Nuclear Mitosis Research Articles

PAPILLARY CYSTADENOCARCINOMA: A CASE REPORT

Papillary cystadenocarcinoma (PCC) is a rare malignant tumor of the salivary glands featured by cysts and papillary endocystic projections. The differential diagnosis includes cystadenoma, papillary-cystic variant of acinic cell carcinoma polymorphous low-grade adenocarcinoma (PLGA), salivary duct carcinoma, and adenoid cystic carcinoma (ACC). Nuclear pleomorphism, mitosis, and infiltrative growth pattern affirm the malignancy of PCC. A 66-year-old man presented with a swelling in the upper alveolar ridge and hard palate. Intraorally, an exophytic, friable and ulcerated lesion was observed. Computed tomography scan showed a large soft tissue mass destroying the left maxilla. An incisional biopsy was performed. Based on the histopathologic features of papillary projections extending into the cystic lumen, the diagnosis of PCC was confirmed. The patient was referred to an oncology center where chemotherapy and radiotherapy were chosen as the appropriate treatment. Currently, no signs of recurrence were detected after 2 years of clinical follow-up. Papillary cystadenocarcinoma (PCC) is a rare malignant tumor of the salivary glands featured by cysts and papillary endocystic projections. The differential diagnosis includes cystadenoma, papillary-cystic variant of acinic cell carcinoma polymorphous low-grade adenocarcinoma (PLGA), salivary duct carcinoma, and adenoid cystic carcinoma (ACC). Nuclear pleomorphism, mitosis, and infiltrative growth pattern affirm the malignancy of PCC. A 66-year-old man presented with a swelling in the upper alveolar ridge and hard palate. Intraorally, an exophytic, friable and ulcerated lesion was observed. Computed tomography scan showed a large soft tissue mass destroying the left maxilla. An incisional biopsy was performed. Based on the histopathologic features of papillary projections extending into the cystic lumen, the diagnosis of PCC was confirmed. The patient was referred to an oncology center where chemotherapy and radiotherapy were chosen as the appropriate treatment. Currently, no signs of recurrence were detected after 2 years of clinical follow-up.

CDK12 Activity-Dependent Phosphorylation Events in Human Cells.

We asked whether the C-terminal repeat domain (CTD) kinase, CDK12/CyclinK, phosphorylates substrates in addition to the CTD of RPB1, using our CDK12analog-sensitive HeLa cell line to investigate CDK12 activity-dependent phosphorylation events in human cells. Characterizing the phospho-proteome before and after selective inhibition of CDK12 activity by the analog 1-NM-PP1, we identified 5,644 distinct phospho-peptides, among which were 50 whose average relative amount decreased more than 2-fold after 30 min of inhibition (none of these derived from RPB1). Half of the phospho-peptides actually showed >3-fold decreases, and a dozen showed decreases of 5-fold or more. As might be expected, the 40 proteins that gave rise to the 50 affected phospho-peptides mostly function in processes that have been linked to CDK12, such as transcription and RNA processing. However, the results also suggest roles for CDK12 in other events, notably mRNA nuclear export, cell differentiation and mitosis. While a number of the more-affected sites resemble the CTD in amino acid sequence and are likely direct CDK12 substrates, other highly-affected sites are not CTD-like, and their decreased phosphorylation may be a secondary (downstream) effect of CDK12 inhibition.

A Case of Recurrent Uterine Leiomyosarcoma Treated with Complete Laparoscopic Resection

Video Objective Uterine leiomyosarcoma (uLMS) is aggressive mesenchymal neoplasm and is associated with a high risk of recurrence and poor prognosis. The 5year overall survival rate is about 60% even in FIGO stage I disease. There is no firm evidence of chemotherapy, so surgical resection should be considered to control the disease in case of localized recurrence. We will report a case underwent total laparoscopic complete resection for recurrent mass involved sigmoid colon and right ureter. Setting Gynecology and Obstetrics department of a general hospital. Interventions The patient was a 56-year-old woman underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy for enlarged 9cm cervical leiomyoma. The pathological examination of the uterus resected showed cytologic atypia,nuclear mitoses and coagulative necrosis, she was diagnosed as primary uLMS, stageⅠB. She rejected to receive adjuvant chemotherapy. After 7months, the isolated metastasis in pelvic and lung was suspected. Magnetic resonance imaging revealed that the 4cm tumor possibly be involved sigmoid colon and right lower ureter. Resection of the recurrent mass with segmental bowel resection and partial resection of ureter with ureteroneocystotomy was performed laparoscopically without any complications. Complete tumor resection with histologic negative margins was achieved. She had postoperative adjuvant chemotherapy with doxorubicinfor 6 cycles and additional surgery for lung meta is scheduled. Also, we experienced another three salvage cases with successful resection in combination with laparoscope and thoracoscope. Conclusion The surgical indications for recurrent uLMS should be selected, but the complete resection of localized recurrence may lead to control the disease. Minimally invasive approach may be one of the feasibleoption.

