Antineoplaston

Torsional stress in double-stranded DNA enables and regulates facets of chromosomal metabolism, replication and transcription, and requires regulatory enzymatic systems including topoisomerases and histone methyltransferases. As such, this machinery may be subject to deleterious effects from reactive mutagens, including ones from carcinogenic polycyclic aromatic hydrocarbon (PAH) adduct formation with DNA. Supercoiled plasmid DNA was investigated for its torsional responses to adducts formed in vitro from PAH benzylic carbocation reactive intermediates created spontaneously by release of leaving groups...

BACKGROUND: Recently, the direct intratumoral (i.t.) injection of anticancer agents has been investigated. A newly synthesized Antineoplaston A10 analog 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) showed an antitumor activity in human breast cancer cell line. Unfortunately, MPD suffered from poor water solubility. MATERIALS AND METHODS: Pseudoternary phase diagram of oil (isopropyl myristate), surfactant (Tween 80), cosurfactant (ethanol), and water was plotted...

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A10, (3-phenylacetylamino-2,6-piperidinedione), is a natural peptide with broad antineoplastic activity. Recently, in vitro antitumor effect of a new A10 analog [3-(4-methoxybenzoylamino)-2,6-piperidinedione] (MPD) has been verified. However, poor aqueous solubility represents an obstacle towards intravenous formulation of MPD and impedes successful in vivo antitumor activity. To surmount such limitation, MPD microemulsion (MPDME) was developed. A 31 22 full factorial design using Design-Expert® software was adopted to study the influence of different parameters and select the optimum formulation (MPDME1)...

Background. The purpose of this study is to understand the oral mucosal immune status of cancer patients and to make clear whether antibacterial proteins such as salivary secretory immunoglobulin (SIgA) and lysozyme in saliva were influenced by patients' health status and certain medical treatment therapy. Materials and Methods. This study included 221 patients with malignant tumor receiving antineoplastic treatment and 171 age- and gender-matched healthy controls. Results. The results showed that patients suffering malignant tumor had lower level of SIgA and higher level of lysozyme than healthy subjects (P < 0...

Tectal glioma is a midbrain tumor. The patient generally presents with symptoms related to increased intracranial pressure and requires treatment for hydrocephalus. No effective pharmacological treatments have yet been introduced. This report discusses a case of a 13-year-old male diagnosed with tectal glioma who obtained a complete response and long-term survival after the treatment with antineoplastons (ANP) in phase II trial. Prior treatment consisted of placement of a ventriculoperitoneal shunt. After 6 years of stabilization there had been an increase in tumor size with signs of malignant transformation...

BACKGROUND: Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplaston A10 and AS2-1 reportedly control neoplastic growth and do not significantly inhibit normal cell growth. Antineoplastons contain 3-phenylacetylamino-2, 6-piperidinedione (A10), phenylacetylglutamine plus phenylacetylisoglutamine (A10-I), and phenylacetylglutamine plus phenylacetate (AS2-1). This open label, non- blinded randomized phase II study compared the efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil,with or without antineoplastons as a postoperative therapy for colorectal metastasis to the liver...

This review presents data on the antitumor properties of antineoplastons--alternative means of treatment for cancer originally isolated from human blood and urine. It was assumed that antineoplastons (derivatives of peptides and amino acids) are natural regulators of cell differentiation. In experimental studies it was showed that synthetic antineoplastons (A10-3-phenyl-acetyl-amino-2,6-piperidinedione and AS2-1--a mixture of phenylacetic acid and phenylacetylglutamine) were able to prevent the introduction of glutamine into the cell, to block the action of Bcl-2, to activate p53 and p21, to inhibit histone deacetylase, to induce apoptosis...

