Nanomaterials for refining tumor microenvironment and enhancing therapy in head and neck squamous cell carcinoma: a review

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.

IMPACTS OF PENETRATION THERAPY WITH HEAD ELECTRICAL ACUPUNCTURE ON PROLIFERATION OF NEURAL STEM CELLS IN SUBSTANTIA NIGRA OF RAT MODEL OF PARKINSON'S DISEASE

Objective To probe into the function mechanism of penetration therapy with head electrical acupuncture on Parkinson＇s disease. Methods Microinjection of 6-hydroxydopamin （6-OHDA） on the left cor- pus striatum was adopted to prepare rotation model of Parkinson^s disease in rat. Penetration therapy with head electrical acupuncture was administered in treatment. Normal group, sham-operation group, model group and penetration therapy group were set up. （1）lmmunohistochemical （IHC） method was used to test the morphology and count of positive cell of tyrosine hydroxylase （TH）. （2）RT-PCR technology was used to detect the expression of nestin mRNA of neural stem cell （NSC）. Results （1）Compared with model group, in pene- tration therapy group, the expressions of TH-positive neurons in immune response were increased in areal density （AD）, numerical density （ND） and integrating optic density （P〈0.05）. （2）Compared with model group, in penetration therapy group, the expression of nestin mRNA was increased （P〈0. 05）. Conclusion Penetration therapy with head electrical acupuncture promotes the proliferation of endogenous neural stem cells in substantia nigra of rat model of Parkinson＇s disease.

Experimental Study of Vascular Endothelial Growth Factor Gene Therapy for Avascular Necrosis of the Femoral Head

To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression of vascular endothelial growth factor (VEGF) was detected by RNA dot hybridization and immunohistochemical method The repair of the femoral head was observed by histological method The results showed that the expression of VEGF was detectable in the femoral head treated with VEGF gene Angiogenesis in these femoral heads was more abundant than the control Bone repairing was augmented in the femoral head treated with VEGF gene The results suggest that angiogenesis in bone tissue could be augmented by gene transfection of VEGF and bone repairing would be accelerated accordingly

Effects of individual shock wave therapy vs celecoxib on hip pain caused by femoral head necrosis

BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head(ONFH),although significant adverse reactions often follow long-term use.Extracorporeal shock wave therapy(ESWT)can delay the progression of ONFH,alleviate the pain and functional limitations it causes,and avoid the adverse effects of celecoxib.AIM To investigate the effects of individual ESWT,a treatment alternative to the use of celecoxib,in alleviating pain and dysfunction caused by ONFH.METHODS This was a randomized,controlled,double-blinded,non-inferiority trial.We examined 80 patients for eligibility in this study;8 patients were excluded based on inclusion and exclusion criteria.A total of 72 subjects with ONFH were randomly assigned to group A(n=36;celecoxib+alendronate+sham-placebo shock wave)or group B(n=36;individual focused shock wave[ESWT based on magnetic resonance imaging three-dimensional(MRI-3D)reconstruction]+alendronate).The outcomes were assessed at baseline,at the end of treatment,and at an 8-wk follow-up.The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score(HHS)(improvement of 10 points or more from the baseline was deemed sufficient).Secondary outcome measures were post-treatment HHS,visual analog scale(VAS),and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores.RESULTS After treatment,the pain treatment efficiency of group B was greater than that of group A(69%vs 51%;95%CI:4.56%to 40.56%),with non-inferiority thresholds of-4.56%and-10%,respectively.Furthermore,the HHS,WOMAC,and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A(P<0.001).After therapy,the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk(P<0.001),although HHS was only significantly altered at the 2 wk point(P<0.001).On the 1st d and 2nd wk after treatment,HHS and VAS scores were different between groups,with the difference in HHS lasting until week 4.Neither group had severe complications such as skin ulcer infection or lower limb motorsensory disturbance.CONCLUSION Individual shock wave therapy(ESWT)based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.

