Osteoma of paranasal air sinuses—A clinical review

Osteoma of the paranasal air sinuses are rare lesions. This comparative study indicates that osteoma of the sinuses occur more in a younger age group of Indians as compared to the Caucasians. Radiological and tomographical evaluation provides a reliable clue to the extent of the lesion in three dimensional planes, to influence the route of access and the degree of excision. Recurrence, however, occurs more in the younger age group.     

The discordance between primary breast cancer lesions and pulmonary metastatic lesions in expression of aldehyde dehydrogenase 1-positive cancer cells

Background

We evaluated the expression of aldehyde dehydrogenase 1 (ALDH1) between primary breast lesions and pulmonary metastatic (PM) lesions in breast cancer patients.

Methods

We retrospectively analyzed the clinicopathological features and the expression statuses of ER, PR, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions and evaluated the discordance rates in the expressions of these markers between the primary and metastatic lesions, and also the prognostic value of these factors.

Results

None of the PM patients had metastases at any other sites, and all had undergone curative breast cancer surgery. The pulmonary operation was partial resection in 15 (88 %) patients and lobectomy in 2 (12 %) patients. The median overall survival (OS) after resection of the PNs (OS) was 48 months. The discordance rates in the expressions of ER, PR, HER2, Ki67 and ALDH-1 between the primary and metastatic lesions were 0, 29, 21, 43 and 50 %, respectively.

Conclusion

There was significant discordance in the biomarkers between the primary tumors and the metastatic lesions.     

Endemic (African) Kaposi sarcoma: Presenting as pathological fracture of left tibia and fibula

Kaposi sarcoma is a malignant vascular tumour of multifocal origin from undifferentiated vasoformative spindle cell. It presents frequently as cutaneous lesions, and musculoskeletal involvement is rare. Presented is a 52-year-old male farmer with inability to walk and pain of two months duration with cutaneous lesion noticed 3 years prior to presentation. Clinical, radiological and histopathological evaluation revealed cutaneous Kaposi sarcoma with a rare complication of pathological fracture of the left tibia and fibula with dystrophic calcification of the adjoining soft tissue. He had cytotoxic chemotherapy with poor outcome in cutaneous and skeletal lesions. Kaposi sarcoma if neglected presents with significant morbidity. Health promotion on early presentation and diagnosis are recommended for improved outcome.     

Importance of formalin fixing conditions for HER2 testing in gastric cancer: immunohistochemical staining and fluorescence in situ hybridization

Background

Accurate and reliable assessment of human epidermal growth factor receptor type 2 (HER2) status is important for selecting patients with gastric cancer who may benefit from trastuzumab treatment. Here we examined the impact of formalin fixing conditions on HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in xenografted tumor tissues.

Methods

Xenografted tumor tissues of the human gastric cancer cell lines NCI-N87, SCH, and SNU-16 were collected and kept at room temperature for 0, 6, or 24 h before being fixed with 10 % neutral buffered formalin (NBF) for 24 h or 5, 7, or 10 days and embedded in paraffin. Use of 10 % NBF, 20 % NBF, or nonbuffered formalin as fixative was investigated.

Results

The HER2 IHC scores for NCI-N87, SCH, and SNU-16 tumors were 3+, 2+, and 1+, respectively, when specimens were fixed with 10 % NBF for 24 h immediately after resection of the tumors. Specimens left for longer than 6 h before fixation had shrinkage of the tumor periphery and decreased immunostaining intensity in this region in all specimens. In SCH and SNU-16 specimens, starting fixation 24 h after tumor tissue collection induced autolysis and reduction of the number of stained cells, and 10-day-fixation lowered the HER2 score. Prolongation of fixation time did not affect FISH results, but if samples were left for more than 6 h before fixation, the FISH score was strongly reduced in SCH specimens (2.3 to 1.3). Reduced IHC staining intensity was observed with 20 % NBF and nonbuffered formalin compared to 10 % NBF.

Conclusions

The time to and length of fixation of tumor specimens can affect HER2 IHC and FISH scores. The fixative used can affect IHC results.     

