Shandong Cancer Hospital & Institute

Jinan, China

Shandong Cancer Hospital & Institute

Jinan, China
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Ma F.,Peking Union Medical College | Li H.,Shandong Cancer Hospital Institute | Wang H.,Peking Union Medical College | Shi X.,Peking Union Medical College | And 6 more authors.
Cancer Letters | Year: 2014

The mechanism underlying the aggressive behaviors of triple negative breast cancer (TNBC) is not well characterized yet. The association between cancer stem cell (CSC) population and the aggressive behaviors of TNBC has not been established. We found the CD44+/CD24- cell population was enriched in TNBC tissues and cell lines, with a higher capacity of proliferation, migration, invasion and tumorigenicity as well as lower adhesion ability. The CD44+/CD24- cell population with cancer stem cell-like properties may play an important role in the aggressive behaviors of TNBC. This discovery may lead to new therapeutic strategies targeting CD44+/CD24- cell population in TNBC. © 2014 Elsevier Ireland Ltd. All rights reserved.

Gao S.,Shandong Cancer Hospital & Institute | Gao S.,University of Jinan | Wu H.,Wuyi County Peoples Hospital Of Hengshui City | Li W.,Shandong Cancer Hospital & Institute | And 7 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2015

Purpose: Angiogenesis is an essential step in tumour development and metastasis. Integrin αvβ3 plays a major role in angiogenesis, tumour growth and progression. A new tracer, 18F-AL-NOTA-PRGD2, denoted as 18F-alfatide, has been developed for positron emission tomography (PET) imaging of integrin αvβ3. This is a pilot study to test the safety and diagnostic value of 18F- arginine-glycine-aspartic acid (RGD) PET/computed tomography (CT) in suspected lung cancer patients. Methods: Twenty-six patients with suspected lung cancer on enhanced CT underwent 18F-alfatide RGD PET/CT examination before surgery and puncture biopsy. Standard uptake values (SUVs) and the tumour-to-blood ratios were measured, and diagnoses were pathologically confirmed. Results: RGD PET/CT with 18F-alfatide was performed successfully in all patients and no clinically significant adverse events were observed. The 18F-alfatide RGD PET/CT analysis correctly recognized 17 patients with lung cancer, 4 patients (hamartoma) as true negative, and 5 patients (4 chronic inflammation and 1 inflammatory pseudotumour) as false positive. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-alfatide RGD PET/CT for the diagnosis of suspected lung cancer patients was 100, 44.44, 80.77, 77.27, and 100 %, respectively. The area under a receiver operating characteristic (ROC) curve was 0.75 (P = 0.038), and ROC analysis suggested an SUVmax cut-off value of 2.65 to differentiate between malignant lesions and benign lesions. The SUV for malignant lesions was 5.37 ± 2.17, significantly higher than that for hamartomas (1.60 ± 0.11; P < 0.001). The difference between the tumour-to-blood ratio for malignant lesions (4.13 ± 0.91) and tissue of interest-to-blood ratio for hamartomas (1.56 ± 0.24) was also statistically significant (P < 0.001). Neither the SUVmax nor the tumour-to-blood ratio was significantly different between malignant lesions and inflammatory lesions or inflammatory pseudotumours (P > 0.05). Sixteen of 26 patients later underwent successful surgery, and pathologic examination confirmed nodes positive for metastasis in 14 of 152 lymph nodes. The sensitivity, specificity, accuracy, PPV, and NPV of PET/CT for lymph nodes was 92.86, 95.65, 95.40, 61.90, and 99.25 %, respectively. Conclusion: Our results suggest that RGD PET/CT with the new tracer 18F-alfatide is safe and potentially effective in the diagnosis of non-small cell lung cancer. It may be used in the diagnosis of lung cancer, successfully distinguishing malignant lesions from hamartoma. However, it is difficult to clearly differentiate inflammatory or inflammatory pseudotumours from malignant lesions. Additional studies with a larger number of patients are needed to validate our findings. © 2015, Springer-Verlag Berlin Heidelberg.

