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1.  Transient myeloproliferative disorder in a newborn with down syndrome treated with rasburicase for the risk of development of tumor lysis syndrome: A case report 
Transient myeloproliferative disorder is a hematologic abnormality characterized by an uncontrolled proliferation of myeloblasts in peripheral blood and bone marrow that primarily affects newborns and babies with Down syndrome. Tumor lysis syndrome is rarely associated with transient myeloproliferative disorder.
Case presentation
Transient myeloproliferative disorder was diagnosed in a seven-day-old baby girl with Down syndrome, who was referred to our department due to hyperleukocytosis. Our patient developed tumor lysis syndrome, successfully treated with rasburicase, as a complication of transient myeloproliferative disorder resulting from rapid degradation of myeloid blasts after initiation of effective chemotherapy.
Tumor lysis syndrome is rarely reported as a complication of transient myeloproliferative disorder. To the best of our knowledge, this is the first case of a newborn with Down syndrome and transient myeloproliferative disorder treated with rasburicase for developing tumor lysis syndrome.
PMCID: PMC3180414  PMID: 21861929
2.  Complement Lysis Activity in Autologous Plasma Is Associated with Lower Viral Loads during the Acute Phase of HIV-1 Infection 
PLoS Medicine  2006;3(11):e441.
To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus.
Methods and Findings
Sera from two groups of patients—25 with acute HIV-1 infection and 31 with chronic infection—were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env) proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies.
Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.
Antibody-mediated complement lysis of HIV virions develops rapidly and is effective already early in the course of HIV infection.
Editors' Summary
If untreated, most people who become infected with the human immunodeficiency virus (HIV) eventually develop acquired immunodeficiency syndrome (AIDS). Over time, HIV infects and kills their CD4 T lymphocytes—immune system cells that stimulate B lymphocytes to make antibodies (proteins that recognize and destroy infectious agents) and that help CD8 T lymphocytes to kill cells that contain viruses and bacteria. The loss of CD4 T lymphocytes—a central player in “adaptive immunity”—leaves patients very susceptible to infections. However, the immune system does not die quietly. It does its best to fight HIV infection by mounting a cell-mediated immune response in which T lymphocytes attack HIV-infected cells. It also mounts a “humoral” immune response in which antibodies that recognize HIV are made. Some of these are neutralizing antibodies, which prevent HIV entering its host cells and replicating. Other antibodies may limit viral spread by inducing destruction of the virus. One way they can do this is by activating another part of the immune system called the complement system, which can break open and kill viruses (this is known as antibody-mediated complement lysis). In addition, antibodies and complement can coat the HIV virus particles so that phagocytes (for instance macrophages—yet another type of immune system cell) engulf and destroy the virus.
Why Was This Study Done?
The role that humoral immunity plays in fighting HIV infection is complex and poorly understood. In particular, it is not clear whether the complement system helps to stop the spread of HIV or whether it inadvertently helps it to spread by facilitating its entry into host cells. It is important to understand as much as possible about the humoral immune response to HIV infection so that vaccines can be designed to provide maximum protection against HIV. In this study, the researchers have investigated whether antibody-mediated complement lysis controls the amount of virus in the blood of patients infected with HIV.
What Did the Researchers Do and Find?
The researchers collected plasma (the liquid part of blood that contains circulating antibodies) from patients recently infected with HIV (acute infection) and patients who had been infected for some time (chronically infected). They also isolated HIV from each of the patients—so-called autologous virus. They then used a sensitive molecular biology assay to test each plasma sample for its ability to lyse the autologous virus (and also a standard virus) when supplied with complement from a healthy donor. Most of the plasma samples were able to lyse HIV, although the samples taken from chronically infected patients generally caused more lysis than those from acutely infected patients. In the chronically infected patients, the level of lysis induced was not related to the amount of virus in the patients' blood (viremia). However, plasma taken from acutely infected patients with higher viral loads was less active in the lysis assay than plasma taken from patients with lower viral loads. Finally, the researchers showed that the levels of antibodies in the various plasma samples to the two envelope proteins of HIV correlated strongly with the ability of each sample to lyse the standard virus and that these antibodies were mainly non-neutralizing antibodies.
