The use of dendritic cells (DC) to prime tumor-associated antigen-specific T-cell responses provides a promising approach to cancer immunotherapy. Embryonic stem cells (ESC) and induced pluripotent ...stem cells (iPSC) can differentiate into functional DCs, thus providing an unlimited source of DCs. However, the previously established methods of generating practical volumes of DCs from pluripotent stem cells (PSC) require a large number of PSCs at the start of the differentiation culture. In this study, we generated mouse proliferating myeloid cells (pMC) as a source of antigen-presenting cells (APC) using lentivirus-mediated transduction of the c-Myc gene into mouse PSC-derived myeloid cells. The pMCs could propagate almost indefinitely in a cytokine-dependent manner, while retaining their potential to differentiate into functional APCs. After treatment with IL4 plus GM-CSF, the pMCs showed impaired proliferation and differentiated into immature DC-like cells (pMC-DC) expressing low levels of major histocompatibility complex (MHC)-I, MHC-II, CD40, CD80, and CD86. In addition, exposure to maturation stimuli induced the production of TNFα and IL12p70, and enhanced the expression of MHC-II, CD40, and CD86, which is thus suggestive of typical DC maturation. Similar to bone marrow-derived DCs, they stimulated a primary mixed lymphocyte reaction. Furthermore, the in vivo transfer of pMC-DCs pulsed with H-2K(b)-restricted OVA257-264 peptide primed OVA-specific cytotoxic T cells and elicited protection in mice against challenge with OVA-expressing melanoma. Overall, myeloid cells exhibiting cytokine-dependent proliferation and DC-like differentiation may be used to address issues associated with the preparation of DCs.
Background The clinical significance of isolated tumor cells (ITC) detected immunohistochemically in the lymph nodes of gastric cancer patients is controversial. The aim of this study was to examine ...the prognostic impact of ITC in patients with gastric cancer. Methods The data of a total of 402 patients with pathological T2N0 and T2N1 gastric cancer who underwent gastrectomy with D2 lymph node dissection between 1984 and 1990 at four participant hospitals were analyzed. All resected lymph nodes were reexamined by serial sectioning with hematoxylin & eosin (H&E) staining, and evaluated by immunohistochemistry using antibody against cytokeratin (AE1/3). The prevalence and prognostic significance of ITC were investigated. Results ITC were detected in 187 of the 402 (47%) patients. A multivariate analysis identified the nodal status, histological type, and tumor size as significant factors predictive of the presence/absence of ITC. The 5-year and 10-year overall survival rates of patients with vs those without ITC were 84.4% (95% confidence interval CI, 79.1-89.0) and 70.4% (95% CI, 64.1-76.7) vs 83.9% (95% CI, 78.6-89.2) and 72.0% (95% CI, 65.4-78.5), respectively. The hazard ratio for death in patients with ITC as compared with those without ITC was 0.90 (95% CI, 0.64-1.26; P = 0.53). Conclusions The presence of ITC in the lymph nodes does not affect the prognosis of patients with gastric cancer who have undergone gastrectomy with D2 lymph node dissection.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The present study investigated the possible correlation between 18F-2-fluorodeoxyglucose (18F-FDG)-uptake parameters and clinicopathological parameters in hypopharyngeal squamous cell carcinoma ...(HPSCC). A total of 53 patients, newly diagnosed with HPSCC, received pretreatment 18F-FDG-positron emission tomography/computed tomography (PET/CT). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) were calculated as 18F-FDG-uptake parameters of the primary tumor. Tumor thickness, depth of invasion and pathological tumor volume were pathologically measured. Upon univariate survival analysis, SUVmax ≥28.5, SUVpeak ≥19, MTV ≥12 and TLG ≥42 were significantly associated with a shorter overall survival (OS) time, and MTV ≥12 and TLG ≥42 were significantly associated with a shorter distant metastasis-free survival (DMFS) time. Upon multivariate analysis with adjustment for clinical T category and treatment group, patients with SUVmax ≥28.5 exhibited a significantly shorter OS time, while TLG ≥42 was significantly correlated with shorter OS and DMFS times. Upon simple regression analysis, TLG was found to be significantly associated with tumor thickness and depth of invasion, while MTV was found to be closely associated with pathological tumor volume. In conclusion, pretreatment 18F-FDG-PET/CT is likely to provide valuable prognostic parameters in HPSCC.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We investigated the molecular species of sulfated sialyl Lewis X determinants, the putative L-selectin ligand, expressed on high endothelial venules (HEV) in human lymph nodes. Comparison of the ...reactivity pattern of HEV with the reactivity of the pure 6-sulfo, 6′-sulfo, or 6,6′-bissulfo sialyl Lewis X determinant with hitherto known anti-sialyl Lewis X antibodies strongly suggested 6-sulfo sialyl Lewis X to be the best candidate for the major sulfated sialyl Lewis X determinant on HEV, followed by 6,6′-bissulfo sialyl Lewis X, whereas 6′-sulfo sialyl Lewis X was unlikely. We newly generated monoclonal antibodies (mAbs) G152 and G72 directed against 6-sulfo sialyl Lewis X, which intensely labeled HEV in immunohistochemical examination and inhibited binding of recombinant L-selectin-IgG to HEV, suggesting that the determinant serves as a ligand for L-selectin. To test the concomitant expression of 6,6′-bissulfo sialyl Lewis X, specific mAbs (G2706, G27011, G27037, and G27039) were generated, but all antibodies failed to react to HEV. Next, we established mAbs (AG97 and AG273) directed against 6-sulfo Lewis X, the asialo form of 6-sulfo sialyl Lewis X. The antibodies were not reactive to untreated HEV, but strongly reacted to sialidase-treated HEV. This indicated the predominance of the sialylated form of 6-sulfo sialyl Lewis X and minimal expression of its asialo form, corroborating that it was synthesized by fucosyltransferase VII, the isoenzyme that preferentially produces the sialylated form of the determinant.