Reduce Tumor Recurrence Research Articles

Bilateral Wilms tumor: 10-year experience from a single center in China.

Nephron sparing surgery (NSS) had become the main surgical treatment for bilateral nephroblastoma. But it remained a challenge for surgeons to balance the dilemma between complete tumor resection to reduce tumor recurrence and renal parenchyma preservation to reduce end-stage renal disease (ESRD). In this study, we summarized our clinical experience for bilateral Wilms tumors managed in our center and evaluated the influence of different surgical approaches on prognosis. The clinical data of patients with bilateral Wilms tumor in our hospital from January 2010 to December 2020 were retrospectively analyzed, and the clinical symptoms, surgical approaches and prognosis of the disease were summarized. We reviewed medical records of 16 patients, including 13 (81.3%) girls and 3 (18.7%) boys. The mean age of the patients was 17.88±11.65 months (range, 6-42 months). Five patients presented with hypertension and two presented with hemihypertrophy. Fifteen cases had synchronous tumors, while only one patient had metachronous bilateral lesions. Thirteen patients received neoadjuvant chemotherapy and only 8 kidneys (30.8%) responded to chemotherapy. Two patients gave up surgery, and the other fourteen patients underwent radical resection, of which 2 patients only underwent unilateral radical nephrectomy (RN); 7 and 5 patients underwent single-stage and two-stage operation for bilateral lesions, respectively. In all surgical patients, RN was performed on 5 kidneys, and NSS was performed on 21 kidneys. The positive margins after NSS were found in 6 kidneys (35.3%). After a median follow-up period of 26.3 months, local tumor recurrence and renal insufficiency occurred in two and one patients. The 5-year overall and event-free survival rates were 78.1% and 58.6%, respectively. In univariable analysis, the survival rate in the initial chemotherapy group (92.3%) was significantly higher than that in the initial surgery group (33.3%) (P=0.048), whereas positive margin and staged operation (P>0.05) appeared not significantly associated with overall survival. The proportion of tumor reduction after preoperative chemotherapy is relatively low for bilateral Wilms tumor, but preoperative chemotherapy could improve overall survival. NSS is recommended for bilateral Wilms tumor, and the customized procedure can be selected according to the location and anatomical features of tumor.

What do we know about craniopharyngioma? Updated review of the main advances and local experience.

Craniopharyngioma is a tumor of benign histology, although it can cause serious sequelae due to its location and growth in the sellar and suprasellar region. It is characterized by being aggressive due to its ability to invade locally, and by its high recurrence rate. Histologically, two distinct tumors have been acknowledged, which were previously considered subtypes. The adamantinomatous craniopharyngioma is the most frequent in children and is caused by an activating mutation of the CTNNB1 gene, which codes for a mutant form of β-catenin. Whereas, papillary craniopharyngioma develops almost exclusively in adults, and it is associated with mutations in the BRAF oncogene and activation of the MAPK signaling pathway. The symptoms of both of these tumor types are secondary to hormonal deficits, hydrocephalus or visual disturbances. Treatment should be performed in centers with experience in them, achieving a balance between a wide resection and protection of hypothalamic function. Radiotherapy has proven to reduce tumor recurrence, with a current focus on the development of medical treatments based on molecular targets.

CaP Scaffold Loaded with Multi-Functional Gel for Bone Repair after Resection of Osteosarcoma

