Coexistence of submandibular epithelioid angiosarcoma and papillary thyroid carcinoma: A case report.

INTRODUCTION: Reports on the coexistence of epithelioid angiosarcoma (EA) and papillary thyroid carcinoma (PTC) are rare. Over the past 50 years, only 2 cases of coexistence of EA and PTC have been reported in English literature. Therefore, we report a rare case of coexistence of EA and PTC treated with surgery and adjuvant radiation therapy. PATIENT CONCERNS: A 64-year-old man visited our hospital with a painless mass in the left submandibular gland, with poor mobility. DIAGNOSIS: Neck ultrasonography revealed nodules in the left submandibular gland and multiple cystic-solid mixed nodules in the left thyroid gland. Pathological findings revealed coexistence of EA in the left submandibular gland area and PTC in the left thyroid gland. INTERVENTIONS: The patient underwent resection of the left submandibular gland, deep maxillofacial tumor, total thyroidectomy, left neck I, II, III, and VI regional lymph node dissection, and recurrent laryngeal nerve exploration under general anesthesia. Two months postoperatively, the patient also received adjuvant radiation therapy in the local and adjacent areas, with 4MV-X IMRT DT50GY at 2Gy/day 25 fractions. OUTCOMES: The follow-up period was 37 months. The patient recovered well without focal neurological deficits, local recurrence, or distant metastasis after surgery, except for grade I skin reaction after adjuvant radiation therapy. CONCLUSIONS: This is a rare case report of the coexistence of EA in the left submandibular gland and PTC in the left thyroid gland. Although multiple examinations were used, precise preoperative diagnosis was challenging owing to the coexistence of EA and PTC. Surgery and radiotherapy were effective treatments for the coexistence of EA and PTC in this case.

The Role, Function, and Mechanism of Long Intergenic Noncoding RNA1184 (linc01184) in Colorectal Cancer.

BACKGROUND: Long intergenic noncoding RNA1184 (linc01184) has been recently discovered; however, its role in human diseases is limited to date. The present study is aimed at investigating the expression pattern and mechanism of linc01184 in colorectal cancer (CRC) tumorigenesis. METHODS: The expression of linc01184 in CRC tissues and cell lines was compared with that in normal controls. The functions of linc01184 in CRC cells were identified by overexpression and small interfering RNA (siRNA) approaches in vitro. Meanwhile, the target gene prediction software, luciferase reporter, RNA pull-down, and western blotting assays were used to analyze the oncogenic mechanism. RESULTS: We found that linc01184 was obviously upregulated in CRC tissues and cells when compared to normal controls, and its upregulation had a positive association with the CRC progression. linc01184 knockdown significantly suppressed CRC cell proliferation and invasion and promoted apoptosis. Besides, linc01184 acted as a competitive endogenous RNA (ceRNA) by directly binding to microRNA-331 (miR-331), and its overexpression resulted in notable increases of human epidermal growth factor receptor 2 (HER2), phosphorylated Ser/Thr kinases (p-Akt), and extracellular regulated protein kinase 1/2 (p-ERK1/2) at posttranscriptional levels in CRC cells, which were antagonized by miR-331. CONCLUSIONS: The findings reveal for the first time that linc01184 is an enhancer for the proliferation and invasion of CRC by functioning as a ceRNA through the linc01184-miR-331-HER2-p-Akt/ERK1/2 pathway regulatory network.

An immune cell infiltration-based immune score model predicts prognosis and chemotherapy effects in breast cancer.

