• 한국임상수의학회지
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• 제17권2호
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• pp.311-315
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• 2000

Recombinant interleukin-2 (IL-2) has been demonstated as an antineoplastic agent in mice and human, and the route of administration is important to IL-2-induced therapeutic responses. Therefore, the current experiment was undertaken to clarify the effect of IL-2 administration route on antitumor response against subcutaneous Meth-A tumor in mice. At the beginning of each experiment, normal BALB/c mice were injected subcutaneously with $5{\times}10^6$ Meth-A tumor cells. Beginning on day 7, experimental groups were treated with a 5-day course of IL-2 (intraperitoneal or subcutaneous injection of 30, 000 IU every 12 hours for 5 days). The result of this experiment revealed that Meth-A tumor grew progressively in control mice. Intraperitoneal IL-2 treatment decreased significantly tumor growth and prolonged survival, compared with control mice. Subcutaneous IL-2 treatment decreased significantly tumor growth until day 11 and tumor cells, grew progressively thereafter, but mice in this group survived longer than control mice.

• Journal of Yeungnam Medical Science
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• 제20권2호
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• pp.117-128
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• 2003

Thallium-201 scintigraphy is used to discriminate the malignant bone tumor from the benign by qualitatively and quantitatively, and to predict the response of preoperative chemotherapy in osteosarcoma, by comparing the changes of thallium uptake ratio after chemotherapy to the tumor necrosis ratio. Thallium-201 scintigraphy scan should be done prior to surgical biopsy. PICKER Prism 2000 gamma camera with high resolution parallel hole collimator is usually used for scanning. The patient is injected with 2-3mCi of Tl-201 and the early phase is checked in 30 minutes and delayed phase in 3 hours. The scan images are visually evaluated by a blinded nuclear medicine physician. We could evaluate true positive, true negative, false positive and false negative by the comparison of results with those of biopsy, and calculate positive and negative predictive value(%), sensitivity(%), specificity(%) and diagnostic accuracy(%). For the quantitative analysis of thallium uptake, we drew the region of interest on the tumor side and contralateral normal side as mirror image, and calculated the uptake ratio with dividing the amount of gamma count in tumor side by normal side. We could calculate the percent changes of thallium uptake ratio in early and delayed phase, and compare them to the ratio of tumor necrosis. Thallium-201 scintigraphy proved as useful imaging study to discriminate malignant bone tumor from benign, but had exception in giant cell tumor and low grade malignant bone tumors. We can use T1-201 scan to differentiate the benign from the malignant tumor, and to evaluate the response of preoperative chemotherapy or radiotherapy, and to determine the residual tumor or local recurrence. For the better result, we need to have a more detail information about false positive cases and a more objective and quantitative reading technique.

• BMB Reports
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• 제45권12호
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• pp.677-685
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• 2012

In the process of tumorigenesis, normal cells are remodeled to cancer cells and protein expression patterns are changed to those of tumor cells. A newly formed tumor microenvironment elicits the immune system and, as a result, a humoral immune response takes place. Although the tumor antigens are undetectable in sera at the early stage of tumorigenesis, the nature of an antibody amplification response to antigens makes tumor-associated autoantibodies as promising early biomarkers in cancer diagnosis. Moreover, the recent development of proteomic techniques that make neo-epitopes of tumor-associated autoantigens discovered concomitantly has opened a new area of 'immuno-proteomics', which presents tumor-associated autoantibody signatures and confers information to redefine the process of tumorigenesis. In this article, the strategies recently used to identify and validate serum autoantibodies are outlined and tumor-associated antigens suggested until now as diagnostic/prognostic biomarkers in various tumor types are reviewed. Also, the meaning of autoantibody signatures and their clinical utility in personalized medicine are discussed.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3213-3218
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• 2012

