Regression Of Tumor Size Research Articles

Fucoidan based polymeric nanoparticles encapsulating epirubicin: A novel and effective chemotherapeutic formulation against colorectal cancer

Colorectal cancer (CRC) is one of the most common and challenging malignancy that needs some effective and safer chemotherapeutic agents for the treatment. In this study, anticancer agent epirubicin (Epi) was loaded in polymeric polyethylene glycol-polylactic acid-nanoparticles (mPEG-PLA-NPs) coated with a marine anti-cancer non-toxic polysaccharide fucoidan (FC), to achieve a synergistic activity against CRC. The characterization of the NPs revealed that they were spherical, monodispersed, stable, with a negative zeta potential, and exhibited good biocompatibility and controlled release. In vitro anti-cancer activity of the NPs on HCT116 cell line was found to be promising, and corroborated well with in vivo studies involving BALB/C mice injected with C26 murine cancer cells. The outcome of MTT assay demonstrated that IC50 value of free Epi was 3.72 µM, and that of non-coated and coated Epi nano-formulations was 33.67 and 10.19 µM, respectively. Higher tumor regression, better survival and reduced off-side cardiotoxicity were observed when this novel NPs formulation was used to treat tumor-bearing mice. Free FC and Epi treated mice showed 37.73 % and 61.49 % regression in tumor size, whereas there was 79.76 % and 90.34 % tumor regression in mice treated with non-coated Epi NPs and coated Epi NPs, respectively. Therefore, mPEG-PLA-FC-Epi-NPs hold a potential to be used as an effective chemotherapeutic formulation against CRC, since it exhibited better efficacy and lower toxicity.

Investigating the anticancer properties of six benzothiazolopyrimidine derivatives on colon carcinoma cells, in vitro and in vivo.

Colorectal cancer (CRC) is the third most common cancer in the world. Despite considerable improvements in the treatment of this cancer, further research to discover novel and more effective agents is ongoing. In this study, possible cytotoxic and apoptotic properties of six benzothiazolopyrimidine derivatives were studied. To assess the IC50 values of these agents, MTT assay was performed on HCT 116, CT26, and NIH/3T3 cells. Moreover, cell death mechanism induced by studied compounds was evaluated by PI/annexin V staining. Then, based on molecular docking results and in vitro experiments, the compounds with the highest anticancer properties were further analyzed in vivo in a mouse model of CRC. MTT results indicated that BTP(1) and BTP(4) had the highest selective cytotoxicity on colorectal cancer cells. Furthermore, flow cytometry results demonstrated a considerable increase in the percentage of the early apoptotic cells in BTP(1)- and BTP(4)-treated groups. In vivo studies confirmed the antitumor properties of the two compounds by a significant regression in tumor size of BTP(1)- and BTP(4)-treated mice compared to control groups. Histopathological examination of tumor tissues showed an increased number of apoptotic cells in these two groups compared to the control animals. Additionally, hematoxylin and eosin staining of the spleen and liver of treated mice did not exhibit considerable tissue damage. Thus, BTP(1) and BTP(4) can be considered promising agents in the treatment of colorectal cancer, although further experiments are required to assess their mechanism of action before their application in clinical studies.

Enhancing Neoadjuvant Virotherapy's Effectiveness by Targeting Stroma to Improve Resectability in Pancreatic Cancer.

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering the infiltration of oncolytic viruses and various therapeutic drugs-such as antibodies, adoptive cell therapy agents, and chemotherapeutic agents-in reaching the tumor site. Recently, a growing emphasis has been placed on targeting major acellular components of tumor stroma, such as hyaluronic acid and collagen, to enhance drug penetration. Oncolytic viruses can be engineered to express proteolytic enzymes that cleave hyaluronic acid and collagen into smaller polypeptides, thereby softening the desmoplastic stroma, ultimately leading to increased viral distribution along with increased oncolysis and subsequent tumor size regression. This approach may offer new possibilities to improve the resectability of patients diagnosed with BR and LA PDAC.

