Hamster Tumor Research Articles

652. Culture and Characterization of Tumor-Infiltrating Lymphocytes of the Syrian Hamster

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has developed into a promising treatment modality for metastatic cancer. However, preclinical animal models for studying TIL therapy are limited to mice and therefore we set out to culture and characterize TIL from another rodent species, the Syrian hamster. First, we examined the presence of CD4+ and CD8+ cells in six implantable syngeneic hamster tumors representing various histologies. A tumor type-dependent pattern of lymphocyte infiltration was observed, with CD8+ cells ranging from 0.08% to 0.93% (of all tumor cells) and CD4+ cells ranging from 0.17% to 3.25%. To establish TIL cultures, excised tumor fragments were cultured in high-dose human interleukin-2 (IL-2) for 10 days. Flow cytometric analyses of Day 10 TIL cultures revealed a predominance of CD4+ cells over CD8+ cells in all tumor types studied. In effector/target assays the TIL cultured from HapT1 (pancreatic adenocarcinoma) and RPMI 1846 (melanoma) exhibited tumor-specific cytolytic activity. In addition, MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, suggesting that cytotoxic CD8+ T-cells were responsible for the observed cytolytic activity. Only partial abrogation was seen with HapT1 TIL suggesting the presence of cytotoxic CD4+ T-cells in the TIL population, which is supported by the observation that HapT1 tumor cells express MHC Class II. To our knowledge, this is the first time tumor-infiltrating lymphocytes of the Syrian hamster have been cultured and characterized. Thorough immunophenotyping of hamster tumors and TIL cultures requires the development of new hamster-specific antibodies in addition to the currently available ones used in this study. In conclusion, our data supports the use of the Syrian hamster as a novel platform for testing TIL protocols in a species other than mouse or human.

414. A Novel System to Systematically Analyze Diverse Types of Conditionally Replicating Adenoviruses Expressing Immunostimulatory Genes in Syngenic Hamster Models

We developed a method to efficiently construct diverse “conditionally replicating adenoviruses regulated with multiple cancer-specific factors” (m-CRAs) for an ideal gene-viro-therapy (Gene Ther 2005), after we had developed the immunological gene therapy, including granulocyte macrophage colony-stimulating factor (GM-CSF) (PNAS 1995, 1996, Cancer Res 1996). We then identified by systematic m-CRA analyses that survivin-responsive m-CRA (Surv.m-CRA), in which E1A is regulated by survivin promoter, could achieve stronger and more cancer-selective potentials than competing m-CRAs (Cancer Res 2005). The new Surv.m-CRA, of which an altered E1B promoter is regulated with another cancer-specific promoter (CS-Pr), further increased cancer specificity without reduced anticancer effects (Cancer Gene Ther 2011). Moreover, the unique feature of the increased effectiveness against cancer stem cells suggests that Surv.m-CRA is promising anticancer agent (J Trans Med 2014). In addition, we have developed a novel m-CRA strategy that specifically eliminates undifferentiated cells in pluripotent stem cell-based regenerative medicine (Mol Ther Methods Clin Dev 2015). Taken altogether, we are about to start its clinical trial in Japan. As the first-in-class oncolytic virus expressing GM-CSF was recently approved, m-CRAs expressing immunostimulatory genes should be promising. In general, the development of oncolytic adenoviruses with cytokines has been hampered by two technical limitations in the vector construction and the viral replication-permissive animals. Here we demonstrate a novel system to efficiently generate diverse types of m-CRAs expressing candidate immunostimulatory genes under candidate promoters, and systematically analyze their potentials in syngenic hamster models. We tested the feasibility of this methodology, and succeeded in the rapid generation of the new Surv.m-CRAs comprising 18 different therapeutic units, including a mouse or human cytokine gene downstream to a ubiquitously active promoter (UA-Pr) or CS-Pr. To test the utility of our experimental system, we first analyzed in vivo antitumor efficiencies and toxicities of Surv.m-CRA expressing GM-CSF under a strong UA-Pr in xenograft syngeneic tumor of syrian hamster. An intratumoral injection of the control Surv.m-CRA without GM-CSF inhibited a tumor growth and extended a survival to some degrees. Whereas Surv.m-CRAs expressing mouse GM-CSF more drastically reduced tumor growth, some of these animals died of excessive GM-CSF expressions (showing the remarkable splenomegaly) within 3 days. The results importantly suggest the necessity of systematical analyses to identify the best combination of cytokine genes and promoters to achieve the optimal cytokine levels (Int J Oncol 2004), and we are now analyzing 18 different Surv.m-CRAs, including those expressing GM-CSF at a moderate level and/or in the cancer-specific manner. In conclusion, we have developed a novel system to efficiently generate the candidate m-CRAs expressing diverse immunostimulatory genes under several promoters and to systematically analyze them in syngenic hamster models.View Large Image | Download PowerPoint Slide

Syngeneic Syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting

ABSTRACTAdoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8+ T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors.

