• Journal of Microbiology and Biotechnology
• /
• 제15권4호
• /
• pp.756-766
• /
• 2005

The signaling mechanism underlying aburatubolactam C-induced FasL upregulation was investigated in human Jurkat T cells. After treatment with aburatubolactam C, the src-family PTKs $p56^{lck}\;and\;p59^{fyn}$, and MAP kinases ERK2 and JNK1, were activated prior to FasL upregulation; Both $p56^{lck}\;and\;p59^{fyn}$ were directly activated 2.4- and 2.2-fold, respectively, in vitro by aburatubolactam C. The aburatubolactam C-induced cellular changes, including the activation of ERK2 and INK1, and FasL upregulation, were completely prevented by the PTK inhibitor genistein. The activation of protein kinase C (PKC$\delta,\;\epsilon\;and\;\mu$ was also induced following aburatubolactam C treatment. Although the activation of $p56^{lck}$ and tyrosine phosphorylation of the cellular proteins were not blocked by the PKC inhibitor GFl09203X, the activation of ERK2 was completely abrogated, along with a detectably enhanced JNK1 activation; FasL upregulation, and apoptosis. However, the FasL upregulation and apoptosis were significantly inhibited by the PKC activator PMA, with a remarkable increase in the ERK2 activation. The cytotoxic effect of aburatubolactam C was reduced in the presence of the anti-Fas neutralizing antibody ZB-4. Although ectopic expression of Bcl-2 failed to completely block the cytotoxicity of aburatubolactam C, it was clearly suppressed. The c-Fos mRNA expression was upregulated in a biphasic manner, where the second phasic expression overlapped with the FasL upregulation. Accordingly, these results demonstrate that aburatubolactam C-induced apoptosis is exerted, at least in part, by FasL upregulation dictated by activation of the PTK ($p56^{lck}\;and\;p59^{fyn}$) /JNKI pathway, which is negatively affected by the concurrent activation of the PKC/ERK2 pathway proximal to PTK activation.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권4호
• /
• pp.447-454
• /
• 1999

The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) are known to be modulated by a variety of factors. Recent study showed that endotoxin-induced NO synthesis and iNOS expression were greatly enhanced by elevation of extracellular glucose concentration in murine macrophages. Although this was suggested to be due to the activation of protein kinase C (PKC) via sorbitol pathway, there was lack of evidence for this speculation. This study was performed to delineate the underlying intracellular mechanisms of glucose-enhancing effect on endotoxin-induced NO production in Raw264.7 macrophages. The levels of NO release induced by lipopolysaccharide (LPS) significantly increased by the treatment of glucose in a concentration dependent manner and also, this effect was observed in LPS-preprimed cells. Concurrent incubation of cells with PKC inhibitors, H-7 or chelerythrine, and LPS resulted in the diminution of NO production regardless of glucose concentration but this was not in the case of LPS-prepriming, that is, chelerythrine showed a minimal effect on the glucose- enhancing effect. PMA, a PKC activator, did not show any significant effect on glucose-associated NO production. Modulation of sorbitol pathway with zopolrestat, an aldose reductase inhibitor, did not affect LPS-induced NO production and iNOS expression under high glucose condition. And also, sodium pyruvate, which is expected to normalize cytosolic $NADH/NAD^+$ ratio, did not show any significant effect at concentrations of up to 10 mM. Glucosamine marginally increased the endotoxin-induced nitrite release in both control and high glucose treated group. 6-diazo-5-oxonorleucine (L-DON) and azaserine, glutamine: fructose- 6-phosphate amidotransferase (GFAT) inhibitors, significantly diminished the augmentation effect of high glucose on endotoxin-induced NO production. On the other hand, negative modulation of GFAT inhibitors was not reversed by the treatment of glucosamine, suggesting the minimal involvement, if any, of glucosamine pathway in glucose-enhancing effect. In summary, these results strongly suggest that the hexosamine biosynthesis pathway and the activation of PKC via sorbitol pathway do not contribute to the augmenting effect of high glucose on endotoxin induced NO production in macrophage-like Raw264.7 cells.