Boron neutron capture therapy: moving towards targeted therapy for locally recurrent head and neck squamous cell carcinoma

Locally recurrent head and neck squamous cell carcinoma(HNSCC)is often unresectable,and a repeat course of radiotherapy is associated with incremental toxicities.Boron neutron capture therapy(BNCT)is a novel targeted radiotherapy modality that can achieve a high dose gradient between cancerous and adjacent normal tissues.However,the relationships among the dose resulting from BNCT,tumor response to BNCT,and survival are not completely understood.Recently,a study published in Radiotherapy and Oncology investigated the efficacy of BNCT in the treatment of patients with locally recurrent HNSCC and the factors associated with favorable treatment response and survival.In this article,the findings,strengths and limitations of this study are discussed in depth,and the significance of the study and motivations for future research are highlighted.

Nutritional Therapy for Head and Neck Cancer

Patients with head and neck cancer face great challenges in maintaining optimal nutrition since both the disease itself and treatments,especially surgery and concurrent chemoradiotherapy,have a significant negative impact on the nutritional status.A fundamental understanding of the nutrient metabolism of patients with head and neck cancer will aid in treatment selection.In this review,metabolic abnormalities presented in patients with head and neck cancer are discussed,together with methods of nutritional support,dietary intervention,and potential roles of phytonutrients,probiotics,and exercise in nutritional therapy for head and neck cancer patients.

Monitoring photodynamic therapy of head and neck malignancies with optical spectroscopies

In recent years there has been significant developments in photosensitizers(PSs), light sources and light delivery systems that have allowed decreasing the treatment time and skin phototoxicity resulting in more frequent use of photodynamic therapy(PDT) in the clinical settings. Compared to standard treatment approaches such as chemo-radiation and surgery, PDT has much reduced morbidity for head and neck malignancies and is becoming an alternative treatment option. It can be used as an adjunct therapy to other treatment modalities without any additive cumulative side effects. Surface illumination can be an option for pre-malignant and early-stage malignancies while interstitial treatment is for debulking of thick tumors in the head and neck region. PDT can achieve equivalent or greater efficacy in treating head and neck malignancies, suggesting that it may be considered as a first line therapy in the future. Despite progressive development, clinical PDT needs improvement in several topics for wider acceptance including standardization of protocols that involve the same administrated light and PS doses and establishing quantitative tools for PDT dosimetry planning and response monitoring. Quantitative measures such as optical parameters, PS concentration, tissueoxygenation and blood flow are essential for accurate PDT dosimetry as well as PDT response monitoring and assessing therapy outcome. Unlike conventional imaging modalities like magnetic resonance imaging, novel optical imaging techniques can quantify PDT-related parameters without any contrast agent administration and enable real-time assessment during PDT for providing fast feedback to clinicians. Ongoing developments in optical imaging offer the promise of optimization of PDT protocols with improved outcomes.

Robustness Evaluation of a Novel Proton Beam Geometry for Head and Neck Patients Treated with Pencil Beam Scanning Therapy

Background: To evaluate the robustness of head and neck treatment using proton pencil beam scanning (PBS) technique with respect to range uncertainty (RU) and setup errors (SE), and to establish a robust PBS planning strategy for future treatment. Methods and Materials: Ten consecutive patients were planned with a novel proton field geometry (combination of two posterior oblique fields and one anterior field with gradient dose match) using single-field uniform dose (SFUD) planning technique and the proton plans were dosimetrically compared to two coplanar arc VMAT plans. Robustness of the plans, with respect to range uncertainties (RU = ± 3% for proton) and setup errors (SE = 2.25 mm for proton and VMAT), in terms of deviations to target coverage (CTV D98%) and OAR doses (max/mean), were evaluated and compared for each patient under worst case scenarios. Results: Dosimetrically, PBS plans provided better sparing to larynx (p = 0.005), oral cavity (p < 0.001) and contralateral parotid (p = 0.004) when compared to VMAT. CTV D98% variations were higher from SE than from RU for proton plans (-1.1% ± 1.3 % vs -0.4% ± 0.7% for nodal CTV and -1.4% ± 1.2 vs -0.4% ± 0.5% % for boost CTV). Overall, the magnitudes of variation of CTV D98% to combined SE and RU were found to be similar to the impact of the SE on the VMAT plans (-1.6% ± 1.9% vs -1.7% ± 1.4% for nodal CTV and -1.9% ± 1.6% vs -1.3% ± 1.5% for boost CTV). Compared to VMAT, a larger range of relative dose deviations were found for OARs in proton plans, but safe doses were maintained for cord (41.8 ± 3.6 Gy for PBS and 41.7 ± 3.9 Gy for VMAT) and brainstem (35.2 ± 8.4 Gy for PBS and 36.2 ± 5.1 Gy for VMAT) in worst case scenarios. Conclusions: Compared to VMAT, proton plans containing three SFUD fields with superior-inferior gradient dose matching had improved sparing to larynx, contralateral parotid and oral cavity, while providing similar robustness of target coverage. Evaluation of OAR dose robustness showed higher sensitivities to uncertainties for proton plans, but safe dose levels were maintained for cord and brainstem.