The embryo sac development of Manfreda elongata (Asparagaceae)

Manfreda Salisb. belongs to the Asparagaceae family and is a genus of a high ornamental potential due to the beauty and varied morphology of its leaves, as well as it provides flowers of different species throughout the year. In spite of its economic relevance, little is known about its sexual reproduction. This work aimed to characterize the female gametophyte development of Manfreda elongata through a stain-clearing technique of whole ovules and then analyzed by confocal microscopy. The female gametophyte development of M. elongata is of the monosporic Polygonum-type. The megaspore mother cell of M. elongata contains a dense and prominent nucleus, and at megasporogenesis, when meiosis II is completed, linear and T-shaped tetrads of megaspores were observed. Of this, only the megaspore closest to the chalaza remains functional. In the process of megagametogenesis, three rounds of free nuclear mitosis produced an eight-nuclei embryo sac. At maturity, a seven-celled embryo sac is formed by an egg apparatus (egg cell and two synergids) at the micropylar end, a central cell (with a diploid nucleus resulted from the fusion of the two polar nuclei). Thus, at the end of its formation, the female gametophyte development of M. elongata is of the monosporic, Polygonum-type.

Protein expression profiles in methicillin-resistant Staphylococcus aureus (MRSA) under effects of subminimal inhibitory concentrations of imipenem

Imipenem is a beta-lactam antibiotic mainly active against gram-negative bacterial pathogens and also could cause cell wall impairment in methicillin-resistant Staphylococcus aureus(MRSA). However, related antibacterial mechanisms of imipenem on MRSA and mixed infections of MRSA and gram-negative bacteria are relatively poorly revealed. This study was to identify proteins in the MRSA response to subminimal inhibitory concentrations (sub-MICs) of imipenem treatment. Our results showed that 240 and 58 different expression proteins (DEPs) in sub-MICs imipenem-treated S3 (a standard MRSA strain) and S23 (a clinical MRSA strain) strains were identified through the isobaric tag for relative and absolute quantitation method when compared with untreated S3 and S23 strains, respectively, which was further confirmed by multiple reactions monitoring. Our result also demonstrated that expressions of multiple DEPs involved in cellular proliferation, metabolism and virulence were significantly changed in S3 and S23 strains, which was proved by gene ontology annotations and qPCR analysis. Further, transmission electron microscopy and scanning electron microscopy analysis showed cell wall deficiency, cell lysis and abnormal nuclear mitosis on S23 strain. Our study provides important information for understanding the antibacterial mechanisms of imipenem on MRSA and for better usage of imipenem on patients co-infected with MRSA and other multidrug-resistant gram-negative bacteria.

Assessment the Incidence of Transitional Cell Carcinoma (TCC) of the Bladder Cancer

