Publications by authors named "Hideaki Takahashi"

281 Publications

Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade.

Cancers (Basel) 2021 Jul 14;13(14). Epub 2021 Jul 14.

Department of Urology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.

Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, MAPK, TGFβ, estrogen receptor (ER), Hedgehog (HH), and PI3K signaling pathway activity scores (PAS) were determined based on the expression levels of target genes. Additionally, 5-alpha reductase type 1 () expression was determined. These markers were related to clinical benefit (complete/partial response or stable disease ≥6 months) and progression-free and overall survival (PFS/OS). expression had the highest general predictive value for clinical benefit and positive predictive value (PPV: 85.7%). AR PAS had the highest negative predictive value (NPV: 93.3%). The fitting of a multivariable model led to the identification of , TGFβ, and Notch PAS as the most predictive combination. High AR, high Notch, high ER, low HH PAS, and high expression were also of prognostic importance regarding PFS and expression levels for OS. AR, Notch PAS, and expression have the potential to predict the clinical benefit of CAB treatment in SDC patients. expression can identify patients that will and AR PAS patients that will not experience clinical benefit (85.7% and 93.3% for PPV and NPV, respectively). The predictive potential of expression forms a rational basis for including SRD5A1-inhibitors in SDC patients' treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13143527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307921PMC
July 2021

Validation of the risk factors for primary control of early T-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma by transoral surgery: a prospective observational study.

Int J Clin Oncol 2021 Jul 21. Epub 2021 Jul 21.

Department of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Background: We had previously identified the following risk factors for insufficient control of early T-stage head and neck cancer by transoral surgery (TOS): (1) tumor thickness > 7 mm on enhanced computed tomography (CT), and (2) poor differentiation in pathological examination. We subsequently used a different patient cohort to validate the usefulness of these factors in determining the need for adaptation of TOS.

Study Setting: A prospective observational study METHODS: Patients who received TOS as a definitive treatment between April 1, 2016 and September 30, 2020 were included. Primary control rates (by single TOS and TOS alone) in relation to the above-mentioned risk factors were calculated. Overall (O), recurrence-free (RF), and disease-free (DF) survival (S) outcomes were evaluated. A combination analysis based on the number of risk factors was also performed.

Results: Patients with tumor thickness > 7 mm had a 2.88-fold [95% confidence interval (CI) 1.01-8.51] higher risk of incomplete primary resection by single TOS, while patients who showed poor differentiation on pathological assessments had a 13.14-fold (95% CI 3.66-47.14) higher risk of insufficient primary control by TOS alone. The 3 year OS, RFS, and DFS rates were 99%, 83%, and 63%, respectively. Patients with both risk factors had a 93.00-fold (95% CI 4.99-1732.00) higher risk of incomplete primary control by TOS alone.

Conclusions: Among patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma, primary control by TOS alone may not be achieved in patients with both risk factors, that is, tumor thickness > 7 mm as measured by enhanced CT and poor differentiation on pathological examination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-01992-yDOI Listing
July 2021

[Ⅲ. Reprogramming of Cancer-Associated Neurons by Mutant p53].

Gan To Kagaku Ryoho 2021 Jul;48(7):900-902

Dept. of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University.

View Article and Find Full Text PDF

Download full-text PDF

Source
July 2021

[Cancer screening rates and characteristics of low-participating groups in Sapporo city].

Nihon Koshu Eisei Zasshi 2021 Jul 15. Epub 2021 Jul 15.

Public Health Office, City of Sapporo.

Objectives The purpose of this study was to assess the situation of regional cancer screening of individuals in Sapporo city through an independent survey and to identify groups with low cancer screening rates.Methods We conducted a self-administered questionnaire survey on 3,000 men aged 40 to 69 years and 4,000 women aged 20 to 69 years living in Sapporo (response rate = 32.4%). The contents of the survey were quoted from the health slips of the Comprehensive Survey of Living Conditions related to cancer screening, as well as basic and cancer-related attributes. We analyzed the relationship between cancer screening participation rate, basic attributes, and cancer-related attributes using the χ test or logistic regression analysis.Results The screening rates recorded in this study for gastric, colon, and lung cancers were 67.4%, 59.2%, and 66.1%, respectively in men, and 48.7%, 47.7%, and 53.4%, respectively in women. The screening rates were 52.7% and 56.1% for uterine and breast cancers, respectively. The participation rate of non-working individuals and those who had National Health Insurance was significantly lower for all cancer types among both men and women. Regarding attributes and cancer screening, the odds ratio of working to non-working individuals was 3.00 to 3.09 in men and 1.41 to 2.46 in women. The odds ratio of non-National Health Insurance individuals was 3.47 to 4.26 in men and 1.47 to 2.52 in women. In addition, there was a significant association between awareness and rates of Sapporo city cancer screening in both men and women, with the exception of stomach cancer screening in women. Furthermore, the odds ratio of awareness was 1.41 to 1.74 in men and 1.24 to 1.48 in women.Conclusion The cancer types with screening rate below 50% were gastric and colon cancers in women. In men, the screening rate for gastric, colon, and lung cancers exceeded 50%. The cancer-screening rate was found to be low among both non-working men and women, those with national health insurance, or those who do not recognize the Sapporo city cancer screening (regional screening). The characteristics of the group with low participation status in Sapporo city, which was the only parameter not reported in the Comprehensive Survey of Living Conditions, has been clarified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11236/jph.21-012DOI Listing
July 2021

FosL1 Regulates Regional Metastasis of Head and Neck Squamous Cell Carcinoma by Promoting Cell Migration, Invasion, and Proliferation.

