Influence of human leukocyte inteferon on squamous cell carcinoma of uterine cervix: Clinical, histological, and histochemical observations

Krusić, J; Kirhmajer, V.; Knezević, M; Ikíc, D.; Maricić, Z; Rode, Bojan; Jusić, D; Sooś, E

doi:10.1007/bf00410116

Cited by 11 publications

(1 citation statement)

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“…As CIGB-300 inhibits CK2 phosphorylation, inducing apoptosis on the target cells, mastocyte death and the subsequent histamine release to the circulation should not be discarded and merits further investigation. However, other drugs such as interferons [17-19], which induce apoptosis by other mechanisms that exclude CK2, have been also locally administrated on the cervix without systemic "allergic-like" reactions. Alternatively, this syndrome could be related to CIGB 300's molecular structure, composed by several predominantly positively charged aminoacids that make it a very basic peptide and, therefore, behave as a potential histamine releaser [20].…”

Section: Discussionmentioning

confidence: 99%

Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies

Solares¹,

Santana²,

Baladrón

et al. 2009

BMC Cancer

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BackgroundCervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL), the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV) has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2) phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies.MethodsThirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 – 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated.ResultsNo maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression. HPV DNA was negative in 48% of the previously positive patients. Long term follow-up did not reveal recurrences or adverse events.ConclusionCIGB 300 was safe and well tolerated. This is the first clinical trial where a drug has been used to target the CK2 phosphoaceptor domain providing an early proof-of-principle of a possible clinical benefit.

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Section: Discussionmentioning

confidence: 99%