A case series of Kimura's disease: a diagnostic challenge.

Kimura's disease (KD) is a rare, benign disorder characterized by subcutaneous masses with regional lymph-node enlargement. It is considered to be due to chronic inflammation of unclear etiology. Most cases have been reported in young, 20-30-year-old men of Asian descent. The diagnosis of KD is based on pathological features and elevated immunoglobulin E levels. Characteristic pathological features include intact lymph-node architecture, florid germinal center hyperplasia, extensive eosinophilic infiltrates, and proliferation of postcapillary venules. However, these features can also be seen in Hodgkin's disease or T-cell lymphoma, therefore, cases presenting as KD pose a diagnostic challenge. We report a case series of two cases with suspected KD at initial presentation, with one patient eventually diagnosed with Hodgkin's disease after clinical progression. The first case was a 45-year-old Asian man who presented with bilateral thigh masses and significantly enlarged inguinal lymph nodes. The histopathology was characteristic and the patient had stable disease on treatment with cetirizine for 20 months. The second case was a 29-year-old African-American man who had progressive enlargement of the right neck lymph nodes extending into the mediastinum, with the original biopsy suggestive of KD. An initial search for Reed-Sternberg cells using immunohistochemical staining for CD15 and CD30 was negative. However, the patient developed neurological symptoms corresponding to tumor extension to the cervical and thoracic neural foramina. A repeat biopsy showed a lack of nodal structure and atypical large cells that were positive for CD30 staining. The patient was treated with chemotherapy with good response. We emphasize the importance of following the clinical course to render an accurate diagnosis. Both cases showed extensive eosinophilic infiltration and other KD-like pathological features. However, KD is rare; not missing a malignant diagnosis lies in high clinical suspicion and repeated exhaustive work up.

Anti-tumor efficacy of Cloretazine (VNP40101M) alone and in combination with fludarabine in murine tumor and human xenograft tumor models.

Cloretazine (VNP40101M), a new sulfonylhydrazine alkylating agent, has demonstrated broad-spectrum anti-tumor activity in preclinical studies. In this study, Cloretazine was evaluated both as a monotherapy and in combination with fludarabine in murine tumor and human tumor xenograft models. Cloretazine significantly inhibited the growth of subcutaneously implanted tumors, including B16F10 murine melanoma in C57BL/6 mice, and H460 human lung carcinoma and WiDr human colon carcinoma in athymic nude CD1 mice. The inhibition of tumor growth by Cloretazine was dose dependent, increasing from 42.2 to 87% as the dose escalated from 100 to 150 mg/kg. Cloretazine showed equivalent efficacy but lower toxicity compared to cyclophosphamide in these models. The combination therapy, consisting of a single dose of 10 mg/kg Cloretazine plus five doses of 70 mg/kg fludarabine, given every other day intraperitoneally, significantly increased the long-term survival of BDF1 mice bearing the L1210 murine leukemia. On Day 65 post-tumor implantation, the combination therapy yielded a 90% survival rate compared to 40% for Cloretazine alone and 0% for fludarabine alone.

Systemic administration of an attenuated, tumor-targeting Salmonella typhimurium to dogs with spontaneous neoplasia: phase I evaluation.

PURPOSE: Genetically modified bacteria are a potentially powerful anticancer therapy due to their tumor targeting capacity, inherent antitumor activity, and ability to serve as efficient vectors for gene delivery. This study sought to characterize the acute and short-term toxicities and tumor colonization rates of a genetically modified Salmonella typhimurium (VNP20009) in dogs with spontaneous tumors, in the context of a phase I dose escalation trial. EXPERIMENTAL DESIGN: Forty-one pet dogs with a variety of malignant tumors received weekly or biweekly i.v. infusions of VNP20009, at doses ranging from 1.5 x 10(5) to 1 x 10(8) cfu/kg. Vital signs and clinicopathologic variables were monitored regularly. Incisional biopsies were obtained before and 1 week following the first infusion for histopathology and bacterial culture. RESULTS: The nominal maximum tolerated dose was 3 x 10(7) cfu/kg, with refractory fever and vomiting being the dose-limiting toxicities. One treatment-related acute death occurred. Bacteria were cultured from tumor tissue in 42% of cases. Thirty-five patients were evaluable for antitumor response. Major antitumor responses were seen in 15% (4 complete response and 2 partial response), and disease stabilization for at least 6 weeks in 10%. CONCLUSIONS: Administration of VNP20009 at doses with acceptable toxicity results in detectable bacterial colonization of tumor tissue and significant antitumor activity in tumor-bearing dogs.

Tumor-targeted Salmonella expressing cytosine deaminase as an anticancer agent.

The study was designed to evaluate whether TAPET-CD, an attenuated strain of Salmonella typhimurium expressing Escherichia coli cytosine deaminase (CD), was capable of converting nontoxic 5-fluorocytosine (5-FC) to the active antitumor agent 5-fluorouracil (5-FU). The antitumor effect of TAPET-CD plus 5-FC against subcutaneously implanted colon tumors was also evaluated. TAPET-CD was given to tumor-bearing mice by a single bolus intravenous administration followed with 5-FC by intraperitoneal administration. TAPET-CD accumulated in tumors at levels 1000-fold higher than that in normal tissues and high levels of 5-FU were detected in tumors in mice treated with both TAPET-CD and 5-FC. No 5-FU could be detected in normal tissues. Inhibition of tumor growth was observed in mice treated with either TAPET-CD alone or TAPET-CD in combination with 5-FC (TAPET-CD/5-FC), but not with 5-FC alone. TAPET-CD/5-FC inhibited tumor growth by 88%-96%, compared to TAPET-CD alone, which inhibited tumor growth by 38%-79%. These data suggest that tumor-targeting Salmonella could be used to deliver prodrug-converting enzyme selectively to tumors and produced anti-tumor effects when the corresponding prodrug was also given.