Immunophenotypic and genetic characterization of a CD8 positive mantle cell lymphoma in a patient with concomitant Mycosis fungoides

Mantle cell lymphoma (MCL) is immunophenotypically characterized by cell surface co-expression of CD19, CD20, CD5, IgM and FMC7. However, the concomitant presence of other antigens distinctive of a particular leukocyte subset, e.g. T-lymphocytes, is an exceptional finding in MCL. Here, the first case of a blastic MCL in leukaemic phase with aberrant expression of the T-cell associated antigen CD8 occurring in a patient with concomitant Mycosis fungoides is described. Comprehensive immunophenotypic analysis showed that the MCL cells expressed the typical B-lymphocytic markers, were CD5 and CD8 positive, but did not express other T-cell proteins, such as CD2, CD3, CD4, CD7, TCRalphabeta and TCRgammadelta. The MCL cells expressed both CD8alpha and CD8beta chains indicating cell surface presence of CD8alphabeta heterodimers. Intriguingly, expression of the cytotoxic enzymes perforin and granzyme A was detected by RT-PCR. Cytogenetic and molecular genetic analysis of the lymphoma cells confirmed cyclin D1 overexpression secondary to the t(11;14)(q13;32) chromosomal translocation. Furthermore, trisomy 11, trisomy 14 and extra copies of t(11;14) translocated chromosomes were detected in sub clones of the analyzed MCL cells. Clinically, an aggressive course of disease including cerebral lymphoma involvement was noted in the reported patient. Hence, systematic studies addressing the incidence, biology and clinical behavior of this form of MCL seem to be justified in future.     

Exercise training raises daily activity stronger than predicted from exercise capacity in patients with COPD

The 6-min walking (6MWD) and 6-min treadmill distance (6MTD) are often used as measures of exercise performance in patients with COPD. The aim of our study was to assess their relationship to daily activity in the course of an exercise training program. Eighty-eight patients with stable COPD (71m/17f; mean +/- SD age, 60 +/-8 year; FEV1, 43+/-14% pred) were recruited, 66 of whom performed a hospital-based 10-day walking training, whereas 22 were treated as control. On day 16MTD, and on days 8 and 10, 6MTD and 6MWD were determined. In addition, patients used an accelerometer (TriTrac-R3D) to record 24 h-activity, whereby training sessions were excluded. In both groups there was a linear relationship (r > or = 0.84 and P < 0.0001) between 6MTD and 24 h-activity, the slope of which was 2.5-fold greater in the training group (P < 0.01). Similar relationships emerged for 6MWD. There was no association between baseline 6MTD, FEV1 or BMI and any of the other measures. These data suggest that daily activity did not markedly vary with exercise capacity under baseline conditions. Participation in a training program increased activity significantly stronger than predicted from the gain in exercise capacity. This underlines the importance of non-physiological, patient-centered factors associated with training in COPD.     

Erythema Chronicum Migrans in Three Soldiers

Three cases of erythema chronicum migrans in soldiers who had returned from active duty in Central Europe were seen within a ten-week period in San Francisco. Typically, the lesions cleared in less than five days with penicillin in two cases and erythromycin in another.     

Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. In light of the very poor 5-year-survival new therapeutic approaches are urgently needed. Recently, evidence has been accumulated that the epidermal growth factor receptor (EGFR) is a promising target for cancer therapy. Several reports indicate that EGFRs are expressed frequently in HCC, most likely contributing to the aggressive growth characteristics of these tumors. METHODS: Erlotinib, an inhibitor of EGFR-tyrosine kinase, potently suppresses the growth of various tumors, but its effect on HCC remains to be explored. We therefore studied the antineoplastic potency of erlotinib in human HCC cells (Huh-7 and HepG2 cell lines). RESULTS: We show that erlotinib inhibited HCC growth in a time- and dose-dependent manner. Moreover erlotinib treatment induced apoptosis and resulted in a dose-dependent arrest at the G1/S checkpoint of the cell cycle. Combining erlotinib with doxorubicin or docetaxel or SN-38 resulted in additive or even synergistic antiproliferative effects. CONCLUSIONS: Our data demonstrate that in human HCC cells the inhibition of EGFR-tyrosine kinase by erlotinib induces growth inhibition, apoptosis and cell cycle arrest. Additionally, erlotinib enhances the antineoplastic activity of conventional cytostatic drugs. Thus, inhibiting EGFR-tyrosine kinase appears to be a promising treatment strategy in HCC.     

Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocellular carcinoma

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. Due to very poor 5-year-survival new therapeutic approaches are mandatory. Gefitinib, an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of various tumors, but its effect on HCC remains unexplored. We therefore studied the antineoplastic potency of gefitinib in human HCC cells. RESULTS: Gefitinib induced a time- and dose-dependent growth inhibition of the human HCC cell lines Huh-7 and HepG2. Gefitinib-treatment induced both mitochondria-dependent and -independent apoptosis. Changes in mitochondrial membrane potential and caspase-8 activation, followed by caspase-3 activation and nuclear degradation, were detected. Moreover, gefitinib induced cell cycle arrest at the G1/S checkpoint and decreased the phosphorylation of mitogen-activated protein kinase ERK1/2. Finally, gefitinib suppressed the expression of antiapoptotic Bcl-2 and Bcl-X(L), further rendering HCC cells prone to apoptosis. CONCLUSIONS: Our data demonstrate that the inhibition of EGFR-TK by gefitinib induced growth inhibition, apoptosis and cell cycle arrest in human HCC cells. Thus, EGFR-TK inhibition appears to be a promising novel approach for future treatment strategies of HCC.     

Enhancement of the immune response to residual intrahepatic tumor tissue by laser-induced thermotherapy (LITT) compared to hepatic resection

BACKGROUND AND OBJECTIVES: In contrast to hepatic resection, thermally destroyed autologous tumor cells remain in situ after laser-induced thermotherapy (LITT). The aim of the study was to evaluate the effect of LITT and hepatic resection on the immune response to residual intrahepatic tumor tissue and the growth of untreated liver metastases. STUDY DESIGN/MATERIALS AND METHODS: Two independent adenocarcinomas (CC531) were implanted into 60 WAG rats, one in the right (control tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to further investigation 24 hours, 96 hours, 7 days, and 10 days after treatment. RESULTS: Ten days after treatment, control tumor volumes were 296+/-46 mm_ after LITT and 1,181+/-192 mm_, 1,387+/-200 mm_ after hepatic resection and no treatment, respectively (P<0.001). Peritoneal tumor spread was detected in 4/20 cases after LITT and in 17/20 cases after hepatic resection. Expression of CD8, B7-2 (CD86), and to lesser extent MHCII, LFA1 (CD11a), and ICAM1 (CD54), was significantly enhanced at the invasion front of control tumors after LITT compared to hepatic resection. CONCLUSIONS: Our results suggest that LITT increases the immune response against untreated intrahepatic tumor tissue, which can lead to reduced tumor growth.     

Duodenal somatostatinoma associated with Von Recklinghausen's disease

Somatostatinomas are rare, malignant, somatostatin-producing neuroendocrine tumors with a prevalence of one in 40 million. The coincidence of Von Recklinghausens disease and duodenal somatostatinoma has been known since 1982. We report the case of a 57-year-old female patient with Von Recklinghausens disease and a tumor of the pancreatic head that was diagnosed due to painless icterus. Histopathological examination after pylorus-preserving pancreatoduodenectomy revealed the existence of a duodenal somatostatinoma with lymph node metastases. Characteristics of the association of von Recklinghausens disease and somatostatinoma, and therapy and prognosis will be discussed. In patients with Von Recklinghausens disease and an ampullary tumor, a somatostatinoma should be considered. In contrast to its pancreatic counterparts, duodenal somatostatinoma is frequently associated with Von Recklinghausens disease, often contains psammoma bodies, is rarely associated with a recognizable somatostatin syndrome, and is hardly ever associated with demonstrable metastases at the time of diagnosis. Small tumors arising in the duodenum may be treated with local excision, whereas larger tumors should be treated by total excision, which may entail a partial pancreatoduodenectomy.     

International health in a globalized development perspective

Eleven issues highlight the relation between globalization and health: