A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer / 中华肿瘤杂志

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib / 中华肿瘤杂志

MET gene is a proto-oncogene, which encodes MET protein with tyrosine kinase activity. After binding to its ligand, hepatocyte growth factor, MET protein can induce MET dimerization and activate downstream signaling pathways, which plays a crucial role in tumor formation and metastasis. Savolitinib, as a specific tyrosine kinase inhibitor (TKI) targeting MET, selectively inhibits the phosphorylation of MET kinase with a significant inhibitory effect on tumors with MET abnormalities. Based on its significant efficacy shown in the registration studies, savolitinib was approved for marketing in China on June 22, 2021 for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations. In addition, many studies have shown that MET TKIs are equally effective in patients with advanced solid tumors with MET gene amplification or MET protein overexpression, and relevant registration clinical studies are ongoing. The most common adverse reactions during treatment with savolitinib include nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. Based on two rounds of extensive nationwide investigations to guide clinicians, the consensus is compiled to use savolitinib rationally, prevent and treat various adverse reactions scientifically, and improve the clinical benefits and quality of life of patients. This consensus was prepared under the guidance of multidisciplinary experts, especially including the whole-process participation and valuable suggestions of experts in Traditional Chinese Medicine, thus reflecting the clinical treatment concept of integrated Chinese and western medicines.

Curcumin targets vascular endothelial growth factor viaactivating the PI3K/Akt signaling pathway and improves brainhypoxic-ischemic injury in neonatal rats

This study aimed to evaluate the effect of curcumin on brain hypoxicischemic(HI) damage in neonatal rats and whether the phosphoinositide 3-kinase(PI3K)/Akt/vascular endothelial growth factor (VEGF) signaling pathway is involved.Brain HI damage models were established in neonatal rats, which received the followingtreatments: curcumin by intraperitoneal injection before injury, insulin-likegrowth factor 1 (IGF-1) by subcutaneous injection after injury, and VEGF by intracerebroventricularinjection after injury. This was followed by neurological evaluation,hemodynamic measurements, histopathological assessment, TUNEL assay,flow cytometry, and western blotting to assess the expression of p-PI3K, PI3K, p-Akt,Akt, and VEGF. Compared with rats that underwent sham operation, rats with brainHI damage showed remarkably increased neurological deficits, reduced right bloodflow volume, elevated blood viscosity and haematocrit, and aggravated cell damageand apoptosis; these injuries were significantly improved by curcumin pretreatment.Meanwhile, brain HI damage induced the overexpression of p-PI3K, p-Akt, and VEGF,while curcumin pretreatment inhibited the expression of these proteins. In addition,IGF-1 treatment rescued the curcumin-induced down-regulated expression of p-PI3K, p-Akt, and VEGF, and VEGF overexpression counteracted the inhibitory effectof curcumin on brain HI damage. Overall, pretreatment with curcumin protectedagainst brain HI damage by targeting VEGF via the PI3K/Akt signaling pathway inneonatal rats.

Curcumin targets vascular endothelial growth factor viaactivating the PI3K/Akt signaling pathway and improves brainhypoxic-ischemic injury in neonatal rats

This study aimed to evaluate the effect of curcumin on brain hypoxicischemic(HI) damage in neonatal rats and whether the phosphoinositide 3-kinase(PI3K)/Akt/vascular endothelial growth factor (VEGF) signaling pathway is involved.Brain HI damage models were established in neonatal rats, which received the followingtreatments: curcumin by intraperitoneal injection before injury, insulin-likegrowth factor 1 (IGF-1) by subcutaneous injection after injury, and VEGF by intracerebroventricularinjection after injury. This was followed by neurological evaluation,hemodynamic measurements, histopathological assessment, TUNEL assay,flow cytometry, and western blotting to assess the expression of p-PI3K, PI3K, p-Akt,Akt, and VEGF. Compared with rats that underwent sham operation, rats with brainHI damage showed remarkably increased neurological deficits, reduced right bloodflow volume, elevated blood viscosity and haematocrit, and aggravated cell damageand apoptosis; these injuries were significantly improved by curcumin pretreatment.Meanwhile, brain HI damage induced the overexpression of p-PI3K, p-Akt, and VEGF,while curcumin pretreatment inhibited the expression of these proteins. In addition,IGF-1 treatment rescued the curcumin-induced down-regulated expression of p-PI3K, p-Akt, and VEGF, and VEGF overexpression counteracted the inhibitory effectof curcumin on brain HI damage. Overall, pretreatment with curcumin protectedagainst brain HI damage by targeting VEGF via the PI3K/Akt signaling pathway inneonatal rats.

