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Recently, circulating tumor cells (CTCs) of cancer patients have been analyzed as a biomarker of disease progression and as a new prognostic tool.We conducted a pilot study to determine whether CTCs present before and after chemotherapy or peptide vaccination predicted outcome in patients with metastatic breast cancer (MBC). CTCs were isolated from the peripheral blood of MBC patients and evaluated using the CellSearch®System (Janssen Diagnostics). The expression of the HLA classⅠ molecule in the CTCs was analyzed simultaneously by using a flow cytometric system. A CTC-positive test result was defined as five or more CTCs/7.5 mL blood. Nine patients (median [range] age, 64.2 years [44-80 years]) were included. Four (57.1%) of 7 MBC patients with Luminal A subtype tested positive for CTC.Of 6 MBC patients, 5 (83.3%) had a decreased mean number of CTCs, from 35.8/7.5 to 0.4/7.5 mL, after 3 courses of systemic chemotherapy. Furthermore, CTC-HLA class Ⅰexpression level was decreased in 2 (66.7%) of 3 patients after cytotoxic chemotherapy but increased in 4 (80.0%) of 5 patients after 6 vaccinations with tumor-specific peptide vaccines. The number of CTCs and CTC-HLA class Ⅰ expression level in the patients with MBC changed after the treatment with systemic chemotherapy or peptide-vaccine therapy.

Background: In this era of precision medicine, monitoring patients requires not only real time but also longitudinal sequence of samples at various time points. Based on this background, we focused on conditioned circumstances on fixation and storage for re-utilization of CTCs., Materials: Instead of actual CTCs, Cell line (H1975) derived from lung cancer was used because of their scarceness of CTCs., Methods: These cells were put on a slide by using an auto-smear device. The slides were evaluated under various centrifuge forces, fixations for the following storages., Results and Discussion: The study indicated that 800 rpm for 1 min centrifuge and fixation by 95% ETOH was excellent. Further at least 5 cells per 1 mL cell solution were required for the following procedures including Fluorescence in situ hybridization (FISH) analysis. This study provides insights of new platform for evaluation of CTCs not only real time but also longitudinal sequence at various time points.

We hypothesized that a large number of circulating tumor cells(CTCs)may be isolated from samples obtained by using the leukapheresis procedures that are utilized to collect peripheral blood mononuclear cells for dendritic cell vaccine therapy. We utilized the CellSearch System to determine the number of CTCs in samples obtained by using leukapheresis in 7 patients with colorectal cancer, 5 patients with breast cancer, and 3 patients with gastric cancer. In all patients, a large number of CTCs were isolated. The mean number of CTCs per tumor was 17.1(range 10-34)in colorectal cancer, 10.0(range 2-27)in breast cancer, and 24.0(range 2-42)in gastric cancer. We succeeded in culturing the isolated CTCs from 7 patients with colorectal cancer, 5 patients with breast cancer, and 3 patients with gastric cancer. In conclusion, compared to conventional methods, a large number of CTCs can be obtained by using leukapheresis procedures. The molecular analyses of the CTCs isolated by using this method should be promising in the development of personalized cancer treatments.

The principle concept of cancer stem cells (CSCs) giving rise to the carcinogenesis, relapse or metastasis of malignancy is broadly recognized. On the other hand, circulating tumor cells (CTCs) also plays important roles in relapse or metastasis of malignancy, and there has been much focused on the association between CSCs and CTCs in cancer cases. The technical innovations for detection of CTCs enabled us to unveil the nature of CTCs. We now realize that CTCs isolated by cell surface antibodies, such as DCLK1, LGR5 indicated CSC properties, and CTCs with epitherial-mesenchymal transition(EMT) phenotype showed characteristics of CSCs.

Metabolome analysis is an approach to investigate cell characteristics from the metabolites that are constantly produced and changed by those cells. We conducted a metabolome analysis of the response of 786-O renal cell carcinoma (RCC) cells to histone deacetylase (HDAC) inhibitors, which are expected to increase anticancer drug sensitivity, and compared the response with that of drug-resistant cells. Trichostatin A (TSA), an HDAC inhibitor, increased the sensitivity of 786-O cells to sunitinib. Moreover, TCA cycle and nucleotide metabolism of the cells were promoted. The findings that acetylated p53 (active form) and early apoptotic cells were increased suggests that the mechanism involved enhancement of mitochondrial metabolism and function. In addition, established sunitinib-resistant RCC cells were exposed to a combination of sunitinib and TSA, resulting in significant growth inhibition. Principal component analysis revealed that the parent and resistant cells were obviously different, but approximately half their fluctuations were illustrated by the same pathways. In summary, it was suggested that TSA reduced sunitinib resistance by triggering intracellular metabolome shifts in energy metabolism. This was the first recognized mechanism of action of TSA as an HDAC inhibitor.

