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World Journal of Clinical Oncology Apr 2024Low-grade myofibroblastic sarcoma (LGMS) is an extremely rare tumor characterized by the malignant proliferation of myofibroblasts. LGMS most commonly develops in...
BACKGROUND
Low-grade myofibroblastic sarcoma (LGMS) is an extremely rare tumor characterized by the malignant proliferation of myofibroblasts. LGMS most commonly develops in adults, predominantly in males, in the head and neck region, oral cavity, especially on the tongue, mandible, and larynx. This article presents 2 cases of LGMS localized to the maxillary sinus and provides an overview of the available literature.
CASE SUMMARY
Two patients with LGMS located in the maxillary sinus underwent surgery at the Department of Head and Neck Surgery. Case 1: A 46-year-old patient was admitted to the clinic with suspected LGMS recurrence in the right maxillary sinus (rT4aN0M0), with symptoms of pain in the suborbital area, watering of the right eye, thick discharge from the right nostril, and augmented facial asymmetry. After open biopsy-confirmed LGMS, the patient underwent expanded maxillectomy of the right side with immediate palate reconstruction using a microvascular skin flap harvested surgically from the middle arm. The patient qualified for adjuvant radiotherapy for the postoperative bed, with an additional margin. Currently, the patient is under 1.5 years of observation with no evidence of disease. Case 2: A 45-year-old man was admitted to our clinic with facial asymmetry, strabismus, exophthalmos, and visual impairment in the right eye. Six months earlier, the patient had undergone partial jaw resection at another hospital for fibromatosis. A contrast-enhanced computed tomography scan revealed a tumor mass in the postoperative log after an earlier procedure. An open biopsy confirmed low-grade fibrosarcoma (rT4aN0M0). The patient qualified for an extended total right maxillectomy with orbital excision and right hemimandibulectomy with immediate microvascular reconstruction using an anterolateral thigh flap. The patient subsequently underwent adjuvant radiotherapy to the postoperative area. After 9 months, recurrence occurred in the right mandibular arch below the irradiated area. The lesion infiltrated the base of the skull, which warranted the withdrawal of radiotherapy and salvage surgery. The patient qualified for palliative chemotherapy with a regimen of doxorubicin + dacarbazine + cyclophosphamide and palliative radiotherapy for bone metastases. The patient died 26 months after surgical treatment. The cases have been assessed and compared with cases in the literature.
CONCLUSION
No specific diagnostic criteria or treatment strategies have been developed for LGMS. The treatment used for LGMS is the same as that used for sinonasal cancer radical tumor excision; adjuvant radiotherapy or chemoradiotherapy should also be considered. They have low malignant potential but are highly invasive, tend to recur, and metastasize to distant sites. Patients should undergo regular follow-up examinations to detect recurrence or metastasis at an early stage. Patients should be treated and observed at the highest referral centers.
PubMed: 38689628
DOI: 10.5306/wjco.v15.i4.566 -
In Vivo (Athens, Greece) 2024Gliomas are the most common and recalcitrant malignant primary brain tumors. All cancer types are addicted to methionine, which is a fundamental and general hallmark of...
Extensive Shrinkage and Long-term Stable Disease in a Teenage Female Patient With High-grade Glioma Treated With Temozolomide and Radiation in Combination With Oral Recombinant Methioninase and a Low-methionine Diet.
BACKGROUND/AIM
Gliomas are the most common and recalcitrant malignant primary brain tumors. All cancer types are addicted to methionine, which is a fundamental and general hallmark of cancer known as the Hoffman effect. Particularly glioma cells exhibit methionine addiction. Because of methionine addiction, [C]-methionine positron emission tomography (MET-PET) is widely used for glioma imaging in clinical practice, which can monitor the extent of methionine addiction. Methionine restriction including recombinant methioninase (rMETase) and a low-methionine diet, has shown high efficacy in preclinical models of gliomas, especially in combination with chemotherapy. The aim of the present study was to determine the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet, combined with radiation and temozolomide (TMZ), on a teenage female patient with high-grade glioma.
