Continued Tumor Growth Research Articles

Результаты хирургического лечения пациентов с нейрогенными опухолями лицевого нерва интратемпоральной локализации

Objectives. To describe surgical outcomes of neurogenic facial nerve tumors (NFNT). Patients and methods. The study included 18 patients with intratemporal NFNT, 12 women and 6 men. The average age was 41,4 ± 18,9 years (range from 3 to 66 years). To assess the facial nerve (FN) function, a 6-step House–Brackmann scale was used. Tumors were removed mainly by the transmastoid route. The translabyrinthine approach was performed in the case of a labyrinth segment of the FN involved. Two patients underwent a combined transmastoid-middle fossa approach in the case of tumor spreading into the middle cranial fossa. Facial nerve reconstruction performed by end-to-end neurorrhaphy or with the sural nerve autograft in the case of a nerve deficiency. Recurrence or continued tumor growth was monitored by contrast-enhanced MRI at the last visit. Results. The most common tumor lesions were the mastoidal (66,7%) and tympanic (55,6%) segments of the FN. Multiple-segment involvement was in 10 cases (55,6%). All patients were admitted for surgical treatment with signs of paresis of mimic muscles of II–VI degree. Improvement of the FN function was achieved in 10 patients (55,6%), in 5 cases with n.suralis autograft. In 6 cases (33,3%), the FN function remained to the preoperative level, in 3 of them, with the use of an autograft. The FN function downgraded in 2 cases (11,1%) without FN reconstruction. Recurrence or continued growth of the residual tumor was detected in 2 patients (11,1%). Hearing improvement was achieved in 12 cases (66,7%), hearing decrease was obtained in 2 cases (11,1%), in 4 cases hearing remained at the preoperative level (22,2%). Conclusion. Surgical approach should be adequate to the spread of the tumor process and consider the possibility of hearing preservation. When the geniculate node and the labyrinth segment of the FN are involved, it is advisable to use access through the middle cranial fossa with socially adequate hearing. Timely and adequate surgical treatment allows maintaining or improving the function of the facial nerve in most cases (88,9%).

Surgical treatment of patients with chest wall metastases

To evaluate postoperative outcomes in patients with chest wall metastases. We analyzed 40 patients who underwent surgery for chest wall metastatic lesions. Fourteen (35%) patients had sternal lesion, 26 (65%) ones - rib metastases. We used implants for chest wall defect closure in 15 (37.5%) patients. Chest wall repair with autologous tissues was performed in 19 (47.5%) patients. Median survival was 17 months. Most patients (n=30, 75%) showed improvement in the quality of life according to Karnofsky and EGOG scale after surgery. Continued tumor growth occurred in 4 (10%) patients within 8-16 months after surgery. There were 2 patients who suffered from tumor recurrence accompanied by other metastatic foci (progression). Complications were diagnosed in 5 (12.5%) patients. Tactical errors were identified in 4 (10%) patients and they were associated with progression of cancer in the form of new metastatic foci within 6 months after surgery. Active surgical approach for bone metastases in patients with favorable cancer-related prognosis can improve quality of life and survival at least in case of solitary lesions. New program for treatment strategy selection based on prognosis of life expectancy and algorithms of surgical treatment will reduce the risk of erroneous management and increase its effectiveness.

Factors influencing the development of recurrence and continued growth of primary extramedullary tumors removed using Nd:YAG laser

Objective. To assess the significance of clinical factors of extramedullary tumors and new methods of their resection as potential predictors of their recurrence and continued growth.Material and Methods. The long-term results of removal of primary extramedullary tumors in 412 patients operated on in 1998–2014 were analyzed comparing the use of standard methods of microsurgical technique for tumor removal (277 patients) and of those with additional use of neodymium laser radiation (135 patients).Results. The use of laser technologies for resection of extramedullary tumors can significantly reduce the number of their recurrences and continued growth, along with other clinical factors is a significant prognostic indicator in determining the nature of the disease course and can be a predictor of their occurrence. The most reliable clinical factors determining the prognosis of a decrease in the incidence of recurrences and continued growth when using laser techniques of surgical resection were repeated operations (p = 0.002), the presence of ependymomas of the cone and cauda equina (p = 0.017), operations for primary tumors in the thoracic spine (p = 0.039) and extramedullary tumors with Grade I anaplasia (p = 0.007). An increase in the number of these conditions was associated with operations on the cervical spine (p = 0.027), the presence of a tumor with Grade II anaplasia (p = 0.007), and a primary extramedullary tumor involving more than three vertebrae (p = 0.017).Conclusion. The use of the laser is indicated for reoperations when removing neoplasms, that have arisen as a result of recurrence or continued growth of extramedullary tumors of any level and length after removal of primary neoplasms with a Grade I malignancy confirmed by intraoperative cytological examination involving no more than three vertebrae in the thoracic, lumbar and sacral spine and during resection of ependymomas with extramedullary growth.

