Efficacy and Adverse Events of Apatinib Salvage Treatment for Refractory Diffuse Malignant Peritoneal Mesothelioma: A Pilot Study.

Objective: To investigate the clinical efficacy and adverse events (AEs) of apatinib salvage treatment for diffuse malignant peritoneal mesothelioma (DMPM) that has failed to respond to the recommended treatments. Methods: 27 patients with refractory DMPM were treated with apatinib at our center from April 2014 to October 2020, at the initial dose of 250 mg/d. The dose was reduced to 125 mg/d when serious adverse events (SAEs) occurred. 28-day was set as a treatment cycle. The frequency of follow up was once every 28 days. The efficacy evaluation was conducted according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and the serum tumor markers before and after apatinib treatment. The safety assessment was performed with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were AEs. Results: The 27 patients completed a median treatment-cycle of 15.0, ranging from 5.1 to 39.4 cycles. At the median follow-up of 14.3 (4.8-51.8) months, median overall survival (OS) was 59.4 months, median apatinib-treatment-related survival (ATRS) was 14.0 (4.8-36.8) months. Complete response (CR) was observed in 0 case (0.0%), partial response (PR) in 4 cases (14.8%), stable disease (SD) in 12 cases (44.4%), and progression disease (PD) in 11 cases (40.7%). The ORR was 14.8%, and DCR was 59.3%. The median serum CA125 values before and after apatinib treatment were 32.9 (7.0-4592.4) U/mL and 29.7 (6.1-4327.4) U/mL, respectively (P=0.009). The common AEs were hypertension (6/27; 22.2%), hand-foot syndrome (5/27; 18.5%), albuminuria (4/27; 14.8%), anemia (4/27; 14.8%), leukopenia (4/27; 14.8%), rash (2/27; 7.4%), fatigue (2/27; 7.4%), oral ulcers (2/27; 7.4%), hoarseness (2/27; 7.4%), nausea/vomiting (2/27; 7.4%), diarrhea (2/27; 7.4%), headache (1/27; 3.7%), and fever (1/27; 3.7%). The incidence rate of grade III/IV AEs was 16.2%. Conclusions: Apatinib is effective in treating refractory DMPM, with promising efficacy and acceptable safety.

Clinical characteristics and prognosis of 196 Chinese patients with colon cancer.

Aims: To analyze the clinical characteristics and prognostic factors of Chinese patients with colon cancer. Methods: A retrospective analysis of the records of patients with colon cancer underwent surgery between 2014 and 2017 was performed. Univariate analysis in combination with Cox proportional hazard regression model was used to analyze the survival data, so as to reveal the prognostic factors of colon cancer. Data record was based on a standard data form. SPSS version 26.0 was used for data analysis (SPSS, Chicago, IL, United States). Results: The 3-year survival rate and the 5-year survival rate was 79.3% and 68.2%, respectively. Univariate analysis showed that radical surgery, laparoscopic surgery, ascites, swollen lymph nodes at the root of the mesentery, liver metastases, nerve invasion, vascular invasion, tumor node metastasis (TNM) staging, positive level of carbohydrate antigen (CA) 19-9, CA125, CA72-4 and combined detection were positive factors in the prognosis of colon cancer (P < 0.05). Multivariate analysis showed that radical surgery and TNM staging were independent factors affecting the prognosis of patients with colon cancer (P < 0.05). Conclusion: Radical surgery and TNM staging have a significant impact on the prognosis of patients with colon cancer.

Clinical significance of five tumor markers in the diagnosis of gastric cancer / 中国基层医药

