High expression of AlkB homolog 5 suppresses the progression of non-small cell lung cancer by facilitating ferroptosis through m6A demethylation of SLC7A11.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is a prevailing LC characterized by poor outcomes. AlkB homolog 5 (ALKBH5) functions as a tumor suppressor in several cancers. This study delved into the role of ALKBH5 in NSCLC development. METHODS: TCGA database predicted ALKBH5 expression in NSCLC patients. ALKBH5 levels in NSCLC and human bronchial epithelial cells were determined. pcDNA3.1-ALKBH5/NC, pcDNA3.1-SLC7A11/NC, and ferrostatin-1 were used to explore the interactions among ALKBH5, SLC7A11, and ferroptosis. SLC7A11 mRNA and its protein levels were measured by RT-qPCR and Western blot. Cell viability, apoptosis, migration, and invasion were assessed by CCK-8, flow cytometry, and Transwell. Total N6-methyladenosine (m6A) quantification and its enrichment on SLC7A11 mRNA were determined, followed by the observation of Ki67, ALKBH5 and SLC7A11-positive cell numbers. Glutathione (GSH), lipid reactive oxygen species (lipid-ROS), malondialdehyde (MDA), and iron ion contents were determined. Animal experiments further analyzed the role of ALKBH5 in tumor development and glutathione peroxidase 4 (GPX4) expression. RESULTS: Bioinformatics analysis revealed the lowly-expressed ALKBH5 in LC patients. ALKBH5 was downregulated in NSCLC cells and its upregulation repressed proliferation activity, invasion, and migration, and facilitated apoptosis. ALKBH5 upregulation decreased GSH, increased lipid-ROS, MDA, and iron ion contents, and downregulated SLC7A11 by reducing m6A modification. SLC7A11 upregulation partly annulled the effect of ALKBH5 overexpression on cell ferroptosis and malignant behaviors. In vivo assays elucidated the suppression of ALKBH5 upregulation on tumor development and GPX4 levels. CONCLUSION: ALKBH5 upregulation downregulates SLC7A11 transcription by decreasing m6A modification, thus promoting NSCLC cell ferroptosis and ultimately repressing NSCLC progression.

Effects of intrathecal pemetrexed on the survival of patients with leptomeningeal metastasis from lung adenocarcinoma: a propensity score matching analysis.

PURPOSE: To explore the impact of intrathecal pemetrexed (IP) on the survival of lung adenocarcinoma (LUAC) patients with leptomeningeal metastasis (LM). METHODS: We analyzed patients with LUAC and LM who received systemic therapy after LM diagnosis at the Fujian Cancer Hospital between July 2018 and March 2022. Patients who underwent IP were assigned to the IP group; those without IP treatment were designated as the non-IP group. Propensity score matching (PSM) was performed between the two groups. RESULTS: 165 patients were enrolled: 83 and 82 in the IP and non-IP groups, respectively. After 1:1 PSM, we included 114 patients in the matched cohort. Median overall survival (OS) was 13.2 months (95% CI 10.8-15.6 months) in the IP group versus 10.1 months (95% CI 5.3-14.9 months) in the non-IP group (P = 0.488). Only Eastern Cooperative Oncology Group Performance Status (ECOG PS) was confirmed as an independent predictor for OS in the matched cohort (hazard ratio (HR) 2.03; P = 0.023). Multivariate competing-risks analysis showed that IP significantly correlated with central nervous system-related death (HR 0.31; P = 0.046). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (PS = 2) (14.3 months vs. 1.6 months; P = 0.003). CONCLUSIONS: Intrathecal pemetrexed did not enhance OS for the entire LUAC patient with LM compared to non-intrathecal chemotherapy. However, it exhibited the potential to reduce the risk of central nervous system-related mortality and improve survival in patients with poor ECOG PS.

Novel nomogram for predicting survival in advanced non-small cell lung cancer receiving anti-PD-1 plus chemotherapy with or without antiangiogenic therapy.

