Sophorae Radix (SR) plays a role in a number of physiologic and pharmacologic functions in many organs. Objective: The aim of this study was to clarify the potential role for transient receptor potential melastatin 7 (TRPM7) channels in SR-inhibited growth and survival of AGS and MCF-7 cells, the most common human gastric and breast adenocarcinoma cell lines. Methods: The AGS and the MCF-7 cells were treated with varying concentrations of SR. Analyses of the caspase-3 and - 9 activity, the mitochondrial depolarization and the poly (ADPribose) polymerase (PARP) cleavage were conducted to determine if AGS and MCF-7 cell death occured by apoptosis. TRPM7 channel blockers ($Gd^{3+}$ or 2-APB) and small interfering RNA (siRNA) were used in this study to confirm the role of TRPM7 channels. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS and MCF-7 cell growth and survival. Results: The addition of SR to a culture medium inhibited AGS and MCF-7 cell growth and survival. Experimental results showed that the caspase-3 and -9 activity, the mitochondrial depolarization, and the degree of PARP cleavage was increased. TRPM7 channel blockade, either by $Gd^{3+}$ or 2-APB or by suppressing TRPM7 expression with small interfering RNA, blocked the SR-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SR-induced cell death. Conclusions: These findings indicate that SR inhibits the growth and survival of gastric and breast cancer cells due to a blockade of the TRPM7 channel activity. Therefore, TRPM7 channels may play an important role in the survival of patients with gastric and breast cancer.
Background: Pemetrexed has been prescribed newly as a second line chemotherapy in advanced non-small cell lung carcinoma (NSCLC). The aim of study was to determine the efficacy and toxicity of pemetrexed in advanced NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC were evaluated from June 2006 to December 2008. The patients had relapsed or progressed after prior chemotherapy treatment. They were treated with intravenous pemetrexed $500mg/m^2$ for 10 min on Day 1 of each 21-day cycle. Results: A total of 89 patients were eligible for analysis. The response rate and disease control rate were 11% and 66%. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (p=0.035) and disease control rate (p=0.009) than squamous cell carcinoma histology. The median survival time was 13 months and the median progression free survival time was 2.3 months. The median survival time of patients with ECOG PS 0~1 was 13.2 months, whereas median survival time was 11.6 months for patients with PS 2 (p=0.002). The median progression free survival time of patients with PS 0~1 were 3.8 months, but 2.1 months for patients with PS 2 (p=0.016). The median progression free survival time of smokers with non-squamous cell carcinoma was 3.4 months, which was significant (p=0.014). Grade 3~4 neutropenia were seen in 7.9% patients. Conclusion: Pemetrexed has efficacy in patients who had prior chemotherapy with advanced NSCLC and less hematologic toxicity.
From Jan.1984 to Dec. 1986, 90 patients with lung cancer were treated at the Department of Radiation Therapy in Hanyang University Hospital. Histopathologically, 67 cases of them were the squamous cell carcinoma,7 cases were the adenocarcinoma, 4 cases were the large cell undiffe rentiated carcinoma and 12 cases were the small cell carcinoma. Among the 78 patients with non small cell carcinoma, 50 patients had received radiation dosage above 4000 cGy.40 patient had follow up from 17 months to 53 months. The complete response rate was $7.3\%$ and partial response rate was $68.3\%$. Overall survival at 1, 2 and 3 years were $47.5\%,\;23.5\%\;and\;6.3\%$ respectively. None was survived longer than 38 months. Median survival was 12.2 month for 40 patient and 9 month for stage III, M1 group and 9.5 month for stage III, MO group. In M1 patient no survival was seen after 2 years while in M0 patient $23.3\%$ survival was seen.
