Knockdown of POLDIP2 suppresses tumor growth and invasion capacity and is linked to unfavorable transformation ability and metastatic feature in non-small cell lung cancer.

The main problem in the treatment of non-small cell lung cancer (NSCLC) is metastasis. Epithelial-mesenchymal transition (EMT) is known as the critical signaling in tumor progression, metastasis, and also the drug resistance. In this study, we reported a novel gene Polymerase delta-interacting protein 2 (POLDIP2) was downregulated in NSCLC tissues and first demonstrated that overexpression of POLDIP2 increased the anchorage-independent growth (AIG) and invasiveness of H1299 cells. In addition, we examined that knockdown of POLDIP2 in H1299 and A549 cells reduced tumorigenicity and metastatic capacity in vitro and also in vivo. Moreover, downregulation of the cell proliferation marker cyclin D1 and EMT markers CDH2, Slug, and Twist was showed in H1299 cells by POLDIP2 knockdown, suggesting that the inhibition of malignancy was affected by modulating key genes for tumor growth and invasiveness. Taken together, our study is the first study that demonstrated that POLDIP2 gene was function as an oncogene in NSCLC and implied the oncogenic ability might be through promoting cell proliferation or EMT.

SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer.

The development of lung cancer is a complex process that involves many genetic and epigenetic changes. Sex-determining region Y (SRY)-box (SOX) genes encode a family of proteins that are involved in the regulation of embryonic development and cell fate determination. SOX1 is hypermethylated in human cancers. However, the role of SOX1 in the development of lung cancer is unclear. We used quantitative methylation-specific polymerase chain reaction (MSP), quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, and web tools to confirm the frequent epigenetic silencing of SOX1 in lung cancer. Stable overexpression of SOX1 repressed cell proliferation, anchorage-independent growth, and invasion in vitro as well as cancer growth and metastasis in a xenograft mouse model. Knockdown of SOX1 by the withdrawal of doxycycline partly restored the malignant phenotype of inducible SOX1-expressing NSCLC cells. Next, we discovered the potential downstream pathways of SOX1 using RNA-seq analysis and identified HES1 as a direct target of SOX1 using chromatin immunoprecipitation (ChIP)-PCR. Furthermore, we performed phenotypic rescue experiments to prove that overexpression of HES1-FLAG in SOX1-expressing H1299 cells partly reversed the tumor-suppressive effect. Taken together, these data demonstrated that SOX1 acts as a tumor suppressor by directly inhibiting HES1 during the development of NSCLC.

Laminin-511 and recombinant vitronectin supplementation enables human pluripotent stem cell culture and differentiation on conventional tissue culture polystyrene surfaces in xeno-free conditions.

Human pluripotent stem cells (hPSCs) are typically cultivated on extracellular matrix (ECM) protein-coated dishes in xeno-free culture conditions. We supplemented mixed ECM proteins (laminin-511 and recombinant vitronectin, rVT) in culture medium for hPSC culture on conventional polystyrene dishes. Three hPSC cell lines were successfully cultivated on uncoated polystyrene dishes in medium supplemented with optimal conditions of laminin-511 and rVT. Excellent colony shape and colony size as well as high expansion fold of hPSCs were found under these conditions, whereas the colony size was small and poor expansion fold was found solely on L-511-coated dishes. A small portion of L-511 in the culture medium supported hPSC adhesion and prevented the adhesion from being too strong on the uncoated dishes, and rVT in the culture medium further supported adhesion of hPSCs on the dishes by maintaining their pluripotency. Having the optimal composition of L-511 and rVT in the culture medium was important for generating good hPSC colony shapes and sizes as well as a high expansion fold. After long-term culture of hPSCs on uncoated dishes supplemented with the mixed proteins, the hPSCs successfully showed pluripotent markers and could differentiate into a specific lineage of cells, cardiomyocytes, with high efficiency.

Purification of Colon Carcinoma Cells from Primary Colon Tumor Using a Filtration Method via Porous Polymeric Filters.