Background: Transitional cell carcinoma (TCC) of the bladder is the second most common malignancy of the genitourinary tract and the third most common cause of death among people with genitourinary tumors, besides, tumors of the bladder are an important source of both morbidity and mortality. Objectives: The purpose of the study are 1. formulate an idea about the number of patients with bladder cancer (TCCs) in sample of Iraqi population. 2. Study the histopathological features of TCCs of bladder 3. Assessment the prevalence of (TCC) of bladder in both sex (male and female) with smoking as risk factor. Patients and Methods: A study was conducted at one institution were identified that teaching-hospital of Baghdad. All patients included in the present study diagnostic with TCC of bladder. The total of subjects participated in the study were 42 patients and 20 subjects as control through six months’ period from July 2014 to January 2015. Results: The mean of participates age was 655.7 years and the youngest was 21years and the oldest was 75 years. Out of 42 patients, the most common age group was 54-64years (52.38%) with Male to female ratio was 5.2:1.32 were male 32 and 10 were females. However, the prevalence bladder cancer (TCCs) was higher in male than in female, with more pronounced decreases in younger age (≤31year) 3(7.14), have been found. In addition, age specific rate was observed higher in the older age groups for most patients with cancer. The population attributable risk for ever smoking in our study was 33(78.57) out of 42 patients. Moreover, current study shows there was a correlation between grade and stage of bladder TCC, 24(57.14%) bladder TCCs that classified as grade I, while 2(4.76%) of bladder TCC were classified as grade II. Conversely, of the bladder TCC lesions (11.9%, 14.28%, 57.14 and 4.76) were stage (pTa-T1-T2-T3) respectively. Although this study showed 5(11.9) little-known stage and grade. The area of histopathological changes included were showed hyperplastic changes, involving the entire bladder lining, that ranged from flat hyperplasia to small areas of nodular and papillary hyperplasia. The smallest recognizable nodular and papillary lesions were associated with angiogenesis in the contiguous stroma. In addition, there were chromatin irregularities and nucleoli of variable numbers, shape and size. Nuclear chromatin irregularity and mitoses were easily identified, these cells continued to have the appearance of hyperplastic epithelium. The changes noted by generalized and orderly proliferative reaction and appeared reparative. Conclusions: Our study has revealed that the bladder TCC, where appeared the high prevalence and incidence rate of TCC of bladder in sample of Iraqi population were of concern, especially for older age groups.

Pale (Clear) Cell Acanthoma of the Palate

Clear cell acanthoma (CCA), also known as pale cell acanthoma, represents a rare benign epidermal tumor with strong predilection for the lower extremities of middle-aged individuals and no frank gender preference. The etiology of CCA is poorly understood, although a localized psoriasiform reaction is favored. Herein, we report on the clinicopathologic and immunohistochemical features, and HPV status of an apparent example of oral CCA. A 58-year-old female presented with a well-circumscribed, asymptomatic, exophytic, sessile and erythematous nodule of the right hard palate, measuring 0.7cm in greatest dimension. Microscopically, the lesion featured parakeratosis and acanthosis with neutrophilic microabscesses and broad elongated rete pegs. In areas, spinous epithelial cells exhibited pale or clear cytoplasm without nuclear pleomorphism, mitoses or cytologic atypia. The supporting connective tissue revealed mild chronic inflammation with few scattered neutrophils and numerous capillary vessels. PAS histochemical stain with and without diastase disclosed the presence of cytoplasmic glycogen in the pale cells. The majority of glycogen-rich epithelial cells stained strongly for EMA and were negative for D2-40. Ki-67 immunostaining was confined only to the basal cell layer of the epithelium. A diagnosis of CCA was rendered. The lesion was negative for human papillomavirus (HPV) infection, as assessed by HPV-DNA PCR using the MY09/11 primers for the L1 conserved region, thus HPV infection does not appear to contribute to the pathogenesis of oral CCA. In conclusion, we report an intraoral example of CCA in order to raise awareness about this entity.

Intracapsular Carcinoma ex Pleomorphic Adenoma

This is the case of a 37-year-old female patient presenting with a 10-year history of a gradually enlarging right infra-auricular mass. A parotidectomy was performed. The surgical pathology specimen consisted of an 18 cm diameter encapsulated nodular mass with a homogenous, cream-tan solid surface. Microscopic section showed an encapsulated neoplasm with abundant chondromyxoid stroma and tubular epithelial elements characteristic of a pleomorphic adenoma. (Figure 1) Randomly scattered within the tumor were foci of haphazard and complex glands. (Figure 2) These glands exhibited nuclear pleomorphism, luminal necrosis, and mitoses compatible with an adenocarcinomatous proliferation. (Figure 3) Based on these features, the case was signed out as an intracapsular carcinoma ex pleomorphic adenoma.
 
