Search PubMed⌕ Search

Biomedical subjects

Chee-Yin Chai

Publications and source records attributed to Chee-Yin Chai.

At least 19 recordsLinked to original sources
PubMed2025

Spike protein-induced VSIR-ISX signaling disrupts metabolic homeostasis and promotes COVID-19-related immune dysfunction.

COVID-19 has caused millions of deaths worldwide since 2019. Vaccination has reduced both transmission and disease severity. However, emerging viral variants have weakened vaccine effectiveness, highlighting the need for new antiviral therapies. This study examines how the SARS-CoV-2-Spike protein (SARS-2-S) induces the VSIR-ISX signaling pathway, leading to metabolic disturbances that may worsen disease progression. Using RNA sequencing, we found that SARS-2-S expression in pulmonary cells activates genes involved in tryptophan and arachidonic acid (AA) metabolism, altering bioactive mediators like kynurenine and prostanoids, which are crucial for inflammation and immune responses. Mechanistically, the ACE2-MYD88 pathway, activated by SARS-2-S, enhances the VSIR-ISX axis through NF-κB signaling, driving these metabolic disruptions. Chromatin immunoprecipitation and genome sequencing revealed that ISX, activated via VSIR-MAPK signaling, upregulates enzymes involved in AA metabolism by binding directly to their gene promoters. Notably, disrupting the VSIR-ISX axis using shRNA interference or NF-κB inhibitors effectively mitigated these metabolic disturbances. Our findings suggest that the VSIR-ISX pathway could be a promising therapeutic target for treating COVID-19 by addressing virus-induced metabolic disruptions.

Humans↗
PubMed2007

Expression of human telomerase reverse transcriptase and cyclin-D1 in olfactory neuroblastoma.

Olfactory neuroblastoma is an uncommon neoplasm. Typically, these tumors are indolent with long-standing symptomatology, but the fact that the lesions are indeed malignant has been proven by the repeated demonstration that they can metastasize to distant organs. Suitable prognostic factors are lacking and therapeutic strategy still remains controversial. Expression of human telomerase reverse transcriptase (hTERT) is associated with most human malignancies and high levels have been correlated with poor prognosis in many cancers. In comparison, overexpression of cyclin-D1 occurs in several malignancies and has been associated with aggressive tumor behavior and poorer prognosis. In this study, we collected 16 olfactory neuroblastomas from the Kaohsiung Medical University Hospital. The aim was to investigate the value of immunoexpression of hTERT and cyclin-D1 in correlation with clinicopathologic features of olfactory neuroblastoma. Low and high cyclin-D1 expression was found in 6 and 10 cases, respectively. For hTERT, low and high protein expression was detected in 5 and 11 tumors, respectively. Cyclin-D1 expression was not correlated with selected parameters. However, high hTERT expression was significantly correlated with high Kadish stage. In conclusion, high hTERT expression can be considered a potential indicator of aggressive olfactory neuroblastoma.

Biomarkers, Tumor↗
PubMed2006

The expression of CD66a and possible roles in colorectal adenoma and adenocarcinoma.

BACKGROUND: The aim of our study was to analyze the expression and possible role of CD66a in colorectal adenoma and adenocarcinoma and the relationship between its expression and pre-operation serum carcinoembryonic antigen (CEA) level and tumor stage in patients with colorectal adenocarcinomas. METHODS: Paraffin-embedded sections from 184 patients including 42 colorectal adenomas with low-grade dysplasia, 43 adenomas with high-grade dysplasia, and 99 adenocarcinomas were collected for this study. Immunohistochemical analysis was performed, and the expression and the location of CD66a were evaluated and were correlated with beta-catenin nuclear expression. RESULTS: The expression of CD66a was found not only in the apical membrane of neoplastic glands but also in secretion within the lumen of the neoplastic glands including adenomas and adenocarcinomas. Expressions of secreted CD66a were of higher level in adenocarcinoma than in adenoma with high-grade dysplasia and adenoma with low-grade dysplasia (p < 0.0001). High expression of secreted CD66a was also associated with tumor stage, invasion, and pre-operation serum CEA level of patients with colorectal adenocarcinoma. CONCLUSIONS: This study implied that CD66a can function both as an epithelial cell adhesion protein or alternatively as secreted CD66a. In addition, a high expression of CD66a was significantly correlated with tumor invasion, stage, and pre-operation serum CEA level.

