Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials.

Objective: This study aims to assess the safety and efficacy of Thymosin Alpha 1 (Tα1) through a comprehensive narrative review of clinical studies involving over 11 000 human subjects in more than 30 trials. The focus was on Tα1's application in COVID-19, autoimmune conditions, and cancer treatment, with implications for future considerations. Methods: We systematically searched articles relevant to critical studies on COVID-19, infectious diseases, cancer, and autoimmune diseases indexed on Pubmed, Google Scholar, and Cochrane Library. Our focus was on evaluating the safety and efficacy of Tα1 in human subjects. Clinical trials conducted worldwide involving diverse populations were analyzed to assess the safety and effectiveness of Tα1. The review examines explicit outcomes in over 11 000 human subjects, emphasizing its role in addressing COVID-19, autoimmune conditions, and cancer treatment. Results: Contrary to the FDA's restriction on Tα1 and 21 additional peptides in 2023, our analysis reveals consistent evidence of Tα1's safety and efficacy. The peptide has demonstrated significant effectiveness in treating various conditions, including COVID-19, autoimmune disorders, and cancer. This review summarizes conclusions drawn from a comprehensive examination of clinical trials worldwide. Conclusions: Based on substantial evidence from clinical trials, Tα1 emerges as a well-tolerated and effective immune modulator. The FDA>s restriction appears unfounded, as Tα1 has shown safety and efficacy beyond the initially specified conditions. Urgent attention and intervention are warranted to ensure the continued availability of this life-saving peptide through prescription. Therefore, it is recommended that the FDA permits 503A compounding pharmacies to compound Tα1, considering its potential to treat a variety of conditions effectively.

Value of Thymosin α1 Combined With Blood Purification to Increase Successful Rescues of Shock Patients.

Context: Septic shock (SS) can pose a high risk of death if rescue efforts in an emergency room aren't started in a timely manner. Thus, rapid and efficient treatment is of great significance to the SS patients' survival. T-α1 can enhance the cellular immune function of patients, and blood purification (BP) can improve the hemodynamics of SS patients by clearing inflammatory mediators in the blood. Objective: The study intended to explore the effects of Thymosin α1 (T-α1) plus blood purification (BP) on SS patients under the emergency green channel (GC), a fast and efficient service system that hospitals provide for acutely and critically ill patients. Design: The research team designed a randomized controlled study. Setting: The study took place in the Emergency Department at the Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, Shaanxi, China. Participants: Participants were 86 SS patients who came to the hospital for treatment between June 2019 and January 2021. Intervention: The research team numbered the patients in sequence according to the admission time of the patients, and then randomly numbered them by the computer, and assigned participants to an intervention or a control group, with 43 participants in the intervention group receiving T-α1 plus BP therapy and 43 participants in the control group receiving BP treatment only. Outcome Measures: The study measured preparation time before treatment, symptom-onset-to-door (SOTD), duration of shock, length of stay in the intensive care unit (ICU), and incidence of adverse reactions. The study also assessed changes between baseline and postintervention in inflammatory cytokines (ICs), immunological function, and myocardial-function markers. Finally, the research team conducted a one-year follow-up to determine participants' prognostic survival. Results: The groups showed no significant differences in the preparation time before treatment, SOTD, rescue success rate, and incidence of adverse events (P > .05), while the intervention group showed a significantly shorter duration of shock and length stay in the ICU and a significantly higher overall response rate (P < .05). The research team observed significant improvements in the T-lymphocyte subsets, ICs, and myocardial function in both groups postintervention, but the changes in the intervention group were significantly greater (P < .05). Follow-up results showed no significant differences in overall survival between the intervention and control groups (P > .05), but the average LC was significantly higher in the intervention group (P < .05). Conclusions: For SS patients, the combination of T-α1 and BP under the emergency GC can effectively improve their immunological and myocardial function, reduce inflammatory reaction, and prolong their LCs, which provides a greater guarantee of the effectiveness of treatment for SS patients in the future.

Adjunctive Thymosin Beta-4 Treatment Influences MΦ Effector Cell Function to Improve Disease Outcome in Pseudomonas aeruginosa-Induced Keratitis.

