• Asian Pacific Journal of Cancer Prevention
• /
• 제14권7호
• /
• pp.4215-4221
• /
• 2013

Purposes: Lung cancer is prevalent worldwide and improvements in timely and effective diagnosis are need. Pentraxin-3 as a novel serum marker for lung cancer (LC) has not been validated in large cohort studies. The aim of the study was to assess its clinical value in diagnosis and prognosis. Methods: We analyzed serum PTX-3 levels in a total of 1,605 patients with LC, benign lung diseases and healthy controls, as well as 493 non-lung cancer patients including 12 different types of cancers. Preoperative and postoperative data were further assessed in patients undergoing LC resection. The diagnostic performance of PTX-3 for LC and early-stage LC was assessed using receiver operating characteristics (ROC) by comparing with serum carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1). Results: Levels of PTX-3 in serum were significantly higher in patients with LC than all controls. ROC curves showed the optimum diagnostic cutoff was 8.03ng/mL (AUC 0.823, [95%CI 0.789-0.856], sensitivity 72.8%, and specificity 77.3% in the test cohort; 0.802, [95%CI 0.762-0.843], sensitivity 69.7%, and specificity 76.4% in the validate cohort). Similar diagnostic performance of PTX-3 was observed for early-stage LC. PTX-3 decreased following surgical resection of LC and increased with tumor recurrence. Significantly elevated PTX-3 levels were also seen in patients with non-lung cancers. Conclusions: The present data revealed that PTX-3 was significantly increased in both tissue and serum samples in LC patients. PTX-3 is a valuable biomarker for LC and improved identification of patients with LC and early-stage LC from those with non-malignant lung diseases.

• Biomolecules & Therapeutics
• /
• 제18권1호
• /
• pp.56-64
• /
• 2010

Pentoxifylline (PTX) has been used for the local reduction of fat tissue in the clinical setting. However, its safety and efficacy have not been proven. The aim of this study was to evaluate the effects of PTX on cell lines established from fat tissue. Newly cultured human preadipocytes and adipocytes from subcutaneous abdominal fat in addition to purchased human lung fibroblasts and keratinocytes were treated with PTX at different concentrations. Cell viability was determined using the Cell counting kit (CCK)-8 assay and lipolysis was evaluated using an Elisa kit. DNA fragmentation, Western blot analysis, Hoechst and Propidium Iodide (PI) staining and fluorescence activated cell scanning analysis were performed to confirm apoptosis. The viability of adipocytes, preadipocytes, keratinocytes and fibroblasts was markedly decreased at concentrations of PTX above 20 mM. Apoptosis was induced at concentrations of PTX over 40 mM in all cell lines. Lipolysis was increased by 60% at concentrations of PTX of 20 mM compared to the control. In conclusion, the results of this study showed that 20 mM of PTX induced lipolysis. At concentrations over 20 mM, PTX reduced the viability of all cells studied including: adipocytes, preadipocytes, fibroblasts and keratinocytes, in a non-specific manner.

• 농업과학연구
• /
• 제47권3호
• /
• pp.657-665
• /
• 2020

The objective of this study was to investigate whether supplementation of pentoxifylline (PTX; phosphodiesterase inhibitor) to thawed boar semen improves the post-thaw motility of sperm and affects the efficiency of artificial insemination (AI) and further development. To determine the concentration of PTX for AI, frozen-thawed semen was incubated with 0, 5, 10, and 20 mM PTX in an extender freezing medium, respectively, after thawing. Kinematic properties of sperm were examined with a computer-assisted semen analysis (CASA) system. In addition, viability and mitochondrial activity were also tested by LIVE/DEAD and a MitoTracker kit. There were no significant differences in the kinetic parameters of thawed sperm between control and treatment groups, but overall assessment parameters such as motility and rapid progressive were higher in the 10 mM PTX group. In the viability and mitochondrial assay, there were no significant differences observed in the PTX treatment, compared to the control. For further analysis, artificial inseminations were performed using frozen semen and 10 mM PTX treated cryopreserved semen, respectively. There were no differences in pregnancy rates and fetus weights among the groups until 30 and 40 days, but litter size was reduced and relatively low-birth weight was observed in the PTX group. In summary, our findings suggest that enhancement of in vitro sperm quality or non-toxicity supplemented by PTX may have detrimental effects on fetus development.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권5호
• /
• pp.467-476
• /
• 2016