Anticancer Res 2021 Jul;41(7):3317-3326

Department of Biology and Function in Head and Neck, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Background/aim: We evaluated the impact of FosL1, a member of the activated protein-1 family, on the pathways leading to regional metastasis of head and neck squamous cell carcinoma (HNSCC).

Materials And Methods: We examined the influence of small interfering RNA (siRNA) and short heparin RNA (shRNA) mediated knockdown of FosL1 on cell migration, invasion, and proliferation in vitro as well as on regional metastasis in vivo. The prognostic significance of FosL1 was also analyzed using the Kaplan- Meier plotter using data from an HNSCC patient database.

Results: Down-regulation of FosL1 inhibited cell migration, invasion, and proliferation in vitro, decreased the incidence of regional metastases, and prolonged the survival of mice in vivo. We also determined that HNSCC patients with higher expression levels of FosL1 had a significantly shorter survival time than those with low expression of FosL1.

Conclusion: FosL1 plays a crucial role in promoting cell migration, invasion, and proliferation in HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15119DOI Listing
July 2021

Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA.

Cancer Sci 2021 Jun 15. Epub 2021 Jun 15.

Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.

Comprehensive genomic profiling (CGP) is being increasingly used for the routine clinical management of solid cancers. In July 2018, the use of tumor tissue-based CGP assays became available for all solid cancers under the universal health insurance system in Japan. Several restrictions presently exist, such as patient eligibility and limitations on the opportunities to perform such assays. The clinical implementation of CGP based on plasma circulating tumor DNA (ctDNA) is also expected to raise issues regarding the selection and use of tissue DNA and ctDNA CGP. A Joint Task Force for the Promotion of Cancer Genome Medicine comprised of three Japanese cancer-related societies has formulated a policy proposal for the appropriate use of plasma CGP (in Japanese), available at https://www.jca.gr.jp/researcher/topics/2021/files/20210120.pdf, http://www.jsco.or.jp/jpn/user_data/upload/File/20210120.pdf, and https://www.jsmo.or.jp/file/dl/newsj/2765.pdf. Based on these recommendations, the working group has summarized the respective advantages and cautions regarding the use of tissue DNA CGP and ctDNA CGP with reference to the advice of a multidisciplinary expert panel, the preferred use of plasma specimens over tissue, and multiple ctDNA testing. These recommendations have been prepared to maximize the benefits of performing CGP assays and might be applicable in other countries and regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.15022DOI Listing
June 2021

Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu-opioid receptor.

J Cell Physiol 2021 May 26. Epub 2021 May 26.

Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

The Mu-opioid receptor (MOR) has been implicated in tumorigenesis and metastasis. Methylnaltrexone (MNTX), an antagonist of MOR, has shown to inhibit tumor growth and metastasis in lung cancer cell lines. The effect of MNTX on other cell lines such as head and neck squamous cell carcinoma (HNSCC) has not been investigated. We measured the expression and activity of the receptor in different HNSCC cell lines. Then, we evaluated the impact of modulating the expression MOR and the effect of MNTX on the proliferation, clonogenic activity, invasion, and migration of two HNSCC (FaDu and MDA686Tu) cell lines expressing MOR and one cell line (UMSCC47) not expressing the receptor. We also evaluated the impact of MNTX on tumor growth and metastasis formation in vivo. Activation of the receptor with [d-Ala2,N-Me-Phe4, Gly5-ol] (DAMGO) caused a significant reduction in cyclic adenosine monophosphate levels in FaDu cells. Knockdown of MOR inhibited in vitro aggressive cell behaviors on FaDu and MDA686Tu cells and correlated with a reduction in markers of epithelial-mesenchymal transition. In vitro studies showed that MNTX strongly inhibited the proliferation, clonogenic activity, invasion, and migration of FaDu and MDA686Tu cells but has no effect on UMSCC47 cells. In vivo experiments demonstrated that MNTX suppresses tumor growth in HNSCC cell tumor-bearing mice. Our studies indicate that MOR could be considered as a therapeutic target to treat HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.30421DOI Listing
May 2021

Disturbance of osteonal bone remodeling and high tensile stresses on the lateral cortex in atypical femoral fracture after long-term treatment with Risedronate and Alfacalcidol for osteoporosis.

Bone Rep 2021 Jun 7;14:101091. Epub 2021 May 7.

Niigata Rehabilitation Hospital, 761 Kizaki, Kita-ku, Niigata-shi, Niigata 950-3304, Japan.

An 83 year-old Japanese woman complained of left lateral thigh pain following a low-energy fall 4 months prior to admission. She had been treated for osteoporosis with Risedronate and Alfacalcidol for the previous five years. She was diagnosed with an atypical femoral fracture (AFF) according to the American Society for Bone and Mineral Research (ASBMR) Task Force revised criteria. Radiographs revealed cortical thickening and a transverse radiolucent fracture line in the lateral cortex of the shaft. MRI showed a high intensity signal on the T2WI image 1 cm long in the lateral cortex. The patient had normal levels of bone resorption and formation biomarkers except for low 25(OH) Vitamin D. Double fluorescent labeling was done preoperatively. Due to significant bowing, a corrective osteotomy and intramedullary nailing were performed, and the resected bone wedge was analyzed by bone histomorphometry. Three ground sections of the lateral cortex at the fracture site showed many and large pores, with or without tetracycline labeling. Histomorphometric assessment was done on intracortical pores, classified by a novel criteria, only to assess size of the pores to know prolonged osteoclastic activity and its characteristics of inner surfaces to assess whether bone formation has been occurring or not in labeling period in remodeling cycle, and coalition of multi-pores. Increased size with widespread variation of pores suggested prolonged osteoclastic activity in the reversal/resorptive phase. Bone labeling showed lamellar bone on the endocortical surface. We hypothesize that the case had developed from a regional disturbance of osteonal remodeling in the lateral cortex, in which accumulated microcracks might have initiated a resorption process resulting in resorption cavities, i.e., pores, which became larger due to prolonged activity of secondary osteoclasts. Various sized pores could form lamellar bone, still forming at the time of biopsy, some had formed lamellar bone, but stopped to form before labeling and not to start to form at all, probably due to incomplete coupling. Endocortical lamellar bone might had started to resorbed to smooth off endocortical surface, followed by formation of lamellar bone. The endocortical bone formation was assessed and its formation period is about 2.7 years. A finite element analysis using preoperative CT data revealed high tensile stresses on the lateral aspect of the femur. Histomorphometric results suggest that there might be more pores in the tensile area than the compressive area. These findings may subsequently connect accumulation of microcracks, an increase of size and number of pores and coalition and subsequent fracture in the lateral cortex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bonr.2021.101091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138479PMC
June 2021

