[Multimorbidity and multi-target-therapy with herbal drugs]. / Multimorbidität und Multi-Target-Therapie in der Phytotherapie.

The active components of herbal drugs and substances are pleiotropic multi-ingredient compounds with multitarget properties including antiinflammatory effects. A pleiotropic inhibition of inflammation could play an important role in mutlimorbide patients as an attempt of prevention or retardation of metastasis. A large number of experimental data for European and non-European herbal drugs as well as various herbal drug combinations suggest such a possibility. Despite the so far small number of clinical studies, such an experimental herbal treatment could appear to be reasonable and acceptable, provided that there are data available on quality and safety of these herbal drugs by treatments of patients with various diseases. Besides, herbal drugs and substances play a growing role the treatment of patients with multimorbidity. Many of these herbal drugs have antiinflammatory effects beside their proved symptomatic efficacy in a lot of other diseases. The specific selection of herbal drugs that are efficacious in specific indications and additionally showed antiinflammatory effects offers the possibility of simultaneous antiinflammatory and specific efficacy. St. John's Wort and milk thistle belong to the oldest and to the best experimentally and clinically examined herbal remedies. The spectrum of internal and external uses of Hypercum perforatum as a multicompound herbal drug includes functional gastro-intestinal complaint and illness, skin disease, mucosal lesion, superficial injury, depressive upset and depression, somatoform disorders, restlessness, nervosity, convalescence, exhaustion and sleep disturbances respectively. The plurivalent character of the multicompound even enables a broad spectrum of activity. This might justify to prefer St. John's Wort to other drugs in a wide range of treatments: In multimorbide patients with depression or in depressive patients with coronary heart disease the anti-inflammatory effects could mean an additional advantage. However, at present there is still a great need and demand for therapy-oriented clinical research.

Reduction of behavioural disturbances in elderly dogs supplemented with a standardised Ginkgo leaf extract.

In this open clinical trial conducted in 10 veterinary practices, Ginkgo leaf extract was administered as a dietary supplement to 42 elderly dogs (mean age 11.4 years) at a daily dose of 40 mg/ 10 kg body weight for 8 weeks. The "severity of the geriatric condition" in dogs with a history of geriatric behavioural disturbances (mean duration 12 months), was significantly reduced after 8 weeks of treatment (P = 0.0002). The positive effect was already apparent after 4 weeks. Thirty-six % of the dogs were completely free of clinical signs at study end. Overall efficacy of treatment as judged by the investigator was good or very good in 79% of the dogs. Five of six clinical sign scores (disorientation, sleep/activity changes, behavioural changes, general behaviour and general physical condition/vitality) also showed a significant decrease over the treatment period. In conclusion, these findings provide promising results that could increase the quality of life in the elderly dog and, as a consequence, that of the pet owner. The Ginkgo leaf extract appears to be an efficacious agent that provides a safe dietary supplement for the elderly dog with age-related behavioural disturbances.

Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia.

BACKGROUND: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. PATIENTS AND METHODS: Sixty otherwise healthy subjects with total cholesterol > or = 5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. RESULTS: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area undercurve: 5.29 +/- 1.62 to 4.99 +/- 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 +/- 1.88 to 5.18 +/- 1.78, p > 0. 1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. CONCLUSIONS: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

Topical tea tree oil effective in canine localised pruritic dermatitis--a multi-centre randomised double-blind controlled clinical trial in the veterinary practice.