Radiosurgical Decompression of Trigeminal Nerve and Its Correlation with Functional Outcome in Tumor-Related Trigeminal Neuralgia

BackgroundThe target selection during gammaknife radiosurgery(GKRS) in cases of tumor related trigeminal neuralgia(TRTGN) is always debatable. Here we discuss the correlation of regression of tumor size, degree of release of the nerve with long term pain control. MethodsTotal 50 cases of TRTGN were treated with GKRS (tumor was targeted) during the period March 2012 and March 2023. Post GKRS radiology was categorised in to three types(Type 1 – tumor volume remained same/reduced, additional segment of nerve not seen, Type 2 – tumor volume reduced, additional segment of trigeminal nerve seen but tumor still adherent to the nerve, Type 3 – tumor volume reduced, adjacent nerve seen completely separated from tumor). Pre and post GKRS pain score(BNI I to III –good, BNI IV&V – poor) was correlated with the above subgroups. ResultAt a median follow up of 46.5 months 18 cases have type 1, 23 showed type 2 and 9 showed type 3 radiological response. Ten(55.5%) patients with type 1, 15(65.21%) with type 2 and 7(77.8%) with type 3 responses had good pain control. The outcome among these three was not statistically significant(p=0.519).Five patients with type 3 radiological response were off medication which was statistically better than type 1 radiological response with three patients(p = 0.012) and type2 radiological response with two patients(p = 0.002). ConclusionPost GKRS tumor volume reduction may show good pain control in TRTGN. This further allows visualization of additional segment of nerve that can be targeted in the second session for treating recurrent or failed cases.

SAT623 Everolimus For Treatment-refractory Prolactinomas

Abstract Disclosure: A.L. Lin: Grant Recipient; Self; Bristol-Myers Squibb. E.B. Geer: None. G. Page-Wilson: None. R.S. Magge: None. R.J. Young: Consulting Fee; Self; Olea Sphere, ICON plc. V. Tabar: None. Introduction: Treatment-refractory prolactinomas are life-limiting tumors without a standard of care treatment option after the oral alkylator, temozolomide, fails to provide tumor control. Methods: We reviewed an institutional database of pituitary tumors for patients with aggressive prolactinomas who progressed following treatment with a dopamine agonist, radiotherapy and temozolomide. In this cohort of patients with aggressive prolactinomas, we identified 4 patients who were treated with everolimus and we report their response to this therapy. Treatment response was determined by a neuroradiologist, who manually performed volumetric assessment and determined treatment response by Response Assessments in Neuro-Oncology (RANO) criteria. Results: 3 of 4 patients who were treated with everolimus had a biochemical response to therapy and all patients derived a clinically meaningful benefit based upon suppression of tumor growth. While the best overall response as assessed by RANO criteria was stable disease for the 4 patients, a minor regression in tumor size was appreciated in 2 of the 4 patients. Conclusion: Everolimus is an active agent in the treatment of prolactinomas that warrants further investigation. Presentation: Saturday, June 17, 2023

Regression of Primary Vitreoretinal Lymphoma (Pvrl) And Perivascular Flower Bud Like Lesions (Pfbls) on Octa After Intravitreal Methotrexate Injection Series

Primary Vitreoretinal Lymphoma (PVRL) is a rare and aggressive type of intraocular lymphoma that affects the eye. PVRL is most commonly diagnosed in individuals in their sixth to eighth decade of life, but it can occur in younger, immunocompromised individuals. PVRL is challenging to diagnose due to its non-specific presentations, and a delay in diagnosis from the onset of symptoms can exceed 12 months. CNS involvement in PVRL is common, and patients may develop CNS involvement within a mean interval of 8-29 months after diagnosis. We present a case of a 73-year-old man who presented to the emergency department with gradual decline in vision in his left eye over the past two years, with acute worsening over the past two weeks. The patient was diagnosed with PVRL with CNS involvement based on exam, imaging and biopsy findings. The patient received intravitreal injection of methotrexate in the left eye and systemic treatment with rituximab and ibrutinib. The patient’s visual acuity improved in the left eye, and regression of tumor size was noted on the fundus exam, OPTOS, and OCTA. Prompt referral to a medical center and early diagnosis are essential in managing PVRL to prevent potential vision loss. Various imaging modalities such as fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography can be helpful in diagnosis and management of PVRL. However, the use of optical coherence tomography angiography has been only described in few case studies. The management of PVRL remains a challenge, with limited treatment options available, including systemic chemotherapy and/or radiation therapy

Papaverine Enhances the Oncolytic Effects of Newcastle Disease Virus on Breast Cancer In Vitro and In Vivo.

