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PubMed1994

Effects of intralesional injection of cisplatin dissolved in urografin and lipiodol on Ehrlich ascites tumor and normal tissues of CD-1 mice.

The response of Ehrlich ascites tumor and the effect on normal tissues (kidney and small intestine) of CD-1 mice were evaluated after intralesional (i.l.) injection of cisplatin dissolved in urografin and lipiodol, which is henceforth termed CUL suspension. The results obtained were compared with the effects of i.p. and i.l. injections of cisplatin dissolved in sterile distilled water. Each of these treatment modalities involves the injection of 10 mg/kg cisplatin. The tumor response was evaluated by tumor growth-delay studies as well as by determining the percentage of cells in the S phase. Toxicity studies were accomplished by evaluation of the change in the body weight of mice and also by S-phase studies. S-phase fraction analyses were done with the use of the Cell Proliferation Kit. This commercial kit was used to measure bromodeoxyuridine (BrdU), a thymidine analogue that is incorporated into cells synthesizing DNA. Tumor, kidney, and small-intestine platinum concentrations were determined by measurement with a flameless atomic absorption spectrophotometer. The results of the tumor growth-delay studies showed that i.p. injection, with water being the drug carrier, produced the weakest antitumor effect, whereas i.l. injection of cisplatin, with lipiodol being the drug carrier, evoked the most enhanced effect. This finding was substantiated by BrdU-uptake analysis of tumor cells, wherein i.p. injections yielded the highest S-phase fraction and CUL treatment gave the lowest. Toxicity studies showed that a very significant decrease in body weight occurred in mice receiving i.p. treatment. No significant decrease in body weight was noted after i.l. treatment. BrdU analysis revealed that DNA synthesis in kidney cells and crypt cells of the small intestine was depressed after i.p. treatment. On the other hand, no significant effect was observed in the kidney or small intestine of CUL-treated mice. A correlation between the effects of the various treatment modalities (on tumors, kidney, and small intestine) and the retention of cisplatin was found.

Animals↗
PubMed1995

Regression of skin recurrences of breast carcinomas treated with intralesional injections of natural interferons alpha and gamma.

Two groups of patients with disseminated breast carcinomas who had failed radiotherapy, chemotherapy, and hormonotherapy were treated with natural interferon alpha (nIFN-alpha) alone or in combination with nIFN-gamma delivered in cycles of 10-12 intralesional (i.l.) injections to recurrent and metastatic lesions. In group, I, 16 skin lesions in 12 patients received nIFN-alpha alone resulting in 7 complete regressions verified histologically (CR), 7 partial regressions (PR), and no regressions (NR) in 2. Group II included 4 patients in whom 7 cutaneous recurrences were treated with nIFN-alpha/nIFN-gamma (5 CR, 2 PR), 2 were injected with nIFN-alpha alone (1 CR, 1 PR), and 1 received nIFN-gamma alone (PR). Two additional patients in group II were given i.l. injections of nIFN-alpha/nIFN-gamma to lymph node metastases (1 CR, 1 PR). Clinical toxicity was experienced by 5 of 12 patients in group I and by all the patients in group II and was controlled in most instances by antipyretics. Systemic antitumor effects were not appreciable clinically. Nevertheless, noninjected lesions exposed only to systemic levels of IFNs, when studied immunohistochemically, displayed an immunological response similar to that of IFN-injected lesions, although less intense. Therefore, IFNs can be useful in controlling locoregional recurrences of breast cancer even in patients who are not responding to other forms of therapy. Furthermore, in addition to the local antitumor actions, they appear to be capable of eliciting systemic immunological effects.

Breast Neoplasms↗
PubMed1988

Improvement of psoriasis vulgaris after intralesional injections of 15-hydroxyeicosatetraenoic acid (15-HETE).

Psoriatic skin lesions are characterized by elevated levels of 5- and 12-lipoxygenase products (leukotrienes B4, C4, and D4, and 12-hydroxyeicosatetraenoic acid [12-HETE]), which can stimulate epidermal proliferation and induce skin inflammation. 15-Hydroxyeicosatetraenoic acid (15-HETE) has the potential to inhibit the activity of 5- and 12-lipoxygenases. The purpose of the present study was to determine the therapeutic effect of intralesional injections of 15-HETE. 15-HETE was formed by oxidation of arachidonic acid by soybean lipoxygenase, purified by reversed-phase high-performance liquid chromatography, and identified by mass spectrometric analysis. Thirteen patients took part in the investigation. Plaques with a diameter of approximately 1 cm were injected with 0.1 ml of 10 mumol/L 15-HETE, 0.1 ml of 1 mumol/L 15-HETE, or 0.1 ml of saline weekly. After 3 weeks the effect was evaluated clinically and histologically by an observer uniformed of the treatment given. We found that plaques injected with 10 mumol/L 15-HETE had cleared completely in four patients and improved considerably in seven. In one patient minimal improvement only was seen and in one patient no change was observed. Injection of 1 mumol/L 15-HETE was without effect in 11 patients and improvement was observed in two patients. Of the plaques injected with saline, minimal improvement was observed in one patient; otherwise the plaques had not changed. Injection of 0.1 ml of 10 mumol/L 15-HEPE (identical to 15-HETE except for five double bonds instead of four) induced only minimal improvement in one of four patients. The results imply that 15-HETE by a dose-dependent and stereospecific mechanism can improve psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗
PubMed1985

