Electrostatically Interactive Injectable Hydrogels for Drug Delivery

BACKGROUND: Several injectable hydrogels have been developed extensively for a broad range of biomedical applications. Injectable hydrogels forming in situ through the change in external stimuli have the distinct properties of easy management and minimal invasiveness, and thus provide the advantage of bypassing surgical procedures for administration resulting in better patient compliance. METHODS: The injectable in situ-forming hydrogels can be formed irreversibly or reversibly under physiological stimuli. Among several external stimuli that induce formation of hydrogels in situ, in this review, we focused on the electrostatic interactions as the most simple and interesting stimulus. RESULTS: Currently, numerous polyelectrolytes have been reported as potential electrostatically interactive in situ-forming hydrogels. In this review, a comprehensive overview of the rapidly developing electrostatically interactive in situ-forming hydrogels, which are produced by various anionic and cationic polyelectrolytes such as chitosan, celluloses, and alginates, has been outlined and summarized. Further, their biomedical applications have also been discussed. CONCLUSION: The review concludes with perspectives on the future of electrostatically interactive in situ-forming hydrogels.

Primary CHOP Chemotherapy Followed by Involved Field Radiation Therapy in Clinical Stage I or II Aggressive Non-Hodgkin's Lymphomas / 대한암학회지

PURPOSE: Although radiation therapy had been the treatment of choice for localized non-Hodgkin's lymphoma(NHL), recent studies have revealed that treatment result after radiation therapy alone is not successful for localized aggressive NHL, if it is not pathologically but clinically staged. A prospective phase II trial was conducted to evaluate the therapeutic results of 4 cycles of CHOP chemotherapy followed by involved field radiation therapy in clinically staged localized aggressive NHL. MATERIALS AND METHODS: Patients with a diagnosis of aggressive NHL(all intermediate grade and immunoblastic histology in NCI working formulation), Ann Arbor stage I or II without poor prognostic factors(presence of B symptoms, bulky diseases, or 2 or more extranodal involvement) were treated with 4 cycles of CHOP(cyclophosphamide, doxorubicin, vincristine, prednisolone) followed by involved field radiation therapy of 3,000~6,000(median: 4,500) cGy. RESULTS: Between April 1990 and March 1995, 62 consecutive patients entered this trial. Forty six patients with measurable diseases were evaluable for response. Complete response was achieved in 41(89.1%) patients after CHOP chemotherapy and 4 more patients after subsequent radiation therapy, making total CR rate of 98%. Progression free survival(PFS) of all 62 patients were 2.2+~73+ months and 5 year PFS rate was 64.6%. Overall survival(OS) were 2.4+~75+ months and 5 year OS rate was 75.2%. Old age (> 60) was the only significant prognostic factor, which-affected overall survival negatively. Treatment was relatively well tolerated, but 3 patients died associated with treatment. CONCLUSIONS: Four cycles of CHOP chemotherapy followed by involved field radiation therapy is highly curative and safe treatment for clinically staged, localized aggressive NHLs.

High-Dose Chemotherapy with Vandervilt Regimen and CSF Support for High-Risk Aggressive Non-Hodgkin's Lymphoma / 대한암학회지

PURPOSE: To detennine the therapeutic effect and toxicities of high-dose chemotherapy with Vanderbilt regimen and colany-stimulating factors(CSF) support for high-risk aggressive non-Hodgkin's lymphoma(NHL). MATERIALS AND METHODS: Between Aug. 1995 and Mar. 1997, 40 patients with high-risk aggressive NHLs were treated with high-dose chemotherapy with Vandebilt regimen and CSF support. If the complete response(CR) was induced, four cycles of CHOP were administered for the maintenance of response. In cases of lymphoblastic lymphomas, CNS prophyiaxis with cranial irradiation and intrathecal methotrexate was done after CR. RESULTS: CR was achieved after Vanderbilt regimen in 62.5%(25/40) of the total patients. CR rste in refractory group(12.5%: 1/8) was significantly lower than in other groups (75%: 24/32)(p=0.001). With a median follow-up of 14 months, the failure free survival (FFS) was 0~18+ months(median 6.1 months). The overall FFS rate at one year was 31.7%. The 1-year FFS rate in refractory group(0%) was significantly lower than in other patients groups(41%)(p=0.001). The range of survival time was 0.5~18+ months, and median survival time was 6.2 months. Grade 4 leukopenia was observed in 100% of chemotherapy cycles and its median duration was 7 days. However, only one patient died due to treatment-relate sepsis. Non-hematological toxicities were tolerable and all reversible. CONCLUSION: High-dose chemotherapy with Vanderbilt regimen was effcctive for induction of CR in high-risk aggressive NHL patients and safe with the CSF support. However, poor CR rate in reftactory group and poor FFS in other groups indicate that a new, more intensive approach is needed for the induction of CR in refractory group and for the maintenance of CR in other high-risk patient groups.