Background: Immune cells have essential auxiliary functions and influence clinical outcomes in cancer, with high immune infiltration being associated with improved clinical outcomes and better response to treatment in breast cancer (BC). However, studies to date have not fully considered the tumor-infiltrating immune cell (TIIC) landscape in tumors. This study investigated potential biomarkers based on TIICs to improve prognosis and treatment effect in BC. Results: We enrolled 5112 patients for analysis and used cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT), a new computational algorithm, to quantify 22 TIICs in primary BC. From the results of univariate Cox regression, 12 immune cells were determined to be significantly related to the overall survival (OS) of BC patients. Furthermore, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to construct an immune prognostic model based on six potential biomarkers. By dividing patients into low- and high-risk groups, a significant distinction in OS was found in the training cohort, with 20-year survival rates of 42.6% and 26.3%, respectively. Applying a similar protocol to validation and test cohorts, we found that OS was significantly shorter in the high-risk group than in the low-risk group, regardless of the molecular subtype of BC. Using the immune score model to predict the effect of BC patients to chemotherapy, the survival advantage for the low-risk group was evident among those who received chemotherapy, regardless of the chemotherapy regimen. In evaluating the predictive value of the nomogram, a decision curve showed better predictive accuracy than the standard tumor-node-metastasis (TNM) staging system. Conclusion: The immune cell infiltration-based immune score model can be effectively and efficiently used to predict the prognosis of BC patients as well as the effect of chemotherapy.

Synchronous primary malignant neoplasms of the cervix and endometrium.

Synchronous multiple malignant neoplasms of the female genital tract are rare, particularly in the uterus. We herein present the case of a patient with synchronous cervical squamous epithelial carcinoma and endometrial adenocarcinoma, and discuss the diagnosis, treatment and prognosis. The patient underwent a cervical biopsy and fractional curettage of the endometrium, followed by abdominal staging surgery, including radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy. The diagnosis was stage Ib1 cervical cancer and stage Ia endometrial cancer, without lymph node metastases. There has been no recurrence during 1 year of followup. Synchronous genital tract neoplasms are more clinically complex compared with single neoplasms and it is crucial to focus on the differential diagnosis between primary and metastatic tumors during the diagnostic process. The treatment of synchronous genital tract neoplasms also differs significantly from that of single neoplasms, although the prognosis of patients with synchronous gynecological malignancies does not appear to be worse.

Combined effects of glutathione S-transferase M1 and T1 polymorphisms on risk of lung cancer: Evidence from a meta-analysis.

Many studies have reported an association between the glutathione S-transferase M1 null and T1 null polymorphisms and lung cancer risk. However, the combined effects of GSTM1 null and GSTT1 null polymorphisms have not been reported previously. We, therefore, performed a meta-analysis to investigate the combined effects. 40 publications with 44 case-control studies were selected in the meta-analysis, including 13,706 cases and 13,093 controls. Significant association was observed between the combined effects of GSTM1 and GSTT1 polymorphisms and lung cancer risk when all the eligible studies were pooled into the meta-analysis. When we performed subgroup analysis, significantly increased lung cancer risk was observed in Caucasians (- - vs. + + : OR = 1.23, 95% CI: 1.07 to 1.41), Asians (- - vs.- +: OR = 1.24, 95% CI: 1.10 to 1.41; recessive model: OR = 1.45, 95% CI: 1.19 to 1.77; dominant model: OR = 1.53, 95% CI: 1.24 to 1.90), Indians (- - vs. + + : OR = 2.53, 95% CI: 1.61 to 3.98; recessive model: OR = 1.69, 95% CI: 1.07 to 2.67; dominant model: OR = 2.11, 95% CI: 1.36 to 3.28), hospital-based studies, and population-based studies. In summary, this meta-analysis indicates that the combined effects of the GSTM1 and GSTT1 polymorphisms are associated with increased lung cancer risk in Asians, Caucasians, and Indians.

Lipoprotein lipase and phospholipid transfer protein overexpression in human glioma cells and their effect on cell growth, apoptosis, and migration.