Introduction: Osteosarcoma resection in clinical settings often causes largeosteopenia, and the cancer cells at the site of the lesion easily lead to the recurrence of osteosarcoma. Therefore, the treatment of osteosarcoma should not only induce bone regeneration, and remove tumor cells from the lesion site, but also avoid bacterial infection. Objective: This study is to develop a multifunctional scaffold that combines chitosan, black phosphorus nanoparticles, and copper ions in a biphasic calcium phosphate matrix to enhance bone regeneration, reduce tumor recurrence, and prevent infections following osteosarcoma surgery. Methods: Herein, a Biphasic Calcium Phosphate (BCP) porous scaffold was prepared by the pore-forming agent method, and the mixed gel of chitosan (CS), Black Phosphorus nanoparticles (BP), and Copper ion (Cu2+) was filled into the porous scaffold to form a composite scaffold (CS/BP/Cu-BCPs). CS/BP/Cu-BCPs were used to treat large bone defects caused by osteosarcoma. The composite scaffolds contain anticancer, bone promoting and bacteriostatic properties, which are mainly put down to the anticancer properties of BCP and BP, the osteoinductivity of BCP and Cu2+, and the antimicrobial effects of CS and Cu2+.Cell and antimicrobial tests demonstrated that the extract of CS/BP/Cu-BCPs displayed good biocompatibility, induced osteogenic differentiation of mesenchymal stem cells (BMSCs), and inhibited the growth of bacteria. Results: In vivo, experiments showed CS/BP/Cu-BCPs had obvious anti-tumor and osteogenic effects. Taken together, the CS/BP/Cu-BCPs prepared in this study possessed good functions such as oncotherapy, bone regeneration, and postoperative anti-infection, and were expected to become a simple therapeutic material for osteosarcoma resection. We investigated the in vitro antibacterial, in vivo osteogenic, and antitumor capabilities of CaP scaffolds loaded with multi-functional gels. Compared with the control group, CaP scaffolds loaded with multi-functional gel showed significant antibacterial, bone-promoting, and anti-tumor effects. Conclusion: The contribution of this study was to confirm that CaP scaffolds loaded with multi-functional gels could eliminate osteosarcoma while repairing critical bone defects and have good antibacterial potential. These results suggested that CaP scaffolds loaded with multifunctional gels may be a potential candidate for repairing bone defects caused by osteosarcoma resection.

Early stage adrenocortical carcinoma-what contributes to poor prognosis after adrenalectomy? A retrospective cohort study.

Adrenocortical carcinoma (ACC) is a rare primary carcinoma originating in the adrenal gland with a poor prognosis and a high recurrence rate. This study evaluated the risk factors associated with recurrence in patients with early stage ACC after curative surgical resection. The present study retrospectively evaluated the risk factors for recurrence in 38 patients with stages 1 and 2 ACC who underwent curative resection between 1995 and 2020. Recurrence was observed in 21 patients (55.3%), with no significant difference between stages 1 and 2 ACC (P = 0.640). The overall recurrence rate was higher in patients who underwent minimally invasive surgery than open adrenalectomy (71.4% vs. 51.6%). Of the 33 patients with gross tumor margins negative for malignancy, 16 (48.5%) experienced tumor recurrence, and all 5 patients with positive and unknown gross resection margins had recurrence. Recurrences were observed in 14 of the 30 patients (46.7%) negative for pathologic resection margins, 6 of the 7 patients (85.7%) with pathologically indeterminate margins, and 1 patient with pathologically positive margins. The recurrence rates are high even in patients with early stage ACC, being higher in patients who undergo minimally invasive surgery than open adrenalectomy. Obtaining clear resection margins during surgery may reduce tumor recurrence; however, gross or pathologic margin safety was not a secure factor in preventing recurrence. None of the factors analyzed was a definitive predictor of poor prognosis.

Persistent luminescence nanoparticles with high intensity for colorectal cancer surgery navigation and precision resection.

Surgical resection remains the main treatment for malignant tumors. Image-guided surgery aims to remove tumor tissue completely while preserving normal tissue, thereby reducing tumor recurrence rates and injury. However, challenges like tissue autofluorescence, limited probe penetration and low contrast restrict its use. Near-infrared (NIR) persistent luminescent nanoparticles (PLNPs) provide a solution by emitting persistent luminescence (PersL) even after excitation ceases, thus circumventing autofluorescence and enabling deep tumor imaging. In this study, we prepared nano-sized (140 nm hydrodynamic size) Cr3+ doped zinc gallogermanate (ZGC) using a removable template method and modified it with folate acid to obtain ZGC-FA, which exhibits NIR (695 nm) PersL with a signal-to-noise ratio of 23.9 in vivo. We utilized a colon cancer model that selectively expressed luciferase for the first time to validate the guiding efficacy of ZGC-FA in precision surgical resection. Post-intraperitoneal injection at 50 minutes, the PersL closely matched the tumor boundaries, achieving an overlap rate of approximately 98%. Complete tumor resection was achieved under PersL guidance, with only 2.3% of healthy tissue removed. This research underscores the potential of ZGC-FA in the field of surgical oncology. The precision of the ZGC-FA guided surgical approach holds promise to enhance surgical outcomes and facilitate postoperative recovery in patients.

