Silent mating type information regulation 2 homolog (SIRT1), a key protein involved in cellular regulation, exhibits altered expression in breast cancer. The study aimed to assess serum Sirtuin 1 level, investigate SIRT1 gene polymorphisms, and examine their association with breast cancer. One hundred seventy-two breast cancer patients and 78 healthy age-matched females were included in the study. Genetic variants of the SIRT1 gene were identified using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism/Sanger Sequencing and serum SIRT1 levels using Enzyme-Linked Immuno Sorbent Assay. Serum SIRT1 levels were significantly higher in breast cancer patients [0.822 (0.72-0.96)] than controls [0.752 (0.66-0.86)], p = 0.0027. Subgroup analyses revealed notable increases in Human epidermal growth factor receptor 2-positive (p = 0.0016), hormone-positive (p = 0.0232), and Triple Negative Breast Cancer groups (p = 0.4426) compared to the control group. The SIRT1 levels were also significantly associated with breast cancer (p = 0.0252). SIRT1 exhibited an Area Under Curve (AUC) of 0.618, with 58% sensitivity and specificity at a cutoff of 0.797, showing poor discriminative ability. rs141528984 had a significant difference in allele frequency between patient group and control group (OR = 3.48, 95% CI: 1.896-6.516), p < 0.0001. There were no significant associations between SIRT1 gene polymorphisms and serum Sirtuin 1 levels in breast cancer patients. The proliferation marker Ki67 showed a significant association (p = 0.0428) with specific SIRT1 variants, rs777323664, rs757804740, and rs184282868. SIRT1 levels are elevated in breast cancer patients indicate its potential as a diagnostic marker. Mutant alleles of rs141528984 were more common in controls compared to case group, indicating its protective function. Ki67 expression was associated with rs777323, rs757804740, and rs1842828683 which may contribute to tumor aggressiveness.

Ovarian cancer (OC) is often detected at an advanced stage of disease and needs complex anticancer treatment regimens to manage it. Anticancer drugs are highly toxic and act on normal and malignant cells, which may increase the occurrence of drug-related problems (DRPs). OC patients undergoing anticancer therapy are anticipated to produce serious adverse health outcomes. DRPs are the events linked to drug therapy that possibly affect healthcare outcomes. Management of such events is challenging. DRPs must be promptly identified and resolved on time to optimize patient care and prevent extra health-related burdens. The Prediction model will help the healthcare team prevent the occurrence of DRPs in patients and reduce adverse effects due to DRPs. The current study was a prospective observational study conducted among OC patients. Enrolled patients were screened for possible DRPs throughout their hospital admission. A prediction model for DRPs was developed and validated using stepwise linear regression. The cumulative medication entries were 1836 among 143 patients. Most patients were in an extreme polypharmacy condition (80.42%). 724 DRPs were observed among 142 patients, consisting of actual DRPs (44.61%, n = 323) and potential DRPs (55.39%, n = 401). 56.34% of the patients had ≥ 5 DRPs. Age, length of stay, stage of cancer, line of anticancer agents, anticancer agent cycle, comorbidities, and number of drugs prescribed were the substantial predictors for DRPs. This study reveals a higher prevalence of DRPs in ovarian cancer patients and triggers the implementation of therapeutic vigilance for early identification and timely management of DRPs. Timely management of DRPs can help reduce the treatment burden.

PROBLEM CONSIDERED Cancer-related cognitive impairment or CRCI is an adverse effect of chemotherapy that reduces executive function, processing speed and memory of cancer patients. Various factors that are associated with CRCI in turn leads to a significant reduction in the quality of life of cancer patients. This study aims to identify the proportion of cancer patients having CRCI and reduced QoL, and assess the respective factors related to the decline of the same. METHODS A cross-sectional study was conducted in a period of 6 months among 138 cancer patients undergoing chemotherapy. Necessary data pertaining to sociodemographic and clinical aspects were collected, and questionnaires Functional Assessment of Cancer Therapy – Cognitive Function and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were administered to assess the cognitive function and QoL, respectively. The data was entered and analysed using SPSS Software version 29. Pearson correlation and Linear regression were used to evaluate the data. RESULTS A weak positive correlation (Pearson’s r = 0.236, p = 0.005) was observed between cognitive function anf quality of life. On univariate analysis, age, comorbidities, alcohol and tobacco use, pre-medications and chemotherapy agents were associated with cognitive function and QoL. After adjustment for covariates, age, comorbidities, and tobacco/areca nut use remained significantly associated with cognitive impairment, whereas none of the assessed factors remained significantly associated with QoL. CONCLUSION Age, comorbidities, and tobacco/areca nut use were independently associated with cognitive impairment among patients receiving chemotherapy, and cognitive function was positively correlated with quality of life; no factors showed an independent association with QoL after adjustment. These findings support individualized screening and management strategies for chemotherapy-related cognitive impairment (CRCI).

