RPEP-00024 · 1985Natural killer (NK) cells are immune cells that destroy virus-infected and cancer cells without needing prior training. Cyclophosphamide (CY), a chemotherapy drug, wiped out NK cell activity in mice.
Interferon alone (30,000 units per mouse) strongly boosted NK cells in healthy mice. But in CY-suppressed mice, interferon by itself did nothing.
The combination worked: thymosin alpha 1 (200 micrograms/kg) given daily for 4 days, followed by a single interferon injection 24 hours before testing, fully restored NK cell activity in the immunosuppressed mice. Thymosin alpha 1 also accelerated NK cell recovery in mice that received bone marrow transplants.
Favalli, C; Jezzi, T; Mastino, A; Rinaldi-Garaci, C; Riccardi, C; Garaci, E · Animal Study
RPEP-00034 · 1985Leukocyte migration inhibition (LMI), a measure of how well immune cells respond to signals, was impaired in 24 head and neck cancer patients compared to healthy people.
Adding thymosin alpha 1 to the lab dish improved LMI in the cancer patients' cells. The improvement appeared independent of T-cell subset levels, meaning thymosin alpha 1 was enhancing the function of existing cells rather than changing which cells were present.
An interesting secondary finding: patients whose LMI was still normal had lower levels of suppressor/cytotoxic T-cells than both healthy people and patients with impaired LMI. This suggests that suppressor cells may contribute to the immune dysfunction in these cancers.
Wolf, G T; Peterson, K A; Lovett, E J · In Vitro
RPEP-00040 · 1987Using a "pan-opioid" antibody that detects all opioid peptides, researchers screened 108 tumors. Every adrenal pheochromocytoma (15 of 15), thyroid medullary carcinoma (6 of 6), and pituitary adenoma (5 of 5) stained positive for opioid peptides.
Most parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), and carcinoid tumors (18 of 26) also stained positive.
Zero non-neuroendocrine tumors showed opioid staining. Lung small-cell carcinomas, skin Merkel-cell tumors, and neuroblastomas were all negative.
The same opioid peptides were found in normal versions of these tissues (adrenal medulla, pancreatic islets, pituitary), suggesting the tumors simply overproduce a normal cellular product.
Bostwick, D G; Null, W E; Holmes, D; Weber, E; Barchas, J D; Bensch, K G · Cross Sectional
RPEP-00043 · 1987IL-2 is a 133-amino acid protein (molecular weight 15,420 daltons) produced by activated T-cells. Its gene sits on chromosome 4. The IL-2 receptor is a 272-amino acid protein (55,000 daltons).
IL-2 does not just make immune cells copy themselves. It moves cells from a resting state (G1) through to DNA synthesis (S phase). During this process, the proto-oncogene c-myb increases 6 to 7 times above normal levels.
The most exciting clinical development: IL-2 could expand LAK cells (lymphokine-activated killer cells) and TIL (tumor-infiltrating lymphocytes) that attack cancer. Early human trials showed both therapeutic promise and significant toxicity.
Thymosin fraction 5 and thymosin alpha 1 could modulate IL-2 receptor expression on human blood cells, potentially increasing the effectiveness of IL-2 therapy.
Fletcher, M; Goldstein, A L · Review
RPEP-00164 · 1990Lung cancer cells have an opioid-based growth suppression system that nicotine can override. All three opioid receptor types participate, and the cancer cells produce their own opioid peptides.
Maneckjee, R; Minna, J D · In Vitro
RPEP-00276 · 1993Cancer pain patients had altered CSF neuropeptide profiles. Spinal opioid therapy changed pain scores and further modified CSF peptide levels.
Samuelsson, H; Ekman, R; Hedner, T · Cross Sectional
RPEP-00292 · 1994Dynorphin-A enhanced macrophage tumoricidal activity under suboptimal activation conditions but not when fully activated.