Cancer stem cells (CSCs) or cancer-initiating cells (CICs) are key factors for tumor generation and metastasis. We investigated a filtration method to enhance CSCs (CICs) from colon carcinoma HT-29 cells and primary colon carcinoma cells derived from patient colon tumors using poly(lactide-co-glycolic acid)/silk screen (PLGA/SK) filters. The colon carcinoma cell solutions were permeated via porous filters to obtain a permeation solution. Then, the cell cultivation media were permeated via the filters to obtain the recovered solution, where the colon carcinoma cells that adhered to the filters were washed off into the recovered solution. Subsequently, the filters were incubated in the culture media to obtain the migrated cells via the filters. Colon carcinoma HT-29 cells with high tumorigenicity, which might be CSCs (CICs), were enhanced in the cells in the recovered solution and in the migrated cells based on the CSC (CIC) marker expression, colony-forming unit assay, and carcinoembryonic antigen (CEA) production. Although primary colon carcinoma cells isolated from colon tumor tissues contained fibroblast-like cells, the primary colon carcinoma cells were purified from fibroblast-like cells by filtration through PLGA/SK filters, indicating that the filtration method is effective in purifying primary colon carcinoma cells.

Promoter hypermethylation of FBXO32, a novel TGF-beta/SMAD4 target gene and tumor suppressor, is associated with poor prognosis in human ovarian cancer.

Resistance to TGF-beta is frequently observed in ovarian cancer, and disrupted TGF-beta/SMAD4 signaling results in the aberrant expression of downstream target genes in the disease. Our previous study showed that ADAM19, a SMAD4 target gene, is downregulated through epigenetic mechanisms in ovarian cancer with aberrant TGF-beta/SMAD4 signaling. In this study, we investigated the mechanism of downregulation of FBXO32, another SMAD4 target gene, and the clinical significance of the loss of FBXO32 expression in ovarian cancer. Expression of FBXO32 was observed in the normal ovarian surface epithelium, but not in ovarian cancer cell lines. FBXO32 methylation was observed in ovarian cancer cell lines displaying constitutive TGF-beta/SMAD4 signaling, and epigenetic drug treatment restored FBXO32 expression in ovarian cancer cell lines regardless of FBXO32 methylation status, suggesting that epigenetic regulation of this gene in ovarian cancer may be a common event. In advanced-stage ovarian tumors, a significant (29.3%; P<0.05) methylation frequency of FBXO32 was observed and the association between FBXO32 methylation and shorter progression-free survival was significant, as determined by both Kaplan-Meier analysis (P<0.05) and multivariate Cox regression analysis (hazard ratio: 1.003, P<0.05). Reexpression of FBXO32 markedly reduced proliferation of a platinum-resistant ovarian cancer cell line both in vitro and in vivo, due to increased apoptosis of the cells, and resensitized ovarian cancer cells to cisplatin. In conclusion, the novel tumor suppressor FBXO32 is epigenetically silenced in ovarian cancer cell lines with disrupted TGF-beta/SMAD4 signaling, and FBXO32 methylation status predicts survival in patients with ovarian cancer.

Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway.

Oncogenic activation of the Wnt signaling pathway is common in cancers, but mutation of beta-catenin in ovarian cancer is rare. In addition to genetic events, epigenetic modification of secreted frizzled-related protein (SFRP) family has been shown to be important in regulating Wnt signaling. Although high degree of homology is observed in the same family, different SFRPs may have opposing effects on the same process. We reported recently that a Wnt antagonist, SFRP5, is downregulated frequently through promoter hypermethylation and that this hypermethylation is associated with overall survival in ovarian cancer. The aim of this study was to analyze the function of SFRP5 in ovarian cancer. Functional assays including measuring cell proliferation, invasion, colony formation and xenograft were performed using ovarian cancer cell lines with overexpression of SFRP5 or a short hairpin RNA silencing. The methylation status of SFRP5 in relation to cisplatin resistance in ovarian cancer patients was analyzed. Restoration of the expression of SFRP5 attenuated Wnt signaling in ovarian cancer cells and suppressed cancer cell growth, invasion of cells and tumorigenicity in mice. These effects were independent of the canonical pathway. The expression of SFRP5 inhibited epithelial-mesenchymal transition (EMT). The restoration of SFRP5 downregulated AKT2 and sensitized ovarian cancer cells to chemotherapy. These effects are consistent with the poor response to platinum-based chemotherapy in patients with methylation of SFRP5. Our data suggested that epigenetic silencing of SFRP5 leads to oncogenic activation of the Wnt pathway and contributes to ovarian cancer progression and chemoresistance through the TWIST-mediated EMT and AKT2 signaling.

Characterization of LMX-1A as a metastasis suppressor in cervical cancer.

