Association of Vitamin D Supplementation with Cardiovascular Events: A Systematic Review and Meta-Analysis.

BACKGROUND: low vitamin D status has been associated with an increased incidence of cardiovascular events. However, whether vitamin D supplementation would reduce the incidence of cardiovascular events remains unclear. PURPOSE: To perform a systematic review and meta-analysis of the effect of vitamin D supplementation on the mortality and incidence of cardiovascular events. DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from their inception until 3 May 2022. STUDY SELECTION: Two authors searched for randomized clinical trials that reported vitamin D supplementation's effect on cardiovascular events outcomes. DATA EXTRACTION: Two authors conducted independent data extraction. DATA SYNTHESIS: We identified 41,809 reports; after exclusions, 18 trials with a total of 70,278 participants were eligible for analysis. Vitamin D supplementation was not associated with the mortality of cardiovascular events (RR 0.96, 95% CI 0.88-1.06, I2 = 0%), the incidence of stroke (RR 1.05, 95% CI 0.92-1.20, I2 = 0%), myocardial infarction (RR 0.97, 95% CI 0.87-1.09, I2 = 0%), total cardiovascular events (RR 0.97, 95% CI 0.91-1.04, I2 = 27%), or cerebrovascular events (RR 1.01, 95% CI 0.87-1.18, I2 = 0%). LIMITATION: Cardiovascular events were the secondary outcome in most trials and thus, might be selectively reported. CONCLUSION: In this meta-analysis of randomized clinical trials, vitamin D supplementation was not associated with a lower risk of cardiovascular events than no supplementation. These findings do not support the routine use of vitamin D supplementation in general.

Lactate dehydrogenase as promising marker for prognosis of brain metastasis.

BACKGROUND: Lactate dehydrogenase (LDH) is a biomarker for cancer. However, the relationship between serum LDH levels and the survival of patients with brain metastasis has been fully revealed. We aimed to evaluate the serum LDH levels and assess its prognostic value in patients with BM. METHODS: The serum LDH levels were collected from 2507 patients with BM. Patients were categorized into four groups according to the quartile of serum LDH levels. The association between serum LDH levels and overall survival (OS) was evaluated using Cox regression models and Kaplan-Meier curves. Three predictive models were used to evaluate patients. RESULTS: The Kaplan-Meier curve for survival by the serum LDH group demonstrates clear separation between four groups (P < 0.001). The participants in the lower group had longer OS than those in the higher group. After adjusting in multivariate Cox regression models remained significant for patients in the Q4 compared with patients in the Q1 (Q4:Q1 OR 1.58, 95% CI 1.38-1.80). Furthermore, the GPA-LDH model generates a pooled area under the curve of 0.630 (95% CI 0.600, 0.660). CONCLUSIONS: Serum LDH levels and OS in patients with brain metastasis is an inverse association. Moreover, Serum LDH levels can improve the prognosis of the GPA model.

Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial.

Background: A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC. Methods: In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964. Results: From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed. Conclusions: Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

Survival outcomes in patients with parotid gland carcinoma treated with postoperative therapies using risk stratification.

BACKGROUND: To evaluate the role of postoperative treatment in parotid gland carcinoma (PGC) based on risk stratification. MATERIAL AND METHODS: A total of 301 PGC patients were retrospectively analyzed using risk stratification. The Kaplan-Meier method and Cox analysis were performed to conduct survival analysis. RESULTS: In the high-risk group, those treated with postoperative radiotherapy (RT) had a better 5-year disease-free survival (DFS) than those treated with surgery alone. In the low-risk group, both surgery + RT and surgery + chemotherapy (CT) significantly improved DFS when compared with surgery alone. Cox analysis showed that patients who underwent surgery + RT or surgery + CT had a lower risk of disease progression than those who underwent surgery alone in the low-risk group. In the high-risk group, patients who underwent surgery + RT had a lower risk of disease progression. CONCLUSIONS: Postoperative RT showed considerable benefit in improving disease control in patients with PGC, even in those without high-risk factors.

Clinical and survival analysis of nasopharyngeal carcinoma with consistently negative Epstein-Barr virus DNA.

