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Colorectal cancer (CRC) is the third most frequently diagnosed cancer with unfavorable clinical outcomes worldwide. circFNDC3B plays as a tumor suppressor in CRC, however, the mechanism of circFNDC3B in CRC remains ambiguous. The stem-like properties of CRC cells were detected by the evaluation of stemness markers, sphere formation assay and flow cytometry. qRT-PCR, FISH, IHC, and western blotting assessed the expression and localization of circFNDC3B, RNF41, ASB6, and stemness markers in CRC. The metastatic capabilities of CRC cells were examined by wound healing and Transwell assays, as well as in vivo liver metastasis model. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assay and co-IP were used to detect the associations among circFNDC3B, FXR2, RNF41, and ASB6. Downregulated circFNDC3B was associated with unfavorite survival in CRC patients, and circFNDC3B overexpression suppressed CRC stemness and metastasis. Mechanistically, studies revealed that YTHDC1 facilitated cytoplasmic translocation of m

Gastric cancer (GC) is the second most common cancer in China. The ToGA study showed that trastuzumab in combination with fluoropyrimidine plus cisplatin prolonged overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced GC (AGC). However, some patients may not be able to receive this regimen. We conducted a clinical study to evaluate the efficacy and safety of trastuzumab in combination with docetaxel+capecitabine (DX) in patients with HER2-positive AGC. This phase II, multi-center, open-label, single arm study enrolled patients with HER2-positive AGC who had not received prior treatment for metastatic disease. Patients were treated with a regimen of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, day 1), capecitabine (1000 mg/m(2) twice daily, days 1-14) and docetaxel (60 mg/m(2), day 1 for 6 cycles) every 3 weeks. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), OS and safety profiles. Sixty-seven patients with AGC were enrolled from 14 centers. 64 were included in the full analysis set (FAS). The median PFS was 8.1 months (95% confidence interval [CI]: 5.6-12.8) and the median OS was 20.9 months (95% CI: 15.1-33.0). Response was evaluated in 59 patients. The ORR was 67.8%. The most common adverse events of Grade ≥3 were neutropenia, leukopenia, hand-foot syndrome, febrile neutropenia and anemia. We concluded that combination treatment with trastuzumab and DX was well-tolerated and highly effective in patients with HER2-positive AGC, and may offer an alternative to current treatments.

Cholangiocarcinoma (CCA) is a rare but lethal malignancy arising from the biliary tract epithelium. It has a poor prognosis largely due to the difficulties of early diagnosis and the lack of effective therapies. It is thus imperative to develop new and effective treatments for CCA, which depends heavily on the mechanistic understanding of the disease. Previous studies have suggested that somatic mutations in KRAS, BRAF, and PIK3CA genes are frequently found in several types of human cancers including colon, breast, and lung carcinomas as well as CCA. Yet, the frequency and the involvement of these oncogenic mutations in CCA in Chinese population have not been investigated. In this study, we evaluated the hotspot mutations of KRAS, BRAF, and PIK3CA genes in 34 Chinese CCA patients. Sequencing analysis revealed 13 (38.2%) and 11 (32.4%) patients bearing KRAS and PIK3CA mutations, in which two (5.9%) of them harbored both KRAS and PIK3CA mutations. Surprisingly, no BRAF mutation was detected in all 34 CCA samples. Our findings indicate that somatic mutations in KRAS and PIK3CA but not BRAF oncogenes are closely associated with the development of CCA in Chinese population and provide new potential targets for future therapeutic treatments of the disease.

