Search results for “carcinoma

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55 articles
Thyroid Cancer Open Access

RET 898-901Del mutant, a variant of unknown significance, has a durable response to Pralsetinib in a Medullary Thyroid Carcinoma patient

Sep 2023 DOI 10.14302/issn.2574-4496.jtc-23-4722

Background Patients with distant metastatic Medullary Thyroid Carcinoma (MTC) have an estimated 40% ten-year survival rate. Gain of function mutations in the REarranged during Transfection or RET gene in MTC can result in an aggressive phenotype resistant to traditional therapy. In this case report, we describe the treatment of an MTC patient with a unique RET kinase deletion mutation. Case presentation Since diagnosis, 21 years ago, this patient has had chronically elevated calcitonin levels (>40,000 pg/mL) that was unable to be controlled by conventual therapy and clinical trials. As result of uncontrolled MTC, metastatic disease was found in the spine, liver, and lungs. Circulating tumor DNA (ctDNA) analysis identified a RET 898-901Del mutation, reported as a variant of unknown significance. The treating physician identified that the deletion was in the activation loop of RET kinase and considered that the mutation was constitutively activating RET kinase. The patient was prescribed Pralsetinib, a small molecule inhibitor targeting the ATP binding site of RET. Pralsetinib treatment achieved a durable response and was able to significantly decrease serum calcitonin levels (<200 pg/mL) and tumor size. Conclusion This RET deletion mutation is a pathogenic mutation with comparable enzymatic activity to the more common RET M918T mutation. The case report highlights the versatility of structural biologic approaches to guide therapeutic decisions.

Massive Hematemesis as Initial Presentation of Advanced Pancreatic Adenocarcinoma

Sep 2023 DOI 10.14302/issn.2641-5518.jcci-23-4743

Pancreatic adenocarcinoma is one of the leading causes of cancer-related death in the United States. Rarely, a tumor at the head of the pancreas can invade adjacent structures to cause a gastrointestinal bleed (GIB). We present a 78-year-old female whose massive upper GIB was the initial presentation of metastatic pancreatic adenocarcinoma. Prior reports have documented GIB in patients with known pancreatic cancer, but in our case, the diagnosis was made after the bleed was controlled, making this presentation rare and associated with a poor prognosis.

RETRACTED: Non-Surgical Removal of Basal Cell Carcinoma by Apis Mellifera L Venom

Dec 2020

This article has been retracted on March 01, 2021. VIEW THE RETRACTION NOTICE (https://openaccesspub.org/jsce/article/2243) Background Apis Mellifera L venom (Honeybees) is potent and safe anticancer drug. The present case is Basal Cell Carcinoma (SBCC), recurrent and invasde the skin of head (upper right, in front of the right ear). The patient was 65 years old in time of first intervention and the origin of BCC was primarily seen as abnormal growths and changes in birth mole on right side of head. Materials & Methods Preparation Bee Venom solution: Bee venom powder (crude) of dose 1gm was dissolved in 1000 ml of sterile distilled water then filtered by 0.22 micron syring filter. That final concentration of the stock bee venom become 1 ug /ml (i.e. 1ul=1 ug), and kept at -20◦C. (1mg (dried BV) + 1ml (water) = Final concentration (1ug/1 ul)). Before this novel intervention, allergy test performed by subcutaneous injection of small dose of bee venom (0.1 ml) and wait for at least one hour. The patient was not hypersensitive to honeybees’ venom. First stage of treatment: 1- Syringe of 1ml volume was used for direct local injection of cancer area by 0.3 ml from prepared Honeybees venom (0.1 % conc.). 2- At the same time, subcutaneous injection of 0.5 ml of bee venom solution infiltrated around the affected ear. 3- Topical application of the bee venom ointment 2% (bee venom in Vaseline) inside affected ear to protect the ear drum. This process repeated daily with cleaning of the ear every time by suitable safe and sterile saline solutions. 2nd stage: daily S/C injection in axillary area upper lymph nodes of 0.3 ml / bee venom ‘total doses 0.6 ml BV’ (left & right). 3rd stage: bee venom dissolved in sterile Clove oil was applied on inner ear above the drum. 4th stage: Management of healing process was enhanced by ascorbic acid solution as topical application on dead cancer cells and to help in removal of exudates and debris. Results The complete removal of malignant growths in affected ear achieved after 1 month from first bee venom injections. However; the cancerous areas under the second surgical intervention were treated during the next month. Conclusions Apis Mellifera L venom as anticancer drug is totally different from using direct stings as a method of Apitherapy, that because collection of bee venom lead to evaporating of most allergic substance that present in bees stings, also it can be used per os in people who exhibit different degrees of allergy against the drug safely.

Pure Small Cell Carcinoma of Prostate in a Patient Presenting with Acute Urinary Retention: A Rare Case Report

Feb 2020 DOI 10.14302/issn.2641-5518.jcci-20-3217

Small cell carcinoma of the prostate is a rare and highly aggressive subtype of prostate cancers. In this case report, we evaluated a patient applied our outpatient clinic with acute urinary retention, whose pathology reported as pure small cell carcinoma of the prostate. A 73-year-old male patient was admitted to our outpatient clinic with acute urinary retention. Digital rectal examination was normal. The PSA value was 1.81 ng/dl. Prostate size was 101 cc. Open prostatectomy was performed. The pathology of the patient was reported as pure small cell prostate carcinoma. Four cycles of etoposide and cisplatin chemotherapy were administered to the patient. The patient died 13 months later after the first diagnosis. We evaluated the pathological and clinical findings of small cell carcinoma of the prostate.

Role of Tie2, CD14, Angiopoietin as Angiogenetic Markers in Hepatocellular Carcinoma Complicating Hepatitis C Virus Infection

Nov 2019 DOI 10.14302/issn.2372-6601.jhor-19-3084

Background Identifying biomarkers for early detection of hepatocellular carcinoma (HCC) remains quite challenging. In this study we aimed to estimate the number of TIE2-expressing monocytes (TEMs) cells, which display pro-tumoral activities and are defined as CD14+, TIE2+, and angiopoietin-2; and its potential use as a possible diagnostic marker in HCC patients complicating HCV induced cirrhosis. Methods Current study was conducted on 112 patients. They were divided into two groups: Group I (78 patients) with HCC complicating HCV induced cirrhosis; and group II chronic hepatitis C patients (34 patients). Both groups were compared to (age and sex-matched) healthy persons as group III (38 persons). Result The number of the circulating TEMs: CD14+ and TIE2+ monocytes were significantly higher in the peripheral blood of HCC patients than HCV LC patients and healthy controls, sensitivity and specificity for HCC diagnosis were respectively: CD14 (89.7%, 83.3%), TIE 2 (76.9%, 83.3%), and Ang-2 (76.9%, 66.7%). Moreover, analysis of the P-value and the odd’s ratio showed that CD14 has the highest predictive value for HCC. Conclusion Our results suggest that TEMs and Ang-2can be used as diagnostic markers for HCC, especially among the high-risk group of patients.

Transmutation of Sweat Glands - Eccrine Porocarcinoma

Jul 2019 DOI 10.14302/issn.2689-5773.jcdp-19-2890

Initially described by Pinkus and Mehregan in 1963 as an  epidermotropic eccrine carcinoma, eccrine porocarcinoma cogitates an exceptional sweat gland malignancy. Eccrine porocarcinoma was adapted as a nomenclature by Mishisma and Morikoin in 1969. The neoplasm is a malignant analogue of eccrine poroma which is a benign tumour of intra-dermal sweat glands. Eccrine porocarcinoma  is an invasive malignancy of eccrine sweat gland with an acrosyringial genesis. Nomenclature includes epidermotropic eccrine carcinoma, eccrine poroepithelioma, malignant  hidroacanthoma simplex, malignant intra-epidermal eccrine poroma, malignant eccrine poroma, malignant syringoacanthoma and dysplastic poroma (1,2). Sweat gland carcinoma are categorized into subgroups with the classical eccrine porocarcinoma  or  eccrine adenocarcinoma as a prevalent subcategory. Lesions are enlisted as          Classic type eccrine adenocarcinoma ( eccrine porocarcinoma). Syringoid eccrine carcinoma                                                                                   Microcystic adnexal carcinoma                                                                 Mucinous eccrine carcinoma                                                           Muco-epidermoid carcinoma                                                                           Adenoid cystic carcinoma                                                                         Aggressive digital papillary adenoma/adenocarcinoma

Chalkley Counting in Oral Tongue Squamous Cell Carcinoma:Does It have A Prognostic Value?

Mar 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2625

Chalkley counting has been regarded as a relatively reliable method of quantifying tumor angiogenesis. In this study we investigated the reliability of Chalkley counting in quantifying tumor angiogenesis in oral tongue squamous cell carcinoma (OTSCC) using CD34; and tumor vasculogenesis using angiotensin converting enzyme, angiotensin II receptor 1 and angiotensin II receptor 2, in 32 OTSCC samples. Chalkley counting was performed by two independent observers. The averages of three ‘hot spot’ counts were compared with known prognostic factors. All four markers showed no correlation with any of the prognostic factors. When comparing the results from the two independent observers, the only marker shown to have a significant moderate correlation was CD34. The other three markers showed no significant correlation. The lack of statistical significance between the independent observers, and known prognostic factors with the four markers used, shows that Chalkley counting is not a reliable prognostic tool in OTSCC.

