Exosomes-mediated tumor treatment: One body plays multiple roles

Exosomes are vesicles secreted by a variety of living cells,containing proteins,RNA and other components,which are nanoscale capsules commonly existed in the body.Exosomes play important roles in a variety of physiological and pathological processes by participating in material and information exchange between cells,which can playmultiple roles in tumor treatment.On the one hand,exosomes can be used as carriers and biomarkers,participate in the apoptosis signaling pathway and improve chemotherapy resistance,thus playing beneficial roles in tumor treatment.On the other hand,exosomes play unfavorable roles in tumor treatment.Tumor cell exosomes contain PD-L1,which is a nuclear weapon for tumor growth,metastasis,and immunosuppression.In addition,exosomes can not only promote the epithelial-mesenchymal transition process,tumor angiogenesis and chemoresistance,but also participate in the autocrine pathway.In this review,the multiple roles of exosomes and their prospects in the treatment of tumor were reviewed in detail.

Engineering hierarchical metal-organic@metal-DNA heterostructures for combinational tumor treatment

Development of simple methods for controlled integration of DNA molecules with metal-organic frameworks(MOFs)is important for various biomedical applications,yet remains a challenge.Herein,a simple and general approach to load DNA on the surface of MOFs is developed via one-pot self-assembly of DNA and FeII ions on nanoscale MOFs,resulting in hierarchical core-shell nanostructures of metal-organic@metal-DNA coordination polymers.The strategy enables assembly of DNA molecules on MOFs with ultra-high contents and precise controllability.By incorporation of a chemotherapeutic drug into the Fe-DNA shell,the systems allow to integrate chemotherapy and gene therapy with photodynamic therapy for combinational tumor treatment.Moreover,the hybrid nanostructures enable light-triggered production of cytotoxic singlet oxygen,which further boosts the endosomal escape of the system for an enhanced gene silencing efficacy and thus improved therapeutic outcome.This work highlights a robust approach for the construction of coordination-based drug delivery systems to combat tumor.

Survival Outcome of Wilms Tumor with Multi-Modality Treatment at Jimma Hospital, Southwest Ethiopia

Background: Wilms’ tumor (WT), the most common malignant neoplasm of the urinary tract of children [1], accounts for 5.9% of childhood cancers and affects one in every 10,000 children worldwide before the age of 15 years. The care of children with Wilm’s tumor in sub-Saharan Africa is compromised due to resource deficiencies that range from inadequate healthcare budgets to paucity of appropriately trained personnel. Childhood Wilms tumor is surging as an important paediatric problem in developing and sub-Saharan Africa countries. The objective of the study is to establish an understanding on the treatment challenges and outcomes of Wilm’s tumor in South West Ethiopia. Results: Forty-three Wilm’s tumor patients who were admitted from January 2017 to December 2021 were included in the study. The most frequent presentation was painless abdominal swelling in 40 (93%) patients. Fourteen patients (32.6%) were hypertensive at the time of diagnosis and the other 13 (30.2%) were normal. In abdominal examination, 31 (72.1%) patients had abdominal mass not crossing the midline and 12 (27.9%) had mass crossing the midline. After multimodal treatment, 37.5% had improvement, 11.6% came back with relapse. Most patients (41.7%) abandoned treatment and 9.3% of the cohort died in the course of treatment. Conclusion: The outcomes in the treatment of Wilms Tumor have been found to be poor in this review. The main reason for poor outcome has been not receiving adequate chemotherapy after surgery. Doses of chemotherapy received after surgery significantly affected treatment outcomes (p = 0.026).

Osteogenic and anti-tumor Cu and Mn-doped borosilicate nanoparticles for syncretic bone repair and chemodynamic therapy in bone tumor treatment

Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells.Herein,Cu and Mn-doped borosilicate nanoparticles(BSNs)were developed for syncretic bone repairing and anti-tumor treatment,which can enhance bone regeneration through the osteogenic effects of Cu^(2+) and Mn^(3+) ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu^(2+) and Mn^(3+) ions.In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs,and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation.Meanwhile,BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment,promote the generation of intracellular reactive oxygen species,and eventually induce tumor cell apoptosis.Besides,subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs.Altogether,Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration,and inhibiting tumor growth for chemodynamic therapy,thus holding a great potential for syncretic bone repairing and anti-tumor therapy.

