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Gut microbiota has a proven link with the development and treatment of cancer. However, the causality between gut microbiota and cancer development is still unknown and deserves exploration. In this study, we aimed to explore the alterations in gut microbiota in murine tumor models and the crosstalk between the tumor and the gut microbiota. The subcutaneous and intravenous murine tumor models using both the colorectal cancer cell line MC38 and lung cancer cell line LLC were constructed. Then fecal samples before and after tumor inoculation were collected for whole metagenomics sequencing. Both subcutaneous and metastatic tumors markedly elevated the α‐diversity of the gut microbiota. Relative abundance of Ligilactobacillus and Lactobacillus was reduced after subcutaneously inoculating tumor cells, whereas Bacteroides and Duncaniella were reduced in metastatic tumors, regardless of tumor type. At the species level, Lachnospiraceae bacterium was enriched after both subcutaneous and intravenous tumors inoculation, whereas levels of Muribaculaceae bacterium Isolate‐110 (HZI), Ligilactobacillus murinus and Bacteroides acidifaciens reduced. Metabolic function analysis showed that the reductive pentose phosphate cycle, urea cycle, ketone body biosynthesis, ectoine biosynthesis, C4‐dicarboxylic acid cycle, isoleucine biosynthesis, inosine 5′‐monophosphate (IMP), and uridine 5′‐monophosphate (UMP) biosynthesis were elevated after tumor inoculation, whereas the cofactor and vitamin biosynthesis were deficient. Principal coordinates analysis (PCoA) showed that subcutaneous and metastatic tumors partially shared the same effect patterns on gut microbiota. Furthermore, fecal microbiota transplantation revealed that this altered microbiota could influence tumor growth. Taken together, this study demonstrated that both colorectal cancer (MC38) and non‐colorectal cancer (LLC) can cause gut dysbiosis and metabolic imbalance, regardless of tumor type and process of tumor inoculation, and this dysbiosis influenced the tumor growth. This research gives novel insights into the crosstalk between tumors and the gut microbiota. [ABSTRACT FROM AUTHOR]

A 54-year-old woman presented with an anterior neck subcutaneous tumor that had appeared one month prior. Mild tenderness was noted. As a diagnosis was difficult to make based on physical examination and ultrasonography, a magnetic resonance imaging (MRI) scan was performed. Both examinations revealed a 1-cm subcutaneous mass with well-defined margins; the MRI scan was hypointense on T1-weighted images and slightly hyperintense with low point foci on T2-weighted images. Subsequently, an excisional biopsy was performed, and the pathologic diagnosis of glomus tumor was obtained. Glomus tumors usually present as a painful subcutaneous mass beneath the nail bed but may be painless or occur in areas other than the fingers. Because glomus tumors in the neck resemble a variety of diseases, their diagnosis may be delayed. This case highlights the importance of considering glomus tumors as a potential cause of neck subcutaneous tumors.

Glioblastoma multiform (GBM) is the most common primary brain tumor with a poor prognosis and few therapeutic choices. In vivo, tumor models are useful for enhancing knowledge of underlying GBM pathology and developing more effective therapies/agents at the preclinical level, as they recapitulate human brain tumors. The C6 glioma cell line has been one of the most widely used cell lines in neuro-oncology research as they produce tumors that share the most similarities with human GBM regarding genetic, invasion, and expansion profiles and characteristics. This review provides an overview of the distinctive features and the different animal models produced by the C6 cell line. We also highlight specific applications of various C6 in vivo models according to the purpose of the study and offer some technical notes for more convenient/repeatable modeling. This work also includes novel findings discovered in our laboratory, which would further enhance the feasibility of the model in preclinical GBM investigations. [ABSTRACT FROM AUTHOR]