A Phase II Study of AP (Doxorubicin, Cisplatin) Chemotherapy in Patients with Advanced Hepatocellular Carcinoma / 대한암학회지

PURPOSE: Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma and is considered to be a highly malignant tumor with poor prognosis. We evaluated the efficacy and toxicities of AP (doxorubicin, cisplatin) comnination chemotherapy in hepatocellular carcinoma. MATERIALS AND METHODS: Between October 1989 and February 1991, 21 previously untreated patients with advanced hepatocellular carcinoma were entered and treated with AP combination chemotherapy (adriamycin 60 mg/m2, D1 and cisplatin 60 mg/m2, D1, repeated every 3 weeks). RESULTS: Among 14 evaluable patients, there was no complete response and 5 patients (36%; 95% C.I=10~62%) achieved partial response. The median survival time of all 21 patients was 17 weeks, and 63 weeks in responders (n=5) and 14 weeks in nonresponders (n=16), and the difference in two groups was statistically significant (p<0.05). The median time to progression of 14 evaluable patients was 13 weeks, and 49 weeks in the responders (n=5) and 6 weeks in the nonresponders (n=9), and the difference in two groups was statistically significant (p<0.05). Myelosuppression was minimal and non-hematologic toxicities were gererally mild and well tolerated. CONCLUSION: The results suggest that the combination chemotherpy of AP seems to be an effective regimen for hepatocellular carcinoma. Further trials are recommended for its true efficacy.

VACOP-B (Etoposide/Doxorubicin/Cyclophosphamide/Vincristine/Prednisolone/Bleomycin) Combination Chemotherapy for the Treatment of Intermediate and High Grade Non-Hodgkin's Lymphoma / 대한암학회지

PURPOSE: To determine the antitumor activity of VACOP-B regimen for advanced non- Hodgkin's lymphoma (NHL) in terms of complete response rate, disease free survival, and overall survival, to assess the toxicities of this regimen, and to analyze the prognostic factors influencing the treatment results.Patients and methods: Between Apr. 1991 and Aug. 1993, thirty-six previously untreated patients with the intermediate or high grade NHL were treated with VACOP-B (etoposide/doxorubicin/cyclophosphamide/vincristine/prednisolone/bleomycin) combination chemotherapy. In case of initial bulky disease or residual disease after chemotherapy, radiation therapy of involved field was added. RESULTS: Complete response (CR) was achieved in 69% (25/36) of the eligible patients after VACOP-B chemotherapy, and 5 of 11 patients who remained in partial response (PR) after chemotherapy achieved CR after additional radiation therapy of involved field, resulting in 83% (30/36) of CR rate. With a median follow-up of 47.2 months, the disease free survival was 1~42.1+ months, and its median was 24 months. The range of survival time was 7~49.1+ months, and the median survival time was not reached at this time. The projected 3-year survival rate was 70%. Leukopenia was observed in 43% of chemotherapy cycles and thrombocytopenia in 2.3%. However, no treatment-related death was observed. For non-hematologic toxicities, nausea and vomiting were observed in 58% of patients, stomatitis in 58%, peripheral neuropathy in 58%, pulmonary toxicity in 3% and congestive heart failure in 3%. These toxicities were tolerable and all reversible. The prognostic factors influencing the complete response rate were performance status of patient (p=0.026) and relative dose intensity of cyclophosphamide (p=0.013). CONCLUSION: VACOP-B regimen is an effective and tolerable regimen for the intermediate and high grade NHL. And long term follow-up and phase III study will be needed for evaluation of these results compared to previous other treatment modality.

Phase II Study of Concurrent Chemotherapy with Etoposide and Cisplatin (EP) and Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer / 결핵

BACKGROUND: Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC), however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, arid survival of concurrent chemotherapy with etoposide and cisplatin(EP) arid radiation therapy for unresectable stage III NSCLC. METHODS: Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without, malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide arid cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. RESULTS: Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient The median survival was l2.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia(> or = grade 3,46%) Thrombocytopenia over grade 3 was found in 1%. Radiation pneumonitis occurred in 13 patients(46%). CONCLUSION: Concurrent chemotherapy(EP) pins radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.