Background: This study aimed to develop and validate a novel nomogram to predict survival in advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD-1) inhibitor plus chemotherapy with or without antiangiogenic therapy. Methods: A total of 271 patients with advanced NSCLC who received anti-PD-1 plus chemotherapy with or without antiangiogenic therapy were enrolled in our center and randomized into the training cohort (n = 133) and the internal validation cohort (n = 138). Forty-five patients from another center were included as an independent external validation cohort. The nomogram was created based on the multivariate Cox regression analysis to predict overall survival (OS) and progression-free survival (PFS). The performance of the nomogram was assessed using the concordance index (C-index), the time-dependent area under the receiver operating (ROC) curves (AUCs), calibration curves, and decision curve analysis (DCA). Results: Four factors significantly associated with OS were utilized to create a nomogram to predict OS: Eastern Cooperative Oncology Group performance status (ECOG PS), programmed cell death-ligand 1 (PD-L1) expression, chemotherapy cycle, and pretreatment lactate dehydrogenase-albumin ratio (LAR). Six variables significantly associated with PFS were incorporated into the development of a nomogram for predicting PFS: ECOG PS, histology, PD-L1 expression, chemotherapy cycle, pretreatment platelet to lymphocyte (PLR), and pretreatment LAR. The C-indexes of the nomogram for predicting OS and PFS were 0.750 and 0.747, respectively. The AUCs for predicting the 6-month, 12-month, and 18-month OS and PFS were 0.847, 0.791, and 0.776 and 0.810, 0.787, and 0.861, respectively. The calibration curves demonstrated a good agreement between predictions and actual observations. The DCA curves indicated that the nomograms had good net benefits. Furthermore, the nomogram model was well-validated in the internal and external cohorts. Conclusion: The novel nomogram for predicting the prognosis of advanced NSCLC receiving anti-PD-1 plus chemotherapy with or without antiangiogenic therapy may help guide clinical treatment decisions.

Vinpocetine enhances cisplatin sensitivity of non-small cell lung cancer cells by reducing the nuclear factor erythroid 2-related factor 2 signaling.

Vinpocetine exerts pharmacological effects against cardiovascular diseases, while few studies focused on its roles in cancer. The present study investigated the roles of vinpocetine in non-small cell lung cancer (NSCLC) and its relationship with cisplatin resistance. A549 cisplatin-resistant cells (A549/DDP) and nuclear factor erythroid 2-related factor 2 (Nrf2)-overexpressing cell lines were established. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay was conducted to determine cell viability. Annexin V-propidium iodide assay was conducted to determine cell apoptosis. RT-quantitative PCR and western blot analysis were conducted to determine the levels of mRNA and protein, respectively. NSCLC cell tumor-bearing model was constructed to determine the effects of vinpocetine on tumor growth. Treatment with vinpocetine inhibited cell proliferation and promoted cisplatin-induced cell apoptosis. In addition, treatment with vinpocetine suppressed protein expression of Nrf2 and inhibited messenger RNA levels of heme oxygenase 1 and NAD(P)H dehydrogenase quinone 1 induced by cisplatin. Interestingly, the overexpression of Nrf2 abolished the antiproliferative effects of vinpocetine on NSCLC cells. In vivo data suggested that vinpocetine (50 mg/kg) inhibited tumor growth and enhanced the antitumor effects of cisplatin in the NSCLC cell tumor-bearing model. Vinpocetine enhances cisplatin sensitivity of NSCLC cells in part by suppressing Nrf2 signaling.

Knockdown of circ-RAD23B inhibits non-small cell lung cancer progression via the miR-142-3p/MAP4K3 axis.

BACKGROUND: The development of non-small cell lung cancer (NSCLC) is associated with the deregulation of circRNAs. The objective of this study was to investigate the effects of circ-RAD23B in NSCLC. METHODS: Circ-RAD23B expression, miR-142-3p and MAP4K3 was detected by qPCR. Cell proliferation was investigated by CCK-8 assay and colony formation assay. Cell migration and invasion were assessed by transwell assay. Angiogenesis ability was assessed by tube formation assay. Cell cycle distribution and cell apoptosis were monitored by flow cytometry. The predicted binding relationship between miR-142-3p and circ-RAD23B or MAP4K3 was verified by dual-luciferase reporter assay. The protein level of MAP4K3 was detected by western blot. Animal models were established to determine the role of circ-RAD23B in vivo. RESULTS: Circ-RAD23B was shown to be upregulated in NSCLC tissues and cells. Knockdown of circ-RAD23B inhibited proliferation, migration, invasion, angiogenesis and promoted cell cycle arrest and apoptosis in NSCLC cells, and circ-RAD23B knockdown also impeded tumor growth in vivo. Circ-RAD23B acted as miR-142-3p sponge to inhibit miR-142-3p expression and thus enrich the expression of MAP4K3, a target of miR-142-3p. Rescue experiments presented that miR-142-3p inhibition reversed the effects of circ-RAD23B knockdown, and MAP4K3 overexpression abolished the effects of miR-142-3p restoration. In addition, we found that circ-RAD23B knockdown led to decreased phosphorylation expression of ERK1/2, JNK and p38, three key groups of the MAPK signaling pathway. CONCLUSIONS: Circ-RAD23B knockdown inhibited NSCLC development by regulating the miR-142-3p/MAP4K3 axis, which might be associated with the inactivation of the MAPK signaling pathway.

