2.Expert consensus on off-label use of small molecule anti-angiogenic drugs in the treatment of metastatic breast cancer.
Chinese Journal of Oncology 2022;44(6):523-530
Breast cancer is the most common cancer in the world, and 5-year survival rate of metastatic breast cancer is about 20%. The treatment of metastatic breast cancer is mainly chemotherapy, endocrine therapy and targeted therapy. However, after multiline treatment, patients with MBC especially the triple negative breast cancer face the problem of drug resistance. Tumor angiogenesis theory suggests that blocking angiogenesis can inhibit tumor growth and migration. Based on this, angiogenesis treatment strategy is proposed. Antiangiogenic drugs mainly include biological macromolecular drugs targeting vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) and small molecule VEGFR inhibitors. Angiogenesis is known to play a key role in the growth and metastasis of breast cancer. Therefore, anti-angiogenetic therapy has potential in metastatic breast cancer patients. Since the approval of tumor drug indications by NPMA in China is often later than the release of the latest research data, the National Health Commission issued "the guiding principles for the clinical application of new antitumor drugs" in 2020. The principle pointed out that under special circumstances such as the absence of better treatment, medical institutions should manage the usage of drugs that are not clearly defined in the instructions but have evidence-based data. Based on the latest research progress in breast cancer, the consensus writing expert group collated published reports, international academic conferences, conducted analysis, discussion and summary, collected data on the use of small molecule anti-vascular targeting drugs for advanced breast cancer, and formulated "expert consensus on the application of small molecule anti-angiogenic drugs in the treatment of advanced breast cancer" . For clinicians' reference only.
Angiogenesis Inhibitors/therapeutic use*
;
Breast Neoplasms/pathology*
;
Consensus
;
Female
;
Humans
;
Neovascularization, Pathologic/pathology*
;
Off-Label Use
;
Vascular Endothelial Growth Factor A/metabolism*
3.Establishment of a rat model of dimethylbenzanthracene-induced vulvar squamous intraepithelial lesions.
Yijin FAN ; Huajun TANG ; Yao LIU ; Chengzhi LI
Journal of Southern Medical University 2018;38(11):1318-1324
OBJECTIVE:
To establish a SD rat model of vulvar squamous intraepithelial lesions.
METHODS:
Seventy female SD rats were randomized into 4 groups, namely the blank control group (=10), mechanical irritation group (=10), acetone solution group (=10), and mechanical irritation with DMBA acetone solution group (=40, model group), and the corresponding treatments were administered 3 times a week for 14 weeks. The changes of the vulvar skin of the rats were observed regularly until the 18th week. The expression of mutant p53 (mtp53) and vascular endothelial growth factor (VEGF) proteins were detected using immunohistochemistry and Western blotting, and the expressions of mtp53 and VEGF mRNA were detected with qRT- PCR in the blank control group and model group.
RESULTS:
No significant differences were found in the morphological or histopathological changes of the skin among the blank control group, mechanical irritation group and acetone solution group. In the model group, low-grade squamous intraepithelial lesions (LSIL) occurred in 28 rats (70%) and high-grade squamous intraepithelial lesions (HSIL) in 11 rats (27.5%) at 14 weeks, with a success rate of 97.5% in inducing vulvar squamous intraepithelial lesions. Compared with the blank control group, the rats in the model group showed significantly increased expressions of mtp53 and VEGF at both the protein level ( < 0.05) and the mRNA level ( < 0.05).
CONCLUSIONS
DMBA in acetone solution combined with mechanical irritation can induce vulvar squamous intraepithelial lesions in female SD rats.
9,10-Dimethyl-1,2-benzanthracene
;
Acetone
;
Animals
;
Blotting, Western
;
Carcinogens
;
Disease Models, Animal
;
Female
;
Friction
;
Immunohistochemistry
;
Precancerous Conditions
;
chemically induced
;
metabolism
;
pathology
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Skin
;
pathology
;
Solvents
;
Tumor Suppressor Protein p53
;
metabolism
;
Vascular Endothelial Growth Factor A
;
metabolism
;
Vulvar Neoplasms
;
chemically induced
;
metabolism
;
pathology
4.Clinical and pathological analysis of renal cell carcinoma bone metastasis.