Histopathological , Enzyme - Histochemical and Immunohistochemical Diagnosis of Mast Cell Tumors in the Skin of Golden Hamster

No previous records in the available literature about the cutaneous mast cell tumors in golden hamster. Two male golden hamsters with cutaneous lumps were brought to the Institute of Veterinary Pathology of Justus Leibig University of Giessen, Germany for diagnositic examination. Cutaneous lumps were taken and processed for histological, histochemical and immunohistochemical examination. Numerous oval and polygonal tumor cells with high mitotic count and basophilic metachromatic granules were observed; while the superjacent epidermis and adnexes were normal. Many unevenly proliferating cells showed positive proliferating cell nuclear antigen (PCNA) reaction and positive chymase activity. The reactions were negative to gene encoding KIT (c-Kit), Cyclooxygenase-2 (COX-2) and tryptase. These results indicated a well- differentiated grade I subcutaneous mast cell tumor. The results are discussed in relation to subcutaneous mast cell tumors in canines.

Ludwik Gross, Sarah Stewart, and the 1950s discoveries of Gross murine leukemia virus and polyoma virus

The Polish-American scientist Ludwik Gross made two important discoveries in the early 1950s. He showed that two viruses— murine leukemia virus and parotid tumor virus— could cause cancer when they were injected into susceptible animals. At first, Gross's discoveries were greeted with skepticism: it seemed implausible that viruses could cause a disease as complex as cancer. Inspired by Gross's initial experiments, similar results were obtained by Sarah Stewart and Bernice Eddy who later renamed the parotid tumor virus SE polyoma virus after finding it could cause many different types of tumors in mice, hamsters, and rats. Eventually the “SE” was dropped and virologists adopted the name “polyoma virus.” After Gross's work was published, additional viruses capable of causing solid tumors or blood-borne tumors in mice were described by Arnold Graffi, Charlotte Friend, John Moloney and others. By 1961, sufficient data had been accumulated for Gross to confidently publish an extensive monograph—Oncogenic Viruses—the first history of tumor virology, which became a standard reference work and marked the emergence of tumor virology as a distinct, legitimate field of study.

GMCSF-armed vaccinia virus induces an antitumor immune response.

Oncolytic Western Reserve strain vaccinia virus selective for epidermal growth factor receptor pathway mutations and tumor-associated hypermetabolism was armed with human granulocyte-macrophage colony-stimulating factor (GMCSF) and a tdTomato fluorophore. As the assessment of immunological responses to human transgenes is challenging in the most commonly used animal models, we used immunocompetent Syrian golden hamsters, known to be sensitive to human GMCSF and semipermissive to vaccinia virus. Efficacy was initially tested in vitro on various human and hamster cell lines and oncolytic potency of transgene-carrying viruses was similar to unarmed virus. The hGMCSF-encoding virus was able to completely eradicate subcutaneous pancreatic tumors in hamsters, and to fully protect the animals from subsequent rechallenge with the same tumor. Induction of specific antitumor immunity was also shown by ex vivo co-culture experiments with hamster splenocytes. In addition, histological examination revealed increased infiltration of neutrophils and macrophages in GMCSF-virus-treated tumors. These findings help clarify the mechanism of action of GMCSF-armed vaccinia viruses undergoing clinical trials.