Glioma is one of the common tumors in brain. The expression level of lipoprotein lipase (LPL) or phospholipid transfer protein (PLTP) may influence glioma progression and its relationship with clinical and pathological parameters. The clinical significance of LPL or PLTP expression in glioma has not been established. In the present study, the LPL and PLTP levels in glioma tumors were investigated and the relationship between the LPL and PLTP level and the grade of malignant glioma was analyzed, with the aim to provide new ideas for the diagnosis and treatment of gliomas in clinical and basic research settings. LPL and PLTP mRNA and protein levels were significantly higher in Grade IV glioma than those in the lower grade tumors (P < 0.01). Double immunofluorescent staining showed that the levels of LPL and PLTP were significantly associated with the pathological grade of glioma (P = 0.005). The levels of LPL and PLTP were increased with the shortened survival of glioma patients (P < 0.001). Knockdown of LPL and PLTP led to decreased cell growth and migration but increased apoptosis in vitro Additionally, cell cycle-related cyclins and their partners were found to be down-regulated while cyclin-dependent kinase inhibitors p16, p21, and Rb were up-regulated. Furthermore, knockdown of LPL or PLTP resulted in the up-regulation of pro-apoptotic molecules and the down-regulation of anti-apoptotic molecules. Ablation of LPL or PLTP in U251 cells resulted in the down-regulation of epithelial mesenchymal transition markers and invasion molecules matrix metalloproteinases. LPL and PLTP appear to be novel glioma-associated proteins and play a role in the progression of human glioma.

Perineal leiomyoma in a postmenopausal woman: A case report.

Leiomyomas in the female reproductive system are commonly located in the uterus and typically regress following the menopause. Vulval leiomyomas are rare, and to the best of our knowledge, perineal leiomyomas in postmenopausal women have not been previously reported in the literature. The present case describes a 60-year-old Chinese woman who experienced perineal tenderness and lumbosacral radiating pain. The patient, who went through the menopause 12 years previously, had presented with a painful perineal mass for 1 year, which was subsequently diagnosed as a postmenopausal perineal leiomyoma. The mass was locally resected, and histopathological examination of the lesion resulted in a diagnosis of benign epithelioid leiomyoma. Immunohistochemical staining identified that the leiomyoma was positive for estrogen receptor and negative for progesterone receptor expression. The patient was followed up for 1 year and did not experience any pain or recurrence. The symptoms of local and lumbosacral radiating pain are extremely rare and may be induced by peripheral nerve stimulation. The etiology of postmenopausal perineal leiomyoma may be associated with infection, dietary, stress and environmental factors, and the role of estrogen cannot be overemphasized in cases of postmenopausal leiomyoma.

Vaginal implantation metastasis of endometrial carcinoma: A case report.

Endometrial cancer is the most common malignancy of the female reproductive system. The three common spread patterns of endometrial cancer are local invasion, lymphatic spread and hematogenous spread. Vaginal metastasis occurs by submucosal lymphatic or vascular metastases in ~10% of patients with clinical stage I disease. Vaginal implantation metastasis of endometrial cancer is extremely rare. Here we present a case of endometrial carcinoma (International Federation of Gynecology and Obstetrics stage IA) spread to the vagina by implantation metastasis as opposed to any of the methods mentioned above. This conclusion was confirmed mainly from pathological examination. This case highlights the occurrence of vaginal implantation metastasis of endometrial carcinoma. Certain changes may be applied during surgery to prevent implantation metastasis in patients with endometrial cancer.

Primary mucinous adenocarcinoma of the vulva: A case report and review of the literature.

Primary vulvar cancer is a rare disease with an incidence of 2-3 per 100,000 women. The vast majority of vulvar carcinomas are of the squamous cell type (90%). Primary vulvar adenocarcinomas rank among the rare gynecological malignancies. We herein present a case of a vulvar mass near the vaginal orifice, the biopsy of which revealed a mucinous adenocarcinoma. Local excision was performed, followed by postoperative chemotherapy. The patient was asymptomatic and developed no recurrence during the 2 years of follow-up after surgery and chemotherapy. We consider local excision, with or without chemotherapy, to be an effective therapeutic approach to this type of tumor. However, further studies are required to support our conclusions for early-stage vulvar mucinous adenocarcinoma.