Summary Objectives To evaluate the clinical response and adverse effects of Photofrin photodynamic therapy (PDT) in patients with relapse nasal pharyngeal cancer. Methods Thirty patients with relapse nasal pharyngeal cancer were randomly divided into PDT group and chemotherapy group. In PDT group, patients received intravenous administration of Photofrin (2 mg/kg b.w.) and 48 h later light (200–300 J/cm) was delivered by a 630 nm diode laser through a cylinder diffuser under endoscopic assistance. Two days after PDT the necrotic tissues were removed and newly identified sites were subject to another round of light irradiation. In chemotherapy group, the routine cisplatin and 5-fluorouracil (DDP/5-FU) remedy was used. Endoscopic and radiological examinations were performed during 6 months follow-up. The Karnofsy Score was used to evaluate the quality of life. Results The local response and nasal cavity obstruction remission rate in PDT group were better than that in chemotherapy group. The Karnofsy Score was also improved in PDT group. Conclusion This pilot study suggests that Photofrin PDT is effective and safe in treatment of advanced nasal pharyngeal cancer and management of nasal obstruction.

To assess the feasibility of usage of microbubbles conjugated with RGD peptides and contrast enhanced ultrasound (CEU) in detection of tumor angiogenesis.Lipid microbubbles (MB) were prepared, and the RGD peptides were covalently conjugated to the lipid shell of MB (MB(RGD)). Six nude mice with tumor created by dorsal inoculation of HepG2 tumor cells were used as the test group. Six nude mice without tumor were served as the control group. 10 minutes after bolus injection of MB and MB(RGD) randomly (30 min interval) via a tail vein catheter, CEU was performed on the tumors of the test group and the thigh skeletal muscles of control group. The video intensity (VI) of tumors and the skeletal muscles were measured. The tumors and the skeletal muscles were harvested for immunohistochemical examination.Only a slight contrast enhancement of the tumor was seen with MB, and the VI was 5.33 ± 1.71. While a remarkable enhancement of the tumor was observed after injection of MB(RGD). The VI was up to 17.03 ± 3.58, 3.18 folds higher as compared with that obtained by injection of MB (P0.05). As expected, there were no obvious contrast enhancement of the skeletal muscles with both MB(RGD) and MB. There was a high expression of αvβ3-integrin in tumor neovascular endothelium, however, no apparent expression of αvβ3-integrin was observed in the skeletal muscle vascular endothelium.CEU with MB(RGD) can be used to effectively evaluate the angiogenesis of tumors, and it may greatly contribute to the early judgement of the nature of tumor.

To investigate the transfection efficiency and the optimal conditions of delivering latent membrane protein-1 (LMP-1) gene to dendritic cells (DCs) by ultrasound exposure combined with contrast agent.Human DCs were cultured in vivo and transfected with the recombinant plasmid pEGFP-C3-LMP1 under varying conditions including ultrasound intensities, exposure time and microbubble contrast agent concentration. The transfection efficiency was assessed by fluorescent microscopy and flow cytometry, and the cell viability by trypan blue exclusion test.An exposure time of 60 s at MI 1.0 with a microbubble contrast agent concentration of 20% resulted in the optimal effect of delivering the recombinant plasmid pEGFP-C3-LMP1 into the DCs, with a transfection efficiency of (14.37∓2.12)%. Over 90% of the transfected cells were viable after the transfection.Microbubble contrast agent combined with ultrasound exposure can enhance the delivery of recombinant plasmid pEGFP-C3-LMP1 into the DCs.

To evaluate the short-term efficacy and toxicity of endostar in combination with XELIRI as the second-line treatment for advanced colorectal cancer.Twenty-one patients with advanced colorectal cancer were treated with intravenous infusion of endostar (15 mg/day for 14 consecutive days) and irinotecan (250 mg/m(2), single dose on the first day), and oral administration of capecitabine (1.0 mg/m(2), twice daily for 14 days), and the treatment cycle was repeated every 21 days. The efficacy and toxicity of the treatments were evaluated according to RECIST and NCI-CTCAE3.0 standard, respectively.The overall response rate was 9.5% in these patients, with a median time to progression (mTTP) of 3.9 months. The main adverse effects associated with the treatment included leucopenia, nausea/vomiting and peripheral neuritis.Endostar combined with XELIRI is effective and safe as the second-line treatment for advanced colorectal cancer, and further clinical investigation is warranted.