Zi Xiong HUANG ; Yi Qing DU ; Xiao Peng ZHANG ; Shi Jun LIU ; Tao XU
Journal of Peking University(Health Sciences) 2018;50(5):811-815
OBJECTIVE:
To analyze the clinical and pathological characteristics of renal cell carcinoma bone metastasis (RCC-BM) patients.
METHODS:
Data of RCC-BM patients from July 2003 to November 2017 were retrospectively reviewed. The patients' baseline characteristics (age, gender), tumor characteristics [specific sites of bone metastasis, time to bone metastasis (TTBM), imaging features of bone disease, coexistence of other metastasis], as well as pathological features (histological classification of primary and bone metastasis, immunohistochemical stain results) were collected. Descriptive analysis and difference analysis were used.
RESULTS:
A total of 113 RCC-BM patients were enrolled with the gender ratio (male:female) of 4:1, mean age of 59.39 years, and all present of osteolysis bone lesions. The common sites of bone metastasis were vertebra (46.0%) and pelvis (38.9%). Other distant metastasis sites coexisted in 28.3%, while 48.18% RCC-BM patients presented with synchronous metastasis (TTBM=0). The median TTBM for metachronous metastasis was 48 months. The majority in this cohort were determined to have primary tumor of clear cell carcinoma. After immunohistochemical examination to 104 RCC-BM patients and sub-group analysis, tendencies of higher positive rates of vascular endothelial growth factor (VEGF) was also found in synchronous group (P=0.097) while tendencies of higher positive rates of carbonic anhydrase (CA)-IX was found in the same group (P=0.100). The patients with clear cell RCC-BM had a significantly higher positive expression of epithelial growth factor receptor (EGFR, P<0.05) than those with non-clear cell RCC-BM group.
CONCLUSION
More male and younger patients with metastatic lesions in axial skeleton were found in this cohort. Tendencies in the expression of CA-IX and VEGF in different TTBM sub-group and EGFR in different histology-derived subgroup indicate that they might be associated with risk and prognostic factors and support further target therapies of RCC-BM.
Age Factors
;
Bone Neoplasms/secondary*
;
Carcinoma, Renal Cell/secondary*
;
Female
;
Humans
;
Kidney Neoplasms/pathology*
;
Male
;
Middle Aged
;
Prognosis
;
Retrospective Studies
;
Sex Factors
;
Vascular Endothelial Growth Factor A
5.Analysis of risk factors on vascular invasion in patients with early gastric cancer.
Zhijian WEI ; Aman XU ; Wenxiu HAN ; Zhangming CHEN
Chinese Journal of Gastrointestinal Surgery 2018;21(7):803-807
OBJECTIVETo explore the risk factors of vascular invasion in patients with early gastric cancer (EGC), and to investigate the influence of vascular invasion on the prognosis of EGC patients.
METHODSFrom January 2014 to December 2015, 449 EGC patients underwent curative gastrectomy at the First Affiliated Hospital of Anhui Medical University, of whom 27 cases (6.0%) developed vascular invasion. Clinicopathological and follow-up data of EGC cases were analyzed retrospectively. The association between clinicopathological features and vascular invasion was analyzed by using the Chi-square test or Fisher exact test, and the independent risk factors influencing vascular invasion were identified with logistic regression. The influence of vascular invasion on overall survival was investigated with Kaplan-Meier curve. This study was approved by Ethics Committee of The First Affiliated Hospital of Anhui Medical University (No. 2018-03-12).
