Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase Ⅱ trial / 中华肿瘤杂志

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Prognostic Analysis of 102 Patients with Synchronous Colorectal Cancer and Liver Metastases Treated with Simultaneous Resection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The liver is the most common site for colorectal cancer (CRC) metastases. Their removal is a critical and challenging aspect of CRC treatment. We investigated the prognosis and risk factors of patients with CRC and liver metastases (CRCLM) who underwent simultaneous resections for both lesions.</p><p><b>METHODS</b>From January 2009 to August 2016, 102 patients with CRCLM received simultaneous resections of CRCLM at our hospital. We retrospectively analyzed their clinical data and analyzed their outcomes. Overall survival (OS) and disease-free survival (DFS) were examined by Kaplan-Meier and log-rank methods.</p><p><b>RESULTS</b>Median follow-up time was 22.7 months; no perioperative death or serious complications were observed. Median OS was 55.5 months; postoperative OS rates were 1-year: 93.8%, 3-year: 60.7%, and 5-year: 46.4%. Median DFS was 9.0 months; postoperative DFS rates were 1-year: 43.1%, 3-year: 23.0%, and 5-year 21.1%. Independent risk factors found in multivariate analysis included carcinoembryonic antigen ≥100 ng/ml, no adjuvant chemotherapy, tumor thrombus in liver metastases, and bilobar liver metastases for OS; age ≥60 years, no adjuvant chemotherapy, multiple metastases, and largest diameter ≥3 cm for DFS.</p><p><b>CONCLUSIONS</b>Simultaneous surgical resection is a safe and effective treatment for patients with synchronous CRCLM. The main prognostic factors are pathological characteristics of liver metastases and whether standard adjuvant chemotherapy is performed.</p>

Impact of Cytoreductive Nephrectomy on Survival in Patients with Metastatic Renal Cell Carcinoma Treated by Targeted Therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The metastatic renal cell carcinoma (mRCC) patients treated with upfront cytoreductive nephrectomy combined with α-interferon yields additional overall survival (OS) benefits. It is unclear whether mRCC patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) will benefit from such cytoreductive nephrectomy either. The aim of the study was to identify variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for mRCC treated with VEGFR-TKI.</p><p><b>METHODS</b>Clinical data on 74 patients enrolled in 5 clinical trials conducted in Cancer Hospital (Institute), Chinese Academy of Medical Sciences from January 2006 to January 2014 were reviewed retrospectively. The survival analysis was performed by the Kaplan-Meier method. Comparisons between patient groups were performed by Chi-square test. A Cox regression model was adopted for analysis of multiple factors affecting survival, with a significance level of α = 0.05.</p><p><b>RESULTS</b>Fifty-one patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 23 patients were treated with targeted therapy alone (noncytoreductive nephrectomy group). The median OS was 32.2 months and 23.0 months in cytoreductive nephrectomy and noncytoreductive nephrectomy groups, respectively (P = 0.041). Age ≤45 years (P = 0.002), a low or high body mass index (BMI <19 or >30 kg/m2) (P = 0.008), a serum lactate dehydrogenase (LDH) concentration >1.5 × upper limit of normal (P = 0.025), a serum calcium concentration >10 mg/ml (P = 0.034), and 3 or more metastatic sites (P = 0.023) were independent preoperative risk factors for survival. The patients only with 0-2 risk factors benefited from upfront cytoreductive nephrectomy in terms of OS when compared with the patients treated with targeted therapy alone (40.0 months vs. 23.2 months, P = 0.042), while those with more than 2 risk factors did not.</p><p><b>CONCLUSIONS</b>Five risk factors (age, BMI, LDH, serum calcium, and number of metastatic sites) seemed to be helpful for selecting patients who would benefit from undergoing upfront cytoreductive nephrectomy.</p>