When patients with advanced breast cancer (ABC) are treated with neoadjuvant chemotherapy (NACT), efficacy is monitored by the extent of tumor shrinkage. Since their publication in 1981, World Health Organization (WHO) guidelines have been widely practiced in clinical trials and oncologic practice, for standardized tumor response evaluation. With advances in cancer treatment and tumor imaging, a simpler criterion based on one-dimensional rather than bi-dimensional (WHO) tumor measurement, named Response Evaluation Criteria in Solid Tumors (RECIST) was introduced in 2000. Both approaches have four response categories: complete response, partial response, stable disease and progressive disease (PD). Bi-dimensional measurement data of 151 patients with ABC were analysed with WHO and RECIST criteria to compare their response categories and inter criteria reproducibility by Kappa statistics. There was 94% concordance and 9/151 patients were recategorized with RECIST including 6/12 PD cases. RECIST therefore under-estimates and delays diagnosis of PD. This is undesirable because it may delay or negate switch over to alternate therapy. Analysis was repeated with a new criteria named RECIST-Breast (RECIST-B), with a lower threshold for PD (${\geq}10%$ rather than ${\geq}20%$ increase of RECIST). This showed higher concordance of 97% with WHO criteria and re-categorization of only 4/151 patients (1/12 PD cases). RECIST-B criteria therefore have advantages of both ease of measurement and calculations combined with excellent concordance with WHO criteria, providing a practical clinical tool for response evaluation and offering good comparison with past and current clinical trials of NACT using WHO guidelines.

• 대한골관절종양학회지
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• 제3권1호
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• pp.1-8
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• 1997

Osteosarcoma is the most common primary bony malignancy and its survivorship has been progressed markedly through refined chemotherapy and surgery. But still there are many non-responders and analysis of prognostic factors may be helpful for them. Two hundred and sixty-six patients were enlisted between Mar, 1985 and Sep. 1994. Among them our inclusion criteria were: 1)primary, nonmetastatic classical osteosarcoma 2)extremity in location 3)no prior treatment at other institute and completed neoadjuvant chemotherapy and surgery according to our protocol. One hundred and eleven cases were eligible. Analyzed factors were:age, sex, location, tumor size, and pathologic response. Statistical methods were log-rank test for univariate and Cox's test for multivariate analysis. Male to female ratio was 69:42 with an average age of 17.2 years. Locations of tumor were distal femur 59, proximal tibia 29, and proximal humerus 8. Tumor size were measured by its maximal diameter and 48 cases were above 10cm and 47 cases were below 10cm. For pathologic response, 57 cases showed more than 90% and 54 cases were less than that. Limb salvage procedure was 101 cases and amputation was 10 cases and their local recurrence rate were 3.6%. Average follow-up period was 24(9-78.2) months and their final status was CDF 86, AWD 8, NED 5, and DOD 12 cases. In univariate study: type of operation(p=0.005), tumor size(p=0.005), and pathologic response(p=0.02) were significant variables. Pathologic response(p=0.03) and type of operation(p=0.01) were meaningful prognostic factors on multivariate analysis. But the latter result was interpreted as a bias, so pathologic response remained as a sole meaningful prognostic factor. More aggressive chemotherapy will be needed to improve the survival.

• IMMUNE NETWORK
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• 제3권3호
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• pp.211-218
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• 2003

Background: Vitamin C is an essential nutrient, taken as a daily supplement by many people. Recently, high-dose vitamin C is considered as a therapeutic regimen in some clinical situations. Until now, few studies have been done with the effects of high-dose vitamin C on the immune response. Methods: In this experiment, the effects of high-dose vitamin C on cell-mediated immune response in immunologically competent mice were evaluated. After intraperitoneal injection of 2.5, 5, or 10 mg/day of vitamin C for 10 days, delayed type hypersensitivity (DTH) was provoked against DNFB in the pinnae as a model for cell-mediated immune response. Severity of DTH reaction was evaluated as the thickness of pinnae, and the vitamin C levels were measured in the serum, liver, kidney, lung, pinnae, and splenocytes. Results: After challenge, the thickness increased at its peak on the $2^{nd}$ day in all groups. On the first day, the pinnae were thicker in the injected groups than in the control. On the contrary, the increment of the pinnae thickness was attenuated and the number of cells infiltrated in the site of DTH decreased proportionately to the amount of vitamin C administered from the second day on. With vitamin C exogenously given, the serum level peaked at 30 min after injection, and returned abruptly to its basal level without accumulation. However, it accumulated in the liver, kidney, and especially in the pinnae inflamed and splenopcytes, proportionately to the amount administered. Conclusion: Based on these results, it is suggested that, in one hand, exogenously administered high-dose vitamin C accumulated in the splenocytes and presumably changed the function of them resulting in the augmented cell-mediated immune response, as was revealed in the first day of DTH reaction. On the other hand, it seems likely that the vitamin C also showed anti-inflammatory effects.

