Pattern and trend of cancer in Saurashtra region in Gujarat state of India, a hospital-based study.

BACKGROUND: Cancer is growing concern for every country. Reliable data is a source to define the magnitude of the problem, which then helps to plan for necessary action. This epidemiological study involves the collection and analysis of hospital registry data to assess the quantum of the problem of cancer over a five-year period from 2012-16 and to plan priority action. MATERIALS AND METHODS: Hospital-based data for five years from 2012-2016 was retrieved from the department of radiotherapy at M. P. Shah Government Medical College, Jamnagar, Gujarat, India, and analysed to define the magnitude of the problem. All data was studied using Microsoft Excel 2016. RESULTS: A total of 7355 patients were registered between 2012 and 2016, out of which 62 percent were male. Cancers of the cervix and uterus were discernibly less common in the Saurashtra region and accounted for only 12.37% of all cancers in females. Lung cancer was the leading cancer as a single site in males (24.13% of all cancers in males) and breast cancer in females (37.36% of all cancers in females). Head and neck cancer, all sites clubbed, was most common in males (42%). Jamnagar taluka represented around 50% of all cases at the study center. CONCLUSION: Tobacco-related cancers were most common in the male population, and stringent implementation of a national tobacco control program is the most appropriate measure to curtail incidences and hence mortality in this male population. Non-modifiable risk factors like gender-related cancer were more common in the female population, and resource-appropriate screening is a suitable option for these diseases. A population-based cancer registry is required to further define the pattern pertinently, or an epidemiological study is required to find causes of the noticeably lower incidence of cancer of the cervix,.

Inhibitory effect of selected Indian honey on colon cancer cell growth by inducing apoptosis and targeting the ß-catenin/Wnt pathway.

Colon cancer is the most prevalent cause of death from cancer across the globe. Although chemotherapy drugs are predominantly used, their toxicity always remains a cause of concern. As an alternative to synthetic drugs, natural compounds or nutraceuticals are comparatively less toxic. Honey is widely used across different cultures as an alternative form of medicine. It represents a prominent source of plant-phenolic compounds and there is demonstrable evidence of its anti-oxidant and anti-microbial activities. The aim of the present work was to investigate the anti-proliferative effect of some Indian honeys and analyze their mechanism of action in colon cancer. In order to establish the composition-activity relationship, we evaluated the bioactive components present in selected honey samples by GC-MS and HPLC analysis. Indian honey samples showed a significant inhibitory impact on cell growth by restricting cell proliferation, causing apoptosis, and restricting the cell cycle in the G2/M phase specifically for colon cancer cells. The apoptotic activities, as imparted by the honey samples, were established by Annexin V/PI staining, real-time PCR, and immunoblot analyses. The treated cells showed increased expressions of p53 and caspases 3, 8, and 9, thus indicating the involvement of both extrinsic and intrinsic apoptotic pathways. The honey samples were also found to inhibit the ß-catenin/Wnt pathway. In the next phase of the study, the efficacy of these honey samples was evaluated in colon carcinoma induced SD-rats. Overall, these findings demonstrated that selected Indian honeys could be established as effective nutraceuticals for the prevention as well as cure of colon cancer.

PET-CT scan-based maximum standardized uptake value as a prognostic predictor in oropharynx squamous cell cancer.

INTRODUCTION: Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET-CT) is clinically useful and extensively used in initial staging and follow-up of patients with head and neck squamous cell carcinoma (HNSCC). We studied the potential prognostic significance of primary tumor maximum standard uptake value (SUVmax) by 18F-FDG PET-CT in oropharyngeal cancer. METHODS: Sixty patients with early and locally advanced histopathologically proven oropharyngeal squamous cell cancer were staged using FDG PET-CT at diagnosis. All patient received radiation therapy and concurrent chemotherapy (in stage III and IVA disease) and were assessed prospectively for treatment outcome. Groups were created based on stage and cut off for SUVmax. The association of SUVmax of primary tumour and stage with disease-free survival and overall survival was analyzed by univariate and multivariate statistics. RESULTS: In univariate analysis, a primary tumour SUVmax of greater than 13.0 and advanced stage (IVA) predicted inferior disease-free survival (P=0.0241 and 0.0005, respectively) and overall survival (P=0.0510, toward significance and 0.0003, respectively). In proportional hazards analysis, stage was significant only when adjusted for primary SUVmax. CONCLUSION: SUVmax failed to demonstrate predictive significance in oropharyngeal cancer, and an increase in primary tumor uptake is possibly a direct effect of advanced disease and consequently increased metabolic activity and aggressiveness.

