• Journal of Yeungnam Medical Science
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• 제39권1호
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• pp.62-66
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• 2022

Immune checkpoint inhibitor (ICI)-associated adrenal insufficiency is rare but may become a serious adverse event in patients treated with ICIs. The present case report documents two cases of adrenal insufficiency developed during chemotherapy plus tislelizumab (百泽安, Baize'an; BeiGene Ltd.) therapy in patients with advanced gastric cancer. Adrenal insufficiency developed after 6 and 13 cycles of treatment and was well controlled with hydrocortisone. The patients also developed hypothyroidism, which was managed with levothyroxine. Two patients showed a partial response, and one patient out of two achieved a near-complete response, sustaining over 11 months. Increased awareness of ICI-related adrenal insufficiency is crucial for early detection and prompt management of patients treated with ICIs.

• Journal of Korean Neurosurgical Society
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• 제38권3호
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• pp.215-220
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• 2005

Objective : Many researchers believe that the hypothermia shows neuro-protective effect on brain injury. To understand the molecular mechanism of the hypothermic treatment, this study investigated its effects on the expression of cell death or survival related proteins such as p53, Bcl-2 and Bax in the rat traumatic brain injury[TBI] model. Methods : Twenty rats [Spraque Dawley, $200{\sim}250g$] were subjected to the brain injury of moderate severity [$2.4{\sim}2.6atm$] using the fluid percussion injury device and five rats were received only same surgery as controls. During 30minutes after the brain injury, the hypothermia group was maintained the body temperature around $34^{\circ}C$ while the control group were maintained that of $36^{\circ}C$. Five rats in each group were sacrificed 12h or 24h after brain injury and their brain sections was analyzed for physical damages by H-E stains and the extent of apoptosis by TUNEL assay and immunohistochemical stains. The tissue damage after TBI was mainly observed in the ipsilateral cortex and partly in the hippocampus. Results : Apoptosis was observed by TUNEL assay and the Bax protein was detected in both sample which harvested 12h and 24h after TBI. In the hypothermia treatment group, tissue damage and apoptosis were reduced in HE stains and TUNEL assay. In hypothermia treatment group rat shows more expression of the Bcl-2 protein and shows less expression of the Bax protein, at both 12h and 24h after TBI. Conclusion : These results show that the hypothermia treatment is an effective treatment after TBI, by reducing the apoptotic process. Therefore, it could be suggested that hypothermia has a high therapeutic value for treating tissue damages after TBI.

• Annals of Surgical Treatment and Research
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• 제95권5호
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• pp.240-248
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• 2018

Purpose: This study aimed to validate the synergistic effect of ABT-737 on docetaxel using MDA-MB-231, a triple negative breast cancer (TNBC) cell line overexpressing B-cell lymphoma-2 (Bcl-2). Methods: Western blot analysis was performed to assess expression levels of Bcl-2 family proteins and caspase-related molecules. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry analysis. Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) was used for pretreatment to assess the role of caspases. Results: Cell viability of MDA-MB-231 after combination treatment with ABT-737 and docetaxel was significantly lower than that after docetaxel or ABT-737 monotherapy based on MTT assay (both P < 0.001), with a combination index of 0.41. The proportion of sub-G1 population after combination treatment was significantly higher than that after docetaxel or ABT-737 monotherapy (P = 0.001, P = 0.003, respectively). Pretreatment with z-VAD-fmk completely restored cell viability of MDA-MB-231 from apoptotic cell death induced by combination therapy (P = 0.001). Although pro-caspase-8 or Bid did not show significant change in expression level, pro-casepase-9 showed significantly decreased expression after combination treatment. Cleaved caspase-3 showed increased expression while poly (ADP-ribose) polymerase cleavage was induced after combination treatment. However, hypoxia-inducible factor 1-alpha and aldehyde dehydrogenase 1 totally lost their expression after combination treatment. Conclusion: Combination of ABT-737 with docetaxel elicits synergistic therapeutic effect on MDA-MB-231, a TNBC cell line overexpressing Bcl-2, mainly by activating the intrinsic pathway of apoptosis. Therefore, adjunct of ABT-737 to docetaxel might be a new therapeutic option to overcome docetaxel resistance of TNBCs overexpressing Bcl-2.

