Combination of anlotinib and irinotecan in the second-line treatment of metastatic colorectal cancer: a multicenter phase 1/2 trial / 中华肿瘤杂志

Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.

A case of advanced mycosis fungoides with comprehensive skin and visceral organs metastasis: sensitive to chemical and biological therapy

Mycosis fungoides is a common cutaneous T-cell lymphoma, which is usually characterized by chronic, indolence progression, with absence of typical symptoms in early stage, metastasis to lymph nodes, bone marrow and visceral organs in later stage and ultimately progression to systemic lymphoma. It can result in secondary skin infection which is a frequent cause of death. At present, no curative therapy existed. Therapeutic purpose is to induce remission, reduce tumor burden and protect immune function of patients. A case of patient with advanced severe mycosis fungoides receiving CHOP plus interferon α-2a was reported here, with disease-free survival of 7 months and overall survival of over 17.0 months, and current status as well as developments of mycosis fungoides were briefly introduced.

Correlation between expression of forkhead box M1 (FOXM1) and clinicopathological features and prognosis in patients with non-small cell lung cancer (NSCLC) / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of forkhead box M1 (FOXM1) and its correlation with clinicopathological features and prognosis in patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The expression of FOXM1 in 68 cases of NSCLC was detected by immunohistochemistry. The FOXM1 expression in 6 tumor tissues (3 cases with negative and 3 cases with positive expression of FOXM1) was analyzed by Western blotting to confirm the immunohistochemical results. The correlation of the expression of FOXM1 with clinicopathalogical features and overall survival of the NSCLC patients was analyzed.</p><p><b>RESULTS</b>The expression of FOXM1 protein was detected in the nuclei or cytoplasms of the tumor cells. The positive expression rate of FOXM1 was 36.8% (25/68). Western blotting confirmed the immunohistochemical results. The expression level of FOXM1 in advanced stage cancer was significantly higher than that in early stage NSCLC (P = 0.001). The median OS was 23.0 months in patients with negative expression of FOXM1 and 13.0 months in those with positive expression (P = 0.001). Univariate analysis revealed that histological grade, lymph nodes status, TNM stage and FOXM1 expression were significantly associated with prognosis in the NSCLC patients (P < 0.05). The Cox multivariate analysis demonstrated that lymph nodes status, TNM stage and FOXM1 expression were independent poor prognostic factors (P < 0.05).</p><p><b>CONCLUSION</b>The expression status of FOXM1 in NSCLC is an independent prognostic factor and negatively correlated with prognosis.</p>

Prognostic value of metastatic lymph node ratio for patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of metastatic lymph node ratio (MLR) for patients with gastric cancer.</p><p><b>METHODS</b>Data collected from 1247 patients with gastric cancer who underwent radical surgery (pT4 cases were excluded) at the First Affiliated Hospital of Nanjing Medical University between 2005 and 2009 were analyzed retrospectively. MLR was compared to pathological N staging (pN) in terms of prognostic accuracy, homogenicity, and applicability.</p><p><b>RESULTS</b>MLR and pN were both positively correlated with the number of retrieved lymph nodes(both P<0.01). Significant differences were found in 5-year cumulative survival rate (5-YCSR) among different pN stages and MLR classification(all P<0.01). Multivariable analysis showed that both pN and MLR were independent prognostic factors(both P<0.01). The area under ROC curve(AUC) of MLR was larger than pN, however the difference was not statistically significant(P>0.05). There were significant differences in 5-YCSR among different MLR stages within the same pN stages(P<0.05), but not among different pN stages within the same MLR stage(P>0.05). Significant differences in 5-YCSR were also found among different retrieved-node groups within the same pN stage (P<0.05), but not within the same MLR stages (P>0.05).</p><p><b>CONCLUSIONS</b>MLR is an independent prognostic factor for patients with gastric cancer. The prognostic homogenicity and applicability of MLR are better than those of pN, however the prediction accuracy is not favorable.</p>

