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PubMed1996

Biodegradable injectable implant systems for long term drug delivery using poly (lactic-co-glycolic) acid copolymers.

Poly (lactide-co-glycolide) (PLG), is one of the most widely employed biodegradable synthetic polymers for sustained-release preparations. In the present work, PLG (50:50) copolymer has been used to deliver diclofenac sodium in the form of microspheres and in situ gel-forming systems, both of which can be injected subcutaneously. The pharmacodynamic and pharmacokinetic studies in the adjuvant-induced arthritic rats showed that the microspheres offered steady therapeutic levels of the drug in the plasma for about 16 days following a single subcutaneous injection. However, the in situ gel-forming system provided a significantly higher maximum plasma concentration and increased inhibition of inflammation, maintained for about 10 days. Injectable microspheres and in situ gel-forming implant systems of PLG (50:50) copolymer may therefore be considered as prospective implantable controlled-release dosage forms to deliver drugs in long-term therapy of chronic ailments.

Animals↗

PubMed1991

Gamma oryzanol-plant sterol supplementation: metabolic, endocrine, and physiologic effects.

The use of gamma-oryzanol and phytosterols is gaining popularity among various athletic populations. These compounds are being consumed in the belief that they elicit anabolic effects ranging from increased testosterone production and release to stimulating human growth hormone release. However, published scientific studies suggest that these compounds are poorly absorbed. Furthermore, animal studies indicate that when these compounds are injected subcutaneously or intravenously, they induce antianabolic or catabolic activity. Normally, less than 5% of orally consumed phytosterols are absorbed from the intestinal tract, with the majority being excreted in the feces. Intravenous or subcutaneous injections of gamma-oryzanol in rats have been shown to suppress luteinizing hormone release, reduce growth hormone synthesis and release, and increase release of the catecholamines, dopamine and norepinephrine, in the brain. Although it hasn't been directly measured, this metabolic milieu, if accurate, may actually reduce testosterone production.

Absorption↗

PubMed2004

Progressive loss of malignant behavior in telomerase-negative tumorigenic adrenocortical cells and restoration of tumorigenicity by human telomerase reverse transcriptase.

Replicative senescence/crisis is thought to act as a tumor suppressor mechanism. Although recent data indicate that normal human cells cannot be converted into cancer cells without telomerase, the original concept of senescence as a tumor suppressor mechanism is that senescence/crisis would act to limit the growth of telomerase-negative tumors. We show here that this concept is valid when oncogene-expressing human and bovine cells are introduced into immunodeficient mice using tissue reconstruction techniques, as opposed to conventional subcutaneous injection. Primary human and bovine adrenocortical cells were transduced with retroviruses encoding Ha-Ras(G12V) and SV40 large T antigen and transplanted in immunodeficient mice using tissue reconstruction techniques. Transduced cells were fully malignant (invasive and metastatic) in this model. They had negligible telomerase activity both before transplantation and when recovered from tumors. When serially transplanted, tumors showed progressively slower growth, decreased invasion and metastasis, shortened telomeres, and morphological features of crisis. Whereas telomerase was not essential for malignant behavior, expression of human telomerase reverse transcriptase enabled cells from serially transplanted tumors that had ceased growth to reacquire tumorigenicity. Moreover, telomerase-negative oncogene-expressing cells were tumorigenic only when transplanted using tissue reconstruction techniques; human telomerase reverse transcriptase was required for cells to form tumors when cells were injected subcutaneously. This work provides a new model to study crisis in an in vivo setting and its effects on malignancy; despite having invasive and metastatic properties, cells are eventually driven into crisis by proliferation in the absence of a telomere maintenance mechanism.

Adrenal Cortex↗

PubMed2004

Mineralo- and glucocorticoid receptor mrnas are differently regulated by corticosterone in the rat hippocampus and anterior pituitary.

