A Case Report on Rare Case of Pancreatic Metastasis from Primary Lung Adenocarcinoma: Treated Through a Non-surgical Approach.

Introduction: Most frequent sites of metastasis from lung cancer are the liver, brain and adrenal. Pancreas is an infrequent site of solitary metastasis from the lung primary with limited treatment options. There is insufficient data on the prognosis and optimal management of such cases. Case Description: We report a case of 44-year-old gentleman diagnosed with locally advanced lung adenocarcinoma Stage T4N3 who was treated radically with chemoradiation therapy, followed by a relapse of solitary pancreatic metastasis, which was treated with targeted therapy, erlotinib, due to the presence of epidermal growth factor receptor (EGFR) mutation. Practical Implications: This case reports an excellent radiological and symptomatic response in a patient who received erlotinib for advanced non-small-cell lung cancer (NSCLC). The use of EGFR-tyrosine kinase inhibitors has led to better prognosis and longer progression-free survival for patients with advanced NSCLC. However, the long-term survival of patients with metastatic NSCLC is limited.

Long-Term Disease Control of Locally Invasive Epithelial-Myoepithelial Carcinoma of Parapharyngeal Salivary Glands With Definitive Radiotherapy.

Epithelial-myoepithelial carcinoma (EMC) is a rare clinical entity that affects glandular tissues, most commonly salivary glands. EMC of parapharyngeal space is exceedingly rare. Surgery is the mainstay of treatment with or without chemotherapy, radiotherapy, or both. Due to the rarity of the disease, select cases where surgery is not possible present a management conundrum. We present a case of locally advanced, stage IVa EMC of parapharyngeal space that was treated with upfront definitive radiotherapy. Radiotherapy treatment alone led to long-term disease control in both clinical and radiological follow-ups. The patient was followed for more than eight years posttreatment with no disease recurrence, enjoying the normal activities of life with no late toxicities including xerostomia. This case report highlights the role of radiotherapy in the management of such patients, and more studies are required in this context for surgical candidates with positive disease margins.

Anticancer genes (NOXA, PAR-4, TRAIL) are de-regulated in breast cancer patients and can be targeted by using a ribosomal inactivating plant protein (riproximin).

BACKGROUND: Anticancer genes are an endogenous defense against transformed cells as they impose antineoplastic effects upon ectopic expression. Profiling the expression of these genes is fundamental for exploring their prognostic and therapeutic relevance in cancers. Natural compounds can upregulate anticancer genes in malignant cells and thus be useful for therapeutic purposes. In this study, we identified the expression levels of anticancer genes in breast cancer clinical isolates. In addition, the purified and sequenced plant protein (riproximin) was evaluated for its potential to induce anticancer genes in two breast cancer cell lines. METHODOLOGY: Expression profiles of three anticancer genes (NOXA, PAR-4, TRAIL) were identified by immunohistochemistry in 45 breast cancer clinical isolates. Breast cancer cells were exposed to riproximin and expression of the anticancer genes was determined by microarray, real-time PCR and western blot methodologies. Lastly, a bioinformatic approach was adopted to highlight the molecular/functional significance of the anticancer genes. RESULTS: NOXA expression was evenly de-regulated among the clinical isolates, while PAR-4 was significantly down-regulated in majority of the breast cancer tissues. In contrast, TRAIL expression was increased in most of the clinical samples. Expression levels of the anticancer genes followed a distinct trend in accordance with the disease severity. Riproximin showed a substantial potential of inducing expression of the anticancer genes in breast cancer cells at transcriptomic and protein levels. The bioinformatic approach revealed involvement of anticancer genes in multiple cellular functions and signaling cascades. CONCLUSION: Anticancer genes were de-regulated and showed discrete expression patterns in breast cancer patient samples. Riproximin effectively induced the expression of selected anticancer genes in breast cancer cells.

Expression profiling of anticancer genes in colorectal cancer patients and their in vitro induction by riproximin, a ribosomal inactivating plant protein.

BACKGROUND: Ectopic expression of anticancer genes (ACGs) imposes antineoplastic effects on transformed cells. Clinically, reduced expression of these genes has been linked with poor prognosis, metastasis and chemo/radiotherapy resistance in cancers. Identifying expression pattern of ACGs is crucial to establish their prognostic and therapeutic relevance in colorectal cancer (CRC). In addition to the clinical perspective, naturally occurring compounds can be explored in parallel for inducing ACGs to achieve cancer cell-specific death. METHODOLOGY: Expression profiles of three ACGs (NOXA, PAR-4, TRAIL) were identified via real-time PCR in CRC clinical isolates. Time lapse-based expression modifications in ACGs were studied in a CRC liver metastasis animal model using microarray methodology. Effects of a purified plant protein (riproximin) on selected ACGs were identified in three primary and metastatic CRC cell lines by real-time PCR. Lastly, importance of the ACGs in a cellular environment was highlighted via bioinformatic analysis. RESULTS: ACGs (except NOXA) were persistently downregulated in clinical isolates when comparing the overall mean expression values with normal mucosa levels. In vivo studies showed a prominent inhibition of NOXA and PAR-4 genes in implanted CRC cells during rat liver colonization. TRAIL showed deviation from this theme while showing marked induction during the early period of liver colonization (days 3 and 6 after CRC cell implantation). Riproximin exhibited substantial potential of inducing ACGs at transcriptome levels in selected CRC cell lines. Bioinformatic analysis showed that vital molecular/functional aspects of a cell are associated with the presence of ACGs. CONCLUSION: ACGs are downregulated in primary and metastatic phase of CRC. Riproximin effectively induces ACGs in CRC cells and can be exploited for clinical investigations over time.

Epidemiology of young breast cancer patients at Gujranwala: A single institution based study.