A Case of Collision Tumor of MALT Lymphoma and Poorly Differentiated Adenocarcinoma Diagnosed Incidentally After Appendectomy for a Clinical Presentation of Acute Appendicitis.

Jan 2019 DOI 10.14302/issn.2641-5518.jcci-18-2552

This report presents a case of collision tumors of low-grade B-cell lymphoma and poorly differentiated adenocarcinoma in the caceum of a 63-year-old woman. Lymphoma was diagnosed incidentally after appendectomy for a clinical presentation of acute appendicitis. Imaging follow-up demonstrated mesenteric lymphadenopathy and liver lesions, and all surgically resected regional mesenteric lymph nodes and liver biopsy were found to be infiltrated by both mucosa-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Systemic chemotherapy was administered for advanced colonic adenocarcinoma with liver metastases. The occurrence of synchronous lymphoma and adenocarcinoma of the colorectal region is rare, and this is a previously unreported case of a patient that was diagnosed during management of acute appendicitis.  

In Vitro Assessment of Estrogenic Potential of Biofield Energy Treatment using Human Endometrial Adenocarcinoma Cell Line

Dec 2018 DOI 10.14302/issn.2381-862X.jwrh-18-2459

The objective of the study was to investigate the effect of Consciousness Energy Healing based DMEM medium on the level of alkaline phosphatase enzyme (ALP) activity in Ishikawa cells. The test item, DMEM medium was divided into two parts. One part of the test item received Consciousness Energy Healing Treatment by a renowned Biofield Energy Healer, Mahendra Kumar Trivedi and was labeled as the Biofield Energy Treated DMEM, while the other part did not receive any treatment, and defined as the untreated DMEM group. The cell viability using MTT assay of the Biofield Energy Treated DMEM group was observed as 108%, which indicated that the test item was safe and non-toxic. The estrogenic potential using ALP level showed a significantly increase by 73.21% in the Biofield Energy Treated DMEM group as compared to the untreated DMEM group. Overall, the experimental data suggested that the Biofield Energy Treated DMEM has significantly improved ALP level, which play a vital role for the promotion and maintenance of estrogen level. Based on the study outcomes, it is concluded that Biofield Energy Healing Treatment showed a significant improved ALP level, which can be used in various estrogenic disorders such as hypophosphatasia, osteoporosis, severe anemia, malnutrition, hypothyroidism, magnesium deficiency, heart surgery, aplastic anemia, chronic myelogenous leukemia, enteritis in children, Wilson’s disease, pernicious anemia, bacterial infection and intrauterine infection is a leading cause of pelvic inflammatory disease, subfertility, infertility, endometritis, early pregnancy loss, fetal defects, and preterm birth.

Squamous Cell Carcinoma of the Conjunctiva (Scc) and Human Immunodefisciency Virus (Hiv): What Reality in Ivory Coast Through 23 Cases?

Sep 2017 DOI 10.14302/issn.2324-7339.jcrhap-17-1694

Introduction: Squamous cell carcinomas of the conjunctiva (SCC) are rare neoplasia but have a high rate of increase and a high rate of mortality, especially when they occur in the context of Human Immunodeficiency Virus (HIV) infection. The objective of this study was to establish an epidemiological and clinical profile of SCC in patients living with HIV and to assess its evolutionary characteristics. Patients and Methods: this was a descriptive cross-sectional study carried out over a period of 5 years in the ophthalmology department of the University Hospital of Treichville. The data collected focused on epidemiological, clinical, pathological, therapeutic and evolutionary elements. Twenty tree eyes of 23 patients were examined during this period. Results: The average age of our patients was 45 years with extremes ranging from 31 to 60 years. A female predominance was observed with a sex ratio of 0.92. The average consultation period was 18 months with extremes ranging from 6 to 60 months. Physically, 35% of our eyes (08 eyes) presented a functional loss of the eye. All our patients had a HIV positive status with 16 cases of HIV1 infection, 4 cases of HIV 2 infection and 3 cases of HIV 1 and 2 co-infection. Lymphocyte typing was performed for 15 patients out of the 23 With CD4 cell counts ˂ 200 in 30.43% of cases, between 200 and 500 in 34.78% of cases. All our tumors had had biopsy excision with pathological examination. A postoperative adjuvant topical chemotherapy in 6 cases. The average follow-up period of our patients was 29 months. In all cases, it was invasive differentiated squamous cell carcinoma. Discussion: HIV infection is a risk factor for the occurrence of conjunctival squamous cell carcinoma, but it is also an aggravating factor especially in the case of low CD4 cell count, particularly in sub-Saharan Africa, where the fight against infection, although boosted in these recent years, is far to achieve all objectives Conclusion: HIV seroprevalence is very often associated with opportunistic infections which include carcinogenic processes such as squamous cell carcinomas of the conjunctiva

Veterinary Healthcare Open Access

Relationship Between Inflammatory Infiltrate Canine Mammary Carcinomas.

Jul 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1586

The mammary tumor is one of the most common cancer in female dogs and, at the present days, there is a big focus on the study of the relation between this kind of tumor in animals and the cells that stay around them, like the inflammatory cells. The objective of this study was to evaluate and show where the inflammatory cells stay in simple mammary carcinomas in female dogs by immunohistochemistry. Samples of simple mammary carcinomas (tumor group; n=26) and mammary gland samples without tumor (control group; n=18) were submitted to immunohistochemical analysis for the detection of T lymphocytes, macrophages, plasma cells and the MHC-II molecule. The mast cells were evaluated by the histochemical technique (toluidine blue). Lymphocytes, macrophages and mast cells were observed distributed in the tumor stroma. MHC-II was detected in tumor cells and in the inflammatory infiltrate. Plasma cells predominated in the peritumoral stroma. Macrophages differed significantly between the two groups and predominated in the tumor group. In the comparison between histological types of mammary carcinomas, mast cells differed significantly between solid tumors of the tubular / papillary types. The cytoplasmic immunodetection of MHC-II was suggested an inefficient antigen presentation. Some of the leukocytes present in the tumor infiltrate, appear to be exerting a pro-tumor effect and allowing the progression of tubular and papillary carcinomas. But in solid carcinomas (may be poorly immunogenic), as they had the lowest proportion of leukocytes present in the tumor site. More studies are necessary to confirm these results, such as the determination of the cytokine profile and the predominant leukocyte subpopulations in the tumor microenvironment.

Neoplasms Open Access

Tumor Growth Dynamics: Dietary Fish Oil Induced Inhibition of Human Breast Carcinoma Growth, A Phenomenon of Reduced Cellular DNA Synthesis or Increased Cell Loss?

Jul 2017 DOI 10.14302/issn.2639-1716.jn-17-1495

Diets high in unsaturated fatty acids, especially those containing high levels of linoleic acid, e.g., corn oil, enhance mammary gland tumorigenesis in experimental animals. In contrast, diets high in long-chain polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), e.g. menhaden oil, appear to have a suppressive effect on this tumorigenic process. Many mechanisms have been proposed to explain the tumor inhibitory action exerted by menhaden oil and other fish oils, e.g., differences in prostaglandin metabolism, energy efficiency, alterations of the immune system, changes in lipid peroxidation, etc. Fundamental to a mechanistic understanding of this phenomenon, however, is an understanding as to whether or not the tumor inhibitory activities of dietary fish oil is mediated via an inhibition of tumor cell proliferation or mediated via an enhancement of tumor cell loss. Whether the amount of dietary fat or the type of fat effects mammary tumorigenic processes, via an effect on tumor cell proliferation or tumor cell loss, has not been clearly established. In the studies described in this communication, three methods were utilized to study tumor cell proliferation, i.e., H3-thymidine autoradiographic analysis, 5-bromo 2'-deoxyuridine (Brdu) flow cytometric analysis, and proliferative cell nuclear antigen (PCNA) flow cytometric analysis. Two methods were used to study tumor cell loss, i.e., a determination of the I125Urd tumor emission rate and a determination of a cell loss factor from the formulas of Steel and Begg. The tumor examined was the human breast carcinoma cell line MDA- MB231 maintained in athymic nude mouse. No significant difference in cell proliferation between carcinomas of mice fed a high corn oil diet (20% w/w) and a diet high in fish oil (19% menhaden oil, 1% corn oil). In contrast, a significant (p<0.05) increase in the rate of I125Urd emission rate and cell loss factor from the carcinomas in the fish oil fed mice compared to the corn oil fed mice was observed. In summary, the decreased tumor volume in the human breast carcinomas maintained in athymic nude mice fed a fish oil diet as compared to those fed a corn oil diet, appears to be due, at least in part, to an increased rate of carcinoma cell loss rather than a decreased rate of carcinoma cell proliferation.