Efficacy of Intravesical BCG in Patients with Bladder Cancer in the Tobruk City Population

Background: The particular pathophysiology of tumors makes it difficult to treat cancer successfully, The survey's goal was to assess the predictive risk factors for bladder cancer and the efficiency of intravesical BCG as a local example of bacterial cancer therapy in reducing tumor recurrence rates The participants in this study were drawn from Tobruk City and the surrounding area, From January 2022 to June 2022, the study was conducted. Result: Overall, there were 47 patients in our statistical data had 47 patients with bladder cancer and was carried out in Tobruk City, Libya, from January 2022 to June 2022. Only 3.6% of the patients were female, with men making up the majority (93.6%). The study's participants' ages ranged from 2 to 87, with a mean of 59. 18 (38.2%) of the 47 individuals received care, compared to 29 (61.7%) who did not. 17 (94%) of the 18 patients who received BCG were men, and only one patient (0.5%) was a woman. 16 (34.0%) of the 47 patients had tumor recurrences, and 3 passed away. Four (25%) of the patients had conditions related to hypertension, diabetes, or the prostate, and 75% of them received BCG. The remaining 31 patients, with an average age of 50 and 6 (1.9%) undergoing BCG, were all in stable condition. Conclusion: The study found that BCG-immunotherapy effectively reduced NMIBC in 18 out of 47 patients in Tobruk City, with minimal side effects. However, specific risk factors reduced the effectiveness of BCG immunotherapy.

High-Throughput Screening of Surface Engineered Cyanine Nanodots for Active Transport of Therapeutic Antibodies into Solid Tumor.

The successful delivery of therapeutic biomacromolecules into solid tumorholds great challenge due to their high resistance to penetrate through the complex tumor microenvironments. Here, active-transporting nanoparticles are harnessed to efficiently deliver biomacromolecular drugs into solid tumors through cell transcytosis. A series of molecularly precise cyanine 5-cored polylysine G5 dendrimers (Cy5 nanodots) with different peripheral amino acids (G5-AA) is prepared. The capability of these positively charged nanodots to induce cell endocytosis, exocytosis, and transcytosis is evaluated via fluorescence-based high-throughput screen. The optimized nanodots (G5-R) are conjugated with αPD-L1 (a therapeutic monoclonal antibody binding to programmed-death ligand 1) (αPD-L1-G5-R) to demonstrate the nanoparticle-mediated tumor active transport. The αPD-L1-G5-R can greatly enhance the tumor-penetration capability through adsorption-mediated transcytosis (AMT). The effectiveness of αPD-L1-G5-R is tested in treating mice bearing partially resected CT26 tumors, mimicking the local immunotherapy of residual tumors post-surgery in clinic. The αPD-L1-G5-R embedded in fibrin gel can efficiently mediate tumor cell transcytosis, and deliver αPD-L1 throughout the tumor, thereby enhancing immune checkpoint blockade, reducing tumor recurrence, and significantly prolonging the survival time. The active-transporting nanodots are promising platforms for efficient tumor delivery of therapeutic biomacromolecules.

Intracranial germ cell tumors: a view of the endocrinologist.

