Development of crizotinib-associated renal cyst in a non-small cell lung cancer patient with ALK fusion: a case report and review of the literature.

BACKGROUND: Crizotinib, an oral first-generation tyrosine kinase inhibitor (TKI), is superior to systemic chemotherapy for the treatment of non-small cell lung cancer (NSCLC) with positive rearrangement of anaplastic lymphoma kinase (ALK). However, an increased incidence of renal and hepatic cysts has been reported in the patients on crizotinib treatment. CASE PRESENTATION: Here, we describe a case of a 71-year-old Chinese women developed multiple cystic lesions in kidney and liver during crizotinib treatment for the primary and metastatic NSCLC. The renal and hepatic cysts were noted by CT scan 3 months after crizotinib treatment, which were spontaneously and significantly regressed after stopping crizotinib. CONCLUSIONS: Based on literature review and our experience in this case report, we concluded that crizotinib-associated renal cyst (CARCs) has features of malignancy and abscess in radiographic imaging, and thus, pathological confirmation is necessary to avoid inappropriate treatment decision. In addition, to benefit the patients with progress-free survival (PFS), switching from crizotinib to alectinib is recommended for the treatment of NSCLC patients who developed CARCs.

Prognostic value of coagulation markers in patients with colorectal caner: A prospective study.

Background and Aims: The occurrence, growth, and metastasis of colorectal cancer (CRC) are connected to the hypercoagulable state of blood (CRC). This study aimed to identify significant coagulation factors to predict metastasis and prognosis of CRC. Methods: Thrombomodulin (TM), thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), and tissue plasminogen activator-inhibitor complex (t-PAIC) were detected by chemiluminescence immunoassay using Sysmex HISCL5000 automated analyzers. The Sysmex CS 5100 automatic blood coagulation analyzer was used to detect d-dimer (DD), fibrin degradation product (FDP), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fbg), and activated partial thromboplastin time (APTT). Area under the curve (AUC) and the receiver operating characteristic curve (ROC) were used to assess the diagnostic efficacy of markers. Kaplan-Meier analysis was used to calculate survival probabilities. Independent prognostic factors and the nomogram were developed using single-factor and multifactor cox regression analysis model. Results: The following indicators (TM, TAT, PIC, t-PAIC, DD, FDP, PT, INR, APTT, and Fbg) were markedly higher in CRC patients than in healthy controls, and they were higher in the metastasis (M) group than in the nonmetastasis (NM) group. The combination "TAT + PIC + DD + FDP + Fbg" can distinguish M from NM with exceptional sensitivity and specificity. Patients with CRC who had high levels of TAT, PIC, DD, FDP, Fbg, TM, tPAIC, PT, and INR had significantly shorter survival. Conclusion: The prognosis of CRC patients can be predicted by coagulation indicators. The independent predictive variables for overall survival were found to be TM and DD. To forecast CRC patient survival, a nomogram was created.

Case Report: Antiangiogenic Therapy Plus Immune Checkpoint Inhibitors Combined With Intratumoral Cryoablation for Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with high incidence and poor prognosis. Common treatment methods include surgery, transcatheter arterial chemoembolization (TACE), ablation, and targeted therapy. In recent years, combination treatment with antiangiogenic therapy and immune checkpoint inhibitors has made great progress in the treatment of advanced HCC. Here, we report the case of a patient with HCC who achieved a durable benefit from anti-vascular therapy and immune checkpoint inhibitors combined with intratumoral cryoablation. Main Body: A 38-year-old male patient initially presented with severe abdominal pain that was identified as an HCC rupture and hemorrhage by computed tomography (CT). The patient underwent emergency surgery and postoperative pathology confirmed HCC. The patient received prophylactic TACE after surgery. Unfortunately, three months after surgery, the patient developed multiple liver metastases. Subsequently, he received systemic anti-vascular therapy and immune checkpoint inhibitors combined with intratumoral cryoablation. After treatment, the patient achieved extensive tumor necrosis and the disease was effectively controlled. Conclusions: Anti-angiogenic therapy and immune checkpoint inhibitors combined with cryoablation can induce a powerful and effective systemic anti-tumor immune response, which is worthy of further research.

