Biomedical subjects

Jeong-Won Lee

Publications and source records attributed to Jeong-Won Lee.

16 recordsLinked to original sources

PubMed2026

Dynamics of HER2 status in recurrent cervical cancer: Highlighting the clinical value of reassessment.

OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugates have emerged as a promising therapy, making accurate HER2 assessment important. We assessed HER2 expression in recurrent cervical cancer, examined clinicopathological factors associated with HER2 positivity at recurrence, and analyzed HER2 discordance between matched primary and recurrent tumors. METHODS: We retrospectively identified patients with recurrent cervical cancer treated at a single center between 2013 and 2024. HER2 immunohistochemistry was performed on recurrent and matched primary tumors and scored according to the 2017 ASCO/CAP guideline for gastroesophageal adenocarcinoma. Tumors scoring 2+ or 3+ were classified as HER2-positive. Factors associated with HER2 positivity were analyzed by logistic regression. RESULTS: Among 118 patients, the HER2-positive rate in recurrent tumors was 15.3% (18/118). HER2 positivity was higher in endocervical adenocarcinoma than in squamous cell carcinoma (30.6% vs 8.6%, P = 0.009). Adenocarcinoma (adjusted odds ratio [OR] 4.80; 95% confidence interval [CI], 1.60-15.66) and recurrence outside the prior radiotherapy field (adjusted OR 7.92; 95% CI, 1.68-77.86) were independently associated with HER2 positivity. Among the 72 matched pairs, HER2 discordance was observed in 7 (9.7%), including HER2 gain in 4 of 61 (6.6%) and HER2 loss in 3 of 11 (27.3%). Adenocarcinoma was the only factor associated with discordance (OR 10.33; 95% CI, 1.99-104.04). CONCLUSIONS: In recurrent cervical cancer, HER2 positivity was associated with endocervical adenocarcinoma and recurrence outside the prior radiotherapy field. Reassessing HER2 by re-biopsy at relapse may inform treatment selection in a subset of patients.

Humans↗

PubMed2006

Phase II study of neoadjuvant chemotherapy with mitomycin-c, vincristine and cisplatin (MVC) in patients with stages IB2-IIB cervical carcinoma.

OBJECTIVE: The efficacy and toxicity of neoadjuvant chemotherapy (NAC) with mitomycin-C, vincristine and cisplatin (MVC) were assessed in bulky cervical carcinoma patients. METHODS: Forty-six patients with stage IB2 to IIB cervical cancer were treated with intravenous combination of mitomycin-C 10 mg/m(2), vincristine 1 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. After three cycles of NAC, the patients either underwent surgery or radiation therapy, depending on their suitability for radical hysterectomy. RESULTS: All 46 patients enrolled in this study were suitable for surgery after NAC. Twenty (44%) patients had risk factors after surgery and received postoperative radiation. Toxic nonhematologic reactions consisted primarily of grades 1-2 nausea and vomiting (87%) and the most common hematologic toxicity was anemia (60%). Clinical responses occurred in 83% (38/46) of patients, including 24% (11/46) with a complete response (CR) and 13% (6/46) with a pathologically determined complete response. For a median follow up period of 28 months, the 3-year disease-free and overall survival rates were 74% and 80%, respectively. Pathologically confirmed lymph node metastasis or parametrial involvement and an initial tumor size > or =4 cm were associated with shorter disease-free survival (P=0.040, P=0.000, P=0.025, respectively). CONCLUSION: Intravenous administration of MVC as a NAC seems to be well tolerated and beneficial in patients with stage IB2 to IIB cervical cancer.

Adult↗

PubMed2006

Squamous cell carcinoma with sarcomatoid features of the vulva: a case report and review of literature.

BACKGROUND: A squamous cell carcinoma with sarcomatoid features of the vulva is an extremely rare malignancy of the female genital tract. This type of tumor is known to grow rapidly and associated with poorer clinical outcomes than those of squamous cell carcinoma of the vulva. CASES: A 43-year-old woman presented to our institute with a 4-month history of an aggravated vulvar mass. A radical local excision, bilateral inguinal lymph node dissection and laparoscopic assisted vaginal hysterectomy were performed. The FIGO stage of the vulvar cancer was stage II (T(2)N(0)M(0)) and the pathologic finding was consistent with a poorly differentiated squamous cell carcinoma with extensive sarcomatoid features. No further treatment was given and there was no clinical evidence of recurrence during the 2 years of follow-up. CONCLUSION: A squamous cell carcinoma with sarcomatoid features of the vulva is a tumor with aggressive biological behavior. To date, there have been only 15 cases of this disease reported in the literature. So, a collection and close study of these cases would be extremely useful in singling out and identifying the best treatment possible for this type of tumor.

