Effects of intratumoral injection therapy of dendritic cells combined with hyperthermia for cancer patients

We proceeded with intratumoral injection therapy of dendritic cells (DC) in combination with hyperthermia for 41 cancer patients in the past two years. We confirmed a total of two CR cases (one of them already reported). We report two successful cases in this paper. Case 1: A uterine cervical cancer patient with metastases in cervical and abdominal lymphnodes was treated with intratumoral DC injection therapy combined with hyperthermia in cervical. She showed a CR not only in cervical but also in abdominal lymph nodes. Case 2: A sialyl grand cancer patient with metastases in cervical and axillary lymphnodes was treated with intratumoral DC injection therapy combined with hyperthermia in cervical. She showed a PR.     

Effect of salinity on denitrification under limited single carbon source by Marinobacter sp. isolated from marine sediment

Marinobacter comprises Gram‐negative, aerobic, motile, and rod‐shaped bacteria within the γ‐subclass of the Proteobacteria and is known to be halophilic or halotolerant, heterotrophic neutrophile. Two strains classified as belonging to Marinobacter, named PAD‐2 and SeT‐1, were isolated from marine sediment. The most closely related species of PAD‐2 and SeT‐1 are M. alkaliphilus and M. guinea, respectively. The strain PAD‐2 exhibited remarkably higher denitrification at concentrations of 0.5 to 1 M NaCl (3–6% w/w) than at other salinities (2 and 3 M NaCl, 12–18% w/w), and optimal denitrification was observed in media with 0.5 M NaCl. The effect of pH on denitrification by strain PAD‐2 was also examined, and the optimum denitrification occurred at neutral pH rather than under alkaline conditions. Overall, strain PAD‐2 appears to be a novel halotolerant species belonging to the genus Marinobacter that shares many characteristics, such as substrate utilization profile and optimum NaCl concentration for growth with M. alkaliphilus. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

A case of carcinosarcoma of the esophagus treated by the chemoradiotherapy]

A 82-year-old man was admitted into our hospital complaining of dysphagia. Endoscopic examination revealed an elevated tumor in the middle esophagus, and biopsy revealed carcinosarcoma. He underwent chemo-radiotherapy, and the size of tumor decreased remarkably and almost disappeared 7 months later. However, a metastatic lesion appeared 11 months later, and eventually he died. Autopsy revealed a sarcomatous element in the metastatic part, but the primary lesion showed no recurrence. We report herein this rare case of carcinosarcoma of the esophagus that was treated with chemo-radiotherapy.     

Radioimmunotherapy with an 211At-labeled anti–tissue factor antibody protected by sodium ascorbate

Tissue factor (TF), the trigger protein of the extrinsic blood coagulation cascade, is abundantly expressed in various cancers including gastric cancer. Anti-TF monoclonal antibodies (mAbs) capable of targeting cancers have been successfully applied to armed antibodies such as antibody-drug conjugates (ADCs) and molecular imaging probes. We prepared an anti-TF mAb, clone 1084, labeled with astatine-211 (²¹¹At), as a promising alpha emitter for cancer treatment. Alpha particles are characterized by high linear energy transfer and a range of 50-100 µm in tissue. Therefore, selective and efficient tumor accumulation of alpha emitters results in potent antitumor activities against cancer cells with minor effects on normal cells adjacent to the tumor. Although the ²¹¹At-conjugated clone 1084 (²¹¹At-anti-TF mAb) was disrupted by an ²¹¹At-induced radiochemical reaction, we demonstrated that astatinated anti-TF mAbs eluted in 0.6% or 1.2% sodium ascorbate (SA) solution were protected from antibody denaturation, which contributed to the maintenance of cellular binding activities and cytocidal effects of this immunoconjugate. Although body weight loss was observed in mice administered a 1.2% SA solution, the loss was transient and the radioprotectant seemed to be tolerable in vivo. In a high TF–expressing gastric cancer xenograft model, ²¹¹At-anti-TF mAb in 1.2% SA exerted a significantly greater antitumor effect than nonprotected ²¹¹At-anti-TF mAb. Moreover, the antitumor activities of the protected immunoconjugate in gastric cancer xenograft models were dependent on the level of TF in cancer cells. These findings suggest the clinical availability of the radioprotectant and applicability of clone 1084 to ²¹¹At-radioimmunotherapy.     

Primary sclerosing cholangitis with marked eosinophilic infiltration in the liver

A 16-year-old boy was diagnosed as having primary sclerosing cholangitis (PSC), based on retrograde cholangiography showing mixed features of narrowing and dilatation of the common hepatic and intrahepatic bile ducts. However, periductal fibrosis was not observed in the needle biopsy liver specimen. The liver biopsy specimen obtained 11 years previously, at the onset of the disease had disclosed a marked infiltration of eosinophils in the portal tract with eosinophilic catinonic protein immunostaining, with marked eosinophilia (54%) being noted. In Japanese reports, eosinophilia of more than 7% was reported in 13 of 32 (40.6%) PSC patients. However, the early stage of PSC, with marked eosinophilia and eosinophilic infiltration in the liver, such as in the present case, has rarely been reported. The findings in this case suggest that eosinocytes are related to the pathogenesis of PSC.     

Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan

Background

X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk.

Methods

This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects.

Results

The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01–2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26–0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02–2.87) and 1.57 (95% CI 1.05–2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418).

Conclusions

The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.Key words: XRCC1 polymorphisms, alcohol consumption, colorectal cancer     

In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy

Background

Cardiac diffusion tensor imaging (cDTI) measures the magnitudes and directions of intramyocardial water diffusion. Assuming the cross-myocyte components to be constrained by the laminar microstructures of myocardium, we hypothesized that cDTI at two cardiac phases might identify any abnormalities of laminar orientation and mobility in hypertrophic cardiomyopathy (HCM).

Methods

We performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE) for detection of regional fibrosis.

Results

Voxel-wise analysis of diffusion tensors relative to left ventricular coordinates showed expected transmural changes of myocardial helix-angle, with no significant differences between phases or between HCM and control groups. In controls, the angle of the second eigenvector of diffusion (E2A) relative to the local wall tangent plane was larger in systole than diastole, in accord with previously reported changes of laminar orientation. HCM hearts showed higher than normal global E2A in systole (63.9° vs 56.4° controls, p = 0.026) and markedly raised E2A in diastole (46.8° vs 24.0° controls, p < 0.001). In hypertrophic regions, E2A retained a high, systole-like angulation even in diastole, independent of LGE, while regions of normal wall thickness did not (LGE present 57.8°, p = 0.0028, LGE absent 54.8°, p = 0.0022 vs normal thickness 38.1°).

Conclusions

In healthy controls, the angles of cross-myocyte components of diffusion were consistent with previously reported transmural orientations of laminar microstructures and their changes with contraction. In HCM, especially in hypertrophic regions, they were consistent with hypercontraction in systole and failure of relaxation in diastole. Further investigation of this finding is required as previously postulated effects of strain might be a confounding factor.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-014-0087-8) contains supplementary material, which is available to authorized users.