Metastatic malignant melanoma, which presents as obstructive jaundice due to common bile duct (CBD) involvement, is exceedingly rare. We present a case of a 36-year-old woman with metastatic malignant melanoma involving multiple organs including the lungs, pancreas, gallbladder, chest wall, and cervix, complicated by obstructive jaundice of unknown primary origin. Diagnostic evaluation revealed widespread metastases confirmed by histopathology and immunohistochemistry, positive for human melanoma black 45 and S-100. Treatment included placement of a self-expanding metallic stent in the CBD and initiation of pembrolizumab immunotherapy. This case highlights the diagnostic challenges and therapeutic considerations in managing metastatic melanoma with unusual biliary tract involvement.

Duodenal neuroendocrine tumors (d-NETs) are rare neoplasms representing a small subset of gastrointestinal NETs. Due to their nonspecific symptoms, such as abdominal pain, vomiting, and weight loss, diagnosis is often delayed. This case series analyzes six patients with well-differentiated d-NETs, highlighting their clinical presentation, diagnostic evaluation, treatment strategies, and follow-up. Diagnosis was established through endoscopic biopsy, imaging modalities including computed tomography (CT) and positron emission tomography-CT, and confirmed by histopathology and immunohistochemistry. Tumors were graded using the World Health Organization/European Neuroendocrine Tumor Society classification, with Ki-67 indices ranging from 1 to 6%, corresponding to grade 1 or 2 NETs. Treatment included endoscopic or surgical resection in localized cases, while somatostatin analog therapy and peptide receptor radionuclide therapy were used in multifocal or metastatic disease. All patients were managed with an individualized, multidisciplinary approach, and demonstrated stable disease on follow-up. This study emphasizes the importance of early detection, accurate grading, and personalized management to optimize outcomes in patients with d-NETs.

Trichoblastic carcinoma is a rare malignancy. Here, we present the case of a man in his mid-40s with a recurrent ulcer. Histological findings are positive for trichoblastic carcinoma. The patient completed radiotherapy and is currently on chemotherapy. Trichoblastic carcinomas have no retraction clefts or peripheral palisade. Immunohistochemistry (IHC) was done to narrow the diagnosis further, showing CD-10 positivity. Since their management methods vary, we emphasise differentiating basal cell carcinoma from trichoblastic carcinoma.

Invasive mole is a type of gestational trophoblastic neoplasia (GTN). It usually occurs after a molar or non-molar pregnancy. Here we would like to present a 47-year-old nulligravida lady who does not give any history of antecedent pregnancy. She had symptoms of abnormal uterine bleeding (AUB) and came to the causality with heavy flow. Beta hCG was very high and MRI showed uterine tumor. She underwent total abdominal hysterectomy with bilateral salpingoopherectomy which showed invasive mole FIGO stage II. Her WHO prognostic score was 9 and hence she received EMA-CO regimen of chemotherapy. GTN can present in different ways, even without a history of previous pregnancy. In such situations a high level of suspicion and a simple Beta hCG level can clinch the diagnosis.

