human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT In anthroposophical medicine , total extracts of Viscum album ( mistletoe ) have been developed to treat cancer patients . The oldest such product is Iscador . Although Iscador is regarded as a complementary cancer therapy , it is the most commonly used oncological drug in Germany . OBJECTIVE To determine whether Iscador treatment prolongs survival time of patients with carcinoma of the colon , rectum , or stomach ; breast carcinoma with or without axillary or remote metastases ; or small cell or non-small-cell bronchogenic carcinoma ; and to explore synergies between Iscador treatment and psychosomatic self-regulation . DESIGN Prospect i ve nonr and omized and r and omized matched-pair studies nested within a cohort study . SETTING General community in Germany . PARTICIPANTS 10,226 cancer patients involved in a prospect i ve long-term epidemiological cohort study , including 1668 patients treated with Iscador and 8475 who had taken neither Iscador nor any other mistletoe product ( control patients ) . INTERVENTION Iscador . MAIN OUTCOME MEASURE Survival time . RESULTS In the nonr and omized matched-pair study , survival time of patients treated with Iscador was longer for all types of cancer studied . In the pool of 396 matched pairs , mean survival time in the Iscador groups ( 4.23 years ) was roughly 40 % longer than in the control groups ( 3.05 years ; P < .001 ) . Synergies between Iscador treatment and self-regulation manifested in a longer survival advantage for Iscador patients with good self-regulation ( 56 % relative to control group ; P = .03 ) than for patients with poor self-regulation . Results of the 2 r and omized matched-pair studies largely confirmed the results of the non-r and omized studies . CONCLUSION Iscador treatment can achieve a clinical ly relevant prolongation of survival time of cancer patients and appears to stimulate self-regulation BACKGROUND Mistletoe extracts such as Iscador are commonly used as complementary/anthroposophic medications for many cancer indications , particularly for solid cancers . The efficacy of this complementary therapy is still controversial . OBJECTIVE Does long-term therapy with mistletoe extracts Iscador show any effect on survival and psychosomatic self-regulation of patients with ovarian cancer ? PATIENTS AND METHODS Prospect i ve recruitment and long-term follow-up in controlled cohort studies . ( 1 ) Two r and omized matched-pair studies : OvarR and ( ovarian cancer patients without distant metastases ; 21 pairs ) and OvarMetR and ( ovarian cancer patients with distant metastases ; 20 pairs ) ; patients having no mistletoe therapy were matched for prognostic factors . By paired r and om allocation , one of the patients of each pair was suggested therapy with mistletoe extracts Iscador to be applied by her attending physician . ( 2 ) Two non-r and omized matched-pair studies : Ovar ( ovarian cancer patients without distant metastases ; 75 pairs ) and OvarR and ( ovarian cancer patients with distant metastases ; 62 pairs ) ; patients that already received therapy with mistletoe extracts Iscador were matched by the same criteria to control patients without therapy with mistletoe extracts Iscador . RESULTS For overall survival in the r and omized studies , the effect in favor of therapy with mistletoe extracts Iscador was significant in OvarMetR and but not in OvarR and ; hazard ratio estimate and 95 % confidence interval : 0.40 ( 0.15 , 1.03 ) and 0.33 ( 0.12 , 0.92 ) , respectively . In the non-r and omized studies Ovar and OvarMet , the results adjusted for relevant prognostic variables were 0.47 ( 0.31 , 0.69 ) and 0.62 ( 0.37 , 1.05 ) . Psychosomatic self-regulation in the Iscador group increases significantly within 12 months on a scale from 1 to 6 compared with the control group in the r and omized study OvarR and as well as in the non-r and omized study Ovar on patients with ovarian cancer without distant metastases ; estimate of the median difference and 95 % confidence interval : 0.58 ( 0.30 , 0.90 ) and 0.30 ( 0.05 , 0.65 ) , respectively . CONCLUSION Mistletoe extracts Iscador might have the effect of prolonging overall survival of ovarian cancer patients . In the short term , psychosomatic self-regulation increases more markedly under Iscador therapy than under conventional therapy alone OBJECTIVE Various immunological effects have been reported during application of mistletoe preparations . Because these data are heterogeneous , we performed a placebo controlled study to investigate ( 1 ) effects on peripheral granulocyte and eosinophil counts , ( 2 ) related cytokine levels and ( 3 ) whether effects are related to mistletoe lectin ( ML ) . METHODS 43 volunteers were r and omized to receive the mistletoe plant extract Iscador Quercus spezial ( IQ ) , purified ML , IQ which was depleted from ML , or placebo subcutaneously twice per week for 8 weeks . Weekly , differential blood count and every four weeks spontaneous and IQ- and ML-induced cytokine production by peripheral blood mononuclear cells ( P BMC ) were analyzed . RESULTS Leukocyte- , granulocyte- , and eosinophil counts were significantly higher during treatment in the IQ- and ML-groups than in the placebo group . Furthermore , a significant increase of antigen-induced production of GM-CSF , IL-5 and IFNgamma by P BMC was observed in the IQ- and ML-group but not in the groups receiving ML-depleted IQ or placebo .  