DNA methylation is important in cancer development and is a promising biomarker for cancer detection. An epigenomic approach used in our previous work showed that LMX-1A is methylation-silenced in cervical cancer. LMX-1A, a LIM-homeobox gene, is known to participate in developmental events; however, there are at present no data on the role of LMX-1A in cancers. In this study, we characterized the function of this transcription factor by examining cell lines, animal models and human cervical neoplastic tissues, and found that over-expression of LMX-1A does not affect cell proliferation or the cell cycle of cervical cancer cell lines but significantly inhibits colony formation and invasion in vitro. Analysis of changes in epithelial-mesenchymal transition (EMT) markers, such as CDH1, CDH2, VIMENTIN, SNAIL, SLUG and TWIST, revealed involvement of the EMT in LMX-1A-mediated cancer invasion; this result was validated in a stable transfectant over-expressing LMX-1A with RNA interference. Xenograft studies using immunocompromised mice confirmed the suppressor effects of LMX-1A on tumour formation and distant metastasis in cervical cancer cell lines. LMX-1A immunohistochemical staining of tissue arrays containing the full spectrum of cervical neoplasms, including normal cervix, low-grade cervical intra-epithelial neoplasia (CIN), high-grade CIN, locally invasive and distant metastatic cancers, demonstrated the critical role of LMX-1A in invasion and metastasis. Furthermore, we found by analysing TGFbeta-BMP signalling that BMP4 and BMP6 are down-regulated by LMX-1A. The results of this study suggest that LMX-1A suppresses cancer invasion and metastasis in cervical cancer through an incomplete EMT.

Culture and differentiation of purified human adipose-derived stem cells by membrane filtration via nylon mesh filters.

Human adipose-derived stem cells (hASCs) cultured for 5 passages were filtered through nylon (NY) mesh filter membranes coated with and without extracellular matrix proteins to obtain the permeation solution. Subsequently, the culture media were filtered via the membranes to obtain the recovery solution. Then, the membranes were cultured in cell culture medium to obtain the migrated cells from the membranes. The hASCs in the permeation solution, through any type of NY mesh filter membrane having 11 and 20 µm pore sizes, had lower osteogenic differentiation ability than conventional hASCs cultured on tissue culture polystyrene (TCP) dishes for passage 5, whereas the hASCs purified by the membrane migration method through NY mesh filter membranes coated with recombinant vitronectin, which have 11 and 20 µm pore sizes, showed a higher proliferation speed as well as higher osteogenic differentiation potential than the conventional hASCs cultured on TCP dishes for passage 5. The membrane filtration and migration methods would be useful for cell sorting for specific cells, such as hASCs with high proliferation and high osteogenic differentiation ability, which do not need antibody binding or genetic modification of the cells for the specific isolation of the cells.

Enrichment of cancer-initiating cells from colon cancer cells through porous polymeric membranes by a membrane filtration method.

Cancer-initiating cells (CICs) or cancer stem cells (CSCs) are primarily responsible for tumor initiation, growth, and metastasis and represent a few percent of the total tumor cell population. We designed a membrane filtration protocol to enrich CICs (CSCs) from the LoVo colon cancer cell line via nylon mesh filter membranes with 11 and 20 µm pore sizes and poly(lactide-co-glycolic acid)/silk screen (PLGA/silk screen) porous membranes (pore sizes of 20-30 µm). The colon cancer cell solution was filtered through the membranes to obtain a permeate solution. Subsequently, the cell culture medium was filtered through the membranes to collect the recovery solution where the cells attached to the membranes were rinsed off into the recovery solution. Then, the membranes were cultivated in the cultivation medium to collect the migrated cells from the membranes. The cells migrated from any membrane had higher expression of the CSC surface markers CD44 and CD133, had higher colony formation levels, and produced more carcinoembryonic antigen (CEA) than the colon cancer cells cultivated on conventional tissue culture plates (control). We established a method to enrich the CICs (CSCs) of colon cancer cells from migrated cells through porous polymeric membranes by the membrane filtration protocol developed in this study.

An epigenetic marker panel for screening and prognostic prediction of ovarian cancer.