RB depletion is required for the continuous growth of tumors initiated by loss of RB.

The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo. In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo.

Photodynamic therapy of the experimental tumors of different morphological types with liposomal boronated chlorin е6

The article summarizes the results of studies of the effectiveness of photodynamic therapy using a new domestic photosensitizer liposomal borated chlorin e6 (LBC) after its parenteral administration (intraperitoneal and intravenous). Antitumor efficacy was evaluated in rats with M-1 sarcoma and PC-1 alveolar liver cancer and mice with B16 melanoma and Ehrlich’s carcinoma, which were transplanted subcutaneously into the thigh area of the animals. The aim of the study was to determine the optimal regimes of photodynamic therapy that would allow achieving the maximum antitumor effect up to 21 days after the photodynamic therapy. The therapy was carried out under the control of the accumulation of the photosensitizer in the tumor and surrounding tissues of the thigh by selecting the doses of the drug and the parameters of laser radiation (energy density and power density). The effectiveness of therapy was assessed by the inhibition of tumor growth, by the percentage of animals with complete tumor regression, by the absolute growth rate in animals with continued tumor growth compared to controls. The results of our studies have shown that the domestic photosensitizer liposomal borated chlorin e6 has high antitumor activity in vivo. In an experimental study of the photosensitizer under certain PDT modes, the maximum antitumor effect (complete tumor regression in 100% of animals) was obtained up to 21 days after PDT in all tumor models used.

Transpupillary laser thermotherapy of retinoblastoma

Introduction. Despite the fact that transpupillary thermotherapy (TTT) is one of the main local methods of small retinoblastoma (RB) destruction, only a few studies have been published on the use of this method, and they are devoted only to certain aspects of the application of TTT.Purpose of the study – to evaluate the effectiveness of TTT in the treatment of children with RB.Material and methods. In the period from 2011 to 2020, 177 children (224 eyes, 1156 tumors) with RB were treated by TTT. Of these, 99 (56 %) patients were boys, 78 (44 %) – girls. The mean age at the time of treatment was 16.8 months (from 0 to 86 months). Bilateral RB was observed in 128 (72.3 %) patients, monolateral – in 49 (27.7 %). In 51 (28.8 %) cases, TTT was performed on an only eye. TTT was performed on eyes that had RB of groups A (n = 43; 19 %), B (n = 81; 36 %), C (n = 31; 14 %), D (n = 63; 28 %), E (n = 6; 3 %). In total, 1156 tumors were treated by TTT. 488 (42 %) tumors were localized post-equatorially (of which 27 were located juxtapapillary, 23 – in the macular zone, 22 – paramacular). 668 (58 %) foci had pre-equatorial localization (on the middle and far periphery of the fundus). The number of foci in one eye varied from 1 to 48 (mean – 5). The mean tumor thickness was 1.1 mm (from 0.2 to 4.5), the mean base diameter was 2.2 mm (from 0.3 to 13.4). TTT was performed using a diode laser with the following parameters: wavelength – 810 nm, spot diameter – 1200 microns, power from 200 to 800 mW (mean – 350 mW), exposure-from 3 to 15 s in the application mode, and continuous in the scanning mode.Results. Complete tumor regression after TTT was achieved in 92 % of cases (1064 tumors). Incomplete regression of the tumor with stabilization was achieved in 0.7 % (8 tumors). The average number of TTT sessions to achieve full regression was 1.7 (from 1 to 10). Complete tumor regression after 1 TTT session was achieved in 54 % of cases (622 tumors), after 2 sessions – in 11 % (132 tumors), after 3 sessions – in 7 % (85 tumors), after 4 or more sessions– in 19 % (225 tumors). In 7 % of cases (82 tumors), due to the progression of the tumor, other treatment methods (brachytherapy, cryotherapy, stereotactic radiosurgery) were applied. 209 (93 %) eyes were preserved. 15 (7 %) eyes were enucleated due to continued tumor growth, total retinal detachment, vitreous hemorrhage, or subatrophy of the eyeball. The mean follow-up after TTT was 35.5 months (from 3 to 112 months).Conclusion. TTT is a highly effective method of RB treatment and can be used for destruction of small primary foci of both post-equatorial and pre-equatorial localization, residual tumors after inefficiency of other local methods. TTT is also effective in the treatment of large cavitary tumors located in functionally significant areas of the retina.

