Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive Ca2+ release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of Ca2+ homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular Ca2+ metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (gamma)-irradiation. In irradiated RKO cells, Ca2+ influx via activation of NCX reverse mode was enhanced and a decline of [Ca2+]i via forward mode was accelerated. The amount of Ca2+ released from the ER in RKO cells by the activation of IP3 receptor was also enhanced by irradiation. An increase in [Ca2+]i via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that gamma-irradiation elicits enhancement of cellular Ca2+ metabolism in radiation-sensitive RKO cells yielding programmed cell death.
Calcium* ; Cell Death ; Colorectal Neoplasms* ; Cytochromes c ; DNA Damage ; Homeostasis ; Humans ; Inositol 1,4,5-Trisphosphate Receptors ; Metabolism* ; Mitochondria

BACKGROUND AND OBJECTIVES: In order to eradicate the disease and preserve function of oropharynx and facial contour, appropriate surgical approach should be chosen for surgical treatment of oropharyngeal cancer. This study was performed to evaluate the usefulness and effectiveness of various surgical approaches in the surgical treatment of oropharyngeal cancer. SUBJECTS AND METHOD: We analyzed 65 patients with oropharyngeal cancer who underwent surgery as a primary treatment from Jan. 1994 to Jun. 2009, retrospectively. Primary tumor site, TNM stage, surgical approach, management of neck, reconstruction method, complication, recurrence rate were analyzed to assess advantages and disadvantages of various surgical approaches. RESULTS: The surgical approaches applied were transoral approach in 25, mandibulotomy in 23, lower cheek flap in 4, trans-pharyngeal in 9, and mandibular lingual releasing approach in 4. Most of T1 lesion was resected by transoral approach (65.0%). For advanced T3 and T4, mandibulotomy was mainly used. Lateral pharyngotomy and mandibular lingual release approach were used for the surgery of moderate size of oropharyngeal cancer. The locoregional recurrence rate did not differ according to different surgical approaches with regard to T and N stages. CONCLUSION: Transoral approach is very useful for the most of small oropharyngeal cancer. Mandibulotomy provides most wide surgical view for advanced T3, T4 oropharyngeal cancer.
Cheek ; Humans ; Neck ; Oropharyngeal Neoplasms ; Oropharynx ; Recurrence ; Retrospective Studies

BACKGROUND AND OBJECTIVES: In the treatment of oral cancer, appropriate surgical approaches should be chosen in order to eradicate cancer while preserving the function of oral cavity and facial contour. This study was performed to evaluate the usefulness and effectiveness of various surgical approaches in the surgical treatment of oral cancer. SUBJECTS AND METHOD: A total of 112 oral cancer patients, excepting those with lip cancer, and who underwent surgery from 1994 to Aug 2008, were enrolled. We reviewed medical records retrospectively and analyzed the primary sites, stage, surgical approaches, management of mandible and neck, reconstruction methods, recurrence and survival rates. RESULTS: Of the 112 patients, 64 were transoral, 23 pull-through, 6 mandibular lingual releasing, 6 upper cheek flap , 5 lower cheek flap , 6 mandibulotomy and 2 visor flap approach. Most of T1, T2 lesions could be resected by transoral (71.6%) or pull-through approach (21.0%). In the advanced T3, T4 lesions, transoral (21.9%), pull-through (37.5%), cheek flap (21.9%), mandibulotomy (15.6%) were used. There was no statistically significant difference with respect to locoregional recurrence and survival rate according to surgical approach. CONCLUSION: The transoral approach was the effective method for the surgery of T1, T2 and part of T3 oral cancer. The pull-through or mandibular lingual releasing approach was the effective method of surgery for T2, T3 tongue or floor of mouth (FOM) cancer while avoiding mandibulotomy.
Cheek ; Humans ; Lip Neoplasms ; Mandible ; Medical Records ; Mouth ; Mouth Floor ; Mouth Neoplasms ; Neck ; Recurrence ; Retrospective Studies ; Survival Rate ; Tongue