Importance of Neutrophil/Lymphocyte Ratio in Squamous-Cell Carcinoma of the Larynx

Jan 2017 DOI 10.14302/issn.2379-8572.joa-16-1399

Aim: The relation between inflammation and cancer has been known since the 19th century. However, investigations on the pathogenesis and pathophysiology of this relation have begun recently. It was demonstrated that increased neutrophil/lymphocyte ratio is a poor prognostic factor in some malignancies. The present study aimed to determine whether preoperative neutrophil/lymphocyte ratio has a prognostic value in larynx cancer. Method: Preoperative blood analyses of 139 patients, who underwent subtotal or total laryngectomy for larynx cancer between 2003 and 2013 at Marmara University School of Medicine, Department of ENT, were retrospectively evaluated. Neutrophil/lymphocyte ratio (NLR) was calculated dividing absolute neutrophil count by absolute lymphocyte count. Optimal cut-off value for NLR was determined by receiver operating characteristics (ROC) curve analysis. Statistical analyses were done using IBM SPSS statistic 22.0 (IBM SPSS, Turkey) and Med Calc 12.3.0 package programs. Results: The sensitivity of NLR in predicting advanced-stage (Stage 3 and 4) squamous-cell carcinoma of the larynx (LSSC), T4 LSSC and lymph node metastasis at different cut-off values were 66.2%, 83.9% and 73.8%, respectively and the specificity was 76.7%, 66.2% and 65.2%, respectively. Staging according to T classification revealed that NLR significantly increases with tumor stage (p<0.001). Statistically significant relation was determined between lymph node metastasis of tumor and neutrophil/lymphocyte ratio (p=0.003). Comparing overall survival (OS) and disease-free survival (DFS) between the cases with NLR <3.02 and the cases with NLR >3.02, it was demonstrated that OS and DFS are significantly lower in the cases with NLR<3.02 (p: 0.001 vs. p<0.05 for OS and p: 0.013 vs. p<0.05 for DFS) Conclusion: NLR increases with the stage of disease in LSSC. NLR is a simple, cheap, repeatable and valuable parameter that can be obtained from routine analyses, gives information about poor prognosis and survival, and is able to predict T4 LSSC, advanced-stage LSSC (stage 3-4) and lymph node metastasis.

Adenosquamous Cell Carcinoma of the Stomach 18F-FDG PET/CT Diagnosis and Review of Literature

Nov 2016 DOI 10.14302/issn.2574-4526.jddd-16-1311

Adenosquamous carcinoma of the stomach (ASCS) is extremely rare with less than one hundred cases published in the world literature. It is defined by combined adenocarcima and squamous cells carcinoma of the stomach. ASCS is clinically aggressive and has a poor prognosis, even when discovered at an early stage. This intriguing entity is characterized by non specific symptoms or radiological signs. Integrate 18F-fluorodeoxyglucose positron emission tomography/computed tomography 18F FDG.PET/CT is useful morphologic and functional modalities for evaluating primary tumor, local extend and invasion beyond gastric wall or distant metastatic and eventually for management. Diagnosis of ASCS requires immunohistochemical confirmation. We report a 77-year-old man who was admitted to hospital because of epigastric pain, vomiting and melena since more than a month. Gastroscopy with biopsies had initially suggested gastric squamous cell carcinoma .Thoracic and abdominal computed tomography scan (CT) showed a huge mass in the gastric body, largely necrotic, infiltrating the adjacent structures without metastases. Partial gastrectomy with resection of the proximal 2/3 of the stomach, the spleen, the body and tail of pancreas and the left transverse colon was performed. Immunohistochemical analysis demonstrated ASCS with mixed adenocarcinomatous and squamous cells carcinoma with invasion of gastric lymph nodes. Unfortunately, two months after surgery, a CT of the abdomen revealed diffuse metastasis and the patient died three months later. In light of this case, we discuss the pathogenesis, staging and monitoring of this rare entity by combined 18F-FDG PET/CT with review of the literature.

Association of Epstein-Barr Virus with Gastric Carcinoma among Sudanese Patients

Oct 2016 DOI 10.14302/issn.2572-3030.jcgb-16-1190

Background: Gastric cancer (GC) ranks as the fourth most common cancer and the second leading cause of cancer deaths worldwide. Epstein-Barr virus is a well-known oncogenic virus, it is responsible for 10% of gastric carcinomas across the world. The aim of study was to determine the prevalence of EBV associated with GC in Sudanese patients. Method: Fifty Paraffin embedded blocks of gastric biopsy specimens diagnosed as gastric carcinoma were collected from Soba university hospital and Ribat teaching hospital, Khartoum, Sudan. DNA was extracted from the paraffin-embedded tissue, and then Epstein-Barr virus gene was detected by polymerase chain reaction (PCR). Result: Among the gastric biopsy specimens 27 (54.0%) were of male and 23(46.0%) were of female. Eleven EBV positive samples were found in gastric carcinomas (22.0%), 8 (72.7%) were of male and 3(27.2%) were of female. The mean age of the patients was 56 years, the most positive cases were between 50-59 years old, and (10%) of them are alive in Khartoum. Conclusions: There exists an association between EBV and gastric carcinoma in some Sudanese patients.

The Bromine, Calcium, Potassium, Magnesium, Manganese, and Sodium Contents in Adenocarcinoma of Human Prostate Gland

Feb 2016 DOI 10.14302/issn.2372-6601.jhor-15-896

Objectives: Adenocarcinoma of prostate is an internationally important health problem of the man, particularly in developed countries. The aim of this exploratory study was to evaluate whether significantchanges in the prostatic tissue levels of calcium (Ca), potassium (K), and magnesium (Mg) as an androgen dependent chemical element, and bromine (Br), manganese (Mn), and sodium (Na), as androgen independent elements, exist in the malignantly transformed prostate. Methodology: Prostatic tissue levels of Br, Ca, K, Mg, Mn, and Na contents were prospectively evaluated in 10 patients with adenocarcinoma and 37 healthy male inhabitants. Measurements were performed using non-destructive instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides. Tissue samples were divided into two portions. One was used for morphological study while the other was intended for chemical element analysis. The reliability of difference in the results between normal and cancerous prostate tissues was evaluated by Student’s t-test. Key Results: Mean values ± standard error of means (M±SΕΜ) for mass fraction (mg/kg on dry mass basis) of chemical element in the normal tissue were:Br32.9±3.6, Ca 2280±178, K 11211±414, Mg 1118±76, Mn 1.24±0.07, and Na 11100±408, respectively. The contents of Br and Mn were significantly higher (approximately 4 and 6 times, respectively) while those of Ca and Mg (nearly 3 times) and K and Na (20% and 30%, respectively) were significantly lower in cancerous tissues than in normal tissues. Major Conclusions: In adenocarcinoma transformed prostate tissue the chemical element metabolism is significantly disturbed.

Comparison of Phosphohistone H3 Immunohistochemical Staining, Ki-67, and H&E Mitotic Count in Invasive Breast Carcinoma

Oct 2015

The mitotic count is the most frequent reason for discordance between pathologists in modified Bloom and Richardson (mBR) scoring. Recently, the phosphohistone H3 (PHH3) immunohistochemical stain has been proposed as a potential surrogate marker for mitotic figures. This study examines the differences between H&E mitotic count, PHH3 mitotic count, and Ki-67 index in invasive breast carcinoma. A retrospective review of invasive breast carcinoma cases from 2013- 2014 was performed. H&E and PHH3 mitotic counts were assigned a mitotic score of 1 to 3 using mBR criteria. Ki-67 index was categorized into a three-grade system: <10% (low), 10 - <20% (intermediate), and >20% (high). A total of 451 cases were evaluated. PHH3 versus H&E mitotic count changed mBR scores in 24% of cases, upgrading in 23% and downgrading in 1%. A total of 431 cases had both Ki-67 and PHH3 available for comparison. Both H&E and PHH3 mitotic scores correlated with Ki-67 in 51% of cases; however, PHH3 had better correlation. We conclude that PHH3 in breast carcinoma allows for a more sensitive and practical approach in the identification of mitotic figures. PHH3 IHC is useful as a confirmatory tool in assessing the final mitotic score for more accurate mBR scoring and grading. In this study, 48 out of 451 (10.6%) of patients had a significant upgrade that may change the patient's treatment plans, including the addition of chemotherapy

Management of Locally Advanced and Metastatic Pediatric Nasopharyngeal Carcinoma. Experience of Children Cancer Hospital – Egypt

Oct 2015 DOI 10.14302/issn.2379-8572.joa-15-691

Background. Nasopharyngeal carcinoma (NPC) is a rare disease in the pediatric age group; it represents 1% of all pediatrics malignancies, however, it is the predominant malignancy arising in the nasopharynx in this age group. Although NPC is a chemo-radiosensitive disease yet, the optimal dose of radiotherapy and optimal timing of chemotherapy is still not standardized. Methods. This is a retrospective study including all the newly diagnosed pediatric NPC who were diagnosed and treated at the Children Cancer Hospital Egypt (CCHE) during the period from July 2007 to December 2012. All imaging studies (e.g., CT or MRI scans) were reviewed by a senior head and neck radiologist for proper staging and assessment of tumor response. Patients were staged according to AJCC staging system. Modified version of the Response Evaluation Criteria in Solid Tumor (RECIST) was used to assess response. Results. Twenty-six patients were diagnosed and received treatment as NPC in CCHE. Median age was 12 years (range 7.8-17 years). There was a male predominance. Eleven patients (42.3%) were stratified as stage 4, and 11 (42.3%) as stage 3. All patients received 3 cycles of neo-adjuvant chemotherapy followed by concurrent chemo-radiotherapy. IMRT was used to deliver radiotherapy in all patients. The overall response rate (CR and PR) to induction therapy was 73%, 19.3% had SD, while 7.7% had PD. By the end of the study, 18 patients (69.2%) were alive in CR, 5 patients (19.2%) had PD, and 3 patients (10%) lost for follow up. The Mean duration of follow up was 35 months, range 5-66 months. The 3 year OS and EFS and rates were 84.6% and 69.3 % respectively. OS for M0 was 91.3% and for M1 33.3% with statistical significance (p =0.032). Conclusion. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy using IMRT lead to good clinical end results with limited toxicity. Metastatic disease at presentation was identified as the adverse prognostic factor.