Aberrant CpG island hypermethylation is a common finding of cancers, which might be detectable in the tissue or serum of affected patients. We analyzed DNA methylation by methylation-specific polymerase chain reaction of 7 genes, which included secreted frizzled receptor proteins 1, 2, 4, 5 (SFRP1, 2, 4, 5), SRY-box 1 (SOX1), paired box gene 1 (PAX1) and LIM homeobox transcription factor 1, alpha (LMX1A) in primary tumor samples from 126 patients with ovarian cancer, 75 with a benign tumor and 14 with borderline malignancy of an ovarian tumor, and in the serum from 26 patients with ovarian cancer and 20 with a benign tumor. Six of 7 genes had higher methylation rates in patients with ovarian cancer than in borderline malignancy or benign tumor (p<0.001). The methylation of SFRP1, SFRP2, SOX1 and LMX1A genes correlated with recurrence and overall survival of ovarian cancer patients. Combining the data for SFRP1, SFRP2 and SOX1 genes gave a relative risk for recurrence of 3.19 (p=0.013) in patients with at least one gene methylation, and combining the data for SFRP1, SOX1 and LMX1A gave an RR for cancer-related death of 6.09 (p=0.010). Methylation analysis of tissues and serum revealed a significant correlation (kappa values, 0.332-0.598) and a highly sensitivity and specificity rates (73.08 and 75%) as a screening marker. In conclusion, promoter hypermethylation of specific genes in critical pathways is common in ovarian cancer and has potential as a prognostic factor and a promising serum marker for early screening.

Association of cortactin, fascin-1 and epidermal growth factor receptor (EGFR) expression in ovarian carcinomas: correlation with clinicopathological parameters.

Cortactin, fascin-1 and EGFR are recognized as important factors in tumor progression. We tested the hypothesis that cortactin, fascin-1 and EGFR expression correlates with clinicopathological parameters of the four most common ovarian surface epithelial carcinomas--serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid adenocarcinoma, and clear cell carcinoma. Immunohistochemical analysis of cortactin, fascin-1 and EGFR was performed using tissue microarrays of 172 specimens comprising 69 serous cystadenocarcinomas, 44 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas and 14 clear cell carcinomas. All ovarian carcinomas showed significant expression of cortactin, fascin-1 and EGFR in staining intensity, tumor percentages and immunostaining scores. In addition, higher immunostaining scores of fascin-1 correlated with more advanced cancer stages (TNM), poorer histological differentiation and poorer survival rate of mucinous cystadenocarcinoma. Similarly, higher immunostaining scores of cortactin correlated with T stages and histological differentiation of serous cystadenocarcinoma. The immunostaining scores of EGFR did not correlate with TNM stages, tumor differentiation or prognosis in the four ovarian surface epithelial carcinomas. Our findings suggest that cortactin and fascin-1 may serve as good biomarkers in evaluating aggressiveness of ovarian serous and mucinous cystadenocarcinoma. And the pharmacological inhibitors of fascin-1 activity may slow down tumor progression and prolong survival time in patients with mucinous cystadenocarcinoma.

Residual ovarian syndrome: A case report with classic symptoms, imaging and pathology findings, and treatment.

OBJECTIVE: Residual ovarian syndrome (ROS) occurs after a hysterectomy in which one or both ovaries have been preserved and cause chronic pelvic pain, an asymptomatic pelvic mass, or dyspareunia. We present a case with classic symptoms and imaging and pathology findings, and review the treatment of residual ovarian syndrome. CASE REPORT: A 35-year-old woman with a diagnosis of ROS. CONCLUSION: Based on previous literature, almost 50% of patients with ROS require surgery for their symptoms. Treatment of ROS with gonadotropin-releasing hormone analogs or high dose progestogens may be helpful. However, there are limited data supporting the efficacy of pharmacologic therapy. Patients receiving pharmacologic therapy should be counseled about the limited data supporting the efficacy of this approach, the lack of a histologic diagnosis, and the risk of ovarian cancer in residual tissue.

Painless ovarian tumor mimics ovarian cancer with all ligaments spontaneously detached: A case report.