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bursectomy, which has been performed so as to resect peritoneal deposits disseminated within the omental bursa, is considered as an essential component of radical surgery for gastric carcinoma in ...Japan. Bursectomy has also been described in the Japanese Treatment Guidelines for Gastric Carcinoma as a mandatory procedure for the treatment of serosa-positive cancer. However, no evidence to support the prognostic significance of this procedure has been reported to date.
Cytologic examination and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of the peritoneal washes obtained from the Douglas pouch, left subphrenic cavity, and inside the omental bursa were performed for 136 patients who underwent potentially curative surgery for gastric carcinoma.
Carcinoembryonic antigen (CEA) or cytokeratin (CK) 20 mRNA was detected in one or more samples from the three different sites of peritoneal washes in 43 of the 136 patients. In 14 patients, the mRNAs were detected in samples obtained from the bursa omentalis (10.3% of all patients and 32.6% of patients with positive RT-PCR results). In 12 of these 14 patients, the mRNAs were also detected in samples taken from either or both of the remaining two sites. Only in the 2 other patients was the sample only from inside the omental bursa positive for CEA.
It is unlikely that viable cancer cells disseminated into the bursa remain restricted to this cavity without migrating into the free abdominal cavity. Routine bursectomy may not be an essential procedure for resecting gastric cancer, from the viewpoint of eliminating microscopic peritoneal deposits within the omental bursa.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Peritoneal recurrence has a much lower incidence in colorectal cancer (CRC) patients than gastric cancer (GC) patients. The aim of this study is to clarify the reason for the rare peritoneal ...recurrence in CRC as compared with GC. The incidence and the abundance of free tumor cells in the peritoneal lavages from 102 CRC and 126 GC patients who underwent curative surgery were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) with carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) as genetic markers. Prognostic significance of CEA and CK20 mRNA was also compared between CRC and GC after 2 years of follow-up by Kaplan-Meyer method with overall and peritoneal recurrence-free survival as endpoints. Positivity rate and average values of CEA and CK20 mRNA in peritoneal lavages of CRC patients, which are correlated to the depth of tumor invasion (pT category), were essentially the same as those of GC cases. Overall survival was significantly (marginally) worse in CEA mRNA (CK20 mRNA)-positive CRC patients than negatives like GC. However, peritoneal recurrence-free survival was not different between CEA (CK20) mRNA-positive and -negative CRC patients, in quite contrast to GC cases. Multivariate analysis showed that CEA mRNA was an independent prognostic factor for overall survival in GC patients, but not in CRC patients. These results suggest that the rare peritoneal recurrence in CRC patients is not due to the low incidence or the small number of intraperitoneal free cancer cells, but more likely reflects due to the low-peritoneal metastatic potential of CRC cells.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The pharmaceutical industry has shown a strong interest in flow synthesis and continuous production. In general, solvent selection is performed based on solubility and reactivity/selectivity, but in ...heterogeneous reactions, solvent properties related to mass transfer can affect the reaction performance. This work presents a model-based analysis of the impact of solvent selection in batch and flow syntheses for heterogeneous hydrogenation, e.g., for doripenem, a commercialized antibiotic. Simulations of reaction conversions under different conditions were conducted. First, a sensitivity analysis was performed, where the effects of individual solvent properties (viscosity, density, Henry’s law constant, and concentration) were examined, followed by solvent selection from six existing candidates. The sensitivity analysis results showed that the individual properties had different impacts on reactions in batch and flow syntheses, and thus the optimal solvent choice varied in each case. The results can be useful for solvent design, such as computer-aided molecular design. A guideline for solvent selection was proposed to assist in reducing dedicated experimental burden and allowing for more deliberate and selective solvent selection.