Sustained Clinical Benefit of Pyrotinib Combined with Capecitabine Rescue Therapy After Trastuzumab Resistance in HER2-Positive Advanced Gastric Cancer: A Case Report.

BACKGROUND: HER2-positive patients with advanced gastric cancer have a poor prognosis, and trastuzumab-resistant patients lack effective treatment. CASE PRESENTATION: We report a 72-year-old male with HER2-positive gastric cancer. The patient had metastatic tumor during adjuvant chemotherapy after surgery, followed by second-line chemotherapy, and achieved a progression-free survival (PFS) of 4.5 months. Subsequent third-line chemotherapy treatment also failed. Fortunately, the patient had a significant tumor response and 8.5 months of PFS on trastuzumab combined with chemotherapy. After trastuzumab resistance, the patient was treated with programmed cell death protein-1 inhibitor combined with apatinib, which selectively inhibited VEGFR2, but the effect was not satisfactory. Finally, the patient was treated with capecitabine combined with pyrotinib, an irreversible TKI, acting on HER2. The tumor shrank significantly after this treatment. CONCLUSION: The mechanism and countermeasures of trastuzumab resistance were discussed in this case. For patients with HER2-positive advanced gastric cancer, pyrotinib can achieve good results after trastuzumab resistance.

Avasimibe Dampens Cholangiocarcinoma Progression by Inhibiting FoxM1-AKR1C1 Signaling.

Avasimibe is a bioavailable acetyl-CoA acetyltransferase (ACAT) inhibitor and shows a good antitumor effect in various human solid tumors, but its therapeutic value in cholangiocarcinoma (CCA) and underlying mechanisms are largely unknown. In the study, we proved that avasimibe retard cell proliferation and tumor growth of CCAs and identified FoxM1/AKR1C1 axis as the potential novel targets of avasimibe. Aldo-keto reductase 1 family member C1 (AKR1C1) is gradually increased along with the disease progression and highly expressed in human CCAs. From survival analysis, AKR1C1 could be a vital predictor of tumor recurrence and prognostic factor. Enforced Forkhead box protein M1 (FoxM1) expression results in the upregulation of AKR1C1, whereas silencing FoxM1 do the opposite. FoxM1 directly binds to promoter of AKR1C1 and triggers its transcription, while FoxM1-binding site mutation decreases AKR1C1 promoter activity. Moreover, over-expressing exogenous FoxM1 reverses the growth retardation of CCA cells induced by avasimibe administration, while silencing AKR1C1 in FoxM1-overexpressing again retard cell growth. Furthermore, FoxM1 expression significantly correlates with the AKR1C1 expression in human CCA specimens. Our study demonstrates a novel positive regulatory between FoxM1 and AKR1C1 contributing cell growth and tumor progression of CCA and avasimibe may be an alternative therapeutic option for CCA by targeting this FoxM1/AKR1C1 signaling pathway.

Gene coexpression network approach to develop an immune prognostic model for pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a nonimmunogenic tumor, and very little is known about the relationship between the host immune response and patient survival. We aimed to develop an immune prognostic model (IPM) and analyze its relevance to the tumor immune profiles of patients with PAAD. METHODS: We investigated differentially expressed genes between tumor and normal tissues in the TCGA PAAD cohort. Immune-related genes were screened from highly variably expressed genes with weighted gene correlation network analysis (WGCNA) to construct an IPM. Then, the influence of IPM on the PAAD immune profile was comprehensively analyzed. RESULTS: A total of 4902 genes highly variably expressed among primary tumors were used to construct a weighted gene coexpression network. One hundred seventy-five hub genes in the immune-related module were used for machine learning. Then, we established an IPM with four core genes (FCGR2B, IL10RA, and HLA-DRA) to evaluate the prognosis. The risk score predicted by IPM was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. Moreover, we found that the patients in the low-risk group had higher cytolytic activity and lower innate anti-PD-1 resistance (IPRES) signatures than patients in the high-risk group. CONCLUSIONS: Unlike the traditional methods that use immune-related genes listed in public databases to screen prognostic genes, we constructed an IPM through WGCNA to predict the prognosis of PAAD patients. In addition, an IPM prediction of low risk indicated enhanced immune activity and a decreased anti-PD-1 therapeutic response.