Polylysine-modified Polyethylenimines as siRNA Carriers for Effective Tumor Treatment

Polyethylenimine-poly（L-lysine） （PEI-PLL） copolymer was synthesized via ring-opening polymerization of L-lysine N-carboxyanhydride （Lys（Z）-NCA） initiated by PEI. The complexation of PEI-PLL with siRNA was studied by particle size and zeta potential measurements. The flow cytometric analysis and confocal imaging showed its excellent intracellular trafficking ability. PEI-PLL displayed higher gene silencing efficiency and lower cytotoxicity than commercial PEI-25k in vitro. In the antitumor study, PEI-PLL was further combined with siVEGF and showed obviously tumor inhibition effect for the treatment of CT26 tumor model. Therefore, PEI-PLL is a promising siRNA carrier candidate for further antitumor treatment in vivo.

Redox-responsive micelles integrating catalytic nanomedicine and selective chemotherapy for effective tumor treatment

Chemotherapy is one of the most conventional modalities for cancer therapy.However,the high multidrug resistance of tumor cells still limited the clinical application of current chemotherapy.Considering the ability of nitric oxide(NO) to modulate potent P-glycoprotein to inhibit multi-drug resistance,a synergistic methodology combining chemotherapy and sustained NO generation is an ideal way to further promote the chemotherapy.Herein,a multi-functional micelle with tumor-selective chemotherapy driven by redox-triggered doxorubicin(DOX) release and drug resistance inhibition based on intracellular NO generation was fabricated for effective tumor treatment.The micelle consists of DOX as core,arginine/glucose oxidase(Arg/GOx) as shell and redox-responsive disulfide bond as a linker,which is denoted as micelle-DOX-Arg-GOx.The Arg serves as the biological precursor of nitric oxide for inhibition of multi-drug resistance to promote chemotherapy and GOx catalyzes glucose to produce hydrogen peroxide(H_(2) O_(2)) for increasing the generation of NO.Moreover,the glucose supply could be simultaneously blocked by the catalytic process,which further enhanced therapeutic efficiency.This micelle requests a tumor-specific microenvironment(a considerable amount of GSH) to perform synergistic therapeutics including chemotherapy,starvation therapy(catalytic medicine),and gas therapy for tumor treatment,which resulted in significant cytotoxicity to tumor tissue.

Novel approaches to therapeutics in pancreatic adenocarcinoma: vitamin C and tumor treatment fields

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease with limited therapeutic options.Despite extensive clinical research over the past several decades,meaningful improvements in care standards have been challenging to achieve.Research efforts are underway on several fronts,including cytotoxic chemotherapy combinations,immunotherapy,and targeted therapy.In this review,we chose to focus less on mainstream avenues of clinical research in PDAC and highlight some novel and innovative research efforts that are typically outside the spotlight of therapies.Examples of these novel approaches include pharmacologic vitamin C and electromagnetic fields.This review’s scope is to present the biological basis of the anti-cancer potential and the early clinical data,as well as the future landscape of these agents,including ongoing clinical trials in these therapeutic avenues.

Endoscopic full-thickness resection and laparoscopic surgery for treatment of gastric stromal tumors

AIM: To assess the effectiveness of endoscopic full-thickness resection (EFR) and laparoscopic surgery in the treatment of gastric stromal tumors arising from the muscularis propria.