Outcomes after stereotactic radiosurgery for schwannomas of the oculomotor, trochlear, and abducens nerves.

Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations. The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed. Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression. SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.

Retinoblastoma Morphology after Local Chemotherapy

Purpose. Determine the nature of tumor regression and possible complications associated with the retinotoxic effect of melphalan and carboplatin with local chemotherapy.Methods. A histological analysis of 19 enucleated eyes from 19 patients with retinoblastoma was performed after combined organ-preserving treatment, including systemic chemotherapy and local chemotherapy in various doses. The enucleated eyes were fixed in 10 % formalin and processed routinely for histological examination.Results. Significant changes in the tumor tissue such as tumor regression associated with the destruction of the tumor tissue and its replacement with fibrous tissue, glia proliferation, and the formation of petrificates were revealed. Complete regression of the tumor was detected in 3 out of 19 eyes, partial in 13 eyes. There were no signs of regression in 3 eyes. Tumor invasion into the choroid was found in 5 cases, into the anterior sector — in 3 cases, into the optic nerve — in 3 cases. The retrobulbar tumor was presented in 1 case. Retinotoxic complications revealed. Hemorrhagic changes associated with focal necrosis of the central retinal vessels (n = 4), destructive changes in retinal pigment epithelium (RPE; n = 10) associated with the accumulation of melphalan in RPE leading to atrophic processes in the retina. Complications in the form of secondary glaucoma, severe fibrosis and retinal detachment, despite the complete resorption of the tumor, led not only to loss of vision, but also hindered visualization of the fundus and substantiated the need for enucleation in 3 cases. In other cases, enucleation was performed due to continued tumor growth (n = 16) or progression during treatment (n = 3).Conclusions. Retinoblastoma can be controlled with local chemotherapy. However, clinical and morphological examinations of enucleated eyes revealed and confirmed, along with tumor resorption, intraocular complications as a result of the toxic effect of the drugs and the presence of active tumor tissue to varying degrees of therapeutic pathomorphism, which can be explained by the resistance of RB to these drugs. Thus, a further search is needed for drugs that destroy the tumor and minimize the retinotoxic effect.

Eighteen-year results of treatment of uveal melanoma using Ruthenium-106 + Rhodium-106 brachytherapy

The objective of the study was to evaluate the results of Ruthenium-106 (106Ru) + Rhodium-106 (106Rh) brachytherapy in uveal melanoma (UM) patients.The data for the period 2001–2018 were taken from the Belarusian Cancer Registry and medical records of patients with clinically diagnosed uveal melanoma who received treatment at the N. N. Alexandrov National Cancer Centre of Belarus. A total of 383 patients were included in the study. 106Ru + 106Rh β-ophthalmic applicators were used for brachytherapy (BT). The calculated dose to the tumor apex was 120–130 Gy, while the reduced 100–110 Gy was administered to tumors close to the optic nerve. To analyze the treatment outcomes, patients were divided into three groups based on a basal diameter of a tumor.Out of a total 383 patients, complete tumor resolution was observed in 282 (73.6 %), tumor stabilization was present in 76 (19.8 %). Continued tumor growth and tumor relapse were observed in 34 (9.13 %) and 50 (13.05 %) patients, respectively. 59 (15.1 %) patients underwent enucleation. The metastatic disease developed in 47 (12.3 %) cases. BT adverse effects were observed in 21.3 % cases. The relapse-free survival in the group of patients with a basal tumor diameter of up to 9 mm was 76.0 ± 6.3 %, which was higher than that in the groups with a large basal diameter (p = 0.002). Over a 15-year follow-up period, almost half of the patients (52.2 ± 15.6 %) with a tumor base of more than 12 mm relapsed.Considering the high rates of the continued tumor growth during treatment in patients with a basal tumor diameter of more than 12 mm, combined therapy must be used in this group.