Adult↗

PubMed2006

High expression of tissue inhibitor of metalloproteinase-2 in serous ovarian carcinomas and the role of this expression in ovarian tumorigenesis.

Tissue inhibitors of metalloproteinases (TIMPs) play key roles in maintaining homeostasis of the extracellular matrix by controlling matrix metalloproteinases (MMPs). In addition to their role in regulating MMPs, TIMPs have also been shown to have pluripotential effects on cell growth, apoptosis, and differentiation. The aim of this study was to evaluate TIMP-2 level in serous ovarian tumor tissues and to understand further the role of TIMP-2 protein in ovarian tumorigenesis. The expression of TIMP-2 was assessed by immunohistochemistry in a total of 57 ovarian specimens, including 5 normal ovaries, 12 benign serous cystadenomas, 20 serous borderline tumors, and 20 serous carcinomas. In addition, we transfected a TIMP-2 plasmid into the gynecologic cancer cell lines SKOV-3, 2774, and HeLa and then assayed cell growth, apoptosis, and MMP-2 activation. We found that TIMP-2 immunostaining was significantly more frequent in serous carcinomas, mainly in tumor epithelium, compared with cells of the other tissues studied. Tissue inhibitor of metalloproteinase-2 overexpression in ovarian cancer cells did not mediate proapoptosis, inhibited cisplatin-induced apoptosis, and induced MMP-2 expression. These findings suggest that TIMP-2 may function to favor tumor growth in serous ovarian tumorigenesis. Additional research is now needed to elucidate further the role of TIMP-2 in the biologic behavior of ovarian serous tumors.

Adult↗

PubMed2006

Expression of CD44 adhesion molecules on human placentae.

OBJECTIVE: This study was performed to characterize CD44 expression in human placentae. STUDY DESIGN: We conducted reverse transcriptase polymerase chain reaction (RT-PCR) analyses of CD44H (hematopoietic form, also called CD44s) and CD44R1 (epithelial form) in 14 normal term placentae, and immunohistochemical analysis of CD44H and CD44v6 in 31 placentae (25 term and 6 first-trimester). RESULTS: All 14 term placentae expressed CD44H (double bands) suggesting expression of alternative isoforms on the placentae. CD44R1 was expressed on 3 of 14 (21.4%) term placentae. Immunohistochemical analysis revealed expression of CD44H in all the placentae examined. However, positive staining for CD44v6 was observed in 3 of 6 (50%) first-trimester and only 6 of 25 (24%) term placentae showing decreased expression on term placentae. Positive staining for CD44v6 was observed on the trophoblast surface of immature villi especially in the sub-chorionic area where hypoxic conditions prevail. CONCLUSION: These results suggest that CD44 splicing variants might play a role in the invasion of trophoblast into maternal tissue in early pregnancy.

Alternative Splicing↗

PubMed2006

Direct interaction between cohesin complex and DNA replication machinery.

Structural maintenance of chromosome 1 (Smc1) is a multifunctional protein, which has been implicated in sister chromatid cohesion, DNA recombination and repair, and the activation of cell cycle checkpoints by ionizing radiation, ultraviolet light, and other genotoxic agents. In order to identify the proteins that interact with Smc1, we conducted the Tandem affinity purification (TAP) technique and analyzed the Smc1-interacting proteins via MALDI-TOF mass spectrometry. We identified minichromosome maintenance 7 (Mcm7), an essential component of the pre-replication complex, as a novel Smc1-interacting protein. Co-immunoprecipitation revealed an interaction occurring between Smc1 and Mcm7, both in vitro and in vivo. Using a GST pull-down assay, we determined that Smc1 interacts physically with Mcm7 via its N-terminal and hinge regions, and Mcm7 interacts with Smc1 via its middle region. Interestingly, we also discovered that Smc1 interacts with other DNA replication proteins, including Mcm6, RFC1, and DNA polymerase alpha. These results suggest that a functional link exists between the cohesin complex and DNA replication proteins.