Hagi, K; Uno, K; Inaba, K; Muramatsu, S · In Vitro
RPEP-00352 · 1996GHRP-2 was considerably more potent than GHRP-6 at stimulating GH release through PKC-dependent pathways, and both caused crosstalk with the cAMP pathway in gsp oncogene-expressing tumors.
Adams, E F; Lei, T; Buchfelder, M; Bowers, C Y; Fahlbusch, R · In Vitro
RPEP-00366 · 1996Conditioned enhancement of NK cell activity depends on mu-opioid receptor activation, with beta-endorphin and met-enkephalin as the key mediating peptides.
Hsueh, C M; Chen, S F; Huang, H J; Ghanta, V K; Hiramoto, R N · Animal Study
RPEP-00367 · 1996Chronic intracerebroventricular beta-endorphin infusion significantly enhanced in vivo NK cell cytotoxicity and altered splenic and peripheral blood lymphocyte phenotypes.
Jonsdottir, I H; Johansson, C; Asea, A; Hellstrand, K; Thorén, P; Hoffmann, P · Animal Study
RPEP-00427 · 1997Hybrid peptides from cecropin A-magainin 2 and cecropin A-melittin showed antitumor activity, with structure-activity relationships enabling separation of cancer-killing from hemolytic effects.
Shin, S Y; Lee, M K; Kim, K L; Hahm, K S · In Vitro
RPEP-00441 · 1997Lactoferricin B at concentrations up to 50 μg/ml induced dose- and time-dependent apoptosis in THP-1 human monocytic leukemia cells, with reactive oxygen species playing a key mechanistic role.
Yoo, Y C; Watanabe, R; Koike, Y; Mitobe, M; Shimazaki, K; Watanabe, S; Azuma, I · In Vitro
RPEP-00445 · 1998GHS-R type 1a (active) and type 1b (inactive) mRNA was detected in human pituitary tumor tissue and rat GH3 cells via RT-PCR, confirming these tumors express the GHRP receptor.
Adams, E F; Huang, B; Buchfelder, M; Howard, A; Smith, R G; Feighner, S D; van der Ploeg, L H; Bowers, C Y; Fahlbusch, R · In Vitro
RPEP-00468 · 1998The cecropin A-magainin 2 hybrid peptide disrupts membranes via a two-step mechanism, and leucine substitution analogs showed enhanced membrane disruption and antitumor activity with preserved low hemolytic toxicity.
Kang, J H; Shin, S Y; Jang, S Y; Lee, M K; Hahm, K S · In Vitro
RPEP-00484 · 1998Dose-escalation of thymosin alpha-1 in triple chemo-immunotherapy (cyclophosphamide + thymosin alpha-1 + interferon) produced dose-dependent increases in anti-tumor efficacy against B16 melanoma in mice.
Pica, F; Fraschetti, M; Matteucci, C; Tuthill, C; Rasi, G · Animal Study
RPEP-00509 · 1999GHS-R was expressed in 28 of 30 pituitary adenomas across all subtypes, not just GH-secreting tumors. Functional studies showed GH secretagogues stimulated hormone release from multiple tumor types in culture.
Barlier, A; Zamora, A J; Grino, M; Gunz, G; Pellegrini-Bouiller, I; Morange-Ramos, I; Figarella-Branger, D; Dufour, H; Jaquet, P; Enjalbert, A · In Vitro
RPEP-00546 · 1999Serial BNP measurements detected doxorubicin-induced cardiotoxicity before clinical symptoms or echocardiographic changes in 30 lymphoma patients, with BNP rising progressively with cumulative drug exposure.
Nousiainen, T; Jantunen, E; Vanninen, E; Remes, J; Vuolteenaho, O; Hartikainen, J · Cohort
RPEP-00557 · 1999Structure-activity analysis identified the amphipathic helix hydrophobic face as essential for antibacterial activity, tryptophan as important for antitumor activity, and specific substitutions that separate antimicrobial potency from hemolytic toxicity.