PURPOSE: This study was designed to evaluate the effectiveness and prognostic factors for patients treated with postoperative radiation therapy following surgery or with radiation therapy alone for squamous cell carcinoma of the esophagus. MATERIALS AND METHODS: We retrospectively analyzed 132 esophageal cancer patients treated with postoperative radiation therapy following surgery or patients who were treated with radiation therapy alone at our institution from 1989 to 2006. Thirty-five patients had stage II disease, 88 patients had stage III disease and nine patients had stage IV disease. Tumors were located at the upper esophagus in 18 patients, the mid esophagus in 81 patients and the distal esophagus in 33 patients. Sixty patients were treated with radiation therapy alone and 72 patients were treated with postoperative radiation therapy following surgery. Eight patients received a dose less than 40 Gy and 78 patients received a dose of 40 to 50 Gy. The remaining 46 patients received a dose of 50 to 60 Gy. The majority of patients who underwent postoperative radiation therapy received a dose of 45 Gy. RESULTS: Actuarial survival rates for all of the patients at two years and five years were 24% and 5%, respectively. The median survival time was 11 months. Survival rates for patients who underwent postoperative RT at two years and five years were 29% and 8%, respectively. The corresponding survival rates for patients who received radiation alone were 18% and 2%, respectively. Survival rates at two years and five years were 43% and 15% for stage II disease, 22% and 2% for stage III disease and 0% and 0% for stage IV disease, respectively; these findings were statistically significant. Two-year survival rates for patients with upper, middle and distal esophageal cancer were 19, 29% and 22%, respectively. Although there was a trend of slightly better survival for middle esophageal tumors, this finding was not statistically significant. Complete response to radiation was achieved in 13 patients (22%) and partial response to radiation was achieved in 40 patients (67%) who received radiation alone. No response to radiation was noted in seven patients (12%). A statistically significant difference in survival rates was seen between patients that had a complete response and patients that had a partial response. Two-year survival rates for patients that had a complete response versus patients that had a partial response were 31% and 17%, respectively. There were no survivors for patients with no response as determined at two-year follow-up. CONCLUSION: We conclude that radiation therapy is an effective treatment for esophageal cancer. Stage and response to radiation therapy were noted to be prognostic factors. A more effective treatment modality is needed to improve long term survival because of the relatively dismal prognosis for this tumor.
Carcinoma, Squamous Cell ; Esophageal Neoplasms ; Esophagus ; Follow-Up Studies ; Humans ; Prognosis ; Retrospective Studies ; Survival Rate ; Survivors

BACKGROUND AND OBJECTIVES: Hypopharynx cancer usually presents with late stage diseases requiring radical resection including total laryngectomy with reconstruction resulting in severe functional deficits. In order to preserve organ function, chemotherapy in combination with radiotherapy was introduced and it showed similar treatment. The aim of this study is to compare the treatment outcomes of surgery and organ preservation therapy. SUBJECTS AND METHOD: A retrospective review of 55 patients who were diagnosed with hypopharynx cancer and underwent curative treatment from 1994 to 2006 was performed. Patients who underwent surgery or surgery plus postoperative radiotherapy were assigned to surgical treatment group and patients who underwent radiotherapy or radiotherapy with chemotherapy were assigned to organ preservation therapy group. RESULTS: Surgical treatment group consisted of 29 patients (52.7%) and organ preservation therapy group consisted of 26 patients (47.3%). The overall 5 year survival rate was 34%. The survival rate was decreased significantly according to the N stage (p=0.02). There was no statistically significant difference in 5 year survival rates between the two groups. The larynx preservation rate was 35.8% for the organ preservation therapy group and 44% for the conservation surgery group. CONCLUSION: Treatment of hypopharynx cancer could be individualized according to the status of diseases.
Humans ; Hypopharyngeal Neoplasms ; Hypopharynx ; Laryngectomy ; Larynx ; Organ Preservation ; Retrospective Studies ; Survival Rate ; Treatment Outcome

