In 1965, Rosenberg reported that platinum compounds not only inhibit growth and cell division of E. coli but also has anti-tumor activity. Since then, through animal and clinical experiments by Welsch(1971), Speer(1972), Rossof(1972), Hill(1974), and Wittes(1975), it was proved that Cis-platinum has excellent supressive effects on malignant tumor, especially on head and neck cancer. Accordingly, Cis-platinum is now widely used, sometimes without any other durg, or sometimes with Bleomycin and Methotrexate etc. Inspite of the strong anticancer effect, the use of Cis-platinum is quite often discouraged because of the reports that Cis-platinum causes auditory impairment at high frequencies above the speech range due to inner ear damage and irreversible change in the renal tubules. Since Kohonen et al(1965), Standnicki et al(1974) reported that Cisplatinum has toxic effects at the basal turn of the cochlea using guinea pig, many studies on ototoxicity after infusion of Cis-platinum have been carried out using animals. But the studies on ototoxicity in human beings can hardly be found except in reports by Piel et al(1974) and Hong et al (1979). So the authors did a study which tried to clarify the ototoxic effect by comparing the hearing level after infusion of Cis-plastinum with the hearing level before infusion of Cis-plastinum in 30 patients who was treated with Cis-platinum and admitted to the dept. of otolaryngology of Yonsei University Hospital during 2 years and a half from July. 1979 to March. 1982 and the following results were obtained. 1) The results of auditory evaluation, using the pure tone average, hearing loss of 4kHz and 8kHz, Speech Reception Threshold, PB score, SISI showed that the difference of dosage does not change the hearing level after infusion of Cis-platinum and before infusion of Cis-platinum. 2) Cis-platinum had no effect on the hearing level of patients with conductive hearing loss, or with sensorineural hearing loss, as well as with normal hearing level. 3) The infusion of Cis-platinum did not cause any change in creatinine clearance, creatinine, uric acid, but only one case showed that Cis-platinum caused severe nephrotoxicity. 4) The infusion of Cis-plastinum did not cause any change in hemoglobin, leukocyte count, platelet count and there was no correlation with the amount of infusion. 5) To see the side effect of hydration practiced with the infusion of Cis-platinum, the electrolytes, particularly the K level in the serum was measured. But the results did not show any change. 6) Judging from the results of this study mentioned above, ototoxicity caused by infusion of Cis-platinum can be prevented by sufficient hydration. Also the results might say that the appropriate method of infusion of Cis-platinum might be effective in the patients with head and neck cancer who had sensorineural hearing loss for whom the infusion of Cis-platinum has been absolutely cotraindicated.
Kim, Cheol-Hyeon;Yoo, Chul-Gyu;Lee, Choon-Taek;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
Tuberculosis and Respiratory Diseases
/
v.45
no.5
/
pp.984-991
/
1998
Background: The 3p deletions has been shown to be the most frequent alteration in lung cancers, strongly suggesting the presence of at least one tumor suppressor gene in this chromosomal region. However, no solid candidate for the tumor suppressor gene(s) on 3p has as yet been identified. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT, which is located in a region that is homozygously deleted in multiple tumor cell lines and disrupted by the hereditary renal cell carcinoma t(3;8) chromosomal translocation breakpoint FHIT also spans FRA3B, the most common fragile sites in the human genome. In the present study, we have analyzed expression of the FHIT gene in lung cancer cell lines. Methods: RNA from 21 lung cancer cell lines (16 NSCLC, 5 SCLC) were extracted using standard procedures. Random-primed. first strand cDNAs were synthesized from total RNA and PCR amplication of coding exons 5 to 9 was performed. The RT-PCR products were electrophoresed in 1.5% ethidium bromide-stained agarose gels. Results: 12 of 21(57%) lung cancer cell lines exhibited absent or aberrant FHIT expression [7 of 16(44%) of non-small cell lung cancer and 5 of 5(100%) of small cell lung cancer cell lines]. Conclusion: The result shows that abnormal transcription of the FHIT gene is common in human lung cancer cell lines, especially in small cell lung cancer.