Our previous work has shown that topical thymosin beta 4 (Tß4) as an adjunct to ciprofloxacin treatment reduces inflammatory mediators and inflammatory cell infiltrates (neutrophils/PMN and macrophages/MΦ) while enhancing bacterial killing and wound healing pathway activation in an experimental model of P. aeruginosa-induced keratitis. This study aimed to mechanistically examine how Tß4 influences MΦ function in particular, leading to reduced inflammation and enhanced host defense following P. aeruginosa-induced infection of the cornea. Flow cytometry was conducted to profile the phenotype of infiltrating MΦ after infection, while generation of reactive nitrogen species and markers of efferocytosis were detected to assess functional activity. In vitro studies were performed utilizing RAW 264.7 cells to verify and extend the in vivo findings. Tß4 treatment decreases MΦ infiltration and regulates the activation state in response to infected corneas. MΦ functional data demonstrated that the adjunctive Tß4 treatment group significantly downregulated reactive nitrogen species (RNS) production and efferocytotic activity. In addition, the in vitro studies showed that both Tß4 alone and adjunctive Tß4 treatment influenced MΦ cellular function following LPS stimulation. Collectively, these data provide further evidence that adjunctive Tß4 + ciprofloxacin treatment offers a more efficacious option for treating bacterial keratitis. Not only does the adjunctive therapy address both the infectious pathogen and corneal wound healing response, but it also influences MΦ infiltration, activation, and function, as revealed by the current study.

Therapeutic effect of Xuebijing combined with thymosin on hemorrhagic fever with renal syndrome: A protocol of systematic review and meta-analysis.

BACKGROUND: The goal of this study is to assess the therapeutic effect of Xuebijing combined with thymosin (XBJ-T) for the treatment of patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We will search the electronic databases of Cochrane Library, PUBMED, EMBASE, PsycINFO, Scopus, Opengrey, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Google scholar, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database from inception to the present. No language and publication status will be employed in this study. Based on the predefined eligibility criteria, selection of study and data extraction will be performed by 2 researchers independently. Study quality will be assessed using Cochrane risk of bias tool. We will apply RevMan 5.3 software to pool and analyze the extracted data. RESULTS: This study will assess the therapeutic effect of XBJ-T for the treatment of patients with HFRS. CONCLUSION: The findings of this study may provide systematic evidence to judge whether XBJ-T is an effective and safety intervention for HFRS. STUDY REGISTRATION NUMBER: INPLASY202040068.

Historical review on thymosin α1 in oncology: preclinical and clinical experiences.

INTRODUCTION: Thymosin α1 (Tα1) is a naturally occurring polypeptide that regulates immune cell development and function, and is also capable of interacting with multiple target cells with relevant biological effects. The rationale of Tα1 use in cancer treatment stems from the consideration that tumor progression is favored by a failure of the immune response and in turn induces immune suppression. This paper will review the historical background of Tα1 use in oncology, aiming to highlight the importance of Tα1 as an immunotherapeutic tool to be used in combination with chemotherapy, a concept that is not yet fully established in clinic. AREAS COVERED: The efficacy and safety of combining Tα1 with chemotherapy and cytokines were first evaluated in murine tumor models, providing essential information about effects, mechanisms of action, doses and treatment protocols. The therapeutic potential of the chemo-immunotherapy protocol on metastatic melanoma and lung cancer has been confirmed in controlled clinical trials. Critical for the efficacy of the chemo-immunotherapy protocol is the dual action of Tα1 on immune effector and tumor cells. EXPERT OPINION: On the basis of the preclinical and clinical results available, the use of the chemo-immunotherapy protocol, in which the role of Tα1 is central, is strongly recommended.

Evaluation of thymosin α 1 in nonclinical models of the immune-suppressing indications melanoma and sepsis.

OBJECTIVES: Recent understanding of the complex pathophysiology of melanoma and severe sepsis suggests that immune-modulating compounds such as thymosin alpha 1 (INN: thymalfasin; abbreviated Ta1) could be useful in the treatment of these two unrelated immune-suppressing indications. RESEARCH DESIGN AND METHODS: Three nonclinical murine models were utilized, including: i) a lung metastasis B16 model; ii) a B16-based tumor growth model; and iii) a cecal-ligation and puncture (CLP) sepsis model. RESULTS: In the lung metastasis model, Ta1 treatment alone led to a 32% decrease in metastases (p < 0.05). Additionally, combinations of Ta1 and an anti-PD-1 antibody led to significantly fewer metastases than vehicle. In the tumor growth model, significant decreases in tumor growth were seen: 34% (p = 0.015) to 46% (p = 0.001) depending on the Ta1 dose. In the CLP sepsis model, Ta1 treatment showed a positive trend towards increased survival and decreased bacterial load. In this CLP model, Ta1 also appeared to have an effect on the levels of some biomarkers. CONCLUSIONS: All three models demonstrated a benefit after treatment with Ta1, with no evidence of toxicity. These initial pilot studies support the hypothesis that immune-suppressive indications, including sepsis and melanoma, may be treated with Ta1 alone or by Ta1 in combination with other immunotherapies.