Guidelines for clinical evaluation of anti-cancer drugs.

Cancer Sci 2021 Jul 8;112(7):2563-2577. Epub 2021 Jun 8.

Office of New Drug V, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.

Clinical studies intended for regulatory approval must demonstrate the clinical benefits of the drug in a target population. Clinical development of a drug proceeds by stepwise clinical studies; after safety and pharmacokinetics are evaluated and the recommended dosage and administration are determined, efficacy and safety are evaluated in an exploratory manner, and finally clinical benefits are compared with conventional standard therapies. Guidelines for the clinical evaluation of anti-cancer drugs in Japan were established in 1991 and amended in 2006 after molecular-targeted drugs were introduced. Recent progress in the development of drugs acting on the immune system and cancer genomic medicine targeting rare but important molecular subtypes have altered the strategy for development of anti-cancer drugs. It is often difficult to conduct a confirmatory randomized controlled study using overall survival as the primary endpoint in rare molecular subtypes, and the primary evaluation of the efficacy of some drugs and subsequent approval is based on the tumor response. As conducting clinical studies for rare subtypes solely within Japan is difficult, drug development needs to be conducted within a global study. However, this requires robust monitoring to detect possible ethnic differences in pharmacokinetics and drug efficacy. Development using the conditional approval system for drugs enforced in 2020 may be considered, when clinical utility is evaluated based on surrogate endpoints. Because of these changes, we have revised the guidelines for the clinical evaluation of anti-cancer drugs in Japan. To promote global development of anti-cancer drugs involving Japan, the guidelines have been translated into English.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253284PMC
July 2021

Mu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma.

Life Sci 2021 Aug 27;278:119541. Epub 2021 Apr 27.

Department of Anesthesiology and Perioperative Medicine, the University of Texas MD, Anderson Cancer Center, Houston, TX 77030, USA; Anesthesiology and Surgical Oncology Research Group, Houston, TX 77030, USA. Electronic address:

Aims: In vitro and in vivo studies suggest that the mu-opioid receptor (MOR) is involved in tumorigenesis, and metastasis in cancer. In humans, the use of MOR agonists (opioids) is associated with head and neck squamous cell carcinoma (HNSCC) progression. In the present study, we aimed to examine the role of MOR activation in MOR (+) HNSCC.

Main Methods: FaDu, MDA686Tu and UMSCC47 cell lines were used in in vitro and in vivo experiments. Cells and animals were treated with a highly selective MOR agonist DAMGO, [D-Ala (2), Me Phe (4), Glycol (5)]-enkephalin] or saline 0.9%.

Key Findings: MOR activation significantly increased the proliferation, colony formation, invasion, and migration of FaDu and MDA6868Tu cells and promoted tumor growth in vivo.

Significance: These findings suggest that MOR is implicated in tumorigenesis of HNSCC. Overall, our findings identify that MOR could be used as a potential therapeutic target in patients with MOR (+) HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119541DOI Listing
August 2021

Pathogenic Role of Immune Evasion and Integration of Human Papillomavirus in Oropharyngeal Cancer.

Microorganisms 2021 Apr 21;9(5). Epub 2021 Apr 21.

Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-Ku, Yokohama 236-0004, Japan.

The incidence of oropharyngeal cancer (OPC) is increasing remarkably among all head and neck cancers, mainly due to its association with the human papillomavirus (HPV). Most HPVs are eliminated by the host's immune system; however, because HPV has developed an effective immune evasion mechanism to complete its replication cycle, a small number of HPVs are not eliminated, leading to persistent infection. Moreover, during the oncogenic process, the extrachromosomal HPV genome often becomes integrated into the host genome. Integration involves the induction and high expression of E6 and E7, leading to cell cycle activation and increased genomic instability in the host. Therefore, integration is an important event in oncogenesis, although the associated mechanism remains unclear, especially in HPV-OPC. In this review, we summarize the current knowledge on HPV-mediated carcinogenesis, with special emphasis on immune evasion and integration mechanisms, which are crucial for oncogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms9050891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143538PMC
April 2021

The Seasonality of Peripheral Venous Catheter-Related Bloodstream Infections.

Infect Dis Ther 2021 Mar 6;10(1):495-506. Epub 2021 Feb 6.

Department of Infection Prevention and Control, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Introduction: Although the seasonality of infectious diseases has been widely reported, the seasonality of peripheral venous catheter-related bloodstream infection (PV-CRBSI) has not been investigated. This study investigated the seasonality of PV-CRBSI and its relationship with meteorological conditions.

