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Comparative evaluation of the efficiency of various Ukrain doses in the combined treatment of breast cancer. Report 1. Clinical aspects of Ukrain application.

This study was carried out in 75 patients with histologically confirmed breast cancer. Patients were divided into three groups of 25. The control group received symptomatic corrective therapy prior to mastectomy. The two other groups were given neoadjuvant therapy with Ukrain injections. The first group received a total course dose of 50 mg Ukrain at single doses of 5 mg injected every second day (a total of 10 injections) and the second group received a total Ukrain dose of 100 mg but with single doses of 10 mg. Five to seven days after the last injection patients from all groups were subjected to mastectomy according to Halsted, Patey or Madden. No allergic reactions or adverse effects were observed after the first course of injections or the whole course of Ukrain therapy, regardless of the dose. After five to six injections some patients noticed slight burning sensations and insignificant morbidity in the tumor area, which, according to a number of authors, testifies to the therapeutic activity of the preparation. Practically all patients who were administered Ukrain noticed remarkable positive changes in the second half of treatment: improvement in appetite, normalization of sleep, disappearance of general weakness and the appearance of confidence in recovery. After the course of treatment with Ukrain, the contours of the tumorous node became more clearly defined, which facilitated mastectomy. Changes in the tumor tissue were one-sided in their qualitative differences in comparison to the control group and were not dose-dependent. Qualitative and quantitative reactions to Ukrain by both intact lymphatic nodes and those affected by the metastatic process contribute to more quantitative and radical performance of the most important stage of mastectomy--removal of the regional cellulose together with the lymphatic nodes. The results of this study showed the efficiency of both doses (50 and 100 mg) of Ukrain with neither performing significantly better than the other.

Adult↗

[The results of a joint project of the State Department of Ukraine on the Implementation of Punishments and UNAIDS to decrease the risk of the spread of HIV in the prisons of Ukraine].

During the period of 1987-1999 altogether 7,800 cases of HIV infection were detected among the prisoners of the penitentiary institutions of the Ukraine. In 1997 the penitentiary system of the Ukraine abolished the mandatory testing and isolation of HIV-positive persons. In April 1998 the realization of measures aimed at reducing the spread of HIV infection started in the penitentiary system. The main trends in the activities aimed at the realization of the Project were information and educational work among prisoners both during investigative detention and after conviction, as well as among the personnel of penitentiary institutions; availability of condoms and disinfectants; ensuring the possibilities of voluntary testing for HIV, as well as pre- and post-test counselling.

Cooperative Behavior↗

[The initial experience of using the preparation Ukrain in treating cancer patients in Ukraine].

The chair of general surgery and the chair of oncology of the Ukrainian State Medical University have made a study into the use of the preparation "Ukrain" in the treatment of oncological patients. Early results of therapy of 23 patients confirm the evidence suggesting to us that "Ukrain" is endowed with cancerostatic activity, has immunopotentiating effect with no toxicity.

Adjuvants, Immunologic↗

Preliminary results of individual therapy of chronic hepatitis C by Ukrain and interferon-alpha.

The effects of Ukrain and recombinant human interferon-alpha 2b (IFN) on the state of the thiol-disulfide ratio (SH/SS) of the blood (Russian Federation patent no. 2150700) were studied in vitro using the amperometric titration method. The blood of 73 chronic hepatitis C (CHC) hepatitis C virus (HCV)-RNA-positive patients was examined. Ukrain was tested in doses of 0.05-2.0 micrograms/ml and IFN in 20-1000 U/ml of blood. After in vitro examination, 59 patients were treated: 28 with Ukrain and 31 with IFN. The first group of 16 patients (including eight with HCV genotype 1b) was treated with individually selected optimal doses of Ukrain (0.5-2.5 mg every second day). The second group of 12 patients was treated with doses of 2.5 mg Ukrain independent of in vitro test results. The third group of 31 patients was treated with individually selected optimal doses of IFN (0.5-2 MU 3 times a week). It was found that 79.4% of CHC patients were sensitive to Ukrain in vitro and 65.1% were sensitive to IFN. CHC patients with genotype 1b were sensitive to IFN only in 16.7% of cases while the figure for Ukrain was 92.3%. CHC patients with other HCV genotypes (3, 1a, 2) were sensitive to Ukrain in 86.7% of cases and to IFN in 70.6%. After 1 month of individual therapy with Ukrain, 87.5% of CHC patients, including six of eight cases with HCV genotype 1b, became PCR-HCV negative. In the group receiving the standard dose of Ukrain, virological response was only 33.3%. After 1 month, 74.2% of CHC patients treated with individual doses of IFN became PCR-HCV negative and after 3 months 90.3% were PCR-HCV negative. The prognostic significance of the method for screening preparations for the treatment of CHC patients was 89.8%. Treatment with Ukrain was without serious negative effects and the number of side effects of IFN in individual therapy was significantly reduced. Ukrain can be used in the treatment of CHC patients, alone or in combination with IFN preparations; in the cases with HCV genotype 1b Ukrain seems more promising than IFN. Individual therapy with Ukrain and IFN increased the efficacy of treatment 2.5-fold in comparison with standard monotherapy with the same preparations, significantly decreased the number of side effects and dramatically improved cost-effectiveness.