Shin, S Y; Kang, J H; Hahm, K S · In Vitro
RPEP-00575 · 2000Arginine-rich hexapeptides identified from peptide libraries blocked VEGF from binding to its receptor (IC50 = 2–4 micromolar) and selectively inhibited VEGF-driven blood vessel growth without toxicity to normal cells.
In animal models, the peptides stopped new blood vessel formation in both chick membrane and rabbit cornea assays. Most notably, one hexapeptide (RRKRRR) blocked both the growth and spread of human colon cancer cells implanted in mice.
Bae, D G; Gho, Y S; Yoon, W H; Chae, C B · Preclinical
RPEP-00579 · 2000Thymosin alpha-1 (0.01-10 μg SC daily for 7 days) increased thymocytes and blood cells, reduced primary tumor weight, and inhibited organ colonization by metastatic cells in tumor-bearing BALB/c mice.
Beuth, J; Schierholz, J M; Mayer, G · Animal Study
RPEP-00581 · 2000Thymic hormones serve dual roles in oncology: as biomarkers correlating with immune status and prognosis, and as therapeutic immunostimulants that enhance anti-tumor immunity when combined with conventional cancer treatments.
Bodey, B; Bodey, B; Siegel, S E; Kaiser, H E · Review
RPEP-00585 · 2000Specific GHS binding sites were detected in normal and neoplastic human thyroid tissue, with highest density in medullary thyroid carcinoma, suggesting GH secretagogues may affect thyroid biology and that GHS-R could serve as a thyroid cancer marker.
Cassoni, P; Papotti, M; Catapano, F; Ghè, C; Deghenghi, R; Ghigo, E; Muccioli, G · In Vitro
RPEP-00591 · 2000Thymosin alpha-1 combined with low-dose IFN or IL-2 shows high efficacy against cancers in both preclinical models and human clinical trials, supporting its role as a cancer immunotherapy adjuvant.
Garaci, E; Pica, F; Rasi, G; Favalli, C · Review
RPEP-00610 · 2000Persistent BNP elevation after anthracycline chemotherapy predicted development of cardiotoxicity, distinguishing at-risk patients from those with only transient, benign BNP rises.
Okumura, H; Iuchi, K; Yoshida, T; Nakamura, S; Takeshima, M; Takamatsu, H; Ikeno, A; Usuda, K; Ishikawa, T; Ohtake, S; Matsuda, T · Cohort
RPEP-00641 · 2001Thymosin alpha-1 demonstrates clinical efficacy in chronic hepatitis B and C (combined with interferon), with emerging evidence for cancer immunotherapy, HIV, and vaccine enhancement, showing excellent tolerability.
Ancell, C D; Phipps, J; Young, L · Review
RPEP-00650 · 2001TFA contamination from peptide synthesis inactivated thymosin alpha-1's clonal growth inhibition activity, demonstrating the need for rigorous purification and biological activity testing of therapeutic peptide preparations.
Bianco-Batlles, D; Naylor, C W; Moshier, J A; Dosescu, J; Naylor, P H · In Vitro
RPEP-00654 · 2001Functional ghrelin and synthetic GHS receptors were identified on human breast, prostate, and lung cancer cells, with receptor subtypes potentially different from those in normal pituitary tissue.
Cassoni, P; Papotti, M; Ghè, C; Catapano, F; Sapino, A; Graziani, A; Deghenghi, R; Reissmann, T; Ghigo, E; Muccioli, G · In Vitro
RPEP-00688 · 2001Thymosin alpha-1 restored T-cell proliferation, NK cell cytotoxicity, and Th1 cytokine production (IL-2, IFN-γ) in cyclophosphamide-immunosuppressed mice, demonstrating broad immune reconstitution capacity.
Ohmori, H; Kamo, M; Yamakoshi, K; Nitta, M H; Hikida, M; Kanayama, N · Animal Study
RPEP-00715 · 2002Thymosin alpha-1 demonstrates clinical efficacy across hepatitis B, hepatitis C (with IFN), cancer (with chemo), and potentially HIV, with excellent tolerability and a favorable safety profile across all studied indications.