The Lymphatic Drainage Pattern of Internal Mammary Sentinel Lymph Node Identified by Small Particle Radiotracer ((99m)Tc-Dextran 40) in Breast / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to detect the lymphatic drainage pattern of internal mammary area and verify the concept of internal mammary sentinel lymph node (IM-SLN) in breast. MATERIALS AND METHODS: A small particle radiotracer ((99m)Tc-Dextran 40) was prepared and tested. (99m)Tc-Dextran 40 was injected into intraparenchyma at the sound breast by a modified radiotracer injection technique. Subsequently, dynamic single-photon emission computed tomography (SPECT), computed tomography (CT), and SPECT/CT combination images were performed to identify the radioactive lymph vessels and internal mammary lymph nodes (IMLNs). The direction of lymph drainage and the location of the IMLNs were identified in the SPECT/CT imaging. RESULTS: The radiochemical purity of (99m)Tc-Dextran 40 was > 95%. (99m)Tc-Dextran 40 could drainage into first, second, and third lymph node and the radioactive lymph node could be detected by the γ detector in the animal experiment. After (99m)Tc-Dextran 40 injecting into intraparenchyma, 50.0% cases (15/30) were identified the drainage lymphatic vessels and radioactive IMLNs by SPECT. The drainage lymphatic vessel was found from injection point to the first IMLN (IM-SLN) after 10.5±0.35 minutes radiotracer injection, and then (99m)Tc-Dextran 40 was accumulated into the IM-SLN. The combination imaging of SPECT/CT showed the second IMLN received the lymph drainage from the IM-SLN. The lymphatic drainage was step by step in the internal mammary area. CONCLUSION: The lymph was identified to drain from different regions of the breast to IM-SLN, and then outward from IM-SLN to other IMLN consecutively. It demonstrated the concept of the IM-SLN and provided more evidences for the application of internal mammary sentinel lymph node biopsy.

Anti-Leukemia Effect and Mechanism of Oridonin on Imatinib-Sensitive and Imatinib-Resistant K562 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the molecular mechanism of resistance to imatinib in K562 cells(K562-R) and the anti-proliferative effect of oridonin (OR), as well as its mechanism in imatinib-sensitive and imatinib-resistant K562 cells (K562-S and K562-R cells).</p><p><b>METHODS</b>The expression of p-Lyn in K562-S and K562-R cells were detected by Western blot. The anti-proliferative effect of OR in K562-S and K562-R cells was assayed by MTT, the morphological changes were examined with microscope, the cell apoptosis was detected by flow cytometry, the expressions of BCL-2 and Akt/mTOR signaling pathway were detected by Western blot.</p><p><b>RESULTS</b>The over-expression of p-Lyn was detcected in K562-R cells, OR inhibited the proliferation of K562-S and K562-R cells and the value of ICwas 4.23±1.30, 4.97±2.23 µmol/L, respectively. The apoptotic rate was obviously enhanced after OR treatment for 24 h, compared with control group. OR down-regulated the expression of p-Lyn, mTOR signaling pathway and BCL-2 protein.</p><p><b>CONCLUSION</b>Over-expression of p-Lyn may be involved in the mechanism of resistance to imatinib. OR can inhibit the proliferation of K562-S and K562-R cells through down-regulating p-Lyn, inhibiting mTOR signaling pathway and down-regulating expression of BCL-2 protein.</p>

Predictors to assess non-sentinel lymph node status in breast cancer patients with only one sentinel lymph node metastasis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The purpose of this study was to investigate the feasibility of avoiding axillary lymph node dissection (ALND) for patients with only one sentinel lymph node (SLN) metastasis. The characteristics and predictive factors for non-sentinel lymph node (NSLN) metastasis of patients with single positive SLN were also analyzed.</p><p><b>METHODS</b>Patients with no and only one SLN metastasis (0/n and 1/n group, n ≥ 2) were selected from 1228 cases of invasive breast carcinoma, who underwent axillary dissection in Shandong Cancer Hospital between November 1999 and December 2011, to compare the characteristics of NSLN metastasis between them. For the 1/n group, the factors that influenced the NSLN metastasis were analyzed by univariate and multivariate analysis.</p><p><b>RESULTS</b>Differences of the NSLN metastasis between the 0/n and the 1/n groups were significant (P < 0.001). There was no significant difference between the axillary lymph node metastasis on level III in 1/n group and 0/n group (P = 0.570). When the total SLN number was ≥ 4 and with one positive case, the NSLN metastasis was not significantly different from that in the 0/n group (P = 0.118). In the 1/n group, clinical tumor size (P = 0.012), over-expression of Her-2 (P = 0.003), tumor grade (P = 0.018) and the total number of SLN (P = 0.047) significantly correlated with non-SLN metastasis. Clinical tumor size (P = 0.015) and the expression of Her-2 (P = 0.01) were independent predictive factors for non-SLN metastasis by the Logistic regression model.</p><p><b>CONCLUSION</b>Under certain conditions, breast cancer patients with single SLN metastasis could avoid ALND.</p>