What Do These Findings Mean?
By showing that antibody-mediated complement lysis of HIV in the laboratory is inversely related to the patients' viral loads during acute infection, these findings suggest (but do not prove) that antibody-mediated complement lysis of HIV contributes to the control of viremia early in HIV infections. But, the importance of this form of humoral immunity in combating HIV infections remains uncertain, since complement has the potential to enhance as well as block viral spread. Further work is needed to unravel which of these effects is dominant in patients and to characterize fully the antibodies that activate complement. Nevertheless, the results of this study suggest that complement-activating antibodies should be considered in future attempts to design an effective HIV vaccine.
Additional Information.
Please access these Web sites via the online version of this summary at
National Institute of Allergy and Infectious Diseases fact sheet on HIV infection and AIDS
US Department of Health and Human Services information on AIDS, including information on vaccines
US Centers for Disease Control and Prevention information on HIV/AIDS
Aidsmap information on HIV and the immune system provided by the charity NAM
Wikipedia pages on the complement system (note: Wikipedia is a free online encyclopedia that anyone can edit)
PMCID: PMC1637124  PMID: 17121450
3.  Hyperuricemia and acute kidney injury secondary to spontaneous tumor lysis syndrome in low risk myelodysplastic syndrome 
BMC Nephrology  2014;15(1):164.
This is a rare instance of acute kidney injury caused by hyperuricemia due to spontaneous tumor lysis syndrome and also the first case of spontaneous tumor lysis syndrome reported in association with myelodysplastic syndrome.
Case presentation
A 53-year-old man presented with abrupt oliguria. Laboratory findings on admission included hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis and rapidly rising serum creatinine, which were consistent with acute tumor lysis syndrome in the absence of precipitating chemotherapy or radiotherapy. After hemodialysis and oral uric acid lowering therapy, serum uric acid levels returned to normal range and renal function rapidly recovered. The patient was diagnosed as myelodysplastic syndrome eleven months later.
Occult malignancy including solid tumors and hematological malignancies should be carefully evaluated in the case of unexplainable acute kidney injury with hyperuricemia. Aggressive investigations should be thoroughly considered and repeated in this population.
PMCID: PMC4209058  PMID: 25304761
Acute kidney injury; Hyperuricemia; Myelodysplastic syndrome; Spontaneous tumor lysis syndrome
4.  Spontaneous acute tumor lysis syndrome with advanced gastric cancer. 
Journal of Korean Medical Science  2001;16(1):115-118.
Acute tumor lysis syndrome (TLS) occurs frequently in hematologic malignancies such as high-grade lymphomas and acute leukemia, which are rapidly proliferating and chemosensitive tumors. It occurs rarely in solid tumors and has never been reported in gastric adenocarcinoma. Typical biochemical findings of acute tumor lysis syndrome are hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia in patients with a malignancy. Rapid changes of these electrolytes may cause cardiac arrhythmia, seizure, acute renal failure and sudden death. Therefore, as soon as it is detected, it should be taken care of immediately. Until now almost all cases of TLS associated with solid tumor have developed after cytoreductive therapy in chemosensitive tumors. We report here a case of spontaneous acute tumor lysis in a patient of advanced gastric cancer with hepatic metastases and multiple lymphadenopathy. The biochemical finding of TLS improved with the management and tumor burden also showed slight response to the one cycled combination chemotherapy but the patient died of progressive pneumonia.
PMCID: PMC3054572  PMID: 11289389
5.  Hyperuricemic Renal Failure in Nonhematologic Solid Tumors: A Case Report and Review of the Literature 
Case Reports in Medicine  2012;2012:314056.
Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive tumor cell lysis. It is commonly associated with hematological cancers like leukemia and lymphoma and uncommonly with solid nonhematologic tumors as well. However, spontaneous tumor lysis syndrome (STLS) without any cytotoxic chemotherapy rarely occurs in solid tumors. We describe a case of STLS in a metastatic adenocarcinoma of unknown primary and review the literature of STLS in solid non-hematologic tumors to identify various risk factors for pathogenesis of this entity.
PMCID: PMC3368227  PMID: 22693518
6.  Prevention and Management of Tumor Lysis Syndrome in Adults With Malignancy 
Tumor lysis syndrome (TLS), an oncologic emergency that typically occurs after the treatment of a malignancy with chemotherapy and/or radiotherapy, is the result of extreme tumor cell lysis with the release of intracellular potassium, nucleic acids, and phosphorus into the systemic circulation. Tumor lysis syndrome occurs most often after administration of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukemia, but it can also occur spontaneously in tumor types that have a high proliferative rate and/or a large tumor burden. The metabolic disturbances of TLS include hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute renal failure. The most important treatment for TLS is prevention. The mainstays of TLS prevention include aggressive hydration, control of hyperuricemia with allopurinol and rasburicase treatment, and close monitoring of electrolyte abnormalities. It is crucial for clinicians to prevent, detect, and treat TLS early to prevent life-threatening complications such as acute renal failure, cardiac dysrhythmia, and seizures. The purpose of this article is to explain the pathophysiology of TLS, identify patients at risk for TLS, and detail strategies for prevention and management of this oncologic emergency.
PMCID: PMC4093415  PMID: 25031988
7.  Rasburicase (Elitek): a novel agent for tumor lysis syndrome 
The overall incidence of tumor lysis syndrome in adults is not well defined, and its occurrence can be unpredictable. Several strategies are available for the prevention and treatment of tumor lysis syndrome, with rasburicase being the most recent. Rasburicase is a recombinant urate oxidase enzyme approved for use by the Food and Drug Administration in patients who are at risk of developing tumor lysis syndrome or for the management of elevated uric acid levels. Clinical trials have demonstrated rasburicase to be effective in both the pediatric and adult populations, although the drug is currently indicated only for use in the pediatric population. Adverse effects associated with rasburicase can be significant, ranging from anaphylactic reactions to methemoglobinemia. To ensure accuracy of uric acid test results, special laboratory handling procedures must be followed while patients receive rasburicase. Compared with allopurinol and intravenous sodium bicarbonate, rasburicase is costly, and therefore judicious use of the medication is warranted.
PMCID: PMC1200736  PMID: 16200184
8.  Activation of Monocyte and Granulocyte Antibody-Dependent Cytotoxicity by Phorbol Myristate Acetate 
Infection and Immunity  1982;35(3):818-825.
We have characterized the effects of phorbol myristate acetate (PMA) on human monocyte and neutrophil oxidative metabolism and antibody-dependent cytotoxicity toward anti-D sensitized human erythrocytes (RBC) and a human lymphoblastoid cell line (CEM). Hexose monophosphate shunt activity was measured by [1-14C]glucose oxidation and target lysis by 51Cr release. PMA produced a dose-dependent stimulation of hexose monophosphate shunt activity. Neutrophils responded with higher hexose monophosphate shunt activity and at a lower PMA concentration than did monocytes. PMA increased monocyte lysis of antibody-sensitized RBC by two-thirds, but did not affect lysis of CEM targets. Neutrophils were unable to lyse either antibody-sensitized or nonsensitized RBC without the addition of PMA. When PMA was added, lysis of both targets increased markedly. Neutrophils without PMA were able to lyse a small number of both antibody-sensitized and nonsensitized CEM targets. PMA also increased neutrophil lysis of these targets. Target lysis by neutrophils from a patient with chronic granulomatous disease, cells unable to produce reactive oxygen species, was not increased by PMA. Chronic granulomatous disease monocytes, however, responded to PMA by more than doubling lysis of antibody-sensitized RBC. Hypoxia inhibited PMA augmentation of antibody-sensitized RBC lysis by neutrophils, but not by monocytes. Generation of reactive oxygen species by the xanthine-xanthine oxidase system inhibited CEM growth, but did not cause lysis, indicating that in some cases oxidative injury may be nonlytic. We suggest that PMA augments neutrophil cytotoxicity to tumor and RBC targets by stimulating reactive oxygen species-mediated lysis, but in monocytes augmentation of lysis is due to activation of a nonoxidative mechanism of lysis.
