Therapy of established tumor with a novel tumor vaccine developed by fusion of tumor cells with GM-CSF genetically modified dendritic cells

Dendritic cells (DC) play a critical role in theinduction of immune responses, and are utilized as potentadjuvants in cancer immunotherapy. Several strategies forloading DC with tumor antigens have been developed.Vaccination with tumor antigen-loaded DC wasdemonstrated to be capable of inducing antitumorimmunity, but some limitations still exist. So it's     

Are epsins a therapeutic target for tumor angiogenesis?

Solid tumor growth requires the formation of new blood vessels to supply nutrients and oxygen to the malignant cells; one approach to cancer therapy is to block this process by inhibiting VEGF signaling. In this issue of the JCI, Pasula et al. demonstrate a surprising role of epsins — proteins involved in endocytosis — in tumor angiogenesis via their modulation of VEGF signaling. Their findings suggest that these proteins might represent a new target for the development of cancer therapeutics. Angiogenesis is the formation of new capillary blood vessels and is a critical component of solid tumor growth (1). Once a new tumor reaches just a few cubic millimeters in size, further growth must be preceded by angiogenesis. Tumor cells secrete soluble factors that stimulate vessel growth and/or suppress factors that prevent angiogenesis. These factors act upon endothelial cells to promote their proliferation and migration, resulting in sprouting and tube formation; those tubes then develop into vessels. Although tumor angiogenesis can be understood as a process required to sustain a cancer’s blood supply, the vascular network induced as a result of tumor angiogenesis is highly aberrant, altering the tumor microenvironment and profoundly influencing the manner in which cancers grow, escape the host’s immune system, and metastasize (2). Unlike the organized microvasculature of normal tissue, tumor microvessels are dilated and tortuous, with disorganized patterns of interconnection and branching (3). The erratic tumor vasculature and the resultant hypoxia have additional consequences for tumors: cancer cells undergo epigenetic changes in hypoxic conditions that accelerate their malignant phenotype and the epithelial-to-mesenchymal transition, producing a greater metastatic potential (2). In addition, the cytotoxic functions of immune cells that infiltrate a tumor are compromised in hypoxic and low pH conditions, further contributing to the malignant phenotype (4).     

Human kallikrein 10: a novel tumor marker for ovarian carcinoma?

BACKGROUND: Human kallikrein 10 (hK10, encoded by KLK10 gene) is a recently discovered member of the human kallikrein family. hK10 is a secreted serine protease. With the development of a highly sensitive and specific immunoassay for hK10, quantification of hK10 in the circulation is now feasible. Our aim was to investigate whether hK10 concentration in serum changes in various malignancies. METHODS: We used a highly specific and sensitive immunofluorometric assay to quantify hK10 protein in 374 serum samples from healthy individuals and patients with various malignancies. RESULTS: Serum hK10 concentration was found to be significantly elevated in 56% of the ovarian cancer patients and such an increase was not observed in serum of healthy individuals or in serum of patients with other types of cancer, with the exception of approximately 15% of patients with gastrointestinal cancer. This hK10 elevation does not correlate well with CA 125. We have further demonstrated that hK10 concentration changes during ovarian cancer progression. CONCLUSION: This is the first report describing that hK10 serum concentration is significantly elevated in the majority of ovarian cancer patients. Our results indicate that hK10 may be a potential new serological marker for ovarian cancer diagnosis and monitoring.     

25 month relief of bone pain due to metastatic multiple tumor of bone following mammary tumor by Boning:a case report

Bonemetastasisofmammarytumoriscommoninclinicandcomprehensivetreatmentconcentratedonchemotherapyissuggested．Short－termreliefsuchaspaindecrease，improvementofsymptomsisavailablebutlong－termreliefwasunavailable．Inthecurrentstudy，acasewithmultiplebonemetastasisofmammarytumorsshowedfavor－ablereliefincludingbonepainrelief，completeabsorptionofbonemetastasisloci．Thispatientshassurvivedfor２５monthshealthful－ly．Hereisthereport．１ClinicaldataFemalepatientaged５９yearsoldunderwentmammarytumor…     

Gastrointestinal stromal tumor (GIST) presenting in a Meckel’s diverticulum

A meckel’s diverticulum is a congenital abnormality of the GI tract seen in approximately 3% of the population. Tumor arising within this entity is a rare, although know complication. We report a gastrointestinal tumor arising within a Meckel’s diverticulum in a 28-year-old male.     

Plasma S100β is not a useful biomarker for tumor burden in neurofibromatosis

ObjectivesNeurofibromatosis 1 (NF1), NF2, and schwannomatosis are characterized by a predisposition to develop multiple neurofibromas and schwannomas. Currently, there is no blood test to estimate tumor burden in patients with these disorders. We explored whether S100β would act as a biomarker of tumor burden in NF since S100β is a classic immunohistochemical marker of astrocytes, oligodendrocytes and Schwann cells and a small study showed S100β concentrations correlate with the volume of vestibular schwannomas.Design and methodsWe calculated whole-body tumor burden in subjects with NF1, NF2, and schwannomatosis using whole-body MRI (WBMRI) and measured the concentration of S100β in plasma using ELISA. We used chi-square tests and Spearman rank correlations to test the relationship between S100β levels and whole-body tumor burden.Results127 consecutive patients were enrolled in the study (69 NF1 patients, 28 NF2 patients, and 30 schwannomatosis patients). The median age was 40 years, 43% were male, and median whole-body tumor volume was 26.9 mL. There was no relationship between the presence of internal tumors and the presence of detectable S100β in blood for the overall group or for individual diagnoses (p > 0.05 by chi-square for all comparisons). Similarly, there was no correlation between whole-body tumor volume and S100β concentration for the overall group or for individual diagnoses (p > 0.05 by Spearman for all comparisons).ConclusionsPlasma S100β is not a useful biomarker for tumor burden in the neurofibromatoses. Further work is needed to identify a reliable biomarker of tumor burden in NF patients.     

