Publications by authors named "Takayuki Nagasawa"

Background: The quality of life (QOL) of ovarian cancer patients is often impaired by refractory ascites. Cell-free and concentrated ascites reinfusion therapy (CART) is a palliative treatment for refractory ascites, but adverse events, such as fever, are problematic. Several cytokines have been suggested to be responsible for the adverse events, but they have not been investigated in detail.

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: The usefulness of bevacizumab (BEV) as first-line chemotherapy for advanced ovarian clear cell carcinoma (CCC) was retrospectively evaluated at Tohoku Gynecologic Cancer Unit institutions. : A total of 81 patients (52 patients without BEV and 29 with BEV) with advanced ovarian CCC who received initial platinum-based chemotherapy were enrolled. We selected 26 patients each without and with BEV according to propensity score matching methods, and compared the platinum-resistant recurrence rate, response rate, progression-free survival (PFS), overall survival (OS), and adverse events between the two groups.

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  • * Traditional chemotherapy options like paclitaxel-carboplatin, bevacizumab, and PARP inhibitors have improved outcomes, but effective treatments for recurrent, platinum-resistant OC are still lacking.
  • * Mirvetuximab soravtansine is a new antibody-drug conjugate recently approved for treating specific recurrent epithelial OC cases, with ongoing clinical trials exploring similar agents targeting various tumor types in OC.
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  • Hypersensitivity reactions (HSRs) to chemotherapy, particularly carboplatin, are significant adverse events that can affect cancer drug therapy, prompting a study on desensitization methods.
  • The study included 136 patients with gynecological cancers undergoing carboplatin desensitization therapy between 2016 and 2020, tracking their treatment responses and HSR symptoms.
  • Findings revealed a 75% success rate for desensitization, with common symptoms like erythema and itching, while no deaths occurred during the study, indicating the need for awareness of potential HSRs.
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  • The Proactive Molecular Risk Classifier for Endometrial Cancer identifies four risk groups, but the effectiveness of the lenvatinib/pembrolizumab treatment in relation to this classification is not well understood.
  • This study analyzed 20 patients who received this treatment at Iwate Medical University Hospital, assessing their responses and adverse effects over a median follow-up period of 17.8 months.
  • Results showed a 60% overall response rate, with the p53 abnormal group experiencing significantly shorter progression-free survival compared to the mismatch repair-deficient group, highlighting the poor prognosis for the p53 abnormal classification despite treatment.
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Recurrent non-squamous cell carcinoma (non-SCC) of the uterine cervix is resistant to treatment and has a poor prognosis. The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent non-SCC was examined in a phase II study. Fifteen patients were enrolled between August 2013 and March 2023.

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Background/aim: In recent years, the usefulness of poly ADP-ribose polymerase (PARP) inhibitors as subsequent maintenance therapy with poly ADP-ribose polymerase (PARP) inhibitors has been reported. However, it has been reported shown that platinum-based chemotherapy has a low response rate and short progression-free survival for recurrent platinum-sensitive ovarian cancer during treatment with PARP inhibitor therapy. This retrospective study evaluated platinum-based chemotherapy with bevacizumab (BEV) followed by BEV maintenance in these recurrent patients.

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Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC.

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Background: Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we report a retrospective study conducted at the Tohoku Gynecologic Cancer Unit.

Patients And Methods: The study included 453 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer who received first-line platinum-based chemotherapy.

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  • This study focuses on assessing the efficacy and safety of platinum rechallenge therapy in patients with platinum-resistant ovarian cancer who had a platinum-free interval of at least 6 months.
  • A total of 49 patients were evaluated, with notable results showing 55% response and 76% disease control rates, as well as median progression-free survival (PFS) of 8.5 months and overall survival (OS) of 35.8 months.
  • Despite some serious adverse events leading to treatment discontinuation, the therapy was generally manageable and demonstrates potential as a viable treatment option for this challenging type of cancer.
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Nitrogenase employs a sophisticated electron transfer system and a Mo-Fe-S-C cofactor, designated the M-cluster [(cit)MoFe S C]), to reduce atmospheric N to bioaccessible NH . Previously, we have shown that the cofactor-free form of nitrogenase can be repurposed as a protein scaffold for the incorporation of a synthetic Fe-S cluster [Fe S (SEt) ] . Here, we demonstrate the utility of an asymmetric Mo-Fe-S cluster [Cp*MoFe S (SH)] as an alternative artificial cofactor upon incorporation into the cofactor-free nitrogenase scaffold.

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Objective: This multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel-carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer.

Methods: Patients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible. The participants received paclitaxel (175 mg/m), carboplatin (AUC 5), and bevacizumab (15 mg/m) every three weeks until disease progression or unacceptable adverse events occurred.