Adenocarcinoma↗
PubMed2006

Leptin suppresses human chorionic gonadotropin-induced cyclooxygenase-2 expression and prostaglandin production in cultured human granulose luteal cells.

OBJECTIVE: In a previous study, we demonstrated that high leptin levels at the time of human chorionic gonadotropin (hCG) injection impaired the pregnancy rate for women undergoing in vitro fertilization. In this study we examine leptin's effect on prostaglandin formation and cyclooxygenase (COX) expression induced by hCG in human granulose luteal (GL) cells. METHODS: Human GL cells were obtained from women undergoing ovarian hyperstimulation. COX expression and microsomal prostaglandin E synthase (mPGES) expression, as well as prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) production were studied. This was done in both the presence and absence of leptin following hCG stimulation. PGE(2) and PGF(2alpha) were determined by enzyme-linked immunosorbent assay (ELISA). The expressions of COX and mPGES were investigated by using immunocytochemical techniques in addition to Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. RESULTS: HCG and leptin do not affect COX-1 expression. However, leptin blocked COX-2 and mPGES expression induced by hCG. Moreover, while leptin, in various concentrations, did not affect PGE(2) and PGF(2alpha) levels, it inhibited the elevation of PGE(2) and PGF(2alpha) concentrations in response to hCG. CONCLUSIONS: The study confirms that the expression of COX-2 is up-regulated by hCG in human GL cells. Leptin suppresses hCG-induced PGE(2) formation through the inhibition of COX-2 and mPGES expression. The preliminary results suggest a potential inhibiting effect of leptin on human GL cells induced by hCG.

Adult↗
PubMed2006

Expression of DPC4/Smad4 gene in stone-containing intrahepatic bile duct.

BACKGROUND AND OBJECTIVES: Hepatolithiasis is etiologically related to cholangiocarcinoma. We underwent this study with an attempt to examine the expression of DPC4/Smad4 gene in stone-containing intrahepatic bile ducts (IHD) and intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: The immunohistochemical method and RT-PCR analysis were used to study the expression of DPC4/Smad4 gene in normal IHD, stone-containing IHD, and ICC. All the specimens were from hepatic resection. RESULTS: The immunohistochemical study showed that all specimens from 24 normal IHD had marked expression of DPC4/Smad4 gene, while there was 4.4% (2/46) and 33.3% (3/9) loss of DPC4/Smad4 expression in stone-containing IHD and ICC, respectively. Among the specimens of stone-containing IHD, all the hyperplastic epithelial cells showed normal expression of DPC4/Smad4 gene while dysplastic epithelial cells showed 20% (2/10) loss expression of DPC4/Smad4. The RT-PCR analysis showed that the normal IHD had the highest content of DPC4/Smad4 mRNA, which was threefold and sixfold higher than that of stone-containing IHD and ICC, respectively. CONCLUSION: Loss expression of DPC4/Smad4 gene was found both in stone-containing IHD and ICC. Dysplastic epithelium of stone-containing IHD had higher potential for malignant transformation.

Adult↗
PubMed2006

Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma.

BACKGROUND: Constitutive activation of signal transducer and activator of transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated with many types of human cancers. However, its potential roles and biological effects in hepatocellular carcinoma (HCC) are not well established. AIM: To explore whether an altered p-STAT3 (tyr705) expression is associated with angiogenesis or proliferation and thereby plays a part in HCC development. METHODS: Paraffin-wax-embedded sections from 69 patients with HCC were collected in this study. Using a semiquantitative immunohistochemical staining method, the expression patterns of p-STAT3 (tyr705) in both HCC lesions and the adjacent non-tumorous liver parenchyma were analysed. The results obtained were further correlated with intratumour microvessel density (MVD), Ki-67 expression, clinicopathological parameters and overall survival. RESULTS: A strong p-STAT3 (tyr705) nuclear staining was observed in 49.3% of HCC lesions, but was reported only in 5.8% of the adjacent non-tumorous liver parenchyma (p<0.001). The expression of p-STAT3 (tyr705) in HCC lesions was significantly and positively correlated with the intratumour MVD (p = 0.002), but not with Ki-67 expression. No significant correlation of p-STAT3 (tyr705) was found in addition to histological grading (p = 0.019). Multivariate Cox regression analysis showed that p-STAT3 (tyr705) expression was a significant predictor of overall survival for HCC (p = 0.036), although the Kaplan-Meier survival curves showed no significant difference between the high and low p-STAT3 (tyr705) expression subgroups. CONCLUSIONS: The results showed that p-STAT3 (tyr705) expression was closely correlated with histological grading and intratumour MVD in HCC. Thus, the potential role of p-STAT3 (tyr705) in HCC development may be through these correlations.