Expression of HER-2 and leptin in gastric cancer and their clinical significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the expression of HER-2 and leptin in gastric cancer and evaluate their relationship with VEGF expression and clinicopathological features, and their prognostic value for gastric cancer patients.</p><p><b>METHODS</b>One hundred and ten gastric cancer specimens and the corresponding metastatic lymph nodes were detected for HER-2 by immunohistochemistry (IHC). All primary cancer tissues were detected for leptin, OB-Rb and VEGF. Ninty-six specimens of normal gastric mucosa served as the control.</p><p><b>RESULTS</b>The expression level of HER-2, leptin and OB-Rb in gastric cancer tissues were significantly higher than those in normal tissues (19.1% vs. 8.0%, 49.1% vs. 34.0%, and 60.9% vs. 46.0%, P < 0.05). HER-2 overexpression was moderately homogenous in primary gastric cancer and matastatic lymph nodes (P = 0.607, Kappa = 0.581). There was a correlation between the expression of HER-2 and leptin, both of which were significantly correlated with tumor invasion depth, metastatic lymph nodes ratio (NR), distal metastasis, TNM stage and VEGF expression. However, there was no significant correlation between OB-Rb expression and the clinicopathological features evaluated. Cox regression multivariate analysis showed that tumor size, histological grade, NR, stage, chemotherapy and HER-2 expression were independent prognostic factors.</p><p><b>CONCLUSIONS</b>HER-2 is stably expressed in primary gastric cancer and metastatic lymph nodes. HER-2 and leptin play an important role in the progression and angiogenesis of gastric cancer. High expression of HER-2 is a prognostic factor for poor outcome.</p>

Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer / 癌症

Studies have shown cell-free microRNA (miRNA) circulating in the serum and plasma with specific expression in cancer, indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy. This study was to investigate whether plasma miRNA-21 (miR-21) can be used as a biomarker for the early detection of non-small cell lung cancer (NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum-based chemotherapy. We used real-time RT-PCR to investigate the expression of miR-21 in the plasma of 63 NSCLC patients and 30 healthy controls and correlated the findings with early diagnosis, pathologic parameters, and treatment. Thirty-five patients (stages IIIB and IV) were evaluable for chemotherapeutic responses: 11 had partial response (PR); 24 had stable and progressive disease (SD+ PD). Plasma miR-21 was significantly higher in NSCLC patients than in age- and sex-matched controls (P < 0.001). miR-21 was related to TNM stage (P < 0.001), but not related to age, sex, smoking status, histological classification, lymph node status, and metastasis (all P > 0.05). This marker yielded a receiver operating characteristic (ROC) curve area of 0.775 (95% CI: 0.681- 0.868) with 76.2% sensitivity and 70.0% specificity. Importantly, miR-21 plasma levels in PR samples were several folds lower than that in SD plus PD samples (P = 0.049), and were close to that in healthy controls (P = 0.130). Plasma miR-21 can serve as a circulating tumor biomarker for the early diagnosis of NSCLC and is related to the sensitivity to platinum-base chemotherapy.

Down-regulation of mTOR activity and survivin expression during tamoxifen-induced apoptosis in hepatoblastoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the changes in mTOR activity and survivin expression in liver cancer cell line HepG2 cells treated with tamoxifen.</p><p><b>METHODS</b>Survivin transcription level and p70S6K was demonstrated by PCR, dual-luciferase reporter assay and Western blot analysis, respectively, and the apoptosis in the HepG2 cells was detected by flow cytometry.</p><p><b>RESULTS</b>Tamoxifen leads to apoptosis of the cells and reduction in survivin expression, as well as a dramatic reduction in the activated form of p70S6K. Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduced the survivin protein level but not affected the survivin transcription, indicating that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells.</p><p><b>CONCLUSIONS</b>Our results suggest that tamoxifen down-regulates survivin expression in HepG2 cells and it is mediated by transcriptional and post-transcriptional level via PI3K/Akt/mTOR pathway to induce apoptosis.</p>

Capecitabine combined with cisplatin as first-line therapy in Chinese patients with advanced gastric carcinoma-a phase II clinical study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC).</p><p><b>METHODS</b>141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles.</p><p><b>RESULTS</b>Of the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death.</p><p><b>CONCLUSION</b>Capecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.</p>

Insulin/PI3K signalling pathway regulates the expression of survivin in liver cancer HepG2 cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the expression level changes of survivin, a inhibitor of apoptosis protein, followed by activation of insulin receptors in human hepatocellular carcinoma HepG2 cell line, and to investigate the signalling pathway involved in the regulation.</p><p><b>METHODS</b>Human hepatocellular carcinoma HepG2 cells were treated with insulin alone or pre-treated with LY294002, a specific inhibitor of PI3K signalling pathway, to determine whether blocking PI3K signaling can attenuate the up-regulation of survivin expression. Real time RT-PCR and Western blot analysis were used to measure survivin mRNA and protein changes before and after treatment, respectively.</p><p><b>RESULTS</b>Without serum supplement, HepG2 cells expressed a small amount of survivin. Insulin induced survivin expression in a dose- and time-dependent fashion. Survivin expression was blocked if cells were pre-treated with LY294002 prior to insulin stimulation.</p><p><b>CONCLUSION</b>Insulin induces survivin expression via PI3K signalling pathway, suggesting that to interfere the key gene in this signalling pathway may block survivin expression, therefore, promoting apoptosis in hepatocellular carcinoma cells.</p>