Breast cancer is a lethal disease in females worldwide and needs effective treatment. Targeting cancer cells with selective and safe treatment seems like the best choice, as most chemotherapeutic drugs act unselectively. Papaverine showed promising antitumor activity with a high safety profile and increased blood flow through vasodilation. At the same time, it was widely noticed that virotherapy using the Newcastle disease virus proved to be safe and selective against a broad range of cancer cells. Furthermore, combination therapy is favorable, as it attacks cancer cells with multiple mechanisms and enhances virus entrance into the tumor mass, overcoming cancer cells' resistance to therapy. Therefore, we aimed at assessing the novel combination of the AMHA1 strain of Newcastle disease virus (NDV) and nonnarcotic opium alkaloid (papaverine) against breast cancer models in vitro and in vivo. Methods. In vitro experiments used two human breast cancer cell lines and one normal cell line and were treated with NDV, papaverine, and a combination. The study included a cell viability MTT assay, morphological analysis, and apoptosis detection. Animal experiments used the AN3 mouse mammary adenocarcinoma tumor model. Evaluation of the antitumor activity included growth inhibition measurement; the immunohistochemistry assay measured caspase protein expression. Finally, a semiquantitative microarray assay was used to screen changes in apoptotic proteins. In vitro, results showed that the combination therapy induces synergistic cytotoxicity and apoptosis against cancer cells with a negligible cytotoxic effect on normal cells. In vivo, combination treatment induced a significant antitumor effect with an obvious regression in tumor size and a remarkable and significant expression of caspase-3, caspase-8, and caspase-9 compared to monotherapies. Microarray analysis shows higher apoptosis protein levels in the combination therapy group. In conclusion, this study demonstrated the role of papaverine in enhancing the antitumor activity of NDV, suggesting a promising strategy for breast cancer therapy through nonchemotherapeutic drugs.

Does the number of cycles of neoadjuvant therapy affect the efficacy of neoadjuvant chemoimmunotherapy for non-small cell lung cancer in locally advanced stage? Retrospective experience based on a single center.

The number of cycles of neoadjuvant therapy programmed cell death 1 (PD-1) inhibitor for locally advanced non-small cell lung cancer (NSCLC) remains controversial. From October 2019 to March 2022, neoadjuvant chemoimmunotherapy followed by radical surgery for NSCLC patients with stage II-III were retrospectively reviewed in Shanghai Pulmonary Hospital. The radiologic response was assessed according to the Response Evaluation Criteria for Solid Tumors version 1.1. The major pathological response was defined as no more than 10% residual tumor. Student'st-test, chi-square test, and Mann-Whitney test were used for univariate analysis, logistic regression analysis was used for multivariate analysis. All statistical analyses were calculated by SPSS software (version 26). Among 108 patients, the number of patients who received 2-cycle (2-cycle group) and more than 2-cycle (>2-cycle group) neoadjuvant chemoimmunotherapy were 75 (69.4%) and 33 (30.6%), respectively. Compared with patients inthe >2-cycle group, patients in the 2-cycle group had significantly smaller diagnostic radiological tumor size (37.0mm vs. 49.6mm, p=0.022) and radiological tumor regression rate (36%vs. 49%, p=0.007). However, no significant difference in pathological tumor regression rate was observed between patients in the 2-cycle group and>2-cycle group. Further logistic regression analysis demonstrated that the neoadjuvant chemoimmunotherapy cycle could independently affect the radiographic response (odds ratio [OR]: 0.173, 95% confidence interval [CI]: 0.051-0.584, p=0.005) but not for pathological response (OR: 0.450, 95% CI: 0.161-1.257, p=0.127). For patients diagnosed with stage II-III NSCLC, the number of neoadjuvant cycles administered can significantly influence the radiographic efficacy of chemoimmunotherapy.

Hepatic arterial infusion with nanoliposomal irinotecan leads to significant regression of tumor size of colorectal liver metastases in a CC531 rat model.

Long-term therapy for unresectable colorectal liver metastases remains challenging. Intraarterial treatments aim to avoid systemic adverse effects of chemotherapy. Nanoliposomal cytotoxic drugs manage to increase the drug concentration within the tumor while reducing toxicity in healthy tissue. In this study we analyzed the effect of hepatic arterial infusion (HAI) with nanoliposomal irinotecan with or without the combination of embolization particles in a rat model for colorectal liver metastases. For the study 32 WAG/Rij rats received subcapsular tumor implantation with CC531 rat colonic adenocarcinoma cells. After ten days tumor size was assessed via ultrasound and animals underwent HAI. One group served as control receiving NaCl 0.9 % (Sham), the three treatment groups received either nanoliposomal irinotecan (HAI nal iri), Embocept® S (HAI Embo) or Embocept® S and nanoliposomal irinotecan (HAI Embo+nal iri). Three days after treatment animals were sacrificed after assessment of tumor size. As a result all treatment groups showed a significant reduction in tumor growth compared to Sham (p<0.05). Expression of the apoptosis marker caspase-3 was enhanced in HAI nal iri and HAI Embo+nal iri compared to Sham and HAI Embo and even significantly enhanced after HAI Embo+nal iri in comparison to Sham (p<0.05). We were able to show thatHAI with Embocept® S led to significantly reduced tumor growth while HAI with nanoliposomal irinotecan alone or in combination with Embocept® S even led to a reduction of tumor size. Thus, we demonstrate that intraarterial treatment with nanoliposomal irinotecan effectively inhibits tumor growth in a rat model of colorectal liver metastases and demands further investigation.