MiR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer.

MicroRNAs (miRNAs) regulate cell proliferation, apoptosis and carcinogenesis by targeting related mRNAs in different types of cancer. miR-331-3p has been found to regulate the development and progression of various types of cancer cells. However, little research has been conducted on the role of miR-331-3p in colorectal cancer (CRC). The present study aimed to explore the function of miR-331-3p in CRC. We found that miR-331-3p was significantly downregulated in CRC tissues and cells compared to the level in healthy colon tissues and cells. Overexpression of miR-331-3p by transfection with pre­miR-331-3p inhibited cell proliferation, promoted apoptosis and activated caspase-3. Furthermore, the protein expression level of apoptosis-related protein Bcl-2 was downregulated and Bax was upregulated by pre­miR­331-3p. Downregulation of the expression of miR-331-3p by transfection with AS-miR-331-3p had the opposite effect. Moreover, we found that HER2 was overexpressed in the CRC cell lines, and the expression level of HER2 was negatively regulated by miR­331-3p. Additionally, knockdown of HER2 inhibited cell proliferation and phosphorylation of Akt and ERK1/2 induced by AS-miR-331-3p. Overall, we identified that miR­331-3p is underexpressed in CRC and contributes to cell growth regulation by targeting HER2 through activating the PI3K/Akt and ERK1/2 signaling pathways.

Ipsilateral breast metastasis from a pulmonary adenocarcinoma: a case report and a focused review of the literature.

Metastases to the breast from extramammary malignancies are extremely rare. Ruling out the diagnosis of primary breast tumor is important in order to decide on clinical management and predict prognosis. We report a case of metastasis to the breast from a pulmonary adenocarcinoma, with extensive micropapillary component, diagnosed concomitantly with the primary tumor. A 52 year-old female patient presented with mammary gland tingling and dyspnea accompanied with fatigued of 4 months duration and a nodular shadows in the front of the upper lobe was found on a chest computed tomography (CT) scan. The original clinical diagnosis was right breast cancer with lung and bone metastasis, or breast and lung double primary cancers. In addition,on physical examination a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent thoracocentesis and breast biopsy. By imageology, cytology, histology and immunohistochemistry, we diagnosed primary lung cancer with metastases to the right breast and bone. The metastatic anatomic sites demonstrated histologically extensive micropapillary component, which is recently recognized as an important prognostic factor. The patient was administered 4 cycles of cisplatin and docetaxel, although no clinical response was seen, the patient is still alive 9 months after diagnosis. The result of immunohistochemistry is a useful supplement in differential diagnosis.

Report of six kidney disease-associated Castleman's disease cases.

Castleman's disease (CD) is an uncommon, benign, non-neoplastic, lymphoproliferative disease of uncertain etiology. Here, we report 6 cases of kidney disease-associated CD in China. All patients exhibited multicentric CD (MCD) with involvement of the mediastinum, neck, bilateral axillary, and bilateral inguinal regions. Clinical manifestations included fever, fatigue, edema, and swollen lymph nodes. Laboratory examinations of all 6 patients found proteinuria or renal insufficiency. Two of the patients were diagnosed with hyaline vascular type MCD, and 4 patients were diagnosed with plasma cell type CD. The case 1 and case 4 patients had mesangial proliferative glomerulonephritis, case 3 had type I membranoproliferative glomerulonephritis, case 2 and case 5 had interstitial nephritis, and case 6 had AA type amyloidosis nephropathy. Three patients were treated with prednisone plus cyclophosphamide, 1 patient received COP therapy (cyclophosphamide, vincristine and prednisone), and 2 patients received COP therapy supplemented by small doses of radiation therapy delivered to local lymph nodes. In all cases, the clinical manifestations of MCD, including fever, fatigue, edema, swollen lymph nodes, and proteinuria, were alleviated or abolished by treatment. One patient responded to treatment with complete MCD remission, and another 4 patients survived. However, 1 patient died due to renal failure. In conclusion, common diagnosis and treatment techniques are suitable for kidney disease-associated CD. However, treatment efficacy might be difficult to predict, and some cases may have poor prognosis with this treatment strategy. Therefore, additional studies investigating kidney disease-associated CD and treatment outcomes in larger patient populations are needed.