Methods: A retrospective cohort study of PV-CRBSI at Tokyo Medical University Hospital (Tokyo, Japan), from 2009 to 2019, provided the data for descriptive and time series analyses used to evaluate the number of PV-CRBSI cases per 1000 admissions that occurred each month for each causative organism. By performing univariate and multivariate analyses, the researchers investigated the seasonality of cases and the relationships between meteorological conditions, other external factors, and PV-CRBSIs.

Results: This study included a total of 184 PV-CRBSI cases. The mean numbers of PV-CRBSI cases per 1000 admissions caused by all organisms, Bacillus cereus, Gram-positive cocci, and Gram-negative rods were 0.67, 0.15, 0.37, and 0.16 per month, respectively, during the study period. The time series analysis showed that the incidences of PV-CRBSI cases associated with B. cereus and Gram-negative rods were significantly different in the winter/spring from those in the summer/autumn (P < 0.05). The incidence of PV-CRBSI cases caused by B. cereus peaked during summer. The incidence of PV-CRBSI cases caused by B. cereus was significantly positively associated with average monthly temperature, whereas the incidence of PV-CRBSIs caused by Gram-negative rods was significantly negatively associated with average daylight hours.

Conclusion: The incidence of PV-CRBSIs caused by B. cereus showed seasonality, peaking during the summer, and a significant correlation was found between PV-CRBSIs caused by B. cereus and average monthly temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-021-00407-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954888PMC
March 2021

Practical Application of Miyazaki Jitokko Chickens Selected for a Superior Allele at a Single Nucleotide Polymorphism Site in the Cholecystokinin Type A Receptor Gene.

J Poult Sci 2021 Jan;58(1):12-20

Institute of Livestock and Grassland Science, NARO, Tsukuba 305-0901, Japan.

This study aimed to examine 1) whether selection for a superior allele at a single nucleotide polymorphism site (SNP; AB604331, g.420 C>A) of the chicken cholecystokinin type A receptor () gene in Miyazaki Jitokko chickens is detectable in commercial poultry farms, and 2) whether the reproductive traits of the Kyushu Rhode hens, as a maternal stock line of the Miyazaki Jitokko chickens, are affected by SNP selection. Conventional and A-allele fixed (improved) Miyazaki Jitokko chicks were hatched on the same day and raised in a battery cage until 7 days of age. The chicks were then deposited at two commercial poultry farms and reared until slaughter at 126 and 163 days for cockerels and pullets, respectively. Body weight on the day of hatching (day 0), at 5 days of age, and at slaughter were measured. The differences in the body weights of the farm and test groups at slaughter were analyzed using the generalized linear model. A-allele fixation increased the body weight at slaughter by approximately +123.5 g and +131.9 g in cockerels and pullets, respectively. No significant differences between the conventional and improved hens were detected in terms of egg-laying rate, fertilization rate, and hatchability in the Kyushu Rhode hens. The data suggest that fattening chicks can be supplied as usual, even if Kyushu Rhode hens are switched from the conventional to improved type. In conclusion, genetic improvements using the SNP site as a marker were effectively established in terms of the growth of the Miyazaki Jitokko chickens in commercial farms and the reproductive traits of the Kyushu Rhode hens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2141/jpsa.0190127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837808PMC
January 2021

FOLFIRINOX in advanced pancreatic cancer patients with the double-variant type of UGT1A1 *28 and *6 polymorphism: a multicenter, retrospective study.

Cancer Chemother Pharmacol 2021 03 2;87(3):397-404. Epub 2021 Jan 2.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.

Background: UGT1A1 *28 and *6 polymorphism is associated with reduced enzyme activity and severe toxicities of irinotecan, especially in patients with homozygous or heterozygous for UGT1A1*28 or *6 polymorphism for both UGT1A1*28 and *6 (double-variant-type of UGT1A1 polymorphism, UGT1A1-DV). FOLFIRINOX is one of the standard treatments for metastatic pancreatic cancer (PC). The optimal dose of irinotecan as a component of the FOLFIRINOX has not been established yet for patients with UGT1A1-DV.

Patients And Methods: Advanced PC patients with UGT1A1-DV who had received at least one cycle of FOLFIRINOX from December 2013 to March 2016 were collected retrospectively conducted at multicenter in Japan. We evaluated the patient characteristics, efficacy and safety of FOLFIRINOX and investigate the optimal initial dose of irinotecan in Japanese advanced PC patients with UGT1A1-DV.

Results: A total of 31 patients were enrolled. Grade 4 neutropenia was seen more frequently (67%; 4/6) in patients who had received irinotecan at an initial dose of  ≥ 150 mg/m than in those who had received the drug at an initial dose of  ≤ 120 mg/m (20%; 5/24). The response rate (RR) and progression-free survival (PFS) in patients given irinotecan of  ≤ 120 mg/m were 21.4% and 8.1 months, respectively, which were consistent with previous report for patients without UGT1A1-DV.

Conclusion: Based on our findings, we recommend that in Japanese advanced PC patients with UGT1A1- DV treated with FOLFIRINOX, irinotecan be administered at an initial dose of  ≤ 120 mg/m.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-020-04206-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889544PMC
March 2021

Multicenter Retrospective Analysis of Chemotherapy for Advanced Pancreatic Acinar Cell Carcinoma: Potential Efficacy of Platinum- and Irinotecan-Containing Regimens.

Pancreas 2021 01;50(1):77-82

Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo.

Objectives: The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC).

Methods: Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument.