In most cell lines and animal tissues, glucocorticoid receptors undergo downregulation after exposure to corticosterone. However, corticosterone treatment has not shown a consistent effect on mineralocorticoid (MR) and glucocorticoid receptors (GR) in the hippocampus, and it has been rarely assessed in the anterior pituitary. In this study we investigated dose-dependent effects of corticosterone on MR and GR mRNAs in the hippocampus and anterior pituitary. Adrenalectomized rats substituted with corticosterone in drinking fluid were injected subcutaneously with vehicle or 1, 10, 50, 100, or 200 mg of corticosterone, and sacrificed 4 h later. In the hippocampus we found a progressive decrease in MR and GR mRNAs with increasing doses of corticosterone. This was significant with 50 and 100 mg corticosterone for MR mRNA and with 10-200 mg corticosterone for GR mRNA at plasma corticosterone levels above 30 microg/dl. The anterior pituitary did not show significant changes at any dose. A time-course with 2 mg of corticosterone (non-response dose range at 4 h) revealed a significant decrease in MR and GR mRNAs in the hippocampus 8 h after the subcutaneous injection. In the anterior pituitary both mRNAs showed an increase that was significant 24 h after injection for MR and from 8 to 24 h for GR. In the hippocampus, adrenalectomy (absence of corticosterone) induced a significant increase in MR and GR mRNAs on day 3, but not on days 1, 8 and 21 after adrenalectomy. In the anterior pituitary there were no significant changes at any time after adrenalectomy. In summary, we have found an in vivo corticosterone dose- and time-dependent downregulation of MR and GR mRNAs in the hippocampus, whereas anterior pituitary MRs and GRs seem relatively insensitive to the excess or the absence of corticosterone, suggesting the lack of an autoregulatory effect in this tissue. Significant mRNA changes appearing later in time could suggest a secondary response via a glucocorticoid-induced gene product. Corticosteroid receptor downregulation in the hippocampus could prevent overstimulation or tissue damage when plasma corticosterone is high, while increased corticosteroid receptors in the anterior pituitary could buffer the excessive brain drive on the pituitary during chronic stress or pathological conditions associated with increased plasma glucocorticoids, such as depression.

Animals↗

PubMed1994

Enhancement of the anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with an F(ab')2 fragment of murine monoclonal antibody against rIL-2.

We have investigated the biological properties of an immune complex composed of recombinant interleukin-2 (rIL-2) and an F(ab')2 fragment of a monoclonal antibody against rIL-2 in mice for the induction of killer cells and anti-tumor activity, as well as the pharmacokinetic properties of the immune complex injected subcutaneously into mice. The immune complex demonstrated sustained serum rIL-2 levels, with a 2.4-times longer "mean-residence-time" than free rIL-2. A more significant portion of rIL-2 was detected in lymph nodes after the subcutaneous injection of the immune complex than with rIL-2 alone. Splenic lymphocytes from mice given the immune complex showed higher killer cell activity against YAC-1 and P815 cells than those from mice given rIL-2 alone. The immune complex also exerted a more significant anti-tumor effect in a dose-dependent manner in Meth-A fibrosarcoma-bearing mice than dit rIL-2 alone.

Animals↗

PubMed1976

[Effects of synthetic sex steroids on the pituitary responsiveness to luteinizing hormone releasing hormone (LH-RH) (author's transl)].

Effects of short and long term administrations of an oral contraceptive preparation on the pituitary responses to the synthetic LH-RH were compared in the present experiment. Five normal cycling women were used as controls in the late proliferative phase. Five healty volunteers taking an oral contraceptive agent (1.0 mg norethindrone with 0.05 mg mestranol) for less than 10 cycles were served as short term group and other 4 women taking the same preparation for more than 40 cycles were studied as long term group. Volunteers in each group were kept fasting overnight and 5 ml of blood was drawn at 9 to 10 am on the day of experiment. Ten minutes after drawing blood, 200 mug synthetic LH-RH was injected subcutaneously in the late proliferative phase in the normal cycling women. According to the same procedure, women taking pills were administered LH-RH on the 7th to 12th day after the beginning of taking the first tablet in each cyle. Three ml of blood was taken at 15, 30, 60, 120 minutes and 24 hours, and serum LH and Fsh were determined by the double antibody radioimmunoassay. The 2nd IRP-HMG was used as the standard materials and expressed as mIU/ml of serum. Mean baseline serum LH and FSH concentrations were not suppressed in a short term administration of norethindrone-mestranol combination. Fifteen minutes after the subcutaneous injection of LH-RH, mean LH level was significantly elevated, and thereafter the level was not significantly changed as compared with that seen in the late proliferative phase of the cycle. Concerning the FSH response to LH-RH, a short term administration did not induce a significant rise. ...

