The expression and clinical significance of PLK1/p-PLK1 protein in NK/T cell Lymphoma.

AIMS: To investigate the expression of polo-like kinase 1 protein (PLK1) and its phosphorylation level (p-PLK1) in extranodal NK/T cell lymphoma (NKTCL) and their correlation with clinical characteristics and prognosis. METHODS: We collected 40 cases of NKTCL (referred to as the experimental group), which received diagnoses at the First Affiliated Hospital of Zhengzhou University between January 2018 and October 2022. Concurrently, we assembled a control group, including 20 cases afflicted with nasopharyngeal mucosal lymphoid hyperplasia diseases during the same timeframe. We utilized immunohistochemical techniques to evaluate the levels of PLK1 and p-PLK1 expression in both the experimental and control groups. Subsequently, we conducted an analysis to identify disparities in their expression and explore their relationships with clinical characteristics and patient prognosis. RESULTS: Among the 40 NKTCL patients, there were 27 males and 11 females, with a median age of 51 years (range 12-80 years). Compared to the control group, the tissue samples of NKTCL patients exhibited significantly elevated expression levels and active phosphorylation levels of PLK1 (P < 0.05). Correlation analysis of the immunohistochemical H score and Ki-67 positive rate of PLK1 and p-PLK1, revealed a significant positive correlation for both (P < 0.0001, each). No statistically significant differences were observed in the distribution of PLK1 and p-PLK1 expression in NKTCL patients with respect to gender, age, Ann Arbor stage, PINK-E score, B-symptoms, lactate dehydrogenase, ß2-microglobulin, blood EBV-DNA, bone marrow invasion, and lymph node metastasis (p > 0.05). Grouping based on PLK1 and p-PLK1 immunohistochemical H-scores revealed that the high expression of PLK1 and p-PLK1 was associated with poor prognosis. CONCLUSIONS: The expression levels and active phosphorylation levels of PLK1 were significantly increased in NK/T cell lymphoma, and patients with overexpression of PLK1 and p-PLK1 had a poorer prognosis.

Clinicopathological features of CD5-positive splenic marginal zone lymphoma.

AIMS: To investigate the clinicopathological features, immunophenotypes and differential diagnosis of CD5-positive splenic marginal zone lymphoma (SMZL). METHODS: We retrospectively analysed 16 CD5-positive cases of SMZL. Assess their clinicopathological features and survival outcomes to evaluate their similarities and differences with a control group of 25 CD5-negative cases of SMZL. RESULTS: Compared with CD5-negative patients, CD5-positive SMZL tends to be more prone to B symptoms, peripheral lymphadenopathy and extranodal infiltration, high Ann Arbor stage, high International Prognostic Index scores, high serum lactic dehydrogenase and high rates of bone marrow involvement. The 5-year survival rate was significantly shorter than that of the CD5-negative group (52.1% and 81.8%, respectively). CONCLUSIONS: There are many similarities between CD5-positive SMZL and classical CD5-negative SMZL in clinical presentations, morphology and immunohistochemistry, but the former may have a more aggressive clinical course with a poorer prognosis.

A retrospective study on the clinicopathological and molecular features of 22 cases of natural killer/T-cell lymphoma in children and adolescents.

Natural killer/T-cell lymphoma (NKTCL) in children and adolescents is a rare type of T/NK cell neoplasms. The aim of the present study was to analyze the clinicopathological and genetic features of this rare entity of lymphoma. We evaluated the clinical, histopathological and molecular features of 22 young people with NKTCL, including 15 males and 7 females, with a median age of 15 years. The results revealed that the nasal site was the most involved region while non-nasal sites were observed in 27.3% out of all cases. The tumor cells were composed of small­sized to large cells and 19 (86.4%) cases exhibited coagulative necrosis. The neoplastic cells in all patients were positive for CD3 and the cytotoxic markers. Nineteen (86.4%) cases were positive for CD56. Reduced expression of CD5 was observed in all available cases. CD30 was heterogeneously expressed in 15 (75.0%) cases. All 22 patients were EBV positive. Seven (36.8%) out of all the 19 patients during the follow-up died of the disease, and the median follow­up period was 44 months. Moreover, patients treated with radiotherapy/chemotherapy showed significantly inferior OS compared with the untreated patients. High mutation frequencies were detected including KMT2C (5/5), MST1 (5/5), HLA-A (3/5) and BCL11A (3/5), which involved in modifications, tumor suppression and immune surveillance. These results suggest that NKTCL in children and adolescents exhibits histopathological and immunohistochemical features similar to the cases in adults. Active treatment is necessary after the diagnosis of NKTCL is confirmed. Furthermore, genetic analyse may provide a deep understanding of this rare disease.