A potential effective therapy for diffuse intrinsic pontine glioma (DIPG) is far to be developed. There are no "shortcuts" to reach this goal. Only a rigid, scientific, and ethically correct approach can help develop effective therapeutic approaches for such a devastating brain tumor. There are no alternative ways. The children affected by DIPG deserve to become the focus of serious collaborative researches. For these children, there are many "lacks" which should be promptly corrected such as the lack of knowledge, the lack of basic and clinical scientists' passion to the problem of finding "the solution" for DIPG, the lack of rigid methods to run research in this frustrating field, the lack of research proposals, and the lack of serious, despite not magic, protocols to offer them...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Brainstem gliomas (BSG) are relatively rare tumors of which recurrent pediatric diffuse intrinsic pontine gliomas (RPDIPG) comprise a distinct group. Numerous trials have been conducted on RPDIPG, none of which have resulted in identifying any proven pharmacological treatment benefit. This study included 40 patients diagnosed with different types of BSG, but it was decided to describe first the encouraging results in the most challenging group of RPDIPG. MATERIALS AND METHODS: This single-arm phase II study evaluated the efficacy and safety of the combination of antineoplastons A10 and AS2-1 (ANP) in patients with RPDIPG...

Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. antineoplastons have been shown to control neoplastic growth. In the present study, we investigated demethylation effect of the antineoplaston AS2-1 (a mixture of phenylacetylglutamine and phenylacetate in the ratio of 1:4) on various genes in colon cancer cells. An HpaII-MspI methylation microarray was used to investigate the methylation status of 51 genes at the promoter region in HCT116 and KM12SM human colon cancer cells before and after treatment of AS2-1...

Pediatric gliosarcoma (GS) is a rare variant of glioblastoma multiforme. The authors describe the case of an unusual pontine location of GS in a 9-year-old boy who was initially diagnosed with low-grade astrocytoma (LGA) that was successfully controlled for 4 years. Subsequently, his brain tumor transformed into a GS. Prior treatment of his LGA included subtotal tumor resection 3 times, standard radiation therapy, and Gamma Knife procedure twice. His LGA was also treated with a standard chemotherapy regimen of carboplatin and vincristine, and his GS with subtotal resection, high-dose cyclophosphamide, and thiotepa with stem cell rescue and temozolomide...

Antineoplaston AS2-1 exhibits cytostatic growth inhibition of human hepatocellular carcinoma cells in vitro and showed minimum adverse effects in a phase I clinical trial. Liver cancer is difficult to control because of multicentricity and underlying liver disease. We reviewed two clinical cases of liver cancer (hepatocellular carcinoma and multiple liver metastases from colon cancer) in whom we believe antineoplaston A2-1 was useful as a maintenance therapy after transcatheter arterial embolization (TAE) and microwave coagulation necrosis (MCN)...

As our ongoing work, a series of peptidomimetic L-iso-glutamine derivatives derived from antineoplaston AS2-5 scaffold were prepared and their APN/CD13 and MMP-2 inhibitory activities were evaluated hereby. The results displayed that these compounds exhibited selective inhibition against APN as compared with MMP-2, with IC(50) values in micromole range. Compounds A1 and A2 showed comparable APN inhibitory activities than the positive control bestatin.

Overexpression of zinc-dependent metalloproteinase, aminopeptidase N (APN/CD13), is considered to be involved in the process of tumor invasion and metastasis. Herein we describe the synthesis and in vitro enzymatic inhibition assay of antineoplaston AS2-5 scaffold peptidomimetic compounds. The results demonstrated that most of these L-iso-glutamine derivatives displayed selective inhibitory activity against APN as compared with MMP-2, with IC(50) values in the micromole range. The structure-activity relationships were also briefly discussed...

We have investigated protein kinase C (PKC) signaling, a putative differentiation-related and metastasis suppressor gene Cap43/NDRG1/Drg-1, and Y-box binding protein-1 (YB-1) to identify new molecular targeting for breast cancer. PKC is a family of serine/threonine kinases that is involved in the regulation of cell growth. We have demonstrated that PKC caused G(1) arrest in a breast cancer cell line through a mechanism involving a PKC-ERK MAPK-JNK-Rb protein signaling pathway. We have also characterized a novel mechanism through which all-trans retinoic acid (ATRA) and antineoplaston, anticancer drug, caused cell growth inhibition in breast cancer cells through effects on intracellular pathways...