PURPOSE: To determine the patterns of evaluation and treatment in patients with breast cancer after mastectomy and treated with radiotherapy. A nationwide study was performed with the goal of improving radiotherapy treatment. MATERIALS AND METHODS: A web-based database system for the Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Randomly selected records of 286 eligible patients treated between 1998 and 1999 from 17 hospitals were reviewed. RESULTS: The ages of the study patients ranged from 20 to 80 years (median age 44 years). The pathologic T stage by the AJCC was T1 in 9.7% of the cases, T2 in 59.2% of the cases, T3 in 25.6% of the cases, and T4 in 5.3% of the cases. For analysis of nodal involvement, N0 was 7.3%, N1 was 14%, N2 was 38.8%, and N3 was 38.5% of the cases. The AJCC stage was stage I in 0.7% of the cases, stage IIa in 3.8% of the cases, stage IIb in 9.8% of the cases, stage IIIa in 43% of the cases, stage IIIb in 2.8% of the cases, and IIIc in 38.5% of the cases. There were various sequences of chemotherapy and radiotherapy after mastectomy. Mastectomy and chemotherapy followed by radiotherapy was the most commonly performed sequence in 47% of the cases. Mastectomy, chemotherapy, and radiotherapy followed by additional chemotherapy was performed in 35% of the cases, and neoadjuvant chemoradiotherapy was performed in 12.5% of the cases. The radiotherapy volume was chest wall only in 5.6% of the cases. The volume was chest wall and supraclavicular fossa (SCL) in 20.3% of the cases; chest wall, SCL and internal mammary lymph node (IMN) in 27.6% of the cases; chest wall, SCL and posterior axillary lymph node in 25.9% of the cases; chest wall, SCL, IMN, and posterior axillary lymph node in 19.9% of the cases. Two patients received IMN only. The method of chest wall irradiation was tangential field in 57.3% of the cases and electron beam in 42% of the cases. A bolus for the chest wall was used in 54.8% of the tangential field cases and 52.5% of the electron beam cases. The radiation dose to the chest wall was 45~59.4 Gy (median 50.4 Gy), to the SCL was 45~59.4 Gy (median 50.4 Gy), and to the PAB was 4.8~38.8 Gy, (median 9 Gy) CONCLUSION: Different and various treatment methods were used for radiotherapy of the breast cancer patients after mastectomy in each hospital. Most of treatment methods varied in the irradiation of the chest wall. A separate analysis for the details of radiotherapy planning also needs to be followed and the outcome of treatment is needed in order to evaluate the different processes.
Breast Neoplasms ; Breast* ; Chemoradiotherapy ; Drug Therapy ; Humans ; Korea* ; Lymph Nodes ; Mastectomy* ; Mastectomy, Radical ; Radiotherapy ; Thoracic Wall

Na+ -Ca2+ exchanger (NCX) transports Ca2+ coupled with Na+ across the plasma membrane in a bi-directional mode. Ca2+ flux via NCX mediates osteogenic processes, such as formation of extracellular matrix proteins and bone nodules. However, it is not clearly understood how the NCX regulates cellular Ca2+ movements in osteogenic processes. In this study, the role of NCX in modulating Ca2+ content of intracellular stores ([Ca2+](ER)) was investigated by measuring intracellular Ca2+ activity in isolated rat osteoblasts. Removal of extracellular Na+ elicited a transient increase of intracellular Ca2+ concentration ([Ca2+](i)). Pretreatment of antisense oligodeoxynucleotide (AS) against NCX depressed this transient Ca2+ rise and raised the basal level of [Ca2+](i). In AS-pretreated cells, the expression and activity of alkaline phosphatase (ALP), an osteogenic marker, were decreased. However, the cell viability was not affected by AS-pretreatment. Suppression of NCX activity by the AS-pretreatment decreased ATP-activated Ca2+ release from intracellular stores and significantly enhanced Ca2+ influx via store operated calcium influx (SOCI), compared to those of S-pretreated or control cells. These results strongly suggest that NCX has a regulatory role in cellular Ca2+ pathways in osteoblasts by modulating intracellular Ca2+ content.
Alkaline Phosphatase/metabolism ; Animals ; Calcium/*metabolism ; Cell Membrane/metabolism ; Cell Survival ; Cells, Cultured ; Cytoplasm/metabolism ; Endoplasmic Reticulum/metabolism ; Intracellular Space/metabolism ; Oligodeoxyribonucleotides, Antisense/pharmacology ; Osteoblasts/drug effects/*physiology ; Rats ; Signal Transduction ; Sodium/physiology ; Sodium-Calcium Exchanger/*physiology

