Dynamics in the Prostate Immune Microenvironment Induced by Androgen Deprivation Therapy.

Background: The influence of testosterone on the prostate's immune microenvironment remains unclear. This study aims to elucidate the dynamics of immune cells in the prostate following androgen deprivation therapy (ADT).

Methods: We retrospectively compared prostate needle biopsy and radical prostatectomy specimens from 33 patients who underwent both procedures, along with neoadjuvant ADT at a single institution.

Loss of phosphatase and tensin homolog expression castration-sensitive prostate cancer predicts outcomes in men after prostatectomy.

Objectives: This study aimed to investigate the potential for using the phosphatase and tensin homolog (PTEN) gene as a prognostic marker in post-prostatectomy patients with castration-sensitive prostate cancer (PCa).

Methods: A total of 180 patients with castration-sensitive PCa who underwent radical prostatectomy at our institution were included in this study. PTEN expression was evaluated using immunohistochemistry, and patients were classified into two groups based on the staining intensity: PTEN-Normal and PTEN-Loss.

3D layered co-culture model enhances Trastuzumab Deruxtecan sensitivity and reveals the combined effect with G007-LK in HER2-positive non-small cell lung cancer.

Human epidermal growth factor receptor 2 (HER2) aberrations are observed in various cancers. In non-small cell lung cancer, genetic alterations activating HER2, mostly exon 20 insertion mutations, occur in approximately 2-4% of cases. Trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody-drug conjugate has been approved as the first HER2-targeted drug for HER2-mutant lung cancer.

In vitro throughput screening of anticancer drugs using patient-derived cell lines cultured on vascularized three-dimensional stromal tissues.

The development of high-throughput anticancer drug screening methods using patient-derived cancer cell (PDC) lines that maintain their original characteristics in an in vitro three-dimensional (3D) culture system poses a significant challenge to achieving personalized cancer medicine. Because stromal tissue plays a critical role in the composition and maintenance of the cancer microenvironment, in vitro 3D-culture using reconstructed stromal tissues has attracted considerable attention. Here, a simple and unique in vitro 3D-culture method using heparin and collagen together with fibroblasts and endothelial cells to fabricate vascularized 3D-stromal tissues for in vitro culture of PDCs is reported.

Pathological complete response to neoadjuvant chemotherapy may improve antitumor immune response via reduction of regulatory T cells in muscle-invasive bladder cancer.

The prognosis for patients who achieve a pathologic complete response in bladder cancer is excellent, but the association between their prognosis and the tumor microenvironment is unclear. We investigated the tumor immune microenvironment of those with pathological complete response after platinum-based neoadjuvant chemotherapy for cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. Our retrospective study included 12 patients with pathological complete response who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer.

Novel knock-in mouse model for the evaluation of the therapeutic efficacy and toxicity of human podoplanin-targeting agents.

Podoplanin is a key molecule for enhancing tumor-induced platelet aggregation. Podoplanin interacts with CLEC-2 on platelets via PLatelet Aggregation-inducing domains (PLAGs). Among our generated antibodies, those targeting the fourth PLAG domain (PLAG4) strongly suppress podoplanin-CLEC-2 binding and podoplanin-expressing tumor growth and metastasis.

A novel mechanism of EML4-ALK rearrangement mediated by chromothripsis in a patient-derived cell line.

Introduction: EML4-ALK is a driver oncogene in non-small-cell lung cancer (NSCLC) and has been developed into a promising molecular target for antitumor agents. Although EML4-ALK is reported to be formed by inversion of chromosome 2, other mechanisms of this gene fusion remain unknown. This study aimed to examine the mechanism of EML4-ALK rearrangement using a novel cell line with the EML4-ALK fusion gene.

Identification of CD20 C-terminal deletion mutations associated with loss of CD20 expression in non-Hodgkin's lymphoma.

Purpose: Rituximab is commonly incorporated into CD20-positive B-cell lymphoma therapy to improve response and prognosis. With increasing use, resistance to rituximab is a continuing concern, but CD20 mutation as a cause of resistance has not previously been reported.

Experimental Design: Freshly collected lymphoma cells from 50 patients with previously untreated or relapsed/resistant non-Hodgkin's B-cell lymphomas (diffuse large B cell, n = 22; follicular, n = 7; mucosa associated lymphoid tissue, n = 16; chronic lymphocytic leukemia, n = 2; small lymphocytic lymphoma, n = 1; lymphoplasmacytic, n = 1; mantle cell lymphoma, n = 1) were assessed for CD20 expression by flow cytometry, and CD20 gene sequencing was done on extracted DNA.

Pilot study of MDR1 gene transfer into hematopoietic stem cells and chemoprotection in metastatic breast cancer patients.

A major problem in high-dose chemotherapy with autologous hematopoietic stem cell transplantation is insufficient function of reconstituted bone marrow that limits the efficacy of post-transplantation chemotherapy. Because transduction of hematopoietic stem cells with the multidrug resistance 1 (MDR1) gene might circumvent this problem, we conducted a pilot study of MDR1 gene therapy against metastatic breast cancer. Peripheral blood stem cells were harvested, and one-third of the cells were transduced with MDR1 retrovirus.

Differential regulation of eotaxin-1/CCL11 and eotaxin-3/CCL26 production by the TNF-alpha and IL-4 stimulated human lung fibroblast.