• Journal of Gastric Cancer
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• 제23권1호
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• pp.207-223
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• 2023

Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8475-8478
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• 2014

Purpose: This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed-based chemoradiotherapy in treating patients with locally advanced or metastatic esophageal cancer. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for relevant patients were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: For pemetrexed-based regimens, 4 clinical studies including 47 patients with locally advanced or metastatic esophageal cancer were considered eligible for inclusion. Systematic analysis showed that, in all patients, the pooled RR was 51% (24/47). Major adverse effects of grade III/IV were esophagitis, neutropenia, thrombocytopenia, anemia anorexia, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusion: This systematic analysis suggests that pemetrexed based radiotherapy is associated with reasonable activity and good tolerability in treating patients with locally advanced or metastatic esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1993-1995
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• 2015

Purpose: This analysis was conducted to evaluate the efficacy and safety of irinotecan based regimens as second-line chemotherapy in treating patients with small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of irinotecan based regimens as second-line chemotherapy for patients with small cell lung cancer were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In irinotecan based regimens as second-line chemotherapy, 4 clinical studies which including 155 patients with small cell lung cancer were considered eligible for inclusion. In all chemotherapy consisted of irinotecan with or without nedaplatin. Pooled analysis suggested that, in all patients, the pooled RR was 27.1% (42/155) in irinotecan based regimens. Nausea, vomiting, diarrhea and myelosuppression were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with the irinotecan based treatments. Conclusion: This systemic analysis suggests that irinotecan based regimens as second-line chemotherapy are associated with mild response rate and acceptable toxicity for patients with small cell lung cancer.

• The Plant Pathology Journal
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• 제22권4호
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• pp.339-347
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• 2006

Riboflavin caused induction of systemic resistance in chickpea against Fusarium wilt and charcoal rot diseases. The dose effect of 0.01 to 20 mM riboflavin showed that 1.0 mM concentration was sufficient for maximum induction of resistance; higher concentration did not increase the effect. At this concentration, riboflavin neither caused cell death of the host plant nor directly affected the pathogen's growth. In time course observation, it was observed that riboflavin treated chickpea plants were inducing resistance 2 days after treatment and reached its maximum level from 5 to 7 days and then decreased. Riboflavin had no effect on salicylic acid(SA) levels in chickpea, however, riboflavin induced plants found accumulation of phenols and a greater activities of phenylalanine ammonia lyase(PAL) and pathogenesis related(PR) protein, peroxidase was observed in induced plant than the control. Riboflavin pre-treated plants challenged with the pathogens exhibited maximum activity of the peroxidases 4 days after treatment. Molecular weight of the purified peroxidase was 42 kDa. From these studies we demonstrated that riboflavin induced resistance is PR-protein mediated but is independent of salicylic acid.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9763-9766
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• 2014

Background: This systemic analysis was conducted to evaluate the efficacy and safety of an ifosfamide-containing regimen in treating patients with osteosarcoma. Methods: Clinical studies evaluating the efficacy and safety of Ifosfamide-containing regimen on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: When ifosfamide-containing regimens were evaluated, 4 clinical studies which including 134 patients with osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 44.8% (60/134) in ifosfamide-containing regimens. Major adverse effects were neutropenia, leukopenia, and fatigue inIfosfamide-containing regimens; No treatment related death occurred in cantharidin combined regimens. Conclusion: This systemic analysis suggests that ifosfamide-containing regimens are associated with good response rate and acceptable toxicity in treating patients with osteosarcoma, but this result should be confirmed by randomized clinical trials.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9813-9815
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• 2014

Background: This analysis was conducted to evaluate the efficacy and safety of cisplatin based chemotherapy for treating patients with cutaneous squamous cell carcinoma. Methods: Clinical studies evaluating the efficacy and safety of cisplatin based regimens on response and safety for patients with cutaneous squamous cell carcinoma were identified using a predefined search strategy. Pooled response rates (RR) of treatment were calculated. Results: In cisplatin based regimens, 4 clinical studies which including 50 patients with advanced cutaneous squamous cell carcinoma were considered eligible for inclusion. Regimens included cisplatin, doxorubicin, or vindesine. Pooled analysis suggested that, in all patients, the pooled RR was 60% (30/50) in cisplatin based regimens. Nausea and vomiting were the main side effects. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred with the cisplatin based treatments. Conclusion: Evidence based analysis suggests that cisplatin based regimens are associated with a good response rate and acceptable toxicity for treating patients with cutaneous squamous cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4797-4800
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• 2015

Background: This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer. Materials and Methods: Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In crizotinib based regimens, 3 clinical studies which including 128 Chinese patients with EML4-ALK positive non-small-cell lung cancer and treated with crizotinib based regimen were considered eligible for inclusion. Pooled analysis suggested that, in all patients, the pooled RR was 59.3% (76/128) in crizotinib based regimens. ALT/AST mild visual disturbances, nausea, and vomiting were the main side effects. No treatment related death occurred in these crizotinib based treatments. Conclusions: This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.