Ephedra Herb is defined in the 17th edition of the Japanese Pharmacopoeia as the terrestrial stem of Ephedra sinica STAPF., Ephedra intermedia SCHRENK et C.A. MEYER, or Ephedra equisetina BUNGE (Ephedraceae) which contains more than 0.7% ephedrine alkaloids (ephedrine and pseudoephedrine). The primary effects and adverse effects of Ephedra Herb are traditionally believed to be mediated by ephedrine alkaloids. We recently reported that Ephedra Herb extract (EHE) exhibits antimetastatic and antitumor effects by suppressing the hepatocyte growth factor-c-Met signaling pathway through the inhibition of c-Met tyrosine kinase activity. We confirmed that the non-alkaloidal fraction of EHE had c-Met-inhibitory activity. Moreover, we discovered herbacetin glycosides in EHE and demonstrated that herbacetin, the aglycone of the glycosides, shows c-Met-inhibitory activity and analgesic action. These findings suggest that some pharmacological actions of EHE may be produced by its non-alkaloidal fraction, which does not cause the adverse effects of ephedrine alkaloids. Therefore, we prepared ephedrine alkaloids-free EHE (EFE) by removing ephedrine alkaloids from EHE using ion-exchange column chromatography. EFE had c-Met-inhibitory action, analgesic effects, and antiinfluenza activity similar to EHE but had no toxicity. Now, we are evaluating the safety of EFE in healthy volunteers and its efficacy in patients to obtain licensing approval for its therapeutic use in the future.

Darinaparsin, an active ingredient of DARVIAS® Injection 135 mg, is a novel organic arsenical compound of dimethylated arsenic conjugated to glutathione. Darinaparsin is thought to induce apoptosis and cell-cycle arrest and suppress tumor growth by disrupting mitochondrial functions and increasing production of intracellular reactive oxygen species. Darinaparsin is processed at the cell surface by y-glutamyltranspeptidase (y-GT), leading to formation of dimethylarsino-cysteine, which is imported via a cystine transporter expressed on cell surface membranes. Numerous tumor cells express high levels of y-GT and cystine transporter, to maintain high levels of glutathione as an intracellular antioxidant. Darinaparsin is a novel antineoplastic agent designed to exploit the characteristics of tumor cells and to be efficiently taken up by tumor cells to inhibit their growth. In a global phase 2 pivotal study of darinaparsin in Asian patients with relapsed or refractory peripheral T-cell lymphoma (r/r PTCL), the overall response rate was 19.3% (90% confidence interval: 11.2-29.9%) and grade >3 drug-related adverse events with an incidence rate >5% included neutropenia (9.2%, n = 6), anemia (6.2%, n = 4) and thrombocytopenia (6.2%, n = 4) in 65 patients receiving darinaparsin. Based on the results of this phase 2 trial, which demonstrated the antitumor activity and acceptable safety profile of darinaparsin in patients with r/r PTCL, Solasia pharma K.K. received approval for darinaparsin for the treatment of r/r PTCL in June 2022, and Nippon Kayaku Co., Ltd. launched this drug in August 2022. Darinaparsin is expected to contribute to the clinical practice of PTCL as a new treatment option for this disease. [ABSTRACT FROM AUTHOR]

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Copyright of Nishinihon Journal of Urology is the property of West Japan Urological Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Nishinihon Journal of Urology is the property of West Japan Urological Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Folia Pharmacologica Japonica is the property of Japanese Pharmacological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Folia Pharmacologica Japonica is the property of Japanese Pharmacological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antibody-drug conjugates (ADCs) combine the specific antibody and cytotoxic agent by a linker and represent a promising drug class with a wider therapeutic window than conventional chemotherapeutic agents by substantiating efficient and specific drug delivery to antigen-expressing tumor cells. However, there are rooms for improvement in terms of efficacy, safety, physicochemical property; therefore, the development of promising ADC drugs across multiple indications are eagerly awaited. In 2015, Daiichi Sankyo initiated the first-in-human study of HER2 ADC, trastuzumab deruxtecan (T-DXd, ENHERTU®) which possesses DNA topoisomerase I inhibitor, exatecan derivative and proprietary linker, in Japan. Based on the provocative results in phase 1 study, the global development program has been accelerated to show the high and durable efficacy in patients with HER2 positive breast cancer pretreated with trastuzumab emtansine. As a result, T-DXd was approved based on single arm phase 2 study in the US (Dec 2019) and Japan (March 2020) by leveraging the breakthrough designation and conditional early approval system, respectively, at the first time for the HER2 positive breast cancer. In addition, T-DXd was recently approved in gastric cancer through Sakigake designation in Japan based on a randomized phase 2 study. T-DXd is also being developed in the earlier lines or other indications where no anti-HER2 therapies were approved to date. Combination studies with other agents, such as immune checkpoint inhibitors are underway. In the near future, we hope that more patients worldwide can enjoy the therapeutic benefits of T-DXd through our continuous efforts to expand its indications. [ABSTRACT FROM AUTHOR]