Zhang Q.S.,Shandong Cancer Hospital & Institute
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2010

To explore the overlap ratio of the target volume in different respiratory statuses of active breath control (ABC) and their differences during external-beam partial breast irradiation (EB-PBI), and from the perspective of target volume overlap to determine the influence of the ABC-assisted breathing condition on intra-fractional target movement of EB-PBI. The patients, who received breast-conserving surgery with silver clips marked at the margins of the cavity and were suitable for EB-PBI, were immobilized on the breast bracket to undertake CT simulation assisted by ABC device, six sets of CT simulation images including two sets of image in state of moderate deep inspiration breathing control (mDIBH), two sets of images in state of free breath (FB) and two sets of images in state of deep expiration breathing control (DEBH) were obtained. The six sets of images were transferred to Pinnacle(3) treatment planning system (TPS), then automatic fusion and registration between two sets of mDIBH images, two sets of FB images, two sets of DEBH images and mDIBH image and DEBH image were achieved separately. Thereafter, the overlap ratios of GTV with GTV, CTV with CTV, PTV with PTV were calculated by the Pinnacle(3) TPS. The differences between the overlap ratios of the three kinds of targets in the same registered image and the difference between the overlap ratios of the same kind of target in the different registered images were statistically analyzed using statistical package of SPSS 11.5. Based on mDIBH/mDIBH registration, the overlap ratios of GTV/GTV, CTV/CTV and PTV/PTV were (83.54 ± 11.41)%, (93.00 ± 6.49)%, and (95.26 ± 4.90)%, respectively, and the differences of the overlap ratios between GTV/GTV and CTV/CTV, GTV/GTV and PTV/PTV were all statistically significant (P < 0.05), but statistically not significant between CTV/CTV and PTV/PTV (P > 0.05). Based on FB/FB registration, the overlap ratios of GTV/GTV, CTV/CTV and PTV/PTV were (72.55 ± 29.10)%, (89.36 ± 9.53)% and (92.47 ± 7.25)%, respectively, and the differences of the overlap ratios between GTV/GTV and CTV/CTV, CTV/CTV and PTV/PTV were all not statistically significant (P > 0.05), but statistically significant between GTV/GTV and PTV/PTV (P < 0.05). Based on DEBH/DEBH registration, the overlap ratios of GTV/GTV, CTV/CTV and PTV/PTV were (79.48 ± 22.31)%, (92.83 ± 6.77)% and (95.05 ± 4.81)%, respectively, and the differences of the overlap ratios between GTV/GTV and CTV/CTV (P = 0.000), CTV/CTV and PTV/PTV (P = 0.037), GTV/GTV and PTV/PTV (P = 0.000) were statistically all significant (P = 0.000). The differences of the overlap ratios of GTV/GTV, CTV/CTV, and PTV/PTV (P = 0.000) between mDIBH/mDIBH and DEBH/DEBH, mDIBH/mDIBH and FB/FB, FB/FB and DEBH/DEBH were all statistically significant (P = 0.000), and not statistically significant between mDIBH/mDIBH and mDIBH/DEBH, FB/FB and mDIBH/DEBH. During the delivering of EB-PBI assisted by ABC, the intra-fractional overlap ratios of the target volume between the same breathing state is increasing in the order of GTV/GTV → CTV/CTV → PTV/PTV. The difference of the overlap ratios of the target volumes between mDIBH and mDIBH, FB and FB, DEBH and DEBH is not significant, and the overlap ratios of PTV/PTV in the three breathing statuses of mDIBH, FB and DEBH reaches a higher level. Therefore, from the perspective of target volume overlap, if the setup error is corrected online before delivering, the necessity of breathing control during delivering of EB-PBI is worthy discussing.

Zheng G.,Shandong Cancer Hospital & Institute
Zhonghua yi xue za zhi | Year: 2011

To explore the studies and application status of sentinel lymph node biopsy (SLNB) in breast cancer in China by statistically analyzing the relevant domestic literature. The literatures published from January 1999 to December 2005 were searched in the databases of China, Info, CBM and CNKI retrieval system with "breast tumor, SLN and SLNB" as the key words. A total of 88 manuscripts were selected with 2 new reports of SLNB. The successful rate, accuracy, false-negative rate and sensitivity of SLNB were analyzed by SPSS 10.0 statistical analysis software. Among a total of 6282 patients, the detection rate of SLNB was 90.82% (5705/6282) and the overall false-negative rate 9.69% (259/2671). The prediction sensitivity, specificity, false positive rate, accuracy, negative and positive predictive value of SLN for axillary lymph nodes status were 90.30%, 99.64%, 0.41%, 86.52%, 92.11% and 99.55% respectively. SLNB can accurately predict the axillary lymph node metastasis. And its detection rate is correlated with patient age and tumor location. The detection rate and false-negative rate has nothing to do with the tracer injection site. A combined regimen has a higher detection rate and a low false negative rate. Affecting the whole breast, SLN is not correlated with a particular area of breast. The validation phase of SLNB in breast cancer is currently feasible in China.