BACKGROUND: To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein-Barr virus (EBV) DNA level. METHODS: Propensity score matching (PSM) method was used to create well-balanced cohorts. Kaplan-Meier method and Cox proportional hazards models were performed to conduct survival analysis. RESULTS: Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p < .001; p = .015). And patients with consistently negative EBV level were significantly associated with preferable 3-year DFS (95.0% vs. 84.4%, p = .004), DMFS (98.3% vs. 89.4%, p = .009), and OS (100% vs. 97.6%, p = .004). CONCLUSIONS: NPC patients with consistently negative EBV DNA level performed an earlier clinical stage and negative EBV DNA level was related to preferable survival outcomes.

A novel inhibitor of Rho GDP-dissociation inhibitor α improves the therapeutic efficacy of paclitaxel in Lewis lung carcinoma.

Molecular-targeted therapies are considered a promising strategy for the treatment of most types of human cancer. Rho GDP-dissociation inhibitor α (RhoGDIα), which functions mainly by controlling the cellular distribution and activity of Rho GTPases and is associated with tumor progression and poor prognosis of cancer patients, has become a new promising target for anticancer treatment. Recently, a specific RhoGDIα inhibitor (no. SKLB-163) was developed via computer-aided drug design and de novo synthesis. Previous studies have shown that SKLB-163 had extremely good antitumor activities against diverse cancer cell lines. In the present study, SKLB-163 was used in combination with paclitaxel in order to determine the synergistic effect of the antitumor activity. The findings showed that the combination therapy clearly inhibited cell proliferation and induced apoptosis of LL/2 in vitro. The LL/2 mice model also showed that the combination therapy inhibited tumor growth in vivo. Proliferative cell nuclear antigen (PCNA) immunohistochmeistry and terminal deoxynucleotidyl transferase dUTP nick end-labeling showed that combination therapy inhibited cell proliferation and increased apoptosis compared to the treatment with SKLB-163 or paclitaxel alone. The data suggests that the combination therapy exerted synergistic antitumor effects, providing a novel way to augment the antitumor efficacy of cytotoxic chemotherapy.

Phase I study of postoperative radiotherapy concurrent with S-1 in patients with gastric cancer.

Postoperative chemoradiotherapy (CRT) with concurrent 5-fluorouracil is the standard care for gastric cancer patients after curative surgery. The previous studies revealed that the subgroup of patients with high recurrence risk would benefit most from adjuvant CRT. S-1, a novel oral fluorouracil, has showed very effective in metastatic gastric cancer and became the standard option for gastric cancer with D2 dissection. The safety and dosage of S-1 combined with postoperative radiotherapy have not yet been evaluated. This study is to determine the maximum tolerate dose (MTD) and dose-limiting toxicity (DLT) of S-1 given concurrently with postoperative high-dose radiotherapy in gastric cancer. Patients with more advanced stage (pT4 and/or pN+) after R0 resection were recruited. Eligible patients received one cycle standard SOX (S-1 plus oxaliplatin) chemotherapy, then S-1 monotherapy with concurrent radiotherapy for 6 weeks, followed by additional three cycles of SOX. During the concurrent CRT, S-1 was administered on every radiotherapy treatment day according to a predefined dose-escalation schedule. Radiotherapy (3D-RT or IMRT) was given to a total dose of 50.4 Gy in 28 fractions. DLT was defined as grade 3 or 4 hematologic and non-hematologic toxicity. From March 2011 to October 2012, 21 patients were enrolled at five dose levels: 40 (n = 3), 50 (n = 3), 60 (n = 6), 70 (n = 6) and 80 mg/m(2)/day (n = 3). D2-dissection was performed in 18 patients (85.7 %) and 15 patients (71.4 %) had stage III disease. The most common dose-related toxicity was anorexia, nausea and vomiting, fatigue and leucopenia. DLT was occurred in one patient at 60 mg/m(2)/day (grade 3 fatigue), one patient at 70 mg/m(2)/day (grade 3 vomiting and anorexia), two patients at 80 mg/m(2)/day (one with grade 3 vomiting and anorexia; another with grade 3 febrile leucopenia). Four patients did not complete CRT as planned. Overall, this phase I study demonstrated that postoperative CRT with daily S-1 was feasible in gastric cancer and the MTD of S-1 concurrent with radiotherapy was 70 mg/m(2)/day. This S-1-based postoperative CRT will be investigated in a multicenter phase III study in West China.