Contraceptives, Oral↗

PubMed1999

Antihypertensive effect of insulin via nitric oxide production in the Zucker diabetic fatty rat, an animal model for non-insulin-dependent diabetes mellitus.

It has been reported that insulin treatment improves hypertension in patients with diabetes mellitus. The mechanisms of the antihypertensive effect of insulin, however, remain to be fully elucidated. In the present study, we investigated a possible involvement of nitric oxide (NO) in insulin-induced reduction of blood pressure using the Zucker diabetic fatty (ZDF) rat, an animal model of non-insulin-dependent diabetes mellitus. The animals were divided into three groups and treated for 4 weeks with daily subcutaneous injections of insulin (25U/kg body weight) with or without oral administration of l-nitro-arginine methyl ester (L-NAME, 50mg/kg/day body weight as drinking water), an inhibitor of NO synthase (NOS). Saline solution was injected subcutaneously in the control groups. During the experimental period, body weight gain was greater in the insulin-treated groups than in the control groups whereas water intake was considerably decreased in the insulin-treated groups. Insulin treatment resulted in a decrease in plasma glucose and blood pressure, and an increase in both NO metabolites (NOx) in the plasma and NOS activity in the aorta tissue. L-NAME treatment blunted not only the antihypertensive effect of insulin but also the changes in NOx and NOS activity. These findings suggest that insulin reduces blood pressure in the ZDF rat by stimulating NOS activation and NO production.

Animals↗

PubMed2005

Optimum dose of LH-RH analogue Fertirelin Acetate for the induction of superovulation in mice.

The optimum dose for establishing superovulation in mice of Fertirelin Acetate (FA), an LH-RH analogue, was examined. Mice were subcutaneously injected with 5 IU of hCG at 17:00 (Day 0), and with various doses of FA (0.001 to 1.0 microg) five times at 4 h intervals on and after 22:00 on Day 0. To induce ovulation, 5 IU of hCG was again injected subcutaneously at 17:00 on Day 2. In the groups administered with doses ranging from 0.01 to 0.5 microg of FA, the number of ovulated eggs was significantly (p<0.05) larger than in the control group (12.9 +/- 5.9). The greatest number of ovulated eggs (22.6 +/- 7.3) was obtained in the group administered with 0.025 microg of FA. The results indicate that the effective dose of LH-RH analogue, FA, is between 0.1 and 0.5 microg for superovulation induction in mice.

Animals↗

PubMed1992

Appropriate conditions for the plaque forming cell (PFC) assay in rats and effects of cyclophosphamide on PFC response.

The appropriate conditions for the plaque forming cell (PFC) assay using rat splenocytes were determined and effects of cyclophosphamide on PFC response were investigated using these conditions. The number of PFCs produced by immunization with a suspension of sheep red blood cells (SRBCs) was higher with i.v. injection than with i.p. injection. Subcutaneous injection of the suspension did not produce PFCs. The highest PFC response was observed when the number of PFCs was determined 4 days after i.v. immunization with 0.5 ml of a 1% SRBC suspension. Cyclophosphamide (3, 10, 30, 100 and 300 mg/kg, p.o.) dose-dependently decreased PFC response under the above-mentioned optimal conditions, and decreased PFC responses were noted even at the very low dose of 3 mg/kg: a dose at which a decrease in the number of PFCs has not been reported in studies using mice. From these results, the appropriate conditions for the PFC assay in rats are considered to be i.v. immunization with 0.5 ml of a 1% SRBC suspension and determination of the number of PFCs 4 days after immunization. Furthermore, it is considered that the PFC assay using rats might be more sensitive to immunosuppressive agents than that using mice.

Age Factors↗

PubMed1988

Effect of hypophysectomy and hormone replacement on fatty elongation in isolated microsomes of rat testes.

