Purpose : To evaluate the role of postoperative chemoradiotherapy in locally advanced rectal cancer, we retrospectively analyzed the treatment results of patients treated by curative surgical resection and postoperative chemoradiotherapy. Materials and Methods : From April 1989 through December 1998, 119 patients were treated with curative surgery and postoperative chemoradiotherapy for rectal carcinoma in Gyeongsang National University Hospital. Patient age ranged from 32 to 73 years, with a median age of 56 years. Low anterior resection was peformed in 59 patients, and abdominoperineal resection in 60. Forty-three patients were AJCC stage II and 76 were stage III. Radiation was delivered with 6 MV X rays using either AP-PA two fields, AP-PA both lateral four fields, or PA both lateral three fields. Total radiation dose ranged from 40 Gy to 56 Gy. In 73 patients, bolus infusions of 5-FU $(400\;mg/m^2)$ were given during the first and fourth weeks of radiotherapy. After completion of radiotherapy, an additional four to six cycles of 5-FU were given. Oral 5-FU (Furtulone) was given for nine months in 46 patients. Results : Forty $(33.7\%)$ of the 119 patients showed treatment failure. Local failure occurred in 16 $(13.5\%)$ patients, 1 $(2.3\%)$ of 43 stage II patients and 15 $(19.7\%)$ of 76 stage III patients. Distant failure occurred in 31 $(26.1\%)$ patients, among whom 5 $(11.6\%)$ were stage II and 26 $(34.2\%)$ were stage III. Five-year actuarial survival was $56.2\%$ overall, $71.1\%$ in stage II patients and $49.1\%$ in stage III patients (p=0.0008). Five-year disease free survival was $53.3\%$ overall, $68.1\%$ in stage II and $45.8\%$ in stage III (p=0.0006). Multivariate analysis showed that T stage and N stage were significant prognostic factors for five year survival, and that T stage, N stage, and preoperative CEA value were significant prognostic factors for five year disease free survival. Bowel complication occurred in 22 patients, and was treated surgically in 15 $(12.6\%)$, and conservatively in 7 $(5.9\%)$. Conclusion : Postoperative chemoradiotherapy was confirmed to be an effective modality for local control of rectal cancer, but the distant failure rate remained high. More effective modalities should be investigated to lower the distant failure rate.
Park, Cheol;Jin, Cheng-Yun;Choi, Tae Hyun;Hong, Su Hyun;Choi, Yung Hyun
Journal of Life Science
/
v.23
no.9
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pp.1118-1125
/
2013
Naringenin, a naturally occurring citrus flavonone, is a potentially valuable candidate for cancer chemotherapy. However, the cellular and molecular mechanisms responsible for its anticancer activity are largely unknown. In the present study, we attempted to elucidate the mechanisms responsible for naringenin-induced apoptosis in human leukemic U937 cells. We found that naringenin markedly inhibited the growth of U937 cells by decreasing cell proliferation and inducing apoptosis, which was associated with the activation of caspases. A pan-caspase inhibitor, z-VAD-fmk, significantly inhibited naringenin-induced U937 cell apoptosis, indicating that caspases are key regulators of apoptosis in response to naringenin in U937 cells. Although the levels of antiapoptotic Bcl-2 and proapoptotic Bax proteins remained unchanged in naringenin-treated U937 cells, Bcl-2 overexpression attenuated naringenin-induced apoptosis. Furthermore, combined treatment with naringenin and HA14-1, a small-molecule Bcl-2 inhibitor, effectively increased the apoptosis through enhancement of XIAP down-regulation, Bid cleavage, and caspase activation, suggesting that the synergistic effect was at least partially mediated through the death receptor-mediated apoptosis pathway.