Accumulated genetic mutations leading to accelerated initiation and progression of colorectal cancer in a patient with Gardner syndrome: A case report.

RATIONALE: Gardner syndrome is a rare autosomal dominant disorder with a high degree of penetrance, which is characterized by intestinal polyposis, osteomas, and dental abnormalities. Majority of patients with Gardner syndrome will develop colorectal cancer by the age of 40 to 50 years. Mutations in the adenomatous polyposis coli gene are supposed to be responsible for the initiation of Gardner syndrome. PATIENT CONCERNS: A 22-year-old Chinese female was admitted to our hospital due to abdominal pain and bloody stool. DIAGNOSIS: The patient presented with multiple intestinal polyposis, desmoid tumors, and dental abnormalities was diagnosed as Gardner syndrome and further examination revealed a colon tumor. INTERVENTIONS AND OUTCOMES: Patients were implanted with stents to alleviate bowel obstruction, and were treated with oxaliplatin combined with 5-Fu for 4 cycles, but the efficacy was not good. We performed next generation sequencing of 390 genes for the tumor specimens. We detected adenomatous polyposis coli E1538Ifs∗5, KRAS G12D, NF1 R652C, loss of SMAD4, TP53 R175H, IRF2 p.R82S, TCF7L2 p.A418Tfs∗14, and SMAD4 p.L43F in this patient. LESSONS: We reported serial mutations in key genes responsible for initiation and progression of colorectal cancer from a patient with Gardner syndrome.

The Expression and Clinical Significance of Aldo-Keto Reductase 1 Member B1 in Gastric Carcinoma.

To study the expression of aldo-keto reductase 1 member B1 (AKR1B1) in gastric carcinoma (GC), the correlation between AKR1B1 and the clinicopathological characteristics of GC patients, and provide reference for the diagnosis and prognosis of GC patients. One hundred thirty-six patients with GC were collected, and the expression level of AKR1B1 in GC and adjacent tissues was detected by immunohistochemistry assays. The clinicopathological features and prognosis of GC patients were collected to analyze the relationship with AKR1B1 expression. The positive expression of AKR1B1 in GC tissues was significantly higher than that of adjacent nontumor tissues. The difference of AKR1B1 expression between GC tissues and paired adjacent nontumor tissues was statistically significant (p < 0.001). AKR1B1 was closely related to tumor size, regional lymph node (N), metastases (M), and tumor-node-metastasis (TNM) stage (p < 0.05). The overall survival of patients with low expression of AKR1B1 was significantly better than that of patients with high expression of AKR1B1 by Kaplan-Meier survival analysis (p < 0.001). AKR1B1 plays an important role in the occurrence and development of GC, and it has a certain reference value for the prognosis of GC patients.

ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

BACKGROUND: A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. METHODS: mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro. RESULTS: ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens. CONCLUSIONS: The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

ADAM-17 expression is enhanced by FoxM1 and is a poor prognostic sign in gastric carcinoma.

BACKGROUND: The ADAMs proteases are a multifunctional family of proteins, many of which participate in the pathogenesis of cancers. The expression and regulation of ADAMs has not yet been fully examined in gastric cancer. MATERIALS AND METHODS: Using reverse transcription-PCR, messenger RNA expression of ADAM-9, ADAM-10, ADAM-11, ADAM-12, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 was detected in gastric cancer. ADAM-10, ADAM-17, ADAM-28, and FoxM1 expression in gastric cancer was detected by Western blot and immunohistochemistry. The correlation between ADAM-17 and FoxM1 was analyzed in vivo and in vitro. RESULTS: The messenger RNA levels of ADAM-9, ADAM-10, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 were increased in tumor tissues compared with adjacent normal tissue, especially ADAM-10, ADAM-17, and ADAM-28. FoxM1 expression correlated significantly with ADAM-17 expression. FoxM1 regulates ADAM-17 expression in vivo and in vitro, which in turn influences proliferation and tumor growth of gastric cancer cells. Furthermore, Cox regression analysis revealed that FoxM1 and ADAM-17 are independent prognostic factors for patients with gastric cancer. CONCLUSIONS: These results indicate that overexpression of ADAMs may contribute to gastric cancer progression and that ADAM-17 is a downstream target of FoxM1. Overall, the present study highlights the potential for FoxM1 and ADAMs as potential therapeutic targets for patients with gastric carcinoma.