A retrospective study of 94 hypercalcemic dogs was performed to find out most common causes that lead to hypercalcemia through investigating dogs referred to the Veterinary Teaching Hospital of Konkuk University from 2002 to 2004. During the study period, hypercalcemia was found in 94 dogs of 19 breeds, and they were evaluated as case group. Control group was made up of 94 dogs of 18 breeds without hypercalcemia admitted for the same study period. For general signalments, there were no significant differences between case and control group with the exception of age distribution. Shih-tzu(17.02%) and Yorkshire terrier(26.60%) was the most common breed in case and control group, respectively. The most common diseases associated with hypercalcemia were chronic renal failure (18.09%), acute renal failure(14.89%), and renal calculi(6.38%). Malignant neoplasia(lymphoma, hemangiosarcoma, chronic lymphocytic leukemia, mammary gland tumor, and multiple myeloma) and endocrinopathies(hyperadrenocorticism, hyperthyroidism, hypoadrenocorticism, and hypothyroidism) occupied 8.5% and 6.4%, respectively. This report is a first retrospective study of hypercalcemic dogs in South Korea.
The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (${\chi}^2$-test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor.
Purpose: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the development of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabino-furanosyi-5-[$^{124/125}I$]iodo- uracil ([$I^{124/125}I$]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. Material and Methods: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [$^{125}I$]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [$^{124}I$]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. Results:, Specific accumulation of [[$^{125}I$]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [$^{125}I$]FIAU uptake was linearly correlated (R2 =0.964, p =0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [$^{125}I$]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small animal PET, [$^{124}I$]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. Conclusion: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.
Purpose : Conservative management of multicystic dysplastic kidney(MCDK) without nephrectomy has recently been advocated. The purpose of this study was to determine the clinical course of conservatively managed MCDK and to find out possible predictive factors for involution of MCDK by ultrasonography(US). Methods : A retrospective analysis was made on 45 patients(26 boys and 20 girls) in whom MCDK was detected and had been traced by US between Dec. 1993 and Aug. 2005 at Severance Hospital. Results : Median follow-up time was 30 months(range 2-102 months). All patients under-went radionuclide scans and voiding eystourethrograms. The serial follow-up US showed complete involution in 11(24%), partial involution in 19(41%), and no interval change or increased in cyst size in 13(28%) patients. Nephrectomy was done in 3 patients(7%) due to relapsing urinary tract infection(UTI) and severe abdominal distension. The mean age of complete involution of MCDK was 37 months(range 12-84 months). Episodes of UTI were present in 17 patients(37%) and additional genitourinary(GU) abnormalities were found in 22 patients(44%). Hypertension and renal insufficiency was complicated in one patient. No child developed malignant tumor. Univariate analysis showed that five variables were associated with complete involution of the MCDK; gender, site, UTI episode, additional GU abnormalities, and renal length on initial US. After adjusting using the Pearson model, the presence of additional GU abnormalities was exclusively associated with complete involution among the 5 variables(P=0.034). Conclusion : In our review of 46 cases of MCDK, non-surgical approach for patients with MCDK was advisable and we could predict poor prognosis when MCDK is associated with other GU anomalies.
A case is reported of a man with malignant fibrous histiocytoma (MFH) in right thigh who developed streptococcal toxic shock syndrome (STSS) during postoperative radiotherapy. Before radiotherapy, a patient complained wax and wane lymphedema following wide excision of tumor mass which was confirmed as MFH. He took some nonsteroidal antiinflammatory drug (NSAID) for about one month. He suffered preexisting hepatitis C virus (HCV) infection, diabetes and well-controlled hypertension. The patient received conventional radiotherapy to right thigh with a total dose of 32.4 Gy at 1.8 Gy per day. At last radiotherapy fraction, cutaneous erythematous inflammation was suddenly developed at his affected thigh. At that time, he also complained of oliguria, fever and chills. The patient was consulted to internal medicine for adequate evaluation and management. The patient was diagnosed as suggested septic shock and admitted without delay. At admission, he showed hypotension, oliguria, constipation, abnormal renal and liver function. As a result of blood culture, Streptococcus pyogenes was detected. The patient was diagnosed to STSS. He was treated with adequate intravenous antibiotics and fluid support. STSS is one of oncologic emergencies and requires immediate medical intervention to prevent loss of life. In this patient, underlying HCV infection, postoperative lymphedema, prolonged NSAID medication, and radiotherapy may have been multiple precipitating factors of STSS.