To assess the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in ultrasound-guided local ablation of malignant liver tumors.Thirteen patients with 35 local residual tumor foci following previous tumor ablation underwent (18)F-FDG PET-CT and ultrasound-guided local ablation with intratumoral alcohol injection.After the second local ablation guided by (18)F-FDG PET-CT and ultrasound, radioactive defects were detected in the corresponding location in 31 of the 35 residual foci, and after the third local ablation, the other 4 foci also showed radioactive defects.(18)F-FDG PET-CT can sensitively and accurately identify tissue necrosis and residual tumors, and serves as an excellent approach for ultrasound-guided local ablation of local residual tumors.

To investigate the clinical significance of vascular endothelial growth factor (VEGF) levels in serums of colorectal cancer patients at stage IV.Using enzyme linked immunosorbent assay (ELISA) to detect the VEGF levels in serums of 45 colorectal cancer patients at stage IV, and 20 healthy served as normal control.The mean concentration of VEGF in 45 colorectal cancer patients at the 7 day after operation were significantly lower than that before operation (P0.01). The mean concentration of VEGF in the patients who benefit from bevacizumab showed no statistical difference from the levels of who did not benefit (P=0.554).The VEGF levels in colorectal patients at stage IV are lowed as the load of tumor decrease. The circulating levels of VEGF seem not predict the response to bevacizumab in colorectal cancer patients at stage IV.

To study the feasibility of transfecting breast cancer BA46 gene into dendritic cells (DCs) using adeno-associated virus (AAV) to induce specific cellular immunity.Mononuclear cells (DC precursor) were isolated from the peripheral blood of healthy donors by density gradient centrifugation and infected with rAAV/BA46/Neo virus stock (transfection group) or pulsed with 293 cell lysate (control group). In both groups, maturation of the DC precursor was induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor-alpha(TNF-alpha). On day 7, the DCs were collected and mixed with T cells at the ratio of 1 to 20 to induce cytotoxic T lymphocytes (CTL). The capacity of the DCs in stimulating T lymphocyte proliferation was assessed using (3)H-thymidine incorporation assay. The expressions of interferon-gamma (IFN-gamma), IL-4, CD4, CD8, CD25 and CD69 in the CTLs were analyzed with cytometry, and the cytotoxicity of the CTLs was evaluated with (51)Cr-release assay using BA46-positive breast cancer cell line Hs578T as the target.The DCs transfected with BA46 gene exhibited potent capacity to stimulate T lymphocyte proliferation. The CTL population induced by the transfected DCs expressed high levels of CD8, CD69 and IFN-gamma, and showed strong cytotoxicity against BA46-positive breast cancer cell line Hs578T, which was BA46 antigen-specific and MHC-limited.The success in BA46 gene transfer in the DCs that induce specific cellular immunity provides the experimental basis for breast cancer immunotherapy using genetically modified cells.

Our aim was to determine the usefulness of fluorescence examination and photodynamic therapy (PDT) for the management of perianal extramammary Paget's disease. A 75-year-old woman underwent two courses of PDT. The first treatment was carried out with topically applied 5-aminolevulinic acid (ALA) to the affected area (2.5 x 2.5 cm(2)) 3 h before light treatment. We used ALA/protoporphyrin IX (PpIX)-mediated fluorescence to visualize the lesion and its margins. The lesion was treated with a 630 nm laser at 120 J/cm(2). Forty days later, the residual lesion was given a second treatment at the same light dose after topical application of ALA and intravenous injection of HiPorfin. ALA/PpIX-mediated fluorescence served as a useful tool to visualize the lesion's location. Complete cure was achieved after the second course of PDT. During 7 months of follow up, no recurrence, scarring or functional loss was noticed. We concluded that ALA-assisted fluorescence examination can be a useful tool to determine the lesion and its margins. ALA-PDT is effective for superficial lesions, but, for thicker and deeper lesions, the systemic administration of photosensitizer is needed.

