Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children and adolescents. The rarity of its occurrence in infant poses a great difficulty in terms of diagnosis and management. Here, we report an aggressive case of alveolar rhabdomyosarcoma in an infant who presented with neck swelling and neurological complications. The Magnetic Resonance Imaging (MRI) revealed a soft tissue swelling of the neck with intraspinal extension and spinal cord compression, raising the possibility of a neurogenic or malignant nerve sheath tumour. Histopathological examination revealed a primitive, small round cell tumour with no rhabdoid differentiation. The clinical presentation, neurological symptoms, tumor location and the histopathologic features were highly suggestive of neuroblastoma. However, the tumour cells were positive for desmin with focal and weak nuclear positivity for myogenin and MyoD1; immunoexpressions which were in favour of rhabdomyosarcoma. Fluorescent in situ hybridization (FISH) confirmed the presence of a translocation t(2;13)(q35;q14), supporting the diagnosis of alveolar rhabdomyosarcoma. Despite chemotherapy, patient succumbed to death after two months due to septic shock. Rhabdomyosarcoma is highly aggressive mesenchymal neoplasm which may present with diagnostic difficulty. This case highlights the importance of molecular studies in making an accurate diagnosis so that appropriate chemotherapy may be instituted.

Chronic myeloid leukemia (CML) patients who have BCR-ABL T315I mutation, usually present in the advance phase of the disease with overall survival (OS) shorter than those without the mutation. This study aimed to determine the prevalence of T315I mutation amongst imatinib mesylate (IM) resistant CML patients and to compare the OS between T315I-mutated and non-T315I-mutated patients. Sixty consecutive CML patients who were treated with IM for at least 18 months and their treatment responses, were recorded. The mutation analysis was done using allele-specific oligonucleotide reverse transcriptase-polymerase chain reaction (RT-PCR) assay followed by direct sequencing technique. Forty-two patients (70%) were found to have IM-resistance. Five out of 42 patients had detectable T315I mutation. Median OS of IM-resistant T315I-mutated patients was 96 months (95% CI:54-138) compared to 84 months (95% CI:48-120) in non T315I-mutated patients, although this was found to be statistically insignificant (p = 0.43). The present study showed a higher prevalence of T315I mutation as compared to a few local studies. Median OS of T315I-mutated patients were observed to be longer than non-T315-mutated patients. Further studies encompassing larger cohort of patients are required to confirm this finding

Objective: To investigate the effects of doxorubicin on the expressions of DNA-damage/repair-related proteins BRCA1 (breast cancer-associated protein 1) and PARP-1 [poly(ADP-ribose) polymerase-1] in BRCA1 wild-type breast cancer MCF-7 cells. Methods: The MCF-7 cells were treated with doxorubicin, then the expressions of BRCA1 and PARP-1 and the activity of PARP-1 in the cells recovering after different time peroids were detected by Western blotting. The apoptotic rates of MCF-7 cells and SKBR3.0 cells (BRCA1 mutant-type breast cancer cells) after intervention with doxorubicin and PARP-1 inhibitor 3-ABA (3-aminobenzamide) were detected by FCM (flow cytometry). Results: After MCF-7 cells were treated with different concentrations of doxorubicin for 24 h and then recovered for 12 h, the expression of PAR [poly(ADP-ribose)], an active product of PARP-1, was increased in a dose-dependent manner (P < 0.01), but the expression of full-length PARP-1 (the molecular mass is 1.13×10 5) was in a slightly decrease accompanied by more cleavage fragments of PARP-1 (the molecular mass is 8.9×104), while the expression of BRCA1 was firstly increased and then decreased (P < 0.01). After MCF-7 cells were treated with 1 μmol/L doxorubicin for 24 h and then recovered for different time peroids, the activity of PARP-1 (PAR) was increased gradually over time peroid of recovery (P < 0.01), but the expression of full-length PARP-1 had no significant change with less cleavage fragments of PARP-1, while the expression of BRCA1 was decreased gradually (P < 0.01). The activity of PARP-1 was significantly inhibited by 3-ABA (P < 0.01) via inducing its cleavage, which didn't affect BRCA1 expression (P > 0.05). Both doxorubicin and 3-ABA alone could significantly induce the apoptosis of MCF-7 cells (P < 0.05), and the combination of the two could further increase the apoptosis of BRCA1 wild-type breast MCF-7 cells (P < 0.05). Doxorubicin in combination with 3-ABA could also induce the apoptosis of BRCA1 mutant-type SKBR3.0 cells, and this effect was stronger than that in MCF-7 cells (P < 0.05). Conclusion: Doxorubicin intervention can affect the activity of DNA-damage/repair-related protein PARP-1 and the expression of BRCA1. Both doxorubicin and PARP-1 inhibitor 3-ABA can induce the apoptosis of MCF-7 cells, and the combination of the two can increase this apoptosis-inducing effect. Copyright © 2013 by TUMOR.