The effect of chronic stress on anti-angiogenesis of sunitinib in colorectal cancer models.

Epidemiological and experimental evidence has shown that psychological stress can propel cancer progression. However, its role in anti-angiogenic therapy is not well understood. We previously found that exogenous norepinephrine attenuated the effect of sunitinib, a multi-targeted anti-angiogenic agent, in a mouse melanoma model. Here, we further evaluated the effects of chronic stress on sunitinib therapy in colorectal cancer models. We found that chronic restraint stress markedly weakened the efficacy of sunitinib, primarily through promoting the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) to stimulate tumor angiogenesis in vivo. This effect could be sufficiently mimicked by exogenous norepinephrine and blocked by the ß-antagonist propranolol. In vitro, norepinephrine up-regulated expression of VEGF and IL-8 in sunitinib-treated cancer cells mainly through the ß-adrenoceptor-cAMP-PKA signaling pathway. Norepinephrine also abrogated sunitinib-induced inhibition of cancer cell migration, but had no effect on direct anti-proliferative activity of sunitinib on cancer cells. These findings suggest that psychological stress might attenuate anti-angiogenic therapy primarily through activating beta-adrenergic signaling to promote tumor angiogenesis. It is also suggested that ß-blockers might improve anti-angiogenic outcome under psychological stress.

Plasmid-encoding vasostatin inhibited the growth and metastasis of human hepatocellular carcinoma cells.

The growth and metastasis of solid tumors depends on angiogenesis. Anti-angiogenesis therapy may represent a promising therapeutic option. Vasostatin, the N-terminal domain of calreticulin, is a very potent endogenous inhibitor of angiogenesis and tumor growth. In this study, we attempted to investigate whether plasmid-encoding vasostatin complexed with cationic liposome could suppress the growth and metastasis of hepatocellular carcinoma in vivo and discover its possible mechanism of action. Apoptosis induction of pSecTag2B-vasostatin plasmid on murine endothelial cells (MS1) was examined by flow cytometric analysis in vitro. Nude mice bearing HCCLM3 tumor received pSecTag2B-vasostatin, pSecTag2B-Null, and 0.9 % NaCl solution, respectively. Tumor net weight was measured and survival time was observed. Microvessel density within tumor tissues was determined by CD31 immunohistochemistry. H&E staining of lungs and TUNEL assay of primary tumor tissues were also conducted. The results displayed that pSecTag2B-vasostatin could inhibit the growth and metastasis of hepatocellular carcinoma xenografts and prolong survival time compared with the controls in vivo. Moreover, histologic analysis revealed that pSecTag2B-vasostatin treatment increased apoptosis and inhibited angiogenesis. The present data may be of importance to the further exploration of this new anti-angiogenesis approach in the treatment of hepatocellular cancer.

Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model.

BACKGROUND: Sunitinib alone exhibits satisfactory efficacy in several mouse homografts and xenografts but unsatisfactory efficacy in many kinds of solid tumors in clinic. Different from animals, receiving a diagnosis of cancer impacts chronic stress on patients. Here, we examine whether norepinephrine (NE), one of the most potent stress related hormones, leads to the difference in the efficacy of sunitinib between clinical and preclinical trials. METHODS: The influence of NE on mouse melanoma B16F1 cells under sunitinib was evaluated in vitro and in vivo. The ß-AR/cAMP/PKA (ß-adrenoceptor/cyclic adenosine monophosphate/protein kinase A) signaling pathway was also evaluated in human lung adenocarcinoma cells. RESULTS: We found that NE upregulated the expression of VEGF, IL-8 and IL-6 in vitro and stimulated tumor growth in vivo, which was mediated by ß-AR/cAMP/PKA signaling pathway and could be inhibited by propranolol, a ß-blocker for hypertension for decades. CONCLUSIONS: This research indicates exogenous norepinephrine attenuates the efficacy of sunitinib, and a combination of sunitinib and propranolol might be suggested as a new strategy in solid tumor in clinic.

Loss of RASSF1A expression in colorectal cancer and its association with K-ras status.