Serum cytokine levels in patients with advanced non-small cell lung cancer: correlation with clinical outcome of erlotinib treatment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Serum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients. This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.</p><p><b>METHODS</b>A total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study. Blood samples were collected before the initiation of erlotinib treatment, and the levels of IL-1, IL- 2R, IL-6, and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA). Cutoff points were defined as the median levels of IL-1 (low (≥26.5 pg/ml) and high (>26.5 pg/ml)), IL-2R (low ( = 115 pmol/L) and high (>15 pmol/L)), IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)), and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ml)). Kaplan-Meier analysis was used to estimate the survival time, and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes, including time to progression (TTP) and overall survival (OS).</p><p><b>RESULTS</b>Between January 2007 and May 2011, 162 patients were enrolled. Their median age was 58 years. In this group, 109 were males and 53 were females, 74 were former or current smokers and 88 were non-smokers. A total of 122 patients had adenocarcinoma, 27 had squamous cell carcinoma, and 13 had tumors with other types of histology. And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1, while 23 scored at 2-3. Expression of IL-1, IL-2R, and IL-6 was not significantly associated with age, gender, ECOG performance status, smoking status, or histology and stage of tumor. Only TNF-α was associated with smoking status (P = 0.045). Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTP and OS than patients with high expression (P < 0.05). These cytokines remained significant upon multivariate analysis (P < 0.05).</p><p><b>CONCLUSION</b>IL-6 or TNF-α may serve as potential predictive biomarker for the efficacy of erlotinib.</p>

A novel technique for scintigraphic visualization of internal mammary sentinel lymph nodes in breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the effects of different injection techniques of radiotracer on the visualization rate of internal mammary sentinel lymph nodes (IMSLN) in breast cancer patients.</p><p><b>METHODS</b>A series of 137 consecutive breast cancer patients was included in this prospective study. Fifty-eight patients (group A) received the radiotracer (99)Tc(m)-sulphur colloid injected only into 1-2 points in the breast parenchyma in one quadrant, and seventy-nine patients (group B) received the radiotracer injection into the breast parenchyma in two quadrants of the breast. The differences of IMSLN visualization rates of the two groups were compared and the relevant affecting factors were analyzed.</p><p><b>RESULTS</b>The IMSLN visualization rate of the group B (70.9%, 56/79) was significantly higher than that of the group A (13.8%, 8/58) (P < 0.001). Both techniques seemed to be reliable to identify sentinel lymph node in the axilla (98.7% vs. 98.3%, P = 0.825). In addition, the visualization rate of internal mammary hotspots (82.2%) was more commonly seen in patients receiving injection of a larger volume of radiotracer ( ≥ 0.5 ml/point) than those receiving a smaller volume of radiotracer (<0.5 ml/point, 55.9%, P = 0.011).</p><p><b>CONCLUSIONS</b>The modified injection technique (two quadrants, large volume radiotraver, and ultrasound guidance) can significantly improve the visualization rate of IMSLN. Our findings should make the biopsy of IMSLN widely implemented and provide an effective and minimally invasive technique to evaluate the internal mammary lymph node status.</p>

Apoptosis effects of drug sensitivity leukemia cells induced by nano-realgar / 中国中药杂志

