ABSTRACT
Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.
ABSTRACT
The occurrence of carcinoma in a congenital uterine anomaly is uncommon. Indeed, malignancy of the uterine fundus with congenital uterine anomaly is quite rare, with fewer than 50 cases reported in the world liturature. Many patients go through life without the knowledge of their presence, and they are discovered at autopsy. Early diagnosis and proper management is necessary to decrease the high mortality. We present a case of endometrial carcinoma in a single horn of a bicornuate uterus.
Subject(s)
Animals , Female , Humans , Autopsy , Early Diagnosis , Endometrial Neoplasms , Horns , Mortality , UterusABSTRACT
Myelodysplastic syndrome (MDS) is a relatively uncommon hematological disorder, charactedzed by cytopenia in the peripheral blood and normo-or hypercellularity in the bone marrow with morphological dysplastic change. Ineffective hematopoiesis leads to hematological failures in this syndrome. MDS is largeIy affected in older individuaIs with a median age of 60-75. It's association with pregnancy is even rarer. Although the exact incidence of MDS in pregancy is unknown, it is likely to be less than 1 per 100,000 pregnancies annually. Recently, we experienced a case of MDS presented initially during pregnancy in a 34-year-old primipara and managed with intensive hematologic support. Uerine rupture occurred in pregnancy complicated with MDS at 34 gestation weeks and a healthy infant was successfully delivered by Cesarean section. We report this case with a brief review of the literature.
Subject(s)
Adult , Female , Humans , Infant , Pregnancy , Bone Marrow , Cesarean Section , Hematopoiesis , Incidence , Myelodysplastic Syndromes , Rupture , Uterine RuptureABSTRACT
Myelodysplastic syndrome (MDS) is a relatively uncommon hematological disorder, charactedzed by cytopenia in the peripheral blood and normo-or hypercellularity in the bone marrow with morphological dysplastic change. Ineffective hematopoiesis leads to hematological failures in this syndrome. MDS is largeIy affected in older individuaIs with a median age of 60-75. It's association with pregnancy is even rarer. Although the exact incidence of MDS in pregancy is unknown, it is likely to be less than 1 per 100,000 pregnancies annually. Recently, we experienced a case of MDS presented initially during pregnancy in a 34-year-old primipara and managed with intensive hematologic support. Uerine rupture occurred in pregnancy complicated with MDS at 34 gestation weeks and a healthy infant was successfully delivered by Cesarean section. We report this case with a brief review of the literature.
Subject(s)
Adult , Female , Humans , Infant , Pregnancy , Bone Marrow , Cesarean Section , Hematopoiesis , Incidence , Myelodysplastic Syndromes , Rupture , Uterine RuptureABSTRACT
Primary ovarian pregnacy is a rare form of ectopic pregnacy of which an estimated overall incidence is highly variable, but improved diagnosis of acute hemoperitoneum of ovarian may reveal a higher incidence than reported earlier. Ovarian pregnancy is uaually accompanied with the rupture of the ovary and massive hemoperitoneum. It usually presents with abdominal pain, menstural irregularities, vaginal bleeding, a palpable adnexal mass and other symptoms which are very similar to those of tubal ectopic pregnacy and hemorrhgic corpus luteum cysts. Risk factors to ovarian pregnancy include a history of pelvic inflammatory disease (PID), prior pelvic surgery, and use of an intrauterine contraceptive devices (IUD). We have experienced three cases of ovarian pregnancy, which are presented with a brief review of the literature.
Subject(s)
Female , Pregnancy , Abdominal Pain , Diagnosis , Hemoperitoneum , Incidence , Intrauterine Devices , Ovarian Cysts , Ovary , Pelvic Inflammatory Disease , Pregnancy, Ectopic , Risk Factors , Rupture , Uterine HemorrhageABSTRACT
Primary ovarian pregnacy is a rare form of ectopic pregnacy of which an estimated overall incidence is highly variable, but improved diagnosis of acute hemoperitoneum of ovarian may reveal a higher incidence than reported earlier. Ovarian pregnancy is uaually accompanied with the rupture of the ovary and massive hemoperitoneum. It usually presents with abdominal pain, menstural irregularities, vaginal bleeding, a palpable adnexal mass and other symptoms which are very similar to those of tubal ectopic pregnacy and hemorrhgic corpus luteum cysts. Risk factors to ovarian pregnancy include a history of pelvic inflammatory disease (PID), prior pelvic surgery, and use of an intrauterine contraceptive devices (IUD). We have experienced three cases of ovarian pregnancy, which are presented with a brief review of the literature.
Subject(s)
Female , Pregnancy , Abdominal Pain , Diagnosis , Hemoperitoneum , Incidence , Intrauterine Devices , Ovarian Cysts , Ovary , Pelvic Inflammatory Disease , Pregnancy, Ectopic , Risk Factors , Rupture , Uterine HemorrhageABSTRACT
OBJECTIVE: This study investigated changes of voice and hearing in premenopausal and postmenopausal woman METHODS: We studied forty postmenopausal and forty premenopausal women. Each women was asked to describe their subjective vocal symptoms and phonate a vowel /a/ sound for 3 seconds. The phonated sound in each case was recorded and analysed by the computerized speech lab (LSL 4300B, KAY Elemetrics Corp. USA). we also conducted audiometric pure-tone threshold testing on the same group. Statistical analysis of voice and hearing parameters was done by paired T test RESULTS: Jitter in menopausal group was significantly increased compared with premenopausal group, but other voice parameters showed no significant differences. There were no significant changes of vocal parameters between menopausal patients with or without vocal symptoms. And there were no significant changes of hearing parameters, either CONCLUSION: The change of voice parameters was objectively identified in menopausal women, and so therapist of menopausal symptoms must take the voice changes into consideration.