Free Triiodothyronine Is Independently Associated with Nonalcoholic Fatty Liver Disease in Hospitalized Type 2 Diabetes Mellitus Patients.

OBJECTIVE: Free triiodothyronine (FT3) is an independent risk factor for nonalcoholic fatty liver disease (NAFLD) in patients with euthyroid. However, whether FT3 has an independent effect on NAFLD in a population of type 2 diabetes remains unknown. The purpose of this study was to identify the potential role of FT3 in NAFLD with T2DM. DESIGN: A cross-sectional study. Patient. A total of 859 T2DM patients who met the inclusion criteria were included. There were 506 T2DM patients without NAFLD and 353 T2DM patients with NAFLD. METHODS: The independent samples t-test or Wilcoxon rank sum test were used for continuous variables of different distribution types, while the chi-square test was used for categorical variables. Pearson correlation analysis and linear regression were used to analyze the correlation between FT3 and clinical measurements and biochemical indicators. Multivariate logistic regression analysis was used to determine independent predictors. RESULTS: Patients with NAFLD had higher BMI, SBP, and DBP, longer duration of T2DM, and higher islet function index, blood glucose index, liver function index, renal function index, blood lipid index, and FT3. We also found that FT3 was affected by other five indicators, including ALT, CR, GGT, TC, and LDL-C only in the NAFLD group but not in the non-NAFLD group. FT3 was significantly associated with NAFLD in T2DM patients, and the prevalence of NAFLD increased gradually from the lowest FT3 tertile to the highest FT3 tertile (P for trend < 0.001). CONCLUSION: FT3 is independently associated with NAFLD in hospitalized T2DM patients after rigorous adjustment for various metabolic parameters.

Greater Performance of Exotic Elodea nuttallii in Response to Water Level May Make It a Better Invader Than Exotic Egeria densa During Winter and Spring.

The strategy of producing rapid initial growth and establishing early in the growing season is important, and it is employed by invasive macrophytes. Elodea nuttallii and Egeria densa, two Hydrocharitaceae species, became weeds after invading many countries in recent years. Comparative studies on their invasive traits in relation to native species during winter and spring are limited. In the present study, we compared the growth performance of these two exotic species with a perennial native species, Potamogeton maackianus, in different water depths (1, 2, and 3 m) during winter (January and February) and spring (March and April). Three morphological traits (shoot number, root number and shoot length), total biomass, relative growth rate (RGR) and two physiological photosynthetic traits (total chlorophyll content and the maximum quantum yield of PSII [Fv/Fm]) were measured for each macrophyte. All three species could overwinter as entirely leafy plants. Biomass, RGR, morphological traits and physiological traits were all different among species. However, water depths had a significant effect only on morphological traits. At all water depths, E. nuttallii had significantly higher values for morphological traits, total biomass and RGR than P. maackianus, while E. densa had significantly fewer roots and a lower total chlorophyll content than P. maackianus. Except for Fv/Fm at a 3 m water depth, morphological and physiological photosynthetic traits, biomass and RGR of E. nuttallii were significantly higher than those of E. densa. In addition, a large number of adventitious roots developed from E. nuttallii but not from the other two species. These results indicate that the advantages of E. nuttallii to grow in winter and spring may make it more prone to expansion than E. densa in China.

Experimental evidence of good efficacy and reduced toxicity with peptide-doxorubicin to treat gastric cancer.