Lysophosphatidic Acid Inhibits Apoptosis Induced by Cisplatin in Cervical Cancer Cells.

Cervical cancer is the second most common cause of cancer death in women worldwide. Lysophosphatidic acid (LPA) level has been found significantly increased in the serum of patients with ovarian, cervical, and colon cancers. LPA level in cervical cancer patients is significantly higher than in healthy controls. LPA receptors were found highly expressed in cervical cancer cells, suggesting LPA may play a role in the development of cervical cancer. The aim of this study is to investigate the effect of LPA on the apoptosis induced by cisplatin (DDP) in cervical cancer cell line and the underlying changes in signaling pathways. Our study found that cisplatin induced apoptosis of Hela cell through inhibiting expression of Bcl-2, upregulating the expression of Bax, Fas-L, and the enzyme activity of caspase-3 (p < 0.05); LPA significantly provided protection against the apoptosis induced by cisplatin by inhibiting the above alterations in apoptotic factor caused by cisplatin (p < 0.05). Moreover, PI3K/AKT pathway was found to be important for the LPA antiapoptosis effect, and administration of PI3K/AKT partially reversed the LPA-mediated protection against cisplatin-induced apoptosis (p < 0.05). These findings have shed new lights on the LPA bioactivity in cervical cancer cells and pointed to a possible sensitization scheme through combined administration of PI3K inhibitor and cisplatin for better treatment of cervical cancer patients, especially those with elevated LPA levels.

Rab31 promoted hepatocellular carcinoma (HCC) progression via inhibition of cell apoptosis induced by PI3K/AKT/Bcl-2/BAX pathway.

Rab31 belongs to the Ras superfamily of small GTP-binding proteins, which has been found to regulate the vesicle transport from the Golgi apparatus to early and late endosomes. The investigation here detected the expression of Rab31 in 96 patients with hepatocellular carcinoma (HCC) and tried to identify its significance on outcome of HCCs after liver resection. By immunohistochemistry staining, it was found that Rab31 expression in HCC tissues was remarkably higher than that in adjacent liver tissues. Aberrant Rab31 overexpression in HCC tissues was identified to be associated with worse prognosis after liver resection. Univariate analysis showed that advanced tumor-nodes-metastasis (TNM) staging of HCC, intrahepatic metastases, portal vein invasion, and higher Rab31 were the predictive factors of poor prognosis. Multivariate analysis demonstrated that intrahepatic metastases and higher Rab31 were the independent prognostic factors. Furthermore, forced expression of Rab31 in Huh7 cells was found to promote cell growth via upregulation of Bcl-2/BAX ratio induced by PI3K/AKT. Correspondingly, silencing Rab31 induced cell apoptosis and in turn suppressed the growth capacity of MHCC97 cells in vitro. Taken together, this study provides the evidence of Rab31 overexpression in HCC, and Rab31 is potentially used as a novel biomarker of poor prognosis in patients with HCC. PI3K/AKT/Bcl-2/BAX axis was involved in Rab31-promoting HCC progression.

GPER in CAFs regulates hypoxia-driven breast cancer invasion in a CTGF-dependent manner.