Objective: To investigate the effect of short hairpin RNA (shRNA)-targeting special ATrich sequence-binding protein-1 (SATB 1) on the apoptosis of human lung cancer cell line A549, and to explore the possible mechanism. Methods: The recombined plasmid SATB1-shRNA of shRNA-targeting SATB 1 was constructed and transfected into A549 cells by LipofectAMINE 2000. The expression levels of SATB1, Bcl-2 and Bax mRNAs were examined by RT-PCR, and the expression levels of SATB1, Bcl-2, Bax, and caspase 3 proteins were examined by Western-blotting. The apoptosis rate of A549 cells was detected by flow cytometry (FCM). Results: The recombined plasmid SATB1-shRNA was successfully constructed and transfected into the A549 cells. After transfection with SATB1-shRNA, the expression levels of SATB1 and Bcl-2 mRNAs and proteins were decreased (P <0.05), whereas the expression levels of Bax mRNA and protein and the caspase 3 protein were increased (P <0.05). The apoptosis rate of A549 cells after transfection with SATB1-shRNA was higher than that of the A549 cells without transfection with SATB1-shRNA [(14.18±1.59) % vs (1.84±0.57) %, P <0.01]. Conclusion: SATB1-shRNA can significantly down-regulate the expression level of SATB1 in human lung cancer cell line A549 and induce the apoptosis. The mechanism may be related to the cascade effect induced by the down-regulation of Bcl-2 expression. Copyright © 2012 by TUMOR.

Chromosomal translocations are very common in human cancer. The molecular mechanisms of chromosomal translocations are complex and unclear. Recent studies show that the organization of genomes is higher-order in the nucleus and every chromosome or chromatin has its preferential position and territory. Intermingling of chromosome territories in interphase maintains the transcriptional networks of genes. The spatial arrangements of chromosomes and gene loci in the interphase nucleus are responsible for nonrandom chromosomal translocations in human cancer. Chromosomal translocations are favored in neighbor chromosomes or genes in spatial proximity within the nucleus. These findings may lead to new approaches in early diagnosis and target therapy of cancer. © 2012 by Tumor.