Results: The most commonly selected treatment regimens were gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens. The overall response rate in the patients who received first-line chemotherapy were 7% and 38%, respectively, and the median overall survival was 13.2 months. When the data for all the treatment lines were aggregated, the response rates to gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens were 7%, 18%, 40%, and 29%, respectively. The overall survival tended to be better in patients who had received a platinum-containing regimen (hazard ratio, 0.50; 95% confidence interval, 0.23-1.11; P = 0.08) or irinotecan-containing regimen (hazard ratio, 0.42; 95% confidence interval, 0.15-1.19; P = 0.09) at least once in the treatment course as compared with those who had not.

Conclusions: Our findings suggested that platinum- and irinotecan-containing regimens exhibited some potential efficacy in patients with advanced PACC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748047PMC
January 2021

Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (edition 2.1).

Int J Clin Oncol 2021 Feb 29;26(2):233-283. Epub 2020 Nov 29.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.

Background: To promote precision oncology in clinical practice, the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association, jointly published "Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment" in 2017. Since new information on cancer genomic medicine has emerged since the 1st edition of the guidance was released, including reimbursement for NGS-based multiplex gene panel tests in 2019, the guidance revision was made.

Methods: A working group was organized with 33 researchers from cancer genomic medicine designated core hospitals and other academic institutions. For an impartial evaluation of the draft version, eight committee members from each society conducted an external evaluation. Public comments were also made on the draft. The finalized Japanese version was published on the websites of the three societies in March 2020.

Results: The revised edition consists of two parts: an explanation of the cancer genomic profiling test (General Discussion) and clinical questions (CQs) that are of concern in clinical practice. Particularly, patient selection should be based on the expectation that the patient's post-test general condition and organ function will be able to tolerate drug therapy, and the optimal timing of test should be considered in consideration of subsequent treatment plans, not limited to treatment lines.

Conclusion: We expect that the revised version will be used by healthcare professionals and will also need to be continually reviewed in line with future developments in cancer genome medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-020-01831-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819967PMC
February 2021

Intraductal Papillary Mucinous Neoplasm with Pancreatogastric Fistula.

Intern Med 2021 Apr 23;60(8):1211-1215. Epub 2020 Nov 23.

Department of Internal Medicine, Division of Gastroenterology, Sapporo Shirakabadai Hospital, Japan.

We herein report a rare case of intraductal papillary mucinous neoplasm with a pancreatogastric fistula in an elderly Japanese man admitted to our hospital. The pancreatogastric fistula was confirmed using endoscopic retrograde pancreatography via a cannulated guidewire placed in the stomach. Six months after admission, the patient was diagnosed with intraductal papillary mucinous carcinoma. A pancreatogastric fistula is generally a rare complication of intraductal papillary mucinous neoplasm. It was caused by mechanical penetration in this case. Interestingly, we also observed endoscopic and histochemical mucosal changes in the fistula.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.5889-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112989PMC
April 2021

Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients.

Cancers (Basel) 2020 Nov 18;12(11). Epub 2020 Nov 18.

Department of Otorhinolaryngology, Head and Neck Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.

No real-world, long-term outcomes of immunotherapy with nivolumab for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have yet been reported. Furthermore, the prognostic impact of the best overall response (BOR) of this therapy remains unclear. We conducted a multi-institutional cohort study of the long-term efficacy and safety of this therapy and investigated prognostic factors associated with survival. Further, we evaluated the relationship between BOR and survival. Median follow-up time was 25.9 months. Median overall survival (OS) was 9.6 months, and two-year survival rate was 25.0%. Median progression-free survival (PFS) was 3.7 months, and two-year PFS rate was 19.6%. BOR was assessed as complete response (CR) in 6%, partial response (PR) in 13%, stable disease (SD) in 30%, and progressive disease (PD) in 52% of the patients. Overall response rate was 18%, and disease control rate was 48%. For immune-related adverse events (irAEs), 38 irAEs were detected in 29 patients. On multivariate analysis, the development of irAEs was significantly associated with better OS and PFS. Better BOR was significantly associated with longer OS and PFS. These findings demonstrate the long-term efficacy and safety of nivolumab therapy for R/M SCCHN in a real-world setting. The magnitude of BOR and the development of irAEs might be useful surrogate markers of survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12113427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699139PMC
November 2020

Effects of the linagliptin, dipeptidyl peptidase-4 inhibitor, on bone fragility induced by type 2 diabetes mellitus in obese mice.

Drug Discov Ther 2020 Nov 29;14(5):218-225. Epub 2020 Oct 29.

Department of Clinical Pharmacotherapy, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.

Recently, it has been suggested that glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), which play important roles in the homeostasis of glucose metabolism, could be involved in the regulation of bone metabolism. Inhibitors of dipeptidyl peptidase 4 (DPP-4), an enzyme that degrades GIP and GLP-1, are widely used clinically as a therapeutic agent for diabetes. However, the effects of DPP-4 inhibitors on bone metabolism remain unclear. In this study, we investigated the effects of linagliptin, a DPP-4 inhibitor, on bone fragility induced by type 2 diabetes mellitus (T2DM). Non-diabetic mice were used as controls, and T2DM mice were administered linagliptin orally on a daily basis for 12 weeks. In T2DM mice, decreased bone mineral density was observed in the lower limb bones along with low serum osteocalcin levels and high serum tartrate-resistant acid phosphatase-5b (TRAP) levels. In contrast, the decreased serum osteocalcin levels and increased serum TRAP levels observed in T2DM mice were significantly suppressed after the administration of linagliptin 30 mg/kg. Bone histomorphometric analysis revealed a reduced osteoid volume and osteoblast surface with an increase in the eroded surface and number of osteoclasts in T2DM mice. This decreased bone formation and increased bone resorption observed in the T2DM mice were suppressed and trabecular bone volume increased following the administration of 30 mg/kg linagliptin. Collectively, these findings suggest that linagliptin may improve the microstructure of trabecular bone by inhibiting both a decrease in bone formation and an increase in bone resorption induced by T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5582/ddt.2020.03073DOI Listing
November 2020

Multicentre, retrospective study of the efficacy and safety of nivolumab for recurrent and metastatic salivary gland carcinoma.