The Reproducibility of Patient Setup for Head and Neck Cancers Treated with Image-Guided and Intensity-Modulated Radiation Therapies Using Thermoplastic Immobilization Device

The reproducibility of patient setup is an important issue for head and neck cancers treated with intensity-modulated radiation therapy (IMRT). In this study, an image-guided radiation therapy (IGRT) system has been used to minimize the uncertainty of patient setup while standard thermoplastic masks were used to provide adequate immobilization for the head and neck. However, they do not provide sufficient immobilization of the shoulders, which is an important requirement in comprehensive nodal irradiation. Therefore, we investigated the setup and rotational shifts in head and neck cancer patients undergoing IMRT for which this immobilization device had been used together with an IGRT system. The setup and rotational shifts of patients were analyzed using the ExacTrac X-ray 6D IGRT system. The patients were classified as having head and neck tumors in the upper or lower regions. The upper neck nodes included lymph nodal level II while the lower neck nodes included lymph nodal levels III and IV. Clinical data from 227 treatment sessions of 12 head and neck cancer patients were analyzed. The random translational error in inter-and intra-fraction errors of the anterio-posterior (AP) direction might influence the rotational errors of pitch and roll in the upper region. At the same time, the random translational error in the inter-and intra-fraction errors of the AP direction might influence the rotational error of roll in the lower region. We believe that these random translational errors should be considered during treatment. We found variability in random translational errors for different regions in the anatomy of head and neck cancer patients due to rotational shifts. Depending on the location of the primary lesion or the selected nodal treatment targets, these relative positional variations should be considered when setup and rotational shifts are corrected with IGRT systems before treatment.

Usability of Deformable Image Registration for Adaptive Radiotherapy in Head and Neck Cancer and an Automatic Prediction of Replanning

Deformable image registration (DIR) has been an important component in adaptive radiotherapy (ART). Our goal was to examine the accuracy of ART using the dice similarity coefficient (DSC) and to determine the optimal timing of replanning. A total of 22 patients who underwent volume modulated arc therapy (VMAT) for head and neck (H&N) cancers were prospectively analyzed. The planning target volume (PTV) was to receive a total of 70 Gy in 33 fractions. A second planning CT scan (rescan) was performed at the 15th fraction. The DSC was calculated for each structure on both CT scans. The continuous variables to predict the need for replanning were assessed. The optimal cut-off value was determined using receiver operating characteristic (ROC) curve analysis. In the correlation between body weight loss and DSC of each structure, weight loss correlated negatively with DSC of the whole face (rs = -0.45) and the face surface (rs = -0.51). Patients who required replanning tended to have experienced rapid weight loss. The threshold DSC was 0.98 and 0.60 in the whole face and the face surface, respectively. Patients who showed low DSC in the whole face and the face surface required replanning at a significantly high rate (P < 0.05 and P < 0.01). Weight loss correlated with DSC in both the whole face and the face surface (P < 0.05 and P < 0.05). The DSC values in the face predicted the need for replanning. In addition, weight loss tended to correlate with DSC. DIR during ART was found to be a useful tool for replanning.

