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Tadashi Yoshino

Publications and source records attributed to Tadashi Yoshino.

At least 19 recordsLinked to original sources

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee.

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.

Advisory Committees↗

Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5.

Intravascular large B-cell lymphoma (IVLBCL) is pathologically distinct with a broad clinical spectrum and immunophenotypic heterogeneity. A series of 96 patients with IVLBCL (median age, 67 years; range, 41-85 years; 50 men) was reviewed. Anemia/thrombocytopenia (84%), hepatosplenomegaly (77%), B symptoms (76%), bone marrow involvement (75%), and hemophagocytosis (61%) were frequently observed. The International Prognostic Index score was high or high-intermediate in 92%. For 62 patients receiving anthracycline-based chemotherapies, median survival was 13 months. CD5, CD10, Bcl-6, MUM1, and Bcl-2 were positive in 38%, 13%, 26%, 95%, and 91% of tumors, respectively. All 59 CD10- IVLBCL cases examined were nongerminal center B-cell type because they lacked the Bcl-6+MUM1- immunophenotype. CD5 positivity was associated with a higher prevalence of marrow/blood involvement and thrombocytopenia and a lower frequency of neurologic abnormalities among patients with CD10-IVLBCL. Compared with 97 cases of de novo CD5+CD10-diffuse LBCL, 31 cases of CD5+CD10-IVLBCL exhibited higher frequencies of poor prognostic parameters, except age. Multivariate analysis in IVLBCL revealed that a lack of anthracycline-based chemotherapies (P<.001, hazard ratio [HR]: 9.256), age older than 60 years (P=.012, HR: 2.459), and thrombocytopenia less than 100x10(9)/L (P=.012, HR: 2.427) were independently unfavorable prognostic factors; CD5 positivity was not. Beyond immunophenotypic diversity, IVLBCL constitutes a unique group with aggressive behavior.

Adult↗

Deviated VH4 immunoglobulin gene usage is found among thyroid mucosa-associated lymphoid tissue lymphomas, similar to the usage at other sites, but is not found in thyroid diffuse large B-cell lymphomas.

It remains unclear whether or not diffuse large B-cell lymphomas of extranodal sites arise from mucosa-associated lymphoid tissue (MALT) lymphomas. We studied the clinicopathological features of MALT lymphoma and diffuse large B-cell lymphoma in the thyroid gland, with special reference to VH usage of immunoglobulin gene rearrangement, to clarify the relationships between these two types of lymphomas. In addition, t(11; 18) (q21; q21) translocation was examined by multiplex reverse transcription-polymerase chain reaction. We examined 58 patients with primary thyroid lymphoma: 31 (male seven and female 24) with MALT lymphoma and 27 (male three and female 24) with diffuse large B-cell lymphoma. Interestingly, the sequence of VH genes revealed that the two subtypes differed significantly in their use of the VH4 family (P < 0.05). Of the seven MALT lymphomas, three used the VH4 family and the other four used the VH3 family, whereas eight out of nine diffuse large B-cell lymphoma used the VH3 family, one used the VH1 family, and none used the VH4 family. It was also interesting that, in one diffuse large B-cell lymphoma patient with MALT lymphoma, the diffuse large B-cell lymphoma component used the VH3 family and the MALT lymphoma component used the VH4 family. These data imply that, in a subset of cases, these two subtypes do not share a common origin and that at least some diffuse large B-cell lymphomas have a de novo origin. No t(11; 18) (q21; q21) was detected in thyroid lymphomas, which are different from MALT lymphoma of the stomach, lungs, large intestine and ocular adnexa. This strongly indicated that the presence of t(11; 18) (q21; q21) in MALT lymphoma is organ-specific.

Adult↗

Effect of nicotine on IL-18-initiated immune response in human monocytes.

