1.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
2.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
3.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
4.Usefulness of Cell Blocks From Forceps and Brush Washing Fluid in Bronchoscopy
Mamiko KURIYAMA ; Makoto NAKAO ; Ryosuke KINOSHITA ; Hiroko KIYOTOSHI ; Masahiro SUGIHARA ; Norihisa TAKEDA ; Miki FUKAI ; Kazuyoshi YAMADA ; Masateru KITAJIMA ; Takuji TSUYUKI ; Hideki MURAMATSU
Journal of the Japanese Association of Rural Medicine 2023;72(4):307-313
Background: Cell blocks (CBs) from pleural fluid are frequently used in the practice of respiratory medicine, but there have been few reports on the use of CBs from forceps and brush washing fluid in bronchoscopy for pathological diagnosis. We retrospectively analyzed the usefulness of CBs from forceps and brush washing fluid. Patients and Methods: Patients who underwent bronchoscopy and had CBs made from forceps and brush washing fluid in bronchoscopy at our institution between June 2016 and May 2021 were included. Cases in which additional information was obtained from CBs were reviewed in detail. Results: In total, 138 patients had CBs made from forceps and brush washing fluid in bronchoscopy during the study period. EBUS-GS (endobronchial ultrasound-guide sheath) was used for 102 of these patients. The final diagnosis was lung cancer in 114 cases, infection disease in 10 cases, metastatic lung tumor in 8 cases, lymphoproliferative disease in 2 cases, sarcoidosis in 1 case, and organizing pneumonia in 1 case. There were 13 cases with additional information obtained from CBs, all of which were cases of malignant tumors. Conclusions: CBs from forceps and brush washing fluid in bronchoscopy were useful for pathological diagnosis in some cases.
5.A Case of Diffuse Large B-Cell Lymphoma Successfully Diagnosed Using Multiple Modalities to Evaluate Specimens From Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Ryosuke KINOSHITA ; Makoto NAKAO ; Saori TOMITA ; Syuntaro HAYASHI ; Masahiro SUGIHARA ; Yuya HIRATA ; Sosuke ARAKAWA ; Mamiko KURIYAMA ; Kohei FUJITA ; Kazuki SONE ; Yu ASAO ; Hideki MURAMATSU
Journal of the Japanese Association of Rural Medicine 2022;70(6):643-648
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is useful for diagnosing mediastinal lymph node lesions. Cell blocks prepared from the needle washing fluid and flow cytometry of tissue samples are helpful in making the diagnosis, but the combination of both examinations is not routinely performed. A 77-year-old woman with fever, dyspnea, and anorexia was admitted to our hospital. Computed tomography showed enlarged mediastinal lymph nodes with calcification and left ureteral calculus; however, no focus of infection was identified. We suspected lymph node tuberculosis or malignant lymphoma, and EBUS-TBNA was performed to evaluate the mediastinal lymph node lesions. Because a cell block prepared from the needle rinse fluid was suspicious for malignant lymphoma, we changed the puncture needle from 22 G to 19 G and performed a second EBUS-TBNA. Diffuse large B-cell lymphoma (DLBCL) was diagnosed based on the results of flow cytometry of the EBUS-TBNA samples. Here we report this case of DLBCL in which mediastinal lymph node tuberculosis was suspected and cell block preparation and flow cytometry using EBUS-TBNA specimens were useful for the diagnosis.
6.Evaluation of topotecan monotherapy for relapsed small-cell lung cancer after amrubicin monotherapy failure
Kohei FUJITA ; Makoto NAKAO ; Sosuke ARAKAWA ; Kazuki SONE ; Hidefumi SATO ; Hideki MURAMATSU
Journal of Rural Medicine 2021;16(4):250-255
Objective: The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy.Patients and Methods: We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital.Results: The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18–51), and 112 days (95% CI = 55–267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections.Conclusion: The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.
7.Active Tuberculosis With Rapidly-Growing Pulmonary Lesion in a Hospitalized Dermatomyositis Patient Below Age 40
Kohei FUJITA ; Makoto NAKAO ; Ayano WATANABE ; Mamoru SUGIHARA ; Sosuke ARAKAWA ; Yusuke SAKAI ; Yuto SUZUKI ; Hidefumi SATO ; Kaneshige SASAKI ; Hideki MURAMATSU
Journal of the Japanese Association of Rural Medicine 2020;69(2):165-170
A 38-year-old man was admitted to our hospital with fever and skin rash, and he was diagnosed as having dermatomyositis. He was treated with anti-inflammatory steroid and immunosuppressive agents. On hospital day 48, chest computed tomography (CT) revealed a nodule measuring approximately 2 cm in size in the lower lobe of the right lung (S9). Bacterial and/or fungal infection was suspected, but there was no response to antibiotic or antifungal treatment. A week later, repeat chest CT revealed the tumor now measuring approximately 6 cm in size in the lower lobe of the right lung. We performed bronchoscopy, and bacteriological examination of the transbronchial biopsy specimen revealed pulmonary tuberculosis. Interferongamma release assay (IGRA) before the initiation of immunosuppressive treatment was negative, so we did not administer treatment for latent tuberculosis infection. He was, however, treated with isoniazid, rifampicin, ethambutol, and pyrazinamide for 9 months, following which radiological features improved gradually. Here we describe in detail this rare case of a negative IGRA result before immunosuppressive therapy in a relatively young Japanese man who went on to develop active tuberculosis with a rapidly-growing pulmonary lesion during hospitalization.