Clinicopathological Characteristics and Prognosis of Colorectal Cancer in Chinese Adolescent Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Colorectal adenocarcinoma rarely occurred in adolescent. Clinical feature and prognosis of this population are not clear until now. In addition, DNA mismatch repair (MMR) status may relate to the early disease occurrence. The present study aimed to perform a retrospective analysis of adolescent patients with colorectal cancer, including clinicopathological characteristics and prognosis.</p><p><b>METHODS</b>The medical records of 11,503 patients diagnosed as colorectal cancer in Cancer Hospital, Chinese Academy of Medical Sciences from January 1999 to December 2009 were retrospectively reviewed. Finally, 19 patients who were between 10 and 20 years old were selected as the study group. We summarized the clinicopathological characteristics, analyzed the association with prognosis and assessed the expression of MMR protein by immunohistochemical method.</p><p><b>RESULTS</b>The most common primary site was the right colon in 7 patients. Ten patients had Stage III colorectal cancer, 5 patients had Stage IV disease. Signet ring cell carcinoma was the most frequent pathological type (7/19). Deficient MMR was identified in 2 patients. The 5-year survival rate and median survival time were 23.2% and 26 months. Distant metastasis was identified as an independent prognostic factor (P = 0.02).</p><p><b>CONCLUSIONS</b>Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage III/IV disease with signet ring cell carcinoma. The prognosis was relatively poor.</p>

Neuroendocrine tumors: analysis of 252 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the epidemiology, diagnosis, and treatment status of neuroendocrine tumors (NETs) in our hospital.</p><p><b>METHODS</b>Medical records of 252 patients with neuroendocrine tumors diagnosed and treated in our hospital from January 1, 2004 to December 31, 2009 were collected and retrospectively reviewed in this study. The clinicopathological data including age of onset, initial symptoms, primary site, pathological conditions (Sny, CgA, Ki-67), disease stage at diagnosis, treatment, and follow up were analyzed.</p><p><b>RESULTS</b>The gender ratio M/F of the 252 cases was 1.9:1, with mean age of 55.2 years, and the high incidence was in age of 60-69 years. The tumors were located in the gastrointestinal tract (117 cases, 46.4%), broncho-pulmonary system (74 cases, 29.4%), other sites (61 cases, 24.2%) and unknown primary site (2 cases, 0.8%). Their first clinical symptoms vary, depending on the primary site. The common symptoms of primary rectal NETs were changes in bowel habits (29.3%) and diarrhea or constipation (17.5%), and most gastric NETs presented epigastric discomfort (86.4%). Most patients (71.4%) were diagnosed with stage I, II, III disease. Among the 252 cases, there were 110 carcinoids (43.7%), 108 neuroendocrine carcinomas (42.9%), 23 atypical carcinoids (9.1%), five neuroendocrine tumors (2.0%), four Merkel cell tumors (1.6%), and two composite carcinoids (0.8%). 206 patients (81.7%) received surgery, 39 (15.5%) received chemotherapy, and 31 cases (12.3%) were treated by palliative radiotherapy.</p><p><b>CONCLUSIONS</b>This single-center retrospective analysis of data demonstrated that males have a higher incidence rate than females. The most common primary sites of NETs are the digestive tract and lungs. The initial symptoms of NETs are different depending on their primary sites. Good prognosis can be achieved in the majority of patients after surgery, chemotherapy and palliative radiotherapy.</p>

Analysis of prognostic factors after radical resection in 628 patients with stage II or III colon cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic factors related to recurrence and metastasis of stage II or III colon cancer after radical resection.</p><p><b>METHODS</b>The clinical and pathological data of 628 patients with stage II or III colon cancer after radical resection from Jan. 2005 to Dec. 2008 in our hospital were retrospectively reviewed and analyzed.</p><p><b>RESULTS</b>The overall recurrence and metastasis rate was 28.5% (179/628). The 5-year disease-free survival (DFS) rate was 70.3% and 5-year overall survival (OS) rate was 78.5%. Univariate analysis showed that age, smoking intensity, depth of tumor invasion, lymph node metastasis, TNM stage, gross classification, histological differentiation, blood vessel tumor embolus, tumor gross pathology, multiple primary tumors, preoperative and postoperative serum concentration of CEA and CA19-9, and the regimen of adjuvant chemotherapy were correlated to recurrence and metastasis of colon cancer after radical resection. Multivariate analysis showed that regional lymph node metastasis, TNM stage, the regimen of postoperative adjuvant chemotherapy, and preoperative serum concentration of CEA and CA19-9 were independent factors affecting the prognosis of colon cancer patients.</p><p><b>CONCLUSION</b>Regional lymph node metastasis, TNM stage, elevated preoperative serum concentration of CEA and CA19-9, the regimen of postoperative adjuvant chemotherapy with single fluorouracil type drug are independent risk factors of recurrence and metastasis in patients with stage II-III colon cancer after radical resection.</p>