Overexpression of SLC38A1 is associated with poorer prognosis in Chinese patients with gastric cancer.

BACKGROUND: Current literature has demonstrated that host glutamine depletion facilitates tumorigenesis. Likewise, the glutamine transporter SLC38A1 is putatively associated with malignant transformation and tumor progression. Taken together, this forms the premise for undertaking the current study. The twofold aim of this study was to provide insight into whether or not a variance in the expression of SLC38A1 exists between human gastric cancer and healthy human tissues, and to determine how silencing the SLC38A1 gene could affect the proliferation, viability, migration, and invasion of gastric cancer cells. METHODS: Immunohistochemical staining was used to analyze the expression of SLC38A1 in gastric cancer tissues and adjacent healthy mucosa in 896 patients with pathologically confirmed gastric cancer who had underwent R0 resection. SH-10-TC cells (a gastric cancer cell line) were used to examine whether silencing SLC38A1 with siRNA could affect cell viability, migration and invasion. RESULTS: The SLC38A1 protein was very low or undetectable in healthy gastric mucosa. In contrast, strong staining of SLC38A1 protein was found in the cytoplasm in 495 out of the 896 gastric cancer samples. More pronounced SLC38A1 expression in gastric cancer tissues was significantly associated with age, differentiation status, lymph node metastasis, TNM stage and PCNA (proliferating cell nuclear antigen) expression. Upon univariate survival analysis, SLC38A1 expression was correlated with poor survival. Multivariate survival analysis revealed that SLC38A1 was an independent prognostic factor. CONCLUSION: SLC38A1 is overexpressed in gastric cancer, which suggests that it is contributory to tumor progression. These results encourage the exploration of SLC38A1 as a target for intervention in gastric cancer.

Psychological stress induced zinc accumulation and up-regulation of ZIP14 and metallothionein in rat liver.

BACKGROUND: Zinc is necessary for normal liver function; and vice versa, the liver plays a central role in zinc homeostasis. The aim of present study is to assess the effects of repeated psychological stress (PS) on the zinc metabolism and related mechanism involved in zinc homeostasis in rat liver. METHODS: In present study, we used communication box to create PS model and investigated the serum corticosterone (CORT), zinc level in serum and liver, liver metallothionein (MT) content and ZRT/IRT-like Protein 14 (ZIP14) mRNA expression. RESULTS: The results showed that the serum CORT level increased and serum zinc level decreased significantly after 7 d and 14 d PS treatment. Meanwhile, zinc and MT contents in liver were elevated after 14 d PS exposure, while those in 7 d PS exposure group did not change. ZIP14 mRNA was expressed markedly at 7 d after the onset of PS, while Zip14 mRNA expression in the liver after 14 d PS exposure reached normal level compared with control group. CONCLUSIONS: The results suggest that PS exposure could induce hypozincemia, which might be related to liver zinc accumulation because of high level of MT through glucocorticoid-mediated MT synthesis and ZIP14 expression induced by interleukin-6.

Twist1 promotes gastric cancer cell proliferation through up-regulation of FoxM1.

Twist-related protein 1 (Twist1), also known as class A basic helix-loop-helix protein 38 (bHLHa38), has been implicated in cell lineage determination and differentiation. Previous studies demonstrate that Twist1 expression is up-regulated in gastric cancer with poor clinical outcomes. Besides, Twist1 is suggested to be involved in progression of human gastric cancer. However, its biological functions remain largely unexplored. In the present study, we show that Twist 1 overexpression leads to a significant up-regulation of FoxM1, which plays a key role in cell cycle progression in gastric cancer cells. In contrast, knockdown of Twist 1 reduces FoxM1 expression, suggesting that FoxM1 might be a direct transcriptional target of Twist 1. At the molecular level, we further reveal that Twist 1 could bind to the promoter region of FoxM1, and subsequently recruit p300 to induce FoxM1 mRNA transcription. Therefore, our results uncover a previous unknown Twist 1/FoxM1 regulatory pathway, which may help to understand the mechanisms of gastric cancer proliferation.