Antitumor activity of C-phycocyanin from Arthronema africanum (Cyanophyceae)

ABSTRACT Pure C-phycocyanin (C-PC) was isolated from Arthronema africanum to evaluate its potential antitumor effects in vivo and in vitro. Experimental myeloid Graffi tumor in hamsters was used as a model. The cell proliferation assay showed that C-PC treatment, at concentration of 100 µg mL -1 for 24 h, significantly inhibited the growth of Graffi tumor cells (51.4% viability). Agarose gel electrophoresis of the genomic DNA of treated cells displayed time- and concentration-dependent fragmentation pattern, typical for apoptosis. Apoptotic process was related to the increase in cellular manganese and copper/zinc superoxide dismutases and glutathione reductase activities, coupled with a low catalase activity. In vivo C-PC administration (5.0 mg kg -1 body weight) suppressed the tumor transplantability and growth, while the mean survival time of the tumor-bearing hamsters was increased. The results revealed promising antitumor activities of A. africanum C-PC and suggested the potential of this natural biliprotein pigment for future pharmacological and medical applications. The study provided new data on the mechanism of the C-PC-induced apoptosis in which the imbalance of antioxidant enzymes that favoured hydrogen peroxide accumulation might play a leading role. Key words: Antitumor activity, Arthronema africanum , In vivo , In vitro , C-pycocyanin, Myeloid Graffi tumor

The combination of i-leader truncation and gemcitabine improves oncolytic adenovirus efficacy in an immunocompetent model

Adenovirus (Ad) i-leader protein is a small protein of unknown function. The C-terminus truncation of the i-leader protein increases Ad release from infected cells and cytotoxicity. In the current study, we use the i-leader truncation to enhance the potency of an oncolytic Ad. In vitro, an i-leader truncated oncolytic Ad is released faster to the supernatant of infected cells, generates larger plaques, and is more cytotoxic in both human and Syrian hamster cell lines. In mice bearing human tumor xenografts, the i-leader truncation enhances oncolytic efficacy. However, in a Syrian hamster pancreatic tumor model, which is immunocompetent and less permissive to human Ad, antitumor efficacy is only observed when the i-leader truncated oncolytic Ad, but not the non-truncated version, is combined with gemcitabine. This synergistic effect observed in the Syrian hamster model was not seen in vitro or in immunodeficient mice bearing the same pancreatic hamster tumors, suggesting a role of the immune system in this synergism. These results highlight the interest of the i-leader C-terminus truncation because it enhances the antitumor potency of an oncolytic Ad and provides synergistic effects with gemcitabine in the presence of an immune competent system.

The effects of radiation on antitumor efficacy of an oncolytic adenovirus vector in the Syrian hamster model

We report that radiation enhances the antitumor efficacy of the oncolytic adenovirus vector VRX-007 in Syrian hamster tumors. We used tumor-specific irradiation of subcutaneous tumors and compared treatment options of radiation alone or combined with VRX-007 and cyclophosphamide (CP). Radiation therapy further augmented the VRX-007-mediated inhibition of tumor growth, in both CP-treated and non-CP-treated hamsters, even though radiation did not lead to increased viral replication in tumors when compared to those treated with VRX-007 alone. Moreover, tumor growth inhibition was similar in tumors irradiated either one week before or after injection with VRX-007, which suggests that radiation exerts its antitumor effect independently from vector therapy. Thus, our results demonstrate that these two therapies do not have to be provided simultaneously to enhance their combined effectiveness against subcutaneous hamster tumors.

The role of cyclophosphamide in enhancing antitumor efficacy of an adenovirus oncolytic vector in subcutaneous Syrian hamster tumors

We have previously reported that intratumoral injection of VRX-007—an Ad5-based vector overexpressing ADP (Adenovirus Death Protein)—can suppress the growth of subcutaneous HaK (hamster renal cancer) tumors. VRX-007 replication and tumor growth inhibition are enhanced when the hamsters are immunosuppressed by a high dose of cyclophosphamide (CP), an immunosuppressive and chemotherapeutic agent. Here we report that continuous immunosuppression with CP was not required for increased oncolytic activity of VRX-007 because short-term dosing or continuous dosing with the drug yielded similar antitumor results. Prolonged viral replication was found only in animals on continuous CP treatment. We used 007-Luc, a replication-competent, luciferase-expressing vector similar to VRX-007 to investigate the replication of the vector over time. Tumor growth inhibition was similar in hamsters given CP treatment either one week before or one week after 007-Luc injection, which suggests that CP exerts its antitumor efficacy independently of vector therapy. 007-Luc did not spread far from the inoculation site, even in immunosuppressed, CP-treated animals. Our results indicate that the enhanced effectiveness that is produced by the combination of VRX-007 and CP therapies is due to their two independent mechanisms and that they do not have to be given simultaneously for the improved outcome shown.