Immunomodulation with thymopentin:in vitro studies

Immunomodulation is interpreted as a temporary alert in a certain part of the immune system. The activation of immune competent cells is presented as a possible basic mechanism of this phenomenon. In the absence of a primary stimulus, immunomodulation remains physiologically silent, but it results in a modified immune response if the corresponcling targets are being stimulated. For practical reasons it is suggested that distinctions be made between preventive and regulative immunomodulation. The PWM-induced IgG production of PBMCs was used as a model for the demonstration of the modulatory effect of thymopentinin vitro. Depencling on the concentration of thymopentin used in the cultures, this pentapeptide can either stimulate or inhibit the induced IgG production. It also influences PGE₂ production and catabolism in the cultures stimulated with PWM. Indomethacin abolishes the modulatory effect of thymopentin on IgG production in this model. It is suggested that the possibility of interactions between an immune modulator and therapeutic approaches which can influence the proportions or functions of the corresponcling target cells be considered.     

Curcumin induces apoptosis of HepG2 cells via inhibiting fatty acid synthase

Fatty acid synthase (FAS) is highly expressed in many kinds of human cancers, including liver cancer. Curcumin is the major active ingredient of Curcuma longa and has long been used to treat a variety of maladies. In the present study, we investigated the potential use of curcumin as a kind of FAS inhibitor for chemoprevention of liver cancer. Curcumin induced HepG2 cell apoptosis with the IC₅₀ value of 8.84 μg/ml. It inhibited intracellular FAS activity, and downregulated expression and mRNA level of FAS in a dose-dependent manner. In addition, sodium palmitate could rescue cell apoptosis induced by curcumin. Further studies reviewed that siRNA of FAS showed similar results as curcumin. These findings suggested that curcumin might be useful for preventing or treating liver cancer.     

Detection of TMPRSS2-ERG fusion gene in benign prostatic hyperplasia

The Ets-related gene fusions are among the most common molecular alterations in prostate cancer (PCa) and are detected in more than 50 % of PCas. Transmembrane protease serine 2 and Ets-related gene fusion (TMPRSS2-ERG) is the most frequently identified chimeric gene and has been associated with undifferentiated and invasive phenotypes. TMPRSS2-ERG has also been detected in prostate intraepithelial neoplasia (PIN) lesions and more rarely in benign prostatic hyperplasia (BPH) regions mainly in PCa-bearing glands. The possibility that the fusion TMPRSS2-ERG may be present in BPH samples in the absence of apparent PCa was addressed. Out of 115 BPH samples, three were found positive employing RT-PCR. The presence of the fusion gene was confirmed by FISH for these samples, and an additional four samples were found to carry the TMPRSS2-ERG fusion out of 43 tested by the later approach. The presence of the TMPRSS2-ERG fusion did not result in altered expression of 12 putative downstream targets. These findings indicate that TMPRSS2-ERG may or may not lead to PCa development.     

Experiences with Cryosurgery in Otolaryngological Practice

70 patients with a benign, premalignant or malignant lesion of the head and neck were treated by cryosurgery. Good results have been obtained in the treatment of various benign lesions like haemangioma, papilloma etc. Cryotherapy was found to be satisfactory in the treatment of leukoplakia, where the lesions could be eliminated completely without severe scar formation or functional disability. Palliative cryosurgery was employed in 3 uncurable tumours and the results, apart from pain relief have been disappointing. 29 localised malignant lesions were treated by cryosurgery with an intent to cure. Local Tumour control was seen in 85.3% of cases.     