Brachytherapy for retinoblastoma: a 13 year experience

Brachytherapy (BT) is a method of radiation therapy with radioactive source contacting the tumor. It was proposed by P. Moore and H. Stallard in 1929. Despite those 50 years of experience with the use of BT in ophthalmic oncology, there are only a few studies on the use of Ru-106 BT for retinoblastoma (RB), and no publications on the use of Sr-90 BT have been found.Purpose. To present our own experience with the use of ruthenium and strontium ophthalmic applicators for BT in retinoblastoma.Materials and methods. 120 patients (137 eyes and 194 RB foci) received BT as a local treatment in the period from 2007 to 2020. At the time of treatment the age of the patients varied from 4 to 109 months (mean age 26 months). In 32% of cases (44 eyes) there were monofocal lesions, and in 68% of cases (93 eyes) — multifocal. In 36 cases (30%) BT was performed in the single eye. 79 patients (87 eyes) were treated with the use of ruthenium ophthalmic applicators (OAs), 25 patients (26 eyes) — with the use of strontium OAs, and for the treatment of 16 patients (24 eyes) both ruthenium and strontium OAs were used.Results. Clinically complete tumor regression was achieved in 62 % of cases (120 foci), partial tumor regression — in 31% of cases (60 foci). In 6% of cases (12 foci) continuous tumor growth was observed, and tumor recurrence occurred in 1% of cases (2 foci) within 4 to 6 months after BT. Local tumor control was achieved in 93% of cases.The single eyes were preserved in 92% of cases. BT complications of different intensity were reported in 38% of cases (46 patients — 49 eyes) with the mean follow-up duration of 55 months (3 to 157 months). In 92 % of cases (42 patients — 45 eyes) complications were associated with the use of ruthenium OAs, and only in 8% of cases (4 patients — 4 eyes) — with the use of strontium OAs. Risk factors for radiation-induced complications were identified: focus size (height more than 2.5 mm [P =0.0005], extension more than 7.3 mm [P <0,0001]), sclera dose more than 626 Gr (P = 0,0002), and the central localization of the tumor (P <0.0001).Conclusions. Ruthenium-106 and strontium-90 brachytherapy is a highly effective treatment modality for the management of RB.

Tumor-Derived Extracellular Vesicles: Modulation of Cellular Functional Dynamics in Tumor Microenvironment and Its Clinical Implications.

Cancer can be described as a dynamic disease formed by malignant and stromal cells. The cellular interaction between these components in the tumor microenvironment (TME) dictates the development of the disease and can be mediated by extracellular vesicles secreted by tumor cells (TEVs). In this review, we summarize emerging findings about how TEVs modify important aspects of the disease like continuous tumor growth, induction of angiogenesis and metastasis establishment. We also discuss how these nanostructures can educate the immune infiltrating cells to generate an immunosuppressive environment that favors tumor progression. Furthermore, we offer our perspective on the path TEVs interfere in cancer treatment response and promote tumor recurrence, highlighting the need to understand the underlying mechanisms controlling TEVs secretion and cargo sorting. In addition, we discuss the clinical potential of TEVs as markers of cell state transitions including the acquisition of a treatment-resistant phenotype, and their potential as therapeutic targets for interventions such as the use of extracellular vesicle (EV) inhibitors to block their pro-tumoral activities. Some of the technical challenges for TEVs research and clinical use are also presented.