CASE REPORT
A 16-year-old girl was diagnosed with high-grade glioma. Magnetic resonance imaging (MRI) showed a left temporal-lobe tumor with compression to the left lateral ventricle and narrowing of sulci in the left temporal lobe. After the start of methionine restriction with o-rMETase and a low-methionine diet, along with TMZ combined with radiotherapy, the tumor size shrunk at least 60%, with improvement in the left lateral ventricle and sulci. The patient's condition remains stable for 19 months without severe adverse effects.
CONCLUSION
Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with radiation and TMZ as first-line chemotherapy, were highly effective in a patient with high-grade glioma.
Topics: Humans; Female; Glioma; Carbon-Sulfur Lyases; Temozolomide; Methionine; Adolescent; Magnetic Resonance Imaging; Brain Neoplasms; Treatment Outcome; Neoplasm Grading; Positron-Emission Tomography; Recombinant Proteins; Combined Modality Therapy
PubMed: 38688589
DOI: 10.21873/invivo.13591 -
Molecules (Basel, Switzerland) Apr 2024Chalcones are polyphenols that belong to the flavonoids family, known for their broad pharmacological properties. They have thus attracted the attention of chemists for...
Chalcones are polyphenols that belong to the flavonoids family, known for their broad pharmacological properties. They have thus attracted the attention of chemists for their obtention and potential activities. In our study, a library of compounds from 2'-hydroxychalcone's family was first synthesized. A one-step mechanochemical synthesis via Claisen-Schmidt condensation reaction under ball mill conditions was studied, first in a model reaction between a 5'-fluoro-2'-hydroxyacetophenone and 3,4-dimethoxybenzaldehyde. The reaction was optimized in terms of catalysts, ratio of reagents, reaction time, and influence of additives. Among all assays, we retained the best one, which gave the highest yield of 96% when operating in the presence of 1 + 1 eq. of substituted benzaldehyde and 2 eq. of KOH under two grinding cycles of 30 min. Thus, this protocol was adopted for the synthesis of the selected library of 2'-hydroxychalcones derivatives. The biological activities of 17 compounds were then assessed against , parasite development, as well as melanoma cell lines by inhibiting their viability and proliferation. Compounds and are the most potent against exhibiting IC values of 2.33 µM and 2.82 µM, respectively, better than the reference drug Miltefosine (3.66 µM). Compound presented the most interesting antimalarial activity against the 3D7 strain, with IC = 3.21 µM. Finally, chalcone gave the best result against IGR-39 melanoma cell lines, with an IC value of 12 µM better than the reference drug Dacarbazine (IC = 25 µM).
Topics: Chalcones; Humans; Cell Line, Tumor; Plasmodium falciparum; Leishmania donovani; Antimalarials; Antineoplastic Agents; Cell Proliferation; Cell Survival; Molecular Structure
PubMed: 38675640
DOI: 10.3390/molecules29081819 -
International Journal of Molecular... Apr 2024Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its...
Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its high cytotoxic activity and antitumor efficacy against glioma was shown. In this work, using immortalized and patient-derived cells with different sensitivity to VV-GMCSF-Lact, we evaluated the cytotoxic effect of chemotherapy agents. Additionally, we studied the combination of VV-GMCSF-Lact with temozolomide which is the most preferred drug for glioma treatment. Experimental results indicate that first adding temozolomide and then the virus to the cells is inherently more efficient than dosing it in the reverse order. Testing these regimens in the U87 MG xenograft glioblastoma model confirmed this effect, as assessed by tumor growth inhibition index and histological analysis. Moreover, VV-GMCSF-Lact as monotherapy is more effective against U87 MG glioblastoma xenografts comparing temozolomide.
Topics: Humans; Animals; Oncolytic Virotherapy; Oncolytic Viruses; Temozolomide; Xenograft Model Antitumor Assays; Cell Line, Tumor; Mice; Glioma; Vaccinia virus; Granulocyte-Macrophage Colony-Stimulating Factor; Brain Neoplasms; Mice, Nude; Antineoplastic Agents; Glioblastoma; Combined Modality Therapy
PubMed: 38673835
DOI: 10.3390/ijms25084244 -
CNS Neuroscience & Therapeutics Apr 2024Besides the hallmark of H3K27M mutation, aberrant amplifications of receptor tyrosine kinases (RTKs) are commonly observed in diffuse midline glioma (DMG), a highly...