Evidence is mounting that there is a significant gap between the antitumor efficacy of nanodrugs in preclinical mouse tumor models and in clinical human tumors, and that differences in tumor models are likely to be responsible for this gap. Herein, we investigated the enhanced permeability and retention (EPR) effect in mouse lung cancer models with different tumor growth rates, volumes and locations, and analyzed the nanodrug tumor targeting behaviors limited by tumor vascular pathophysiological characteristics in various tumor models. The results showed that the fast-growing tumors were characterized by lower vascular tight junctions, leading to higher vascular paracellular transport activity and nanodrug tumor accumulation. The paracellular transport activity increased with the growth of tumor, but the vascular density and transcellular transport activity decreased, and as a result, the average tumor accumulation of passive targeting nanodrugs decreased. Orthotopic tumors were rich in blood vessels, but had low vascular transcellular and paracellular transport activities, making it difficult for nanodrug accumulation in orthotopic tumors via passive targeting strategies. The antitumor efficacy of passive targeting nanodrugs in various lung cancer-bearing mice validated the aforementioned nanodrug accumulation behavior, and nanodrugs based on the angiogenesis-tumor sequential targeting strategy achieved obviously improved efficacy in orthotopic lung cancer-bearing mice. These results suggest that the EPR effect varies in different tumor models and should not be used as a universal targeting strategy for antitumor nanodrugs. Besides, attention should be paid to the animal tumor models in the evaluation of nanodrugs so as to avoid exaggerating the antitumor efficacy. [Display omitted] • The enhanced permeability and retention (EPR) effect varies in mouse tumor models. • Mouse tumor models affect the tumor vascular pathophysiological characteristics. • Tumor vascular characteristics affect the tumor targeting behavior of nanodrugs. • Rational mouse models are essential for the efficacy evaluation of nanodrugs. • Nanodrug targeting strategy should be based on the tumor vascular characteristics. [ABSTRACT FROM AUTHOR]

Introduction Mammary‐type myofibroblastoma is a rare benign tumor, mainly arising along the embryonal mammary ridge. We report a rare case of mammary‐type myofibroblastoma of the perineum. Case presentation A 37‐year‐old Japanese man presented with a 20 mm, progressively‐growing painless mass in the right perineum. Computed tomography showed a subcutaneous tumor with a strong contrast effect. Upon total resection, pathology showed a spindle‐cell tumor positive for desmin but negative for CD34. Further immunohistochemistry showed loss of Rb expression, leading to differential diagnosis. We could not evaluate the exact rarity of the perineal location due to categorization in past reports. Conclusion Due to the similarities between mammary and anogenital tissue, we suggest that tallying perineal and vulvar areas separately from the embryonic mammary ridge sites may be beneficial in gaining insight into the pathophysiology of this tumor.

Abstract is missing (Short communication)

Multimodal cancer therapies are often required for progressive cancers due to the high persistence and mortality of the disease and the negative systemic side effects of traditional therapeutic methods. Thus, the development of less invasive modalities for recurring treatment cycles is of clinical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation. The system is composed of poly(caprolactone) microparticles of 200 μm size containing molybdenum disulfide (MoS 2 ) nanosheets as the photothermal agent and hydrophilic doxorubicin or hydrophobic violacein, as model drugs. Upon irradiation, the nanosheets heat up to ≥50 °C leading to polymer softening and release of the drug. MoS 2 nanosheets exhibit high photothermal conversion efficiency and require low-power laser irradiation. A machine learning algorithm was applied to acquire the optimal laser operation conditions. In a mouse subcutaneous model of 4T1 triple-negative breast cancer, 25 microparticles were intratumorally administered, and after 3-cycle laser treatment, the system conferred synergistic phototherapeutic and chemotherapeutic effects. Our on-demand, pulsatile synergistic treatment resulted in increased median survival up to 39 days post start of treatment compared to untreated mice, with complete eradication of the tumors at the primary site. Such a system is therapeutically relevant for patients in need of recurring cycles of treatment on small tumors, since it provides precise localization and low invasiveness and is not cross-resistant with other treatments.

Ependymomas are slowly growing glial tumors derived from the ependymal cells and usually occur in the central nervous system (CNS). Ependymomas rarely occur outside of the CNS and they are called extraspinal ependymomas. In spite of their metastatic potential, extraspinal ependymomas can be misdiagnosed for other benign mass like pilonidal cysts. The diagnosis is confirmed by histopathology and most of the cases are known to show glial fibrillary acidic protein (GFAP), S-100 protein, and keratin (AE1AE3) immunoreactivity. Herein, we present a case of GFAP-negative ependymoma, which presented as asymptomatic subcutaneous tumor of the left buttock and was clinically misdiagnosed as epidermal cyst. Our case indicates that ependymomas cannot be ruled out by lack of GFAP immunoreactivity and an asymptomatic subcutaneous mass could be a malignant tumor like ependymomas, which requires careful examinations.

A parasitic leiomyoma has no connection with the uterus itself and obtains its blood supply from the surrounding tissues. A parasitic leiomyoma that develops iatrogenically is called an iatrogenic parasitic leiomyoma. Clinical reports on parasitic leiomyoma are common in gynecology but not in plastic surgery. We report a rare case of an iatrogenic parasitic leiomyoma in a 46-year-old woman who was referred to our plastic surgery department. She presented with the main complaint of a subcutaneous mass in the lower right abdomen and had a history of laparoscopic myomectomy eight years ago. Magnetic resonance imaging showed two masses in the subcutaneous tissue of the lower right abdomen and the posterior rectus abdominis. The excision of these masses was performed through an abdominal wall incision. Histopathological examination revealed that the extracted mass was a leiomyoma. Plastic surgeons must keep in mind the appropriate management of rare cases of parasitic leiomyoma., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fujita et al.)