Nicotine is thought to inhibit the production of proinflammatory cytokines from macrophages through an anti-inflammatory pathway that is dependent on nicotinic acetylcholine receptor alpha7 subunit (alpha7-nAChR). IL-18, an important proinflammatory cytokine, is reported to induce the expression of adhesion molecules on monocytes, thus enhancing cell-to-cell interactions with T-cells and contributing to IL-18-initiated cytokine production. Accordingly, inhibition of IL-18 suppresses systemic inflammatory responses. In the present study, we found that nicotine inhibited the IL-18-enhanced expression of ICAM-1, B7.2, and CD40 on monocytes, and the production of IL-12, IFN-gamma, and TNF-alpha by PBMC. A nonselective and a selective alpha7-nAChR antagonist, mecamylamine, and alpha-bungarotoxin abolished the effects of nicotine, suggesting that this depends on alpha7-nAChR stimulation. It is reported that nicotine induces prostaglandinE2 (PGE(2)) production in PBMC through the up-regulation of cyclooxygenase (COX)-2 expression. PGE(2) is known to activate the EP2/EP4-receptor, leading to an increase in cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity. Consistent with this, we found that COX-2 and PKA inhibitors prevented the effects of nicotine on adhesion molecule expression and cytokine production, indicating that the mechanism of action of nicotine may be via endogenous PGE(2) production.

Antigens, CD↗

alpha7 Nicotinic acetylcholine receptor stimulation inhibits lipopolysaccharide-induced interleukin-18 and -12 production in monocytes.

Nicotine inhibited interleukin (IL)-18 and -12 production in lipopolysaccharide (LPS)-stimulated monocytes, and the action of nicotine was antagonized by a non-selective and a selective alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) antagonist, suggesting that the stimulation of alpha7-nAChR may be involved in the action of nicotine. Nicotine is reported to induce prostaglandin E(2) (PGE(2)) production in monocytes through the up-regulation of cyclooxygenase (COX)-2 expression. PGE(2) is known to increase cAMP levels and to activate protein kinase A (PKA). COX-2 and PKA inhibitors prevented the action of nicotine, indicating that the mechanism of action of nicotine may be via endogenous PGE(2) production.

Bungarotoxins↗

Prognostic significance of T-cell or cytotoxic molecules phenotype in classical Hodgkin's lymphoma: a clinicopathologic study.

PURPOSE: Classical Hodgkin's lymphoma (CHL) is characterized by Hodgkin's and Reed-Sternberg (H-RS) cells, most of which are derived from germinal-center B cells. Nevertheless, one or more markers for T cells and follicular dendritic cells (FDC) may be expressed in a minority of H-RS cells in some CHL patients, although the clinical significance of this remains controversial. The aim of this study was to clarify the association between phenotypic expression and clinical outcome in CHL. PATIENTS AND METHODS: Participants were 324 consecutive CHL patients, comprising 132 patients with nodular sclerosis (NS), 35 patients with NS grade 2 (NS2), and 157 patients with mixed cellularity (MC). We evaluated the presenting features and prognosis of patients on categorization into four phenotypically defined groups: B-cell (CD20+ and/or CD79a+; n = 63), T-cell and/or cytotoxic molecules (CD3+, CD4+, CD8+, CD45RO+, TIA-1+, and/or granzyme B+; n = 27), FDC (CD21+ without B-cell marker; n = 22), and null-cell types (n = 212). Other potential prognostic factors were examined. RESULTS: The T-cell and/or cytotoxic molecules group showed a significantly poorer prognosis than the other three groups (P < .0001). This finding was seen consistently in multivariate analyses. Morphologic subtyping (NS/NS2/MC) and Epstein-Barr virus positivity were not identified as independent prognostic factors. CONCLUSION: The presence of T-cell and/or cytotoxic antigens in H-RS cells may represent a poor prognostic factor in CHL, even if their expression is not regarded as lineage specific. Examination of T-cell and/or cytotoxic molecules phenotype in CHL patients is recommended as a routine pathologic practice.