8.A Case of Amylase-producing Small Cell Lung Cancer Complicated by Cushing's Syndrome
Ayana ISHIGURO ; Makoto NAKAO ; Yoshiharu OZAWA ; Yuto SUZUKI ; Yusuke SAKAI ; Sosuke ARAKAWA ; Kohei FUJITA ; Hidefumi SATO ; Etsuko YAMAMORI ; Hideki MURAMATSU
Journal of the Japanese Association of Rural Medicine 2019;68(4):535-542
A 68-year-old man was admitted to our hospital with complaints of fatigue, polyuria, and loss of appetite, and was diagnosed with diabetic ketosis. Chest and abdominal computed tomography (CT) showed a pulmonary tumor on the right S3 and multiple liver tumors. Blood chemistry revealed elevated levels of amylase and hepatobiliary enzymes. Pathological examination of a biopsy specimen from the liver tumor showed a small cell carcinoma. Based on the imaging and pathological findings, we made a diagnosis of extensive disease small-cell lung cancer (ED-SCLC), cT1aN3M1b (HEP, ADR). Treatment with carboplatin and etoposide evoked partial response and the serum level of amylase decreased. Immunohistochemical staining of liver biopsy specimen was positive for amylase, leading to a diagnosis of SCLC with amylase production. About 22 months after the diagnosis of SCLC, he was admitted to our hospital with fatigue, muscular weakness, edema, and hyperpigmentation. Laboratory findings showed elevated serum levels of hepatobiliary enzymes, adrenocorticotropic hormone (ACTH), and cortisol, and a decreased serum potassium level. Urinary potassium level was elevated. Pituitary magnetic resonance imaging showed a normal morphology. We made a diagnosis of SCLC complicated by Cushing’s syndrome. We report this rare case of SCLC with amylase and ACTH production, which was detected in the course of treatment of SCLC.
9.Diagnostic Efficacy of FeNO Testing in Patients With Cough
Aiko TATEMATSU ; Masaya HIGUCHI ; Chinari FURUICHI ; Masahiko SODA ; Makoto NAKAO ; Hideki MURAMATSU
Journal of the Japanese Association of Rural Medicine 2019;67(6):683-687
Cough is one of the most common respiratory complaints leading to medical consultation. Fractional exhaled nitric oxide (FeNO) testing detects eosinophilic inflammation of the airway. We evaluated the diagnostic efficacy of FeNO testing in patients with cough. Patients who presented to the respiratory medicine department of our hospital with a chief complaint of cough and underwent FeNO testing were included in this study and divided into asthma and non-asthma groups. Patients with confounding factors such as allergic rhinitis and atopic predispositions were also identified and those with and without confounding factors, respectively, were further divided into the asthma and non-asthma groups. Median FeNO in the asthma and non-asthma groups was respectively 31 and 19 ppb in all patients and 31 and 18 ppb in those without confounding factors, with significant differences between the groups in both populations. The corresponding values in patients with confounding factors were 46 and 23 ppb, with no significant difference between the groups. A cut-off of 27 ppb differentiated between the asthma and non-asthma groups with sensitivity of 0.603 and specificity of 0.776. These results suggest FeNO testing is effective in the differential diagnosis of cough in patients without confounding factors.
10.Sasa veitchii extract protects against carbon tetrachloride-induced hepatic fibrosis in mice.
Hiroki YOSHIOKA ; Tsunemasa NONOGAKI ; Shiori FUKAYA ; Yoshimi ICHIMARU ; Akito NAGATSU ; Masae YOSHIKAWA ; Hirohisa FUJII ; Makoto NAKAO
Environmental Health and Preventive Medicine 2018;23(1):49-49
BACKGROUND:
The current study aimed to investigate the hepatoprotective effects of Sasa veitchii extract (SE) on carbon tetrachloride (CCl)-induced liver fibrosis in mice.
METHODS:
Male C57BL/6J mice were intraperitoneally injected with CCl dissolved in olive oil (1 g/kg) twice per week for 8 weeks. SE (0.1 mL) was administered orally once per day throughout the study, and body weight was measured weekly. Seventy-two hours after the final CCl injection, mice were euthanized and plasma samples were collected. The liver and kidneys were collected and weighed.
RESULTS:
CCl administration increased liver weight, decreased body weight, elevated plasma alanine aminotransferase, and aspartate aminotransferase and increased liver oxidative stress (malondialdehyde and glutathione). These increases were attenuated by SE treatment. Overexpression of tumor necrosis factor-α was also reversed following SE treatment. Furthermore, CCl-induced increases in α-smooth muscle actin, a marker for hepatic fibrosis, were attenuated in mice treated with SE. Moreover, SE inhibited CCl-induced nuclear translocation of hepatic nuclear factor kappa B (NF-κB) p65 and phosphorylation of mitogen-activated protein kinase (MAPK).
CONCLUSION
These results suggested that SE prevented CCl-induced hepatic fibrosis by inhibiting the MAPK and NF-κB signaling pathways.
Animals
;
Carbon Tetrachloride
;
toxicity
;
Liver Cirrhosis
;
chemically induced
;
drug therapy
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Plant Extracts
;
pharmacology
;
Protective Agents
;
pharmacology
;
Random Allocation
;
Sasa
;
chemistry


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