scholarly journals SPDR-2 Histopathological investigation of the oligodendroglial tumors resected following alkylating agent chemotherapy

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi3-vi4
Author(s):  
Nakaya Masato ◽  
Tokunori Kanazawa ◽  
Kentaro Ohara ◽  
Yohei Kitamura ◽  
Kazunari Yoshida ◽  
...  
Keyword(s):  
Alkylating Agent ◽  
Tumor Volume ◽  
Lower Grade ◽  
Ki 67 ◽  
Histological Changes ◽  
Oligodendroglial Tumors ◽  
Chemotherapeutic Response ◽  
Grade 3 ◽  
Nuclear Degradation ◽  
Volume Decrease

Abstract Oligodendrogliomas, i.e., lower grade gliomas with 1p/19q codeletion, are often responsive to chemotherapy, however, those tumors eventually recur and life-limiting in the majority of patients despite initial chemotherapeutic response. We have been treating those patients with upfront chemotherapy and subsequent resection following tumor volume decrease since 2006. This study aimed to elucidate the histological changes and the mechanism of recurrence after alkylating agent chemotherapy in oligodendrogliomas. Fifteen oligodendrogliomas (Grade 2: 12, Grade 3: 3) resected following tumor volume decrease after alkylating agent chemotherapy were included and compared with their pre-chemotherapy specimens. Histological changes were investigated using hematoxylin-eosin staining, and changes in proliferative activity, status of glioma stem cells (GSCs), and tumor-infiltrating macrophages were assessed using immunohistochemistry. The frequent histological findings following chemotherapy included a sparse glial background, abundant foamy cell infiltration, gliosis, calcification, and nuclear degradation. The Ki-67/MIB-1 index decreased and the number of macrophages increased after chemotherapy. Moreover, the ratio of GSCs to total tumor cells increased after chemotherapy. GSCs and macrophages constitute the mechanism of resistance to and recurrence after alkylating agent chemotherapy in oligodendrogliomas.

scholarly journals PATH-59. HISTOPATHOLOGICAL INVESTIGATION OF THE 1p/19q-CODELETED GLIOMAS RESECTED FOLLOWING ALKYLATING AGENTS CHEMOTHERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi156-vi156
Author(s):  
Tokunori Kanazawa ◽  
Kentaro Ohara ◽  
Kazunari Yoshida ◽  
Hikaru Sasaki
Keyword(s):  
Alkylating Agents ◽  
Progression Free Survival ◽  
Lower Grade ◽  
Histopathological Changes ◽  
Ki 67 ◽  
Free Survival ◽  
Foamy Cell ◽  
Histopathological Investigation ◽  
Volume Decrease ◽  
Mib 1

Abstract BACKGROUND Little is known about histopathological changes after chemotherapy in lower-grade gliomas (LrGGs). METHODS We investigated 15 1p/19q-codeleted gliomas resected following tumor volume decrease after alkylating agents chemotherapy in comparison with their pre-chemotherapy specimens. Histopathological changes by chemotherapy were evaluated by hematoxilyn-eosin staining and immunohistochemistry for Ki-67/MIB-1, CD68 as pan macrophage/monocyte marker, CD163 as presumed marker of M2 polarity, and nestin and CD133 as markers of glioma stem cells (GSCs). RESULTS Histologically, there were several presumed chemotherapy-related changes in the post-chemotherapy specimens, with the most frequent findings being sparse glial background and abundant foamy cell infiltration. The Ki-67/MIB-1 indices significantly decreased, and CD68+ cells significantly increased after chemotherapy. The increasing rate of CD68+ cells in the post-/pre-chemotherapy specimens was prone to be associated with patients’ progression-free survival (PFS) and overall survival (OS), but not tumor response. The number of CD163+ cells and the ratio of nestin+ cells and CD133+ cells significantly increased after chemotherapy. The number of CD163+ cells, the ratio of nestin+ cells and CD133+ cells, and M2 (CD163+)/M1+M2 (CD68+) ratio in the post-chemotherapy specimens were negatively correlated with patients’ PFS and OS. There was no difference between chemotherapy regimens (temozolomide versus nitrosourea-based) in the number of CD163+ cells and the ratio of nestin+ and CD133+ cells. CONCLUSIONS GSCs in conjunction with M2 macrophages constitute the mechanism of resistance to and recurrence after alkylating agents chemotherapy in LrGGs.