<p><b>OBJECTIVE</b>To explore apoptosis-inducing effects of realgar nanoparticle (nano-realgar) on drug-sensitive leukemia cells.</p><p><b>METHOD</b>Preparation of nano-realgar was mechanical milled using a high-energy planetary ball mill. Using drug-sensitive leukemia cells (K562) as target cells, MTT assay was used to detect the proliferating activity of K562 cells, and the cellular apoptosis was investigated with double staining of FITC-Annexin V and propidium iodide (PI) by flow cytometry. Flow cytometry (FCM) was employed to detect expression of intracellular Bax, Bcl-2, P-53 protein and the activity of Caspase-3.</p><p><b>RESULT</b>The raw realgar was made to ultra-fine powder by ball milling, and the average diameter of the nanoparticle was (72.72 +/- 22.18) nm measured with electron microscopes. Nano-realgar significantly inhibited the proliferation of K562 cells, Treated for 24, 48 and 72 hours, the 50% inhibitory concentration (IC50) was 43.48, 20.52, 16.07 mg x L(-1). After exposure to 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 hours, the apoptosis of K562 cells detected by Annexin V/PI staining was increased, the apoptotic rate of K562 cells was 10. 52% and 73.25%. After the target cells were treated with 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 h, the expression of P-53, Bax, Bcl-2 markedly increased in a time and dose-dependent manner. After administration of 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 h, the percentage of BCRP+, P-gp+ and co-expressing P-gp and BCRP cell population in K562 cells incrased dramatically.</p><p><b>CONCLUSION</b>Nano-Realgar significantly induced apoptosis of drug-sensitive leukemia cells.</p>

Analysis of clinicopathological factors associated with false-negative rate of sentinel lymph node biopsy in breast cancer patients: experience of a single center / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this study was to investigate the clinicopathologic factors associated with false-negative rate of sentinel lymph node biopsy (SLNB) in breast cancer, and to explore how to reduce the false-negative rate of SLNB.</p><p><b>METHODS</b>The clinicopathological data of 2265 patients with invasive breast carcinoma who underwent sentinel lymph nodes biopsy (SLNB) in Shandong Cancer Hospital between November 1999 and December 2011 were retrospectively analyzed. We screened 1228 patients who received axillary lymph node dissection after SLNB, and studied the clinicopathological factors that could be associated with false-negative rate of SLNB.</p><p><b>RESULTS</b>The false negative rate of this group was 10.7% (73/683), accuracy rate was 94.1% (1155/1228), and negative predictive value was 88.2% (545/618). Clinical tumor size (all P < 0.05), calendar year of surgery (all P < 0.05) and numbers of detected SLNs (all P < 0.05) were significantly related with false negative rate and accuracy rate of SLNB, determined by single factor analysis. Logistic regression model analysis showed that calendar year of surgery (P = 0.034) and numbers of detected SLNs (P = 0.012) were independent predictive factors for the false negative rate of SLNB.</p><p><b>CONCLUSIONS</b>False negative rate and accuracy rate of SLNB are significantly related to the calendar year of surgery and number of detected SLNs. Strict case selection, standard operation procedure, increaseing numbers of detected SLNs, and improvement of the skill of operators are effective measures to reduce the false negative rate of SLNB.</p>

A prospective comparison of molecular assay and touch imprint cytology for intraoperative evaluation of sentinel lymph nodes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients for axillary lymph node dissections during the same operation, reducing the need for a second operation. The present study aimed to prospectively compare the GeneSearch(TM) Breast Lymph Node (BLN) Assay with touch imprint cytology (TIC) for intraoperative evaluation of SLNs.</p><p><b>METHODS</b>SLNs were sectioned in 1.5 - 3.0 mm pieces. TIC was performed on all pieces and the BLN Assay and postoperative histology evaluations were performed on different alternating node pieces. Overall performance of the BLN Assay was compared with that of TIC relative to the postoperative histology results.</p><p><b>RESULTS</b>A total of 90 patients enrolled in the study. Complete intraoperative data for both the BLN Assay and TIC were collected in 86 patients. The sensitivity, specificity, and overall accuracy of the BLN Assay were 82%, 97%, and 92%, respectively on a per patient basis compared with those of TIC which were 67%, 100%, and 90%.</p><p><b>CONCLUSIONS</b>Performance of the BLN Assay was superior to that of TIC and the additional application of TIC did not help improve the total sensitivity and accuracy of the intraoperative assessment. The existence of ectopic breast tissue might be a possible cause of false positive for the BLN assay. In addition, the BLN Assay complements histopathology assessment and can minimize sampling error without increasing pathologists' workload.</p>