Severe side effects did not occur in any of the subjects . CONCLUSIONS Treatment with IQ or ML stimulates the production of GM-CSF , IL-5 and IFNgamma by P BMC , and this is accompanied by an increase of eosinophil- and granulocyte-counts . These observations may , therefore , open rational therapeutic indications for mistletoe extracts St and ardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine . A multicentric , r and omized , open , prospect i ve clinical trial was conducted in three oncological centers in the People 's Republic of China in Bejing , Shenyang and Tianjin . Following the guidelines of " Good Clinical Practice " ( GCP ) this study was performed to get information on efficacy safety and side-effects of the st and ardized mistletoe extract ( sME ) .  Two hundred and thirty-three patients with breast ( n=68 ) , ovarian ( n=71 ) and non-small cell lung cancer ( NSCLC ; n=94 ) were enrolled into this study . Two hundred and twenty-four patients fulfilled the requirements for final analysis ( n=115 treated with sME HELIXOR A ; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan ) . All patients were provided with st and ard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol . Biometrically , the patients of the control and sME treatment group were comparable regarding distribution , clinical classification ( WHO ) and treatment protocol s. Analysis was performed according to the " Intention to treat principle " . Quality of life ( QoL ) was significantly ( p<0.05 ) improved for patients who were complementarily treated with sME , as determined by the question naires FLIC ( Functional Living Index-Cancer ) , TCM ( Traditional Chinese Medicine Index ) and the KPI ( Karnofsky Performance Index ) in comparison to the control group . Additionally , the occurrence of adverse events ( AEs ) was less frequent in the sME than in the control group ( total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group , most of them due to chemotherapy ) . Only one serious AE was allocated to complementary treatment in each group ( 1 angioedema in sME group ) . All other side-effects of the sME  ( 7 harmless local inflammatory reactions at subcutaneous injection site , 4 cases with fever ) were self-limiting and did not dem and therapeutic intervention . This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life PURPOSE Adjuvant intravesical immunotherapy with bacillus Calmette-Guerin ( BCG ) for noninvasive superficial bladder cancer has been shown to decrease tumor recurrence significantly . However , serious local and systemic side effects of this treatment have promoted the use of other immunoactive substances , which to date have failed to show efficacy equal to that of BCG immunotherapy . MATERIAL S AND METHODS In the current phase I/II clinical trial an aqueous mistletoe extract st and ardized to mistletoe lectin was administered intravesically to 30 patients with superficial urothelial bladder carcinoma . About 4 weeks after transurethral resection each patient received 6 instillations at weekly intervals of 50 ml extract with mistletoe lectin concentrations between 10 and 5,000 ng/ml , which was retained in the bladder for 2 hours . Three patients per group received a dose , which was then doubled in the next group . Clinical followup consisted of examinations with cystoscopy , cytology and r and om biopsies . To detect cytokines and tumor necrosis factor-p75 receptor venous blood and urine sample s were taken before instillation , and 2 , 6 and 24 hours thereafter . RESULTS The tolerability of intravesically administered mistletoe extract was good at all applied concentrations . None of the patients had local or systemic side effects according to WHO classification 1 - 4 . Within the 12-month observation time study patients with pTa G2 and pT1 G2 tumors showed a recurrence rate of 33 % , comparable to that in a local historical control group of patients with equal stage and grade who were treated with adjuvant BCG . Comparison of urine cytokine levels before instillation , and 2 , 6 and 24 hours thereafter brought about no significant alterations in all measured cytokines . CONCLUSIONS From these results it is concluded that st and ardized mistletoe extract could be a potential alternative adjuvant therapy for superficial bladder cancer . Nevertheless , the optimal intravesical treatment regimen has yet to be defined With the techniques of vital microscopic and reflection spectrometric imaging , representative characteristics of microcirculation and immunology of white blood cells were evaluated before , during and after  radiotherapy and chemotherapy of patients suffering from ear , nose and throat carcinomas .  