Biomechanical stimuli derived by interstitial flow regulate morphogenesis of multicellular systems including both physiological and pathological cells. For example, hepatocytes construct three-dimensional structures in directional interstitial flow conditions. Protrusions of tumor cells are also induced by interstitial flow, resulting in enhanced tumor cell invasion. Interestingly, the direction of tumor cell invasion in response to directional interstitial flow differs depending on the type of tumor cells. Furthermore, endothelial cells form capillary networks against the direction of interstitial flow in a magnitude-dependent manner. Taken together, interstitial flow is an important factor for regulating morphogenesis of multicellular systems. [ABSTRACT FROM AUTHOR]

A 74-year-old man visited a nearby hospital because of vomiting and abdominal pain. An abdominal CT scan revealed a tumor measuring 35mm in the terminal ileum, accompanied by calcification, as well as dilation of the proximal small bowel. Four years earlier, a similar tumor was incidentally pointed out, but no further investigation was conducted at that time. Although the size of the tumor had not increased since the previous examination, the patient had developed bowel obstruction, requiring surgical intervention after improvement of bowel distension. Since the possibility of malignancy could not be ruled out, a laparoscopic ileocecal resection was performed, including lymphadenectomy of the surrounding small bowel mesentery. Macroscopic examination of the resected specimen showed a yellowish, well-circumscribed lesion with calcification inside. The histopathological examination revealed a nodular lesion measuring 40×35×32 mm, primarily involving the muscularis propria in the terminal ileum. The tumor was positive for desmin and α-SMA, while c-kit was negative by immunohistochemical staining and leiomyoma was diagnosed. The patient was discharged on the 7th postoperative day. At the one-year follow-up, no recurrence of the leiomyoma was observed. [ABSTRACT FROM AUTHOR]

Copyright of Mokuzai Gakkaishi is the property of Japan Wood Research Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Seikagaku Journal of Japanese Biochemical is the property of Japanese Biochemical Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Seikagaku Journal of Japanese Biochemical is the property of Japanese Biochemical Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Seikagaku Journal of Japanese Biochemical is the property of Japanese Biochemical Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Nihon Daicho Komonbyo Gakkai Zasshi is the property of Japan Society of Coloproctology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Seikagaku Journal of Japanese Biochemical is the property of Japanese Biochemical Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Since insurance coverage for the “cancer gene panel test” began in June 2019 in Japan, there has been significant anticipation for cancer genome medicine in pediatric brain tumors. The BRAF p.V600E mutation in gliomas is a notable actionable gene mutation that is effectively targeted by molecular targeted drugs. This is evidenced by numerous clinical trials showing promising results with such therapies. We experienced three pediatric malignant brain tumor cases in which the BRAF p.V600E mutation was detected using the cancer gene panel test (Foundation OneⓇ), and discuss the current status of these tests for pediatric brain tumors. Case 1 involved an 18-year-old female with a left temporal lobe tumor that was discovered during an investigation of epileptic seizures. Following tumor resection, she was diagnosed with epithelioid glioblastoma. Despite the standard therapy, the tumor progressed rapidly. She was considered for molecular targeted therapy targeting the BRAF p.V600E mutation under a patient-directed care program. However, due to her deteriorating condition, she could not participate in the trial and died on day 215. In Case 2, a 13-year-old female exhibited intratumoral hemorrhage in the interhemispheric fissure, which was found during a headache investigation. Eleven days after intracranial tumor resection, she experienced sudden intraspinal hemorrhage with paraplegia due to spinal dissemination. Diagnosed with epithelioid glioblastoma in both lesions, she was also considered for the same molecular targeted therapy as in Case 1. Unfortunately, similar to Case 1, her condition worsened, preventing trial participation, and leading to death on day 154. Case 3 describes an 11-year-old female with recurrent absence seizures. A neoplastic lesion in the right temporal lobe was diagnosed as ganglioglioma with anaplastic features. Given the partial anaplasia in the pathological findings, postoperative treatment was necessary. However, concerns about potential adverse effects of radiation therapy, such as secondary malignancies, were prominent. Therefore, she was enrolled in the Patient’s Advised Treatment Program and started receiving molecular targeted therapy for the BRAF p.V600E mutation. All three patients underwent cancer gene panel testing up to the expert panel level. However, only one patient received the molecular targeted therapy. The low rate of access to these drugs is a significant issue in cancer genomic medicine. For rapidly progressing malignancies, as seen in Cases 1 and 2, expedited cancer panel testing and institutional improvement are crucial. In addition, easing the conditions for clinical trial participation is essential. Conversely, there is often hesitation in treating malignant pediatric brain tumors with chemotherapy or radiation due to potential late complications that can impact development and quality of life. Case 3 demonstrates that molecular targeted agents might offer a new treatment avenue for pediatric malignant brain tumors, potentially reducing late complications while maintaining treatment efficacy. [ABSTRACT FROM AUTHOR]