Cancer Research and Treatment

Case Reports

A Case of Paratesticular Leiomyosarcoma Successfully Treated with Orchiectomy and Chemotherapy: Bong Suk Ko, Nae Yu Kim, Ah Jung Ryu, Dong Soon Kim, Soo Jung Gong, Dae Kyung Kim, Hyun Jin Son, Jung-Ae Lee; Cancer Res Treat. 2012;44(3):210-214. Published online September 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.3.210

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.

Citations

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Para-testicular Sarcoma: An Extreme Rarity
Anurag Mishra, Tridibes Mandal
Journal of Medical Evidence.2024;[Epub] CrossRef
Scrotal wall leiomyosarcoma: a case report and review of the literature
Zahra Erfani, Aileen Azari-yam, Seyed Reza Yahyazadeh
Journal of Medical Case Reports.2021;[Epub] CrossRef
Commentary on “A Case of Paratesticular Leiomyosarcoma Successfully Treated with Orchiectomy and Chemotherapy”
Edoardo Virgilio, Stefania Uccini, Paolo Marchetti, Paolo Mercantini
Cancer Research and Treatment.2016; 48(1): 422. CrossRef
Adult Urological Soft Tissue Sarcomas: A Multicenter Study of the Anatolian Society of Medical Oncology (ASMO)
Olcun Umit Unal, Ilhan Oztop, Serkan Menekse, Zuhat Urakci, Oktay Bozkurt, Melike Ozcelik, Yusuf Gunaydin, Nurgul Yasar, Dogan Yazilitas, Hilmi Kodaz, Burcu Yapar Taskoylu, Asude Aksoy, Umut Demirci, Murat Araz, Onder Tonyali, Alper Sevinc, Ahmet Ugur Yil
Asian Pacific Journal of Cancer Prevention.2015; 16(11): 4777. CrossRef
A Rare Case of Paratesticular Leiomyosarcoma
Shankar Haran, Vikram Balakrishan, Greg Neerhut
Case Reports in Urology.2014; 2014: 1. CrossRef

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A Case of Synchronous Double Primary Cancer of the Penis and Urinary Bladder: Yong Soo Cho, Jung-Ae Lee, Si Bum Kim, Soo Jung Gong, Joo Heon Kim, Seon Min Youn, Eun Tak Kim; Cancer Res Treat. 2010;42(1):53-56. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.53

Abstract PDF PubReader ePub

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.

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Citations to this article as recorded by

A rare case report of synchronous renal cell carcinoma and penile carcinoma
Indra Prakash Mandal, Krishnendu Maiti, Debansu Sarkar
Annals of Medical Science & Research.2025; 4(2): 108. CrossRef
Synchronous Double Primary Cancer of the Penisand Urinary Bladder
Deora H
MOJ Surgery.2017;[Epub] CrossRef

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2 Crossref

Original Articles

Brain Metastasis and Leptomeningeal Carcinomatosis in Breast Cancer: Yoon Soo Chang, Jeong Hun Seo, Ruth Lee, Joong Bae Ahn, Kwang Yong Shim, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Chang Ok Suh, Joo Hang Kim, Jae Kyung Rho, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):464-474.

Abstract PDF: 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.

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Clinical Significance of Urokinase - type Plasminogen Activator Receptor ( uPAR ) Expression in Breast Cancer Tissues: Soo Jung Gong, Sun Young Rha, Hei Chul Jung, Joon Oh Park, Nae Choon Yoo, Jae Kyung Roh, Woo Ick Yang, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 2000;32(1):53-59.

Abstract PDF: 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.

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Gene Transfer Effects of Thymidine Kinase Gene of Herpes Simplex Type 1 on Ganciclovir Cytotoxicity in Gastric Cancer Cell Line: Jae Kyung Roh, Soo Jung Gong, Joo Hang Kim, Hyo Dong Um, Nae Chun Yoo, Jin Hyuk Choi, Jae Jin Song, Sun Young Rha, Hyun Cheol Chung, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1998;30(1):20-30.

Abstract PDF: 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.

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A Phase I/II Trial of DA3030 in Chemotherapy Induced Neutropenia: Hyun Cheol Chung, Sun Young Rha, Soo Jung Gong, Hwa Young Lee, Hei Cheol Chung, Churl Woo Ahn, Wook Jin Chung, Rutha Lee, Bo Young Choung, Seung Keun Lee, Yoon Soo Chang, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Bum Soo Park, Mi Young Bahng; J Korean Cancer Assoc. 1997;29(5):886-898.