Effect of hypophysectomy on fatty acid elongation was investigated in isolated rat testicular microsomes incubated with [14C]malonyl CoA. Hypophystectomy resulted in a 40% decrease in total incorporation of 14C into fatty acids of microsomes. Several 18- and 20-carbon fatty acids of testicular microsomes from hypophysectomized rats had less 14C than did those from nonhypophysectomized ones, whereas only docosa-7,10,13,16-tetraenoic acid (22:4w6) had more 14C. Testosterone injected subcutaneously into hypophysectomized rats at a dose of 0.5 mg per day for eight days posthypophysectomy had no apparent effect on either the total 14C incorporated or the distribution of the 14C in the various fatty acids. Daily subcutaneous injections of 50 or 100 micrograms follicle stimulating hormone (FSH) had some effect on both total incorporation and distribution of 14C. Addition of 0.5 mg testosterone to the 50 micrograms FSH gave the same results as the FSH alone. Smaller amounts of stearic acid (18:0) and linoleic acid (18:2) and increased amounts of docosa-4,7,10,13,16-pentaenoic acid (22:5w6) were present in the microsomes of hypophysectomized compared to nonhypophysectomized rats. Testosterone replacement did not affect these differences, but FSH administration was partially effective in altering the values toward those observed in nonhypophysectomized rats. Results obtained in these experiments indicate that there is inhibition of the testicular microsomal fatty acid elongation system in hypophysectomized rats and that, although testosterone is not at all effective in relieving the inhibition, FSH administration is at least partly effective.

Animals↗

PubMed1988

Cell turnover in ciliary epithelium compared to other slow renewing epithelia in the adult mouse.

Adult albino mice received tritiated thymidine either injected subcutaneously (333 microCi) every 6 hours for up to 36 hours, or administered in their drinking water for up to 74 days (about 45 microCi/day). Tissue sections were examined with autoradiography to determine the distribution of the label. Animals receiving subcutaneous injections showed no labeled cells in the choroid plexus epithelium and only one cell of 6600 cells counted in the ciliary epithelium was labeled. Animals exposed to the isotope in their drinking water for 74 days showed considerable uptake of label in hepatocytes (15%) and cortical kidney tubules (17%), whereas ciliary and choroid epithelia showed very low uptake at 0.25% and 0.01%, respectively. The data show that the ciliary and choroid epithelia have a very slow turnover rate compared to other slow renewing tissues, and, under normal conditions, these tissues are not renewed in the animal's adult life span.

Animals↗

PubMed1985

Transmission of leprosy in nude mice.

Nude mice in groups of 10 were exposed to M. leprae by subcutaneous injection and topically through the nose, lungs, mouth, stomach and skin, broken and unbroken. Animals injected subcutaneously and those topically exposed to M. leprae through the nose developed localized disease which in the course of time became generalized. The nose seems to be the site of entry of M. leprae in this model. To the extent that these results can be generalized to humans exposed to M. leprae, it would seem that leprosy bacilli impact topically on the nasal mucosa or are inoculated subcutaneously.

Animals↗

PubMed1999

Pain-induced analgesia mediated by mesolimbic reward circuits.

We tested the hypothesis that noxious stimuli induce pain modulation by activation of supraspinal structures. We found that intense noxious stimuli (i.e., subdermal injection of capsaicin or paw immersion in hot water) induced profound attenuation of the jaw-opening reflex in the anesthetized rat; forepaw subdermal capsaicin also elevated the mechanical hindpaw-withdrawal threshold in the awake rat. These antinociceptive effects were blocked by previous injection of either a dopamine antagonist (flupentixol) or an opioid antagonist (naloxone) into the nucleus accumbens. Additional experiments in anesthetized animals showed that the antinociceptive effect of noxious stimulation by either capsaicin (>/=100 micrograms) or hindpaw immersion in hot water (>/=45 degrees C for 4 min) correlated with the intensity of the stimulus. The maximal antinociceptive effect of capsaicin was similar in magnitude to that of a high dose of morphine (10 mg/kg) injected subcutaneously. Injection of the GABA(A)-receptor agonist muscimol, but not naloxone, into the rostroventral medulla, a major component of descending pain modulation systems, blocked capsaicin-induced antinociception. Although it is widely thought that painful stimuli may induce analgesia by activating forebrain structures, this is the first demonstration that such a mechanism exists. Furthermore, this mechanism can be engaged by naturalistic stimuli in awake animals. These observations imply that painful stimuli might under certain conditions be rewarding.

Analgesia↗

PubMed1999

Pain management of pancreatic cancer.