GNAQ T96S mutation abrogates the ability of wild-type GNAQ to induce apoptosis by phosphorylating annexin A2 in natural killer/T cell lymphoma.

Our previous study identified annexin A2 (ANXA2) as a Gaq-interacting partner in natural killer/T cell lymphoma (NKTCL) cells transfected with the GNAQ T96S mutation vector by immunoprecipitation and mass spectrometry; however, the detailed molecular mechanisms by which GNAQ T96S might regulate ANXA2 remain to be defined in NKTCL. Herein, we found that the GNAQ T96S mutation significantly promotes the phosphorylation of ANXA2 at the Y24 site, whereas phosphorylation of ANXA2 abolishes the ability of WT GNAQ to trigger cell apoptosis. Further investigation revealed that a GNAQ T96S peptide inhibitor induced apoptosis by competing with ANXA2 binding to GNAQ T96S in NKTCL cells. In vivo animal experiments showed that a GNAQ T96S peptide inhibitor suppresses the growth of NKTCL cells carrying the GNAQ T96S mutation. Our current data suggest a role for GNAQ T96S/Src/ANXA2 in mediating the apoptosis of NKTCL cells, and the GNAQ T96S peptide could be a promising agent for therapy in NKTCL patients.

Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma.

Background: E2F transcription factors is a family of transcription factors, and lots of studies have shown that they play a key role in the occurrence and development of many tumors. However, the association between expression, prognostic value, and immune infiltration in the tumor microenvironment of the eight E2Fs members in ccRCC is still unclear. Method: s. We used online databases, such as ONCOMINE, UALCAN, Kaplan-Meier plotter, GEPIA, Metascape, TIMER, and cBioPortal, to analyze the effect of mRNA expression of E2Fs family members in ccRCC on the prognosis of patients and the relationship with immune infiltration. Results: Except for E2F5, other seven members of the family of E2Fs mRNA expression levels in ccRCC tissues were significantly higher than control tissues. And the high expression of E2Fs mRNA in ccRCC patients was related to cancer stage and tumor grade. Survival analysis results suggested that elevated mRNA expression levels of E2F1/2/3/4/7/8 were significantly related to the shorter overall survival (OS) in ccRCC patients (P = 3.9E - 06), while high mRNA expression of E2F6 is not related to OS (P = 0.061). Mutations of E2Fs were correlated with shorter OS of ccRCC patients (P = 7.094E - 5). In addition, mRNA expression of E2F1/2/3/4/7/8 was positively correlated with infiltration of six types of immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions: These results indicate that E2F1/2/3/4/7/8 may be used as a prognostic marker for the survival of ccRCC patients and laid the foundation for studying the immune infiltration role of E2Fs family members in tumors.

Distinctive genomic characteristics in POLE/POLD1-mutant cancers can potentially predict beneficial clinical outcomes in patients who receive immune checkpoint inhibitor.