PMCID: PMC351121  PMID: 7068217
9.  Tumor Lysis Syndrome in a Patient with Metastatic Colon Cancer after Treatment with 5-Fluorouracil/Leucovorin and Oxaliplatin: Case Report and Literature Review 
Development of tumor lysis syndrome (TLS) may occur after chemotherapy or spontaneously in bulky or rapidly growing tumors. This syndrome is frequent but preventable in patients with hematologic malignancies. TLS following therapy has been reported infrequently in various types of solid tumors. TLS associated with oxaliplatin containing chemotherapy in a solid tumor has never been reported. A 59-year-old man received 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy for metastatic colon cancer. Development of TLS occurred three days after administration of chemotherapy. Two days later, his abnormal laboratory findings were recovered with appropriate management. To the best of our knowledge, the current case is the first report on development of acute TLS following oxaliplatin containing chemotherapy in a patient with colon cancer. We also review the literature on tumor lysis syndrome in patients with colorectal cancer.
PMCID: PMC4022831  PMID: 24851114
Tumor lysis syndrome; Oxaliplatin; Colon
10.  Severe acute tumor lysis syndrome in patients with germ-cell tumors 
Germ-cell tumors are a high-proliferative type of cancer that may evolve to significant bulky disease. Tumor lysis syndrome is rarely reported in this setting. The reports of three patients with germ-cell tumors who developed severe acute tumor lysis syndrome following the start of their anticancer therapy are presented. All patients developed renal dysfunction and multiorgan failure. Patients with extensive germ-cell tumors should be kept on close clinical and laboratory monitoring. Physicians should be aware of this uncommon but severe complication and consider early admission to the intensive care unit for the institution of measures to prevent acute renal failure.
PMCID: PMC2684391  PMID: 19468517
Acute renal failure; germ-cell tumors; tumor lysis syndrome
11.  Spontaneous Tumor Lysis Syndrome in the Setting of B-Cell Lymphoma 
Case Reports in Medicine  2010;2010:610969.
Tumor lysis syndrome (TLS) presenting in absence of chemotherapy is a rare occurrence. One of the true oncological emergencies, it can lead to significant morbidity and mortality. TLS is a phenomena usually associated with tumor cell death after treatment. The etiology of the spontaneous TLS is not well understood, which complicates the diagnosis. TLS is well known to oncologists but physicians outside of this specialty have little or no experience with this condition. Early recognition and treatment are the keys to limiting the sequela of the condition. Spontaneous tumor lysis syndrome is rare but presents added risks to the patient because of the potential for delayed diagnosis and no benefit of pretreatment. Diagnosis may be further delayed because this may be the first symptom of underlying malignancy. Therefore, it is imperative that all clinicians are familiar with the syndrome to assure timely recognition.
PMCID: PMC2836528  PMID: 20300188
12.  Tumor lysis syndrome associated with chemotherapy in primary retroperitoneal soft tissue sarcoma by ex vivo ATP-based tumor chemo-sensitivity assay (ATP-TCA) 
Tumor lysis syndrome (TLS), a result of rapid cell lysis following tumor therapy, is a well recognized complication during the treatment of rapidly growing tumors. TLS rarely occurs in solid tumors. We present a case report of TLS in a patient with primary retroperitoneal soft tissue sarcoma. TLS occurred in the patient after four days’ combinational chemotherapy with cisplatin, adriamycin, and dacarbazine. These drugs were selected on the basis of an ex vivo ATP-based tumor sensitivity assay. TLS was properly controlled in the patient with concomitant remission of the sarcoma. Therefore, precautions should be taken to avoid this potentially fatal complication during treatment of solid tumors, especially with tumors highly sensitive to drugs.