MicroRNA Profiling of Differentiated, Poorly Differentiated and Anaplastic Thyroid Carcinoma, a Comparative Approach

May 2015 DOI 10.14302/issn.2572-3030.jcgb-14-495

Thyroid carcinomas encompass a wide spectrum ranging from differentiated thyroid carcinoma (DTC) to poorly differentiated (PDC) and anaplastic thyroid carcinoma (ATC). DTC of both follicular (FTC) and papillary (PTC) types can progress to PDC and AC. The aim of our study was to evaluate if there is differential microRNA (miRNA) expression in various tumor subtypes during this progression. The miRNA profile of differentiated carcinomas (Follicular and Papillary) and ATC were compared with that of PDCs either by itself or in a background of differentiated carcinomas and anaplastic carcinomas. Unsupervised hierarchical clustering analysis revealed that FTC and PDC tend to cluster together in the absence of ATC. Interestingly, in cases with presence of all components i.e. FTC, PDC and ATC, the miRNA profile of poorly differentiated component clusters with that of the Anaplastic carcinoma component. miR-494 and miR-125a-5p were found to be differentially regulated in tumors with an anaplastic component and even the well-differentiated component (FTC) of these tumors were found to be aligned with the anaplastic profile. In addition, we also discovered some differentially regulated miRNAs in follicular variant of papillary thyroid carcinoma as compared to follicular thyroid carcinoma (miR-486-5p and miR-31).

Ophthalmic Science Open Access

Central Retinal Vein Occlusion in Hepatocellular Carcinoma

May 2015 DOI 10.14302/issn.2470-0436.jos-14-527

A 66 year old Chinese male with a medical history of hypertension, diabetes mellitus and hepatitis B carrier was diagnosed with hepatocellular carcinoma in 2009. He underwent treatment with selective internal radiation spheres and sorafenib, and multiple cycles of chemotherapeutic agents such as bevacizumab, erlotinib, OXAFI ( intravenous oxaliplatin and doxorubicin given on days 1, 8 and 15 in a 28-day cycle, a daily continuous infusion of fluorouracil and subcutaneous interferon alfa-2b 5 million units administered thrice weekly), thalidomide, capecitabine, and rapamycin over the course of four years. Along the course of treatment, he developed pulmonary embolism and was initially started on anti-coagulation. Two months later, he developed hemoptysis and the anti-coagulants were stopped. During his routine ophthalmology visit for diabetic eye evaluation, he complained of blurring of vision of his left eye for the past four to five weeks. He was found to have central retinal vein occlusion (CRVO) of the left eye, associated with macular edema. Visual acuity was 6/15 for the right eye and 6/60 for the left eye. Eyelids, conjunctiva, cornea, anterior chamber, pupils, lens and ocular motility were normal. Humphrey visual field testing showed a superior arcuate and basal defect. This is the first reported case of CRVO in hepatocellular carcinoma. The etiology of CRVO is multifactorial, withhepatic malignancy, previous major surgery, multiple cycles of chemotherapy and cessation of anticoagulant therapyas possible aetiological factors. His background medical problems of diabetes and hypertension are further contributors.

The Combination of Fractionated Erbium:YAG Laser Skin Microporation and Topical Imiquimod Is A New, Safe And Efficient Strategy for the Treatment of Actinic Keratosis and Basal Cell Carcinoma: Report of Two Pilot Studies

Feb 2015 DOI 10.14302/issn.2471-2175.jdrt-14-552

Two pilot studies evaluate fractional Er:YAG laser microporation to enhance topical imiquimod delivery for actinic keratosis and basal cell carcinoma. The approach seeks to increase epidermal penetration while limiting systemic exposure. Early results suggest acceptable tolerability and lesion response, supporting larger controlled trials.

Thyroid Cancer Open Access

Outcomes of Differentiated Thyroid Cancer Patients Treated with Surgery and Radioactive Iodine at SQCCCRC

Jun 2026 DOI 10.14302/issn.2574-4496.jtc-26-6304

Objective To evaluate the treatment outcomes of patients with Differentiated thyroid cancer (DTC) who underwent total thyroidectomy followed by RAI therapy at the Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC) in Oman. Methods This is a retrospective observational clinical study conducted at SQCCCRC. The study included all patients diagnosed with DTC who were admitted to SQCCCRC between June 2021 and November 2023. A total of 255 patients were identified and met the inclusion criteria for this study. Results The mean age at diagnosis was 39.9 ± 12.4 years (range: 14–79), with 78% of patients being female. The mean BMI was 30.3 ± 6.4 kg/m², with nearly half of the cohort (48.2%) classified as obese (BMI ≥ 30). Most patients had papillary thyroid carcinoma (92.9%), while follicular and Hürthle cell carcinoma accounted for 5.9% and 0.8% of cases, respectively. Based on the American Joint Committee on Cancer (AJCC) staging, 86.3% of the patients were classified as stage I and 3.9% as stage II. Six patients (2.4%) had stage IVB disease. According to American Thyroid Association (ATA) risk stratification the majority were low-risk. Patient age was strongly associated with disease stage. The distribution of metastatic cases varied by region, with the highest proportion observed in Dhofar. Most patients (87.1%) received a single dose of radioactive iodine (RAI), with a median cumulative dose of 3.7 mCi). At six months post-treatment, 70.2% of patients had a TG level < 0.2 ng/mL. Conclusion The outcome of therapy in majority of our patients is favorable with 72% having excellent biochemical response at last follow up. None of the patients with distant metastasis achieved excellent response and a high proportion of them came from the Dhofar governorate, a targeted intervention would be of benefit. Low risk patients require special attention and may need radioactive iodine during follow up, unlike other regions and hence warrant very close follow up and further review to establish the best practice guidelines in our region.

Immunotherapy Usage Has Not Increased Sub-Lobar Pulmonary Resections Despite Reduced Pneumonectomies

Feb 2026

Objective The landscape of non-small cell lung cancer (NSCLC) has changed due to liberalized utilization of computed tomography, developments in immunotherapy and targeted treatments, and guidelines encouraging sublobar resections. We analyzed the implications of these advances for surgical procedures over a 16-year period. Methods The National Cancer Database was used to identify NSCLC incident cases from 2004 to 2020. Histology, stage, grade, and treatment were analyzed using descriptive statistics and logistic regression. Results 2,028,553NSCLC patients were identified. Each year was associated with an increase in Stage I for NSCLC (OR1.05, 95%CI 1.05-1.05) and histological subtypes (adenocarcinoma: OR1.03, 95%CI 1.03-1.04; squamous: OR1.02, 95%CI 1.02-1.02; neuroendocrine: OR1.11, 95%CI 1.11-1.12), with no change in adenosquamous histology. A similar increase was observed for well- or moderately-differentiated histology (OR1.04, 95%CI 1.04-1.04). The proportion of patients receiving chemotherapy decreased (OR0.98, 95%CI 0.98-0.98), while more patients were treated with immunotherapy or targeted therapy, including an increase of 14% using immunotherapy or targeted therapy as first-line treatment. There was a decrease in the likelihood of receiving pneumonectomy (OR 0.91, 95%CI 0.91-0.91). Despite guidelines advocating sublobar resections, these procedures only increased by 1.1% per year. Conclusions Over the 16-year study period, there was a significant trend towards diagnosis of Stage I NSCLC. The most pronounced change in treatment patterns has been more patients receiving immunotherapy and less chemotherapy. Despite a promising decrease in pneumonectomies, the frequency of sublobar resections remains stagnant, indicating limited uptage in current practice.

Pancreas Open Access

Pancreatic cancer in a Non-Tertiary Center: CEA and Bilirubin More Predictive than CA 19-9 at Initial Presentation

Aug 2025

Background This study was undertaken to delineate the most predictive pattern at presentation for patients with non-metastatic pancreatic cancer compared to patients with metastatic pancreatic cancer who present to a medium sized hospital. Methods Data were collected at a medium sized hospital from 2009-2014 for patients with newly diagnosed pancreatic adenocarcinoma. Laboratory values, CT scans, pathology reports and ERCP results were obtained. Data are presented as mean (median +/- standard deviation). Results Fifty-two patients met the criteria for inclusion and were clinically diagnosed with pancreatic cancer. The median age was 71 years old. CEA levels for metastatic pancreatic cancer were 107.9 (20.6 +/- 166.7) ng/dl and 9 (6 +/- 11.6) ng/dl for non-metastatic cancer (P-value<0.05). Bilirubin levels for metastatic pancreatic cancer were 4.1 (0.7 +/- 6.6) mg/dl and 10.3 (10.4 +/- 8.1) mg/dl for non-metastatic cancer (p=0.009). CA19-9 levels for metastatic pancreatic cancer were 37,529 (644 +/- 88,352) U/ml and 5,150 (668 +/- 16,985) U/ml for non-metastatic cancer. Conclusion Elevated total bilirubin alongside low CEA appears to be a stronger predictor of non-metastatic disease at presentation compared to CA 19-9 alone.

