Recent advances in treatment of nodal and gastrointestinal follicular lymphoma

Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis.However,primary FL of the gastrointestinal tract has been increasingly detected in Japan,especially due to recent advances in small bowel endoscopy and increased opportunities for endoscopic examinations and endoscopic diagnosis.However,many cases are detected at an early stage,and the prognosis is good in many cases.In contrast,in Europe and the United States,gastrointestinal FL has long been considered to be present in 12%-24%of Stage-IV patients,and the number of advanced gastrointestinal cases is expected to increase.This editorial provides an overview of the recent therapeutic advances in nodal FL,including antibody-targeted therapy,bispecific antibody therapy,epigenetic modulation,and chimeric antigen receptor T-cell therapy,and reviews the latest therapeutic manuscripts published in the past year.Based on an understanding of the therapeutic advances in nodal FL,we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL,especially in advanced cases.

Gene targeted and immune therapies for nodal and gastrointestinal follicular lymphomas

Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.

Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)].Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

Treatment strategies for nodal and gastrointestinal follicular lymphoma:Current status and future development

In recent years,therapies for follicular lymphoma (FL) have steadily improved.A series of phase Ⅲ trials comparing the effect of rituximab with chemotherapy vs chemotherapy alone in treating FL have indicated significant improvements in progression-free survival (PFS) and overall survival.Recent studies have found that prolonged response durations and PFS were obtained with maintenance therapy using rituximab or interferon after completion of first line therapy.For patients with relapsed or refractory FL,phase Ⅱ studies have assessed the effectiveness of combination therapies using a Toll-like receptor-9 agonist (1018ISS),oblimersen sodium (a Bcl-2 antisense oligonucleotide),bendamustine,and rituximab,as well as veltuzumab,a new humanized anti-CD20 antibody,and epratuzumab.In addition,the effectiveness of yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab as radioimmunotherapies has been reported.Furthermore,three phase Ⅲ studies on an idiotype vaccine are near completion.Unfortunately,these vaccines,which appeared highly effective in phase Ⅰ and Ⅱ trials,do not appear to result in prolonged PFS.This report will summarize the current knowledge on therapies for treatment of FL,and will conclude with a brief discussion of feasiblefuture options for effective treatments.Lastly,we added descriptions of the management of gastrointestinal FL,which is considered to be controversial because it is rare.

Crk adaptor protein-induced phosphorylation of Gab1 on tyrosine 307 via Src is important for organization of focal adhesions and enhanced cell migration

在生长因素刺激之上，支架蛋白质， Gab1，是酷氨酸 phosphorylated 并且随后适配器蛋白质， Crk，从 Gab1 播送信号。我们以前证明了没有细胞外的刺激， Crk overexpression，在各种各样的人的癌症可检测，导致 Gab1 的酷氨酸 phosphorylation。在现在的学习，内在的机制进一步被调查。CrkII 的 Mutational 分析证明 SH2 领域，然而并非 SH3 (N) 或 CrkII 的规章的 Y221 残余，为 Gab1-Y307 phosphorylation 的正式就职是批评的。CrkII 的 SH2 变化也减少了和 Gab1 的相互作用。在 GST 下拉试金，而 Crk-SH3 (N) 与 Gab1 异种交往了， Crk-SH2 跳了到野类型的 Gab1，它缺乏聚类的酷氨酸区域(残余 242-410 ) 。Gab1 的酷氨酸 phosphorylation 被表明适配器的所有 Crk 家庭蛋白质，然而并非另外的包含 SH2 导致。Src 家庭 kinase 禁止者， PP2，废除 Gab1 的导致 Crk 的酷氨酸 phosphorylations。Y307 phosphorylation 在缺乏 Src，是，和 Fyn 的成纤维细胞是无法发现的，甚至在 Crk 的 overexpression 之上，而缺乏仅仅是和 Fyn 的房间仍然与 phosphorylated Y307 包含了 Gab1。而且， Crk 导致了 Src-Y416 的 phosphorylation；因此，在 Crk 和 Csk 之间的相互作用被增加。Gab1-Y307F 异种没能近甚至在 HGF 之上本地化血浆膜刺激和减少的房间移植。而且， Gab1-Y307F 扰乱了 Crk， FAK，和 paxillin 的本地化，它是焦点的粘附的典型部件。一起拿，这些结果显示 Crk 通过 Src 便于 Gab1-Y307 的酷氨酸 phosphorylation，贡献焦点的粘附和提高的房间移植的组织，可能从而支持人的癌症开发。