Abstract Background Ectopic hamartomatous thymoma, which usually occurs in the lower neck, is a rare benign tumor containing spindle cells, epithelial nests, and adipose tissue. Although the origin of this tumor is still unknown, recent reports suggest that the designation of this tumor is inappropriate. Case presentation A 38-year-old with an anterior cervical mass in the suprasternal region of her neck was referred to our hospital. An ultrasound examination showed that the well-defined oval mass was 31 × 23 × 17 mm in size. A non-enhanced computed tomography scan of the neck revealed that the distinct neck mass in the subcutaneous tissue had a mixture of soft tissue and fatty components. The cervical tumor was clinically diagnosed to be an unusual lipoma with degeneration. The patient underwent the neck mass extirpation. During the surgery, the cervical mass was well demarcated and did not adhere to the surrounding tissues. The postoperative course was uneventful. The gross pathology report showed that the neck mass measured 3.0 × 2.5 × 2.0 cm. Microscopically, the tumor was composed of spindle cells, epithelial nests, and mature adipose tissue. Immunohistochemical examination revealed that both spindle cells and epithelial nests were positive for cytokeratin AE1/AE3. These histopathological findings were consistent with the features of ectopic hamartomatous thymoma. Over a follow-up period of 30 months, this patient exhibited no evidence of recurrence. Conclusions Ectopic hamartomatous thymoma should be considered in the differential diagnosis of subcutaneous tumors in the lower neck, when the CT shows the tumor has the mixed components of fat and soft tissues.

Objective To optimize 3.0 T functional MRI parameters for evaluating subcutaneous tumor model of human colorectal cancer in nude mice. Methods Twenty nude mice were randomly divided into groups A (10 mice) and B (10 mice) to establish a subcutaneous tumor model of human colorectal cancer SW480 cell line in nude mice. MRI was performed when the tumor grew to 1-1.5 cm. Two scanning schemes with the same sequences and different parameters were designed for transverse T1—, T2— and contrast—enhanced T1—weighted imaging. For transverse T1—weighted MRI (T1WI) without and with contrast, the nude mice in group A were scanned with 256x224 matrix and group B with 256x256 matrix. The remaining parameters were the same. All nude mice were scanned by intravoxel incoherent motion diffusion—weighted imaging (IVIM—DWI) to assess water molecular diffusion movement providing information about cell density. Three—dimensional artery spin labeling imaging (3D—ASL) provided microcirculation information of subcutaneous tumors in all mice. Signal to noise ratio (SNR) and contrast to noise ratio (CNR) on T1—, and contrast—enhanced Tr weighted imaging; apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*) on IVIM—DWI; perfusion fraction (0 and blood flow (BF) value on 3D—ASL of all tumors and muscles were measured on the same sections. Results 10 mice in group A and 5 mice in group B showed tumor formation on MRI. The transverse TN], the enhanced sequence, the SNR and CNR of transverse MRI without and with contrast were significantly higher in group A than those in group B (P<0.05). ADC, D, and D* values in tumors were all significantly lower than that in muscles (F1/40.05) whereas f and BF values in tumors were significantly higher than that in muscles (F1/40.05). The subcutaneous tumor was histologically diagnosed as low—differentiated colorectal adenocarcinoma with abundant blood supply and high cell density. Conclusion Reducing the matrix of transverse T1WI allows high quality anatomical MRI of nude mice. IVIM-DWI and 3D-ASL reflect the cell density and microangiogenesis in subcutaneous tumors, respectively. [ABSTRACT FROM AUTHOR]

