Acute leukemias in pregnant women: Results of a retrospective study at a local tertiary-care hospital in Japan.

Leukemia may rarely develop in a woman during pregnancy, posing clinical challenges to the patient, fetus, family, and medical staff managing malignancy and pregnancy. We retrospectively analyzed cases of pregnancy-associated leukemia consecutively diagnosed and treated at a local tertiary-care hospital in Nagano, Japan, over the past 20 years. Five cases were identified among 377,000 pregnancies in the area (one in every 75,000 pregnancies), all involving acute leukemia (three acute myelogenous leukemia [AML] and two acute lymphoblastic leukemia [ALL]). The cases were diagnosed in the first trimester (n = 1), second trimester (n = 3), or third trimester (n = 1). There were no apparent pregnancy-associated delays in diagnosing and treating the cases. Three patients underwent induction chemotherapy during pregnancy, two of whom eventually delivered healthy babies. One of the five patients chose abortion before chemotherapy initiation. Two cases showing high-risk features at the diagnosis (AML with an FLT3-ITD mutation [n = 1] and relapsed ALL [n = 1]) eventually died despite consolidative allogeneic hematopoietic stem cell transplantation. Our results suggested that patients with pregnancy-associated acute leukemia can be treated similarly to nonpregnant patients, although pregnancy imposes particular clinical challenges that should be resolved with multidisciplinary care.

Tenosynovial Giant Cell Tumor, Localized Type With Extensive Chondroid Metaplasia: A Case Report With Immunohistochemical and Molecular Genetic Analysis.

Tenosynovial giant cell tumor (TSGCT) of localized type is a common disease occurring mostly in the hands. Diagnosis of this tumor is relatively easy to render with hematoxylin-eosin-stained sections as compared with that of TSGCT of diffuse type. However, very rare cases with chondroid metaplasia that have recently been reported mainly in diffuse type can make pathological differentiation from soft tissue cartilaginous tumors extremely difficult. In this article, the authors present the second reported case of TSGCT of localized type showing extensive chondroid metaplasia. Pathological interpretation was difficult without utilizing immunohistochemistry and fluorescence in situ hybridization. One must be careful not to misdiagnose this lesion as cartilaginous tumors of soft tissue, and we suspect at least some chondroblastoma-like chondroma could be reclassified as TSGCT of localized type with extensive chondroid metaplasia. Morphological, immunohistochemical, and molecular genetic characteristics are presented and discussed.

Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas.

Expression of matrix metalloproteinase 7 (MMP7) is increased in the human colorectal carcinomas, and correlates with malignant progression. However, its contribution to colon cancer pathogenesis is not understood thoroughly. To investigate the roles of MMP7 in colon cancer progression, we introduced an Mmp7 knockout mutation into the cis-Apc/Smad4 mutant mouse, a model of invasive colon cancer in which SMAD4-dependent TGF-beta family signaling is inactivated. We demonstrate here that lack of MMP7 reduces the number and size of tumors in the cis-Apc/Smad4 mice. On the other hand, MMP7-deficiency does not affect the depth of tumor invasion, number of stromal fibroblasts or levels of extracellular matrix components in the tumors. These results indicate that MMP7 is required for tumor formation, but not for the invasion or fibrosis of the colon cancer whose SMAD4-dependent TGF-beta family signaling is blocked.

Complement C5a stimulates food intake via a prostaglandin D(2)- and neuropeptide Y-dependent mechanism in mice.

We have recently found that prostaglandin (PG) D(2) stimulates food intake via DP(1) receptor. Here we show that complement C5a stimulates food intake by activating the orexigenic PGD(2) system. C5a (30-100 pmol/mouse), after intracerebroventricular administration, stimulated food intake in non-food-deprived mice. The orexigenic activity of C5a was blocked by co-administration of a DP(1) receptor antagonist, BWA868C. Central administration of C5a elevated the hypothalamic mRNA expression of COX-2 but not COX-1, and the food intake stimulation of C5a was inhibited by pretreatment with a COX-2 inhibitor, celecoxib, suggesting that C5a activates COX-2 upstream of the PGD(2)-DP(1) system. The orexigenic activity of C5a was also inhibited by an antagonist for neuropeptide Y (NPY) Y(1) receptor, which was activated downstream of the PGD(2)-DP(1) system. These results suggest that C5a stimulates food intake via a PGD(2)- and NPY-dependent mechanism. C5a is the first example of orexigenic peptides acting through the PGD(2)-NPY system in the central nervous system.

Central prostaglandin D(2) stimulates food intake via the neuropeptide Y system in mice.

We found that prostaglandin (PG) D(2), the most abundant PG in the central nervous system, stimulates food intake after intracerebroventricular administration in mice. The orexigenic effect of PGD(2) was mimicked by a selective agonist for the DP(1) receptor among two receptor subtypes for PGD(2), and abolished by its antagonist. Central administration of an antagonist or antisense oligodeoxynucleotide for the DP(1) receptor remarkably decreased food intake, body weight and fat mass. Hypothalamic mRNA levels of lipocalin-type PGD synthase were up-regulated after fasting. The orexigenic activity of PGD(2) was also abolished by an antagonist for neuropeptide Y (NPY) Y(1) receptor. Taken together, PGD(2) may stimulate food intake through central DP(1) receptor coupled to the NPY system.

Id2 deletion attenuates Apc-deficient ileal tumor formation.

The expression level of inhibitor of DNA binding 2 (Id2) is increased in colorectal carcinomas and is positively correlated with poor prognosis. However, the functional significance of Id2 in intestinal tumorigenesis has not been fully defined using genetic approaches. Here, we show that Id2 promotes ileal tumor initiation in Apc-deficient mice. Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc(+/Δ716) (Apc(Δ716)) mice. Genetic depletion of Id2 in Apc(Δ716) mice caused ∼80% reduction in the number of ileal polyps, but had little effect on tumor size. Notably, the lack of Id2 increased the number of apoptotic cells in the normal crypt epithelium of the mice. Furthermore, DNA microarray analysis revealed that the expression level of Max dimerization protein 1 (Mxd1), known as a c-Myc antagonist, was specifically increased by Id2 deletion in the ileal intestinal epithelium of Apc(Δ716) mice. In contrast, the protein level of c-Myc, but not the mRNA level, was decreased by loss of Id2 in these mice. These results indicate that loss of Id2 inhibits tumor initiation by up-regulation of Mxd1 and down-regulation of c-Myc in Apc(Δ716) mice.