Adverse effects of radiotherapy and chemotherapy on the microcirculation and the immune system were decreased and reconstitution processes were accelerated by complementary administration of a st and ardized mistletoe extract ( Iscador ) Even though mistletoe extracts have been in clinical use for centuries their exact mode of action is still unknown . Currently , the application scheme for registered preparations is a dose-escalating scheme to thus reduce side effects . In this study , healthy controls and patients were evaluated for their immunologic response to treatment with a st and ardized mistletoe extract ( Iscador ) . It shows a strong effect as adjuvant that induces TNF-α and IL-12 , which was partly mediated via CD14 . Desensitization of the TNF-α response could be shown after repeated application in vitro and in vivo . Furthermore , Iscador induces a specific lymphocyte sensitization upon multiple injections and production of IgG1- and IgG3-mistletoe antibodies . Remarkably , a systemic byst and er effect ( heterologous immunity against other recall antigens ) was observed after long-term treatment . In conclusion , dose-escalation reduces the monocyte-related clinical side effects . A T-lymphocyte sensitization stimulates mainly a specific Th1 response . The most interesting clinical long-term effect is the byst and er stimulation of various memory T cells that might mediate in vivo antitumor and antiinfectious T-cell response under mistletoe-extract immunization Malignant glioma patients were prospect ively enrolled into a clinical trial . All the patients were provided with the internationally recommended oncologic st and ard treatment ( neurosurgery , radiation , basic clinical care according to protocol and indication ) and r and omly divided into a treatment group ( receiving complementary immunotherapy with a galactoside-specific lectin from mistletoe , ML-1 ) and a control group ( without additional complementary treatment ) . Whereas the beneficial effects of ML-1 treatment on immunological rescue and quality of life have been recently shown , evaluation of relapse free/overall survival was performed after a 50 months follow up time . Non-stratified analysis of all the patients revealed non-relevant prolongation of relapse-free intervals/overall survival time for the treatment group . However , analysis of stratified stage III/IV glioma patients demonstrated : 1 . a tendency for a prolongation of relapse-free survival for patients of the treatment group ( 17.43 + /- 8.2 months ) vs. the control group ( 10.45 + /- 3.9 months ) 2 . a statistically significant ( BRESLOW p = 0.035 ) prolongation of the overall survival for the treatment group ( 20.05 + /- 3.5 months ) as compared to the control group ( 9.90 + /- 2.1 months ) . These promising data warrant confirmation in a GCP-based prospect ively r and omized ( multicenter ) study , which is currently under 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT In anthroposophical medicine , total extracts of Viscum album ( mistletoe ) have been developed to treat cancer patients . The oldest such product is Iscador . Although Iscador is regarded as a complementary cancer therapy , it is the most commonly used oncological drug in Germany . OBJECTIVE To determine whether Iscador treatment prolongs survival time of patients with carcinoma of the colon , rectum , or stomach ; breast carcinoma with or without axillary or remote metastases ; or small cell or non-small-cell bronchogenic carcinoma ; and to explore synergies between Iscador treatment and psychosomatic self-regulation . DESIGN Prospect i ve nonr and omized and r and omized matched-pair studies nested within a cohort study . SETTING General community in Germany . PARTICIPANTS 10,226 cancer patients involved in a prospect i ve long-term epidemiological cohort study , including 1668 patients treated with Iscador and 8475 who had taken neither Iscador nor any other mistletoe product ( control patients ) . INTERVENTION Iscador . MAIN OUTCOME MEASURE Survival time . RESULTS In the nonr and omized matched-pair study , survival time of patients treated with Iscador was longer for all types of cancer studied . In the pool of 396 matched pairs , mean survival time in the Iscador groups ( 4.23 years ) was roughly 40 % longer than in the control groups ( 3.05 years ; P < .001 ) . Synergies between Iscador treatment and self-regulation manifested in a longer survival advantage for Iscador patients with good self-regulation ( 56 % relative to control group ; P = .03 ) than for patients with poor self-regulation . Results of the 2 r and omized matched-pair studies largely confirmed the results of the non-r and omized studies . CONCLUSION Iscador treatment can achieve a clinical ly relevant prolongation of survival time of cancer patients and appears to stimulate self-regulation BACKGROUND Mistletoe extracts such as Iscador are commonly used as complementary/anthroposophic medications for many cancer indications , particularly for solid cancers . The efficacy of this complementary therapy is still controversial . OBJECTIVE Does long-term therapy with mistletoe extracts Iscador show any effect on survival and psychosomatic self-regulation of patients with ovarian cancer ? PATIENTS AND METHODS Prospect i ve recruitment and long-term follow-up in controlled cohort studies . ( 1 ) Two r and omized matched-pair studies : OvarR and ( ovarian cancer patients without distant metastases ; 21 pairs ) and OvarMetR and ( ovarian cancer patients with distant metastases ; 20 pairs ) ; patients having no mistletoe therapy were matched for prognostic factors . By paired r and om allocation , one of the patients of each pair was suggested therapy with mistletoe extracts Iscador to be applied by her attending physician . ( 2 ) Two non-r and omized matched-pair studies : Ovar ( ovarian cancer patients without distant metastases ; 75 pairs ) and OvarR and ( ovarian cancer patients with distant metastases ; 62 pairs ) ; patients that already received therapy with mistletoe extracts Iscador were matched by the same criteria to control patients without therapy with mistletoe extracts Iscador . RESULTS For overall survival in the r and omized studies , the effect in favor of therapy with mistletoe extracts Iscador was significant in OvarMetR and but not in OvarR and ; hazard ratio estimate and 95 % confidence interval : 0.40 ( 0.15 , 1.03 ) and 0.33 ( 0.12 , 0.92 ) , respectively . In the non-r and omized studies Ovar and OvarMet , the results adjusted for relevant prognostic variables were 0.47 ( 0.31 , 0.69 ) and 0.62 ( 0.37 , 1.05 ) . Psychosomatic self-regulation in the Iscador group increases significantly within 12 months on a scale from 1 to 6 compared with the control group in the r and omized study OvarR and as well as in the non-r and omized study Ovar on patients with ovarian cancer without distant metastases ; estimate of the median difference and 95 % confidence interval : 0.58 ( 0.30 , 0.90 ) and 0.30 ( 0.05 , 0.65 ) , respectively . CONCLUSION Mistletoe extracts Iscador might have the effect of prolonging overall survival of ovarian cancer patients . In the short term , psychosomatic self-regulation increases more markedly under Iscador therapy than under conventional therapy alone OBJECTIVE Various immunological effects have been reported during application of mistletoe preparations . Because these data are heterogeneous , we performed a placebo controlled study to investigate ( 1 ) effects on peripheral granulocyte and eosinophil counts , ( 2 ) related cytokine levels and ( 3 ) whether effects are related to mistletoe lectin ( ML ) . METHODS 43 volunteers were r and omized to receive the mistletoe plant extract Iscador Quercus spezial ( IQ ) , purified ML , IQ which was depleted from ML , or placebo subcutaneously twice per week for 8 weeks . Weekly , differential blood count and every four weeks spontaneous and IQ- and ML-induced cytokine production by peripheral blood mononuclear cells ( P BMC ) were analyzed . RESULTS Leukocyte- , granulocyte- , and eosinophil counts were significantly higher during treatment in the IQ- and ML-groups than in the placebo group . Furthermore , a significant increase of antigen-induced production of GM-CSF , IL-5 and IFNgamma by P BMC was observed in the IQ- and ML-group but not in the groups receiving ML-depleted IQ or placebo .  Severe side effects did not occur in any of the subjects . CONCLUSIONS Treatment with IQ or ML stimulates the production of GM-CSF , IL-5 and IFNgamma by P BMC , and this is accompanied by an increase of eosinophil- and granulocyte-counts . These observations may , therefore , open rational therapeutic indications for mistletoe extracts St and ardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine . A multicentric , r and omized , open , prospect i ve clinical trial was conducted in three oncological centers in the People 's Republic of China in Bejing , Shenyang and Tianjin . Following the guidelines of " Good Clinical Practice " ( GCP ) this study was performed to get information on efficacy safety and side-effects of the st and ardized mistletoe extract ( sME ) .  Two hundred and thirty-three patients with breast ( n=68 ) , ovarian ( n=71 ) and non-small cell lung cancer ( NSCLC ; n=94 ) were enrolled into this study . Two hundred and twenty-four patients fulfilled the requirements for final analysis ( n=115 treated with sME HELIXOR A ; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan ) . All patients were provided with st and ard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol . Biometrically , the patients of the control and sME treatment group were comparable regarding distribution , clinical classification ( WHO ) and treatment protocol s. Analysis was performed according to the " Intention to treat principle " . Quality of life ( QoL ) was significantly ( p<0.05 ) improved for patients who were complementarily treated with sME , as determined by the question naires FLIC ( Functional Living Index-Cancer ) , TCM ( Traditional Chinese Medicine Index ) and the KPI ( Karnofsky Performance Index ) in comparison to the control group . Additionally , the occurrence of adverse events ( AEs ) was less frequent in the sME than in the control group ( total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group , most of them due to chemotherapy ) . Only one serious AE was allocated to complementary treatment in each group ( 1 angioedema in sME group ) . All other side-effects of the sME  ( 7 harmless local inflammatory reactions at subcutaneous injection site , 4 cases with fever ) were self-limiting and did not dem and therapeutic intervention . This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life PURPOSE Adjuvant intravesical immunotherapy