Radiosurgical treatment of patients with intracranial pilocytic astrocytomas

The study objective is to assess the outcomes after stereotactic radiosurgical treatment (SRS) in patients with pilocytic astrocytomas after non-radical surgery and after continued tumor growth.Materials and methods. The report includes 56 patients (37 males and 19 females) who have undergone SRS in N. N. Burdenko National Medical Research Center of Neurosurgery from March 2005 to January 2018.Results. The majority of patients (75 %) were children. Almost 43 % of patients underwent SRS as part of the primary treatment after biopsy or incomplete removal, other patients – in the event of continued tumor growth after non-total surgery. Tumors involved the cerebellum (41 %), brainstem (23 %), thalamus (19.6 %) and cerebral hemispheres (16.1 %). The median tumor volume was 1.9 cm3 (0.14–19.00 cm3), 23 % of patients had cysts in the tumor. The prescribed dose was 12 to 22 Gy (median 18 Gy) over 50–80 % isodose line. The follow-up was available for 54 (96.4 %) patients. The median follow-up was 67 months (3–151 months). All patients were alive at the end of the follow-up examination. In 14 (25 %) patients, the development of pseudo-progression (PSP) was noted. The median detection of PSP is 11 months (3–65 months). Of these, in 7 (50 %) patients PSP was accompanied by clinical deterioration: in 5 – an increase in general cerebral symptoms and in 1 patient – an episode and an increase in cerebellar symptoms. Eight (57 %) patients with PSP were reoperated: 4 underwent removal of the tumor, 4 – emptying of the cyst and placement of the Ommaya reservoir, which led to regression of the existing symptoms. No other toxicity was observed in patients. At the time of the completion of the follow-up examination (with a given median follow-up), no relapses were detected. There was no clinical deterioration after SRS.Conclusion. Radiosurgical treatment is an effective and safe method of radiation treatment for patients with primary pilocytic astrocytomas and recurrent pilocytic astrocytomas, providing control over tumor growth in all patients with a low risk of complications.

The first experience of application of remote radiotherapy in combination with hyperthermia and electrotherapy (oncothermia) in the treatment of patients with primary gliomas of the brain of a high degree of malignancy

High-grade brain gliomas are characterized by a rapid clinical course and a 2-year survival rate of 8-12%. Despite the improvement of methods of surgery, radiotherapy( RT), and systemic drug therapy, it is still not possible to significantly increase the overall and relapse-free survival in patients with this neuro-oncological pathology, and the combination of RT and CT with hyperthermic electrotherapy (oncothermy) (OT) looks like a promising method that helps to increase the effectiveness of special treatment.
 At the same time, oncothermia does not cause brain edema and does not worsen the quality of life of neuro-oncological patients. At the same time, a possible alternative to further progress in improving the results of treatment of primary brain gliomas (WHO Grade III-IV) is not only to optimize the radiotherapy program, but also to combine standard methods of radical treatment with hyperthermic electrotherapy.
 This article presents preliminary immediate results of treatment of 20 patients who received special treatment in the RSCRR with an assessment of the toxicity and safety of its implementation and with an assessment of the likely resumption of continued tumor growth 1.5 and 3 months after the end of treatment. In General, the data obtained indicate the safety of the developed method of special treatment of this category of neuro-oncological patients,
 which confirms the results obtained in 28.09.2019 patent for an invention. However, for final conclusions, further clinical studies are required on a larger group of patients with longer follow-up periods, followed by a thorough analysis of the results.

Open vertebroplasty for cervical spine aggressive hemangioma

Objective.To analyze results of open vertebroplasty for aggressive hemangioma of the cervical spine.Material and Methods. Surgical treatment was performed in 12 patients with aggressive hemangioma of the cervical spine. Vertebroplasty was performed through an open anterolateral approach under the control of an image intensifier.Results. Pain intensity was 7.0 ± 1.0 on VAS before surgery and 1.8 ± 1.2 immediately after surgery. Neck disability index (NDI) was 17.5 ± 6.5 before surgery and 4.3 ± 1.7 after surgery. One month after surgery VAS and NDI scores were 0. There were no complications in the postoperative period. A control study visualized from 82 % to 98 % completeness of filling the bone defect with polymethyl methacrylate. Bone composite migration outside the vertebral body was not detected in any of the operated patients. Control images taken 6 and 12 months after surgical treatment did not reveal continued tumor growth and signs of any osteonecrotic processes in bone tissue as a response to PMMA bone cement in any case.Conclusion. Despite the widespread and rather long period of using vertebroplasty, the issues of the choice of approaches when performing it on the cervical spine are still debatable. In order to reduce the risk of iatrogenic complications in cervical vertebroplasty, the open approach can be used which increases the treatment effectiveness.