Phyllanthus species versus antiviral drugs for chronic hepatitis B virus infection.

BACKGROUND: Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists. When compared with placebo or no intervention, we were unable to identify convincing evidence that phyllanthus species are beneficial in patients with chronic hepatitis B. Some randomised clinical trials have compared phyllanthus species versus antiviral drugs. OBJECTIVES: To evaluate the benefits and harms of phyllanthus species compared with antiviral drugs for patients with chronic HBV infection. SEARCH METHODS: Searches were performed in The Cochrane Hepato-Biliary Gorup Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expended, and the Chinese Biomedical CD Database, China Network Knowledge Information, Chinese Science Journal Database, TCM Online, and Wanfang Database. Conference proceedings in Chinese were handsearched. All searches were conducted until 31st October 2012. SELECTION CRITERIA: Randomised clinical trials comparing phyllanthus species with antiviral drugs for patients with chronic HBV infection. We included trials irrespective of blinding, publication status, or language. DATA COLLECTION AND ANALYSIS: Two authors selected the trials and extracted the data independently. The RevMan software was used for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CI). We assessed the risk of bias to control for systematic errors. We calculated the number of patients needed (required information size) to be randomised in order to make reliable conclusions. We assessed the cumulative findings with trial sequential analysis to control for random errors. MAIN RESULTS: We identified five randomised clinical trials with 290 patients. All trials were considered to have high risk of bias. Patients in the experimental group received compound phyllanthus for three months to 12 months. Patients in the antiviral drug group received lamivudine, interferon alpha, thymosin, or thymosin alpha 1. None of the trials reported mortality, hepatitis B-related morbidity, quality of life, or liver histology. Phyllanthus seemed to have a superior effect on clearance of serum HBeAg at the end of treatment in conventional meta-analysis (RR 0.76; 95% CI 0.64 to 0.91, P = 0.002; I(2) = 0%), but not when trial sequential analysis was applied. Phyllanthus had no significant effect on clearance of serum HBsAg (RR 1.00; 95% CI 0.93 to 1.08, P = 0.92; I(2) = 0%) or HBV DNA (RR 0.83; 95% CI 0.53 to 1.31, P = 0.43; I(2) = 70%) when compared with antiviral drugs. Data on HBeAg seroconversion was reported in one trial and no significant difference was found comparing phyllanthus versus lamivudine (RR 0.89; 95% CI 0.71 to 1.11). No data were reported on adverse events in the five trials. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support or refute the use of phyllanthus for patients with chronic hepatitis B virus infection. Researchers who are interested in conducting further randomised clinical trials on phyllanthus ought to monitor both beneficial and harmful effects and should primarily test the herb against placebo in addition to antiviral drugs that are known to offer more benefit than harm. Only in this way new interventions can be assessed without compromising personal ethical considerations.

Interventions for preventing infection in nephrotic syndrome.