Sci Rep 2020 10 12;10(1):16988. Epub 2020 Oct 12.

Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital, Tokyo, 108-8329, Japan.

Although immune-checkpoint inhibitors (ICIs) are effective against various cancers, little is known regarding their role in salivary gland carcinoma (SGC) treatment. Therefore, we evaluated the efficacy and safety of nivolumab monotherapy in patients with recurrent and/or metastatic SGC. In this multicentre retrospective study, nivolumab (240 mg) was administered every 2 weeks. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were examined; the correlation between treatment outcomes and clinicopathological factors was analysed. Twenty-four patients were enrolled; the most common histopathology was salivary duct carcinoma. Eleven tumours were PD-L1-positive; no tumour was microsatellite instability-high. The ORR was 4.2%, and the median PFS and OS were 1.6 and 10.7 months, respectively. One patient continued nivolumab for 28 months without disease progression. One patient showed grade 4 increase in creatine phosphokinase levels and grade 3 myositis. Biomarker analysis revealed significantly increased OS in patients with performance status of 0; modified Glasgow prognostic score of 0; low neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and C-reactive protein; and high lymphocyte-to-monocyte ratio and in patients who received systemic therapy following nivolumab. Although nivolumab's efficacy against SGC was limited, some patients achieved long-term disease control. Further studies are warranted on ICI use for SGC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-73965-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552420PMC
October 2020

Establishment of PDX-derived salivary adenoid cystic carcinoma cell lines using organoid culture method.

Int J Cancer 2021 01 7;148(1):193-202. Epub 2020 Oct 7.

Department of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan.

To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX-derived organoid cells were evaluated for the presence of MYB-mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC-derived organoids were successfully generated in three-dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short-term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short-term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC-derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33315DOI Listing
January 2021

The incidence of newly diagnosed secondary cancer; sub-analysis the prospective study of the second-look procedure for transoral surgery in patients with T1 and T2 head and neck cancer.

Int J Clin Oncol 2021 Jan 14;26(1):59-65. Epub 2020 Sep 14.

Department of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Background: Our prospective study of patients with early T-stage head and neck cancer indicated a high incidence of newly diagnosed secondary malignancies during the follow-up period. We aimed to determine the incidence rate and risk factors of secondary malignancies in early-stage head and neck cancer patients.

Methods: We sub-analyzed the patient data of a previous study focusing on secondary cancer incidence. The endpoints were statistical analyses of risk factors and survival and incidence rates.

Results: The incidence rate of secondary cancer was 37%, the crude incidence of second primary cancers was 10.6 per 100 person-years, and the 5 year secondary cancer-free survival rate was 63%. The hypopharynx as the primary site was an independent significant predictive factor (odds ratio 3.96, 95% confidence interval 1.07-14.6, p = 0.039).

Conclusions: Early stages of laryngeal, oropharyngeal, and hypopharyngeal cancer had a risk of secondary cancer, especially hypopharyngeal cancer. Attention to the secondary cancer has to be paid during the follow-up period after controlling the early-stage disease. These findings highlight the need for awareness of the incidence of secondary cancer in cases of early-stage primary head and neck cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-020-01779-7DOI Listing
January 2021

Salvage Chemotherapy After Nivolumab for Recurrent or Metastatic Head and Neck Carcinoma.

Anticancer Res 2020 Sep;40(9):5277-5283

Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan.

Background/aim: The treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has remained challenging. The effect of salvage chemotherapy (SCT) after nivolumab has been identified recently in other cancer types. The aim of this study was to examine the efficacy of SCT after nivolumab treatment in patients with R/M HNSCC.

Patients And Methods: A retrospective study was conducted at four institutions in Japan. Fifty-six patients were enrolled in the study.

Results: The overall survival (OS) in SCT patients was significantly longer than that in best supportive care (BSC) patients. In the SCT patients, the median OS, median progression-free survival (PFS) and objective response rate (ORR) were 7.3 months, 2.3 months and 36%, respectively. Prognostic factor for OS and ORR was performance score (PS) and previous radiation, respectively.

Conclusion: SCT after nivolumab is associated with better clinical outcomes in patients with R/M HNSCC compared to those receiving BSC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.14532DOI Listing
September 2020

Whole-exome Sequencing Reveals New Potential Susceptibility Genes for Japanese Familial Pancreatic Cancer.

Ann Surg 2020 Aug 18. Epub 2020 Aug 18.

Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.

Objective: The primary objective of this study was to identify novel genes that predispose people in the Japanese population to FPC.

Summary Of Background Data: Familial history of pancreatic cancer is an important risk factor but, to date, few genes predisposing individuals to increased risk of developing FPC have been identified.

Methods: We performed whole-exome sequencing of germline DNA from 81 Japanese FPC patients. We also investigated somatic gene alterations in 21 matched tumor tissues through whole-exome sequencing and copy number analysis.

Results: Our germline variants identified previously known FPC susceptibility genes such as ATM and BRCA2, and several novel tumor suppressor genes with potentially deleterious variants for FPC. Interestingly, somatic whole-exome analysis demonstrated that most tumor samples with suspicious loss of heterozygosity of candidate genes were KRAS wild-types, implying that these cases may not have required KRAS activation as a driver event for carcinogenesis.