with bacillus Calmette-Guerin ( BCG ) for noninvasive superficial bladder cancer has been shown to decrease tumor recurrence significantly . However , serious local and systemic side effects of this treatment have promoted the use of other immunoactive substances , which to date have failed to show efficacy equal to that of BCG immunotherapy . MATERIAL S AND METHODS In the current phase I/II clinical trial an aqueous mistletoe extract st and ardized to mistletoe lectin was administered intravesically to 30 patients with superficial urothelial bladder carcinoma . About 4 weeks after transurethral resection each patient received 6 instillations at weekly intervals of 50 ml extract with mistletoe lectin concentrations between 10 and 5,000 ng/ml , which was retained in the bladder for 2 hours . Three patients per group received a dose , which was then doubled in the next group . Clinical followup consisted of examinations with cystoscopy , cytology and r and om biopsies . To detect cytokines and tumor necrosis factor-p75 receptor venous blood and urine sample s were taken before instillation , and 2 , 6 and 24 hours thereafter . RESULTS The tolerability of intravesically administered mistletoe extract was good at all applied concentrations . None of the patients had local or systemic side effects according to WHO classification 1 - 4 . Within the 12-month observation time study patients with pTa G2 and pT1 G2 tumors showed a recurrence rate of 33 % , comparable to that in a local historical control group of patients with equal stage and grade who were treated with adjuvant BCG . Comparison of urine cytokine levels before instillation , and 2 , 6 and 24 hours thereafter brought about no significant alterations in all measured cytokines . CONCLUSIONS From these results it is concluded that st and ardized mistletoe extract could be a potential alternative adjuvant therapy for superficial bladder cancer . Nevertheless , the optimal intravesical treatment regimen has yet to be defined With the techniques of vital microscopic and reflection spectrometric imaging , representative characteristics of microcirculation and immunology of white blood cells were evaluated before , during and after  radiotherapy and chemotherapy of patients suffering from ear , nose and throat carcinomas .  Adverse effects of radiotherapy and chemotherapy on the microcirculation and the immune system were decreased and reconstitution processes were accelerated by complementary administration of a st and ardized mistletoe extract ( Iscador ) Even though mistletoe extracts have been in clinical use for centuries their exact mode of action is still unknown . Currently , the application scheme for registered preparations is a dose-escalating scheme to thus reduce side effects . In this study , healthy controls and patients were evaluated for their immunologic response to treatment with a st and ardized mistletoe extract ( Iscador ) . It shows a strong effect as adjuvant that induces TNF-α and IL-12 , which was partly mediated via CD14 . Desensitization of the TNF-α response could be shown after repeated application in vitro and in vivo . Furthermore , Iscador induces a specific lymphocyte sensitization upon multiple injections and production of IgG1- and IgG3-mistletoe antibodies . Remarkably , a systemic byst and er effect ( heterologous immunity against other recall antigens ) was observed after long-term treatment . In conclusion , dose-escalation reduces the monocyte-related clinical side effects . A T-lymphocyte sensitization stimulates mainly a specific Th1 response . The most interesting clinical long-term effect is the byst and er stimulation of various memory T cells that might mediate in vivo antitumor and antiinfectious T-cell response under mistletoe-extract immunization Malignant glioma patients were prospect ively enrolled into a clinical trial . All the patients were provided with the internationally recommended oncologic st and ard treatment ( neurosurgery , radiation , basic clinical care according to protocol and indication ) and r and omly divided into a treatment group ( receiving complementary immunotherapy with a galactoside-specific lectin from mistletoe , ML-1 ) and a control group ( without additional complementary treatment ) . Whereas the beneficial effects of ML-1 treatment on immunological rescue and quality of life have been recently shown , evaluation of relapse free/overall survival was performed after a 50 months follow up time . Non-stratified analysis of all the patients revealed non-relevant prolongation of relapse-free intervals/overall survival time for the treatment group . However , analysis of stratified stage III/IV glioma patients demonstrated : 1 . a tendency for a prolongation of relapse-free survival for patients of the treatment group ( 17.43 + /- 8.2 months ) vs. the control group ( 10.45 + /- 3.9 months ) 2 . a statistically significant ( BRESLOW p = 0.035 ) prolongation of the overall survival for the treatment group ( 20.05 + /- 3.5 months ) as compared to the control group ( 9.90 + /- 2.1 months ) . These promising data warrant confirmation in a GCP-based prospect ively r and omized ( multicenter ) study , which is currently under 
    Output:
    