A Case of Non-Hodgkin's Lymphoma Associated with Hepatocellular Carcinoma / 대한내과학회지

Multiple primary malignant neoplasms (MPMN) are defined by the presence of multiple primary cancers of multicentric origin and/or different tissues. The incidence of MPMN is less than 1% in Korea and recently seems to be increased due to early detection of cancer and prolonged survival of cancer patients. Previous investigations suggest that non-Hodgkin's lymphoma (NHL) may be associated with chronic liver disease and hepatocellular carcinoma (HCC). The pathogenesis of this association is thought to be due to chronic antigenic stimulation, the presence of HBsAg, and immunosuppressive therapy. We report a case of synchronous NHL and HCC in a 54-year-old man which is thought to be associated with hepatitis B virus infection. Pathological examination and immunohistochemical study of neck lymph node and liver mass biopsies showed diffuse large cell lymphoma and HCC, respectively. He was treated initially with EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide and prednisolone) chemotherapy for NHL and transarterial chemoembolization with doxorubicin, mitomycin-c, lipiodol, and gelfoam for HCC.

Three Cases of Interstitial Pneumonitis Developed after Anticancer Chemotherapy Containing Cyclophosphamide / 대한내과학회지

Development of diffuse pulmonary infiltrates in patients receiving chemotherapy is a major diagnostic challenge. Diffuse pulmonary infiltrates may be due to infection, pulmonary hemorrhage, pulmonary edema or drug-induced lung injury. Among these, pulmonary toxicity caused by antineoplastic agent is being recognized more frequently. Cyclophosphamide, an alkylating cytotoxic drug, is used widely in the treatment of malignancies including lymphoma. The incidence of pulmonary toxicity is probably less than 1 percent, and its relation with total dosages and schedule of the drug is not yet defined. The typical pictures of cyclophosphamide-induced pulmonary toxicity are non-productive cough, dyspnea, fever, hypoxemia with respiratory alkalosis and interstitial pneumonitis. However, relatively infrequent pulmonary toxicity of cyclophosphamide and frequent development of infectious pulmonary infiltrate in the patients treated with chemotherapy may hamper the early diagnosis of cyclophosphamide toxicity. Interstitial pattern and unresponsiveness to antibiotics of the pneumonitis might be the clues of suspicion. The best ways to treat the patients with cyclophosphamide toxicity are early diagnosis, discontinuation of the drug and early corticosteroid trial, although usefulness of steroid has not been firmly established. Recently, we experienced three cases of interstitial pneumonitis developing during cyclophosphamide-containing chemotherapy for non-Hodgkin's lymphoma in the absence of neutropenia or thrombocytopenia. Early use of corticosteroid in later two cases could resolve the pulmonary complication completely, whereas the pneumonitis failed to improve in spite of the massive use of multiple antibiotics in the first case.

A Case of Pyloric Obstruction Caused by Self-expandable Metallic Stent for Palliation of Malignant Dysphagia / 대한암학회지

Placement of the self-expandable metallic stents for palliative treatment of malignant esophagogastric strictures has been thought to be easy, fast and effective method than conventional methods (bypass procedures, radiation therapy, laser treatment, esophageal intubation, etc.). The expandable metallic stent tubes were found to overcome some of the limitations of nonexpandable conventional tubes. Their implantation is better tolerated and safer than that of nonexpandable tubes, because the risks of migration and perforation are lower.On our knowledge, there has been no report of pyloric obstruction after this metallic stent insertion.We hereby report a case of pyloric obstruction caused by a migrated self-expandable metallic stent for palliative treatment of malignant esophageal stricture.

Prognostic Factor Analysis of Small Cell Lung Cancer: Appropriateness of Two Staging System / 대한암학회지