Intracranial germ cell tumors (iGCTs) are rare malignant neoplasms that mainly affect children and adolescents. The incidence, clinical presentation, and prognosis of iGCTs exhibit high heterogeneity. Previous studies have primarily focused on eliminating tumors, reducing tumor recurrence, and improving survival rates, while neglecting the impact of the tumors and their treatment on neuroendocrine function. Throughout the entire course of the disease, neuroendocrine dysfunction may occur and is frequently overlooked by oncologists, neurosurgeons, and radiologists. Endocrinologists, however, are more interested in this issue and have varying priorities at different stages of the disease. From onset to the diagnostic phase, most patients with iGCTs may present with symptoms related to impaired neuroendocrine function, or even experience these symptoms as their first indication of the condition. Particularly, a minority of patients with sellar/suprasellar lesions may exhibit typical imaging features and elevated tumor markers long after the onset of initial symptoms. This can further complicate the diagnosis process. During the peritumor treatment phase, the neuroendocrine function shows dynamic changes and needs to be evaluated dynamically. Once diabetes insipidus and dysfunction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes occur, hormone replacement therapy should be administered promptly to ensure successful tumor treatment for the patient. Subsequently, during the long-term management phase after the completion of tumor treatment, the evaluation of growth and development as well as corresponding hormone replacement therapy are the most concerning and complex issues. Thus, this paper reviews the interest of endocrinologists in iGCTs at different stages.

Lenvatinib delivery using a Gd/Fe bimetallic MOF: Enhancing antitumor immunity following microwave-based thermal therapy

Microwave (MW) thermal therapy has been developed as an effective clinical strategy that can achieve pronounced antitumor activity and also has the potential to trigger antitumor immunity. However, patients generally face high rates of tumor recurrence following MW treatment, limiting the long-term benefits of such treatment. The combination of MW treatment and immunomodulatory strategies may represent a promising means of reprogramming the immunosuppressive tumor microenvironment (TME) in a manner conducive to lower recurrence rates. In this study, a Lenvatinib-loaded Gd/Fe metal-organic framework (Gd/FeMOF) was designed as a promising approach to enhancing such antitumor immunity. MW-enhanced dynamic Gd/FeMOF sensitization can facilitate high levels of reactive oxygen species production under MW irradiation, resulting in stronger immunogenic tumor cell death. In parallel, the Lenvatinib released from Gd/FeMOF preparations can serve as an immune adjuvant that suppresses programmed death ligand 1 (PD-L1) expression and drives the reprogramming of the immunosuppressive TME. The Gd and Fe present within this MOF preparation also imbue it with magnetic resonance imaging capabilities. Importantly, in vivo animal model experiments confirmed the ability of GdFeMOF treatment to significantly enhance antitumor immunity while protecting against recurrence. Accordingly, this study offers a foundation for promising strategies aimed at the integrated diagnosis and durable treatment of cancer. Statement of SignificanceHigh rates of tumor recurrence following MW thermal therapy limit the long-term benefits of such treatment. We found that the administration of Lenvatinib-loaded Gd/FeMOF nanoparticles significantly reduced tumor recurrence after MW thermal therapy. Under MW irradiation, the Gd/FeMOF nanoparticles were found to augment the immune response due to facilitation of the process of immunogenic cell death. In addition, the released Lenvatinib could act as an immune adjuvant to downregulate the expression of PD-L1 and reprogram the immunosuppressive state of the tumor microenvironment, thus further enhancing the immune response. This is significant because MW-induced immune responses are relatively weak and usually fail to effectively prevent tumor recurrence. The combination of MW treatment with an immunomodulatory strategy may solve this problem.

In Situ Insonation of Alkaline Buffer Containing Liposomes Leads to a Net Improvement of the Therapeutic Outcome in a Triple Negative Breast Cancer Murine Model.

Breast cancer is characterized by an acidic micro-environment. Acidic extracellular pH gives cancer cells an evolutionary advantage, hence, neutralization of the extracellular pH has been considered as a potential therapeutic strategy. To address the issue of systemic pH alteration, an approach based on the targeted delivery of the buffering solution to the tumor region is investigated. The method relies on the use of low frequency ultrasound and sono-sensitive liposomes loaded with buffers at alkaline pH (LipHUS). After the i.v. injection of LipHUS, the application of ultrasound (US) at the sites of the pathology induces a local increase of pH that results highly effective in i) inhibiting primary tumor growth, ii) reducing tumor recurrence after surgery, and iii) suppressing metastases' formation. The experiments are carried out on a triple negative breast cancer mouse model. The results obtained demonstrate that localized and triggered release of bicarbonate or PBS buffer from sonosensitive liposomes represents an efficient therapeutic tool for treating triple-negative breast cancer. This approach holds promise for potential clinical translation.