To investigate the effects of matrine on the cell cycle and apoptosis in human colon adenocarcinoma SW620 cells and explore the possible mechanisms.The effect of matrine on cell proliferation was assessed using MTT assay, and the cell cycle arrest induced by matrine was determined by flow cytometry. The changes of cell morphology were observed through optical microscope, fluorescence microscope and electron microscope, and the cell apoptosis was detected using Annexin V-FITC apoptosis assay.Matrine inhibited the proliferation of SW620 cells in a dose- and time-dependent manner. Compared with the control group, the matrine-treated cells showed increased cell percentage arrested in G 0/G1 phase with decreased S-phase cells. Morphologically, the SW620 cells treated with matrine exhibited cell shrinkage, cell size reduction, plasma condensation, cytoplasmic vacuolar changes, and formation of apoptotic body with also the presence of the signet-ring cells, all typical of apoptotic cells.Matrine exposure of SW620 cells inhibits the cell proliferation, causes cell cycle arrest at G 0/G1 phase, and induces apoptosis in a dose- and time- dependent manner.

To evaluate safety and effect of percutaneous chemotherapy pump placement for portal vein chemotherapy in management of colorectal cancer with hepatic metastasis.Twenty-three cases of colorectal cancer with liver metastasis were treated with percutaneous chemotherapy pump placement for portal vein chemotherapy, and the therapeutic effect of this treatment was observed.Partial remission of the hepatic lesions was achieved in 13 (56.5%) of the patients following the treatment, and the condition was stabilized in 5 patients (21.7%). No severe complications were observed in these patients.Percutaneous chemotherapy pump placement for portal vein chemotherapy can be safe and effective for management of hepatic metastasis of colorectal cancer.

To evaluate the efficacy of Avastin in combination with irinotecan for metastatic colorectal cancer.Ninety patients were randomly divided into 3 equal groups to receive Avastin plus irinotecan (group A), FOLFIRI (group B) and FOLFOX7 (group C) for two cycles, respectively. The response rate and changes in tumor maker levels were observed.The tumor response rate was 43.3% in group A, 27.7% in group B and 30.0% in group C. The disease control rate (complete response+partial response+stable disease) was 80% in group A, 53.3% in group B and 50.0% in group C. Obvious changes in tumor marker levels were observed in the 3 groups after treatment, which were most conspicuous in group A (P0.05).The addition of Avastin to irinotecan chemotherapy results in significant improvement of clinical efficacy in patients with metastatic colorectal cancer.

To study the specific killing effect of the Photofrin-Herceptin immunoconjugate on the tumor cells expressing HER-2.Photofrin (porfimer sodium) was covalently coupled to Herceptin (trastuzumab) via [1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide hydrochloride](EDCI) , and the killing effect of this conjugate was evaluated by means of MTT assay on SK-BR-3, MCF-7 and A549 cell lines expressing HER-2 at different levels.The conjugate had weaker immunoactivity than Herceptin, but possessed stronger killing effect on the cell lines expressing HER-2 than Photofrin, Herceptin, as well as the mixture of Photofrin and Herceptin (P0.05). In the cell lines negative for HER-2 expression, the killing effect of the conjugate was similar to that of Photofrin, Herceptin, and their mixture.Photofrin-Herceptin immunoconjugate can specifically kill HER-positive cells in vitro.

To investigate the efficacy and toxicity of recombinant humanized anti-Her-2/neu antibody (Herceptin) and Taxol for patients with Her-2/neu overexpressing metastatic breast cancer.Sixty patients with Her-2/neu overexpressing metastatic breast cancer were investigated. Of the 60 cases, 22 were treated with Herceptin and Taxol and 38 with Taxol and doxorubicin.The total response rate (RR) of Herceptin and Taxol was 68.2%, and that of Taxol and doxorubicin was 44.7%. The RR of patients with Her-2/neu(+++) was 75%, while that of patients with Her-2/neu(++) was 50%. The major adverse effects were gastro-intestinal tract reactions, myopathy, bone marrow suppression and alopecia.The treatment with Herceptin and Taxol is effective and safe for patients with Her-2/neu overexpressing metastatic breast cancer. The therapeutic effect is related to the degree of Her-2/neu overexpression.