• Asian-Australasian Journal of Animal Sciences
• /
• 제2권2호
• /
• pp.115-121
• /
• 1989

A comparative slaughter feeding experiment with steer calves weighing 280 kg and a concurrent digestion trial with wether lambs was conducted to study the energy value of rice straw as influenced by ammonia treatment and mixing with alfalfa hay. Steers were ad libitum fed one of nine completely mixed experimental diets: basal (high concentrate); 25 or 50% of untreated rice straw (URS) or ammoniated (plastic covered bales, 4.6% $NH_3$ by weight) rice straw (ARS) proportionately replacing part of the basal; a 50:50 % mixture of URS or ARS and alfalfa replacing a proportion of the basal at 25 and 50%. Digestibility of the nine complete diets (pelleted to prevent sorting) was determined with four ad libitum fed lambs. Ammoniation increased crude protein level (from 3.6 to 10.8%) and in vitro dry matter digestibility of the rice straw by 15%. The improvement in DE, NEm and NEg by ammoniation of rice straw was 20, 52 and 117%, respectively. Ammoniation of rice straw fed as 50% of the diet improved gains over the diet containing 50% URS, but no significant influence on animal performance was observed when rice straw was fed at the 25% level. Each 10% addition of URS to basal diet decreased empty body gain of steers by 116 gram per day compared with a decrease of 70 gram per day when rice straw had been ammoniated. There was no beneficial effect of ammoniation when the roughage component of the diet was a 50:50 mixture of rice straw and alfalfa. Ammoniation of straw and inclusion of alfalfa generally increased the concentration of total volatile fatty acids in rumen fluid. Ammoniation resulted in reduced concentrations of acetic and propionic acid, but increased concentration of butyric acid. Digestibility of URS was improved by mixing with alfalfa. However, alfalfa hay did not influence digestibility of ARS. Diets in which ARS replaced the basal mixture at 25 and 50% had higher NEm and NEg values than comparable URS diets. The same pattern was observed in the straw: alfalfa mixtures, but differences between URS and ARS were significant only for the 50% roughage diets.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권10호
• /
• pp.4147-4152
• /
• 2014

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권21호
• /
• pp.9301-9305
• /
• 2014

Background: Pain is one of the most terrifying symptoms for cancer patients. Although most patients with cancer pain need opioids, complete relief of pain is hard to achieve. This study investigated the factors influencing persistent pain-free survival (PPFS) and opioid efficiency. Materials and Methods: A prospective study was conducted on 100 patients with cancer pain, hospitalized at the medical oncology clinic of Akdeniz University. Patient records were collected including patient demographics, the disease, treatment characteristics, and details of opioid usage. Pain intensity was measured using a patient self-reported visual analogue scale (VAS). The area under the curve (AUC) reflecting the pain load was calculated from daily VAS tables. PPFS, the primary measure of opioid efficacy, was described as the duration for which a patient reported a greater than or equal to two-point decline in their VAS for pain. Predictors of opioid efficacy were analysed using a multivariate analysis. Results: In the multivariate analysis, PPFS was associated with the AUC for pain (Exp (B)=0.39 (0.23-0.67), P=0.001), the cumulative opioid dosage used during hospitalisation (Exp (B)=1.00(0.99-1.00), P=0.003) and changes in the opioid dosage (Exp (B)=1.01 (1.00-1.01), P=0.016). The change in VAS score over the standard dosage of opioids was strongly associated with current cancer treatment (chemotherapy vs. others) (${\beta}=-0.31$, T=-2.81, P=0.007) and the VAS for pain at the time of hospitalisation (${\beta}=-0.34$, T=-3.07, P= 0.003). Conclusions: The pain load, opioid dosage, concurrent usage of chemotherapy and initial pain intensity correlate with the benefit received from opioids in cancer patients.

