Targeting KRAS in Pancreatic Cancer.

Pancreatic cancer is mainly driven by mutations in the KRAS oncogene. While this cancer has shown remarkable therapy resistance, new approaches to inhibit mutated KRAS, KRAS activators and effectors show promise in breaking this therapeutic deadlock. Here, we review these innovations in therapies that target RAS signaling in pancreatic cancer from a clinical point of view. A number of promising approaches are currently in clinical trials or in clinical development. We focus on small-molecule drugs but also discuss immunotherapies and tumor vaccines.

Evaluation of Attitude and Knowledge of Endodontic, Pedodontic and SBARD Residents in Saudi Arabia toward Regenerative Endodontics-A National Survey.

Background and Objectives: There are no guidelines on the regenerative endodontic procedures that should be followed in dental treatment. Thus, it is essential to learn the knowledge, attitudes, and opinions about regenerative endodontics among dental practitioners, particularly endodontists, as they are the first providers of this type of dental treatment. Aim: This study aimed to assess the knowledge and attitudes among residents of the Saudi Board of Advanced Restorative Dentistry (SBARD) in Saudi Arabia. Methods & Materials: A questionnaire-based survey was conducted among 128 residents of endodontics, pedodontics, and the SBARD in Saudi Arabia. The questionnaire was distributed to participants using the available electronic measures such as emails and social media. The questionnaire was made by Google Forms, and responses were received directly in the excel sheet in the email. The data were exported as an excel file, coded, and analyzed, and the p-value < 0.05 was set as significant. Results: More than 50% (74 dentists) of the participants reported receiving continuing education in regenerative treatment, with a significant difference found among specialty (p = 0.023). No significant association was found between knowledge, gender, and type of postgraduate study. The vast majority (89.1%) of the participants believed regenerative endodontics should be incorporated into dentistry curricula. About two-thirds (78.2%) of the participants declared their ability to attend future training courses in a regenerative endodontic, whereas 10.9% did not, and 10.9% were unsure. Conclusions: The dental practitioners were enthusiastic and interested in regenerative and stem cell treatment. The results also suggested incorporating regenerative treatment into the dental curriculum and signaled the need for more continued training courses.

Molar Incisor Hypomineralization (MIH) in a Child with Congenital Chronic Intestinal Pseudoobstruction (CIPO).

Molar incisor hypomineralization (MIH) is a qualitative enamel defect of systemic origin affecting 1-4 permanent first molars (PFMs) frequently in association with affected permanent incisors (PIs). The exact etiology of MIH is still unclear but considered to be multifactorial. This present case report to the best of our knowledge is the first case reported which acknowledges MIH in a patient with chronic intestinal pseudoobstruction (CIPO) with underlying neurological disease due to somatic mitochondrial disorder. It also elicits the availability of various contemporary treatment options and their proper selection and early intervention to manage the functional and aesthetic problems caused by enamel defects and to improve the quality of life in the patients.

A study on nutritional status and tooth crown size among 6-9-year-old children: An observational cross-sectional study.

BACKGROUND: Numerous factors contribute to variation in tooth size. This is broadly described as genetic, epigenetic, and environmental factors. A strong genetic contribution has been shown, but environmental factors may also play a role. AIM: The aim of this study was to determine the relationship between nutritional status and tooth crown size. DESIGN: An observational cross-sectional survey was conducted among 100 school-going children of 6-9 years. The value obtained was plotted on age- and gender-specific percentile curves chart given by the Centers for Disease Control and Prevention; individuals were categorized based on body mass index criteria. The participants were examined for the mesiodistal width of primary second molar and permanent first molar by three different observers using a Vernier Caliper. Data obtained were statistically analyzed. RESULTS: total of 45, 40, and 15 belonged to underweight, normal, and overweight category, respectively. The tooth size of primary molar between healthy, overweight, and underweight children was 9.87 ± 0.23, 9.47 ± 0.48, and 9.61 ± 0.7, respectively, and for permanent molar between healthy, overweight, and underweight children was 10.63 ± 0.2, 10.56 ± 0.5, and 10.57 ± 0.6, respectively. CONCLUSION: The correlation between tooth crown size with an exogenous chronic stressor, i.e., malnutrition, was found to be nonsignificant when compared with the healthy individuals. The findings indicate that nutritional status does not significantly influence the determination of tooth size in humans.

A Single Versatile Appliance for Habit Interception and Crossbite Correction.

Digit sucking is a common childhood behavior, which has an adaptive value for children up to the fourth year of life. It is usually associated with oral pleasure and self-comforting behavior. But chronic practice may produce deleterious effect in the form of dental and skeletal deformities. Adjunctive therapy using bluegrass appliance as a permanent reminder and quadhelix appliance as a reminder as well as a slow palatal expander has proven successful in intercepting digit-sucking habit and expanding the arch for crossbite correction. In the present case, a versatile modified quadhelix appliance incorporating a roller was designed to clinically correct the habit and its resulting dentofacial deformities.

Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma.

Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor tissues. Immunohistochemical labeling of tumor tissue microarrays for validation of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of 98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly reduced cell proliferation, colony formation and invasion of gastric cancer cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK activation and suggest that CAMKK2 could be a novel therapeutic target in gastric cancer.

Juxtaoral Organ of Chievitz, an Obscure Anatomical Structure Masquerading as Perineural Invasion of Mucoepidermoid Carcinoma: Case Report and Review of Literature.

The juxtaoral organ was first described by Chievitz in 1885. This is typically located deep to the medial pterygoid muscle (unilaterally or bilaterally) in the pterygomandibular space. Juxtaoral organ of Chievitz (JOOC) is usually incidentally detected in biopsies or resection specimen of other tumors but exceptionally, it can present as mass lesions. Awareness of this normal anatomic structure is important, because the epithelial islands in this area could be misinterpreted as an invasive carcinoma, mucoepidermoid carcinoma, an odontogenic tumor such as ameloblastoma or adenomatoid odontogenic tumor, or a perineural invasion by carcinoma. When a portion of the juxtaoral organ of Chievitz is accidentally exposed by frozen biopsy, there is an even higher risk of mistaking these cells for an invasive cancer or a perineural invasion of carcinoma. We report this to create awareness about this obscure structure and to draw attention to its differential diagnosis.

Pediatric Hodgkin lymphoma in a South Indian regional cancer center: its immunomorphology, tumor-associated macrophages, and association with Epstein-Barr virus.

Pediatric Hodgkin lymphoma (HL) comprises approximately a fifth of all patients with HL in India. Seventy-four cases of pediatric classical Hodgkin Lymphoma (cHL) from a regional cancer center in southern India were analyzed on a tissue microarray (TMA) for the stage of B-cell differentiation of the Hodgkin/Reed Sternberg (HRS) cell by immunohistochemistry (IHC) using CD10, bcl6, MUM1/IRF4, and CD 138. Fifty-two of seventy-four (70.3%) cases were of late germinal center/early post-germinal center phenotype (CD10-/bcl6-/MUM1+/CD138-). Epstein-Barr virus (EBV) association using Epstein-Barr virus encoded RNA (EBER) RISH and EBV-LMP1 immunohistochemistry (IHC) revealed an EBV association of 93%. Tumor-associated macrophages (TAM) in the microenvironment were also assessed on the TMA by CD68 IHC, and most cases (59.7%) showed >25% TAMs, with no case showing ≤5%. These findings indicate that pediatric cHL in India is a tumor, predominantly, of late germinal center/early post-germinal center B cells, is almost invariably EBV associated, and with a high number of TAMs in the microenvironment. This latter finding suggests that criteria other than TAM scores need to be developed for risk stratification of pediatric EBV-associated HL especially in developing countries.

Boon of MTA Apexification in Young Permanent Posterior Teeth.

Single visit apexification using mineral trioxide aggregate (MTA) is a new boon in effective management of nonvital tooth with an open apex which has steadily gained popularity with clinicians; also it shortens the treatment period and improves patient compliance. Importance of this approach lies in expedient cleaning and shaping of the root canal system, followed by its apical seal with MTA. There are several case reports available describing the use of MTA as an apexification agent in incisors and premolar, but presented cases are the unique case reports demonstrating successful apexification procedure using MTA in young permanent mandibular molars. After eight-month follow-up, teeth were without any abnormal clinical symptoms; rather there were radiographic resolution of the periapical lesion and induction of root end closure with new hard tissue formation over MTA.

Neurofibromatosis type I with breast cancer: not only for women!

The association of neurofibromatosis type I with invasive male breast cancer is a rare clinical entity with only one case in literature reported in 1953. Women with NF1 are at risk of developing breast cancer and men also may be at risk but there is scarce data on the risk and association of NF1 with male breast cancer due to its rarity. Established clinical trials in male breast cancer patients are lacking and the results are extrapolated from female breast cancer patients. The treatment of male breast cancer is followed as per the guidelines of premenopausal female breast cancer and tamoxifen is the hormone treatment in them. Mendes et al suggests that silencing of NF1 gene confers resistance to tamoxifen. Our conclusions are that since NF1 is mutated or deleted in one third of sporadic breast cancers, its role as a molecular driver for treatment has to be further explored.

Foreign body oesophagus in a neonate: a common occurrence at an uncommon age.

Neonatal ingestion of foreign body is a very uncommon occurrence. We describe a 25-day-old neonate who had a large-sized stone impacted in the cervical oesophagus. The stone was accidently lodged by one of the elder siblings while playing. The stone, after failure to be retrieved endoscopically, was successfully removed by open esophagotomy. The case describes the unusual occurrence at a very uncommon age. It also re-affirms the successful role of open surgery in such situations, which are otherwise commonly treated endoscopically.