Aim: The objective of this study is to investigate prognostic factors affecting survival of patients undergoing concurrent or sequential chemoradiotherapy (CRT) for stage III non-small-cell lung cancer (NSCL). Methods and materials: We retrospectively reviewed the clinical records of 148 patients with advanced, inoperable stage III NSCLC, who were treated between 2007 and 2015. Results: The median survival was found to be 19 months and 3-year overall survival was 27%. Age (<65 vs ${\geq}65years$, p=0.026), stage (IIIA vs IIIB, p=0.033), dose of radiotherapy (RT) (<60 vs ${\geq}60Gy$, p=0.024) and treatment method (sequential chemotherapy+RT vs concurrent CRT, p=0.023) were found to be factors affecting survival in univariate analyses. Gender, histological subtype, weight loss during CRT, performance status, induction/consolidation chemotherapy and presence of comorbidities did not affect survival (p>0.050). Conclusion: Young age, stage IIIA, radiotherapy dose and concurrent chemoradiotherapy may positively affect survival in stage III NSCL cases.
Reappraisal measurements of apparent half survival time of red cell by $^{51}Cr$ method was made and effects of blood-letting over red cell survival were observed. The study was performed on 53 normal male subjects under three different experimental conditions. 1. Group 1 Mean $^{51}Cr$ red cell half survival by ACD wash method was 29.7 days. $T\frac{1}{2}$ of Ascorbic acid method was 29.0 days in group with 100 mg dose and 29.1 days in group with 50 mg dose respectively. There was no difference between these two methods in regards to red cell half survival. No difference were noted in amount of ascorbic acid administered. 2. Group 2 As daily amount of blood loss is increased the shortening of red cell half survival was noted. Rapid phase was seen when blood loss ranged 10 to 25 ml per day, while slow phase noted when more loss amounted 25 ml or more daily. Thus, it was clear that there was more than an exponential relation between $T\frac{1}{2}$ and the amount of blood loss. 3. Group 3 $T\frac{1}{2}$ measured by cpm per whole blood was within normal range and $T\frac{1}{2}$ measured by cpm per red cell mass showed shortening tendency when compared with the former in the group measured after blood loss (from 25 ml daily up to 100 ml daily in 10 days). In the group with rather constant blood loss of 100 ml daily for 10 consecutive days revealed the significant difference in two measurements (P<0.01). 4. $T\frac{1}{2}$ in non-steady state When red cell production is increased compared with red cell destruction, $T\frac{1}{2}$ measured by cpm per red cell mass being shorter than that by cpm per whole blood. Shortening of $T\frac{1}{2}$ measured by cpm per whole blood is more prominent. if red cell destrction is enhanced and exceeds production. 5. It is clear that when expressing red cell destruction rate, $T\frac{1}{2}$ measured by cpm per whole blood is more adequate and production more consistent with cpm red cell mass. 6. $T\frac{1}{2}$ measured during blood-letting, when corrected by amount of blood loss, it remains normal. It is erroneous to use conventional equational when measuring $T\frac{1}{2}$ in non-steady. $T\frac{1}{2}$ measured by cpm per whole blood is considred more applicable in clinical evaluation.
These experiments were carried out to examine the effect of rapid thawing (500$^{\circ}C$/min) on the survival of 8-cell mouse embryos cooled slowly (0.5-1$^{\circ}C$/min) to precooling temperatures between -10 and 070$^{\circ}C$ before direct transfer ofembryos to -196$^{\circ}C$, and to compare the survival of embroys thawed slowly (20$^{\circ}C$/min) and rapidly (500$^{\circ}C$/min) after in vitro culture. In addition, the sensitivity of 8-cell mouse embroys to the rate of addition and removal of cryoprotectant at room temperauture, and the effect of developing stages on the survival of embryos frozen-thawed slowly were investigated. The results obtained were summarized as follows: 1. Embryos were survived in rapid thawing (500$^{\circ}C$/min) only when slow cooling was terminated at relatively high subzero teperaure (-20 to -60$^{\circ}C$). The highest survival rate(77.0%) in in vitro culture of embryos thawed rapidly was obtaeined after transfer to -196$^{\circ}C$ from -40$^{\circ}C$. 2. For the survival of embryos in slow thawing (20$^{\circ}C$/min.), slow cooling to lower subzero temperature (-50$^{\circ}C$ and below) was required before transfer of embryos to -196$^{\circ}C$. These results indicate that embryos transferred to -196$^{\circ}C$ from high subzero temprature contain much interacellular ice to damage them during slow warming but to permit survival of embryos after rapid warming. 3. The Survival rate (72.7%) of 8-cell mouse embryos after rapid addition and removal of cryoprotectant, DMSO at room temperature was similar to that (83.9%) after slow addition and removal of cryoprotectant at same temperature. 4. The survival rates of 1-, 2-, 4- and 8-cell embryos frozen-thawed slowly were 26.7, 76.4, 70.0 and 83.9%, respectively.