• 대한한방내과학회지
• /
• 제36권1호
• /
• pp.58-68
• /
• 2015

목 적: 소세포 폐암 및 전이성 폐암은 폐암 중에서도 가장 예후가 불량하고 생존율도 상대적으로 낮은 암으로 알려져 있다. 난치성 폐암 환자에 대해 한방치료가 생존 기간 연장 및 삶의 질 관리면에 있어서 효과가 있음을 보여주고자 한다. 연구방법 및 대상: 본원에서 입원 및 통원치료를 병행한 소세포폐암 환자 1명과 원발성 간암에서 폐로 전이된 전이성 폐암 환자 1명에 대하여 한방치료의 효과 및 임상경과를 후향적으로 조사하였다. 치료기간은 각각 2000년 1월-2009년 12월과 2004년 9월-2014년 2월이었으며 한약치료는 평균 1개월 간격으로 행해졌으며 입원기간 동안에는 한약치료를 포함한 침구치료를 추가로 시행하였다. 치료효과 및 경과 판정을 위해 흉부 방사선 검사 및 혈액검사를 평균 1개월 간격으로 시행하였으며 내원시마다 환자의 증상 및 상태를 확인하였다. 결 과: 2명의 폐암 환자 모두 꾸준한 한방치료를 받으며 진단시점부터 9년 이상의 상당히 오랜 기간 동안 비교적 좋은 삶의 질을 유지하면서 종양으로 인한 임상경과 또한 완만하게 진행이 되었다. 결 론: 본 증례는 한방치료가 불응성 폐암 환자에 대해 삶의 질을 양호하게 유지하고 증상 조절 및 종양의 진행양상을 완화시켜 주며 나아가 생존기간 연장에도 효과가 있음을 보여준다.

• The Korean Journal of Pain
• /
• 제6권2호
• /
• pp.275-279
• /
• 1993

Reflex sympathetic dystrophy is a syndrome characterized by persistent, burning pain, hyperpathia, allodynia & hyperaesthesia in an extremity, with concurrent evidence of autonomic nervous system dysfunction. It generally develops after nerve injury, trauma, surgery, et al. The most successful therapies are directed towards blocking the sympathetic intervention to the affected extremity by regional sympathetic ganglion block or Bier block with sympathetic blocker; other traditional treatments include transcutaneous electrical stimulation, immobilization with cast & splint, physical therapy, psychotherapy, administration of sympathetic blocker, calcitonin, corticosteroid and analgesic agents. The purpose of this report is to evaluate and describe the effects of magnetic resonance following unsatisfactory results with traditional treatments of RSD. A 17 year old female patient, 1 year earlier, had received excision and drainage of pus at the right femoral triangle due to an injury caused by a stone. Afterwards, she experienced burning pain, knee joint stiffness, and muscle dystrophy of the right thigh, especially when standing and walking. Despite a year of number of traditional treatments such as: lumbar sympathetic block, continuous epidural analgesia, transcutaneous electrical stimulation, & administration of predisolone, her pain did not improve. Surprisingly, the patients was able to walk free from pain and difficulty after just one application of magnetic resonance. The patient has been successfully treated with further treatment of two to three times a week for approximately ten weeks. More recently, magnetic resonance has been demonstrated to produce effective results for the relief of pain in a variety of diseases. From our experiences we recognize magnetic resonance as a therapeutic modality which can provide excellent results for the treatment of RSD. It has been suggested that polysynaptic reflex which are disturbed in RSD may be modulated normally on the spinal cord level through the application of magnetic resonance.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제34권2호
• /
• pp.100-105
• /
• 2012