BACKGROUND: The RAS-association domain family 1 A (RASSF1A) is a classical member of RAS effectors regulating cell proliferation and apoptosis. Loss of RASSF1A expression may shift the balance towards a growth-promoting effect without the necessity of activating K-ras mutations. Its potential association with K-ras mutations in colorectal cancer (CRC) is unclear. METHODS: RASSF1A expression was examined in normal mucosa, adenoma, and tumor tissues of colon and rectum, respectively. We examined the association of RASSF1A expression, mutations of K-ras, and EGFR status in 76 primary CRCs. The relationship between clinicopathological characteristics and RASSF1A expression was also analyzed. RESULTS: RASSF1A expression level decreased progressively in normal mucosa, adenoma and, tumor tissues, and the loss of RASSF1A expression occurred more frequently in tumor tissues. Of 76 primary CRCs, loss of RASSF1A expression and/or K-ras mutations were detected in 77% cases. Loss of RASSF1A expression was more frequent in K-ras wild-type than in mutation cases (63% versus 32%, P = 0.011). CONCLUSIONS: Our study indicates that loss of RASSF1A may be involved in pathogenesis of CRC, its expression was found predominantly in K-ras wild-type CRCs, suggesting that it may be another way of affecting RAS signaling, in addition to K-ras mutations.

A rare adolescent case of female pseudohermaphroditism with adrenocortical carcinoma and synchronous teratoma.

A patient with female pseudohermaphroditism is chromosomally and gonadally a female individual but has male or ambiguous external genitalia. In this paper, we report a 12-year-old Chinese girl who was diagnosed with female pseudohermaphroditism characterized by clitoridauxe, hirsutism, acne, hypertension, and karyotype 46 XX. Computed tomography scan revealed a huge left abdominal mass with distant metastases to bilateral lungs and a concomitant pelvic teratoma. Because the left abdominal mass was unresectable, the patient underwent a biopsy of the abdominal mass and a radical resection of the pelvic teratoma. Histopathology confirmed that the left abdominal mass was an adrenocortical carcinoma (ACC) and the pelvic teratoma was a mature cystic teratoma originating from the left ovary. After surgery, the patient received a transcatheter arterial chemoembolization of ACC, combined with 2 g mitotane daily for systemic treatment. It was a pity that she died 8 months later after diagnosis. So far, as we know, the simultaneous occurrence of pseudohermaphroditism, ACC, and ovarian teratomas has not been reported in the literatures before.

Different combination schedules of gemcitabine with endostar affect antitumor efficacy.

PURPOSE: Antiangiogenic drugs inhibit tumor growth by decreasing blood supply and causing transient "normalization" of the tumor vasculature, thereby improving the delivery of systemic chemotherapy. A higher dose of antiangiogenic drugs may lead to a more marked decrease in intratumoral blood flow but may concomitantly cause a decrease in delivery of chemotherapeutic agents. The purpose of this study was to define an optimal schedule for the combination of gemcitabine with a recombinant endostatin, endostar. METHODS: We evaluated the antitumor effects with different schedules of gemcitabine combined with or without endostar. The changes of vascular endothelial growth factor (VEGF) levels in tumor extracts and sera after gemcitabine treatment were examined. Endostar was also assessed for its abilities to inhibit the increase in VEGF levels. Apoptotic cells and microvessel density within tumor tissue were also examined. RESULTS: Endostar administered simultaneously with or following gemcitabine improved the inhibition of tumor growth, compared with gemcitabine alone. VEGF levels decreased immediately after gemcitabine treatment, but increased in the following several days. Endostar administered simultaneously with or following gemcitabine could inhibit the increase in VEGF levels, thereby cause a decreased vessel density and an increased apoptosis in tumor tissue. CONCLUSIONS: Our finding suggested that endostar given simultaneously with or following gemcitabine might be optimal to enhance the antitumor effect.

Comparative proteomic approach identifies PKM2 and cofilin-1 as potential diagnostic, prognostic and therapeutic targets for pulmonary adenocarcinoma.

