• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1311-1315
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• 2012

Objectives: Thrombotic risk is increased in patients with cancer and there are important implications for those who suffer a venous thromboembolism (VTE). We undertook this study to determine the frequency, clinical patterns, and outcome of VTE in Saudi patients with cancer. Methods: Cancer (solid tumors and lymphoma) patients who developed VTE from January 2004 to January 2009 were studied retrospectively. Demographics and clinical characteristics related to thrombosis and cancer were evaluated. Results: A total of 701 patients with cancer were seen during the study period. VTE was diagnosed in 47 (6.7%) patients (median age 52, range 18-80 years). Lower limb DVT was the most common type, seen in 47% patients, followed by PE in 19%, and 19% patients had both DVT & PE. Thrombosis was symptomatic in 72% patients while it was an incidental finding on routine workup in 28%. Cancer and VTE were diagnosed at the same time in 38% of patients, and 47% patients developed VTE during the course of disease after the cancer diagnosis. The majority of VTE post cancer diagnoses occurred during the first year (median 4 months, range 1-14). Additional risk factors for VTE were present in 22 (47%) patients and 14 (30%) of these patients were receiving chemotherapy at the time of thrombosis. Only 5 (10.6%) patients were receiving thrombo-prophylaxis at the time of VTE diagnosis. Most common types of tumors associated with thrombosis were breast cancer, non-Hodgkin's lymphoma and lung cancer. The majority of the affected patients (79%) had advanced stage of cancer. After a median follow-up of 13 (range 0.5-60) months, 38 (81%) patients had died. There was no difference in the mortality of patients with symptomatic or asymptomatic thrombosis (82% vs 78.6%). Conclusions: Thrombotic complications can develop in a significant number of patients with cancer, and almost half of the patients have additional risk factors for VTE. Thrombosis is usually associated with advanced disease and can be asymptomatic in more than a quarter of cases. Thromboprophylaxis in cancer patients is under-utilized. Community based studies are needed to accurately define the extent of this problem and to develop effective prophylactic strategies.

• 한국임상약학회지
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• 제18권2호
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• pp.75-83
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• 2008

Purpose: Currently lung cancer ranks second in cancer for incidence rate and is a disease that ranks first for a death rate by cancerous growth because it is already advanced at the time of diagnosis. The purpose of this paper was to analyze the factors that affect the effectiveness of and rash occurrence by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) in patients with non-small cell lung cancer. Methods: A retrospective chart review of 100 patients, who took EGFR TKI (erlotinib, gefitinib) among patients who were diagnosed with non-small cell lung cancer in a Hospital in Korea between May 2005 and February 2008, was conducted. The drug effectiveness was evaluated by Response Evaluation Criteria In Solid Tumor. Results: EGFR mutation was the only factor associated with drug response (complete response and partial response). When stable disease was added to drug response as the evaluation parameter, ECOG and rash as well as EGFR mutation were found to be important factors. Survival, however, was not affected by EGFR mutation. The factors influenced on survival were older age (${\geq}65$), low ECOG ($1{\sim}2$), adenocarcinoma and rash. In the case of rash, group with EGFR mutation or low ECOG showed significantly higher chance of occurrence. There was no significant difference in rash occurrence between gefitinib and erlotinib groups. Conclusions: Based on the results, EGFR mutation positive and low ECOG ($1{\sim}2$) were significantly important factors for both effectiveness of EGFR TKI and rash occurrence. Also, rash itself was found to be an independently significant factor for the disease control and survival. Therefore, while administering EGFR TKI, patients who have the factors associated with rash occurrence should be closely monitored for effective and safe drug therapy.

• Childhood Kidney Diseases
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• 제21권1호
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• pp.21-25
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• 2017

Severe hypercalcemia is rarely encountered in children, even though serum calcium concentrations above 15-16 mg/dL could be life-threatening. We present a patient having severe hypercalcemia and azotemia. A 14-year-old boy with no significant past medical history was referred to our hospital with hypercalcemia and azotemia. Laboratory and imaging studies excluded hyperparathyroidism and solid tumor. Other laboratory findings including a peripheral blood profile were unremarkable. His hypercalcemia was not improved with massive hydration, diuretics, or even hemodialysis, but noticeably reversed with administration of calcitonin. A bone marrow biopsy performed to rule out the possibility of hematological malignancy revealed acute lymphoblastic leukemia. His hypercalcemia and azotemia resolved shortly after initiation of induction chemotherapy. Results in this patient indicate that a hematological malignancy could present with severe hypercalcemia even though blast cells have not appeared in the peripheral blood. Therefore, extensive evaluation to determine the cause of hypercalcemia is necessary. Additionally, appropriate treatment, viz., hydration or administration of calcitonin is important to prevent complications of severe hypercalcemia, including renal failure and nephrocalcinosis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5217-5221
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• 2016