Adult↗

Fibronectin and laminin increase resistance to ionizing radiation and the cytotoxic drug Ukrain in human tumour and normal cells in vitro.

PURPOSE: Cell-extracellular matrix (ECM) interactions are thought to mediate drug and radiation resistance. Dependence of cell survival, beta1-integrin expression and cell cycling on the ECM proteins and beta1-integrin ligands fibronectin (FN) and laminin (LA) were examined in malignant and normal cells exposed to the cytotoxic drug Ukrain plus/minus irradiation. MATERIALS AND METHODS: Human A549 lung cancer and MDAMB231 (MDA231) breast cancer cells and normal fibroblasts (HSF1) grown on FN, LA, bovine serum albumin (BSA) or polystyrene were treated with Ukrain (1 microg ml(-1), 24 h) plus/minus irradiation (2-8 Gy) and the effects studied using colony formation assays, flow cytometry (beta1-integrin, DNA analysis) and adhesion assays. RESULTS: FN and LA reduced the cytotoxic effect of single Ukrain treatment compared with polystyrene and BSA. FN and LA also abolished Ukrain-dependent radiosensitization in A549 cells and decreased the radiosensitivity of MDA231 and HSF1 cells. Single Ukrain exposure on polystyrene significantly reduced beta1-integrin expression and promoted G2-phase accumulation of A549 cells. In contrast, Ukrain-treated MDA231 and HSF1 cells showed elevated beta1-integrin expression and no Ukrain-specific cell cycle effect. Under Ukrain-radiation exposure, irradiation, FN or LA abolished Ukrain-mediated reduction of beta1-integrin expression and G2-phase accumulation in A549 cells, whereas in MDA231 cells and fibroblasts beta1-integrin expression and cell cycle distribution were stabilized. Cell adhesion to FN or LA was significantly impaired (A549) or improved (MDA231, HSF1) upon Ukrain treatment. CONCLUSIONS: The data corroborate the findings of other groups that cell adhesion-mediated resistance to either single or combined drug and radiation exposure is tightly correlated to specific ECM proteins. By demonstrating a strong modulatory impact of FN and LA on the radiosensitivity-modifying activity of the drug Ukrain, the set findings are also highly important for the assessment of drug and radiation effects within in vitro cytotoxicity studies. The data give the first mechanistic insights into specific FN- and LA-modulated cellular resistance mechanisms as well as into the important role for beta1-integrins using the unique cytotoxic and radiosensitivity-modifying drug Ukrain.

Alkaloids↗

Modulation of immune effector cell cytolytic activity and tumour growth inhibition in vivo by Ukrain (NSC 631570).

