Latest Research News on Tumor Vasculature: Feb 2021

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Latest Research News on Tumor Vasculature: Feb 2021

March 1, 2021 Cancer and Tumor 0

Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy

Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. The widely held view is that these antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Here, I review emerging evidence supporting an alternative hypothesis—that certain antiangiogenic agents can also transiently “normalize” the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. Drugs that induce vascular normalization can alleviate hypoxia and increase the efficacy of conventional therapies if both are carefully scheduled. A better understanding of the molecular and cellular underpinnings of vascular normalization may ultimately lead to more effective therapies not only for cancer but also for diseases with abnormal vasculature, as well as regenerative medicine, in which the goal is to create and maintain a functionally normal vasculature. [1]

Transport of molecules across tumor vasculature

The vascular-extravascular exchange of fluid and solute molecules in a tissue is determined by three transport parameters (vascular permeability, P, hydraulic conductivity, Lp, and reflection coefficient, σ); the surface area for exchange, A; and the transluminal concentration and pressure gradients. The transport parameters and the exchange area for a given molecule are governed by the structure of the vessel wall. In general, tumor vessels have wide interendothelial junctions; large number of fenestrae and transendothelial channels formed by vesicles; and discontinuous or absent basement membrane. While these factors favor movement of molecules across tumor vessels, high interstitial pressure and low microvascular pressure may retard extravasation of molecules and cells, especially in large tumors. These characteristics of the transvascular transport have significant implications in tumor growth, metastasis, detection and treatment. [2]

Cancer Treatment by Targeted Drug Delivery to Tumor Vasculature in a Mouse Model

In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels. When coupled to the anticancer drug doxorubicin, two of these peptides—one containing an αv integrin–binding Arg-Gly-Asp motif and the other an Asn-Gly-Arg motif—enhanced the efficacy of the drug against human breast cancer xenografts in nude mice and also reduced its toxicity. These results indicate that it may be possible to develop targeted chemotherapy strategies that are based on selective expression of receptors in tumor vasculature. [3]

Dexamethasone as a Means Not Only for Controlling Vascular Pain Caused by the Administration of Oxaliplatin Via the Peripheral Vein But Also for Controlling Oxaliplatin-Induced Hypersensitivity Reactions

Background and Aims: With the recent development of capecitabine and oxaliplatin (XELOX) therapy, implantation of a Central Venous (CV) port can be now avoided. However, vascular pain occasionally requires switching of the drip infusion route. Some investigators reported that addition of steroids to oxaliplatin drip infusion is useful in controlling vascular pain. However, the pharmacological use of steroids can make oxaliplatin unstable due to the elevation of pH; further, the effectiveness of steroid in this therapy is unknown. This study was undertaken to evaluate the effectiveness of dexamethasone (DEX) for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein.
Study Design: Retrospective study.
Place and duration of the Study: Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, between April 2010 and November 2011.
Methodology: The study included 69 patients who received XELOX + bevacizumab therapy for advanced or recurrent colorectal cancer. In all the patients, oxaliplatin (130 mg/m2) was administered in combination with DEX (6.6 mg) via the peripheral vein.
Results: Vascular pain developed in 47 patients (68.1%), but it was transient. No patients required CV port implantation. Grade 3 or higher hemotoxicity was noted in 14.5% of the patients, and grade 3 or higher nonhematological toxicity was noted in 20.3% of the patients. The response rate was 59.4%. One patient experienced hypersensitivity reactions to oxaliplatin.
Conclusions: The recorded response rate combined with the use of DEX suggests that DEX probably does not exert adverse effects on the therapy, ie, it does not affect the stability of oxaliplatin by elevating the pH. DEX may be useful not only for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein but also for controlling oxaliplatin-induced hypersensitivity reactions. [4]

Bilateral Combined Retinal Vascular Occlusion: An Ocular Presentation in Central Nervous System Re-relapse of Non-Hodgkins Lymphoma

Aim: We describe an atypical case of central nervous system (CNS) involvement in non-Hodgkins lymphoma (NHL), presenting with ocular manifestations.

Presentation: Here we present an extremely rare case of a 63 year old male with past history of relapsed NHL in remission with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, primarily presenting with bilateral sequential acute loss of vision without any systemic manifestations of relapse. On ophthalmological evaluation, he was found to have mixed central retinal artery and central retinal vein obstruction (CRAO & CRVO). CSF (cerebro-spinal fluid) evaluation revealed large B cell lymphoma cells. Management was initiated with triple intrathecal chemotherapy.

Discussion: NHL is the commonest type of ocular lymphoma, which is often the first manifestation of systemic relapse in cases of previous therapy. However, CRVO secondary to NHL is extremely rare. To the best of our knowledge, there are no previous reports of bilateral CRVO as a result of re-relapse of DLBCL presenting with features of ophthalmoplegia.

Conclusion: Re-relapse as isolated CNS lymphoma at second remission in a patient with systemic NHL is quite rare. Although unlikely, bilateral combined CRAO & CRVO may be the first manifestation of relapsed CNS lymphoma. Hence, clinicians should have a raised index of suspicion in cases of NHL presenting primarily with sudden, total loss of vision. [5]

Reference

[1] Jain, R.K., 2005. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science307(5706), pp.58-62.

[2] Jain, R.K., 1987. Transport of molecules across tumor vasculature. Cancer and Metastasis Reviews6(4), pp.559-593.

[3] Arap, W., Pasqualini, R. and Ruoslahti, E., 1998. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science, 279(5349), pp.377-380.

[4] Yoshida, Y., Hoshino, S., Aisu, N., Shiwaku, H., Beppu, R., Tanimura, S. and Yamashita, Y. (2012) “Dexamethasone as a Means Not Only for Controlling Vascular Pain Caused by the Administration of Oxaliplatin Via the Peripheral Vein But Also for Controlling Oxaliplatin-Induced Hypersensitivity Reactions”, Journal of Advances in Medicine and Medical Research, 2(2), pp. 132-141. doi: 10.9734/BJMMR/2012/918.

[5] Chakrabarti, A., Samal, P. and Chakrabartty, J. (2016) “Bilateral Combined Retinal Vascular Occlusion: An Ocular Presentation in Central Nervous System Re-relapse of Non-Hodgkins Lymphoma”, Ophthalmology Research: An International Journal, 5(4), pp. 1-5. doi: 10.9734/OR/2016/26848.

 

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