scholarly journals NI-06 MOLECULAR DIAGNOSIS, 11C-METHIONINE UPTAKE AND PROGNOSIS IN GRADE 2 AND 3 GLIOMAS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii26-ii26
Author(s):  
Kaoru Tamura ◽  
Yaeko Furuhashi ◽  
Motoki Inaji ◽  
Daisuke Kobayashi ◽  
Takahiro Ogishima ◽  
...  
Keyword(s):  
Who Classification ◽  
Genetic Alterations ◽  
Normal Brain ◽  
Lower Grade ◽  
Who Grade ◽  
Oligodendroglial Tumors ◽  
Integrated Diagnosis ◽  
Lower Grade Glioma ◽  
Methionine Uptake ◽  
Grade 3

Abstract OBJECT The revised 2016 WHO Classification of Tumours of the Central Nervous System incorporates genetic alterations into the classification system, with the goal of creating more homogenous disease categories with greater prognostic value. In this study, we reclassified 103 consecutive lower grade gliomas using the revised 2016 WHO classification and examined for 11C-methionine uptake and prognosis. METHODS 103 consecutive lower grade glioma patients (Grade 2 in 41 patients, Grade 3 in 62 patients) treated at Tokyo Medical and Dental University Hospital from 2000 to 2018 were included in this study. The IDH1/2, ATRX and 1p19q status were analyzed using tumor samples. The tumor-to-normal ratio (T/N) of 11 C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. RESULT In the integrated diagnosis, 11 astrocytomas and 17 anaplastic astrocytomas were diagnosed as “IDH-mutant”, while 14 astrocytomas and 29 anaplastic astrocytomas were diagnosed as “IDH-wild”. In the 32 oligodendroglial tumors, 12 oligodendrogliomas and 9 anaplastic oligodendrogliomas were diagnosed as “IDH-mutant and 1p/19q-codeleted”. The concordance rate with 1p19q co-deletion and ATRX retention was 94.7%. The median T/N ratios in oligodendroglial tumors with “IDH-mutant and 1p/19q-codeleted” were 1.83 in Grade 2 and 2.83 in grade 3, which were significantly higher than those in astrocytic tumors with “IDH-mutant” (G2: 1.38, G3:1.62). Kaplan-Meier survival analysis revealed that oligodendroglial tumors with “IDH-mutant and 1p/19q-codeleted” had significantly better outcomes regardless of WHO grade. Overall survival was 90.9% at 5 years and 77.9% at 10 years in oligodendroglial tumors with “IDH-mutant and 1p/19q-codeleted”. CONCLUSIONS The results indicated that lower grade glioma categories reclassified with molecular classification correlate with the T/N ratio of methionine and the prognosis.

PATH-17. POSSIBLE ASSOCIATION BETWEEN OLIGODENDROGLIAL HISTOLOGICAL FEATURES OF IDHMUT/CODEL LOWER GRADE GLIOMAS AND PATIENT'S FAVORABLE PROGNOSIS, BUT NOT IN IDHMUT/NONCODEL AND IDH-WILDTYPE TUMORS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi118-vi118
Author(s):  
Eriel Pareira ◽  
Makoto Shibuya ◽  
Kentaro Ohara ◽  
Yu Nakagawa ◽  
Tokunori Kanazawa ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Methylation Status ◽  
Molecular Characteristics ◽  
Lower Grade ◽  
Histological Feature ◽  
Genetic Characteristics ◽  
Histological Features ◽  
Favorable Prognosis ◽  
Oligodendroglial Tumors ◽  
Chemotherapeutic Response