Regenerative Surgery for the Rehabilitation of a Patient after Surgery and Radiation Therapy for Head and Neck Cancer: A Case Report

Oral cancer is usually treated combining surgery, radiation therapy and chemotherapy, following effective therapeutic protocols. Severe maxillary and mandibular bone atrophy resulting after therapies are usually treated with autologous bone grafting procedures even though these techniques often present a significant risk of postoperative complications and disadvantages. We describe the case of a 59-year-old woman presenting severe bone defect after being treated with surgery and radiotherapy for recurrent oral verrucous squamous cell carcinoma. We performed bone regeneration using Platelet-Derived Growth Factors (PDGF) in combination with autologous bone chips. Our procedure of bone regeneration allowed the placement of dental implants and the achievement of a good aesthetic and functional result. Regenerative surgery may enable the regeneration of substantial bone defects. Moreover, PDGF application decreases the risk of implant failure in irradiated patients.

脂肪间充质干细胞来源外泌体改善放射性口腔黏膜炎

背景:头颈肿瘤放疗极易引起放射性口腔黏膜炎,严重影响患者的健康及肿瘤的治疗计划。间充质干细胞在多种疾病中表现出治疗潜力,外泌体是其发挥功能的重要因素之一。目前尚无脂肪间充质干细胞来源外泌体应用于放射性口腔黏膜炎的相关研究。目的:探讨脂肪间充质干细胞来源外泌体在放射性口腔黏膜炎中的作用。方法:提取脂肪间充质干细胞及脂肪间充质干细胞来源外泌体并进行鉴定。通过3 Gy X射线辐射口腔黏膜上皮细胞诱导放射性口腔黏膜炎体外模型,在造模前给予脂肪间充质干细胞或脂肪间充质干细胞来源外泌体预处理48 h,EdU实验和克隆形成实验检测口腔黏膜上皮细胞的增殖能力。通过3 Gy X射线辐射构建放射性口腔黏膜炎小鼠模型,将脂肪间充质干细胞和脂肪间充质干细胞来源外泌体分别注入放射性口腔黏膜炎小鼠尾静脉,采用苏木精-伊红染色和免疫组化评估口腔黏膜上皮组织的炎症变化。结果与结论:(1)与对照组相比,脂肪间充质干细胞及脂肪间充质干细胞来源外泌体均可促进口腔黏膜上皮细胞克隆形成,增加口腔黏膜上皮细胞EdU阳性率;(2)脂肪间充质干细胞及脂肪间充质干细胞来源外泌体均能够缓解辐射处理小鼠口腔黏膜上皮组织的炎症;口腔黏膜上皮组织中CD45阳性细胞均减少,PCNA阳性细胞均增加。结果表明,脂肪间充质干细胞来源外泌体可促进口腔黏膜上皮细胞增殖,对放射性口腔黏膜炎小鼠口腔黏膜炎症具有缓解作用。

The value of postoperative hepatic regional chemotherapy in prevention of recurrence after radical resection of primary liver cancer

INTRODUCTIONIn China,primary liver cancer (PLC) ranks secondin cancer mortality since the 1990s.In the field ofPLC treatment,surgical resection remains the best,which includes large PLC resection,small PLCresection,re-resection of subclinical recurrence,aswell as cytoreduction and sequential resection forunresectable PLC.However,recurrence

Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy:A case report

Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.