Physiological Relevance of Angiotensin Converting Enzyme 2 As a Metabolic Linker and Therapeutic Implication of Mesenchymal Stem Cells in COVID-19 and Hypertension.

Severe acute respiratory syndrome corona virus - 2 (SARS-CoV-2) is a single stranded RNA virus and responsible for infecting human being. In many cases the individual may remain asymptomatic. Some recently reported studies revealed that individuals of elderly age group and with pre-existing medical conditions such as hypertension, diabetes mellitus had severe consequences, even may lead to death. However, it is not clearly delineated whether hypertension itself or associated comorbidities or antihypertensive therapy contributes to the grave prognosis of COVID-19 infections. This review is aimed to decipher the exact mechanisms involved at molecular level from existing evidence and as reported. It has been reported that SARS-CoV-2 enters into the host cell through interaction between conserved residues of viral spike protein and angiotensin converting enzyme 2 (ACE2) receptor which is highly expressed in host's cardiac and pulmonary cells and finally transmembrane protease, serine-2 (TMPRSS2), helps in priming of the surface protein. Subsequently, symptom related to multi organ involvement is primarily contributed by cytokine storm. Although various clinical trials are being conducted on renin- angiotensin- system inhibitor, till to date there is no standard treatment protocol approved for critically ill COVID-19 positive cases with pre-existing hypertension. Recently, several studies are carried out to document the safety and efficacy outcome of mesenchymal stem cell transplantation based on its immunomodulatory and regenerative properties. Therefore, identification of future novel therapeutics in the form of mesenchymal stem cell either alone or in combination with pharmacological approach could be recommended for combating SARS-CoV-2 which might be dreadful to debilitating elderly people. Graphical Abstract.

An Assessment on Impact of COVID-19 Infection in a Gender Specific Manner.

Coronavirus disease 2019 (COVID-19) is caused by novel coronavirus Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first time reported in December 2019 in Wuhan, China and thereafter quickly spread across the globe. Till September 19, 2020, COVID-19 has spread to 216 countries and territories. Severe infection of SARS-CoV-2 cause extreme increase in inflammatory chemokines and cytokines that may lead to multi-organ damage and respiratory failure. Currently, no specific treatment and authorized vaccines are available for its treatment. Renin angiotensin system holds a promising role in human physiological system specifically in regulation of blood pressure and electrolyte and fluid balance. SARS-CoV-2 interacts with Renin angiotensin system by utilizing angiotensin-converting enzyme 2 (ACE2) as a receptor for its cellular entry. This interaction hampers the protective action of ACE2 in the cells and causes injuries to organs due to persistent angiotensin II (Ang-II) level. Patients with certain comorbidities like hypertension, diabetes, and cardiovascular disease are under the high risk of COVID-19 infection and mortality. Moreover, evidence obtained from several reports also suggests higher susceptibility of male patients for COVID-19 mortality and other acute viral infections compared to females. Analysis of severe acute respiratory syndrome coronavirus (SARS) and Middle East respiratory syndrome coronavirus (MERS) epidemiological data also indicate a gender-based preference in disease consequences. The current review addresses the possible mechanisms responsible for higher COVID-19 mortality among male patients. The major underlying aspects that was looked into includes smoking, genetic factors, and the impact of reproductive hormones on immune systems and inflammatory responses. Detailed investigations of this gender disparity could provide insight into the development of patient tailored therapeutic approach which would be helpful in improving the poor outcomes of COVID-19. Graphical abstract.

Acute Thyroid Profile Changes During External Beam Irradiation of Neck.