Objective To investigate the value of the combined test of five tumor markers for gastric cancer diagnosis.Methods The electrochemical luminescence analyzer was used to measure the serum concentrations of CEA,CA125,CA199,CA724 and AFP in 127 gastric patients and 186 controls,and calculated the sensitivity and specificity.Results The concentrations of CEA (52.9 ±25.5)ng/mL,CA125 (54.2 ±40.6)U /mL,CA199 (42.4 ± 28.8)U /mL,CA724 (9.3 ±6.6)U /mL and AFP (22.6 ±11.4)ng/mL in the gastric cancer group were significantly higher than those in the controls,and the differences were statistically significant (t =6.006,7.118,6.033,6.683, 5.362,all P <0.05 ).The sensitivity in gastric cancer diagnosis with the combined test of five tumor markers (88.2%)was higher than the test of CEA (63.8%),CA125 (59.1%),CA199 (41.7%),CA724 (37.0%)and AFP (46.5%)alone,and the differences were statistically significant (χ2 =20.733,27.754,60.209,71.046, 50.270,all P <0.05).Moreover,the specificity in gastric cancer diagnosis with the combined test of five tumor markers (90.3%)was higher than the test of CA125 (79.3%),while lower than the test of CA724 (97.3%),and the differences were statistically significant (χ2 =9.137,7.832,all P <0.05).Conclusion The combined test of five tumor markers (CEA,CA125,CA199,CA724 and AFP)could increase the rate of gastric cancer diagnosis.

Effect of Xihuang Capsules in adjuvant treatment of colon cancer patients with liver metastases and on IL-17 and IL-6 in serum of patients / 中草药

To investigate the effect and side effects of Xelox program combined with Xihuang Capsules on therapy to liver metastasis after resection of colon cancer and its impacts on IL-17 and IL-6 levels in serum of patients. Patients with liver metastasis of colorectal cancer after operation (120 cases) were randomly divided into two groups, namely the experimental group and the control group, 60 cases in each group. The patients in the control group were treated with Xerox program, while the patients in the experimental group were treated with the Xelox program and Xihuang Capsules. Twenty healthy cases were controlled. ELISA was used to detect the changes of serum IL-6 and IL-17 of the patients in the experimental group and the control group. Detecting the toxic reaction and hematological tumor makers of the 120 cases after treatment and taking 20 healthy people as control. The effective rates in the experimental group and the control group were 56.67% and 35.59% respectively, which showed the higher in the experimental group than the control group with the significant difference between the two (P < 0.05). The part of toxic reaction and hematological tumor makers in the experimental group were lower than those in the control group, which had significant difference. The levels of IL-17 and IL-6 in serum of the patiente in the experimental group and control group were higher than those in the healthy group (P < 0.05). The levels of IL-17 and IL-6 in the experimental group and control group decreased after the treatment, which the levels of them in the experimental group were more obviously decreased than those in the control group (P < 0.05). Curative efficacy of Xihuang Capsules in adjuvant treatment to colon cancer is reliable, which can reduce chemotherapy part of toxicity and hematological tumor markers, decrease the levels of IL-17 and IL-6, and effectively regulate immune function.

Polimorfismos genéticos e carcinoma de pulmão de células não pequenas: os paradigmas do futuro / Genetic polymorphisms and non-small-cell lung cancer: future paradigms

O presente artigo faz uma abordagem de questões atuais sobre os polimorfismos genéticos, que têm sido objeto de estudo translacional no contexto do carcinoma de pulmão de células não pequenas. Além disso, discute os novos potenciais biomarcadores de risco e prognóstico.

This article addresses some current issues about genetic polymorphisms studied in the non-small-cell lung cancer translational field. Furthermore, it discusses about new potential biomarkers regarding lung cancer risk and prognosis.

Comparison of nuclear grade and immunohistochemical features in situ and invasive components of ductal carcinoma of breast / Comparação do grau nuclear e perfil imunoistoquímico nos componentes in situ e invasivo de carcinoma mamário

PURPOSE:To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS:We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple-positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS:There was a significant correlation between nuclear grade (p<0.0001), expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a significant association with the triple-negative phenotype in IBC, but a negative association among DCIS. CONCLUSIONS: Our results suggest that classical prognostic and predictive features of IBC are already determined in the preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma may be different from the precursor lesions.