Evolutionary Science Open Access

Rbm45 Phylogenetics, Protein Domain Conservation, and Gene Architecture in Clade Metazoa

Mar 2024 DOI 10.14302/issn.2689-4602.jes-24-4982

Mammalian Rbm45 is predominately expressed in neuronal tissue and is integral in brain development and neuronal differentiation under physiological conditions. Dysregulation of Rbm45 has been strongly associated with neurodegenerative disorders in humans and can drive hepatocellular carcinoma through reprogramming lipid metabolism. Intriguingly, Rbm45 is an ancient protein, evolutionarily conserved throughout metazoans, including in sponges which lack a nervous system. Curiously, the evolution of Rbm45 gene structure and protein domain conservation across kingdom Animalia is largely unknown. We performed phylogenetic analysis of Rbm45 nucleotide and amino acid sequences from 36 species representing 9 phyla: Porifera, Cnidaria, Priapulida, Mollusca, Brachiopoda, Arthropoda, Echinodermata, Hemichordata, and Chordata. While the tree from Rbm45 nucleotide sequence data resulted in clades Protostomia and Deuterostomia showing paraphyly, the phylogeny derived from Rbm45 amino acid sequence largely recapitulated known monophyletic relationships among metazoans. Human RBM45 protein structure includes three RNA-binding domains (RBD), a homo-oligomerization association (HOA) domain, a nuclear localization sequence (NLS), and a nuclear export sequence (NES). Multiple sequence alignment across the same 36 taxa used for phylogenetic analysis revealed conservation of all three RBDs, the HOA, and NLS; in contrast the NES was only detected in clade Craniata and not in clades Ambulacraria and Protostomia. Rbm45 gene structure analysis revealed increasing gene complexity concomitant with increasing evolutionary complexity. Rbm45 from non-bilaterian taxa had from 2 to 4 large exons, while bilaterian taxa had between 6 to17 small exons. These findings demonstrate that Rbm45 is an ancient, highly conserved gene among metazoans suggesting a function in a breadth of neural/sensory systems.

Primary Breast Sarcoma

Oct 2022 DOI 10.14302/issn.2641-5518.jcci-22-4323

Introduction Primary sarcomas of the breast are <0.1% of all malignant tumours of the breast. To date, there are 13 major breast sarcoma series in English literature. This study adds to these series characterizing primary breast sarcoma among Philippine patients. Methods All breast biopsies from the pathology records of the University of the Philippines-Philippine General Hospital (UP-PGH) were searched for breast sarcoma cases from January 2000 to December 2010. Metaplastic carcinomas and phyllodes tumors were excluded. Results There were 52 patients (45 female, 7 male) ranging in age 25-83 years (median 46 years). Majority had lump, ten cases with pain. No history of previous cancer was given. No history of prior radiation was found. Histopathological diagnoses were spindle cell sarcoma (n=13), fibrosarcoma (n=6), liposarcoma (n=6), MPNST (n=5), stromal sarcoma (n=5), angiosarcoma (n=4), MFH (n=4), leiomyosarcoma (n=3), rhabdomyosarcoma (n=3), chondrosarcoma (n=2), and synovial sarcoma (n=1). Tumors were with grade 1 (n=18), grade 2 (n=8), and grade 3 (n=10). Necrosis was noted in 6 cases. Simple mastectomy was done in 19 cases (37%), MRM in 31 cases (59%), while 2 far advanced had no surgery (3%). None had adjuvant radiotherapy or chemotherapy. The duration of follow-up for 45 patients ranged from 1 – 117 months, excluding those who were lost to follow-up. All 15 deaths were due to progressive disease. Recurrences were observed in 9 patients. The disease-free survival (DFS) and overall survival (OS) was 73%and 75%, respectively. On multivariate analysis, DFS and OS were significantly correlated with size (HR=113.63; p=0.019 and HR=77.36; p=0.037), grade (HR=20.73 ; p=0.003andHR= 39.57; p= 0.004), and having a histology of angiosarcoma (HR=35.20 ; p=0.005and HR= 50.74; p=0.007), respectively. Conclusion Sarcoma remains an important clinical entity among primary breast cancers.

Evolution of the Solid Human Tumor Cells Properties in Various Experimental Systems in Vitro

Jan 2022 DOI 10.14302/issn.2372-6601.jhor-22-4061

Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation.

Evaluation of Gall Bladder Mucosal Changes in Relation to the Type of Stones in Patients Undergoing Laparoscopic Cholecystectomy: A Retrospective Study of 394 Patients

Dec 2020 DOI 10.14302/issn.2578-2371.jslr-20-3362

Background and Aim Gallbladder (GB) cancer is a highly fatal malignancy and approx. 10% new cases are diagnosed every year in India. The GB cancer has poor prognosis due to progressive nature. Understanding of risk factors that lead to GB development is urgently required for better management of the disease. Presence of stones in gall bladder generates varied mucosal reactions, which leads to different types of histopathological changes in mucosa. Here, our aim is to study the correlation between various types of mucosal responses e. g. inflammation, hyperplasia, metaplasia and carcinoma with different characteristics e. g. number and morphology of gallstones both in males and females. Materials and Methods A retrospective study of gallstones was performed on 438 cases of cholecystectomies operated laparoscopically based on the histological changes. Out of 438 cases, 394 (89.95%) were associated with gallstones and the rest 44 (10.05%) belonged to acalculous cholecystitis. The mucosal changes in calculous gall bladder were studied in 394 cases and its correlation with number and types of observed gallstones were evaluated. Tissue sections were taken from the fundus, body, neck and abnormal area of gallbladder for histopathological studies. Results Our study has revealed the higher incidence of inflammatory changes in males, while gall bladder hyperplasia, intestinal metaplasia and cancer cases were found mostly in females. Conclusion Our study showed that changes in the number and morphology of gallstones are directly associated with the mucosal changes in gallbladder e.g. inflammation, hyperplasia, metaplasia and gall bladder carcinoma.

A Case Report on Challenging Management of Multiple Neoplasms in Elderly

Dec 2020 DOI 10.14302/issn.2474-7785.jarh-20-3628

Multiple primary malignancies especially in the head and neck region is no longer a rare occurrence and the prevalence is increasing. They were described as synchronous when the malignancies present within 6 months of another or metachronous tumors if the subsequent malignancy presents 6 months later. Many etiologies had been hypothesised including similar carcinogens exposure, genetic susceptibility and mutation, immunodeficiency or treatment of the index tumor. Among the hypotheses, the most accepted theory was field cancerisation in which the occurrence of multiple primaries in the aerodigestive tract was due to persistent exposure of similar carcinogens through inhalation or oral intake . However the co-incidence of thyroid and aerodigestive malignancies is relatively low. Hereby we would like to report a case of a 74 years old lady with known esophageal squamous cell carcinoma presented with metachronous laryngeal squamous cell carcinoma and papillary micro carcinoma of thyroid.

Veterinary Healthcare Open Access

Investigation of Neoplastic Cells in the Bone Marrow of Female Dogs with Mammary Gland Tumors

Jul 2020 DOI 10.14302/issn.2575-1212.jvhc-20-3434

Background The mammary glands are the second most common tumor development site in female dogs. One of the ways of staging such tumors is to evaluate the presence or absence of distant metastasis, including in bone marrow. Such findings in human medicine are associated with poor survival of women with breast tumors. However, in veterinary medicine, this clinical staging is used more for patients with lymphomas and mastocytomas. Studies using bone marrow biopsies as a staging method for mammary tumors are scarce. Objectives The present study was to evaluate mammary lesions and bone marrow in 23 female dogs, searching for disseminated tumor cells or metastatic foci. Results: Grade I carcinoma in mixed tumors was the type most observed (22.4%), and there was no statistical difference in relation to tumor size or presence of metastasis in lymph nodes. In the bone marrow of one female dog with carcinosarcoma (4.35%), there was cytoplasmic marking of a probable disseminated tumor cell of epithelial origin, and immunohistochemical evaluation showed presence of cytokeratin-19 antibodies. None of the female dogs presenting reduced cellularity or medullary fibrosis, confirmed through Masson’s trichrome technique, had cell marking in immunohistochemical analyses. Conclusions Bone marrow evaluation can be used as a staging method for mammary gland tumors in female dogs, since disseminated tumor cells present the potential to become secondary lesions and to disseminate to distant foci, thereby causing tertiary metastases over an indeterminate period of time.

Identity Crisis - Common Tumors in Exceptional Locations, A Case Series

May 2020 DOI 10.14302/issn.2641-4538.jphi-20-3289

Mucoepidermoid carcinoma (MEC) accounts for only 5% of all salivary gland tumors and is most often seen in the parotid glands. MEC occurrence in the larynx is, however, rare. The incidence of primary squamous cell carcinoma (SCC) of salivary glands is also scarce and comprises only about 1.6% of all salivary gland malignancies. Hereby, we share our experience in managing two patients with rare and opposite variants of malignancy which were diagnosed at the same time; MEC of the larynx and SCC of the parotid. In MEC tumors, the presence of the intermediate and mucous cells with positivity in mucicarmine stain are the significant features. For SCC tumors, identification of the usual tumor markers (p40, CK 5/6 and p63) are pathognomonic. Although MEC and SCC are common in the head and neck regions, the existence of these malignancies in exceptional locations must be considered. The key features mentioned in our comparison table can help distinguish both these tumors and to deliver the correct treatment modalities. The prevalence of genomic and carcinogenic factors in the occurrence of these tumors in uncommon locations needs to be explored in future studies.