Adolescent↗

t(8;14)(q24;q32) in two patients with CD10-negative primary thyroid diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) with the 8q24 translocation is occasionally seen in the gastrointestinal tract, but has rarely been reported in the thyroid gland. We experienced two cases of primary thyroid DLBCL having t(8;14)(q24;q32). The immunophenotype and karyotype of Case 1 (66-year-old female) and Case 2 (70-year-old female) were: CD10-, CD20+, BCL-2+/add(13)(q34), t(8;14)(q24;q32) and CD10-, CD20-, CD79a+, BCL-2-/t(8;14)(q24;q32), respectively. Although long-term complete remission could be achieved in both of our patients by conventional chemotherapy with/without radiation therapy, accumulation of further such cases is necessary to develop a standard treatment protocol and also to elucidate the pathogenesis of t(8;14)(q24;q32)-positive primary thyroid DLBCL.

Aged↗

Accurate diagnosis of musculoskeletal lesions by core needle biopsy.

BACKGROUND: Percutaneous needle biopsy has many advantages over open biopsy in the treatment of neoplasms. However, the accuracy of needle biopsy in the diagnosis of musculoskeletal lesions has not yet been established. Here, we evaluate the accuracy and limitations of the procedure for musculoskeletal lesions. METHODS: The diagnoses of 163 needle biopsies (bone, 91; soft tissue, 72) performed on 157 consecutive patients using a Jamshidi needle or an Ostycut needle for bone lesions, or a Tru-cut needle for soft tissue lesions were compared with the final diagnoses made by open biopsy and/or a definitive operation. RESULTS: One hundred forty-three specimens (88%) were determined to be adequate for histological examination. Obtaining undamaged cores from very hard bony lesions or sclerotic cyst walls proved difficult. A pathologist with experience in musculoskeletal lesions was able to differentiate malignant tumors from benign lesions in 97% of the cases (bone, 100%; soft tissue, 94%) and arrive at a specific diagnosis in 88% (bone, 96%; soft tissue, 78%) when adequate cores were obtained. Differentiating a well-differentiated liposarcoma from a benign lipoma and inflammatory lesions from benign tumorous conditions, was difficult. The overall accuracy was 77% (bone, 85%; soft tissue, 68%). There was no morbidity related to the procedure. CONCLUSION: The results indicate that needle biopsy is safe and accurate for diagnosing musculoskeletal lesions.

Adolescent↗

Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice.

Cholangiocellular carcinoma (CC), the second most common primary liver cancer, is associated with a poor prognosis. It has been shown that CCs harbor alterations of a number of tumor-suppressor genes and oncogenes, yet key regulators for tumorigenesis remain unknown. Here we have generated a mouse model that develops CC with high penetrance using liver-specific targeted disruption of tumor suppressors SMAD4 and PTEN. In the absence of SMAD4 and PTEN, hyperplastic foci emerge exclusively from bile ducts of mutant mice at 2 months of age and continue to grow, leading to tumor formation in all animals at 4-7 months of age. We show that CC formation follows a multistep progression of histopathological changes that are associated with significant alterations, including increased levels of phosphorylated AKT, FOXO1, GSK-3beta, mTOR, and ERK and increased nuclear levels of cyclin D1. We further demonstrate that SMAD4 and PTEN regulate each other through a novel feedback mechanism to maintain an expression balance and synergistically repress CC formation. Finally, our analysis of human CC detected PTEN inactivation in a majority of p-AKT-positive CCs, while about half also lost SMAD4 expression. These findings elucidate the relationship between SMAD4 and PTEN and extend our understanding of CC formation.

Animals↗

Hypothesis: the antitumor activities of statins may be mediated by IL-18.

Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase, are thought to reduce the risk of cancer through the inhibition of Ras farnesylation and serum lipid level. A pleiotropic proinflammatory cytokine, interleukin-18 (IL-18), is reported to exhibit significant antitumor activities through the activation of cytotoxic T lymphocytes and natural killer cells and the inhibition of angiogenesis. Previously, we found that pravastatin, fluvastatin, and simvastatin induced the production of IL-18 in human monocytes. The addition of mevalonate abolished the IL-18 production induced by pravastatin, fluvastatin, and simvastatin, indicating that the IL-18 production might be a result of the inhibition of HMG-CoA reductase. We present a new hypothesis that the production of IL-18 might play roles in the action of statins on cancer.