Abstract 485: Hypoxia inducible factor (HIF) inhibitor 64B has superior anti-tumor effects compared to two different tyrosine kinase inhibitors when tested in mouse models of uveal melanoma

Abstract Uveal melanomas (UMs) arise from melanocytes along the uveal tract and are distinct from cutaneous melanomas, with different molecular events in their pathogenesis. While primary treatment generally results in good local control, UMs spread systemically in approximately 50% of patients, most commonly to the liver. Patients who develop metastases are more likely to express the hypoxia-induced transcription factor HIF-1α and the HIF-regulated genes CXCR4 and c-Met when compared to patients who do not develop metastatic disease1, suggesting that blocking HIF function might be clinically beneficial for the management of UM, a tumor type that fails to respond to treatments that are effective for treating cutaneous melanoma. 64B is a small molecule therapeutic that inhibits the function of hypoxia inducible factors (HIFs) by disrupting the recruitment of the transcription co-factor paralogs, p300/CBP, while leaving intact p300/CBP’s ability to function with multiple other transcription factors. As a consequence, 64B is well tolerated and blocks transcription of multiple genes that help tumor cells survive and spread, including genes involved in angiogenesis, multidrug resistance, invasion and metastases. Using several different UM tumor cell lines implanted in the uveal tract of mice, we previously showed that 64B given systemically inhibits primary tumor growth and metastases1. We now compare the anti-cancer efficacy of 64B to two different tyrosine kinase inhibitors (TKIs) that are in clinical testing for UM, sunitinib and selumetinib. Sunitinib is a TKI that suppresses the function of the growth factor receptors c-kit and VEGFR, proteins that are highly expressed in UM. Selumetinib is a highly selective MEK1/2 inhibitor, targeting the MEK pathway that is activated in UM due to the GNAQ/11 activation that occurs in about 85% of UMs. Human UM cells (92.1; GNAQ Q209P mutant) were implanted in the flank of nude mice, and systemic treatment (i.p.) with 64B was started once the s.c tumor reached 100 mm3. 64B was far superior to either sunitinib or selumetinib at causing a regression in tumor size and in reducing the number and size of liver metastases. The metastases that were observed in 64B-treated animals were very small and did not show evidence of tumor vascularization, unlike the control tumors which were much larger and were vascularized. The tumor-bearing animals receiving 64B were behaviorally normal and were healthier than control mice or mice receiving either sunitinib or selumetinib, some of which died in the non-64B groups. The efficacy of 64B at causing tumor regression and reducing metastases combined with its safety profile support advancing 64B to clinical testing for metastatic UM. 1 Dong L et al, Clin Cancer Res. 2019;25(7):2206-18. Citation Format: Hua Yang, Hans E. Grossniklaus, Erwin G. Van Meir, Margaret K. Offermann. Hypoxia inducible factor (HIF) inhibitor 64B has superior anti-tumor effects compared to two different tyrosine kinase inhibitors when tested in mouse models of uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 485.

Effect of Tamoxifen on the Management of Dopamine Agonist-Resistant Prolactinomas: A Systematic Review.

The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy. The presence of estrogen receptors on pituitary tumors, and the variable behavior of pituitary tumors in the presence of estrogen, prompted investigation of the role of anti-estrogen in the treatment of DA-resistant prolactinomas. The goal of this paper is to perform a systematic review of the role of tamoxifen in the treatment of DA-resistant prolactinomas. A systematic review was conducted. Inclusion criteria were case reports, case series, and experimental studies using tamoxifen in DA-resistant prolactinomas. Exclusion criteria included review articles, DA-sensitive prolactinomas, and those that were not previously treated with DA. Data were analyzed using descriptive statistics. For continuous data, the mean was used. For dichotomous data, frequencies and percentages were used. Data on 22 patients were extracted from the seven included studies. Twenty patients (90.9%) responded positively to the use of tamoxifen with a mean reduction in prolactin levels of 57.4%. Ten patients (45.5%) showed normalization of prolactin post-tamoxifen administration. Regression of tumor size and stability of tumor growth were reported in four out of 22 cases (18.2%). Combination therapy with DA and tamoxifen increased DA sensitivity and had a clinically significant inhibitory effect on prolactin secretion. Furthermore, tamoxifen may be considered an effective adjuvant for tumor size control. Therefore, further studies are needed to draw more clinically and statistically robust conclusions.