Introduction Tyrosine kinase inhibitors (TKIs), although considered less toxic than conventional chemotherapy, are not short of adverse drug reactions (ADRs). Cutaneous toxicities are among the most frequently reported ADRs; when severe, they can cause substantial morbidity, often requiring dose reduction or drug cessation. Objectives 1. To estimate the frequency and pattern of mucocutaneous adverse reactions of TKI. 2. To grade the adverse reactions based on the severity scale of CTCAE v 5.0. Materials and Methods This was a hospital-based observational study of 105 patients on TKI chemotherapy, attending the outpatient departments of dermatology and medical oncology, at Justice K.S. Hegde Charitable Hospital, Mangalore, from October 1, 2022, to April 30, 2024. Mucocutaneous adverse reactions after the initiation of TKI were recorded and graded according to the severity scale of CTCAE v 5.0. and causality was assessed using WHO-UMC criteria. Results Among 105 patients, a majority of 34 (32.4%) patients belonged to the age group of 51 to 60 years, with a male predominance of 2:1. The most frequent cancer was lung in 38 (36.2%) patients, followed by CML in 21 (20.0%) patients. The most common class of TKI agent used was EGFR inhibitors in 51 (48.6%) patients, with gefitinib being the most common TKI agent in 46 (43.8%) patients. The most frequently reported ADRs were xerosis in 45 (42.9%) patients, followed by eczematous changes in 37 (35.2%) patients. The papulopustular rash was most commonly seen with EGFR inhibitors in 25 (49.0%) patients, eczematous changes with BCR-ABL inhibitors in 14 (50.0%), and hand-foot skin reaction with multikinase inhibitors in 12 (54.4%) patients. A statistically significant association was noted between papulopustular rash and paronychia among patients on EGFR inhibitors. Additionally, a statistically significant association was noted between hand-foot skin reaction and subsequent dose reduction. Conclusion An awareness regarding the various ADRs of TKIs and interdisciplinary cooperation between oncologists and dermatologists will help in precise diagnosis and early identification of various cutaneous toxicities.

In this article, the following changes have been made to the affiliation section: Affiliations numbered 1, 5, 6, and 7 have been revised. The corresponding author has been updated to Vijith Shetty. The corresponding author’s email address has been updated to: drvijithshetty@gmail.com

Objectives: Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. The epidermal growth factor receptor (EGFR) signalling pathway plays a vital role in the progression of HCC by influencing cell proliferation, survival, and resistance to apoptosis. This study aimed to identify the microRNAs (miRNAs) that regulate EGFR signalling in HCC using in silico approaches. Material and Methods:The differential expression of EGFR and its correlation with patient survival in HCC were first established by analysing relative gene expression and overall survival using the University of Alabama at Birmingham Cancer (UALCAN) data analysis portal. Further, EGFR-associated genes and the regulatory transcription factors (TFs) were identified through STRING and Network Analyst tools, respectively. The protein-protein interaction (PPI) network of EGFR-associated genes was then constructed using Cytoscape. The differentially expressed miRNAs (DE-miRNAs) in HCC were identified by analysing the GSE dataset GSE147889 using the GEO2R tool. The miRWalk database was extensively mined to predict miRNAs targeting EGFR and its associated genes. Finally, a regulatory network was built to map the interactions between the miRNAs, TFs, and EGFR-associated genes. Results: The UALCAN analysis revealed that EGFR is downregulated in liver carcinoma, but there is no significant correlation with patient survival. The PPI network analysis identified 21 critical genes and 30 TFs involved in EGFR regulation. Among the 18 differentially expressed miRNAs, hsa-miR-216 b-5p, hsa-miR-214-3p, hsa-miR-325, hsa-miR-199a/b-3p, and hsa-miR-200a-3p were identified as key regulators of EGFR expression. Furthermore, the regulatory network analysis revealed that 15 DE-miRNAs regulate EGFR by targeting 14 EGFR-associated genes and interacting with 23 TFs. Conclusion: This in silico study identifies hsa-miR-216b-5p, hsa-miR-214-3p, hsa-miR-325, hsa-miR-199a-3p, hsa-miR-200a-3p, and hsa-miR-199b-3p as hub miRNAs regulating EGFR in HCC. Although further experimental validation is required, these miRNAs may have the potential to develop as diagnostic or prognostic markers, as well as therapeutic targets, in the management of liver carcinomas.

