intrinsic factor produced by the parietal cells and is absorbed in the distal ileum. After total gastrectomy, megaloblastic anemia is developed due to the absence or deficiency of the intrinsic factor. Concomitant iron deficiency states such as various malabsorption syndromes and alcoholism induce that the bone marrow erythroid megaloblastosis and peripheral blood macroovalocytosis are masked because of countervailing the tendency of iron deficiency to produce microblasts and hypochromic microcytic erythrocytes. We experienced a case of Vitamin B12 deficiency anemia with low RBC mean corpuscular volume (MCV) due to combined with iron deficiency anemia in 42 year-old female patient and report the case with literature review.
Subject(s)
Adult , Female , Humans , Alcoholism , Anemia , Anemia, Iron-Deficiency , Anemia, Megaloblastic , Bone Marrow , DNA , Erythrocyte Indices , Erythrocytes , Gastrectomy , Ileum , Intrinsic Factor , Iron , Malabsorption Syndromes , Masks , Rabeprazole , Vitamin B 12 Deficiency , Vitamin B 12 , VitaminsABSTRACT
PURPOSE: Transforming Growth Factor-beta1(TGF-beta1) is the most potent inhibitor of the progression of normal mammary epithelial cells through the cell cycle. However, advanced breast cancers are mostly refractory to TGF-beta mediated growth inhibition and produce large amounts of TGF-beta, which may enhance tumor cell invasion and metastasis by its effects on extracellular matrix. Yet, little is known about the association of TGF-beta1 with progression of malignant disease in vivo. In this study, we evaluated the preoperative and postoperative plama level of TGF- in breast cancer and analyzed the utility of plasma TGF-beta1 as possible tumor marker. MATERIALS AND METHODS: ELISA(enzyme-linked immunosorbent assay) was used to measure plasma TGF-beta1 level in 45 newly diagnosed breast cancer patients and in 15 normal healthy people, and the results were compared with clinicopathologic characteristics. RESULTS: The mean plasma TGF-beta1 levels were 1.73+/-0.47 ng/ml in normal people and 5.05+/-1.41 ng/ml in breast cancer patiens. In 37 operated patients, the preoperative plasma TGF-beta1 level was 6.34+/-1.34 ng/ml and decreased to 4.48+/-1.07 ng/ml in patients with follow-up after surgery and 4.74+/-0.79 ng/ml in patients with chemotherapy. However, there was no significant correlation between plasma TGF-beta1 level and known prognostic factors including tumor size, LN involvement, tumor grade, hormone receptor status, and pathology. CONCLUSION: These findings suggest that the plasma TGF-g level can be a tumor marker in breast cancer patients and the association with progression of breast cancer will be explored in future studies.
Subject(s)
Humans , Breast Neoplasms , Breast , Carcinogenesis , Cell Cycle , Drug Therapy , Epithelial Cells , Extracellular Matrix , Follow-Up Studies , Neoplasm Metastasis , Pathology , Plasma , Transforming Growth Factor beta , Transforming Growth Factor beta1ABSTRACT
PURPOSE: Microsatellite instability in patients with defects in the mismatch repair system resulting in RER has a high risk of accumulating mutations in oncogene and tumor suppressor gene. In this study, we evaluated the incidence of microsatellite instability in breast cancer by comparing PCR-amplified sequences from frozen samples of normal and tumor tissue fram affected patients. We also investigated whether RER was associated with TGF-beta RII mutation. MATERIALS AND METHODS: Fifty surgically resected breast cancer specimens from Jan. 1996 to June, 1997 were used for study. Microsatellite instability(referred to as replication error, RER) at three loci with BAT 26, BAT 40, TA10 was analyzed by polymerase chain reaction and the results were compared with clinicopathologic characteristics. RESULTS: Of the 50 breast cancer patients, 14(28%) were RER(+) at one or more microsatellite loci, and 4(8%) showed TGF-beta RII mutation. Microsatellite instability was significantly correlated with lymph node involvement(especially in case of 4 or more lymph nodes involvement). But we could not find any correlation between RER and other prognostic factors including tumor size, tumor grade, hormone receptor status and pathology. One of fourteen tumors with RER(+) showed TGF-beta RII mutstion. There was no signiticant correlation between RER(+) and TGF-beta type II receptor gene mutation. CONCLUSION: The findings suggest that microsatellite instability would be useful prognostic factor in unilateral breast cancer patients, and the role of targeting to gene mutation will be explored in future studies.