New technologies for nephron-sparing surgery in upper urinary tract cancers.

Nephron-sparing surgery (NSS) is the preferred treatment in patients with low-risk upper tract urothelial carcinoma (UTUC). Improving both instruments and topical chemotherapy regimens efficacy is crucial to achieve better outcomes. The purpose of this review is to summarize the most recent evidence on technological advances for the conservative management of UTUC with implications on diagnosis and treatment. Novel diagnostic tools, lasers, and topical chemotherapy systems delivery have been implemented to optimize NSS outcomes for UTUC. Photodynamic ureteroscopy has been reported to improve cancer detection rate as compared with conventional imaging or ureteroscopy, especially in case of carcinoma in situ. However, refinements in photosensitizer administration and dedicated instruments are needed. The armamentarium of lasers for UTUC ablation is composed of several devices with peculiar characteristics. Together with Ho:YAG and Tm:YAG lasers, the Thulium Fiber Laser (TFL) is gaining momentum in UTUC ablation. Strengths and weaknesses of each laser must be considered to maximize oncological and safety outcomes. Several novel endocavitary chemotherapy delivery systems have been tested to reduce tumor recurrence and progression after NSS. Administration of gel-based chemotherapeutic agents has been proven to be effective in humans; conversely, drug-eluting ureteral stent systems are still conceptual.

Surgical Excision Margins in Primary Care and Plastic Surgery for Keratinocytic Cancers Diagnosed via Teledermatology: Retrospective Observational Cross-Sectional Study

Background The incidence of keratinocytic cancers is increasing. In New Zealand, surgical treatment of skin cancers is often undertaken in primary care. In the Waikato district, general practitioners (GPs) are encouraged to confirm diagnoses via teledermatology. Histological examination should confirm clear surgical margins to reduce tumor recurrence. International guidelines recommend a lateral margin of ≥3 mm for basal cell carcinomas (BCCs) and ≥4 mm for squamous cell carcinomas (SCCs). Objective This study aimed to determine lateral and deep margins in keratinocytic cancer excisions performed by GPs (in a private setting) and plastic surgeons (in a private or public setting) after a teledermatologist had confirmed that excision was necessary. Demographic, clinical, and histological features were recorded. Methods A retrospective observational cross-sectional study was conducted. The sample in the electronic dermatology referral database included keratinocyte cancers recommended for excision from March to May 2022. Results Histological reports revealed that excision was complete in 186 of 201 confirmed cases of keratinocyte cancer. The lateral margins of resection were considered in 10 tumors and deep margins in 8 tumors. All incomplete excisions were carried out by GPs, 11 of which were on the head and neck. There were 133 BCCs, 100 of which were excised by a GP, 3 by a private plastic surgeon, and 30 by a public hospital surgeon. In total, 52 BCCs were present on the head and neck (25 excised by GPs, 25 by hospital plastic surgeons, and 2 by private plastic surgeons) and 81 were present on other sites (75 excised by GPs, 5 by hospital plastic surgeons, and 1 by a private plastic surgeon). Lateral margins were considered in 9 cases (of which 5 cases involved head and neck tumors). The minimum distance from the tumor to the lateral margin was <3 mm in 80 tumors: 64 were excised by a GP, 2 by private plastic surgeons, and 14 by hospital plastic surgeons. This distance was ≥3 mm in 44 tumors (27 excised by GPs, 1 by a private plastic surgeon, and 16 by hospital plastic surgeons). These data show significant adherence to surgical margin recommendations among plastic surgeons compared to that among GPs (odds ratio 2.873, CI 1.274-6.477; P=.009). There were 68 SCCs: 57 were excised by a GP, 2 by a private plastic surgeon, and 9 by a public hospital surgeon. In total, 21 SCCs were on the head and neck (14 excised by GPs, 6 by hospital plastic surgeons, and 1 by a private plastic surgeon) and 47 were on other sites (43 excised by GPs, 3 by hospital plastic surgeons, and 1 by a private plastic surgeon). Lateral margins were considered in 1 head and neck SCC case and were not reported in others. The minimum distance from the tumor to the lateral margin was <4 mm in 35 cases: 31 were excised by a GP, 1 by a private plastic surgeon, and 3 by a hospital plastic surgeon. This distance was ≥4 mm in 31 cases (24 excised by GPs, 1 by a private plastic surgeon, and 6 by hospital plastic surgeons). These data do not show significant difference in adherence to surgical margin recommendations between GPs and plastic surgeons (P>.05). Conclusions Complete resection reduces the risk of recurrence of keratinocytic tumors. GPs in our study were less likely than specialist surgeons to respect surgical margin recommendations established in international guidelines for managing keratinocytic cancer. Conflicts of Interest None declared.