Purpose: In general, the surgical treatment for mandibular retrognathism is represented by two methods, distraction osteogenesis (DO) and mandibular osteotomy surgery. The DO is mostly preferred when the degree of advancement of mandible is large. However, the postoperative stability of mandibular advancement using DO have not been actively investigated. Therefore, in the present study we have compared the postoperative stability between DO and bilateral sagittal split ramus osteotomy (BSSRO) in mandibular retrognathism. Methods: Seven patients who had been treated by DO and thirteen patients with BSSRO were included in this study. Serial lateral cephalograms were analyzed by manual tracing and the amount of the mandibular elongation was measured. To evaluate the postoperative stability, positional changes of the condylar position and B point were analyzed. Results: Mean amount of mandibular advancement was $6.51{\pm}3.57mm$ for BSSRO group and $12.43{\pm}4.35mm$ for DO group, respectively. There was no significant difference in age between the two groups (P>0.05). Mean follow up periods were 10.77 months for BSSRO group and 11.28 months for DO group, respectively. After mandibular advancement, mean positional changes in the condyle were $0.56{\pm}1.43mm$ horizontally and $0.72{\pm}1.61mm$ vertically for BSSRO group and $0.53{\pm}1.56mm$ horizontally and $0.56{\pm}1.75mm$ vertically for DO group, respectively. Mean change of distance from B point to Y-axis was $-1.76{\pm}0.83mm$ for BSSRO group and $-2.14{\pm}1.82mm$ for DO group, respectively. According to the condylar position and B point, there were no significant differences in postoperative stability between the two groups (P>0.05). Conclusion: There was no significant difference in postoperative stability between DO and BSSRO group according to condylar position and B point. Based on the results of the present study, it is hypothesized that DO would be a good treatment choice for severe mandibular retrognathism because DO could achieve more mandibular advancement and concurrent soft tissue elongation.

• Journal of Yeungnam Medical Science
• /
• 제31권2호
• /
• pp.82-88
• /
• 2014

Background: Lung cancer is the most common cause of cancer-related death worldwide and in Korea, and small cell lung cancer (SCLC) is the most deadly tumor type in the different lung cancer histology. Chemotherapy is the main strategy of the treatment for SCLC, and etoposide and platinum regimen has been the only standard chemotherapy for about 30 years. To test feasibility of weekly divided dose irinotecan and carboplatin for Korean patients is the aim of this study. Methods: Patients with histologically or cytologically confirmed extensive stage SCLC were included. Patients with limited stage (LD), who could not tolerate concurrent chemoradiotherapy were also included. All the patients received irinotecan $60mg/m^2$, carboplatin 2 area under the curve at day 1, 8, and 15 every 4 weeks. Study regimen was discontinued when the disease progressed or intolerable side effects occurred. No more than 6 cycles of chemotherapy were given. Results: Total 47 patients were enrolled, among them 9 patients were LD. Overall response rate was 74.5% (complete response, 14.9%; partial response, 59.6%). Side effects greater than grade 3 were neutropenia (25.5%), fatigue (12.8%), thrombocytopenia (8.5%), sepsis (4.3%), and pancytopenia (2.1%). There was no treatment related death. Conclusion: Weekly divided irinotecan and carboplatin regimen is effective, and safe as a first line therapy for both stage of SCLC. Large scaled, controlled study is feasible.

• 대한두경부종양학회지
• /
• 제34권2호
• /
• pp.11-15
• /
• 2018

Background/Objectives: The efficacy of radiotherapy alone versus chemoradiotherapy has been studied in patients with T2N0M0 laryngeal squamous cell carcinoma. Materials & Methods: Thirty nine patients with newly diagnosed T2N0M0 laryngeal squamous cell carcinoma were treated with either radiotherapy(RT group, 66-70Gy) or chemoradiotherapy(CRT group, cisplatin based concurrent chemoradiation with or without 2 cycles induction chemotherapy including cisplatin, $5-FU{\pm}$ docetaxel / radiation therapy same with above mentioned). The mean follow-up was 73.5 months. Results: The overall survival (OS), disease specific survival (DSS), disease free survival (DFS), and larynx preservation survival (LPS) at 5 years were 70%, 79%, 67%, and 71%. The complete response rate was 82.4% in RT group, and was 95.5% in CRT group. OS (57% vs 80%), DSS (69% vs 86%), DFS (52% vs 77%), and LPS (63% vs 77%) at 5 years were higher in CRT group than RT group, but it was not statistically significant. In subsite analysis, CRT group tends to improve DFS, compared to RT group, in glottic cancer (p=0.06). The toxicities were tolerable and no fatal case was observed in both groups. Conclusion: Chemoradiotherapy is effective as primary therapy for T2 laryngeal squamous cell carcinoma and showed manageable treatment induced toxicity.