BACKGROUND AND OBJECTIVES: Surgery with postoperative radiotherapy has been the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the prognosis still remains dismal. To increase survival rate and organ preservation rate, alternative approach is needed. Incorporating the taxane regimen into the treatment of HNSCC, the new treatment strategy of sequential therapy has been introduced. The purpose of this study is to determine the efficacy of neoadjuvant chemotherapy, followed by concurrent chemoradiotherapy for the HNSCC. SUBJECTS AND METHOD: Between January 2001 and June 2005, 19 patients with HNSCC were treated with neoadjuvant chemotherapy, followed by concurrent chemoradiotherapy. The sites of primary tumors were hypopharynx in eight patients, oropharynx in six patients, and larynx in five patients. Neoadjuvant chemotherapy included 70 mg/m2 of docetaxel on day 1, 70 mg/m2 of cisplantin on day 2 and 800 mg/m2 of 5-fluorouracil on day 2-4. The cycles were repeated every three weeks. Concurrent chemoradiotherapy starts after two cycles of neoadjuvant chemotherapy. Radiation dose was 200 cGy/dayx5/week with a total of 6,000-7,000 cGy, and the concurrent chemotherapy of 20 mg/m2 of docetaxel or 20 mg/m2 of cisplantin was given weekly. RESULTS: The median follow-up was 21 months. The overall 2-year survival rate was 70.1% and the 2-year organ preservation rate was 59.4%. The survival rate and organ preservation rate of larynx cancer patients were higher than those of hypopharynx and oropharynx cancer patients, but it was not statistically significant (p=0.09, 0.16). The patients of the lower stage showed higher survival rate and organ preservation rate, but it was not statistically significant (p=0.19, 0.48). The most common Grade 3 or 4 toxicities of neoadjuvant chemotherapy were leukopenia, anorexia, nausea and vomiting, whereas the most common Grade 3 or 4 toxicities during concurrent chemoradiotherapy were mucositis, stomatitis, and leukopenia. One patient died due to sepsis during treatment. CONCLUSION: Neoadjuvant chemotherapy with three combined regimens followed by concurrent chemoradiotherapy might be effective treatment modality for HNSCC. Further studies with large number of patients and longer follow-up will be needed.
Anorexia ; Carcinoma, Squamous Cell* ; Chemoradiotherapy ; Drug Therapy* ; Fluorouracil ; Follow-Up Studies ; Head and Neck Neoplasms ; Head* ; Humans ; Hypopharynx ; Laryngeal Neoplasms ; Larynx ; Leukopenia ; Mucositis ; Nausea ; Neck* ; Neoadjuvant Therapy ; Organ Preservation ; Oropharyngeal Neoplasms ; Oropharynx ; Prognosis ; Radiotherapy ; Sepsis ; Stomatitis ; Survival Rate ; Vomiting