BACKGROUND
Besides the hallmark of H3K27M mutation, aberrant amplifications of receptor tyrosine kinases (RTKs) are commonly observed in diffuse midline glioma (DMG), a highly malignant brain tumor with dismal prognosis. Here, we intended to evaluate the efficacy and safety of a multitarget RTK inhibitor anlotinib in patients with H3K27M-DMG.
METHODS
A total of 40 newly diagnosed H3K27M-DMG patients including 15 with anlotinib and 25 without anlotinib treatment were retrospectively enrolled in this cohort. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed and compared.
RESULTS
The median PFS and OS of all patients in this cohort were 8.5 months (95% CI, 6.5-11.3) and 15.5 months (95% CI, 12.6-17.1), respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the disease control rate in the anlotinib group [93.3%, 95% confidence interval (CI), 70.2-98.8] was significantly higher than those without anlotinib (64%, 95% CI: 40.5-79.8, p = 0.039). The median PFS of patients with and without anlotinib was 11.6 months (95% CI, 7.8-14.3) and 6.4 months (95% CI, 4.3-10.3), respectively. Both the median PFS and OS of DMG patients treated with anlotinib were longer than those without anlotinib in the infratentorial patients (PFS: 10.3 vs. 5.4 months, p = 0.006; OS: 16.6 vs. 8.7 months, p = 0.016). Multivariate analysis also indicated anlotinib (HR: 0.243, 95% CI: 0.066-0.896, p = 0.034) was an independent prognosticator for longer OS in the infratentorial subgroup. In addition, the adverse events of anlotinib administration were tolerable in the whole cohort.
CONCLUSIONS
This study first reported that anlotinib combined with Stupp regimen is a safe and feasible regimen for newly diagnosed patients with H3K27M-DMG. Further, anlotinib showed significant efficacy for H3K27M-DMG located in the infratentorial region.
Topics: Humans; Male; Indoles; Quinolines; Female; Retrospective Studies; Middle Aged; Adult; Brain Neoplasms; Glioma; Temozolomide; Mutation; Young Adult; Cohort Studies; Adolescent; Chemoradiotherapy; Aged
PubMed: 38644565
DOI: 10.1111/cns.14730 -
CNS Neuroscience & Therapeutics Apr 2024To elucidate the relationship between USP19 and O(6)-methylguanine-DNA methyltransferase (MGMT) after temozolomide treatment in glioblastoma (GBM) patients with...
OBJECTIVE
To elucidate the relationship between USP19 and O(6)-methylguanine-DNA methyltransferase (MGMT) after temozolomide treatment in glioblastoma (GBM) patients with chemotherapy resistance.
METHODS
Screening the deubiquitinase pannel and identifying the deubiquitinase directly interacts with and deubiquitination MGMT. Deubiquitination assay to confirm USP19 deubiquitinates MGMT. The colony formation and tumor growth study in xenograft assess USP19 affects the GBM sensitive to TMZ was performed by T98G, LN18, U251, and U87 cell lines. Immunohistochemistry staining and survival analysis were performed to explore how USP19 is correlated to MGMT in GBM clinical management.
RESULTS
USP19 removes the ubiquitination of MGMT to facilitate the DNA methylation damage repair. Depletion of USP19 results in the glioblastoma cell sensitivity to temozolomide, which can be rescued by overexpressing MGMT. USP19 is overexpressed in glioblastoma patient samples, which positively correlates with the level of MGMT protein and poor prognosis in these patients.
CONCLUSION
The regulation of MGMT ubiquitination by USP19 plays a critical role in DNA methylation damage repair and GBM patients' temozolomide chemotherapy response.