Lymphoma outbreak in a GASH:Sal hamster colony

We have detected a high incidence of lymphomas in a colony of GASH:Sal Syrian golden hamsters (Mesocricetus auratus). This strain is characterised by its ability to present convulsive crises of audiogenic origin. Almost 16 % (90 males and 60 females) of the 975 animals were affected during a 5-year period by the development of a progressing lymphoid tumour and exhibited similar clinical profiles characterised by lethargy, anorexia, evident abdominal distension, and a rapid disease progression resulting in mortality within 1 to 2 weeks. A TaqMan® probe-based real-time PCR analysis of genomic DNA from different tissue samples of the affected animals revealed the presence of a DNA sequence encoding the hamster polyomavirus (HaPyV) VP1 capsid protein. Additionally, immunohistochemical analysis using HaPyV-VP1-specific monoclonal antibodies confirmed the presence of viral proteins in all hamster tumour tissues analysed within the colony. An indirect ELISA and western blot analysis confirmed the presence of antibodies against the VP1 capsid protein in sera, not only from affected and non-affected GASH:Sal hamsters but also from control hamsters from the same breeding area. The HaPyV genome that accumulated in tumour tissues typically contained deletions affecting the noncoding regulatory region and adjacent sequences coding for the N-terminal part of the capsid protein VP2.

PP073: Inhibitory effects of Zengshengping water fraction on DMBA-induced buccal pouch carcinogenesis in hamsters

The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of water extracts from ZSP, a Chinese herbal drug, on 7,12-dimethlbenz(a) anthracene (DMBA) induced oral tumors in hamsters. The study also investigated the anti-cancer mechanisms of the ZSP water extraction on oral carcinogenesis. DMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6–8 weeks old) three times per week for 6 weeks in order to induce the development of oral tumors. Then ZSP water fraction is applied topically to the oral tumor lesions at varying dosages (0.35 g/100 ml; 0.7 g/100 ml; 1.4 g/100 ml) to animals with oral tumors for 18 weeks. Tumor volume was measured by histopathological examination. Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels. The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting. Liver and kidney toxicity were also detected. Average tumor number in each treatment group is lower than positive control group. Moderate-dose group decreased from 2.3 ± 1.8 to 1.5 ± 1.1 (P < 0.05); high-dose group reduced to 1.2 ± 1.0 (P < 0.01). The average tumor volume had not significant difference. It showed that there were no apparent liver and kidney toxicity in the long-term. Topical application of ZSP water fraction also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of mitogen-activated protein kinase (MAPK). In addition, ZSP water fraction promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production. The water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating apoptosis in oral cancer suggesting that these fractions have chemopreventive effects on DMBA induced oral carcinogenesis.

A Novel Therapeutic Regimen to Eradicate Established Solid Tumors with an Effective Induction of Tumor-Specific Immunity

The efficacy of oncolytic viruses depends on multiple actions including direct tumor lysis, modulation of tumor perfusion, and stimulation of tumor-directed immune responses. In this study, we investigated whether a sequential combination of immunologically distinct viruses might enhance antitumor efficacy through the induction of tumor-specific immunity and circumvention or mitigation of antiviral immune responses. The Syrian hamster as an immune-competent model that supports replication of both adenovirus and vaccinia virus was evaluated in vitro and in vivo. The antitumor efficacy of either virus alone or sequential combination of the two viruses was examined in pancreatic and kidney cancer models. The functional mechanism of the regimen developed here was investigated by histopathology, immunohistochemistry staining, CTL assay, and T-cell depletion. The Syrian hamster is a suitable model for assessment of oncolytic adenovirus and vaccinia virus. Three low doses of adenovirus followed by three low doses of vaccinia virus resulted in a superior antitumor efficacy to the reverse combination, or six doses of either virus alone, against pancreatic and kidney tumors in Syrian hamsters. A total of 62.5% of animals bearing either tumor type treated with the sequential combination became tumor-free, accompanied by the induction of effective tumor-specific immunity. This enhanced efficacy was ablated by CD3+ T-cell depletion but was not associated with humoral immunity against the viruses. These findings show that sequential treatment of tumors with oncolytic adenovirus and vaccinia virus is a promising approach for cancer therapy and that T-cell responses play a critical role.

