Dysregulation of Hedgehog (Hh) signaling pathway has been documented in mammary gland development and breast cancer (BC) progression. Despite the remarkable progress in therapeutic interventions, BC related mortality in Bangladesh increased in the last decade. Triple negative breast cancer (TNBC) still presents a critical therapeutic challenge. Thus effective targeted therapy is urgently needed. In this study, we report the clinicopathological characteristics and prognosis of BC patients from Bangladesh. Routine immunohistochemical analysis and high throughput RNA-Seq data from the TCGA library were used to analyze the expression pattern and association of high and low level of Shh expression in a collection of BC patients with a long-term follow-up. High levels of Shh were observed in a subset of BC tumors with poor prognostic pathological features. Higher level of Shh expression correlated with a significantly poorer overall survival of patients compared with patients whose tumors expressed a low level of Shh. These data support the contention that Shh could be a novel biomarker for breast cancer that is involved in mediating the aggressive phenotype of BC. We propose that BC patients exhibiting a higher level of Shh expression, representing a subset of BC patients, would be amenable to Shh targeted therapy.
Serum from one hundred and ten breast cancer patients and thirty healthy female volunteers, were prospectively collected and evaluated for serum levels of Shh and IL-6 using human Shh and IL-6 specific enzyme-linked immunoassays. All patients were regularly monitored for event free survival (EFS) and overall survival (OS). Overall outcome analysis was based on serum Shh and IL-6 levels. In patients with progressive metastatic BC, both serum Shh and IL-6 concentrations were elevated in 44% (29 of 65) and 63% (41 of 65) of patients, respectively, at a statistically significant level [Shh (p = 0.0001) and IL-6 (p = 0.0001)] compared to the low levels in healthy volunteers. Serum levels tended to increase with metastatic progression and lymph node positivity. High serum Shh and IL-6 levels were associated with poor EFS and OS opposite to the negative or lower levels in serum Shh and IL-6. The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC. Further studies are warranted for validating these biomarkers as prognostic tools in a larger patient cohort and in a longer follow-up study.
Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAM high cells compared to the cisplatin sensitive counterpart. EpCAM high populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAM high populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAM high populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAM high populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAM high populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAM high populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAM high populations.
This study had been planned to see the histomorphological pattern of gastric mucosal biopsy, demonstrate the organism H .Pylori and correlate with endoscopic findings. The study was carried out in the department of the Pathology Rajshahi Medical College, Rajshahi, Bangladesh, during the period from January 2006 to December 2007. Endoscopic biopsy specimens were obtained from 105 cases of gastro duodenal lesions. According to endoscopic findings out of 105 cases 69(65.7%) had gastric carcinoma, 06 (5.71%) had gastric ulcer, 05 (4.76%) had duodenal ulcer, 05 (476%) had gastritis and 20 (19.04%) had normal mucosa, reported as non-ulcer dyspepsia. Of the 69 endoscopically gastric carcinoma 59 (85.50%) were diagnosed histologically as adenocarcinoma and 10 (14.50%) were diagnosed histologically as chronic gastritis in which H.Pylori was positive in 27.5% and 14.50% positive in chronic gastritis. Of 06 gastric ulcer 03 (50%) was diagnosed histologically as gastritis and 03 (50%) were diagnosed histologically as gastric carcinoma. H. Pylori was positive in cent percent of gastritis. Of 05 duodenal ulcer 03 (60%) were diagnosed histologically as gastritis and 02 (40%) were diagnosed histologically as intestinal metaplasia H. Pylori was positive in 66.6% of duodenal ulcer. Of 05 gastritis were diagnosed histologically as gastritis 60% were postive for H.Pylori. Of 20 NUD 18 (90%) were diagnosed histologically as gastritis, 01 (05%) was diagnosed histologically as ulcer and 01 (05%) was diagnosed histologically as normal mucosa, all these cases no H. Pylori was found. Key Words: Helicobacter Pylori; Gastroduodenal Lesion; Association DOI: http://dx.doi.org/10.3329/akmmcj.v2i2.8164 AKMMC J 2011; 2(2): 06-10
Background: Clinical presentation hospital admission and outcome of COVID-19 pandemic are different from one country to another. So every country should have their own data regarding COVID-19. Subjects and Methods: This was an online cross-sectional survey carried out in RT-PCR positive COVID-19 adult patient. A preformed questionnaire adapted in Google form and circulated through online to collect data. Informed consent was ensured before participation in this study. Results: We have studied of 305 RT-PCR positive COVID-19 patients mean age was 36.32(+/-12.369) years with male predominance and majority were doctor 46.9%. 48.8% of the patients family members affected along with them. After COVID-19 pandemic 31.7% did not go out of their house. For prevention (72.4%)of the patients used mask and 38.8% used hand gloves during outing. 28.7% reported to be affected while working in hospital 21.8%were affected in their office. Fever (80.1%) cough (57.7%) pain in throat (50.8%) rhinitis (45.9%) and loss of smell (45%) and taste sensation (45.6%) were the most common symptoms. Sample was given average 3 (+/- 3.384) days after onset of the symptoms and report was delivered average 4.57 days after giving sample. After getting result 32.1% of the patients seek treatment in telemedicine and 23% directly consulted in Government hospital only 2% reported to be treated by the Government designated telephone number. 73.1% of the patient took both steam inhalation and warm water gargling. Paracetamol and antihistamine was the most commonly use drugs 69.8% and 71.5% respectively besides 47.5% took ivermectin 41.6% took azithromycin 35.1% steroid 34.8% took doxycyclin and 21.6% hydroxychloroquine. Among the patients only 20.3% needed hospital admission. The patients admitted in hospital average 5 (+/-3.922) days after onset of symptoms and hospital staying was 9.2 days (average). Breathless (54.83%) was the major cause of hospital admission and 19.35% patients admitted due to fear. 14% patients needed oxygen and average duration of oxygen was 4.84 days. 81.3% patients has taken oxygen in hospital and 18.8% at their home. Among the patient 2.2% needed ICU and artificial ventilation needed for 1.1% patients. The patients recovered after 17.74 days (average) from the onset of symptom. COVID-19 became negative (RT-PCR) at15th day from onset of symptom. 91.8%) were in mental stress to become the cause of infection spread to other family members 20.7%) reported that they were anxious that they would not get oxygen or ICU if required and 27.9% were suffering from fear of death. Weakness was the most common post disease symptom in 57.4% cases. Average time required for coming back to normal life was 21.59 days (+/-7.901) ranging a wide range from 5 to 60 days. Conclusion: COVID-19 patients were mostly male health worker. Fever cough pain in throat were most common symptoms. Hospital admission required in only one-fifth cases and ICU required for only 2% patients. Weakness was the most common post disease symptom. Keywords: COVID Bangladesh oxygen ivermectin Correspondence Dr. Ratindra Nath Mondal President Society of General Physician Founder-Daktarkhana (GP center) Rangpur Bangladesh Email dr.ratinmondal@gmail.com.
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