• 대한영상의학회지
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• 제84권3호
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• pp.676-685
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• 2023

목적 본 연구는 무증상 여성의 유방 초음파에서 발견된 군집 미세낭종의 발생률, 임상적 결과 및 영상 소견을 알아보고, 적절한 조치 가이드라인을 제시하고자 한다. 대상과 방법 2014년 8월부터 2019년 12월까지 무증상 여성에서 시행한 유방 초음파에서 발견된 군집 미세낭종 병변에 대해 분석하였다. 최종 진단은 병리학적 결과 및 12개월 이상의 추적관찰로 하였다. 결과 100명의 환자에서 117개 병변이 후향적으로 연구되었으며, 군집 미세낭종의 발생률은 1.5%였다. 총 117개의 병변 중, 3개(2.6%)는 악성, 2개(1.7%)는 고위험 병변, 112개(95.7%)는 양성이었다. 악성 병변 중 2개는 관상피내암이었고, 1개는 침윤성 유관암이었다. 이중, 유방 촬영술에서 의심스러운 미세석회화 또는 초음파에서 내부 혈류를 보인 2개의 병변은 category 4로 분류되었다. 나머지는 12개월 뒤 시행한 초음파에서 echo pattern의 변화를 보인 위 음성의 증례였다. 결론 무증상 여성에서 시행한 유방 초음파에서 군집 미세낭종의 유병률은 1.5%였으며, 악성률은 2.6%였다. 군집 미세낭종의 악성률과 양성 및 악성 영상 소견을 아는 것은 영상의학과 의사들이 병변을 분류하고 적절한 조치를 권유하는 데 도움이 될 것이다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권5호
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• pp.373-384
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• 2001

Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

• Tuberculosis and Respiratory Diseases
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• 제46권4호
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• pp.523-532
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• 1999

연구배경: 폐암은 조기진단이 어려운 대표적인 종양이다. 최근 정상세포에서 악성조직으로 진행되는 각각의 과정에 대한 연구가 활발해 지면서 폐암의 발병과 진행에 관계하는 여러 유전자와 염색체의 이상들이 발견되고 있다. 이에 근거하여 폐암 중에서도 객담 세포진검사나 기관지내시경 검사 등으로 진단이 용이하고, 조기진단의 의의가 높은 편평상피 폐암을 대상으로 종양세포와 인접 정상 세포에서의 p53 및 c-erbB2의 발현율과 그 의의를 알아보았다. 대상 및 방법: 1995년 5월부터 1996년 11월까지 15개월 동안 편평상피 폐암으로 진단되어 폐절제술을 받은 25명의 환자를 대상으로 하여, 종양부위 및 그 인접 정상세포에서의 p53과 c-erbB2의 발현 여부를 면역조직화학적 검사법을 이용하여 조사하고 폐암의 병리적 병기 및 환자의 생존기간에 따른 발현율의 차이를 후향적으로 조사하였다. 결 과: 25명의 환자 중에서 병리적 병기 I, II가 각각 5명, IIIA가 8명, IIIB가 4명 및 IV가 3명이었다. 종양조직에서의 p53은 12명(48%), erb-B2는 3명(12%)에서 발현되었다. 인접 정상 기관지세포에서는 erb-B2는 3명(12%)에서 발현되었으나 p53은 한 예에서도 발현되지 않았다. 종양세포에서, 병기 II기 이하인 군 10명과 IIIA기 8명 및 IIIB와 IV기의 7명으로 나눠서 비교한 결과 p53이 발현된 경우는 각각 2예, 4예 및 6예로 병기가 진행될수록 발현율은 유의하게 높아졌다(p=0.009 by test of trend). 그러나 종양세포에서 이들의 발현여부에 따른 생존기간은 차이가 없었다. 결 론: p53은 정상 기관지세포에서는 전례에서 발현되지 않았으나 페종양조직에서는 발현율이 48%로 나왔으며, 발현율은 병기가 진행할수록 높아졌다. 따라서 기관지 생검조직에 p53을 이용한 면역조직화학적검사를 병행할 경우 편평상피세포 폐암의 경우 조기진단이나 병기판정에 도움이 될 것으로 추정되나 더 많은 환자를 대상으로 한 연구가 필요할 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4347-4351
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• 2012