Objective: To investigate the effects of gene silencing and overexpression of RACK 1 (receptor for activated C kinase 1) on the proliferation of large-cell lung cancer H460 cells and lung adenocarcinoma A549 cells, and to explore the possible mechanism. Methods: The RACK1 siRNA (small interfering RNA) targeting RACK 1 gene and recombinant vector pCMV-sport6-RACK1 were transfected into both of H460 cells and A549 cells, respectively. MTT method and colony formation assay were used to detect the effect of RACK 1 gene expression on the proliferation of lung cancer cells. Flow cytometry was used to examine the change of cell cycle. The association and interaction of RACK 1 gene expression with the proliferation of lung cancer cells were analyzed by yeast two-hybrid system, co-immunoprecipitation, laser scanning confocal microscopy and co-immunoprecipitation of phosphoproteins. Results: The expression levels of RACK1 protein in the H460 cells and A549 cells were both decreased after transfection with RACK1 siRNA, and the abilities of proliferation and colony-formation were also weakened. The proportion of lung cancer cells arrested at phase S was significantly declined (P <0.01). Meanwhile, the expression level of RACK1 protein was increased after transfection with pCMV-sport6-RACK1, and the abilities of proliferation and colony-formation of lung cancer cells were both strengthened with a prolonged doubling time. The proportion of lung cancer cells arrested at phase S was significantly increased (P <0.01). The results of yeast two-hybrid system and co-immunoprecipitation revealed that RACK1 could directly interact with MCM7 (minichromosome maintenance protein 7). The phosphorylation of MCM7 protein was strengthened through binding to RACK1 which translocated into the cell nucleus. Conclusion: RACK1 promotes the proliferation of lung cancer cells through activating the phosphorylation of MCM7 binding to RACK1. Copyright© 2012 by TUMOR.

Objective: To investigate the pathologic characteristics and differential diagnosis of pancreatic cancer among residents in Shanghai urban area. Methods: A population-based large case-control study was performed in patients with pancreatic cancer between December 2006 and January 2011 in Shanghai urban area. The pathologic slides from 387 cases of pancreatic cancer were collected and reviewed by five experienced pathologists. The pathologic diagnosis was determined according to WHO Classification of Tumors of the Digestive System, Fourth Edition (2010). Results: Three hundred and fifty cases (90.4%) were confirmed as pancreatic cancer. Most of the pathologic slides were obtained from resected tissues of pancreatic cancer (311/350, 88.9%). The average diameter of the tumor was 4 cm, and 56.6% (n = 198) of the tumors were located in the head of pancreas. The ductal adenocarcinoma was the most common histologic subtype (n = 311, 89.0%), followed by pancreatic neuroendocrine tumors (n = 15, 4.3%). The most common histologic grades were II/III (n = 252). According to TNM staging system, 40 cases had stage IA, 209 cases had stages IB/IIA, and 80 cases had stage IIB. The perineural invasion was identified in 175 cases, and the lymphovascular and/or venous emboli were identified in 56 cases. Only one case was misdiagnosed. Conclusion: The understanding of pathology of pancreatic cancer in Shanghai urban area was improved through this pathologic review. Copyright© 2012 by TUMOR.

Objective: To investigate the effect of short hairpin RNA (shRNA) targeting Xenopus kinesin-like protein 2 (TPX 2) gene on the apoptosis of human lung adenocarcinoma A549 cells and to explore its possible mechanism. Methods: The combination vector of shRNA targeting TPX2 gene was established and then it was transfected into A549 cells. The expression levels of TPX2, Aurora-A, p53 and Bcl-2 mRNAs in A549 cells after transfection with combination vector were detected by RT-PCR, and the expression level of TPX2 protein was determined by Western-blotting. The cell cycle distribution and the apoptosis were analyzed by flow cytometry (FCM). Results: The combination vector of pMagic4.1-shRNA-TPX2 was successfully established. The expression levels of TPX2, Aurora-A and Bcl-2 mRNAs were down-regulated whereas the expression level of p53 mRNA was up-regulated in A549 cells after transfection with pMagic4.1-shRNA-TPX2, and the expression level of TPX2 protein was down-regulated. The apoptosis rate of A549 cells was increased after transfection with pMagic4.1-shRNA-TPX2, and the cell cycle was arrested at S phase. These changes in the pMagic4.1-shRNA-TPX2- transfected group were significantly different from those in the blank control group (without transfection with combination vector) and the negative control group (transfection with pMagic4.1-shRNA-NC) (P<0.05). Conclusion: The shRNA targeting TPX 2 gene can induce the apoptosis of A549 cells, and this effect may be related to up-regulation of p53 expression and down-regulation of Bcl-2 expression. Copyright© 2011 by TUMOR.