The Follicular Benignancy- Desmoplastic Trichoepithelioma

Feb 2020 DOI 10.14302/issn.2689-5773.jcdp-20-3218

Trichoepithelioma is a benign, cutaneous neoplasm originating from the hair follicle and is categorized into singular trichoepithelioma, multiple trichoepithelioma and desmoplastic trichoepithelioma wherein desmoplastic trichoepithelioma is cogitated as an  exceptional, cutaneous adnexal tumour. Desmoplastic trichoepithelioma was initially scripted by Hartzell in 1904 wherein the lesion was  described  as a benign, cystic epithelioma. Desmoplastic trichoepithelioma can be additionally nomenclated as epithelioma adenoides cysticum, morphea - like epithelioma or  sclerosing epithelial hamartoma 1. Familial instances of desmoplastic trichoepithelioma are  infrequent and can be misdiagnosed on account of adjunctive  benign, cutaneous, adnexal neoplasms depicting  subtle clinical features, excepting a nodular basal cell carcinoma. Cogent clinical and histological features can assist the diagnosis of desmoplastic trichoepithelioma 12.

Veterinary Healthcare Open Access

Relationship Between the Immunodetection of Alpha-Smooth Muscle Actin and the Aggressiveness of Mammary Papillar Tumors in Female Dog

Dec 2019 DOI 10.14302/issn.2575-1212.jvhc-19-3101

Papillary carcinoma is a mammary neoplasia of women and female dogs characterized by papillary fibrovascular projections lined by epithelial cells. Evaluation on the biology of these tumors can be done by immunohistochemistry through detection of alpha-smooth muscle actin protein in the papillary myoepithelium, which lacks such a molecule during malignant proliferations. Thus, this study aimed at determining the malignancy degree of papillary mammary tumors of female dogs by immunohistochemistry. Twenty samples of mammary neoplastic tissues collected from female dogs treated in the Veterinary Hospital at FCAV were evaluated by Hematoxylin and Eosin staining (H&E) and tumor cells were immunolabelled with monoclonal antibody to alpha-smooth muscle actin (α-SMA). Five out of 20 cases showed positive immunolabeling greater than 10% of the total immunolabeling. The remaining fourteen cases presented immunostaining lesser than 10% showing decrease or absence of α-SMA labeling in the myoepithelium of the papilla tumors. All those cases in which immunostained cell was over 10% of the neoplasm (5 immunostains of 20 total cases) were classified as benign whereas those below 10% of immunostained in the slid were considered as malignant. Therefore, immunohistochemistry played an essential role in differentiating benign and malignant papillary tumors of bitches as already described for female. Tumor classification by conventional methods, such as H&E staining, can lead to erroneous interpretations on the real biological behavior of the papillary mammary tumor.

Bilobed Flap in Reconstruction of Nasal Defect

May 2019 DOI 10.14302/issn.2641-5518.jcci-19-2816

Basal cell carcinoma (BCC) is the most common type of skin cancer, which arises from the basal layer of the epithelium. It is a slow growing tumor and has a low metastatic potential, it accounts for 70–80% of all cutaneous malignancies in the head face and neck region .Defects near nasal tip and ala of the nose are one of the most difficult site to cover in a single stage, bilobed flap is reported to be used very effectively to close the defect in these areas. This article reports a case of basal cell carcinoma involving the ala of the nose which was excised and the reconstruction was done using bilobed flap.

Melanoma of the Breast with Smoothened (SMO) Mutation: Case Report and review of the Literature

Feb 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2581

We report the case of a 75 year-old female with past history of ampullary adenocarcinoma presenting with a rapidly enlarging breast mass, initially misclassified on fine needle aspiration as a probable sarcoma, which was ultimately diagnosed as melanoma on resection in the absence of a known cutaneous primary lesion. Next-generation sequencing (NGS) of the tumor revealed a mutation in the Smoothened oncogene (SMO) of unknown significance and wild-type BRAF. To our knowledge, SMO mutation in melanoma of any site has not been previously reported, though the effectiveness of SMO inhibitors has been studied in both in vivo and in vitro models of melanoma. Currently, these inhibitors have not been studied in SMO mutant melanoma. The patient declined further therapy after resection due to multiple comorbidities. She expired two years after presenting with the breast mass from complications of high grade urothelial carcinoma.

Thyroid Cancer Open Access

Image Guided Ablations for Thyroid Tumours

Feb 2019 DOI 10.14302/issn.2574-4496.jtc-19-2657

Image guided ablations might be regarded as a promising effective and safe alternative for treatment of recurrent thyroid cancer in particular in patients with high surgical risk or refusing surgery. Furthermore, image guided ablations seems to represent a promising alternative to surgery or observation for micropapillary thyroid carcinoma, with the aim of providing an effective treatment with minimal invasiveness. Further studies are necessary to confirm the role in this setting

Demonstration of the Capabilities of Transabdominal Ultrasonography in Assessment of Structures and Functional Disorders of Locally Advanced Gastric Cancer of Diverse Localization

Dec 2018 DOI 10.14302/issn.2574-4526.jddd-18-2521

Introduction: Ultrasound study of locally advanced gastric cancer that has spread to adjoining tissue and lymph nodes. This tumor can be associated with T2 to T4 stages of cancer. A “Locally advanced gastric cancer” is a tumor, which may be categorized as ‘resectable’ cancer when compared with M1 advanced cancer. Objective: The aim of this study was to evaluate the Capabilities of transabdominal ultrasonography in assessment of structures and functional disorders of the locally advanced gastric cancer of diverse localization Materials and Methods: A total of61 patients with locally advanced gastric cancer were analyzed of which 36 (59,0%) were males (mean age 62.7 years) and 25 (41,0%) were females (mean age 59.3 years). All patients were managed surgically and underwent preoperative X-ray, virtual gastroscopy techniques, multidetector computed tomography and transabdominal ultrasonography (USG). Histopathology results found, in 58 (95,1%) cases adenocarcinoma, in 3 (4,9%) – ring-cell carcinoma (cricoidal) gastric cancer was established. Stage T2 was diagnosed in 16 (26.2%) cases, T3 - in 41 (67.2%) cases, T4 - in 4 (6.6%) cases. The stomach tumor in 29 (47.5%) cases was localized mainly in the antrum, 27 (44.3%) – in the body, 5 (8.2%) in the cardia and fundus (Table 1). In 24 (39,3%) cases, pyloric stenos was diagnosed - of which in 6 (9,8%) it was compensated, in 18 (29,5%) - sub compensated. All patients underwent preoperative X-ray, virtual gastroscopy techniques, multidetector computed tomography and transabdominal ultrasonography (USG). Normal ultrasound features were observed in 35 patients without gastric pathology. Ultrasonography was carried out with the convex and micro convex transducers in the frequency range of 2-5 MHz and 4-7 MHz respectively in B and color Doppler modes. Results: The polypoid type of gastric cancer was detected in 3 (4,9±2,8%) cases, the ulcerative type – in 18 (29,5±5,8%), the infiltrative ulcerative type – in 27 (44,3±6,4%) and the diffuse infiltrative type – in 13 (21,3%±5,2%) cases respectively. In 24 (39,3%) cases, pyloric stenos was diagnosed - of which in 6 (9,8%) it was compensated, in 18 (29,5%) – sub compensated. The layers of the gastric wall were not differentiated in all patients with sub compensated pyloric stenos. The gastric wall thickness of the affected area was 10,2±2,9mm in the case compensated pyloric stenosis, the length was 27,1±6,2mm, the diameter of the pylorus was 8,3±0,8mm. Among patients with sub compensated pyloric stenos, the thickness of the gastric wall was 19,8±4,1mm, the length was 43,6±4,5mm, the pyloric diameter was 4,3±1,1mm. Among the 61 patients studied, pathological vascularization was detected in 42 (68.8%) cases. It was observed that, all 4 (6.5%) patients with gastric cancer were stage T4 and 38 (62.3%) were stage T3. Vascularization was weak in 13 cases, in 24 cases - moderate, and in 5 cases - enhanced. Metastases to the regional lymph nodes were diagnosed in 52 cases. Ultrasonographically, they were detected only in 37 (71.2%) cases. Conclusions: In the diagnosis of locally advanced gastric cancer, ultrasonography demonstrates good capabilities for determining the extent and depth of the affected area. Color doppler mode allows the study of vascularisation of a locally thickened area, as well as nearby enlarged lymph nodes, which is very important to ascertain the degree of malignancy of the hyperplastic process. ltrasonography can independently determine the degree of pyloric stenosis in patients with distal gastric cancer.

Metabolic Correction Therapy as Adjuvant Treatment for Breast Cancer Patients: A Case Report

Jan 2018

Breast cancer is the most common cancer in women worldwide. In the United States, is the second leading cause of cancer deaths in women. In Puerto Rico between 2008 and 2012, breast cancer was the most diagnosed type of cancer and the leading cause of cancer deaths among women. This is a case of 54 years old female diagnosed with stage IV right breast carcinoma. The patient complaints were weakness and a right breast ulcer. She started a metabolic correction therapy, which consisted of high intravenous vitamin C infusions, a nutritional supplementation plan, and Paleolithic diet. During treatment, both Glycohemoglobin and Carcinoembryonic Antigen levels decreased significantly, the right breast ulcer decreased in size, and the patient’s quality of life improved. Over the years, vitamin C studies have demonstrated a cytotoxic action against malignant cells. Based on the results from this case, we advocate continue studying possible adjuvant treatments for cancer patients, involving IV infusions of vitamin C and metabolic correction plans.

First Evidences of Epithelial-Mesenchymal Transition and Cancer Stem-Cell Phenotype Acquisition in Dermo-Epidermal Junction of BPV-Infected Neoplasms

Dec 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1869

Introduction Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).