Chung Eun Ji;Lee Hyung Sik;Moon Sun Rock;Kim Gwi Eon;Loh John Juhn-Kyu
Radiation Oncology Journal
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v.9
no.1
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pp.65-72
/
1991
One hundred and thirty five patients with carcinoma of the nasopharyx were treated by radiation therapy in the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University between August 1977 and July 1987. Of the 30 patients omitted: 8 had distant metastases at initial diagnosis or during radiotherapy; 18 Patients refused or did not receive a full course of radiation therapy, and four had not been confirmed histologically. The remaining 105 patients were analysed to determine the incidence and pattern of distant metastases. Diagnosis of distant metastases was made based on clinical signs and radiography, even though histologic confirmation was not made. Twenty-six patients developed distant metastases after definite irradiation of nasopharyx and neck, an incidence rate of $24.8\%$ . The common sites of distant metastases were, in descending order, bone, lung, liver, and brain. There was a strong correlation between Ho's N stage and distant metastases rate. But sex, age, histologic subtype (squamous cell and undifferentiated cell), AJC T and N stage, treatment modalities (radiotherapy alone and radiotherapy combined with chemotherapy) were not significant. Of those patients who developed distant metastases, $80.8\%$ were discovered within 2 years of their radical radiotherapy. The prognosis for nasopharyngeal carcinoma patients developing distant metastases was poor: median survival was nine months and $80\%$ of those patients died within two years of the initial diagnosis of distant metastasis.
A clinical study of 36 cases of pulmonary tuberculosis that had had a surgical resection during the period of 13 years from January 1979 to December 1992 was performed in the Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Hospital The ratio between male and female was 3.5 1 and the age of peak incidence was in the 2nd and 3rd decades. The common prodromal symptoms were chest pain (38.9 %) and hemoptysis or blood tinged sputum (36.1 %). Preoperative diagnostic examination of sputum positivity for AFB stain despite antituberculosis chemotherapy was noticed in 22.8 oyo . Surgical indications were destroyed lobe or segment with or without cavity (58.3 oyo), mass unable to differentiate from lung cancer (16.7 %), total destroyed lung (13.9 %), bronchostenosis with atelectasis and distal bronchiectasis (11.1 %). Types of resection were pneumonectomy in 16.7%, lobec omy and segmentectomy 2.7%, lobectomy 50 %, segmentectomy 27.8%, and wedge resection 2.7%. Postoperatively, pulmonary function Improved compared to the preoperative examination, although these changes were not statistically significant. One patient died of ulcerative colitis due to drug hypersensitivity, and the postoperative complications were remnant dead space in 11.1 %, spreading of tuberculosis in 5.5%, and empyema with BPF in 5.5%.
Sulforaphane (SFN) is an isothiocyanate, isolated from glucoraphanin in broccoli and other cruciferaous vegetables. Recent studies have revealed that SFN induces anti-proliferation and apoptosis by cell cycle arrest in various cancer cells. In this study, we investigated the effect of SFN induced apoptosis in chondrosarcoma HTB-94 cells. SFN caused suppression of proliferation and apoptosis in a dose-dependent manner as determined by cell phenotype, MTT assay and FACS analysis in HTB-94 cells. Treatment of SFN led to caspase-3 activation and p53 accumulation as determined by Western blot analysis. Also, SFN significantly induced DNA fragmentation and nuclear degradation though activation of caspase-3, as detected by DNA electrophoresis and immunostaining, respectively. Our results indicate that SFN-induced apoptosis was regulated by p53 and caspase-3 dependent pathways. Furthermore, SFN may act as a potent anti-proliferation agent, and as a promising candidate for molecular-targeting chemotherapy against human chondrosarcoma cells.
Background: Most antitumor agents have the side effect of chemotherapy-induced peripheral neuropathy (CIPN). Cancer patients who take antitumor agents suffer from CIPN, but there is no known treatment for it. Unlike the central nerve system, the peripheral nerve can self-repair, and the Schwann cell takes this mechanism. Objectives: In this study, we researched the effect of YideungJetong-Tang (YJT) extract on taxol-induced sciatic nerve damage, through in vitro and in vivo experiments. Also, we studied the effect of YJT extract on neurite recovery and anti-inflammatory effect after compression injury of sciatic nerve in vivo. Methods: Vehicle, taxol and taxol+YJT were respectively applied on sciatic nerve cells of rat in vitro, then the cells were cultured. The sciatic nerve cells and Schwann cells were then observed using Neurofilament 200, Hoechst, ${\beta}$ -tubulin, S-$100{\beta}$, caspase-3 and phospho-Erk1/2. CIPN was induced by taxol into the sciatic nerve of rat in vivo, then YJT extract was taken orally. The axons, Schwann cells and neurites of the DRG sensory nerve were then observed using Neurofilament 200, ${\beta}$-tubulin, Hoechst, S-$100{\beta}$, phospho-Erk1/2 and caspase-3. YJT was taken orally after sciatic nerve compression injury, and the changes in axon of the sciatic nerve, Schwann cells and TNF-${\alpha}$ concentration were observed. Results: The taxol and YJT treated group showed significant effects on Schwann cell recovery, neurite growth and recovery. In vivo, YJT compared with control group showed Schwann cell structural improvement and axons recovering effect after taxol-induced Schwann cell damage. After sciatic nerve compression injury, recovery of distal axon, changes of Schwann cell distribution, and anti-inflammatory response were observed in the YJT. Conclusions: Through this study, we found that after taxol-induced neurite damage of sciatic nerve in vivo and in vitro, YJT had significant effects on sciatic nerve growth and Schwann cell structural improvement. In vivo, YJT improved recovery of distal axons and Schwann cells and had an anti-inflammatory effect.
Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.
Choi, Sungim;Choi, Heun;Park, Seong Yeon;Kwak, Yee Gyung;Song, Je Eun;Shin, So Youn;Baek, Ji Hyeon;Shin, Hyun-IL;Oh, Hong Sang;Kim, Yong Chan;Yeom, Joon-Sup;Han, Jin-Hee;Kim, Min Jae
Parasites, Hosts and Diseases
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v.60
no.1
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pp.39-43
/
2022
Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.
Background: The treatment results of the advanced lung carcinoma is not satisfactory with the present therapeutic modalities: surgical resection, anti-cancer chemotherapy, and radiotherapy or combination therapy. To predict the prognosis of the non-small-cell lung carcinoma, TNM classification has been was as the basic categorization; however, it has been not satisfactory. It is necessary to consider the causes and the prognosis of the lung carcinoma from another points of view rather the conventional methods. We intended to find out the relationship between the major apoptotic factor, p53 gene and the prognosis of the patient with lung carcinoma. Material and Method: Three hundreds and fifty-nine patients with lung carcinoma who underwent surgery were analysed. We observed p53 protein accumulated in the cellular nuclei. The p53 protein was detected by immuno-histo-chemical method. We collected information of the patient retrospectively. Result: p53 protein densities were observed in 40% in average as a whole. The protein density was 44 percent in man, 25 percent in woman, 49 percent in the squamous cell carcinoma, and 38 percent in the adenocarcinoma. There were significant correlations between the p53 protein density and the mortality in the squamous cell carcinoma (p=0.025), follow-up duration in TNM stage I group (p=0.010), and follow-up duration in the lobectomy patient group (p=0.043), and tumor cell differentiation (p=0.009). p53 protein densities were significantly different between the lobectomy and the pneumonectomy group (p=0.044). Conclusion: The authors found that p53 protein had some correlations with the prognosis of the lung cancer partially in some factors. We suggest the p53 protein density could be used as a marker of prognosis in the non-small-cell lung carcinoma.
The retrospective analysis was performed on 37 patients with stage III non small cell lung cancer who received the radiotherapy from Feb. 1986 to Dec. 1990 at the Dept. of Radiation Oncology, National Medical Center. This analysis, with 29 patients $(78.4\%)$ having been followed from 10 to 60 months, was done to know the survival rate and significant prognostic factor. The actuarial 2,5-year survival rates were $20.6\%,6.9\%$ in our all patients and median survival time was 10 months. Of patients with KPS (Karnofsky prformance status) greater than $80\%,$ the 2, 5 year survival rate and median survival time were $29.2\%,9.7\%$ and 13 months, respectively. The 2-year survival rate and median survival time of patients with KPS less than $80\%\;were\;13.7\%$ and 7 months, respectively. The survival difference according to performance status was statisticaly significant $(29.2\%\;vs.\;13.7\%)(p<0.05).$ In stage IIIa, the 2,5-year survival rate and median survival rate and median survival time were $29.2\%,9.7\%$ and 12 months, respectively. The 2-year survival rate and metian survival time of stage IIIb were $8.6\%$ and 10 months, respectively. The survival difference between stage IIIa and IIIb did not show statistical significance (p>0.1). Of the prognostic factors, the difference of survival rate by initial performance status was statistically significant (p<0.05). But the difference of survival rates by pathologic cell type, stage, total radiation dose, radiotherapy response, and cmbination with chemotherapy were not statistically significant.
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