RESULTSOf 449 EGC patients, 325 were males and 124 were females (ratio 2.6:1.0) with the mean age of (60.8±10.5) (27 to 87) years; 228 were diagnosed as T1a stage and 221 were diagnosed as T1b. Univariate analysis showed that incidence of vascular invasion in EGC patients with ulceration or scar was 8.4%(18/225), which was higher than 3.8%(9/234) in those without ulceration, and the difference was statistically significant (χ²=4.061, P=0.044). The incidence of vascular invasion in patients with low differentiated tumor was 8.8% (20/226), which was significantly higher than 3.1%(7/223) in those with middle-high differentiated tumor(χ²= 8.363, P=0.012). The incidence of vascular invasion in patients staging T1b was 10.9% (24/221), which was significantly higher than 1.3% (3/228) in those staging T1a (P=0.000); The incidence of vascular invasion in patients with lymph node metastasis was 27.3% (15/55), which was significantly higher than 3.0%(12/394) in those without lymph node metastasis (χ²=50.122, P=0.000). However, there were no significant associations of vascular invasion with gender, age, surgical type, multiple tumor, tumor deposit, tumor location and tumor size (all P > 0.05). Multivariate analysis showed that T1b stage (RR=4.653, 95%CI:1.293-16.747, P=0.019) and lymph node metastasis(RR=7.302, 95%CI: 3.063-17.408, P=0.000) were independent risk factors for vascular invasion in EGC patients. Among 449 EGC patients, 444 received complete follow-up(98.9%), including 26 cases with vascular invasion and 418 cases without vascular invasion. The overall survival in vascular invasion group was significantly lower than that in non-vascular invasion group (χ²=60.463, P=0.000). Besides, 198 EGC patients gained follow-up for 3 years, and the 3-year survival rates of 11 vascular invasion cases and 187 non-vascular invasion cases were 54.5% and 96.8% respectively.
CONCLUSIONSThe risk of vascular invasion is higher in EGC patients with lymph node metastasis and tumor infiltrating the submucosa. The prognosis of EGC patients with vascular invasion is poor.
Adult ; Aged ; Aged, 80 and over ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; pathology ; surgery ; Vascular Neoplasms
6.Report on the External Quality Assessment Scheme for Molecular Diagnostics in Korea (2017).
Man Jin KIM ; Mi Hye YOON ; Ji Yun SONG ; Sung Im CHO ; Sung Sup PARK ; Moon Woo SEONG
Journal of Laboratory Medicine and Quality Assurance 2018;40(4):199-210
Quality control for genetic analysis has become more important with a drastic increase in testing volume and clinical demands. The molecular diagnostics division of the Korean Association of Quality Assurance for Clinical Laboratory conducted two trials in 2017 on the basis of molecular diagnostics surveys, involving 53 laboratories. The molecular diagnostics surveys included 37 tests: gene rearrangement tests for leukemia (BCR-ABL1, PML-RARA, AML1-ETO, and TEL-AML1), genetic tests for Janus kinase 2, FMS-like tyrosine kinase 3-internal tandem duplication, FMS-like tyrosine kinase 3-tyrosine kinase domain, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2), Avellino (TGFBI), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-raderd Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome, apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, and ABO genotyping. Molecular genetic surveys revealed excellent results for most participants. The external quality assessment program for genetic analysis in 2017 proved useful for continuous education and the evaluation of quality improvement.
Achondroplasia
;
Acidosis, Lactic
;
Angelman Syndrome
;
Apolipoproteins
;
Brain Diseases
;
Breast
;
Deafness
;
Education
;
Epilepsies, Myoclonic
;
Fragile X Syndrome
;
Gene Rearrangement
;
Hearing Loss
;
Hepatolenticular Degeneration
;
Huntington Disease
;
Janus Kinase 2
;
Korea*
;
Laboratory Proficiency Testing
;
Leukemia
;
Li-Fraumeni Syndrome
;
Methylenetetrahydrofolate Reductase (NADPH2)
;
Molecular Biology
;
Multiple Endocrine Neoplasia
;
Muscular Atrophy, Spinal
;
Muscular Disorders, Atrophic
;
Muscular Dystrophy, Duchenne
;
Optic Atrophy, Hereditary, Leber
;
Ovarian Neoplasms
;
Pathology, Molecular*
;
Phosphotransferases
;
Quality Control
;
Quality Improvement
;
Spinocerebellar Ataxias
;
Vascular Endothelial Growth Factor Receptor-1
7.Idiopathic Cervicosyringomyelia in 2 year-old Boy.