PURPOSE: The two staging system, which divides the tumors into limited disease (LD) and extensive disease (ED) has been widely accepted as a major prognostic determinant in small cell lung cancer (SCLC). However this system has provoked several controversial issues in defining stage categories, for instance, ipsilateral pleural effusion as LD or ED. Furthermore, identification of favorable subgroups in the same stage has been recognized as an important factor to determine appropriate treatment strategies. In this study, we performed a retrospective analysis in an attempt to resolve the controversial issues about staging and identify the patient group with favorable prognosis based on this two staging system. MATERIALS AND METHODS: The clinical data of 233 patients with SCLC treated from 1990 to 1996 at Korea Cancer Center Hospital were retrospectively analyzed for this study. All patients were treated with chemotherapy containing cisplatin and/or radiotherapy. The independent prognostic factors for survival were identified by multivariate analysis using Cox's proportional hazards model. RESULTS: Performance status (relative risk of death [RR]:2.89), number of metastasis (RR:2.2), response to treatment (RR:2.2) as well as stage (RR:1.77) were identified as independent prognostic factors for survival in patient with SCLC. The median survival of patients with ipsilateral pleural effusion (13 months) which was categorized as ED was similar to that of patients with contralateral mediastinal or supraclavicular lymph nodes (13.8 months) or other LD patients (13.7 months). This result suggests that ipsilateral pleural effusion should be categorized as LD. In LD, response to treatment was the only independent prognostic factor (RR:2.34) and thoracic radiotherapy moderately improved survival as compared with combination chemotherapy alone (17.7 months vs. 10.4 months, p=0.06). In ED, the patient group with a good performance status (ECOG 0-1), normal range of serum alkaline phophatase, and metastasis less than 2 sites showed significantly prolonged survival, comparing with other ED patients (11.2 months vs. 7.2 months, p=0.0001). CONCLUSION: As a result of survival analysis, we confirmed independent prognostic factors such as stage and performance status in SCLC. We could recommend that LD category include patients with ipsilateral pleural effusion as well as those with contralateral lymphadenopathy. In ED, the survival in patients with favorable prognostic factors was comparable to LD, suggesting this patient group may be a candidate for aggressive therapy.

A Case of Primary Mediastinal Germ Cell Tumor Associated with Klinefelter's Syndrome / 결핵

Klinefelter's syndrome is characterized by small testes, azoospermia, gynecomastia, and elevated levels of plasma gonadotropins in men with two or more X chromosomes. Previous investigators reported that patients with Klinefelter's syndrome are predisposed to the development of a non-seminomatous germ cell tumor in the mediastinum. It is suggested that this linkage may be due to the hormonal imbalance in Klinefelter's syndrome and consequently, the formation of dysgenetic germ cell and/or abnomal migration of germ cell. We report here a case of Klinefelter's syndrome in a 24-years-old man who was presented with anterior mediastinal mass. The clinical and laborarotory findings were compatible with Klinefelter's syndrome and he was found to have 47 XXY karyotype. Pathological findings for mediastinal mass revealed mixed germ cell tumor composed of mature cystic teratoma and endodermal sinus tumor. He was treated with cis-platin containing chemotherapy and followed up in partial remission.

A Case of Cushing's Syndrome Associated with Ectopic Corticotropin Production in Patient with Small-Cell Lung Cancer / 결핵

Small cell lung cancer(SCLC) is frequently associated with paraneoplastic syndromes, which occur in approximately 20% of patients at presentation. Clinical Cushing's syndrome secondary to ectopic ACTH production is uncommon, occurring in approximately 5% of all SCLC patients. However, biochemical evidence of hypercortisolism can be detected in up to 50% of patients. Patients with Cushing's syndrome from ectopic ACTH production show hypertension, weakness, hyperglycemia, and hypokalemic metabolic alkalosis, but differ from patients with classic Cushing's disease in that symptoms develop more rapidly. Ectopic ACTH production is associated with a poor response to chemotherapy, short survival, and a high risk of treatment-related complications. We report a case of Cushing's syndrome associated with ectopic corticotropin production in 59-year-old male patient with extensive stage of SCLC.

1991 cancer incidence in Seoul, Korea: results of the Implementation Study of the Seoul Cancer Registry

This article presents the results of the Implementation Study of the Seoul Cancer Registry, which started in July, 1991 as a population based cancer registry in Seoul, Korea. The completeness and validity of the registered data were evaluated using Mortality/Incidence ratio (M/I ratio), Histologically Verified Cases (HV%), Primary Site Uncertain (PSU%), and Age Unknown (Age UNK%). Owing to the additional active surveillance, the completeness of the data turned out to be fairly acceptable, except for the aged over 75(Mortality/Incidence ratio was over 100%). Eventhough the Seoul cancer registry(SCR) has further way to go in the completeness especially among elderly persons, the validity of SCR data was also acceptable in terms of HV%, PSU%, and Age UNK%. However, PSU% and Age UNK% might need to be further reduced to be comparable with other well established cancer registries. The age standardized incidence rates(ASR) of all cancers between July 1, 1991 and June 30, 1992 were 232.4/100,000 in males and 147.9/100,000 in females. The top five major sites of cancers in Seoul were the stomach, liver, lung, colo-rectum, and bladder in order in males, and the uterine cervix, stomach, breast, colo-rectum, and liver in females. Those 5 cancer sites comprised 68.9% and 64.7% of the total cancer incidence in males and females, respectively.