Adult↗
PubMed2006

Arsenic carcinogenesis in the skin.

Chronic arsenic poisoning is a world public health issue. Long-term exposure to inorganic arsenic (As) from drinking water has been documented to induce cancers in lung, urinary bladder, kidney, liver and skin in a dose-response relationship. Oxidative stress, chromosomal abnormality and altered growth factors are possible modes of action in arsenic carcinogenesis. Arsenic tends to accumulate in the skin. Skin hyperpigmentation and hyperkeratosis have long been known to be the hallmark signs of chronic As exposure. There are significant associations between these dermatological lesions and risk of skin cancer. The most common arsenic-induced skin cancers are Bowen's disease (carcinoma in situ), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Arsenic-induced Bowen's disease (As-BD) is able to transform into invasive BCC and SCC. Individuals with As-BD are considered for more aggressive cancer screening in the lung and urinary bladder. As-BD provides an excellent model for studying the early stages of chemical carcinogenesis in human beings. Arsenic exposure is associated with G2/M cell cycle arrest and DNA aneuploidy in both cultured keratinocytes and As-BD lesions. These cellular abnormalities relate to the p53 dysfunction induced by arsenic. The characteristic clinical figures of arsenic-induced skin cancer are: (i) occurrence on sun-protected areas of the body; (ii) multiple and recrudescent lesions. Both As and UVB are able to induce skin cancer. Arsenic treatment enhances the cytotoxicity, mutagenicity and clastogenicity of UV in mammalian cells. Both As and UVB induce apoptosis in keratinocytes by caspase-9 and caspase-8 signaling, respectively. Combined UVB and As treatments resulted in the antiproliferative and proapoptotic effects by stimulating both caspase pathways in the keratinocytes. UVB irradiation inhibited mutant p53 and ki-67 expression, as well as increased in the number of apoptotic cells in As-BD lesions which resulted in an inhibitory effect on proliferation. As-UVB interaction provides a reasonable explanation for the rare occurrences of arsenical cancer in the sun-exposed skin. The multiple and recurrent skin lesions are associated with cellular immune dysfunction in chronic arsenism. A decrease in peripheral CD4+ cells was noticed in the inhabitants of arsenic exposure areas. There was a decrease in the number of Langerhans cells in As-BD lesion which results in an impaired immune function on the lesional sites. Since CD4+ cells are the target cell affected by As, the interaction between CD4+ cells and epidermal keratinocytes under As affection might be closely linked to the pathogenesis of multiple occurrence of arsenic-induced skin cancer. In this review, we provide and discuss the pathomechanisms of arsenic skin cancer and the relationship to its characteristic figures. Such information is critical for understanding the molecular mechanism for arsenic carcinogenesis in other internal organs.

Arsenic↗
PubMed2006

A simple and economical method for the manual construction of well-aligned tissue arrays.

Tissue array technology has allowed a substantial progression of studies correlating molecular and immunohistochemical findings with clinico-pathological information. Array construction presents technical difficulties and tissue arrayers are expensive, particularly for small and medium sized laboratories. We describe a simple manual method for producing well-aligned tissue arrays using a hand-made paper mold which can successfully perform immunohistochemical staining. All 200 tissue samples were collected and constructed into blocks by the paper mold. The tissue arrays were smoothly sectioned using a standard microtome and performed for a panel of immunohistochemical study with satisfactory results. This alterative method for building custom arrays could be applied in any laboratory and is both simple and economical.