BACKGROUND: Mutations in POLE /POLD1 proofreading domain can cause deficiencies in DNA repair, conferring ultramutated cancer phenotypes. Preliminary clinical studies have revealed an association between POLE/POLD1 mutations and beneficial clinical outcomes to immune checkpoint inhibitor (ICI) therapy This study aims to investigate the genomic characteristics of POLE/POLD-mutant tumors and the prognostic value of POLE/POLD mutation for ICI treatment. METHODS: Genomic data of 21,074 patients with 23 cancer types were retrieved from Burning Rock variant database (BR VarDB). The prevalence and spectra of POLE and POLD1 mutations were assessed and compared with that in The Cancer Genome Atlas (TCGA) samples. The correlations of POLE/POLD1 mutation with tumor mutational burden (TMB) and microsatellite instability (MSI) were investigated. The prognostic value of POLE/POLD1 mutations was also explored in 2,487 ICI-treated patients from published studies. RESULTS: BR VarDB samples displayed a similar mutational prevalence of POLE (3.2% vs. 3.2%) and POLD1 (1.4% vs. 1.6%, P=0.248) versusTCGA samples, but a slightly lower frequency of POLE and POLD1 co-mutations (0.21% vs. 0.43%, P<0.001). POLE/POLD1-mutant tumors harbored increased TCT→TAT and TCG→TTG transversions, and genomic signatures associated with DNA mismatch repair (MMR) deficiency and ultra-hypermuation. Furthermore, tumors with POLE/POLD1 proofreading mutation showed a significantly higher TMB than tumors with non-proofreading mutations (P<0.01), although both possessed a higher TMB than POLE/POLD1 wild-type (WT) tumors (P<0.0001 and P<0.0001, respectively). MSI was commonly observed in tumors harboring dominant clone of POLE/POLD1 mutation (10.2%), but occurred rarely in POLE/POLD1 WT tumors (0.5%) and tumors with accumulating sub-cloned POLE/POLD1 mutation (0%). Survival analysis revealed that POLE/POLD1 mutation was not independently correlated with longer survival after adjusting for TMB and other factors (HR =0.86, P=0.372). However, patients harboring POLE/POLD1 mutation demonstrated a higher response rate than patients with POLE/ POLD1 WT tumors (35.2% vs. 19.6%, P=0.0165). CONCLUSIONS: We delineated distinctive genomic characteristics in POLE/POLD1-mutant tumors, suggesting the potential predictive role of POLE/POLD1 mutations, especially those in the proofreading domain, for beneficial outcomes of immunotherapy. Our results also suggest that MSI caused by a loss-of-function mutation in the MMR pathway tends to result from POLE/POLD1 proofreading deficiency in POLE/POLD1-mutant tumors with MSI.

[Retracted] HNF1A­AS1 promotes growth and metastasis of esophageal squamous cell carcinoma by sponging miR­214 to upregulate the expression of SOX-4.

Following the publication of this paper, it was drawn to the authors' attention by an interested reader that the Transwell invasion assay images in Fig. 3A had been duplicated and re­presented within the same Figure. Furthermore, the same data were strikingly similar, in spite of their different presentation, to data featured in Fig. 2A of an article appearing in Oncology Research [Gu J, Cui, C­F, Yang, L, Wang L and Jiang X­H: Emodin inhibits colon cancer cell invasion and migration by suppressing epithelial­mesenchymal transition via the Wnt/ß­catenin pathway. Oncol Res 27: 193­202, 2019]. Finally, some of the tumour images featured in Fig. 6A of the above paper were strikingly similar to those featured in several other publications. The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, and they responded to request that the paper be retracted from International Journal of Oncology. All the authors agreed that the article should be retracted. The Editor apologizes to the readership for any inconvenience caused.[the original article was published in International Journal of Oncology 51: 657­667, 2017; DOI: 10.3892/ijo.2017.4034].

Study of the mechanism by which dinaciclib induces apoptosis and cell cycle arrest of lymphoma Raji cells through a CDK1-involved pathway.

OBJECTIVE: This study aimed to identify and evaluate the mechanism by which apoptosis and cell cycle arrest were induced by dinaciclib in lymphoma Raji cells. METHODS: The colony formation assay was used to detect cell proliferation of Raji cells. Cell cycle arrest and cell apoptosis were determined by flow cytometry and TUNEL assays, respectively. Protein expression related to the Raji cell state was evaluated by Western blot. The Raji/Dinaciclib drug-resistant cell line was established, where the regulating functions of CDK1-involved pathway were verified. In addition, the effect of dinaciclib in vivo was examined in orthotopically implanted tumors in nude mice. RESULTS: Cell apoptosis was induced, and DNA synthesis ability was decreased in a time-dependent manner in dinaciclib-treated lymphoma Raji cells. Furthermore, the cell cycle was found to be blocked in the G2/M Phase. Further study indicated that CDK1-involved pathway played a key regulatory role in this process. It was revealed by cell transfection that the expression of cell cycle proteins was downregulated after treatment with dinaciclib through a CDK1-involved pathway, which eventually led to apoptosis. Knockdown of CDK1 restored the sensitivity of the Raji/Dinaciclib cells to dinaciclib. Xenograft model of nude mice showed that dinaciclib treatment in vivo could effectively inhibit tumor growth, consistent with the experiment results mentioned before. CONCLUSION: In this study, we clarified the mechanisms through which dinaciclib induces Raji cell apoptosis and blocks the cell cycle through a CDK1-involved pathway, which supported that dinaciclib had potential values in the treatment of lymphoma.

