• Journal of Microbiology and Biotechnology
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• 제34권4호
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• pp.920-929
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• 2024

As a pivotal defensive line against multitudinous malignant tumors, natural killer (NK) cells exist in the tumor microenvironment (TME). RAD18 E3 Ubiquitin Protein Ligase (RAD18) has been reported to foster the malignant progression of multiple cancers, but its effect on NK function has not been mined. Here, the study was designed to mine the mechanism by which RAD18 regulates the killing effect of NK cells on colorectal cancer (CRC) cells. Expression of E2F Transcription Factor 7 (E2F7) and RAD18 in CRC tissues, their correlation, binding sites, and RAD18 enrichment pathway were analyzed by bioinformatics. Expression of E2F7 and RAD18 in cells was assayed by qRT-PCR and western blot. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay verified the regulatory relationship between E2F7 and RAD18. CCK-8 assay was utilized to assay cell viability, colony formation assay to detect cell proliferation, lactate dehydrogenase (LDH) test to assay NK cell cytotoxicity, ELISA to assay levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and immunofluorescence to detect expression of toxic molecules perforin and granzyme B. High expression of RAD18 and E2F7 was found in CRC tissues and cells. Silencing RAD18 could hamper the proliferation of CRC cells, foster viability and cytotoxicity of NK cells, and increase the secretion of GM-CSF, TNF-α, IFN-γ as well as the expression of perforin and granzyme B. Additionally, ChIP and dual-luciferase reporter assay ascertained the binding relationship between RAD18 promoter region and E2F7. E2F7 could activate the transcription of RAD18, and silencing RAD18 reversed the inhibitory effect of E2F7 overexpression on NK cell killing. This work clarified the inhibitory effect of the E2F7/RAD18 axis on NK cell killing in CRC, and proffered a new direction for immunotherapy of CRC in targeted immune microenvironment.

• Restorative Dentistry and Endodontics
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• 제9권1호
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• pp.15-24
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• 1983

Irradiation is frequently employed as the sole therapy for oral cancer. These irradiated patients presents peculiar and progressive dental problems. But there is only scanty informations concerning specific approaches to endodontic treatment for head and neck cancer patients who have been subjected to tumorcidal doses of radiation therapy. The purpose of the present study was to determine the effects of cobalt-60 radiation on the pulpal healing of dogs after the direct pulp capping. As the experimental animals, 10 dogs (above 7-8 months after birth) were divided into 3 groups (Control, Group I, Group II). The cobalt-60 was irradiated to the Group I and Group II each 1,009 and 1,562.5 rads as single dose. As the capping material Dycal$^{(R)}$(L.D. Caulk company) was selected. After the direct pulp capping the dogs were sacrified 1, 2, 3, 4, week interval and made the original slides cut with a thickness of 8 microns and stained with hematoxylin and eosin. After examination and comparision of all specimen, the results of this study were drawn as follows; 1. The formation of reparative dentin was observed from the 1st week in the Control group, the 2nd week in the Group I & II. The few and irregular tuble structure was appeared in the 4th week in the Control group only, but failed in the Group I & II. 2. The continuity of dentin bridge was appeared in the 3rd week in all group and the degeneration of odontoblast in the 1st week of the Group II. 3. The congestion and hemorrhage in the pulp tissue were observed in all groups until 3rd week. The inflammation was appeared within the 2nd week in the Group I and especially marked in the Group II, but absent in the Control group. 4. In cases Dycal into the pulp tissue deeply, the local necrosis of pulp and decrease of dentin formation was observed.

• Archives of Plastic Surgery
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• 제33권6호
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• pp.711-714
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• 2006

