Publications by authors named "Takashi Iwata"

Article Synopsis
  • A study explored the effectiveness of the oral human papillomavirus (HPV) vaccine IGMKK16E7 in treating cervical intraepithelial neoplasia, showing promising results where some patients experienced a complete histological response.
  • Researchers analyzed cervix-exfoliated cell samples from 42 patients to identify biomarkers that could predict the success of the vaccine, focusing on various gene expressions related to immune response.
  • The key finding was that lower levels of the biomarker CD86 correlated with a higher likelihood of achieving a complete response to the vaccine, with CD86-low patients demonstrating a significantly increased response rate compared to those with higher CD86 levels.
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Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming.

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Purpose: To compare the acute effects of electrical stimulation (ES) of the lower extremities on postprandial hyperglycemia and arterial stiffness during oral glucose tolerance testing (OGTT).

Methods: In a randomized crossover study, eight healthy young men completed three experimental trials in which they underwent ES for 30 min, starting 60 min before (Before) or 30 min after (After) ingesting 75 g of glucose; ES was not performed in the control trial (Control). The subjects' blood glucose levels and brachial-ankle pulse wave velocity (baPWV) were measured as an index of arterial stiffness at baseline and 30, 60, and 120 min after glucose ingestion.

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Stearoyl-CoA desaturase 1 (SCD1) is an attractive target for cancer therapy. However, the clinical efficacy of SCD1 inhibitor monotherapy is limited. There is thus a need to elucidate the mechanisms of resistance to SCD1 inhibition and develop new therapeutic strategies for combination therapy.

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The concept of gastric-type mucinous carcinoma of the uterine cervix (GAS) has been accepted worldwide because of its aggressive clinical behaviour and the absence of high-risk human papilloma virus infection. The World Health Organization (WHO) 2020 classification divides cervical tumours into two categories: human papilloma virus-associated and human papilloma virus-independent. Hence, GAS is now classified as an human papilloma virus-independent gastric type.

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We report a patient with idiopathic intracranial hypertension (IIH) with bilateral transverse sinus occlusion treated by a lumboperitoneal shunt. A 45-year-old woman presented with visual disturbance and chronic headache. Magnetic resonance (MR) venography and three-dimensional computed tomography angiography (3D-CTA) showed occlusion of both transverse sinuses.

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Purpose: Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs).

Materials And Methods: In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment.

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Background: The efficacy of intermittent cerebrospinal fluid (CSF) drainage compared with that of continuous CSF drainage in patients with subarachnoid hemorrhage (SAH) remains undetermined to date. Therefore, we investigated whether intermittent CSF drainage is effective in reducing secondary chronic hydrocephalus (sCH) after aneurysmal SAH.

Methods: Overall, 204 patients (69 men and 135 women) treated for aneurysmal SAH between 2007 and 2022 were included in this study.

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Article Synopsis
  • A clinical trial tested an oral vaccine, IGMKK16E7, derived from lacticaseibacillus to treat patients with HPV-16-positive cervical lesions, aiming to promote local immune responses as opposed to systemic ones.
  • Results showed that among high-dose recipients, 31.7% experienced complete regression of lesions compared to only 12.5% in the placebo group, indicating potential effectiveness of the vaccine.
  • The study found no significant difference in adverse effects between high-dose and placebo groups, suggesting that IGMKK16E7 is safe while leading to promising immune responses against HPV-16.
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Human papillomavirus type 31 (HPV31) is detected less frequently in cervical cancer than two major causative types, HPV16 and HPV18. Here, we report a comprehensive analysis of HPV31 genome sequences in cervical lesions collected from Japanese women. Of 52 HPV31-positive cervical specimens analyzed by deep sequencing, 43 samples yielded complete genome sequences of around 7900 base pairs and 9 samples yielded partially deleted genome sequences.

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We previously reported that the inhibition of stearoyl-CoA desaturase 1 (SCD1) enhances the antitumor function of CD8 T cells indirectly via restoring production of DC recruiting chemokines by cancer cells and subsequent induction of antitumor CD8 T cells. In this study, we investigated the molecular mechanism of direct enhancing effects of SCD1 inhibitors on CD8 T cells. In vitro treatment of CD8 T cells with SCD1 inhibitors enhanced IFN-γ production and cytotoxic activity of T cells along with decreased oleic acid and esterified cholesterol, which is generated by cholesterol esterase, acetyl-CoA acetyltransferase 1 (ACAT1), in CD8 T cells.

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Purpose: Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, is an unremitting problem for cancer patients. Anamorelin has become available for cancer-associated cachexia, but early discontinuation is common in clinical practice. This study aimed to explore factors related to the early discontinuation of anamorelin and its relationship to survival.