Blocking OLFM4/HIF-1α axis alleviates hypoxia-induced invasion, epithelial-mesenchymal transition, and chemotherapy resistance in non-small-cell lung cancer.

Hypoxia is a common biological hallmark of solid cancers, which has been proposed to be associated with oncogenesis and chemotherapy resistance. The purpose of the present study was to investigate the role and underlying mechanisms of olfactomedin 4 (OLFM4) in the hypoxia-induced invasion, epithelial-mesenchymal transition (EMT), and chemotherapy resistance of non-small-cell lung cancer (NSCLC). We observed dramatically upregulated expression of OLFM4 in several NSCLC cell lines, and this effect was more pronounced in A549 and H1299 cells. In addition, our data revealed that OLFM4 expression was remarkably increased in both A549 and H1299 cells under hypoxic microenvironment, accompanied by enhanced levels of hypoxia-inducible factor (HIF)-1α protein. The HIF-1α level was elevated in response to hypoxia, resulting in the regulation of OLFM4. Interestingly, OLFM4 was a positive regulator of hypoxia-driven HIF-1α production. Moreover, depletion of OLFM4 modulated multiple EMT-associated proteins, as evidenced by the enhanced E-cadherin levels along with the diminished expression of N-cadherin and vimentin in response to hypoxia, and thus blocked invasion ability of A549 and H1299 cells following exposure to hypoxia. Furthermore, ablation of OLFM4 accelerated the sensitivity of A549 cells to cisplatin under hypoxic conditions, implying that OLFM4 serves as a key regulator in chemotherapeutic resistance under hypoxia. In conclusion, OLFM4/HIF-1α axis might be a potential therapeutic strategy for NSCLC.

Clinicopathological analysis of the hydroa vacciniforme-like lymphoproliferative disorder with natural killer cell phenotype compared with cutaneous natural killer T-cell lymphoma.

Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is defined as a distinctive clinicopathological type of cutaneous lymphoma and a subset of patients with this disease exhibit the natural killer (NK)-cell phenotype. The HVLPD-NK cell phenotype may be difficult to distinguish from cutaneous natural killer T-cell lymphoma (CNKTL), as these two diseases share similar immunophenotypic markers. Therefore, the aim of the present study was to analyze the clinicopathological features of this rare disease and compare these features with those of CNKTL. The clinical, histopathological and molecular features of 5 patients with the HVLPD-NK cell phenotype and 11 patients with CNKTL were evaluated. As well as certain subtle histopathological differences, there marked differences the age, distribution of lesions and clinical course differed between patients with these two diseases. These results suggest that the HVLPD-NK cell phenotype should be classified as a separate disorder and treated accordingly.

HNF1A­AS1 promotes growth and metastasis of esophageal squamous cell carcinoma by sponging miR­214 to upregulate the expression of SOX-4.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies in the world, marked by dysphagia and weight loss, bringing great suffering to patients. HNF1A­AS1 (HAS1), a long non-coding RNA (lncRNA), has been identified prevalently involved in various human cancers. However, the exact effects and molecular mechanisms of HAS1 in ESCC progression are still elusive. In this study, upregulated expression of HAS1 was detected in ESCC tissues and four human ESCC cell lines (KYSE70, KYSE450, EC109 and EC970) compared with normal tissues and cell lines. Small interfering RNA (siRNA)-mediated knockdown of HAS1 largely suppressed cell proliferation and promoted cell apoptosis in KYSE70 and EC109 cells. The decreased expression of proliferation marker proteins and elevated level of apoptosis marker proteins further verified that HAS1­siRNA suppressed cell viability in ESCC cells. Besides, the silence of HAS1 strongly reduced the wound closing rate and the number of invasive cells compared with control group. HAS1-siRNA also restrained the expression of migration marker proteins matrix metalloproteinase-9 (MMP-9) and vascular endothelial cell growth factor (VEGF). In addition, miR­214 was predicted as a direct target of HAS1 by bioinformatics analysis. Downregulated expression of miR­214 was elevated in KYSE70 and EC109 cells transfected with HAS1-siRNA. Subsequently, elevated expression of miR­214 was suppressed by co-transfecting with miR­214 inhibitor in EC109 cells pretreated with HAS1-siRNA. The result of luciferase activity assay showed that luciferase activity was strongly weakened by the combination of LncR-HAS1 WT and miR­214 mimic. Moreover, the expression of SOX-4, a predicted target gene of miR­214, was suppressed by HAS1-siRNA and was increased by miR­214 inhibitor. HAS1-siRNA counteracted the effect of miR­214 inhibitor on cell viability and mobility in EC109 cells. Finally, the in vivo experiment revealed that HAS1-siRNA abated the role of miR­214 inhibitor in promoting tumor growth and metastasis. miR-214 also mediated the effect of HAS1 on upregulating the expression of SOX-4 in vivo. Taken together, our study indicated a HAS1-miR­214-SOX-4 pathway in regulating the growth and metastasis of ESCC, providing a promising target for ESCC therapy.