BACKGROUND: To compare the efficacy and toxicity of peptide-doxorubicin (PDOX) and doxorubicin (DOX) on nude mice models of human gastric cancer. RESULTS: Both PDOX and DOX could significantly inhibit tumor growth compared with Control (P < 0.05) in both subcutaneous and orthotopic models. Animal survival was much better in PDOX group than DOX group. In peripheral blood test, PDOX group had significantly higher levels of platelets than the Control (P < 0.05), and lymphocyte lower than Control (P < 0.05). There were no significant differences on liver, kidney and cardiac function parameters among three groups (P > 0.05). Immunohistochemistry showed that treatment groups had much higher Tunel than Control (P < 0.05), and PDOX had significantly lower Ki-67 than doxorubicin and Control group (P < 0.01). Western blotting showed that PDOX caused much higher expressions of P53, P21, Aparf-1, pro- and cleaved-caspase 3, compared with DOX. CONCLUSION: Compared with DOX, PDOX has increased effects but much decreased toxicity in treating animal model of gastric cancer. MATERIALS AND METHODS: Animals in subcutaneous model were randomized into Control, doxorubicin, PDOX-L, PDOX-M, and PDOX-H groups. Animals in surgical orthotopic implantation model were randomized into Control, doxorubicin and, peptide-doxorubicin groups. The animals were treated, monitored and examined following a set protocol.

Development of a Scalable, Chromatography-Free Synthesis of t-Bu-SMS-Phos and Application to the Synthesis of an Important Chiral CF3-Alcohol Derivative with High Enantioselectivity Using Rh-Catalyzed Asymmetric Hydrogenation.

A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).

Effects of Water Quality Adjusted by Submerged Macrophytes on the Richness of the Epiphytic Algal Community.

Submerged macrophytes and epiphytic algae play significant roles in the functioning of aquatic ecosystems. Submerged macrophytes can influence the epiphytic algal community by directly or indirectly modifying environmental conditions (nutrients, light, etc.). From December to June of the following year, we investigated the dynamics of the dominant winter species Potamogeton crispus, its epiphytic algae, and water quality parameters in the shallow Liangzi Lake in China. The richness of epiphytic algae had a trend similar to that of P. crispus coverage, which increased in the first four months and then decreased in the following three months. The structural equation model (SEM) showed that P. crispus affected the richness of epiphytic algae by reducing nutrient concentrations (reduction in total organic carbon, total nitrogen and chemical oxygen demand) and enhancing water transparency (reduction in turbidity and total suspend solids) to enhance the richness of epiphytic algae. The results indicated that high amounts of submerged macrophyte cover can increase the richness of the epiphytic algal community by changing water quality.

Two-dimensional active raypath separation using examination of the roots of the spectrum polynomial.

The application of the root multiple signal classification algorithm for raypath separation was motivated by the dramatic reduction in processing time of the multiple-signal classification algorithm. However, the algorithm provides classification only in the direction of the arrival domain and fails to separate raypaths arriving at the array with similar directions of arrival. Moreover, for many applications in shallow water (such as ocean acoustic tomography and active sonar), the emitted signal is known and can be used as a priori information to improve the resolution. Thus, in this study, a two-dimensional active wideband classification algorithm is developed using the examination of the roots of the spectrum polynomial in the angle versus time domain. A two-step strategy is developed to enable extension to the two-dimensional case. The results of simulations confirm that the proposed algorithm achieves almost identical resolution as the existing two-dimensional algorithms while offering a significant reduction in computation time.

Active wideband higher-order raypath separation in multipath environment.

Multiple raypaths propagation is caused by reflection and refraction at the surface and the bottom of the water column. In this study, an active wideband higher-order separation is proposed, which enables the separation of raypaths interrupted by colored noise (as traditionally found in ocean environments) in the angle-vs-time domain. A comparative study shows that the proposed algorithm achieves a more accurate separation than other algorithms. Moreover, with the proposed approach, it is not necessary to assume that the number of sensors is larger than that of the sources. Furthermore, numerical results validate the noise suppression property of the proposed method.

Anti-cancer effects of novel doxorubicin prodrug PDOX in MCF-7 breast cancer cells.

Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 µmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.

Synthesis, identification and in vivo studies of tumor-targeting agent peptide doxorubicin (PDOX) to treat peritoneal carcinomatosis of gastric cancer with similar efficacy but reduced toxicity.