Cytotoxic and Apoptogenic Potential of Red Microalgal Polysaccharides

ABSTRACTThe efforts of scientists are aimed at finding anti-cancer agents of natural origin which have high biological activity, low toxicity and broad spectrum of therapeutic activity. This study was designed to determine the cytotoxic properties of polysaccharides derived from the red microalgae Dixoniella grisea and Porphyridium cruentum and to elucidate the mechanism of their action on two permanent human cell lines MCF-7 (breast adenocarcinoma) and HeLa (cervical carcinoma), as well as on primary culture from Graffi myeloid tumor in hamsters. Our investigations indicated that both algal polysaccharides showed high cytotoxic and apoptogenic activities on cancer cells and may be a promising alternative to synthetic substances.

Different metastasis promotive potency of small G-proteins RalA and RalB in in vivo hamster tumor model

BackgroundPreviously we have shown that oncogenic Ha-Ras stimulated in vivo metastasis through RalGEF-Ral signaling. RalA and RalB are highly homologous small G proteins belonging to Ras superfamily. They can be activated by Ras-RalGEF signaling pathway and influence cellular growth and survival, motility, vesicular transport and tumor progression in humans and in animal models. Here we first time compared the influence of RalA and RalB on tumorigenic, invasive and metastatic properties of RSV transformed hamster fibroblasts.MethodsRetroviral vectors encoding activated forms or effector mutants of RalA or RalB proteins were introduced into the low metastatic HET-SR cell line. Tumor growth and spontaneous metastatic activity (SMA) were evaluated on immunocompetent hamsters after subcutaneous injection of cells. The biological properties of cells, including proliferation, clonogenicity, migration and invasion were determined using MTT, wound healing, colony formation and Boyden chamber assays respectively. Protein expression and phosphorylation was detected by Westen blot analysis. Extracellular proteinases activity was assessed by substrate-specific zymography.ResultsWe have showed that although both Ral proteins stimulated SMA, RalB was more effective in metastasis stimulation in vivo as well as in potentiating of directed movement and invasion in vitro. Simultaneous expression of active RalA and RalB didn't give synergetic effect on metastasis formation. RalB activity decreased expression of Caveolin-1, while active RalA stimulated MMP-1 and uPA proteolytic activity, as well as CD24 expression. Both Ral proteins were capable of Cyclin D1 upregulation, JNK1 kinase activation, and stimulation of colony growth and motility. Among three main RalB effectors (RalBP1, exocyst complex and PLD1), PLD1 was essential for RalB-dependent metastasis stimulation.ConclusionsPresented results are the first data on direct comparison of RalA and RalB impact as well as of RalA/RalB simultaneous expression influence on in vivo cell metastatic activity. We showed that RalB activation significantly more than RalA stimulates SMA. This property correlates with the ability of RalB to stimulate in vitro invasion and serum directed cell movement. We also found that RalB-PLD1 interaction is necessary for the acquisition of RalB-dependent high metastatic cell phenotype. These findings contribute to the identification of molecular mechanisms of metastasis and tumor progression.

Red Mold Rice Mitigates Oral Carcinogenesis in 7,12‐Dimethyl‐1,2‐Benz[a]anthracene‐Induced Oral Carcinogenesis in Hamster

The prevalence of oral tumor has exponentially increased in recent years; however, the effective therapies or prevention strategies are not sufficient. Red mold rice is a traditional Chinese food, and several reports have demonstrated that red mold rice had an anti-tumor effect. However, the possible anti-tumor mechanisms of the red mold rice are unclear. In this study, we examined the anti-tumor effect of red mold rice on 7,12-dimethyl-1,2-benz[a]anthracene (DMBA)-induced oral tumor in hamster. The ethanol extract of red mold rice (RMRE) treatment significantly decreases the levels of DMBA-induced reactive oxygen species, nitro oxide and prostaglandin E2 than those of the lovastatin-treated group (P < .001). Moreover, RMRE decreases the formation of oral tumor induced by DMBA. Monacolin K, monascin, ankaflavin or other red mold rice metabolites had been reported to decrease inflammation and oxidative stress and exerted anti-tumor effects. Therefore, we evaluated the anti-inflammation and anti-oxidative stress effects of monacolin K, monascin, ankaflavin and citrinin in lipopolysaccharide-treated RAW264.7 cells. We found that RMRE reduced the LPS-induced nitrite levels in RAW264.7 cells better than monacolin K, monascin, ankaflavin or citrinin (P < .05).