Subject(s)
Humans , Breast Neoplasms , Breast , DNA Mismatch Repair , Genes, Tumor Suppressor , Incidence , Lymph Nodes , Microsatellite Instability , Microsatellite Repeats , Oncogenes , Pathology , Polymerase Chain Reaction , Prognosis , Transforming Growth Factor betaABSTRACT
PURPOSE: Gastric cancer is the most common malignancy in Korea. Although treatment such as surgery, chemotherapy, and immunotherapy has greatly improved, the mortality rate of gastic cancer is still high, A new therapeutic trial is necessary to improve the cure rate of gastric cancer. Therefore we investigated the pre-clinical significance of HSV-tk gene therapy using retroviral vector for gastric cancer cell lines. MATERIALS AND METHODS: LNC/HSV-tk retroviral vector and PA317/LNC/HSV-tk producer cell line were constructed. HSV-tk gene transduction and expression were detected by PCR. An in vitro ganciclovir(GCV) sensitivity test was performed by MTT assay. To evaluate in vivo GCV sensitivity, GCV was intraperitoneally injected after tumor formation in the nude mice. Bystander effect was observed in vitro MTT assay using YCC- S-2 cell line and in vivo using N87 and YCC-S-2 cell lines. RESULTS: The in vitro GCV sensitivity test showed that the growth inhibition was 30~32% with 0.5 uM GCV and 52~77% with 500 uM GCV in the HSV-tk transduced cell line in comparison with 0- 5% with 0.5 and 500 uM GCV in the parent cell line. The in vivo GCV administration showed that the tumors induced by HSV-tk transduced N87 cell line and YCC-S-2 cell line decreased completely, while the tumors with the parent cell lines continued to grow in nude mice. We observed no tumor cells in tissue specimen of the tumor induced by the N87/HSV-tk cell line after. GCV administration. In vitro and in vivo bystander effects were observed in HSV-tk/GCV system due to the resultant cell death exceeding the proportion of HSV-tk transduced cells in the mixtures of HSV-tk transduced and parent cells. CONCLUSION: HSV-tk transduced gastric cancer cell lines showed sensitivity to GCV and a bystander effect was observed. These results suggested that HSV-tk/GCV system should be evaluated in the clinical settings.
Subject(s)
Animals , Humans , Mice , Bystander Effect , Cell Death , Cell Line , Drug Therapy , Ganciclovir , Genetic Therapy , Herpes Simplex , Immunotherapy , Korea , Mice, Nude , Mortality , Parents , Polymerase Chain Reaction , Stomach Neoplasms , Thymidine Kinase , Thymidine , ZidovudineABSTRACT
PURPOSE: We compared the differences between parent hepatoma cell lines and interleukin-2 (IL-2) transduced hepatoma cell lines using N2A/IL-2 and LNC/IL-2 retrovirus with regards to in vitro sensitivity to peripheral blood monocytes and in vivo tumorigenic activity. MATERIALS AND METHODS: Retroviral vector and producer cell line were constructed and IL-2 gene was transduced into the human hepatoma cell lines (SK-Hep1, Hep-G2, Hep-3B). IL-2 secretion after IL-2 transduction was measured by ELISA. MTT assay for in vitro sensitivity to peripheral blood monocytes was performed and the tumorigenic activity was observed in BALB/c mice and nude mice. RESULTS: IL-2 secretion was 186 pg/10 degrees C cells/24 hrs in SK-Hep1 cell line and was 147 pg/10 (6) cells/24 hrs in Hep-3B cell line with N2A/IL-2 retroviral vector and was 55,000 pg/10 (6) cells/24 hrs with LNC/IL-2 retroviral vector. In vitro sensitivity to peripheral blood monocytes was increased by 163.8~254% in IL-2 transduced hepatoma cell lines (Hep -3B/N2A/IL-2, Hep-G2/N2A/IL-2) compared to those of the parent cell lines. The tumorigenicity was observed in 1 of 3 BALB/c mice and all 3 nude mice. Simultaneous injection of 1 X 10 (7) cells of the parent cell line (Hep-3B) into the right flank and IL-2 transduced cell line (Hep-3B/LNC/IL-2) into the left flank of the three BALB/c mice and of 5 X 10 (5) cells for the three nude mice resulted in a complete regression of the IL-2 modified tumor cell line (Hep-3B/LNC/IL-2) in 3 weeks and the parent cell line (Hep-3B) in 5 weeks. But, after the injection of 1.5 X 10 (7) cells for other five nude mice, the tumor of the IL-2 transduced hepatoma cell line (Hep-3B/LNC/IL-2) was gradually disappeared, and the tumor of the parent hepatoma cell line (Hep-3B) was initially decreased and then gradually regrew 20 days later. CONCLUSION: IL-2 transduced hepatoma cell lines secreting IL-2 became more sensitive to peripheral blood monocytes and resulted in the increased antigenicity to the tumors formed by IL-2 transduced hepatoma cell line and parent cell line, and finally resulted in the regression of the tumors in experimental animals.