BACKGROUND: Infection is one of the most common complications and still remains a significant cause of morbidity and occasionally mortality in patients, especially children with nephrotic syndrome. Many different prophylactic interventions have been used or recommended for reducing the risks of infection in nephrotic syndrome in clinical practice. Whether the existing evidence is scientifically rigorous and which prophylactic intervention can be recommended for routine use based on the current evidence is still unknown. OBJECTIVES: To assess the benefits and harms of any prophylactic intervention for reducing the risk of infection in children and adults with nephrotic syndrome. SEARCH METHODS: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library), MEDLINE and Pre-MEDLINE (from 1966), EMBASE (from 1980), China Biological Medicine Database (1979 to December 2009), Chinese Science and Technique Journals Database (to December 2009), China National Infrastructure (to December 2009), WangFang database (to December 2009), reference lists of nephrology textbooks, review articles, relevant studies and abstracts from nephrology meetings without language restriction.Date of last search: 6 February 2012 SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing any prophylactic interventions (pharmacological or non-pharmacological) for preventing any infection in children and adults with nephrotic syndrome. DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (appearance of infection, mortality, quality of life and adverse events). Results were expressed as risk ratios (RR) for dichotomous outcomes or as mean differences (MD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Twelve studies conducted in China, including 762 children with nephrotic syndrome were identified. No studies were identified in adults. All studies compared one kind of prophylactic pharmacotherapy (intravenous immunoglobulin (IVIG), thymosin, oral transfer factor, mannan peptide tablet, Bacillus Calmette-Guerin (BCG) vaccine injection, polyvalent bacterial vaccine (Lantigen B) and two kinds of Chinese medicinal herbs: a compound of Chinese medicinal herbs (TIAOJINING) and Huangqi (astragalus) granules) plus baseline treatment with baseline treatment alone. No RCTs were identified comparing antibiotics, non-pharmacological prophylaxis, or pneumococcal vaccination. Four studies showed a significantly beneficial effect of IVIG on preventing nosocomial or unspecified infection in children with nephrotic syndrome (RR 0.47, 95% CI 0.31 to 0.73). Thymosin (RR 0.50, 95% CI 0.26 to 0.97), oral transfer factor (RR 0.51, 95% CI 0.35 to 0.73), BCG vaccine injection (RR 0.68, 95% CI 0.48 to 0.95), Huangqi granules (RR 0.62, 95% CI 0.47 to 0.83) and TIAOJINING (RR 0.59, 95% CI 0.43 to 0.81) were also effective in reducing the risk of infection in children with nephrotic syndrome. However mannan peptide tablet (RR 0.46, 95% CI 0.21 to 1.01) and polyvalent bacterial vaccine (RR 0.24, 95% CI 0.06 to1.00) were not superior to baseline treatment in reducing the risk of infection for nephrotic children. No serious adverse events were reported. AUTHORS' CONCLUSIONS: IVIG, thymosin, oral transfer factor, BCG vaccine, Huangqi granules and TIAOJINING may have positive effects on the prevention of nosocomial or unspecified infection with no obvious serious adverse events in children with nephrotic syndrome. However the methodological quality of all studies was poor, the sample sizes small, and all studies were from China, and thus there is no strong evidence on the effectiveness of these interventions.

Immunological modifications during treatment with thymosin alpha1 plus antiviral therapy in chronic hepatitis C.

The current standard therapy for the treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin, although many patients fail to clear the virus and their retreatment options are still unsatisfactory. Thymosin alpha1 (Talpha1) is an immunomodulating agent that has been proposed as complementary therapy for chronic HCV, especially in the setting of difficult-to-treat patients. The aim of this study was to evaluate, in patients nonresponsive to previous Peg-based therapy, the effect of standard antiviral therapy with or without Talpha1 on peripheral lymphocyte subsets. Twenty-four patients, 12 receiving Talpha1 and 12 standard therapy, were enrolled. Peripheral subpopulations were analyzed by flow cytometry. Although the addition of Talpha1 did not seem to significantly modify the T-lymphocyte subpopulations, as comparable behaviors were observed in the CD4 and CD8 longitudinal evaluation, Talpha1 produced an earlier increase of natural killer cells. An accurate selection of HCV patients who can benefit from immunomodulation is needed.

Protection of thymosin beta-4 on corneal endothelial cells from UVB-induced apoptosis.

Cornea absorbs most of daily ultraviolet (UV) light. An excess of UV damages results in not only keratopathy and cataract but also maculopathy. It has been reported that thymosin beta-4 (Tbeta4) promotes wound healing, decreases inflammatory response and prevents apoptosis of corneal epithelial cells. However, it is not clear whether Tbeta4 protects UVB-induced corneal injury, particularly in corneal endothelial cells because of its non-proliferation in nature. The purpose of this study is to compare the protective effects of Tbeta4 on bovine corneal endothelial (BCE) cells from low- and high-dose UVB damage. In this study, 1 microg/ml of Tbeta4 was added to BCE cells 2 h before low (12.5 mj/cm2) or high dosage (100 mj/cm2) UVB exposure. Using a fluorogenic substrate cleavage assay, we found that Tbeta4 diminished the reactive oxygen species level in BCE cells elicited by UVB. However, the protection of viability by Tbeta4 could only be detected under low-dose UVB exposure. Moreover, both caspase-9 activity and annexin V/propidium iodine staining demonstrated that Tbeta4 only protected BCE cells from low-dose UVB-induced apoptosis but not high-dose UVB-induced necrosis. Together, Tbeta4 protected corneal endothelial cells from UVB-induced oxidative stress and apoptosis after low-dose UVB exposure. The results support further investigation towards topical use or anterior chamber injection of this small hydrophilic peptide in treating and preventing UVB-induced corneal endothelial damage.

