Pharmacokinetics of eight active ingredients of Salviae Miltiorrhizae Radix et Rhizoma-Puerariae Lobatae Radix combination in rats / 中国中药杂志

To reveal the rationality of compatibility of Salviae Miltiorrhizae Radix et Rhizoma(SMRR) and Puerariae Lobatae Radix(PLR) from the perspective of pharmacokinetics, this study established a UPLC-MS/MS method for quantitative determination of PLR flavonoids(3'-hydroxy puerarin, puerarin, puerarin 6″-O-xyloside, 3'-methoxy puerarin, puerarin apioside) and salvianolic acids and tanshinones(salvianolic acid B, cryptotanshinone, and tanshinone Ⅱ_A) in plasma of rats. Rats were given SMRR extract, PLR extract, and SMRR-PLR extract by gavage and then plasma was collected at different time. UPLC separation was performed under the following conditions: Eclipse C_(18) column(2.1 mm×50 mm, 1.8 μm), 0.1% formic acid in water(A)-0.1% formic acid in acetonitrile(B) as mobile phase for gradient elution. Conditions for MS are as below: multiple reaction monitoring(MRM), ESI~(+/-). Comprehensive validation of the UPLC-MS/MS method(specifically, from the aspects of calibration curve, precision, accuracy, repeatability, stability, matrix effect, extract recovery) was performed and the result demonstrated that it complied with quantitative analysis requirements for biological samples. Compared with SMRR extract alone or PLR extract alone, SMRR-PLR extract significantly increased the AUC and C_(max) of PLR flavonoids and tanshinones in rat plasma, suggesting that the combination of SMRR and PLR promoted the absorption of the above components. The underlying mechanism needs to be further studied.

Efficacy and Prognostic Factors of Cetuximab Therapy in Treating KRAS or All RAS Wild-type Metastatic Colorectal Cancer / 中国医学科学院学报

Objective To explore the efficacy and prognostic factors of cetuximab therapy for KRAS or all RAS wild-type(WT)metastatic colorectal cancer(mCRC).Methods We screened mCRC patients receiving at least two cycles of cetuximb and chemotherapy from those with KRAS WT(before November 2013)or all-RAS-WT(after November 2013)in the Department of Medical Oncology,Peking Union Medical College Hospital from November 2007 to December 2016. The relationship between the clinicopathological characteristics and the efficacy was retrospectively analyzed.Results A total of 60 patients were included. For the 34 patients receiving cetuximab as first-line treatment,the objective response rate(ORR)was 55.9%,and the progression-free survival and overall survival(OS)was 10 and 24 months,respectively. All-RAS-WT mCRC had significantly lower risk of progression than those with KRAS-only-WT(P=0.012),and left-sided colorectal cancer had higher ORR than right-sided colon cancer(62.1% vs. 0,P=0.033)during the first-line treatment. The median OS of the eight patients continuing cetuximab beyond first-line progression was 35.0(95%CI:23.6-46.4)months.Conclusions The efficacy of cetuximab for left-sided colorectal cancer was better than for right-sided colon cancer,and patients with all-RAS-WT have lower risk of progression than those with KRAS-only-WT. Patients benefiting from first-line cetuximab and continuing cetuximab beyond progression survive longer.

Correlation between KRAS mutations and clinicopathologic features in colorectal carcinomas / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate mutations of KRAS gene and clinicopathological characteristics of colorectal carcinomas (CRC) in Chinese.</p><p><b>METHODS</b>Tumor cells were collected by microdissection from paraffin-embedded tumor specimens and adjacent normal colon tissues from 167 CRC patients. Genomic DNA was extracted and mutations of KRAS gene (codons 12 and 13) were detected by scorpions amplification refractory mutation system (Scorpions ARMS).</p><p><b>RESULTS</b>KRAS mutations were identified in 66 patients (39.5%), including G13D (21 cases, 12.6%), G12D (15 cases, 9.0%), G12V (13 cases, 7.8%), G12C (6 cases, 3.6%), G12A (5 cases, 3.0%), G12S (4 cases, 2.4%) and G12R (2 cases, 1.2%). Female patients had a higher KRAS mutation rate than male (50.0%, 29/58 vs.33.9%, 37/109, P < 0.05). However, KRAS mutations did not correlate with the patient age, tumor sites, histological types and grades (P > 0.05). Additionally, 7 of 18 patients with metastatic CRC had KRAS gene mutations. Overall, KRAS gene mutation was identified in 59 patients among 149 primary CRC (39.6%). There was no significant difference in KRAS mutation between primary and metastatic tumors (P > 0.05).</p><p><b>CONCLUSIONS</b>The detection rate of KRAS mutation is higher in female CRC patients than the males. The presence of KRAS mutation does not significantly correlate with the patients' age, tumor site, differentiation grades and histological types. There was no significant difference in KRAS mutation between the primary and metastatic tumors.</p>

