Research Advances in Bacteria-based Microrobot.

The concept of bacteria-based microrobot has been well recognized. It has shown great advantages and potentials for the early diagnosis and early treatment of malignant tumor and in reducing chemotherapy toxicities. In this article we review the concept,structure,and potential clinical applications of bacteria-based microrobot.

Curcumin inhibits lung cancer progression and metastasis through induction of FOXO1.

Recent population studies provide clues that the use of curcumin may be associated with reduced incidence and improved prognosis of certain cancers. In the present study, we demonstrated that curcumin acted as a growth inhibitor for lung cancer cells. Our results found that curcumin inhibited cell proliferation, which was associated with upregulation of the cyclin-dependent kinase inhibitors, p27 and p21, and downregulation of cyclin D1. In addition, we showed that curcumin induced the expression of forkhead box protein O1 (FOXO1) through activation of extracellular signal-regulated kinase 1/2 signaling. These findings provide evidence for a mechanism that may contribute to the antineoplastic effects of curcumin and justify further work to explore potential roles for activators of FOXO1 in the prevention and treatment of lung cancer.

Increased expression of programmed death (PD)-1 and its ligand PD-L1 correlates with impaired cell-mediated immunity in high-risk human papillomavirus-related cervical intraepithelial neoplasia.

Impaired local cellular immunity contributes to the pathogenesis of persistent high-risk human papillomavirus (HR-HPV) infection and related cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms remain unclear. Recently, the programmed death 1/programmed death 1 ligand (PD-1/PD-L1; CD279/CD274) pathway was demonstrated to play a critical role in attenuating T-cell responses and promoting T-cell tolerance during chronic viral infections. In this study, we examined the expression of PD-1 and PD-L1 on cervical T cells and dendritic cells (DCs), respectively, from 40 women who were HR-HPV-negative (-) or HR-HPV-positive (+) with CIN grades 0, I and II-III. We also measured interferon-γ, interleukin-12 (IL-12) and IL-10 in cervical exudates. The most common HPV type was HPV 16, followed by HPV 18, 33, 51 and 58. PD-1 and PD-L1 expression on cervical T cells and DCs, respectively, was associated with HR-HPV positivity and increased in parallel with increasing CIN grade. The opposite pattern was observed for CD80 and CD86 expression on DCs, which decreased in HR-HPV+ patients in parallel with increasing CIN grade. Similarly, reduced levels of the T helper type 1 cytokines interferon-γ and IL-12 and increased levels of the T helper type 2 cytokine IL-10 in cervical exudates correlated with HR-HPV positivity and CIN grade. Our results suggest that up-regulation of the inhibitory PD-1/PD-L1 pathway may negatively regulate cervical cell-mediated immunity to HPV and contribute to the progression of HR-HPV-related CIN. These results may aid in the development of PD-1/PD-L1 pathway-based strategies for immunotherapy of HR-HPV-related CIN.

N-acetylcysteine administration is associated with reduced activation of NF-kB and preserves lung dendritic cells function in a zymosan-induced generalized inflammation model.

PURPOSE: In severe sepsis, functional impairment and decreased numbers of dendritic cells (DCs) are essential reasons for immune function paralysis, secondary organ infection, and organ failure. We investigated the effects of N-acetylcysteine (NAC) administration on protecting lung DCs function in a zymosan-induced generalized inflammation (ZIGI) model. METHODS: ZIGI was initiated in 80 Balb/c mice by intraperitoneal injection of zymosan (ZYM; 900 mg/kg). Mice were divided into 4 groups: (1) SHAM+Vehicle; (2) SHAM+NAC; (3) ZYM+Vehicle; and (4) ZYM+NAC. NAC (100 mg/kg) was administered at different time after ZYM injection. After 48 h, we assessed: lung tissue pathological changes; arterial blood gas values; purified lung DCs surface expressions of MHC-II/I-A(d) and co-stimulatory molecules CD80, CD83, and CD86; lung DCs mRNA levels of chemokine receptors CCR5 and CCR7; lung DCs apoptosis; lung DCs ultrastructure by transmission electron microscopy; lung DCs NF-kB transcription factor activity; and LPS-stimulated lung DCs in vitro production of IL-12 and IL-10 were examined. RESULTS: NAC treatment resulted in: significant improvements in ZYM-induced lung tissue damage and impaired lung function; inhibited lung DCs ZYM-induced increased expression of MHC-II/I-A(d), CD83, and CD86, but not CD80; reduced lung DCs ZYM-induced CCR5 and CCR7 mRNA levels; suppressed ZYM-induced lung DCs apoptosis; ameliorated ZYM-induced lung DCs ultrastructural abnormalities; inhibited ZYM-induced lung DCs NF-κB activity; and enhanced lung DCs production of IL-12 and inhibited their production of IL-10. CONCLUSIONS: Repeated injections of NAC during the early stage of severe sepsis effectively inhibited lung DCs activation and their apoptosis, which could preserve DCs function.