Yap, Ning Yi;Ng, Keng Lim;Ong, Teng Aik;Pailoor, Jayalakshmi;Gobe, Glenda Carolyn;Ooi, Chong Chien;Razack, Azed Hassan;Dublin, Norman;Morais, Christudas;Rajandram, Retnagowri
Asian Pacific Journal of Cancer Prevention
/
v.14
no.12
/
pp.7497-7500
/
2013
Background: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms. Materials and Methods: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis. Results: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, $9.5{\pm}4.3cm$, was larger than non palpable masses, $5.3{\pm}2.7cm$ (p<0.001). Conclusions: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.
Background: Many institutes are interested in lung metastatectomy than before because of the improved long term survival, low mortality, and low morbidity after lung metastatectomy. However, prognostic factors affecting long term survival are controversial. We attempt to analyze the prognostic factors affecting retrospectively by comparing the results of lung metastasectomy. Material and Method: Between Jan. 1990 and Dec. 1997, 74 operations were taken in 63 patients with pulmonary metastases in various primary sites. We analyzed the postoperative long term survival according to sex, cell type, laterality, disease free interval(DFI), operation, the number of metastases, and the size of the largest metastasis. Result: There were 27 male and 36 female patients. Sex did not appeared to affect survival time(p=0.849). The primary tumor was carcinoma in 32, sarcoma in 28, and others in 3. Cell type, considering carcinoma and sarcoma, did not relate to survival time(p=0.071). DFI had no influence on the outcome(p=0.902). The type of operative procedure had no influence on the outcome(p=0.556). The laterality of metastases, 47 unilateral(74.6%) and 16 bilateral(25.4%), had no influence on the outcome(p=0.843). The number of metastases excised(one, two or three, four or more) did not appear to affect survival(p=0.263). The size of largest metastasis(<=10mm, 11mm-30mm, and >30mm) did not appear to affect survival(p=0.751). Previous factors were evaluated in both the carcinoma and sarcoma patients respectively. DFI was the only significant prognostic factor in metastatic lung sarcoma(p=0.0026). Conclusion: Survival was not related to sex, cell type, laterality, DFI, operative procedure, number of metastases, nor the size of the largest metastasis. DFI was related to the survival time in sarcoma group but further study is needed.