Cell Cycle Proteins↗

PubMed2006

Preliminary results of neoadjuvant chemotherapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery.

AIM: This study was performed to evaluate the efficacy of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who were inadequate for primary optimal surgery. METHODS: Patients with histologically confirmed epithelial ovarian cancer at International Federation of Gynecology and Obstetrics stages IIIc/IV that was unresectable according to computed tomography findings were eligible for this study. Three cycles of paclitaxel plus cisplatin NAC were administered and the response was evaluated. Patients were then selected for interval debulking surgery or three cycles of additional chemotherapy with the same regimen according to the resectability and response. Interval debulking surgery followed by second-line chemotherapy was applied to patients with no response to NAC. During the same period, patients who did not agree to the protocol were treated by the conventional method of tumor debulking surgery followed by adjuvant chemotherapy, and served as the control group. A comparison of both groups of patients was carried out. RESULTS: A total of 40 patients were involved in the study. All patients were evaluable. Eighteen patients underwent NAC and 22 patients were treated by conventional therapy. Optimal debulking was possible in 14 patients (77.8%) in the NAC group and in 10 patients (45.5%) in the conventional therapy group (P = 0.04). The mean estimated blood loss was 620 cc (range: 300-1500 cc) in the NAC group and 1061 cc (range: 300-3500 cc) in the conventional therapy group (P = 0.04). However, no significant differences were found in the disease-free and overall survival rates between the two groups (P = 0.48 and P = 0.61, respectively). CONCLUSION: NAC provided a higher rate of optimum cytoreduction and equivalent survival with less invasive surgery and reduced morbidity compared with conventional therapy in patients with advanced epithelial ovarian cancer inadequate for primary optimum surgery. Therefore, NAC may be a valuable alternative treatment for these patients.

Adult↗

PubMed2006

Germline mutations of BRCA1 in two Korean hereditary breast/ovarian cancer families.

Testing for cancer susceptibility gene, in particular mutations in the BRCA1 gene in association with hereditary breast/ovarian cancer has been extensively studied. We investigated germline mutations in the BRCA1 gene from two Korean hereditary breast/ovarian cancer families using direct DNA sequencing. Blood samples of the thirteen family members were studied. We found three missense mutations; 3232 Aright curved arrow G, 2731 Cright curved arrow T, 3667 Aright curved arrow G. These mutations were involved in the altered coding of amino acids. According to the BIC database, clinical significance of these mutations is regarded as favor polymorphisms. Therefore, these genetic variations are not believed to be involved in the development of the disease, but may be associated with breast/ovarian cancers in another yet undefined way. For further clinical significance of these variations, additional study such as a case-controlled haplotyping study is needed.

BRCA1 Protein↗

PubMed2005

Decreased galectin-3 expression during the progression of cervical neoplasia.

PURPOSE: Galectin-3 is expressed widely in epithelial and immune cells and the level of expression varies in many cancer cells relative to the normal tissues from which they arise. We investigated whether the expression of galectin-3 is associated with the progression of cervical neoplasia. METHODS: Galectin-3 expression was evaluated in fresh frozen tissues of cervical carcinoma using real-time quantitative RT-PCR. In addition, galectin-3 expression was evaluated at the protein level by immunohistochemistry in 90 formalin-fixed paraffin-embedded cervical tissues, 10 normal cervical specimens, 20 low-grade squamous intraepithelial lesions (LSILs), 20 high-grade squamous intraepithelial lesions (HSILs), and 40 invasive squamous cell carcinomas (ISCCs). RESULTS: Real-time quantitative RT-PCR revealed that galectin-3 expressions in tumor cells were significantly downregulated compared with corresponding normal tissue (P=0.005). Moreover, immunohistochemistry showed that galectin-3 expression was strong in all normal cervical squamous epithelia and gradually decreased in accordance with the histopathologic grades in order LSIL>HSIL>ISCC (P<0.001). CONCLUSIONS: These data constitute the first observation that the expression of galectin-3 is downregulated in cervical cancer tissues and suggest that the decreased expression of this galactoside-binding lectin is associated with the progression of cervical neoplasia.

Disease Progression↗

PubMed2005

eIF-4E expression is associated with histopathologic grades in cervical neoplasia.