Lung cancer is the leading cause of cancer-related death in the world. Non-small cell lung carcinomas (Non-SCLC) account for almost 80% of lung cancers, of which 40% were adenocarcinomas. For a better understanding of the molecular mechanisms behind the development and progression of lung cancer, particularly lung adenocarcinoma, we have used proteomics technology to search for candidate prognostic and therapeutic targets in pulmonary adenocarcinoma. The protein profile changes between human pulmonary adenocarcinoma tissue and paired surrounding normal tissue were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-DE) based approach. Differentially expressed protein-spots were identified with ESI-Q-TOF MS/MS instruments. As a result, thirty two differentially expressed proteins (over 2-fold, p<0.05) were identified in pulmonary adenocarcinoma compared to normal tissues. Among them, two proteins (PKM2 and cofilin-1), significantly up-regulated in adenocarcinoma, were selected for detailed analysis. Immunohistochemical examination indicated that enhanced expression of PKM2 and cofilin-1 were correlated with the severity of epithelial dysplasia, as well as a relatively poor prognosis. Knockdown of PKM2 expression by RNA interference led to a significant suppression of cell growth and induction of apoptosis in pulmonary adenocarcinoma SPC-A1 cells in vitro, and tumor growth inhibition in vivo xenograft model (P<0.05). In addition, the shRNA expressing plasmid targeting cofilin-1 significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. While additional works are needed to elucidate the biological significance and molecular mechanisms of these altered proteins identified in this study, PKM2 and cofilin-1 may serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets for pulmonary adenocarcinoma.

Comparative proteomic analysis of irinotecan-sensitive colorectal carcinoma cell line and its chemoresistant counterpart.

In this study, we used two-dimensional gel electrophoresis and MALDI-Q-TOF-MS/MS analysis to examine the global protein expression of a pair of colorectal carcinoma cell lines, SW620 and irinotecan-resistant SW620. Of the 30 spots identified as differentially expressed proteins (±over twofold, P<0.05) between the two cell lines, 26 spots (corresponding to 26 unique proteins) were positively identified by MALDI-Q-TOF-MS/MS analysis. These proteins could be grouped into main classes including metabolism (15.38%), cell SSproliferation/differentiation (11.53%), molecular chaperone (11.53%), mRNA splicing (11.53%), and so on. The proteins, which might be involved in the development of tumor drug resistance, such as α-enolase, cofilin, and thioredoxin-dependent peroxide 1, have been validated by western blot analysis and have been discussed. The proteins identified in this study may be useful in showing the mechanisms underlying irinotecan resistance.

Interleukin-15 enhances T-cell responses by stimulation with dendritic cells.

INTRODUCTION: Cytokines play important roles in regulating immune responses. Interleukin-2 (IL-2) has usually been used as an adjuvant to enhance antitumour immune responses. However, its crucial role in activation-induced cell death, inhibition of homeostatic proliferation of CD8+ memory T cells and its notable biological side effects impair its prospect of application. IL-15 has several similar functions to IL-2 and shows potential advantages over IL-2, and is being investigated to enhance antitumour dendritic cell (DC) vaccine strategies in our ongoing studies. OBJECTIVE: In this preliminary study, we evaluated the ability of IL-15, compared with IL-2, to act as an adjuvant to enhance T-cell responses activated by DCs in vitro. MATERIALS AND METHODS: Bone marrow-derived DCs (BMDCs) were pulsed with tumour antigens and used to stimulate lymphocyte responses in the presence of IL-15 or IL-2. The activated T lymphocytes were examined by flow cytometric analysis, and interferon-γ (IFN-γ) enzyme-linked immunospot and cytotoxicity assays. RESULTS: IL-15 was observed to activate lymphocytes with comparable phenotype characteristics of activated/memory CD8+ lymphocytes, compared with IL-2. Both in primary and secondary stimulation with DCs, when using IL-15 as an adjuvant, activated lymphocytes showed higher proportions of IFN-γ-secreting subsets. In secondary stimulation with BMDCs in the presence of IL-15, the activated lymphocytes showed a stronger cytotoxicity to antigen-specific tumour target cells. CONCLUSIONS: Our study suggested that IL-15 might be a prospective adjuvant for a DC vaccine strategy against cancers. The further observation that IL-15 acts as an adjuvant for an antitumour DC vaccine strategy is worth investigating.

Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes.

BACKGROUND: It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first-line chemotherapy. METHODS: Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety-nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated. RESULTS: Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression-free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C). CONCLUSIONS: The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes.