Human umbilical cord mesenchymal stromal cells mitigate chemotherapy-associated tissue injury in a pre-clinical mouse model.

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have been shown to be a promising candidate for tissue regeneration and cancer therapy. However, their therapeutic potential against chemotherapy-induced side-effects remains unclear. METHODS: We treated murine Lewis lung carcinoma (LLC) and xenograft human colon tumors with adriamycin (ADM) for 3 consecutive days followed by one intravenous (i.v.) injection of human umbilical cord (hUC) MSC for several cycles. RESULTS: MSC treatment mitigated ADM-induced cardiomyopathy, reduced the extent of ADM-induced apoptosis in intestinal crypts, suppressed body weight loss in mice treated with ADM and increased the survival rate of mice treated with a lethal dose of ADM. The examination of hematologic parameters indicated a moderate recovery in MSC-injected mice. Systemic administration of MSC did not increase the growth of murine LLC cells and human colon carcinoma in vivo while it strongly inhibited the lung metastases of LLC cells. CONCLUSIONS: We evaluated the prophylactic and therapeutic action of hUC MSC on the chemotherapy agent ADM-induced side-effects in two different tumor models. Our observations suggest that MSC can be used as auxiliary means in chemotherapy for certain tumor types.

Epidermal growth factor receptor expression in acute myelogenous leukaemia is associated with clinical prognosis.

The epidermal growth factor receptor (EGFR) family belongs to type I receptor tyrosine kinases. Overexpression or mutation of EGFR/ErbB1 gene has been detected in a large number of human solid tumours. According to some previous report, this gene is not expressed in hematological malignancies. However, two recent clinical case reports showed that erlotinib caused complete remission of acute myeloid leukaemia (AML)-M1 in patients who had both AML-M1 and non-small-cell lung cancer. These results are supported by preclinical studies in which EGFR tyrosine kinase inhibitors have anti-proliferative effects on AML. These findings prompted us to determine whether EGFR is expressed in human AML, through a large-scale screening of both leukaemic cell lines and clinical samples. Our results show that EGFR is expressed by about 33% of human AML (containing M1 to M7 subtypes) and by some human leukaemia cell lines (K562, MEG-01, CEM and SKO-007). Its expression is not limited to certain AML types but has been detected in many leukaemic cells. In addition, EGFR expression was intimately associated with the poor clinical outcomes. Finally, we find that only EGFR-positive leukaemic cells respond to antibody-dependent cellular cytotoxicity of cetuximab, the monoclonal antibodies against EGFR.

Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.

ETV6 is an important hematopoietic regulatory factor and ETV6 gene rearrangement is involved in a wide variety of hematological malignancies. In this study, we sought to investigate the incidence of ETV6-associated fusion genes in B- and T-lineage acute lymphoblastic leukemia (ALL) by multiplex-nested reverse transcription-polymerase chain reaction (RT-PCR) in 176 adult ALL patients. Total RNA was extracted from bone marrow samples of ALL patients including 136 B- and 40 T-lineage ALL, and ETV6 fusion genes were detected by multiplex-nested RT-PCR. Changes of ETV6 fusion gene mRNA transcript levels were examined by real-time RT-PCR. We detected a total of 15 ETV6 gene rearrangements with a positive rate of 8.5%, involving seven ETV6-associated fusion genes in 13 B-ALL (13/136, 9.6%) and 2 T-ALL patients (2/40, 5.0%). ETV6-RUNX1 were observed in six cases (3.4%), ETV6-JAK2 in three cases (1.7%), ETV6-ABL1 in two cases (1.1%), and ETV6-ABL2, ETV6-NCOA2, ETV6-SYK, and PAX5-ETV6 each in one case (0.6%). ETV6-JAK2 was found in both B-ALL and T-ALL patients. Furthermore, real-time quantitative RT-PCR assays showed that the ETV6-RUNX1 mRNA transcript levels decreased during conventional chemotherapy or hematopoietic stem cell transplantation. This study shows that multiplex-nested RT-PCR is an effective and accurate tool to identify ETV6 rearrangements in adult ALL, which provides some clues into the diagnosis and prognosis of ALL but also molecular markers for the detection of minimal residual disease in adult ALL.