Epidermal growth factor induces FoxO1 nuclear exclusion to activate MMP7-mediated metastasis of larynx carcinoma

The molecular mechanism underlying cancer invasiveness and metastasis of larynx carcinoma remains elusive. Here we reported a strong correlation between phosphorylated epidermal growth factor receptor (EGFR) and matrix metalloproteinase-7 (MMP7) levels in larynx carcinoma patients. To examine whether a causal link exists, we used a human larynx carcinoma line, Hep-2, to study the molecular basis of EGFR signaling and MMP7 activation. We found that EGF-induced EGFR phosphorylation in Hep-2 cells resulted in activation of MMP7 and, consequently, an increase in cancer invasiveness. An EGFR inhibitor efficiently blocked this EGF-induced activation of MMP7. Moreover, an inhibitor for PI3 kinase (PI3K)/Akt, but not an inhibitor for mitogen-activated protein kinase (MAPK) or an inhibitor for c-Jun N-terminal kinase (JNK), significantly inhibited the EGF-induced activation of MMP7, suggesting that PI3K/Akt signaling cascades may be responsible for EGF-activated MMP7. Further dissection of the pathway revealed that nuclear exclusion of Akt downstream target, FoxO1, was induced by EGF-induced Akt activation and could be inhibited by either the EGFR inhibitor or by the PI3K/Akt inhibitor. Expression of a constitutive nuclear form of FoxO1 significantly inhibited MMP7 activation induced by EGF. Taken together, these findings suggest that EGF/EGFR signaling activates downstream PI3K/Akt to induce FoxO1 nuclear exclusion, which activates MMP7 to promote larynx carcinoma metastasis. Thus, Akt and FoxO1 appear to be promising therapeutic targets for preventing the metastasis of larynx carcinoma.     

Diagnostic and prognostic significance of serum glycoprotein (fucose) level in patients with head and neck tumours

Sera from 25 healthy subjects, 10 patients with benign neoplastic lesions and 30 patients having malignant lesions of Head and Neck region, were analysed for protein bound fucose levels. The levels were significantly elevated in the malignant group, as compared to other two groups. In 10 cases of the malignancy, the fucose levels were repeated after one week of complete removal of the growth, whence the values were found to be lowered to normal range in 7 patients. Thus serum protein bound fucose estimation is a useful adjunct to clinical examination in the diagnosis and prognosis of Head and Neck malignancies.     

Thermal vestibulometry in peripheral labyrinthine lesions

Nystagmus is said to be the most important expression of vestibular disease. It can be observed with the naked eye but behind a Frenzel’s glass it can be observed better. For accurate reading, electrical recording is necessary and for that purpose the change in the corneo-retinal potential consequent upon the movement of the eye has been utilised. This technique of recording is called Electronystagmography (E.N.G.). With the electronystagmograph one can determine the amplitude, frequency and velocity of the slow component. It also helps in recording nystagmus behind the closed eyes or with the eyes open in darkness and in light. It is universally agreed that the maximum information that can be gained is by calculating the maximum velocity of the slow component (Henriksson 1955, Van Egmond and Torok (1954), Aschan et al 1956 and Sokolovski, 1966.).     

AIDS : An epidemeological survey of head and neck symptoms and sensorineural hearing loss

Over 80% of AIDS afflicted patients present first to an otolaryngologist with head and neck complaints such as neck nodes, upper respiratory tract infections and skin lesions. Though the desease is rapidly reaching epidemic proportions in many parts of the world, epidemeological surveys charting symptom profiles and etiology are few and far between. In this article, the author investigated a random sample of (male), AIDS positive jail inmates in West Germany. The overwhelming majority admitted to ENT symptoms. Furthermore, a number of them had a mild to moderate sensorineural hearing loss, with a characteristic pattern on pure tone audiometry. This symptom has not yet been reported in world literature, and could possibly be due to immune processes in the inner ear. It is hoped that pilot studies of this nature would help develop a “high-risk” profile which warns the otolaryngologist of the need to rule out AIDS as early as possible. Further studies in this direction would include increasing the size of the patient pool, detailed audio-metric profiles, and recovery of perilymph for immunoassay from AIDS positive patients with coincidental otosclerosis or other conditions requiring access to the inner ear.     