Ukrain is a semisynthetic compound consisting of alkaloids from Chelidonium majus L. conjugated to thiophosphoric acid, with immunomodulatory and therapeutic properties in cancer patients. The present in vitro studies demonstrate that Ukrain is an effective biological response modifier augmenting, by up to 48-fold, the lytic activity of splenic lymphocytes obtained from alloimmunized mice. The lytic activities of interleukin-2 (IL-2) treated spleen cells and peritoneal exudate lymphocytes were also significantly increased by the addition of Ukrain to the cell mediated lysis (CML) assay medium. The highest Ukrain-induced enhancement of splenic lymphocytolytic activity in vitro was found to occur at day 18 after alloimmunization was dose-dependent and specific for the immunizing P815 tumour cells. Since Ukrain was present only during the CML assays, its mode of action is thought to be via direct activation of the effector cells' lytic mechanism(s). The effect of Ukrain on the growth of Balb/c syngenic mammary adenocarcinoma was also evaluated. Intravenous, but not subcutaneous or intraperitoneal, administration of this drug was found to be effective in delaying tumour growth in an actual therapeutic protocol initiated five days after tumour implantation. No deleterious side-effects were observed using these in vivo treatment modalities. The role of macrophages in the observed retardation of tumour development was investigated, using peritoneal exudate macrophages (PEM) in cytotoxicity assays. Previous studies showed that PEM of mammary tumour-bearing mice lose their capacity to kill a variety of tumour target cells including the in vitro cultured homologous tumour cells (DA-3). Pretreatment of PEM from normal mice with 2.5 microM Ukrain for 24 h, followed by stimulation with either IFN-gamma or with lipopolysaccharide (LPS) plus IFN-gamma enhanced their cytotoxic activity. Treatment of PEM from tumour-bearing mice with 2.5 microM Ukrain and LPS results in a reversal of their defective cytotoxic response against DA-3 target cells. Furthermore, Ukrain alone, in the absence of a secondary signal, induced the activation of tumouricidal function of PEM from tumour-bearing, but not from normal, mice. These data indicate that Ukrain's in vivo effects against the development of mammary tumours may be due, at least in part, to its ability to restore macrophage cytolytic function.

Adjuvants, Immunologic↗

Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation.

PURPOSE: Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L., has demonstrated a promising impact on chemotherapy in a variety of malignancies. The effects of the drug on cell survival, alteration of the cell cycle and induction of apoptosis were examined without and in combination with ionizing radiation (IR). The TP53 status of the cell lines used was also investigated. MATERIALS AND METHODS: Exponentially growing human tumour cell lines MDA-MB-231 (breast), PA-TU-8902 (pancreas), CCL-221 (colorectal), U-138MG (glioblastoma), and human skin and lung fibroblastic cells, HSF1, HSF2 and CCD32-LU were studied by colony assay, flow cytometry (cell-cycle, annexin-V staining for apoptosis) and Western blotting. Ukrain was used in concentrations from 0.1 to 50 microg ml(-1) for 1, 3 and 24 h and radiation as single doses of 1-10Gy. Combined drug-radiation exposure employed 1 microg ml(-1) Ukrain for 24h plus 2-8 Gy. RESULTS: Ukrain cytotoxicity was time- and dose-dependent. The combination of Ukrain plus IR gave enhanced toxicity in CCL-221 and U-138MG cells, but not in MDA-MB-231 and PA-TU-8902 cells. Most strikingly, a radioprotective effect was found in normal human skin and lung fibroblasts. Flow-cytometry analyses supported the differential and cell line-specific cytotoxicity of Ukrain. CCL-221 and U-138MG cells accumulated in G2 after 24-h Ukrain treatment, whereas no alterations were detected in the other tumour cells and normal fibroblasts tested. Western blotting of TP53 demonstrated non-functional overexpression in all tumour cell lines without affecting p21. HSF1 presented wild-type TP53 and a p21 response after IR. Flowcytometric analyses of annexin-V staining showed no induction of apoptosis after Ukrain treatment in comparison with untreated controls. CONCLUSIONS: Differential effects of Ukrain in modulating radiation toxicity of human cancer cell lines and its protective effect in normal human fibroblasts suggest that this alkaloid may have potential properties for clinical radiochemotherapy.

Adjuvants, Immunologic↗

Ukrain (NSC-631570) in the treatment of pancreas cancer.

The aim of this study was to investigate the effects of Ukrain in the treatment of pancreatic cancer. Most patients with advanced pancreas cancer experience pain and have to limit their daily activities because of tumor-related symptoms. Currently, there is no satisfactory treatment for pancreas cancer. The 12-month survival rate is approximately 18% for patients treated with gemcitabine and only around 2% for those treated with 5-fluorouracil. Between January 1, 1996 and December 31, 1999 42 patients with advanced symptomatic pancreas cancer were randomly assigned to receive either vitamin C (5.4 g every second day, repeated 10 times) and Ukrain (10 mg every second day, repeated 10 times) (21 patients), or vitamin C (5.4 g every second day x 10) and normal saline (10 ml) (control group, 21 patients). The primary measure of efficacy was overall survival. Other evaluation criteria included change in body weight, pain intensity (measured by analgesic consumption) and Kamofsky performance status. The one-year survival was 81% in the Ukrain group compared with 14% in the control group. The 2-year survival was 43% in the Ukrain group compared with 5% in the control group. In a recent study of 126 patients treated with gemcitabine or 5-fluorouracil, none of the patients survived beyond 19 months. The longest survival in the Ukrain group was 54 months after the start of therapy (from March 1996 to date). The last follow-up of other patients was on September 6, 2000. Median survival was 17.17 months for Ukrain-treated patients and 6.97 months for the control group and mean survival was 21.86 and 8.92 months for the Ukrain and control groups, respectively (p = 0.001). Ukrain treatment was well tolerated. We conclude that Ukrain prolongs survival of pancreas cancer patients. To determine whether and to what extent this drug can be used as standard therapy in pancreas cancer, a phase III study should be carried out.