Prognostic significance of CD30 expression in nasal natural killer/T-cell lymphoma.

The present study aimed to investigate the expression of tumor necrosis factor receptor superfamily member 8 (CD30) in extranodal natural killer/T-cell lymphoma (ENKTL) using immunohistochemistry, and to evaluate the association between CD30 and clinicopathological and prognostic significance. CD30 expression was detected using immunohistochemistry on paraffin-embedded sections obtained from 122 patients with ENKTL prior to treatment. In total, 70 of these patients with complete clinical data were collected for prognostic analysis. The level of CD30 expression, of the 122 patients with ENKTL, was grouped on the basis of a 5-tiered scale as follows: 0%, no staining; 1+, <25% positive cells; 2+, 25-50% positive cells; 3+, 50-75% positive cells; and 4+, >75% positive cells). In total, 36 (29.5%) were classified as 0; 46 (37.7%) as 1+; 22 (18.0%) as 2+; 12 (9.8%) as 3+; and 6 (4.9%) as 4+. Among the 86 patients with scores between 1+ and 4+, the membranous staining patterns of CD30 expression were sporadic (33.7%), focal (43.2%), diffuse (15.1%) and angiocentric (8.1%). When considering a score of ≥3+ as CD30 positivity (CD30+), the CD30+ group had significantly shorter overall survival rates (P=0.0023) and progression-free survival rate (P=0.0008) compared with CD30 negative group. However, no statistically significant association was found between CD30 expression and clinicopathological features (P<0.05). The present study found that the expression of CD30 (≥3+) was significantly associated with poor prognosis but was not associated with clinical and histopathological parameters in ENKTL. Therefore, CD30 may be a useful prognostic marker in ENKTL.

KRAS-related noncoding RNAs in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor overall prognosis. However, curative resection during the early stages of the disease can greatly improve survival rates, highlighting the importance of early screening and detection. Studies of noncoding RNAs, primarily microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), provide important insights into strategies for the early detection of KRAS-driven PDAC. Here, we summarize our studies and review current reports on research investigating KRAS-related miRNAs and lncRNAs, emphasizing their aberrant expression, mechanisms, carcinogenic effects, and prognostic and predictive capacities in PDAC.

Inhibitor of DNA binding 4 functions as a tumor suppressor and is targetable by 5-aza-2'-deoxycytosine with potential therapeutic significance in Burkitt's lymphoma.

Epigenetic gene silencing due to promoter methylation is observed in human neoplasia, including lymphoma and certain cancer types. One important target for gene methylation analysis in non-Hodgkin lymphoma (NHL) is inhibitor of DNA binding 4 (ID4). The present study aimed to investigate the gene methylation status of ID4, the expression of ID4 protein and the effect of demethylating agent 5-aza-2'-deoxycytosine (CdR) in the Raji human Burkitt's lymphoma cell line in vitro. Following assessment of the inhibition of Raji cell growth by various concentrations of CdR, the effects of CdR on the expression of ID4 protein were assessed using the immunocytochemical streptavidin-peroxidase method and semi-quantitative analysis, while apoptosis and cell cycle were determined by flow cytometry. The ID4 gene methylation status of Raji cells was tested using methylation-specific polymerase chain reaction analysis. ID4 was methylated and its protein expression was low in the control group, while ID4 was partly or completely demethylated and its protein expression was upregulated in Raji cells treated with CdR. In addition, CdR induced apoptosis and cell cycle arrest in Raji cells in a dose- and time-dependent manner. These results demonstrated that ID4 is hypermethylated and its protein expression is low in Burkitt's lymphoma cells, while CdR reversed the abnormal DNA methylation and induced re-expression of ID4 protein. Hypermethylation of ID4 promotes the proliferation of Burkitt's lymphoma cells; ID4 may function as a tumor suppressor and can be targeted with demethylating compounds such as CdR for the treatment of Burkitt's lymphoma.