[Advanced dermatofibrosarcoma protuberans treated with imatinib mesylate].

OBJECTIVE: To evaluate the efficacy, side effects and toxicity of imatinib mesylate in the treatment of patients with locally advanced and/or metastatic dermatofibrosarcoma protuberans (DFSP). METHODS: Twenty-four cases of advanced DFSP diagnosed by pathology and treated in our hospital from Nov. 2004 to Oct. 2009 were included in this study. The patients were treated with imatinib mesylate (dosage: 400 mg, po, qd) and carefully observed for treatment efficacy, side effects and survival time. There were 2 patients taking the drug as second line therapy, and other 22 patients as third or more than third line therapy. RESULTS: The 24 patients were evaluable for the efficacy. There were 8 patients (33.3%) with CR, 10 pts (41.7%) PR, 2 patients (8.3%) SD, and 4 patients (16.7%) PD. The disease control rate (DCR = CR+PR+SD) was 83.3%. The median response time in 18 cases with CR and PR was 5.6 months. The median survival time in 20 cases with disease control was 30 months, however, that in nonresponse (PD) cases was only 10 months. Side reactions related to imatinib mesylate included nausea and vomiting (20.8%), neutropenia (12.5%), and edema (8.3%). CONCLUSIONS: Our results are consistent with previous reports in the literature. Imatinib is a safe and effective moleucular target drug used for Chinese. Only mild adverse reactions occur in the treated patients. It is worth using imatinib in the treatment of advanced DFSP patients.

Clinical features and prognostic factors in 190 cancer patients with brain metastases.

BACKGROUND: Brain metastases significantly reduce the survival of cancer patients. However, detailed researches on the clinical manifestations and prognoses of patients with brain metastases are lacking. The aim of this study was to investigate the clinical features and prognostic factors of cancer patients with brain metastases. METHODS: A retrospective study was conducted on patients with brain metastases who were treated in our hospital between January 2014 and January 2019. Comparison of overall survival (OS) was performed by the Kaplan-Meier method. Multivariate Cox regression models was used to identify prognostic factors for OS. RESULTS: A total of 190 patients with complete data and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 were enrolled. Patients with brain metastases from different primary sites had significantly different survival time (P=0.001). Patients who had a longer survival time included female patients (47.4%) (34 vs. 19 months, P=0.002), those with age <65 years (63.7%) (29 vs. 18 months, P=0.002), with ECOG 0 or 1 (44.2%) (32 vs. 21 months, P=0.005), with ≤3 brain lesions (61.1%) (29 vs. 20 months, P=0.041), and with small molecular targeted therapy (48.4%) (21 vs. 18 months, P=0.006). Furthermore, multivariate analysis revealed that female, age <65 years, ≤3 brain lesions, small molecular targeted therapy were independent favorable prognostic factors of OS. CONCLUSIONS: Female, younger patients with ≤3 brain metastases predicted a better survival. To improve the poor outcomes of these patients, it is necessary to find clinically significant genetic abnormalities and administer the small molecular targeted therapy early in the course of treatment.

[Effect of Fluorouracil-inducible GM-CSF gene therapy regulated by Egr-1 promoter on chemotherapeutic hematopoietic damage of tumor-bearing mice].