Humans↗

Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes.

The present study demonstrates a possible mechanism for the improvement of gastrointestinal cancer patients' prognosis by the histamine receptor type 2 (H2R) antagonist cimetidine. This agent, but not the H2R antagonists ranitidine and famotidine, induced the production of an antitumor cytokine, interleukin (IL)-18, by human monocytes and dendritic cells (DC). In fact, ranitidine and famotidine antagonized cimetidine-induced IL-18 production. Cimetidine induced the activation of caspase-1, which is reported to modify immature IL-18 to mature/active IL-18, and the elevation of intracellular cAMP, leading to the activation of protein kinase A (PKA). The PKA inhibitor H89 abolished the IL-18 production induced by cimetidine. Moreover, the effects of cimetidine on IL-18 production were reproduced in peripheral blood mononuclear cells from wild-type mice, but not in those from H2R knockout mice. In conclusion, cimetidine, a partial agonist for H2R, has a pharmacological profile different from ranitidine and famotidine, possibly contributing to its antitumor activity on gastrointestinal cancers.

Animals↗

Dendritic cells interacting mainly with B cells in the lymphoepithelial symbiosis of the human palatine tonsil.

The lymphoepithelial symbiosis (LES) of the human palatine tonsil is composed of spindle- or star-shaped epithelial cells forming a loose meshwork, containing numerous lymphocytes and dendritic cells (DCs). In the present study, we immunohistochemically characterized DCs in the LES (LES-DCs). LES-DCs were phenotypically immature DCs that were S100beta+, fascin-, HLA-DR+, CD1a-, CD80-, CD83-, CD86-, and CD123-. The most characteristic feature of LES-DCs was that they contacted many B cells, which were mostly IgM+ IgD+ resting naive B cells. Langerhans cells (LCs) located in the nonsymbiotic squamous epithelium were immature DCs that were S100beta+, fascin-, and CD1a+ and did not contact lymphocytes. In contrast to LES-DCs, interdigitating dendritic cells (IDCs) in the T zone were mature DCs that were HLA-DR+, CD1a-, fascin+, CD80+, CD83+, and CD86+ and contacted numerous CD4+ T cells. Two subsets of IDC, S100beta+ fascin+ IDC (IDC-1) and S100beta- fascin+ IDC (IDC-2), were identified, and the majority of IDCs are IDC-2. In contrast to IDCs, which were distributed in the T-cell area in groups, LES-DCs were distributed along the crypt as if forming a barrier. These findings suggest that LES-DCs are a novel type of DC playing an important role in the induction of humoral immune response against incoming air- or food-borne pathogenic antigens.

B-Lymphocytes↗

Multicenter phase II study of the CyclOBEAP (CHOP-like + etoposide and bleomycin) regimen for patients with poor-prognosis aggressive lymphoma.

Our aim was to study the efficacy of the addition of etoposide and bleomycin to a [cyclophosphamide (CPA), doxorubicin (DXR), vincristine (VCR), and prednisone (PDN)] CHOP-like regimen for the treatment of aggressive lymphoma. The CyclOBEAP regimen was administered over a total period of 12 weeks. Doxorubicin, 50 mg/m(2), was given every 2 weeks in combination with either cyclophosphamide, 1,000 mg/m(2), (weeks 1, 5, 9) or etoposide, 70 mg/m(2) qd x4 (weeks 3, 7, 11). During the alternate weeks, non-myelosuppressive vincristine, 1.4 mg/m(2) (maximum, 2.0 mg/body), was given either with bleomycin, 10 mg/m(2) (weeks 2, 6, 10), or alone (weeks 4,8,12). Prednisolone, 40 mg/m(2), was administered daily for 14 days during weeks 1-2, 5-6, and 9-10. There were 121 eligible patients and median age of 51 years. A complete response was achieved in 106 patients (88%) and a partial response in 11 patients. The 5-year overall survival (OS) rate was 72% and progression-free survival (PFS) rate was 62%. When the patients were divided according to the International Prognostic Index (IPI), the 5-year OS and PFS rates did not significantly differ among risk groups. When the patients with DLBCL were divided according to the IPI, the 5-year OS and PFS rates also did not significantly differ. World Health Organization (WHO) grade 4 neutropenia was observed in 91 patients and thrombocytopenia in 13 patients. No treatment-related deaths were observed. The addition of etoposide and bleomycin to CHOP therapy may enhance the effect of CHOP therapy for aggressive lymphoma. We will perform a prospective study of CyclOBEAP regimen combined with rituximab and test its safety and efficacy.