Adult↗

High rates of neural tube defects in Ukraine.

BACKGROUND: Oral consumption of synthetic folic acid can prevent neural tube defects (NTDs), which are some of the most severe congenital anomalies. The prevalence of NTDs in Ukraine and other countries of the former U.S.S.R. has not been well studied. We determined the prevalence of NTD-affected pregnancies in Northwestern Ukraine as background for policy decisions related to flour fortification in this country. METHODS: The Ukrainian-American Birth Defects Program was established in 1999 and conducts population- based surveillance of birth defects in several oblasts (states) of Ukraine. We determined the prevalence of NTDs in the Volyn and Rivne oblasts of Northwestern Ukraine for three years, 2000-2002. RESULTS: There were 75,928 births in the two oblasts in 2000-2002. There were 159 cases of NTDs among live births, stillbirths, and induced abortions. The prevalence of NTDs in the two oblasts in Northwestern Ukraine is 2.1 per 1000 births. CONCLUSIONS: The prevalence of NTD-affected pregnancies we found in Northwestern Ukraine is almost four times what it should be. This prevalence suggests that population folate deficiency is widespread in Ukraine. Universal folic acid fortification of flour milled in Ukraine is urgently needed to end this epidemic of birth defects. Such fortification would be expected to prevent folate deficiency anemia, heart attacks, and strokes.

Female↗

Six-week treatment with Ukrain in rabbits. Part II: Serum levels of gonadal hormones.

The effect of 6-week treatment with Ukrain at doses of 0.3, 1.5, and 3.0 mg/kg i.v. on the serum levels of steroid hormones, i.e., estradiol, testosterone, and progesterone, was studied in rabbits of both sexes. It is demonstrated that Ukrain treatment exerts minor changes in serum hormone levels. The level of estradiol was increased in the serum of male rabbits following Ukrain treatment only at the dose of 1.5 mg/kg i.v. Similarly, the estradiol serum level was increased after Ukrain given at 1.5 mg/kg i.v. in female rabbits. In male rabbits Ukrain application at 0.3 mg/kg i.v. increased the serum testosterone level. Serum testosterone levels were not altered following Ukrain administration up to 3.0 mg/kg i.v. in female rabbits. Ukrain raised the serum progesterone levels in male rabbits at the doses of 0.3 and 3.0 mg/kg i.v. in females, only the highest dose of Ukrain produced a significant increase of serum progesterone.

Alkaloids↗

The dynamics of concentration of the main fluorescent component of Ukrain in the tissues and blood plasma of rats with W-256 tumor after a single intravenous injection.

We determined the blood plasma and tissue concentrations of the main fluorescent component of free Ukrain after a single intravenous injection of this substance (0.25 mg/kg) to intact and carcinosarcoma W-256 bearing rats using ion-pair high-performance liquid chromatography with fluorescent detection. The plasma and tissue concentrations of Ukrain were lower than expected, assuming its uniform tissue distribution and first-order kinetics. W-256 tumor tissue was the only tissue that showed accumulation of Ukrain (its concentration at 45 min after injection was up to 2.84-fold higher than in the blood plasma). Based on the elevation of Ukrain concentration in tissues at approximately 15 min after injection and taking into account its high molecular weight as well as the high dimensions of the Ukrain molecule or ion at physiological pH values, we conclude that the preparation penetrates into tissues by active transport or by favored diffusion. Due to the existence of such transport systems together with excretion of Ukrain and probably also its biotransformation, the disappearance of the preparation from the blood cannot be described using a one-compartment model. A relatively higher affinity for Ukrain was observed in tumor tissue and liver, while affinity was lowest in the brain and muscles. The presence of tumors decreased Ukrain concentrations in plasma and normal tissues in comparison with those in control animals.