Interaction of green tea polyphenol epigallocatechin-3-gallate with sunitinib: potential risk of diminished sunitinib bioavailability.

Sunitinib, a novel oral multi-targeted tyrosine kinase inhibitor for patients with metastatic renal cell carcinoma (mRCC) and advanced gastrointestinal stromal tumor, has a good prospect for clinical application and is being investigated for the potential therapy of other tumors. We observed the phenomenon that drinking tea interfered with symptom control in an mRCC patient treated with sunitinib and speculated that green tea or its components might interact with sunitinib. This study was performed to investigate whether epigallocatechin-3-gallate (EGCG), the major constituent of green tea, interacted with sunitinib. The interaction between EGCG and sunitinib was examined in vitro and in vivo. (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy and mass spectrometry (MS) were used to analyze the interaction between these two molecules and whether a new compound was formed. Solutions of sunitinib and EGCG were intragastrically administered to rats to investigate whether the plasma concentrations of sunitinib were affected by EGCG. In this study, we noticed that a precipitate was formed when the solutions of sunitinib and EGCG were mixed under both neutral and acidic conditions. (1)H-NMR spectra indicated an interaction between EGCG and sunitinib, but no new compound was observed by MS. Sticky semisolid contents were found in the stomachs of sunitinib and EGCG co-administrated mice. The AUC(0-∞) and C (max) of plasma sunitinib were markedly reduced by co-administration of EGCG to rats. Our study firstly showed that EGCG interacted with sunitinib and reduced the bioavailability of sunitinib. This finding has significant practical implications for tea-drinking habit during sunitinib administration.

Primary precursor B cell lymphoblastic lymphoma of uterine corpus: case report and review of the literature.

INTRODUCTION: Primary lymphomas of the female genital tract are rare. Most involve the cervix rather than the uterine corpus. Many cases of primary endometrial lymphoma are diagnosed as diffuse large B cell type, whereas the precursor B cell lymphoblastic type is extremely rare. MATERIALS AND METHODS: We report a case of precursor B cell lymphoblastic lymphoma of uterine corpus which was successfully treated with surgery and chemotherapy. Staging evaluation revealed tumor limited to the uterine corpus (stage I(E)). After receiving a total abdominal hysterectomy, bilateral salpingooophorectomy, lymph node dissection and combination chemotherapy, the patient is currently free of disease after follow-up of 42 months. CONCLUSION: If correct diagnosis is established and appropriate therapy is chosen, the prognosis of precursor B-LBL of uterine corpus is expected to be good. The literature on primary precursor B cell lymphoblastic lymphoma of the uterine corpus is reviewed.

Therapeutic effects of survivin dominant negative mutant in a mouse model of prostate cancer.

PURPOSE: Patients with localized prostate cancer can usually achieve initial response to conventional treatment. However, most of them will inevitably progress to advanced disease stage. There is a clear need to develop innovative and effective therapeutics for prostate cancer. Mouse survivin T34A (mS-T34A) is a phosphorylation-defective Thr34 → Ala dominant negative mutant, which represents a potential promising target for cancer gene therapy. This study was designed to determine whether mS-T34A plasmid encapsuled by DOTAP-chol liposome (Lip-mS) has the anti-tumor activity against prostate cancer, if so, to further investigate the possible mechanisms. METHODS: In vitro, TRAMP-C1 cells were transfected with Lip-mS and examined for apoptosis by PI staining and flow cytometric analysis. In vivo, subcutaneous prostate cancer models were established in C57BL/6 mice, which were randomly assigned into three groups to receive i.v. administrations of Lip-mS, pVITRO2-null plasmid complexed with DOTAP-chol liposome (Lip-null) or normal saline every 2 days for eight doses. Tumor volume was measured. Tumor tissues were inspected for apoptosis by TUNEL assay. Microvessel density (MVD) was determined by CD31 immunohistochemistry. Alginate-encapsulated tumor cell test was conducted to evaluate the treatment effect on angiogenesis. RESULTS: Administration of Lip-mS resulted in significant inhibition in the growth of mouse TRAMP-C1 tumors. The anti-tumor response was associated with increased tumor cell apoptosis and decreased microvessel density. CONCLUSIONS: The present study may be of importance in the exploration of the potential application of Lip-mS in the treatment of a broad spectrum of tumors.