Psychological stress-induced lower serum zinc and zinc redistribution in rats.

In humans, long-term exposure to uncontrollable and unpredictable life stressors is a major precipitant in the development of depressive disorders. There are strong evidences that depression is accompanied by lower serum zinc. The aim of present study is to assess the effects of repeated psychological stress (PS) on the zinc metabolism in rat. The rats were divided into control group and PS group which were subdivided into three subgroups: 7-day group, 14-day group, and recovery group (ten rats in each subgroup). PS model was created by a communication box which contains room A and room B. Rats in room A were only exposed to the responses of rats which were randomly given electrical shock for 30 min in room B. PS was given to rats for 30 min every morning for 14 days. The serum corticosterone (CORT), zinc in serum and tissues, and zinc apparent absorption after PS exposure were investigated. The results showed that the serum CORT increased and serum zinc decreased after 7 and 14 days of PS treatment. The zinc concentration in the liver was increased by 14 days PS exposure, whereas its concentration in the hippocampus was decreased by 7 and 14 days of PS exposure. There were no significant changes in zinc concentration in the heart, spleen, kidney, duodenum, cortex, and cerebellum. A decrease in the zinc apparent absorption was observed in the 7- and 14-day PS groups. The increased serum CORT and liver zinc concentrations and decreased serum zinc and apparent absorption of zinc recovered to normal concentrations 7 days away from PS exposure. The results suggest that PS could induce lower serum zinc, which might be correlated with decreased zinc absorption in the small intestine and increased liver zinc accumulation after PS exposure. The consequent effects of decreased hippocampal and serum zinc and increased CORT concentration after PS exposure on stress-related diseases await further research.

Inhibition of SENP6-induced radiosensitization of human hepatocellular carcinoma cells by blocking radiation-induced NF-κB activation.

Hepatocellular carcinoma is the most common type of liver cancer. Radiotherapy combined with chemotherapy is the treatment of choice for hepatocellular carcinoma, but radioresistance of the cancer remains a significant therapeutic hindrance. Here, we provided several lines of evidence that small ubiquitin-like modifier (SUMO)-specific protease 6 (SENP6) could be an attractive molecular target for the treatment of hepatocellular carcinoma. By using immunohistochemical and real-time PCR, we showed that SENP6 was overexpressed in more than half of the hepatocellular carcinoma tissues. The growth retardation and radiosensitization were caused by silencing of SENP6 in the hepatocellular carcinoma cell lines using lentiviral shRNA. Moreover, SENP6 was required for radiation-induced NF-κB activation and the half-life of IκBα, a well-known inhibitor of NF-κB, and was extended by SENP6 silencing. Thus, our data demonstrated that SENP6 is an attractive drug target for anticancer therapy and radiosensitization.

Overexpression of p-4ebp1 in Chinese gastric cancer patients and its correlation with prognosis.

BACKGROUND/AIMS: We sought to reveal the status of phosphorylated 4E-binding protein 1 (p-4ebp1) expression in Chinese gastric cancer patients and its correlation with tumor prognosis. METHODOLOGY: Tissue microarray blocks containing gastric cancer tissue and matched noncancerous gastric tissue specimens from 286 patients were constructed. The expression of 4E-binding protein 1 (4ebp1) and p-4ebp1 of these specimens was analyzed using immunohistochemical studies. RESULTS: The expression rates of 4ebp1 and p-4ebp1 in gastric cancer were 68.5% (196 of 286) and 49.7% (142 of 286) respectively. The expression of 4ebp1 was correlated with node metastasis and poor differentiation, while the expression of p-4ebp1 was correlated with tumor size, node metastasis and TNM stage. p-4ebp1 overexpression has a significant inverse correlation with median survival time. CONCLUSIONS: p-4ebp1 expression is correlated with later TNM stage and is a prognostic factor of survival time after surgery.

Pemetrexed versus docetaxel in second line non-small-cell lung cancer: results and subsets analyses of a multi-center, randomized, exploratory trial in Chinese patients.