Novel Zebrafish Patient-Derived Tumor Xenograft Methodology for Evaluating Efficacy of Immune-Stimulating BCG Therapy in Urinary Bladder Cancer.

Bacillus Calmette-Guérin (BCG) immunotherapy is the standard-of-care adjuvant therapy for non-muscle-invasive bladder cancer in patients at considerable risk of disease recurrence. Although its exact mechanism of action is unknown, BCG significantly reduces this risk in responding patients but is mainly associated with toxic side-effects in those facing treatment resistance. Methods that allow the identification of BCG responders are, therefore, urgently needed. Fluorescently labelled UM-UC-3 cells and dissociated patient tumor samples were used to establish zebrafish tumor xenograft (ZTX) models. Changes in the relative primary tumor size and cell dissemination to the tail were evaluated via fluorescence microscopy at three days post-implantation. The data were compared to the treatment outcomes of the corresponding patients. Toxicity was evaluated based on gross morphological evaluation of the treated zebrafish larvae. BCG-induced toxicity was avoided by removing the water-soluble fraction of the BCG formulation prior to use. BCG treatment via co-injection with the tumor cells resulted in significant and dose-dependent primary tumor size regression. Heat-inactivation of BCG decreased this effect, while intravenous BCG injections were ineffective. ZTX models were successfully established for six of six patients based on TUR-B biopsies. In two of these models, significant tumor regression was observed, which, in both cases, corresponded to the treatment response in the patients. The observed BCG-related anti-tumor effect indicates that ZTX models might predict the BCG response and thereby improve treatment planning. More experiments and clinical studies are needed, however, to elucidate the BCG mechanism and estimate the predictive value.

361. EARLY RECURRENCE PATTERNS AFTER ESOPHAGECTOMY FOR ESOPHAGEAL CANCER IN PATIENTS UNDERGOING CROSS NEOADJUVANT THERAPY

Abstract Chemoradiotherapy (CROSS regimen) has been regarded as standard preoperative treatment for patients with locally advanced esophageal cancer, but some patients still developed early recurrence after such intensive therapy. The present study aimed to determine the factors associated with early recurrence for patients with ESCC treated by CROSS therapy within 6 months. Patients were identified from single institution from 2019 to 2021. All patients with locally advanced ESCC who underwent CROSS regimen NCRT and following R0 esophagectomy were reviewed. Total 115 patients were included. 19 patients (16.52%) recurred within 6 months post-surgery. 8 patients (6.96%) had local-regional recurrence with most common location was cervical lymphnodes; 11 patients (9.56%) had distant recurrence and most often occured in lung. In univariate analysis: BMI before CROSS (p = 0.03), tumor size regression (p = 0.03), ypN≧1 (p = 0.002) and neck metastases (p = 0.01) were significantly associated with local-regional recurrence. In multivariate analysis: ypN≧1 (HR = 9.08, p = 0.05) was only independent covariate. For distant recurrence, tumor size regression (p = 0.02), ypN≧1 (p &amp;lt; 0.0001) and TRG3/4 (p = 0.01) were risk factors in univariate analysis, ypN≧1 (HR = 15.60, p = 0.01) was also independent covariate in multivariate analysis. For patients after CROSS neoadjuvant therapy, if there are still positive lymph nodes in clinical evaluation, M staging should be performed more carefully to avoid ineffective surgery with early postoperative distant recurrence.

Successful Management of Locally Advanced Primitive Neuroectodermal Tumor (PNET) of the Urinary Bladder: a Case Report and Literature Review