Effect of arsenic pentaoxide on proliferation and apoptosis of human umbilical vein endothelial cell / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of arsenic pentaoxide (As2O5) on the proliferation and apoptosis of endothelial cells and compare the effect of As2O5 and arsenic trioxide (As2O3) in vitro.</p><p><b>METHODS</b>Human umbilical vein endothelial cells (HUVEC) were incubated with or without As2O5 or As2O3 for a certain period. The proliferation profile of HUVEC was determined by methyl thiazolyl tetrazolium (MTT) method. The apoptosis of HUVEC was detected by microscopy and flow cytometry (FCM).</p><p><b>RESULTS</b>As shown by MTT assay, the viabilities of HUVEC were (72.5 +/- 13.8)%, (52.9 +/- 6.2)%, (15.0 +/- 12.8)%, and (13.8 +/- 13.2)%, respectively, in 0.5, 1.0, 5.0, and 10.0 mg/L As2O5 groups, of which the viabilities of HUVEC at 1.0, 5.0, and 10.0 mg/L of As2O5 were significantly lower than controls (P = 0.006, 0.007, and 0.008); however, the viability was not significantly different between 5.0 and 10.0 mg/L As2O5 groups (P = 0.119). In 1.0 mg/L As2O5 group, the cell viabilities were (88.4 +/- 6.3)%, (53.1 +/- 8.8)%, (30.7 +/- 7.9)%, and (16.3 +/- 4.6)%, respectively, at 24, 48, 72, and 96 h, of which the cell viabilities at 48, 72, and 96 h were significantly lower than controls (P = 0.042, 0.025, and 0.012). As2O5-induced apoptosis of HUVEC was observed by phase contrast microscope and flow cytometry with Annexin V/PI staining. After 48 hours of incubation, the IC50s of As2O5 and As2O3 were 1.1 and 0.3 mg/L, respectively.</p><p><b>CONCLUSIONS</b>As2O5 can inhibit the proliferation of HUVEC and the minimum effective concentration is 1 mg/L. Apoptosis is the main way that As2O5 induces the death of HUVEC. The inhibitory effect of As2O5 on HUVEC is weaker than that of As2O3.</p>

Clinical analysis of 81 cases with primary small cell carcinoma of the esophagus / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the clinical characteristics, treatment and prognostic factors in patients with primary small cell carcinoma (SmCC) of the esophagus.</p><p><b>METHODS</b>Eighty-one esophageal SmCC patients were treated from 1999 to 2007 in our department, and their clinical data were retrospectively reviewed.</p><p><b>RESULTS</b>Of the 81 patients, 52 (64.2%) were in limited stage (LS) and 23 (28.4%) in extensive stage (ES). The 1-, 3- and 5-year survival rates were 55.6%, 6.2% and 2.5%, respectively, with a median survival time of 13.5 months for the whole group; 69.2%, 7.3% and 3.6%, respectively, with a median survival time of 15 months for the LS group; while only 25.2%, 0 and 0, respectively, with a median survival time of 6 months for the ES group. Multivariate analysis showed that disease stage, performance status, multidisciplinary comprehensive therapy and mode of treatment were independent prognostic factors.</p><p><b>CONCLUSION</b>Esophageal small cell carcinoma is a rare but highly aggressive malignant tumor. Disease stage and performance status are important prognostic factors. Appropriate treatment may play a key role in improving the survival of the patients.</p>

Expression of HCN4 Gene during Development of Heart in Rats / 实用儿科临床杂志

0.05),but there were statistically difference within E15,E19,P2,P10(Pa