 Carcinoma ex pleomorphic adenoma is a carcinoma arising from a pre-existing pleomorphic adenoma. The antecedent benign tumor may either be a long-standing one, often with a history measured in decades, or characterized by a protracted history of excisions and multiple recurrences.1,2 The carcinoma on the other hand is either epithelial or myoepithelial in derivation. By morphologic sub-type, the most commonly reported carcinoma arising in a pleomorphic adenoma is a salivary duct carcinoma or an adenocarcinoma that is not otherwise specified (NOS).1,3 Residual pleomorphic adenoma tissue is identifiable either in its typical morphology, a chondromyxoid stroma, or a hyalinized sclerotic nodule.1
 
 Aside from the type of carcinoma arising from the pleomorphic adenoma, another parameter that has to be reported is the extent of involvement by the carcinomatous component. A carcinoma that is entirely limited to within the parent tumor that is still enclosed by a complete capsule is termed an “intracapsular” or “non-invasive” carcinoma ex pleomorphic adenoma.1,2 Once the carcinoma breaches the capsule and infiltrates the surrounding tissue, then it is considered invasive. If the invasion is less than 4 – 6 mm beyond the capsular border, the tumor is termed “minimally invasive”. Carcinomatous elements that extend beyond this threshold is termed “widely invasive”.1 This threshold is greater than the previous threshold of 1.5 mm recommended in an earlier edition of the WHO classification although the present edition does state that this threshold is preliminary and requires further validation.1,2,4 It has to be pointed out though that quantifying invasion may not always be possible in tumors that have positive margins, those that are intrinsically unencapsulated such as minor salivary gland tumors, and those with complex multinodular growth patterns such as in recurrent pleomorphic adenoma.1 This difficulty has to be stated in the report and what conditions preclude quantifying the degree of invasion.
 
 Non-invasive carcinoma ex pleomorphic adenoma has quite a good outcome with very low reported rates of recurrence or regional metastasis. In a review of thirty cases and a report of an additional three cases, only one case showed recurrence or metastasis.3 This favorable outcome certainly contrasts with that of the widely invasive type where metastasis is reported to occur in up to 70% of cases.1 Another review of ten cases showed one case developing metastasis, and recommended that non-invasive cases should thus still be followed up closely after primary treatment because regional or distant metastasis can occur.2 
 
 To the best of our knowledge, there are no published local data on the incidence of early malignant transformation of pleomorphic adenomas in the Filipino population. Hence, we take this opportunity to report this case. Awareness of the entity and prudent liberal sampling of these tumors may help address this gap.

Clinicopathological analysis of cervical basaloid squamous cell carcinoma

Objective: To investigate the clinical and histopathological features of cervical basal squamous cell carcinoma (BSCC). Methods: A retrospective analysis of 10 cases of cervical BSCC was carried out. The clinical data and all the pathological sections were reviewed, the related immunohistochemical results were statistically analyzed, the clinicopathological features were analyzed, and then followed the prognosis. Results: (1) Clinical features: the median onset age of BSCC in cervix was 51 years old (ranged 35-69 years old), 5 of them were postmenopausal women. Vaginal bleeding was often seen in clinic (7 cases). Of the 10 cervical BSCC patients, 5 tested HPV types. All of them were HPV positive, including 2 cases of HPV 16 positive and 1 case of high-risk HPV positive. At the time of colposcopy, 3 cases showed exogenous nodular mass, 3 cases showed endogenous infiltrating mass, and 4 cases had unclear type of mass.(2)Treatment: of the 10 patients, 8 underwent hysterectomy+bilateral adnexal excision+pelvic lymphadenectomy, of which 6 underwent radiotherapy or chemotherapy after operation.Radiotherapy and chemotherapy were performed only in 2 cases. (3) Pathological features: histologically, the tumor cells were nests and stripe like growth, which were composed of basal like tumor cells. The cells had obvious heteromorphosis, less cytoplasm, deep dyed nuclei and common nuclear mitosis, and there were often palisade like structures around the cell nests, and some cells in the center of the cell nests were found to have acne like necrosis. It could be mixed with normal squamous cell carcinoma and squamous epithelial lesion. Among the 10 patients, 6 had immunohistochemical results. BSCC mainly expressed p16 and squamous cell markers such as p63, cytokeratin (CK) 5/6 and p40 protein, the positive expression rates were 3/3, 3/3, 2/2 and 3/3, respectively. A few expressed CK7 protein, and the positive expression rate was 1/3. (4) Prognosis: follow-up time ranged from 1 week to 64 months, and 2 cases were lost to follow-up. Among the 8 follow-up patients, 3 had iliac bone, lung or skin metastasis, and 5 had no recurrence or metastasis during the follow-up period. Conclusions: BSCC of cervix is a rare malignant tumor of cervix associated with high-risk HPV infection, p16 is more positive. The treatment is similar to that of normal cervical squamous cell carcinoma. Surgical resection and radiotherapy and chemotherapy are the most effective methods according to the clinical stage. At present, the disease is considered to be highly aggressive and the poor prognosis.