OBJECTIVE: In order to explore the regulating effects of Egr-1 promoter sequences in transcriptional targeting by 5-fluorouracil (5-Fu) on the expression of hematopoietic growth factor genes. METHODS: The human GM-CSF cDNA and enhanced green fluorescent protein (EGFP) cDNA were linked together with IRES and then inserted into the expression vector pCIneo under control of the Egr-1 promoter (Egr-EG). The vector was transferred into human bone marrow stromal cell line HFCL by lipofectin(TM). The transfected cell clones (HFCL/EG) have been selected by the addition of G418. The cells are exposed to the clinically important anticancer agent 5-fluorouracil. The activity of EGFP in HFCL/EG cells was detected by flow cytometry. The post-chemotherapeutical expression of GM-CSF in HFCL/EG was confirmed with ELISA and Western blot and RT-PCR respectively. The effect of N-acetylcysteine (a free radical scavenger) on GM-CSF production post-exposure to 5-Fu was examined. The HFCL/EG cells were transplanted intravenously into B16 melanoma in C. B-17 combined immunodeficient (SCID) mice. 5-Fu was given i.p. at Day 3. The white blood cell number in peripheral blood, the expression of EGFP and GM-CSF and in human stromal cell engrafted in recipient mice were detected by flow cytometry and RT-PCR respectively. Tumor volume in tumor-bearing mice was calculated. RESULTS: The results indicated that the activity of EGFP and the amounts of secreted GM-CSF in HFCL/EG cells exposed to 5-Fu increased as compared to non-5-Fu group with flow cytometry, RT-PCR and ELISA respectively. N-acetylcysteine significantly decreased the concentration of GM-CSF in HFCL/EG cells treated with 5-FU. In contrast to two control groups, HFCL/EG (Egr-1 regulatory element-derived expression of GM-CSF gene therapy) resulted in a proportionally obvious increase in the number of white blood cell after chemotherapy and no significant difference was found for tumor inhibition in recipient mice. CONCLUSIONS: These in vitro data provide an experimental basis for use of gene therapy of hematopoietic growth factor gene regulated by Egr-1 promoter to protect hematopoiesis from 5-Fu-injury effects.

The role of miR-92b in cholangiocarcinoma patients.

PURPOSE: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. METHODS: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan-Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. RESULTS: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.

Clinical outcome of 30 patients with bone marrow metastases.

OBJECTIVE: Cancer patients with bone marrow metastases are rare and dismal. The study was to identify the clinical features and prognostic factors in cancer patients with bone marrow metastases. PATIENTS AND METHODS: A total of 30 patients with bone marrow metastases were reviewed between September 2007 and September 2013. Bone marrow metastases were identified by bone marrow aspiration. RESULTS: The median age was 56.5 years (range, 8-85 years). The two most common primary tumor sites were the stomach (7, 23.3%), breast (5, 16.7%). Bone metastases (27, 90.0%) were the most common concurrent metastases. The most common cause for bone marrow aspiration was anemia and thrombocytopenia (10, 33.3%). The median survival time was 3 months (range, 0.5-82 months). Patients with good performance status (n = 19) had a longer median survival time than patients with poor performance status (n = 11) (8 months vs. 1 months, P = 0.041). Patients with primary unknown origin (n = 5) had a significantly shorter overall survival time than patients with known origin (n = 25) (1 month vs. 6 months = 0.010). The median survival time was 9 months in the systemic therapy group (n = 21) and 1 month in the best supportive care group (n = 9) (P = 0.000). CONCLUSION: To make primary origin clear and start systemic antitumor therapy is beneficial for patients with bone marrow metastases.

[Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients. METHODS: Clinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/m2 per day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated. RESULTS: Among 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 109/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%). CONCLUSION: Decitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.

[HER-2 and ER expression in prediction of chemo-sensitivity of taxane for advanced breast cancer].