Background: Primitive neuroectodermal tumors (PNETs) are highly malignant neoplasms arise from neuroectodermal cells that have cholinergic features. These tumours are closely related to osseous or extraosseous Ewing’s sarcomas, with which they share the same chromosomal abnormality. Over the last few years, PNETs have been increasingly reported to occur in various organs, which may be due to recent progress in immunohistochemical techniques. PNETs arising in the urinary bladder are extremely rare, but more frequent in older adults. Case presentation: A 16 years Moroccan men old, who consults for a total hematuria and dysuria evolving for 2 months in a context of deterioration of the general state. Cyst biopsy was performed. The morphological result in favor of an undifferentiated round cell tumor process infiltrating the bladder muscle, the immu-histochemical study was in favor of a round cell tumor of the Ewing sarcoma/PNET type. Pelvic Magnetic resonance imaging MRI revealed the presence of an endovesical process invading the left antero-inferior pre-vesical fat. We decided, after a multidisciplinary consultation meeting, to start with two cycles of neoadjuvant chemotherapy, then to propose locoregional treatment, either radiotherapy or partial resection. The patient was put on the VAC/IE protocol with a clear regression in tumor size after two cycles. Conclusion: Both clinician and pathologist must be aware of this rare entity during diagnosis and management. Surgery or radiotherapy supported with chemotherapy should be considered an option, especially in advanced disease. Studies of more cases of primary PNET of the urinary bladder with longer follow-up periods are needed to clarify the clinical features and treatment.

Spinal screening, malignancy, medical therapy, and surgical correction of deformity in pediatric patients with neurofibromatosis type 1: a systematic review.

The objective of this systematic review was to synthesize evidence regarding spinal screening recommendations, types of spinal and thoracic neurofibromatosis type 1 (NF1) tumors, medical therapy for NF1-associated neoplasms, and treatment with magnetically controlled growing rods (MCGRs) or cervical kyphosis correction in pediatric patients with NF1. We queried PubMed, Embase, Cochrane Library, Web of Science, Scopus, Clinicaltrials.gov, and medRxiv for studies reporting spinal screening recommendations, prognosis, and medical therapy for NF1-associated spinal tumors and MCGR use or cervical kyphosis correction in pediatric NF1 patients, yielding 758 publications, 33 of which were included. There is no consensus on spinal screening interval. Computed tomography is recommended for postoperative monitoring. Patients with gangliomas and spinal neurofibromas had nearly complete symptom resolution after resection. Plexiform neurofibromas were most commonly treated with resection and laminectomy; some patients reported tumor enlargement after intervention. Malignant nerve sheath tumors have high rates of metastasis even after chemoradiation and resection. MEK-inhibitors produced limited regression in tumor size. Sirolimus and thalidomide reduced tumor size but caused more severe adverse effects than MEK-inhibitors. Improvements in major curves and T1-T12 height gain were reported after MCGR intervention. Anteroposterior arthrodesis produced the greatest correction of dystrophic cervical kyphosis. There may be value in establishing standardized spinal screening protocols for pediatric NF1 patients. Surgical correction of NF1-associated spinal deformity is effective, though current medical therapies for spinal tumors have limited success. Areas for further investigation include determining appropriate screening intervals, choice of medical therapy for spinal tumors, and long-term outcomes of MCGRs. Level of Evidence: IV.

Traitement par chimiothérapie orale (sonidegib) de carcinomes basocellulaires étendus, à propos de 4 cas

Basal cell carcinoma (BCC) is the most frequent cutaneous carcinoma. Its incidence is constantly increasing, primarily due to sun exposure during the two first decades of life. The lower lid and medial canthus are the most common locations. In the majority of cases, surgery with sufficient margins is the first-line treatment. In the case of inoperable tumors (extensive lesions, poor general health, high surgical morbidity, unacceptable cosmetic sequelae), oral chemotherapy can be suggested. We report the follow-up of 4 patients with advanced non-metastatic basal cell carcinoma (BCC) treated with oral chemotherapy (sonigegib). All patients were female with a mean age of 80years. The first patient had an infiltrative BCC of the right lower lid with orbital invasion, the second a nodular BCC of the right inferior lid with massive cutaneous and orbital invasion extending to the controlateral medial canthal angle, the third an advanced infiltrative BCC invading both orbits and nasal cavities, and the fourth, an infiltrative BCC with extension to the ipsilateral skin of the face. The diagnosis of BCC was confirmed by multiple biopsies in our four patients prior to starting chemotherapy. Because of the locally advanced lesions, surgery was contraindicated in all cases, chemotherapy was undertaken (sonidegib 200mg daily), and ophthalmological and dermatological examinations were performed every 3months. In all 4 patients, the outcome was very favorable, with one clear regression in tumor size and infiltration and 3 partial regressions. Many side effects were noted, including nausea, muscle cramping, dysgeusia resulting in significant weight loss, and malnutrition in the elderly patients. The treatment had to be discontinued after 11months in the patient with total macroscopic regression because of major side effects. The treatment is still underway for the other patients and will be continued as long as a clinical benefit is observed. The treatment will be discontinued if intolerable side effects develop. Oral chemotherapy (sonidegib) is an effective alternative treatment when surgery cannot be realized, especially in the case of extensive infiltrative non-metastatic BCC.