Purpose: Contralateral reduction mammaplasty at the time of breast reconstruction using autogenous tissue gives aesthetically improved results in the patients with mammary hypertrophy or ptosis. It also reduces required flap size for reconstruction and permits discarding zones of poor perfusion, decreasing flap size-related problems such as partial flap loss or fat necrosis. Considering the high rate of bilaterality of breast cancer, it also provides a good opportunity for exploration and occult cancer diagnosis in such high risk group patients. Methods: We retrospectively reviewed 45 consecutive patients who underwent simultaneous breast reconstruction and contralateral reduction mammaplasty was performed about surgical technique, pathologic diagnosis, and subsequent treatment. Results: Three occult breast cancers were found in 45 patients(6.7%); one was microinvasive, and the other two were invasive carcinomas and their mean diameter was 1.2 cm. One patient underwent subsequent breast conserving mastectomy, adjuvant radiation and chemotherapy. The others underwent only radiation and hormone therapy. They were followed up for 10 to 42 months without evidence of recurrence or metastasis. Conclusion: Occult breast cancer diagnosed in reduction mammaplasty specimen will lead to good prognosis due to its early detection. Treatment options depend on pathologic finding, stage, marginal status, and the timing of diagnosis. We recommend adequate markings for orientation and margins, excision with sufficient margin, and confirmation by frozen biopsy for suspected lesions.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제37권
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• pp.7.1-7.7
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• 2015

Background: Osteoradionecrosis is a delayed complication from radiation therapy which causes chronic pain, infection and constant deformity after necrosis. Most of the osteoradionecrosis occurs spontaneously or after the primary oncologic surgery, dental extraction or by trauma of prosthesis. The treatment of osteoradionecrosis relies on both conservative measures and surgical measures. The fibular osteocutaneous free flap has become more popular choice for reconstruction of maxillofacial defects as a treatment of osteoradionecrosis. Methods: We presented our experiences from 7 patients with osteoradionecrosis who have had reconstruction surgery with fibular osteocutaneous free flap at National Cancer Center during the recent 5 years. We performed segmental mandibular resection with fibular osteocutaneous free flap for all 7 patients of advanced osteoradionecrosis who were not controlled by conservative treatment such as wound irrigation, debridement, and antibiotics. Results: A wide range of techniques were available for the reconstruction of composite defects resulted from the treatment of advanced mandibular osteoradionecrosis. Significant improvement was noted in relieving pain and treating trismus after the surgery however difficulty in swallowing and xerostomia showed less improvement. Conclusions: We concluded that fibular osteocutaneous free flap can be performed safely in patients with osteoradionecrosis and yields positive outcomes with significantly increased success rate. The fibular osteocutaneous free flap was our preferred choice for the mandibular reconstruction due to its versatility and predictability.

• Journal of Radiation Protection and Research
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• 제14권1호
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• pp.1-7
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• 1989

우라늄 피폭으로 발생하는 다뇨증과 급성 신부전증의 원인을 밝히기 위하여, 질산 우라늄을 정맥주사한 후 소변으로 배설되는 $Na^{+},\;K^{+}$의 전해질 양과 $Na^{+}-K^{+}$ adenosine triphosphatase($Na^{+}-K^{+}$ATPase) 활성도 변화를 측정하였다. 질산 우라늄 투여 24시간 이내에 $Na^{+},\;K^{+}$의 배설량이 크게 증가 하였고, 투여 3일 후에는 대조군과 비교하여 유의하게 감소하였다. 이때 $Na^{+},\;K^{+}$의 소변내 농도도 정상 대조군 범위 이하였다. 한편 $Na^{+}-K^{+}$ATPase활성은 투여 3일후에 고농도 질산 우라늄 투여 (30mg/kg BW) 시에만 감소 하였고, 저농도 투여군(5mg/kg BW, 15mg/kg BW) 에서는 활성 변화가 없었다.

• Journal of Ginseng Research
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• 제36권1호
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• pp.68-77
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• 2012

In this study, we investigated the protective effects of processed Panax ginseng, sun ginseng (SG) against the UVB-irradiation on epidermal keratinocytes and dermal fibroblasts. Pretreatment of SG in HaCaT keratinocytes and human dermal fibroblasts reduced UVB-induced cell damage as seen by reduced lactate dehydrogenase release. We also found that SG restored the UVB-induced decrease in anti-apoptotic gene expression (bcl-2 and bcl-xL) in these cells, indicating that SG has an anti-apoptotic effect and thus can protect cells from cell death caused by strong UVB radiation. In addition, SG inhibited the excessive expression of c-jun and c-fos gene by the UVB in HeCaT cells and human dermal fibroblasts. We also demonstrated that SG may exert an anti-inflammatory activity by reducing the nitric oxide production and inducible nitric oxide synthase mRNA synthesis in HaCaT keratinocytes and human dermal fibroblasts. This was further supported by its inhibitory effects on the elevated cyclooxygenase-2 and tumor necrosis factor-${\alpha}$ transcription which was induced by UVB-irradiation in HaCaT cells. In addition, SG may have anti-aging property in terms of induction of procollagen gene expression and inhibition of the matrix metalloprotease-1 gene expression caused by UVB-exposure. These findings suggest that SG can be a potential agent that may protect against the dermal cell damage caused by UVB.