OBJECTIVE: To investigate the predictive value of HER-2 and ER expression for chemosensitivity of taxane in the treatment of advanced breast cancer. METHODS: Of 268 advanced breast cancer patients treated: 71 were by paclitaxel alone, 32 by docetaxel alone, 110 by paclitaxel combined with anthracylines or gemcitabine or platins and 55 by docetaxel-based combinations. HER-2 and ER expression of all patients treated by taxane underwent immunohistochemical (IHC) assay. RESULTS: Univariate analysis showed: the response rate (RR) in HER-2 overexpression group was 56.7%, and in HER-2 weak expression group 33.3% (P = 0.003). The response rate in ER positive group and ER negative group was 33.3% and 48.9%, respectively, with a significant difference (P = 0.015). The RR was 67.6% in ER negative but HER-2 overexpression group. However, in ER positive but HER-2 weak expression group and the other groups, the RR were around 35% (P < 0. 01). Multivariate analysis showed that overexpression of HER-2 was the only significant factor to predict the chemosensitivity of taxane (P = 0. 007), but the ER, Karnofsky performance score (KPS), anthracylines, metastatic sites were not the statistically significant chemo-sensitivity predictive factors for taxane. CONCLUSION: ER negative and/or HER-2 overexpression, especially latter, may be associated with good response in advanced breast cancers treated by taxane.

[Inhibitory effect of antisense oligodeoxynucleotides targeting HER-2 mRNA on growth of breast cancer: experiment in vivo with mice].

OBJECTIVE: To investigate the inhibitory effect of antisense oligodeoxynucleotides targeting HER-2 mRNA on growth of breast cancer. METHODS: Human breast cancer cells of the line SK-BR-3 that overexpresses HER-2 were injected subcutaneously into BALB/c nude mice. Seven to ten days after tumors were collected and made into homogenate. Antisense oligodeoxynucleotide HA6722 targeting HER-2 mRNA and its control sequence Scramble were synthesized. Forty-nine BALB/c nude mice were injected with homogenate of SK-BR-3 cells and then randomly divided into 7 equal groups: Group 1, injected intravenously with docetaxel (TXT) 7.5 mg.kg(-1).d(-1) once a week twice; Group 2, injected intravenously with TXT 15 mg.kg(-1).d(-1) once a week twice; Group 3, injected intravenously with TXT 7.5 mg.kg(-1).d(-1) once a week twice + HA6722 5 mg.kg(-1).d(-1) for 12 days; Group 4, injected intravenously with HA6722 5 mg.kg(-1).d(-1) for 12 days; Group 5, injected intravenously with TXT 7.5 mg.kg(-1).d(-1) once a week twice + Scramble6722 5 mg.kg(-1).d(-1) for 12 days; and Group 7, injected with normal saline. After the drug administration the mice were observed for additional 3-4 weeks to measure the size of tumor every other day. Then the mice were killed and the tumors were taken out to be examined. The inhibition rate was calculated. RESULTS: The inhibition rate of tumor in Group 3 was 88.3%, not significantly different from that in Group 2 (88.7%, P > 0.05). The inhibition rate in Group 4 was 76.3%. The inhibition rates of tumor of Groups 2, 3, and 4 were all significantly higher than that in Group 7. However, the inhibition rate of tumor of Group 6 was not significantly different from that in Group 7. CONCLUSION: Antisense oligodeoxynucleotides targeting HER-2 mRNA inhibits the growth of breast cancer in a sequence specific and dose-dependent manner.

[Relation of dose intensity and efficacy, toxicity in paclitaxel as a single agent for advanced breast cancer].

OBJECTIVE: To evaluate the relation of dose intensity and efficacy, toxicity in advanced breast cancer treated with paclitaxel as a single agent. METHODS: Seventy-one patients with advanced breast cancer received paclitaxel as a single agent with different dose intensities. According to the phase I or phase II trial, the standard dose intensity of paclitaxel was defined as 58.3 mg.(m(2))(-1).week(-1). The dose of paclitaxel was 175 mg/m(2) given every three weeks, ranging 33.3 - 70.3 mg.(m(2))(-1).week(-1) [median delivered dose intensity 58.82 mg.(m(2))(-1).week(-1)]. Efficacy and toxicity was evaluated. RESULTS: The overall response rate in this group of advanced breast cancer was 40.8%. Responses were seen in lungs, soft tissue, bone and liver, with the response rates of 52.0%, 38.0%, 12.5%, 7.7%, respectively. When the relative dose intensity (RDI) was > 1.0, 0.9 - 1.0, < 0.9, the response rates were 44.2%, 47.6%, 0, respectively. The difference between the group (RDI >/= 0.9% - 1.0%) in 7 patients and the group (RDI < 0.9) was significant (P < 0.05). Toxicity was well tolerated, with the efficacy decreased as soon as the RDI had been reduced without embarrassing the toxicity. CONCLUSION: Paclitaxel as a single agent therapy with standard dose intensity is effective and well tolerated by patients with advanced breast cancer.