Komakech, Alfred;Im, Ji-Hye;Gwak, Ho-Shin;Lee, Kyue-Yim;Kim, Jong Heon;Yoo, Byong Chul;Cheong, Heesun;Park, Jong Bae;Kwon, Ji Woong;Shin, Sang Hoon;Yoo, Heon
Journal of Korean Neurosurgical Society
/
v.63
no.5
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pp.566-578
/
2020
Objective : Radiation is known to induce autophagy in malignant glioma cells whether it is cytocidal or cytoprotective. Dexamethasone is frequently used to reduce tumor-associated brain edema, especially during radiation therapy. The purpose of the study was to determine whether and how dexamethasone affects autophagy in irradiated malignant glioma cells and to identify possible intervening molecular pathways. Methods : We prepared p53 mutant U373 and LN229 glioma cell lines, which varied by phosphatase and tensin homolog (PTEN) mutational status and were used to make U373 stable transfected cells expressing GFP-LC3 protein. After performing cell survival assay after irradiation, the IC50 radiation dose was determined. Dexamethasone dose (10 μM) was determined from the literature and added to the glioma cells 24 hours before the irradiation. The effect of adding dexamethasone was evaluated by cell survival assay or clonogenic assay and cell cycle analysis. Measurement of autophagy was visualized by western blot of LC3-I/LC3-II and quantified by the GFP-LC3 punctuated pattern under fluorescence microscopy and acridine orange staining for acidic vesicle organelles by flow cytometry. Results : Dexamethasone increased cell survival in both U373 and LN229 cells after irradiation. It interfered with autophagy after irradiation differently depending on the PTEN mutational status : the autophagy decreased in U373 (PTEN-mutated) cells but increased in LN229 (PTEN wild-type) cells. Inhibition of protein kinase B (AKT) phosphorylation after irradiation by LY294002 reversed the dexamethasone-induced decrease of autophagy and cell death in U373 cells but provoked no effect on both autophagy and cell survival in LN229 cells. After ATG5 knockdown, radiation-induced autophagy decreased and the effect of dexamethasone also diminished in both cell lines. The diminished autophagy resulted in a partial reversal of dexamethasone protection from cell death after irradiation in U373 cells; however, no significant change was observed in surviving fraction LN229 cells. Conclusion : Dexamethasone increased cell survival in p53 mutated malignant glioma cells and increased autophagy in PTEN-mutant malignant glioma cell but not in PTEN-wildtype cell. The difference of autophagy response could be mediated though the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway.
The authors evaluated 200 cases of primary carcinoma of lung in terms of the cell type, operability, resectability and survival rate, that proved by histopathologic examination at the Dept. of Thoracic and Cardiovascular Surgery, Catholic Medical College during the period of 11 years from Jan., 1977 to Dec., 1987. The results are as follows; 1] The peak incidence was observed in the 7th decade of life [34%] and followed by 6th [30%] 8 5th decade [25%]. Male to female ratio was 3.4:1. 2] Histopathologic classifications were squamous cell carcinoma 48% [96 cases], adenocarcinoma 27% [34 cases], small cell carcinoma 13%[26 cases], ;bronchioloalveolar cell carcinoma 5% [10 cases], large cell carcinoma 4.5% [9 cases], adenosquamous cell carcinoma 1.5% [3 cases] and adenoalveolar cell carcinoma 0.5% [1 case]. 3] Among 200 cases of primary lung cancer, the operability was 47.5% [95 cases], refusal of operation 6.0% [12 cases] and inoperability 46.5% [93 cases]. 4] Ninety five cases [47.5%] were operated. Of these, post-surgical stage I was 18.9% [18 cases], stage II 24.2% [23 cases] and stage III 56.8% [54 cases]. Among 54 cases of stage III, 32 cases were unresectable, while 22 cases were resectable. Consequently, the resectability was 31.5% [63 cases] from the total numbers of 200 cases, and the resectability for the operable 95 cases was 66.3% [63 cases]. 5] Surgical complications were empyema with bronchopleural fistula [4 cases], G-I bleeding [1 case], tedious pleural effusion [1 case] and acute respiratory insufficiency [1 case]. Operative mortality was 3.2% [2 cases], which caused by massive G-I bleeding [1 case] and respiratory insufficiency [1 case]. 6] On the long term follow-up of resectable 63 cases, overall 3 year survival rate was 35%, 5 year 22% and 9 year 2%. Five year survival rate was 39% in stage l, 30% in stage II and 0% in stage III. As for the cell types, the higher 5 year survival rate was observed in resectable squamous cell carcinoma [35%] as compared to adenocarcinoma [15%], alveolar cell carcinoma [14%], small cell carcinoma [0%] and large cell carcinoma [0%].
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