Abstract PDF: PURPOSE
We planned to evaluate the toxicity and efficacy of DA-3030 to determine the recommended dose for phase III clinical trial based on the biologically active doses from phase I/II clinical trial.
MATERIALS AND METHODS
Open non-randomized phase I/II study was carried out in 64 cancer patients with chemotheray-induced myelosuppression. After 1 cycle of control period (chemotherapy without DA-3030), DA-3030 was started 24 hours after the second cycle of chemotherapy to 4 groups of patients with the doses of 50 microgram/m2/day (step I), 100 microgram/m2/day (step II), 150 microgram/m2/day (step III), 200microgram/m2/day (step IV) by once-a-day subcutaneous administration for 10 days.
RESULTS
Of the 64 enrolled patients, 46 patients were evaluable. Tmax reached after 2 hours of injection in step I and 4 hours in step II-IV. Terminal half life was 1.8 hours in step I and 3.2 hours in step II, 3.3 hours in step III, 3.0 hours in step IV. Area under the curve (AUC) and AUMC increased dose dependently from step I through step IV. Total clearance rate decreased in a dose dependent manner but the volume of distribution showed no differences between the steps.The mean nadir count of total WBC and neutrophil increased in all 4 steps of DA-3030 administration. Also the duration of leukopenia, equal to or less than 2,000/uL or neutropenia and the recovery time of WBC or neutrophil from nadir decreased with DA-3030 administration in all 4 steps. But no differece of DA-3030 effect was found among 4 steps. When we compared the clinical efficacy of DA-3030 with total WBC and neutrophil criteria, it was 58.3% and 58.3% in step I, 90.0% and 80.0% in step II, 91.7% and 91.7% in step III, 75.0% and 70.0% in step IV. Although the duration of antibiotics administration showed no difference between control and DA-3030 administration period in step I, it decreased with DA-3030 administration in step II-IV. Infection was found only in step I. Life-threatening side effect was not found in all steps. Only mild myalgia was found without any dose relationship.
CONCLUSION
When we considered the efficacy, toxicity and pharmacokinetic parameters, we suggest that 100microgram/m2 is an appropriate dosage for the phase III clinical trial.

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Clinical Significance of Urokinase-type Plasminogen Activator (uPA) Expression from Serum and Tissue of Gastric Cancer Patients: Hyun Cheol Chung, Joon Oh Park, Hyun Ja Kwon, Tae Soo Kim, Hei Cheol Chung, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):765-773.

Abstract PDF: PURPOSE
We measured the gastric cancer tissue uPA and plasminogen activator inhibitor-1 (PAI-1) levels and compared them to those of the peripheral and portal blood levels to evaluate the correlation.
MATERIALS AND METHODS
Tissue uPA and PAI-1 levels were measured by ELISA assay (Monozyme, Netherland) in paired 85 normal and cancer tissues resected from gastric cancer patients. In 50 patients, blood uPA and PAI-1 levels were measured from pre- operative peripheral and portal blood, post-operative portal blood.
RESULTS
Gastric cancer tissue uPA and PAI-1 levels increased from the early stage. The elevated cancer-to-normal ratios of the uPA and PAI-1 were constant from stage I to IV. There were correlations of uPA between normal and cancer tissues (r2=0.38) and between peripheral and pre-resection portal blood level (r2=0.64). There were no correlations between tissue PAI-1 level and blood PAI-1 levels. However, there were correlations in PAI- 1/uPA ratio between cancer tissue and peripheral blood (r2=0.25), peripheral blood and pre- resection portal blood (r2=0.60).
CONCLUSION
Even if the cancer tissue levels of uPA and PAI-1 increased from the early stage of gastric cancer, only blood uPA level correlated with tissue uPA level. A modest correlation found in PAI-1/uPA ratio between cancer tissue and blood suggests applicability of blood PAI-1/uPA ratio in predicting tissue uPA, PAI-1 expression.

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A Study of Retrovirus-mediated p53 Gene Transduction Into Human Gastric Cancer Cell Lines: Joo Hang Kim, Yoo Sun Moon, Dong Hwan Shin, Jae Jin Song, Soo Jung Gong, Sun Young Rha, Soo Kyoung Kim, Sook Jung Jeong, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):754-764.

Abstract PDF: PURPOSE
The development of new therapeutic modalities such as gene therapy, which still requires further investigation, is clearly important to improve the prognosis of gastric cancer. This study was conducted to evaluate the effect on the growth and the tumorigenicity of retrovirus-mediated p53 gene transduction into gastric cancer cells.
MATERIALS AND METHODS
Human gastric cancer cell lines were cultured and their DNAs were analyzed to evaluate the p53 status with PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and DNA sequencing. Retroviral supernatants were obtained from each producer cell line, PA317/LNCX and PA317/LNC/p53, after construction of retroviral vector LNC/p53 containing human p53 cDNA and producer cell line PA 317/ LNC/p53. To investigate the effect of retrovirus-mediated p53 gene transduction in human gastric cancer cell lines, the in vitro growth rates and in vivo tumorigenicities of the N-87 cell line having mutant p53 and the YCC-S-2 cell line having wild-type p53 were compared before and after infection with LNC/p53 retrovirus. RESULTS: The following results were obtained: 1) The growth inhibition of N-87 cells after p53 transduction was signficant when compared to that of the parent N-87 cells. The growth of the p53 transduced YCC-S-2 cells and the parent YCC-S-2 cells was not different. 2) In nude mice, the growth of tumors formed by N-87 cells was modestly inhibited after retrovirus-mediated wild-type p53 gene transduction. However, the growth of tumors formed by YCC-S-2 cells was not inhibited by retrovirus-mediated p53 gene transduction. 3) The expression rate of p53 protein after p53-containing retroviral infection in the KATO-III cell lines, which have no p53 gene, was dose-dependent on the m.o.i. of retrovirus, although it was not more than 15% with the m.o.i. of 100 upon immunohistochemical analysis.
CONCLUSION
The growth inhibition by retrovirus-mediated p53 transduction in human gastric cancer cells was significant in a gastric cancer cell line having mutant p53 in vitro, and the growth of tumor masses formed by a gastric cancer cell line having mutant p53 was modestly inhibited after p53 transduction using retroviral vector in nude mice, although it was not statistically significant. Only modest inhibition of tumor growth using retrovirus-mediated p53 gene transduction in vivo is most likely to be due to low transduction efficiency.

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Effects of Interleukin-2 Transduction into the Human Hepatoma Cell Lines Using Retroviral Vector: Soo Jung Gong, Nae Chun Yoo, Joo Hang Kim, Dong Hwan Shin, Hyo Dong Uhm, Sook Jung Jeong, Jae Yong Cho, Sun Young Rha, Yeon Soo Kim, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(4):555-564.

Abstract PDF: 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.

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Clinical Relevance of Urokinase-type Plasminogen Activator ( uPA ) , uPA Receptor , Plasminogen Activator Inhibitor-1 Co-expression from Tissue and Serum of Breast Cancer as Targets of Biotherapy: Sun Young Rha, Joon Oh Park, Soo Jung Gong, Se Ho Park, Nae Choon Yoo, Woo Ick Yang, Jae Kyung Roh, Jin Sik Min, Kyong Sik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1999;31(2):256-266.

Abstract PDF: 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.

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Anti-tumor Effects of Growth Factor Inhibitors and Anti-metastatic Agents in Human Gastric Cancer Cell Lines: Sun Young Rha, Hee Cheol Chung, Soo Jung Gong, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(3):391-403.

Abstract PDF: PURPOSE
For tumor growth, invasion and metastasis, a cascade of linked sequential biological events is essential; overproduction of growth factors, activation of proteolytic enzymes, induction of tumor angiogenesis, and enhanced tumor cell motility and attachment. We tried to test whether the biological therapy against the biological targets can modulate the specific biological characteristics, and furthermore increased anti-tumor effects can be induced when the biological therapy and cytotoxic chemotherapy were combined.
MATERIALS AND METHODS
YCC-1, 2, 3, 7, and AGS human gastric cancer cell lines were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor (HBGF) inhibitor, Tranexamic acid as a plasmin inhibitor, Adriamycin as a chemotherapeutic agent, were selected. The methods were Northern blot analysis for the detection of Midkine (MK) expression, soft agar assay for autocrine tumorigenicity. The expression of uPA, PAI-1 was determined by ELISA, while the MMPs activities were evaluated by zymography. The effects of each drug on tumorigenicity and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively.
RESULTS
YCC-3, 7, AGS cell lines expressed MK mRNA, whereas YCC-1, 2 did not. YCC-2 cell line showed increased expression of uPA and MMP activities. Only MK expressing YCC-3 and 7 cell lines showed the tumorigenicity. PPS suppressed the colony forming activities as much as Adriamycin did (PPS; 8~24%, Adriamycin; 12~40%), but it showed only cytostatic effects in cell proliferation assay (PPS; 60~103%, Adriamycin; 22~97%). When PPS was combined with Adriamycin on the Adriamycin resistant, MK expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that of PPS or Adriamycin single treatment was 40%, 22%, respectively (p=0.001).
CONCLUSION
The modulation of specific biological targets can induce the anti-tumor effects. This suggests the possible clinical application of biological therapy in gastric cancer.