To evaluate the clinical efficacy and adverse effects of Photofrin photodynamic therapy (PDT) in patients with advanced cancers.Forty patients with advanced cancers in stage IV with lumen obstruction, who failed to respond positively to other treatment regimens, received intravenous administration of Photofrin as the photosensitizer at the dose of 2 mg/kg.b.w. 48 h before PDT by 630 nm light (DIOMED) delivered through cylinder diffusing tip quartz fibers that passed through the biopsy channel of a flexible endoscope. PDT endoscopy was repeated, the necrotic tissue removed and, if necessary, the primary sites and other newly identified sites were subjected to a second exposure 8 h later. Two days after the second exposure, endoscopy was again performed and the necrotic tissue removed. Endoscopy was repeated one month after PDT and periodically thereafter as needed to treat symptomatic residual tumor.The total rate of response to the treatment was 74% in these patients, and the rate of lumen obstruction due to the tumors decreased from 90% to 10% after PDT, with significantly improved Karnofsky performance score.Photofrin PDT is effective and safe in the treatment of advanced cancer, which may relieve lumen obstruction and improve patient quality of life.

To investigate the relationship between the survival time and the expressions of progesterone receptor (PR) and HER2 in the tumor tissues of patients with breast cancer, thereby to explore the possibility of using the 2 indices as the indicator for the prognosis of the patients.Immunohistochemical staining for PR and HER2 was performed on paraffin embedded tumor specimens obtained from 185 patients with breast cancer, and follow-up studies were conducted and the survival time of the patients recorded.In the 120 patients (64.9%) with complete followed-up data, 28 patients died (15%), with the record of the other 65 patients (35.1%) not available for this study. Immunohistochemical detection found that the positivity rates for HER2 and PR were 57.8% and 62.7% respectively in the total specimens examined, and HER2 and PR showed significant difference in their respective associations with the survival rate of the patients (P0.01). Specifically, HER2 was inversely associated with the survival rate, to which PR was positively related. The univariant analysis suggested the hazards posed by HER2 expression to reduce the overall survival of the patients (P0.01, OR=1.566), while PR, playing the protective role, was associated with a significantly longer overall survival time (P0.01, OR=0.547). In the multivariate analysis, however, only PR expression was of significant prognostic value in the patients (P 0.012).Both HER2 and PR can be used as independent indicators for the prognosis of patients with breast cancer, and high HER2 expression may indicate poor prognosis, while PR is associated with a longer survival time and a higher survival rate.

To explore the possibility of evaluating the short-term therapeulic effect of radiofrequency ablation (RFA) in cancer treatment by positron emission tomography.The radioactivity intensity of the tumor was detected by PET before and after RFA.Radioactivity blank was observed in all 33 cases with 54 lesions, indicating the elimination of the tumor was destroyed.PET is of great significance in evaluating the short-term effect of RFA.

Objective To evaluate the clinical significance of ultrasound-guided needle biopsy in diagnosis of enlarged lymph nodes by analyzing the data of 308 patients who received ultrasound-guided lymph node biopsy.Methods Data of 308 patients who underwent ultrasound-guided lymph node biopsy in the Oncology Center of Nanfang Hospital from Jan.1,2003 to Jun.30,2010 were collected.The age,sex,lymph node size and location,and pathological types of the patients were analysed.Simultaneously,the influence of lymph node size,location and pathological type on pathological diagnosis was studied.Results The average age of 308 patients,including 192 males and 116 females,was 53.4 years,ranging from 12 to 87 years.There were 307 satisfactory specimens from 308 cases with which definite histological diagnosis accuracy reaching 99.7%.In 232 cases malignancy was found(75.3%),benign lesions in 41(13.3%),false negative was found in 25(8.1%),and uncertain in 9(2.9%),poor specimen in 1(0.3%),and the diagnosis of malignant lymphoma was found in 82.8% of the first biopsy specimens.Conclusion Ultrasound-guided biopsy for superficial lymph node is a safe and effective method which can not be substituted in diagnosis of lymph node pathology.In addition,due to the use of 16G cutting needle,it also has better diagnostic value in the diagnosis of malignant lymphoma.