• Molecules and Cells
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• 제42권2호
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• pp.151-160
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• 2019

Ultraviolet (UV) radiation of the sunlight, especially UVA and UVB, is the primary environmental cause of skin damage, including topical inflammation, premature skin aging, and skin cancer. Previous reports show that activation of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) in human skin fibroblasts and keratinocytes after UV exposure induces the expression and release of proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), and subsequently leads to the production of matrix metalloproteases (MMPs) and growth factor basic fibroblast growth factor (bFGF). Here, we demonstrated that TNFR2-SKEE and TNFR2-SKE, oligopeptides from TNF receptor-associated factor 2 (TRAF2)-binding site of TNF receptor 2 (TNFR2), strongly inhibited the interaction of TNFR1 as well as TNFR2 with TRAF2. In particular, TNFR2-SKE suppressed UVB- or $TNF-{\alpha}$-induced nuclear translocalization of activated $NF-{\kappa}B$ in mouse fibroblasts. It decreased the expression of bFGF, MMPs, and COX2, which were upregulated by $TNF-{\alpha}$, and increased procollagen production, which was reduced by $TNF-{\alpha}$. Furthermore, TNFR2-SKE inhibited the UVB-induced proliferation of keratinocytes and melanocytes in the mouse skin and the infiltration of immune cells into inflamed tissues. These results suggest that TNFR2-SKE may possess the clinical potency to alleviate UV-induced photoaging in human skin.

• Korean Journal of Radiology
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• 제25권10호
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• pp.876-886
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• 2024

Objective: To develop a nomogram that integrates clinical-pathologic and imaging variables to predict ipsilateral breast tumor recurrence (IBTR) in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS). Materials and Methods: This retrospective study included consecutive women with DCIS who underwent BCS at two hospitals. Patients who underwent BCS between 2003 and 2016 in one hospital and between 2005 and 2013 in another were classified into development and validation cohorts, respectively. Twelve clinical-pathologic variables (age, family history, initial presentation, nuclear grade, necrosis, margin width, number of excisions, DCIS size, estrogen receptor, progesterone receptor, radiation therapy, and endocrine therapy) and six mammography and ultrasound variables (breast density, detection modality, mammography and ultrasound patterns, morphology and distribution of calcifications) were analyzed. A nomogram for predicting 10-year IBTR probabilities was constructed using the variables associated with IBTR identified from the Cox proportional hazard regression analysis in the development cohort. The performance of the developed nomogram was evaluated in the external validation cohort using a calibration plot and 10-year area under the receiver operating characteristic curve (AUROC) and compared with the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. Results: The development cohort included 702 women (median age [interquartile range], 50 [44-56] years), of whom 30 (4%) women experienced IBTR. The validation cohort included 182 women (48 [43-54] years), 18 (10%) of whom developed IBTR. A nomogram was constructed using three clinical-pathologic variables (age, margin, and use of adjuvant radiation therapy) and two mammographic variables (breast density and calcification morphology). The nomogram was appropriately calibrated and demonstrated a comparable 10-year AUROC to the MSKCC nomogram (0.73 vs. 0.66, P = 0.534) in the validation cohort. Conclusion: Our nomogram provided individualized risk estimates for women with DCIS treated with BCS, demonstrating a discriminative ability comparable to that of the MSKCC nomogram.