Wang Y.S.,Shandong Cancer Hospital & Institute
Zhonghua yi xue za zhi | Year: 2011

To evaluate the clinical value of GeneSearch(TM) BLN Assay as an intra-operative diagnostic method of sentinel lymph node (SLN) for breast cancer patients. A total of 479 consecutive patients from six centers were involved in this prospective study. The SLNs were identified, dissected and then sectioned along the short axis into multiple blocks. The odd blocks were tested intra-operatively by the above-mentioned assay and the even blocks assessed post-operatively by histopathologic examination. The 4 - 6 μm thick stepwise sectioning permanent HE slides were prepared every 150 μm and one block yielded 6 slides. In addition, the even blocks of 136 patients were prepared for frozen section (FS) and all blocks of 156 patients evaluated intra-operatively by touch imprint cytology (TIC). In the node basis analysis, its accuracy, sensitivity, specificity, positive predict value (PPV) and negative predict value (NPV) were 93.0%, 85.6%, 94.6%, 76.6% and 96.9% respectively. Its sensitivity was similar to that of FS (84.9%, P = 0.885) and significantly higher than that of TIC (70.0%, P = 0.007). When assessing nodes with macro-metastases, its sensitivity was similar to that of FS (93.6% vs 95.6%, P = 0.558) and significantly higher than that of TIC (93.6% vs 80.9%, P = 0.011). When assessing nodes with micro-metastases, it had a higher sensitivity than that of FS (57.5% vs 44.4%, P = 0.356) and TIC (57.5% vs 30.8%, P = 0.094). In the patient basis analysis, the accuracy, sensitivity, specificity, PPV and NPV were 91.4%, 87.5%, 92.9%, 81.8% and 95.3% respectively. Its sensitivity was similar to that of FS (84.5%, P = 0.576) and significantly higher than that of TIC (75.0%, P = 0.049). After adjustment, it had the accuracy, sensitivity, specificity, PPV and NPV of 91.7%, 83.5%, 95.2%, 88.3% and 93.0% respectively. Its sensitivity was higher than that of FS (72.1%, P = 0.054) and significantly higher than that of TIC (66.7%, P = 0.011). The two had no significant difference in the sensitivity and specificity. After a learning curve of around 10 cases, it could be performed in a median time of around 35 min. The threshold cycle time values of MG and CK-19 were 36 and 31 respectively. The type of metastases could be estimated approximately according to the cycle time values. The cycle time values of MG under 33 indicated SLN macro-metastases and those of 33-36 denoted micro-metastases. The values of CK-19 under 29 indicated SLN macro-metastases and those of 29-31 denoted micro-metastases. As an accurate and rapid intra-operative assay for breast sentinel lymph nodes, the GeneSearch(TM) BLN Assay may replace FS and TIC in general medical practice.

PubMed | Shandong Cancer Hospital & Institute
Type: Evaluation Studies | Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology | Year: 2016