A single-center experience with giant cell tumors of sphenoid bone and clivus.

To present pathologic, clinical, and treatment findings for giant cell tumors (GCTs) of sphenoid bone and clivus. We describe the optimal treatment algorithm in patients with a histopathologic diagnosis of bone GCT by presenting the effects of denosumab treatment in both pediatric and adult patients with GCT undergoing endoscopic transnasal surgery. Clinicopathologic correlation is crucial for the differential diagnosis of GCT and the choice of treatment modality. GCT of bone is a local aggressive tumor that accounts for about 3%-7% of all bone tumors. GCTs located in the cranium are extremely uncommon neoplasms. There are no defined guidelines for the treatment of GCTs in skull base. Following surgical resection of the tumor, the addition of denosumab treatments to radiotherapy has a significant role in preventing the recurrence of GCT and in promoting regression of residual tumor size.

Vaccination against PD-L1 with IO103 a Novel Immune Modulatory Vaccine in Basal Cell Carcinoma: A Phase IIa Study.

Simple SummaryBasal cell carcinoma is the most common skin cancer and new treatments for patients with widespread and numerous tumors are lacking. In a previous study treating patients with multiple myeloma with a peptide vaccine called IO103 against an immune checkpoint molecule called programmed death ligand 1, two cases of basal cell carcinoma regressed. The aim of the present study was to assess the effect of vaccination with IO103 in ten patients with basal cell carcinoma. Patients were vaccinated with Montanide as adjuvant up to nine times during six months. Regression in tumor size of at least 30% was seen in five of 18 tumors, two of which showed complete regression. Vaccinations resulted in immune responses against the vaccine in blood samples from nine of ten patients and in skin samples from five of nine patients. The findings suggest that the vaccine may be effective against some basal cell carcinomas.Antitumor activity of immune checkpoint blocking antibodies against programmed death 1 (PD-1) in basal cell carcinoma (BCC) has been described. IO103 is a peptide vaccine against the major PD-1 ligand PD-L1. A phase IIa study of vaccination with IO103 and Montanide adjuvant was conducted in patients with resectable BCC (NCT03714529). Vaccinations were given six times every 2 weeks (q2w), followed by three vaccines q4w in responders. Primary endpoints were clinical responses of target tumors, change in target tumor size and immune responses to the vaccine. Secondary endpoint was safety. One tumor per patient was designated target tumor and biopsied twice during the course of vaccination. Synchronous non-target BCCs were not biopsied during vaccinations. Ten patients were vaccinated (six patients received six vaccinations and four patients received nine vaccinations). A partial response (PR) was seen in two target tumors. Two complete responses (CR) and one PR were observed in eight non-target tumors in four patients. No tumors progressed. Related adverse events were grade 1 and reversible. Immune responses against IO103 were induced in blood samples from nine of ten and skin-infiltrating lymphocytes from five of the nine patients. The regressions seen in non-target tumors suggest that IO103 may be effective against a subtype of BCC.

Abstract PS19-26: Trigonella foenum (fenugreek) extract and ectopic miR-34a inhibit stemness characteristics and enhance sensitivity of (CD44+/CD24−/ALDH1+) breast cancer stem cells subpopulation to doxorubicin by targeting notch1/ALDH1signaling pathways

