Intra-arterial chemotherapy with gemcitabine (GEM) for unresectable pancreatic cancer

PURPOSE: Most patients with pancreatic cancer are unresectable because of local invasion and liver metastasis at the time of diagnosis. To date, no treatment has had a significant impact on this disease. To deliver a high concentration of drug to the cancer, intra-arterial chemotherapy with GEM was performed in two patients with unresectable advanced cancer. PATIENTS AND METHODS: One patient, a 70-year-old man with liver metastasis, was treated with arterial infusion of GEM 1,000 mg/body. Another patient, a 55-year-old woman with local invasion and distant metastatic lymphadenopathy, was given intra-arterial infusion of GEM 400 mg and intra-venous infusion of GEM 1,000 mg/body. The patients were given GEM weekly for 3 weeks followed by a week of rest. RESULTS: In the first patient, the pain went away and CEA was decreased for 6 months. After that, the patient died due to intra-abdominal dissemination within 4 months. In the other patient, the pain went away. Tumor markers, such as CEA and CA19-9, were normalized and primary pancreatic cancer was reduced locally. The patient currently has a metastatic liver tumor, but she has had a significant improvement in performance status. CONCLUSION: Intra-arterial chemotherapy with GEM may be tolerated in patients with unresectable pancreatic cancer.     

A case of giant epidermoid cyst occupying the testis

A case of a giant epidermoid cyst of the testis is presented. A 65-year-old man was incidentally pointed out to have left scrotal painless swelling. Physical examination revealed an over hen-egg sized enlargement of the left scrotal contents. Ultrasonography revealed a 7.5 X 5.5 X 4.0 cm solid tumor with heterogeneous echogenicity. No other abnormal findings were observed including tumor markers. Since preoperative examination did not rule out malignancy, we performed left high orchiectomy. Pathological diagnosis was a epidermoid cyst of the testis with a small portion of atrophic testis. Although the preoperative diagnosis of testicular epidermoid cyst is possible, it may be considerably difficult when a giant epidermoid cyst is occupying the testis.     

Active chemotherapy with gemcitabine, carboplatin and docetaxel for three patients with MVAC-resistant liver metastasis of urothelial carcinoma

We report three cases with methotrexate-vinblastin-adriamycin-cisplatin (MVAC) resistant multiple liver metastases of urothelial carcinoma that responded to combination chemotherapy consisting of gemcitabine plus carboplatin (GC) with additional docetaxel (GCD) as salvage chemotherapy. Case 1: A 55-year-old man underwent left nephroureterectomy for ureteral cancer (TCC, G3, pT3pN1M0). Three courses of GC followed by three courses of GCD were given via intra-hepatic arterial infusion for multiple liver metastases, which appeared after adjuvant high-dose MVAC therapy. Complete response was obtained and maintained for 11 months. Case 2: A 46-year-old man underwent radical cystectomy for locally advanced bladder cancer (TCC G3 + adenocarcinoma. pT3pN0M0). Two courses of GC followed by 2 courses of GCD systemic therapies were performed for multiple liver metastases, which appeared after adjuvant high-dose MVAC therapy. Partial response was obtained and maintained for six months. Case 3: A 66-year-old man received three courses of MVAC for multiple metastases of the bladder cancer (TCC, G3, > pT2), which resulted in disease progression. Eight courses of GC followed by six courses of GCD were administrated via intra-hepatic arterial infusion. Partial response was obtained and maintained for 12 months. Although the response duration was still short, GC and GCD may be promising salvage chemotherapeutic regimens for the patients with MVAC-resistant liver metastases of urothelial carcinoma.     

2,3,7,8-tetrachlorodibenzo-p-dioxin augments the modulation of gene expression mediated by the thyroid hormone receptor

Previously, we reported on genes whose expression was highly modulated by T3 in the HeLaTR cells that stably expressed the thyroid hormone receptor (TR). In this study, we examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on TR-mediated gene expression. In the HeLaTR cells, T3 induced the expression of the reporter gene in a thyroid hormone responsible element (TRE)-dependent manner. When the cells were cultured in the presence of T3, the addition of TCDD but not 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl (PCB-OH), bisphenol A (BPA), or di(2-ethylhexyl)phthalate (DEHP) to the culture media further enhanced the T3-induced expression of the reporter gene. RT-PCR revealed that mRNA levels of 4-1BB, fmfc, PSCA, PSG7, RANTES, and TRAF1, which were highly increased by T3, were further elevated in cells exposed to T3 and TCDD. Also, the mRNA level of BMP6, which was decreased by T3, further declined in the cells exposed to both T3 and TCDD. In contrast to the effect of TCDD, PCB-OH suppressed the modulation of these gene expressions by T3. Neither TCDD nor PCB-OH alone affected the expression of 4-1BB, fmfc, PSCA, PSG7, RANTES, TRAF1, or BMP6. These results indicate that TCDD augments the cellular responses to T3 by hyperactivating TR-mediated gene expression, whereas PCB-OH suppresses cellular responses to T3 by negatively regulating it. Based on these findings, enzyme-linked immunosorbent assay (ELISA) for the PSCA protein in the HeLaTR cells was established. Such assays will be useful to monitor the effects of endocrine disrupting chemicals (EDCs) on TR-mediated gene expression.     

Loss of von Hippel-Lindau protein causes cell density dependent deregulation of CyclinD1 expression through hypoxia-inducible factor

Loss of the von Hippel-Lindau gene (VHL) expression ca-uses deregulation of contact inhibition of cell growth, which might be one of the bases of the tumor suppressor function of VHL. Here we show that this function of the VHL gene product (pVHL) depends on cell autonomous events. To identify the target gene of pVHL, which is directly involved in the contact inhibition, we compared the gene expression profile between VHL-deficient renal carcinoma 786-O cells and those infected with an adenovirus vector encoding VHL. In addition to known pVHL-regulated genes, such as vascular endothelial growth factor and carbonic anhydrase, we found cyclinD1 as a new target of pVHL at a high cell density. In VHL-expressing cells (VHL (+) cells), the cyclinD1 mRNA expression level diminishes at a high cell density, while it remains at a relatively high level in VHL-deficient cells (VHL (-) cells). The cyclinD1 expression level was also abnormally high in VHL (-) cells at a high cell density. Consequently, the phosporylation level of the retinoblastoma (Rb) protein remained high in these cells, whereas there was no phosporylated Rb in VHL (+) cells under the contact inhibition. The abnormal expression of cyclinD1 at a high cell density was observed even in VHL (+) cells under the hypoxic state. Moreover, ectopic expression of a HIF mutant resistant to pVHL-mediated proteolysis causes the abnormal cyclinD1 expression in VHL (+) cells. Taken together, these observations indicate that VHL is required for the downregulation of cyclinD1 at a high cell density through HIF.