[Presence of B-cell clones in angioimmunoblastic T cell lymphoma].

OBJECTIVE: To study the significance of B-cell clones in angioimmunoblastic T cell lymphoma (AITL) and the correlation with Epstein-Barr virus (EBV) and prognosis. METHOD: The histopathologic features, T cell clonality and EBV positivity in 33 cases of AITL and 10 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) collected from May 2010 to February 2014 were analyzed by immunohistochemistry, PCR gene rearrangement and in situ hybridization. Follow-up data were also collected. RESULTS: Of the 33 cases with AITL, seven cases (21.2%) exhibited clonal rearrangement of Ig genes; 21 cases (63.6%) were EBV positive. Seven cases had B-cell clones and all (7/7) were EBV positive; 14 of the 26 (53.8%) cases without B-cell clones were EBV positive. The difference between the two groups was statistically significant (P = 0.032). Four levels were made according to the number of EBV-labeled cells, Ig gene rearrangements, but there was no significant difference among levels 1, 2 and 3. There was no correlation between B-cell clones and prognosis (P = 0.263). CONCLUSION: Clonal rearrangement of Ig genes is a common finding in AITL, and it is highly associated with EBV positivity, but not with the number of EBV-labeled cells. The clinical significance remains unclear; further study with more samples is warranted.

Primary natural killer/T cell lymphoma of the cervix: case report and clinicopathological analysis.

OBJECTIVE: To present pathological and molecular characterizations of a rare case that was diagnosed as nasal-type natural killer (NK)/T cell lymphoma primarily arising in the cervix. CASE REPORT: An Asian woman was admitted to hospital with a hysteromyoma, and laparotomy was performed. A large tumor of the uterus was found, which was limited to the cervix. Pathological examination showed NK/T cell lymphoma, which was supported by histological and immunohistochemical studies and was confirmed by evidence of Epstein-Barr virus infection. Less commonly, this case concerned a cytotoxic T cell phenotype, as molecular studies showed evidence of a clonal T cell receptor γ chain gene rearrangement. Microscopically, prominent and extensive necrosis was the distinctive feature of this case, which reminded us of considering it as a tumor. CONCLUSION: Primary NK/T lymphoma of the cervix is rare. Our experience in this case provided variable information on both pathological and molecular studies. This case may be of value in the differential diagnosis of lymphoid lesions and other small cell tumors of the cervix.

Follicular dendritic cell sarcoma of the pharyngeal region.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm arising most commonly from follicular dendritic cells in the lymph nodes. It is exceedingly rare in extranodal sites, particularly in the pharyngeal region. The present study reports 3 cases occurring in the pharyngeal region. Case 1 had tonsil and cervical lymph node involvement, while case 3 also had tonsil involvement. Cases 1 and 3 relapsed locally at 3 and 17 months after surgery, respectively. Case 2 was diagnosed with a tumor in the parapharyngeal space and the patient succumbed to the disease 5 months after treatment with combined surgery and chemotherapy. All 3 cases were misdiagnosed initially. Pathological biopsy examination, including histopathology and immunohistochemistry, was essential for diagnosis. The data for 52 cases, including cases from the literature and the present cases, were analyzed. The results indicated that 57% (26/46) of the initial diagnoses were inaccurate, while the recurrence, metastasis and mortality rates were 40, 16 and 10%, respectively. The statistics supported the theory that FDCS of the pharyngeal region is a low-grade sarcoma. Involvement of the tonsils (52%, 27/52) and parapharyngeal space (19%, 10/52) were observed most commonly, while FDCS at various sites showed different prognoses. The various survival rates were calculated in the present study. The large tumors (≥4 cm) had a poorer prognosis than the small tumors (<4 cm; P<0.05). Among the 50 cases with available follow-up data, 46% (23/50) were treated with surgery alone, 52% (26/50) with combination therapy (surgery followed by chemotherapy and/or radiotherapy) and 2% (1/50) with surveillance. There was no statistically significant evidence (P>0.05) that combination therapy improves survival rates, compared with surgery alone.

Comparison of Xilei-san, a Chinese herbal medicine, and dexamethasone in mild/moderate ulcerative proctitis: a double-blind randomized clinical trial.