A myeloproliferative disorder known as chronic myeloid leukemia (CML) is caused by the clonal proliferation of haematopoietic progenitor stem cell leading to a marked raise in the granulocyte series of cells in the peripheral blood and bone marrow. The present study focused on evaluating clinical and haematological parameters. It is an observational study conducted over a period of 3 years which constitutes 50 diagnosed CML patients. Clinical and haematological details were collected. Prognostic Sokal and European treatment and Outcomes Study (EUTOS) scoring were applied to stratify different risk groups of patients. Study population showed male preponderance. The most common presenting symptom was splenomegaly (98%) followed by anaemia (94%). The patients were divided into Chronic Phase (CP), Accelerated Phase (AP) and Blast phase (BP) in males and females. In males, there was a significant reduction in haemoglobin levels as the disease progressed whereas in females, there was a reduction in haemoglobin levels. Haemoglobin count reflected the anaemic picture and was lowest in the blast phase. The blood cell indices and differential counts were within their normal range in both male and female patients. There was variation in the levels of lymphocytes among males and females but lower than the normal range. Basophil levels were significant between the different phases in females whereas platelet count was significant in males. The current study expected that there would be significant variations between male and female CML patients in a number of haematological measures which can be used as a good prognostic indicator.

Despite the advancement in understanding tumour biology, diagnosis, and treatment of cancer patients, overall survival is still a major concern among the medical fraternity. Drug resistance accounts for about 90 % of chemotherapy failure, which is often linked to gene expression. Thus, understanding the molecular mechanism of the novel genes in cancer development, prognosis, and survival could bring a milestone change in cancer management. Small proline-rich proteins (SPRR1), particularly SPRR1A and SPRR1B, have been reported as an emerging molecule in cancer. Generally, SPRR1A or SPRR1B genes have been found to be overexpressed in the lung's cancer, melanoma, breast cancer, colon cancer, pancreatic cancer, lymphoma, and bladder cancer, whereas they are often found to be downregulated in esophageal cancer, gastric cancer, cervical cancer, etc. However, SPRR1A/SPRR1B expressions are frequently altered in head and neck cancer and reported to influence cancer prognosis and outcomes, but their expression remains uncertain as they show both up and down regulation. Thus, up or down-regulation of SPRR1A/1B due to dysregulation of pathways such as RAS/RAF/MEK/ERK, Wnt/β-catenin, Notch, Hedgehog, TGF-β, and JAK/STAT accelerates tumorigenesis either by promoting proliferation, metastasis, or by affecting survival and drug response. Although there are limited studies on their implications in chemoresistance, SPRR1A/1B can be used as a theranostic marker for cancer, further exploring its relevance in the field of precision medicine.

Background and Objectives Metastatic gastric carcinoma makes the current treatment options unsatisfactory. There is HER2 directed therapy like transtuzumab are used in metastatic gastric cancer. This study aimed to determine the tissue HER2/neu status by immunohistochemistry (IHC) and find their relation with clinicopathological parameters for assessing the prognosis. Study Design, Materials, and Methods In this descriptive study, 30 patients of gastric cancer with metastasis were studied for HER2/neu expression by IHC. The chi-square test was used to determine the association between HER2/neu expression and clinicopathological parameters of patients. Results and Conclusion The majority of samples (90%) were endoscopic biopsies from patients with a mean age of 61.4 years. Tumors were majorly of intestinal type (67%) with moderately differentiated grade located at the fundus of the stomach. The common site of metastasis was the lymph node (53.33%) followed by lymph node and liver metastasis (13.33%). The overexpression of HER2/neu by IHC was observed in 13.3% of cases. Furthermore, no significant association was observed between HER2/neu and gender, diet, age, tumor site, subtype, and grade. Overall, HER2/neu overexpression can be considered an independent prognostic factor for carcinoma stomach. Therefore, the patients identified with HER2/neu overexpression are targeted for trastuzumab therapy.