Topics: Humans; Temozolomide; DNA Repair Enzymes; DNA Modification Methylases; Antineoplastic Agents, Alkylating; Animals; Cell Line, Tumor; Drug Resistance, Neoplasm; Tumor Suppressor Proteins; DNA Methylation; Mice, Nude; Brain Neoplasms; Glioblastoma; Mice; Male; Female; Dacarbazine; DNA Repair; Endopeptidases; Xenograft Model Antitumor Assays; Ubiquitination
PubMed: 38644551
DOI: 10.1111/cns.14711 -
Acta Biochimica Et Biophysica Sinica Jun 2024UBE2C is overexpressed in gliomas, and its overexpression has been reported to be correlated with the drug resistance of gliomas to some extent. In this study, we...
UBE2C is overexpressed in gliomas, and its overexpression has been reported to be correlated with the drug resistance of gliomas to some extent. In this study, we explore the role of UBE2C in regulating temozolomide (TMZ) resistance in glioma and investigate the underlying mechanisms involved. Twenty normal brain tissues and 100 glioma tissues from 50 TMZ-resistant patients and 50 TMZ-sensitive patients are included in this study. TMZ-resistant cell lines are constructed to explore the role of UBE2C in regulating glioma cell viability and TMZ resistance. Our results show that both the mRNA and protein levels of UBE2C are significantly elevated in the brain tissues of glioma patients, especially in those of TMZ-resistant patients. Consistently, UBE2C expression is markedly upregulated in TMZ-resistant cell lines. Overexpression of UBE2C rescues glioma cells from TMZ-mediated apoptosis and enhances cell viability. In contrast, downregulation of UBE2C expression further enhances TMZ function, increases cell apoptosis and decreases cell viability. Mechanistically, UBE2C overexpression decreases p53 expression and enhances aerobic glycolysis level by increasing ATP level, lactate production, and glucose uptake. Downregulation of p53 level abolishes the role of UBE2C downregulation in inhibiting TMZ resistance and aerobic glycolysis in glioma cells. Moreover, an animal assay confirms that downregulation of UBE2C expression further suppresses tumor growth in the context of TMZ treatment. Collectively, this study reveals that downregulation of UBE2C expression enhances the sensitivity of glioma cells to TMZ by regulating the expression of p53 to inhibit aerobic glycolysis.
Topics: Temozolomide; Humans; Drug Resistance, Neoplasm; Glioma; Ubiquitin-Conjugating Enzymes; Tumor Suppressor Protein p53; Glycolysis; Cell Line, Tumor; Animals; Brain Neoplasms; Antineoplastic Agents, Alkylating; Mice, Nude; Gene Expression Regulation, Neoplastic; Mice; Apoptosis; Male; Cell Survival; Female
PubMed: 38634120
DOI: 10.3724/abbs.2024033 -
International Journal of Radiation... Apr 2024Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin...
Involved-site Radiation Therapy is Equally Effective and Less Toxic Than Involved-field Radiation Therapy in Patients Receiving Combined Modality Treatment for Early-stage Unfavorable Hodgkin Lymphoma-An Analysis of the Randomized Phase 3 HD17 Trial of the German Hodgkin Study Group.
PURPOSE
Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin lymphoma. The international standard of care for consolidation RT, involved-site/involved-node radiation therapy (ISRT/INRT), has never been evaluated in a randomized phase 3 trial against the former standard involved-field radiation therapy (IFRT).
METHODS AND MATERIALS
In the multicenter phase 3 GHSG (German Hodgkin Study Group) HD17 trial, patients with early-stage unfavorable Hodgkin lymphoma were randomized between the standard Combined modality treatment group and a positron-emission tomography (PET)-guided group. In the standard group, patients received 2 cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy IFRT. In the experimental group, patients received no further therapy if postchemotherapy PET was negative and 30 Gy GHSG INRT, comparable to and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET-positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT.
RESULTS
A total of 1100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival were 96.8% (95% CI, 91.6%-98.8%) in the IFRT group and 95.4% (95% CI, 89.9%-97.9%; HR, 1.40; 95% CI, 0.44-4.42) in the ISRT group. The pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade 3/4 toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (P = .03).
CONCLUSIONS
For the first time, consolidation INRT/ISRT was randomly compared with IFRT in a phase 3 trial. Regarding progression-free survival, no advantage of IFRT could be demonstrated. In summary, our data confirm the status of INRT/ISRT as the current standard of care.