Conclusions: Our findings indicate that FPC patients harbor potentially deleterious causative germline variants in tumor suppressor genes, which are known to acquire somatic mutations in pancreatic cancer, and that somatic loss of heterozygosity of some FPC susceptibility genes may contribute to the development of FPC in the absence of somatic KRAS-activating mutation. Genetic testing for a wider variety of FPC-predisposition genes could provide better screening approach for high-risk groups of pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004213DOI Listing
August 2020

Chemotherapy-induced neutropenia as a prognostic factor in patients with pancreatic cancer treated with gemcitabine plus nab-paclitaxel: a retrospective cohort study.

Cancer Chemother Pharmacol 2020 08 6;86(2):203-210. Epub 2020 Jul 6.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan.

Objectives: Chemotherapy-induced neutropenia (CIN) is a common adverse event of chemotherapy. Several reports have suggested that CIN could be an important prognostic factor in chemotherapy of various cancers. However, whether CIN is a prognostic factor in unresectable pancreatic cancer (PC) treated with gemcitabine plus nab-paclitaxel (GnP) is unknown. The primary endpoint of this study was to compare overall survival (OS) between patients with severe CIN (grade ≥ 3) and those with absent/mild CIN (grade ≤ 2) in unresectable PC cases treated with GnP as first-line chemotherapy.

Methods: A retrospective, cohort study was conducted using data from a computerized database. A total of 290 patients with pathologically confirmed PC treated with GnP as first-line chemotherapy were analyzed (severe CIN: ≥ grade 3, n = 174; absent/mild CIN: ≤ grade 2, n = 116).

Results: The median OS was longer in the severe CIN group than in the absent/mild CIN group (19.2 months vs 11.3 months, respectively; P < 0.001). After adjustment, severe CIN was an independent predictive factor for OS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38-0.74; P < 0.001). After adjustment by time-varying covariates, severe CIN was still a significant prognostic factor for OS (HR, 0.79; 95% CI 0.69-0.91, P = 0.001).

Conclusion: The present results show that severe CIN is an independent and useful prognostic factor in PC patients treated with GnP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-020-04110-3DOI Listing
August 2020

Age-based efficacy and safety of nivolumab for recurrent or metastatic head and neck squamous cell carcinoma: A multicenter retrospective study.

Asia Pac J Clin Oncol 2020 Dec 23;16(6):340-347. Epub 2020 Jun 23.

Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Tokyo, Japan.

Aim: This study retrospectively investigated the efficacy and safety of nivolumab for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) classified using age <65 years as the cutoff.

Methods: Overall, 88 patients with R/M HNSCC treated with nivolumab were classified into the young group (<65 years; n = 39) and elderly group (≥65 years; n = 49). Efficacy was evaluated using overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). Safety was evaluated considering immune-related adverse events (irAEs).

Results: The median OS was 9.7 and 8.6 months in the young and elderly groups, respectively. The 1-year OS rate was 42.0% and 29.4% in the young and elderly groups, respectively. The median PFS was 3.0 and 4.2 months in the young and elderly groups, respectively. The 1-year PFS rate was 30.0% and 27.9% in the young and elderly groups, respectively. In the young group, the ORR was 10.3% and DCR was 33.3%. In the elderly group, the ORR was 18.4% and DCR was 53.1%. There were no significant differences in OS, PFS, ORR, and DCR (P = 0.36, 0.53, 0.29 and 0.06, respectively). Interstitial lung disease (ILD) as an irAE occurred in the young group at a significantly higher rate (20.5% vs 4.1%; P = 0.02).

Conclusions: There were no significant differences in OS, PFS, ORR, and DCR between the young and elderly groups. DCR tended to be better in the elderly group (P = 0.06). ILD occurred at a significantly higher rate in the young group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajco.13374DOI Listing
December 2020

Phase II clinical trial of gemcitabine plus oxaliplatin in patients with metastatic pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or personal history of breast/ovarian/prostate cancer (FABRIC study).

Int J Clin Oncol 2020 Oct 13;25(10):1835-1843. Epub 2020 Jun 13.

Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.

Background: A family/personal history of breast, ovarian, or pancreatic cancer is a useful predictive marker for response to platinum-based chemotherapy in treating patients with pancreatic cancer. These cancers, and prostate cancer, are known as BRCA-related malignancies. We evaluated the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with metastatic pancreatic cancer with a family/personal history of these cancers.

Methods: Chemotherapy-naïve patients with metastatic pancreatic cancer with a family history of pancreatic/breast/ovarian/prostate cancer or a personal history of breast/ovarian/prostate cancer were included. Patients received fixed dose-rate gemcitabine (1000 mg/m) and oxaliplatin (100 mg/m) every 2 weeks. The primary endpoint was 1-year survival, and the threshold and expected values were set at 30 and 50%, respectively. The target sample size was determined to be 43, with a one-sided alpha value of 5% and power of 80%. A total of 45 patients were enrolled.

Results: Among the first 43 enrolled patients, the 1-year survival rate was 27.9% [90% confidence interval (CI) 17.0-41.3], which did not meet the primary endpoint. Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0-10.7), 4.0 months (95% CI 2.0-4.6), and 26.7% (95% CI 14.6-41.9), respectively, in all registered patients. The GEMOX regimen was generally tolerated; the most common grade three or higher adverse events were hematological toxicities.

Conclusion: GEMOX did not show the expected efficacy in patients with metastatic pancreatic cancer with a family or personal history of pancreatic/breast/ovarian/prostate cancer. Selection of GEMOX based on family/personal history is not recommended.

Trial Registration Number: UMIN000017894.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-020-01721-xDOI Listing
October 2020

Surgical management of carcinomas of the infratemporal fossa and skull base: patterns of failure and predictors of long-term outcomes.