BACKGROUND:Chemotherapy is the most commonly utilized therapeutic strategy among the numerous cancer treatments. These chemotherapeutic agents have a variety of adverse reactions, one of which is taste alteration (TA), which substantially influences the patient's nutritional status and quality of life (QoL). OBJECTIVE:The study aims to assess TAs, associated factors, and the nutritional status and QoL of cancer patients undergoing chemotherapy. METHODS:An observational cross-sectional study was carried out for 6 months, among cancer patients diagnosed with TA. Data was collected using a chemotherapy-induced taste alteration scale (CiTAS). Demographic details of the patients, factors associated with TA, details regarding chemotherapeutic agent used, number of current chemotherapy cycles etc, were recorded using a self-designed data collection form. Nutritional status and QoL on cancer patients were collected using Mini nutritional assessment - short form (MNA-SF) and EuroQol 5 dimension 5 levels (EQ5D5L), respectively, and statistical package for the social sciences (SPSS) software version 29 was used for the analysis of data. RESULTS:A significant association was observed between TA and QoL. There was also a significant association between TA and predisposing factors such as nausea and dry mouth, which was obtained from the Chi-square test. Male patients were found to have higher TA than female patients. TA has also affected various aspects of QoL, such as mobility, pain, and discomfort. Patients experiencing mouth dryness or xerostomia had higher TA than others. A negative association was seen between TAs and nutritional status. CONCLUSION:This study shows a significant relationship between gender and TA, dry mouth, nausea, and TA. Several QoL factors like mobility, pain/discomfort, and TA were also observed. Despite this study not observing any statistical association between nutritional status and TA, clinically, most of the patients with higher TA were malnourished. This study concluded that there was a relationship between TA and QoL and that nausea and dry mouth are the predisposing factors for TA.

Among non-Hodgkin's lymphomas (NHLs), anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a relatively uncommon subtype that accounts for 3% of all adult NHLs. It typically affects young males, with a prevalence of three to one. Most cases present with nodal disease at the time of presentation. An extranodal involvement is seen in 60% of cases and skin involvement is seen in only 8 to 21% of cases. Cutaneous involvement in ALCL can manifest as primary cutaneous ALCL or secondary to systemic ALCL, and while CD30 positivity is common to both, ALK is not expressed by the former. A secondary skin involvement is usually associated with a poorer prognosis. We report a rare case of an isolated cutaneous relapse of systemic ALK-positive ALCL in a 62-year-old woman following the second cycle of chemotherapy. The acute febrile, widespread papulonodular eruption clinically resembled mycosis fungoides and lymphomatoid papulosis. With the introduction of oral crizotinib, a drastic improvement in the skin lesions and an exceptional response on positron emission tomography-computed tomography were noted.

Introduction The sirtuin (Silent mating type information regulation 2 homolog)1(SIRT1) protein plays a vital role in many disorders such as diabetes, cancer, obesity, inflammation, and neurodegenerative and cardiovascular diseases. The objective of this in silico analysis of SIRT1's functional single nucleotide polymorphisms (SNPs) was to gain valuable insight into the harmful effects of non-synonymous SNPs (nsSNPs) on the protein. The objective of the study was to use bioinformatics methods to investigate the genetic variations and modifications that may have an impact on the SIRT1 gene's expression and function. Methods nsSNPs of SIRT1 protein were collected from the dbSNP site, from its three (3) different protein accession IDs. These were then fed to various bioinformatic tools such as SIFT, Provean, and I- Mutant to find the most deleterious ones. Functional and structural effects were examined using the HOPE server and I-Tasser. Gene interactions were predicted by STRING software. The SIFT, Provean, and I-Mutant tools detected the most deleterious three nsSNPs (rs769519031, rs778184510, and rs199983221). Results Out of 252 nsSNPs, SIFT analysis showed that 94 were deleterious, Provean listed 67 dangerous, and I-Mutant found 58 nsSNPs resulting in lowered stability of proteins. HOPE modelling of rs199983221 and rs769519031 suggested reduced hydrophobicity due to Ile 4Thr and Ile223Ser resulting in decreased hydrophobic interactions. In contrast, on modelling rs778184510, the mutant protein had a higher hydrophobicity than the wild type. Conclusions Our study reports that three nsSNPs (D357A, I223S, I4T) are the most damaging mutations of the SIRT1 gene. Mutations may result in altered protein structure and functions. Such altered protein may be the basis for various disorders. Our findings may be a crucial guide in establishing the pathogenesis of various disorders.