BACKGROUND: Xilei-san is a traditional Chinese herbal medicine that has proven to be of possible use in the treatment of ulcerative proctitis (UP) in a pilot study. OBJECTIVES: This study was intended to compare Xilei-san with dexamethasone enemas in subjects with mild-to-moderate active UP. METHODS: A double-blind randomized study was performed in 35 subjects. During the initial 8 weeks, the subjects received an enema of Xilei-san or dexamethasone at bedtime, then discontinued the treatment and were followed for 12 weeks. All of the subjects received 3 g/day oral mesalazine during the entire study. The disease activity was assessed at inclusion and at weeks 4, 8, and 20. RESULTS: Both treatments showed significant improvement in clinical, endoscopic, and histological grades in comparison with the baseline. CONCLUSIONS: Xilei-san enemas are comparable to dexamethasone enemas in this study. This medicine is safe, well accepted, and may be an alternative drug in the treatment of mild-to-moderate active UP.

Dickkopf3 overexpression inhibits pancreatic cancer cell growth in vitro.

AIM: To elucidate the role of dickkopf3 (Dkk3) in human pancreatic cancer cell growth. METHODS: Dkk3 mRNA and protein expression in human pancreatic cancer cell lines were detected by real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blotting and immunofluorescence. Methylation of the Dkk3 promoter sequence was examined by methylation-specific polymerase chain reaction (MSP) and Dkk3 mRNA expression was determined by real-time RT-PCR after 5-aza-2'-deoxycytidine (5-aza-dC) treatment. The effects of Dkk3 on cancer cell proliferation and in vitro sensitivity to gemcitabine were investigated by CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS) after transfecting the Dkk3 expression plasmid into human pancreatic cancer cells. The expression of ß-catenin, phosphorylated extracellular signal-regulated protein kinases (pERK) and extracellular signal-regulated protein kinases (ERK) was also examined by real-time RT-PCR and Western blotting after upregulating Dkk3 expression in human pancreatic cancer cells. RESULTS: The results show that the expression levels of both Dkk3 mRNA and protein were low in all pancreatic cancer cell lines tested. The Dkk3 promoter sequence was methylated in the MIA PaCa-2 and AsPC-1 cell lines, which showed reduced Dkk3 expression. These two cell lines, which initially had a methylated Dkk3 promoter, showed increased Dkk3 mRNA expression that was dependent upon the dosage and timing of the DNA demethylating agent, 5-aza-dC, treatment (P < 0.05 or P < 0.01). When Dkk3 expression was upregulated following the transfection of a Dkk3 expression plasmid into MIA PaCa-2 cells, the ability of cells to proliferate decreased (P < 0.01), and the expression of ß-catenin and pERK was downregulated (P < 0.01). Sensitivity to gemcitabine was enhanced in Dkk3 expression plasmid-transfected cells. CONCLUSION: Our findings, for the first time, implicate Dkk3 as a tumor suppressor in human pancreatic cancer, through the downregulation of ß-catenin expression via the ERK-mediated pathway.

[Significance of chemokine receptor CXCR3 expression in breast cancer].

OBJECTIVE: To investigate the expression of CXCR3 and its association with clinicopathologic features in breast carcinoma. METHODS: The expression level of CXCR3 in 18 samples of breast cancer and corresponding normal tissues was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR analysis. Immunohistochemistry was carried out to examine the expression of CXCR3 in 80 breast cancers, 20 fibroadenomas and 15 normal breast tissues. RESULTS: (1) RT-PCR and real-time RT-PCR analysis showed a higher level of CXCR3 in breast cancer tissues than that in the corresponding normal breast tissues (P < 0.05). (2) Immunohistochemistry analysis showed that the positive rate of CXCR3 in breast cancer tissues was significantly higher than that in fibroadenomas and the normal breast tissues (P < 0.05). The expression level of CXCR3 in the lymph node-positive group was higher than that in the lymph node-negative group (P < 0.05). The expression of CXCR3 was positively correlated with the number of lymph nodes involved by metastasis, tumor size and pTNM tumor stage (P < 0.05). CONCLUSIONS: Chemokine receptor CXCR3 was up-regulated in breast cancer, and was associated with the progression of breast cancer. CXCR3 might be a novel molecular marker to predict lymph node metastasis and prognosis of breast cancer.