Tea tree oil, a volatile oil, is well known for its broad antibacterial and antifungal activity. A standardised and stabilised 10% tea tree oil cream was tested against a commercial skin care cream (control cream) in the management of canine localised acute and chronic dermatitis. Fifty-seven dogs with clinical manifestations of mostly pruritic skin lesions or alterations, skin fold pyodermas and other forms of dermatitis, corroborated by predominantly positive fungal and bacterial skin isolates, were enrolled by seven practising veterinarians and randomly allocated to two study groups (28:29) and were treated twice daily with a blinded topical preparation. After 10 days of treatment, success rates of 71% for the tea tree oil cream and 41% for the control cream (over-all efficacy documented by the veterinary investigator) differed significantly (p = 0.04), favouring tea tree oil cream treatment. Accordingly on day 10, the tea tree oil cream caused significantly faster relief than the control cream (p = 0.04) for two common clinical dermatitis signs, pruritus (occurring in 84 % of dogs) and alopecia. Only one adverse event was reported in the tea tree oil group (suspected not to be causally related to the study drug) and none in the control cream group. The tested herbal cream appears to be a fast-acting safe alternative to conventional therapy for symptomatic treatment of canine localised dermatitis with pruritus.

[Development of 'Ordnungstherapie' by Bircher-Benner in naturopathy of the 20th century]. / Entwicklung der Ordnungstherapie durch Bircher-Benner in der Naturheilkunde im 20. Jahrhundert.

BACKGROUND: The German term 'Ordnungstherapie' is one of the five therapeutics which defines naturopathy in German-speaking countries. OBJECTIVE: Who formed the term Ordnungstherapie in naturopathy and what does it mean? MATERIAL AND METHODS: Heuristics and criticism of literature of the 20th century as well as database research. RESULTS: Nowadays in German-language medical books Ordnungstherpie belongs to the five therapeutics which define European naturopathy. Yet, the interpretation ranges from health education to body-orientated forms of psychotherapy. The term Ordnungstherapie is often related with the German priest and hydropath Sebastian Kneipp, however, term and definition have been founded by the Swiss physician Maximillian Bircher-Benner. In 1937 he defined Ordnungstherapie as a complex concept of natural healing. It is based upon the rather nosological idea that health is order/harmony in the human body (physically, psychologically), the environment and the daily course. Illness occurs if disorder appears in one of these fields. The therapeutic setting of Ordnungstherapy is defined by 9 rules of conduct to maintain order, which include nutrition, the skin as an organ (exposure to light, air, water), breathing, movement, rhythm of life, and psyche. For all these aspects Bircher-Benner himself uses the terms somatotherapy (dietotherapy, sun and light therapy, hydrotherapy, exercise therapy, breathing technique, order of the rhythm of live) and psychotherapy. He chose these complementary methods subjectively after learning them from 1897 onwards in an eclectic manner and after gaining therapeutic empiricism. Nevertheless his ideas of the Ordnungstherapie correlate with the socio-political context of the 1940ies. CONCLUSIONS: The term Ordnungstherapie was introduced by Bircher-Benner as an umbrella term in 1937 to describe a complex concept of naturopathic therapies. It comprises, with certain limitations for phytotherapy, the therapies which nowadays define European naturopathy. Yet, in European naturopathy today Ordnungstherapie is mostly considered as one out of 5 constituents of naturopathy (dietotherapy, hydrotherapy, exercise therapy, phytotherapy, Ordnungstherapie). The classification of Ordnungstherapie as one of the 5 pillars of the Kneipp therapy was only done by Kneipp physicians in the middle of the 20th century and needs to be thought over.

Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast).

BACKGROUND: Despite a long-standing use of herbal drugs with dyspeptic symptoms, little attention has been paid to their clinical evaluation. AIM: To assess efficacy and safety of the herbal drug preparation STW 5 (containing, e.g. Iberis, peppermint, chamomile) in the treatment of functional dyspepsia. METHODS: Research in electronic databases, consultation of experts and of the producer identified STW 5 (Iberogast) as descriptor in six randomized-controlled trials. The raw data of three placebo-controlled studies which met the selection criteria, were reanalysed and pooled for meta-analysis; one reference-controlled study supported the safety analysis (STW 5: n = 199, control: n = 198). RESULTS: Pooled data showed verum (n = 138) to be more effective than placebo (n = 135) with regard to the severity of the most bothersome gastrointestinal symptom (P-value: 0.001, odds ratio: 0.22, 95% CI: 0.11-0.47). A fourth randomized-controlled trial showed no significant difference between STW 5 and cisapride. As to safety, adverse events were similar with verum and placebo; no serious adverse events occurred. DISCUSSIONS: From the point of view of efficacy and safety, the herbal medicinal product STW 5 appears to be a valid therapeutic option for patients seeking phytotherapy for their symptoms of functional dyspepsia.

