Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice bearing the immunosuppressive plasmacytoma TEPC-183 exhibit a marked splenic hyperplasia. We have characterized these tumor-reactive splenocytes on the basis of cell surface marker expression, nonspecific esterase activity, and morphology. Although splenocyte numbers increased progressively throughout tumor growth, B- and T-lymphocytes, as defined by surface immunoglobulin and Thy-1 antigen expression, respectively, did not increase significantly. Fourteen days after tumor implantation, T-lymphocytes decreased from 70 million to 50 million per spleen. However, cells expressing Mac-1 antigen or nonspecific esterase activity increased from 10 to 65 million. This constituted a 6-fold increase in splenic macrophages. Further studies utilizing the expression of PC.2 antigen in conjunction with morphological examination indicated that metastatic TEPC-183 cells comprise approximately 5% of the tumor-host splenocyte population 14 days after implantation. Ablation of plasmacytoma by cyclophosphamide inhibited the tumor-associated splenocytosis and led to an increase in splenic T-cells (from 70 to 120 million). In addition, macrophage numbers returned to normal. This study also assessed the ability of splenocytes from animals with either actively growing tumors or those from cyclophosphamide-treated tumor-bearing mice to mediate an antitumor response. Splenocytes, when assessed 1 wk following tumor ablation by cyclophosphamide, demonstrated antitumor activity in Winn neutralization assays. This activity was not detectable in splenocytes from animals with progressively growing tumors. Additional studies revealed that the cell population involved in the antitumor effect was glass nonadherent, nylon-wool nonadherent, and expressed Thy-1 antigen. These observations were consistent with the expansion of the splenic T-lymphocyte population following cyclophosphamide treatment. However, the immune response directed against primary TEPC-183 tumor cells was not inhibitory to metastatic tumor cells.
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PMID:Cellular changes and antitumor responses in the plasmacytoma-bearing mouse following cyclophosphamide treatment. 286 30

Tumor-selective oncolytic vesicular stomatitis viruses (VSVs) are being evaluated in clinical trials. Here, we report that the MPC-11 murine plasmacytoma model is so extraordinarily susceptible to oncolytic VSVs that a low dose of virus leads to extensive intratumoral viral replication, sustained viremia, intravascular coagulation, and a rapidly fatal tumor lysis syndrome (TLS). Rapid softening, shrinkage and hemorrhagic necrosis of flank tumors was noted within 1-2 days after virus administration, leading to hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, increase in plasma cell free DNA, lymphopenia, consumptive coagulopathy, increase in fibrinogen degradation products, decreased liver function tests, dehydration, weight loss, and euthanasia or death after 5-8 days. Secondary viremia was observed but viral replication in normal host tissues was not detected. Toxicity could be mitigated by using VSVs with slowed replication kinetics, and was less marked in animals with smaller flank tumors. The MPC-11 tumor represents an interesting model to further study the complex interplay of robust intratumoral viral replication, tumor lysis, and associated toxicities in cases where tumors are highly responsive to oncolytic virotherapy.
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PMID:Robust Oncolytic Virotherapy Induces Tumor Lysis Syndrome and Associated Toxicities in the MPC-11 Plasmacytoma Model. 2766 55