Humans↗
PubMed2006

Analysis of mastoid findings at surgery to treat middle ear cholesteatoma.

OBJECTIVES: To analyze mastoid findings, such as facial nerve dehiscence (FND), labyrinthine fistula, and dural exposure; to review its incidence at cholesteatoma surgery; to analyze its association with semicircular canal fistula; and to elucidate its relationship with dural exposure. DESIGN: One hundred fifty-two patients (65 males and 87 females; 155 ears) were enrolled in a retrospective study of tympanoplasty with or without mastoidectomy. SETTING: Medical university center hospital. RESULTS: The incidence of FND after exenteration of disease was 29.7% (46/155 ears) for total surgical procedures, 29.7% (43/145 ears) for initial procedures, and 30% (3/10 ears) for revision procedures. The prevalence of FND in the tympanic segment only was 87%, with 8.7% in the vertical segment only and 4.3% in both segments. Three patients (2.0%) developed facial palsy postoperatively, with 8 lateral semicircular canal fistulas (5.2% of total ears operated on), half of these with concomitant FND. The incidence of dural exposure of the mastoid tegmen in the entire surgical group was 16.8% (26 ears), 38.5% with concomitant FND. CONCLUSIONS: The overall incidence of FND in our sample was high at 29.7%, with rates of lateral semicircular canal fistula and dural exposure of 5.2% and 16.8%, respectively. The relationship between FND incidence and presence of lateral semicircular canal fistula was positive in our study. The surgeon should bear in mind that the location of FND with cholesteatoma coincides with the most common area of iatrogenic facial nerve injury during otologic surgery.

Adolescent↗
PubMed2006

Comparative genomic hybridization study of perivascular epithelioid cell tumor: molecular genetic evidence of perivascular epithelioid cell tumor as a distinctive neoplasm.

Perivascular epithelioid cell tumor (PEComa) is a neoplasm composed chiefly of HMB-45-positive epithelioid cells with clear to granular cytoplasm and a perivascular distribution. Such tumors have been reported in different organs under a variety of designations. The cytogenetic features of these neoplasms have not been well studied. We collected 9 tumors (5 of kidney, 1 of prostate, 1 of urinary bladder, 1 of the pelvic cavity soft tissue, and 1 of uterus) from 8 patients, including one patient with tuberous sclerosis complex. The paraffin blocks of tumor tissue were submitted for comparative genomic hybridization analyses. Gross chromosomal aberrances were observed in all cases. The frequent imbalances were losses on chromosome 19 (8 cases), 16p (6 cases), 17p (6 cases), 1p (5 cases), and 18p (4 cases) and gains on chromosome X (6 cases), 12q (6 cases), 3q (5 cases), 5 (4 cases), and 2q (4 cases). The frequent deletion of 16p in which TSC2 gene is located indicates the oncogenetic relationship of PEComas with angiomyolipoma as a TSC2-linked neoplasm. From a molecular genetic perspective, the recurrent chromosomal alterations in both renal and extrarenal tumors further support the concept of PEComa as a distinctive tumor entity regardless of anatomic location.

Adolescent↗
PubMed2006

Role of TTF-1, CK20, and CK7 immunohistochemistry for diagnosis of primary and secondary lung adenocarcinoma.

Thyroid transcription factor-1 (TTF-1), and cytokeratin 7 (CK7) and cytokeratin 20 (CK20) have recently been reported to be useful to distinguish between primary and metastatic lung adenocarcinoma. The aim of this study was to determine the usefulness of the staining patterns of pulmonary adenocarcinoma with antibodies to TTF-1, CK7, and CK20 in differentiating primary from metastatic pulmonary adenocarcinoma. Of the 66 lung adenocarcinoma specimens that were enrolled in our study, there were 40 primary lung adenocarcinomas, 12 metastatic adenocarcinomas from breast, 13 metastatic adenocarcinomas from colon, and 1 metastatic adenocarcinoma from stomach. The expression of TTF-1, CK7, and CK20 was assessed by immunohistochemistry. We found that 73% of primary lung adenocarcinomas expressed TTF-1, whereas all nonpulmonary adenocarcinomas lacked TTF-1 staining. CK7 expression was significantly more frequent in adenocarcinomas of pulmonary and breast origin than gastrointestinal (GI) origin (p < 0.001). In contrast, CK20 expression was significantly more prevalent in adenocarcinoma that originated in the GI tract than that of pulmonary or breast origin (p < 0.001). A combination of TTF-1+CK7+CK20- was highly significantly associated with primary adenocarcinoma of lung (vs GI tract, p < 0.001; vs breast, p < 0.001). A combination of TTF-1-CKCK20+ was highly significantly associated with adenocarcinoma of GI origin (vs lung, p < 0.001; vs breast, p < 0.001). Our study has confirmed that expression of CK7, CK20, and TTF-1 is a useful immunohistochemical marker for diagnosis of lung tumors and for differential diagnosis of primary pulmonary adenocarcinomas from extrapulmonary adenocarcinomas metastatic to the lung. Application of this panel of antibodies might be expected to increase the accuracy of diagnosis.