OBJETIVO: Comparar características prognósticas e preditivas entre os componentes in situ e invasivo de carcinomas ductais da mama. MÉTODOS: Selecionamos 146 amostras mamárias consecutivas com carcinoma ductal in situ (CDIS) associado com carcinoma invasivo (CI) adjacente. Avaliamos grau nuclear e a expressão imunoistoquímica de receptor de estrogênio (RE), receptor de progesterona (RP), receptor do fator de crescimento epidérmico humano 2 (HER2), citoqueratina 5/6 (CK5/6) e o receptor do fator de crescimento epidérmico (EGFR) em ambos componentes, in situ e invasor, e a porcentagem de células marcadas pelo Ki-67 no componente invasivo. CDIS e CI foram classificados nos tipos moleculares, determinados pelo perfil imunoistoquímico, como luminal (RE/RP-positivo/HER2-negativo), triplo-positivo (RE/RP/HER2-positivo), HER2-puro (RE/RP-negativo/HER2-positivo) e triplo-negativo (RE/RP/HER2-negativo). A discriminação entre luminal A e Luminal B não foi feita por motivos estatísticos. Correlações entre as categorias dos dois grupos foram feitas pelo método de correlação de Spearman. RESULTADOS: Houve significante associação entre grau nuclear (p<0,0001), expressão de RE/RP) (p<0,0001), superexpressão de HER2 (p<0,0001), expressão de EGFR (p<0,0001) e perfil molecular (p<0,0001) entre os componentes in situ e invasivo. CK5/6 mostrou distribuição distinta em CDIS e CI, apresentando significante associação com o fenótipo triplo-negativo em CI, mas uma associação negativa ente os CDIS. CONCLUSÕES:Nossos resultados sugerem que as características prognósticas e preditivas clássicas dos CI estão já determinadas no estágio pré-invasivo da doença. Entretanto, o papel da CK5/6 no carcinoma invasivo pode ser diferente daquele das lesões precursoras.

The expression and relationship of high-mobility group A, MIB labeling index and let-7 in retinoblastoma / 中华眼底病杂志

Objective To observe the expression and relationship of high-mobility group A(HMGA) 1,HMGA2,MIB-1 labeling index (LI) and let-7 in retinoblastoma (RB).Methods Forty-four RB samples were studied,including 11 poorly differentiated samples,33 well-differentiated samples; eight invasive and 36 non-invasive samples.The expression of HMGA1,HMGA2 and MIB-1 LI in RB were analyzed by immunohistochemitry.The HMGA1,HMGA2 were scored on a scale of 0 to high expression.0: no expression ; low: 1％ - 10 ％ ; medium: 11 ％ - 50 ％ ; high: ＞50 ％.The MIB LI were scored on a scale of 0to high expression.O: no expression;low: 1％ - 40％;high: ＞ 40％.Semiquantitative reverse transcription-polymerase chain reaction was used to assay the let-7 expression level: ≥ 80％ showed no significantly decreased expression; 60％ - 79％ showed medium decrease in expression; ＜ 60％ highly decreased in expression.Results In 44 RB samples,there were 14 cases with no HMGA1 expression (32％),11 cases with low expression (25％),10 cases with medium expression (23％),and nine cases with high expression (20％).Expression level of HMGA1 was significantly higher in poorly differentiated RB than in well-differentiated RB (x2 =11.3,P＜0.01) ; however,no statistically significant difference was found between invasive tumors and noninvasive tumors (x2 -5.9,P＞0.05).There were 11 cases with no HMGA2 expression (25％),11 cases with low expression-(25％),nine cases with medium expression (20％),and 13 cases with high expression (30％).Expression level of HMGA2 was significantly higher in poorly differentiated and invasive RB than in well differentiated and noninvasive RB respectively (x2=20.9,8.7; P＜0.05).There were 4 cases with no MIB-1 LI expression (9％),18 cases with low expression (41％),and 22 cases with high expression (50％).Expression level of MIB1 LI was significantly higher in poorly differentiated RB than in well-differentiated RB (t=5.2,P＜0.05).Higher expression of MIB-1 LI was found in invasive tumors than in noninvasive tumors,with no significant difference (t=-1.1,P＞0.05).Twenty seven cases had no significantly decreased expression of let-7 (61％).There were eight cases with medium decreased expression (18％) and nine cases with highly decreased expression (21％).Correlation analyses revealed that MIB1 LI expression significantly correlated with HMGA1and HMGA2 proteins (r=0.327,0.602; P＜0.05).A significantly inverse correlation existed between let-7 expression and HMGA1,HMGA2 proteins and MIB-1LI respectively (r=-0.247,-0.310,-0.392; P＜0.05).Conclusions Overexpression of HMGA1,HMGA2 and MIB-1 LI and down regulation of let-7 were demonstrated in RB.Supplying let-7 to RB cells can possibly inhibit HMGA1 and HMGA2 expression.