PMCID: PMC2840581  PMID: 20360879
tumor lysis syndrome; retroperitoneal soft tissue sarcoma; ATP-based tumor sensitivity assay (ATP-TCA)
13.  Tumor lysis syndrome developing intraoperatively 
Tumor lysis syndrome is a potentially life threatening condition which is most commonly encountered in patients being treated with chemotherapy. We report a case of spontaneous tumor lysis syndrome that developed intraoperatively in a patient with undiagnosed Burkitt's lymphoma. Characteristic electrolyte disturbances and white emulsion like urine following laparotomy and tumor handling intraoperatively suggested the diagnosis. This is a rare perioperative complication and the report emphasizes the importance of being vigilant in recognizing the same.
PMCID: PMC3214572  PMID: 22096300
Continuous venous-venous hemodialysis; Burkitt lymphoma; intraoperatively; tumor lysis syndrome; ventricular arrhythmia
14.  Tumor Lysis Syndrome in a Solid Tumor: A Case Report of a Patient with Invasive Thymoma 
Tumor lysis syndrome (TLS) has rarely been observed in solid tumors. We report on a case of a patient with advanced invasive thymoma who developed tumor lysis syndrome after chemotherapy. The potential complications of TLS should be considered in treatment of extensive thymoma.
PMCID: PMC3893332  PMID: 24454007
Thymoma; Drug therapy; Tumor lysis syndrome; Hyperuricemia; Acute kidney injury
15.  Pitfalls, prevention, and treatment of hyperuricemia during tumor lysis syndrome in the era of rasburicase (recombinant urate oxidase) 
Biologics : Targets & Therapy  2008;2(1):129-141.
Along with hydration and urinary alkalinization, allopurinol has been the standard agent for the management of hyperuricemia in patients with a high tumor burden at risk of tumor lysis syndrome; however, this agent often fails to prevent and treat this complication effectively. Rasburicase (recombinant urate oxidase) has been shown to be effective in reducing uric acid and preventing uric acid accumulation in patients with hematologic malignancies with hyperuricemia or at high risk of developing it. Rasburicase acts at the end of the purine catabolic pathway and, unlike allopurinol, does not induce accumulation of xanthine or hypoxanthine. Its rapid onset of action and the ability to lower pre-existing elevated uric acid levels are the advantages of rasburicase over allopurinol. Rasburicase represents an effective alternative to allopurinol to promptly reduce uric acid levels, improve patient’s electrolyte status, and reverse renal insufficiency. The drug, initially studied in pediatric patients with acute lymphoblastic leukemia and aggressive non-Hodgkin lymphoma, seems to show comparable benefit in adults with similar lymphoid malignancies or at high risk of tumor lysis syndrome. Current and future trials will evaluate alternative doses and different schedules of rasburicase to maintain its efficacy while reducing its cost. The review provides a comprehensive and detailed review of pathogenesis, laboratory, and clinical presentation of TLS together with clinical studies already performed both in pediatric and adult patients.
PMCID: PMC2727789  PMID: 19707436
tumor lysis syndrome; urate oxidase; rasburicase; allopurinol; uric acid
16.  Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia 
The New England Journal of Medicine  2011;365(8):725-733.
We designed a lentiviral vector expressing a chimeric antigen receptor with specificity for the B-cell antigen CD19, coupled with CD137 (a costimulatory receptor in T cells [4-1BB]) and CD3-zeta (a signal-transduction component of the T-cell antigen receptor) signaling domains. A low dose (approximately 1.5×105 cells per kilogram of body weight) of autologous chimeric antigen receptor–modified T cells reinfused into a patient with refractory chronic lymphocytic leukemia (CLL) expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo, with delayed development of the tumor lysis syndrome and with complete remission. Apart from the tumor lysis syndrome, the only other grade 3/4 toxic effect related to chimeric antigen receptor T cells was lymphopenia. Engineered cells persisted at high levels for 6 months in the blood and bone marrow and continued to express the chimeric antigen receptor. A specific immune response was detected in the bone marrow, accompanied by loss of normal B cells and leukemia cells that express CD19. Remission was ongoing 10 months after treatment. Hypogammaglobulinemia was an expected chronic toxic effect.