Lumbar Laminoplasty for Resection of Myxopapillary Ependymoma of the Conus Medullaris: 2-Dimensional Operative Video.

Myxopapillary ependymomas are slow-growing tumors that are located almost exclusively in the region of the conus medullaris, cauda equina, and filum terminale of the spinal cord. Surgical intervention achieving a gross total resection is the main treatment modality. If, however, a gross total resection cannot be achieved, surgery is augmented with radiation therapy. In this video, we present the case of a 27-yr-old male with persistent back pain and radiculopathy who was found to have a myxopapillary ependymoma that was adherent to the conus. Preoperative imaging demonstrated that the tumor was displacing the conus and nerve roots ventrally. A laminoplasty at L1-L2 was performed with near-total resection because of the intimate involvement of neural tissue. The key features of the video include performing laminoplasty and rationale, and performing maximum safe tumor resection with a combination of bipolar cautery, suction, and ultrasonic aspiration augmented with frequent stimulation, gel foam pledgets intradurally, and achieving a watertight closure of the dura and fascia. The patient tolerated the surgery well without any complications. Given his gross residual disease along the conus and young age, he was at a high risk for continued tumor growth without adjuvant therapy, with a recurrence rate of roughly 33% to 45% in patients who underwent subtotal resection. With the addition of adjuvant radiation therapy, the recurrence rate is 20% to 29%.1,2 He was discharged to home with a plan for conventional fractionated external beam radiation. At the most recent follow-up, he reported decreased back pain and radiculopathy. Appropriate patient consent was obtained.

Results of chemoembolization in hepatocellular cancer and metastatic liver damage

Treatment of patients with hepatocellular cancer remains a complex problem in modern oncology.
 The purpose was to evaluate the effectiveness of chemoembolization in hepatocellular cancer and metastatic liver disease.
 Results: During and after the procedure, the risk of complications was minimal: in 2 cases (0.25%), liver necrosis and death from cardiovascular insufficiency were recorded after five therapy courses. Eleven patients (23.9%) with a continued tumor growth showed a negative response and were administered symptomatic treatment.
 Conclusion: In primary hepatocellular cancer and metastatic liver lesions, chemoembolization is one of the priorities in interventional radiology and a stage of complex treatment. This method is low-traumatic due to a minimal toxic effect of the chemotherapy drug. This method is indicated for inoperable liver tumors because a high concentration of an anticancer drug is delivered right to the focus and ensures a prolonged tumor exposure, with minimal risk of complications during and after the procedure. In our observations, complications in the form of necrosis and death occurred in 2 (0.25%) cases.

Results of chemoembolization in hepatocellular cancer
 and metastatic liver damage

Relevance: Treatment of patients with hepatocellular
 cancer remains a complex problem in modern oncology.
 Purpose: To evaluate the effectiveness of chemoembolization in hepatocellular cancer and metastatic liver disease.
 Results: During and after the procedure, the risk
 of complications was minimal: in 2 cases (0.25%), liver
 necrosis and death from cardiovascular insufficiency
 were recorded after five therapy courses. Eleven patients (23.9%) with a continued tumor growth showed a negative response and were administered symptomatic treatment.
 Conclusion: In primary hepatocellular cancer and
 metastatic liver lesions, chemoembolization is one of the
 priorities in interventional radiology and a stage of complex treatment. This method is low-traumatic due to a minimal toxic effect of the chemotherapy drug. This method is indicated for inoperable liver tumors because a high concentration of an anticancer drug is delivered right to the focus and ensures a prolonged tumor exposure, with minimal risk of complications during and after the procedure. In our observations, complications in the form of necrosis and death occurred in 2 (0.25%) cases

Combination treatment with immunogenic and anti-PD-L1 polymer-drug conjugates of advanced tumors in a transgenic MMTV-PyMT mouse model of breast cancer