Translation initiation factor eIF-4E (eukaryotic initiation factor 4E) is a 25 kd messenger RNA cap-binding phosphoprotein and is involved in the initiation of protein synthesis. The expression is known to be elevated in several carcinomas as compared with normal tissues and benign lesions. In the present study, we undertook to determine whether eIF-4E expression is associated with progression in cervical neoplasia. eIF-4E expression was evaluated by immunohistochemistry in 88 formalin-fixed, paraffin-embedded cervical tissues; 10 normal cervical specimens; 19 low-grade cervical intraepithelial neoplasias (CINs); 19 high-grade CINs; and 40 invasive squamous cell carcinomas (ISCCs). In addition, eIF-4E expression was evaluated at the RNA level in fresh frozen cervical carcinoma tissues by real-time quantitative reverse transcriptase polymerase chain reaction. Immunohistochemical staining showed that eIF-4E expression was undetectable in most normal cervical squamous epithelial tissues (90%), but variable staining was observed in the basal layer of all normal endocervical glands. eIF-4E expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with histopathologic grade in the order low-grade CIN < high-grade CIN < ISCC (P < .001) and, in particular, was strongly detected in all ISCC cases. Furthermore, real-time quantitative reverse transcriptase polymerase chain reaction revealed that eIF-4E expression in tumor was significantly enhanced versus normal cervical tissues (P = .037). These results suggest that eIF-4E may play a significant role in tumor progression of cervical neoplasia and may represent useful markers for malignant transformation of cervical squamous cells.

Biomarkers, Tumor↗

PubMed2005

Adenoid cystic carcinoma of the Bartholin's gland: report of two cases and review of the literature.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the Bartholin's gland is a rare malignancy of the female genital tract and there have been 62 cases of ACC of the Bartholin's gland in the literature. CASES: Two cases of ACC of the Bartholin's gland are reported. CONCLUSION: There is no consensus on optimal treatment of ACC of the Bartholin's gland. Most commonly, wide local excision and radical vulvectomy with or without lymph node dissection, are performed. More long-term follow up is recommended to evaluate optimal primary treatment and roles of radiotherapy and chemotherapy because ACC of the Bartholin's gland recurs and metastasizes long after primary treatment.

Adult↗

PubMed2005

Increased expression of matriptase is associated with histopathologic grades of cervical neoplasia.

Matriptase is an epithelial-derived, integral serine protease that has been implicated in the progression of epithelial tumors. We investigated whether the expression of matriptase is associated with the progression of cervical neoplasia. Using immunohistochemistry, we evaluated the matriptase expression in 89 formalin-fixed paraffin-embedded cervical tissues that included 10 normal cervical specimens, 19 low-grade squamous intraepithelial lesions, 20 high-grade squamous intraepithelial lesions, 20 invasive squamous cell carcinomas (ISCC) without lymph node (LN) metastasis, and 20 ISCC with lymph node metastasis. We also used the reverse transcriptase-polymerase chain reaction technique to determine the expression of matriptase transcripts in normal cervical and ISCC tissues. The immunohistochemical staining showed that the expression of matriptase was undetectable in all normal cervical squamous epithelia, but had cytoplasmic and membranous staining in the normal endocervical glands. Staining gradually increased in accordance with the histopathologic grades from low-grade squamous intraepithelial lesions to high-grade squamous intraepithelial lesions and ISCC ( P < .001); matriptase was detected in most cases (95%) of ISCC. In addition, matriptase transcripts were expressed in all (n = 26) of the ISCC cases by microdissection and reverse transcriptase-polymerase chain reaction, whereas none of the normal squamous epithelia cases (n = 3) expressed matriptase transcripts. These results suggest that matriptase may play a significant role in the development of cervical carcinoma and may serve as a useful marker of the malignant transformation of cervical squamous cells. Further studies could potentially lead to the development of novel approaches for early detection and therapy for this disease.

Biomarkers, Tumor↗

PubMed2005

Increased expressions of claudin-1 and claudin-7 during the progression of cervical neoplasia.