Epithelioid trophoblastic tumor (ETT) is the rarest type of gestational trophoblastic neoplasia. It has variable presentations and is an aggressive tumor. Because of its rarity, it is difficult to establish an appropriate diagnosis, management, and follow-up. A woman of age 45 years postmenopausal status with an antecedent term pregnancy 13 years back was diagnosed to have ETT in the hysterectomy specimen. She had come with urinary retention as the tumor was infiltrating the bladder. Beta-human chorionic gonadotropin levels were normal. Immunohistochemistry confirmed the diagnosis. Though metastatic workup was normal, adjuvant multiagent chemotherapy was given as the bladder flap margin was not free of tumor cells and antecedent pregnancy was > 4 years. Every new case of ETT needs to be reported to bring about more awareness of the unusual presentations, and it may help come to a consensus for appropriate management.

Introduction:The sirtuin (Silent mating type information regulation 2 homolog)1(SIRT1) protein plays a vital role in many disorders such as diabetes, cancer, obesity, inflammation, and neurodegenerative and cardiovascular diseases. The objective of this in silico analysis of SIRT1's functional single nucleotide polymorphisms (SNPs) was to gain valuable insight into the harmful effects of non-synonymous SNPs (nsSNPs) on the protein. The objective of the study was to use bioinformatics methods to investigate the genetic variations and modifications that may have an impact on the SIRT1 gene's expression and function. Methods:nsSNPs of SIRT1 protein were collected from the dbSNP site, from its three (3) different protein accession IDs. These were then fed to various bioinformatic tools such as SIFT, Provean, and I- Mutant to find the most deleterious ones. Functional and structural effects were examined using the HOPE server and I-Tasser. Gene interactions were predicted by STRING software. The SIFT, Provean, and I-Mutant tools detected the most deleterious three nsSNPs (rs769519031, rs778184510, and rs199983221). Results:Out of 252 nsSNPs, SIFT analysis showed that 94 were deleterious, Provean listed 67 dangerous, and I-Mutant found 58 nsSNPs resulting in lowered stability of proteins. HOPE modelling of rs199983221 and rs769519031 suggested reduced hydrophobicity due to Ile 4Thr and Ile223Ser resulting in decreased hydrophobic interactions. In contrast, on modelling rs778184510, the mutant protein had a higher hydrophobicity than the wild type. Conclusions:Our study reports that three nsSNPs (D357A, I223S, I4T) are the most damaging mutations of the SIRT1 gene. Mutations may result in altered protein structure and functions. Such altered protein may be the basis for various disorders. Our findings may be a crucial guide in establishing the pathogenesis of various disorders.

AbstractChoriocarcinoma can be gestational and nongestational. Gestational choriocarcinoma is rare with an incidence of 9.2 in 40,000 pregnancies in Asian population. They can occur following molar, partial molar pregnancy, abortion, or delivery. It is detected by elevated levels of serum beta-human chorionic gonadotropin (beta-hCG) and by imaging modality. The need for histopathological diagnosis for choriocarcinoma is debatable. Six cases of choriocarcinoma are described with variable presentations and outcomes. Out of six cases, three were following vaginal delivery, two were after abortion, and one case was perimenopausal with antecedent pregnancy 10 years ago, unclear whether it was the cause for choriocarcinoma. Brain and lung metastasis were seen in three cases each; one case, which had metastasis to all organs, had worse prognosis and succumbed to the disease. All belonged to high-risk group according to International Federation of Gynaecology and Obstetrics score (8–13). The prognosis is usually very good, provided that prompt diagnosis and treatment are initiated early. Long-term follow-up with beta-hCG levels needs to be done to detect recurrence but it did not act like a prognostic indicator in our case series.

Cancer is known as a disease with a high morbidity and mortality rate. There are several short-term and long-term complications of cancer, leading to poor quality of life. Cancer in advanced stage and malignant tumors requiring a multisystem involvement makes the treatment challenging. The diverse health impact of cancer requires a multidisciplinary approach for treatment. The oncology pharmacy has facilitated a revolutionary approach for preparing and training specialised pharmacists to deal with a variety of health challenges faced by cancer patients. Oncology pharmacists or oncopharmacists are the experts in designing drug therapy and individualizing it in accordance with the requirements. The conventional and novel role of pharmacists in clinical pharmacy practice is documented to positively impact the health of cancer patients, including cancer survivors. Hence, this review tries to summarize the potential role of oncopharmacists.