Accumulating data are showing that the humoral immune response against tumors could favor tumor progression. However, no B lymphocyte pathology has been reported in cancer. Using anti-IgM Ab we nonspecifically depleted B cells in tumor-bearing mice, a treatment that resulted in significant reduction of tumor burden. We analyzed the B lymphocyte phenotype of abdominal lymph nodes and peripheral blood from advanced colon cancer patients by flow cytometry, and compared the B cell phenotype with that found in samples from normal donors. In both lymph nodes and peripheral blood of cancer patients, abnormal populations of B lymphocytes appeared that express an increased CD21 and/or sTn antigens on their cell surface. All patients showed a reduction of CD19+ cells. In a limited clinical test, we analyzed the effects of a partial B cell depletion with Rituximab. The treated patients did not develop any side-effects; the CD21-hyperpositive lymphocytes were reduced, but the proportion of sTn-positive lymphocytes remained unaffected. Apparent reduction of the tumor burden was reported in 50% of the patients when the treatment was ended.

Background. The authors compared the therapeutic effects of doxorubicin in two formulations: free in saline suspension and encapsulated in sterically stabilized liposomes composed of hydrogenated soy phosphatidylcholine/2cholesterol/polyethylene glycol‐distearoyl‐phosphatidyl‐ethanolamine (Doxil, Liposome Technology, Inc., Menlo Park, CA). Results. Laser scan microscope and microfluoro‐meter studies showed that the liposome‐encapsulated drug entered the liver, the kidneys, and the tumor in greater quantity and remained in the liver and in the tumor longer than the free drug. The liposome formulation produced a 25‐fold increase in doxorubicin at the disease site. Doxil was significantly more effective than the free drug in inhibiting growth and in effecting cures and had only minor and temporary systemic toxic effects. Conclusions. The current study demonstrated the therapeutic efficacy of doxorubicin, encapsulated in sterically stabilized liposomes, against prostate carcinoma. Decreased systemic elimination, increased penetration into the tumor, and long liposome presence with slow drug release into the tumor probably accounted for the enhanced therapeutic effect of doxorubicin in sterically stabilized liposomes. Cancer 1994; 73:1478–84. Method. The drug formulations were injected intravenously to treat human prostate carcinoma PC‐3, implanted subcutaneously into nude Swiss mice. Confocal laser scan microscopy and microfluorometry were used to determine tissue distribution and to quantitate drug uptake.

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The liver is an important hematopoietic organ during fetal In previous work, two anatomically distinct-liver sinusoid life. After birth, liver hematopoiesis ceases; however, the abilendothelial cells (LEC): LEC-1 and LEC-2, have been deity of the liver to support hematopoiesis can be reestablished scribed. We also reported that extramedullary hepatic hemaunder certain conditions. [1][2][3] In an in vivo experimental model topoiesis occurs only in close contact with LEC-1, suggesting of extramedullary hematopoiesis, we have reported the forthat these cells may provide the microenvironment necessary mation of hematopoietic colonies within the hepatic sinufor the maintenance and growth of hematopoietic cells. In the soids. 4,5 These results indicate that critical hematopoietic mipresent work, we studied the capacity of LEC-1 and LEC-2 croenvironment (HM) components are probably expressed to maintain in vitro hematopoiesis. LEC-1 and LEC-2 were within the liver sinusoids. We have also reported that the isolated and cloned from livers of adult mice. Bone marrow sinusoidal walls of the liver are composed of two kinds of cells (BM) enriched with primitive hematopoietic progenitors liver endothelial cells (LEC), type-1 and type-2 (LEC-1 and were isolated from day-2, post-5-FU-treated mice (5-FUBMC).LEC-2, respectively). 6,7 LEC-1 supported the maintenance and differentiation of he-The formation of hematopoietic foci during liver extramatopoietic progenitors for more than 6 weeks in vitro. In medullary hematopoiesis occurs only in the periportal docontrast, LEC-2 cells poorly supported the proliferation of mains of the liver, in close contact with LEC-1; 4,6,7 that locahematopoietic cells for only two weeks of the co-culture. LECtion suggests the possibility that these LECs may provide 1 and 5-FUBMC cocultures showed cobblestone-area formavarious factors necessary for the maintenance and growth of tion and the presence of hematopoietic progenitors that are the circulating hematopoietic stem cells. This evidence also able to form colonies (CFC) in the adhering fraction after six suggests that in vivo there is a differential capacity to support weeks of coculture. LEC-1 co-cultures treated with a cocktail hematopoiesis by LEC-1 and LEC-2 which are located in the of cytokines (stem cell factor, interleukin [IL] 1 a, IL-3, and hepatic sinusoids. The HM is a complex system composed, Epo) showed that megakaryocyte (CFU-Mk) and erythrocyte mainly, of stromal cells, such as endothelial cells, fibroblasts, progenitors (BFU-e) were present during the entire period of adipocytes, osteoclasts, and monocytes which secrete cytothe culture. Granulocyte-macrophage progenitors (CFU-GM) kines, produce extracellular matrix, and mediate direct celluwere present only during the first three weeks of the culture. lar contact that regulates in vivo and in vitro hematopoieThese results suggest that LEC-1, but not LEC-2, provide an sis. [8][9][10]