• Radiation Oncology Journal
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• 제34권4호
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• pp.305-312
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• 2016

Purpose: The objective of this prospective study was to evaluate the relationship between the circulating lymphocyte subpopulation counts during preoperative chemoradiotherapy (CRT) and tumor response in locally advanced rectal cancer. Materials and Methods: From August 2015 to June 2016, 10 patients treated with preoperative CRT followed by surgery were enrolled. Patients received conventional fractionated radiotherapy (50.4 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. The absolute blood lymphocyte subpopulation was obtained prior to and after 4 weeks of CRT. We analyzed the association between a tumor response and change in the lymphocyte subpopulation during CRT. Results: Among 10 patients, 2 (20%) had evidence of pathologic complete response. In 8 patients with clinically node positive, 4 (50%) had nodal tumor response. All lymphocyte subpopulation counts at 4 weeks after CRT were significantly lower than those observed during pretreatment (p < 0.01). A high decrease in natural killer (NK) cell, count during CRT (baseline cell count - cell count at 4 weeks) was associated with node down staging (p = 0.034). Conclusion: Our results suggest that the change of lymphocyte subset to preoperative CRT may be a predictive factor for tumor response in rectal cancer.

• Korean Journal of Radiology
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• 제22권3호
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• pp.366-375
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• 2021

Objective: To evaluate the radiological tumor response patterns and compare the response assessments based on immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1 in metastatic clear-cell renal cell carcinoma (mccRCC) patients treated with programmed cell death-1 (PD-1) inhibitors. Materials and Methods: All mccRCC patients treated with PD-1 inhibitors at Henan Cancer Hospital, China, between January 2018 and April 2019, were retrospectively studied. A total of 30 mccRCC patients (20 males and 10 females; mean age, 55.6 years; age range, 37-79 years) were analyzed. The target lesions were quantified on consecutive CT scans during therapy using iRECIST and RECIST 1.1. The tumor growth rate was calculated before and after therapy initiation. The response patterns were analyzed, and the differences in tumor response assessments of the two criteria were compared. The intra- and inter-observer variabilities of iRECIST and RECIST 1.1 were also analyzed. Results: The objective response rate throughout therapy was 50% (95% confidence interval [CI]: 32.1-67.9) based on iRECIST and 30% (95% CI: 13.6-46.4) based on RECIST 1.1. The time-to-progression (TTP) based on iRECIST was longer than that based on RECIST 1.1 (median TTP: not reached vs. 170 days, p = 0.04). iRECIST and RECIST 1.1 were discordant in 8 cases, which were evaluated as immune-unconfirmed PD based on iRECIST and PD based on RECIST 1.1. Six patients (20%, 6/30) had pseudoprogression based on iRECIST, of which four demonstrated early pseudoprogression and two had delayed pseudoprogression. Significant differences in the tumor response assessments based on the two criteria were observed (p < 0.001). No patients demonstrated hyperprogression during the study period. Conclusion: Our study confirmed that the iRECIST criteria are more capable of capturing immune-related atypical responses during immunotherapy, whereas conventional RECIST 1.1 may underestimate the benefit of PD-1 inhibitors. Pseudoprogression is not rare in mccRCC patients during PD-1 inhibitor therapy, and it may last for more than the recommended maximum of 8 weeks, indicating a limitation of the current strategy for immune response monitoring.

• Radiation Oncology Journal
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• 제7권2호
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• pp.213-225
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• 1989

