• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3173-3181
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• 2015

Background: It has been hypothesized that IL-18 (pro-) and IL-10 (anti-) inflammatory genetic variants at -607 C/A-137G/C and -819C/T,-592C/A, respectively, may generate susceptibility and severity risk with various modes of tobacco exposure in prostate carcinoma (PCa) patients. IL-18 is a pro-inflammatory cytokine expressed on various cells including prostate gland elements, and is a key mediator of immune responses with anti-cancerous properties. IL-10 is an anti-inflammatory cytokine that is associated with tumour malignancy which causes immune escape. Materials and Methods: The present study was conducted with 540 subjects, comprising 269 prostate carcinoma patients and 271 controls. Genotyping was performed by PCR-RFLP and confirmed by real time PCR probe-based methods. Results: The findings indicated that the mutant heterozygous and homozygous genotype CC and GC+CC showed significant negative associations (p=0.01, OR=0.21; 95% CI: 0.08-0.51 and p=0.011, OR=0.43; 95% CI: 0.22-0.81, respectively) thus, less chance to be diagnosed as cancer against GG genotype of tobacco smoking patients. In addition, a heterozygous GC genotype at the same locus of IL-18 pro-inflammatory cytokine may aggravate the severity (OR=2.82; 95%CI 1.09-7.29 :p=001) so that patients are more likely to be diagnosed in advanced stage than with the GG wild homozygous genotype. Our results also illustrated that anti-inflammatory cytokine (IL-10) genetic variants, although showing no significant association with susceptibility to cancer of the prostate, may gave profound effects on severity of the disease, as -819 TC (OR=4.60; 95%CI 1.35-15.73), and -592 AC (OR=5.04; 95%CI 1.08-25.43) of IL-10 in tobacco chewers and combined users (both chewers and smokers) respectively, are associated with diagnosis in more advanced stage than with other variants. Conclusions: We conclude that promoter genetic variants of IL-18 and IL-10 with various modes of tobacco exposure may affect not only susceptibility risk but also severity in prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6197-6208
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• 2013

Cancers will continue to be a threat to health unless they can be controlled by combinations of treatment modalities. In this review, evaluate the role of resveratrol (RSV) as a radiosensitizing agent was evaluated and underlying mechanisms holistically explored in different cancer models focusing on therapeutic possibilities. The ability of RSV to modify the effect of radiation exposure in normal and cancer cells has indeed been shown quite convincingly, the combination of RSV and IR exhibiting synergistic effects on different cancer cells. This is relevant since controlled exposure to IR is one of the most frequently applied treatments in cancer patients. However, radiotherapy (XRT) treatment regimes are very often not effective in clinical practice as observed in patients with glioma, prostate cancer (PCa), melanoma, for example, largely due to tumour radioresistant properties. Sensitization of IR-induced apoptosis by natural products such as RSV is likely to be relevant in cancer control and treatment. However, all cancers do not respond to RSV+IR in a similar manner. Therefore, for those such as the radioresistant PCa or melanoma cells, the RSV+IR regime has to be very carefully chosen in order to achieve effective and desirable outcomes with minimum toxicity to normal cells. They are reports that the highest concentration of 100 ${\mu}M$ RSV and highest dose of 5 Gy IR are sufficient to kill cells by induction of apoptosis, indicating that RSV is effective in radiosensitizing otherwise radioresistant cells. In general, it has been shown in different cancer cells that RSV+XRT effectively act by enhancing expression of anti-proliferative and pro-apoptotic molecules, and inhibiting pro-proliferative and anti-apoptotic molecules, leading to induction of apoptosis through various pathways, and cell death. If RSV+XRT can suppress the signature of cancer stemness, enhance the radiosensitivity by either targeting the mitochondrial functionality or modulating the tumour necrosis factor-mediated or Fas-FasL-mediated pathways of apoptosis in different cancers, particularly in vivo, its therapeutic use in the control of cancers holds promise in the near future.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1285-1290
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• 2014