Allergic asthma and allergic dermatitis are chronic inflammatory diseases and are characterized by an accumulation of eosinophils at sites of inflammation. Eotaxin-1/CCL11 and eotaxin-3/CCL26 are members of the CC chemokine family, which are known to be potent chemoattractants for eosinophils. We observed that a human lung fibroblast, HFL-1 produces eotaxin-1 and -3 in response to TNF-alpha plus IL-4 stimulation, accompanied with NF-kappaB and STAT6 activation.

Blockade of bulky lymphoma-associated CD55 expression by RNA interference overcomes resistance to complement-dependent cytotoxicity with rituximab.

Recently, anti-CD20 (rituximab) and anti-Her2/neu (trastuzumab) antibodies have been developed and applied to the treatment of malignant lymphoma and breast cancer, respectively. However, bulky lymphoma is known to be resistant to rituximab therapy, and this needs to be overcome. Fresh lymphoma cells were collected from 30 patients with non-Hodgkin's lymphoma, the expression of CD20 and CD55 was examined by flow cytometry, and complement-dependent cytotoxicity (CDC) assays were carried out.

Autologous stem cell transplantations for recurrent adult T cell leukaemia/lymphoma using highly purified CD34+ cells derived from cryopreserved peripheral blood stem cells.

We performed double autologous PBSCT in one fulminantly relapsed ATL patient. Cryopreserved PBSCs containing tumour cells were thawed, and CD34+ cells were selected for by immunomagnetic beads, with the aim of decreasing the number of re-infused tumour cells. The patient received 0.

An unusual association of monoclonal gammopathy, paroxysmal nocturnal haemoglobinuria and myelodysplastic syndrome transformed into acute myeloid leukaemia: coexistence of triple clonal disorders.

An unusual association of paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and monoclonal gammopathy is reported. A 60-year old male, who had a history of IgA monoclonal gammopathy, presented with haemoglobinuria and colic pain. Flow cytometry showed CD55negative/59dim peripheral red cells, and bone marrow examination disclosed MDS.

[Biomodulation of 5-fluorouracil by interferon].

The biomodulation (BM) of 5-fluorouracil (5-FU) by interferon (IFN) is reviewed both preclinically and clinically, stressing clinical relevance. A number of preclinical evaluations of a combination of 5-FU and IFN were performed before Wadler et al. developed an active biomodulation therapy with a combination of 5-FU and IFN.

[Antitumor activity of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea, LY 186641 against various human cancers using subrenal capsule assay].

An analog of diarylsulfonylurea, LY 186641 has a broad spectrum activity against murine solid tumors including Colon 26 and LX-1. Preclinical evaluation of the anticancer activity of LY 186641 using the subrenal capsule assay was performed in fresh human tumor samples derived from 87 patients with various cancers and 70 (80%) samples were evaluable. The overall chemosensitivity rate of LY 186641 was 37% and the average tumor growth inhibition rates (TGIRs) of malignant lymphoma, esophageal cancer and colorectal cancer were 51 +/- 19%, 51 +/- 20% and 48 +/- 12%, respectively.

[Phase II study of combination chemotherapy with epirubicin, cyclophosphamide and ftorafur in metastatic breast cancer].

Twenty-nine patients with metastatic breast cancer were treated with a combination chemotherapy consisting of Epirubicin 50 mg/m2 IV on day 1, Cyclophosphamide 500 mg/m2 IV on day 1 and Ftorafur 800 mg/day PO every day (ECF therapy). The therapy was repeated every 3 weeks until progression or until a cumulative dose of 700 mg/m2 for epirubicin. Of 25 evaluable patients, there were one with complete response (CR), 11 with partial response (PR), 10 with no change and 3 with progressive disease (PD).

[Preclinical evaluation of a new anthracycline derivative, SM-5887 by subrenal capsule assay].

SM-5887, a new totally synthetic anthracycline derivative was evaluated the antitumor activity by subrenal capsule assay (SRCA) and the activity was compared to that of doxorubicin. The method of SRCA was the same originally developed by Bogden et al and 200 mg/kg of bredinin was administered subcutaneously 3 times every 2 days in order to induce immunosuppression of mice. Mice were given a single intravenous dose of either 30 mg/kg of SM-5887 or 15 mg/kg of doxorubicin.

A comparison of a new nitrosourea derivative, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea with various antitumor agents with respect to therapeutic ratios in L1210 leukemia systems.

In order to further evaluate the antitumor activity of 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077), the therapeutic ratios (a ratio of the optimal dose versus the dose showing 25% increase in life span) of TA-077 were examined using two L1210 leukemia systems and the results were compared with those of twenty-six antitumor agents for reference. In the i.p.

Enhanced antitumor activity of 5'-deoxy-5-fluorouridine against Lewis lung carcinoma in aged hybrid (C57BL/6 x DBA/2) F1 mice.

The antitumor activity of 5'-deoxy-5-fluorouridine (5'-DFUR) against Lewis lung carcinoma was examined by implanting the tumor subcutaneously into young (8-11 weeks) and old (24-41 weeks) hybrid (C57BL/6 x DBA/2)F1 (BDF1) male mice. Oral administration of 5'-DFUR induced a small (7 of 100) but significant (p less than 0.05) number of 70-d survivors in young mice.