Display omitted
•Model-based analysis of solvent selection on batch and flow syntheses using heterogeneous hydrogenation.•Different impact of individual solvent property on batch and flow syntheses.•Variations in ideal solvents between batch and flow syntheses.•Guideline for better solvent selection when changing from batch to flow synthesis.
Full text
Available for:
GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: L1, a 200-220 kDa transmembrane glycoprotein of the immunoglobulin superfamily, has been shown to affect prognosis
of various types of cancer and was shown to enhance peritoneal ...metastasis in ovarian cancer in vivo. Patients and Methods:
Immunostaining with anti-L1 antibody was performed with 72 surgically resected pT3-stage gastric cancer specimens. Correlation
of immunoreactivity with clinicopathological variables was evaluated and survival curves were compared between L1-positive
and negative cases. Results: L1 was detected in 15 specimens (21%), more often among the intestinal-type cancer. No correlation
was observed between L1 expression and presence of free cancer cells in the peritoneal cavity or development of peritoneal
carcinomatosis during the follow-up. Nevertheless, prognosis of patients with L1-positive cancer was significantly inferior
(p=0.024), particularly among the diffuse-type cancer cases. Conclusion: L1 was associated with poor outcome in gastric carcinoma.
However, its association with the formation of peritoneal metastases or the presence of free cancer cells in the abdominal
cavity was not observed. Further study to identify the role of L1 in gastric cancer progression and metastasis is warranted.
The presence of gastric cancer cells in the peritoneal cavity detected by cytologic examination is an important prognostic factor. A reverse transcriptase-polymerase chain reaction (RT-PCR) technique ...amplifying carcinoembryonic antigen mRNA was recently introduced to detect these cells more sensitively.
Five-year followup was completed for 284 gastric carcinoma patients who underwent CEA RT-PCR testing. Analyses to assess the accuracy and prognostic value of this procedure were performed, along with univariate and multivariable analyses to evaluate RT-PCR as a technique with peritoneal carcinomatosis and cancer death as the outcomes variables.
CEA mRNA levels exceeded the cutoff value defining a positive result in 9.5%, 29%, 66%, and 81% of patients with pT1, pT2, pT3, and pT4 stage disease, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for peritoneal carcinomatosis within 5 years of surgery were 88.5%, 81.6%, 64.5%, and 94.9%, respectively. Multivariable analysis revealed that a positive CEA mRNA result was an independent risk factor for cancer death (hazard ratio 2.82, 95% CI 1.17 –3.07) among 274 patients (10 patients with no record of nodal status were excluded from the analysis) and for peritoneal carcinomatosis (hazard ratio 1.57, 95% CI 1.07–2.29) among 242 patients who had no peritoneal deposits at operation.
CEA RT-PCR is useful as a prognostic marker for increased risk of cancer death and peritoneal carcinomatosis, and might be useful in the clinical setting for selecting patients for various adjuvant treatments.
Full text
Available for:
GEOZS, NUK, OILJ, SBCE, SBJE, UL, UPUK
Head and neck squamous cell carcinoma (HNSCC) may be curable with surgery, radiation and chemotherapy in its early stages. However, recurrence and metastasis often prevail following primary treatment ...in advanced stage cases and are associated with significant morbidity and mortality. In this study we investigated the combination therapy of gemcitabine and cetuximab for HNSCC. The UM-SCC-6 and UM-SCC-23 HNSCC cell lines were analyzed following treatment with gemcitabine and cetuximab. To determine the mechanism of action of this combination treatment, the cell cycle distributions following gemcitabine and/or cetuximab treatment were analyzed by flow cytometry and apoptosis assay. Gemcitabine and cetuximab combination treatment exerted an enhanced cytotoxic effect. The cell cycle analysis demonstrated that cells accumulated in the S phase following gemcitabine treatment and G1 arrest occurred following cetuximab treatment. An increase in sub-G1 phase cells was also observed following treatment with the two drugs. In an apoptosis assay, caspase 3/7 activity was found to be higher when administering a combination of gemcitabine and cetuximab compared to each agent administered alone. Gemcitabine and cetuximab are individually effective against HNSCC and an enhanced growth inhibitory effect may be expected when these agents are used in combination.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