Clinical Application of Individualized 3D-Printed Chest Wall Conformal Device in IMRT for Post-Mastectomy Breast Cancer.

Background Breast cancer is the most common malignant tumour in women. Radical mastectomy with postoperative radiotherapy is now the standard treatment for locally advanced breast cancer. Intensity-modulated radiotherapy (IMRT) has now been developed, which employs linear accelerators to deliver precise radiation to a tumour while minimizing the dose to surrounding normal tissue. It significantly improves the efficacy of breast cancer treatment. However, there are still some flaws that must be addressed. Objective To assess the clinical application of the three-dimensional (3D)-printed chest wall conformal device for breast cancer patients who need to be treated by chest wall intensity modulated radiotherapy (IMRT) after radical mastectomy. Methods The 24 patients were divided into three groups. During a computed tomography (CT) scan, patients in the study group were fixed by a 3D-printed chest wall conformal device, nothing in control group A, and a traditional 1-cm thick silica gel compensatory pad on the chest wall in control group B. The parameters of mean Dmax, Dmean, D2%, D50%, D98%, the conformity index (CI), and the homogeneity index (HI) of the planning target volume (PTV) are compared. Results The study group had the best dose uniformity (HI = 0.092) and the highest conformation (CI = 0.97), the worst in control group A (HI = 0.304, CI = 0.84). The mean Dmax, Dmean, and D2% of the study group were lower than control groups A and B (p<0.05). The mean D50% was higher than control group B (p<0.05), while the mean D98% was higher than control groups A and B (p<0.05). The mean Dmax, Dmean, D2%, and HI of control group A were higher than control group B (p<0.05), whereas the mean D98% and CI were lower than control group B (p<0.05). Conclusion By improving the efficacy of postoperative radiotherapy for breast cancer, using 3D-printed chest wall conformal devices may greatly improve the accuracy of repeating position fixation, increase the dose on the skin surface of the chest wall, optimise the dose distribution of the target area, and thus further reduce tumour recurrence and prolong patients' survival.

The potential role of human endogenous retrovirus K in glioblastoma.

The most active human endogenous retrovirus K (HERV-K) subtype, HML-2, has been implicated as a driver of oncogenesis in several cancers. However, the presence and function of HML-2 in malignant gliomas has remained unclear. In this issue of the JCI, Shah and colleagues demonstrate HML-2 overexpression in glioblastoma (GBM) and its role in maintaining the cancer stem cell phenotype. Given that stem-like cells are considered responsible for GBM heterogeneity and treatment resistance, targeting the stem cell niche may reduce tumor recurrence and improve clinical outcomes. The findings provide a foundation for future studies to determine whether antiretroviral and/or immunotherapy approaches targeting HML-2 could be used as therapeutics for GBM.

A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence

Recurrences frequently occur following surgical removal of primary tumors. In many cancers, adjuvant therapies have limited efficacy. Surgery provides access to the tumor microenvironment, creating an opportunity for local therapy, in particular immunotherapy, which can induce local and systemic anti-cancer effects. Here, we develop a surgically optimized biodegradable hyaluronic acid-based hydrogel for sustained intraoperative delivery of Toll-like receptor 3 agonist poly(I:C) and demonstrate that it significantly reduces tumor recurrence after surgery in multiple mouse models. Mechanistically, poly(I:C) induces a transient interferon alpha (IFNα) response, reshaping the tumor/wound microenvironment by attracting inflammatory monocytes and depleting regulatory Tcells. We demonstrate that a pre-existing IFN signature predicts response to the poly(I:C) hydrogel, which sensitizes tumors to immune checkpoint therapy. The safety, immunogenicity, and surgical feasibility are confirmed in a veterinary trial in canine soft tissue tumors. The surgically optimized poly(I:C)-loaded hydrogel provides a safe and effective approach to prevent cancer recurrence.