OBJECTIVE: Ovarian tumor is a frequently encountered gynecological disease. The tumor is usually anchored by a pedicle. In rare cases, it may detach and derive nourishment from other abdominal structures to which it adheres. Even rarer is for the tumor to be freely mobile, with no ligamentous attachment. CASE REPORT: A 21-year-old woman with delayed menstruation and chronic low abdominal pain for months, had a well-defined cystic lesion of approximately 9 × 9 cm in the middle of the pelvis, identified on transabdominal sonography and abdominal computed tomography. During an exploratory laparotomy, we found an ovarian tumor on the left side of the pelvis, in which the pedicle had spontaneously detached; it was removed without dissection or resection. The tumor was well-encapsulated and suspended without any ligament attachments. CONCLUSION: Freely mobile ovarian tumors with all ligaments spontaneously detached may be misdiagnosed because there is no pain caused by torsion. The absence of blood flow leads to internal necrosis, easily mistaken for malignancy or other diseases. Also, the location may change from the time images are captured until surgery. Surgery is the best option, regardless of the final diagnosis.

Flow mediated dilatation of Taiwanese women with normal singleton pregnancies.

OBJECTIVE: To determine the normal values of flow mediated dilatation (FMD) in Taiwanese women with normal singleton pregnancies for the early detection of preeclampsia. MATERIALS AND METHODS: Data of women with normal singleton pregnancies seen at the Tri-Service General Hospital and Taiji Clinic between January 2014 and December 2015 were collected and analyzed. FMD was measured using high-resolution ultrasonography of the brachial artery for the assessment of endothelial function at the first and second trimester. The relationship between the FMD values and maternal gestational age was analyzed. RESULTS: A total of 122 pregnant women were included in the study. Systole FMD values first and second trimester were 9.05 ± 3.72 and 10.93 ± 3.74, respectively; and the diastole were 9.24 ± 3.64 and 11.18 ± 3.93, respectively. FMD and gestational age were positively correlated (systole, p = 0.0175; diastole, p = 0.0149). CONCLUSION: The normal values of FMD in Taiwanese women with normal singleton pregnancies were established, and data suggests that both systolic and diastolic FMD increase with gestational age. Because of the high failure rate, measurement of FMD may not be suitable as a routine clinical examination.

Asymptomatic uterine incarceration at term: Successful management of a rare complication in pregnancy.

OBJECTIVE: Incarcerated gravid uterus is a rare complication of pregnancy and can become a critical condition during delivery. For extremely uncommon cases that persist to the third trimester, correct diagnosis before delivery and appropriate management of the associated complications are important. CASE REPORT: This was the first case of a full-term pregnancy with incarcerated gravid uterus, reported at a medical center. The condition was not diagnosed during pregnancy, which led to serious complications during the cesarean delivery; however, the prognosis was favorable because of the timely management. CONCLUSION: Based on the previous case reports and clinical presentation of this case, early diagnosis with ultrasound and pelvic examination is the key to successful treatment. Vertical and more cephalad uterine incision reduces the risk of bladder perforation and injury to the cervix and vagina. A successful teamwork of obstetricians, gynecologists, urologists, and anesthesiologists can ensure favorable outcomes for both mother and fetus.

Pregnancy and childbirth in a patient with multiple sclerosis: A case report of successful management.

OBJECTIVE: Multiple sclerosis (MS) preferentially affects females of reproductive age, making reproduction an important issue for women with MS. An increased incidence of poor labor progress often results in assisted vaginal delivery or a cesarean section. However, with good pre-pregnancy counseling and management, women with MS can conceive and give birth safely. Here, we present a case of pregnancy with MS, which was carried to term uneventfully and ended with unassisted vaginal delivery. CASE REPORT: A 36-year-old woman was treated for MS for three years before she conceived. Because of her mild clinical presentation, medication was discontinued when her pregnancy was confirmed. Counseling was completed, and she had a smooth pregnancy course and gave birth vaginally at 38 weeks and two days. CONCLUSION: Based on this case report, women with mild clinical presentation of MS before pregnancy can conceive and carry successfully to term with no or improved disease presentation.

The impact of prenatal group B streptococcus screening as a national health policy in Taiwan.

OBJECTIVE: There was no national data on group B streptococcus (GBS) infections in Taiwan. Until 2012, when prenatal GBS screening was introduced to obstetric practices as a national health policy aimed at reducing neonatal GBS infections. The purpose of this study was to examine the impact of this national health policy on the incidence of maternal GBS colonization and neonatal GBS infection rate. Relatedly, the clinical characteristics of neonatal GBS infection were investigated to determine the correlations between the incidence of maternal GBS colonization and the neonatal GBS infection rate. MATERIALS AND METHODS: This population-based nationwide study used data for 2012-2013 from the National Health Insurance Research Database of Taiwan. A total of 789 newly diagnosed pregnant women with genital GBS infection were recruited. RESULTS: The maternal GBS screening rate was 93.2%. The maternal colonization rate of GBS was around 8.2%, and the incidence of neonatal GBS infection was 22.6%. The data indicate that no sepsis was developed in any of the cases, while fever was found in 3 cases (3/179, 1.7%) and UTI was found in 1 case (1/179, 0.6%). CONCLUSIONS: We conclude that a policy calling for universal maternal rectovaginal cultures for GBS with intrapartum antibiotic prophylaxis is a good national policy for reducing morbidity due to GBS infections in neonates in Taiwan.