Abstract Comprehensive diagnostic using histological and molecular characteristics began to be implemented in WHO 2016 but the relevance of oligodendroglial histological features to patients’ prognoses is still controversial. To elucidate the connection between oligodroglial histology and patient’s prognoses we analyzed 93 LrGGs resected for about 2 decades were reassessed for histological features based on WHO2007 with special interest to pure oligodendroglial diagnosis (namely, oligodendroglioma or anaplastic oligodendroglioma) and presence of classic for oligodendroglioma (CFO) features. Those histological features, patients’ OS, and tumor chromosomal/genetic characteristics were correlated each other in each of the 3 IDH-1p/19q based molecular groups. The reassessed morphology-based diagnosis was shown to be most strict for astrocytic, but loosened for oligodendroglial tumors as compared with the original institutional diagnoses and WHO2016. The pure oligodendroglial diagnosis by reassessment was associated with longer OS in IDHmut/codel group, but not in IDHmut/noncodel and IDH-wildtype groups. The presence of CFO was not associated with patients’ OS in any molecular groups. Gain of 8q was associated with the oligodendroglial diagnosis in IDHmut/noncodel group. Neither the oligodendroglial diagnosis nor CFO was predictive for the methylation status of the MGMT gene in any of the 3 molecular groups. NGS of the IDHmut/codel tumors suggested that mutations in the FUBP1 and CIC genes might be associated with poor prognosis. The oligodendroglial histological feature is not independently predictive for either patients’ prognosis or chemotherapeutic response in LrGGs, except the oligodendroglial diagnosis in IDHmut/codel tumors.

PP455 Cost-effectiveness Of Ixazomib-Based Regimen Compared With Bortezomib-Based Regimen In Chinese Patients With Relapsed/Refractory Multiple Myeloma: A Retrospective Study

2020 ◽  
Vol 36 (S1) ◽  
pp. 36-37
Author(s):  
Pei Wang ◽  
Jing Li ◽  
Yang Yang ◽  
Peng Liu
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Staging System ◽  
Chinese Patients ◽  
Disease Stage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lower Grade ◽  
Refractory Multiple Myeloma ◽  
Grade 3

IntroductionThe treatment of relapsed/refractory multiple myeloma (RRMM), a common hematological malignancy, remains a great challenge in China, partially due to the limited accessibility to novel agents and inadequate public health insurance coverage. Ixazomib, a novel oral proteasome inhibitor (PI), was approved by the China Food and Drug Administration (CFDA) for RRMM in 2018. While bortezomib, a traditional PI, is the recommended agent in the clinical guideline for MM. Here, we compared their costs and effectiveness.MethodsRRMM patients who has received an ixazomib-based regimen (at least 2 cycles) were analyzed. Using a propensity score matching method, we generated a control group of RRMM patients who received the bortezomib-based regimen. The criteria included the number of treatment lines, age, and the revised international staging system stage (R-ISS) which representing the disease stage for myeloma, and paired at a ratio of 1:2 (allowing one control to match multiples). The difference in hospitalization stay, grade 3/4 adverse events rates, overall response rate (ORR), mortality during treatment, and treatment costs was then compared.ResultsNineteen patients received ixazomib and twenty-seven that received bortezomib were included. The ixazomib-group demonstrated a shorter hospital stay (9 days versus 27 days, p < 0.001), lower grade 3–4 adverse events rates (42.1% versus 55.6%, p < 0.001), higher ORR (63.2% versus 48.1%, p = 0.228), and lower mortality rate during treatment (0% versus 7.4%, p = 0.169) than that of bortezomib-group. The ixazomib group had lower total costs (127,620CNY versus 156,424CNY [18,033USD versus 22,103USD], p > 0.05), lower drug costs (98,376CNY versus 103,307CNY [13,901USD versus 14,598USD], p > 0.05), and the lower costs of supportive treatment (5,507CNY versus 14,701 CNY [778USD versus 2,077USD], p < 0.001). Only in terms of self-funded costs, the bortezomib-based regimen was significantly lower (37,127CNY versus 11,521CNY [5,246USD versus 1,628USD], p < 0.001).ConclusionsCompared with the bortezomib-based regimen, the ixazomib-based regimen has better therapeutic effects on MM patients while saving costs. Hence, it may be preferable for use in the treatment of RRMM in China.