Hypoxia inducible factor-1 is involved in growth factor,glucocorticoid and hypoxia mediated regulation of vascular endothelial growth factor-A in human meningiomas

In meningiomas, neovascularization through angiogenesis is essential for tumor expansion. As the vascular endothelial growth factor-A (VEGF-A) plays an outstanding role in this process, we have studied basal VEGF-A release and some aspects of its regulation in 46 meningiomas and in Ben-Men-1 cells in vitro. Among two putative VEGF-A stimulating growth factors tested, TGF-1β was more potent than TGF-α in enhancing VEGF-A secretion. Hypoxia-mimicking conditions induced by CoCl₂ treatment also strongly increased VEGF-A secretion. The synthetic glucocorticoid dexamethasone (DEX) potently suppressed both basal and growth factor or CoCl₂-induced VEGF-A release. All these effects were also seen in the Ben-Men-1 cell line in which studies on the role of HIF-1 in the regulation of VEGF-A showed that not only hypoxia but also the growth factors induced HIF-1α and DEX suppressed HIF-1α induction. Therefore, in Ben-Men-1 cells with HIF-1α knock-down the effects of hypoxia, growth factors and DEX on VEGF-A production were strongly impaired. This clearly indicates that HIF-1 not only regulates hypoxia-induced VEGF-A production but also mediates at least in part the effects of growth factors and DEX on VEGF-A synthesis and release. Our findings show the complexity of VEGF-A regulation in meningiomas and point to new options for the pharmacological treatment of these tumors.     

A clinico-pathological study on cancer in sclerosing adenosis

Background

Cancer in sclerosing adenosis includes the following 2 types: cancer genuinely arising from sclerosing adenosis and cancer arising near a sclerosing adenosis lesion and infiltrating into it. This study aimed to elucidate the features of the former by comparing both types.

Methods

This study included 28 lesions in 27 cases of cancer in sclerosing adenosis for which surgery was performed during a 2-year period from January 2006 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. We determined the proportions of cancer in sclerosing adenosis relative to the overall lesion of ductal carcinoma in situ. They were compared for 13 clinico-pathological factors by dividing the lesions into 2 groups: those involving cancer in 50 % or more (cancer in sclerosing adenosis predominant type—inner type) and those involving cancer in less than 50 % (cancer out of sclerosing adenosis predominant type—outer type).

Results

There were 20 lesions (71 %) of the inner type and 8 lesions (29 %) of the outer type. The comparison between the 2 types revealed significant differences in the following 3 factors. Bilateral breast cancer was observed in 5 cases (26 %) of the inner type and in none (0 %) of the outer type, indicating that there were significantly more cases of bilateral breast cancer for the inner type (p = 0.04). Regarding the subtypes of ductal carcinoma in situ, there were significantly more cases of the non-comedo type for the inner type (p = 0.002). Significantly fewer cases were positive for human epidermal growth factor receptor type 2 (HER2) for the inner type (p = 0.007).

Conclusion

The results of this study suggest that cancer genuinely arising in sclerosing adenosis may often have biological features of bilateral breast cancer, non-comedo type in subtype, and being negative for HER2.     

Resistance to the antiproliferative effect induced by a short-chain ceramide is associated with an increase of glucosylceramide synthase,P-glycoprotein,and multidrug-resistance gene-1 in cervical cancer cells

Purpose

Ceramide is glycosylated to glucosylceramide or lactosylceramide, and this glycosylation is a novel multidrug-resistance (MDR) mechanism. In this work, a short-chain ceramide (C6), lactosylceramide (LacCer), and an inhibitor of ceramide glycosylation (d-threo-1-phenyl-2-decanoylamino-3-1-propanol, PDMP) were evaluated on the proliferation of cervical cancer cells. The participation of glucosylceramide synthase (GCS), P-glycoprotein (P-gp), and multidrug-resistance gene-1 (MDR-1) in the resistance to the antiproliferative effect induced by C6 was also evaluated.

Methods

Cell proliferation was determined by crystal violet staining. GCS and MDR-1 mRNA expression was evaluated by real-time RT-PCR assay. GCS and P-gp protein expressions, as well as Rhodamine 123 uptake, which is a functional test for P-gp efflux activity, were determined by flow cytometry.