PMCID: PMC3387277  PMID: 21830940
17.  Acute Kidney Injury in Lymphoma: A Single Centre Experience 
Background. Acute kidney injury (AKI) is a common but least studied complication of lymphoma. Objective. To determine the frequency and predictors of AKI in lymphoma and to study the impact of AKI on hospital stay and mortality. Methods. Retrospective review of medical records of hospitalized lymphoma patients aged ≥14 years between January 2008 and December 2011 was done. Results. Out of 365 patients, AKI was present in 31.8% (116/365). Multivariate logistic regression analysis showed that independent predictors for AKI included sepsis (odds ratio (OR) 3.76; 95% CI 1.83–7.72), aminoglycosides (OR 4.75; 95% CI 1.15–19.52), diuretics (OR 2.96; 95% CI 1.31–6.69), tumor lysis syndrome (OR 3.85; 95% CI 1.54–9.59), and R-CVP regimen (OR 4.70; 95% CI 1.20–18.36). AKI stages 2 and 3 was associated with increased hospital stay (OR 2.01; 95% CI 1.19–3.40). Conclusion. AKI was significantly associated with sepsis, aminoglycoside, diuretics, presence of tumor lysis syndrome, and use of R-CVP regimen. Presence of AKIN (Acute Kidney Injury Network) stages 2 and 3 AKI had increased hospital stay. AKI was also associated with increased mortality.
PMCID: PMC3930139  PMID: 24639896
18.  Tumor lysis without syndrome in adenocarcinoma of the lung: Case report 
Tumor lysis syndrome TLS is commonly seen during the treatment of rapidly proliferating. However TLS is rarely reported in Non-small cell Lung Cancer. This may because of low proliferative rate and chemo-resistant nature of NSCLC. We are reporting a case of tumor lysis without concomitant syndrome in a patient with adenocarcinoma of Lung.
PMCID: PMC3920411
Tumor lysis; Adenocarcinoma; Cyst
19.  A case of gouty arthritis following percutaneous radiofrequency ablation for hepatocellular carcinoma 
Percutaneous radiofrequency thermal ablation (RFA) is considered an effective technique for providing local control in the majority of Hepatocellular carcinoma (HCC) patients. Although RFA is generally well tolerated, recent studies have reported complications associated with RFA. We describe a case of acute gouty arthritis in a 71-year-old man with chronic renal failure who was treated with RFA for a HCC lesion and who had hepatitis B-associated cirrhosis and mild renal insufficiency. Regular surveillance of the patient detected a 3.5 cm HCC lesion. Because the patient had declined surgery, RFA was chosen for therapy. On the third post-procedural day, the laboratory results showed increases in his uric acid and potassium levels, which were compatible with a tumor lysis syndrome. On the 6th post-procedural day, the patient complained of new right knee pain. Subsequent joint aspiration revealed monosodium urate monohydrate crystals. We made the diagnosis of acute gouty arthritis arising from tumor lysis and liver infarction caused by HCC ablation, which was aggravated by acute renal insufficiency. After adequate hydration and administration of oral colchicines, the patient’s right knee pain subsided and the uric acid serum level returned to normal. This is the first described case of acute gouty arthritis after RFA for a HCC lesion in a patient with underlying chronic renal insufficiency. To avoid hyperuricemia and an acute attack of gout after RFA therapy for HCC, early identification of patients at risk is warranted, such as those with a large tumor, rapid tumor growth, and renal insufficiency, and preventative measures should be considered.