Objective: To investigate the effect of regenerating gene IV (Reg IV) and its carbohydrate-recognition domain (CRD)on angiogenesis of colorectal carcinoma xenografts in nude mice. Methods: The LoVo human colorectal carcinoma cells were transfected with recombinant plasmids pcDNA3.1-Reg IV (LoVo/RegIV group), pcDNA3.1-RegIV ΔCRD (LoVo/RegIV ΔCRD group) or empty vector (LoVo/negative group), and then the LoVo/RegIV, LoVo/RegIV ΔCRD, LoVo/negative and LoVo cells were transplanted subcutaneously in nude mice, respectively. The expression levels of RegIV and RegIV/ΔCRD mRNAs in xenograft tissues were detected by RT-PCR. The expression levels of vascular endothelial growth factor (VEGF) and CD34 proteins in xenograft tissues were determined by immunohistochemistry assay. The microvessel density (MVD) in xenograft tissues was calculated. Results: The expression level of VEGF in the xenograft tissues in LoVo/RegIV group was higher than those in the other three groups (P < 0.05), and there was no difference in VEGF expression among the LoVo/RegIV ΔCRD, LoVo and LoVo/negative groups (P > 0.05). The MVD value of xenograft tissues in LoVo/RegIV group was higher than those in the other three groups (P < 0.05), and there was no difference among the LoVo/IV ΔCRD, LoVo and LoVo/negative groups (P > 0.05). Conclusion: RegIV participates the angiogenesis of colorectal carcinoma, and this effect may be correlated with its CRD. Copyright© 2011 by TUMOR.

Objective: To investigate the expression of histone deacetylase 2 (HDAC2) in esophageal squamous cell carcinoma (ESCC), and to explore the effects of downregulation of HDAC2 expression on cell proliferation, cell cycle and apoptosis of EC9706 cells and their possible molecular mechanisms. Methods: The expression of HDAC2 protein in ESCC tissues was detected by immunohistochemistry. HDAC2 small interfering RNA (siRNA) and control siRNA were transfected into ESCC EC9706 cells, and then the EC9706 cells were randomly divided into three groups, including untreated group, siRNA control group and HDAC2 siRNA group. The expression of HDAC2 protein in EC9706 cells was detected by Western blotting. The cell proliferation status was examined by cell counting Kit-8 (CCK-8) method. The cell cycle and apoptosis were detected by flow cytometry (FCM). The expressions of proteins related to cell proliferation, cell cycle and apoptosis were detected by Western blotting. Results: The positive expression rate of HDAC2 in ESCC tissues (79.71%) was significantly higher than those in normal esophageal mucosa (51.11%) and paracancerous tissues (dysplasia, 23.19%), and there was a significant difference among these three tissues (χ2=44.121, P=0.000). The expression of HDAC2 protein wasnot associated with age and gender of patients with ESCC (both P>0.05), but closely associated withhistological grade, invasive depth, TNM stage and lymph node metastasis (all P<0.05). HDAC2 siRNA effectively down-regulated the expression of HDAC2 protein, obviously inhibited the cell proliferation, arrested cell cycle at G0/G1 phase and induced apoptosis of EC9706 cells. In addition, the result of Western blotting showed that down-regulation of HDAC2 expression could markedly increase the expressions of p21 protein and apoptosis-related bax protein while decrease the expressions of cyclin D1 and bcl-2 proteins. Conclusion: HDAC2 may play an important role in occurrence and development of ESCC. The downregulation of HDAC2 expression-mediated proliferation inhibition, cell cycle arrest and apoptosis of EC9706 cells may be tightly associated with the increased expression levels of p21 and baxas well as the decreased expression levels of cyclin D1 and bcl-2. Copyright© 2011 by TUMOR.