Objective: A study of primary cancer morbidity among children and subsequent calculation of average annual incidence were carried out for boys and girls, and young men and women in Kazakhstan. Methods: The investigated population lived in three areas of the Aral Sea region: designated catastrophe (Aral, Kazalt, Shalkar regions), crisis (Zhalagash, Karmakshy, Shiely regions), pre-crisis (Irgiz, Arys, Ulytau regions). Zhanaarka region of Karaganda oblast was applied as a control. Parameters were retrospective analyzed for the 10 years from 2004 to 2013. Result: The results indicate that indices of children cancer morbidity were slightly higher in the Aral Sea region than in the control district, but they were comparable with similar data from studies in other regions. In all areas of the Aral Sea region, except for Ulytau, primary cancer morbidity exceeded the control level by 1.3-2.7 times (4.7%000). Hematological malignancies, including solid tumors - tumors of musculoskeletal system and skin, digestive system, brain and central nervous system predominated. Stress levels in zones of the Aral Sea region were slightly higher in the crisis zone than in the catastrophe zone that can be explained by the phenomenon of wave-like dynamics of disease growth risk. Gender differences in characteristics of malignancy formation were not more pronounced in the studied region. Conclusion: Indices of children cancer are slightly higher in the Aral Sea region than in the control area of Kazakhstan, but they are comparable to results for other regions.

• 대한의생명과학회지
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• 제3권2호
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• pp.71-76
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• 1997

실험적 자궁암 치료제로서 본 연구소에서 합성한 마이토센유사체를 인체 자궁암세포주인 SiHa, C33A, HeLa, CaSki에 처리하여, 체외 항암활성 측정시 합성 마이토센유사체들은 이 들 세포주에 대하여 대조 항암제들에 비하여 의의있는 세포독성을 보였으며, SiHa 세포주를 이용한 종양클론형성 억제검사에서는 22번 화합물만이 종양성장 억제활성이 가장 우수하였고 다른 화합물들은 대조항암제들에 비하여 활성이 낮았다. 이 마이토센유사체들에 대한 체외 항암감수성결과는 향후 전임상적인 자궁경부암 화합요법제의 기초자료로 유용할것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1117-1122
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• 2015

Background: Cisplatin is still used as a first-line medication for solid tumors. Nephrotoxicity is a serious side effect that can decrease renal function and restrict applicable doses. This research aimed to obtain the profile of cisplatin-induced nephrotoxicity and its associated factors in adult cancer patients at Dharmais National Cancer Hospital (DNCH). Materials and Methods: The design was cross-sectional with data obtained from patient medical records. We retrospectively reviewed adult cancer patients treated with cisplatin ${\geq}60mg/m^2$ for at least four consecutive chemotherapy cycles from August 2011 to November 2013. The nephrotoxicity criterion was renal function decline characterized by creatinine clearance <60 ml/min using the Cockroft-Gault (CG) equation. Results: Eighty-eight subjects received at least four chemotherapy cycles of cisplatin. The prevalence of cisplatin nephrotoxicity was 34.1%. Symptoms could be observed after the first cycle of chemotherapy, and the degree of renal impairment was higher with increased numbers of cycles (r=-0.946, $r^2=89.5%$). Factors that affected the decline of renal function were patient age (p=0.008, OR=3.433, 95%CI= 1.363-8.645) and hypertension (p=0.026, OR=2.931, 95%CI=1.120-7.670). Conclusions: Cisplatin nephrotoxicity occurred in more than one-third of patients after the fourth cycle of chemotherapy and worsened after each cycle despite preventive strategies such as hydration. The decline of renal function induced by cisplatin ${\geq}60mg/m^2$ was affected by age and hypertension.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.305-309
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• 2007