[Natural remedies during pregnancy and lactation]. / Naturheilmittel während Schwangerschaft und Stillzeit.

Up to date there is a lack of systematically gathered data on the use of natural remedies (phytotherapeutic, homeopathic, anthroposophic, spagyric, Bach and Schussler remedies) during pregnancy and lactation. The aim of this non-representative pilot study on 139 women, who came for delivery to three institutions between mid-1997 and the beginning of 1998, was to receive data about how often and within which spectrum natural remedies are used during pregnancy and lactation. During pregnancy 96% and within the lactation period 84% of the women consumed at least 1 natural remedy. Phytotherapeutic drugs were used most frequently. In contrast to the widespread use of natural remedies by pregnant women and nursing mothers in this study, little information on the effectiveness and possible risks is available. Therefore it seems necessary to examine and evaluate natural remedies used during pregnancy and lactation.

[Complementary medicine: phytotherapy and soyaisoflavones as phytoestrogens]. / Komplementärmedizin, Phytotherapie und Sojaisoflavone als Phytoöstrogene.

After a introduction concerning complementary medicine, naturopathy and phytotherapy a general view of soy isoflavones as phytoestrogens will be given. In german speaking countries the term and topic naturopathy has a tradition of 150 years regarding theoretical development and practical use among lay people and health professionals in European culture. In contrary the term complementary medicine has been used for approximately 15 years in englisch speaking countries as a kind of collective name for European and Non-European medical cultures and traditions. Complementay medicine summarizes a huge variety of cultural, medical and qualitywise different medical methods and treatments which can be a contribution to conventional medicine. One of the oldest and intensly researched fields in European and Non-European complementary medicine is the use of herbal drugs (phytotherapy). Soy isoflavones serve as an example to show the differences between phytotherapy based on multicompounds and dietary supplements (neutraceuticals) based on monosubstances. The differing preparations of soy isoflavones are not phytotherapeutic medicine. A review of the experimental and clinical data concerning soy isoflavones as phytoestrogens for the prevention of cancer, menopausal complaints, osteoporosis or cardiovascular diseases indicates that the consumption of food containing phytoestrogens seems to be health protective. Yet, the relevance of supplementation of single phytoestrogens for an additional health effect is not sufficiently proven.

[Fennel tea: risk assessment of the phytogenic monosubstance estragole in comparison to the natural multicomponent mixture]. / Fencheltee: Risikoabschätzung der phytogenen Monosubstanz Estragol im Vergleich zum natürlichen Vielstoffgemisch.

For centuries, fennel fruits have been used as traditional herbal medicine in Europe and China. For the treatment of infants and sucklings suffering from dyspeptic disorders, fennel tea is the drug of first choice. Its administration as a carminativum is practiced in infant care in private homes and in maternity clinics as well where it is highly appreciated for its mild flavor and good tolerance. The long standing positive experience is astonishingly contrasted by a recent statement of the German 'Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin' (BgVV, May 11, 2001), where consumers are advised to reduce their intake of foods containing estragole and methyleugenol, e.g. tarragon, basil, anis, star anis, jamaica pepper, nutmeg, lemon grass as well as bitter and sweet fennel fruits for reasons of health. These warnings are based on experiments with rats and mice where estragole, a natural ingredient of fennel fruits, proved to be carcinogenic. Meanwhile, criticism arose amongst experts concerning the interpretation of these studies. The crucial points of criticism concern the transfer of data obtained in animal models to the human situation as well as the high doses of the applied monosubstance, which do not at all represent the amounts humans are exposed to as consumers of estragole-containing foods and phytopharmaceuticals. Furthermore, studies on estragole metabolism revealed at least quantitative differences between the estragole metabolism of mice and men. In addition, it has been shown that an agent when administered in its isolated form may have significantly different effects and side effects than the same agent applied as a constituent in naturally occurring multicomponent mixtures. Thus, a multicomponent mixture such as fennel tea contains various antioxidants known to be protective against cancer. These differences were not considered in the risk assessment. A well done risk assessment should be based on appropriate data collected in humans. Considering the long traditional use of fennel tea and the total lack of epidemiological and clinical studies indicating a well founded cancerogenic potential, the probability of a serious risk connected with the consumption of fennel tea seems to be negligibly small.

Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis.

Hormone replacement therapy is contraindicated in women with breast cancer. Extracts from the rhizomes of Cimicifuga racemosa, have gained acceptance as a natural alternative for the treatment of menopausal symptoms. In the present study we investigated the antiproliferative activity of C. racemosa extracts (isopropanolic and ethanolic) on the estrogen receptor positive MCF-7 and estrogen receptor negative MDA-MB231 breast cancer cells by WST-1 assay. Down regulation of the proliferative activity and cell killing by isopropanolic and ethanolic extracts occurred in a clear dose-dependent response with a 50% growth inhibitory concentration of 54.1 +/- 11.4 and 80.6 +/- 17.7 micro g/ml in MCF-7 cells and of 29.5 +/- 3.0 and 58.6 +/- 12.6 microg/ml in MDA-MB231 cells, respectively. Further, the mode of cell death was identified as apoptosis by microscopic inspection and confirmed by light scatter characteristics and by detection of Annexin V adherence to phosphatidylserine by flow cytometry. In addition, the involvement of activated caspases was supported by the cleavage of cytokeratin 18 detected with M30 antibody. Increases in the level of M30-antigen of about 4-fold and 2-fold over untreated controls were observed in C. racemosa -treated MCF-7 and MDA-MB231 cells. These results indicate that C. racemosa extract exerts no proliferative activity, but kills the estrogen receptor positive MCF-7 as well as estrogen receptor negative MDA-MB231 cells by activation of caspases and induction of apoptosis.

Dietary support with Boswellia resin in canine inflammatory joint and spinal disease.

An open multi-centre veterinary clinical trial, comparing conditions before and after treatment with a herbal dietary supplement consisting of a natural resin extract of Boswellia serrata, was conducted by 10 practicing veterinarians in Switzerland. This traditional plant-based supplement is known for its anti-rheumatic and anti-inflammatory properties. 29 dogs with manifestations of chronic joint and spinal disease were enrolled. Osteoarthritis and degenerative conditions were confirmed radiologically in 25 of 29 cases. The resin extract (BSB108, product of Bogar AG) was administered with the regular food at a dose of 400 mg/10 kg body weight once daily for 6 weeks. Already after two weeks of treatment, an overall efficacy of the dietary supplement was evident in 71% of 24 eligible dogs. A statistically significant reduction of severity and resolution of typical clinical signs in individual animals, such as intermittent lameness, local pain and stiff gait, were reported after 6 weeks. Effects of external factors that aggravate lameness, such as "lameness when moving" and "lameness after a long rest" diminished gradually. In 5 dogs, reversible brief episodes of diarrhea and flatulence occurred, but only once was a relationship to the study preparation suspected. Because quality and stability of the resin extract were ensured, these data suggest that a standardized preparation can be recommended as a herbal dietary supplement providing symptomatic support in canine osteoarthritic disease.

Iberis amara L. and Iberogast--results of a systematic review concerning functional dyspepsia.

