Metastasis of hepatocellular carcinoma presented as a tumor of the maxillary sinus and retrobulbar tumor

Introduction. Hepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of the liver. It is usually seen in the 6th and 7th decades of life and chronic hepatitis B is the most frequent cause. Extrahepatic metastasis of HCC is an indicator of a poor prognosis and the most common sites are lungs, bones, lymph nodes, kidneys and adrenal glands. We reported a case of isolated metastasis in the right maxilla, which had been found initially, before the tumor in the liver was diagnosed. Case report. A 70-year-old man underwent dental surgery of the upper right molar. Prolonged bleeding control was difficult for up to two weeks, so the biopsy was performed. Histopathological analysis revealed a metastatic hepatocellular carcinoma. Computerized tomography (CT) of the abdomen revealed a diffusely heterogeneous liver parenchyma with irregular borders and two foci of mass lesions. There were metastasis in the spleen and also two pathological retroperitoneal lymph nodes were detected, but no ascit, liver cirrhosis, cholestasis or portal vein thrombosis were seen. CT of the orbital and maxillary regions revealed a tumor mass in the right maxillary sinus, spreading to the alveolar sinus, nasal cavity and partially infratemporal space. A tumor mass was in the right orbit as well, infiltrating the surrounding bones and muscles. Clinically, there was proptosis of the right eye accompanied by amaurosis. The treatment started with chemotherapy based on 5-fluorouracil (sorafenib was not available). After three cycles, control CTs showed a stable disease in the liver, but progression in the right maxillary sinus and orbit. Enucleation of the right eye was performed and postoperative radiotherapy was planed. The patient deteriorated rapidly and died, about 6 months after the disease had been diagnosed. Conclusion. Extrahepatic metastasis of HCC represents a progressive phase of the disease with poor prognosis, so the main aim of the treatment should be palliation and care of symptoms

Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.

Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PTEN tumor suppressor on TNBC clinical behavior, prognosis, and multidrug resistance (MDR), using immunohistochemistry and copy number analysis by quantitative real-time PCR. Our results revealed that loss of PTEN and high expression of PI3K and mTOR proteins are associated with poor outcome of TNBC patients. PTEN deletions appeared as a major cause of reduced or absent PTEN expression in TNBC. Importantly, homozygous deletions of PTEN (and not hemizygous deletions) are a potential molecular marker of metastasis formation and good predictors of TNBC outcome. In conclusion, we believe that concurrent examination of PTEN/PI3K/mTOR protein expression may be more useful in predicting TNBC clinical course than the analysis of single protein expression. Specifically, our results showed that PTEN-reduced/PI3K-high/mTOR-high expression constitutes a 'high risk' profile of TNBC

Uticaj tumor supresorskih gena TP53 i PTEN na odgovor na različite načine lečenja raka dojke

Rak dojke (RD) je najčešći tip maligniteta i vodeći uzrok smrti od raka kod žena širom sveta. RD je izuzetno heterogena bolest i stoga su neophodni različiti modaliteti lečenja da bi se pokrile ove razlike. Cilj našeg istraživanja je bio da se ispita uticaj inaktivacije TP53 i PTEN tumor supresorskih gena (TSG) na odgovor RD na različite modalitete lečenja, kao i njihova moguća saradnja u tome, na postoperativnim uzorcima RD. Metode. Pacijentkinje su klasifikovane, na osnovu primenjene adjuvantne terapije, u četiri različite grupe: one koje su primale samo hormonsku terapiju (HT), hormonsku terapiju u kombinaciji sa hemoterapijom (HT/CHT), hormonsku terapiju u kombinaciji sa hemoterapijom i biološkom terapijom (HT/CHT/H) i druge sistemske terapije koje isključuju HT. Funkcionalna inaktivacija TP53 i PTEN TSG je proučavana analizom mutacionog statusa, gubitka heterozigotnosti (LOH) i metilacionog statusa. Rezultati. Naši rezultati su pokazali da je TP53 gen izmenjen kod 63 od 90 pacijenata (70%), dok je učestalost promena PTEN gena bila nešto niža, 54 od 90 (60%). Simultana inaktivacija je detektovana u 43 testirana uzorka (48%) sa značajnom povezanošću između dva analizirana TSG-a. Dalje, pokazali smo da status TP53 ima značajan uticaj na odgovor pacijenata na terapiju. Suprotno ovome, nismo pokazali značajnu asocijaciju između mutacionog statusa PTEN-a i različitih modaliteta lečenja. Međutim, utvrđena je značajna povezanost između primenjenih terapija i simultanih inaktivacija ova dva TSG-a (p = 0,00001). Zaključak. Pacijenti sa wtTP53 pokazuju značajno bolji terapijski odgovor bez obzira na vrstu terapije u poređenju sa nosiocima mutiranog TP53 gena.Introduction. Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. BC is exceptionally heterogeneous disease and therefore distinct treatment modalities are necessary to address these differences. The aim of our study was to investigate the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC response to different treatment modalities and their possible cooperation, on post-operative BC samples. Methods. Patients were classified, based on applied adjuvant therapy, into four distinct groups: those that received hormonal therapy (HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic therapies that exclude HT. Functional inactivation of TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and hypermethylation analysis. Results. Our results revealed that TP53 gene was altered in 63 out of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower, 54 out of 90 (60%). Simultaneous inactivation was detected in 43 tested samples (48%) with significant association between two analyzed TSGs. Further, we found that TP53 status has significant influence on patients’ therapy response. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association was found between the type of applied therapy and simultaneous alterations of these two TSGs (p = 0.00001). Conclusion. Patients with wtTP53 show significantly better therapy response regardless of the type of therapy, compared to carriers of altered TPp53 gene

Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer

Background: Triple negative breast cancer (TNBC) is characterized by aggressive clinical course and is unresponsive to anti-HER2 and endocrine therapy. TNBC is difficult to treat and is often lethal. Given the need to find new targets for therapy we explored clinicopathological significance of copy number gain of FGFR1 and c-MYC. Our aim was to determine the impact of FGFR1 and c-MYC copy number gain on clinical course and outcome of TNBC. Methods: FGFR1 and c-MYC gene copy number alterations were evaluated in 78 archive TNBC samples using TaqMan based quantitative real time PCR assays. Results: 50% of samples had increased c-MYC copy number. c-MYC copy number gain was associated with TNBC in contrast to ER positive cancers. Our results showed significant correlation between c-MYC copy number gain and high grade of TNBCs. This suggests that c-MYC copy number could be an useful prognostic marker for TNBC patients. c-MYC copy number gain was associated with high pTNM stage as well as lobular and medullary tumor subtypes. 43% of samples had increased FGFR1 copy number. No correlations between FGFR1 copy number gain and clinicopathological variables were observed. Conclusions: We identified c-MYC copy number gain as a prognostic marker for TNBC. Our results indicate that c- MYC may contribute to TNBC progression. We observed no significant association between c-MYC and/or FGFR1 copy number status and patient survival

Amplification of cycline D1, c-myc and EGFR oncogenes in tumour samples of breast cancer patients

Background: Breast cancer is the most common form of cancer in women. It arises from multiple genetic changes in oncogenes and tumor suppressor genes. Among so far studied oncogenes relatively few, including epdermal growth factor receptor (EGfR), cyclinD1 (CCNDİ)and c-myc, have been found to play an important role in progression of this type of human malignancy. The aim of this study was to examine the prognostic potential of CCND1, c-myc and EGFR amplification and their possible cooperation in breast carcinogenesis. Methods: Copy number analyses of CCND1 and c-myc genes were done by TaqMan based quantitative real time PCR. Amplification status of EGFR was determined by differential Pcr. Results: Amplification of CCND1, c-myc and EGFR oncogene has been found in 20.4%, 26.5% and 26.5% of breast cancer cases, respectively. Analysis showed that amplification of CCND1 oncogene was significantly associated with the stage II of disease while amplification of EGFR gene was significantly associated with overexpression of HER-2/neu. Tumour stage and expression of HER-2/neu appeared to be significant predictors of patient's outcome. Stage I patients lived significantly longer then stage III patients (p=0.04) while patients with HER-2/neu overexpression had worse prognoses and lived significantly shorter (p=0.001). Finally, survival of patients who underwent hormone therapy only was significantly longer (p=0.001) then survival of the rest of patients. Conclusions: Amplification of CCND1 or EGFR oncogene is associated with the progression of breast cancer and bad prognosis. No co-ordination in amplification of CCND1, c-myc and EGFR oncogenes were established in this cohort of breast cancer patients.Uvod: Kancer dojke je najčešći tip maligniteta koji se javljaju kod žena. Tumori dojke nastaju kao rezultat akumulacije genetičkih promena kako u onkogenima tako i u tumor supresorskim genima. Među mnogim onkogenima čija je uloga u genezi tumora dojke ispitivana do danas, samo se neki smatraju značajnim za razviće ovih karcinoma. U tu se grupu svakako ubrajaju receptor za epidermalni factor rasta (EGFR), c-myc i ciklinD1 (CCND1). Cilj rada je bio utvrditi prognostički značaj amplifikacije CCND1, c-myc i EGFR onkogena u razviću tumora dojke kao i eventualne međusobne koalteracije ovih gena. Metode: Amplifikacioni status CCND1 i c-myc gena određen je kvantitativnim PCR-om u realnom vremenu, a amplifikacioni status EGFR onkogena je definisan diferencijalnim PCR-om. Rezultati: Amplifikacija CCND1 gena detektovana je kod 20.4%, a c-myc i EGFR onkogena kod 26.5% ispitanih uzoraka. Analize su pokazale da je amplifikacija CCND1 onkogena statistički značajno povezana sa stadijumom II tumora dojke kao i da amplifikacija EGFR-a značajno korelira sa povećanom ekspresijom HER2/neu. Analize kliničkih i histopatoloških parametara su jasno pokazale da stadijum tumora i nivo ekspresije HER2/neu gena predstavljaju značajne pokazatelje daljeg toka bolesti, odnosno sudbine pacijenta. Utvrđeno je da pacijentkinje sa tumorima dojke stadijuma I žive značajno duže od onih sa tumorom stadijuma III (p= 0.04) kao i da pacijentkinje sa HER2/neu pozitivnim statusom imaju goru prognozu i žive značajno krace (p=0.001). Na kraju, studija je pokazala da pacijentkinje podvrgnute samo hormonskoj terapiji imaju najbolju prognozu i žive značajno duže od ostalih (p=0.001). Zaključak: Amplifikacija CCND1 i EGFR onkogena je povezana sa lošom prognozom i progresijom karcinoma dojke. U ispitivanom tumorskom uzorku nisu detektovane nikakve koalteracije CCND1, c-myc i EGFR onkogena.Projekat ministarstva br. III 41031 i br. ON17304