The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

• 생명과학회지
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• 제29권8호
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• pp.904-915
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• 2019

전립선암은 전이성 종양 중의 하나로 치료를 위해 호르몬 요법이나 외과 적 거세 방법이 주로 수행되지만 많은 부작용을 나타내었다. 최근 많은 연구자들이 이러한 상황을 해결하기 위해 종양 미세 환경을 연구하고 있으며 그 중 면역 세포, 특히 대식세포는 종양 미세 환경의 중요한 구성요소이다. 정상적인 조건에서 대식세포는 여러 암세포에 대해 약한 종양 살균 활성을 갖으나 $interferon-{\gamma}$ 또는 lipopolysaccharide에 의해 활성화되면, 염증성 사이토카인 및 케모카인을 분비함으로써 암세포를 직접 또는 간접적으로 사멸 시키게 된다. 본 연구에서는, 마우스 대식세포인 RAW 264.7 세포에 Phellinus linteus 추출물을 처리하여 산화질소의 방출과 pro-inflammatory cytokine들을 real-time PCR과 ELISA 방법으로 분석하였다. RAW 264.7의 조정 배지는 48시간 동안 전립선 암세포처리하여 상피간엽세포전이 관련 유전자의 발현을 측정 하였다. 그 때에 mesenchymal 관련 유전자들인 N-cadherin, snail, twist, slug 및 cadherin 11이 감소했을 뿐만 아니라 epithelial 관련 유전자인 E-cadherin은 증가하였다. 또한 암 전이 및 신생 혈관 형성에 관여하는 vimentin, ccl2 및 vegfa가 감소되었는데, 이는 EMT가 암세포의 이동과 침범에 밀접한 관련이 있기 때문이다. 따라서 Phellinus linteu에 의해 자극된 RAW 264.7 세포의 조정 배지는 인간 전립선 암세포주인 PC-3 세포의 이동과 전이를 억제하고 EMT 경로를 조절한다는 것을 나타낸다.

• 대한영상의학회지
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• 제83권5호
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• pp.1059-1070
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• 2022

목적 계산형 확산강조영상 b2000과 실제 획득한 확산강조영상 b2000 사이에 전립선암 발견을 위한 민감도 및 관찰자 간 일치도를 비교하였다. 대상과 방법 근치적 전립선 절제술 및 확산강조영상(b, 0, 100, 1000, 2000 s/mm²)을 포함한 수술 전 3 Tesla 자기공명영상을 통해 전립선암으로 진단받은 총 88명의 환자가 연구에 포함되었다. 계산형 확산강조영상 b2000은 실제 획득한 확산강조영상 b0, 100, 1000으로부터 단일 지수 감쇠 모델에 의해 계산되었다. 두 명의 독립된 검토자가 4주 간격으로 무작위 순서로 두 영상 세트를 검토하여, 가장 큰 종양에 대해 관심 영역을 그렸고, Prostate Imaging-Reporting and Data System 2.1에 기반한 점수를 기록하였다. 전층 절편 조직 검사가 참고 기준으로 제공되었다. 결과 연구에 포함된 환자의 글리슨 점수는 6 (n = 16), 7 (n = 53), 8 (n = 9), 9 (n = 10)로 구성되었다. 두 명의 검토자 모두 계산형 확산강조영상 b2000과 실제 획득한 확산강조영상 b2000 간 전립선암 발견에 대한 민감도 차이는 없었다(검토자 1, 모두 94% [83/88]; 검토자 2, 모두 90% [79/88], 모두 p = 1.000). 관찰자 간 PI-RADS 점수에 대한 일치도는 계산형 확산강조영상에서 0.422 (95% 신뢰구간, 0.240-0.603), 실제 획득한 확산강조영상에서 0.495 (95% 신뢰구간, 0.308-0.683)였다. 결론 계산형 확산강조영상 b2000과 실제 획득한 확산강조영상 b2000은 전립선암 발견 민감도에 차이가 없고, 관찰자 간 일치도는 유지되었다.