BACKGROUND: Pemetrexed and docetaxel are established therapies in second line non-small cell lung cancer (NSCLC). Comparative data, concerning the two agents in the designated settings, however, are lacking in Chinese patients who account for the largest lung cancer population in the world. METHODS AND PATIENTS: We designed and performed a multi-center, randomized, exploratory clinical trial of pemetrexed compared with docetaxel in second line chemotherapy in Chinese NSCLC patients. Eligible patients with histological or cytological diagnosis of stage IIIB or IV NSCLC, who were not suitable for curative therapy and had failed from prior first line chemotherapy regimen for at least 4 weeks, were randomized to receive either pemetrexed 500 mg/m(2) intravenously day 1 with vitamin B12, folic acid, and dexamethasone, or docetaxel 75 mg/m(2) intravenously day 1 with dexamethasone. Both regimens were implemented once every 21 days for 2 cycles. This study was designed to be a non-inferiority trial that compared tumor response for overall response rate (ORR) between the two drugs as primary endpoint. The secondary endpoints included disease control rate (DCR), Karnofsky performance status (KPS) scores and toxicities. RESULTS: 260 patients were enrolled and randomly assigned to receive chemotherapy of either pemetrexed (132 patients) or docetaxel (128 patients). 106 patients in pemetrexed arm and 102 patients in docetaxel arm were evaluable for efficacy. The efficacy of pemetrexed was equivalent to that of docetaxel in the second-line treatment for Chinese NSCLC (ORR: pemetrexed vs. docetaxel = 9.4% vs. 4.9, p = 0.285, DCR: pemetrexed vs. docetaxel = 67.2% vs. 69.6%, p = 0.685). And pemetrexed seemed to slightly promote patients' average KPS score when comparing with docetaxel, although the difference was without statistical significance (changes of average KPS scores: pemetrexed vs. docetaxel = 0.28 ± 5.93 vs. -1.67 ± 8.57, p = 0.149). Patients receiving pemetrexed experienced significantly lower incidences of grade 3/4 neutropenia (7.0% vs. 27.6%, p < 0.001) and leucocytopenia (4.7% vs. 22.8%, p < 0.001) than those who received docetaxel. Also, there were lower incidences of alopecia, stomatitis, and neural abnormality for patients receiving pemetrexed than those receiving docetaxel. Incidence of serum glutamic oxaloacetic transaminase elevation, however, was higher in pemetrexed arm than in docetaxel arm (32.3% vs. 14.9%, p = 0.013). In addition, age ≥ 60 patients benefit from pemetrexed with equivalent efficacies yet much lower toxicities compared to docetaxel (DCR: pemetrexed vs. docetaxel = 66.67% vs. 81.58%, p = 0.146; grade 3/4 hematologic toxicities: pemetrexed vs. docetaxel = 17.25% vs. 39.6%, p = 0.016). CONCLUSION: Treatment with pemetrexed resulted in equivalent efficacy outcomes and better safety profiles compared with docetaxel in second-line therapy for advanced NSCLC in Chinese lung cancer population. And age ≥ 60 patients may benefit from second-line single pemetrexed.

Preventive effects of zinc against psychological stress-induced iron dyshomeostasis, erythropoiesis inhibition, and oxidative stress status in rats.

Psychological stress (PS) could cause decreased iron absorption and iron redistribution in body resulting in low iron concentration in the bone marrow and inhibition of erythropoiesis. In the present study, we investigated the effect of zinc supplementation on the iron metabolism, erythropoiesis, and oxidative stress status in PS-induced rats. Thirty-two rats were divided into two groups randomly: control group and zinc supplementation group. Each group was subdivided into two subgroups: control group and PS group. Rats received zinc supplementation before PS exposure established by a communication box. We investigated the serum corticosterone (CORT) level; iron apparent absorption; iron contents in liver, spleen, cortex, hippocampus, striatum, and serum; hematological parameters; malondialdehyde (MDA); reduced glutathione (GSH); and superoxide dismutase (SOD). Compared to PS-treated rats with normal diet, the PS-treated rats with zinc supplementation showed increased iron apparent absorption, serum iron, hemoglobin, red blood cell, GSH, and SOD activities; while the serum CORT; iron contents in liver, spleen, and regional brain; and MDA decreased. These results indicated that dietary zinc supplementation had preventive effects against PS-induced iron dyshomeostasis, erythropoiesis inhibition, and oxidative stress status in rats.