A Combined Nomogram Model to Preoperatively Predict Histologic Grade in Pancreatic Neuroendocrine Tumors.

The purpose of this study is to develop and validate a nomogram model combing radiomics features and clinical characteristics to preoperatively differentiate grade 1 and grade 2/3 tumors in patients with pancreatic neuroendocrine tumors (pNET).Experimental Design: A total of 137 patients who underwent contrast-enhanced CT from two hospitals were included in this study. The patients from the second hospital (n = 51) were selected as an independent validation set. The arterial phase in contrast-enhanced CT was selected for radiomics feature extraction. The Mann-Whitney U test and least absolute shrinkage and selection operator regression were applied for feature selection and radiomics signature construction. A combined nomogram model was developed by incorporating the radiomics signature with clinical factors. The association between the nomogram model and the Ki-67 index and rate of nuclear mitosis were also investigated respectively. The utility of the proposed model was evaluated using the ROC, area under ROC curve (AUC), calibration curve, and decision curve analysis (DCA). The Kaplan-Meier (KM) analysis was used for survival analysis. An eight-feature-combined radiomics signature was constructed as a tumor grade predictor. The nomogram model combining the radiomics signature with clinical stage showed the best performance (training set: AUC = 0.907; validation set: AUC = 0.891). The calibration curve and DCA demonstrated the clinical usefulness of the proposed nomogram. A significant correlation was observed between the developed nomogram and Ki-67 index and rate of nuclear mitosis, respectively. The KM analysis showed a significant difference between the survival of predicted grade 1 and grade 2/3 groups (P = 0.002). The combined nomogram model developed could be useful in differentiating grade 1 and grade 2/3 tumor in patients with pNETs.

Overexpression of IGF2 and IGF2 receptor in malignant solitary fibrous tumor with hypoglycemia: a case report

BackgroundSolitary fibrous tumor (SFT) is a prototypical mesenchymal neoplasm that induces non-islet cell tumor hypoglycemia (NICTH) due to overproduction of insulin-like growth factor 2 (IGF2). We here report the case of a malignant SFT associated with a hypoglycemia attack.Case presentationAn 81-year-old man with a large subphrenic mass presented with hypoglycemia and loss of consciousness. His serum insulin and IGF1 levels were relatively low, suggesting an excessively high serum IGF2 levels. Preoperative Western blotting of serum confirmed the overproduction of high-molecular-weight IGF2. After total tumor resection, the patient recovered from hypoglycemia without the need for further treatment. Histological examination revealed proliferation of spindle cells and frequent nuclear mitoses with STAT6 and CD34 immunoreactivity, which led to the diagnosis of malignant SFT. IGF2 was strongly upregulated in the tumor upon immunohistochemistry, consistent with the report of NICTH. In addition, the tumor expressed IGF2 receptor (IGF2R) but not IGF1R.ConclusionsThe present results indicate that the tumor co-expressed IGF2 and IGF2R. IGF2R has not previously been recognized as a tyrosine kinase receptor participating in cell signal transduction. Thus, further case series are required to determine whether IGF2R overexpression reflects the action of an unknown autocrine/paracrine system involving IGF2 for cell proliferation or for the scavenging and degradation of IGF2.

RNA-seq Analysis Reveals Gene Expression Profiling of Female Fertile and Sterile Ovules of PinusTabulaeformis Carr. during Free Nuclear Mitosis of the Female Gametophyte.