Ependymomas are slowly growing glial tumors derived from the ependymal cells and usually occur in the central nervous system (CNS). Ependymomas rarely occur outside of the CNS and they are called extraspinal ependymomas. In spite of their metastatic potential, extraspinal ependymomas can be misdiagnosed for other benign mass like pilonidal cysts. The diagnosis is confirmed by histopathology and most of the cases are known to show glial fibrillary acidic protein (GFAP), S-100 protein, and keratin (AE1AE3) immunoreactivity. Herein, we present a case of GFAP-negative ependymoma, which presented as asymptomatic subcutaneous tumor of the left buttock and was clinically misdiagnosed as epidermal cyst. Our case indicates that ependymomas cannot be ruled out by lack of GFAP immunoreactivity and an asymptomatic subcutaneous mass could be a malignant tumor like ependymomas, which requires careful examinations. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxides (SPION-4) were modified using pH-/reduction-responsive alginate and prepared for magnetic-targeted delivery of doxorubicin (DOX) to inhibit tumor growth in hepatocellular carcinoma xenografted subcutaneous tumor of BALB/c nude mice. The release profile of DOX-loaded SPION-4 showed the best fitting in the Makoid–Banakar model with faster release rates under higher concentrations of glutathione. The introduction of disulfide bonds into SPION-4 greatly elevated its release capabilities, thus leading to high DOX concentrations in the cytoplasm and nucleus in vitro and in tumor tissues in vivo, in the presence of an external magnet. Additionally, the DOX concentration in heart tissues after being treated by DOX-loaded SPION-4 was significantly lower than that dressed with free DOX. The in vivo results showed that the DOX-loaded SPION-4-magnet group displayed the best effects on inhibiting tumor growth, with an extensively larger necrotic area and enhanced antivascular effects on the vascular endothelial growth factor and CD34 inhibition when compared to the other groups. This obvious improvement in anticancer efficacy of DOX-loaded SPION-4 supports its potential application as an effective chemotherapeutic agent for inhibiting tumor growth. [ABSTRACT FROM AUTHOR]

Ossifying fibromyxoid tumor (OFMT) is a rare, slow-growing, mesenchymal tumor with intermediate malignant potential, predominantly affecting middle-aged individuals. Histologically, it presents as a fibrous capsule or pseudocapsule, with a complete or incomplete lamellar bone shell surrounding oval/polygonal cells within a fibromyxoid matrix. Advances in immunohistochemistry have facilitated OFMT identification, with S100 protein expression and INI-1 loss being notable features. CD10 expression is also reported in a small minority of cases. Recent studies highlight a translocation of the PHF-1 gene, proposing a possible etiology for tumorigenesis. Treatment involves wide excision, with long-term follow-up for recurrence or metastasis. In this case, a 61-year-old White male presented to the outpatient surgical office with a painless mass on his right shoulder. The patient reported that the mass first appeared three to four years prior and that it had been growing slowly since the initial presentation. On examination, the patient had a well-circumscribed, 1.5 x 1.5 cm, soft, nontender, nonmobile subcutaneous mass on his right shoulder. The mass was initially suspected to be a subcutaneous cyst based on physical exam, but surgical excision and histopathology established the diagnosis of OFMT that extended to the margins of the specimen. The patient underwent a wider excision for margins and has had a benign postoperative course. The patient was referred to dermatology and oncology for continuation of care. This case demonstrates the necessity for a thorough work-up, appropriate excision, and histopathologic examination to rule in diagnoses of lower incidence with the potential for a worse prognosis. Appropriate and timely diagnoses can guide proper screening for cancer recurrence and management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nash et al.)

Ossifying fibromyxoid tumour (OFMT) is a rare subcutaneous soft tissue neoplasm, with unclear lineage and intermediate differentiation. Typically presenting as a benign growth, however it can recur locally, and malignant variants have been reported. We present an unusual case of OFMT occurring as a subcutaneous mass on the right upper back. A 29-year-old gentleman presented with one-year history of a painless, slowly enlarging mass on his right upper back. He had no relevant medical history, was not on any medications, and had no family history of skin cancer. Physical examination revealed a 25mm x 25mm skin-coloured, stony-hard, well circumscribed mass. The initial clinical diagnosis was a calcified epidermoid cyst. The lesion was excised and sent for histopathology, which revealed well-circumscribed cellular spindle cells with low mitotic index. Immunohistochemistry showed variable S100 positivity. Due to its rarity, the diagnosis was delayed as the biopsy required a second opinion from a tertiary hospital. The final pathological diagnosis confirmed OFMT. This case describes the very rare presentation of OFMT in a dermatology clinic, highlighting the importance of recognising this neoplasm due to its potential for recurrence and metastasis. This unusual case of OFMT broadens the dermatological differential diagnosis for a subcutaneous mass., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yeo et al.)