Antitumor effect of intralesional injection with formalin-fixed Toxoplasma gondii organisms on Lewis lung carcinoma in Toxoplasma-infected mice.

The antitumor effect of formalin-fixed Toxoplasma organisms (f-Tp) as an immunostimulant was examined in Toxoplasma-infected female C57BL/6 mice using a syngeneic Lewis lung carcinoma (3LL). Toxoplasma-infected mice, intradermally inoculated with the tumor cells mixed with 10(5), 10(6) or 10(7) f-Tp, developed a marked antitumor effect, inhibition of tumor growth and prolongation of life-span, in direct relation to the strength of the delayed-type hypersensitivity (DTH) reaction induced by f-Tp. The antitumor effect could also be observed even if an intralesional injection with f-Tp was performed 1, 3 or 5 days after the tumor inoculation. In a control, the injection with 2.5 X 10(6) live Mycobacterium bovis (BCG) in BCG-sensitized mice induced a significant antitumor effect, only when the BCG was injected in the mixture of tumor cells. These results demonstrate that the injection with f-Tp can induce a potent antitumor activity in mice with Toxoplasma infection.

Animals↗
PubMed2003

Regression of primary murine colon cancer and occult liver metastasis by intralesional injection of lyophilized preparation of insect cells producing murine interferon-beta.

We investigated the efficacy of interferon (IFN)-beta therapy against colon cancer using a novel approach mediated by a lyophilized preparation of High 5 (H5) insect cells transduced with a recombinant baculovirus encoding murine IFN-beta (H5BVIFN-beta). The orthotopic model of CT-26 murine colon cancer in syngeneic BALB/c mice was used in the study, and H5BVIFN-beta was intratumorally delivered. Two injections of H5BVIFN-beta (on days 14 and 21 after tumor cell implantation), but not lyophilized H5 cells (control), significantly reduced the size of cecal tumors and the number of liver metastases. Immunohistochemical analysis revealed that cecal tumors injected with saline or H5 contained many proliferating cells (PCNA+) and few apoptotic cells (TUNEL+). In sharp contrast, H5BVIFN-beta-treated tumors contained fewer PCNA+ cells and significantly more TUNEL+ cells. The H5BVIFN-beta-treated tumors were infiltrated by a large number of CD8+ and F4/80+ cells and expressed a high level of inducible nitric oxide synthase (iNOS). Immunofluorescent double staining technique demonstrated a significant increase of apoptotic endothelial cells (CD-31+/TUNEL+) in tumors treated with H5BVIFN-beta. In conclusion, the data show that intralesional injections of H5BVIFN-beta can suppress the progressive growth of established orthotopic tumors of colon cancer cells and occult liver metastasis. The therapeutic effects directly correlate with destruction of tumor vasculature.

Animals↗
PubMed1986

Regression of cutaneous metastatic melanoma by intralesional injection with human monoclonal antibody to ganglioside GD2.

In this study we used human monoclonal antibody (Hu-mAb) L72 as an intratumoral injection of cutaneous metastasis of melanoma to study its anti-tumor effects in human patients. Hu-mAb L72 was developed by transforming peripheral blood lymphocytes from a melanoma patient in vitro with the Epstein-Barr virus, forming a human lymphoblastoid cell line that produces 2-5 micrograms of IgM per ml. This IgM Hu-mAb was shown to react specifically with ganglioside GD2 and have a strong cytotoxic effect on human melanoma cells in the presence of complement. Patients with cutaneous metastatic melanoma were given intralesional injections on a daily or weekly injection schedule. Regression was seen in all tumors except in those of two patients whose tumors were shown to have low antigenicity. Histopathological data showed tumor degeneration, fibrosis, free melanin, and some degree of lymphocyte or macrophage infiltration. One patient with melanoma satellitosis treated with Hu-mAb showed complete regression with no sign of recurrence 20 months after the initial treatment. With the exception of mild erythema, no side effects were observed in any patient.