Current Bioanalysis of Molecularly Targeted Drugs Using Liquid Chromatography–Tandem Mass Spectrometry

Molecular targeted drugs (MTDs), such as tyrosine kinase inhibitors, have been actively developed and widely used in recent years due to their high selectivity and therapeutic efficacy compared to conventional cytotoxic chemotherapeutic agents. Bioanalysis of MTDs for therapeutic drug monitoring (TDM) is performed by many medical and clinical laboratories, and the implementation of TDM for MTDs can lead to better control of tumor progression, reduce tumor recurrence, and minimize side effects. Since bioanalysis of MTDs often requires high detection sensitivity with a limit of quantitation of 1 ng/mL or less, many of the reported analytical methods are performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This review highlights recent bioanalytical methods for MTDs using LC-MS/MS. We selected articles on bioanalysis of MTDs of signal transduction inhibitors that (1) were published after 2017, (2) used human samples (whole blood, plasma, serum, urine), and (3) underwent analytical validation. Typical analytical conditions, notable pretreatment techniques, LC separations, and measurement techniques are outlined.

A transformable nanoplatform with multiple therapeutic and immunostimulatory properties for treatment of advanced cancers

Cancer is a complex pathological phenomenon that needs to be treated from different aspects. Herein, we developed a size/charge dually transformable nanoplatform (PDR NP) with multiple therapeutic and immunostimulatory properties to effectively treat advanced cancers. The PDR NPs exhibit three different therapeutic modalities (chemotherapy, phototherapy and immunotherapy) that can be used to effectively treat primary and distant tumors, and reduce recurrent tumors; the immunotherapy is simultaneously activated by three major pathways, including toll-like receptor, stimulator of interferon genes and immunogenic cell death, effectively suppresses the tumor development in combination with an immune checkpoint inhibitor. In addition, PDR NPs show size and charge responsive transformability in the tumor microenvironment, which overcomes various biological barriers and efficiently delivers the payloads into tumor cells. Taking these unique characteristics together, PDR NPs effectively ablate primary tumors, activate strong anti-tumor immunity to suppress distant tumors and reduce tumor recurrence in bladder tumor-bearing mice. Our versatile nanoplatform shows great potential for multimodal treatments against metastatic cancers.

Spheno-Orbital Meningioma - Treatment Outcomes and Factors Influencing Recurrence.

To determine treatment outcomes, recurrence rates, and predictors of recurrence, to inform future therapeutic approaches for spheno-orbital meningiomas (SOM). A retrospective single-center study of SOM treated from 1990 to 2021 was conducted with comprehensive neuro-ophthalmologic follow-up at Columbia University Medical Center (CUMC). Recurrence requiring reintervention was defined clinically as worsening of visual acuity, visual field defect, or ocular motility after an initial period of stabilization or 6 months of improvement following treatment, or radiologically as either a regrowth with an increase in tumor size by 20% at the site of previous growth or a new region of tumor growth. In total 46 patients met the inclusion criteria. The mean follow-up was 106 months (range 1-303). Dictated by the phenotype of the disease, patients underwent either gross- (50%), near- (17%), or subtotal resection (26%). Removal of the anterior clinoid process (ACP) was performed in 52% of patients. Nine patients (20%) required an enucleation or exenteration. Radiotherapy was employed at some point of treatment in 50% of cases. Inherited cases (24%) were referred to CUMC for treatment following 1 or more recurrences. The total recurrence rate, including inherited cases, was 54%, occurring at a mean interval of 43 months. The recurrence rate of patients treated solely at CUMC was 40%, occurring at a mean interval of 41 months. A subset of patients (32%) had 2 or more recurrences. Histopathology at the first surgery was WHO grade I (87%) and II (13%) and at the final surgery was WHO grade I (74%), II (21%), and III (4%). A subset of grade I tumors that received radiotherapy (35%) evolved to a higher grade or developed multiple recurrences without a change in histologic grade I. Grade II tumors and treatment with radiotherapy increased the odds of recurrence. Removal of the ACP and gross total resection decreased the odds of recurrence. Due to the routinely long interval to tumor recurrence, lifelong surveillance of patients with SOM is prudent. ACP resection and gross total resection, where possible, reduce tumor recurrence and the need for further treatment. Radiotherapy should be reserved for higher-grade meningiomas and select grade I tumors.