Blockade of Programmed Cell Death Protein-1 Pathway for the Treatment of Melanoma

Nov 2017 DOI 10.14302/issn.2471-2175.jdrt-17-1760

Metastatic melanoma is a very deadly type of skin cancer with poor prognosis and low 5-year survival rates. Until recently, patients with metastatic melanoma had very few treatment options, which only included dacarbazine and aldesleukin. In 2011, the first checkpoint blocker, ipilimumab was approved for the treatment of unresectable metastatic melanoma but its success was eclipsed by low response rates and high incidence of adverse events. Later in 2014, anti-PD-1 antibodies, nivolumab and pembrolizumab were approved for the treatment of metastatic melanoma. With comparatively high response rates and manageable safety profile, PD-1 blockers were remarkably successful in the treatment of melanoma and also other cancer subtypes such as non-small cell lung cancer and metastatic urothelial carcinoma. This article highlights the success of anti-PD-1 antibodies, discusses the mechanism of PD-1:PD-L1/2 pathway, responses of melanoma patients to PD-1 blockers and the research on improving response rates to PD-1 blockers.

Study of VCAM-1 Gene Expression in Normal and Tumoral Tissues in Patients with Colorectal Cancer

Nov 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1744

Aim: Colorectal cancer is one of the most commonly diagnosed cancers in the world. Cell adhesion molecules play an important role in the progression of various cancers. It has been shown that the high level expression of some Cell adhesion molecule could be a new diagnostic factor for several cancers. Vascular cell adhesion molecule 1(VCAM1) is a cell surface glycoprotein that is expressed in the endothelium activated by cytokine. Generally, VCAM-1 expression level is very poor in normal adult tissue endothelial cells. According to the above explanation, this study was conducted to investigate the expression of VCAM-1 in tumoral tissues and adjacent normal tissues in Iranian colorectal cancer patients to its relation with clinicopathological Features in patients with cancer. Methods: In this study, 60 tumoral tissues and 39 adjacent normal tumor tissues were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) technique. Conclusion: A significant correlation was found between VCAM-1 expression level and the stage, lymph nodes involvement, tumor progression factor of cancer and sex. Interestingly, VCAM-1 expression not observed in tumors with stage0. No association was seen between VCAM-1 expression and other clinical features such as age, size of the tumor, metastasis and the number of lymph nodes. These findings suggest that VCAM-1 expression level may reflected disease progression and elevation in VCAM-1 has prognostic significance in patients with colorectal carcinoma.

Left Brachiocephalic Vessel Venous Tumor Thrombus in a Laryngeal Cancer Patient Detected with PET-CT Imaging

Aug 2017 DOI 10.14302/issn.2379-8572.joa-17-1672

Accurate diagnosis of tumor thrombus and distinguishing benign thrombus from tumor thrombus avoid unnecessary anticoagulant treatment of oncological patients and it is important for patient management. In this case report, the role of FDG PET/CT in the presentation of a suspicious tumor thrombus in the left brachiocephalic vein of a patient with known laryngeal carcinoma and leiomyosarcoma diagnosis is presented.

Non-Syndromic Multiple Keratocystic Odontogenic Tumor: A Case Report

Aug 2017 DOI 10.14302/issn.2379-8572.joa-17-1668

A Keratocystic Odontogenic Tumor (KCOT) is a benign odontogenic lesion that is well-known for its histopathological features and invasive clinical behaviors. KCOTs may be non-syndromic or syndromic, and the syndromic type presents a higher risk of recurrence and invasive behaviors. Non-syndromic KCOTs are uncommon and account for only 5% of the cases. The purpose of the present case report is to conduct clinical, radiographic and pathologic evaluations and treat a 37-year-old man with non-syndromic nevoid basal cell carcinoma. Syndromic and non-syndromic keratocysts present more invasive behaviors than the solitary type. The initial symptoms of syndromic keratocysts appear as multiple keratocysts of the mandible and maxilla that are diagnosed by a dentist; as a result, the diagnosis and treatment of the disease is very crucial.

Compliance to Company Based Colorectal Cancer Screening in Germany using Fecal Immunochemical Test (FIT) - Results of Almost Half a Million FIT Tests

Aug 2017 DOI 10.14302/issn.2471-7061.jcrc-17-1624

Background Despite the existence of the statutory early cancer detection program in Germany and the removal of financial barriers, which is frequently reported in the literature to be the main obstacle in screening, uptake of colorectal cancer screening remains quite low. The campaign for colorectal cancer screening in German companies reported in this article started in 2010. It was initiated because of the low compliance with opportunistic public colorectal cancer screening efforts. Its goal is to improve participation by offering an organized screening program using a simple test (FIT). Methods An offer for company employees is publicized through posters, company newsletters and the intranet. The difference between the positivity rates of those who returned the kits within 20 days and later than 20 days was assessed using the Z-test. The average time between a positive result and colonoscopy was estimated using the Poincaré plot method. The positive predictive values were calculated for carcinomas, advanced adenomas or any lesions. The sensitivity and specificity of immoCare-C published by Vogel et al. and Hundt et al. were used to derive the confidence intervals for the positive likelihood ratio (for carcinoma and any kind of adenoma). Results A total of 312,147 kits were returned and analyzed (return rate 70.2%). 5.6% gave a positive result. The PPV for cancer aged between 55 and 74 was 4.6% for men and women (95% CI: 2.38%-6.76% and 1.28%-7.99%, respectively), but 22% for men (95% CI: 17.93%-26.65%) and 8% for women (95%CI: 3.63%-12.26%) for advanced adenomas. The PPV for any lesion was higher for those with familial risk (49.3%) and 42.6% for those without familial risk (95% CI: 40.2%-45.0%), but with overlapping confidence intervals. Conclusions The reported sample is not representative. Although, offering CRC screening in companies may be an effective way of increasing uptake in the target population. Differences in the test performance between men and women need further evaluation.

Antioxidant Activity Open Access

The Assessment of Alchornea Cordifolia Activity in Aflatoxicosis Reduction in Rat.

Jul 2017 DOI 10.14302/issn.2471-2140.jaa-17-1630

Introduction: Aflatoxins are cytotoxic andserve as one of the key risk factors of hepatocellular carcinoma. Currently, plants and extract are widely used as potential scavenging substances for the detoxification of mycotoxins. Thus, this study aims to investigate the activity of the crude ethanolic leaves extract from Alchorneacordifolia in aflatoxicosis prevention. Material and Methods: The phytochemical screening was performed through qualitative analysis based on coloring and/or precipitation reactions. Groups of rats were treated daily with a mixture dose of aflatoxin B1 (AFB1) at 150 µg/kg and the crude extract of Alchorneacordifolia at doses of 50, 100, and 300 mg/kg for 21 days. The body weight, biochemical, and histological assessments were determined. Results: The phytochemical screening revealed the presence of polyphenols, flavonoids, sterols and terpenoids, quinoid compounds, tannins catechic and alkaloids. AFB1 treatmentcaused a significant increase of transaminases, urea, and creatinine abundances but reduced the rates of albumin and total proteins. Alchorneacordifolia administration alleviated biochemical parameters and body weight gain compared with the AFB1 group (p<0.05). The histological lesions of organs (liver and kidney) caused by AFB1 were significantly improved after administration of the extract at a dose of 300 mg/kg. Conclusion: This plant plays a beneficial role in AFB1-induced injury and may be used in the treatment of aflatoxicosis.

The Comparison of Functional Outcomes Between Supraglottic Horizontal Laryngectomy and Supracricoid Partial Laryngectomy

Jan 2017 DOI 10.14302/issn.2379-8572.joa-16-1364

Objectives The aim of this study was to compare the functional outcomes (including swallowing, respiration and phonation) of supraglottic horizontal laryngectomy (SGHL) and supracricoid partial laryngectomy (SCPL). Methods The clinical and pathological data were evaluated for 36 previously untreated patients who were diagnosed with laryngeal carcinoma and underwent SGHL or SCPL at the Department of Otorhinolaryngology-Istanbul Training and Research Hospital from 2010 to 2016. Removal of the nasogastric tube, decannulation and hospitalisation times were recorded in both groups and postoperative complications were noted. Results The SGHL group contained 15 patients and the SCPL group contained 21 patients (14 cases of cricohyoidoepiglottopexy (CHEP) and 7 cases of cricohyoidopexy (CHP)). The mean age of the subjects was 57.4 years in the SGHL group, and 59.7 in the SCPL group. Patients in the SGHL group were decannulated after 65.2 days, whereas the average decannulation time was 72.6 days in the SCPL group. This difference in decannulation time between the groups was not statistically significant (p>0.05). The mean hospitalisation time was 23 days, with no statistically significant difference between the groups (>0.05). The nasogastric tube was removed from the patients after 37.9 days in the SGHL group and after 35.8 days in the SCPL group. No statistically significant difference was determined in the time to start feeding between the groups (p>0.05). Surgical wound infection, the occurrence of pharyngo-cutaneous fistulas and rupture of the pexy sutures were complications. Conclusion Functional outcomes of SCPL were similar to those of patients who underwent SGHL. The preservation of the hyoid bone is the most important consideration for preserving the swallowing function.