Breast dynamic contrast enhanced MRI: fibrocystic changes presenting as a non-mass enhancement mimicking malignancy

We aimed to analyse the morphokinetic features of breast fibrocystic changes (nonproliferative lesions, proliferative lesions without atypia and proliferative lesions with atypia) presenting as a non-mass enhancement (NME)in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examination. Forty-six patients with histologically proven fibrocystic changes (FCCs) were retrospectively reviewed, according to Breast Imaging Reporting and Data System (BI-RADS) lexicon. Prior to DCE-MRI examination, a unilateral breast lesion suspicious of malignancy was detected clinically, on mammography or breast ultrasonography. The predominant features of FCCs presenting as NME in DCE-MRI examination were: unilateral regional or diffuse distribution (in 35 patients or 76.1%), heterogeneous or clumped internal pattern of enhancement (in 36 patients or 78.3%), plateau time-intensity curve (in 25 patients or 54.3%), moderate or fast wash-in (in 31 patients or 67.4%).Nonproliferative lesions were found in 11 patients (24%), proliferative lesions without atypia in 29 patients (63%) and lesions with atypia in six patients (13%), without statistically significant difference of morphokinetic features, except of the association of clustered microcysts with proliferative dysplasia without atypia. FCCs presenting as NME in DCE-MRI examination have several morphokinetic features suspicious of malignancy, therefore requiring biopsy (BI-RADS 4). Nonproliferative lesions, proliferative lesions without atypia and proliferative lesions with atypia predominantly share the same predefined DCE-MRI morphokinetic features.Radiology and Oncology (2017), 51(2): 130-13

Amplification of cycline D1, c-myc and EGFR oncogenes in tumour samples of breast cancer patients