The abdominal tumors in children are different from those of adult. These tumors are the third most common one, preceded by leukemia and brain tumors, in children under 15 years. X-ray examination is the most important method among diagnostic approaches. The role of diagnostic imaging is to identify the precise anatomic location and extent of pathologic process with the minimal number of imaging procedures. 23 cases of abdominal tumors were reviewed in respect of age incidence, site of origin, radiologic findings. The results are briefly summarized as follows : 1. Neuroblastoma was the most common(6 cases) and wi1m's tumor(5 cases), choledocal cyst(4 cases), ovarian mass(3 cases), hydronephrosis(2 cases), were descending order in frequency. 2. The most common site was retroperitoneum(60%). Kidney was the single most common site of origin. 3. Radiologic findings. The most common findings of plain radiography was ill defined soft tissue mass and this method was helpful in the presence of calcification especially in neuroblastoma. Ultrasonographic pattern was anechoic(cystic), echoic or mixed pattern, but this method provide less precise anatomical details, nevertheless ultrasonography wes paticullary useful imaging modality for the pediatric abdominal tumors. IVP findings were renal displacement, caliceopelvic system distortion or nonvisualization of kidney, these information was helpful in determining the location of tumors. CT scan showed homogenous or inhomogenous, cystic or solid, mass with their anatomic location. 4. Ultrasonography was the most widely used specific diagnostic method, but had limited value in detecting the anatomic location of tumors. CT scan was superior to ultrasound for determining the extent of tumors.
Pt-complexes is currently one of the most compounds used in the treatment of solid tumors. However, its used is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogues containing 1, 2-diaminocyclohexane (dach) as carrier ligand and 1, 3-bis (diphenylphosphino) propane (DPPP)/1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of (KHPC-001) [Pt (trans-1-dach)(DPPP)] $2NO_3$ and (KHPC-002) [Pt (trans-1-dach)(DPPE)] $2NO_3$ were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. KHPC-001 and KHPC-002 demonstrated acceptable antitumor activity aganist P-388, L-1210 lymphocytic leukemia cells and significant activity as compared with that of cisplatin. The toxicity of KHPC-001 and KHPC-002 was found quite less than that of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells and human kidney cortical cells.
Trigeminal neuralgia is defined as "a sudden, usually unilateral, brief stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve" by the International Association for the Study of Pain(IASP). Trigeminal neuralgia is classified as an idiopathic trigeminal neuralgia with no apparent cause and a symptomatic trigeminal neuralgia which is caused by a structural lesion such as brain tumor. Over 80% of the tumors are meningioma, acoustic neuroma, and epidermoid tumors. Symptomatic trigeminal neuralgia can not be excluded even if old-aged patient does not have abnormal neurologic sign and symptom, and good response to pharmacotherapy. Therefore, initial examinations such as MRI or CT are essential to exclude symptomatic trigeminal neuralgia. When compared with CT, MRI, especially gadolinium enhanced MRI, has an increased sensitivity in the detection of intracranial lesions. The most effective medical treatment of trigeminal neuralgia is carbamazepine. The most common side effects of carbamazepine include drowsiness, dizziness, unsteadiness, nausea, anorexia. Hepatotoxicity, bone marrow depression are the most feared side effect of carbamazepine therapy but occurs rarely. It require periodic complete blood cell counts as well as hepatic and renal function tests. It has been recommended that complete blood cell counts is done every 2 weeks for the first 2months and then quaterly thereafter. Oxcarbazepine can be used if neutropenia occurs.
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