Endoscopic treatments for small gastric subepithelial tumors originating from muscularis propria layer

Minimally invasive endoscopic resection has become an increasingly popular method for patients with small(less than 3.5 cm in diameter) gastric subepithelial tumors(SETs) originating from the muscularis propria(MP) layer. Currently, the main endoscopic therapies for patients with such tumors are endoscopic muscularis excavation, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection. Although these endoscopic techniques can be used for complete resection of the tumor and provide an accurate pathological diagnosis, these techniques have been associated with several negative events, such as incomplete resection, perforation, and bleeding. This review provides detailed information on the technical details, likely treatment outcomes, and complications associated with each endoscopic method for treating/removing small gastric SETs that originate from the MP layer.

Diagnosis and treatment of solid-pseudopapillary tumor of the pancreas

BACKGROUND: Solid-pseudopapillary tumor (SPT) of the pancreas is a rare exocrine pancreatic tumor. Despite the increasing recognition of the tumor in recent years, its pathogenesis and apparent therapeutic algorithm remain unclear. This study was designed to define the clinical, imaging, and pathologic features and to improve the diagnosis and treatment of this rare disease. METHOD: The clinical, imaging, and pathologic findings of 9 SPT patients managed in our hospital between 2001 and 2005 were retrospectively analyzed, and related literatures were reviewed. RESULTS: In the 9 patients aged from 14 to 68 years, 8 were female and 1 male. The mean age of these patients at diagnosis was 30 years. Initially, 8 patients complained of vague abdominal pain and one patient had pancreatic mass detected incidentally by abdominal CT. The levels of blood and urine amylase and tumor markers were all within the normal range. B-US, CT and MRI demonstrated that tumors were well encapsulated and contained some degree of internal hemorrhage or cystic degeneration. The mean transverse diameter of these tumors was 5.4 cm (range, 2-10.5 cm). The tumors were located at the head (2 patients), body (2), body and tail junction (4), and tail (1) of the pancreas. Surgical procedures included pancreaticoduodenectomy, distal pancreatectomy, distal pancreatectomy with splenectomy, and enucleation. Histological examination showed solidified cystic areas and papillary protrusions. Two malignant tumors demonstrated retroperitoneal metastases and vascular invasion. Follow-up for 2.5 years on average showed that one patient died of tumor recurrence at 10 months and the rest were alive. CONCLUSIONS: SPT exhibits unique clinical and pathologic features and is readily diagnosed by its characteristic imaging and histological appearance. Surgical resection of the primary tumor and metastases is the treatment of choice.

Real-world treatment patterns of gastrointestinal neuroendocrine tumors: A claims database analysis

AIM To describe real-world treatment patterns of gastrointestinal neuroendocrine tumors(GI NET).METHODS In this retrospective cohort study,we used 2009-2014 data from 2 United States commercial claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included somatostatin analogues(SSA),cytotoxic chemotherapy(CC),targeted therapy(TT),interferon(IF) and combinations. We identified patients at least 18 years of age,with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who initiated pharmacologic treatment from 7/1/09-6/30/14. A 6 mo clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment or the study end date,whichever was first.RESULTS We identified 2258 newly treated GI NET patients: mean(SD) age was 55.6 years(SD = 9.7),47.2% of the patients were between 55 and 64 years,and 48.8% were female. All regions of the United States were represented. 59.6% started first-line therapy with SSA monotherapy(964 with octreotide LAR,380 with octreotide SA,and 1 with lanreotide),33.3% CC,3.6% TT,and 0.5% IF. The remainder received combinations. Mean follow up was 576 d. Overall mean first-line therapy duration was 361 d(449 d for SSA,215 for CC,267 for TT). 58.9% of patients had no pharmacological treatment beyond first line. The most common secondline was combination therapy with SSA. In graphical pattern analysis,there was no clear pattern visible after first line therapy.CONCLUSION In this study,60% of patients initiated treatment with SSA alone or in combination. The relatively long time to discontinuation suggests possible sustained effectiveness and tolerability.