[Clinical trial with a new immunomodulatory strategy: treatment of severe sepsis with Ulinastatin and Maipuxin].

OBJECTIVE: To evaluate the efficacy of treatment of severe sepsis by combining anti-inflammatory and immune-enhancing agents. METHODS: Multiple-center, prospective, randomized, controlled designs. Cases were from surgical or general ICU of 26 university teaching hospitals. Totally, 433 adult patients developing severe sepsis with Marshall score 5-20 were enrolled. Patients received either standard treatment based on SSC direction (as group control), or additional Ulinastatin (urinary trypsin inhibitor) 300 K units per day+thymosin alpha1 (Maipuxin) 1.6 mg per day for 7 days (as treatment group 1, adopted in the first trial), or double dosage of the above agents (as treatment group 2, adopted in the second trial). The outcome of 28 and 90 days, APACHEII and Marshall score, monocyte HLA-DR/CD14+ at several points until 28 days, and the lengths of ICU stay, antibiotics usage and mechanical ventilation were determinated. RESULTS: In the first trial (91 cases), there was no significant difference in variables between treatment group 1 and control at 28 days. In the second trial (342 cases), the mortality of treatment group 2 decreased from 38.32% to 25.14% (P=0.0088), compared with group control at 28 days, and from 52.10% to 37.14% (P=0.0054) on 90 days. APACHEIIalso decreased from 14.32 to 12.70 (P=0.0384) and monocyte HLA-DR/CD14+ increased from 40.13% to 51.65% (P=0.0092) on 28 days in treatment group 2. Other variables had no significant differences between two groups. CONCLUSION: Treatment by the combining anti-inflammatory and immune enhancing agents can significantly improve the outcome of severe sepsis. The efficacy of this therapy seems to be dose dependent on.

Symptom combinations associated with outcome and therapeutic effects in a cohort of cases with SARS.

Severe acute respiratory syndrome (SARS) is an infectious disease and some of its symptoms were clinically indistinguishable of those from similar diseases. This study aimed to find the symptom combinations associated with adverse outcome and the therapeutic effects in a cohort of patients with probable SARS retrospectively. In 2003, 123 SARS cases in Beijing were subjected to a strictly western medicine (WM) treatment, or a combined treatment (WM plus Herba houttuyniae injection, addition of individualized herbal treatments when necessary), of which 115 were followed till death or discharge; 8 were transferred and lost to follow-up. In both treatment groups, clinical manifestations were evaluated daily; development of signs and symptoms, and their possible relationship with outcome, were assessed. The relationships between these sign/symptom complexes and outcome under two treatment protocols were evaluated and differences were noted. Dynamic symptom combinations, dividing into the early, the medium-term and the durational symptom clusters, were identified as likely being related to the adverse outcomes of SARS (p < 0.05, p < 0.01). Compared with a strictly WM treatment, the combined treatment resulted in a longer hospital stay (p = 0.028), a non-statistically significant mortality rate decrease (combined treatment: 9.6% versus WM: 11.1%), and a significant improvement of arthralgia and myalgia (p < 0.05) in the early symptom cluster. Additionally, the combined protocol improved arterial oxyhemoglobin saturation significantly at day 22 (p < 0.05). In conclusion, the progress and outcome of SARS may be associated with specific temporal patterns of development in combination of several non-specific signs and symptom complexes, which are also helpful for evaluating the therapeutic effects on SARS patients.

Immunomodulatory therapy for chronic hepatitis B virus infection.

Hepatitis B virus (HBV) is one of the most prevalent viral pathogens of man with around 350 million chronically infected patients. It has been postulated that in persistently infected individuals the HBV-specific immune response is too weak to eliminate HBV from all infected hepatocytes, but sufficiently strong to continuously destroy HBV-infected hepatocytes and to induce chronic inflammatory liver disease. The primary aim in the treatment of chronic hepatitis B is to induce sustained disease remission and prevent serious complications like liver failure and/or hepatocellular carcinoma. The recent emergence of drug-resistant HBV mutants and post-treatment relapse as a consequence of nucleoside analogue monotherapy emphasizes that the principal goal should be to stimulate a successful immune response. In this paper we will focus on the immune response to HBV and we will review reported data on immunotherapeutic strategies like immunomodulatory drugs (cytokines and Thymic derivates) and vaccine therapies using currently available recombinant anti-HBV vaccines, lipopeptide-based T cell vaccine and newly developed genetic vaccines.