Young Hoon CHO ; Hunmin KIM ; Byung Chan LIM ; Hee HWANG ; Jong Hee CHAE ; Ki Joong KIM ; Ji Eun CHOI ; Su mi SHIN
Journal of the Korean Child Neurology Society 2017;25(3):187-190
Syringomyelia is a disorder in which a cavity has formed within the spinal cord. Idiopathic syringomyelia is not associated with identifiable causes such as Chari type 1 malformation, spinal cord tumor, vascular malformation, tethered cord, arachnoiditis, hydrocephalus, or previous spinal surgery. The main neurologic symptoms of idiopathic syringomyelia are toe-walking, constipation, incontinence, abnormal reflexes, and lower extremity weakness. Patients may present with various symptoms such as scoliosis, cutaneous markers, pain in the lower extremities or back, or may be asymptomatic. Herein, we report a young child with idiopathic syringomyelia presenting with subtle neck pain. A 23-month-old boy visited the neurologic clinic after 3 months of right occipital area neck pain. He had no history of trauma or central nervous system infection, and neurologic examination results were normal except for right posterior neck hyperesthesia. Brain and spinal magnetic resonance imaging showed an ovoid intramedullary cystic lesion (9.7×5.0×4.7 mm) at C6/7 of the spinal cord. There was no evidence of Chiari malformation or other lesions that can be primary pathologies of syringomyelia. Electromyogram/nerve conduction velocity results were normal. The subject was diagnosed as idiopathic syringomyelia. His symptoms and neurologic/radiologic indications showed no change at a 1-year follow-up. Idiopathic syringomyelia symptoms are varied and may be overlooked by physicians. Pediatricians may consider syringomyelia if patients complain about persistent sensory abnormality. All patients who present with syringomyelia should undergo detailed neuroimaging of the entire neuraxis to elucidate the proximate cause of the lesion.
Arachnoid
;
Arachnoiditis
;
Brain
;
Central Nervous System Infections
;
Child
;
Constipation
;
Follow-Up Studies
;
Humans
;
Hydrocephalus
;
Hyperesthesia
;
Infant
;
Lower Extremity
;
Magnetic Resonance Imaging
;
Male*
;
Neck
;
Neck Pain
;
Neuroimaging
;
Neurologic Examination
;
Neurologic Manifestations
;
Pathology
;
Reflex, Abnormal
;
Scoliosis
;
Spinal Cord
;
Spinal Cord Neoplasms
;
Syringomyelia
;
Vascular Malformations
8.Surgical Treatment Strategies of Intravenous Leiomyomatosis withRight Cardiac Cavities Extension.
Guo-Tao MA ; Qi MIAO ; Xing-Rong LIU ; Chao-Ji ZHANG ; Yue-Hong ZHENG ; Jiang SHAO ; Ning-Hai CHENG ; Shun-da DU ; Jian-Zhou LIU ; Chao JIANG
Acta Academiae Medicinae Sinicae 2016;38(4):438-443
Objective To investigate the diagnosis and surgical treatment strategies of intravenous leiomyomatosis(IVL)extending through inferior vena cava into the right cardiac cavities. Methods Thirty patients of IVL extending through inferior vena cava into the right cardiac cavities were treated in Peking Union Medical College Hospital from November 2002 to January 2015.The following variables were studied: age,cardiopulmonary bypass time,deep hypothermic circulatory arrest time,origins of IVL,blood loss,duration of post-operative hospital stay,hospitalization expenses,edema of lower extremity,blood transfusion,postoperative complication,residual IVL,and re-grow or recurrence. Results Thirteen of 30 patients reported double lower limb edema. The cardiopulmonary bypass was applied in 27 cases,and the average duration of cardiopulmonary bypass was(106.9±53.7)min. Then,21 patients were treated with the deep hypothermic circulatory arrest,and the mean time was(28.2±11.6) min. The tumors originated from the genital veins in 9 cases,the iliac vein in 13 cases,and both veins in 8 cases. The average intra-operative blood loss volume was (2060.5±2012.3)ml,and 21 patients received blood transfusion. The average hospitalization time was(18.9±8.3)days and the average hospitalization expenses was (80 840.4±28 264.2)RMB yuan. While 14 patients had postoperative complications,there was no serious postoperative complication or death.All patients have shown a favorable outcome.Conclusions Tumor embolus extending through inferior vena cava into the right cardiac cavities should be suspected in patients with multiple hysteromyoma. Successful therapy for IVL with right cardiac cavities extension is dependent on reasonable surgical treatment strategies. Surgical removal of the ovaries is vital to avoid IVL re-grow or recurrence.