The climate impact on female acute pyelonephritis in Taiwan: A population-based study.

OBJECTIVE: Urinary tract infection (UTI) is the main reason of community-acquired infection which causes large losses in social economy. The individual as well as climate factors make changes on the incidence. Acute pyelonephritis (APN) is one of the most serious UTI in female. The object of our study is to analyze whether climate factors will have effect on the incidence of female APN in Taiwan. MATERIALS AND METHODS: This study consisted of 14,568 female patients with APN from 2001 to 2013 in Taiwan and patients with repeated APN were excluded. The monthly climate data was collected from the Central Weather Bureau. The available monthly climate data included highest, lowest, and average level of temperatures, humidity, rainfall, total rain days, and sunshine hours. RESULTS: The total incidence of female APN was 23.44 each 10,000 populations. The incidence of APN was positively correlated with temperature (r = 0.66), sunshine hours (r = 0.45), rainfall (r = 0.42), rain days (r = 0.29), and humidity (r = 0.23) per month. There is the strongest correlation between the average monthly temperature and the incidence of APN (ß = 0.54). The correlation with the incidence of APN was also followed by rain days (ß = 0.28) and humidity (ß = 0.27). CONCLUSION: There is a significant expression on the incidence of female APN affected by seasonality and climate parameters. The monthly average temperature has the strongest correlation with female APN. The results of this research may facilitate the potential preventive strategies on female APN.

Dandy-Walker syndrome with duplex kidney abnormalities in trisomy 18 - A rare case report.

OBJECTIVE: Trisomy 18 is one of the major numerical chromosomal disorders. The incidence of trisomy 18 is approximately one in 6000 live births. Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, with an incidence of about one in 5000 live births. The incidence of trisomy 18 associated with DWM is rare and long-term survival rate is very low. CASE REPORT: A case involving a 39-year-old pregnant female with a case of trisomy 18 associated with DWM. CONCLUSION: The incidence of trisomy 18 associated with DWM is rare, and our report presents an unusual case that supplements our knowledge of this condition. We report a case involving a 39-year-old pregnant female with a case of trisomy 18 associated with Dandy-Walker malformation (DWM). Fetal ultrasonography showed hypoplasia of the cerebellar vermis and dilatation of the fourth ventricle and was characterized by an enlarged posterior fossa. Fetal magnetic resonance imaging showed inferior vermian hypoplasia and a large posterior fossa cyst communicating with the fourth ventricle causing high insertion of the torcular herophili, which was compatible with DWM. Furthermore, the karyotyping report revealed trisomy 18. The incidence of trisomy 18 associated with DWM is rare, and our report presents an unusual case that supplements our knowledge of this condition.

Short-term starvation with a near-fatal asthma attack induced ketoacidosis in a nondiabetic pregnant woman: A case report.

Life-threatening refractory metabolic acidosis due to starvation ketoacidosis is rarely reported, even among nondiabetic pregnant women, and may be overlooked. Furthermore, stressful situations may increase the acidosis severity.In the present case, a nondiabetic multiparous woman was admitted for a near-fatal asthma attack and vomiting during the third trimester of pregnancy. She was intubated and rapidly developed high anion gap metabolic acidosis. We diagnosed the patient with starvation ketoacidosis based on vomiting with concomitant periods of stress during pregnancy and the absence of other causes of high anion gap metabolic acidosis. She responded poorly to standard treatment, although the ketoacidosis and asthma promptly resolved after an emergency caesarean section. The patient and her baby were safely discharged.Short-term starvation, if it occurs during periods of stress and medication, can result in life-threatening ketoacidosis, even among nondiabetic women during the third trimester of pregnancy. Awareness of this condition may facilitate prompt recognition and proactive treatment for dietary and stress control, and emergent interventions may also improve outcomes.