Quality of life is receiving increasing attention as a criterion for the assessment of treatment, not least for surgery, in pancreatic cancer. In exocrine pancreatic cancer there are three main symptoms that must be dealt with: pain, loss of weight and jaundice. All of them seriously impair quality of life, but most often pain is the most feared by the patients. Despite this, the intensity and the quality of the pain is all too often only scantly described. In 85 consecutive patients with newly diagnosed pancreatic cancer we have prospectively registered the quality and quantity of their pain and correlated it to tumor and patient characteristics. It was found that about one fourth of the patients were totally pain free and half of all suffered a pain described by two or less on a Visual Analogue Scale. Only one in ten had severe pain. Although more and more patients were treated with morphine, it was still about one third of all patients that had no or only little pain in the last part of their life. Pain had a strong correlation to survival. This may be due to secondary effects like depressing the mood of the patient and reducing the food intake, but is probably more often a reflection of that generalized cancer induces more pain. Analgesic drugs are the cornerstone of the pharmacologic management of pain due to pancreatic cancer. A significant part of the patients do well with only paracetamol and nonsteroidal antiinflammatory agents. Combining these agents with narcotic analgesics can enhance pain control while lessening the dose of narcotics. A wide range of narcotics are available as well as different modes for delivery: regular pills, slow release forms, injections, subcutaneous injections, epidural etc. Each patient's pain management should be individualized, based on the intensity of pain, the type of pain and the side effects. It is essential not only to describe the medication, but also to follow-up the development of the pain and the patient's total experience of the situation. As an alternative to narcotics, plexus celiac blocks have been used with somewhat different result; in the hands of the experts the percutaneous approach is usually sufficient, but in the hands of other also poor results are reported. During the last years thoracoscopic splanchnicectomy has been tried as a complement giving long-standing pain relief with little or no side effects in the majority of patients. With this approach the sympathetic fibers lead by the symphathetic chain and further by the nervus splanchnicus major, minor and minors are divided. The denervation is easily done and can be performed bilateraly in one seance. This method will probably be used more often as the technique is now well described.

Humans↗

PubMed2002

[Feasibility of using hepatitis B virus surface antigen as target antigen in immunogen therapy against cancer].

OBJECTIVE: To investigate the feasibility of using hepatitis B virus surface antigen (HbsAg) as a tumor-associated antigen in immunogen therapy against tumor. METHODS: (1) Dendritic cells (DCs) were extracted from bone marrow of mice and cultured. Mature DCs were transfected with adenovirus vector highly expressing HBsAg and enhanced green fluorescence protein (EGFP) (DC-HBsAg). Eight C57BL/6J mice were immunized by intravenous injection of 1 x 10(6) DC-HBsAg. Seven days after, the immunization procedure was boosted by injection of the DC-HBsAg with the same dosage once more. Another eighteen mice were divided into 3 groups, 6 in each, to be injected with DC-EGFP (DCs transfected with 1 x 10(6) adenovector expressing only EGFP), 1 x 10(6) DCs, and PBS of the same volume as controls. One week after the second injection, subcutaneous injection of 7X105 mouse melanoma cells B16 or B16-HBsAg (B16 cells expressing HBsAg) was performed to each mouse. The size of tumor was measured every 2 - 3 days. When the tumor grew to the size of 2cm or caused ulcer the tumor-carrying mice were killed. The mice in the DC-HBsAg group that showed no tumorigenesis 30 days after inoculation of B16-HBsAg were re-inoculated with 7X105 B16-HBsAg. Three normal B6 mice of the same age and sex were used as controls. (2) Other patch of mice were divided into 4 groups and injected with DC-HBsAg, DC-EGFP, HBsAg (1 ug/mouse), and PBS in the same way as mentioned above. One week after the second injection at least 5 mice in each group were inoculated with 7X105 B16-HBsAg and 2 mice in each group were killed to have their serum anti-HbsAg titers examined. RESULTS: (1) Seven days after inoculation of B16-HbsAg tumor began to grow in all mice in the three control groups. Tumor was found in 5 of the 8 mice in the DC-HBsA group and the other 3 mice in this group remained free of tumor. However, the size of tumor in these 5 mice was significantly smaller than thate in other groups (P < 0.01). B16-HBsAg was re-inoculated to the three mice that showed no tumor growth 30 days after the first inoculation of B16-HBsAg. However, still no tumor could be found in them. After inoculation of wild type melanoma cell B16 tumorigenesis was seen in the two immunization groups. (2) The titer of anti-HBsAg antibody induced by DC-HBsAg was obviously lower than that induced by recombinant HBsAg vaccine. However, the size of tumor in HBsAg group was obviously smaller than that in recombinant HBsAg group. CONCLUSION: DC-HBsAg induces HBsAg-specific antitumor effect, stronger than that induced by recombinant HBsAg vaccine although the humoral immune response elicited by DC vaccine is much weaker that that induced by recombinant HBsAg vaccine. HBsAg can be used as a target antigen in immunogen therapy for treatment of cancer.