Using intra-operative GeneSearchTM Breast Lymph Node Assay to detect breast cancer metastases in sentinel lymph nodes: results from a single institute in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sentinel lymph node (SLN) biopsy has become a common procedure for early breast cancer patients. The GeneSearch(TM) Breast Lymph Node (BLN) Assay is a real-time RT-PCR assay for the detecting nodal metastases larger than 0.2 mm. China Breast Cancer Clinical Study Group (CBCSG)-001a is a prospective multi-center clinical trial that was conducted to validate the GeneSearch(TM) BLN Assay in China.</p><p><b>METHODS</b>The SLNs from 90 consecutive patients were identified and dissected, and then sectioned along the short axis into multiple blocks. Intra-operatively, the odd blocks were tested by BLN assay and the even ones were used for frozen section, while all the blocks were evaluated by touch imprint cytology. Post-operatively, the remaining tissues were assessed by histological evaluation.</p><p><b>RESULTS</b>A total of 189 SLNs was tested by BLN assay. The sensitivity, specificity, positive predictive value, and negative predictive value were 88.9%, 97.4%, 88.9% and 97.4%, respectively, for BLN assay, 75.0%, 100%, 100% and 94.4%, respectively, for frozen section, and 63.9%, 100%, 100% and 92.2%, respectively, for touch imprint cytology. The sensitivity of BLN assay was higher than that of touch imprint cytology (P = 0.01) and frozen section (P = 0.13). When assessing the nodes with micro-metastases, BLN assay had a significant higher sensitivity than frozen section (P = 0.023) and touch imprint cytology (P = 0.005).</p><p><b>CONCLUSION</b>The GeneSearch(TM) BLN Assay is an accurate and rapid intra-operative assay for breast SLNs and it is suitable for application in general medical practice.</p>

Value of intraoperative GeneSearch(TM) BLN assay to detect breast cancer metastases in sentinel lymph nodes / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the value of GeneSearch(TM) BLN assay as an intraoperative diagnostic method of sentinel lymph node metastases in breast cancer patients.</p><p><b>METHODS</b>Ninety consecutive patients were involved in this study. SLNs were intraoperatively identified and dissected, and then sectioned vertically to the long axis into multiple blocks. The odd blocks were tested by BLN assay and even ones prepared for frozen sectioning (FS), while all blocks were evaluated by touch imprint cytology (TIC). Post-operatively, residual tissues of the even blocks were assessed by histopathologic examination (4 - 6 µm thick serial sectioning permanent H&E slides were performed every 150 µm and one block made 6 slides).</p><p><b>RESULTS</b>BLN assay could be performed within less than 35 min after learning curve of 10 cases. A correlation was found between cycle time values of mammaglobin or cytokeratin-19 and size of metastases, with Spearman correlation coefficients of 0.67 and 0.71, respectively. The accuracy, sensitivity, specificity, positive predict value (PPV) and negative predict value (NPV) of the assay were 95.6%, 93.3%, 96.7%, 93.3% and 96.7%, While FS had the sensitivity, specificity, PPV, NPV of 76.7%, 100%, 100%, 89.6%, and TIC of 73.3%, 100%, 100%, 88.2%, respectively. The sensitivity of the assay was higher than that of FS (P = 0.07), and was significantly higher than that of FS (P = 0.04). When assessing patients with micro-metastases, the assay had a sensitivity of 85.7%, which was significantly higher than that of FS and TIC (P = 0.03).</p><p><b>CONCLUSION</b>GeneSearch(TM) BLN Assay can replace FS and TIC for the intraoperative assessment of SLN.</p>

Detection of epidermal growth factor receptor gene mutations in non-small cell lung cancer using bi-loop probe specific primer quantitative PCR / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the sensitivity of bi-loop probe and specific primer quantitative PCR (BPSP-qPCR) in the detection of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>BPSP-qPCR was employed to examine the presence of mutations of EFGR exon 19 through 21. Correlation of the mutations with clinicopathological characteristics and types of tumor samples were performed.</p><p><b>RESULTS</b>In the cohort of 265 specimens, 30.2% (80/265) mutations were found to be 19-del and/or L858R. Females (39.7%, 31/78), non-smokers (41.0%, 43/105) and adenocarcinoma patients (37.8%, 51/135) had a higher mutation rate (P<0.05) among 184 patients whose profiles were available. T790M combined with 19-del and/or L858R accounted for 3.3% (6/184) of the mutations. Male metastatic tumors (29.6%, 8/27), pleural fluids of females (42.9%, 9/21) and non-smokers (40.7%, 11/27) were found to have higher percentage of 19-del and/or L858R mutations, in contrast, no mutations were found in the metastatic lesions of non-adenocarcinoma patients (P>0.05).</p><p><b>CONCLUSIONS</b>BPSP-qPCR is a robust method in detection of EGFR mutations with high consistency and sensitivity. The difference of EGFR mutations in primary tumors, metastatic lesions and pleural fluids suggests that EGFR tyrosine kinase inhibitors (EGFR-TKI) treatment may have variable treatment effects depending on the tumor sites.</p>