BACKGROUND: This work aimed to synthesize a cathepsin B (CTSB)-cleavable tumor-targeting prodrug peptide doxorubicin (PDOX) and study the in vivo efficacy and toxicities on an animal model of gastric peritoneal carcinomatosis (PC). METHODS: PDOX was synthesized using doxorubicin (DOX) attaching to a CTSB-cleavable dipeptide Ac-Phe-Lys and a para-amino-benzyloxycarbonyl (PABC) spacer. PC model was established by injecting VX2 tumor cells into the gastric sub-mucosa of 40 rabbits, which then were randomized into 4 groups: the Control (n = 10) without treatment, the HIPEC (n = 10) receiving cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the PDOX (n = 10) and the DOX (n = 10) receiving systemic chemotherapy with PDOX 50.0 mg/kg or DOX 5.0 mg/kg, respectively, after CRS + HIPEC. RESULTS: The median overall survivals (OS) were 23.0 d (95% CI: 19.9 d - 26.1 d) in the Control, 41.0 d (36.9 d - 45.1 d) in the HIPEC, 65.0 d (44.1 d - 71.9 d) in the PDOX, and 58.0 d (39.6 d - 54.4 d) in the DOX. Compared with the Control, the OS was extended by 70% in the HIPEC (p < 0.001) and further extended by 40% in the DOX (p = 0.029) and by 58% in the PDOX (p = 0.021), and the PC severity was decreased in the HIPEC and further decreased in the PDOX and DOX. Animals receiving DOX treatment showed hematological toxicities with marked reduction of white blood cells and platelets, as well as cardiac toxicities with significant increases in creatine kinase mb isoenzyme, evident myocardium coagulation necrosis, significant nuclear degeneration, peri-nucleus mitochondria deletion, mitochondria-pyknosis, and abnormal intercalated discs. But these toxicities were not evident in the PDOX. CONCLUSIONS: PDOX is a newly synthesized tumor-targeting prodrug of DOX. Compared with DOX, PDOX has similar efficacy but reduced hematological and cardiac toxicities in treating rabbit model of gastric PC.

[Exploratory analysis of the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma].

OBJECTIVE: To explore the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma (RCC) . METHODS: A total of 136 patients with advanced RCC were treated with sunitinib from 2008 to 2011. There were 91 males and 45 females with an average age of 56 years. Their 6-week therapy cycle was 4 weeks of sunitinib 50 mg daily followed by 2-week off-treatment (schedule 4/2). The median follow-up time was 15 months. Correlation between toxicities and overall survival (OS) was evaluated in a Cox model using log-transformed levels after adjusting for MSKCC model.Log-rank test and Cox proportional hazard model were used to assess the value of drug toxicity as the prognostic factors. RESULTS: The increased hemoglobin on cycle 1 day 14 (HR:0.950, 95%CI:0.923-0.978) and the increased lymphocytes on cycle 1 days 28 and 42 (HR:0.405, 95%CI:0.203-0.809, HR:0.394, 95%CI:0.179-0.867) were significantly associated with OS (P adj = 0.001, 0.014 and 0.022 respectively). Hypertension class III/IV (HR:0.066, 95%CI:0.008-0.582), and the number of neutrophils screening and lymphocyte count ratio (HR:2.537, 95%CI:1.182-5.404) were the survival prognosis independent predictors. CONCLUSION: Early hematopoietic toxicities may potentially predict the outcomes of advanced RCC after a therapy of sunitinib.

Targeting therapy of hepatocellular carcinoma with doxorubicin prodrug PDOX increases anti-metastatic effect and reduces toxicity: a preclinical study.

BACKGROUND: This study was to investigate the effects and safety of cathepsin B-cleavable doxorubicin (DOX)-prodrug (PDOX) for targeting therapy of metastatic human hepatocellular carcinoma (HCC) using DOX as a positive control drug. METHODS: The orthotopic nude mice model of highly metastatic HCC was established and the animals were randomized and treated with PDOX, DOX and saline, respectively. Hematology, biochemistry and tumor markers were studied. At autopsy, liver tumor weight and size, ascites, abdominal lymph nodes metastases, experimental peritoneal carcinomatosis index (ePCI), and tumor-host body weight ratio were investigated. Immunohistochemical studies and western blotting were done to investigate key molecules involved in the mechanism of action. RESULTS: Compared with Control, both PDOX and DOX could similarly and significantly reduce liver tumor weight and tumor volume by over 40%, ePCI values, retroperitoneal lymph node metastases and lung metastases and serum AFP levels (P < 0.05). The PDOX group had significantly higher WBC than the DOX group (P < 0.05), and higher PLT than Control (P < 0.05). Serum BUN and Cr levels were lower in the PDOX group than DOX and Control groups (P < 0.05). Compared with Control, DOX increased CK and CK-MB; while PDOX decreased CK compared with DOX (P < 0.05). Multiple spotty degenerative changes of the myocardium were observed in DOX-treated mice, but not in the Control and PDOX groups. PDOX could significantly reduce the Ki-67 positive rate of tumor cells, compared with DOX and Control groups. PDOX produced the effects at least via the ERK pathway. CONCLUSION: Compared with DOX, PDOX may have better anti-metastatic efficacy and reduced side effects especially cardio-toxicities in this HCC model.

