Solid tumors regression

The Combretastatin A-4 analogues, containing a variety of heterocyclic moieties, such as imidazoles, thiazoles and tetrazoles, not only display efficient inhibition of tubulin polymerization but also exert potent cellular growth inhibition in different cancer lines including MDR cancer cells. It is worthy to note that some of Combretastatin A-4 analogues, such as imidazole-based Combretastatin A-4 exhibited oral availability leading to solid tumor regression in vivo tumor models. 

Depending on the site of maturation, specific surface markers, and functions, the lymphocytes are divided into T (thymus), B (bone marrow or bursa), NK, and LAK cells. T lymphocytes mature in the thymus and are involved in DTH and in anticancer and antifungal immunity. T helper (Th) and T suppressor (Ts) cells play a central role in immune regulation. The NK cells provide spontaneous and nonspecific immunity against tumor cells, virally infected, and chemically modified cells. The LAK cells are the primary blood or spleen lymphocytes that acquire the ability to kill certain tumors in vitro, when cultured with interleukin (IL)-2. They have been reported to cause regression of solid tumors when administered to experimental animals or patients with cancer and suppress the formation of metastases. 

Immune factors appear to be involved in the progression of melanoma more often than in most other solid tumors. Spontaneous cancer regressions are rare, but are a weU-documented phenomenon seen in melanoma. Focal regression in primary melanoma has also been reported. The regression of tumor appears to be associated with host immunity. 

Wang S, Sun W, Yu S et al (2011) Highly potent and optimized small-molecule inhibitors of MDM2 achieve complete tumor regression in animal models of solid tumors and leukemia. Abstract LB-204. AACR 102nd annual meeting, Orlando, EL... 

Although much is known about the processes of cancer formation, or carcinogenesis, comparatively little is known about the processes of cancer regression. The former will be explored as an introduction to the latter, and both involve the biological and chemical functions of the body, stated in terms of normal cells vs. cancerous ones. Surgical excision and radiation treatment are excluded from the discussion, though they can be selective if, say, the solid tumor is localized and has not yet spread or metastasized — and if the operations or treatments in themselves do not cause metastasis. 

Subcutaneous tumors that developed after implantation of human mammary carcinoma cells (MX-1) in athymic mice regressed following local injection of hypericin 1 and exposure to visible light [167]. Tissue uptake and distribution of hypericin 1 was measured in rabbits and in nude mice xenografted with P3 human squamous cell carcinoma to assess the value of this naphthodianthrone as in vivo sensitizer for laser photoactivation of solid tumors. Maximum Hypericum levels were seen in... 

Fig. 2 EPR effect and drug accumulation in solid tumor. (A) and (B) CT scan of human liver with hepatocellular carcinoma. When SMANCS/Lipiodol was infused arterially it was selectively taken up in the tumor. CT scan of (A) was obtained 2 days after the initial arterial infusion via a catheter, in which SMANCS/Lipiodol was selectively accumulated in the massive carcinoma seen as white area in the liver (due to high electron density of Lipiodol ). After 6 months with intermitted infusions of SMANCS two more times, tumor size (containing SMANCS) has remarkably regressed (B). (C) EPR effect in mouse sarcoma S-180 in mouse skin. Two dark blue circular areas are tumors marked by 0, where putative macro-molecular drug, Evans blue/albumin (MW 70 kDa), accumulated selectively. Note that the background of the normal skin shows no uptake of blue albumin. Mouse was killed at 6 h after the injection of Evans blue and it was quantified after extraction...

Wennerberg, E., Kremer, V., Childs, R., Lundqvist, A. (2015). CXCLlO-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo. Cancer Immunology, Immunotherapy, 64(2), 225-235. http //dx.doi.Org/10.1007/s00262-014-1629-5. 

In Phase II clinical trials, emetine as an antineoplastic agent was shown to exert moderate and reversible toxicity, consisting mainly of muscular weakness, local pain, and transient cardiac arrhythmias. However, no complete or partial regression of solid tumors was observed.The studies so far do not appear to indicate that emetine treatment results in tumor response with an acceptable degree of drug related toxicity in epidermoid bronchogenic carcinoma. ... 

Hamuro J, Hadding U, Bitter-Suermann (1978) Solid phase activation of alternative pathway of complement by p-l,3-glucans and its possible role for tumor regressing activity. Immunol 34 695-705... 

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