Cryoablation inhibits the recurrence and progression of bladder cancer by enhancing tumour‐specific immunity

Recurrence and metastasis of bladder cancer are major factors affecting patient prognosis. Endoscopic cryoablation achieved a better clinical outcome among clinical patients and could be synergistic with ICIs. Thus, this study aimed to evaluate the immunological mechanism of cryoablation for bladder cancer to reveal the therapeutic mechanism. We systematically reviewed the clinical prognosis of patients underwent cryoablation at Huashan Hospital in these first-in-human studies (ChiCTR-INR-17013060). Murine models were constructed to explore cryoablation-induced tumour-specific immunity, which was further confirmed by primary bladder tumour organoids and autologous lymphocytes cocultured system. Cryoablation improved progression-free survival and recurrence-free survival respectively. Assessment of murine models after cryoablation confirmed microenvironment remodelling and tumour-specific T cells expansion. Enhanced antitumour effects were found after coculture of organoids with autologous lymphocytes collected from post-cryoablation. We also demonstrated cryoablation-induced tumour elimination required IFNGR expression on tumour cells. In addition, a long-lasting antitumour memory response is achieved by cryoablation and could be enhanced after combination with ICIs. This study revealed endoscopic cryoablation is an efficient and safe therapy for bladder tumour treatment. The tumour-specific immune responses induced by cryoablation could reduce tumour recurrence and metastasis.

Targeted Nanodrugs to Destroy the Tumor Extracellular Matrix Barrier for Improving Drug Delivery and Cancer Therapeutic Efficacy.

One of the main reasons why most cancer patients do not respond well to chemotherapy is that drugs cannot accumulate in tumors at an optimal dose, eventually resulting in failure to prevent cancer cell growth. To improve drug delivery efficiency, we engineered a highly efficient tumor-targeted and stroma-breaking nanocarrier by the modification of iron oxide nanoparticles (IONPs) with a tumor-targeting peptide c(RGDyK) and a hyaluronidase (HAase) on the surface. The yielding nanocomplex, c(RGDyK)-HAase-IONP, targeted the tumor by binding integrin αvβ3 and went deeply into the tumors by the degradation of hyaluronic acid (HA), which was highly expressed in the tumor extracellular matrix (ECM). Good biostability and a low pH preferred drug release profile were characterized for c(RGDyK)-HAase-IONP carrying DOX in vitro. c(RGDyK)-HAase-IONP showed an improved tumor-targeting (2.5 times higher) effect after intravenous injection in the MC38 tumor-bearing mice model, as determined by whole-body fluorescence imaging compared to the non-targeted IONPs without HAase. After 5 systemic treatments, c(RGDyK)-HAase-IONP/DOX (5 mg/kg of equivalent dose of DOX) significantly inhibited MC38 tumor growth (22.1 ± 7.4 times relative to the non-treated group). Elevated apoptosis and reduced proliferation in the tumor cell were detected in the c(RGDyK)-HAase-IONP/DOX treated tumors compared to the control groups. Overall, the highly efficient targeted nanocarrier c(RGDyK)-HAase-IONP demonstrated tremendous potency for improving drug delivery and tumor therapy efficacy by targeted degradation of the dense HA barrier in the tumor ECM. We determined that such a tumor stroma-degrading nanosystem was capable of reducing tumor recurrence and drug resistance and could ultimately improve clinical tumor treatment responses.