Recent advances indicate that cancer­associated fibroblasts (CAFs) play a key role in cancer progression by contributing to invasion, metastasis and angiogenesis. Solid tumors often experience low oxygen tension environments, which induce gene expression changes and biological features leading to poor outcomes. The G-protein estrogen receptor (GPER) exhibits a stimulatory role in diverse types of cancer cells and in CAFs under hypoxic conditions. We investigated the role of CAFs and hypoxia in breast cancer aggressiveness, and examined the effect of GPER in CAFs on hypoxia-driven breast cancer progression. The results showed that hypoxia upregulated HIF-1α, GPER and α-SMA expression in CAFs, and induced the secretion of Interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) in CAFs. However, GPER silencing abrogated the above hypoxia-driven cytokine expression in CAFs. Moreover, knockdown of GPER in CAFs suppressed breast cancer cell invasion induced by CAF conditioned media (CM). Furthermore, GPER silencing in CAFs inhibited hypoxia-increased CTGF expression in CAFs and breast cancer cells cultured with CM from CAFs under hypoxic conditions. In addition, CTGF is responsible for the observed effects of GPER on CAFs activation and breast cancer invasion. Our findings further extend the molecular mechanisms through which the tumor microenvironment may contribute to cancer progression.

[Pathological and immunological changes of renal transplant rejection: report of 56 cases].

OBJECTIVE: To investigate the pathological and immunological changes of renal grafts in recipients experiencing graft rejection. METHODS: The clinicopathologic data of 56 renal needle biopsy samples obtained from renal transplant recipients were analyzed retrospectively. The specimens were classified histopathologically according to the Banff 2009 classification system and analyzed by immunohistochemical labeling and immunofluorescence. RESULTS: In the 56 recipients, 1 (1.79%) experienced hyperacute rejection, 8 (14.29%) had suspected acute rejection, 12 (21.43%) developed acute T-cell rejection, 6 (10.71%) had acute antibody-mediated rejection, 2 (3.57%) had acute T-cell rejection with acute antibody-mediated rejection, 12 (21.43%) had chronic active T cell-mediated rejection, 2 (3.57%) had chronic active antibody-mediated rejection, 2 (3.57%) had chronic active T cell-mediated rejection with antibody-mediated rejection, 8 (14.29%) had non-specific interstitial fibrosis and tubular atrophy, and 3 (5.36%) had normal graft function. The expression levels of immune markers CD3, CD4, CD8, CD20, GrB and perforin differed with the types of T cell-mediated graft rejection, and the positivity and expression levels of these markers tended to increased with the severity of graft rejection. The expression of C4d was positive in all cases with antibody-mediated graft rejection. CONCLUSIONS: The pathological characteristics of the renal biopsy specimens and expression levels of the immune markers allow timely and accurate evaluation of graft rejection type to provide a reliable pathological and etiological basis for clinical treatment and prognostic assessment.

Affinity peptide developed by phage display selection for targeting gastric cancer.

AIM: To develop an affinity peptide that binds to gastric cancer used for the detection of early gastric cancer. METHODS: A peptide screen was performed by biopanning the PhD-12 phage display library, clearing non-specific binders against tumor-adjacent normal appearing gastric mucosa and obtaining selective binding against freshly harvested gastric cancer tissues. Tumor-targeted binding of selected peptides was confirmed by bound phage counts, enzyme-linked immunosorbent assay, competitive inhibition, fluorescence microscopy and semi-quantitative analysis on immunohistochemistry using different types of cancer tissues. RESULTS: Approximately 92.8% of the non-specific phage clones were subtracted from the original phage library after two rounds of biopanning against normal- appearing gastric mucosa. After the third round of positive screening, the peptide sequence AADNAKTKSFPV (AAD) appeared in 25% (12/48) of the analyzed phages. For the control peptide, these values were 6.8 ± 2.3, 5.1 ± 1.7, 3.5 ± 2.1, 4.6 ± 1.9 and 1.1 ± 0.5, respectively. The values for AAD peptide were statistically significant (P < 0.01) for gastric cancer as compared with other histological classifications and control peptide. CONCLUSION: A novel peptide is discovered to have a specific binding activity to gastric cancer, and can be used to distinguish neoplastic from normal gastric mucosa, demonstrating the potential for early cancer detection on endoscopy.

[Biological behaviour of colon cancer cells transfected with C-erbB2 shRNA plasmid].