Hepatitis B infection in China.

Chronic HBV infection is a serious health threat in the Asian-Pacific region. The introduction of lamivudine has greatly improved the hope of these patients and is undoubtly a milestone in the management of chronic HBV infection. The combination of lamivudine with another nucleotide or nucleoside analogue or immunomodulatory agent to improve its therapeutic efficacy further must be investigated. Also, the use of lamivudine to prevent HBV reactivation on withdrawal of immunosuppressive therapy should be explored.

Tratamiento de las hepatitis virales crónicas B y C según la medicina basada en la evidencia / Evidence-based medicine treatment of chronic viral hepatitis B and C

En todo el mundo, la hepatitis viral es la principal causa de ictericia, enfermedad hepática crónica, cirrosis y hepatocarcinoma. Aunque se han realizado importantes avances en el tratamiento y en la prevención , no existe un tratamiento totalmente satisfactorio para cada una de estas dos enfermedades. Ambas representan un porcentaje elevado de la etiología de las hepatitis virales y tienen una alta tendencia a la cronicidad y al desarrollo de cirrosis, conllevando gran consumo de recursos sanitarios. Por otra parte los tratamientos son prolongados y con fármacos de precio elevado. Por ello es necesario aplicar la medicina basada en la evidencia en este tipo particular de patología para alcanzar la mejor relación coste/beneficio. En la presente revisión, analizamos los diferentes fármacos y regímenes de tratamiento empleados en las hepatitis crónicas virales B y C, así como las respuestas obtenidas (AU)

[The effect of thymosin fractions on the development of compression edema-swelling of the brain]. / Vliianie fraktsii timozina na razvitie kompressionnogo oteka-nabukhaniia golovnogo mozga.

The search for pathogenetically drugs for the treatment and prevention of edema-swelling of the brain (ESB) is one of the urgent problems of modern biology and medicine. Immune reactions take part in the development of pathological reactions in ESB formation. The antiedemic action of drugs affecting simultaneously the processes in the nervous and immune systems was studied. Such properties are possessed by regular peptides--thymosin fractions. It was demonstrated on a model that the antiedemic effect of thymic peptides under study was due to the influence of the mediator systems: serotonin and adrenergic. The data obtained allowed the antiedemic mechanism of the effect of thymoptin to be associated with its immunostimulating effect. At the same time, the antiedemic effect of thymalin is not connected directly with the immunostimulating action of the drug.

Plasma levels of a viral protein during adjuvant treatment: reflection of murine mammary tumor status and therapeutic effect.

The mouse mammary tumor and its associated virus, mouse mammary tumor virus, were chosen to test the possibility of using plasma levels of a Mr 52,000 viral glycoprotein (gp52) as a means for monitoring changes in tumor status during surgical adjuvant cyclophosphamide:doxorubicin (Adriamycin):5-fluorouracil treatment. Analysis of tumor recurrence and plasma gp52 concentrations during the postoperative period demonstrated that both parameters were significantly decreased in the group receiving cyclophosphamide:doxorubicin:5-fluorouracil treatment. This observation suggests that plasma gp52 levels may be a useful alternative measure of therapeutic effect during surgical adjuvant treatment. A retrospective analysis of gp52 plasma levels and tumor status of individuals during treatment has revealed the following associations. (a) An early sharp postsurgical elevation in plasma gp52 level was associated with subsequent death of treated animals. (b) Maintenance of postsurgical gp52 levels at a low level (less than or equal to 4.2 ng/ml) during and after treatment was characteristic of all tumor-free survivors. (c) A gradual rise in plasma gp52 level accompanied CAF-delayed tumor recurrence. gp52 levels increased in all treated animals 2 wk prior to detectable tumor regrowths, resulting in a statistically significant increase in mean gp52 level (2.2 to 5.4 ng/ml). However, the magnitude of this increase was small for the majority of animals with tumor regrowths, and greater, more definitive elevations in plasma gp52 levels were only detected at the time of frank tumor recurrence. In addition, comparisons of early mean gp52 levels (8 to 10 days after surgery) for controls and for animals receiving various forms of alternative treatment have indicated that differences in gp52 levels reflect subsequent differences in recurrence rates. The present data, obtained during surgical adjuvant treatment of BALB/c X DBA/8 F1 mice and viewed in a retrospective fashion, demonstrate that plasma gp52 concentrations reflected therapeutic effects.