Billich, Andreas · Review
RPEP-00725 · 2002Bovine lactoferricin inhibited tumor growth in immunodeficient mice, proving a direct cytotoxic antitumor mechanism independent of immune system activation, likely through cancer cell membrane disruption.
Eliassen, Liv Tone; Berge, Gerd; Sveinbjørnsson, Baldur; Svendsen, John S; Vorland, Lars H; Rekdal, Øystein · Animal Study
RPEP-00729 · 2002Synthetic peptidyl GH secretagogues inhibited proliferation of human CALU-1 lung carcinoma cells that express high levels of GHS receptors, demonstrating antiproliferative rather than growth-promoting activity in this cancer type.
Ghè, Corrado; Cassoni, Paola; Catapano, Filomena; Marrocco, Tiziana; Deghenghi, Romano; Ghigo, Ezio; Muccioli, Giampiero; Papotti, Mauro · In Vitro
RPEP-00735 · 2002Prostate cancer cells expressed ghrelin, GHS-R1a, and GHS-R1b (autocrine system), with biphasic proliferative response: low ghrelin concentrations slightly stimulated while higher concentrations inhibited cell growth.
Jeffery, P L; Herington, A C; Chopin, L K · In Vitro
RPEP-00751 · 2002Thymosin alpha-1 significantly inhibited NMU-induced mammary carcinogenesis in Fisher rats, reducing both tumor incidence and multiplicity, demonstrating cancer prevention through immune enhancement.
Moody, Terry W; Tuthill, Cynthia; Badamchian, Mahnaz; Goldstein, Allan L · Animal Study
RPEP-00756 · 2002Thymosin alpha-1 restored suppressed bone marrow hematopoiesis in T-cell lymphoma mice, increasing colony-forming units (CFU-GM, BFU-E, CFU-GEMM) and peripheral blood counts across all lineages.
Paul, Saki; Sodhi, Ajit · Animal Study
RPEP-00763 · 2002Bovine lactoferricin induced apoptosis in human HL-60 leukemia cells more potently than intact lactoferrin, with activity dependent on native protein structure, demonstrating structure-specific anti-leukemic killing.
Roy, M K; Kuwabara, Y; Hara, K; Watanabe, Y; Tamai, Y · In Vitro
RPEP-00773 · 2002Thymosin alpha-1 activated anti-tumor macrophages through p38 MAPK and ERK signaling pathways, with pathway inhibition blocking the anti-tumor effect, identifying the specific intracellular mechanism of thymosin alpha-1's immunostimulatory action.
Sodhi, Ajit; Paul, Saki · In Vitro
RPEP-00814 · 2003Bulky aromatic amino acid substitutions and lipophilic modifications enhanced bovine lactoferricin antitumor activity in a 15-residue fragment, with tryptophan residues identified as essential for cancer cell killing through membrane-disrupting mechanisms.
Eliassen, Liv Tone; Haug, Bengt Erik; Berge, Gerd; Rekdal, Oystein · In Vitro
RPEP-00819 · 2003Thymosin alpha-1 combined with low-dose cytokines and chemotherapy produced superior anti-tumor effects across experimental and human cancers, validating the triple-combination immunotherapy approach.
Garaci, Enrico; Pica, Francesca; Sinibaldi-Vallebona, Paola; Pierimarchi, Pasquale; Mastino, Antonio; Matteucci, Claudia; Rasi, Guido · Review
RPEP-00821 · 2003Cellular immunodeficiency precedes and promotes cancer across multiple tumor types, and immunological correction with thymosin alpha-1 and cytokines alongside conventional therapy consistently improves patient outcomes.
Hadden, John W · Review
RPEP-00823 · 2003The thymosin family comprises functionally distinct members: prothymosin alpha (gene regulation), thymosin alpha-1 (immune modulation), parathymosin (chromatin), and beta-thymosins (cytoskeleton/wound healing) — each with unique therapeutic potential.