Expression of DNA methyltransferases 1,3a,and 3b in retinoblastoma / 中华眼底病杂志

Objective To observe the expressions of DNA methyltransferases (DNMTs) 1,3a and 3b in retinoblastoma (RB).Methods Sixty-two RB samples and six normal retinas were studied,including 17 poorly differentiated and 45 well differentiated samples; 16 invasive and 46 non-invasive samples.The expressions of DNMT1,3a,and 3b,and Ki-67 were detected using immunohistochemical analysis.Brown staining of nuclei was considered to represent the positive stain for DNMT1,3a and 3b,and ki-67,blue staining as negative.The level of high expression of nuclear staining was,positive cells in DNMT1≥65 ％,in DNMT3a≥60％ and in DNMT3b≥40％.The correlations of DNMT1,3a and 3b expression in RB samples,and MIB-1 labeling index were analyzed.Results Viewed under the light microscope,negative expressions of DNMT1,3a and 3b were demonstrated in normal retinas,however,positive expression was observed in RB samples,with 100％ in DNMT1,98％ in DNMT3a and 92％ in DNMT3b.Comparing well differentiated RB samples with poorly differentiated samples,significant differences were found in high expression of DNMT1 (x2 =12.57,P＜0.05) and DNMT3a (x2 =10.54,P＜0.05) ; also in the positive cells of DNMT1 (U=179,P＜0.05) and DNMT3a (U=198,P＜0.05).No significant difference was found comparing high expression (x2=1.5,P＞0.05) and positive cells (U=307,P＞0.05) of DNMT3b.When comparing invasive tumor tissues with non-invasive tumors,significant differences were shown between high expression (x2 =4.72,P＜0.05) and positive cells comparing DNMT1 (U=236,P＜0.05).No significant difference was shown in high expression (x2=3.53,0.84; P＞0.05) in DNMT3a and DNMT3b,or in comparison with positive cells (U=338,257; P＞0.05).The expression of DNMTs was positively correlated with the MIB-1 labeling index in RB tissues (R2=0.554,0.376,0.219; P＜0.05).Conclusion There are high expressions of DNMT1,3a,and 3b in RB.

Initial investigation of serum homocysteine as cancer biomarker / 国际外科学杂志

Objective To study the expression of homocysteine in serum of patients with common malignant tumor,and initially investigate the possibility of serum homocysteine as cancer biomarker.Methods Expression levels of homocysteine and caner biomarkers (CEA,AFP,CA125,CA199) in serum of 180 patients with established malignant tumor and 30 healthy controls (control) were measured,the results of homocysteine were compared with that of the cancer biomarkers based on the cutoff value used in clinic.Results The expression levels of homocysteine was significantly higher in patients with malignant tumor than in controls [(13.89 ± 4.95) μmol/L-(21.40 ± 9.38) μ mol/L vs (11.40 ± 3.13) μmol/L,P ＜ 0.05)].Conclusions The positive predictive rate of homocysteine is higher than the four kind of cancer biomarkers in lung cancer,breast cancer,esophageal cancer.The increase of homocysteine in tumors may be universal,and Homocysteine may be used as cancer biomarker in lung cancer,breast cancer and esophageal cancer.

The clinical value of combined diagnosis in the diagnosis of early breast cancer / 中国医师进修杂志

Objective To investigate the clinical value of serum tumor makers CA15-3,19 fragments of cellular keratin antigen(CYFRA21-1)combined with the color Doppler ultrasound and mammography X-ray in diagnosis of early breast cancer.Methods According to the postoperative pathologic diagnosis,collected 106 cases of patients with breast cancer (breast cancer group) and 50 cases of patients with benign breast lesions (control group),the serum tumor makers CA15-3,CYFRA21-1,the color Doppler ultrasound and mammography X-ray were compared with postoperative pathology and statistical analyzed retrospectively.Results The sensitivity of CA15-3 was 63.2%(67/106),specificity was 94.O% (47/50);the sensitivity of CYFRA21-1 was 73.6%(78/106),specificity was 88.0%(44/50);the sensitivity of color Doppler ultrasound was 77.4%(82/106),specificity was 90.0%(45/50);the sensitivity of mammography X-ray was 75.5%(80/106),specificity was 92.0%(46/50);the sensitivity of the four combined detections was 96.2%(102/106),specificity was 80.0%(40/50).The sensitivity of combined detection was higher than any of them individually,there was statistical significance (P<0.05).Conclusions Combined diagnosis is an effective way of early breast cancer detection.It has high positive rate of diagnosis and reliable guidance significance for diagnosis and treatment.