Immune checkpoint blockade has revolutionized the treatment of tumors with immunogenic microenvironments. However, low response rate and acquired resistance are still major challenges. Herein we used a more clinically relevant model of transgenic MMTV-PyMT tumor that more closely mimics the development of human breast cancer in an immunocompetent background to investigate a polymer-based chemo-immunotherapy. We have found that tumors acquired an increased degree of immune suppression during progression, rendering them unresponsive to anti-PD-L1 therapy. To treat large tumors at their advanced stage, we applied a combination strategy consisting of two polymer-drug conjugates that could induce immunogenic cell death (ICD) and disrupt the PD-L1/PD-1 interaction, respectively. Although ICD-inducing conjugate remodeled tumor immune microenvironment by facilitating significant CD8+ T cell infiltration, advanced tumor adapted the immune suppressive mechanism of elevating PD-L1 expression on both cancer cells and myeloid cells thereafter to enable continued tumor growth. Concurrent treatment of PD-L1 blocking conjugate not only abrogated the PD-L1 expression from the two disparate cellular sources, but also considerably reduced the number of immunosuppressive myeloid cells, thereby leading to a significant shrinkage of advanced tumors. Our data provide evidence that combinatory strategy of ICD–inducing and PD-L–blocking modalities could reverse immune suppression and establish a basis for the rational design of cancer immunotherapy.

α3 integrin-binding peptide-functionalized polymersomes loaded with volasertib for dually-targeted molecular therapy for ovarian cancer

Ovarian cancer (OC) is a high-mortality malignancy in women with a five-year survival rate of 30-40%. There is an urgent need to develop high-efficacy and low toxic treatments for OC. Herein, we report an appealing strategy that combines α3 integrin targeted polymersomes (A3-Ps) and targeted molecular drug, polo-like kinase 1 (PLK1) inhibitor volasertib (Vol) for dually targeted molecular therapy of OC in vivo. A3-Ps had good Vol loading of 7.7-8.0 wt.% and small size of 25-32 nm, depending on the density of α3 integrin binding peptide A3. Interestingly, cellular uptake studies using FITC-labeled Vol revealed that A3-Ps with 20% peptide gave 2.3 and 3.3-fold better internalization in SKOV-3 OC cells compared with non-targeted Ps and free Vol, respectively. Accordingly, Vol loaded in A3-Ps showed the best inhibitory activity to SKOV-3 cells with an IC50 of 49 nM, which was 3.5 times lower than free Vol. Importantly, the in vivo experiments demonstrated that A3-Ps-Vol proficiently repressed the growth of SKOV-3 tumors in mice while continuous tumor growth was observed for Ps-Vol and free Vol-treated mice. A3-Ps-Vol besides boosting anti-OC activity also reduced the systemic toxicity of Vol. This dually targeted molecular drug nanoformulation has appeared to be an especially potent and low toxic treatment modality for human ovarian cancers. Statement of significanceVolasertib provides a potential molecular therapy for PLK1-positive advanced OC patients. The initial clinical outcomes, nevertheless, showed a suboptimal efficacy, possibly resulting from its fast clearance, deficient tumor deposition and dose-limiting toxicities. Here, we show for the first time that dually targeted molecular therapy of OC using α3 integrin-binding peptide-modified polymersomes as a vehicle gives markedly improved potency, better toleration, and depleted adverse effects in SKOV-3 tumor models, greatly outperforming free volasertib. This dually targeted strategy has emerged as an appealing treatment for malignant PLK1-positive ovarian tumors.

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector.

This protocol describes the allotransplantation of tumors in Drosophila melanogaster using an auto-nanoliter injection apparatus. With the use of an autoinjector apparatus, trained operators can achieve more efficient and consistent transplantation results compared to those obtained using a manual injector. Here, we cover topics in a chronological fashion: from the crossing of Drosophila lines, to the induction and dissection of the primary tumor, transplantation of the primary tumor into a new adult host and continued generational transplantation of the tumor for extended studies. As a demonstration, here we use Notch intracellular domain (NICD) overexpression induced salivary gland imaginal ring tumors for generational transplantation. These tumors can first be reliably induced in a transition-zone microenvironment within larval salivary gland imaginal rings, then allografted and cultured in vivo to study continued tumor growth, evolution, and metastasis. This allotransplantation method can be useful in potential drug screening programs, as well as for studying tumor-host interactions.