Antitumor effects of Auraptene in 4T1 tumor‐bearing Balb/c mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza. Shiran ◽  
Davar Amani ◽  
Abolghasem Ajami ◽  
Mahshad Jalalpourroodsari ◽  
Maghsoud Khalizadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Tumor Volume ◽  
Serum Levels ◽  
Ki 67 ◽  
Tumor Bearing ◽  
Paraffin Oil ◽  
Anti Cancer ◽  
Before And After ◽  
Ifn Γ

Abstract Objectives Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide. Methods In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels. Results There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment. Conclusions In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.

scholarly journals PCV chemotherapy alone for WHO grade 2 oligodendroglioma: prolonged disease control with low risk of malignant progression

2021 ◽  
Author(s):  
Jonathan Weller ◽  
Sophie Katzendobler ◽  
Philipp Karschnia ◽  
Stefanie Lietke ◽  
Rupert Egensperger ◽  
...  
Keyword(s):  
Stereotactic Biopsy ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Who Grade ◽  
Free Survival ◽  
First Relapse ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
Histological Progression

Abstract Introduction The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy. Methods Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed. Results PFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS. Conclusions PCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.

Antitumor effects of antiprogesterones on human meningioma cells in vitro and in vivo

1994 ◽  
Vol 80 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Yasuhiro Matsuda ◽  
Keiichi Kawamoto ◽  
Katsuzo Kiya ◽  
Kaoru Kurisu ◽  
Kazuhiko Sugiyama ◽  
...  
Keyword(s):  
Marked Reduction ◽  
Tumor Volume ◽  
Collagen Gel ◽  
Antitumor Effects ◽  
Histological Changes ◽  
Content Type ◽  
The Relationship ◽  
Fine Print

✓ The presence of the progesterone receptor (PR) in meningioma tissue has been confirmed by previous investigations. Studies have shown that the antiprogesterone drug, mifepristone, is a potent agent that inhibits the growth of cultured meningioma cells and reduces the size of meningiomas in experimental animal models and humans. However, these studies have not fully examined the relationship between the antitumor effects of an antiprogesterone agent and the expression of the PR. The present study examined the antitumor effects of mifepristone and a new potent antiprogesterone agent, onapristone; a correlation between the antitumor effects of these antiprogesterones and the presence of PR's in meningiomas in vitro and in vivo was also investigated. Meningioma tissue surgically removed from 13 patients was used in this study. In the in vitro arm of the study, mifepristone and onapristone exhibited cytostatic and cytocidal effects against cultured meningioma cells, regardless of the presence or absence of PR's; however, three PR-negative meningiomas showed no response to any dose of mifepristone and/or onapristone. In the in vivo arm, meningioma cells, embedded in a collagen gel, were implanted into the renal capsules of nude mice. Antiprogesterone treatment resulted in a marked reduction of the tumor volume regardless of the presence or absence of PR's. No histological changes in the meningioma cells suggestive of necrosis or apoptosis were detected in any of the mice treated with antiprogesterones. These findings suggest that mifepristone and onapristone have an antitumor effect against meningioma cells via the PR's and/or another receptor, such as the glucocorticoid receptor.

scholarly journals Tumor Volume Decrease at 8 Weeks Is Associated with Longer Survival in EGFR-Mutant Advanced Non–Small-Cell Lung Cancer Patients Treated with EGFR TKI

2013 ◽  
Vol 8 (8) ◽  
pp. 1059-1068 ◽  
Author(s):  
Mizuki Nishino ◽  
Suzanne E. Dahlberg ◽  
Stephanie Cardarella ◽  
David M. Jackman ◽  
Michael S. Rabin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Tumor Volume ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Volume Decrease

scholarly journals Current Paradigm of Treatment for Pancreatic Neuroendocrine Tumor