An estimate on three markers in the monitoring of blood metastasis of lung cancer / 肿瘤研究与临床

Objective To understand the clinical value on the detection of carcinoembryonic antigen mRNA (CEA mRNA), cytokeratin 19 mRNA (CK19 mRNA) and telomerase in blood for the monitoring of blood metastasis of lung cancer. Methods CEA mRNA and CK19 mRNA were detected by reverse transcriptase-nested primers-polymerase chain reaction, telomerase was detected by telomeric repeat amplification protocol-hybridism-enzyme-linked immunosorbent assay in peripheral blood. Results The positive rates of the three tumor markers in lung cancer group were much higher than the non-tumor group and the health group (P<0.001). The sensibility of CEA mRNA and telomerase were much higher than CK19 mRNA (P<0.01). The positive rates of the markers in TNM stages Ⅲ and Ⅳ were much higher than in stages Ⅰ (P<0.05 to P<0.01). Conclusion It had high value that detecting CEA mRNA, CK19 mRNA and telomerase in peripheral blood on the discovery of blood metastasis of lung cancer. Among them, the clinical value of CEA mRNA and telomerase are higher than CK19 mRNA, and combined assay of the markers can improve the sensibility.

Serum markers of hepatocellular carcinoma / 肿瘤研究与临床

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor with increasing incidence worldwid.Most of patients with HCC are diagnosed at a late stage.Threrfore,the prognosis of HCC patients is generally poor with a 5-year survival rate of 20% if withoutoperration. Screening strategies including α-fetoprotein (AFP) and ultrasound every 6 months in patients with liver cirrhosis,the major risk factor for HCC development, have been recommended to detect HCC at earlier stages amenable to effective treatment strateges.AFP, however,is a marker with poor sensitivity and specificity and the ultrasound is highly dependent on the operator's experience.Apart from AFP, lens culinaris agglutinin-reactive AFP and des-gamma carbexyprothrombin and several other biomarkers(e.g., glypican-3,human hepatocyte growth factor,and insulin-like growth factor) have been proposed as markers for HCC detection.In addition,with recently employed techniques,such as gene-expressing microarrays and proteomics,it is to be expected that new HCC-specific markers will become available in the near future.For all such proposed markers,however,the clinical usefulness has to be carefully evaluated and validated.

The expression of DOG1 in gastrointestinal stromal tumors / 中华普通外科杂志

Objective To evaluate DOG1 as an immunohistochemical marker for GIST.Methods From Jan 1987 to Sep 2008,210 consecutive cases including 137 GISTs as well as 73 non-GIST sarcoma were evaluated for clinicopathological characteristics and immunostained for DOG1 antibodies.Result Immunoreactivity for DOG1 was detected in 110 of 137 GIST cases (80.3%),3 out of 11 CD117negative GISTs were DOG1-positive.Only 1 of 73 non-GIST case was positive for DOG1.The expression of DOG1 in GIST is associated with the location of tumor,cell density,nuclear pleomorphism and Fletcher grading criteria.The postoperative 1-,3-,5-year overall survival for DOG1 negative and positive patients was 81.3%,74.5%,74.5% and 98.5%,85.9%,83.2%,respectively,P = 0.034.Conclusion DOG1 was a sensitive and specific marker for GIST in gastrointestinal mesenchymal tumors (GIMT).

Advancement in bladder cancer markers in urine / 中国癌症杂志

Bladder cancer is a common type of tumor in the urinary system. Its incidence has been increasing and the disease has a high rate of recurrence. Cystoscopy and cytology are the main methods for the diagnosis and the early detection of recurrence for bladder transitional cell carcinoma. Since cystoscopy is expensive and invasive, and although cytology is non-invasive but it is not very sensitive, many tumor makers have recently been studied in the diagnosis of the disease. So how to choose tumor makers with high sensitivity and specificity for the diagnosis of the disease so that the patients with bladder cancer could be treated at the earliest stages is important, the biomarkers may play a very important role in clinical application. In this review we discussed the development of biomarkers for bladder cancer.