Adenocarcinoma↗
PubMed2006

Aberrant p53 expression and the development of gallbladder carcinoma and adenoma.

Gallbladder carcinoma (GBC) is a highly lethal but relatively rare neoplasm of the digestive tract. The progression from gallbladder adenoma to carcinoma remains unclear. The p53 gene is the most frequently mutated tumor suppressor in human cancers. In this study, we analyzed the expression patterns of the p53 protein in 22 cases of GBC, 17 cases of precursor lesions (16 gallbladder adenomas and 1 cystadenoma), and 15 cases of normal epithelia using immunohistochemical analysis. The results were correlated with clinicopathologic characteristics. We found that p53 expression was significantly increased in 59.1% (13/22) of GBC cases and in 17.6% (3/17) of gallbladder adenoma cases (p = 0.009). There was no p53 expression in the 15 cases of normal epithelia, and a significant difference was shown between normal epithelium and GBC cases (p < 0.001). In addition, the expression pattern of p53 protein did not show any significant correlation with the histologic type and the differentiation grade of GBC. In conclusion, we suggest that the aberrant p53 expression may play a role in the occurrence of GBC.

Adenoma↗
PubMed2006

A rare case of combined small-cell lung cancer with unusual soft tissue metastasis.

Combined small-cell lung carcinoma (SCLC) is a rare tumor. We report a case of combined SCLC of the lung, including adenocarcinoma and spindle-shaped cell tumor, with an unusual initial presentation. The patient suffered from a right shoulder mass, subsequently undergoing biopsy. A lung nodule was noted later after complete examination. The diagnosis turned out to be combined cell carcinoma with three different components (small-cell carcinoma, adenocarcinoma, and spindle-shaped cell tumor) after examination upon total removal of the lung nodule by lobectomy. In addition to the rarity of the three components in such a tumor, soft tissue metastasis also made it an unusual case.

Adenocarcinoma↗
PubMed2006

Positive association between STAT3 and Ki-67 in cervical intraepithelial neoplasia.

Signal transducer and activator of transcription 3 (STAT3) has been regarded as an oncogene in many types of cancers. However, its role in cervical carcinogenesis is not well determined. The purpose of this study was to evaluate the expression patterns of STAT3 in cervical intraepithelial neoplasia (CIN), normal cervix (NC), and squamous cell carcinoma (SCC) to explore its possible role in cervical carcinogenesis. Paraffin-embedded sections from 83 patients including 20 CIN 1, 10 CIN 2, 26 CIN 3, and 27 comparative cases of 10 NC and 17 stage Ib SCC were collected in this study. Immunohistochemistry was performed to analyze the expression patterns of STAT3, and the results obtained were categorized by a semiquantitative method and were further correlated with the CIN histopathologic grade and the proliferation marker, Ki-67, using the chi2 test. Our results showed that nuclear STAT3 expression was predominantly in the squamous epithelial cells, and that high-grade CIN and stage Ib SCC lesions had a higher nuclear STAT3 expression when compared with NC and CIN 1. Furthermore, the nuclear STAT3 expression in CIN was significantly correlated with Ki-67 expression (p = 0.025), but not CIN lesion grade. In summary, our results indicate that an altered STAT3 expression in CIN is correlated with cell proliferation but may not have a direct contribution to cervical carcinogenesis.