P38MAPK pathway regulates COX-2 and caspase-3 expression in a mouse model of Parkinson disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of p38 mitogen-activated protein kinase (p38MAPK) on the expression of COX-2 and caspase-3 in the substania nigra (SN) of mice with MPTP-induced Parkinson disease (PD).</p><p><b>METHODS</b>C57BL/CN mice were treated with MPTP to prepare a subacute PD model, and their behavioral changes following the treatment were observed. Immunohistochemistry and Western blotting were performed to detect the expression of tyrosine hydroxylase (TH), COX-2 and phosphorylation of P38MAPK in the SN and their changes following treatment with SB203580, a specific inhibitor of P38MAPK.</p><p><b>RESULTS</b>The 7-day model group showed typical symptoms of PD with decrements of TH-positive neurons and TH protein level in the SN of the midbrain by about 65% and 75%, respectively (P<0.01). In the 3-day model group, the COX-2-, caspase-3- and phosphorylated P38MAPK-immunoreactive cells and their protein levels in the SN increased markedly with obvious loss of TH-positive neurons. Administration of SB203580 obviously lessened the above changes (P<0.01).</p><p><b>CONCLUSION</b>P38MAPK regulates the inflammation and apoptosis in the SN of the mouse model of subacute PD, and SB203580 may provide some neuroprotective effect.</p>

Study on the target movement in external-beam partial breast irradiation with active breathing control after breast-conserving surgery / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the displacement of surgical clip and cavity during different respiratory status, intrafraction and interfraction for the patients treated by external-beam partial breast irradiation (EB-PBI) assisted by active breathing control (ABC) device after breast-conserving surgery.</p><p><b>METHODS</b>After breast-conserving surgery, twenty-five patients with stage I/II breast cancer who was identified to be feasible for EB-PBI underwent CT-simulation positioning assisted with ABC device. Five series of CT images were done during three respiratory status, which included one series of images during free breathing status (FB), two series of images during moderate deep inspiration breath hold (mDIBH), two series of images during deep expiration breath hold (DEBH) at 75% maximum inspiration capacity, and all of the five series of images were transferred to ADAC Pinnacle3 treatment planning system. This procedure was repeated after 10 - 15 days. The targets were delineated and the first appeared clips were marked by the same radiotherapist on the CT images in mDIBH and DEBH status from the first CT simulation positioning to analyze the displacement of the targets produced by respiratory status. The targets were also delineated and all of the clips were marked by the same radiotherapist on another two series of CT images during mDIBH from the first and repeated CT-simulation positioning for analyzing the intrafraction and interfraction movement of cavity and clips, respectively.</p><p><b>RESULTS</b>There was a significant difference between mDIBH and DEBH in the movement of the point of interest (POI) of the first appeared clip in the directions of X (0.22 cm), Y (1.27 cm) and Z axis (0.50 cm) (chi2 =9.558, P = 0.008); and this was also found to be present in the movement of POI of the cavity in the directions of X (0.10 cm), Y (1.08 cm) and Z axis (0.50 cm) (chi2 = 20.44, P <0.01). Regardless of the clip and the cavity, the movement extent along the direction of Y axis was the biggest. However, no significant difference was found in the displacements of POI of the geometric form constructed by all clips in the directions of X (0.09 cm, 0.68 cm), Y (0.14 cm, 0.37 cm) and Z axis (0.25 cm, 0.50 cm) in the same respiratory status of mDIBH at different moment in the intrafraction and interfraction, respectively; and this was also found in the displacements of POI of the cavity in the direction of X (0.15 cm, 0.66 cm), Y (0.17 cm, 0.45 cm) and Z axis (0.25 cm, 0.75 cm)in the same respiratory status of mDIBH at different moment in the intrafraction and interfraction, respectively.</p><p><b>CONCLUSION</b>The margin of planning target volume for external beam partial breast irradiation in different respiratory status is found to be different, the margin displacement along the different axis is also different in free breathing status. However, it can be controlled almost at the same extent in moderate deep inspiration breath hold if assisted by active breathing control device.</p>