Bacterial infections increased greatly in cancer patients who accepted cytotoxic chemotherapeutics. VCS parameters of neutrophils were reported to be an indicator for acute bacterial infection accompanied by increased WBC counts. Here we explored the possibility of VCS parameters of neutrophils, monocytes and lymphocytes in indicating the local bacterial infection in cancer patients. A total of 310 cancer patients and 90 healthy controls were retrospectively analyzed, and 190 of them were diagnosed as acute local bacterial infection. The VCS parameters acquired from a Beckman Coulter LH750 haematology analyzer were investigated to determine which VCS parameters could indicate local bacterial infection in cancer patients with leucopenia caused by cytotoxic agents. VCS parameters of cancer patients were significantly affected by infection. For diagnosing bacterial infection of cancer patients, the best single indicator was mean monocyte light scatter (MMS) with a sensitivity of 95.12 % and a specificity of 58.82 % and the area under the curve (AUC) was 0.792. A combination of the following five parameters: mean neutrophil volume (MNV), MMS, mean lymphocyte conductivity (MLC), mean lymphocyte light scatter (MLS) and neutrophil volume distribution width (NDW) could provide a better index in diagnosing bacterial infection than any single parameter (sensitivity 75.8 %, specificity 64.72 %, AUC 0.763). Taking WBC counts into consideration, VCS parameters could better indicate bacterial infection for cancer patients with abnormal WBC level than that with normal WBC level. Aside from neutrophils, the VCS of monocytes and lymphocytes were also ideal indicators for bacterial infection. The combination of VCS parameters could increase the sensitivity, specificity and accuracy of diagnosis of cancer patients.

PubMed | Shandong Academy of Sciences, Shandong University and Shandong Cancer Hospital & Institute
Type: | Journal: OncoTargets and therapy | Year: 2016

To investigate the potential dosimetric benefits from four-dimensional computed tomography (4DCT) compared with three-dimensional computed tomography (3DCT) in radiotherapy treatment planning for external-beam partial breast irradiation (EB-PBI).3DCT and 4DCT scan sets were acquired for 20 patients who underwent EB-PBI. The volume of the tumor bed (TB) was determined based on seroma or surgical clips on 3DCT images (defined as TB3D) and the end inhalation (EI) and end exhalation (EE) phases of 4DCT images (defined as TBEI and TBEE, respectively). The clinical target volume (CTV) consisted of the TB plus a 1.0 cm margin. The planning target volume (PTV) was the CTV plus 0.5 cm (defined as PTV3D, PTVEI, and PTVEE). For each patient, a conventional 3D conformal plan (3D-CRT) was generated (defined as EB-PBI3D, EB-PBIEI, and EB-PBIEE).The PTV3D, PTVEI, and PTVEE were similar (P=0.549), but the PTV coverage of EB-PBI3D was significantly less than that of EB-PBIEI or EB-PBIEE (P=0.001 and P=0.025, respectively). There were no significant differences in the homogeneity or conformity indexes between the three treatment plans (P=0.125 and P=0.536, respectively). The EB-PBI3D plan resulted in the largest organs at risk dose.There was a significant benefit for patients when using 3D-CRT based on 4DCT for EB-PBI with regard to reducing nontarget organ exposure. Respiratory motion did not affect the dosimetric distribution during free breathing, but might result in poor dose coverage when the PTV is determined using 3DCT.

PubMed | Shandong Cancer Hospital & Institute
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

7044 Background: Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field radiotherapy (IFRT) in patients with stage III non-small cell lung cancer (NSCLC).Patients with inoperable stage III NSCLC were enrolled and patients with previous treatment were ineligible, as were those with supraclavicular nodal metastases, pleural effusion, the Karnofsky performance status of <80 or a weight loss exceeding 10% of baseline in the preceding 3 months. Two-hundred patients were treated with concurrent chemo-radiotherapy and randomized into IFRT group or ENI group. Two cycles of cisplatin-based chemotherapy (CHT) were delivered before radiotherapy, and another 2-3 cycles were followed after radiotherapy by the same or changed regime according to different response to the first 2 cycles of CHT. Radiotherapy was delivered using 3D treatment planning in once-daily fractions of 2 Gy to 68-74 Gy for IFRT or 60-64 Gy for ENI. The involved field consisted of the pre-CHT (or greatest) tumor volume, and any mediastinal nodes confirmed by biopsy or with a short-axis diameter of 1 cm on CT.193 patients had complete follow-up data. Radiation pneumonitis rate of patients with ENI was higher than patients with IFRT (29% vs. 17%, P = 0.044 ).The main cause of failure was local failure in 49% patients with ENI group and 41% with IFRT within 2 years. Only 7% of patients with IFRT developed a failure in an elective nodal region. Patients in IFRT group achieved a better overall response than ENI group (90% vs. 79%, P = 0.032). The overall survival at 1, 2, and 3 years was 59.7%, 25.6%, and 19.2% for ENI group vs. 67.2%, 38.7, and 27.3%for IFRT (P = 0.048).Local and distant failures remain the overwhelming modes of failure for stage III NSCLC patients. The omission of ENI did not result in any increase in isolated nodal failures, and it allowed a dose of 68-74 Gy to be safely administered to a substantial proportion of patients with inoperable Stage III NSCLC. Dose-escalation by conformal IFRT combined with CHT may improve the outcome for stage III NSCLC. No significant financial relationships to disclose.