Folfox4 regimen administered through combined hepatic arterial and systemic infusion for treatment of colorectal cancer with unresectable liver metastases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases.</p><p><b>METHODS</b>Twenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAI of oxaliplatin 85 mg/m(2) and L-folinic acid 200 mg/m(2), followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m(2), then continuous HAI of 5-FU 600 mg/m(2); 2nd day: infusion of L-folinic acid 200 mg/m(2) i.v. followed by an intravenous bolus injection of 5-Fluorouracil 400 mg/m(2), then continuous infusion of 5-fluorouracil 600 mg/m(2) i.v. The patients received HAI during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles.</p><p><b>RESULTS</b>A total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P < 0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/thrombocytopenia.</p><p><b>CONCLUSIONS</b>The Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.</p>

Endostar combined with chemotherapy for treatment of metastatic colorectal and gastric cancer: a pilot study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Antiangiogenesis is a promising field of cancer therapy. Endostar, a novel recombinant human endostatin, is one of the few approved drugs acting as angiogenesis inhibitors of cancer in China. However, there are few clinical studies about Endostar in gastrointestinal cancer. This pilot study aimed to evaluate the efficacy and safety of the combination of Endostar and chemotherapy in patients with metastatic colorectal and gastric cancers.</p><p><b>METHODS</b>From March 2007 to October 2009, 23 patients were enrolled. Patients received Endostar intravenously at a dose of 15 mg daily from day 1 to 14 and day 1 to 7 when combined with 3- and 2-week chemotherapy regimens, respectively, which were determined according to patients' previous chemotherapy history. Treatment was repeated until disease progression, unacceptable toxicity or patients' refusal.</p><p><b>RESULTS</b>Seven, six and ten patients received Endostar as first-, second- and third-line therapy, respectively. A total of 75 cycles were administered. Twenty-one patients were assessable for responses. The overall response rate and disease control rate were 19.0% and 47.6%, respectively. All the four partial responses were among patients receiving Endostar as first-line therapy, whose response rate was 57.1%. The median time to progression and overall survival were 2.6 months (95%CI, 2.0 - 3.2 months) and 10.3 months (95%CI, 3.9 - 16.7 months), respectively. Toxicity was tolerable, with grade 3-4 toxicities observed for leucopenia (30.4%), neutropenia (34.8%), thrombocytopenia (17.4%) and anemia (13.0%). Three patients (13.0%) encountered transient sinus bradycardia with spontaneous remission.</p><p><b>CONCLUSION</b>Endostar combined with chemotherapy is well-tolerated in patients with metastatic colorectal and gastric cancers, and it is relatively effective as a first-line therapy.</p>