Arsenic compounds have been used to treat various diseases including cancer in oriental medicine. Arsenic trioxide ($As_2O_3,\;Trisenox^{(R)}$) has been used for the treatment of leukemia and its anti-solid tumor activity has also been reported recently. Tetra-arsenic oxide ($As_4O_6,\;TetraAs^{(R)}$) is a newly developed arsenic compound which has shown an anticancer activity in some human cancer cell lines. The purpose of this study was to evaluate the anti-gastric cancer potential of TetraAs and to search for an agent with synergistic interaction with TetraAs against human gastric cancers. We analysed anti-proliferative effect of TetraAs when given alone and in combination with other chemotherapeutic agents such as 5-FU, paclitaxel, and cisplatin in SNU-216, a human gastric cancer cell line. The $IC_{50}$ of these 4 anti-cancer drugs ranged from 5.8 nM to $7.5\;{\mu}M$ with a potency rank of order paclitaxel>TetraAs>cisplatin>5-FU. TetraAs showed 10-fold greater potency than 5-FU and cisplatin at the same effect level of $IC_{50}$. TetraAs+5-FU and TetraAs+paclitaxel showed synergistic and additive interaction, respectively. On the other hand, TetraAs with cisplatin group appeared to be strongly antagonistic. Apoptotic population was measured and compared between single and combination treatment. The apoptotic cells for the combination of TetraAs+5-FU showed significant increase compared to single TetraAs treatment. On the contrary, TetraAs+cisplatin showed less apoptotic cells compared to TetraAs or cisplatin alone treatment. Overall, our results indicate that TetraAs can be effectively combined with 5-FU or paclitaxel, but not with cisplatin for synergistic anti-cancer effect, which warrants further evaluation using in vivo models.

• 대한한의학회지
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• 제31권3호
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• pp.8-16
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• 2010

Objective: This study aimed to investigate the antitumor effects of water extracts of Panax notoginseng (WEPN) in NCI-H460 human lung cancer cell xenografted nude mice. Materials and Methods: We cultured NCI-H460 cell lines and xenografted them to nude mice. The mice were divided into 3 groups; positive control group, NCI-H460+150 mg/kg WEPN-treated group, and NCI-H460+300 mg/kg WEPN-treated group. They had been raised and treated in 28 days. We checked their body weight and tumor weight and volumes twice a week and their absolute organ weight and microhistological observation at the final day. We also calculated their tumor inhibition rate (I.R.), mean survival time and percent increase in life span (% ILS). Results: Body weight of WEPN (300 mg/kg) treated mice tended to slightly greater increase than those of the positive control group, but had no significance. Tumor volume (measurement with a caliper) of WEPN-treated mice tended to be lower than that of the positive control group. Inhibition rate (I.R.) of the WEPN group decreased more than the positive control group, but had no significance. Results of tumor weights and volume (plethysmography) had no significance. Mean survival time and percent increase in life span (% ILS) in the WEPN 300 mg/kg treatment group were higher than those of any other group (p<0.05). In absolute organ weights, the WEPN (150-300 mg/kg) treatment group decreased liver weights (p<0.05). Liver tissue of mice treated with WEPN (300 mg/kg) did not show any specific lesions. Conclusion: We suggest that WEPN may have potential as a growth inhibitor of solid tumors induced by NCI-H460 without any side effects. However, this study has limitations in proving anti-tumor effects of WEPN, so further studies to overcome those limitations will be needed.

• Environmental Analysis Health and Toxicology
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• 제22권3호
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• pp.263-269
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• 2007

Chitosan is a depolymerized and partially deacetylated derivative of chitin. We investigated the cytotoxicity of chitosan in cancer cell lines, such as P388, L1210, HCT-15, SK-HepG-1 and mouse splenocytes as a normal cell by MTT assay. To clarify whether chitosan enhances cytotoxicity of anticancer drugs, we also examined the cytotoxicity of combined treatment with chitosan and anticancer drugs, such as cisplatin, mitomycin C, and 5-fluorouracil in cancer cell lines in vitro. Chitosan ($37.5\;{\mu}g/mL,\;75\;{\mu}g/mL,\;112.5\;{\mu}g/mL,\;and\;150\;{\mu}g/mL$) showed concentration-dependent cytotoxicity in the cancer cell lines. In addition, chitosan showed relatively lower cytotoxicity in normal cells than in the cancer cell lines. Particularly, this trend was significant at high doses of chitosan, i.e. $112.5\;{\mu}g/mL,\;and\;150\;{\mu}g/mL$. Thus, these results suggest that chitosan may selectively induce the growth inhibition in cancer cell lines, compared to normal cells. Furthermore. the co-treatment of chitosan and anticancer drugs exhibited an apparant synergistic cytotoxicity in murine lymphoma cell lines, i.e. P388 and L1210 at $37.5\;{\mu}g/mL$ of chitosan rather than at $75\;{\mu}g/mL$ of chitosan, but such phenomenon could not be observed in solid tumor cell lines, i.e. HCT-15 and SK-HepG-1. However, chitosan did'nt reduced the cytotoxicity against normal mouse splenocytes induced by anticancer drugs. Therefore, it is concluded that the combination of chitosan and anticancer drugs might be useful for the cancer chemotherapy.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.418-426
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• 2022

Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1⁺ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8⁺ T cells having CD8⁺CD44⁺CD62L^low phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.