[Hematologic adverse effects in patients with renal cell carcinoma treated with sunitinib].

OBJECTIVE: To explore the hematologic adverse effects in patients with renal cell carcinoma treated with sunitinib. METHODS: A total of 136 patients with advanced renal cell carcinoma were treated with sunitinib at our hospital from 2008 to 2011. There were 91 males and 45 females with an average age of 55.5 years. They received sunitinib in repeated 6-week cycles consisting of 4 weeks of sunitinib 50 mg per day followed by 2 weeks of treatment (schedule 4/2). The hematologic toxicities, collected at baseline and 14, 28, 42 (after a 2-week rest period) days, were graded according to the National Cancer Institute common terminology criteria for adverse events version 3.0. The paired Wilcoxon test was used to evaluate the kinetics of hematologic adverse effects at days 14, 28, and 42 post-treatment. RESULTS: The hematologic toxicities included leukopenia (n = 91, 66.9%), neutropenia (n = 95, 69.8%), lymphopenia (n = 58, 46.2%), thrombopenia (n = 89, 65.4%) and hypohemoglobinemia (n = 48, 35.3%). Among them, 31 cases (22.8%) had the high-grade (including grades 3 and 4) toxicity of thrombopenia. There were depressions in hematopoietic cell populations including leukocytes, neutrophils, and platelets at days 14, 28 and 42 versus the baseline level (all P < 0.05). The median hemoglobin level transiently increased at days 14 and 28 (both P < 0.01) and returned to the level of baseline at days 42 (P = 0.754). CONCLUSIONS: The incidence of hematologic adverse effects of sunitinib slightly varies with what have been observed in previous studies. And the incidence of high-grade toxicity of thrombocytopenia is higher than that reported in studies conducted in the US and Europe.

Anticancer effects of Ac­Phe­Lys­PABC­doxorubicin via mitochondria­centered apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway in MGC­803 cells.

Ac­Phe­Lys­PABC­DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. The present study aimed to elucidate the molecular mechanisms of action of PDOX using MGC­803 gastric cancer cells as a model. The cells were treated with both PDOX and DOX, and cytotoxicities, cell cycle analysis, reactive oxygen species (ROS) generation, mitochondrial damage and ERK1/2 signaling pathway alterations were studied. Abundant cathepsin B expression was observed in the MGC­803 cells, and treatment with PDOX and DOX triggered dose­dependent cytotoxicity and resulted in a significant reduction in cell viability. IC50 of PDOX and DOX was 14.9 and 4.9 µM, respectively. Both PDOX and DOX significantly decreased p­ERK1/2, increased ROS generation, reduced mitochondrial membrane potential, caused mitochondrial swelling and arrested the cell cycle at the G2/S phase, and these effects were more pronounced for PDOX than for DOX. PDOX and DOX have different mechanisms of action, particularly the mitochondria­centered intrinsic apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway.

Primary yolk sac tumor of seminal vesicle: a case report and literature review.

BACKGROUND: Yolk sac tumor (endodermal sinus tumor) is a rare malignant germ cell tumor arising in the testis or ovary. Extragonadal yolk sac tumor is even rarer and has only been described in case reports. Due to the rarity of the tumors, the appropriately optimal treatment remains unclear. We report a case of yolk sac tumor in the seminal vesicle. CASE: A 38-year-old Asian male presented with gross hematuria and hemospermia. Transrectal ultrasound scan showed a solid mass in the left seminal vesicle and the scrotal sonography showed no abnormalities. Bilateral seminal vesicles were resected, and histopathological examination showed a typical pattern of yolk sac tumor (YST). The patient responded poorly to comprehensive treatment of radiotherapy, chemotherapy and surgeries, developed systemic multiple metastases, and died of cachexia one and half years after diagnosis.