An analysis has been made of two hundred seven patients who were treated at the department of Radiation Oncology of Korea University Hospital for lung cancer from January 1981 through December 1986. There were 137 patients of nonsmall cell carcinoma (137/207, 66%), 26 patients of small cell carcinoma (26/207, 12.5%) and 44 patients of unproven histology. By aims of treatment, there were 104 patients (104/207, 50%) treated for cure, 89 patients (89/207, 42.9%) for palliation and 14 patients treated postoperatively. In 22 out of 207 patients, chemotherapy was done with radiotherapy, 12 of which were patients with small cell carcinoma. Stage II patients were 49 (49/207, 23.6%), stage III patients were 157 (157/207, 75.8%) and one patient had an occult cancer The tumor was initial Iy measured by CAT scan and chest X-rays in the 165 (165/207, 79.7%) patients, among which 117 patients had tumor diameter more than 5cm and 48 patients less than 5cm. Radiation therapy was given with Cobalt 60 teletherapy unit and the treatment volume encompassed primary tumor and the mediastinum. For curative aim, daily tumor dose of 180 cGy was given up to the range of 5,400~6,120cGy/30~34F/6~7 week period and for palliative aim, daily tumor dose of 300 cGy was given up to the range of 3,600~4,500 cGy/12~15F/2~3 week period. Postoperatively, mediastinum was treated for total dose of 5,040 cGy/28F/5.5 week period. 123 patients (123/207, 59%) were followed up after completion of radiotherapy for 14 months to 7 years. Local tumor response to the irradiation was measured by chest X-ray taken at one month follow up and was evaluated for response rate, if they were regressed more than 50% or less than 50% of the initial tumor size. The treatment results were as follows; 1. The median survival time was 8.5 months and survival rates for 1 year, 2 year and 5 year was 25%, 3.5% and 1% of nonsmall cell lung ca of 74 evaluable patients. 2. More than 50% of local tumor response rate was obtained in about half of overall cases; 90.5% for small cell ca, 50% for squamous cell ca, 25% for adenoca and 57% for large cell ca. 3. Response rate more than 50% was seen in the 50% of the patient group with tumor diameter more than 5cm and in the 55% of those with tumor diameter less than 5cm. 4. By total raidation dose given, patient group which was given 5,400~6,120 cGy equivalent dose or higher showed tumor response rate more than 50% in 53% of the patients, whereas the group with dose less than 5,400cGy equivalent, in 25% of the patients. 5. Survival rate for 6 month, 1 year and 2 year was compared between the group of local tumor response rate more than 50% vs. group with response rate less than 50%; 74% vs. 43%, 33% vs, 23%, 10% vs. 1%, respectively. 6. Local failure was seen in 21%(44/207) of the patients, which occured mostly within 15 months after completion of radiation therapy. Distant metastases were seen in 49.7%(103/207) of the patients, of which 43 cases were found before initiation of radiotherapy. The most common metastatic sites were bone and brain. In this sutdy, 1 year,2 year and S year survival rates were somewhat poor compared to the other studies. It mainly seems to be due to the poor general status of the patients and the far-advanced stage of the disease. In nonsmall cell cancer patients who had limited local disease and had small primary tumor size, we observed better local response. In addition, dose higher than 6,000 cGy group showed better tumor control than lower dose group. Survival rate was better for the local control group. For imporvement of local control of the lung cancer and hence, the survival of the patients with lung cancer, proper radical radiotherapy with high dose for localized disease is needed. New modality of treatment such as high LET beam in radiation therapy or drugs for the advanced disease as well as early diagnosis is also needed.

• 대한예방한의학회지
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• 제5권1호
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• pp.103-115
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• 2001

Background : Gamisamryungbaekchul-san(加味蔘?白朮散) is a herbal medicine which has been used for the traditional therapeutic agent of augmentation of the spleen and reinforcement of the Qi. Objective : This Study was performed to investigate the effect of Gamisamryungbaekchul-san on the tumor and immune response in the moose B16 melanoma tumor model. Materials and Methods : The tumor was induced by subcutaneous inoculation of B16BL6 melanoma cells in the shaved dorsal region of mice. Mice were orally administered with Gamisamryungbaekchul-san extract(26.3mg/mouse) for 14days after inoculation. For making examination of antitumor effect, the Increase of life span, Tumor growth inhibition rate, change of body weight were measured and evaluated. For the immune response increasing effect, the percentage of T lymphocyte and B Lymphocyte in the peripheral blood, the percentage of CD4+ T-cell, CD8+ T-cell and CD4+/CD8+ ratio in the peripheral blood and spleen, interleukin-2 productivity were measured and evaluated. Results : Gamisamryungbaekchul-san showed 16.59% increase of life span, 31.64% tumor growth inhibition rate and increase of body weight. Gamisamryungbaekchul-san increased the percentage of T lymphocyte in the peripheral blood, CD4+ T cell percentage of peripheral blood and spleen, and Interleukin-2 productivity as compared with the Control group. Whereas Gamisamryungbaekchul-san had no effect on the percentage of B lymphocyte in the peripheral blood, the percentage of CD8+ T cell, CD4+/CD8+ T-cell ratio in both of peripheral blood and spleen as compared with the Control group. Conclusion : This study shows that Gamisamryungbaekchul-san has anti-tumor effects and immunoregulatory effects on the B16 melanoma tumor model. It is suggested that Gamisarmyungbaekchul-san could be a useful immunomodulator and anti-tumor agent.