OBJECTIVES: Claudin proteins represent a large family of integral membrane proteins crucial for tight junction formation and function and they have been shown to be expressed differently in various cancers. We investigated whether the expressions of claudin-1 and claudin-7 are associated with the progression of uterine cervical neoplasia. METHODS: We analyzed 89 formalin-fixed paraffin embedded cervical tissues that included 10 normal cervical epithelium, 19 low-grade squamous intraepithelial lesion (LSIL), 20 high-grade squamous intraepithelial lesion (HSIL), 20 invasive squamous cell carcinoma (ISCC) without lymph node (LN) metastasis, and 20 ISCC with LN metastasis. The expressions of claudin-1 and claudin-7 were determined by immunohistochemistry. RESULTS: The expressions of claudin-1 and claudin-7 were undetectable in normal cervical squamous epithelium, but had variable staining in the basal layer of normal endocervical glands. The expressions of both proteins, mainly as membranous staining, gradually increased in accordance with the progression from LSIL to HSIL and ISCC (both P values are <0.001) and were detected in all cases of ISCC. CONCLUSIONS: These results suggest that claudin-1 and claudin-7 may play a significant role in tumor progression of cervical neoplasia and may represent useful markers for malignant transformation of cervical squamous cells. Further studies would likely result in the development of novel approaches for early detection and therapy for this disease.

Carcinoma, Squamous Cell↗

PubMed2005

Selected adnexal cystic masses in postmenopausal women can be safely managed by laparoscopy.

The aim of this study was to assess the efficacy and safety of laparoscopic treatment for adnexal cystic masses that were predicted to be benign in postmenopausal women. Postmenopausal women found to have an adnexal cystic mass were retrospectively evaluated with transvaginal ultrasonography, and serum CA-125 levels. The selection criteria were adnexal cystic masses greater than 3 cm but less than 10 cm, the masses were in the benign range (4-8) of Sassone's scoring system for transvaginal ultrasonography, and the patients had serum CA-125 levels less than 65 IU/mL. Two hundred nineteen women fulfilled the criteria and underwent operative laparoscopy. Almost all the masses (99.5%) were accurately predicted to be benign except for one borderline ovarian tumor. Two hundreds thirteen (97.3%) women were successfully managed by operative laparoscopy and six (2.7%) required laparotomy. For the patients managed by laparoscopy, the mean operative time was 51.3 min; the mean hospital stay was 2.5 days. There was no significant morbidity and surgery-related mortality. The combination of the Sassone's scoring system for transvaginal ultrasonography and serum CA-125 level can accurately predict benign cystic masses, and operative laparoscopy is technically feasible and safe for the management of adnexal mass in postmenopausal women.

Adnexal Diseases↗

PubMed2003

Determination of substrate specificity and putative substrates of Chk2 kinase.

Chk2/hCds1, the human homolog of Saccharomyces cerevisiae Rad53p and Schizosaccharomyces pombe Cds1p, plays a critical role in the DNA damage checkpoint pathway. While several in vivo targets of Chk2 have been identified, the other target proteins of Chk2 responsible for multiple functions, such as cell cycle arrest, DNA repair, and apoptosis, remain to be elucidated. We utilized the GST-peptide approach to identify physiological substrates for Chk2. Mutational analyses using GST-linked Cdc25A containing serine 123 revealed that residues at positions -5 and -3 are critical determinants for the recognition of the Chk2 substrate. We determined the general phosphorylation consensus sequence and identified in vitro targets of Chk2 using GST peptides as substrates. The newly identified in vitro target proteins include Abl1, Bub1R, Bub1, Bub3, Psk-H1, Smc3, Plk1, Cdc25B, Dcamkl1, Mre11, Pms1, and Xrcc9.

Amino Acid Sequence↗

PubMed2002

Differential expressions of Fas and Fas ligand in human placenta.

To investigate the expressions of Fas and Fas ligand (FasL) in human placenta, we studied the expressions of Fas and FasL in placenta with RT-PCR, immunoblotting and immunostaining. We observed amplified products of Fas and FasL transcripts, the band of Fas (52 kDa) and multiple bands of FasL (42-52 kDa) in placenta. Fas and FasL localized mainly on fetal vessels and on syncytiotrophoblasts respectively. The differential distribution of Fas and FasL in human placenta may reflect intrinsic expressions of them by trophoblasts during differentiation. The increased expression of Fas in trophoblasts may promote apoptosis of placenta in pathologic condition such as preeclampsia.

Fas Ligand Protein↗