Alkaloids↗

Prevalence of diabetes mellitus and its complications in the Ukraine.

Analysis of the prevalence of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) in various climato-geographic and administrative regions of the Ukraine was performed. The prevalence of diabetes mellitus (DM) complication in the west and north zones of the Ukraine was studied. The role of prophylactic measures in decreasing the number of complications was elucidated. The statistical reports from the specialized endocrinologic institutions of the Ukraine were analysed in the Laboratory of Epidemiology of Endocrine disease of Institute and results from 3450 and 673 diabetic patients in the west and north zone of the Ukraine were used, respectively. In various administrative regions of the Ukraine the prevalence of IDDM significantly varied from 1740 to 3813 patients per 1 million population. Significant differences in the prevalence of NIDDM were found. Generally in the west zone of the Ukraine the prevalence of DM was less than that of average in the Ukraine. Angiopathy of the lower extremities, neuropathy and retinopathy were registered in 92, 24, and 21% of diabetes cases in the west zone, respectively. Prophylactic measures directed at a decrease in patient weight, the normalization of metabolism, arterial pressure and the elimination of pernicious habits promoted a decrease in the number of complications.

Adolescent↗

Efficacy of ukrain in the treatment of pancreatic cancer.

BACKGROUND: This monocentric study evaluated the effect of ukrain in the treatment of pancreatic cancer. MATERIAL AND METHODS: Between January 1996 and December 1999 we treated 21 patients with 10 mg ukrain every second day x10. The control group received supportive treatment only. RESULTS: Ukrain treatment was well tolerated. Mean values on pain measure and Karnofsky index were significantly better in the ukrain group than in controls ( P<0.05). One-year survival was 76% in the ukrain group, compared to 9.5% in the control group. Median survival after treatment with ukrain was 574 days, compared to 197 days in the control group. CONCLUSIONS: Our data demonstrate that ukrain improves quality of life in patients suffering from advanced pancreatic cancer and significantly prolongs survival time in these patients.

Adult↗

Ukrain therapy of stage T1N0M0 bladder cancer patients.

The aim of the present study was to evaluate the efficacy of Ukrain as a new treatment modality in 28 patients with stage T1N0M0 bladder cancer. The tumor dimensions varied from 0.5 x 0.5 cm to 3 x 4 cm. The first group (nine patients) was treated with a total dose of 100 mg Ukrain, the second group (10 patients) received 200 mg Ukrain, and the third group (nine patients) was treated with 300 mg Ukrain. In all patients Ukrain was administered i.v. at a dose of 10 mg per day. In the patients from the second and third group each course of treatment, consisting of 10 injections, was followed by 14 days of no treatment. Ukrain, at a total dose from 100-300 mg as neoadjuvant therapy in patients with T1N0M0 bladder cancer, resulted in either complete or partial regression of tumors in 60.7 +/- 9.2% of cases. The best treatment regime included three courses of Ukrain at 2-week intervals.

Adult↗

Six-week treatment with Ukrain in rabbits. Part III: Serum levels of thyroid hormones.

The influence of 6-week treatment with Ukrain at doses of 0.3, 1.5 and 3.0 mg/kg i.v. on serum levels of thyroid hormones, i.e., thyroxine and triiodothyronine, was studied in rabbits of both sexes. Ukrain affected the serum levels of both hormones in males. An increase in the thyroxine level was found after Ukrain used at a dose of 1.5 and 3.0 mg/kg i.v., whereas increased triiodothyronine was noted when Ukrain was given at all studied doses. In females the thyroxine level was not altered by Ukrain administration, whereas the triiodothyronine concentration was increased following Ukrain at 0.3, 1.5 and 3.0 mg/kg i.v. it is probable the altered thyroid hormone levels as a result of Ukrain application may contribute to the drug's potent immunomodulatory action.

Adjuvants, Immunologic↗

A comparative evaluation of the influence of the complex drug Ukrain and its components on the effects of radiation.