Background: Breast cancer is the most common cancer of women and the principal cause of death in middle aged women. The objective of this study was to describe the trend of breast cancer and its management in Aden and adjacent south-eastern governorates of Yemen during the last 20 years. Patients and Methods: This is a retrospective analysis of previous studies on patients with breast cancer in Aden and adjacent south-eastern governorates, Yemen (January 1989 through December 2007). The studied variables were: sex, age, time and type of presentation, disease stage, pathological types and the performed surgical treatment. The sources of information were the treatment registry of Aden health office, archives of Al-Gamhouria teaching hospital; major referral and other public and private hospitals in Aden and Aden Cancer Registry. Results: The total number of patients was 476, 99% being females. The age range was 19-88 years. The most affected age was 30-50 years (60.5%), 95% presenting after one month of having breast symptoms. Forty-five percent presented with signs of advanced local disease, while 59.2% had palpable axillary lymph nodes on presentation. Early breast cancer (stages I-II) occurred in 47%, and late breast cancer (stages III-IV) in 51.5%. Invasive ductal carcinoma was the commonest pathology (89.3%). The main surgical treatment was mastectomy (modified radical mastectomy (50%). Conclusion: Breast cancer is predominantly a disease of young with late presentation and advanced disease. Improving health awareness and earlier diagnosis of the disease by health education, encouraging breast self-examination, and providing the mammography equipment and mammary clinics in hospitals are recommended. Establishment of oncology and radiotherapy centers in Aden is a necessity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4507-4511
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• 2014

Background: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with many targeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy for triple negative breast cancer has been discovered to date and hence further research is needed. Aim: The aim and objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC) in North-East India and to compare the clinicopathological parameters in two study groups defined by immunohistochemistry (IHC) - "TNBC" and "Others". Materials and Methods: We carried out a retrospective study in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr. B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3 years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into two groups - "TNBC" and "Others". All relevant clinicopathological parameters were compared in both. TNBC were defined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while those positive for any of these markers were defined as "Others". Results: In this study, out of total 972 cases 31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as "Others" based on IHC markers. Compared to the "Others" category, TNBC presented at an early age (mean 40 years), were associated with high grade large tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC. Conclusions: TNBC accounts for a significant portion of breast cancers in this part of India and commonly present at younger age and tend to be large high grade tumours.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1833-1837
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• 2015

An aristolactam-type alkaloid, isolated from Orophea enterocarpa, is enterocarpam-III (10-amino-2,3,4,6-tetramethoxyphenanthrene-1-carboxylic acid lactam). It is cytotoxic to various human and murine cancer cell lines; however, the molecular mechanisms remain unclear. The aims of this study were to investigate cytotoxic effects on and mechanism (s) of human cancer cell death in human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells compared to normal murine fibroblast NIH3T3 cells. Cell viability was determined by MTT assay to determine $IC_{10}$, $IC_{20}$ and $IC_{50}$ levels, reactive oxygen species (ROS) production with 2',7'-dichlorohydrofluorescein diacetate and the caspase-3, -8 and -9 activities using specific chromogenic (p-nitroaniline) tetrapeptide substrates, viz., DEVD-NA, IETD-NA and LEHD-NA and employing a microplate reader. Mitochondrial transmembrane potential (MTP) was measured by staining with 3, 3'-dihexyloxacarbocyanine iodide ($DiOC_6$) and using flow cytometry. The compound was cytotoxic to HepG2 and MDA-MB-231 cells with the $IC_{50}$ levels of $26.0{\pm}4.45$ and $51.3{\pm}2.05{\mu}M$, respectively. For murine normal fibroblast NIH3T3 cells, the $IC_{50}$ concentration was $81.3{\pm}10.1{\mu}M$. ROS production was reduced in a dose-response manner in HepG2 cells. The caspase-9 and -3 activities increased in a concentration-dependent manner, whereas caspase-8 activity did not alter, indicating the intrinsic pathway activation. Enterocarpam-III decreased the mitochondrial transmembrane potential (MTP) dose-dependently in HepG2 cells, suggesting that the compound induced HepG2 cell apoptosis via the mitochondrial pathway. In conclusion, enterocarpam-III inhibited HepG2 and MDA-MB-231 cell proliferation and induced human HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway and induction of caspase-9 activity.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.262-266
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• 2007