The development of the female gametophyte (FG) is one of the key processes of life cycle alteration between the haploid gametophyte and the diploid sporophytes in plants and it is required for successful seed development after fertilization. It is well demonstrated that free nuclear mitosis (FNM) of FG is crucial for the development of the ovule. However, studies of the molecular mechanism of ovule and FG development focused mainly on angiosperms, such as Arabidopsis thaliana and further investigation of gymnosperms remains to be completed. Here, Illumina sequencing of six transcriptomic libraries obtained from developing and abortive ovules at different stages during free nuclear mitosis of magagametophyte (FNMM) was used to acquire transcriptome data and gene expression profiles of Pinus tabulaeformis. Six cDNA libraries generated a total of 71.0 million high-quality clean reads that aligned with 63,449 unigenes and the comparison between developing and abortive ovules identified 7174 differentially expressed genes (DEGs). From the functional annotation results, DEGs involved in the cell cycle and phytohormone regulation were highlighted to reveal their biological importance in ovule development. Furthermore, validation of DEGs from the phytohormone signal transduction pathway was performed using quantitative real-time PCR analysis, revealing the dynamics of transcriptional networks and potential key components in the regulation of FG development in P. tabulaeformis were identified. These findings provide new insights into the regulatory mechanisms of ovule development in woody gymnosperms.

Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny.

The phylum Apicomplexa encompasses deadly pathogens such as malaria and Cryptosporidium. Apicomplexa cell division is mechanistically divergent from that of their mammalian host, potentially representing an attractive source of drug targets. Depending on the species, apicomplexan parasites can modulate the output of cell division, producing two to thousands of daughter cells at once. The inherent flexibility of their cell division mechanisms allows these parasites to adapt to different niches, facilitating their dissemination. Toxoplasma gondii tachyzoites divide using a unique form of cell division called endodyogeny. This process involves a single round of DNA replication, closed nuclear mitosis, and assembly of two daughter cells within a mother. In higher Eukaryotes, the four-subunit chromosomal passenger complex (CPC) (Aurora kinase B (ARKB)/INCENP/Borealin/Survivin) promotes chromosome bi-orientation by detaching incorrect kinetochore-microtubule attachments, playing an essential role in controlling cell division fidelity. Herein, we report the characterization of the Toxoplasma CPC (Aurora kinase 1 (Ark1)/INCENP1/INCENP2). We show that the CPC exhibits dynamic localization in a cell cycle-dependent manner. TgArk1 interacts with both TgINCENPs, with TgINCENP2 being essential for its translocation to the nucleus. While TgINCENP1 appears to be dispensable, interfering with TgArk1 or TgINCENP2 results in pronounced division and growth defects. Significant anti-cancer drug development efforts have focused on targeting human ARKB. Parasite treatment with low doses of hesperadin, a known inhibitor of human ARKB at higher concentrations, phenocopies the TgArk1 and TgINCENP2 mutants. Overall, our study provides new insights into the mechanisms underpinning cell cycle control in Apicomplexa, and highlights TgArk1 as potential drug target.

Antitumor Efficacy of Huqizhengxiao (HQZX) Decoction Based on Inhibition of Telomerase Activity in Nude Mice of Hepatocarcinoma Xenograft.

Objective: Huqizhengxiao (HQZX) decoction is a mixture of traditional Chinese medicines comprising 10 herbs, with inhibitory effects on hepatocarcinoma. The aim of the study is to observe the antitumor efficacy and mechanism of HQZX decoction in nude mice with hepatocellular carcinoma xenografts. Methods: HepG2-luc subcutaneous hepatocarcinoma was established in nude mice. The mice were divided into 5 groups: control, cinobufagin, HQZXS, HQZXM, and HQZXH with doses 13.52, 27.03, and 54.06 g/kg, respectively. HQZX decoction was prepared for intraperitoneal intragastric administration for 3 weeks. Tumor growth was measured with Vernier calipers and in vivo imaging system. α-Fetoprotein (AFP) was determined by radioimmunoassay. Tumor necrosis factor–α (TNF-α) was measured with enzyme-linked immunosorbent assay (ELISA) assay. Telomerase activity was measured with polymerase chain reaction–ELISA. Nuclear mitosis and necrosis were observed with hematoxylin-eosin stain. Apoptotic proteins of caspase-3, Bcl-2, and Bax were examined by Western blot. Signaling molecules of ERK, mTOR, and STAT3 were measured with Luminex assay. Results: HQZX decoction showed good inhibition of HepG2-luc xenografts. Compared with control group, the relative tumor proliferation rate was less than 60% in the HQZXH and HQZXS. The tumor inhibition rate of HQZXH group reached 52% ± 15%. Relative average optical density values of the HQZXS and HQZXH groups decreased significantly. The mitotic index in HQZXS, HQZXM, and HQZXH groups decreased greatly. Telomerase activity of HQZXS was clearly reduced, and, the caspase-3 expression upregulated in HQZXH group. Bcl-2 expression was downregulated in HQZXS and HQZXH. The ratios of p-ERK/ERK and p-STAT3/STAT3 in HQZXS group were significantly downregulated. Conclusion: HQZX decoction can clearly inhibit the growth of hepatocellular carcinoma and induce tumor apoptosis. Its antitumor mechanism may be related to reducing telomerase activity and regulating the STAT3 and ERK signal pathway.