Solid malignancies complicated with pulmonary embolism: clinical analysis of 120 patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pulmonary embolism, a potentially fatal event, occurs more frequently in cancer patients than in the general population. To offer an accurate diagnosis and effective treatment to such patients in China, we analyzed the incidence rate and clinical features of pulmonary embolism in patients with solid tumor hospitalized in the Peking Union Medical College (PUMC) Hospital.</p><p><b>METHODS</b>A retrospective analysis was made of the hospitalized patients with solid malignancies complicated with pulmonary embolism who had been admitted into the PUMC Hospital from January 2002 to December 2008.</p><p><b>RESULTS</b>The incidence of pulmonary embolism in hospitalized patients with solid malignancies was 0.27% (120/43 967). The median age at diagnosis was 57.5 years. The male to female ratio was 1.0:1.4 (49:71). Patients with non-small-cell lung cancer (NSCLC) constituted the largest proportion of the 120 patients (37.5%), followed by patients with breast (9.2%), ovarian (8.3%), pancreatic (6.7%), and liver cancer (6.7%). Eighty patients (66.7%) had stage IV cancer. Bone was the most common site of distant metastasis (46.3%). D-dimer level was elevated in 90.9% of the 66 tested patients. The incidence of bleeding due to anti-coagulation therapy was 3.6%. Thirty-six (30.0%) of the 120 patients had concurrent deep venous thrombosis in the lower extremities. Seventeen patients developed acute pulmonary embolism within 2 weeks after surgery, 3 of whom died suddenly. Four patients presented with deep venous thrombosis and 1 with pulmonary embolism prior to the identification of malignancy.</p><p><b>CONCLUSIONS</b>Patients with cancer of the lung, ovarian, breast, pancreas, and liver are more likely to be complicated with pulmonary embolism than those with other types of solid tumors. Patients with distant metastasis are at a higher risk of pulmonary embolism. Pulmonary embolism without concurrent deep venous thrombosis is more frequently observed than concurrence of both disorders in the clinical setting.</p>

Expression of transcription factors T-bet/GATA-3 mRNA and its effect on Tc1/Tc2 balance in asthmatic children / 中华儿科杂志

<p><b>OBJECTIVE</b>In contrast to CD(4)(+) helper T-lymphocytes (T(H)), little is known about the transcriptional regulation of CD(8)(+) cytotoxic T-lymphocytes (Tc) and its role in the pathogenesis of asthma is unclear. This study was conducted to investigate the effect of T-bet and GATA-3 mRNA expression on profiles of type 1 and type 2 cytotoxic T lymphocytes in asthmatic children.</p><p><b>METHOD</b>Totally 38 asthmatic children, including acute attack group composed of 20 cases (age 3 - 13 years, mean 6.2 +/- 2.9), remission group with 18 cases (age 3 - 12 years, mean 6.1 +/- 2.5) and 20 healthy control children (age 3 - 12, 6.9 +/- 2.7) were recruited in this study from Sep. 2005 to Mar. 2006. The mRNA expression of T-bet and GATA-3 in the peripheral blood mononuclear cells were detected by using semi-quantitative PCR and Tc1, Tc2 cell numbers by flow cytometry analysis system.</p><p><b>RESULT</b>T-bet mRNA in asthmatic children was lower than that in control group and lower in attack stage than in remission stage (0.14 +/- 0.04, 0.21 +/- 0.03, 0.28 +/- 0.03, P < 0.05). In contrast, GATA-3 mRNA was higher in asthmatic children than in control group and higher in attack stage than in remission stage (0.49 +/- 0.09, 0.44 +/- 0.08, 0.37 +/- 0.04, P < 0.05). It was shown that Tc1 percentage was lower in asthmatic children than those of control group and lower in attack stage than those of remission stage (6.6 +/- 2.4, 14.2 +/- 4.3, 31.2 +/- 3.8, P < 0.05). Tc2 percentage in asthmatic children was higher than that of control group and higher in attack stage than that of remission stage (10.0 +/- 4.2, 5.4 +/- 2.2, 3.5 +/- 1.1, P < 0.05). Spearman correlation analysis revealed that T-bet mRNA was positively correlated with Tc1 percentage (r = 0.704) and negatively correlated with Tc2 percentage (r = -0.629). GATA3 mRNA was negatively correlated with Tc1 percentage (r = -0.612) and positively correlated with Tc2 percentage (r = 0.673). The T-bet/GATA-3 mRNA ratio was positively correlated with Tc1 percentage (r = 0.731) and Tc1/Tc2 (r = 0.773), while negatively correlated with Tc2 percentage (r = -0.642).</p><p><b>CONCLUSION</b>The imbalance of T-bet/GATA-3 mRNA expression is closely correlated with skewed Tc2 dominance in asthmatic children.</p>