Double Bronchial Lesions Detected by Bronchoscopic Examination / 결핵

OBJECTIVES: Multiple lung cancers and/or precancerous lesions can be developed because many bronchi are exposed to carcinogens simultaneously according to the concept of 'Field Cancerization'. We had performed a careful bronchoscopic examination and analysed the patients of double bronchial lesions who received the separate pathologic evaluation. METHODS: We studied 21 patients of double bronchial lesions among 1855 patients of bronchoscopic examination from April 1990 to December 1993 in Korea Cancer Center Hospital. We classified the patients into three groups(double malignancies of different histology, double malignancies of same histology, and combination of malignant and benign lesions) and analysed the histologic type, location, radiologic findings, and clinical parameters. RESULTS: Among 21 patients, six patients had double malignancies of different histology, eight had double malignancies of same histology, and seven had combination of malignant and benign lesions. Out of 14 double malignant cases, 11 cases are considered as synchronous multiple primary lung cancers. Combination of squamous cell carcinomas was found in 5 cases, combination of small cell carcinoma and squamous cell carcinoma was found in 4 cases. Combination of adenocarcinoma and squamous cell carcinoma and combination of squamous cell carcinoma and poorly differentiated carcinoma were found in 1 case respectively. All patients of synchronous multiple primary lung cancers were male and had long smoking history(average 40 pack years). Among 21 cases of double bronchial lesions, only one lesion could be detected by prebronchoscopic radiologic examination including chest CT in 15 cases. CONCLUSIONS: The presence of double bronchial lesions including multiple primary lung cancers and the limitation of radiologic examination to detect early bronchial lesions encourage us to examine the whole bronchi carefully and to perform pathologic evaluations.

A Phase II Trial of Combination Chemotherapy with Cisplatin & Etoposide in Small Cell Lung Cancer / 결핵

BACKGROUND: The objective responses of cisplatin and etoposide (PVP) combination chemotherapy as second-line therapy following CAV was high (40~50%) and, in several reports, PVP yields survival results that are at least as good as those obtained with cyclophosphamide or doxorubicin-based regimens and with less host-related toxicity in chemotherapy-naive patients. We conducted a phase II study to evaluate the effect of a combination of cisplatin and etoposide as a first-line therapy in patients with small cell lung cancer. METHODS: Sixty-one previously untreated small cell lung cancer patients with measurable lesion(s) received cisplatin(30 mg/m2 IV, day 1~3) and etoposide(100 mg/m2 IV, day 1~3). In patients with limited disease, after completion of 6 cycles of PVP chemotherapy, chest and prophylatic brain irradiation was performed in case of complete responder, chest irradiation only in partial responder. RESULTS: 1) Of 55 evaluable patients, 13(24%) had a complete response and 29(53%) had a partial response. 2) The median survival time was 55.8 weeks for all patients(N=55), 61.1 weeks for limited disease(N=31), 51.3 weeks for extensive disease(N=24). 3) The response duration was 29.1 weeks for responders(N=42). 4) There was no significant prognostic factors iufluencing response rates. 5) The toxicity was tolerable and there was no treatment-related deaths. CONCLUSION: The PVP combination chemotherapy as a first-line therapy was effective and well-tolerated in patients with small cell lung cancer.

Overcome of acquired resistance to cisplatin by buthionine sulfoximine in human stomach and lung cancer cell lines / 대한암학회지

No abstract available.

Loss of the retinoblastoma gene in non-small cell lung cancer / 결핵

No abstract available.

Effects of combination timing of recombinant human interferon-?and adriamycin on cytotoxicity to human stomach cancer cells / 대한면역학회지

No abstract available.

Induction of antileukemic cytotoxicity from peripheral blood lymphocytes of patients with acute myeloid leukemia / 대한암학회지

No abstract available.

Transcription of class II MHC gene by interferon-gamma in FRTL-5 cells

The intracellular mechanism by which interferon-gamma induces the expression of class II major histocompatibility complex (MHC) antigen in nonlymphoid cells is not clear. The effect of recombinant rat interferon-gamma (IFN-gamma), and cycloheximide on the expression of class II MHC gene was studied using the techniques of immunocytochemical staining and northern blot analysis. IFN-gamma induced de novo transcription of class II MHC gene and class II MHC antigen expression on the cell surface. Cycloheximide did not inhibit IFN-gamma-induced class II MHC antigen expression in a dose-dependent manner indicating translational blockade. These results suggest that IFN-gamma induces class II MHC antigen expression via de novo transcription of class II MHC gene leading to synthesis of new class II MHC molecule.