Adult↗
PubMed2006

Primary pulmonary synovial sarcoma: a case report.

We report a rare case of primary synovial sarcoma of the lung. A57-year-old man had a well-defined tumor in the right middle lobe seen on chest computed tomography, and underwent lobectomy. Grossly, the nonencapsulated tumor measured 4.5 cm in greatest diameter, with a solid and tan-white cut surface. Histologically, the tumor was mainly composed of a dense proliferation of spindle cells. Immunohistochemical studies were focally positive for epithelial membrane antigen, and diffusely positive for CD99 and Bcl-2. Cytokeratin, S-100 protein, desmin, smooth muscle act in, and CD34 were absent. SYT-SSX1 gene fusion transcript was detected by reverse transcription-polymerase chain reaction, which is diagnostic of primary synovial sarcoma of the lung. We also review the literature with regard to the clinicopathologic, immunohistochemical, and molecular studies of primary pulmonary synovial sarcoma.

Humans↗
PubMed2006

The prognostic value of proliferating cell nuclear antigen (PCNA) and p53 protein expression in patients with advanced nasopharyngeal carcinoma.

CONCLUSION: p53 protein and proliferating cell nuclear antigen (PCNA) were not ideal prognostic indicators in advanced nasopharyngeal carcinoma (NPC). Further investigation in searching for other potential biomarkers is needed to enhance the prediction of treatment outcome. OBJECTIVE: To assess the prognostic significance of p53 protein and PCNA expression in patients with advanced NPC. PATIENTS AND METHODS: This study included 46 patients with advanced NPC who had received treatment and regular follow-up for at least 5 years. We used immunohistochemistry (IHC) staining to assess p53 protein expression and PCNA labeling index, and correlate them with pathological subtypes, TNM stage, the presence of locoregional recurrence, and 5-year survival rate. RESULTS: p53 nuclear staining was positive in 32 patients (69.6%). All cases had positive PCNA nuclear staining with labeling index (LI) ranging from 6.5% to 92.9% (mean 53.4%). Only advanced T stage was found to be associated with high PCNA LI. Overexpression of p53 and PCNA LI had no impact on 5-year survival in this study group.

Adult↗
PubMed2006

Effects of sildenafil on pulmonary hypertension and levels of ET-1, eNOS, and cGMP in aorta-banded rats.

Sildenafil, an oral phosphodiesterase Type 5 inhibitor, has vasodilatory effects through a cGMP-dependent mechanism. We previously showed that aortic banding could result in left ventricular overloading and pulmonary hypertension (PH). In this study, we investigated whether early administration of sildenafil, either immediately after or 2 weeks after aortic banding, could ameliorate the development of PH and alter gene expression of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS), and alter the levels of cGMP in rats undergoing an ascending aortic banding. Rats (n = 32) were divided into sham-operated and banding groups with or without treatment. The banded rats were further divided into three groups: (i) receiving saline on Days 1-28 (AOB28; n = 8), (ii) receiving saline on Days 1-14 followed by treatment with 50 mg/kg/day sildenafil on Days 15-28 (AOB28/Sil(15-28); n = 8), and (iii) receiving 50 mg/kg/day sildenafil on days 1-28 (AOB28/Sil(1-28); n = 8). The sham-operated rats were administrated saline on Days 1-28 (n = 8). Four weeks after banding, there was a significant development of PH with pulmonary vascular remodeling. Although both sildenafil-treatment groups had significant increases in cGMP and had reductions in the thickening in the medial layer of pulmonary arteriole, notable attenuation of PH occurred only in the AOB28/Sil(1-28) group. PreproET-1 and eNOS messenger RNA (mRNA) expressions were measured by competitive reverse transcription polymerase chain reaction, and eNOS protein was determined by Western blotting. Sildenafil did not alter the elevated ET-1 or preproET-1 mRNA in banded rats. Interestingly, pulmonary eNOS increased in the AOB28/Sil(1-28) group. In conclusion, early treatment with sildenafil inhibited the rise in pulmonary arterial pressure and pulmonary vascular remodeling in PH secondary to heart failure, and cGMP, but not ET-1, might be involved. Clinically, early repeated administration of sildenafil may offer an alternative in protecting against PH in heart failure.

Animals↗