Adult↗
PubMedDate not supplied

High levels of gene transduction in human lung tumors following intralesional injection of recombinant adenovirus.

To effect gene transfer into large solid malignancies for the purpose of clinical application, new treatment strategies using intralesional administration of adenovirus were studied. Replication-deficient adenovirus Ad5LacZ, containing the Escherichia coli beta-galactosidase (beta-gal) gene (LacZ), was injected directly into 1-cm x 1-cm subcutaneous xenograph tumors of human large cell lung cancers (H460 and H1299). Each tumor received a single injection or three injections of purified virus, diluted in 200 microL of phosphate-buffered saline. The tumors were harvested 3 days after the last injection, serially sectioned, and stained with X-gal. The cells expressing beta-gal were counted by using digital image analysis and the percentage of tumor cells transduced was calculated. After a single viral injection of 1 x 10(9) PFU, 5 x 10(9) PFU, or 1 x 10(10) PFU solid tumor transduction increased significantly with dose escalation. At a dose of 1 x 10(10) PFU, transduction of the H1299 and H460 tumors was 80.2% and 46.7%, respectively. Dividing the viral dose into three injections given on alternating days had no significant effect on viral transduction. These data demonstrate that a large portion of an established human lung cancer cell line tumor undergoes gene transduction after a single intralesional injection of recombinant adenovirus.

Adenoviridae↗
PubMed1994

A phase I/II study of the intralesional injection of ricin-monoclonal antibody conjugates in patients with hepatic metastases.

A phase I/II study of the intralesional administration of ricin-labelled monoclonal antibodies was conducted in patients with hepatic metastases of gastrointestinal origin. The anti-carcinoembryonic antigen (CEA) antibody I-1 was conjugated to blocked ricin via a disulphide bridge. After a test dose of antibody, patients were injected with ricin-antibody conjugates under computed tomography (CT) guidance on two occasions 1 week apart. Patients with stable or responding disease would receive a third course. The dose of ricin relative to surface area was increased in a predefined manner in cohorts of 3 patients. A total of 27 patients with hepatic metastases were entered into this study. All patients had metastatic colorectal cancer (26 patients) or adenocarcinoma of unknown primary with elevated CEA levels (1 patient). The presence of malignancy was documented cytologically in 9 of 11 patients tested. Minor responses were seen in 7 patients. However, no major objective responses or changes in the growth rate of injected lesions were observed. Toxicity was generally mild, the most common being hepatic capsular pain 24-48 h after each injection. 6 patients experienced rigors. One patient had anaphylaxis. Human anti-mouse and anti-ricin antibody responses were observed. Although substantial amounts of ricin conjugated to monoclonal antibodies were delivered into single lesions, this therapeutic approach was unsuccessful. Future studies of ricin-labelled antibodies should incorporate the systemic administration of immunoconjugates.

Adenocarcinoma↗
PubMed1994

[Experimental study of the effects of hormonal therapy and intralesional injections of interleukin 2, activated macrophages on mouse prostate cancer models].

In order to establish a more effective and safer therapy for androgen-dependent prostate cancer, to be used in addition to hormonal therapy, the anti-tumor effects of intralesionally administered macrophages activated with recombinant interferon-gamma (INF-gamma), alone or in combination with recombinant interleukin-2 (IL-2) were studied in mouse prostate cancer models. Firstly, in terms of cellular adoptive immunotherapy, phagocytosis against Latex bead and cytotoxicity against Shionogi 115 cancer cell line (SC115) of macrophages activated with INF-gamma for 24 hour were investigated. One ml of 0.25% glycogen solution was intraperitoneally administered to male DS mice. Three days later, fluid was aspirated from the abdominal cavity and macrophages were separated for use in this experiment. Phagocytosis INF-gamma-dose-dependently increased and macrophages activated with 100 U/ml INF-gamma phagocytosed 78.3 +/- 4.5% (mean +/- SD) Latex bead. Cytotoxicity (modified MTT assay) of SC 115 by macrophages activated with 100 U/ml INF-gamma increased remarkably in comparison with non-activated macrophages and there was a significant increase in the effector-to-target-cell ratio to 40 in the activated group 77 +/- 4.3% (mean +/- SD) relative to 50 +/- 6.3% (mean +/- SD) in the non-activated group. Based on these in vitro findings, hormonal therapy and adoptive local immunotherapy, alone or together, were studied in mouse prostate cancer models. The prostate cancer model was prepared through the subcutaneous transplantation of SC115 in male DS mice and the treatments were initiated after tumors were palpable. The therapy protocols were as follows: Group I control and Group II received 20 mg/kg/day diethylstilbestrol diphosphate (DES-P) subcutaneously for 10 days, Group III received DES-P in combination with ten thousand units of IL-2 administered five times intralesionally, Group IV received DES-P in combination with 2 x 10(6) macrophages activated with 100 U/ml INF-gamma administered three times intralesionally, Group V received DES-P and IL-2 in combination with activated macrophages. The therapeutic efficiencies were evaluated by calculating the tumor volume and survival time. The results of the tumor volume on the 40th day post tumor transplantation were as follows (mean +/- SD): Group I 7,049 +/- 1,477 mm3, Group II 4,495 +/- 654 mm3, Group III 2,050 +/- 724 mm3, Group IV 2,782 +/- 970 mm3, Group V 1,555 +/- 514 mm3. The therapeutic groups showed significant tumor reduction relative to the control. Furthermore, intralesionally IL-2, the activated macrophages injected groups, alone or together, were more effective relative to the group receiving only DES-P.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Intralesional injection of bleomycin sulphate into resistant warts in renal transplant recipients versus non-transplant warty patients.