ENPP2, a 125 kDa secreted lysophopholipase D which originally identified as a tumor-motogen, Autotaxin, enhances cellular locomotion, cell proliferation, angiogenesis and cell survival by generating the signal molecule lysophosphatic acid or sphingosine-1-phosphate. Previous studies have suggested that expression of Autotaxin is associated with invasive phenotype in advanced breast carcinomas. Thus, to determine whether genetic alterations of ENPP2 gene are involved in the development or progression of breast cancer, we analyzed its somatic mutation in 85 breast carcinomas by single-stranded conformational polymorphism and sequencing. Overall, six ENPP2 mutations were found (7.0%), comprising five missense and one nonsense mutation (s). To our knowledge, this is the first report on ENPP2 mutation in breast carcinoma, and the data indicate that ENPP2 is occasionally mutated in breast carcinomas, and suggest that ENPP2 mutation may contribute to the tumor development in some breast carcinomas.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제11권1호
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• pp.203-220
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• 1989

Ever since the expression of new tumor-specific antigens was reported during malignant transformation, studies on separation, purification and characterization of these proteins have been so activated recently. Following experiment was performed to observe tumor-specific antigens by implanting DMBA pellet into submaxillary gland of rat for inducing salivary gland tumor. After dividing 280 rats into 2 groups, in control group, sham operation was performed on right submaxillary gland and, in experimental group, DMBA pellet (5mg) was implanted into right submaxillary gland. Then proteins from excised submaxillary gland by killing 10 rats every two weeks for 28 weeks were extracted with 3M KCl, and SDS-PAGE and PAS-staining were carried out for biochemical examination. The obtained results were summarized as follows; 1) At 12th week since implantation of DMBA pellet, tumor mass formation was inspected. And dysplasia at 6th week and invasive epidermoid carcinoma at 10th week were observed by microscope. 2) In control group, the weight ratio of both submaxillary glands had no any change, however, in experimental group, the ratio was increased remarkably. And at 28th week after DMBA implantation, there was more than 15 times of differences in weight between control and experimental group. 3) There was no DMBA remnant after 22nd experimental week. 4) In the SDS-PAGE, high molecular protein bands (more than 100 kd) were appeared much, and new prominent protein bands (66, 48, 41.5, 39, 37, 37.5 kd) were appeared after 4th week since DMBA implantation. However, 38, 27, 22kd protein bands were disappeared. 5) In PAS-staining, high molecular proteins were proteins were all glycoproteins and 37.5kd protein was proved as to be glycoprotein. And 38kd glycoprotein was disappeared after 4th week since DMBA implantation.

• 대한두경부종양학회지
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• 제12권1호
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• pp.26-31
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• 1996

Radiation therapy in T1 glottic cancer offers an excellent cure rate with preservation of voice. From 1983 to 1992 eighty nine patients with TNM staged T1N0M0 invasive squamous cell carcinoma of the glottis were treated at the Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University. There were 84 men and 5 women with median age of 59 years. All patients were treated either with Co-60 teletherapy unit or 4MV linear accelerator with an median dose of 6400 cGy(6000-7000 cGy), 200 cGy per day, 5 days in a week. Fourteen local failures have been observed and the median time to local recurrence was 17 months. There were no nodal failure without local recurrence or distant metastases. The 5 year local control rate was 84.3%. The 5 year actuarial surivival rate and the 5 year disease free survival rate were 89.2%, 87.5%, respectively. The 5 year actuarial survival rate and the 5 year disease free survival rate of the nineteen patients with anterior commissure involvement were 77.8% and 74.5% which were lower than those of seventy patients without anterior commissure involvement(91.6%, 90.6%)(p < 0.05). Among the several influencing factors, anterior commissure involvement was the significant prognostic foctor. Final local control rate, taking into account the salvage surgery, was 89.9% at 5 years.

• Journal of Chest Surgery
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• 제50권3호
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• pp.153-162
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• 2017

Background: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. Methods: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. Results: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. Conclusion: C HIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.