PURPOSE: To evaluate the effectiveness of postoperative radiation therapy in cervical cancer patients and define the prognostic factors to affect survival rates. MATERIALS AND METHODS: Eighty one patients with cervical cancer who were treated with postoperative radiation therapy following surgery at our institution between May 1992 and April 2000 were retrospectively analyzed. Forty two patients had stage IB disease, 17 had stage IIA disease, and remaining 22 had stage IIB disease, respectively. Histological examination revealed 76 squamous cell carcinoma and 5 adenocarcinoma. Sixty one patients were noted to have stromal invasion greater than 8 mm and 20 patients were noted to have stromal invasion 7 mm or less. Sixteen patients had parametrial invasion and 65 patients did not. Positive vaginal resection margin was documented in only eight patients and positive lymphovascular invasion was in twelve patients. All of the patients were treated with external beam radiation therapy alone. Majority of the patients were treated with 4 field brick technique to encompass whole pelvis. Total of 5,500 cGy was delivered to the primary surgical tumor bed. Minimum follow up period was four years. RESULTS: Actuarial disease free survival rates for entire group of the patients were 95% and 89% at 2 and 5 years, respectively. Five year disease free survival rates for patients with stage IB, IIA, and IIB disease were 97%, 87% and 70%, respectively. Local recurrences were documented in 5 patients. Cumulative local failure rate at 3 years was 6%. Five year disease free survival rates for patients with stromal invasion greater than 8 mm and 7 mm or less were 88% and 92%, respectively (p>0.05). Five year disease free survival rate for patients with parametrial invasion was significantly lower than those with no invasion (72% vs 92%, p<0.05). Also there was significantly lower survival in patients with positive vaginal resection margin, compared with patients with negative resection margin (64% vs 94%, p<0.05). However, lymphovascular invasion was not a statistically significant prognostic factor. Parametrial invasion and positive surgical resection margins were noted to be significant prognostic factors. Conclusions: Postoperative radiation therapy appears to be beneficial in controlling local disease in cervical cancer patients with high pathologic risk factors. Parametrial invasion and positive resection margins were noted to be significant prognostic factors to affect survival and more effective treatment should be investigated in these patients.
Adenocarcinoma ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Pelvis ; Recurrence ; Retrospective Studies ; Risk Factors ; Survival Rate ; Uterine Cervical Neoplasms*

PURPOSE: To determine the patterns of evaluation and treatment in the patient with early breast cancer treated with conservative surgery and radiotherapy and to improve the radiotherapy techiniques, nationwide survey was performed. MATERIALS AND METHODS: A web-based database system for Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Two hundreds sixty-one randomly selected records of eligible patients treated between 1998~999 from 15 hospitals were reviewed. RESULTS: The patients ages ranged from 24 to 85 years(median 45 years). Infiltrating ductal carcinoma was most common histologic type (88.9%) followed by medullary carcinoma (4.2%) and infiltrating lobular carcinoma (1.5%). Pathologic T stage by AJCC was T1 in 59.7% of the casses, T2 in 29.5% of the cases, Tis in 8.8% of the cases. Axillary lymph node dissection was performed in 91.2% of the cases and 69.7% were node negative. AJCC stage was 0 in 8.8% of the cases, stage I in 44.9% of the cases, stage IIa in 33.3% of the cases, and stage IIb in 8.4% of the cases. Estrogen and progesteron receptors were evaluated in 71.6%, and 70.9% of the patients, respectively. Surgical methods of breast-conserving surgery was excision/lumpectomy in 37.2%, wide excision in 11.5%, quadrantectomy in 23% and partial mastectomy in 27.5% of the cases. A pathologically confirmed negative margin was obtained in 90.8% of the cases. Pathological margin was involved with tumor in 10 patients and margin was close (less than 2 mm) in 10 patients. All the patients except one recieved more than 90% of the planned radiotherapy dose. Radiotherapy volume was breast only in 88% of the cases, breast+supraclavicular fossa (SCL) in 5% of the cases, and breast+SCL+posterior axillary boost in 4.2% of the cases. Only one patient received isolated internal mammary lymph node irradiation. Used radiation beam was Co-60 in 8 cases, 4 MV X-ray in 115 cases, 6 MV X-ray in 125 cases, and 10 MV X-ray in 11 cases. The radiation dose to the whole breast was 45~9.4 Gy (median 50.4) and boost dose was 8~20 Gy (median 10 Gy). The total radiation dose delivered was 50.4~70.4 Gy (median 60.4 Gy). CONCLUSION: There was no major deviation from current standard in the patterns of evaluation and treatment for the patients with early breast cancer treated with breast conservation method. Some varieties were identified in boost irradiation dose. Separate analysis for the datails of radiotherapy planning will be followed and the outcome of treatment is needed to evaluate the process.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal ; Carcinoma, Lobular ; Carcinoma, Medullary ; Estrogens ; Humans ; Korea* ; Lymph Node Excision ; Lymph Nodes ; Mastectomy, Segmental* ; Radiotherapy