Objective: To prospectively evaluate the accuracy of ultrasound in defining the specific nature of superficial soft tissue masses as well as determining malignancy.Materials and Method: Eight hundred twenty-three superficial soft tissue masses were prospectively evaluated with ultrasound by one of five experienced musculoskeletal radiologists. The radiologist at the time of examination provided one to three specific differential diagnoses and the perceived level of confidence with regard to each diagnosis. Clinical and ultrasound diagnoses were compared with the histological diagnosis to determine accuracy. Tumor malignancy was determined by histology or clinical/imaging follow-up.Results: Histological correlation was present for 219 (26.6%) of the 823 masses. Compared with histology, the accuracy of clinical and ultrasound examination for determining specific tumor type was 25.6% and 81.2% respectively considering all differential diagnoses provided. Radiologists were "fully confident" with the ultrasound diagnosis in 585 (71.1%) of 823 masses overall. In this setting, when compared with histology, the diagnostic accuracy of ultrasound was 95.5%. When the radiologist was "not fully confident," accuracy was 41.3% for the first differential diagnosis and 60.9% for all differential diagnoses. Diagnostic accuracy improved with increasing radiologist experience. Sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound for identifying malignant tumor were 93.3%, 97.9%, 45.2%, and 99.9% respectively.Conclusions: One can be "fully confident" at characterizing over two-thirds of superficial soft tissue masses based on ultrasound appearances and, in this setting, diagnostic accuracy is very high. Ultrasound examination is also highly accurate at discriminating benign from malignant superficial soft tissue masses. [ABSTRACT FROM AUTHOR]

Objective We aimed to investigate the effects of Biejiajian Pills on MHCC-97H hepatoma cells and whether Biejiajian Pills regulate the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway through miR-885-5p. Methods SPF SD rats (n = 10) were randomly divided into the blank group and the Biejiajian Pills (1.1 g/kg) group to prepare blank and Biejiajian Pills-containing serum. MHCC-97H cells in the logarithmic growth phase were divided into the model group, blank serum groups with different concentrations (5%, 10%, 15%, and 20%), the serum containing Biejiajian Pills group, and the blank group without cells. Cell proliferation was detected by the CCK-8 assay, and the optimal intervention time and concentration of drug-containing serum were screened. MHCC-97H cells were divided into the blank control group (no intervention), the Biejiajian Pills-containing serum group (20% Biejiajian Pills-containing serum), the miR-885-5p mimics group (transfected with miR-885-5p mimics), the miR-NC group (transfected with miR-885-5p NC), and the Biejiajian Pills-containing serum + miR-885-5p mimics group (treated with 20% Biejiajian Pills-containing serum and transfected with miR-885-5p mimics). Cells in each group were cultured for 72 hours. A dual luciferase reporter assay was conducted to verify the targeting relationship between miR-885-5p and EGFR. Cell proliferation was detected by the CCK-8 assay, cell migration and invasion abilities were detected by the cell scratch assay and the Transwell invasion assay. Annexin V-APC/PI double staining was performed to detect the apoptosis level, and real-time fluorescence quantitative PCR (RT-qPCR) analysis was conducted to determine the mRNA expression levels of miR-885-5p, EGFR, MEK, and ERK1/2. The expression levels of EGFR, p-EGFR, MEK, p-MEK, ERK1/2, p-ERK1/2, matrix metalloproteinase 1 (MMP1), and CyclinD1 were determined by Western blotting analysis. The subcutaneous tumor model of MHCC-97H hepatoma cells in nude mice was established by subcutaneous injection to observe the inhibitory effect of Biejiajian Pills of different doses(0.55, 1.1, 2.2 g/kg). Results The optimal concentration and intervention time of Biejiajian Pills-containing serum were 20% and 72 hours, respectively. Meanwhile, the dual luciferase reporter assay showed that miR-885-5p could directly target EGFR. No statistical significances between the blank control group and the miR-NC group were observed (P>0.05). Compared with the blank control group, the proliferation rates of MHCC-97H hepatoma cells in the Biejiajian Pills-containing serum group, the miR-885- 5p mimics group, and the Biejiajian Pills-containing serum + miR-885-5p mimics group were significantly decreased (P<0.01), and their migration and invasion abilities were significantly decreased (P<0.05, P<0.01). At the same time, the protein expression levels of CyclinD1 and MMP1, which are closely related to cell proliferation and invasion, were significantly downregulated (P<0.05, P<0.01). The proportions of late apoptotic cells and the proportion of total apoptotic cells were significantly increased (P<0.01). In the Biejiajian Pills- containing serum group, the miR-885-5p mimics group, and the Biejiajian Pills-containing serum + miR-885-5p mimics group, miR-885-5p mRNA was significantly upregulated (P<0.01) and EGFR, MEK, and ERK1/2 were significantly downregulated at the mRNA level (P<0.05, P<0.01). EGFR, MEK, and ERK1/2 phosphorylation was inhibited (P<0.01), and the Biejiajian Pills-containing serum + miR-885-5p mimics group showed the best effect (P<0.05, P<0.01). The subcutaneous liver tumor model in nude mice verified that Biejiajian Pills can inhibit tumor growth in a dose-dependent manner. Conclusion Biejiajian Pills can promote apoptosis of MHCC-97H hepatoma cells and inhibit their proliferation, invasion, and migration. The mechanism may be related to the targeted regulation of the EGFR/MAPK/ERK signaling pathway by miR-885-5p. [ABSTRACT FROM AUTHOR]