J Neurosurg 2020 Jun 12;134(5):1392-1398. Epub 2020 Jun 12.

4Department of Neurosurgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Objective: Infratemporal fossa (ITF) tumors are unique in histological characteristics and difficult to treat. Predictors of patient outcomes in this context are not known. The objective of this study was to identify independent predictors of outcome and to characterize patterns of failure in patients with ITF carcinoma.

Methods: All patients who had been surgically treated for anterolateral skull base malignancy between 1999 and 2017 at the authors' institution were retrospectively reviewed. Patient demographics, preoperative performance status, tumor stage, tumor characteristics, treatment modalities, and pathological data were collected. Primary outcomes were disease-specific survival (DSS) and local progression-free survival (LPFS) rates. Overall survival (OS) and patterns of progression were secondary outcomes.

Results: Forty ITF malignancies with skull base involvement were classified as carcinoma. Negative margins were achieved in 23 patients (58%). Median DSS and LPFS were 32 and 12 months, respectively. Five-year DSS and OS rates were 55% and 36%, respectively. The 5-year LPFS rate was 69%. The 5-year overall PFS rate was 53%. Disease recurrence was noted in 28% of patients. Age, preoperative performance status, and margin status were statistically significant prognostic factors for DSS. Lower preoperative performance status and positive surgical margins increased the probability of local recurrence.

Conclusions: The ability to achieve negative margins was significantly associated with improved tumor control rates and DSS. Cranial base surgical approaches must be considered in multimodal treatment regimens for anterolateral skull base carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.3.JNS192630DOI Listing
June 2020

Verification of the Effectiveness of an SNP Marker in the Cholecystokinin Type A Receptor Gene for Improving Growth Traits in Okumino-kojidori Chickens.

J Poult Sci 2020 Apr;57(2):107-113

Institute of Livestock and Grassland Science, NARO, Tsukuba 305-0901, Japan.

A significant association was reported between a single nucleotide polymorphism (SNP; AB604331, g.420 C>A) in the cholecystokinin type A receptor gene and growth traits in some Japanese slow-growing chickens. Demonstration tests of the genetic improvement effect by comparing the superior allele-A fixed chickens with conventional ones were carried out considering the effect of different seasons on growth traits in other slow-growing chickens. Meat-type Okumino-kojidori chickens from Gifu Prefecture are a three-way cross of Gifu-jidori improved, White Plymouth Rock, and Rhode Island Red breeds. We used a total of 468 meat-type Okumino-kojidori: 264 individuals from a private hatchery as conventional chickens and 204 A-allele fixed individuals from the Gifu Prefectural Livestock Research Institute as improved chickens. We performed fattening experiments over two seasons: summer and winter. In each season, experimental birds of both sexes were hatched on the same day, raised in the same chicken house, and fed the same diet for 12 weeks. Body weight was recorded at 3, 6, 9, and 12 weeks of age. SNP genotypes were determined using the mismatch amplification mutation assay. Association between the SNP and growth traits was analyzed using generalized linear models built on sex-based, seasonal, additive, and dominance genetic effects. The observed AA, AC, and CC genotype frequencies in the conventional chickens were 0.158, 0.479, and 0.363, respectively; body weight at 12 weeks and average daily gain from 3 to 12 weeks was superior for the A allele compared to the C allele. The improved chickens were heavier than the conventional ones at 12 weeks. Body weight at 12 weeks in allele-A fixed chickens increased by 3.2% compared to the conventional chickens. We concluded that g.420 C>A is a good selective marker that increases slaughter weight in the meat-type Okumino-kojidori chickens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2141/jpsa.0190078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248005PMC
April 2020

Is a Single Nucleotide Polymorphism Marker in the Cholecystokinin A Receptor Gene Practically Suitable for Improving the Growth Traits of Hinai-jidori Chickens?

J Poult Sci 2020 Apr;57(2):99-106

Institute of Livestock and Grassland Science, NARO, Tsukuba 305-0901, Japan.

We have previously reported a significant association between the single-nucleotide polymorphism (SNP; g.420 C>A) in the cholecystokinin type A receptor gene () and the growth traits of Hinai-dori, a breed of chicken that is indigenous to Japan. Moreover, we have demonstrated that the minor allele of this SNP improved the growth rate in a low-growth line of the Hinai-dori breed. Hence, in the present study, we verified the association between this SNP and the growth traits of the Hinai-jidori chicken: a cross between a Hinai-dori sire and Rhode Island Red dam. In addition, we verified whether the growth rate was improved in Hinai-jidori chickens produced from the parent stocks in which the SNP A/A genotype was fixed by selection (improved Hinai-jidori chickens). The Hinai-jidori female chicks at 4 weeks of age, were subdivided into three genotypic groups (A/A, A/C, and C/C), with 20 chicks in each group, and reared in an open-sided poultry shed until 23 weeks of age. The results showed that the body weight at 23 weeks of age and the average daily gain after 14 weeks of age were significantly higher in group A/A than in group C/C. Subsequently, the improved and the conventional Hinai-jidori chickens were reared until they reached 22 weeks of age to verify the effects on their growth traits. The body weight of the improved Hinai-jidori chickens at 22 weeks was significantly greater than the conventional Hinai-jidori chickens. Moreover, the association between the SNP and body weights of Hinai-jidori chickens at market age (24 weeks) on the production farms showed that the A allele was significantly superior to the C allele. In conclusion, the g.420 C>A SNP improves the growth rate of commercial Hinai-jidori chickens and could be a candidate marker for improving the growth performance in selective breeding of Hinai-jidori chickens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2141/jpsa.0190041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248008PMC
April 2020
-->