Thyroid Cancer Open Access

Evaluation of Household Radiation Exposure and Safety after Ambulatory Radioiodine Ablation Therapy

Aug 2016 DOI 10.14302/issn.2574-4496.jtc-16-1129

Objective: Radiation exposure to the general public and patients undergoing diagnostic or therapeutic procedures is of great concern, especially to the medical community. Revision of Nuclear Regulatory Commission rules several years ago yield new recommendations for the administration of therapeutic doses of 131-Iodine that included the release criteria. The guidelines for ambulatory treatment included patient education and radiation safety measures to minimize exposure and contamination. Our goal in this study was to evaluate patient compliance with the radiation safety instruction protocols given to them before the therapeutic dose and monitor radiation levels in different house areas at different times after an ablation therapy of 3700MBq or more. Method: Patients with well differentiated thyroid cancer being evaluated for ablation therapy with 131-Iodine were invited to participate. A thorough set of instructions on radiation protection were given verbally and in writing. Patient house was assessed with a Geiger Muller detector at 24 and 72 hours or above to obtain direct radiation levels in several areas. Patient radiation levels were also monitored. Results: A total of 12 patients have been included, 11 females and 1 male, median age was 53 years. Tumor histology was 10 papillary, 2 papillary-follicular variant and 1 follicular carcinoma; 92% of the cases were T1, N0, M0. Home location was urban in 77% and rural in 33% of the patients; 67% of the patients had an educational level between 9-12 grade. Radioiodine doses range from 3441-5994MBq. None of the patients had a relatives or companion in the house. Mean patient exposure 24 hours after the dose at 1 meter was 12mrem/hr, 0.120mSv/h; this represented a retained dose of 2181MBq (59mCi). Only one patient (T1, Nx, M1) had an exposure rate at 1 meter of 100mrem/hr (1mSv/hr) at 24 hours. At 72 hours the exposure changed to 4mrem/hr, 0.040mSv/hr, retained dose of 725.2MBq (19.6mCi). Higher exposure rates in the house were at 24 hours in the bed and pillows (7mrem/hr), kitchen trash (13mrem/hr) and bathroom sink (8mrem/hr). The exposure rates at the toilet and shower were similar (3-4mrem/hr). There was a significant decreased in the exposure rate at 72 hours in all house areas. Patients with the higher exposure rates were those with metastatic disease, and small living facilities. Patients living in rural or urban location had no difference in the exposure rate. The educational levels were not related either to the exposure rate. Conclusion: Patient compliance with radiation protection instructions and Nuclear Regulatory Commission release criteria was good. Radiation exposure levels in the house areas are safe. Special instructions must be design to minimize contamination in the bathroom and kitchen Caution is recommended in the release of patients with extensive metastatic disease and doses of 5920MBq or more.

Application of a Cardiac Septal Occluder in a Patient Affected by Enteroatmospheric Fistula

Jun 2016 DOI 10.14302/issn.2471-7061.jcrc-14-579

Enteroatmospheric fistula is a challenging and emerging clinical situation, mainly related to “open abdomen” technique in damage control surgery for trauma and in case of multiple laparotomies. We report the case of a 61-year-old male patient, affected by rectal carcinoma, submitted to standard surgical treatment and gradually evolving in persistent proximal jejunal fistula. The positioning of a cardiac septal occluder (Amplatzer®) was associated with immediate and late favourable effects. The procedure was conducted “bed-side” and turned out to be easy and safe.

Thyroid Cancer Open Access

Thyroid Transcription Factor-1 Activity is Required for the Proliferation of Human Thyroid Cancer Cells 8505C

Feb 2016 DOI 10.14302/issn.2574-4496.jtc-15-838

Thyroid transcription factor-1 (TTF-1) is known to play key roles in thyroid organogenesis, in thyroid cell proliferation and in the expression of genes involved in thyroid differentiated function. Many human thyroid cancer cell lines keep producing TTF-1 despite the loss of differentiated gene expression, raising a question about the role of the factor in these cells. In order to investigate this point, we used a chimeric protein acting as a functional antagonist of TTF-1 transcriptional activity that was expressed conditionally in 8505C cells originating from an anaplastic thyroid carcinoma. We observed a growth arrest of 8505C thyroid cancer cells when the endogenous TTF-1 transcriptional activity was inhibited. It correlated with decreased levels of several mRNAs encoding positive effectors of cell proliferation like CDK1 and cyclinB1, and increased levels of various mRNAs encoding negative regulators of cell division like CDKN2B and DUSP6. In conclusion, the persistence of TTF-1 expression observed in the dedifferentiated human thyroid cancer cell line 8505C reflects the need of TTF-1 activity for the proliferation of these tumor cells.

Overexpression of Prostate Apoptosis Response Protein-4 In Colon Cancer Cells Can Inhibit Metastasis by Upregulating E-cadherin Expression

May 2015 DOI 10.14302/issn.2471-7061.jcrc-14-574

Colon cancer has a five-year survival of 64.7%, and about 50,000 people are expected to die from colon cancer this year. Patients with metastatic colorectal cancer have a significantly worse prognosis, a 12.9% five-year survival. This emphasizes the need for strategies to inhibit the growth and metastases of colorectal cancer. Prostate apoptosis response protein 4 (Par-4) is a pro-apoptotic protein that has been shown to mediate apoptosis in response to stimuli, such as chemotherapeutics and radiation. Recombinant Par-4 protein has been shown to reduce the occurrence of Lewis lung carcinoma metastases in-vivo; however, the mechanism by which Par-4 can inhibit metastasis has not been elucidated. In this study, human colon cancer cell lines - SW480 and SW620 - were transfected with Par-4 plasmid or anti-Par-4 shRNA, and the effect on metastasis was examined. Par-4 overexpression inhibited cell migration and invasion, while Par-4 knockdown promoted it. Moreover, the morphology of SW620 cells was altered when Par-4 levels were increased. The change was characteristic of a mesenchymal-to-epithelial transition (MET) in these cells. MET can be induced by upregulation of E-cadherin expression, and RT-PCR and Western blot analyses showed that E-cadherin mRNA and protein levels, respectively, were increased in the Par-4 overexpressing cells concomitant with a decrease in vimentin. The results of this study demonstrate the potential of Par-4 in colon cancer therapy, not only in primary tumors but also in metastatic cells.

Epidemiology and the Histopathological Pattern of Diagnosis of Thyroid Diseases in a University Hospital in Riyadh, Saudi Arabia

May 2015 DOI 10.14302/issn.2372-6601.jhor-14-382

Background/Aims: Thyroid disorders are a common, worldwide clinical problem in general practice.It presents predominantly as a thyroid nodule. Each thyroid nodule has a risk of cancer. The incidence of thyroid cancer is much more common in Saudi Arabia in comparison to the West. There is a worldwide increase in the incidence of thyroid cancer. The objective of this study is to highlight in details the wide spectrum of histopathologic diagnosis encountered in patient undergoing thyroid surgery in the population of Riyadh region of Saudi Arabia. Patients and Methods: Retrospective review of all thyroid samples for 256 patients whom underwent thyroid surgery at King Khalid University Hospital, King Saud University, Riyadh, during the period between 2000 and 2009. Of those, 171 cases were non neoplastic and 85 neoplastic lesions. Females constitute 80% of non neoplastic lesions and 79% of all thyroid malignancies. The peak incidence of thyroid cancer was in the third decade. Papillary thyroid carcinoma was the most common cancer (71%). Conclusion: Thyroid cancer is a common cancer in Saudi Arabia; it is the second most common cancer in females. The increasing rates of thyroid cancer occur predominantly in women. Papillary thyroid carcinoma accounted for the bulk of this increase. Additional studies are needed to explain the rise in papillary thyroid carcinoma incidence in Saudi Arab as well as throughout the world and to search potential risk factors that are currently unrecognized.

Correlation of Oncotype DX Recurrence Score with the Expression of Insulin Receptor Substrate Proteins in Estrogen Receptor + Breast Cancer

May 2014 DOI 10.14302/issn.2572-3030.jcgb-13-369

Insulin receptor substrate (IRS) 1 and 2 are downstream signaling proteins that influence breast pathophysiology. IRS-1 promotes carcinoma cell proliferation; whereas IRS-2 regulates cell motility, invasion, and glycolysis. Our lab has shown that distinct cellular localization of IRS-2 also plays a role in carcinoma cell function. Oncotype DX (Genomic Health) (ODX) is a 21-gene expression profile used to classify carcinomas with low, intermediate, and high risk recurrence scores (RS). Our aim is to correlate expression and cellular localization of IRS proteins in breast carcinomas with their ODX RS. 97 breast carcinomas sent for ODX testing from 2006-2009 were collected and grouped according to their RS (low, intermediate or high). Immunohistochemistry for IRS-1/-2 was performed. Specific criteria were used to evaluate IRS staining patterns. Follow-up data, ranging from 3-6 years, was available. Statistical analysis was performed to correlate staining patterns of IRS-1/-2 with the three RS groups. IRS-1 staining, predominantly nuclear, did not significantly correlate with RS (P=.5645). IRS-2 expression patterns did show statistical significance amongst the three RS groups (P=.0371). Tumors with intermediate and low RS were more likely to exhibit punctate and diffuse cytoplasmic expression of IRS-2, and cell membrane expression was uncommon in this group. Expression and cellular localization of IRS proteins play an important role in breast cancer cell biology, and expression patterns for IRS-2 do demonstrate a significant correlation with ODX RS. Further studies are required to elucidate the significance of cellular localization of IRS-1/-2 proteins in breast carcinoma cells and their relationship to ODX scores.

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