Animals↗

PubMed1992

The immunomodulating preparation Ukrain does not induce anaphylactic sensitization in mice and guinea pigs.

The ability of Chelidonium majus L. alkaloids derivative Ukrain to induce an anaphylactic sensitization was tested on mice and guinea pigs. The levels of IgE antibody in the mouse sera, and IgG1a, IgG1b as well as IgE antibody levels in guinea pig sera, were evaluated by passive cutaneous anaphylaxis (PCA) tests. Ukrain alone or adsorbed on aluminium hydroxide gel (alum) introduced into BALB/c mice in several subcutaneous injections was unable to stimulate measurable anti-Ukrain IgE antibody response. Moreover, Ukrain introduced together with ovalbumin (OA) into mice in the course of immunization with OA induced lower anti-OA antibody response as compared to the response induced by OA alone. Ukrain adsorbed on alum and injected subcutaneously into guinea pigs did not induce measurable IgG1a, IgG1b and IgE antibody response. The present results suggest that the immunomodulating preparation Ukrain could be therapeutically safe at least as far its inability to induce anaphylaxis is concerned.

Adjuvants, Immunologic↗

PubMed1992

Lymph nodal vital staining with newer carbon particle suspensions compared with India ink: experimental and clinical observations.

CH40 and CH1500AA are newly prepared carbon suspensions which were examined as vital staining dyes for their usefulness in visualizing lymphatics at operation and to blacken lymph nodes. In mice, these carbon suspensions at 0.001 ml/g of body weight and India ink were injected subcutaneously into the footpad of the right hindpaw. Regional lymph nodes were visualized and were examined stereomicroscopically to determine how intensely these nodes blackened with carbon suspensions. Compared with India ink, CH40 and CH1500AA blackened the regional lymph nodes much faster and more vividly (1-8 min. after subcutaneous injection). As analyzed by centrifugal particle size distribution, CH40 and CH1500AA are narrowly distributed with a small particle size (150 and 167 nm, respectively, in mean diameter). By contrast, India ink is comprised of widely distributed and relatively large particles in suspension (mean diameter--254 nm). In 10 patients undergoing radical gastrectomy for treatment of stomach cancer, CH40 blackened 69% of regional lymph nodes with metastases (38 of 55) and 76% of those nodes without metastases (387 of 512).

Animals↗

PubMed2005

In vivo and in vitro effect of baicalein on human prostate cancer cells.

We investigated the in vitro effects of baicalein and baicalin on human umbilical vein endothelial cells (HUVECs) and on human prostate tumor cells (DU-145 and PC3) as well as the effect of orally administered baicalein on the growth of DU-145 cells after subcutaneous injection into SCID mice. In vitro effects of baicalein and baicalin treatment on human prostate cancer cell lines DU-145 and PC-3 were assessed by employing cell proliferation (MTS) assay, cytotoxicity (LIVE/DEAD) assay, and TUNEL assay. In vitro anti-proliferative and anti-angiogenic properties of baicalein and baicalin were studied on HUVECs by sprout assay. The effect of orally administered baicalein on tumor growth in SCID mice was studied in four groups (n=10) of animals injected subcutaneously with DU-145 cells and treated daily for 28 days. The control group received only vehicle (carboxymethylcellulose), whereas the other three groups received escalating doses of baicalein (10, 20, and 40 mg/kg per day). Baicalein and baicalin exhibit dose-dependent growth inhibitory effects on human prostate cancer cells and umbilical vein endothelial cells in vitro. Also, treatment by these two flavonoid compounds significantly decreased the average number and length of sprouts formed by the endothelial cell aggregates in a dose-dependent manner. In vivo, treatment of mice with baicalein demonstrated a statistically significant tumor volume reduction (p<0.01) when compared to the control. This is the first study demonstrating an in vivo growth inhibitory effect of orally administered baicalein on human prostate tumors in mice.

Administration, Oral↗