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This study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate-risk stage I and II or high-risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel-epirubicin-carboplatin (TEC), paclitaxel-anthracycline (doxorubicin)-carboplatin (TAC), or dose-dense paclitaxel-carboplatin (ddTC). The primary end-point was the completion rate (CRate) of six cycles of treatment.

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Ovarian cancer has the worst prognosis among gynecological cancers. In particular, clear cell and mucinous carcinomas are less sensitive to chemotherapy. The establishment of new therapies is necessary to improve the treatment outcomes for these carcinomas.

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We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m administered intravenously], topotecan [1.25 mg/m intravenously], paclitaxel [80 mg/m intravenously], or gemcitabine [1000 mg/m intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m intravenously).

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: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes.

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The incidence of ovarian cancer, which has had a poor prognosis, is increasing annually. Currently, the prognosis is expected to improve with the use of molecular-targeted drugs and immune checkpoint inhibitors as maintenance therapies after the first-line chemotherapy. The GOG218 and ICON7 studies reported the usefulness of bevacizumab and the SOLO-1 and PRIMA (A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy) studies have reported the usefulness of olaparib and niraparib, respectively.

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The molecular mechanisms responsible for the progression of ovarian cancer remain incompletely understood. By targeting multiple cancer-related genes, microRNAs (miRNAs) have been identified as key regulators of cancer development and progression. In addition, the microenvironment, which constitutes cancer glands and the surrounding stromal tissue at the invasive front, has an important role in cancer progression.

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Immune checkpoint inhibitors (ICIs) have demonstrated marked clinical effects worldwide, and "cancer immunotherapy" has been recognized as a feasible option for cancer treatment. Significant treatment responses have already been attained for malignant melanoma and lung cancer, ahead of gynecologic cancer. In cervical cancer, however, results are only available from phase II trials, not from phase III trials.

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  • * Bevacizumab beyond PD (BBP) has shown to extend overall survival in recurrent colorectal cancer and prolong progression-free survival in recurrent breast and lung cancers.
  • * Two key studies, MITO16/MaNGO-OV2B and JGOG3023, evaluated BBP for ovarian cancer, indicating its potential to improve treatment outcomes for patients with difficult-to-treat cases.
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  • - Cervical cancer is the fourth most common cancer among women globally, with advancements in treatment through angiogenesis inhibitors but a median survival of only 16.8 months for advanced cases.
  • - The current 5-year survival rate for all stages of cervical cancer stands at 68%, highlighting the need for better treatment options.
  • - Immunotherapy has shown promise in various cancers and is being explored in cervical cancer, with ongoing clinical trials aimed at defining its future role in treatment.
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  • - In Japan, bevacizumab is not established as effective or safe for treating recurrent cervical cancer; however, this study presents two cases where it was used successfully alongside chemotherapy after pelvic radiation.
  • - Case 1 involved a 62-year-old woman with stage IIIB cervical cancer who received chemotherapy with paclitaxel, carboplatin, and bevacizumab, resulting in a complete response.
  • - Case 2 featured a 52-year-old woman with stage IIB cervical cancer who underwent chemotherapy with paclitaxel, cisplatin, and bevacizumab, achieving stable disease; side effects were mostly manageable, with minimal severe reactions observed.
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Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) contribute to invasive and metastatic abilities of ovarian cancer (OC) cells. In the present study, we attempted to identify the role of CAF- and EMT-related proteins in OCs, including serous carcinoma, mucinous carcinoma, endometrioid carcinoma and clear cell carcinoma using an immunohistochemical approach. The following CAF-related markers were used: CD10, podoplanin, fibroblast activating protein (FAP), platelet derived growth factor receptor (PDGFRα), PDGFRβ, S100A4 and α-smooth muscle actin (α-SMA).

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  • Primary ovarian leiomyosarcoma (POLMS) is a rare type of cancer, and the best treatment approach is still unclear.
  • A 40-year-old woman had her left ovary surgically treated for what was initially thought to be a benign leiomyoma, but later developed metastatic leiomyosarcoma after recurrence and spread of the disease.
  • She underwent gemcitabine and docetaxel (GD therapy) for treatment, which led to significant tumor shrinkage and she is still alive after 24 cycles, suggesting GD therapy may be promising for treating POLMS.
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This phase 1, open-label, dose-escalation study was conducted to determine the safety, tolerability, pharmacokinetics and preliminary efficacy of veliparib with carboplatin and weekly paclitaxel in Japanese women with newly diagnosed, advanced ovarian cancer. Patients received veliparib at 100 or 150 mg b.i.

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