Hannappel, Ewald; Huff, Thomas · Review
RPEP-00841 · 2003A macrocyclic peptide incorporating beta-aminophosphotyrosyl mimetic achieved potent Grb2 SH2 domain binding through conformational restriction, demonstrating macrocyclic drug design for cancer signaling disruption.
Lee, Kyeong; Zhang, Manchao; Liu, Hongpeng; Yang, Dajun; Burke, Terrence R · In Vitro
RPEP-00869 · 2003Lactoferricin demonstrates antibacterial, antifungal, antiviral, antiparasitic, antitumor, and immunomodulatory activities — establishing it as a remarkably multi-functional peptide derived from the common milk protein lactoferrin.
Wakabayashi, H; Takase, M; Tomita, M · Review
RPEP-00875 · 2003Met-enkephalin (OGF) inhibited cancer proliferation through OGFr nuclear translocation and activation of p16/p21 cell cycle inhibitors across pancreatic, colon, and squamous cell cancers — a non-classical opioid anti-cancer mechanism.
Zagon, Ian S; McLaughlin, Patricia J · In Vitro
RPEP-00876 · 2003Adrenomedullin is overexpressed in many cancers where it promotes tumor growth, drives angiogenesis (tumor blood vessel formation), and may suppress anti-tumor immunity — positioning it as a multi-mechanism cancer therapy target.
Zudaire, E; Martínez, A; Cuttitta, F · Review
RPEP-00881 · 2004Cyclic peptides targeting CDK2's substrate recruitment site (not catalytic site) selectively induced tumor cell apoptosis through the E2F pathway, with crystal structures confirming the novel binding mechanism.
Andrews, Martin J I; McInnes, Campbell; Kontopidis, George; Innes, Lorraine; Cowan, Angela; Plater, Andy; Fischer, Peter M · In Vitro
RPEP-00947 · 2004Ghrelin stimulated human adrenal zona glomerulosa cell proliferation via p42/p44 MAPK activation and simultaneously inhibited apoptosis through functional GHS-R — dual proliferogenic and anti-apoptotic adrenal effects.
Mazzocchi, Giuseppina; Neri, Giuliano; Rucinski, Marcin; Rebuffat, Piera; Spinazzi, Raffaella; Malendowicz, Ludwik K; Nussdorfer, Gastone G · In Vitro
RPEP-00976 · 2004Thymosin alpha-1 reprogrammed tumor-associated macrophages from immunosuppressive to tumoricidal phenotype, enabling them to kill cancer cells directly — overcoming a key immune evasion mechanism of the tumor microenvironment.
Shrivastava, P; Singh, S M; Singh, N · Animal Study
RPEP-00977 · 2004Thymosin alpha-1 promoted differentiation of tumor-associated macrophages into functional dendritic cells with enhanced antigen presentation and antitumor activity — converting tumor immune suppressor cells into effective cancer fighters.
Shrivastava, Pratima; Singh, Sukh Mahendra; Singh, Nisha · Animal Study
RPEP-00992 · 2004A hydrocarbon-stapled BH3 alpha-helix peptide activated apoptosis in vivo in a mouse leukemia model, producing tumor reduction — the first demonstration that stapled peptide technology achieves in-vivo anticancer efficacy through intracellular target engagement.
Walensky, Loren D; Kung, Andrew L; Escher, Iris; Malia, Thomas J; Barbuto, Scott; Wright, Renee D; Wagner, Gerhard; Verdine, Gregory L; Korsmeyer, Stanley J · Animal Study
RPEP-01036 · 2005Lactoferricin demonstrates comprehensive bioactivities: antibacterial (gram+ and gram-), antifungal, antiviral (HSV, HIV, CMV), antiparasitic, antitumor (direct cytotoxicity), and immunomodulatory — the most versatile natural antimicrobial peptide characterized.
Gifford, J L; Hunter, H N; Vogel, H J · Review