Hibernoma Mimicking Atypical Lipomatous Tumor: 64 Cases of a Morphologically Distinct Subset.

Hibernoma is a benign adipocytic tumor with predilection for subcutaneous tissue of the thigh, upper trunk, and neck of middle-aged adults. 11q13 rearrangement resulting in MEN1/AIP codeletion is characteristic. Hibernomas are composed, in varying proportions, of brown fat cells, mature adipocytes, and microvacuolated lipoblast-like cells. Examples containing predominantly multivacuolated lipoblast-like cells are uncommon and distinction from atypical lipomatous tumor (ALT) is important for clinical management. We herein present the clinicopathologic features of 64 hibernomas histologically mimicking ALT. MDM2 and CDK4 immunohistochemistry as well as MDM2 fluorescence in situ hybridization were performed in a subset of cases. Clinical and follow-up information were obtained from referring pathologists. Thirty-four patients were male and 30 female, with a median age of 43 years (range, 24 to 78 y). The tumors were well circumscribed and mostly deeply located (53/64 cases, 83%) with a median tumor size of 12.9 cm (range, 3.5 to 23 cm) and predilection for the thigh (42/64 cases, 66%). Histologically, large cells with prominent lipoblast-like cytoplasmic fatty vacuoles and small central nuclei were present to a prominent degree in all cases, along with mature univacuolated adipocytes and smaller numbers of large, finely vacuolated cells with eosinophilic granular cytoplasm. Nuclear atypia and mitoses were absent. None of the 39 cases tested showed CDK4 and MDM2 overexpression or MDM2 amplification. Follow-up, available for 16/64 cases (median, 47 mo; range, 1 to 165 mo), revealed no recurrences or metastases. Hibernoma mimicking ALT shows predilection for deep soft tissue, especially in the thigh. These tumors behave in a benign manner and MDM2/CDK4 negativity may be useful in excluding ALT.

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer

Objective: A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Methods: Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. Results: While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p < 0.036). Furthermore, a correlation was found between Del-1 expression and an aggressive histological grade, nuclear mitosis, and polymorphism, suggesting a possible role in tumor progression. In the survival analysis, a worse distant disease-free survival trend was noted for the group overexpressing Del-1. Conclusion: While all the investigated breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients.

An Unusual and Rare Case of Primary Oral Malignant Melanoma Involving the Mandible in a Young Female

Background: Primary oral malignant melanomas (POMM) are rare and have been estimated to represent 1.6% of all oral malignancies and 0.2-8% of all melanomas. Most cases of melanomas involve palate and maxillary gingiva (80%) and about 20% involve mandible. The purpose of this article is to report a very unusual and rare case of melanoma in a young female involving mandible causing extreme destruction of bone. Methods and Findings: A 23 year-old female presented with a painful swelling over right mandible since 3 months. The growth extended from right preauricular region to submandibular region, was nodular and bluish black in colour and bled on touching. It caused displacement of mandibular premolars and molars. A provisional diagnosis of malignant osteolytic tumor was made. The patient underwent right hemimandibulectomy. Intraoperatively, the tumor was seen involving the entire mandibular body. On gross examination, right hemimandibulectomy specimen was received in pieces measuring 12 × 9.5 × 5.2 cm containing seven teeth. The tumor had perforated the lingual cortical plate. Cut surface was friable and black in colour. Microscopy showed a biphasic high grade neoplasm comprising of round to spindled tumor cells exhibiting marked nuclear pleomorphism and brisk mitosis, laden with granular brownish pigment melanin. The findings were consistent with the diagnosis of pigmented malignant melanoma and confirmed on immunohistochemistry as the tumor expressed vimentin and HMB45 and was negative for CK, EMA and p40. Conclusion: Involvement of mandibular bone by melanoma is rare. However, when they involve the bone, they are indistinguishable from other lytic malignant tumors or osteomyelitis. The present case emphasizes the need to learn the unusual location, the possible presentation of oral melanoma and inclusion of this rare tumor in the differential diagnosis of lytic bone tumors.