Attenuated Salmonella typhimurium carrying the hepatocyte growth factor and keratinocyte growth factor genes repairs gastrointestinal mucosal damage caused by chemotherapy.

Radiotherapy and chemotherapy are the main therapeutic approaches for patients with malignant tumours, especially advanced tumours. However, they can cause adverse effects, one of which is gastrointestinal mucosal damage, which can greatly affect patients' quality of life. Until now, there have been no effective therapies to avoid or treat these adverse effects. In this study, we used attenuated Salmonella typhimurium (S. typhimurium) to deliver the hepatocyte growth factor (HGF) or keratinocyte growth factor (KGF) to murine gastrointestinal mucosa. We found that attenuated S. typhimurium carrying the HGF or KGF genes can effectively reduce the ratio of tumour to non-tumour carcass weight, repair damage to the gastrointestinal mucosal from chemotherapy, improve the immune response, and reduce the mortality rate of mice. Oral administration of attenuated S. typhimurium with HGF and KGF may be promising as a way of improving the quality of life of patients undergoing radiotherapy and chemotherapy.

Demethylation of cancer/testis antigens and CpG ODN stimulation enhance dendritic cell and cytotoxic T lymphocyte function in a mouse mammary model.

BACKGROUND: Cancer/testis antigens (CTAs) are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG) methylation in their promoter regions, so that tumor cells have low immunogenicity. METHODS: We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs) by immunizing BALB/c (H-2(d)) mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN) immune adjuvant. RESULTS: We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells both in vitro and in vivo. CONCLUSIONS: Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.

Detection and clinical significance of gene rearrangements in Chinese patients with adult acute lymphoblastic leukemia.

This study aimed to develop a novel multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) assay to accurately and effectively detect 10 common gene rearrangements in adult acute lymphoblastic leukemia (ALL) and to examine the clinicopathologic characteristics and other genetic aberrations of patients with ALL expressing different fusion genes. Our RT-nPCR assay had a positive detection rate of 35.15% (90/256) for the 10 fusion genes. BCR-ABL1, FUS-ERG, MLL-AF4, ETV6-RUNX1, E2A-PBX1, dupMLL, MLL-AF10, MLL-ENL, SET-NUP214 and SIL-TAL1 were detected in 36 (14.06%), 14 (5.47%), 14 (5.47%), four (1.56%), four (1.56%), five (1.95%), four (1.56%), two (0.78%), two (0.78%) and five patients (1.95%), respectively. The RT-nPCR results were further confirmed by split-out PCR, and cytogenetic and fluorescence in situ hybridization (FISH) analysis revealed corresponding translocations and fusions in 63 and 74 cases, respectively. JAK2 and IKZF1 mutations were commonly detected in patients with BCR-ABL1 ALL, and HOX overexpression was highly correlated with MLL fusions and SET-NUP214. This study demonstrates that RT-nPCR is an effective method for identifying 10 gene rearrangements in adult ALL, and it could potentially be developed for diagnostic use and prognostic studies of ALL.

Massive hemoptysis and hemothorax: a rare but fatal complication of intralobar sequestration.

Intralobar sequestration (ILS) is an uncommon abnormality that accounts for 75% of all pulmonary sequestrations. Over the years there have been several reports of various presenting signs of which hemoptysis was commonly described, however, massive hemoptysis and hemothorax is extremely rare in literature. We present a case of a 45-year-old man who died of fatal complication from an ILS. This case report shows an uncommon presentation of ILS with massive hemoptysis and hemothorax resulting in a dramatic course of disease and a fatal outcome, and for this reason in the absence of trauma or other causes for massive hemoptysis, hemothorax, or lung hematoma, this possibility should be kept in mind so as to avoid misdiagnosis, and resection of the sequestered tissue should be considered in all patients.