A systematic review referring to efficacy and tolerability of the herbal combination Iberogast (Iberis amara planta totalis, Chelidonii herba, Cardui mariae fructus, Melissae folium, Carvi fructus, Liquiritiae radix, Angelicae radix, Matricariae flos, Menthae piperitae folium) was performed in patients with functional dyspepsia. Three placebo-controlled trials and a reference-controlled trial showed a statistical significant and therapeutical relevant reduction of the gastrointestinal symptom-scores in 595 patients. The therapeutic efficacy was also found in one observational study (2267 patients). In accordance with the available evidence Iberogast seems to be an effective phytotherapeutic preparation to reduce the symptoms of dyspepsia yet, without central nervous side effects.

A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II.

A placebo controlled, randomised, parallel group, multicentre trial conducted in accordance with the guidelines of Good Clinical Practice (GCP) shows the efficacy and safety of a standardised extract of fresh berries of Crataegus oxyacantha L. and monogyna Jacq. (Crataegisan) in patients with cardiac failure NYHA class II. A total of 143 patients (72 men, 71 women, mean age of 64.8 (8.0 years) were recruited and treated with 3 times 30 drops of the extract (n = 69) or placebo (n = 74) for 8 weeks. The primary variable for the evaluation of efficacy was the change in exercise tolerance determined with bicycle exercise testing, secondary variables included the blood pressure-heart rate product (BHP). Subjective cardiac symptoms at rest and at higher levels of exertion were assessed by the patient on a categorical rating scale. An overall assessment of efficacy at the final visit was provided by the patient and the investigator. In the ITT population there was a significant increase in exercise tolerance in both groups between visit 1 and visit 3. The difference between the treatment groups was 8.3 watts in favour of the standardised extract of fresh Crataegus berries (p = 0.045). The result is confirmed in the PP population (p = 0.047). Changes in BHP at 50 watts and at comparable maximum load were in favour of Crataegus extract but the results are not statistically significant. The subjective assessment of cardiac symptoms at rest and at higher levels of exertion did not change significantly and the patient and investigator overall assessment of efficacy were similar for the two groups. The medication was well tolerated and had a high level of patient acceptability. The significant improvement, due to the fact that dyspnoea and fatigue do not occur until a significantly higher wattage has been reached in the bicycle exercise testing allows the conclusion that the recruited NYHA II patients may expect an improvement in their heart failure condition under long term therapy with the standardised extract of fresh Crataegus berries.

Systematic reviews of herbal medicines--an annotated bibliography.

OBJECTIVE: To provide a comprehensive collection and a summary of systematic reviews of clinical trials on herbal medicines. METHODS: Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of herbal medicines; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. RESULTS: From a total of 79 potentially relevant reviews preselected in the screening process 58 met the inclusion criteria. 30 of the reports reviewed ginkgo (for dementia, intermittent claudication, tinnitus, and macular degeneration), hypericum (for depression) or garlic preparations (for cardiovascular risk factors and lower limb atherosclerosis). The quality of primary studies was criticized in the majority of the reviews. Most reviews judged the available evidence as promising but definitive conclusions were rarely possible. CONCLUSIONS: Systematic reviews are available on a broad range of herbal preparations prescribed for defined conditions. There is very little evidence on the effectiveness of herbalism as practiced by specialist herbalists who combine herbs and use unconventional diagnosis.

[St. John' Wort (Hypericum perforatum L.)--multicompound preparations versus single substances]. / Johanniskraut (Hypericum perforatum L.)--Vielstoffgemische kontra phytogene Einzelstoffe.

Aqueous alcoholic extracts of St. John s wort are used for the treatment of mild to moderate depression. Recently, Hypericum extracts were also shown to inhibit the growth of various human malignant cells. We promote the hypothesis that the various biological activities of aqueous Hypericum extracts are based on synergistic interactions of all compounds present therein and not on the pharmacological activities of single compounds.