In the present study, we examined the effect of pertussis toxin (PTX) administered centrally in a variety of stress-induced blood glucose level. Mice were exposed to stress after the pretreatment of PTX (0.05 or 0.1 mg) i.c.v. or i.t. once for 6 days. Blood glucose level was measured at 0, 30, 60 and 120 min after stress stimulation. The blood glucose level was increased in all stress groups. The blood glucose level reached at maximum level after 30 min of stress stimulation and returned to a normal level after 2 h of stress stimulation in restraint stress, physical, and emotional stress groups. The blood glucose level induced by cold-water swimming stress was gradually increased up to 1 h and returned to the normal level. The intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX, a $G_i$ inhibitor, alone produced a hypoglycemia and almost abolished the elevation of the blood level induced by stress stimulation. The central pretreatment with PTX caused a reduction of plasma insulin level, whereas plasma corticosterone level was further up-regulated in all stress models. Our results suggest that the hyperglycemia produced by physical stress, emotional stress, restraint stress, and the cold-water swimming stress appear to be mediated by activation of centrally located PTX-sensitive G proteins. The reduction of blood glucose level by PTX appears to due to the reduction of plasma insulin level. The reduction of blood glucose level by PTX was accompanied by the reduction of plasma insulin level. Plasma corticosterone level up-regulation by PTX in stress models may be due to a blood glucose homeostatic mechanism.

• 생명과학회지
• /
• 제17권10호
• /
• pp.1447-1451
• /
• 2007

해양생물 유래 항암활성을 가지는 천연물의 탐색과정에서 해면동물에서 유래된 PTX-2는 p53 결손 암세포에서 세포독성 효과가 높은 것으로 보고된 바 있다. 본 연구에서는 인체 간암세포 모델을 이용하여 PTX-2의 효능을 조사한 결과는 p53 결손 Hep3B 세포에서 p53 정상 HepG2에 비하여 항암활성이 매우 높았으며, 이는 apoptosis 유발과 연관성이 있음을 확인하였다. PTX-2에 의한 Hep3B 세포의 apoptosis 유발은 DFF family의 발현 변화, pro-apoptotic Bax 및 Bcl-xS 단백질의 발현 증가, caspases (-3, -8 및 -9)의 활성화 등이 관여함을 알 수 있었다. PTX-2는 또한 Hep3B 세포에서 AKT 및 ERK1/2의 활성화를 유도하였으며, caspase-3, AKT 및 ERK1/2의 특이적 저해제에 의하여 PTX-2에 의한 세포증식 억제 효능이 유의적으로 감소되었다. 본 연구는 PTX-2에 의한 Hep3B 세포에서의 apoptosis 유도에 AKT 및 ERK1/2 신호 전달 경로가 중요한 역할을 하고 있음을 보여주는 결과이다.

• Mycobiology
• /
• 제48권1호
• /
• pp.1-8
• /
• 2020

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor (PRR), which is produced by several kinds of cells, such as neutrophils, dendritic cells, macrophages, and epithelial cells. PTX3 is known to play an important protective effect against Aspergillus. Genetic linkage in gene-targeted mice and human PTX3 plays a non-redundant role in the immune protection against specific pathogens, especially Aspergillus. Recent studies have shown that the polymorphism of PTX3 is associated with increased susceptibility to invasive aspergillosis (IA). In this review, we provide an overview of these studies that underline the potential of PTX3 in diagnosis and therapy of IA.

• Clinical and Experimental Pediatrics
• /
• 제48권12호
• /
• pp.1378-1384
• /
• 2005

목 적 : ADR 유발성심근증 생쥐 모델에서 PTX와 DXR의 심근증에 대한 예방 및 치료 효과를 알아보고자 하였다. 방 법 : 생후 6주된 Sprague-Dawley rat를 정상대조군(n=4), 질환대조군(n=6), DXR군(n=5), PTX군(n=6), 병용치료군(n=5)으로 나누고 정상 대조군을 제외한 4군에 ADR(5 mg/kg)을 1주 간격으로 2회 미정맥으로 투여하여 심근증을 유발하였다. DXR군은 매 ADR 투여 30분 전에 DXR(100 mg/kg)을 미정맥으로 주사하였다. PTX군은 3주간 매일 PTX(50 mg/kg/day)을 경구투여하였다. 5군 모두 3주 뒤에 희생시켜 좌심실 조직의 광학현미경적소견을 관찰하여 심근증의 정도를 분석하였다. 면역조직학적 염색을 통해 Bcl-2 발현의 변화를 조사하였고 $TNF-{\alpha}$와 CTGF에 대한 RT-PCR을 시행하였다. 결 과 : 광학현미경 소견상 세포질의 공포형성과 과수축 밴드괴사 그리고 섬유화는 정상대조군에 비해 질환대조군에서 유의하게 증가하였고 병용치료군에서 감소하였다(P<0.01). 심근 섬유화는 PTX군과 병용치료군에서 ADR군에 비해 유의하게 감소하였다. Bcl-2의 발현은 질환대조군에서 낮았으며 DXR군과 병용치료군에서 질환대조군에 비해 Bcl-2의 발현이 증가하여 호전되었다(P<0.05). $TNF-{\alpha}$는 mRNA와 단백질의 발현상 정상대조군과 질환대조군에서 차이가 없었다. 결 론 : ADR 유발성심근증에 DXR과 PTX를 함께 투여하였을 경우 DXR은 bcl-2의 발현을 증가시키고 심근세포의 자멸사를 억제하였고 PTX는 심근 섬유화를 억제하였다. 그리고 ADR과 PTX를 병용 투여하였을 경우 최대의 심근증 예방 효과를 볼 수 있었다.