AIM: To study the changes of the cell growth, cell cycle distribution and cell apoptosis of colon cancer cell, HT-29, when C-erbB2 gene was knockdown by shRNA against C-erbB2. METHODS: Cell growth, cell cycle distribution and cell apoptosis were compared among three groups including plasmid experimental group(PEG), transfected reagent control group(TRCG)and negative plasmid control group(NPCG). Cell growth was measured by MTT assay. Cell cycle distribution and cell apoptosis were detected by flow cytometry. RESULTS: The inhibition rate of cell growth of PEG, TRCG and NPCG were 39.65%, 7.23% and 8.05% respectively. The cell growth was significantly inhibited in PEG(P<0.01). The cells of G0/G1 phase were 74.93%, 67.19%, 68.05% respectively in PEG, TRCG and NPCG. The cells of G0/G1 phase in PEG were significantly more than those in TRCG and NPCG(P<0.05).While the cells of S phase were 7.81%, 14.02%, 13.70% in PEG, TRCG and NPCG respectively. The cells of S phase in PEG were significantly less than those in TRCG or NPCG(P<0.05).The cell apoptosis rate were 19.21%, 3.13%, 4.08% in PEG, TRCG and NPCG respectively. The cell apoptosis rate in PEG was significantly higher than those in TRCG or NPCG(P<0.01). CONCLUSION: Cell growth was inhibited by shRNA against C-erbB2 gene. Cell cycle was blocked in G0/G1 phase and apoptosis was induced by C-erbB2 shRNA. This indicates C-erbB2 gene plays important roles in the carcinogenesis and development of colon cancer.

RNAi-mediated ERBB2 gene knockdown sensitizes human colorectal cancer cells to radiation.

This study aimed to investigate the involvement of c-erbB-2, encoded by the receptor tyrosine kinase ERBB2 gene, in the pathogenesis of colorectal cancer and to validate its potential as an anticancer target. Immunohistochemical and histopathological analyses were applied in tissue samples derived from 80 colorectal cancer patients. ERBB2 stable small hairpin RNA (shRNA) knockdown in HT29 human colorectal cancer cells was confirmed by RT-PCR and western blotting. Cell cycle profile and apoptosis were measured using PI or Annexin V-PI dual staining. A significant correlation between ERBB2 levels and Dukes' stage of colorectal cancer, in both the primary malignancy and lymph node metastatic tissues, was observed. ERBB2-depleted HT-29 cells exhibited increased sensitivity to radiation compared to control cells, likely due to enhanced G0/G1 phase cell cycle arrest and apoptosis. ERBB2 may be involved in the malignancy and metastasis of colorectal cancer. Overexpressed ERBB2 may constitute a potential target for colorectal cancer therapy.

[Construction and identification of CerbB-2 siRNA expression plasmid and its transfer into human colon cancer cell lines HT-29].

OBJECTIVE: To construct a plasmid carrying small interfering RNA (siRNA) targeting human C-erbB2 gene (pGenesil- erbB2) and test its effect on Her-2 expression at the post-transcriptional level in human colon cancer cell lines HT-29 cells that highly express erbB2. METHODS: A HT-29 cell line that highly expressed CerbB-2 was selected using immunohistochemical method. The double-stranded siRNA targeting human CerbB-2 cDNA and the negative control fragment were cloned into pGenesil-1 vector, and after identification and sequence analysis, the constructed pGenesil-erbB2 plasmid was transfected into the selected HT-29 cell line. RESULTS: The pGenesil-erbB2 plasmid was successfully constructed and stably transferred into HT-29 cells. The transfection resulted in significant inhibition of Her-2 protein expression in the HT-29 cells, as shown by Western blotting. CONCLUSION: The pGenesil-erbB plasmid we constructed can be stably transfected into HT-29 cells to inhibit the expression of Her-2 protein, and can be useful in further studies of increasing the radiosensitivity of HT-29 cell lines.