Adolescent↗

The immunosuppressive effects of ciprofloxacin during human mixed lymphocyte reaction.

Interleukin (IL)-18, which is elevated in the plasma during acute rejection after organ transplantation, is known to induce the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes, the production of interferon (IFN)-gamma and IL-12 and the proliferation of lymphocytes during the human mixed lymphocyte reaction (MLR). Ciprofloxacin (CIP), which is useful for the clinical treatment of infections due to its antibacterial properties after transplantation, was shown to suppress the IFN-gamma and IL-12 production, the lymphocyte proliferation and the ICAM-1, B7.1, B7.2 and CD40 expression on monocytes during MLR in the presence of IL-18. CIP also induced the production of prostaglandin (PG) E2. In order to determine whether the effects of CIP on the expression of the activation markers were due to CIP-dependent production of PGE2, we examined the effect of cyclooxygenase (COX)-2 and protein kinase A (PKA) inhibitors on the actions of CIP. Thereby, the inhibitors were found to abolish the actions of CIP. These results therefore suggest that CIP might exert its immune modulatory effects via the production of PGE2.

B7-1 Antigen↗

Radiofrequency ablation of normal lungs after pulmonary artery embolization with use of degradable starch microspheres: results in a porcine model.

PURPOSE: The present study was performed to evaluate the effect of pulmonary artery embolization on radiofrequency (RF) ablation of normal porcine lungs. MATERIALS AND METHODS: RF ablation zones (n=34) were created in the normal lungs of five domestic pigs (five zones in each of the first two pigs and eight zones in each of the remaining three pigs) with an expandable multitined electrode with use of bilateral thoracotomy. RF ablation was performed without pulmonary artery embolization (group 1, n=8), immediately after embolization (group 2, n=11), 15 minutes after embolization (group 3, n=7), and 30 minutes after embolization (group 4, n=8) with degradable starch microspheres. Among them, 12 ablation zones were excluded from this study because they were considerably limited by the presence of the pleura or large bronchi. The remaining 22 zones were included (n=7, n=5, n=4, and n=6 in groups 1, 2, 3, and 4, respectively). Coagulation necrosis volumes in the ablation zones were measured and compared among the groups. RESULTS: Coagulation necrosis volumes were 0.9+/-0.5 cm3, 2.1+/-0.4 cm3, 2.1+/-1.0 cm3, and 1.9+/-0.6 cm3 in groups 1, 2, 3, and 4, respectively. Groups 2-4 showed significantly larger coagulation volumes than group 1 (P=.012, P=.023, and P=.010 in groups 2, 3, and 4, respectively). CONCLUSION: Pulmonary artery embolization contributed to larger volumes of coagulation necrosis after RF ablation of normal lungs.

Animals↗

The effect of ciprofloxacin on CD14 and toll-like receptor-4 expression on human monocytes.