Targeting head and neck tumoral stem cells： From biologicalaspects to therapeutic perspectives

Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

Application of fluorodeoxyglucose positron emission tomography in the management of head and neck cancers

The use of fluorodeoxyglucose positron emission to-mography(FDG PET) scan technology in the manage-ment of head and neck cancers continues to increase. We discuss the biology of FDG uptake in malignant lesions and also discuss the physics of PET imaging. The various parameters described to quantify FDG up-take in cancers including standardized uptake value, metabolic tumor volume and total lesion glycolysis are presented. PET scans have found a significant role in the diagnosis and staging of head and neck cancers. They are also being increasingly used in radiation ther-apy treatment planning. Many groups have also used PET derived values to serve as prognostic indicators of outcomes including loco-regional control and overall survival. FDG PET scans are also proving very useful in assessing the efficacy of treatment and management and follow-up of head and neck cancer patients. This review article focuses on the role of FDG-PET com-puted tomography scans in these areas for squamous cell carcinoma of the head and neck. We present the current state of the art and speculate on the future applications of this technology including protocol de-velopment, newer imaging methods such as combinedmagnetic resonance and PET imaging and novel ra-diopharmaceuticals that can be used to further study tumor biology.

Preoperative defining system for pancreatic head cancer considering surgical resection

AIM: To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members.METHODS: A retrospective analysis of the medical records of 113 patients who underwent surgery for pancreas head cancer from January 2008 to December 2012 was performed. We developed preoperative defining system of pancreatic head cancer by describing &#x0201c;resectability - tumor location - vascular relationship - adjacent organ involvement - preoperative CA19-9 (initial bilirubin level) - vascular anomaly&#x0201d;. The oncologic correlations with this reporting system were evaluated.RESULTS: Among 113 patients, there were 75 patients (66.4%) with resectable, 34 patients (30.1%) with borderline resectable, and 4 patients (3.5%) with locally advanced pancreatic cancer. Mean disease-free survival was 24.8 mo (95%CI: 19.6-30.1) with a 5-year disease-free survival rate of 13.5%. Pretreatment tumor size &#x02265; 2.4 cm [Exp(B) = 3.608, 95%CI: 1.512-8.609, P = 0.044] and radiologic vascular invasion [Exp(B) = 5.553, 95%CI: 2.269-14.589, P = 0.002] were independent predictive factors for neoadjuvant treatment. Borderline resectability [Exp(B) = 0.222, P = 0.008], pancreatic head cancer involving the pancreatic neck [Exp(B) = 9.461, P = 0.001] and arterial invasion [Exp(B) = 6.208, P = 0.010], and adjusted CA19-9 &#x02265; 50 [Exp(B) = 1.972 P = 0.019] were identified as prognostic clinical factors to predict tumor recurrence.CONCLUSION: The suggested preoperative defining system can help with designing treatment plans and also predict oncologic outcomes.

OBSERVATION ON THERAPEUTIC EFFECT OF ELECTROACUPUNCTURE HEAD PONINT-THROUGH-POINT BY PENETRATING TWO POINT ON ISCHEIC STROKE

Objective To probe methods and therapeutic effects of Head Acupuncture on ischemic stroke. Methods One hundred and twelve cases were randomly divided into observation group (head acupuncture group) and control group (body acupuncture group). After treatment of 28 days, changes of linguistic function and paralysis level of limbs before and after treatment were investigated. Results The total effective rate was 96.6% in the observation group and 90.7%, in the control group, with a significant difference between the two groups (P<0.05). Conclusion The electroacupuncture head point-through-point by penetrating two point therapy is one of effective methods for ischemic stroke.

Changing the paradigm：the potential for targeted therapy in laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.

Intensity-modulated Radiotherapy for Sinonasal Teratocarcinosarcoma

Surgical excision and postoperative radiotherapy are widely accepted therapeutic modalities for sinonasal teratocarcinosarcoma （SNTCS）. Previous studies have shown that intensity-modulated radiation therapy （IMRT） is safe and effective for the treatment of some sinonasal malignancies. We hypothesize that use of IMRT for SNTCS may result in clinical benefits. We report here two cases of SNTCS that were treated by IMRT. One patient was given extensive IMRT involving elective neck irradiation. Follow-up examinations revealed no recurrence and metastasis 3.5 years after IMRT. Another patient simultaneously suffered from multiple systematical diseases and was administered involved-field radiotherapy. He was found to have a marginal recurrence during the follow up and eventually died 8 months after disease diagnosis. It was suggested in this study that appropriate use of IMRT for the treatment of SNTCS may achieve excellent local control.