Results

C6 inhibited proliferation of CaLo and CasKi cells with an IC₅₀ of 2.5 μM; however, 50 % proliferation of ViBo cells was inhibited with 10 μM. LacCer increased the proliferation of all cells. When cells were treated with PDMP plus C6, no additional effect on antiproliferation induced by C6 was observed in CaLo and CasKi cells; however, proliferation diminished in comparison with C6 alone in ViBo cells. C6 increased GCS and MDR-1 expression in all cells, as well as P-gp expression in CasKi cells.

Conclusions

Cells that have more capacity to glycosylate ceramide and express a higher level of GCS, MDR-1, and P-gp, are more resistant to the antiproliferative effect induced by C6.     

Tiam1 siRNA enhanced the sensitivity of sorafenib on esophageal squamous cell carcinoma in vivo

Our previous study demonstrated that Tiam1 was highly expressed in esophageal squamous cell carcinoma (ESCC) tissues. In the present study, we investigated the therapeutic role of Tiam1 siRNA in combination with sorafenib in xenografted human ESCC. Our results demonstrated that expression of Tiam1 protein in EC9706 cells was significantly higher than those in ESCC cells (Eca109 and EC1) and normal esophageal epithelial cells Het-1A (P?siRNA markedly suppressed Tiam1 protein expression in tumor tissues of nude mice, but sorafenib did not alter Tiam1 level. In addition, Tiam1 siRNA or sorafenib alone evidently inhibited tumor growth, reduced Ki-67 proliferation index, and induced cell apoptosis in xenografted nude mice, and their combinations had the strongest effect. Notably, Tiam1 siRNA or sorafenib alone obviously increased p27 level, but reduced Mcl-1 and bcl-2 levels in xenografted nude mice, and their combinations reached the best effect. These findings suggest that combination of Tiam1 siRNA with sorafenib may be the novel molecular therapy target for the patients with ESCC.     

Laryngeal mucormycosis

The mycotic infections of the larynx include histoplasmosis, aspergillosis, actinomycosis, blastomycosis, coccidiodomycosis and sporotrichosis. Mucormycosis has been known as an acute and fulminating fungal infection, described under obvious clinical types i.e. rhinofaciocranial, pulmonary, gastrointestinal or abdominopelvic and cutaneous mucormycosis, but no case of laryngeal mucormycosis could be found in the literature up to date. Further, chronic granulomatous lesions in an otherwise healthy person are infrequent in the case of mucormycosis. Herewith are dealt various aspects of mucormycosis, along with the first reported case of primary localized mucormycosis of larynx presenting as a vocal cord polyp.     

Targeted radiosensitization with PARP1 inhibition: optimization of therapy and identification of biomarkers of response in breast cancer

Sustained locoregional control of breast cancer is a significant issue for certain patients. Inhibition of PARP1 is a promising strategy for radiosensitization (RS). We sought to optimize therapy with PARP1 inhibition and radiation (RT) by establishing the most effective treatment schedule, degree of PARP1-mediated RS, and identify early biomarkers predictive of efficacy in breast cancer models. Using clonogenic survival assays, we assessed intrinsic radiosensitivity and RS induced by PARP1 inhibition in breast cancer cell lines. Potential biomarkers of response were evaluated using western blotting, flow cytometry, and immunofluorescence with validation in vivo using tumor xenograft experiments. Across a panel of BC and normal breast epithelial cell lines, the PARP1 inhibitor ABT-888 preferentially radiosensitizes breast cancer (vs. normal) cells with enhancement ratios (EnhR) up to 2.3 independent of intrinsic BC subtype or BRCA mutational status. Concurrent and adjuvant therapy resulted in the highest EnhR of all schedules tested. The degree of RS did not correlate with pretreatment markers of PARP1 activity, DNA damage/repair, or cell cycle distribution. Increases in PARP1 activity 24 h after RT were associated with sensitivity after combination treatment. Findings were confirmed in breast cancer xenograft models. Our study demonstrates that PARP1 inhibition improves the therapeutic index of RT independent of BC subtype or BRCA1 mutational status and that PARP1 activity may serve as a clinically relevant biomarker of response. These studies have led to a clinical trial (TBCRC024) incorporating intratreatment biomarker analyses of PARP1 inhibitors and RT in breast cancer patients.