The objective of this study was to illustrate the statistical and medical characteristics of females younger than 40 years presenting with breast cancer at GINUM. A descriptive case series in which 235 patients who fulfilled the inclusion and exclusion criteria were included. The majority of the patients had advanced disease at presentation. Family history was positive in 59 (25.11%) patients. Patients having grade III and II disease were 142(60.42%) and 89 (37.87%) respectively. Thirteen (5.5%) patients had Right-sided breast cancers in our series. No significant association of null parity with breast cancer was found. Receptor status studies revealed only 2.55% increased oestrogen receptor/progesterone receptor (ER/PR) positive patients as compared to oestrogen receptor/progesterone receptor (ER/PR) negative patients. Our population shares slightly different features as compared to Western population because there were slightly increased right-sided tumours and majority of our patients were parous.

Blood-based gene expression profile of oxidative stress and antioxidant genes for identifying surrogate markers of liver tissue injury in chronic hepatitis C patients.

Oxidative stress is the process by which reactive molecules and free radicals are formed in cells. In this study, we report the blood-based gene expression profile of oxidative stress and antioxidant genes for identifying surrogate markers of liver tissue in chronic hepatitis C (CHC) patients by using real-time PCR. A total of 144 untreated patients diagnosed with CHC having genotype 3a and 20 healthy controls were selected for the present study. Liver biopsy staging and grading of CHC patients were performed using the METAVIR score. Total RNA was extracted from liver tissue and blood samples, followed by cDNA synthesis and real-time PCR. The relative expression of genes was calculated using the ΔΔCt method. The expression profile of 84 genes associated with oxidative stress and antioxidants was determined in liver tissue and blood samples. In liver tissue, 46 differentially expressed genes (upregulated, 27; downregulated, 19) were identified in CHC patients compared to normal samples. In blood, 61 genes (upregulated, 51; downregulated; 10) were significantly expressed in CHC patients. A comparison of gene expression in liver and whole blood showed that 20 genes were expressed in a similar manner in the liver and blood. The expression levels of commonly expressed liver and blood-based genes were also correlated with clinical factors in CHC patients. A receiver operating curve (ROC) analysis of oxidative stress genes (ALB, CAT, DHCR24, GPX7, PRDX5, and MBL2) showed that infections in patients with CHC can be distinguished from healthy controls. In conclusion, blood-based gene expression can reflect the behavior of oxidative stress genes in liver tissue, and this blood-based gene expression study in CHC patients explores new blood-based non-invasive biomarkers that represent liver damage.

Primary Mammary Small Cell Carcinoma.

Neuroendocrine breast cancer was defined in 2003 by WHO as a separate and unique breast cancer subtype. Primary small cell carcinoma of the breast, an exceptionally uncommon and aggressive tumor, is frequently characterised by early progression and worse outcome. Moreover, it is essential to distinguish between small cell carcinoma arising primarily in the breast and the metastatic disease to the breast. We had a patient of primary small cell carcinoma of breast. As her initial metastatic workup was negative for disease elsewhere, so she was started on neoadjuvant chemotherapy to which she responded well. Her modified radical mastectomy (MRM) was done followed by completion of chemotherapy up to 6 cycles and local radiotherapy of chest wall. However, the disease behaved aggressively afterwards as she developed recurrence twice at 9 and 19 months interval, respectively, for which she was considered for second and third line chemotherapy. An accurate management of the primary small cell carcinoma of the breast still lacks a consensus. Relevant studies were also reviewed to enhance knowledge and expertise in diagnosis, clinicopathologic features, management, and outcome of this tumor.

Association of TP53 codon 72 polymorphism in women suffering from endometriosis from Lahore, Pakistan.

OBJECTIVE: To investigate TP53 gene codon 72 polymorphism in women with endometriosis and compare it with healthy samples. METHODS: This case-control study was carried out at Jinnah Hospital, Services Hospital and Sheikh Zayed Hospital, Lahore, Pakistan, from 2014 to 2016, and comprised patients with endometriosis and healthy controls. SPSS 21 was used for statistical analysis. RESULTS: Of the 176 participants, 88(50%) were healthy controls and 88(50%) were endometriosis patients. The observed genotype frequencies for controls and patients were 14(15.9%) and 31(35.3%) for proline/proline, 46(52.3%) and 35(39.8%) for proline/arginine, and 28(31.8%) and 22(25%) for arginine/arginine, respectively. The association of different genotypes was not significant in patients with moderate-to-severe endometriosis (p=0.574). The presence of pro/pro genotype enhanced the chances/odds of getting the disease (p<0.05). However, the risk further increased with the advancement of age, particularly in the 27-46 age group (p<0.05). CONCLUSIONS: In Pakistani women the association of TP53 gene codon 72 arginine/proline polymorphism was present..

Colors as catalysts in enzymatic reactions.

We studied the effects of visible range irradiation (in vitro) on the enzyme solutions (glucose oxidase, cholesterol oxidase + cholesterol esterase and lipase) in order to infer the changes produced in the human body after chromotherapy. The glucose oxidase showed enhanced activity to the color purple (464 nm), while the activity of the other enzymes, cholesterol esterase + cholesterol oxidase and lipase, increased when exposed to dark violet (400 nm). Purple is being used in conventional chromotherapy for diabetes, as supported by the experimental observation in which purple enhanced the activity of enzymes responsible for the oxidation of glucose. Specific wavelengths regulate living processes by acting as catalysts in enzyme activity, while some wavelengths may reduce enzyme activity. The irradiation of specific wavelengths effect enzymatic processes, which as a consequence, accelerated biochemical reactions. This particular frequency when provided to the enzymes (in vitro) lead to changes which may well be occurring in vivo.