Thyroid gland is irradiated to a considerable dose in conventional radiotherapy of head neck cancer and significant proportion of patients later develop hypothyroidism. This study is an effort to shed light on acute changes in thyroid function after irradiation those are less clearly defined. Values were recorded before radiation treatment, after 4 week of irradiation, after completion of treatment, 1 month after completion of treatment and after 4 months of completion of treatment. A repeated measures ANOVA with a Greenhouse-Geisser correction determined that mean T3, T4 and TSH levels differed statistically significantly between time points. Post hoc test using the Bonferroni correction revealed statistical significance difference in values of T3, T4 and TSH done at specific intervals. External irradiation in cancer therapeutic doses affects thyroid function and sets at a new point with increased TSH, but in reference ranges, to maintain required thyroxin level.

Prognostic significance of tumor volume as determined on 3D ultrasound scan in uterine cervix cancer treated by radiotherapy.

AIMS: The aim of this prospective study is to evaluate prognostic significance of tumor volume determined by three-dimensional (3D) ultrasound scan in uterine cervix cancer patients treated by radiotherapy. PATIENTS AND METHODS: A total of 67 patients of Stage IB2-IIIB were studied and analyzed. Cervical tumor volume was determined by 3D ultrasound scan. Two groups were made on the basis of volume on ultrasound scan (Group 1 <40 cc = 36 and Group 2 >40 cc = 31). Both groups received external beam radiotherapy (EBRT) and intracavitary radiation therapy (ICRT). Cisplatin 40 mg/m 2 every week was given concurrently with external irradiation. Tumor volumes were taken by 3D USG every week during EBRT, after each fraction of ICRT, and after 8 weeks of completion of treatment. Primary end point was disease-free survival (DFS), and secondary endpoints were 5-year survival and toxicities. RESULTS: After 2 months of completion of treatment, 1 out of 36 patients of Group A was having residual and 7 out of 31 of Group B were having residual diseases (P = 0.034). DFS and 5-year survival were significantly different in the groups (log rank test P = 0.0014, hazard ratio (HR) =2.3622 95% confidence interval (CI) 1.3090-4.2625 and P = 0.0421, HR = 1.9274 95% CI 0.9998-3.7156, respectively). CONCLUSIONS: Ultrasound is a cheap, simple, and useful in predicting the outcome of treatment and DFS based on the tumor volume.

Identification of quinazoline compounds as novel potent inhibitors of Wnt/ß-catenin signaling in colorectal cancer cells.

The Wnt/ß-catenin signaling pathway is critical for the initiation and progression of most colon cancers, and has emerged as one of the most promising targets for colorectal cancer chemoprevention and treatment. In this study, we have discovered a structurally related series of quinazolines as potent inhibitors of Wnt/ß-catenin signaling in colorectal cancer cells harboring mutations in CTNNB1 or APC. We showed that the quinazoline leads suppressed Wnt/ß-catenin signaling without altering the level of ß-catenin protein in colorectal cancer cells, suggesting that they act on the downstream elements of the pathway. Moreover, the quinazoline leads displayed potent anticancer activities with IC50 values between 4.9 and 17.4 µM in colorectal cancer cells. Importantly, we also found that a structurally related quinazoline lacking inhibitory effect on Wnt/ß-catenin signaling was unable to suppress colorectal cancer cell proliferation. Together, these results suggest that the quinazoline lead compounds identified in this study have therapeutic potential for the prevention and treatment of colorectal cancer.

14-Alkoxy- and 14-acyloxypyridomorphinans: µ agonist/δ antagonist opioid analgesics with diminished tolerance and dependence side effects.

In the search for opioid ligands with mixed functional activity, a series of 5'-(4-chlorophenyl)-4,5α-epoxypyridomorphinans possessing alkoxy or acyloxy groups at C-14 was synthesized and evaluated. In this series, the affinity and functional activity of the ligands were found to be influenced by the nature of the substituent at C-14 as well as by the substituent at N-17. Whereas the incorporation of a 3-phenylpropoxy group at C-14 on N-methylpyridomorhinan gave a dual MOR agonist/DOR agonist 17h, its incorporation on N-cyclopropylmethylpyridomorphinan gave a MOR agonist/DOR antagonist 17d. Interestingly, 17d, in contrast to 17h, did not produce tolerance or dependence effects upon prolonged treatment in cells expressing MOR and DOR. Moreover, 17d displayed greatly diminished analgesic tolerance as compared to morphine upon repeated administration, thus supporting the hypothesis that ligands with MOR agonist/DOR antagonist functional activity could emerge as novel analgesics devoid of tolerance, dependence, and related side effects.