Background: Breast cancer is the most common form of cancer in women. It arises from multiple genetic changes in oncogenes and tumor suppressor genes. Among so far studied oncogenes relatively few, including epdermal growth factor receptor (EGfR), cyclinD1 (CCNDİ)and c-myc, have been found to play an important role in progression of this type of human malignancy. The aim of this study was to examine the prognostic potential of CCND1, c-myc and EGFR amplification and their possible cooperation in breast carcinogenesis. Methods: Copy number analyses of CCND1 and c-myc genes were done by TaqMan based quantitative real time PCR. Amplification status of EGFR was determined by differential Pcr. Results: Amplification of CCND1, c-myc and EGFR oncogene has been found in 20.4%, 26.5% and 26.5% of breast cancer cases, respectively. Analysis showed that amplification of CCND1 oncogene was significantly associated with the stage II of disease while amplification of EGFR gene was significantly associated with overexpression of HER-2/neu. Tumour stage and expression of HER-2/neu appeared to be significant predictors of patient's outcome. Stage I patients lived significantly longer then stage III patients (p=0.04) while patients with HER-2/neu overexpression had worse prognoses and lived significantly shorter (p=0.001). Finally, survival of patients who underwent hormone therapy only was significantly longer (p=0.001) then survival of the rest of patients. Conclusions: Amplification of CCND1 or EGFR oncogene is associated with the progression of breast cancer and bad prognosis. No co-ordination in amplification of CCND1, c-myc and EGFR oncogenes were established in this cohort of breast cancer patients.Uvod: Kancer dojke je najčešći tip maligniteta koji se javljaju kod žena. Tumori dojke nastaju kao rezultat akumulacije genetičkih promena kako u onkogenima tako i u tumor supresorskim genima. Među mnogim onkogenima čija je uloga u genezi tumora dojke ispitivana do danas, samo se neki smatraju značajnim za razviće ovih karcinoma. U tu se grupu svakako ubrajaju receptor za epidermalni factor rasta (EGFR), c-myc i ciklinD1 (CCND1). Cilj rada je bio utvrditi prognostički značaj amplifikacije CCND1, c-myc i EGFR onkogena u razviću tumora dojke kao i eventualne međusobne koalteracije ovih gena. Metode: Amplifikacioni status CCND1 i c-myc gena određen je kvantitativnim PCR-om u realnom vremenu, a amplifikacioni status EGFR onkogena je definisan diferencijalnim PCR-om. Rezultati: Amplifikacija CCND1 gena detektovana je kod 20.4%, a c-myc i EGFR onkogena kod 26.5% ispitanih uzoraka. Analize su pokazale da je amplifikacija CCND1 onkogena statistički značajno povezana sa stadijumom II tumora dojke kao i da amplifikacija EGFR-a značajno korelira sa povećanom ekspresijom HER2/neu. Analize kliničkih i histopatoloških parametara su jasno pokazale da stadijum tumora i nivo ekspresije HER2/neu gena predstavljaju značajne pokazatelje daljeg toka bolesti, odnosno sudbine pacijenta. Utvrđeno je da pacijentkinje sa tumorima dojke stadijuma I žive značajno duže od onih sa tumorom stadijuma III (p= 0.04) kao i da pacijentkinje sa HER2/neu pozitivnim statusom imaju goru prognozu i žive značajno krace (p=0.001). Na kraju, studija je pokazala da pacijentkinje podvrgnute samo hormonskoj terapiji imaju najbolju prognozu i žive značajno duže od ostalih (p=0.001). Zaključak: Amplifikacija CCND1 i EGFR onkogena je povezana sa lošom prognozom i progresijom karcinoma dojke. U ispitivanom tumorskom uzorku nisu detektovane nikakve koalteracije CCND1, c-myc i EGFR onkogena.Projekat ministarstva br. III 41031 i br. ON17304

Amplification of Cycline D1, C-Myc and Egfr Oncogenes in Tumour Samples of Breast Cancer Patients

Background: Breast cancer is the most common form of cancer in women. It arises from multiple genetic changes in oncogenes and tumor suppressor genes. Among so far studied oncogenes relatively few, including epdermal growth factor receptor (EGFR), cyclinD1 (CCND1) and c-myc, have been found to play an important role in progression of this type of human malignancy. The aim of this study was to examine the prognostic potential of CCND1, c-myc and EGFR amplification and their possible cooperation in breast carcinogenesis. Methods: Copy number analyses of CCND1 and c-myc genes were done by TaqMan based quantitative real time PCR. Amplification status of EGFR was determined by differential PCR. Results: Amplification of CCND1, c-myc and EGFR oncogene has been found in 20.4%, 26.5% and 26.5% of breast cancer cases, respectively. Analysis showed that amplification of CCND1 oncogene was significantly associated with the stage II of disease while amplification of EGFR gene was significantly associated with overexpression of HER-2/neu. Tumour stage and expression of HER-2/neu appeared to be significant predictors of patients outcome. Stage I patients lived significantly longer then stage III patients (p=0.04) while patients with HER-2/neu overexpression had worse prognoses and lived significantly shorter (p=0.001). Finally, survival of patients who underwent hormone therapy only was significantly longer (p=0.001) then survival of the rest of patients. Conclusions: Amplification of CCND1 or EGFR oncogene is associated with the progression of breast cancer and bad prognosis. No co-ordination in amplification of CCND1, c-myc and EGFR oncogenes were established in this cohort of breast cancer patients

The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients

Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen

Semiconductor Gas Sensors: Materials, Technology, Design, and Application

This paper presents an overview of semiconductor materials used in gas sensors, their technology, design, and application. Semiconductor materials include metal oxides, conducting polymers, carbon nanotubes, and 2D materials. Metal oxides are most often the first choice due to their ease of fabrication, low cost, high sensitivity, and stability. Some of their disadvantages are low selectivity and high operating temperature. Conducting polymers have the advantage of a low operating temperature and can detect many organic vapors. They are flexible but affected by humidity. Carbon nanotubes are chemically and mechanically stable and are sensitive towards NO and NH3, but need dopants or modifications to sense other gases. Graphene, transition metal chalcogenides, boron nitride, transition metal carbides/nitrides, metal organic frameworks, and metal oxide nanosheets as 2D materials represent gas-sensing materials of the future, especially in medical devices, such as breath sensing. This overview covers the most used semiconducting materials in gas sensing, their synthesis methods and morphology, especially oxide nanostructures, heterostructures, and 2D materials, as well as sensor technology and design, application in advance electronic circuits and systems, and research challenges from the perspective of emerging technologies