Down-regulated SPARCL1 is associated with clinical significance in human gastric cancer.

BACKGROUND: SPARC-like protein 1 (SPARCL1), a member of extracelluar matrix glycoprotein, is involved in many physiological functions. METHODS: Tissue microarray (TMA) blocks were constructed based on 1,072 Chinese patients, containing both gastric cancer (GC) tissues and adjacent normal mucosa tissues. We analyzed the expression of SPARCL1 from both mRNA and protein level, using Real-time quantitative polymerase chain reaction (qRT-PCR), semi-quantitative PCR, immunohistochemistry (IHC), and Western blotting. Loss of heterozygosity analysis at the SPARCL1 gene locus was carried out using ten paired tumor and matched normal tissues. RESULTS: SPARCL1 mRNA was significantly reduced in tumor specimens compared with normal tissues. Down-regulation of SPARCL1 protein was detected in 413 cases (38.7%) of 1,072 primary gastric tumor tissues. Kaplan-Meier survival curves demonstrated that SPARCL1-positive patients had better median survival time than SPARCL1-negative patients (59 months vs. 28 months, P = 0.001). Multivariate survival analysis revealed that SPARCL1 was an independent prognostic factor in gastric adenocarcinoma patients with no metastasis and well/moderately differentiated. The incidence of LOH for each individual marker was 12.5% (1/8) for D4S2462, 20% (2/10) for D4S2929, and 33.3% (3/9) for SPARCL1. CONCLUSIONS: Our study revealed the clinical significance of SPARCL1 expression, providing a basis that the loss of SPARCL1 is a negative event in GC progression and prognosis. Furthermore, SPARCL1 protein might be considered to be a potential differentiation marker.

[Clinical observation of prophylactic lactulose for prevention of oral morphine-induced constipation].

OBJECTIVE: To evaluate the effects of different doses of lactulose on preventing oral morphine-induced constipation. METHODS: From January 2011 to May 2012, a total of 112 patients received oral lactulose solution to prevent morphine-induced constipation at our hospital and their clinical data were retrospectively analyzed. The doses of morphine were adjusted according to the pain scores and lactulose was taken simultaneously. There were 52 males and 60 females. They were randomized into Group 30 ml/d (n = 40), Group 60 ml/d (n = 43) and Group 90 ml/d (n = 29). The incidences of constipation and adverse reactions were obtained at 1 week after the start of medicine. The measurement data were analyzed with analysis of variance. And the enumeration data were analyzed with χ(2), Kruskal-Wallis and Mann-Whitney U tests. RESULTS: The incidence of constipation was 67.5% (27/40) in Group 30 ml/d, 46.5% (20/43) in Group 60 ml/d, and 37.9% (11/29) in Group 90 ml/d. And there were statistical differences (P = 0.036). The incidence of constipation in Group 30 ml was significantly higher than Group 90 ml/d (P = 0.015). No statistical difference existed in the incidence of constipation between Groups 30 ml/d and 60 ml/d (P = 0.054) or Groups 60 ml/d and 90 ml/d (P = 0.471). The incidence of vomiting was 34.5% (10/29) in Group 90 ml/d and it was significantly higher than 10.0% (4/40) in Group 30 ml/d (P = 0.013) and 9.3% (4/43) in Group 60 ml/d (P = 0.009). No statistical difference existed in the incidence of vomiting between Groups 30 ml/d and 60 ml/d (P = 0.915). The incidence of diarrhea was 17.2% (5/29) in Group 90 ml/d and it was significantly higher than 0 (0/40) in Group 30 ml/d (P = 0.007). No statistical difference existed in the incidence of diarrhea between Groups 30 ml/d and 60 ml/d (4.7% (2/43), P = 0.170) or Groups 60 ml/d and 90 ml/d (P = 0.072). CONCLUSION: The correct dosage of lactulose for the prevention of oral morphine-induced constipation is 60 ml/d.