• Journal of Radiation Protection and Research
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• 제32권4호
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• pp.140-156
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• 2007

본 연구는 방사선 조사선량에 따른 난소조직의 형태학적 변화과정을 규명하고자 하였다. X-선을 생쥐에 전신조사한 후, BrdU, TUNEL, p53, p21, PCNA, $inhibin-{\alpha}$ 등을 면역조직화학반응을 통하여 확인하였으며, 난포의 미세구조적 변화를 고배율의 전자현미경을 이용하여 관찰하였다. X-선을 조사한 난소조직은 방사선량이 증가함에 따라 성장 난포의 형태적 변화가 뚜렷하였으며, 특히 과립층세포의 변성에 의한 핵은 응축과 투명대의 변화가 현저하였다. 또한 Masson's trichrome 염색과 세망섬유 염색을 통한 조직화학반응의 결과 과립층세포의 변화와 난포기저막의 변형, 그리고 세망섬유의 비정상적 배열이 확인되었다. BrdU 반응결과, 방사선 조사량이 증가함에 따라 양성반응을 보이던 정상난포의 과립층세포가 급격히 감소하였으며, 세포예정사(apoptosis)를 확인하기 위한 TUNEL 반응에서는 정상난소의 퇴화난포에서만 양정반응을 보이던 과립층세포들이, 방사선량의 증가에 따라 성장난포 및 원시난포 등으로 확대되었으며, X-선 600 cGy 조사량에서는 난모세포의 세포예정사도 확인되었다. 세포주기 조절단백질인 p53 단백질의 난소 내 발현을 면역조직화학반응으로 관찰한 결과, 방사선량의 증가에 따라 p53의 발현도 증가하였으며, X-선 600 cGy 조사된 실험군에서는 난포막세포를 포함한 난포의 거의 모든 세포에서 광범위한 발현이 확인되었다. 또한 유사분열 억제단백질인 p21 단백질의 발현은 난포의 과립층세포에서 현저하였으며, 조사량이 증가함에 따라 난포강 주위에서 강한 양성반응이 관찰되었다. 생식세포의 증식을 확인하기 위한 PCNA 반응에서는 정상 대조군의 성장난포와 성숙난포 및 원시난포 등에서 모두 강한 양성반응을 보였으나, 방사선량이 증가함에 따라 반응도가 현저히 감소되었다. 특히 난모세포 주위의 과립층세포가 난포막에 인접한 세포에 비해 반응도의 차이가 심한 점으로 미루어, 난모세포와 난포동에 인접한 세포들이 방사선 조사에 의해 가장 먼저 손상을 받는 것이 확인되었다. 난포의 $inhibin-{\alpha}$ 단백질의 발현은 난포의 성장시기에 따라 차이를 보여, 난포동이 형성된 성숙난포에서 강한 양성반응을 보였다. 난포막 주변의 과립층세포에서 강한 양성반응이 관찰되었으나, 난포막을 구성하는 난막세포에서는 전혀 발현되지 않았다. 방사선 조사에 의해 $inhibin-{\alpha}$의 발현은 정상 대조군에 비해 현저히 감소하였으나, X-선 600 cGy의 선량에서는 약간 증가하는 양상을 보였는데, 이는 과립층세포의 세포사에 따른 현상인 것으로 추정되었다. 방사선 조사에 따른 난소조직의 미세구조 변화를 관찰하기 위하여 고배율의 전자현미경으로 관찰한 결과, 방사선량의 증가에 따라 성장난포의 과립층세포에서 핵과 세포질의 미세구조 변형이 급격히 증가하였으며, 난포동에서는 세포사의 부산물인 세포 잔유체들과 백혈구 및 대식세포 등이 관찰되었다. 과립층세포의 미세구조적 변형은 주로 핵의 응축에 의한 전자밀도의 증가와 핵의 분절화, 그리고 세포질의 위축 등, 전형적인 세포예정사의 특성을 나타내고 있었다. 세포의 괴사도 일부 확인되었으나 그다지 현저하지 않았으며, apoptotic body와 함께 대식세포가 산재되어 있었다. 방사선(X-선) 조사 및 선량증가에 따라 정상 난소조직의 난포액의 불균질 물질의 생성, 난포의 기저막의 염색성출현, 세포예정사 발생, 대식세포들의 변화 등을 확인하였다. 이 결과를 통하여 여성 자궁암을 방사선치료 시 방사선조사범위내에 포함되는 정상 난소조직에 초래 될 수 있는 방사선 생물학적 장해를 이해할 수 있다 하겠다.