Alimentotherapy in tumor patients

This article explained the importance of alimentotherapy in tumor patients in 6aspects i.e.aim of ,chlassification,principle,pathway,daily utrition support of alimentotherapy,and treatment of comon symptoms.     

Fas/FasL expression in tumor biopsies: a prognostic response factor to fluoropyrimidines?*

Various studies suggested that cytotoxicity induced by 5-fluorouracil (5-FU) is an apoptotic mechanism possibly mediated by the Fas/FasL system. In this preliminary work, we studied retrospectively the role the Fas/FasL expression as a predictive response factor with fluoropyrimidine-based chemotherapies. We developed a real-time PCR method for measuring Fas and FasL expression in various biopsies from patients treated with a FUFOL-like protocol. No correlation was found between Fas or FasL expression and overall survival or partial response. However, the PCR assay was simple and convenient to use for quantitation of Fas/FasL in tumor biopsies.     

Pediatric patients with a malignant bone tumor: when does functional assessment make sense?

Purpose  

The diagnosis of a malignant bone tumor in the lower limb is a risk factor for physical disability, limiting physical performance. Walking ability especially, which is essential for most activities of daily living, is limited in those patients. In the present study, the extent of limitations during the course of treatment was investigated to determine when the assessment of functional parameters is meaningful in those patients.     

Mouse and human iNKT cell agonist β-mannosylceramide reveals a distinct mechanism of tumor immunity

Type 1 or invariant NKT (iNKT) cell agonists, epitomized by α-galactosylceramide, protect against cancer largely by IFN-γ-dependent mechanisms. Here we describe what we believe to be a novel IFN-γ-independent mechanism induced by β-mannosylceramide, which also defines a potentially new class of iNKT cell agonist, with an unusual β-linked sugar. Like α-galactosylceramide, β-mannosylceramide directly activates iNKT cells from both mice and humans. In contrast to α-galactosylceramide, protection by β-mannosylceramide was completely dependent on NOS and TNF-α, neither of which was required to achieve protection with α-galactosylceramide. Moreover, at doses too low for either alone to protect, β-mannosylceramide synergized with α-galactosylceramide to protect mice against tumors. These results suggest that treatment with β-mannosylceramide provides a distinct mechanism of tumor protection that may allow efficacy where other agonists have failed. Furthermore, the ability of β-mannosylceramide to synergize with α-galactosylceramide suggests treatment with this class of iNKT agonist may provide protection against tumors in humans.     

Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-β–like signaling pathway

The four-and-a-half LIM (FHL) proteins belong to a family of LIM-only proteins that regulate cell proliferation, differentiation, and apoptosis. The exact functions of each FHL protein in cancer development and progression remain unknown. Here we report that FHL1, FHL2, and FHL3 physically and functionally interact with Smad2, Smad3, and Smad4, important regulators of cancer development and progression, in a TGF-β–independent manner. Casein kinase 1δ, but not the TGF-β receptor, was required for the FHL-mediated TGF-β–like responses, including increased phosphorylation of Smad2/3, interaction of Smad2/3 and Smad4, nuclear accumulation of Smad proteins, activation of the tumor suppressor gene p21, and repression of the oncogene c-myc. FHL1–3 inhibited anchorage-dependent and -independent growth of a human hepatoma cell line in vitro and tumor formation in nude mice. Further analysis of clinical samples revealed that FHL proteins are often downregulated in hepatocellular carcinomas and that this correlates with decreased TGF-β–like responses. By establishing a link between FHL proteins and Smad proteins, this study identifies what we believe to be a novel TGF-β–like signaling pathway and indicates that FHL proteins may be useful molecular targets for cancer therapy.     

Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter

The nuclear factor-κB (NF-κB) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. We have cloned a novel NF-κB-based reporter system (five tandem repeats of NF-κB responsive genomic element (NF; 14?bp each)) to drive the expression cassette for both a fusion between the yeast cytosine deaminase and uracil phosphoribosyltransferase (CU) as a therapeutic gene and the secreted Gaussia luciferase (Gluc) as a blood reporter, separated by an internal ribosomal entry site (NF-CU-IGluc). We showed that malignant tumor cells have high expression of Gluc, which correlates to high activation of NF-κB. When NF-κB was further activated by tumor necrosis factor-α in these cells, we observed up to 10-fold increase in Gluc levels and therefore transgene expression in human glioma cells served to greatly enhance the sensitization of these cells to the prodrug, 5-fluorocytosine both in cultured cells and in vivo subcutaneous tumor xenograft model. This inducible system provides a tool to enhance the expression of imaging and therapeutic genes for cancer therapy.