The development of cancer therapy is associated with an increased application of therapeutic schedules that combine radiation and different drugs. Ukrain is a promising drug proved to be efficient in the treatment of different tumors when used either before, during or after radiation therapy. Therefore, the issue of the influence of this drug on the effects of radiation is of interest. In previous studies, the ability of Ukrain to ameliorate the harmful consequences of irradiation was demonstrated. Ukrain is a semi-synthetic thiophosphoric derivative of Chelidonium majus L. alkaloids, i.e., it is a complex preparation. Therefore, it is necessary to elucidate which of its components are the active agents that mediate its antiradiation effects. The aim of this study was to compare the radioprotective effects of Ukrain and its components in experiments with animals irradiated by doses within a broad range (from LD50/30 to LD100/30). A total of 1,240 outbred male white mice were gamma-irradiated with an IGUR apparatus using 137Cs as the radiation source. Doses applied ranged from 5.25-7.5 Gy with a 0.75 increment between dosages. Dose rate was 1.41 Gy/min. The experiments have shown that the radioprotective effects of Ukrain are far superior to all its components taken separately, both measured by survival of mice irradiated by different doses, and by the protection coefficient a. These observations suggest that the influence of Ukrain on radiation effects does not result from the antiradiation properties of its components but rather from the concerted action of the specific combination found in Ukrain.

Alkaloids↗

Comparative evaluation of blood plasma and tumor tissue amino acid pool in radiation or neoadjuvant preoperative therapies of breast cancer with the antitumor drug Ukrain.

This study comparatively evaluated free amino acid pool formation in patients with T1-3N0-2M0 breast cancer treated with the drug Ukrain (25 patients, i.v. 100 mg/course) in combination with preoperative radiation or neoadjuvant therapies (25 subjects, total dose 20 Gy). All the patients underwent radical mastectomy. Preoperative radiation did not essentially change the range of the blood plasma parameters studied. However, we observed decreased concentrations of blood plasma ornithine and citrulline and a reduced content of aminobutyric acid, as compared with levels on admission, which may indicate an acceleration of detoxication processes in the liver. In comparison with healthy mammary gland tissue, the tumor tissue of the patients subjected to radiation therapy showed 1.5- to twofold increased concentrations of cysteate, taurine, aspartate, glutamate, proline, glycine, alanine, valine, tyrosine and histidine, which substantiates the idea of tumor tissue being a trap for numerous energy and plastic substrates and indicates active transport of the above compounds into the tumor. The application of Ukrain had virtually no influence on concentrations of the majority of blood plasma amino acids and derivatives: the total concentration of the compounds studied as well as the essential and nonessential amino acid pools remained unchanged. As compared with healthy breast tissue, the considerably increased levels of thiol-containing amino acids, such as methionine, cystine, cysteate and taurine, in the tumor tissue of patients receiving neoadjuvant therapy with Ukrain, indicates high activity of trans-sulfuration processes in this tissue. Simultaneously, in contrast to radiation therapy, Ukrain induced a marked dose-dependent increase in the concentration of proline in breast tumor tissue. The above changes were consistent with the results of the morphological study which confirmed the emergence of numerous foci of necrosis in the tumor and indicated activation of Ukrain-induced proteolytic and degradation processes in the tumor. The results obtained have led us to conclude that a mechanism of Ukrain's cancerostatic effect is to control the transport and reactions of intermediate amino acid metabolism as well as to activate proline biosynthesis in the tumor, causing enhanced development of connective tissue. It is suggested that an important practical conclusion from the present study is the lack of damaging effect of preoperative radiation therapy in the above regimen and the favorable (normalizing) action of Ukrain, at a course dose of 100 mg, on the amino acid pool formation in the organism of patients with breast cancer.

Adult↗

Mitogenic properties of Ukrain (NSC-6315170) on human peripheral blood monocytes: clinical implications.

Using a cell-proliferation assay, the authors examined and compared the mitogenic effects of Ukrain and phytohaemagglutinin (PHA) on human peripheral blood mononuclear cells (PBMCs), as well as their synergic effects. It was found that even a short period of pretreatment of the cell with Ukrain had a potent synergic effect on PHA mitogenesis resulting in significantly higher cell stimulation indices than those of PHA alone. Moreover, it was found that a short period of PHA treatment of the cells is almost imperative for Ukrain to exert its mitogenic effects. The mitogenic effect of Ukrain on human PBMCs is consistent with a previous clinical report which found that circulating lymphocytes were significantly increased in cancer patients treated with Ukrain. Thus the in vitro assay used in these studies may serve as a prognostic assay for potential patient responsiveness to Ukrain treatment, as well as a clinical parameter during Ukrain therapy.

Alkaloids↗