Radiotherapy is a crucial treatment modality for cancer patients, with approximately 60% of individuals undergoing ionizing radiation as part of their disease management. In recent years, there has been a growing trend toward minimizing irradiation fields through the use of image-guided dosimetry and innovative technologies. These advancements allow for selective irradiation, delivering higher local doses while reducing the number of treatment sessions. Consequently, computer-assisted methods have significantly enhanced the effectiveness of radiotherapy in the curative and palliative treatment of various cancers. Although radiation therapy alone can effectively achieve local control in some cancer types, it may not be sufficient for others. As a result, further preclinical research is necessary to explore novel approaches including new schedules of radiotherapy treatments. Unfortunately, there is a concerning lack of correlation between clinical outcomes and experiments conducted on mouse models. We hypothesize that this disparity arises from the differences in irradiation strategies employed in preclinical studies compared to those used in clinical practice, which ultimately affects the translatability of findings to patients. In this study, we present two comprehensive radiotherapy protocols for the treatment of orthotopic melanoma and glioblastoma tumors. These protocols utilize a small animal radiation research platform, which is an ideal radiation device for delivering localized and precise X-ray doses to the tumor mass. By employing these platforms, we aim to limit the side effects associated with irradiating healthy surrounding tissues. Our detailed protocols offer a valuable framework for conducting preclinical studies that closely mimic clinical radiotherapy techniques, bridging the gap between experimental results and patient outcomes., Competing Interests: Disclosures M.E.R.R. reports receiving research funding from Roche and Highlight Therapeutics. She also has received speaker's bureau honoraria from AZ, BMS and ROCHE., (Copyright © 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training and similar technologies.)

Abstract 5-Aminolevulinic acid (ALA) based photodynamic therapy (PDT) is a modality for the treatment of cancers. However, due to its hydrophilicity and zwitterionic nature, the transdermal delivery of ALA is limited for the PDT of subcutaneous tumor. To address this problem, tip-loaded fast-dissolving microneedles made of sodium hyaluronate (HA) were fabricated by two casting method. 122 μg of ALA was loaded per microneedle patch and mainly distributed in the tips, which could improve the utilization of drug and avoid the waste of drug residue in the base of microneedle patch after use. The HA microneedles could pierce stratum corneum with insertion depth about 200 μm in isolated skin. After insertion, HA microneedles were rapidly dissolved to release the encapsulated drug to improve patients' convenience and compliance. Importantly, in a subcutaneous mouse tumor model established in BALB/c nude mice, the PDT efficacy of ALA-loaded HA microneedle group was much better than ALA injection group in spite of a relatively lower ALA dose with HA microneedles. The tumor inhibition rate of ALA-loaded HA microneedle group (containing 0.61 mg of ALA) was up to 97%, while the tumor inhibition rate of ALA injection group (containing 1.65 mg of ALA) was just 66%. In addition, microchannels created by microneedle patch were quickly recovered within 3 h after insertion. Overall, the tip-loaded fast-dissolving HA microneedle patch with ALA as drug was promising and might improve topical PDT efficacy of subcutaneous tumor in an efficient and safe manner. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Objective: To study the effect of artesunate on the growth and radiosensitivity of lung cancer cells subcutaneously transplanted subcutaneously in nude mice. Methods: Lung cancer cells were inoculated subcutaneously in nude mice, intraperitoneal injection of artesunate, the radiation treatment was also recorded as a combined group, set the artesunate group at the same time(not irradiation), radiation group(intraperitoneal injection of normal saline) and control group(intraperitoneal injection of saline, no radiation treatment), measurement of tumor volume, tumor tissues were collected and weighed tumor weight, TUNEL method was used to detect the apoptotic level in the tissues, the levels of Cleaved Caspase-3, STAT3, p-STAT3, p38 MAPK and p-p38 MAPK in tissues were detected by Western and blot. Results: Artesunate group, radiotherapy group and combined group subcutaneous transplantation tumor volume and weight were significantly lower than the control group, the combined group of tumor weight and volume was significantly lower than that of artesunate group and radiation group, the differences were statistically significant(P<0.05). Artesunate group, radiotherapy group and combined group tumor cell apoptosis rate and level of Cleaved Caspase-3 and p-p38 MAPK/p38 MAPK were significantly higher than the control group, combination group tumor cell apoptosis rate, the Cleaved Caspase-3 level and p-p38 MAPK/p38 MAPK level were higher than that of artesunate group and radiation group, the differences were statistically significant(P<0.05). Artesunate group, radiotherapy group and combined group p-STAT3/STAT3 in tumor tissues was significantly lower than the control group, the level of p-STAT3/STAT3 in tumor tissue in the combined group was significantly lower than artesunate group and radiation group, the differences were statistically significant(P<0.05). Conclusion: Artesunate can inhibit the growth of lung cancer cells subcutaneously transplanted in nude mice, promoting apoptosis of cancer cells, increased radiosensitivity, the mechanism of action may be related to p38 MAPK and STAT3 signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract: A subcutaneous tumor accompanied by tenderness has a myriad of differential diagnoses. Indeed, using physical findings alone to achieve a diagnosis is often challenging. In this study, we focused on schwannomas and angioleiomyomas, which usually develop as hard subcutaneous tumors and are often associated with tenderness. We aimed to determine significant differentiating features between the tumor types, using ultrasonography. We compared clinical findings and ultrasonographic imaging and calculated the statistical significance for each item. In total, we analyzed 11 schwannomas and 13 angioleiomyomas of the extremities, trunk and head. There was no significant difference in patient characteristics or clinical findings. Meanwhile, the mean maximum diameter (P = 0.002), localization (P = 0.04) and entering or exiting nerves (P = 0.01) were significantly different according to ultrasonography findings. Thus, ultrasonography provides excellent information for the initial assessment of a slow‐growing, painful, subcutaneous soft tissue mass. According to our study, it is difficult to identify a single, differentiating feature between angioleiomyoma and schwannoma on ultrasonography, but including multiple findings during the work‐up can facilitate differential diagnosis. [ABSTRACT FROM AUTHOR]