CD14/toll-like receptor (TLR)-4 complex on monocytes/macrophages can bind lipopolysaccharide (LPS) and transduce the signals intracellularly. An antibacterial drug, ciprofloxacin (CIP), has been reported to modulate the inflammatory and immune responses. In the present study, we examined the effects of CIP on the LPS-induced activation of monocytes isolated from human peripheral blood mononuclear cells (PBMC). CIP suppressed the expression of CD14, TLR-4, intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, and CD40 and the production of tumor necrosis factor (TNF)-alpha induced by LPS in monocytes. CIP induced the production of prostaglandin (PG)E2 and increased intracellular cyclic adenosine monophosphate (cAMP) levels. Cyclooxygenase (COX)-2 inhibitors, NS398 and indomethacin, reversed the effects of CIP on TNF-alpha production and reduced the levels of different surface antigens, whereas a protein kinase A (PKA) inhibitor, H89, did not. Therefore, CIP might regulate the TNF-alpha production induced by LPS by inhibiting the expression of LPS receptor complex, which seems to be mediated by COX-2 but not the cAMP/PKA pathway.

Antigens, CD↗

Stimulation of alpha7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes.

The lipopolysaccharide (LPS)-receptor complex, CD14/toll-like receptor 4, is known to play a role in the immune responses during sepsis. Excessive inflammation and tumor necrosis factor (TNF)-alpha synthesis have been reported to cause morbidity and mortality in endotoxemia and sepsis. Cell-to-cell interaction through the engagement between intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and their ligands on T cells has been suggested to play a role in the inflammatory response such as TNF-alpha and interleukin 10 production. Nicotine, with the stimulation of the nicotinic acetylcholine receptor alpha7 subunit (alpha7-nAChR), has now become the focus of attention because of its anti-inflammatory effects. However, little is known about the mechanism of the inhibitory effects induced by nicotine on the LPS-induced immune responses. In the present study, we found that nicotine suppressed the expression of CD14, toll-like receptor 4, intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and the production of TNF-alpha, but not interleukin 10, in human peripheral blood mononuclear cells in the presence of LPS. The actions of nicotine were reversed by a nonselective and a selective alpha7-nAChR antagonist, mecamylamine and alpha-bungarotoxin, respectively. Therefore, nicotine might inhibit the LPS receptor complex expression via alpha7-nAChR, thus leading to a decrease in the adhesion molecule expression and TNF-alpha production. Moreover, we demonstrated that a nuclear factor-kappaB and a p38 mitogen-activated protein kinase inhibitor mimicked the actions of nicotine in the presence of LPS. These results suggested that the nuclear factor-kappaB and p38 mitogen-activated protein kinase might be involved in the actions of nicotine.

Cells, Cultured↗

Epstein-Barr virus involvement is a predictive factor for the resistance to chemoradiotherapy of gastric diffuse large B-cell lymphoma.

Primary gastric diffuse large B-cell lymphomas are generally well controlled by non-surgical treatment with combination chemotherapy followed by radiotherapy. We have previously reported that over 90% of patients achieved complete response (CR) with this therapeutic strategy: three cycles of cyclophosphamide, adriamycin, vincristine and prednisone followed by radiotherapy (40.5 Gy). Although the CR rate was very high, some patients still showed resistance to this combination therapy. In order to clarify the factors related to therapy resistance, we examined the relationship between Epstein-Barr virus (EBV), which was examined using an in situ hybridization technique, and the patients' clinical courses. Out of the 50 patients, four were EBV positive; over half of lymphoma cells were positive for EBV by in situ hybridization. Of the three EBV-positive patients, two showed progressive disease and one achieved partial response (PR). Two of the patients died of disease progression. The other patient achieved CR, but the lymphoma recurred with distant metastasis in the cerebellum 3 months after remission. In the present study, eight patients did not achieve CR or they relapsed, four patients showed progressive disease, one patient achieved PR, and three patients achieved CR with recurrence. Therefore, half of these unfavorable patients were EBV positive. This finding strongly indicated that EBV-associated gastric diffuse large B-cell lymphomas frequently show resistance to standard chemoradiotherapy, although some other adverse factors remain unclear.

Antineoplastic Combined Chemotherapy Protocols↗