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The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma: Sun Young Rha, Soo Jung Gong, Hee Cheol Chung, Kwang Yong Shim, Joong Bae Ahn, Nae Choon Yoo, Hyn Cheol Chung, Joo Hang Kim, Hae Kyung Roh, Jin Sik Min, Byung Soo Kim, Kyu Ho Shin, Woo Ick Yang, Chong In Lee; J Korean Cancer Assoc. 1999;31(1):134-143.

Abstract PDF: 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.

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Synchronous Expression of Circulating Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) During Gastric Cancer Progression: Hei Cheol Chung, Joon Oh Park, Sun Young Rha, Hyun Cheol Chung, Soo Jung Gong, Choong Bae Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Sung Hoon Noh; J Korean Cancer Assoc. 1997;29(1):81-92.

Abstract PDF: PURPOSE
The circulating forms of ICAM-1 (cICAM-1) and VCAM-1 (cVCAM-1) has been reported from supernatant of cytokine activated endothelial cells, cancer cells and from cancer patient serum even though the biological significance of the cCAMs are not fully elucidated.
MATERIALS AND METHODS
To evaluate the correlation of the expression of cICAM-1 and cVCAM-1 and prognosis in gastric cancer, we measured cICAM-1 and cVCAM-1 levels in 20 healthy volunteers and 142 gastric cancer patients' sera by ELISA assay. Also we compared cCAMs levels with vascular endothelial growth factor (sVEGF) and FP. Ninety-five patients were operable and 47 patients were advanced or relapsed state at the time of the study. In 28 operable patients, we simultaneously sampled portal and peripheral vein and measured the cCAMs.
RESULTS
The cCAMs level and positive rate in serum increased with cancer progression from healthy control, operable to advanced or relapsed gastric cancer. In advanced cancer, cICAM-1 level increased with liver metastasis. The cICAM-1 level in portal blood was correlated modestly with that in peripheral blood. And in cVCAM-1 positive subgroup, cCAM-1 level correlated with cVCAM-1 level. The peripheral cICAM-1 level decreased in 6% compared to that of portal cICAM-1 level while peripheral cVCAM-1 level increased in 1% compared to that of portal level. Synchronous expression of both cCAMs was found in 58.3% of the patients with liver metastasis and 22.9% of the patients without liver metastasis (p=0.03). But, there were no correlation between cCAMs and FP expression regardless of liver metastasis. The sVEGF level correlated with neither cICAM-1 nor cVCAM-1 level regardless of liver metastasis. The median disease-free and overall survival of patients with synchronous cICAM-1 and cVCAM-1 expression was 8 months and 9 months, while in patients without co-expression it was more than 24 months and 23 months respectively.
CONCLUSION
We suggest that synchronous cICAM-1 and cVCAM-1 elevation may be a useful monitor of tumor burden and progression in gastric cancer, especially in liver metastasis.

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Evaluation of Biologic Phenotype by Midkine Gene Expression in Gastric Cancer as a Target for Biotherapy: Hyun Cheol Chung, Sun Young Rha, Hei Cheol Chung, Hyun Joo Kwak, Jae Yong Cho, Soo Jung Gong, Sung Hoon Noh, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(1):69-80.

Abstract PDF: PURPOSE
We studied biological phenotypes of gastric cancer cell lines based on a novel heparin-binding growth/differentiation factor, midkine (MK) expression.
MATERIALS AND METHODS
Nine gastric cancer cell lines and 25 gastric cancer tissues were tested for MK expression by Northern blot analysis. Soft agar assay for in vitro tumorigenesis, cross- feeding assay for paracrine angiogenic activity, ELISA for uPA and PAI-1 measurement were performed.
RESULTS
MK expression was found in 67% (6/9) of the gastric cancer cell lines, and 56% (14/25) of the primary gastric cancer tissues. Gastric cancer cell lines with MK expression were more tumorigenic in soft agar assay and endothelial cell growth stimulatory in cross-feeding assay than cells which did not express MK. However, urokinase-type plasminogen activator (uPA) expression did not correlate with MK expression. Growth of MK expressing cells was inhibited by a heparin-binding blocking agent, pentosan polysulfate (PPS). In cancer tissues, MK expression correlated with tumor size, suggesting in vivo autocrine and paracrine activity.
CONCLUSION
Gastric cancer cells with increased MK gene expression showed increased tumorigenic and angiogenic activity. Therefore, this proliferation promoting activity of MK can be targeted by an anti-heparin binding agent as a biotherapy model in gastric cancer treatment.