Application of cystoscope in surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus

Development of portal vein tumor thrombus deteriorates the prognosis of hepatocellular carcinoma, while surgical treatment can offer a promising prognosis for selected patients. However, the possibility of residual lesions in portal vein after conventional thrombectomy is a main risk factor leading to postoperative recurrence. Therefore, ensuring the complete removal of tumor thrombus during operation is critical to improve prognosis. For the first time, we report here one case of hepatocellular carcinoma with portal vein tumor thrombus in which cystoscope was successfully applied as a substitute of intravascular endoscope to visualize the cavity of the portal vein. The patient was a 61-year-old man with a 7-cm tumor in the right lobe of the liver, with tumor thrombus invading the right branch and adjacent to the conjunction of the portal vein. After removal of the tumor, the Olympus CYF-VA2 cystoscope was used to check the portal vein from the opening stump of the right branch of the portal vein. In this case, residual thrombus tissue was found near the opening stump and the conjunction of the portal vein. The residual lesion was carefully retrieved from the stump after retraction of the cystoscope. The procedure was repeated until no residual lesion was found. The whole duration time of thrombectomy was 22.5(15 + 7.5) min. The patient was free from recurrence at 8 months after the procedure. Our work indicated that the cystoscope is a suitable substitute, with a proper size and function to check the portal vein system and ensure the curability of thrombectomy. Although welldesigned clinic trails are still needed, this procedure may further improve the postoperative prognosis of hepatocellular carcinoma with portal vein tumor thrombus.

Analysis of clinical characteristics and treatment of pancreatic cystic tumors

Objective： To summarize experience in the diagnosis and treatment of pancreatic cystic neoplasms.Methods： This is a retrospective study of 207 patients who were diagnosed with pancreatic cystic tumors at Peking Union Medical College Hospital between Jan 2009 and Mar 2014. Clinical data, such as clinical manifestations, radiologieal and pathological images and surgical recordings, were collected. Results： Of the 207 included patients, females accounted for 76.81%, and the mean patient age was 52.04 years. Malignancy was more common in older patients who presented with marasmus and jaundice. Other risk factors included solid components in the tumor, a large tumor size, and elevated levels of tumor markers. Surgical treatment was required when a malignant tumor was suspected. The operation approach was selected based on the location, size and characteristics of the tumor. The position of the tumor relative to the pancreatic duct also played a significant role.

Antitumor effects of electrochemical treatment

Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas. This treatment is noted for its great effectiveness, minimal invasiveness and local effect. Several studies have been conducted worldwide to evaluate the anfitumoral effect of this therapy. In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained. By this reason, researchers have suggested various mechanisms to explain how direct electric current destroys tumor ceils. Although, it is generally accepted this treatment induces electrolysis, electroosmosis and electroporation in tumoral tissues. However, action mechanism of this alternative modality on the tumor tissue is not well understood. Although the principle of Electrochemical treatment is simple, a standardized method is not yet available. The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process. The present work analyzes the latest and most important research done on the electrochemical treatment of tumors. We conclude with our point of view about the destruction mechanism features of this alternative therapy. Also, we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy. In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done. Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.

Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy

Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal diseases,with an average 5-year survival rate of less than 10%.Unfortunately,the majority of patients have unresectable,locally advanced,or metastatic disease at the time of diagnosis.Moreover,traditional treatments such as chemotherapy,surgery,and radiation have not been shown to significantly improve survival.Recently,there has been a swift increase in cancer treatments that incorporate immunotherapybased strategies to target all the stepwise events required for tumor initiation and progression.The results in melanoma,non-small-cell lung cancer and renal cell carcinoma are very encouraging.Unfortunately,the application of checkpoint inhibitors,including anti-CTLA4,anti-PD-1,and anti-PD-L1 antibodies,in pancreatic cancer has been disappointing.Many studies have revealed that the PDAC microenvironment supports tumor growth,promotes metastasis and consists of a physical barrier to drug delivery.Combination therapies hold great promise for enhancing immune responses to achieve a better therapeutic effect.In this review,we provide an outline of why pancreatic cancer is so lethal and of the treatment hurdles that exist.Particular emphasis is given to the role of the tumor microenvironment,and some of the latest and most promising studies on immunotherapy in PDAC are also presented.