• Macromolecular Research
• /
• 제17권2호
• /
• pp.99-103
• /
• 2009

We evaluated the efficacy of pH-sensitive micelles, formed by methoxy poly(ethylene glycol)-b-poly($\beta$)-amino ester) (PEG-PAE), as carriers for paclitaxel (PIX), a drug currently used to treat various cancers. PTX was successful encapsulated by a film hydration method. Micelles encapsulated more than 70% of the PTX and the size of the PTX-encapsulated micelles (PTX-PM) was less than 150 nm. In vitro experiments indicated that the micelles were unstable below pH 6.5. After encapsulation of PTX within the micelles, dynamic light scattering (DLS) studies indicated that low pH had a similar demicellization effect. An in vitro release study indicated that PTX was slowly released at pH 7.4 (normal body conditions) but rapidly released under weakly acidic conditions (pH 6.0). We demonstrated the safety of micelles from in vitro cytotoxicity tests on HeLa cells and the in vivo anti-tumor activity of PTX-PM in B16F 10 tumor-bearing mice. We concluded that these pH-sensitive micelles have potential as carriers for anti-cancer drugs.

• Journal of Gastric Cancer
• /
• 제21권4호
• /
• pp.418-425
• /
• 2021

Purpose: We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. Materials and Methods: Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m²/day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m² on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m², and the dose escalation was set in units of 20 mg/m² up to 80 mg/m². Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. Results: Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m². Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. Conclusions: The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m², when combined with a systemic SOX regimen.

• Journal of Plant Biology
• /
• 제38권1호
• /
• pp.87-93
• /
• 1995

최근에 Synechocystis sp. PCC 6803 중에 한 균주가 고체 한천 배지상에서 일정한 조명(300-1000 lux) 방향을 따라 활주 운동하는 것을 관찰하여 이 종을 S. 6803 PTX라고 명명하고 이의 주광성 운동에 대한 생리학적 특징을 이해하기 위하여 몇 가지 대사 억제제와 신호 전달 차단제의 주광성 운동에 미치는 효과를 조사하였다. DCMU는 광계 II로부터 광계 I의 일차 전자 수용체인 플라스토퀴논으로의 비순환성 광합성 전자전달을 억제하는 억제자로서 $100\;\mu\textrm{M}$의 농도에서는 주광성 운동을 억제하지 못하였다. 그러나 호흡에 의한 전자전달 억제제인 sodium azide를 처리하였을 경우에는 S. 6803 PTX에서 심하게 장해를 받았다. 이러한 관찰 결과는 주광성 운동의 주동력원이 광인산화 과정보다는 호흡에 의한 산화적인 인산화과정에 주로 연관되어 있음을 보여주었다. 또한, 세포를 CCCP나 DNP와 같은 막상의 uncoupler를 처리하였을 때, 세포내 ATP 농도를 저하시키거나 세포질막에 수소 이온의 전기화학구배($\Delta\mu_{H}+$)를 제거시키나, 이러한 화합물들은 주광성 운동에 뚜렷한 영향은 주지 못하였다. 이러한 결과와는 달리, H+-F0F1 ATPase에 민감하게 억제 작용을 나타내는 DCCD나 NBD의 처리는 세포내 ATP만 고갈시키고 막상에서 $\Delta\mu_{H}+$는 그대로 유지시키는 작용을 하는데, 이러한 DCCD나 NBD는 주광성 운동에 대해서는 심하게 억제 현상을 나타내었다. 또한, 특이성 calcium ionophore 중의 하나인 A23187의 처리는 양성 주광성에 심하게 장해를 주었다. 아마도 Ca2+ 유동은 주광운동 방향성의 신호전달 과정에 중요하게 관련되어 있는 것으로 나타났다. 마지막으로 S-adenosyl methionine과 같은 메틸 공여체의 고갈이 S. 6803 PTX 균주의 주광성 반응에 영향을 주는지를 알아보기 위하여 에티오닌을 BG11을 한천 배지에 첨가하였다. 이 생물종의 광운동은 에티오닌의 농도가 증가됨에 따라 일정하게 억제되다가 0.5mM에서 주광성 운동을 완전히 억제시켰다. 이것은 광수용 기작이 Escherichia coil나 Salmonella typhimurium에서 발견된 메틸기 수용 주화성 단백질과 같은 메틸화/탈메틸화 과정에 의하여 조절될 가능성을 보여주고 있음을 의미한다.