Thermoelectric Properties of Misfit Layered Bismuth-Based Rhodium Oxides, (Bi,Pb)₂Sr₂Rh₂O_y

Rhodium oxides, including a misfitlayered structure with alternate stacking of a rock salttype layer and a hexagonal RhO2 layer, are expected to have good thermoelectric properties. Among them, the thermoelectric properties (electrical conductivity (σ), Seebeck coefficient (S), Figure of merit (ZT) and calculated thermal conductivity (κ) by S, σ, ZT, and absolute temperature (T)) of bismuth-based rhodium oxides ((Bi1-x,Pbx) 2Sr2Rh2Oy, x = 0 and 0.02, hereafter BSR and BPSR, respectively) were investigated. In comparison with Bi2Sr2Co2Oy (BSC) at 700°C, S and κ enhanced (increased S, 110 (BSR) and 105 μV K-1 (BPSR) from 85 μV K-1 (BSC) and decreased κ, 0.32 (BSR) and 0.50 W m-1 K-1 (BPSR) from 1.75 W m-1 K-1 (BSC)), whereas σ decreased (15 (BSR) and 31 S cm-1 (BPSR) from 70 S cm-1 (BSC)). BPSR reached the highest ZT value of 0.067 at 700°C, compared to those of 0.056 (BSR) and 0.027 (BSC).

Solitary pituitary metastasis resulting from pulmonary large cell neuroendocrine carcinoma

Solitary pituitary metastasis is a rare phenomenon in human neoplasms. We report a case of lung cancer with the initial manifestation of endocrinopathy resulting from pituitary metastasis. The patient's initial diagnosis was a poorly differentiated carcinoma, however, morbid anatomy revealed a definite diagnosis of large cell neuroendocrine carcinoma(LCNEC). Clinical physicians should be aware of potential initial manifestations such as endocrine abnormalities including panhypopituitarism and diabetes insipidus due to solitary pituitary metastasis. This case demonstrates that an endocrine abnormality such as panhypopituitarism could be an initial manifestation of LCNEC.

Recent advances in treatment of follicular lymphoma: efficacy of PI3Kα/δ inhibitor (TQ-B3525)

The commented study reports the results of monotherapy using TQ-B3525,a novel phosphatidylinositol-3 kinase(PI3K)inhibitor developed in China,in patients with refractory/relapsed follicular lymphoma(r/r FL).

Extract of Yokukansan improves anxiety-like behavior and increases serum brain-derived neurotrophic factor in rats with cerebral ischemia combined with amyloid-β42 peptide

OBJECTIVE: To examine the effects of Yokukansan(YKS) extract on two endogenous modulators of anxiety, brain-derived neurotrophic factor(BDNF)and serotonin (5-HT)_(2A) receptors pharmacologically, in the ischemic rat model of dementia.METHODS: The cerebral ischemia(CI) was induced by bilateral occlusion of the vertebral and common carotid arteries(4-vessel occlusion ischemia). The CI was combined with the amyloid-β42 peptide(A42) injected intracerebroventricularly, and referreβdto as CI+Aβ. Anxiety-like behaviors were assessed by elevated plus maze(enclosed arm), light/dark transition test(dark chamber), and open-field test.Wet-dog shakes were induced by the 5-HT_(2A) receptor agonist 2, 5-dimethoxy-4-iodoamphetamine(DOI). The concentration of BDNF in serum was determined by enzyme-linked immuno sorbent assay.RESULTS: CI + Aβ increased anxiety, as demonstrated by the increase of time spent in the enclosed arms and dark chambers, and locomotion in the outer zone of the open field(thigmotaxis). CI + Adecreased the serum concentration of BDNF. YKS reβ-duced the anxiety-like behaviors, suppressed the DOI-induced wet-dog shakes and increased serum BDNF concentrations.CONCLUSION: Our findings suggest that YKS extract improves CI + Aβ-induced anxiety by antagonizing 5-HT_(2A) receptors and increasing BDNF.