PubMed: 38631539
DOI: 10.1016/j.ijrobp.2024.04.015 -
ACS Applied Materials & Interfaces May 2024While temozolomide (TMZ) has been a cornerstone in the treatment of newly diagnosed glioblastoma (GBM), a significant challenge has been the emergence of resistance to...
While temozolomide (TMZ) has been a cornerstone in the treatment of newly diagnosed glioblastoma (GBM), a significant challenge has been the emergence of resistance to TMZ, which compromises its clinical benefits. Additionally, the nonspecificity of TMZ can lead to detrimental side effects. Although TMZ is capable of penetrating the blood-brain barrier (BBB), our research addresses the need for targeted therapy to circumvent resistance mechanisms and reduce off-target effects. This study introduces the use of PEGylated mesoporous silica nanoparticles (MSN) with octyl group modifications (C8-MSN) as a nanocarrier system for the delivery of docetaxel (DTX), providing a novel approach for treating TMZ-resistant GBM. Our findings reveal that C8-MSN is biocompatible in vitro, and DTX@C8-MSN shows no hemolytic activity at therapeutic concentrations, maintaining efficacy against GBM cells. Crucially, in vivo imaging demonstrates preferential accumulation of C8-MSN within the tumor region, suggesting enhanced permeability across the blood-brain tumor barrier (BBTB). When administered to orthotopic glioma mouse models, DTX@C8-MSN notably prolongs survival by over 50%, significantly reduces tumor volume, and decreases side effects compared to free DTX, indicating a targeted and effective approach to treatment. The apoptotic pathways activated by DTX@C8-MSN, evidenced by the increased levels of cleaved caspase-3 and PARP, point to a potent therapeutic mechanism. Collectively, the results advocate DTX@C8-MSN as a promising candidate for targeted therapy in TMZ-resistant GBM, optimizing drug delivery and bioavailability to overcome current therapeutic limitations.
Topics: Temozolomide; Glioblastoma; Docetaxel; Silicon Dioxide; Blood-Brain Barrier; Animals; Nanoparticles; Humans; Mice; Drug Resistance, Neoplasm; Brain Neoplasms; Cell Line, Tumor; Porosity; Drug Carriers; Mice, Nude; Antineoplastic Agents; Apoptosis
PubMed: 38629735
DOI: 10.1021/acsami.4c04289 -
Infectious Agents and Cancer Apr 2024Little is known about the outcome for HIV-associated Hodgkin lymphoma (HIV-HL) as this is less common than HIV-negative lymphoma. Therefore, we performed a multi-center...
Outcome in patients with HIV-associated Hodgkin lymphoma treated with chemotherapy using Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine in the combination antiretroviral therapy (cART) era: results of a multicenter study from China.
Little is known about the outcome for HIV-associated Hodgkin lymphoma (HIV-HL) as this is less common than HIV-negative lymphoma. Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-HL patients in China. Nineteen cases of HIV-HL were diagnosed and treated at three center and including the sixth people's hospital of Zhengzhou, Peking union medical college hospital, and Chongqing university cancer hospital, between December 2013 and June 2022. Data on the clinical features, laboratory results, response, and prognosis were collected and analyzed. The median age at diagnosis was 43(22-74) years. All patients were infected with HIV through sexual transmission, with ten cases transmitted through man having sex with man (MSM) and nine cases transmitted through heterosexual transmission. Seven patients were diagnosed with lymphoma and found to be infected with HIV. Four cases were in stage III, and fifteen cases were in stage IV. After a median follow up of 46.8(4.0-112.9) months, 17 cases were alive after ABVD regimen chemotherapy combined with combination antiretroviral therapy (cART). The 5-year progression-free survival (PFS) and overall survival (OS) rate were 83.9% and 89.5%,respectively. HIV-HL exhibits an invasive process in clinical practice, and cART combined with ABVD regimen chemotherapy can achieve long-term survival for patients.
PubMed: 38622727
DOI: 10.1186/s13027-024-00571-w