[St. John's Wort (Hypericum perforatum): a plurivalent raw material for traditional and modern therapies]. / Johanniskraut (Hypericum perforatum): Ein plurivalenter Rohstoff für traditionelle und moderne Therapien.

St. John's Wort is one of the oldest and one of the best experimentally and clinically examined herbal remedies. In various medical cultures and medical systems--that is to say the regions of origin of Hypericum perforatum, like Europe, West Asia and North Africa--St. John's Wort has been used as a remedy for centuries. Preparations from St. John's Wort not only represent medical traditions but also ways of thinking, ideas and experiences from naturopathic healers (non-physicians) as well as patients. The complex multicompound with its evolutionary and coevolutionary developed composition and structure acts as a varied raw material for the production of quantitative and qualitative dissimilar remedies, which are multicompounds themselves. They differ not only analytically but also quite often in their effects. The certain and potential spectrum of internal and external uses includes gastrointestinal complaint and illness, skin disease, mucosal lesion, superficial injury, depressive upset and depression, somatoform disorders, restlessness, nervosity, convalescence, exhaustion, sleep disturbance and nursing treatment. The plurivalent character of the multicompound even enables a broad spectrum of activity. This might justify to prefer St. John's Wort to other drugs in a wide range of treatments: In tumor patients with depression the antioxidative effect and the experimentally documented induction of apoptosis could mean an additional advantage, and in depressive patients with coronary heart disease the same applies to the anti-inflammatory and antioxidative effects.

Echinacea powder: treatment for canine chronic and seasonal upper respiratory tract infections.

An open multi-centered veterinary clinical trial, comparing conditions before and after treatment with a herbal preparation, containing the powdered root of Echinacea purpurea, was conducted by 6 practicing veterinarians in Switzerland. The plant-based immune stimulant was administered to 41 dogs with manifestations of chronic and seasonal upper respiratory tract infections, including pharyngitis/tonsillitis, bronchitis and kennel cough. Each animal was at an individual stage of the disease, with various symptoms and different severity scores, at start of treatment. There was no control group. Echinacea powder (1:3) was administered with the food at a dose of 1.0 g/10 kg body weight once daily for 8 weeks. Overall efficacy showed significant improvement for 92% of 39 dogs after 4 weeks of treatment and this was confirmed after 8 weeks. Significant reductions of severity and resolution of typical clinical symptoms, of clear nasal secretions, enlargement of lymph nodes, dry cough, dyspnea and dry lung sounds, were evident after 4 weeks. Only two adverse effects, not suspected to be attributable to the study drug, were recorded. Because quality and stability of the Echinacea powder were defined, using an analytical standard and purity tests, these data suggest, that the Echinacea preparation can be recommended as a well tolerated alternative treatment of canine upper respiratory tract infections.

Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation.

Mistletoe extracts are used as alternative cancer treatment in addition to standard chemotherapy and radiation treatment and have an immunostimulatory and pain-relieving effect. A direct antitumour effect of mistletoe extracts against tumour cells of lymphoid origin has been linked to the D-galactoside-specific mistletoe lectin I. In this study, we investigated the cellular effect of bacterially expressed, recombinant mistletoe lectin alone or in combination with ionising radiation in a genetically defined p53-wild-type and p53-deficient E1A/ras-transformed murine tumour cells system. Downregulation of the proliferative activity and cell killing by recombinant mistletoe lectin occurred in a clear dose response (0.1-1 ng ml(-1)). Induction of apoptosis was p53-independent, but apoptosis-associated factor-1-dependent. Cellular treatment with lectin in combination with ionising radiation resulted in both p53-wild-type and p53-deficient tumour cells in an at least additive, antiproliferative effect and enhanced activation of caspase-3. Combined treatment with ionising radiation and lectin revealed a similar cytotoxic effect in human, p53-mutated adenocarcinoma cells. Thus, recombinant mistletoe lectin alone and in combination with ionising radiation bypasses often prevalent apoptotic deficiencies in treatment-resistant tumour cells.