Antitumor activity of quaternized chitosan-based electrospun implants against Graffi myeloid tumor

Nanofibrous implants containing quaternized chitosan (QCh), poly( l-lactide-co- d,l-lactide) (coPLA), and the antitumor drug doxorubicin (DOX) were fabricated by electrospinning. The surface chemical composition and the morphology of the implants were characterized by XPS and SEM. In vitro cell viability studies demonstrated that QCh- and DOX-based implants exhibited high cytotoxicity against Graffi tumor cells. The implants efficiently inhibited the growth of Graffi tumor in hamsters with minimum weight loss. Insertion of QCh/coPLA/DOX implants in the place of removed tumor led to an increase in the animal survival rate and to a decrease in the percentage of recurrences.

Imaging study of pancreatic ductal adenocarcinomas in Syrian hamsters using X‐ray micro‐computed tomography (CT)

X-ray computed tomography (CT) has been used for diagnoses of human pancreatic cancer. Although micro-CT is a useful approach to evaluate macromorphology of organs/tissue also in animal models, reports on pancreatic tumors are limited. In this study, the utility of micro-CT was assessed in characterizing chemically induced pancreatic tumors in Syrian hamsters. Hamsters treated with or without N-nitrosobis(2-oxopropyl)amine (BOP) were injected with the antispasmodic agent, scopolamine butylbromide, and contrast agents, 5 or 10 mL/kg body weight of iopamidol or Fenestra VC at 18-38 weeks, then examined by micro-CT scanning with a respiratory gating system. Both peristaltic and respiratory movements were substantially suppressed by the combination of scopolamine butylbromide treatment and the respiratory gating system, resulting in improvements of image qualities. Iopamidol clearly visualized the pancreatic parenchyma and contrasted the margins among the pancreas and other abdominal organs/tissue. Meanwhile Fenestra VC predominantly contrasted abdominal vascular systems, but the margins among pancreas and other organs/tissue remained obscure. Six pancreatic tumors of 4-13 mm in diameter were detected in four of 15 animals, but not the five tumors of 1-4 mm in diameter. The inner tumor images were heterogeneously or uniformly visualized by iopamidol and Fenestra VC. Overall, iopamidol could clearly contrast between pancreatic parenchyma and the tumors as compared with Fenestra VC. All tumors confirmed were histopathologically diagnosed as pancreatic ductal adenocarcinomas. Thus, micro-CT could be useful to evaluate the carcinogenic processes and preventive methods of pancreatic cancer in hamsters and to assess the novel contrast agents for detection of small pancreatic cancer in humans.

Spontaneous differentiated squamous cell carcinoma of cheek pouch in a Syrian hamster

Summary A 2-year-old male hamster was presented because of left facial swelling and salivation. Necropsy was performed and affected cheek pouch with tissue samples of regional and internal organs were submitted for histopathological study. In histopathological examination it was found that the tumor consisted of cords and islands of tumoric epithelial cells which were diffused in the dermis. Vacoulation of cytoplasm in many cells were striking features. The lesion was infiltrated by mononuclear cells. These findings were consistent with differentiated squamous cell carcinoma, which restricted only to the left cheek pouch. There was no evidence of tumoral invasion to the other organs. Cheek pouch spontaneous tumors in hamsters have been rarely reported.

Effect of diazoxide on golden hamsters with chronic hypoglycemia due to a transplantable islet-cell tumor.

The development of the transplantable islet-cell tumor in the golden hamster induces, within six to eight weeks, a severe fasting hypoglycemia and a significant increase in the circulating levels of plasma insulin. The chronic oral administration of diazoxide (250 mg/kg/day) induces a significant increase in blood sugar in fed animals. The elevation of blood sugar is not significant in overnight-fasted animals. The diazoxide-induced hyperglycemia is not accompanied by any reduction in plasma insulin level. The acute intraperitoneal infection of diazoxide (100 mg/kg) markedly increases blood glucose in normal overnight-fasted hamsters; concomitantly, circulating plasma insulin levels are significantly reduced. In the overnight-fasted tumor-bearing animals, the acute injection of diazoxide induces a rise in blood sugar usually accompanied by a paradoxical rise in plasma immunoreactive insulin. Neither depletion of the catecholamine stores by previous administration of reserpine nor β-receptor blockade by propranolol administration can suppress the hyperglycemic response to the acute injection of diazoxide. These data clearly indicate that, in hamster bearing the transplantable islet-cell tumor, the hyperglycemic action of diazoxide does not result from an inhibition of insulin secretion and strongly suggest that this effect is independent of catecholamine release. This conclusion is supported by the lack of effect of diazoxide on both tumor and adrenal catecholamine content.