Squash cytology findings of subependymomas: A report of three cases and differential diagnosis.

Subependymomas are slowly growing glial tumors, corresponding to WHO grade I. Few descriptions of the cytologic features of this neoplasm are available. This study describes the cytologic features of three subependymomas, as well as their differential diagnosis based on cytology. Three men, aged 52, 56, and 63 years, presented with headache. Magnetic resonance imaging revealed a nodular intraventricular mass in all three patients. Intraoperative squash cytology specimens from the three intraventricular tumors showed nodular clusters with microcystic changes. Nuclei were round to oval in shape, but showed no evidence of severe nuclear atypia or mitoses. Histological examination showed features of subependymoma. Squash cytology findings, including nodular clusters, mild cellular atypia, microcystic changes, and mucoid material, are useful in the rapid intraoperative diagnosis of subependymoma.

Evaluation in situ of genotoxicity and stress in South American common toad Rhinella arenarum in environments related to fluorite mine

Little attention has been paid to the impact of wastewater generated by mining activities on fluoride. In this study, we evaluated the hematology responses of common South American toad Rhinella arenarum inhabiting natural and artificial environments associated with a fluorite mine from central Argentina. We analyzed three sampling stations associated with the fluorite mine: (I) Los Cerros Negros stream (CN), which runs on granitic rock with a high fluorite content; (II) Los Vallecitos stream (LV), which runs on metamorphic rock with low fluorite content; and (III) artificial decantation ponds (DP) containing sediments produced by fluorite flotation process. We calculated frequencies of micronuclei, erythrocyte nuclear abnormalities, mitosis, and immature erythrocytes. In addition, we performed a differential leukocyte count and determined neutrophils/lymphocyte ratio as a stress response estimator. We found high micronucleus (MN) and erythrocyte nuclear abnormality (ENA) frequencies in DP and CN but low frequencies in LV. The neutrophil/lymphocyte ratio was different among sites, with a significant increase in individuals from DP. Values registered in DP could be caused by exposure to mixture of compounds registered in dams that hold wastewater, while high values registered in CN stream might be due to natural concentrations of fluoride. Our results suggest that blood is an effective and non-destructive sensitive indicator for monitoring genotoxic agents in freshwater ecosystems.

Differential proteomic analysis revealing the ovule abortion in the female-sterile line of Pinus tabulaeformis Carr.

Ovule abortion affects the yield and quality of Pinus tabulaeformis Carr. seeds. Research into ovule abortion has importance for improving the seed setting rate and establishing artificial seed production techniques. Fertile line (FL) ovules (FL-E) and sterile line (SL) ovules (SL-E) in the early stage of free nuclear mitosis of megagametophyte (FNMM), FL ovules (FL-L) and SL ovules (SL-L) in the late stage of FNMM of P. tabulaeformis were collected as materials. 4192 proteins were identified by isobaric tags for relative and absolute quantitation (iTRAQ)-based analysis. Bioinformatics analysis implied that in SL ovules, substances and energy might be deficient, perhaps leading to abnormal DNA replication. Because the incomplete antioxidant system and the abnormal expression levels of enzymes involved in cell signal transduction, DNA DSBs probably occurs. Facing the abnormities of DNA replication and damage, the cell cycle was arrested and the DNA damage failed to be repaired, potentially resulting in the occurrence of PCD. Taken together, an inference can be drawn from our study – substance and energy deficiencies, reactive oxygen stress, and the failure of both cell cycle progression and DNA damage repair, which possibly hinder FNMM, leading to ovule abortion in the female-sterile line of P. tabulaeformis.