Sixteen adult renal transplant patients and 20 non-transplant patients with warts underwent intralesional therapy with bleomycin sulphate. One unit/ml bleomycin sulphate was injected in 93 warts in renal transplant recipients and 100 warts in non-transplant patients with proven resistance to conventional treatment for at least 6 months. The treatment was compared with a normal saline placebo injected into the paired warts in the same patient. Thirty-four out of 93 warts (37%) in renal transplant recipients vs. 59 out of 100 warts (59%) in non-transplant patients were completely cured after one to three injections. We found bleomycin completely ineffective in 56 warts (60%) in renal transplant recipients, but ineffective in only 17 warts (17%) in non-transplant warty patients. None of the patients treated experienced any side effects except for local pain which was well tolerated, especially by non-transplant patients.

Adolescent↗
PubMed1996

Cushing's syndrome in postburn children following intralesional triamcinolone injection.

Intralesional triamcinolone acetonide has been used extensively for the treatment of hypertrophic and keloid scars. Complications are few, usually being local skin color changes, prominent vascular markings, or subcutaneous atrophy. Cushing's syndrome following intralesional administration of triamcinolone acetate has only been described twice, both in adult patients. This paper reports on two pediatric cases of Cushing's syndrome following treatment of hypertrophic burn scars with intralesional triamcinolone acetonide. The first child, 10 years of age, was treated for hypertrophic burn scars of the back. The second child, age 21 months, was treated for hypertrophic burn scars of the face. In both, intralesional triamcinolone acetate therapy was initiated 3 months postburn injury and in neither child was the maximum recommended dose exceeded. In both children, Cushing's manifestations developed 1 to 2 weeks postinjection and resolved in 6 to 8 weeks with no treatment or permanent sequelae. Consultation with endocrinologists revealed no concurrent disease process. It appears that these two pediatric patients may have had a form of hypersensitivity to triamcinolone acetonide, as Cushing's syndrome was not the result of an overdose. In conclusion, intralesional triamcinolone acetonide should be used with an increased degree of caution in the pediatric population.

Anti-Inflammatory Agents↗
PubMed2002

Solitary mastocytoma improved by intralesional injections of steroid.

Solitary mastocytoma is an uncommon disease characterized by monotonous infiltrations of mast cells that extend from papillary dermis to subcutaneous fat. They usually resolve by adulthood, and there is no satisfactory treatment other than waiting. A two-month-old Korean male infant with deep solitary mastocytoma was treated intralesionally with triamcinolone acetonide. His mastocytoma in medial malleolus was very distressing because it was very sensitive to friction, and he was just reaching the crawling stage. After three injections, his skin lesion flattened with marked decrease of erythema and subjective symptoms. His skin lesion has continued to have a good clinical response for 9 months after the last treatment.

Foot Dermatoses↗
PubMed2006

Possible mechanisms of action of the compounds injected intralesionally in the treatment of cutaneous leishmaniasis, in addition to their direct effects on the parasites.