PMCID: PMC2817069  PMID: 20135729
Radiofrequency thermal ablation; Hepatocellular carcinoma; Gout; Tumor lysis syndrome; Complications
20.  Tumor cell anti-oxidant defenses. Inhibition of the glutathione redox cycle enhances macrophage-mediated cytolysis 
The basis of resistance to oxidative injury was studied in six murine tumor cell lines that differed 54-fold in their resistance to enzymatically generated H(2)0(2). The tumors varied 56.7-fold in their specific activity of catalase, 5.3-fold in glutathione peroxidase (GPO), 3.3-fold in glutathione reductase (GR), and 2.7-fold in glutathione. There was no correlation among the levels of the three enzymes, and tumor cell resistance to lysis by H(2)0(2). However, the logarithm of the flux of H(2)0(2) necessary to cause 50 percent lysis of the tumor cells correlated with their content of glutathione (r = 0.91). The protective role of glutathione was analyzed by blocking GR and GPO, the catalysts of the glutathione redox cycle. This was facilitated by the demonstration that the anti-neoplastic agent 1,3-bis-(2- chloroethyl)-l-nitrosourea (BCNU) was a potent inhibitor of GR in intact tumor cells. BCNU inactivated tumor cell GR with a 50 percent inhibitory dose of 11 μM and a t(l/2) of inhibition of 30 s. Complete inhibition of GR was attained with no effect on GPO or catalase. Tumor cells whose GR was inactivated by BCNU could be lysed by fluxes of H(2)0(2) to which they were otherwise completely resistant. They could be killed by phorbol myristate acetate (PMA)-stimulated, bacilli Calmette-Guerin-activated macrophages in numbers which were otherwise insufficient, and by nonactivated macrophages, which otherwise were ineffective. BCNU-treated target cells were also much more sensitive to antibody-dependent, macrophage-mediated cytolysis. However, such tumor cells were no more sensitive than controls to lysis by alloreactive T cells or by antibody plus complement. Next, we deprived tumor cells of selenium by passage in selenium-deficient mice. GPO was inhibited 85 percent in such cells, with no effect on GR or catalase. Tumor cells with reduced GPO activity were markedly sensitized to lysis by small fluxes of H(2)0(2) or by PMA-stimulated macrophages or granulocytes. In contrast, inhibition of catalase with aminotriazole had no effect on the sensitivity of three tumors to peroxide-mediated lysis, and had modest effects with two others. Thus, the oxidation-reduction cycle of glutathione serves as one of the major defense mechanisms of tumor cells against three related forms of oxidant injury: lysis by fluxes of H(2)0(2), by PMA-triggered macrophages, and by macrophages in the presence of anti-tumor antibody.
PMCID: PMC2186135  PMID: 7252413
21.  Bacteriolytic therapy of experimental pancreatic carcinoma 
AIM: To investigate the effectiveness of Clostridium novyi (C. novyi)-NT spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic, immunocompetent Panc02/C57Bl/6 model.
METHODS: C. novyi-NT spores were applied intravenously to animals carrying established pancreatic tumors of three different sizes. Systemic immune responses in peripheral blood and spleen were examined by flow cytometry. Supplementary, cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed.
RESULTS: Application of spores identified, that (1) small tumors (< 150 mm3) were completely unaffected (n = 10); (2) very large tumors (> 450 mm3) responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n = 6); and (3) an optimal treatment window exists for tumors of approximately 250 mm3 (n = 21). In this latter group, all tumor-bearing animals had complete tumor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed (tumor volume at day 28: 197.8 ± 87.3 mm3 vs 500.1 ± 50.9 mm3, P < 0.05). These effects were accompanied by systemic activation of immune response mechanisms predominantly mediated by the innate arm of the immune system.
CONCLUSION: The observed complete tumor regression is encouraging and shows that immunotherapy with C. novyi-NT is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes.