Cardiopulmonary Bypass
;
Circulatory Arrest, Deep Hypothermia Induced
;
Female
;
Heart Neoplasms
;
surgery
;
Humans
;
Leiomyomatosis
;
surgery
;
Length of Stay
;
Neoplasm Recurrence, Local
;
Ovary
;
Postoperative Complications
;
Vascular Neoplasms
;
surgery
;
Veins
;
pathology
;
Vena Cava, Inferior
;
pathology
9.Vascular Endothelial Growth Factor and Cluster of Differentiation 34 for Assessment of Perioperative Bleeding Risk in Gastric Cancer Patients.
Mu-Qing HE ; Mu-Qun HE ; Jian-Feng WANG ; Bao-Ling ZHU ; Ni SUN ; Xiao-Hai ZHOU ; Rong-Xin YAO
Chinese Medical Journal 2016;129(16):1950-1954
BACKGROUNDAngiogenesis is the formation of new blood vessels to supply nutrients to tumors. Vascular endothelial growth factor (VEGF) and cluster of differentiation 34 (CD34) are important signaling proteins involved in angiogenesis. Many studies have demonstrated that VEGF and CD34 are related to tumor progression. This study focused on the relationship between VEGF, CD34, and perioperative hemorrhage in patients with gastric cancer.
METHODSTo observe the relationship between VEGF and CD34, we tracked 112 patients with advanced gastric cancer for 5 years to assess factors related to hemorrhage, using immunohistochemistry. The results were subjected to statistical analysis using a 2 × 2 contingency table, logistic regression, and receiver operating characteristic (ROC) test.
RESULTSThe concentrations of VEGF and CD34 were critically correlated with perioperative hemorrhage and neural invasion in patients with gastric cancer (P < 0.05). Expression of VEGF and CD34 was related (P < 0.05, χ2 = 6.834). VEGF and CD34 co-expression strongly increased the risk of preoperative bleeding (area under the ROC curve >0.7, P < 0.05).
CONCLUSIONSExpression of VEGF and CD34 was critically correlated with perioperative hemorrhage in gastric cancer patients. Co-expression of VEGF and CD34 could be an effective indicator for evaluating the risk of perioperative bleeding in gastric cancer patients.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; metabolism ; Female ; Gastrointestinal Hemorrhage ; etiology ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neovascularization, Pathologic ; complications ; metabolism ; Prognosis ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; metabolism ; pathology ; surgery ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult
10.Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis.
Sheng-Li YANG ; Quan-Guang REN ; Lu WEN ; Jian-Li HU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(3):321-327
Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.
Adenocarcinoma
;
diagnosis
;
genetics
;
mortality
;
pathology
;
Biomarkers, Tumor
;
genetics
;
metabolism
;
Carcinoma, Non-Small-Cell Lung
;
diagnosis
;
genetics
;
mortality
;
pathology
;
Carcinoma, Squamous Cell
;
diagnosis
;
genetics
;
mortality
;
pathology
;
Humans
;
Hypoxia-Inducible Factor 1, alpha Subunit
;
genetics
;
metabolism
;
Lung Neoplasms
;
diagnosis
;
genetics
;
mortality
;
pathology
;
Lymphatic Metastasis
;
Neoplasm Grading
;
Neoplasm Staging
;
Odds Ratio
;
Prognosis
;
Receptor, Epidermal Growth Factor
;
genetics
;
metabolism
;
Survival Analysis
;
Vascular Endothelial Growth Factor A
;
genetics
;
metabolism

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