2021 ◽  
Vol 26 (1) ◽  
pp. 24-32
Author(s):  
Min Je Sung ◽  
Moon Jae Chung
Keyword(s):  
Cell Proliferation ◽  
Medical Treatment ◽  
Neuroendocrine Tumor ◽  
Standard Treatment ◽  
Pancreatic Neuroendocrine Tumor ◽  
Somatostatin Analogues ◽  
Proliferation Index ◽  
Ki 67 ◽  
Grade 3 ◽  
Cell Proliferation Index

Pancreatic neuroendocrine tumor (PNET) refer to tumors originating from the islet of Langerhans and shows various prognosis based on the presence or absence of symptoms due to hormone secretion, the Ki-67 cell proliferation index, and the histologic grade, and according to the degree of disease progression defined by the tumor-node-metastasis (TNM) stage classification. The purpose of medical treatment for PNET is to control symptoms or inhibit tumor growth. Somatostatin analogues can be administered for the purpose of controlling symptoms caused by the secretion of specific hormones, and are accepted as effective drugs for inhibiting the progression of G1/G2 tumors based on World Health Organization (WHO) classification with a Ki-67 cell proliferation index less than 20%. Among the molecularly targeted agents, everolimus and sunitinib can be considered in patients with WHO G1/G2 PNET showing progression after somatostatin analog therapy. Cytotoxic chemotherapy is generally administered to patients with large tumor volume and rapidly progressing metastatic NET, and etoposide/cisplatin combination therapy has been considered as a standard treatment. For the patient group of Grade 3 PNET (well differentiated) newly classified by the WHO 2017 classification, guidelines for standard treatment have not yet been established. As it has been reported, studies are needed to evaluate the treatment response rate of somatostatin analogues or molecularly targeted therapies for the patient with Grade 3 PNET. It is important to consider a multidisciplinary approach with all possible treatment options including medical treatment, radical resection of primary or metastatic lesions, liver-directed therapies, and peptide receptor radionuclide therapy for the patients with PNET.

Psoralidin exerts anti-tumor, anti-angiogenic, and immunostimulatory activities in 4T1 tumor‐bearing balb/c mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Davar Amani ◽  
Elham Shakiba ◽  
Ehsan Motaghi ◽  
Hiva Alipanah ◽  
Mahshad Jalalpourroodsari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Serum Level ◽  
Tumor Volume ◽  
Treated Group ◽  
The Body ◽  
Ki 67 ◽  
Tumor Bearing ◽  
Anti Cancer ◽  
Ifn Γ

Abstract Background Psoralidin as a compound of the Psoralea corylifolia seeds exhibited several anti-cancer potentials in various cancers. Materials and methods In this study, 4T1 tumor‐bearing Balb/c mice were treated by intraperitoneal administration of Psoralidin, and Paraffin, as a control group to investigate anti-tumor, anti-angiogenic, and immunostimulatory activities in breast cancer. Body weight and tumor volume measurement were performed. Hematoxylin and Eosin (H&E) staining as well as immunohistochemistry for Ki-67, CD31 and VEGF markers were conducted. In addition, ELISA assay was performed for evaluating the serum level of IFN-γ and IL-4. Moreover, real time assay was performed to evaluate the expression of angiogenesis and immunostimulatory related genes. Results There were no significant changes in the body weight of all animal groups. The anti-cancer effects of Psoralidin were significantly observed after 24 days of the last treatment, confirmed by smaller tumor volume and also H&E staining. The expression level of Ki‐67, CD31 and VEGF were significantly decreased in tumor tissues of the Psoralidin-treated group in comparison with Paraffin-treated group. Moreover, there was a significant reduction in the serum level of IL-4 in tumor-bearing mice after Psoralidin treatment while the serum level of IFN-γ was significantly augmented in all groups. Moreover, the reduction in expression of VEGF-a and IL-1β was observed. Interestingly Psoralidin treatment led to expression increase of FOXp3. Conclusions Psoralidin shows the anti-cancer potential in an animal model of breast cancer; however, further studies are recommended to elucidate its mechanisms of action.

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