PMCID: PMC2909554  PMID: 20653063
Bacteriolytic immunotherapy; Clostridium novyi-NT; Immune response; Pancreatic carcinoma
22.  Emerging role of rasburicase in the management of increased plasma uric acid levels in patients with hematologic malignancies 
Tumor lysis syndrome (TLS) is defined as a group of metabolic derangements that result from the massive and abrupt release of cellular components into the bloodstream after rapid lysis of tumor cells. Breakdown of released materials leads to a number of electrolyte abnormalities, including elevated uric acid concentrations in the blood (hyperuricemia), which carries potentially serious consequences. The diagnosis, prevention, and management of TLS is complicated by variability in definitions, differences in risk factors based on patient- and tumor-specific characteristics, and practitioner preferences in terms of pharmaceutical management strategies. The best prevention and management option for a particular patient depends on the patient’s baseline risk for TLS development, the severity of symptoms in the event of TLS development, practical management considerations, and financial implications of treatment.
PMCID: PMC3262356  PMID: 22287858
tumor lysis syndrome; uric acid; rasburicase
23.  Tumor lysis and acute renal failure in Burkitt's lymphoma: A review on pathophysiology and management 
Indian Journal of Nephrology  2009;19(3):83-86.
Morbidity and mortality in patients with hematologic malignancies are significantly increased by development of acute renal failure. This is more likely in the developing world where facilities for renal replacement therapy are scarce. This review discusses the pathophysiology of acute renal failure due to tumor lysis syndrome in patients with Burkitt's lymphoma, the commonest hematological malignancy in the pediatric age group in sub-Saharan Africa, and evaluates the possible management options. Tumor lysis can also develop in association with other hematologic malignancies, both spontaneously and following treatment, and these principles are applicable in all such cases.
PMCID: PMC2859483  PMID: 20436725
Acute renal failure; tumor lysis syndrome; Burkitt's lymphoma; hematologic malignancies; lymphoma; leukemia; management
24.  Tumor lysis syndrome in multiple myeloma treated with bortezomib 
A 65 year old male diagnosed as multiple myeloma was started on bortezomib developed tumor lysis syndrome. Bortezomib induced tumor lysis is rare and suitable precautions should be considered in these patients.
PMCID: PMC4008916  PMID: 24799821
Bortezomib; multiple myeloma; tumor lysis syndrome
25.  Reduction in susceptibility to natural killer cell-mediated lysis of human FO-1 melanoma cells after induction of HLA class I antigen expression by transfection with B2m gene. 
Journal of Clinical Investigation  1991;88(1):282-289.
Induction of HLA class I antigens on cultured melanoma cells FO-1 after transfection with a human or a mouse B2m gene was associated with a statistically significant reduction in their susceptibility to natural killer (NK) cell-mediated lysis. These results indicate that the structural differences between human and mouse beta 2-mu do not abolish the ability of the HLA class I molecular complex to modulate NK cell-mediated lysis of melanoma cells FO-1. The role of HLA class I antigens in the phenomenon is corroborated by the ability of anti-HLA class I MAb to enhance, although to a different extent, the susceptibility of transfected FO-1 cells to NK cell-mediated lysis. Gamma interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) significantly reduced the susceptibility to NK cell-mediated lysis of transfected FO-1 cells. Surprisingly, TNF-alpha reduced the extent of lysis more than IFN-gamma, although the latter cytokine enhanced HLA class I antigen expression more than the former one. This finding, in conjunction with a reduction in the susceptibility to NK cell-mediated lysis of untransfected FO-1 cells incubated with IFN-gamma or TNF-alpha, suggests that the two cytokines reduce NK cell-mediated lysis of transfected cells by modulating not only the expression of HLA class I antigens, but also that of other structures. Induction of HLA class I antigens and their modulation with IFN-gamma did not affect the susceptibility to lymphokine-activated killer (LAK) cell-mediated lysis of transfected FO-1 cells. Characterization of the molecular mechanism(s) underlying abnormalities in HLA class I antigen expression by melanoma cells and of the role of these molecules in the interactions of melanoma cells with various types of effector cells may suggest novel immunotherapeutic approaches to melanoma.
PMCID: PMC296030  PMID: 1905328

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