Ependymomas commonly arise in the central nervous system. Extraneural presentation is quite rare. Herein, we describe a primary extraneural ependymoma in a young female. The mass was located in the right inguinal area. The cut surface of the 7.5 mm × 6.5 mm × 4.5 mm sized tumor was brownish-yellow in color. Histologically, it was hypercellular exhibiting pseudorosette or rosette formations and some papillary structures. Mitosis was counted as high as 10 per 10 high power fields. Neither necrosis nor vascular endothelial proliferation within the tumor was observed. Tumor cells showed strong glial fibrillary acidic protein immunoreactivity. On epithelial membrane antigen, intracytoplasmic dot-like immunostaining was observed. This is the first report presenting a primary extraneural anaplastic ependymoma arising in the inguinal subcutaneous region.

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Glioblastoma multiform (GBM) is the most common primary brain tumor with a poor prognosis and few therapeutic choices. In vivo, tumor models are useful for enhancing knowledge of underlying GBM pathology and developing more effective therapies/agents at the preclinical level, as they recapitulate human brain tumors. The C6 glioma cell line has been one of the most widely used cell lines in neuro-oncology research as they produce tumors that share the most similarities with human GBM regarding genetic, invasion, and expansion profiles and characteristics. This review provides an overview of the distinctive features and the different animal models produced by the C6 cell line. We also highlight specific applications of various C6 in vivo models according to the purpose of the study and offer some technical notes for more convenient/repeatable modeling. This work also includes novel findings discovered in our laboratory, which would further enhance the feasibility of the model in preclinical GBM investigations., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Interleukin-1 receptor associated kinase 1 (IRAK1), as a down-stream of toll-like receptor (TLR) signaling, plays important roles in series of malignancies. However, the role of IRAK1 in hepatocellular carcinoma (HCC) remains little known. Methods: In our study, reverse transcription-PCR (RT-PCR), Western Blot, and immunohistochemical staining were used to assess the mRNA and protein levels of IRAK1 in clinical samples and cell lines. Cell counting assay and flow cytometry were employed to analyze the effect of IRAK1 on cell cycle and apoptosis. Transwell assay was used to study the role of IRAK1 in cell migration. Moreover, subcutaneous xenograft tumor models predict the efficacy of targeting IRAK1 against HCC in vivo. Results: IRAK1 was over-expressed in HCC tissues and cell lines. Suppression of IRAK1 by small interference RNA (siRNA) or a pharmaceutical IRAK1/4 inhibitor impeded cell growth, induced apoptosis and lessened HCC xenograft tumor growth. Particularly, IRAK1/4 inhibitor treatment caused G1/S cell cycle arrest and apoptosis, confirming IRAK1 as a new therapeutic target for HCC. Conclusion: IRAK1 promotes cell proliferation and protects against apoptosis in HCC, and can be a novel target for HCC treatment. [ABSTRACT FROM AUTHOR]

There are still some gaps in existing knowledge in the field of cancer nanotheranostics, e.g ., the efficiency of nanoparticle-loaded cells for targeted delivery. In the current study, gold nanoparticles (Au NPs) were delivered to tumors in both subcutaneous tumor and lung metastasis tumor models by intravenous injection of either free Au NPs or of human bone marrow mesenchymal stem cells (MSCs), which were loaded with endocytosed Au NPs. By making injections with the same dose of administrated Au NPs, it was possible to directly compare tumor targeting of both delivery modes. Hereby, the passive targeting of tumor by the plain Au NPs was facilitated by the enhanced permeation and retention (EPR) effect. Au NP retention by tumors, as well as tumor penetration, were found to be improved up to 2.4-to-9.3-fold when comparing the MSC-mediated delivery of Au NPs to the delivery of the plain Au NPs via EPR effect on day 7 post administration. While the absolute retention of Au NPs in the tumor remained low, our data show that, upon injection of the same amount of Au NPs, in fact MSC-mediated delivery is quantitatively higher than EPR-mediated delivery of NPs by half an order of magnitude.

Preclinical development of cancer treatments including radiotherapy (RT) is now crucial to optimize all the treatment aspects for a better efficacy and to help clinicians to build new clinical trials based on robust results. More and more teams use preclinical irradiators to deliver radiotherapy in a comparable way to clinical treatments (image-based RT, arc therapy, stereotactic body RT…). In daily conditions, users usually need to develop easy to use techniques (for applicator technicians for example), allowing to treat many mice per day with a high level of reproducibility. Besides, the best compromise between a satisfying dose coverage to the tumor and nearby organs at risk sparing has to be ensured. We describe here new a home-made immobilization device to irradiate grafted tumors, as well as the different steps to develop the treatment planning and generate an easy procedure to routinely irradiate subcutaneous tumor model., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The identification of novel immune-related targets that can reactivate or enhance antitumor immunity is a very active field of cancer research. In this context, syngeneic tumor models are often used during the preclinical development of immunotherapies to assess their efficacy and analyze the immune system and tumor cell interaction. Here, we present the practical procedures to generate subcutaneous tumors and experimental lung metastases used to evaluate the antitumor activity of your immunotherapy of interest. We also describe a method to quantify contrasted lung metastasis burden by imaging. Finally, we present a protocol to perform orthotopic injection of breast tumor cells in the mammary fat pad followed by tumor resection for the study of spontaneous metastases and evaluation of neoadjuvant immunotherapy., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatocellular carcinomas make up 90% of primary liver cancers. The association between the hepatic carcinoma and virus B and C infection has been already proven. Hepatocellular carcinoma develops, in most cases, on a background of cirrhosis and rarely in hepatitis. The case we have chosen to report distinguishes itself due to the unusual extra-hepatic metastatic location of a hepatocellular carcinoma in a patient with Chronic HCV hepatitis. [ABSTRACT FROM AUTHOR]

FLT3 subtype acute myeloid leukemia (AML) has a poor prognosis with currently available therapies. A number of small molecule inhibitors of FLT3 and/or CDK4/6 are currently under development. A more complete and quantitative understanding of the mechanisms of action of FLT3 and CDK4/6 inhibitors may better inform the development of current and future compounds that act on one or both of the molecular targets, and thus may lead to improved treatments for AML. In this study, we investigated in both subcutaneous and orthotopic AML mouse models, the mechanisms of action of three FLT3 and/or CDK4/6 inhibitors: AMG925 (Amgen), sorafenib (Bayer and Onyx), and quizartinib (Ambit Biosciences). A composite model was developed to integrate the plasma pharmacokinetics of these three compounds on their respective molecular targets, the coupling between the target pathways, as well as the resulting effects on tumor burden reduction in the subcutaneous xenograft model. A sequential modeling approach was used, wherein model structures and estimated parameters from upstream processes (e.g. PK, cellular signaling) were fixed for modeling subsequent downstream processes (cellular signaling, tumor burden). Pooled data analysis was employed for the plasma PK and cellular signaling modeling, while population modeling was applied to the tumor burden modeling. The resulting model allows the decomposition of the relative contributions of FLT3 and CDK4/6 inhibition on downstream signaling and tumor burden. In addition, the action of AMG925 on cellular signaling and tumor burden was further studied in an orthotopic tumor mouse model more closely representing the physiologically relevant environment for AML. [ABSTRACT FROM AUTHOR]