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Unlabelled: Ovarian cancer has a poor prognosis and is difficult to detect in early stages. Therefore, developing new diagnostic markers for early-stage ovarian cancer is critical. Here, we developed a diagnostic marker for early-stage ovarian cancer on the basis of fatty acid metabolism characteristics of cancer cells.

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Article Synopsis
  • - In Japan, the first HPV vaccine for HPV 16 and 18 was approved in 2009, showing effectiveness in reducing high-grade cervical lesions in young women, but lacking evidence for effects on invasive cervical cancer (ICC). - A study analyzed cancer registry data and found a significant decline in ICC cases among women aged 20-29 from 2016-2019, with cases falling from 3.6 to 2.8 per 100,000 women-years, and from 256 to 135 cases annually between 2011-2020. - The study also noted a decrease in HPV 16/18 prevalence in ICC diagnosed in women under 40, particularly in those aged 20-29, suggesting potential population-level
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Article Synopsis
  • Japan's health insurance covers multigene panel testing for gynecologic cancer, and this study assessed its availability and effectiveness in clinical settings.
  • Among 102 patients, various types of gynecologic cancers were studied, with most showing druggable gene alterations; notably, the PIK3CA mutation was the most common.
  • Despite many patients having actionable genetic changes, only 10.8% received targeted therapy, highlighting issues with timely treatment and the need to consider patient conditions before testing.
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Metastatic pancreatic cancer is a rare condition and cases of pancreatic metastasis from cervical cancer are infrequently reported. Furthermore, the incidence rates of pancreatic tumors as the cause of pancreatitis and of pancreatitis in patients with pancreatic tumors are similarly low. Pancreatitis may occur when a tumor obstructs the pancreatic duct.

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Objective: To identify candidate predictors for the prognosis of cervical intraepithelial neoplasia 2 (CIN2) lesions and evaluate the prognostic value of the local immune response.

Methods: One hundred fifteen CIN2 patients were enrolled. The percentage of p16-, minichromosome maintenance complex component 2- or apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G)-positive cells was determined immunohistochemically.

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Background: Human papillomavirus (HPV) type 67 is phylogenetically classified into Alphapapillomavirus species 9 (alpha-9) together with other carcinogenic types (HPV16, 31, 33, 35, 52 and 58), but is the only alpha-9 type defined as possibly carcinogenic. This study aimed to determine whole-genome sequences of HPV67 isolated from Japanese women with cervical cancer or cervical intraepithelial neoplasia (CIN) to better understand the genetic basis of the oncogenic potential of HPV67.

Methods: Total cellular DNA isolated from cervical exfoliated cells that were single positive for HPV67 (invasive cervical cancer, n = 2; CIN3, n = 6; CIN 2, n = 1; CIN1, n = 2; the normal cervix, n = 1) was subjected to PCR to amplify HPV67 DNA, followed by next generation sequencing to determine the complete viral genome sequences.

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The present study investigated the effects of dietary supplementation combined with fish oil containing relatively low levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the inflammatory and nutritional status of patients with epithelial cancer. Fish oil capsules (498 mg EPA and 213 mg DHA) and dietary supplements (100 kcal and 5 g protein) were administered for 8 weeks to 20 patients with cancer and inflammation [C-reactive protein (CRP) ≥0.30 mg/dl].

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Although geographical differences in the distribution of human papillomavirus genotypes have been observed worldwide, no studies have reported on national differences in the prevalence of human papillomavirus types in Japan. Here, we report a cross-sectional study to explore regional differences in the prevalence of human papillomavirus types among Japanese women with cervical intraepithelial neoplasia or invasive cervical cancer. Using human papillomavirus genotyping data from the nationwide prospective study on human papillomavirus vaccine effectiveness, we compared the frequency of detection of 15 high-risk and two low-risk human papillomavirus types in each disease category between the women who visited hospitals located in eastern Japan and those who visited hospitals located in western Japan.

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Background: Understanding the mechanisms of non-T cell inflamed tumor microenvironment (TME) and their modulation are important to improve cancer immunotherapies such as immune checkpoint inhibitors. The involvement of various immunometabolisms has recently been indicated in the formation of immunosuppressive TME. In this study, we investigated the immunological roles of stearoyl-CoA desaturase 1 (SCD1), which is essential for fatty acid metabolism, in the cancer immune response.

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Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double-blind, placebo-controlled KEYNOTE-826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m  + cisplatin 50 mg/m or carboplatin AUC 5) with or without bevacizumab 15 mg/kg.

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