Abstract Breast cancer stem cells (BCSCs) have been implicated as the root of tumorinitiation, therapeutic resistance, relapse, and metastasis due to their uniqueabilities of self-renew, differentiation potentials and resistance to mostconventional therapies.Signaling pathways of stemness markers, Notch-1, ALDH1 andmicroRNAs, a class of emerging small non-coding RNAs, are importantregulators of BCSC functions and self-renewal capacity by modulatingmultiple biological processes via the post-transcriptional regulation of geneexpression and cellular signaling pathways. Understanding the earlymolecular mechanisms and identifying the miRNAs that are involved inchemo-resistance, and their crosstalk with Notch-1 and ALDH1, could be apotential therapeutic option for breast cancer drug resistant.Previously, we showed that Trigonella foenum (Fenugreek) extract (FCE),a traditional herbal plant, has an anti-tumor activity against HepG2 cell line.In the present study, we evaluated and screened a panel of aberrant expressedmiRNAs (i.e. miR-142, let-7a, let-7b and miR-34a) that might have a crosstalkwith Notch-1 and ALDH1 in isolated (CD44+/CD24−/ALDH1+)subpopulation treated with or without FCE extract alone or in combinationwith Doxorubicin for different time intervals.Our results revealed that FCE treatment alone for 48 h showed a significantdecrease in cell viability, clonogenicity and invasion capacity of(CD44+/CD24−/ALDH1+) BCSCs subpopulation compared to untreatedcells. Furthermore, FCE-inhibited Notch-1 and ALDH1 expression that wasassociated with a significant decrease in miR-142 by 4.6-folds and an increasein expression levels of let-7a, let-7b and miR-34a by 4.5, 7.7 and 15.4 foldsrespectively. Moreover, ectopic miR-34a expression significantly reduce cellproliferation and increase apoptotic induction consistent with downregulationof Notch-1 and ALDH1 expression in treated cells extract alone or incombination with Doxorubicin for 24h, suggesting that miR-34a expressionmight play a role in the breast cancer potential.Furthermore, FCE treated (CD44+/CD24−/ALDH1+) subpopulationectopically expressing miR-34a showed an increase in chemosensitivity todoxorubicin at low doses after 24 h compared to the controls. In initiated(CD44+/CD24−/ALDH1+) BCSC tumor xenografts ectopically expressingmiR-34a, FCE/Doxorubicin combined treatment showed a significant regression in tumor size by 62% after 72h compared to untreated controls orDoxorubicin alone.All in all, the aberrant expression of selected miRNAs, such as of miR-34a, might regulate a crosstalk with stemness characteristic markers, Notch-1and ALDH1, that are involved in the pathogenesis of breast cancer. Citation Format: Rana H. Ateya, Ahmed S. Sultan. Trigonella foenum (fenugreek) extract and ectopic miR-34a inhibit stemness characteristics and enhance sensitivity of (CD44+/CD24−/ALDH1+) breast cancer stem cells subpopulation to doxorubicin by targeting notch1/ALDH1signaling pathways [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-26.

Abstract PS19-28: Thymoquinone and tamoxifen co-treatment synergistically inhibit proliferation, invasion and induce apoptosis in human breast cancer cell lines in vitro and in vivo

Abstract Epidemiological studies and experimental analysis indicate that dietary factors influence thedevelopment of breast cancer, suggesting the role of natural products as modifying factors againstbreast cancer. Thymoquinone (TQ) (a dietary phytochemical compound) the main active ingredientof the volatile oil of black seed (Nigella sativa) has been used to be safe when administered to awide variety of normal cells. In addition, Tamoxifen (TAM), a nonsteroidal triphenylethylene derivateand selective ER modulator, has been used as a single agent in the treatment of ER positive breastcancer.In the present study, we report the possible chemo-sensitizing effect of TQ as a promisingconventional chemotherapeutic agent, using a panel of human breast cancer cell lines, MCF-7, ZR-75-1, T-47D and BT-20 respectively in vitro and in vivo.Our data revealed that TQ, TAM or combined treatments significantly inhibited cell viability of MCF-7, T-47D, ZR-75-1 but slightly of BT-20 cell lines consistently with down-regulation of signaltransducer and activator of transcription 3 (STAT 3), mTOR, cyclin D1, oncogenic β-catenin,signaling a specific transcription factor and PPAR-gamma in a dose dependent manner. Mostimportantly, combined treatment enhanced inhibition of cell viability, DNA fragmentation andapoptosis induction through Caspase-3 activation and Bcl-2 down regulation in all tested cell linesbut this effect was limited in BT-20 cells compared to controls. Moreover, our data was supported bymicroscopic examination using electron scanning microscopy that revealed many apoptoticalterations after combined treatment compared to each TQ or TAM. Furthermore, confocalfluorescence microscopy examination revealed that only combined treatment showed a significantinhibition of filopodia formation as a sign of invasion inhibition in both BT-20 and MCF-7 humanbreast cancer cell lines. In vivo, tumor xenotransplants of human ZR-75-1 cells revealed that onlycombined treatment showed a significant regression in tumor size by 53% after 72h and enhancedE-cadherin expression as analyzed by immunohistochemistry and confocal fluorescencemicroscopy.Taken together, our findings provide strong in vitro and in vivo molecular evidences in support ofour hypothesis that Thymoquinone synchronized as chemo-preventive agent with Tamoxifen to inhibithuman breast cancer cell lines proliferation, invasion and induce apoptosis that might have a potentialimplication in breast cancer prevention and treatment. Citation Format: Islam Yahiya, Heba Helmy, Ahmed Sultan. Thymoquinone and tamoxifen co-treatment synergistically inhibit proliferation, invasion and induce apoptosis in human breast cancer cell lines in vitro and in vivo [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-28.