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Effect of Combined Modality Treatment and Clinical Significance of P-Glycoprotein Overexpression in Patients with Osteosarcoma: Yong Seok Yun, Jae Kyung Roh, Hyun Cheol Chung, Jae Yong Cho, Kyoo Ho Shin, Soo Bong Han, Beom Seok Kim, Joon Oh Park, Soo Jung Gong, Sun Young Rha, Nae Choon Yoo, Joo Hang Kim, Jin Sik Min, Byung So; J Korean Cancer Assoc. 1996;28(6):1104-1117.

Abstract PDF: Osteosarcoma is a highly malignant bone tumor and usually encountered in the first three decades of life. The Prognosis of osteasarcoma treated with surgery alone had been poor, with 20% of the patients surviving 5 years. The addition of adjuvant chemotherapy after surgery has siginificantly improved the outcome of osteosarcoma. The new concept of pre-operative chemotherapy has permitted histological assessment of treatment effect and limb salvage procedures. As the role of chemotherapy has been raised, the resistance of tumors to multiple drugs, such as p-glycoprotein overexpression, has become a major problem in the treatment of osteosarcoma. We retrospectively reviewed the clinical records of 53 patients with stage IIB osteosarcoma who were treated at Yonsei Medical Center and Yonsei Cancer Center between March 1, 1986 and June 30, 1996. The purpose of this study was to assess the efficacy and toxicity of cisplatin(IA)-adriamycin(IV) combination pre-operative chemotherapy and the clinical significance of p-glycoprotein status and histologic response as prognostic factors. Among 53 patients, 33 were male and 20 were female with a median age of 21 years(range: 5~61). The tumor locations were as follows: distal femur 24(45.3%), proximal tibia 17(32.1%), humerus 7(13.2%), proximal femur 3(5.4%), fibular 1(1.9%), radius 1(1.9%). Histologic subclassifications were as follows: osteoblastic type 42(78.2%), telangiectatic type 4(7.5%), chondrablastic type 3(5.7%), fibroblastic type 2(3.8%) and undetermined 2(2.8%). The three year overall survival and disease-free survival rates were 66.1% and 61.9% respectively in all patients. Thirty-two patients were treated by pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy and 21 patients were taken only post-operative adjuvant chemotherapy. No significant difference was found between the two groups in probability of survival and recurrence rates. The histological response ta pre-operative chemotherapy was scored by degree of tumor necrosis. Twenty-two patients had a good response [grade IV, 13(40.6%);grade III, 8(25.0%)] and 11 patients had a poor response [grade II, 6(18.8%);grade I, 5(15.6%)]. The histological response was not significantly related to the probability of the survival rate. However, the recurrence rate was higher in the poor-response group(p=0.04). Overexpression of p-glycoprotein was found in tumors from 11 of l8 patients(61.1%) who were given only post-operative adjuvant chemotherapy. No relation was found between the p-glycoprotein expression and survival rate. The degree of tumor necrosis after pre-operative chemotherapy and initial serum alkaline-phosphatase level were considered as prognositic factors. Other clinicopathologic features including age, gender, anatomical site, histological subclassification,operation types,tumor size.p-glycoprotein expression were not associate with patient outcome. Treatment-related side effects were relatively tolerable and reversible by conservative treatment. Pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy in our study did not show improved survival than conventional post-operative chemotherapy with limited follow-up duration. The degree of histologic response after chemotherapy and the initial alkaline phosphatase level were found to be the major predictor for tumor recurrences, while p-glycoprotein overexpression did not alter the clinical outcome. Further studies are warranted to improve the efficacy of adjuvant chemotherapy and to evaluate the significance of multiple resistance gene overexpression in osteosarcoma.

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Plasma TGF-beta1 as a Tumor Marker in Breast Cancer Patients: Hwa Young Lee, Sun Young Rah, Soo Jung Gong, Joong Bae Ahn, Kwang Yong Shim, Joon Oh Park, Hyun Ja Kwon, Nae Choon Yoo, Sook Jung Jeong, Hyun Cheol Chung, Joo Hang Kim, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Jae Kyung Roh; J Korean Cancer Assoc. 1998;30(5):935-942.

Abstract PDF: 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.

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Microsatellite Instability Correlate with a Prognosis in Breast Cancer: Hwa Young Lee, Chengshi Quan, Soo Jung Gong, Joon Oh Park, Joong Bae Ahn, Kwang Yong Shim, Sun Young Rha, Nae Choon Yoo, Woo Ick Yang, Joo Hang Kim, Jae Kyung Roh, Kyong Sik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(5):914-920.

Abstract PDF: 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.

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