Reconstruction and transplantation of the composite skin comprising epithelial growth factor gene-transfected keratinocytes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the epithelial growth factor (EGF) expression of EGF gene-transfected keratinocytes and its effect on cell proliferation after grafting.</p><p><b>METHODS</b>Newborn Balb/c mouse keratinocytes and gene transfected keratinocytes were seeded on the surface of acellular dermal matrix and cocultured in different ratios as follows: 1:1, 1:3, or 1:5 1 week after culture. The composite skin was grafted onto the full-thickness wound in Balb/c mouse. Specimen was harvested at interval after grafting and underwent the immunohistochemistry staining for EGF and proliferating cell nuclear antigen (PCNA).</p><p><b>RESULTS</b>Immunohistochemical staining showed EGF was expressed in the newly generated epidermis 1-2 week after grafting of the composite skin comprising Balb/c mouse keratinocytes and gene-transfected keratinocytes (at the ratio of 1:5). One week after surgery, Anti-PCNA positive basal cells were more than that in composite skin containing Balb/c mouse keratinocytes alone (P<0.01).</p><p><b>CONCLUSION</b>The gene-transfected keratinocytes expresses EGF and promotes the proliferation of keratinocytes in the early stage after transplantation.</p>

5589del8: the recurrent mutation of BRCA1 gene in Chinese breast cancer patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the "hot spot" of BRCA1/2 gene mutations in Chinese mainland breast cancer population.</p><p><b>METHODS</b>The known BRCA1/2 gene mutations in author's previous studies were reanalyzed by denaturing high performance liquid chromatography and DNA sequencing method in 177 patients with early onset breast cancer or affected relatives and 426 sporadic breast cancer patients from four breast cancer centers in China.</p><p><b>RESULTS</b>Three cases were found with BRCA1 5589del8 mutation out of 247 hereditary-predisposing breast cancer patients (70 patients in previous study and 177 patients in current study) and 2 cases with BRCA1 5589del8 mutation out of 426 sporadic breast cancer patients. They had similar even same haplotype.</p><p><b>CONCLUSION</b>BRCA1 5589del8 mutation is likely to be the "founder mutation" in Chinese population, but it should be confirmed by further studies.</p>

BRCA1 germ line mutations in Chinese early-onset breast cancer patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the role of disease associated germ line mutations in BRCA1 gene among Chinese early-onset breast cancer patients.</p><p><b>METHODS</b>A total of 188 early-onset breast cancer patients, who were diagnosed with breast cancer before 41-year-old, were enrolled from four breast cancer clinical centers in China. Thirty-nine of them (20.7%) also had family history of breast/ovarian cancer. DNA extracted from lymphocytes was amplified by polymerase chain reaction (PCR) for the entire exons and the splicing sites of BRCA1. Twenty-two of the patients were screened by single strand conformation polymorphism (SSCP), and the other 166 of them were screened by denaturing high performance liquid chromatography (DHPLC). The abnormal fragments recognized were ascertained by DNA direct sequencing. For those samples with the same recurrent mutation, five BRCA1-linked markers (D17S855, D17S1322, D17S1323, D17S1326 and D17S1327) were used for the allelotype analysis.</p><p><b>RESULTS</b>Twelve disease-associated mutations were identified in 15 (8.0%) patients, among which BRCA1 1100delAT and 5589del8 were identified in 3 and 2 patients respectively. Nine (23.1%) of them were identified in those with breast/ovarian cancer family history. The difference of BRCA1 mutation frequency between the patients with and without family history was statistically significant (P=0.001). Allelotype analysis showed the two BRCA1 5589del8 mutation carriers shared the same allelotype in all the 5 STR sites, and two of the three 1100delAT mutation carriers, who came from the northern China, also shared the same allelotype in all the 5 STR sites, which were different from those of the 5589del8 mutation carriers'.</p><p><b>CONCLUSION</b>This is a relatively very large scale multi-hospital-based study of BRCA1 mutations in Chinese early-onset breast cancer patients up to now. It seems reasonable to give genetic consultations and genetic test of BRCA1 gene to early-onset breast cancer patients in China, especially for those with breast/ovarian cancer family history. The two recurrent mutations might be founder mutations of Chinese population. It might be cost-effective to analyze these two mutations before whole gene analysis.</p>