By injecting uninfected rabbits intradermally with one of the test compounds or the isotonic saline (0.9% NaCl) used as a control, the possible mechanisms of the indirect action of some drugs used intralesionally in the treatment of human cutaneous leishmaniasis [sodium stibogluconate, 2% zinc sulphate, and hypertonic (7% NaCL) saline] were explored. The 24 injected rabbits (six for the control and six for each test compound) were followed up for 30 days, both macroscopically, with checks for erythema and increases in skin thickness, and microscopically, with the histopathological examination of sections of biopsies from the injection sites. Although the microscopy revealed inflammatory-cell infiltration, beginning with eosinophils, followed by lymphocytes and finally by the proliferation of fibroblasts, at all of the injection sites, these changes were most intense with the sodium stibogluconate and 2% zinc sulphate, less marked with the hypertonic saline, and minimal and relatively short-lived with the isotonic saline. Presumably as a result of their metal content, sodium stibogluconate and zinc sulphate each probably induce tissue damage and, subsequently, severe inflammatory changes. The antileishmanial activity of hypertonic saline, however, may be entirely attributable to its osmotic effects.

Animals↗
PubMed1987

[Clinico-pathological evaluation of keloids treated with intralesional injections of corticoid].

37 keloid patients were treated with triamcinolone intralesionally every 15 days, in all 6 inoculations. Histologically after the treatment we observed alterations in dermal vascularization, in morphology, in color characteristics and in the arrangement of the collagen bundles. The disappearance of mucin and the presence of palisade granulomas was observed in some cases probably because of the corticoid deposited. There was regression of pruritus and pain in all the patients. We believe that the intralesionally infiltration of corticoid is even today one of the best methods of treatment, and it may also be effected together with other technics.

Adolescent↗
PubMed1983

Complications in the intralesional injection of triamcinolone acetonide by jet injector (Dermojet).

Two patients with lichenified eczematous lesions on the dorsal aspect of the hands were treated intralesionally with triamcinolone acetonide injected with an air-powered high-pressure device, Dermojet. The therapy was complicated by tendon rupture in one patient and by the development of a subcutaneous nodule, which was suspected to be a foreign body granulomatous reaction, in the other patient.

Aged↗
PubMed1998

Augmentation of tumor immunity in mice by intralesional injection of vitamin A.

We investigated the antitumor effect of vitamin A(VA) using the double grafted tumor technique to examine whether VA administered into a primary tumor (intralesionally or i.l.) accelerates antitumor immune reactions so that growth of the secondary tumor may be more effectively inhibited than by other systemic administration routes. In the double grafted tumor system, where BALB/c mice were inoculated with MethA fibrosarcoma cells into the right inguinal region (1 x 10[6] cells) on day 0 and later into the left (3 x 10[6] cells) on day 10, the injection of VA at a dose of 1000 IU/mouse i.l., s.c., i.p., and i.v. on days 3 through 7 inhibited the growth of the secondary tumor to the same extent, while VA at the i.l. dose of 100 IU/mouse into the primary tumor inhibited more effectively than by any other administration route. VA did not inhibit the secondary MethA growth in BALB/c (nu/nu) mice. The spleen cells taken from VA-treated tumor-bearing mice prevented the growth of MethA tumors in naive BALB/c mice when given as a mixture with the MethA inoculum (the Winn assay). The delayed-type hypersensitivity (DTH) response to methylated bovine serum albumin (MBSA) antigen was augmented when VA (1000 IU) was injected at the site of the antigen injection. These results suggest that the direct interaction of VA with the tumor cells may be necessary for the tumor immunity-potentiating effect of VA, and that T-lymphocyte-mediated tumor immunity is involved in the anti-tumor effect of VA. The antitumor mechanism of VA seems to involve retinoid receptors, because the benzoic acid derivative Am80, which has been reported to exert retinoidal activity by binding to specific retinoid receptors, also showed activity.

Animals↗
PubMed1987

Immunotherapy of bladder cancer with intralesional injection with BCG.

Immunotherapy of bladder cancer with non specific immunostimulants, such as bacillus Calmette Guerin (BCG), has been shown to significantly reduce tumor recurrences, and, when applied through intravesical BCG instillation to induce the regression of some established tumors, including carcinomas "in situ" and even some invasive tumors. Since in other tumors, namely melanomas, BCG has been proved to be most successful when infected directly into the tumor, intralesional therapy with BCG (1.5 x 10 BCG weekly for four weeks) has been applied in 20 patients affected by bladder cancer (T1 - T2). The local reaction has induced substantial reduction of the tumor mass and, in some cases, (four) total disappearance of the tumor. On the sixteen patients without total disappearance of the tumor, TUR was applied. The successive follow-up of these patients offer at present the following figures: 3 out of the four patients with remission after BCG alone are disease-free after 26-30 months, whereas one has developed after 18 months a papilloma surgically removed; 15 out of the sixteen patients treated with BCG followed by TUR are disease-free after 26-30 months. These data, compared with literature findings, support the idea that intratumoral BCG instillation of bladder cancer permits a longer disease-free period than other therapeutical approaches.

Adult↗