PubMed | Shandong University and Shandong Cancer Hospital & Institute
Type: | Journal: Future oncology (London, England) | Year: 2016

We assessed risk factors for bone metastasis in patients with completely resected non-small-cell lung cancer (NSCLC).A total of 374 NSCLC patients who had undergone a complete resection from January 2008 to May 2012 were included in this retrospective study. The Kaplan-Meier method and multivariate Cox regression analysis were used to evaluate risk factors for bone metastasis.A total of 47 (47/374; 12.6%) patients developed bone metastasis up until the last follow-up time. The patients with bone metastasis included 33 adenocarcinoma patients and 6 (4.9%) squamous cell carcinoma patients (p = 0.001). There were 17 (10.2%) patients with pathological stage (P-stage) I disease, 9 (9.5%) patients with P-stage II disease and 21 (18.8%) patients with P-stage III disease (p = 0.007) among all the bone metastasis patients. For patients without or with bone metastasis, the overall survival ratio at 3 years was 71.6% compared with 46.8% (p < 0.0001), respectively.Adenocarcinoma and P-stage III disease were related to a high risk of bone metastasis.

PubMed | Shandong Cancer Hospital & Institute
Type: Journal Article | Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2016

To inquire into the influence of silencing HMGB1 expression by small interfering RNA (siRNA) on cell growth, proliferation, invasion and metastasis of colorectal cancer LoVo cells both in vitro and in vivo.Lentivirus-mediated HMGB1 siRNA was transfected into LoVo cells to silence the HMGB1 expression. The HMGB1 mRNA and protein expression after siRNA transfection was detected by RT-PCR and Western blot. MTT assay was used to observe the cell proliferation and to draw a growth curve. Cell cycle was measured by flow cytometry. The ability of invasion and speed of cell migration were evaluated by transwell chamber invasion and cell scratch assay. The influence of HMGB1 silencing on the proliferation of LoVo cells in vivo was observed in LoVo tumor-bearing nude mice.Lentivirus-mediated siRNA was successfully transfected into colorectal cancer cell line LoVo. The expression of HMGB1 mRNA and protein in the HMGB1-siRNA group were 0.240.04 and 0.210.03, respectively. Compared with the HMGB1-siRNA-Neg group (0.820.13, 1.150.18) and control group (0.930.15, 1.210.20), the difference was significant (P<0.05). MTT assay showed that the cell proliferation in the HMGB1-siRNA group was significantly inhibited when compared with that in the HMGB1-siRNA-Neg group and control group (P<0.05). Flow cytometry showed that the proliferation index (PI) of HMGB1-siRNA group was 38.271.32, significantly lower than 54.661.74 in the HMGB1-siRNA-Neg group and 57.431.29 in the control group (P<0.05). The transwell assay showed that the number of penetrated cells in the HMGB1-siRNA group was 14.03.5, significantly lower than 51.06.7 in the HMGB1-siRNA-Neg group and 68.05.3 in the control group (P<0.05). Similarly, the scrape wound recovered significantly slower in the HMGB1-siRNA group (83.6123.21) m than that in the other two groups (202.8646.46) m and (214.5857.38) m(P<0.05). The nude mouse xenograft tumor experiment showed that the final tumor volume was (52134) mm3 in the HMGB1-siRNA group, significantly smaller than that in the HMGB1-siRNA-Neg group of (76346) mm3 and control group of (80251) mm3 (P<0.05).Lentivirus-mediated HMGBl-siRNA can effectively inhibit the HMGB1 expression in colorectal cancer LoVo cells both in vitro and in vivo. HMGB1 gene silencing can slow the growth of colorectal cancer cells, extend the cell proliferation cycle, decrease their invasion and migration, and significantly inhibit the growth of xenograft tumor in nude mice.

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