REFLECTIONS ON SURGICAL TREATMENT OF 214 CASES OF PRIMARY MEDIASTINAL TUMOR

Our hospital documented 214 cases of primary mediastinal tumor from May 1957 to July 1995. They were treated surgically, There were 184 benign cases (85. 98% ), and 30 malignant cases (14.02 % ). Among them, there were 63 cases of neurogenic tumor (29.43 % ), 48 cases of thymic tumor (22. 4% ), 41 cases of teratoid tumor (19. 16% ), 12 cases of bronchial cyst (5. 61% ), and 9cases of intrathoracic adenoma of thyroid (4. 21%). The authors mainiy discuss the early diagnosis,tumor variety, operating incisions, and operating essentials.

SURGICAL TREATMENT OF METASTATIC SPINAL TUMOR

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Clinical-Pathological Features and Treatment Modalities of Primary Brain Tumors in Tanzania—4 Years of Institutional Experience

Background: The profile of primary brain tumors and treatment modalities employed in Tanzania remains largely unknown. The study aimed to describe the baseline clinical-pathological profile and treatment modalities for primary brain tumors in adults treated at the Ocean Road Cancer Institute (ORCI) from 2017 to 2020. Materials and Methods: This was a retrospective study conducted at ORCI by reviewing 61 medical records of patients with primary brain tumors over the age of 15 from January 2017 to December 2020. A structured questionnaire was used to retrieve information on sociodemographic, clinical-pathological characteristics, and treatment modalities. The 2007 WHO classification system and the International Classification of Cancer Diseases (ICD-0-3) were used for classification and diagnosis. The X2 test and Fisher’s exact test were used to compare the proportions and an independent t-test was used to compare the means. A P-value less than 0.05 was deemed statistically significant. The Results: The mean age of the females was 41.8 years and the mean age of males was 42.9 years. Overall M: F ratio was 1:1.2. Meningioma was the only tumor that was more commonly found in women with M:F of 1:2.1. The most prevalent symptom was headache (57.4%). Glioblastoma (GBM) was the most common tumor among adults (38%), followed by astrocytomas (23%) and meningioma (18%). Approximately 91.8% of all tumors occurred in the supratentorial region. The Frontal lobe was the most common site (29.5%). Approximately 81.9% of patients received surgery. The gross tumor resection (GTR) rate was 26.2%, and the subtotal tumor resection (STR) rate was 55.7%. Roughly 18% of the tumors were inoperable. An estimated 80.3% of respondents received radiation therapy. The radiotherapy technique was 3DCRT in two-thirds of the patients and the rest received conventional 2D radiotherapy. The mean equivalent dose in the 2 Gy fractions (EQD2) was 43.9 Gy. Respondents with low-grade intracranial tumors were treated with a mean EQD2 of 47.3 Gy, while those with high-grade intracranial tumors were treated with a mean EQD2 of 44.3 Gy and the difference was statistically significant. Only half of the patients who received adjuvant radiotherapy received it concurrently with chemotherapy. Temozolomide was the most widely used cytotoxic medication. Conclusion: Mean age of the patients was 41 years old. Most tumors were in the supratentorial area and GBM was the most common tumor. Only meningioma was a bit more common amongst females. Overall, radiotherapy doses and the gross tumor resection rates were low. Concurrent chemotherapy with radiotherapy was given to a few patients.

Operational Techniques and Combination Treatment for the Recurrent Sacro－coccygeal Tumor

This article presents 6 cases of recurrent sacro-coccygeal tumor with analysis of the causes of recurrence, operational technique for second-time operation and concomitant treatment.It is suggested that combined abdominal and sacro-coccygeal approaches be used to excise maximal mass of the tumor,surrounding affected tissues be curetted out and the space be filled up with adriamycin-bone-cement to destroy remaining tumor cells and to strengthen the stability of pelvis. Besides,the patients should be subject to supersegregation radiotherapy in order to minimize the possibility of recurrence.